MED627 - Cerebrovascular Disease and Disorders of Consciousness

Question 1

Define transient loss of consciousness

Answer 1

• Spontaneous LOC with complete recovery

- TLOC/blackout/syncope

Question 2

Describe the epidemiology of TLOC

Answer 2

• Increases with age
• Increase in incidence rate was steeper starting at 70yrs
• Rates similar among men and women
• Survival worst for patients with cardiovascular disease

Question 3

What are the clinical challenges of TLOC?

Answer 3

• Main witness unconscious
• Eyewitness account unreliable but essential
• Unpredictable, hence difficult to record
• Occasionally life threatening
• Driving restrictions, health and safety
• Initial diagnosis often inaccurate - Results in a delay

Question 4

What are the risks of TLOC?

Answer 4

Can be the first symptom of fatal arrhythmia - >100,000 deaths every year in the UK

Sudden deaths often attributed to cardiac arrhythmias - Inherited cardiomyopathies in people under the age of 30

Syncope may result in injuries to patients or others as a result of accidents

Question 5

Name some differentials of TLOC

Answer 5

Neurally mediated (reflex) syncope
o Vasovagal
o Situational – cough/micturition
o Carotid sinus hypersensitivity

Cardiac syncope

Neurological
o	Epilepsy 
o	Sleep disorders
o	Raised ICP
o	Psychogenic non epileptic attacks 

Orthostatic hypotension
o Drugs
o Neurodegenerative disorders

Metabolic disorders

Question 6

What would you include in a history following a TLOC?

Answer 6

Before the attack
o	Any warning? – typical aura
o	Any provoking features
o	Associated symptoms
o	In what circumstances the attacks occur 
o	Can the attacks be prevented?

During the attack
o	Actual LOC
o	Duration of attack
o	Change in complexion 
o	Verbal/tactile responsiveness
o	Movement/limb jerking
o	Injuries
o	Pulse
o	(Tongue biting and urine incontinence) – only indicative of epilepsy if very severe 

After an attack
o	Recovery – rapid/prolonged
o	Confused or sleepy
o	The duration
o	How much does the patient remember?
o	(muscle pain)

Frequency

Question 7

Describe vasovagal syncope

Answer 7

• No comprehensive theory for vasovagal syncope
• 0.5% of the population faint per annum (women>men)
• 1:200 referrals to A&E
• 75,000 attendances per annum in UK
• Posture, provocation, prodromal
• Convulsive movements common
• Diagnosis depends on history
• Lack of post-ictal confusion, hearing people around you before you can respond and recurrence of blackout on regaining upright posture helpful in diagnosis
• Common sense

Question 8

Describe micturition syncope

Answer 8

• Fainting shortly after or during urination
• Micturition involves relaxation, not straining unless (male patient) has an enlarged prostate or stricture
• Role of pelvic venous plexus

Question 9

Describe cardiac syncope and give an example

Answer 9

• Temporary but sudden reduction in blood supply and hence oxygen to the brain as a result of cardiovascular conditions
• The temporary but sudden reduction in blood supply triggering syncope is caused by vasodilation, hypotension, arrhythmia
• The onset of syncope is relatively rapid and recovery from LOC is spontaneous, complete and usually prompt
• E.g. Long QT syndrome

Question 10

What suggests epilepsy as the underlying cause of TLOC?

Answer 10

• Description of an aura - Patient normally finds it difficult to describe
• Brief attack
• Prolonged post ictal confusion
• Head turning or posturing of body
• Stiffening of body and myoclonic jerking (not oscillation)
• Abnormal behaviour of which patients do not remember
• Severe tongue biting

Question 11

What suggests a diagnosis of NEAD in a history? And what suggests a diagnosis of epilepsy?

Answer 11

NEAD
o	Scant description from patient
o	Frequent or long seizures
o	Different types of seizures
o	Crying during recovery

Epilepsy
o	Injury
o	Tongue biting
o	Incontinence
o	Seizures in sleep

Question 12

Describe NEAD

Answer 12

• Common – more likely to witness NEAD than an epileptic seizure
• Gradual onset, undulating motor activity with pauses
• Sinusoidal and asynchronous arm and leg movements
• Prolonged atonia, rhythmic pelvic movements, side to side head movements
• Post ictal crying, high anxiety in carers
• Prolonged attack with prolonged/unexpected sudden recovery

Question 13

How do you make of a diagnosis of NEAD?

Answer 13

o Description/nature of seizure changes with time – good documentation
o Unusually frequent, drug-unresponsive seizures, sometimes provoked by stress
o History of somatoform/multiple unexplained symptoms, multiple surgical procedures
o History of personality disorder, alcohol abuse, self har, parasuicide, childhood abuse, psychiatric treatment
o Video the attack

Question 14

What are the risks of misdiagnosing NEAD?

Answer 14

o Inappropriate treatment – risk of adverse effects of anti-epileptic drugs, including teratogenicity
o Ineffective treatment – when there is an effective treatment
o Reinforcement of abnormal illness behaviour
 Evolution of functional symptoms
 Incapacity
 Financial and social dependency

Question 15

What are some suitable investigations following a TLOC?

Answer 15

ECG
o Rule out cardiac causes
o Always do it

EEG
o Not normally used to distinguish epilepsy from other TLOC
o Non-specific abnormalities common
o Very useful if it captures the event

Neuroimaging
o Not normally used to distinguish epilepsy from other TLOC
o Nonspecific and co-incidental abnormalities common

Question 16

Define seizure

Answer 16

the clinical manifestation of an abnormal, excessive excitation and synchronization of a population of cortical neurons

Question 17

Define epilepsy

Answer 17

a tendency to recurrent seizures >24hrs apart which are not provoked by systemic or acute neurologic insults

Question 18

What is an EEG?

Answer 18

• Electroencephalography
• Records cortical electrical activity – usually from the scalp
• Most important neurophysiological study for the diagnosis, prognosis, and treatment of epilepsy
• Electrodes usually attached in the 10/20 system

Question 19

Briefly describe the 1981 ILAE classification of seizures

Answer 19

Partial

• Simple partial
• Complex partial
• Secondarily generalised

Generalised

• Absence
• Myoclonic
• Atonic
• Tonic
• Tonic-clonic

Question 20

Describe absence seizures

Answer 20

• Type of generalised seizure
• Brief staring spells with impairment of awareness
• 3-20 seconds
• Sudden onset and sudden resolution
• Often provoked by hyperventilation
• Onset typically between 4 and 14 years of age, and resolve by age 18
• Normal development and intelligence

Question 21

What EEG finding would be seen during an absence seizure?

Answer 21

Generalised 3 Hz spike-wave discharges

Question 22

Describe myoclonic seizures

Answer 22

• Generalised
• Brief, shock-like jerk of a muscle or group of muscle
• Differentiate from benign, non-epileptic myoclonus (e.g. when falling asleep)

Question 23

What EEG finding would be seen during a myoclonic seizure?

Answer 23

Generalised 4-6 Hz polyspike-wave discharges

Question 24

Describe tonic seizures

Answer 24

• Symmetric, tonic muscle contraction of extremities with tonic flexion of waist and neck
• Not the same as the tonic phase of a tonic clonic seizures
• Duration – 2-20 seconds

Question 25

What EEG finding would be seen during a tonic seizure?

Answer 25

Sudden attenuation with generalised, low-voltage fast activity (most common) or generalised polyspike-wave

Question 26

Describe atonic seizures

Answer 26

- Sudden loss of postural tone - When severe often results in falls - When milder produces head nods or jaw drops

Question 27

What EEG finding would be seen during a atonic seizure?

Answer 27

Sudden diffuse attenuation or generalised-polyspike wave

Question 28

Described generalised tonic clonic seizures

Answer 28

- Associated with loss of consciousness and post-ictal confusion/lethargy - Duration – 30-120 seconds - Tonic phase – stiffening and fall, often associated with ictal cry (caused by stiffening of pharynx muscles - Clonic phase – rhythmic extremity jerking

Question 29

What EEG finding would be seen during a generalised tonic-clonic seizure?

Answer 29

generalised polyspikes

Question 30

Describe simple partial seizures

Answer 30

- Same thing as an aura - Patient aware throughout - Diverse range, leading to diagnostic challenges - Symptoms depend on where in the brain is affected o Somatosensory o Motor o Visual/ auditory/ olfactory o Autonomic sensations o Psychic/ experiential o Clonic seizure - Seizure always the same for the patient – it does not change from seizure to seizure - Patients usually struggle to describe what happens

Question 31

Describe complex partial seizures

Answer 31

- Impaired consciousness – loss of awareness - Clinical manifestations vary with site of origin and degree of spread o Presence and nature of aura o Automatisms – semi purposeful movement o Other motor activity - Duration typically <2 minutes

Question 32

Describe secondary generalised tonic clonic seizures

Answer 32

- Begins focally, with or without focal neurological symptoms - Tonic and clonic phases with variable symmetry, typical duration 1-3 minutes - Post ictal confusion - Can have transient focal deficit after seizure – Todd’s paresis

Question 33

What are epilepsy syndromes?

Answer 33

``` - Grouping of patients that share similar o Seizure types o Age of onset o Natural history/prognosis o EEG patterns o Aetiology/ Genetics ```

Question 34

What are epilepsy syndromes divided in to?

Answer 34

o Idiopathic – when the disorder was not associated with other neurological or neuropsychological abnormalities o Symptomatic – when there was a neurological or neuropsychological abnormality, and the cause was known o Cryptogenic – when there was a neurological or neuropsychological abnormality and the cause was unknown

Question 35

Describe temporal lobe epilepsy

Answer 35

- Common – temporal lobe most common location for localised seizure - Onset at any age - EEG shows temporal lobe epileptiform discharges o EEG changes when seizure not occurring o Not always seen - Simple partial, complex partial and secondary GTCS - May be symptomatic or cryptogenic - Hippocampus sclerosis can be a cause

Question 36

Describe juvenile myoclonic epilepsy

Answer 36

- Juvenile onset - Myoclonic seizures, brief subtle absence, GTCS - Seizures have morning predominance, exacerbated by sleep deprivation and alcohol - Idiopathic o Otherwise well and neurologically intact - EEG shows generalised spike or polyspike/wave discharges - Often photosensitive (30-40%)

Question 37

Describe West syndrome

Answer 37

- Infantile onset - Hypsarrhythmic EEG - Infantile (epileptic spasms) - Cryptogenic vs symptomatic

Question 38

Describe the development of epilepsy classification in 2010

Answer 38

Published in epilepsia 2010 - Focal reconceptualised o Focal epileptic seizures are conceptualised as originating within networks limited to one hemisphere o These may be discretely localised or more widely distributed - Generalised reconceptualised o Generalised epileptic seizures are conceptualised as originating at some point within, and rapidly engaging, bilaterally distributed networks o Can include cortical and subcortical structures but not necessarily include the entire cortex - Introduced concept of networks - Language and structure for organising epilepsies

Question 39

What was partial, simple partial and complex partial seizures changed to under the new classification (2010)?

Answer 39

Focal, focal with impaired awareness (for both simple and complex)

Question 40

What was secondary generalised TCS changed to under the new classification (2010)?

Answer 40

Focal evolving to bilateral convulsive seizure

Question 41

What was cryptogenic changed to under the new classification (2010)?

Answer 41

Unknown

Question 42

What was symptomatic changed to under the new classification (2010)?

Answer 42

Structural/metabolic

Question 43

What was idiopathic changed to under the new classification (2010)?

Answer 43

Genetic

Question 44

What are the rules for classifying seizures (2017)?

Answer 44

- Onset – Decide whether seizure onset is focal or generalised, using an 80% confidence level - Awareness – For focal seizures, decide whether to classify by degree of awareness or to omit awareness as a classifier - Impaired awareness at any point – a focal seizure is a focal impaired awareness seizure if awareness is impaired at any point during the seizure - Onset predominance – classify a focal seizure by its first prominent sign or symptom but do not count transient behaviour arrest - Behaviour arrest – A focal behavioural arrest seizure shows arrest of behaviour as the prominent feature of the entire seizure - Motor/non-motor – a focal aware or impaired awareness seizure maybe further sub-classified by motor or non-motor characteristics. Alternatively, a focal seizure can be characterised by motor or non-motor characteristics, with specifying level of awareness.

Question 45

According to the 2017 classification of seizures, what are focal seizures now divided in to? Give examples

Answer 45

Motor onset - Automatisms - Atonic - Clonic - Epileptic spasms - Hyperkinetic - Myoclonic - Tonic Non-motor onset - Autonomic - Behaviour arrest - Cognitive - Emotional - sensory

Question 46

Describe EEG technique

Answer 46

Digital + video o Patient is filmed – useful if they have a seizure Electrodes o Using 19 electrodes o Prefrontal, Frontal, temporal, occipital, central regions o Even numbers on right side of head, odd numbers on the left, zero (Z) in midline

Question 47

Name some common variable seen in EEG

Answer 47

``` Age - EEG in child is chaotic Artefacts - e.g. chewing Conscious level - e.g. sleeping, anaesthetic Drugs Cerebral pathology - e.g. cerebral palsy ```

Question 48

Name some techniques that can be used to trigger a seizure when undertaking an EEG

Answer 48

Photic stimulation o Strobe light used on patient o If seizure triggered – photosensitive epilepsy Hyperventilation o Common trigger in childhood absence epilepsy Sleep and sleep deprivation o Sleep deprivation is known as a trigger of epilepsy

Question 49

When can long-term monitoring be useful and describe the two types?

Answer 49

- Useful if EEG is normal but seizures persist - Ambulatory o EEG monitoring for 24 or 48 hours o Takes measurements when not constricted to the examination room - Video-telemetry o EEG, microphone and camera set up around a hospital bed o Aim to capture 3 or more episodes to help diagnose epilepsy

Question 50

What cannot an interictal EEG do?

Answer 50

o Exclude epilepsy | o Prove epilepsy

Question 51

Describe the sensitivity of EEG

Answer 51

- Poor sensitivity for routine wake EEGs – only around 50% of epileptic patients will have EEG changes on their first EEG - To increase yield o Sleep EEG increases sensitivity (80%) o Repeat wake and sleep EEG provides the best yield (92%) – but still not 100%

Question 52

Describe the specificity of EEGs

Answer 52

- Specificity of EEG (correctly excluding epilepsy) is better than sensitivity at around 78-98% (Smith, 2005) - EEG epileptiform is found in 0.5-4% of healthy adults - BUT population is not healthy - Other cerebral disease o Cerebrovascular disease, migraine, cerebral palsy Alzheimer’s disease - Drugs o Psychotropics - These factors can all cause abnormal EEGs

Question 53

How is EEG useful for the classification of epilepsy?

Answer 53

Focal vs Generalised o EEG can be helpful in determining whether the seizure is focal or generalised in origin o Sometimes clinical diagnosis is difficult of focal seizures that cause a secondary generalised seizure Syndrome identification o Some types of epilepsies are classified into syndromes o Use of EEG can identify a syndrome and help with specific treatment o Inter-ictal, ictal and both

Question 54

What is the role of EEG in the management of Status Epilepticus?

Answer 54

Convulsive o Diagnosis if possibility of NEAD o Monitoring of treatment if paralysed and ventilated Non-convulsive o Diagnosis o Monitoring treatment

Question 55

What is the role of EEG in the work up for epilepsy surgery?

Answer 55

- EEG vs MRI abnormality o Does the EEG localise the seizure to the abnormality on EEG? - Epilepsy surgery only performed if high suspicion that an abnormality is the cause - EEG can help determine this

Question 56

Describe the abuses of EEG in epilepsy

Answer 56

- Monitoring of progress o Not usually helpful o EEG changes can still be present even if seizures well controlled o More useful to take history of seizure frequency - Anti-convulsant withdrawal in adults - Diagnosis in presence of intracerebral disease - Diagnosis where history is of syncope - Driving

Question 57

Describe the EEG NICE guidelines

Answer 57

- An EEG should be performed only to support a diagnosis of epilepsy in adults in whom the clinical history suggests that the seizure is likely to be epileptic in origin - An EEG should be performed only to support a diagnosis of epilepsy in children o If EEG considered necessary – should be performed after the second epileptic seizure o In certain circumstances, as evaluated by a specialist, it can be considered after a first epileptic seizure

Question 58

What is rehabilitation medicine?

Answer 58

- The process of helping a person reach the fullest physical/psychological/social/vocational/educational potential consistent with anatomic or physiological impairment, environmental limitations and desires and life plans - The process of active change by which a patient acquires knowledge and skills necessary for optimal physical, psychological and social function

Question 59

What are some rehabilitation concepts?

Answer 59

- Process of education and retraining - Disabled individual at the centre - Interdisciplinary approach - Goal setting is important - Concepts of activity (disability) and participation (handicap) - Role of personal and environmental factor

Question 60

What is an acquired brain injury?

Answer 60

- An injury to the brain, which is not hereditary, congenital, degenerative or induced by birth trauma - Injury to the brain that has occurred after birth

Question 61

What are the types of acquired brain injury?

Answer 61

``` o Traumatic brain injury (TBI) o Haemorrhagic brain injury (HBI) o Vascular brain injury (VBI) o Anoxic (and metabolic) brain injury (ABI) o Infective brain injury (IBI) ```

Question 62

Define TBI

Answer 62

- Defined as an alteration in brain function, or other evidence of brain pathology, caused by an external force (Common data elements 2013)

Question 63

Describe the epidemiology of TBI

Answer 63

- 1 million patients in the UK attend hospital every year - 50% are under 16 - 275/100,000 are admitted every year - 10-20% likely to have some long-term disability - Physical recovery often better than cognitive or psychosocial recovery - About 1 in 4 adults with TBI is unable to return to work 1 year after injury - Annual acute care and rehab costs = $9-10 billion (NIH consensus development panel on rehabilitation 1999) - Estimated annual costs of survivors in 2000 = $60 billion (Finkelstein 2006)

Question 64

Describe the aetiology of TBI

Answer 64

- Leading cause – RTC (Approx 25-30%) - Falls - 30-35% (elderly) - Assaults – 9-10% - Sports and recreational – 10-20% - In USA – firearms (10%

Question 65

What are contusions?

Answer 65

- Bruising of the brain - Close to bony prominences - Inferior frontal and temporal poles

Question 66

Describe diffuse axonal injury (DAI)

Answer 66

- Severe rotation or deceleration force - Often RTC - Often loss of consciousness or prolonged low awareness - Little haemorrhage - Upon impact the neuron is stretched and compressed - Cell death may be delayed and not evident for up to 72 hours post injury - Only 20% seen on CT - Better seen on MRI - More widespread damage

Question 67

What are the types of intracranial bleeds?

Answer 67

- Extradural haematomas - Most dangerous but good recovery if drained - Subdural haematomas - Subarachnoid bleed - Intracerebral/intraventricular bleed - Basal skull fractures – infection, CSF leaks

Question 68

What are the two mechanisms of injury in TBI?

Answer 68

Primary and Secondary

Question 69

Describe primary injuries in TBI

Answer 69

``` injury at the moment of impact or immediately afterwards o Contusions, bleeding, skull fracture o Coup/contrecoup o Stretch and shearing of neurons o Limited scope for change ```

Question 70

Describe secondary injuries in TBI

Answer 70

further injury caused by subsequent events including poor care o Altered cerebral blood flow – autoregulation o Hypotension – relation to ICP and CPP o Release of neurotoxic compounds  Cellular inflammatory response  Cytokines  Calcium influx  Oxygen free radicals o One episode of hypotension can increase mortality by 50% o Hypoxia, hypotension, free radicals/cytokines/EAA, cerebral oedema, increase ICP, infection, hydrocephalus, herniation

Question 71

When should a CT scan be performed within one hour of presentation with a TBI?

