Neurology 3 Flashcards
What is the presentation of an intracerebral space occupying neoplasm?
presentation is dependent on the rate of growth of the tumour and its anatomical position:
S/s of raised ICP
headache, nausea and vomiting, papilloedema
more common in rapidly growing tumours
malignant glioma, metastatic deposits
Epileptic seizures - adults with epileptic fit have brain tumour until proven otherwise
progressive neurological deterioration
What ‘neurological deterioration’ signs might be seen for Brain neoplasm?
increasing weakness
sensory loss
cranial nerve palsies: 6th
Dysphasia - if involving the dominant hemisphere (left Dom in 98% right hand Dom and also most left hand Doms too)
hat is the management of space occupying neoplasm?
Dexamethasone 4-6mg QDS if any neurological deterioration or drowsiness
anti-convulsants: if presented with epilepsy
refer to neuro-oncology MDT: neurosurgical interventions accessible, often with adjunctive radiotherapy
What is paraneoplastic syndrome?
Cluster of symptoms that occur in patients with cancer, that cannot be explained by the tumour, metastases or the hormones normally secreted by the primary tissue from which the tumour arose
Give examples of paraneoplastic syndromes?
Myasthenia gravis
Lambert-Eaton myasthenic syndrome
paraneoplastic sensory neuropathy
paraneoplastic cerebellar degeneration
What are the three most common adult primary brain tumours?
malignant glioma, meningioma and astrocytoma
What is a malignant glioma? prognosis?
Most common adult primary malignancy, originating from astrocytes
rapidly growing, thus present with signs of raised ICP
Poor prognosis, with death often within 6 months of diagnosis
What is meningioma?
Most common overall cerebral neoplasm
generally benign, slowing tumours arising from the meninges
surgical excision and debunking is undertaken wherever possible
What is an astrocytoma?
benign slow growing tumour that occurs in young people
can turn malignant in later life
Name the other important cerebral tumours
ependymomas (originate from ependymal cells. most common in young people/children). usually malignant, but do not tend to recur
pituitary adenomas: 10% of all diagnosed intracranial neoplasms
Acoustic neuroma: Schwann cells of the acoustic nerve.
more common in neurofibromatosis type II
What tumours most commonly metastasise to the brain?
Bronchus Breast Kidney Colon Thyroid Malignant melanoma
What is meningitis?
Inflammation of the leptomeninges
i.e. arachnoid and pia mater and underlying CSF
What organisms cause meningitis?
70% = neisseria meningitides (classical petechial rash)
streptococcus pneumonia (more common if skull fractures, ear disease or those with congenital CNS lesions)
Other 30% = listeria monocytogenes, haemophilus influenza, staph aureus and TB
Viral: enteroviruses, HSV, VZV
What are the symptoms of meningitis?
Headache
Neck stiffness
Fever
In acute bacterial - high fever with rigors, photophobia, vomiting, intense malaise coming on over hours. Confusion and seizures in more serious cases
What are the signs of meningitis?
Kernig’s sign positive: knee flexed, extend at the knee to cause pain
Brudzinski’s sign positive: passive flexion of the neck leads to flexion of the knees/hip
signs of raised ICP and/or cranial nerve palsies
What is the presentation of meningococcal meningitis?
petechial rash, erythematous, non blanching purpura
How does TB meningitis present?
As per acute bacterial meningitis, but more commonly as an insidious illness with fever, weight loss and progressive confusion/cerebral irritation, eventually leading to coma
What is the management of TB meningitis?
RIPE for 12 months
corticosteroids early on to decrease risk of cerebral oedema
What is the presentation of epidural spinal abscess?
Patient presents with fever, back pain and later spinal root lesions
ddx osteomyelitis
What is encephalitis?
Inflammation of the brain parenchyma, usually viral
similar organisms to viral meningitis
What are the clinical features of encephalitis?
normally mild, headache, drowsiness, fever, malaise, confusion
rarely - serious illness can occur with high fever, mood change and progressive drowsiness over hours / days leading to seizures and comas
What is the cause of severe encephalitis?
HSV-1
HSV1: causes necrotising encephalitis, affecting the temporal lobes
HSV2: causes meningitis in adults
What ix should be done for encephalitis?
Head CT/MRI
diffuse oedema, classically in the temporal lobes
LP: raised opening pressure, raised lymphocytes, raised protein and normal glucose with a positive viral PCR
viral serology: blood and CSF culture
What is the management of HSV encephalitis?
IV acyclovir >10 days
What is the cause of TB meningitis?
blood Bourne spread of M.tuberculosis to the brain, following primary infection of miliary TB
What are the risk factors of TB meningitis?
immunosuppression, malnourishment, multiple co-morbidities and recent contact with TB
What investigations should be done for meningitis?
Bloods: FBC, U+Es, LFTs, clotting, glucose, lactate
Serum PCR for pneumococcal and meningococcal antigens
Blood cultures: prior to Abx if possible, but do not delay
LP: if no clinical suspicion of a mass lesion (send for MCS protein, glucose and meningococcal / pneumococcal / viral PCR)
CT prior to LP (if suspected raised ICP)
Throat swabs: 1 for virology, one for bacteriology
What CSF stains are there and which organisms do they show are present?
Gram +ve intracellular diplococci: pneumococcus
gram negative cocci: meningococcus
ziehl-Neelsen stain for acid-fast bacilli: TB
indian ink: fungi
What is the normal appearance of CSF?
Crystal clear, <5 cells per mm3, low protein and glucose levels
What CSF appearance indicates bacteria?
turbid fluid with high polymorphs and low glucose
What CSF appearance indicates viruses?
clear fluid with high lymphocytes and normal glucose
What does TB do to CSF?
Both raised lymphocytes and polymorphs
What is the management of meningitis?
LP within 1 hour. give empirical abx after blood cultures
If non-blanching rash: BenPen 1.2g IM
2.4mg 4-hourly is then the treatment of choice in hospital
Cefotaxime can be used in penicillin allergic patients
If <60 and not immunocompromised, IV ceftriaxone 2g bd, IV dexamethasone 2 doses 6 hours apart
If >60 or immunosuppressed: IV ceftriaxone 2g bd
IV amoxicillin 2g 4 hourly
IV dexamethasone
ADD IV acyclovir if suspect herpes encephalitis
How should close contacts of patients with meningitis be managed?
Single dose of ciprofloxacin should be given to all close contacts as prophylaxis to eliminate pharyngeal carriage in meningococcal meningitis
What are the acute complications of bacterial meningitis?
Sepsis / DIC
Hydrocephalus
Adrenal haemorrhage: Waterhouse-Friderichsen syndrome
What are the longer term complications of bacterial meningitis?
Brain abscess
Seizure disorders
Cranial nerve palsies: sensorineural hearing loss VIII or gaze palsies
Ataxia / muscular hypotonia
What conditions can give rise to brain abscesses?
Otitis media
Paranasal sinus infections
Bacterial endocarditis
head trauma / neurosurgery
What is the presentation of a brain abscess?
expanding mass lesion, fever and possible systemic illness
What is the treatment of brain abscess?
surgical drainage, broad spectrum antibiotics, high dose corticosteroids
What are the classical features of a generalised seizure (tonic clonic)?
Aura: vague warning phase
loss of consciousness
tonic phase - body becomes rigid for up to a minute, usually falling to ground + tongue biting + incontinence
Clonic phase: generalised convulsion, with frothing of the mouth and rhythmic jerking of muscles (several minutes)
Post-ictal phase: drowsiness, confusion or coma for several hours
What are the different types of syncope?
Vasovagal/cardiogenic
Postural hypotension
Post-prandial hypotension
carotid sinus (excessive vagal response e.g. wearing tight collars), anaemic syndrome, MICTURITION syncope, coughing or exertion
What is a vasovagal / cardiogenic syncope?