Answer 71

- GCS <13 when first assessed or GCS <15 2 hours after injury - Suspected open or depressed skull fracture - Signs of base of skill fracture - Post-traumatic seizure - Focal neurological deficit - >1 episode of vomiting

Question 72

Describe the immediate management of TBI

Answer 72

- ABCDE - Oxygenate/intubate - IV Fluids - Glucose - Seizures – diazepam PR/IV, consider prophylaxis - Drug or alcohol intoxication? - Electrolytes and acid base status - Sedation - Analgesia - Consult neurosurgeons/orthopaedics - CT scan once stable - Surgical treatment (<2%) - Treat ICP if suspected - Steroids have shown no benefits in acute TBI - Seizure prophylaxis beyond 1 week - Antibiotics or vaccine prophylaxis?

Question 73

What should be given in the case of drug or alcohol intoxication? (Specifically to each drug)

Answer 73

``` o Opioids – naloxone o Alcohol – thiamine o Tricyclics (anticholinergics) – physostigmine o Benzodiazepines – flumazenil Also do a toxic profile ```

Question 74

How do you treat ICP?

Answer 74

o Mannitol/hypertonic saline o CSF drain o Tilt head by 30-40 degrees (better blood flow)

Question 75

Describe the classification of head injuries

Answer 75

Mild - GCS 13-15 - Coma <30mins - PTA <1hr Moderate - GCS 9-12 - Coma 30mins-6hrs - PTA 1-24hrs Severe - GCS <9 - Coma >6hrs - PTA >1day

Question 76

Name some neurological sequelae of brain injury

Answer 76

- Cranial nerves o Anosmia, vision, diplopia/strabismus, hearing and balance - Motor o Paralysis (mono-, hemi-, quadriplegia), ataxia, dyspraxia, tremor, spasticity - Sensory o Anaesthesia, pain syndromes - Autonomic o Bladder, bowels, cardiovascular, respiratory, gut, sexual function - Spinal cord injury - Peripheral nerve injury - Epilepsy

Question 77

Name some cognitive changes after brain injury

Answer 77

- Memory - Attention - Communication - Speed of processing - Visuospatial - Problem solving/planning - Mood/anxiety - Fatigue - Judgement - Emotional/behavioural control - Initiation of actions

Question 78

Very briefly describe the evidence for early rehab following a brain injury

Answer 78

- Strong (Grade A) evidence that intensive rehab leads to earlier functional gains o (Cochrane, RCT 351 studies) - Strong (Grade A) evidence that early rehabilitation leads to reduced length of stay in hospital and improved outcomes o (NSF Typology, Non-RCT 1905 studies)

Question 79

Describe post-acute rehab following a brain injury

Answer 79

- Primarily addresses regaining mobility and independence in self-care to allow the individual to manage safely at home - Interventions focus on improving ability and independence (reducing disability) - In-patient pathways to reduce variation

Question 80

What are the ABCs of rehab?

Answer 80

Anticoagulation o Medical o Ted stockings o Flowtron Bladder/bowl Chest complications o PE o Tubes o Infections (Neuro)disability assessment Electrolytes and fluid Feeding – NG, PEG

Question 81

Describe medium to longer term rehab of brain injury

Answer 81

- Best provided in the community - Functional gains to achieve independent living - Vocational rehab – return to work or alternative employment - Addressing emotional and psychological issues - Importance of individual wishes

Question 82

What are some long term issues following a brain injury?

Answer 82

- Employment - Dependents - Psychological support (family) - Cognitive sequelae - Behaviours including alcohol - Driving - Sex - Exercise

Question 83

Name some post head injury symptoms

Answer 83

``` Poor concentration (most common) Irritability Tired a lot Depression Memory problems Headaches Anxiety Trouble thinking Dizziness Blurry or double vision Sensitivity to bright light ```

Question 84

What can post head injury symptoms be assessed by?

Answer 84

The Rivermead post-concussion score

Question 85

What is post-concussion syndrome?

Answer 85

set of symptoms that may continue for weeks, months, or a year or more after a concussion – a mild form of traumatic brain injury - 25% of mild TBIs at 3 months, 10% at 1 year (King 2003) - Physical symptoms decline, psychological increase

Question 86

What is the double insult theory?

Answer 86

mechanical trauma to the limbic circuits with a maladaptive response

Question 87

What are the risk factors for post-concussion syndrome?

Answer 87

``` o Previous brain injury o Female? o Educational level o Past psychiatric history o Genetics? APOE4 ```

Question 88

What are the perpetuating factors for post-concussion syndrome?

Answer 88

``` o Alcohol o Other drugs o Depression/Anxiety o Lack of support o Secondary gain – litigation ```

Question 89

Name some outcome measures for TBI

Answer 89

- Glasgow outcome scale - FIM/FAM, Barthel - Disability rating scale - Handicap (participation restriction) – Rivermead HI FU questionnaire - Symptom measures – Rivermead post-concussion score - BIRCO-39 - QoL measures

Question 90

Describe the extended glasgow outcome scale

Answer 90

Death - Dead Vegetative state - Unable to obey commands Lower severe disability - Dependent on others for care Upper severe disability - Independent at home Lower moderate disability - Independent at home and outside the home but some physical or mental disability Upper moderate disability - Independent at home and outside the home but with some physical or mental disability, with less disruption than LMD Lower good recovery - Able to resume normal activities with some injury related problems Upper good recovery - No injury related problems

Question 91

Name factors that can affect prognosis pre-injury

Answer 91

- Age o Increased mortality in elderly (>65 yrs) and children below 5 yrs - Female, ethnicity, education - Recurrent head trauma o Additive damage - Substance abuse o Increased acute complications, mortality, longer hospitalisations, worse discharge status - Psychosocial factors o Psychiatric illness/personality o Lack of family/social support

Question 92

Name factors about the injury that can affect prognosis

Answer 92

- Aetiology - Severity of injury - Care/resus delay (secondary injury extent) - Unilateral/bilateral - Scan findings - Associated injuries

Question 93

Name factors that can affect prognosis post injury

Answer 93

- Medical care o Delay in care or transportation increases the chances of secondary complications o Hypotension and hypoxia are avoidable complications - Complications o Pulmonary, cardiovascular, haematological or infectious problems associated with poor outcomes - Rehabilitation – both inpatient and community - Family support - Health behaviours e.g. substance abuse - Work – does it protect?

Question 94

How are TBI patients' health and life affected?

Answer 94

- Life expectancy o At least 10 years reduction for severe (McMillan 2013) - People with TBI generally have a propensity towards poor health habits o Alcohol, smoking, substance use, diet, exercise - At risk for secondary complications (including social e.g. poverty, arrests)

Question 95

Describe the SHEFBIT cohort study

Answer 95

- From 2012 onwards - 1322 cases, 1191 at one year - Shows the affect of TBI on patients lives - Less than half of patients returned to full work a year after the injury At 10 weeks o 39.4% no work, 31.7% less work, 28.9% same o 55% depression, 61% anxiety on HOADS o High scores on Rivermead questionnaires At 1 year o 23.8% no work, 27.5% less work, 43.9% same o Depression 41%, anxiety 43% o Still high scores in Rivermead questionnaires

Question 96

Describe seizure timing post TBI

Answer 96

- Immediate seizures – occur <24hrs after injury - Early seizures – occur <1 week after injury - Late seizures – occur >1 week after injury and constitute the diagnosis of post traumatic epilepsy - Concussive seizures – immediately after and not epilepsy – no increased risk

Question 97

What are the risk factors of post traumatic epilepsy?

Answer 97

Systematic review and meta-analysis (Xu et al, 2017) ``` o Male o History of alcohol abuse o Post traumatic amnesia o Focal neurological signs o Loss of consciousness o Skull fracture o Midline shift o Brain confusion o Subdural haemorrhage o Intracerebral haemorrhage o Mild brain injury o Severe brain injury o Acute symptomatic seizure ``` - Also found that the aetiology of TBI (fall accident, traffic accident, others) and initial GCS were not a risk factor nor was the presence of a subarachnoid haemorrhage

Question 98

Describe the risk of seizure following TBI

Answer 98

Population based study published in 1998 (Annegers et al) looked at the probably of seizures after severe, moderate and mild brain injury o All injuries increased risk of epilepsy over 30 years post injury o Severe injury was markedly higher than the other two (15% risk over 30 years) o Mild injury almost the same as baseline A further study published in Lancet in 2009 (Christensen et al) also looked at the long-term risk of epilepsy after traumatic brain injury o Split into mild brain injury, severe brain injury and skull fracture o Found that all groups increased risk o Most increased with severe brain injury less than a year after injury then decreased as years after injury increased

Question 99

Describe the relationship between temporal lobe injury and PTE

Answer 99

- Longitudinal study by Tubi et al argues that early seizures and temporal lobe trauma predict PTE - 90 patients with moderate to severe TBI – 26.7% patients had acute symptomatic seizures, of which 75% had haemorrhagic temporal lobe injury on admission - 46 patients entered long term follow up, of which 45.7% developed PTE within 2 years o 85.6% had haemorrhagic temporal lobe injury on admission (compared to 30.6% who did not develop PTE) o 38.1% had seizures on continuous EEG during acute ICU stay

Question 100

What is the risk of an early seizure following a TBI?

Answer 100

The risk of early seizures ranges from abut 2% (Temkin et al, 1990; Annegers et al, 1998) in population-based studies to 14-30% in patients with severe TBI (Temkin et al, 1990)

Question 101

Describe the epileptogenesis theory following TBI

Answer 101

- Latent period between injury and development of PTE - Proposed latent period events leading to PTE ``` Initial structural injury o Focal (contusions, haemorrhage, penetrating injury) o Diffuse – diffuse axonal injury ``` ``` Secondary injury Excitotoxicity o Apoptosis o Neuroinflammation o Oxidative stress ``` Spontaneous seizures o Neuronal loss, and neurogenesis – network reorganisation o Hippocampal sclerosis o Chronic neuroinflammation

Question 102

What are the risk factors for early seizures following a TBI?

Answer 102

Risk factors for early seizure have been reviewed by Temkin (2003), who reported that depressed skull fracture, intracerebral hematoma, and subdural hematoma were associated with about a 25% risk of immediate or early posttraumatic seizures

Question 103

What are the significance of immediate and early seizures following a TBI?

Answer 103

Immediate seizures and early seizures are risk factors for the development of later epilepsy (Temkin, 2003) and seizures within the first 24 hours have been used to identify patients with a high risk of epilepsy after TBI to select for studies of prevention of PTE (Temkin et al, 1990)

Question 104

Name the non-pharmacological treatment options of epilepsy

Answer 104

- Vagal nerve stimulation (VNS) - Deep brain stimulation (DBS) - Resective surgery/Gamma knife surgery - Dietary approaches

Question 105

What is VNS?

Answer 105

- VNS is suitable for seizures with a focal or generalised onset - Involves implantation of a stimulator (pulse generator) into a pocket of skin, under the collar bone or close to the armpit - Wires, with electrodes, are connected inside the body to the left of the Vagus nerve -The electrodes encase the Vagus nerve in the neck - Aims to reduce seizure activity by interrupting and preventing the electrical irregularities on the surface of the brain that cause seizures

Question 106

What are some additional benefits of VNS?

Answer 106

o Improved alertness o Improved memory o Fewer mood problems

Question 107

What are some disadvantages of VNS?

Answer 107

- Not beneficial across the whole spectrum of patients - Not possible to know in advance who will have seizure reduction - Can take anything from several months to 2yrs to achieve optimal seizure control - Mild side effects

Question 108

What is DBS?

Answer 108

- For patients with seizures of focal onset - May be appropriate for people unsuitable for resective surgery - Involves implanting electrodes into specific areas of the brain - Aims to control excess electrical activity in the rain using regular electrical impulses to reduce the frequency and severity of seizures o During DBS, a thin wire is implanted into the brain which is connected to an electrical stimulator, which is placed under the skin of the chest - Trials show that for some people their seizures become much less frequent while others it has little to no effect (Epilepsy society 2012) - DBS stimulation results in reduced seizure frequency of 69% (medtronic 2015)

Question 109

What are some disadvantages of DBS?

Answer 109

- Almost the same as for VNS - Not widely available in the UK at present – only available in Sheffield for dystonia and PD - The evidence on the efficacy of DBS for refractory epilepsy is limited in both quantity and quality o The evidence on safety shows that there are serious but well-known side effects o Should only be used with special arrangements for clinical governance, consent, and audit or research o (NICE Jan 2012)

Question 110

Describe epilepsy surgeries

Answer 110

- May be suitable for patients with focal onset seizures - If several AEDs trialled and none of them have stopped or significantly reduced seizure frequency (50%) - If a psychical cause for epilepsy, such as scarring on the brain or damage to the brain from a head injury, or following an infection such as meningitis, can be identified on scans and is only in one area of the brain - Around 70% of people become seizure free (Epilepsy society 2013) - Surgical intervention = resective and/or disconnected procedure

Question 111

Describe resective procedures for epilepsy

Answer 111

o Different types of lobectomy (e.g. temporal, frontal etc) o Topectomy – excision of a small area tailored to the seizure focus itself o Hemispherectomy – the ultimate focal resection with the removal of one half of the brain o More likely to result in a cure since they excise

Question 112

Describe disconnective procedures for epilepsy

Answer 112

o Corpus callosotomy o Multiple pial transections o Tend to more palliative rather than curative as they interrupt the propagation of the seizures, limiting their generalisation

Question 113

What are the disadvantages of epilepsy surgery?

Answer 113

- Carries significant risks – death, stroke, paralysis, worsening of epilepsy - Implications for people previously requiring carers, becoming independent and losing their epilepsy - Approx 50% of patients recommended are unable to proceed after formal testing

Question 114

What is gamma knife surgery?

Answer 114

- Narrow beams of radiation targeted to precisely defined volume of tissue within the brain - Highly focused and destructive dose of radiation is given in a single session and avoids potentially harmful radiation to surrounding brain structures - Often a safer option than traditional brain surgery - Total treatment time varies from 45 to 90 minutes

Question 115

What are some side effects of gamma knife surgery?

Answer 115

Almost no initial effects of radiosurgery o Local pain to the scalp, responds to simple, oral pain medication Long range effects after many months o Swelling within the adjacent brain which may cause symptoms such as headache and neurological disturbances o Treat with oral steroids and is self-limiting Permanent cranial nerve dysfunction is rare with modern gamma ray doses

Question 116

What are the benefits of gamma knife surgery?

Answer 116

- Non-invasive - No incision, no need for head shaving, no scars to heal - No hair loss or nausea - Treatment is relatively painless and in most cases a GA is not needed - Patients make a fast recovery and can usually resume their normal activities in a day or two

Question 117

What are ketogenic diet therapies?

Answer 117

- Range of high-fat and low carbohydrate diets which mimic the metabolic effects of prolonged fasting - One treatment option for children whose seizures are not controlled with AEDs - Ketones are formed when the body uses fat for its source of energy - Because the ketogenic diet is very low in carbohydrates, fats become the primary fuel instead - Higher ketone levels often lead to more improved seizure control - Particularly recommended for children with Lennox-Gastaut syndrome - Not usually recommended for adults as the diet is very restrictive

Question 118

Can a ketogenic diet ever be stopped?

Answer 118

- If seizures have been well controlled for some time, usually 2 years, it might be suggested to go off the diet - Patient is gradually taken off over several months – seizures may worsen if the ketogenic diet is suddenly stopped - Children usually continue to take AEDs after stopping the diet

Question 119

What are the potential side effects of a ketogenic diet?

Answer 119

- Kidney stones - High cholesterol levels in the blood - Dehydration - Constipation - Slowed growth or weight gain - Bone fractures

Question 120

What are some potential triggers of photosensitive epilepsy?

Answer 120

o Faulty florescent light strips that flicker o Christmas tree lights (except those put up by public organisations) o Flashing novelty badges o Red flashing bicycle lights (when very close) o Light seen through a fast-rotating ceiling fan o Some films with flashing or flickering images o Strobe lighting (night clubs, theme parks) – in the UK this is restricted o Older TV screens – use LCD screen

Question 121

What are some ways of avoiding a photosensitive seizure?

Answer 121

o Consider covering one eye – reduces the number of brain cells that are stimulated o Any dizziness, blurred vision, loss of awareness or muscle twitching – stop looking at the screen immediately o Take frequent rests

Question 122

What are the psychological associations of epilepsy?

Answer 122

- Co-morbid depression/anxiety – those with refractory epilepsy at high risk - Low self-esteem - Psychosocial problems o Education o Employment o Relationships o Social isolation - Psychosis - Self-harm - Anger issues and violence - Adjustment/acceptance issues - Suicidal thoughts, attempts and actual suicide - Sleep disturbance (Dewhurst 2010)

Question 123

What is the psychological management of epilepsy

Answer 123

- Currently limited evidence for the effectiveness of interventions to improve the health and quality of life in people with epilepsy - Specialist nurse and self-management education have some evidence of benefit - At present it is not possible to advocate any single model of service provision (Cochrane review 2016)

Question 124

What is status epilepticus?

Answer 124

Maximum expression of epilepsy Seizure that last longer than 5 mins or multiple seizures without recovery o Most seizures last less than 5 minutes o Those that last longer do no stop spontaneously o Seizures become self-sustaining with neuronal injury within 15-30 mins

Question 125

What are the types of status epilepticus?

Answer 125

- Generalised status epilepticus - Complex partial status epilepticus - Epilepsia partialis continua

Question 126

Describe the epidemiology of status epilepticus

Answer 126

- Incidence 10-41/100,000 - Lifetime risk 10% in patients with epilepsy - Mortality 9-60% - Severe neurological/cognitive morbidity – 11-16% - Status longer than 30mins = 20% mortality

Question 127

Describe convulsive status epilepticus

Answer 127

- Convulsions associated with rhythmic jerking - Generalised tonic-clonic movements - Mental status impairment - Focal neurological deficit

Question 128

Describe non-convulsive status epilepticus

Answer 128

Seizures activity on EEG without clinical findings of GCSE o Wandering confused, automatisms o Acutely ill, obtunded (less than full awareness) ± motor abnormalities Negative symptoms o Anorexia, aphasia/mutism, amnesia, catatonia, coma, confusion, lethargy, and staring Positive symptoms o Agitation/aggression o Automatisms, blinking, facial twitching o Delusions, echolalia, laughter, nausea/vomiting o Nystagmus/eye deviation o Psychosis

Question 129

Describe the process of seizure to status

Answer 129

Minutes - Receptors move from synaptic membranes and endosomes - GABAergic receptors destroyed – less responsive to neurotransmitter/GABAergic drugs o Metabolic changes within cells o Potency of benzodiazepines reduces by 20-fold after 30 minutes (GABAergic) - NMDA and AMPA (glutamate) receptors move to the synaptic membrane causing further excitation Minutes to hours - Increased proconvulsive neuropeptides depletion of inhibitor neuropeptides – increased excitability Hours to weeks - Long term gene expression changes as result of neuronal death and reorganisation - Seizures inhibit brain synthesis

Question 130

What is the aetiology of status epilepticus?

Answer 130

- Low levels of AED in epilepsy (34%) - Remote brain injury/congenital malformation (24%) - >1 week after an insult that could cause epilepsy - Cerebrovascular accident (22%) - Drug/alcohol withdrawal (10%) - Brain infections/inflammation (5%) - Metabolic problems e.g. low sodium (15%)

Question 131

What problems arise from an ongoing seizure?

Answer 131

``` Sympathetic overdrive o Increased cardiac output o Increased blood pressure o Increased blood sugar o Increased blood lactate ``` ``` Decompensation o Cardiorespiratory collapse o Electrolyte imbalance o Rhabdomyolysis (muscle breakdown) – acute tubular necrosis (kidney failure) o Hyperthermia o Major organ failure o Cerebral oedema ```

Question 132

What is the management in the 1st stage of SE (0-10mins)?

Answer 132

- ABCDEFG - Secure airway - High flow oxygen - Cardiac and respiratory function - Obtain IV access in a large vein - Check blood glucose levels

Question 133

What is the management in the 2nd stage of SE (0-30mins)?

Answer 133

- Regular monitoring - Consider the possibility of NEAD/pregnancy - Emergency AED therapy - Emergency investigations (bloods, arterial gasses) - Consider glucose (dextrose) ± high dose IV pabrinex (vitamin B and C) if low nutrition - Treat severe acidosis

Question 134

What is the management in the 3rd stage of SE (0-60mins) - established status?

Answer 134

Seizures that resolve quickly suggest something is fuelling them o What is the cause? o Is there something else maintaining them? o Are we giving the right treatment? Prolonged seizures are dangerous o Airway: obstruction, secretions, aspiration o Breathing: hypoxia o Cardiovascular instability: hypotension, cardiac arrhythmias o Disability: neurological problems and risk of injury

Question 135

What is the management in the 4th stage of SE (30-90mins) - refractory status?

Answer 135

- ICU - Anaesthesia advantages o Powerful AED effects o Can protect the airways o Can get scans and treat easily ``` - Anaesthesia disadvantages o Pneumonia o Hypotension and cardiac arrhythmias o Not moving is bad – poorer outcomes o Infection ``` - Give more AED? o 70% get inadequate loading dose of first AED

Question 136

What are some consequences of coma/ICU as a result of SE?

Answer 136

``` - Immobility o Pressure sores o DVT o Pneumonia o Muscle weakness ``` - Organ dysfunction o GI tract o Immune system (including hospital acquired infections) - Psychological impacts (PTSD)

Question 137

Why does the patient stopping moving not necessarily mean the seizure has stopped in SE?

Answer 137

o Usually anaesthesia induction requires a paralysing drug o Often paralysis is needed for the ventilation of the patient o After a long seizure movement diminishes

Question 138

How can you determine a seizure has actually ceased in SE?

Answer 138

Use EEG o Can see ongoing seizure activity o Can suggest other causes e.g. Encephalitis, NEAD

Question 139

What is the first line drug in SE?

Answer 139

Benzodiazepines (e.g. Lorazepam, diazepam, midazolam) o Gaba receptor targets o Slow all neurotransmission including consciousness and breathing o Can last a while and can hide and accumulate o Take some time to work o Can be given IV, PR, buccal, IM, orally o Grade A/B evidence – they work

Question 140

What is the second line drug is SE?

Answer 140

- Phenytoin (Ideally fosphenytoin) o Works well – grade B evidence o Risks including cardiac problems

Question 141

What drugs should be given third line and beyond in SE?

Answer 141

o Evidence is limited o Phenobarbitone, levetiracetam, valproate o Anaesthesia – thiopentone, propofol

Question 142

Describe the ongoing management of SE

Answer 142

- Review/continue regular AEDs - Risk of recurrent seizures after status 41% - Get drug history - Drug levels - NG feed and drugs - Consider NEAD/maintaining factors - Consider out of hospital management of seizures - Consider compliance

Question 143

How is refractory status defined?

Answer 143

Seizures that continue despite two o Appropriate AEDs at o Appropriate does Duration not relevant – can go on for months

Question 144

What is the mortality of refractory status?

Answer 144

23-60%

Question 145

What are some predictors of refractory and non-refractory status?

Answer 145

Refractory - Encephalitis - Hyponatraemia - Longer duration - More seizure activity - Poor outcomes if Epilepsy or NICU stay Non-refractory - Low AED levels - 44% admitted to ICU received inadequate prior doses

Question 146

Name some other strategies that could be considered for refractory status

Answer 146

``` o Valproate – risk of encephalopathy o Keppra o Topiramate (via NG tube) o Ketamine o Steroids – if any suspicion of autoimmune encephalitis o Hypothermia – some case reports o Lidocaine o Paraldehyde o Chlormethiazole o Clonazepam o Lacosamide o Ketogenic diet o Electroconvulsive treatment (case report/series) o Vagus nerve stimulation o Surgery (case report, resect epileptogenic lesion) ```

Question 147

What is primary healthcare?

Answer 147

o First point of contact for health care o For new problems (including urgent and emergency) and for ongoing problems o Places – GP practices, Walk-in centres, minor injury units, dentists, opticians, ?999, ?A&E o Wide range of practitioners o Not the same as general practice

Question 148

What is expert medical generalism?

Answer 148

- Provision of health care to all patients with any health care need - Its focus is on the person and not the disease – whole person medicine

Question 149

Describe the relevance of diversity and breadth knowledgebase in GPs

Answer 149

- The diversity and breadth of the GP knowledgebase it its essence - GPs have depth of knowledge in lots of high prevalence diseases o Asthma, COPD, diabetes, hypertension, headache - But they do not have deep knowledge of all conditions especially rare conditions - Therefore – GP requires decision making often without subject specific expertise

Question 150

What clinical skills and clinical reasoning do GPs require?

Answer 150

- History and examination are the essential foundations of good clinical judgement - Need to be able to rapidly take a focused clinical history o GP appointments are only 10 mins long - Need to understand the principles of epidemiology – incidence and prevalence - Pragmatic and rapid clinical examination of all body systems - Make clinical decisions and risk management an issue of shared decision making - Based on trust and longitudinal relationships

Question 151

What is the quality outcome framework (QOF)?

Answer 151

- Part of the GP contract since 2004 - Sets targets (indicators) for clinical outcomes - Meeting targets is associated with additional income - This income reflects the resources required to achieve these targets - Conditions include o Atrial fibrillation o Secondary prevention of coronary heart disease o Hypertension o Diabetes o Dementia o Depression o Cancer o Epilepsy o Cardiovascular disease o Blood pressure o Obesity o Smoking - Important for neurological disease

Question 152

What is the issue of multi-morbidity and evidence based medicine?

Answer 152

- Most of evidence-based medicine is based on a single disease model - But increasingly patients have more than one long-term condition - Technical and practical challenges of managing multi-morbidity o How to manage inconsistencies between guidelines?

Question 153

Describe general practice within the NHS

Answer 153

- General practice is the largest medical/surgical speciality - 34,242 FTE GPs in England - Working in 7,500 practices - Average list size – 6,610-7,171 - Patients per GP – 1,577 - Estimated 372 million GP consultations each year - 90% of all NHS patient contacts occur in general practice - Average member of public sees GP six times per year - GPs make most diagnoses in the NH - Therefore, most neurological diagnoses - 8.39% of NHS funding - Comprehensive primary care lowers the overall cost of healthcare systems - £136 per patient per year for unlimited general practice care - About the same as the cost of a single visit to a hospital outpatient department

Question 154

What is primary care neurology?

Answer 154

- GPs as expert medical generalists - Working in extended teams to diagnose and manage neurological illness - Not a disease-based model but a person-centred model - Providing tailored personalised care - Characterised by on-demand access, continuity and individual relationships - Diagnosis and treatment of disease - But also, prevention of disease and promotion of health - Basing most practice on clinical skills (not investigations) - Clinically effective and cost-effective care

Question 155

Define stroke

Answer 155

an acute onset of focal neurology (or global neurological dysfunction) leading to death, or lasting longer than 24 hours as a result of damage to the CNS that is vascular in origin

Question 156

Define TIA

Answer 156

lasts less than 24 hours by definition but generally less than 1 hour

Question 157

Describe the impact of stroke

Answer 157

- 15 million people/year worldwide suffer a stroke - In UK, approximately 152,000 people have a stroke every year - 4th leading cause of death in UK and major cause of adult disability - Lifetime risk of suffering a stroke in men is 1 in 4 while it is 1 in 5 in women - Majority over the age of 65 but 25% occur in under 65

Question 158

Name some modifiable risk factors for stroke

Answer 158

``` o Hypertension o AF – increases risk by 7-8 times (anticoagulation reduces excess risk by 90%) o High cholesterol o Vascular disease o Diabetes and metabolic syndrome o Heart failure o Smoking/drug use/alcohol abuse o Physical inactivity/obesity/diet o Contraceptive pills o Thrombophilia o Hyperhomocysteinaemia o Obstructive sleep apnoea ```

Question 159

Name some non-modifiable risk factors for stroke

Answer 159

``` o Age o Gender o Ethnicity o Genetic predisposition o Previous TIA/stroke ```

Question 160

Describe cerebral perfusion and its relation to brain health

Answer 160

- CBF – 50ml/100g/min - About 20% of CO - Can compensate until CBF reduced to 20-25ml/100g/min - CBF relatively constant when mean arterial blood pressures are between 50-150mmHg - If CBF <10ml/100g/min all membranes and functions severely affected - Neurons cannot live long at <5ml/100g/min

Question 161

What symptoms would indicate a frontal lobe lesion?

Answer 161

- Disinhibition - Apathy - Irritability - Inappropriate placidity - Obsessional behaviour - Distractibility - Poor planning skills - Utilisation behaviour - Release of primitive reflexes (e.g. pout) - Gait apraxia

Question 162

Name the two types of stroke

Answer 162

- Ischaemic (85%) | - Haemorrhagic (15%)

Question 163

What are the aetiologies of ischaemic stroke?

Answer 163

- Carotid disease and vertebrobasilar disease - Carotid stenosis – chronic atherosclerosis disease - Plaque rupture with either thrombosis (causing stenosis/occlusion) or embolism - Dissection – usually history of trauma with neck pain and can be associated with Horner’s syndrome - Embolic sources - Prothrombotic states - Hypoperfusion

Question 164

Name some embolic sources of stroke

Answer 164

o AF o Paradoxical emboli and PFO (patent foramen ovale) o SBE (subacute bacterial endocarditis) o LV thrombus/post MI o Mechanical valves (usually with suboptimal anticoagulation) o Post-operative carotid/peripheral vascular/valvular/cardiac surgery

Question 165

Name some prothrombotic states

Answer 165

o Antiphospholipid syndrome o Polycythaemia and hyperviscosity syndrome o Malignancy

Question 166

Name some causes of hypoperfusion

Answer 166

o All causes e.g. sepsis, iatrogenic, hypovolaemia o Must look for carotid stenosis – generally hypotension must have been prolonged and severe to cause stroke o Also – inflammatory causes such as vasculitis

Question 167

What are some aetiologies of haemorrhage stroke?

Answer 167

Rupture of vessels ``` o Through excessive pressure (hypertension) o Or friable/damaged vessels  Vasculitis  Amyloid angiopathy  Vascular malformations  Moyamoya o Trauma e.g. traumatic SAH o Malignancy ```

Question 168

What is the presentation of an anterior circulation stroke?

Answer 168

``` o Hemiplegia o Hemisensory loss o Neglect/inattention o Speech problems o Amaurosis fugax ```

Question 169

What is the presentation of a posterior circulation stroke?

Answer 169

``` o Balance problems o Visual field defects o Swallowing problems o Poor coordination o Drowsiness o Cognitive issues (thalamic involvement) ```

Question 170

What is the presentation of haemorrhagic stroke?

Answer 170

Can be any of anterior and posterior circulation defects More commonly associated with headache Drowsiness can be prominent especially in a large bleed

Question 171

Describe the pattern of motor weakness following a stroke

Answer 171

o Hemiparesis o Focal single limb/facial weakness, could be proximal or distal o Pyramidal in pattern o Initially reflexes are down but as spasticity develops will become more pronounced o Plantar reflexes o Palatal weakness – dysphagia, dysarthria o Unilateral

Question 172

What is an example of a peripheral nerve distribution of weakness and therefore not a stroke syndrome?

Answer 172

 Bell’s palsy is not a stroke syndrome |  Stroke is a UMN lesion and therefore is forehead sparing – facial motor output as projection from both hemispheres

Question 173

Describe the patterns of sensory loss in a stroke

Answer 173

``` o Hemisensory loss o Confined to one limb o Unilateral o Does not cross the midline o Generally multimodal o Look for cortical dysfunction such as stereognosis or graphesthesia ```

Question 174

What sensory deficits would suggest it's not a stroke?

Answer 174

o Positive sensory phenomena generally do not occur in stroke o Peripheral nerve distribution o Sensory levels o Bilateral symptoms

Question 175

Describe the oxford classification of stroke

Answer 175

Total anterior circulation syndrome (TACS) o All 3 of unilateral weakness/sensory deficit, homonymous hemianopia, higher cerebral dysfunction (dysphasia, inattention/neglect) Partial anterior circulation syndrome (PACS) o Either 2 of the above or higher cerebral dysfunction alone Posterior circulation stroke syndrome (POCS) o Any of: ipsilateral cranial nerve palsy with contralateral motor and/or sensory deficit, bilateral motor and/or sensory deficit, disorder of conjugate eye movement, cerebellar dysfunction, isolated homonymous visual defect Lacunar stroke syndrome (LACS) o Pure hemi-motor, pure hemi-sensory-moor, ataxic hemiparesis

Question 176

Why are TIAs important for stroke?

Answer 176

- 20% of patients with stroke report a preceding TIA | - Identify and treat if possible high-risk individuals to prevent a subsequent more serious event

Question 177

What is the ABCD2 score and what is it used for?

Answer 177

o Use for triaging high risk patients o Target rapid intervene to high risk patients o Age, Blood pressure, clinical symptoms, duration of symptoms, diabetes

Question 178

What is deemed a high risk TIA?

Answer 178

- AF - Known carotid stenosis - Crescendo TIAs - On anticoagulation - Give specialist review within 24 hours

Question 179

What is large vessel disease?

Answer 179

- Atherosclerosis of large and medium sized arteries

Question 180

Describe the mechanisms for large vessel disease

Answer 180

o Thrombus on lesion causing local occlusion o Embolisation of plaque debris or thrombus in distal vessel o Small vessel origin occlusion by growth of plaque o Severe reduction in diameter of vessel lumen leads to hypoperfusion and infarction of distal watershed areas

Question 181

Describe small vessel disease

Answer 181

- Small penetrating arteries of the brain - Occlusion of these causes infarction – Lacunar - Small vessel arteriopathy – hyaline arteriosclerosis o Muscle and elastic in arterial wall replaced by collagen o Wall thickening with subsequent lumen narrowing - Diabetes, hypertension, age

Question 182

What are some causes of cardioembolism?

Answer 182

- Atrial fibrillation (LA thrombus) – 80% - Myocardial infarction (anterior wall) with hypokinetic wall segment/LV aneurysm - Infective endocarditis - Non-bacterial thrombotic endocarditis - Prosthetic heart valves (mitral) - Paradoxical embolus – PFO, ASD, VSD

Question 183

What is the importance of AF in stroke?

Answer 183

- Overall 5x increased risk of stroke - Around 25% of people over 80 having AF - AF strokes 3x more likely to be classed severe o Clots can form in the left atrial appendage o Can become large before embolising o Fibrin rich clots

Question 184

Name some obscure causes of stroke

Answer 184

- Arterial dissection and trauma - Inflammatory vascular disease o GCA, SLE, antiphospholipid syndrome, RhA - Haematological o Thrombophilia, leukaemia, lymphoma, polycythaemia, sick cell, TTP, DIC - Peri-operative o Anaesthetic – reduces CO, can precipitate irregular heart rhythm - Recreational drugs o Cocaine, amphetamines

Question 185

What can cause primary intracerebral haemorrhage?

Answer 185

- Intracranial small vessel disease – HTN - Cerebral amyloid angiography - AMVs - CNS neoplasms - Anticoagulation

Question 186

What is the estimated cost of stroke in the UK?

Answer 186

At least £7 billion every year

Question 187

Describe blood pressure and its effect on stroke risk

Answer 187

- High = BP> 140/90 - In most countries >30% adults suffer from high blood pressure - Most important modifiable risk factor for stroke - For every 10 deaths from stroke, 4 preventable if BP treated - Blood pressure linked to BMI, physical activity and dietary salt intake - BP tends to increase with age except where obesity is absent, salt intake low and physical exercise high

Question 188

What is the population-based approach to stroke prevention?

Answer 188

Education regarding healthy lifestyle including o Increased exercise o Lower salt intake o Better diet – more fruit and vegetables o Reduced cholesterol intake o Reduced alcohol intake o Stop smoking

Question 189

Describe smoking and stroke

Answer 189

- Doubles the risk of stroke in men and women - Several mechanisms involved – damages endothelial lining, promotes atheroma, enhances clotting, raises LDL, lowers HDL, raised BP - Stopping smoking reduces cardiovascular risk to close of that of a non-smoker

Question 190

Describe cholesterol and stroke

Answer 190

- High total cholesterol, high LDL and low HDL are important risk factors for IHD - Causal association for stroke not so clear - Pooled data suggests high levels of cholesterol risk factor for ischaemic stroke but not ICH - Clear evidence from trials of benefit of lowering cholesterol in patients with history of IHD, PVD or prior stroke on preventing further events

Question 191

Describe the treatment of high cholesterol

Answer 191

Statins! o Reduce cholesterol and have effects on platelets and vascular endothelium o Reduces the risk of MI, of stroke and of revascularisation by at least one third o 5 years of statins prevents major vascular events in about 70 out of 1000 with previous stroke (Heart protection study 2001)

Question 192

Describe social deprivation and its effect on stroke risk

Answer 192

- People living in deprived areas are 3 times more likely to die from stroke than the least deprived - Been attributed to higher rates of smoking, poor diet, obesity, lack of exercise

Question 193

Describe AF and its effect on stroke risk

Answer 193

- NVAF associated with 6-fold increase in risk of stroke - Individuals risk is compounded by other risk factors (E.g. CHF, PVD, high BP, elderly, diabetes, female) - Treatment options include aspirin, warfarin or one of the NAOCs - CHADS2VASC score predicts risk of stroke - HASBLED score predicts individual risk of haemorrhage on treatment

Question 194

Describe the primary prevention of stroke

Answer 194

Targeting at risk groups - Identify high risk population - Regular BP checks - Well man clinics - Diabetes/high cholesterol/AF - Assess overall cardiovascular risk prior to treatment

Question 195

Describe some secondary prevention strategies for stroke

Answer 195

- Rapid assessment of patients with TIA - Address cardiovascular risk factors - BP <130/80, <120/80 in diabetes - Statin for all patients - Antiplatelet – reduces risk by around 20% annually o Clopidogrel or aspirin and dipyridamole combination - Warfarin/DOACs for patients with AF - Carotid endarterectomy for patients with tight symptomatic stenosis

Question 196

Name the two types of haemorrhagic stroke

Answer 196

- Subarachnoid haemorrhage – occurs when a blood vessel on the brain surface ruptures (aneurysm/AVM) - Intracerebral haemorrhage – occurs when a blood vessel bleeds into the tissue deep within the brain

Question 197

Describe intracerebral haemorrhage and its epidemiology

Answer 197

- 10% of strokes - Within bran parenchyma - 12-15/100,000 per year - Incidence >55yrs increases and x2 with each decade until >80yrs then x25 - Previous CVA risk increases risk x23 - Onset usually during activity

Question 198

What is the most common site of an intracerebral haemorrhage?