‘simple faint’ due to sudden reflex bradycardia and peripheral vasodilation
occurs in response to standing, fear, venesection or pain
the patient is unconscious for less than two minutes
recovery is rapid and treatment is not necessary
What is postural hypotension?
Drop in systolic BP or 20mmHg or diastolic of 10 on standing from a sitting/lying position
Measure sitting and then at 1, 2 and 3 minutes after standing up
this occurs as blood pools in the legs due to the influence of gravity.
Risk is increased If fluid depleted, if there is age-related autonomic dysfunction and polypharmacy (vasodilating / diuretic drugs)
What is post-prandial hypotension?
Drop in systolic BP of 20mmHg (or diastolic of 10mmHg) after eating due to pooling of blood in the splanchnic vasculature.
thought to be even more common than postural hypotension
What distinguishes seizures from syncope?
Witness accounts of jerking movements, incontinence, post-episode confusion and amnesia highly suggestive of a fit
How should a recurrent syncope be investigated?
Advise against driving whilst elucidating cause
Bloods: FBC, U&Es, glucose
Lying / standing blood pressure or tilt table tests
ECG / 24-hour tape (heart block, arrhythmias, long QT)
EEG / sleep EEG
Echo / CT head
What is a seizure?
Convulsion or transient abnormal event resulting froth paroxysmal discharge of cerebral neurones
What is epilepsy?
Continuing tendency to have seizures, even if a long time separates the attacks, affecting 1% of the population
What is a partial seizure?
single focus of electrical activity - either:
SIMPLE PARTIAL:
no impairment of consciousness e.g. a single limb jerking, often associated with a sensory aura. Pattern depends on the lobe involved.
Temporal: lip smacking, chewing
Frontal: motor movements, speech arrest, Jacksonian march
Parietal: sensory disturbances, tingling / numbness
Occipital: visual disturbances
Complex partial: consciousness impaired at some stage
What is temporal lobe epilepsy?
Classical aura with a sense of fear / deja-vu and hallucinations
There is then confusion and anxiety and often automatisms e.g. lip smacking and chewing
They can also go on to become secondary generalised seizures
What are generalised seizures?
When there is a widespread focus of electrical activity across both hemispheres.
What are the categories of generalised seizures?
Absence Tonic clonic Tonic clonic myoclonic Atonic
What is an absence seizure?
‘petit mal’ seizures with classical EEG appearance, typically less than 10 seconds in 4-10 year olds, more common in girls, stimulated by hyperventilation and flashing lights
Remit by puberty
What are the secondary causes of seizures?
Structural: trauma, space occupying lesion, stroke, SLE, AVMs
Developmental (cerebral palsy)
Metabolic (hypo, hyper: glycaemia, calcaemia, natremia
Drugs: withdrawal syndrome, cocaine, TCAs, SSRIs, ciprofloxacin
Infection: Encephalitis, HIV, syphilis
What are the important history points of seizures?
risk factors for epilepsy: FH, CVD, tumours, trauma
alcohol: delirium tremens
infection: meningitis, encephalitis
psychiatric conditions: pseudoseizurs
What is the emergency management of a patient having a seizure?
Place patient in recovery position and remove harmful objects.
If seizure >3 minutes, treat as status epilepticus
A-E
IV lorazepam - 4mg bolus and repeat after 10 minutes
finger prick - glucose
IV phenytoin - 15mg/kg slow infusion
ICU if 20 minutes
In community: buccal midazolam
What are the potential causes of status epilepticus?
Epilepsy, hypoxia, stroke, brain injury, metabolic derangements, infections, eclampsia and drug withdrawal / toxicity
What is the mortality of status epilepticus?
10%, decreased according to how quickly seizure activity is initially treated
What investigations are done for epilepsy?
Bloods: FBC, U+Es, LFTs, Ca, Mg, glucose
Toxicology / drugs screen
Head CT/MRI
EEG (can be enhanced by sleep deprivation)
How is drug treatment of epilepsy initiated?
after 2 seizures after ruling out organic causes
aim of treatment is the control of seizures with lowest possible dose with fewest side-effects, starting with one drug and increasing dosage over 2-3 months until control is achieved.