Answer 198

Basal ganglia/ Putamen/ Lentiform Nucleus/ Internal capsule/ Globus pallidus in 50%

Question 199

Name some common arterial feeders

Answer 199

- Lenticulostriates – sources of Putaminal haemorrhages o Possibly secondary to microaneurysms of Charcot Bouchard (caused by chronic hypertension) - Thalamoperforators – supplies thalamus - Paramedian branches of Basilar artery

Question 200

What can cause increased CBF? (and therefore haemorrhagic stroke)

Answer 200

o Haemorrhagic transformation – type 1 and 2 (post ischaemic stroke) o Migraine o Exercise o Cold

Question 201

Name some vascular anomalies

Answer 201

``` o AVM o Aneurysm o Cavernoma o Amyloid angiopathy o Cerebral venous thrombosis ```

Question 202

What types of tumours can cause a hemorrhagic stroke?

Answer 202

``` Metastatic malignant melanoma, renal, thyroid and lung carcinoma, choriocarcinoma, Oligodendroma ependymoma ```

Question 203

Describe the presentation of haemorrhagic stroke

Answer 203

Putaminal o Most common type – especially in hypertensive haemorrhage o Contralateral hemiparesis or hemiplegia Thalamic o Motor and sensory loss o Presentation depends on what part of the thalamus is affected Delayed deterioration can occur o Rebleeding, oedema, hydrocephalus, seizures

Question 204

What investigation should be performed if a haemorrhagic stroke is suspected?

Answer 204

- CT is sensitive diagnostically | - MRI may help to differentiate between hypertensive haemorrhage from other causes

Question 205

Briefly describe the management of haemorrhagic stroke

Answer 205

Standard medical support o Stop antiplatelet drugs, reverse anticoagulation Surgical evacuation depends on location, age and premorbid performance status of patient

Question 206

What are the STICH trials and what did they show?

Answer 206

o Aim- relative benefits and risks of surgery in haemorrhagic stroke o Results – no real benefit in early surgery over conservative (medical) treatment o Infratentorial haematomas are special cases – may warrant surgical evacuation or shunt insertion for hydrocephalus

Question 207

What would indicate surgical treatment for haemorrhagic stroke?

Answer 207

- Symptomatic - Mass effect, oedema, midline shift - 10-30mls - Persistent raised ICP - Rate of deterioration - Favourable location - Age young - Surgery <24 hours

Question 208

What would indicate medical treatment (rather than surgical) in haemorrhagic stroke?

Answer 208

- GCS>10+, awake and subtle hemiparesis - Massive dominant hemisphere haemorrhage - GCS<5, loss of brain stem function - Severe comorbidity and coagulopathy - Age>75, poor tolerance to surgery - Basal ganglia haemorrhage

Question 209

What is cerebral amyloid angiopathy?

Answer 209

- 10% of ICH - Amyloid beta protein is deposited in the walls of small to medium blood vessels of the CNS and meninges - Identical to plaques of Alzheimer’s

Question 210

Describe the epidemiology of subarachnoid haemorrhage

Answer 210

- Spontaneous 75-80% - No cause found in 14-22% - 10/100,000 - Peak age 55-60 - F>M (just) - 50-60% die in 1 month with no treatment - 50% of survivors have a major disability - 7% die and 7% have a severe deficit from spasm - 70-80% aneurysmal, 4-5% AVM - 30% have warning signs 6-20 days before

Question 211

What are the locations of aneurysmal SAH?

Answer 211

- 85-90% carotid system - 5-15% vertebrobasilar system - 30% Anterior communicating artery - 25% Posterior communicating artery - 20% Middle cerebral artery

Question 212

What are the symptoms of SAH?

Answer 212

- Headache - Nausea - Vomiting - Brief LOC - Hemiparesis - Vertigo - Faintness - Confusion

Question 213

What are the risk factors for SAH?

Answer 213

- Hypertension - Smoking - Family history of PCOS - OCP - Diurnal variation in BP - Pregnancy - LP/cerebral angiogram - Age - Cocaine

Question 214

What are some disease states associated with intracranial aneurysm formation?

Answer 214

- Increased blood pressure o FMD, APKD, Aortic coartication - Increased blood flow o AVM, aplastic, hypoplastic, ligated contralateral vessel, persistent carotid-basilar anastomosis - Blood vessel disorders o Granulomatosis angiitis, SLE, Moya Moya disease - Genetic o Ehlers-Danlos, Marfans, OWR syndrome - Congenital o Persistent fetal circulation, hypoplastic arterial circulation - Tumours metastatic to cerebral arteries o Atrial myxoma, choriocarcinoma, undifferentiated carcinoma - Infectious o Bacterial, fungal

Question 215

What are some non-aneurysmal causes of non-traumatic SAH?

Answer 215

- Intracerebral arterial lesions - AV shunts - Vascular lesions in the spinal cord o Spinal AVM, Saccular aneurysms of the spinal artery, cavernous angioma into the cervical cord - Cardiac myxoma - Sickle cell disease - Vasculitis - Unsuspected trauma - Infections - Tumours - Drugs o Cocaine, anticoagulants - Idiopathic perimesencephalic non-aneurysmal SAH - Unknown

Question 216

Describe the Hunt and Hess classification of SAH

Answer 216

0- No SAH 1- Asymptomatic or mild headache, mild nuchal rigidity 2- Moderate to severe headache, nuchal rigidity, no neurological deficit except cranial nerve palsy 3- Drowsiness, confusion, or mild focal deficit 4- Stupor or mild to moderate hemiparesis, possible early cerebral rigidity 5- Deep coma, decerebrate posturing, moribund

Question 217

Describe the Fisher Grade of CT findings

Answer 217

1- No blood detected 2- Diffuse thin layer of SAH (vertical layers <1mm thickness) 3- Localised clot or thick layer of subarachnoid clot 4- Intracerebral or intraventricular blood with diffuse or no subarachnoid blood

Question 218

What is the management of SAH?

Answer 218

- Resuscitation (ABCDE) – continuous monitoring BP, SpO2 - Monitor ECG – arrhythmias common - Inset IV cannula – take bloods and commence IVI - Bloods - Strict bed rest until diagnosis determined - CT o If CT negative proceed to LP - CT/LP positive o Commence nimodipine (calcium channel blocker) o CT angiogram - If aneurysm found o Neurosurgical clipping or endovascular coiling depending on aneurysmal site, clinical condition, comorbidities, local practice

Question 219

What are some of the complications of SAH?

Answer 219

- Rebleeding - Vasospasm - Hydrocephalus - Hyponatraemia - Infarction

Question 220

Describe rebleeding as a complication of SAH

Answer 220

o 30% rebleed first 28 days with no drugs o 70% of these die o More severe clinically than initial bleed – 2x mortality o Risk down to 3.5% per year after around 6 months

Question 221

Describe vasospasm as a complication of SAH

Answer 221

o Risk factors include – young, smoking, raised ICP, dehydration, hypotension, hypoxia, hydrocephalus, hyponatremia, hyperthermia o Clinical vasospasm – 20-30% o Radiographic vasospasm – 30-70% o When two correlate – symptomatic vasospasm o Ischaemic complications 7%, fatal 7% o Day 3-17 (peaks at day 6-8), usually resolved by day 12 o Treat with nimodipine, triple H therapy (induced hypertension, hypervolemia, haemodilution), angioplasty

Question 222

Describe infarction as a complication of SAH

Answer 222

o 4-12 days post SAH o 25% clinical signs and 25% die as result, 10% survivors permanently disabled o Weakness, confusion, dysphasia, incontinence o Multifactorial – vasospasm, hypovolaemia, reduced CPP, renal Na excretion

Question 223

What are the advantages and disadvantages of early surgery for SAH?

Answer 223

``` Advantages o Prevention of rebleeding o Aggressive management of vasospasm o Removal of subarachnoid blood o Evacuation of ICH o Early ambulation o Reduced medical complications o Shorter hospital stay o Psychosocial reassurance o Possible prevention of hydrocephalus ``` ``` Disadvantages o Swollen brain o Unstable patient o Scheduling difficulties o Inexperienced surgeon? ```

Question 224

What are the advantages and disadvantages of delayed surgery for SAH?

Answer 224

``` Advantages o Slack brain o Stabilised patient o Easier dissection o Flexibility in rescheduling o Experienced operative team ``` ``` Disadvantages o Rebleeding o Less aggressive management of vasospasm o Delayed ambulation o Additional medical complications o Longer hospital stay o Psychosocial stress ```

Question 225

What is a arteriovenous malformation?

Answer 225

- Developmental abnormalities of intracranial vasculature o Capillary telangiectasias o Cavernous malformation - Not neoplastic - Raised pressure may cause aneurysmal appearance - Middle meningeal territory

Question 226

What is the presentation of arteriovenous malformations?

Answer 226

- Haemorrhage (40-60%) o Bleed in younger patients 20-40 years o Less severe than SAH bleeds – 10-20% mortality o Small more likely than large o 15% 5 year risk if previously unruptured o Raised risk 1st year then back to unruptured risk - Epilepsy - Neurological deficit - Headache - Cranial bruit

Question 227

What investigations should be performed for arteriovenous malformations?

Answer 227

- CT shows most AVM - MRI choice - Angiography – shows feeder vessels

Question 228

What is the management for arteriovenous malformations?

Answer 228

- Avoid initial bleed/prevent rebleed - Surgical risk vs likely course untouched - 3% rupture risk from ruptured/unruptured - Morbidity + mortality 40% per bleed - Operation – complete excision - Stereotactic radiosurgery (SRS) – obliterate up to 80% <3cm o SRS option preferred for those in eloquent areas and <3cm diameter

Question 229

What is the immediate management of a suspected stroke?

Answer 229

ABCDE assessment + Bloods, BM Brief Hx and exam (time of onset, risk factors, contraindications to thrombolysis) BP (permit moderate hypertension) NIHSS (grade the severity)

Question 230

What is the immediate investigation of choice for a suspected stroke?

Answer 230

Urgent CT head (± CT angiography)

Question 231

What (briefly) is the treatment of a ischaemic stroke?

Answer 231

Thrombolysis ± Mechanical thrombectomy if indicated or Aspirin 300mg

Question 232

What is the secondary management of a ischaemic stroke (following thrombolysis)?

Answer 232

Investigate the cause (history, examination, bloods, imaging) Screen and prevent complications (dehydration, aspiration, VTEs, pressure sores, infection, depression) Establish secondary prevention (lifestyle, medical, surgical) Rehabilitation (physiotherapy, occupational therapy, speech and language therapy)

Question 233

What is the NIHSS?

Answer 233

- National institute of health stroke scaled - Grade and track severity - Monitor response to acute treatments - The higher the score the more severe of a stroke

Question 234

What are the pros and cons of CT in stroke?

Answer 234

``` Pros o Quick o Readily available 24/7 o Sensitive to haemorrhage o May see a hyperdense vessel ``` Cons o Cannot usually diagnose an infarct in the acute phase o Less sensitive than MRI for picking up other abnormalities (demyelination, mass lesions, microhaemorrhages) and for lacunar and posterior circulation infarcts

Question 235

What is thrombolysis?

Answer 235

- Breaking down an acute clot - Intravenous administration of a tissue plasminogen activator e.g. Alteplase 0.9mg/kg - Potentially lifesaving - Timing – within 4.5 hours of symptom onset (or time they were last seen well) - Diagnostic uncertainty – ischaemic stroke isn’t confirmed

Question 236

What is the ischaemic penumbra?

Answer 236

- Area surrounding the ischaemic core – mild to moderate ischemia - Blood flow reduced - Spreading depression - Possible reversible damage in case of recirculation - Ischaemic core – permanently damage brain tissue even after recirculation

Question 237

What care is required post-thrombolysis?

Answer 237

- More aggressive blood pressure monitoring - Vigilance for complications (bleeding) - 24 hour CT head – haemorrhagic transformation

Question 238

What is mechanical thrombectomy?

Answer 238

- Mechanical recanalisation of the culprit vessel - Proximal stenosis - 6-hour time window for anterior circulation stroke (later for basilar thrombosis) - Can be used alongside intravenous thrombolysis - Limited resource

Question 239

What are the purposes of investigations in stroke?

Answer 239

``` o Diagnosis o Rule out stroke mimics o Identify aetiology o Guide risk factor modification o Prevent and treat complications ```

Question 240

What blood tests should be requested for a stroke?

Answer 240

o FBC – Hb (anaemia, hypo-oxygenation), MCV (haemoglobinopathies), WCC (infection), platelet count o ESR – vasculitis, autoimmune disease o U&Es – hydration status, guide drug treatment o Lipid profile o LFTs o CRP – infection o Clotting screen – APTT, PT, Fibrinogen o Glucose and HbA1C – hyper/hypoglycaemic – mimic/risk factor

Question 241

What investigations (other than blood tests) may be useful for stroke?

Answer 241

- EEG (MI, atrial fibrillation/flutter) ± 72 hour tape (paroxysmal AF) - Carotid doppler USS – carotid stenosis - Echocardiogram – endocarditis/thrombus - MRI – confirm diagnosis, look for multi-territory infarcts (delayed CT head if MRI contra-indicated)

Question 242

What may an MRI reveal in the case of stroke?

Answer 242

- Acute/subacute infarcts (up to 2 weeks) - Multiple infarcts in the same vascular territory - ?culprit vessel - Multi-territory infarcts - ?cardioembolic - Absent flow void in vessels – arterial occlusion/dissection

Question 243

What further investigations should be considered in young patient or atypical strokes?

Answer 243

Bloods o HIV and vasculitic screen o Thrombophilia screen o Homocysteine Cardiac investigations o 7 day Holter recorder/implantable loop recorder o Transcranial dopplers o TOE Vascular imaging o CT angiography o MR angiography

Question 244

What healthcare professionals are involved in the treatment of stroke?

Answer 244

- Nursing - Physiotherapy - Occupational therapy - Speech and language therapy - Dieticians - Orthoptics

Question 245

What medical management should be undertaken to prevent complications following a stroke?

Answer 245

``` - VTE assessment o Intermittent pneumatic compression devices - Hydration - NG feeding ± PEG feeding - Spasticity o Physiotherapy o Botox - Monitoring for infection ```

Question 246

What medical management should be undertaken for secondary prevention following a stroke?

Answer 246

- Antiplatelets o Aspirin for 2 weeks, clopidogrel lifelong - Anticoagulation o If in AF or evidence of pAF – may need to wait up to 2 weeks o HASBLED and CHADSVASC scores o Randomised controlled trials currently being undertaken to compare early vs late anticoagulation (DOACs) in AF related stroke – results expected 2021 ``` - Hypertension o Acute (3-4 days without thrombolysis) – risk of hypoperfusion o Chronic – long term blood pressure target <130/80 (higher if severe bilateral carotid stenosis) ``` - Cholesterol o Statin therapy – aim 40% reduction in non-HDL cholesterol

Question 247

When should a CEA be performed for carotid stenosis?

Answer 247

o USS carotid dopplers ± CTA/MRA o Ipsilateral (symptomatic) carotid stenosis  70-99% - carotid endarterectomy (CEA) recommended  50-69% - consider CEA o Alternative – carotid artery stenting

Question 248

What is the treatment of malignant MCA syndrome?

Answer 248

Decompressive hemicraniectomy

Question 249

What does a posterior circulation infarct pose a risk of?

Answer 249

o Risk of hydrocephalus | o Treatment - External ventricular drain (EVD)/posterior fossa decompression

Question 250

What is the ABCD2 score?

Answer 250

- Estimates the 7-day risk of stroke following a TIA - Age over 60, High blood pressure, Clinical features, duration and diabetes - Perry 2011 – large prospective cohort study of 2000 subjects found it performed poorly in the acute setting

Question 251

What investigations should be performed for a TIA clinic?

Answer 251

- ECG – to look for atrial fibrillation and other arrhythmias - TIA imaging o CT o Ultrasound doppler of Carotids – if show stenosis – MR angiography o MRI – most sensitive for TIA mimics

Question 252

What are some cardioembolic causes of TIA?

Answer 252

- Atrial fibrillation - Mural thrombus - Septic embolus (SBE) - Malignancy-atrial myxoma, marantic endocarditis - Thrombosis on a mechanical heart valve - Calcific embolus from aortic valve - Paradoxical embolus/PFO

Question 253

What cardiology investigations could be performed following a TIA?

Answer 253

- Echocardiography - Transcranial doppler - Holter monitor - Heart Brain MDT

Question 254

What are the basic principles of TIA treatment?

Answer 254

- Transient impaired blood supply - Local blockage vs embolus from elsewhere - Unblock the narrowed pipe – endarterectomy - Make blood less sticky – antiplatelets - Prevent thrombosis – anticoagulants - Reduced – atheroma – statins

Question 255

Describe the pharmacological treatment of TIA

Answer 255

- Antiplatelets o Clopidogrel – P2Y12 inhibitor o Aspirin - COX-1 inhibitor o Studies suggest that most benefit is both combined - Statins o Inhibit HMG-CoA reductase o Blocking cholesterol production by cells - Antihypertensives o Under 55 – ACE inhibitor or ARB o Over 55 or black people – CCB - Anticoagulants o Vitamin K antagonists o Direct thrombin inhibitors

Question 256

Describe the RCP guidelines for stroke and TIA (2016)

Answer 256

- Discussion of lifestyle factors - Clopidogrel 300mg loading dose followed by 75mg daily - High intensity statin therapy with atorvastatin 20-80mg daily - Blood pressure lowering therapy - Anticoagulants in all patients with AF unless contraindicated

Question 257

Describe the oxford vascular study

Answer 257

- Change in stroke incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire from 1981 to 2003 - Age-specific incidence of major stroke has fallen by 40% over the past 20% years - In association with increased use of preventive treatments and major reductions in premorbid risk factors

Question 258

What are two types of uncommon causes of stroke?

Answer 258

Arterial and venous ``` Arterial o Inflammatory o Infective o Genetic o Toxic o Cardiac – non-AF o Degenerative o Traumatic o Post radiation ``` Venous o Infective o Inflammatory o Haematological

Question 259

What are some uncommon haematological causes of stroke?

Answer 259

Bleeding o Thrombocytopenia o Dysfunctional platelets o Too much platelet breakdown o Von Willebrand’s – missing or defective clotting protein o Clotting factor cascade – poor production, congenital low levels, haemophilia, lack of vitamin K Thrombosis/arterial o Thrombocytosis o Hereditary or acquired ADMATS13 deficiency Thrombosis/venous o Lack of clotting cascade inhibitors - Protein C and S deficiency

Question 260

What is giant cell arteritis?

Answer 260

o Large vessels including aorta o Acute phase response is induced by pro-inflammatory cytokines, mainly IL 1, 6 and TNF alpha o Produced by activated macrophages in the vessel wall o Symptoms - Headache, jaw claudication, visual symptoms, amaurosis fugax, with blindness, rarely stroke o Diagnosis – raised ESR, temporal artery biopsy

Question 261

What is Takayasu's Arteritis?

Answer 261

o Variant of GCA affecting people younger than 50

Question 262

What is Primary angiitis of the central nervous system?

Answer 262

o Rare disorder affecting medium and small sized vessels o Major symptoms – stroke, headache, encephalopathy o Treatment – combination of high dose steroids and pulsed cyclophosphamide (CYC) o Damage inflamed blood vessels lead to local thrombosis and ischaemia but can also become leaky and cause bleeding

Question 263

What is arterial dissection?

Answer 263

- Carotid artery dissections begin as a tear which allows blood under pressure to enter the wall of the artery and splits its layers - Result is either intramural haematoma or an aneurysmal dilatation – can be a source of microemboli o Aneurysm can cause mass effect on surrounding structures - Occurs most frequently in the fifth decade of life - Can be intracranially and extracranially o Extracranial more common o ICA dissection can be caused by major or minor trauma or it can be spontaneous (genetic, familial or heritable disorders are likely)

Question 264

What infections can cause strokes?

Answer 264

HIV o Vasculitis Varicella zoster virus o Vasculopathy o Altered lipid status o Antiphospholipid antibodies Syphilis

Question 265

What are the symptoms of cerebral venous sinus thrombosis?

Answer 265

Symptoms may include thunderclap headache, focal neurological symptoms or seizures

Question 266

What is the investigation of choice for a venous sinus thrombosis?

Answer 266

CT venogram

Question 267

85% of venous sinus thrombosis patients have identifiable risk factors, name them

Answer 267

o Thrombophilia o Chronic inflammatory conditions e.g. IBD, lupus o Pregnancy o Blood disorders with hyperviscosity o Infections of ENT areas e.g. mastoiditis, sinusitis o Direct injury to the venous sinuses (bull horn)

Question 268

What is the treatment for venous sinus thrombosis?

Answer 268

Heparin infusion to unblock vein and reduce pressure

Question 269

What is antiphospholipid antibody syndrome?

Answer 269

- Autoimmune hypercoagulable state - Antibodies against cell membrane phospholipids - Promotes venous and arterial thrombosis - Treatment – anticoagulants – heparin, warfarin

Question 270

What is a toxic cause of stroke? Explain

Answer 270

- Cocaine - Exact mechanism of cocaine related stroke remains unclear - Vasospasm – possible via endothelin-1 - Cerebral vasculitis - Hypertensive surges – altered cerebral autoregulation - Cocaine is a potent vasoconstrictor due to its sympathomimetic action, preventing the reuptake of noradrenaline, serotonin and dopamine at pre-synaptic nerve terminals - Also has direct effects on calcium channels – promoting intracellular calcium release from the sarcoplasmic reticulum

Question 271

What is amyloidosis (CAA)?

Answer 271

Cerebral amyloid angiopathy - Deposition of amyloid in vessel walls - Reason unclear – possible excess production or reduced clearance proposed mechanisms - Amyloid usually cleared by endocytosis by astrocytes and microglia - Vessels are friable and bleed, microbleeds or lobar haemorrhage

Question 272

What is Moya Moya?

Answer 272

- Premature large vessel arteriopathy of terminal carotids and vessels of circle of Willis - More common in Asian populations - Results in – ischaemia, seizures, haemorrhage

Question 273

Nme two mitochondrial disease? How can they cause stroke?

Answer 273

o MELAS, MERRF o Metabolic stroke like episodes may be non-vascular and due to transient oxidative phosphorylation (OXPHOS) dysfunction within the brain parenchyma

Question 274

What is homocystinuria?

Answer 274

o Cystathionine beta synthetase deficiency o Autosomal recessive inherited disorder of methionine metabolism o Patients tall and thin, some learning problems, seizures, young onset vascular disease o Treatment – folic acid and low methionine diet

Question 275

What is Fabry's disease?

Answer 275

o Results from abnormal deposits of a fatty substance in blood vessel walls o X linked recessive inherited deficiency of galactosidase A o Leads to decreased blood flow and decreased nourishment of the tissues o Particularly affecting vessels in the skin, kidneys, heart, brain and nervous system o Begins in childhood with episodes of pain and burning sensations in the hands and feet o Slowly progressive

Question 276

What is CADASIL?

Answer 276

o Cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy o Inherited o Thickening of the blood vessel walls blocks the flow of blood to the brain o Affects small blood vessels in the white matter of the brain o Migraines and multiple strokes progressing to dementia

Question 277

What is myxoma?

Answer 277

o Most common type of primary heart tumour o Signs and symptoms – dyspnoea, syncope, mild fever, weight loss o Untreated – may result in thrombus formation o Surgical removal is completely curative

Question 278

What cardiac causes, other than myxoma, cause stroke?

Answer 278

Endocarditis | PFO

Question 279

Define stroke rehabilitation

Answer 279

stroke care that aims to reduce disability and promote active participation in ADL, to prevent deterioration, preserve remaining function and train patients to help them achieve their objectives

Question 280

Define stroke recovery

Answer 280

improvements across a variety of outcomes in performance in activity based behavioural measures

Question 281

What are the mechanisms of stroke recovery?

Answer 281

- Adaptation - Regeneration - Neuroplasticity

Question 282

What is adaptation in stroke rehab?

Answer 282

- The reliance on alternative physical movements or devices to compensate for poststroke deficits - E.g. training left hand in right hemiplegia, using stick or shower chair, and using a prism in hemianopia

Question 283

What is the learned disuse phenomenon?

Answer 283

o Patients do not use their affected limb because they have developed habits to complete tasks bypassing the affected limb, even though they have capacity to use it o Harmful to the recovery process

Question 284

What is regeneration in stroke rehab?

Answer 284

- Damage tissue grows back in brain – a limited process - Sprouting of neurons (predominantly dendrites) o Lack of Schwann cells (which lead sprouting) o Gliosis barriers o Oligodendrocytes incomplete myelination and production of inhibitory factors o Low production of growth factors

Question 285

What is neuroplasticity?

Answer 285

- The dynamic potential of the brain to reorganise itself in response to training, injury, rehabilitation, pharmacotherapy, electrical and magnetic stimulation, and stem cell and gene therapy - Rewiring or development of new networks – the key in stroke recovery

Question 286

What is the scientific theory behind neuroplasticity?

Answer 286

- Vicariation – different area of the brain takes over the function - Plasticity of areas of cortical representation – early compensation by recruitment of secondary motor areas (premotor cortex and SMA), followed by reorganisation with more focused brain activity reminiscent of normal pattern - Collateral sprouting – to receive new synaptic dendritic input from sprouting neurons - Synaptic plasticity – cells that fire together wire together (Hebb 1994) - Diaschisis – a focal lesion can lead to changes in brain function far away from the lesion o E.g. cortical infarct can lead to enhance contralateral cerebellar activity

Question 287

What drives the neuroplasticity?

Answer 287

- Rehabilitation interventions must be task specific and goal directed rather than general and nonspecific movements - The goal directed tasks must be challenging and interesting enough to maintain an individual’s attention - The task should allow for repetition through multiple attempts

Question 288

Describe motor recovery following a stroke

Answer 288

- Motor recovery starts proximally (shoulder - elbow -- wrist - fingers) - Swallowing, facial movement and gait – better recovery (bihemispheric representation) - Language, spatial attention and dominant hand movement – are more lateralised and therefore recover more slowly

Question 289

What is EPOS? What did it show?

Answer 289

Early prediction of functional outcome in stroke study o Recovery of UL at 6 months is predicted by voluntary shoulder abduction and finger extension o If present after 48hr – good outcome in 98% o If not present by day 9 – only 14%

Question 290

What hinders stroke recovery?

Answer 290

- Natural history of stroke – recovery plateaus in 3-6 months - Depression - Medication – BZD - Comorbidities – C spine disorders

Question 291

What is the best time to begin stroke rehab, and how intensive?

Answer 291

- Uncertainty - AVERT trial – early mobilisation within 24 hours regardless of stroke intensity, but worse outcome - Subgroup analysis – early, shorter sessions with less intensity – good outcome - Animal model – stroke size increased when they were pushed to do intensive therapy very early

Question 292

Where should stroke patients be treated?

Answer 292

In a specialised stroke unit Stroke unit treatment reduces death and dependency (NNT – 7 for thrombolysis and 9 for HASU-ASU) o Early rehabilitation o Interdisciplinary management o Structural organisation Meta-analysis – of every 100 patients, extra independent 5 returned home when there were treated in stroke units compared to general wards o Langhorne P, Stroke 2001

Question 293

What additional therapies are they for stroke rehab? Are they effective

Answer 293

Gait training with rhythmic acoustic pacing showed better stride length and better walking speed Mirror therapy o Patient gets the visual impression that the limb in the mirror is fully functioning o Weak evidence o Can work through enhancing connections between visual input and the premotor area Device-based therapies, such as robotic arms and bodyweight supported treadmills were not superior to currently used therapies Electric stimulation technique o Applying electrical stimulation to muscles of interest to help produce the desired movements (proved by RCT) o Repetitive stimulation improves motor function o Portable and can be used at home

Question 294

What is constraint induced therapy?

Answer 294

- The unaffected extremity is constrained with a device (mitt) which forces the patient to use the affected side in task specific and repetitive methods - Prevents learned disuse which reduces recovery

Question 295

How should dysphasia be treated?

Answer 295

Speech and language therapy - Integration of available language-related brain regions is more effective than recruiting new brain regions - Total hours of therapy was directly related to outcome (Bhogal et al, Stroke 2003)

Question 296

What is melodic intonation therapy?

Answer 296

o To improve language production o Language is in the dominant hemisphere but singing and melody are in the nondominant hemisphere o Patient retains ability to sing and carry out melody – helps with speech recovery o Most helpful in expressive aphasia

Question 297

Describe dysphagia in stroke. What should be looked for and how should it be managed?

Answer 297

50% of patients, up to 78% when examined by FEES (widespread involvement of different brain area – sensory, motor and premotor cortex, brainstem) Lead cause of mortality in acute stroke – aspiration pneumonia, malnutrition and airway blockage ``` Look for o Gurgling voice o Coughing after drinking o Bubbling respiration o Recurrent respiratory tract infections ``` Management o Modify o NGT/PEG

Question 298

What is spatial neglect?

Answer 298

- Predominantly in right parietal strokes | - Deficit in attention and awareness to space and/or personal perception

Question 299

What therapies can be given for spatial neglect?

Answer 299

o Enforcing perception via the affected side o Alertness training o Visual, proprioception and vestibular stimulation techniques o Cortical stimulation – inhibitory rTMS over the unaffected posterior parietal cortex – showed benefit in a small pilot study (Shindo et al)

Question 300

What is pusher syndrome?

Answer 300

- A misperception of the body’s orientation in the coronal plane – patients use the unaffected side to push away and resist any attempt to passively correct their posture - Seen after posterior thalamus, insula, or post central gyrus unilateral strokes (more in the right) - Treatment (prolonged) – by enhancing sensory-motor input from the collateral side

Question 301

What is apraxia?

Answer 301

Motor agnosia - Patients are not paretic but have lost information about how to perform skilled movements - Affected area - Left inferior parietal lobule, the frontal lobes or the corpus callosum - Severely hinders ADL - Apraxia of speech - Improves with OT

Question 302

Describe the pharmacology of stroke rehab

Answer 302

Flame (USA) or focus – Fluoxetine daily 5-10 days post stroke – improves UL motor function o Likely through neuroplastic mechanisms Neuromodulation improves aphasia o Cholinesterase inhibitors o Glutamergic agents Dopaminergic medications – used to help depression and attention deficit - Insufficient evidence but can be tried clinically as safe profile

Question 303

What medications should not be used in stroke rehab?

Answer 303

- Diazepam, phenytoin, phenobarbital – impede synaptic formation by effect on neurotransmitter - Antihistamine – neuroplasticity - Pain medication and sedatives - Dopamine blockers – typical antipsychotics

Question 304

Describe post-stroke depression

Answer 304

- Very common (30%) - Patients do worse compared with no depression patients even if similar severity - Can manifest as fatigue, reduced motivation and loss of confidence, concentration and attention

Question 305

Describe spasticity in stroke recovery

Answer 305

- Beneficial or harmful o Stiff leg can be useful in some patients or use it to walk - In chronic phase – limits motor function - Pain – decrease QALY ``` - Treatment o Conservative PT and casting o Baclofen orally o Botulinum toxin o Intrathecal baclofen pumps in severe ```

Question 306

Describe driving following a stroke

Answer 306

- Medical clearance – physician makes sure deficit is not interfering with driving - No seizures - No cardiac conditions that can affect driving - Functional assessment – formal driving assessments (private driving test, driving instructor, mock driving test)

Question 307

What are some novel interventions and advances in rehab?

Answer 307

- Telerehabilitation for patients with no access to therapy – assess rehabilitation needs and focus and wellness and self-training - Pharmacologic agent to stimulate recovery - Stem cells and growth factors - TMS, TDCS - Develop biomarker to help patient rehab techniques depending on stroke type, patient goal

Question 308

What is intravenous thrombolysis?

Answer 308

- IV t-PA - Thrombolytic agent - given to promote acute recanalisation of the occluded artery through lysis of the occlusive thrombus - Approved by the FDA in 1996 - remains only approved treatment of acute stroke

Question 309

Describe the NINDS t-PA study

Answer 309

NEJM 1995 - Multicentre, randomised, double blind placebo-controlled trial - 624 patients with acute ischaemic stroke within 3 hours of onset - At 3 months – treatment with IV t-PA within 3 hours increases the chance of excellent recovery by 30%

Question 310

What is the number needed to treat for IV t-PA?

Answer 310

- 8 patients within 3 hours to achieve 1 additional patient with near complete recovery - 3 patients for a 1-point improvement on the modified Rankin scale at 3 months - (Saver JL 2003)

Question 311

Describe the evidence for going IV thrombolysis up to 4.5 hours after stroke onset

Answer 311

- ECASS III – multicentre, double-blind, placebo-controlled trial in Europe - Between 3-4.5 hours of onset - Favourable outcome at 3 months (52.4% vs 45.2%) - Increased risk of symptomatic intracranial haemorrhage (7.9% vs 3.5%) - Slightly lower incidence of death (7.7% vs 8.4%) - NNT = 14 to achieve 1 additional patient with near complete recovery

Question 312

What are the limitations of IV thrombolysis?

Answer 312

- Time window = 4.5hrs (IST study did not reveal any benefits to 6hrs) - Many contraindications - <10% of all stroke patients receive IV t-PA - Unlikely to break down large clot in proximal vessel

Question 313

What are the goals of intra-arterial treatment for acute stroke?

Answer 313

- Increase time window - Increase efficacy - Increase safety

Question 314

What are the intra-arterial treatment options for acute stroke?

Answer 314

- Intra-arterial t-PA - applying thrombolysis directly to the clot - Mechanical thrombectomy - Intracranial angioplasty and stenting

Question 315

Describe the PROACT II trial

Answer 315

Intra-arterial thrombolysis vs heparin alone - Randomised trial of 180 patients within 6 hours from onset with large artery occlusion - Recanalisation rates improved – 66% vs 18% - Favourable outcomes improved at 3 months – 40% vs 25% - Symptomatic ICH increase – 10% vs 2% - No difference in mortality

Question 316

What is the bridging protocol?

Answer 316

- IV t-PA started within 3 hours – 2/3 of standard dose | - Angiography performed and IA t-PA given within 6 hours of onset if thrombus still present

Question 317

Describe the IMS study

Answer 317

- Interventional management of stroke study - IMS I and II - Using the bridging protocol - Compared results to NINDS t-PA and placebo groups - Improved good outcomes vs placebo and IV t-PA - Reduced mortality - No significant different in symptomatic ICH when compared to IV t-PA - (Stroke 2004)

Question 318

Describe some studies which do not support the use of intra-arterial therapies for stroke before the second generation thrombectomy devices

Answer 318

IMS III – stopped early as results due no differences Synthesis expansion study – negative o Endovascular vs IV o Concluded endovascular therapy is not superior MR-rescue study – negative o Phase 2b study o Medical vs endovascular therapy o Randomisation based on whether there was a favourable penumbral pattern or non-penumbral pattern (penumbral pattern = 70% infarct) o Conclusion - A favourable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke, nor was embolectomy shown to be superior to standard care

Question 319

Name two second generation thrombectomy devices

Answer 319

SWIFT - Significantly better outcomes than MERCI retriever (Slaver 2012 Trevo 2

Question 320

Outline the MR CLEAN study

Answer 320

- 502 patients underwent randomisation between 2010 and 2014 in 16 Dutch centres - Thrombolysis vs thrombolysis and IA treatment - Time from onset to groin puncture was 260 mins - Functional independence (MRS 0 to 2) in favour of the intervention - No significant difference in mortality or the occurrence of symptomatic ICH

Question 321

Outline the extend IA study

Answer 321

- IV t-PA vs IV t-PA and endovascular thrombectomy with solitaire device - Stopped early due to efficacy - Reperfusion – 100% vs 37% - Early neurological improvement 80% versus 37% - MRS 90 days (0-2) 70% vs 40%

Question 322

Outline the ESCAPE trial

Answer 322

- IV t-PA vs endovascular treatment - Stopped early due to efficacy - Primary outcome favoured intervention 53% vs 29% - Reduced mortality - No difference in SICH

Question 323

Outline HERMES paper

Answer 323

- Pools patient-level data from 5 trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, EXTEND IA) done between 2010 and 2014 - NNT with endovascular thrombectomy to reduce disability by at least one level on MRS for 1 patient was 2.6 - Mortality at 90 days and risk of parenchymal haematoma and SICH did not differ between populations - Effect sizes favouring endovascular thrombectomy were present in several groups including those aged over 80

Question 324

What are the current NICE guidelines for thrombectomy?

Answer 324

- Thrombectomy should be offered as soon as possible (and within six hours of symptom onset to patients with confirmed ischaemic stroke with occlusion of the proximal anterior circulation) - If there is potential to salvage brain tissue (as shown by imaging) the patients above should also be considered for thrombectomy between 6 and 24 hours after symptom onset, if they were known to be well beforehand. - Should also be offered as soon as possible (and within 24 hours) for patients with confirmed ischaemic stroke of posterior circulation if there is potential to salvage brain tissue. - Only for people with a large vessel occlusion (from angiogram). - People who are functionally well; no biological age limit. - Thrombectomy should usually only be considered in patients with: o A pre-stroke functional status of less than 3 on the Modified Rankin Scale. o A score of more than 5 on the National Institutes of Health Stroke Scale NIHSS

Question 325

Define stroke mimic

Answer 325

Stroke like symptoms that have acute onset and cause transient or persistent focal signs

Question 326

How common are stroke mimics?

Answer 326

- Prehospital or acute hospital admission – stroke diagnoses are 70-85% correct - After a few days picture is more complete – 95% - Long time after event – a challenge - TIA – Oxfordshire study found 60% were not TIA - >300 patients who present with suspected stroke found mimics 31% at the time of final diagnosis (Hand et al, 2006) o The most important variables associated with a correct diagnosis were a definite history of focal neurological symptoms and NIHSS score greater than 10

Question 327

What makes up a good history of a stroke?

Answer 327

- Mode of onset, circumstances of onset - Type of symptoms, temporal course - Any trauma? - Any suggestion of seizures? - Information from witnesses and relatives - Symptoms prior to onset

Question 328

What is the rosier scale?

Answer 328

- Recognition of stroke in the emergency room - 7-point scoring system - Sensitivity 83-97% - Specificity 18-93%

Question 329

How can brain tumours mimic stroke?

Answer 329

One study (Snyder et al, 1993) found that 6% of patients with brain tumours present to an emergency department had symptoms of less than 1 day’s duration Can cause a sudden onset or worsening of symptoms due to o Haemorrhage into tumour o Seizure activity o Displacement of brain tissue in some tumours which are outside the brain like meningiomas

Question 330

How can brain abscesses mimic stroke?

Answer 330

- Can cause sudden onset focal neurologic symptoms and signs - Usually associated with – fever, headache, and seizures

Question 331

How can herpes encephalitis mimic stroke?

Answer 331

- Often prodromal symptoms during a few days – fever, headache, fatigue, nausea - Then – confusion, cognitive symptoms, focal neurological symptoms and signs, seizures (often partial complex)

Question 332

What is Nonketotic hyperosmolar hyperglycaemia?

Answer 332

- Type 2 diabetes - Stupor often associated with focal neurological signs o E.g. hemiparesis, gaze deviation, global aphasia, homonymous hemianopia - There may be a focal region of brain oedema on brain imaging tests - Treatment – Potassium replacement and insulin

Question 333

What can hypoglycaemia present with?

Answer 333

``` o Confusion o Altered behaviour o Deteriorating LOC o Seizures o Or sudden neurological deficit (hemiparesis, aphasia, cerebellar signs) ```

Question 334

What metabolic disorders can mimic a stroke?