Baseline bloods are taken prior to starting the drugs
Avoid triggers
What is the management for generalised seizures?
1st line = valproate or lamotrigine in females of childbearing age
Adjuncts: clozabam, carbamazepine, levetiracetam
Ethosuximide is generally first line for absence seizures
What is the management for partial seizures?
1st line = carbamazepine or lamotrigine in females of childbearing age
multiple adjuncts used
How does valproate act?
Potentiates GABA and causes Na-channel blockade
What are the side effects of valproate?
Rash, sedation, weight gain, hair loss, tremor
Associated with causing birth defects, thrombocytopenia and liver damage
How does lamotrigine act?
Blocks Na-channels and reduces glutamate relese
What are the side effects of lamotrigine?
not highly sedating , risk of bone marrow toxicity
suitable for women of childbearing age
How does carbamazepine act?
Na-channel blocker
What are the Side effects of carbamazepine?
include rashes, dizziness and double vision
cam cause agranulocytosis
induces metabolism of itself and many other drugs, associated with birth defects and liver damage
What are the difficulties with phenytoin?
Side effects: increased gum growth and nystagmus
Displays zero-order kinetics thus requires therapeutic drug monitoring
Metabolism saturates a a variable level leading to disproportionate increases in plasma concentration after this point
Enzyme inducer - can lead to failure of the COCP
What other side effects may come about from anti-epileptic drugs?
May cause leucopenia, rashes and more serious skin effects such as SJS and TEN
In refractory causes, check adherence, alcohol, drug usage or the possibility of an underlying structural lesion.
When can a patient withdraw from anti-epileptic drugs?
Seizure free from 2-4 years
Drug reduced in dose every 4 weeks, with patient stopping driving during withdrawal
How do anti-epileptic drugs affect pregnancy?
Patients should withdraw prior to conception - however treatment is preferable to hypoxic szirues during pregnancy
carbamazepine, valproate and phenytoin lead to NTD although carbamazepine has the lowest incidence
Lamotrigine = 1st line in women of childbearing age and in pregnancy for generalised seizures
Give 5mg folic acid in first trimester and vitamin k in third
What are the laws regarding epilepsy and driving?
Patients must tell DVLA immediately and stop driving if they have had a seizure.
If attack while driving and involved LOC, license revoked
6 months seizure free - can ask for license back.
In true epilepsy, need to be seizure free for a year
What is MS?
Chronic and progressive condition that involves demyelination of the myelinated neurones in the central nervous system
This is caused by an inflammatory process involving activation of immune cells against the myelin.
Describe the epidemiology of MS?
Affects 1 in 1000 UK population twice as common in females Age of onset = 20-45 years aetiology = uncertain Associated with HLA-DR2 phenotype
Where are areas of demyelination often seen in MS?
Optic nerves Angles of the lateral ventricles Cerebellar peduncles Brainstem Dorsal and corticospinal tracts
What symptoms are seen with demyelination of the optic nerve in MS?
visual disturbance:
Central scotoma
optic neuritis - blurring of vision, mild ocular pain worse on movement and loss of colour vision
decreased acuity, colour vision and a pink / swollen optic disc
diplopia also common due to brainstem involvement
What symptoms are seen with involvement of the corticospinal tract in MS?
upper motor neurone deficit:
paraparesis, hemiparesis or mono paresis
What symptoms are seen with involvement of the dorsal tract in MS?
sensory deficit:
Paraesthesia and proprioceptive loss in limb or half of the body
posterior cervical lesions may induce tingling sensations shooting down the arms / legs on neck flexion
What symptoms are seen with involvement of the cerebellar peduncles in MS?
Cerebellar signs: involvement of the cerebellar peduncles:
intention tremor, nystagmus, vertigo and dysarthria
What symptoms are seen with involvement of the brainstem in MS?
Bladder/bowel/sexual dysfunction:
Frequency / urgency followed by defecation
Constipation, urgency of defecation
erectile dysfunction / ejaculatory failure
Describe the cognitive impairment effects of MS?