Answer 334

- Hypo/hyperglycaemia (focal symptoms) - Hyponatraemia (encephalopathy, seizures, focal deficit) - Hypercalcaemia (encephalopathy, seizures) - Hepatic encephalopathy o Due to the livers inability to efficiently remove toxins o E.g. increased tissue concentration of manganese secondary to portal-systemic shunting - Wernicke’s encephalopathy (confusion, ophthalmoplegia, ataxia)

Question 335

What are paroxysmal symptoms of MS?

Answer 335

o Episodes of motor or sensory phenomena o Brief, stereotypic, frequent, triggered by movement or sensory stimuli o Non-synaptic transmission of nerve impulses at previous demyelination site o Not a true exacerbation of MS o Within the brainstem – may cause paroxysmal diplopia, facial paraesthesia, trigeminal neuralgia, ataxia, and dysarthria o Motor system can cause painful tonic spasms of muscles of limbs, trunk and occasionally the face o Typically responds to low doses of carbamazepine o Spontaneously remit after several weeks to months

Question 336

What is a chronic subdural haematoma?

Answer 336

- Symptoms may be transient or fluctuating - Insidious onset of headaches, cognitive impairment, apathy, somnolence, and occasionally seizures - Focal deficits may be either ipsilateral or contralateral

Question 337

What is cervical cord neuropraxia?

Answer 337

- Transient neurologic symptoms following minor trauma in young athletes who have congenital or acquired cervical spine stenosis - Symptoms – sensory (burning, pain, numbness, tingling and loss of sensation), and motor (weakness to quadriplegia) - Complete recovery within 10 to 15 minutes or occasionally over a period of 48 hours

Question 338

Describe HINTS

Answer 338

Head impulse test of skew Used to determine if vertigo has a central cause (such as a stroke) Any 1 of 3 indicates central cause (sensitivity 100%, specificity 98%, better than early DWI-MRI) o Head impulse test (vestibular ocular reflex) o Direction changing horizontal nystagmus o Skew deviation (vertical ocular misalignment)

Question 339

How can you distinguish between stroke and psychological disorders?

Answer 339

- No hard signs – reflexes normal - Voluntary effort intermittent – collapsing weakness - Simultaneous activation of agonists/antagonists - Hoover’s sign - Inconsistencies in performance

Question 340

What is the Hoover's sign?

Answer 340

feel a pressure in the non-paretic leg when the paretic leg is attempted to be raised indicates a organic cause

Question 341

How can you distinguish migraine with aura from a TIA?

Answer 341

- Positive and/or negative symptoms - Most often visual and sensory - Evolving gradually over ≥5 minutes (slower onset than TIA or focal seizure) - Slow spread of positive followed by negative symptoms - Gradual offset sensory symptoms – often arm + perioral - Duration – 5-20mins (less than 60 mins) - Usually followed by headache up to 1 hour later - Personal or family history of migraine

Question 342

Describe panic attacks

Answer 342

- Palpitations, dyspnoea, chest pain, light-headedness, sense of impeding doom, - Associated hyperventilation may result in perioral and distal limb paraesthesias - Minutes to hours - History of anxiety or depressive symptoms, triggering events or stressors

Question 343

What is transient global amnesia?

Answer 343

- Prominent anterograde amnesia (inability to form new memories) and variable retrograde amnesia - Patient is disorientated in time, asking repetitive questions, able to recognise familiar places and individuals - Other cognitive and motor functions spared - Rare in adults younger than 50 - Usually 1 to 10 hours (mean 6 hours) resolves within 24 hours - Clinical diagnosis – diagnosis impossible if no witness available - Negative MRI and toxicology screens

Question 344

What Features that help distinguish cerebral amyloid angiopathy (CAA) from TIA?

Answer 344

- Recurrent, brief (minutes), stereotyped episodes of weakness, numbness, paraesthesias, or other cortical symptoms that can spread smoothly over contiguous body - The present of small haemorrhage in corresponding area (best shown with gradient-echo MRI) - May reflect abnormal activity caused by irritation of the surrounding cortex by the small haemorrhage (focal seizure or spreading depression) - Response to anticonvulsants supports this hypothesis - Starting antithrombotics for a presumed TIA in a patient with CAA can result in bleeding

Question 345

Describe the epidemiology of brain tumours

Answer 345

- 10,981 new cases per year in UK - Incidence 17 per 100,000 - 55% malignant - 3% of all cancers - Commonest cause men under 45 and women under 35 - GP <5 new cases in working lifetime - Common differential diagnosis - Frequent concern is headache is due to a brain tumour

Question 346

Name some types of brain tumour

Answer 346

Over 150 types Meninges – meningiomas Germ cell tumours o Rare paediatric usually cancerous tumours in the pituitary/pineal region Sellar region o E.g. Craniopharyngiomas, a usually benign, cystic tumours ``` Gliomas o Oligodendlgial cells o Astrocytic cells o Ependymal cells o Neuronal cells ``` ``` Cranial nerves (schwannoma) o E.g. eighth nerve – acoustic neuroma ``` Haematopoietic o Lymph cells – primary CNS o Lymphoma

Question 347

What cancers can spread to the brain to cause a secondary tumour?

Answer 347

``` o Lung o Breast o Colorectal o Testicular o Renal cell o Malignant melanoma ```

Question 348

Describe the grading of brain tumours

Answer 348

- Use WHO classification – histology - Do not use TMN system - Grade using morphology into four grades of malignancy - I – most benign, IV – most malignant - WHO classification 2016 – combines histological features with molecular genetic features

Question 349

What are gliomas?

Answer 349

- Most common primary brain tumour - Tumour of glial cells o Astrocytes, oligodendrocytes, ependymal cells - WHO grade I and II – low - WHO grade III and IV – high

Question 350

How are gliomas characterised? WHat are the survival rates?

Answer 350

Characterised histologically o Cellularity/mitotic activity/vascular proliferation/necrosis o Grade II – 10 year survival o Grade III – 3.5 years o Grade IV – 12 months

Question 351

Describe low grade gliomas (grade II).

Answer 351

- Slow growing but will undergo anaplastic transformation - Astrocytomas – 3-5 years - Oligodendroglioma – 7-10 years - Median age 35

Question 352

What are the prognostic factors for low grade gliomas?

Answer 352

``` o Histology type o Age o Size of tumour o Rate of growth o Location ```

Question 353

Describe high grade gliomas (Grade III and IV)

Answer 353

Most common type of brain tumour o 85% of all new cases of malignant primary brain tumour o Either as primary tumour or from pre-existing low grade o Median age of onset 45 for III, 60 for IV

Question 354

What are the causes of brain tumours?

Answer 354

- Majority no cause found - Ionising radiation - 5% family history o Associated genetic syndromes – neurofibromatosis, tuberose sclerosis, von Hippel-Lindau disease - Immunosuppression (CNS lymphoma) - No evidence to link mobile use

Question 355

What are the broad symptoms of a brain tumour?

Answer 355

o Headache o Seizures o Focal neurological symptoms o Other non-focal symptoms

Question 356

What are the characteristics of a headache caused by a tumour?

Answer 356

- Woken by headache - Worse in the morning - Worse lying down - Associated with Nausea and Vomiting - Exacerbated by coughing, sneezing - Drowsiness - 24% first symptom, at presentation 46% - At hospital presentation only 2% isolated headache

Question 357

Name some focal and non-focal symptoms of a brain tumour

Answer 357

``` Focal (progressive over days – weeks) o Weakness o Sensory loss o Visual/speech disturbance o Ataxia ``` Non-focal o Personality change/behaviour o Memory disturbance o Confusion

Question 358

What signs may you find in a patient with a brain tumour?

Answer 358

- Papilloedema - Focal neurological deficit o Hemiparesis o Hemisensory loss o Visual field defect o Dysphasia

Question 359

What red flags would trigger an urgent neurology referral for a suspected brain tumour?

Answer 359

Headache o With features of raised ICP (including papilloedema) o With focal neurology – check for field defect Other urgent referrals o New onset focal seizure o Rapidly progressive focal neurology (without headache) o Past history of other cancer

Question 360

What is the difference in presentation between high and low grade tumours?

Answer 360

Low grade – typically present with seizures (but also can be an incidental finding) High grade – rapidly progressive neurological deficit, symptoms of raised intracranial pressure

Question 361

What investigations should be performed for a patient with a suspected brain tumour?

Answer 361

Brain imaging - CT (with contrast) - MRI - more sensitive ``` Brain biopsy (if tumour identified) - Histology and molecular markers ```

Question 362

What would you see on a brain scan of a high grade tumour?

Answer 362

irregular mass with vasogenic oedema, enhancement often seen

Question 363

What is the low grade glioma scanning protocol?

Answer 363

o Cerebral blood volume o MR spectroscopy o Rate of growth o Enhancement

Question 364

What are some molecular markers for brain tumours?

Answer 364

 IDH mutation – important in prognosis  Chromosome 1p19q co-deletion  ATRX loss  TP53 mutation

Question 365

What is the survival for brain tumours?

Answer 365

- Treatment is non-curative (except for grade I) - Only 19% survive 5 years or more - Only 14% of all brain tumours survive 10 or more years

Question 366

What is the treatment for high grade gliomas?

Answer 366

- Steroids – reduce oedema - Surgery – biopsy or resection o For tissue diagnosis, relief of raised ICP, prolongation of survival - Radiotherapy – mainstay of treatment o Radical vs palliative - Chemotherapy – Temozolomide, PCV - Prognosis – 6 months non treatment/18 months with

Question 367

What is the treatment for low grade gliomas?

Answer 367

- Surgery – early resection or biopsy o Awake craniotomy o With mapping much more successful - Radiotherapy alone – delays disease transformation not overall survival - Radiotherapy and chemotherapy – evidence improves long-term survival

Question 368

What are pituitary tumours?

Answer 368

- Tumours – almost always benign and are usually curable - Excessive hormone production - Local effects of the tumour - Inadequate hormone production by the remaining pituitary gland

Question 369

Describe the epidemiology of sleep disorders

Answer 369

- General sleepiness – 0.5-36% - Insomnia – 4-19% for more chronic forms - Obstructive Sleep Apnoea (OSA)- 2-4% middle aged adults - Delayed sleep phase syndrome – 7% of adolescents - Narcolepsy – 0.03-0.16% - Sleep walking – 1-15% adults - Sleep terrors – 3% children (American Academy sleep medicine 1997)

Question 370

Why are sleeping disorders a serious problem?

Answer 370

Mortality - accidents - 1 in 6 crashes - 1500 fatalities per annum - Patients with obstructive sleep apnoea make more errors than control and drunk group (George 1996) Morbidity - Obesity - Depression - Suicide Poor performance - Work - Relationships

Question 371

Define sleep and coma

Answer 371

- Sleep – unconsciousness from which the person can be aroused by sensory or other stimuli - Coma – unconsciousness from which the person cannot be aroused

Question 372

Describe stage 1 of sleep

Answer 372

- Lightest stage of NREM sleep - Presence of slow eye movements - Can easily be disrupted causing awakenings or arousals - Muscle tone throughout the body relaxes and brain wave activity begins to slow from that of wake

Question 373

Describe stage 2 of sleep

Answer 373

- First actual stage of defined NREM sleep - Slow moving eye movements discontinue - Brain waves continue to slow with specific bursts of rapid activity known as sleep spindles intermixed with sleep structures knowns as K complexes o Both are thought to serve as protection for the brain from awakening from sleep - Body temperature begins to decrease and heart rate begins to slow

Question 374

Describe stage 3 of sleep

Answer 374

- Deep NREM sleep - Most restorative stage of sleep, consists of delta waves or slow waves - Parasomnias (sleepwalking, sleep talking, somniloquy and night terrors) occurring during the deepest stage of sleep

Question 375

Describe REM sleep (including the 2 stages)

Answer 375

- Rapid eye movement – dreaming stage - Eye movements are rapid, moving from side to side and brain waves are more active 1. Tonic stage – desynchronised EEG – low voltage, increased frequency, muscle atonia ``` 2. Phasic stage – rapid eye movements o Fast saccadic eye movements o Irregular breathing o Increased heart rate o Myoclonus o Apnoea o Hyperpnea o Dreaming ```

Question 376

What are arousals and what are the criteria that define them?

Answer 376

- An abrupt shift in EEG frequency, which may include theta, alpha, beta waves but no spindles - Criteria o Subject must be asleep with a minimum of 10 continuous seconds of sleep o The EEG frequency shift must be 3 seconds or longer o Arousals may occur without concurrent increases in submental EMG o Arousals cannot be scored based on increases of submental EMG alone

Question 377

What are the two theories of sleep?

Answer 377

- Passive theory of sleep – excitatory areas of reticular activating system (RAS) in the upper brain stem fatigue and become inactive - Active inhibitory process – stimulation of centre located below the midpontine level of the brainstem inhibiting excitatory areas (RAS) in the upper brainstem leading to sleep

Question 378

What two timings are important for the regulation of sleep?

Answer 378

Circadian timing – lasts about 24 hours o Hypothalamus – suprachiasmatic nucleus o Pineal gland – melatonin ``` Ultradian timing – lasts less than 24 hours o Cycling of sleep stages o Prepontine nuclei o Raphe nuclei o Locus coeruleus ```

Question 379

What should be included in a childhood sleep history?

Answer 379

- Onset of symptoms ``` o Hypersomnia o Insomnia o Behavioural attacks in sleep o Restlessness/limb movements o Sleep disordered breathing o Dreams/nightmares/hallucinations o Emotional trauma ```

Question 380

What should be included in an adult sleep history?

Answer 380

o Bedtime o Sleep onset latency ``` o Arousals  Attacks  Breathing problems  Kicking/restlessness  Dreams/nightmares/hallucinations  Enuresis/nocturia  Other ``` o Rising time o Refreshment o Daytime somnolence (sleepiness) – Epworth Sleepiness score o Daytime dreams o Cataplexy – strong emotion or laughter causes collapse with retained consciousness

Question 381

Name some sleep questionnaires and rating scales

Answer 381

The Epworth sleepiness scale o Rank likelihood of falling asleep in certain situations Restless legs syndrome rating scale o Assess severity of restless leg Parkinson’s disease sleep scale o Assess sleep in PD

Question 382

What are two objective measures of sleep quality?

Answer 382

``` Outpatient neurophysiology studies o Pulse oximetry o Ambulatory EEG o Limited outpatient respiratory monitoring o Actigraphy ``` Inpatient telemetry studies – Polysomnography o Prolonged video EEG telemetry o Respiratory monitoring o Movement detection – EMG, Actigraphy

Question 383

What is the multiple sleep latency test (MSLT)?

Answer 383

o Measures time to fall asleep in a darkened room on at least 4 separate occasions across the day following an instruction to fall asleep o Analyse EEG for sleep onset/REM onset o Severe sleepiness – mean sleep latency <5 mins o Mild-moderate sleepiness – mean sleep latency 6-8 mins o Normal >8 mins o 2 or more sleep onset REM periods compatible with narcolepsy (but not totally specific

Question 384

What is the maintenance of wakefulness test?

Answer 384

o Measures the ability to keep awake (by EEG criteria) during 4 planned naps throughout the day following an instruction to keep awake o The test is stopped at sleep onset or after 40 mins o Severe sleepiness – mean sleep latency <10 mins o Moderate – mean sleep latency 11-20 mins o Mild – mean sleep latency 21-30 mins o Normal – mean sleep latency >31 mins

Question 385

What are vigilance tests?

Answer 385

o Computer based assessment of sustained visual attention o Measures the reaction time take to press a button in response to a stimulus that is presented on a screen at random intervals over a given time period E.g. Olser test, Psychomotor vigilance test (PVT)

Question 386

What is the international classification of sleep disorders?

Answer 386

- Insomnia - Hypersomnia o Sleep disordered breathing o Hypersomnia of central origin - Circadian rhythm disorders - Parasomnias - Movement of disorders of sleep (American academy of sleep medicine 2005)

Question 387

What is insomnia?

Answer 387

- Commonest sleep disorder in the industrialised world - Inability to achieve and maintain sleep - Complaint of poor-quality sleep - >1-month duration - Associated with fatigue, poor memory and concentration is short term sufferers - Transient insomnia may be associated with stress, shift work, jet lag, pain, alcohol, drug withdrawal - Chronic insomnia is usually associated with psychiatric disorders (depression, alcohol/drug abuse, caffeine excess, physical illness (pain, breathlessness), cat naps - PSG/MSLT are usually normal in chronic cases

Question 388

What is the treatment of insomnia?

Answer 388

o Exclude other sleep disorders o Good sleep hygiene o Short term prescription (4 weeks) of hypnotic sedatives (e.g. zolpidem, temazepam) o CBT – treatment of first choice for chronic insomnia (70-80% of patients benefit) o Often difficult to treat

Question 389

What are the differential diagnosis of excessive daytime tiredness?

Answer 389

- Sleep disordered breathing o Obstructive sleep apnoea syndrome o Central sleep apnoea o Obesity hypoventilation syndrome - Hypersomnia of central origin o Narcolepsy with cataplexy o Narcolepsy without cataplexy  Secondary narcolepsy (MS, PD, Head injury, encephalitis, tumour) o Idiopathic hypersomnia o Recurrent hypersomnia – Klein Levin Syndrome - Insufficient sleep syndrome - Drug induced hypersomnia - Hypersomnia due to medical conditions - Depression and anxiety syndromes

Question 390

What is obstructive sleep apnoea (OSA)?

Answer 390

- Obstructive sleep apnoea - repeated upper airway collapse during sleep - Apnoea – ten second pause in breathing activity - Hypopnea – ten second period in which ventilation is reduced by at least 50%

Question 391

What can be used to measure the severity of OSA?

Answer 391

o Apnoea-hypopnea index (AHI)

Question 392

What are the day symptoms of OSA?

Answer 392

``` o Excessive daytime sleepiness o Unrefreshing sleep o Memory disturbances o Morning headache o Depression o Decreased libido o Stomach ache ```

Question 393

What are the night symptoms of OSA?

Answer 393

``` o Snoring o Apnoea o Choking, gasping o Arousals o Sweating o Dry mouth o Palpitation o Nocturia ```

Question 394

What are the risk factors for OSA?

Answer 394

``` o Obesity o Age o Male gender o Positive family history o Alcohol consumption before bedtime o Race o Smoking o Sedatives o Craniofacial anomalies o Hypothyroidism, acromegaly ```

Question 395

What are treatment options for OSA?

Answer 395

``` CPAP o Benefits (randomised controlled trial evidence) o Sleepiness o Cognition o Health status o Driving o Blood pressure ``` MAD/MRS o MAD – mandibular advancement devices o MRS – mandibular repositioning splints o Controlled trial evidence in mild to moderate OSA – reduces AHI, symptoms, sleepiness and BP o RCTs show CPAP gives better outcomes Surgery o Controlled trial evidence that maxillomandibular advancement improves AHI, vigilance to similar extent as CPAP

Question 396

What is narcolepsy? What are its features?

Answer 396

Nocturnal sleep quality is poor – this contributes to excessive daytime sleepiness o Several night-time awakenings o Dreams occur immediately on falling asleep Hypnagogic (sleep onset) and hypnopompic (upon awakening) hallucinations o Auditory, visual, somaesthetic o Feeling of a threatening stranger in bedroom o Scary o Patients are fearful of going to bed ``` Sleep paralysis o Inability to move the limbs, head or breath properly o Terrifying, suffocating o Duration – seconds to minutes o Associated with REM intrusion o Can be terminated if patient is moved ```

Question 397

What is the age of onset for narcolepsy?

Answer 397

o Mean age is 30-40yrs o Bell shaped age of onset graph o Age of onset in middle ages

Question 398

What is cataplexy?

Answer 398

o Sudden drop in muscle tone triggered by emotions o Worsens with poor sleep and fatigue o May affect all striated muscles o May be limited to face or affect entire body o Consciousness is retained o Duration of attack varies – seconds – minutes o Attack occasionally last hours – status cataplecticus – precipitated by withdrawal of anticataleptic drugs

Question 399

How is narcolepsy diagnosed? (with and without cataplexy)

Answer 399

With cataplexy o Excessive day time sleepiness – almost every day for at least 3 months o Cataplexy episodes o Presence of HLA DQB1*0602 o Overnight polysomnogram followed by MSLT – short sleep latency Without cataplexy o Excessive day time sleepiness o Nocturnal polysomnogram followed by MSLT to confirm o Hypersomnia not explained by another condition

Question 400

What is the pathophysiology of narcolepsy?

Answer 400

- Precise cause is unknown – both environmental and genetic factors may play a part - The peptide hypocretin (orexin) may be involved – derived from the hypothalamus o Thought to be involved in sleep/wake cycles, food intake and pleasure-seeking behaviour o Narcolepsy may be caused by the loss of a relatively few neurons that are responsible for producing it in the CNS o Possibly – immunological mechanisms may lead to loss of hypocretin - Possible triggers include – head trauma, infection and change in sleep habits

Question 401

What is the treatment of narcolepsy?

Answer 401

- Planned naps – early afternoon - Good sleep hygiene - Stimulants o Modafinil o Methylphenidate o Amphetamines

Question 402

How can cataplexy be treated?

Answer 402

o SSRIs – fluoxetine, paroxetine, sertraline o Noradrenaline and serotonin reuptake inhibitor – Venlafaxine o Other antidepressants – Effect is immediate but more side effects  TCAs – imipramine, clomipramine, protriptyline

Question 403

Name the movement disorders of sleep

Answer 403

- Restless leg syndrome - Periodic limb movements of sleep - Propriospinal myoclonus - Rhythmic movement disorder of sleep

Question 404

What is restless leg syndrome (RLS)?

Answer 404

- Sensorimotor disorder of extremities - Irresistible urge to move legs - Relieved by movement of legs - Worse towards evening - Common yet frequently undiagnosed

Question 405

Describe primary RLS

Answer 405

o Genetic predisposition o Tends to be earlier onset and more severe than secondary causes o Natural history poorly understood – long delays in seeking attention and few longitudinal studies

Question 406

What can cause secondary RLS?

Answer 406

o Iron deficiency o End stage renal failure o Pregnancy o Drugs – TCAs, antipsychotics

Question 407

What is the treatment of RLS?

Answer 407

``` o Iron o Dopamine agonists o L-dopa o Clonazepam o Pregabalin o Gabapentin o Opiates ```

Question 408

What are the disorders classed as parasomnias?

Answer 408

- Nightmare disorder - Sleepwalking disorder - REM sleep behaviour disorder o Enactment of dreams during REM sleep o Kicking, flailing, shouting, talking, sitting up o Can have underlying cause – drug/alcohol withdrawal, tumours, Parkinson’s, Alzheimer’s

Question 409

Name 3 causative organisms of bacterial meningitis

Answer 409

- Neisseria meningitidis (most common) - Streptococcus pneumoniae - Listeria monocytogenes

Question 410

What are the clinical features of bacterial meningitis?

Answer 410

- Typically, with headache, fever, photophobia, neck stiffness - Cranial nerve palsies (III, IV, VI, VII) - Focal neurological deficits – usually in S. pneumoniae and Haemophilus influenzae - Raised ICP – altered conscious level, hypertension, bradycardia, abnormal respiratory patter, papilloedema (late) - Non blanching rash - Septic shock

Question 411

What investigations should be performed for suspected bacterial meningitis?

Answer 411

- Lumbar puncture – ideally within one hour of presentation - Blood cultures and PCR - CXR for evidence of TB

Question 412

What is the prognosis for bacterial meningitis?

Answer 412

- Fatal in approx. 10% with disease o Approx. 5% with meningitis o Up to 50% with septicaemia o Approaching 100% if untreated - If survive – 1 in 8 suffer long term morbidity o Headache, joint stiffness, epilepsy, hearing loss, learning difficulties - Early antibiotics improve prospect of recovery

Question 413

What is the main treatment of bacterial meningitis?

Answer 413

Prompt antibiotics o IV ceftriaxone or cefotaxime o After blood cultures ± lumbar puncture o Delay associated with increased morbidity

Question 414

Should steroids be used in the treatment of bacterial meningitis?

Answer 414

- Dexamethasone for 4 days if o Organism unknown o Streptococcus pneumoniae confirmed - Vancomycin CSF penetration may be reduced - Efficacy varies developed vs developed countries (De Gans J, et al. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002) However Adjunctive dexamethasone in bacterial meningitis – a meta-analysis - Van de Beed D, et al. Lancet Neurology 2010 - N=2029, 5 RCTS included, 81% with confirmed bacterial meningitis - Concluded dexamethasone does not seem to reduce death or neurological disability - Benefit for all or any subgroup of patients remains unproven

Question 415

What are the current NICE guidelines regarding the use of steroids in meningitis?

Answer 415

2010, updated 2015 Give dexamethasone for suspected or confirmed bacterial meningitis if LP reveals – o Frankly purulent CSF o CSF WBC count greater than 1000 o Raised CSF WBC count with protein concentration greater than 1g/L o Bacteria on gram stain

Question 416

What is the epidemiology of neisseria meningitidis?

Answer 416

- England – predominantly groups B, C, W, Y - Predominantly children <4 years old o Peak in 5 to 6 months - 2nd highest incidence in 15-19-year olds - Mostly sporadic cases - 747 reported cases of invasive meningococcal disease in England 2016/2017 o Decreasing o Due to the introduction of vaccination

Question 417

What is the carriage and transmission of neisseria meningitidis?

Answer 417

- Throat carriage in approx. 10% population o 25% of 15 to 19 years - Person-person spread - Inhalation of respiratory secretions - Close prolonged contact e.g. household members - Direct contact (kissing) - Disease in minority

Question 418

Describe pneumococcal meningitis

Answer 418

- Streptococcus pneumoniae - Main cause of bacterial meningitis in elderly - Contiguous spread – sinuses, middle ear - Neurological sequelae more common - Treatment as for meningococcal meningitis - Alternative antibiotics for penicillin resistant pneumococcus o Think if travelled abroad o E.g. vancomycin

Question 419

Describe listeria monocytogenes meningitis

Answer 419

- 60 cases per year in England and Wales - Acquired by ingestion e.g. meats, dairy - Haematogenous spread in at risk groups o Adults (>55yrs) and immunocompromised o Pregnant women o Neonates - Meningitis in 55-70% - Mortality approx. 25% - Treatment - IV amoxicillin ± gentamicin

Question 420

Name some cause of viral (aseptic) meningitis

Answer 420

- Enteroviruses – most common - Herpes simplex virus - Mumps - Measles - Adenovirus - HIV - Non-viral – lyme disease, syphilis, drugs

Question 421

Describe enterovirus meningitis

Answer 421

- Incubation 2-5 days - Replication in respiratory or GI epithelial cells - Transmission – respiratory or conjunctival secretions – faeco-oral - Diagnosis – PCR (CSF, throat swab, faeces) - Self-limiting - Symptomatic treatment

Question 422

What is the causative agent in TB?

Answer 422

Mycobacterium tuberculosis

Question 423

Name some risk factors of TB

Answer 423

- HIV, alcoholism, - Diabetes, steroids - Anti-TNF agents - Immigration from area of high prevalence

Question 424

Describe the presentation of TB meningitis

Answer 424

- More chronic presentation – days to weeks - Associated symptoms o Weight loss o Night sweats o Cough

Question 425

What investigations should be undertaken for suspected TB meningitis?

Answer 425

- CXR – suggestive of active or previous pulmonary TB in 50% ``` - Contrast enhanced CT brain o Hydrocephalus o Basal enhancement o Infarction o Tuberculoma ``` - TB culture o Sputum sample o CSF sample

Question 426

What is the management of TB meningitis?

Answer 426

- 12 months treatments o Rifampicin, Isoniazid, Pyrazinamide, Ethambutol - Dexamethasone (Thwaites regimen) - Acetazolamide + frusemide, or repeated LP for communicating hydrocephalus - Consider early ventriculo-peritoneal shunting for non-communicating hydrocephalus

Question 427

What is the causative agent of cryptococcal meningitis?

Answer 427

Cryptococcus neoformans

Question 428

What is the epidemiology of cryptococcal meningitis?

Answer 428

``` - Usually only seen if immunocompromised (CD4 <100 cells/ul) o Most common – HIV infection - Global distribution – bird droppings - Inhalation of yeasts - Uniformly fatal if untreated ```

Question 429

What is the presentation of cryptococcal meningitis?

Answer 429

- Onset usually insidious - Classic meningitis symptoms and signs usually absent - Signs of immunodeficiency

Question 430

What is the management of cryptococcal meningitis?

Answer 430

- Treat HIV o Anti-retroviral therapy - Serial lumbar punctures - Liposomal amphotericin B (AmBisome) and Flucytosine (2 weeks) - Subsequent 8 weeks fluconazole o Can be reduced after 8 weeks for secondary prophylaxis o Continued until CD4 >100 cells/microlitre - Aggressive control of raised ICP one of the most important factors in reducing mortality and morbidity - No evidence for use of corticosteroids

Question 431

How is encephalitis distinguished from meningitis?

Answer 431

``` Distinguished from meningitis by abnormalities in brain function o Altered mental status o Motor or sensory deficits o Altered behaviour/personality o Speech or movement disorder ```

Question 432

List some infectious causes of encephalitis

Answer 432

Viruses o Direct invasion of CNS  Herpes viruses  Arboviruses (arthropod-borne viruses) o Immune-mediated post-infection/vaccination  ADEM (acute disseminated encephalomyelitis) – focal neurological signs on MRI  Mumps, measles, rubella, influenza Bacteria o Listeria, mycoplasma, Lyme, syphilis TB Parasites o Cerebral malaria, toxoplasmosis, parastrongylus Fungi

Question 433

List some causes of viral encephalitis

Answer 433

``` Herpes viruses o Herpes simplex 1 and 2 o Varicella zoster virus o Epstein-Barr virus o Cytomegalovirus o Human herpes virus 6, Human herpes virus 7 ``` Enteroviruses o Coxsackie, echoviruses, enteroviruses 70 & 71, parechovirus o Poliovirus Paramyxoviruses o Measles, mumps Others (rarer) o Influenza, adenovirus, parvovirus, rubella

Question 434

Give some examples of geographically restricted viral encephalitis

Answer 434

``` The Americas West nile encephalitis La Crosse St Louis Rabies ``` Europe middle/east Tick-borne encephalitis West nile encephalitis Rabies Africa West nile encephalitis Rabies Asia Japanese encephalitis West Nile encephalitis Rabies Australasia Murray valley encephalitis

Question 435

What is the epidemiology of HSV encephalitis?

Answer 435

- 1-2 cases /250,000/year - Affects all age groups - Mortality 70% if untreated ``` - 2/3 survivors have significant neuropsychiatric sequalae o 69% memory impairment o 45% personality/behavioural change o 41% dysphasia o 25% seizures ```

Question 436

What is the clinical presentation of HSV encephalitis?

Answer 436

- Acute presentation (May be slower in immunocompromised) - Flu-like prodrome - Fever (90%) - Headache - Altered consciousness - Disorientation (76%) - Seizures in 1/3 of patients with HSV-1 encephalitis - Focal neurological signs common - Speech disturbance (59%) - Behavioural change e.g. hypomania, irritability (41%) - Memory impairment

Question 437

How do you confirm a HSV-1 encephalitis diagnosis?

Answer 437

CSF HSV-1 DNA PCR o Sensitivity and specificity >95% between 48 hours and 10 days between onset o Can be negative initially CSF HSV antibody o Detectable from 10 days approx. (sensitivity 50%) Imaging – o CT may be normal initially (50% sensitivity at early stages) o MRI more sensitive EEG o Non-specific focal findings in >80% HSV encephalitis o Diffuse high amplitude slow waves o Periodic lateralised epileptiform discharges

Question 438

Describe the use of acyclovir in the treatment of encephalitis

Answer 438

- Reduces risk of mortality from 70% to 28% - Limits severity of postencephalitic impairment - Poor outcome if delay ≥2 days between hospitalisation and commencing treatment - In suspected encephalitis – perform urgent LP then commence aciclovir ± antibiotics - If LP likely to be delayed or patient deteriorating start presumptive aciclovir ± antibiotics at once

Question 439

When can you stop aciclovir in the treatment of encephalitis?

Answer 439

- 14-21 days in confirmed HSV encephalitis - If clinical suspicion of HSV encephalitis is high but initial CSF PCR negative, continue aciclovir and repeat LP after 48 hours - If repeat PCR negative but clinical suspicion persists then continue IV aciclovir for at least 10 days - If clinical suspicion low or alternative diagnosis apparent, then stop aciclovir after second negative PCR

Question 440

Should corticosteroids be used in the treatment of encephalitis?

Answer 440

- Retrospective non-randomised data – corticosteroid administration improved outcome in 22 of 45 patients with HSV encephalitis given steroids at the same time as aciclovir was initiated - Efficacy not yet proven - Optimal timing unclear - Often used if significant brain oedema or if deterioration despite appropriate antiviral treatment (Kamei et al. Evaluation of combination therapy using aciclovir and corticosteroid in adult patients with HSV encephalitis. J Neurol Neurosurg Psychiatry 2005;76:1544-9)

Question 441

Describe HAND

Answer 441

HIV associated neurocognitive disorder (HAND) - AIDS dementia complex (ADC) / HIV encephalopathy - Minor neurocognitive disorder (MND) - Asymptomatic neurocognitive impairment (ANI) - Treatment – Antiretrovirals to treat HIV o Different antiretrovirals have different amount of CNS penetration

Question 442

What is the classification of infectious causes of encephalitis?

Answer 442

o Acute sporadic – e.g. HSV o Acute parainfectious/post vaccinal – following childhood vaccinations such as measles o Acute epidemic – e.g. JE, WNV o Subacute, chronic and slow – e.g. HIV or CMV, EBV in the immunocompromised

Question 443

What is anti-NMDA receptor encephalitis?

Answer 443

- A multi-centre, population-based study in the UK found 4% of anti-NMDA receptor encephalitis - Young female patients with psychiatric symptoms, amnesia, seizures, frequent dyskinesias, autonomic dysfunction and decreased GCS - All had ovarian or other teratomas o Recently found in patients with no known tumour and in males - Better outcomes if tumour resected - No controlled trial data available – treat with IV methylprednisolone and IV Ig and/or plasma exchange

Question 444

Define awareness and wakefulness

Answer 444

- Awareness – the ability to have, and the having of, experience of any kind - Wakefulness – is a state in which eyes are open and there is a degree of motor arousal – contrasts with sleep – a state of eye closure and motor quiescence (RCP national guidance, 2013)

Question 445

Describe the anatomy of wakefulness

Answer 445

- Ascending reticular activating system in the midbrain and pons projections to the thalamus and cortex - Interlaminar nuclei of thalamus maintains arousal - ARAS contains cholinergic neurons in the medial pontine tegmentum to the thalamus and monoaminergic neurones projecting from the upper brainstem to the thalamus, basal forebrain and cortex

Question 446

Where in the brain is usually damaged in an unresponsive patient?

Answer 446

- Brainstem – disrupt ascending reticular system - Thalamus – most common - Bilateral hemispheres

Question 447

Describe a coma

Answer 447

``` o Unrousable o Unresponsive o >6 hours o Cannot be wakened o Lacks normal sleep-wake cycle o No voluntary actions ```

Question 448

Describe vegetative state (VS)

Answer 448

o Can be diagnosed after 4 weeks (continuing) o Considered permanent if >1 year following traumatic brain injury or >6 months in other mechanisms o Controversial language – permanent vs continuing

Question 449

Describe minimally conscious state (MCS)

Answer 449

o Severely altered consciousness o Minimal evidence of self and environmental awareness o Inconsistent but reproducible responses to surroundings – e.g. crying every time they see a relative o Follow simple commands – yes/no o Crying, smiling, laughing in response to emotional stimuli o Reaching for objects with intent o Eye movement pursuit o Can be diagnosed after 4 weeks of PDOC – continuing o Permanent if >5 years in most cases o Permeant if >3-4 years in diffuse injury, no improvement seen

Question 450

What are the preconditions for the diagnosis of VS or MCS?