IQ and language function affected
Describe the onset of MS?
Episode of neurological deficit appear irregularly throughout the CNS in terms of anatomical site and time: ‘disseminated in space and time’
Over days to weeks, plateau and then gradually resolve (either completely or partially over weeks to months
Recurrence = unpredictable, with no clearly identified precipitating factors, although pregnancy / intercurrent illness may be implicated.
Symptoms classically worse during a fever, hot weather or after exercise as central conduction is slowed by increased body temperature
Describe the categories of MS?
Relapsing remitting MS: 80-90%
Primary progressive MS: 10-20%
Secondary progressive
Fulminating MS: <10%
What is primary progressive MS?
no clear cut relapses / remissions
Diagnosed if progressive deterioration for over one year
What is relapsing remitting MS?
Initial episodes resolve completely
Subsequent events usually result in some residual disability
Patients eventually develop secondary progressive MS - steady progression without remission
What is fulminating MS?
Debilitating progressive deterioration from an early stage
What investigations are used in diagnosing MS?
FBC, U&E, LFT, ESR, TFT, glucose, calcium, B12 and HIV serology Referral to neurology: MRI CSF VER
What are the investigations for MS?
MRI: multiple plaques visible with >10 in clinical relapse
Will show lesions in 85% patients with clinical disease
Lesions are not specific to MS, so clinical features also required
Lumbar puncture: shows OLIGOCLONAL BANDS in the CSF
What will CSF examination in MS show?
Cell count raised, and raised protein
Electrophoresis shows oligoclonal IgG bands in 80%
Popular exam q
What are the ddx of relapsing-remitting MS?
TIAs
SLE with neurological involvement
CNS sarcoidosis
What are the ddx of primary progressive MS?
MND
CNS mass
Spinal / cerebellar degenerative diseases: Alzheimer’s, Parkinson’s, Huntington’s
How is an acute MS relapse managed?
Investigate to rule out other cause
High dose corticosteroids: oral methylprednisolone 0.5g/day for 5 days as soon as possible
OR 1g IV 3-5 days if oral treatment has failed before
Patient education: steroids will reduce attack severity but may cause temporary mental health effects (confusion/depression)
What is the general management of MS?
Exercise to maintain activity and strength
Neuropathic pain can be managed with medication such as amitriptyline or gabapentin
Depression can be managed with antidepressants such as SSRIs
Urge incontinence can be managed with anticholinergic medications such as tolterodine or oxybutynin (although be aware these can cause or worsen cognitive impairment)
Spasticity can be managed with baclofen, gabapentin and physiotherapy
Relapsing-remitting MS: Dimethyl fumarate / teriflunomide
Natalizumab
How are the complications of MS managed?
Fatigue: Amantadine + cognitive approaches
Spasticity: Baclofen and physiotherapy first line
Dantrolene / botulinium toxin injections for refractory spasticity
Ataxia / tremor: no pharmacological treatment
Physiotherapy/OT
Mobility: supervised exercise programme or vestibular rehab
mobility aids
Mental health: CBT for people struggling to adjust to having MS
Marked depression common
Bladder dysfunction: anti-muscarinic such as oxybutynin, tolteridine
Sexual dysfunction: Sildenafil
Pressure sores: Encourage movement / physiotherapy and regular checking for sores
What is the prognosis for MS?
life expectancy: 20-30 years
Prognosis better if sensory onset
Poor prognostic factors: increased age of presentation
early cerebellar involvement
loss of mental function
What Is the clinical triad of Parkinsonism?
Tremor, rigidity and bradykinesia
Describe the Parkinsonian tremor
4-7hz
‘pill rolling’ movements between thumb and finger
occurs at rest, increased if you ask them to do something
Decreased on finger-to-nose test
Increased if clench opposite hand/other muscle group
Positive glabellar tap sign: excessive blinking
Describe righty in Parkinsons
Increased tone throughout the range of limb movement
Equal in opposing muscle groups - lead pipe
Cogwheel
Describe bradykinesia in PArkinsons
Difficulty initiating movement Progressive reduction in speed / amplitude of repetitive actions Ask to 'walk' thumb along fingers ask to write: micrographia spontaneous blinking rate is used
facial immobility: hypomimia
cog wheeling
What are the causes of Parkinson’s?