Answer 450

Cause of condition is known - Cause of the condition should be established as far as possible e.g. brain injury Reversible causes excluded - Influence of drugs - Metabolic causes - Treatable structural causes e.g. collection of blood, hydrocephalus Careful assessment - Assessed by a trained assessor - Under appropriate conditions - Using validated tests

Question 451

Describe some terms used for alteration of consciousness

Answer 451

- Clouding of consciousness – reduced wakefulness and attention, excitability and irritability - Confusion – misinterpreted stimuli associated with a shortened attention span - Delirium – disorientation, fear, irritability, misperception of sensory stimuli and (visual) hallucinations - Obtundation – mental blunting or topidity - Stupor – Rousable unresponsiveness - Coma – total absence of awareness of self and the environment

Question 452

List some common causes of PDOC

Answer 452

Trauma o Direct impact or deceleration injury Vascular o ICH, SAH, CVA Hypoxic or hypo-perfusion o Cardiac arrest, shock Infection or inflammation o Encephalitis, vasculitis Toxic or metabolic o Drug or alcohol poisoning, severe hypoglycaemia

Question 453

Name some chronic states of altered consciousness

Answer 453

- Dementia - Hypersomnia - Akinetic mutism o Silent, alert, immobile, sleep wake cycles, no external evidence of mental activity and no spontaneous motor activity - Apallic syndrome (another name for Persistent vegetative state) o Absent neocortical and preserved brainstem activity

Question 454

Give an example of a coma mimic

Answer 454

Locked in syndrome o Conscious – aware of self and the environment o No voluntary movement o High brainstem pathology with retention of blinking and vertical eye movements o Central pontine myelinolysis o Rapid overcorrection of hyponatraemia o Often iatrogenic

Question 455

Describe the assessment of PDOC

Answer 455

- History o Pursue collateral history – relatives etc ``` - General examination o Skin o Temp o BP o Breath – e.g. pear drops smell = ketones o CVS o Abdomen ``` ``` - Neurological examination o GCS Meningism o Trauma? o Fundoscopy/pupils o Tone o Reflexes o Brainstem reflexes ```

Question 456

Explain the glasgow coma scale

Answer 456

``` Eye opening o Eye-opening spontaneously (4 points) o Eye-opening to sound (3 points) o Eye-opening to pain (2 points) o No response (1 point) ``` ``` Verbal response o Orientated (5 points) o Confused conversation (4 points) o Inappropriate words (3 points) o Incomprehensible sounds (2 points) o No response (1 point) ``` Motor response o Obeys command (6 points) o Localised to pain (5 points) o Withdraws to pain (4 points) o Abnormal flexion response to pain (decorticate posturing) (3 points) o Abnormal extension response to pain (decerebrate posturing) (2 points) o No response (1 point) - Minimum point score of the three - Must report with broken down numbers – e.g. GCS:12, E:4, V:2, M:6

Question 457

Name 3 signs of meningism

Answer 457

- Nuchal rigidity - Brudzinski sign - Kernig’s sign

Question 458

What are you looking for in a fundoscopy/pupil section of neurological exam?

Answer 458

- Papilloedema on fundoscopy – raised ICP - Third nerve palsy o Eyes down and out o Can be caused by uncal herniation - Horner’s syndrome (miosis, ptosis, anhidrosis) o Damage to hypothalamus, cervicothoracic spinal cord, internal carotid

Question 459

What are different breathing patterns seen in a unresponsive patient and what do they signify?

Answer 459

o Cheyne strokes – apnoea followed by hyperpnoea – forebrain o Central neurogenic – hyperpnoea ± neurogenic pulmonary oedema – midbrain/thalamus o Apneustic – inspiratory hold – lower pons o Cluster – clustering of breathing – lower pons o Ataxic – completely random

Question 460

What do different gazes indicate in a unresponsive patient?

Answer 460

``` o Vertical gaze  Rostral brainstem  Hydrocephalus o Lateral gaze  Structural  Irritative  Brainstem ```

Question 461

Name some eye movements that can be seen in a unresponsive patient

Answer 461

``` o Roving – toxic/bi-hemispheric o Ping pong – extreme form of roving eye movements o Retraction nystagmus – tegmental o Nystagmoid jerks – pontine o Ocular bobbing – pontine ```

Question 462

What is the oculocephalic reflex?

Answer 462

o Eye stays fixated when head is moved | o Think of it as quality doll vs cheap doll – quality one eyes will move to stay fixated

Question 463

Describe a brainstem assessment

Answer 463

Breathing Gaze Eye movements

Question 464

Describe localisation in a coma

Answer 464

Supratentorial mass lesion e.g. tumour o Unilateral signs o Third nerve palsy ``` Brainstem o Asymmetric o Eye movement disorder o Large pupils – downward shift o Small pupils – upward shift o Normal CT – basilar artery occlusion ``` ``` Metabolic o Normal pupils o Roving eye movements o Absent vestibular-ocular reflex and oculocephalic reflex o Multifocal myoclonus o Asterixis o Odd forms of rigidity ```

Question 465

What investigations should be performed for a unresponsive patient?

Answer 465

``` - Lab tests o Acidosis, anion gap, osmolar gap (antifreeze) - Drug screen - Blood cultures - Imaging, EEG and CSF ```

Question 466

What is the immediate management of an unresponsive patient?

Answer 466

- Oxygenation - ABC - Correct BP, temperature - 50ml 50% glucose - Naloxone (for opioids), flumenazil (for benzos) - Correct Na, Ca and eliminate toxins - Neurosurgery and ICP - Infection

Question 467

What is the long term management of an unresponsive patient?

Answer 467

- Tracheostomy, PEG, bladder, bowel, infection and DVT prevention - Wean from ventilator - Avoid MRSA and vancomycin resistance - Prevent contractures - Protect skin - Avoid neurostimulation including drugs

Question 468

What indicates a poor prognosis in an unresponsive patient?

Answer 468

- Myoclonic status - Absent corneal/pupil at 3 days - Absent motor at 3 days - Absent SEP - Increased serum neurone specific enolase

Question 469

What defines a brainstem death?

Answer 469

- Known cause - No drugs and >36.5C > SBP 100 mmHg - Eu-volaemia, capnia, oxaemia, BP - Absent brainstem reflexes - Apnoea with no CO2 response when off ventilator

Question 470

How common is a headache as a clinical presentation?

Answer 470

- GP – 4.4 consultations per 100 registered patients - Neurology – 25% referrals - A&E – 1-2% acute presentations - One-year prevalence of headache disorders is 50%

Question 471

Describe the classification of a headache

Answer 471

- Primary – independent disorders not caused by another disease or trauma - Secondary – Headache is a symptom of underlying disease or injury that needs to be treated - Cranial neuralgias – headache that occurs due to a sudden burst of activity in sensory cranial nerves – predominantly the trigeminal nerve (ICHD-3 (2018))

Question 472

Describe the types of pain

Answer 472

- Nociceptive – pain proportional to stimulus - Inflammatory – pain out of proportional to stimulus - Neuropathic – pain out of proportional to stimulus - Headache/neurovascular – how does the pain start? Is it a nociceptive pain with sensitisation?

Question 473

How do we feel pain?

Answer 473

Acute pain o Modulation of nociception occurs via a series of ascending and descending neural networks which supress or facilitate signals o Brain relies on attention, context, emotion and mood for pain perception o Pain matrix – regions active during acute pain, includes primary and secondary somatosensory cortex, insula, anterior cingulate and prefrontal cortices, thalamus but other regions can be active depending circumstances for the individual Chronic pain o May involve different regions of the brain to acute pain

Question 474

Does migraine have a vascular aetiology?

Answer 474

- Many issues with this theory - Stimulation of vessels was focal external stimulation or mechanical dilation - No evidence of physiological relaxation of smooth muscle and resultant dilation can cause pain Timing and topography of cerebral blood flow, aura, and headache during migraine attacks (Jes Olsen et al 1990) o Headache not temporally correlated with either hypo- or hyperperfusion o Migraine begins during hypoperfusion phase o Hyperperfusion may outlast pain

Question 475

Describe the diagnosis of migraine without aura

Answer 475

``` A. 5 attacks fulfilling B-D B. Attacks last 4-72 hours C. Two of the following: a. Unilateral b. Pulsing c. Moderate/severe d. Aggravation by routine physical activity D. During headache at least one of a. Nausea and/or vomiting b. Photophobia and phonophobia E. Not attributed to another disorder ```

Question 476

What can head pain be evoked by?

Answer 476

o Lesions or electrodes in the periaqueductal gray in absence of vasodilation o Stimulation of insular cortex in the absence of vascular change

Question 477

What is migraine now considered?

Answer 477

A disorder of brain excitability

Question 478

Describe the vulnerability to migraine attacks

Answer 478

- Inherited tendency has been noticed - Twin studies have demonstrated the importance of genetics - Now several rare familial hemiplegic migraine genes have been found o FHM1 – Ch19, Calcium channel o FHM2 – Ch1, Sodium/potassium-ATPase o FHM3 – Ch2, sodium channel

Question 479

Describe the theories of how pain is initiated in migraine

Answer 479

Central mechanisms activate peripheral nociception that initiates pain? o Unknown mechanisms activate deep brain structures o Deep structures activate the sensory nerves around the head o Sensory nerves become sensitised due to local release of signal molecules o Sensory nerve activation causes pain Cortex (via cortical spreading depression) activates trigeminal nerve afferents? Brainstem is the migraine generator? Sterile neurogenic inflammation? o But inhibitors of neurogenic protein extravasation clinically not effective Abnormal central interpretation of normal sensory input?

Question 480

What initiates migraines?

Answer 480

- Activation of ipsilateral pons has been seen in migraine - Hypothalamic activation has been seen in migraine - Cortical ‘waves’ have been seen in migraine with aura - Spreading reduction in regional cerebral blood flow seen in migraine without aura (Woods et al, 1994)

Question 481

Describe cortical spreading depression

Answer 481

- In animal models of migraine, it is a wave of activity followed by reduced activity that spreads across the brain surface - Spreads with characteristics that are very similar to clinical symptoms and PET and MRI changes of migraine seen in humans BUT o Classical EEG findings of CSD rarely seen in humans o Most patients do not have neurology expected with classical CSD

Question 482

How is cortical spreading depression related to migraine in humans?

Answer 482

o Migraine may involve waves that are related, but not identical to CSD o Different types of cortical waves may be produced by distinct cellular mechanisms

Question 483

Describe how a migraine attack may be modulated

Answer 483

- Trigeminal nociceptive afferents innervate pain sensitive structures, including vessels, meninges and peri cranial muscles - Activation of TG nociceptive terminals stimulates release of neuropeptides (e.g. CGRP) which can increase the sensitivity of perivascular nociceptors and dilate cranial vessels - Central TG neurons terminate at the trigeminocervical complex (TCC) and CGRP release here can facilitate nociceptive trigeminovascular input - Plastic changes at the TG and TCC result in both peripheral and central activation and is thought to play roles in development of headache caused by sensitisation - TCC is modulated by ascending and descending pain modulation systems at the cortical and subcortical level

Question 484

Describe the theories of the pathophysiology of chronic migraines

Answer 484

Atypical pain processing o Failure to regulate descending pathways modulating pain processing o Cutaneous allodynia is an example (pain to non-painful stimuli to skin) o Recurrent migraine attacks lead to central sensitisation o Cortical hyperexcitability Atypical processing in other brain regions o Sensory, affective and cognitive pain processing Neurogenic inflammation o Excessive release of vasoactive peptides such as CGRP o Excessive levels in chronic migraine vs episodic migraine (consequence or cause?)

Question 485

Describe the pathophysiology behind a medication overuse headache

Answer 485

- Overall the pathogenesis is not clear but - Based on evidence from human and basic science experiments - MOH leads to increased excitability of cortical and TG neurons - May facilitate cortical spreading depression and trigeminal sensitisation - Underlying mechanisms maybe due to central neurotransmitter derangement affecting nociceptive modulating systems and other vegetative functions in vulnerable nervous systems in patients with primary headache syndromes o E.g. serotonin o Low levels may increase CGRP activity in TG ganglion o Low levels may increase expression of cortical receptors and increase CSD

Question 486

What is a chronic daily headache?

Answer 486

- This is only a descriptive term for a headache on ≥15 days per month - A broad differential diagnosis exists

Question 487

What are the differential diagnoses of a primary headache?

Answer 487

``` o Chronic migraine o Chronic tension-type headache o Chronic cluster headache o Chronic paroxysmal hemicranias o Hemicrania continua o New daily persistent headache ```

Question 488

What are the differential diagnoses of a secondary headache?

Answer 488

``` o Medication overuse headache o Chronic post-traumatic headache o Raised intracranial pressure o Low CSF pressure headache o Chronic meningitis ```

Question 489

What is the diagnosis of a medication overuse headache?

Answer 489

- Headache present on ≥15 days/month in a patient with a pre-existing headache disorder - Regular use for >3 months of one or more drugs that can be taken for acute and/or symptomatic treatment of headache - Not better accounted for by another ICHD-3 diagnosis NICE 2012 o Triptans, opioids, ergots or combination analgesics on ≥10 days/month o Paracetamol, aspirin or NSAID, either alone or in any combination, on ≥15 days/month

Question 490

Describe the diagnostic criteria of chronic migraine

Answer 490

- Headache (tension type and/or migraine) ≥15 days/month for at least 3/12 - On ≥8 days/month for at least 3 months headache has fulfilled migraine without aura criteria - No medication overuse and no other causative disorder

Question 491

Give a brief overview of migraine treatment

Answer 491

Episodic or criteria? Episodic o Lifestyle measures to reduce chance of triggering o Acute attack treatment – hit early and hard, then stop o Consider preventive strategy if ≥5 headache days/month Chronic o Detox (will worsen 1-4/52) o Continued foundation of lifestyle o Preventative strategy

Question 492

What are the foundations of a good lifestyle?

Answer 492

- Avoid overuse of acute attack treatment - Stop all caffeine - Fluids ++ (2.5-3 litres per day) - Regular meals - Regular sleep – same times to bed and to get up

Question 493

Describe the chronic migraine approach to treatment

Answer 493

Good lifestyle (initially worse with detox) o Stop acute attack drugs o Stop caffeine o Hydration (2-3L), regular food and sleep times o Possible 40% response rate Preventative drug o 6-12 months o Maximum tolerated dose Consider other treatments o Botox o Nerve blocks etc

Question 494

What are migraine preventative drugs according to NICE?

Answer 494

- Topiramate - Propranolol - Acupuncture - Riboflavin 400mg per day - Consider 3 monthly cranial Botox if poor response to 3 preventative drugs and MOH adequately treated (¾ respond to a varying degree, ¼ no response)

Question 495

Name some emerging treatments for migraine

Answer 495

- CGRP modulation - Neurostimulation o Occipital nerve stimulation o Transcranial magnetic stimulation o Vagal nerve stimulation

Question 496

Name some examples of a non-enzyme inducing AED. What contraceptive should be offered?

Answer 496

Gabapentin, Pregabalin, sodium valproate Contraception the same as other women

Question 497

Name some examples of enzyme inducing AEDs

Answer 497

carbamazepine, phenytoin, topiramate

Question 498

What contraception should be considered in women taking enzyme inducing AEDs?

Answer 498

Reduces the effectiveness of oral contraceptives (combined and mini pill), transdermal patches, the vaginal ring and progestogen-only implants Progesterone injections, IUD or IUS is the recommended contraception The preferred emergency contraception is a copper IUD

Question 499

What does lamotrigine interact with?

Answer 499

oestrogen-based contraceptives o Evidence that it lowers lamotrigine levels in the blood o Some evidence that lamotrigine can lower the amount of progesterone in blood but not oestrogen – but no conclusive evidence that it reduces the effectiveness of the pill

Question 500

What does treatment of sodium valproate in women require?

Answer 500

o Need to be on pregnancy prevention programme o Highest chance of teratogenicity o 4 in 10 babies are at risk of developmental disorders o 1 in 10 are at risk of birth defects

Question 501

What seizure type poses the most risk to pregnancy? What are these risks?

Answer 501

Tonic-clonic o Trauma from falls or burns o Risk of premature labour o Miscarriages o Lowering of the fetal heart rate

Question 502

What happens to seizure frequency in pregnancy?

Answer 502

- Seizure frequency declines or remains the same in the majority of women o However, 15-30% of women may have an increased frequency

Question 503

Why might seizure frequency increase in pregnancy?

Answer 503

- Physiological changes during pregnancy alter the pharmacokinetics of AEDs which may result in lower levels and seizures deterioration o Physiological changes in absorption, increases in renal clearance, altered hepatic clearance, increases in plasma volume distribution and hepatic enzyme induction from female sex steroid hormones - Poor sleep can increase seizures - Increased stress - Possible poor drug compliance during pregnancy

Question 504

What is the management of epilepsy pre-conception?

Answer 504

- Discuss risk of AEDs causing malformations and possible neurodevelopmental in an unborn child – assess the risks and benefits - Likelihood of a woman taking AEDs having a baby with no malformations is at least 90% o Do not stop taking treatment - Prescribe folic acid – to reduce the risk of neural tube defects o 5mg per day

Question 505

What are potentially some antenatal problems seen in women with epilepsy?

Answer 505

``` hyperemesis gravidarum gestational hypertension mild preeclampsia vaginal bleeding anaemia ```

Question 506

What difficulties during labour may women with epilepsy face?

Answer 506

premature labour failure to progress an increased rate of caesarean sections

Question 507

What is the management of epilepsy intrapartum?

Answer 507

- Women should deliver in a centre with adequate facilities for maternal and neonatal resuscitation. - Women should continue to take their anti-epileptic medication in labour. - Birthing pools are not recommended for women with epilepsy. - Intravenous access (in case of seizure). - Hyperventilation and maternal exhaustion should be avoided. - GTC seizures are associated with hypoxia. Continuous cardiotocography (CTG) tracing is recommended in the event of a seizure. - An intravenous benzodiazepine (e.g. lorazepam or diazepam) is recommended to terminate any seizures. - In the event of benzodiazepine being used to terminate the seizure, loss of baseline variability of the fetal heart rate tracing can be expected for approximately one hour

Question 508

What is the management of women with epilepsy postnatally?

Answer 508

- Withdrawal effects in the newborn may occur with some AEDs o Especially with benzodiazepines and phenobarbital - Routine injection of vitamin K at birth minimises the risk of neonatal haemorrhage associated with AEDs - Breastfeeding for most women taking AEDs is generally safe and should be encouraged - Could be an increased risk of seizures due to lack of sleep – advise to get adequate sleep

Question 509

How can a mother reduce the risk of injury to a baby if a seizure occurs?

Answer 509

o Change or feed baby on the floor o Avoid baby slings o Where possible, minimise climbing of stairs o Avoid bathing the baby when alone

Question 510

What are some non-genetic causes of epilepsy?

Answer 510

o Stroke o Head injury o Infections o Metabolic problems

Question 511

What are two types of inherited epilepsy syndromes?

Answer 511

Chromosomal conditions | Single gene disorders

Question 512

Name some single gene disorders

Answer 512

 Neurofibromatosis  Tuberous sclerosis  Autosomal dominant frontal lobe epilepsy  Mitochondrial disorders

Question 513

What are the different risks to a child of inheriting epilepsy?

Answer 513

``` o Population risk – 1% o Dad has IGE – near 1% o Parent with focal epilepsy – 3% o Sibling with inherited epilepsy – 5% o Mum has IGE – 4-8% o Parent has photosensitive IGE – 50% o AD nocturnal frontal lobe epilepsy – 50% ```