Idiopathic: disease
Drug induced: neuroleptics, prochlorperazine, metaclopramide, TCAs, methyldopa
Vascular: multiple cerebral infarcts
Toxin induced: Wilson’s disease
Post-encephalopathy
Parkinson’s plus
What is Parkinson’s plus syndrome?
Rare alternative causes:
Progressive supranuclear palsy Multiple system atrophy Lewy body dementia Vascular Parkinsonism Cortico-basal degeneration
What are the Parkinson’s+ symptoms of progressive supranuclear palsy ?
Symmetrical onset, tremor is unusual
Early postural instability and speech problems
Dementia
Vertigal gaze palsy - limitation of movement in down gaze
What are the Parkinson’s+ symptoms of multiple system atrophy?
neurones of multiple systems in the brain degenerate.
The degeneration of the basal ganglia lead to a Parkinson’s presentation. The degeneration in other areas lead to autonomic dysfunction (causing postural hypotension, constipation, abnormal sweating and sexual dysfunction) and cerebellar dysfunction (causing ataxia and nystagmus)
Pyramidal UMN signs: extensor plantars, hyperreflexia
What are the Parkinson’s+ symptoms of Lewy body dementia?
This is a type of dementia associated with features of Parkinsonism. It causes a progressive cognitive decline
visual hallucinations, delusions, disorders of REM sleep and fluctuating consciousness
What are the Parkinson’s+ symptoms of Vascular Parkinsonism?
Strokes affecting the basal ganglia
symptoms worse in legs than arms
pyramidal signs present
What are the Parkinson’s+ symptoms of corticobasal degeneration?
Akinetic rigidity involving one limb
cortical sensory loss e.g. asteronosis
Describe the pathology of Parkinson’s disease?
Basal ganglia: coordinating habitual movements such as walking or looking around, controlling voluntary movements and learning specific movement patterns.
Part of the basal ganglia called the substantia nigra produces a neurotransmitter called dopamine. Dopamine is essential for the correct functioning of the basal ganglia. In Parkinson’s disease, there is a gradual but progressive fall in the production of dopamine.
Dopamine depletion / Ach excess: Parkinsonism
Dopamine excess / Ach depletion: dyskinesias, psychosis
How does Parkinson’s onset?
Asymmetrical - triad of bradykinesia, tremor, rigidity
What are the other features of Parkinson’s aside from the triad?
Postural - stoop, fixed flexion apart from PIPJ and DIPJ
Gait changes: shuffling and narrow based. Slow and unsteady on turn
Falls common in later stages
Speech changes: monotonous pronounciation progressing to slurring dysarthria
GI/urological: dysphagia, constipation, urinary frequency
Dermatological: excessive sweating, greasy skin
Psychological: cognition preserved, dementia, depression common up to 1 in 3 patients.
REM sleep disorder - physical acting out of dreams
Insomnia
Describe the management of Parkinson’s
MDT
Social needs - OT
Levo-dopa, dopamine receptor antagonists, MAO-B inhibitors and COMT inhibitors
What is levodopa?
This is synthetic dopamine given orally to boost own dopamine levels. It is usually combined with a drug that stops levodopa being broken down in the body before it gets the chance to enter the brain. These are peripheral decarboxylase inhibitors. Examples are carbidopa and benserazide.
Combination drugs are:
Co-benyldopa (levodopa and benserazide)
Co-careldopa (levodopa and carbidopa)
What are the side effects of levodopa?
nausea, vomiting
main side effect of dopamine is when the dose is too high patients develop dyskinesias. Theses are abnormal movements associated with excessive motor activity. Examples are:
Dystonia: This is where excessive muscle contraction leads to abnormal postures or exaggerated movements.
Chorea: These are abnormal involuntary movements that can be jerking and random.
Athetosis: These are involuntary twisting or writhing movements usually in the fingers, hands or feet.
How are dopamine receptor agonists used in Parkinson’s treatment?
mimic dopamine in the basal ganglia and stimulate the dopamine receptors. They are less effective than levodopa in reducing symptoms.
usually used to delay the use of levodopa and are then used in combination with levodopa to reduce the dose of levodopa that is required to control symptoms. One notable side effect with prolonged use is pulmonary fibrosis. Examples are:
Bromocryptine
Pergolide
Carbergoline
Less effective but cause fewer unwanted dyskinesias
Side effects: vomiting and haemolytic anaemia
How do MAO-B inhibitors work?
Normally, MAO-B enzymes break down neurotransmitters such as dopamine, serotonin and adrenaline.
The monoamine oxidase-B enzyme is more specific to dopamine and does not act on serotonin or adrenalin. These medications block this enzyme and therefore help increase the circulating dopamine.
Similarly to dopamine agonists, they are usually used to delay the use of levodopa and then in combination with levodopa to reduce the required dose. Examples are:
Selegiline
Rasagiline
How are anticholinergic agents used in Parkinson’s?
Address the dopamine / acetylcholine imbalance in substantia nigra
help tremor BUT cause confusion in the elderly and a range of anti-cholinergic effects
Describe the prognosis of Parkinson’s disease?
progressive disease - untreated patients will succumb to complications within 10 years
What is MND?
Degenerative disease of upper and lower motor neurones in the spinal cord, cranial nerve motor nuclei and the cortex. There is no sensory involvement.
Sporadic, with the cause unknown
Incidence: 2/100,000 with onset between 50 and 70
What are the four patterns of disease in MND?
Amylotrophic lateral sclerosis = most common and well known specific type
Progressive Bulbar presentation - second most common. It affects primarily the muscles of talking and swallowing.
Progressive muscular atrophy
Primary lateral sclerosis
Describe amylotrophic lateral sclerosis in MND
Most common
Loss of spinal and brain stem lower motor neurones and also cortical upper motor neurones, giving UMN and LMN signs
Progressive plastic tetra paresis with added lower motor neurone signs such as wasting and fasciculation
May be associated with fronto-temporal dementia
LMN disease: Muscle wasting Reduced tone Fasciculations (twitches in the muscles) Reduced reflexes
Signs of upper motor neurone disease:
Increased tone or spasticity
Brisk reflexes
Upgoing plantar responses
What is the presentation of amylotrophic lateral sclerosis?
LMN weakness - starting in the hands and progressing to the upper arms / legs
UMN spastic weakness - starting in the legs and progressing to the arms
Bulbar palsy / pseudo bulbar palsy may also occur
Classical sign: muscle wasting and fasciculation with brisk reflexes and up-going plantars
What is the presentation o progressive muscular atrophy in MND?
Loss restricted to spinal lower motor neurones, giving purely LMN signs
Painless wasting - begins in the small muscles of the hands and spreads
On examination: wasting and fasciculation seen
What is the appearance of primary lateral sclerosis?
Rare, disease confined to cortical UMN, giving purely UMN signs
Progressive tetraparesis
What is the bulbar presentation in MND?
Bulbar symptoms with preservation of limb function in early stages
Poor prognosis due to early respiratory involvement
How is MND diagnosed?
Diagnosis can be clinical in presence of mixed upper/lower motor neurone signs in multiple limbs but ix usually helpful to establish diagnosis
Bloods - rule out differentials
Spinal cord MRI - rule out myelopathy / radiculopathy
EMG: evidence of denervation, can be diagnostic
What is the management of MND?
SPECIALIST MDT
social and carer assessments
Disease modifying therapy: Riluzole - increases pre-synaptic glutamate release
Nutritional support: from early stage can contribute to quality of life and prognosis
Gastrostomy tubes may be placed late in the disease if swallowing function is lost
Respiratory support: NIPPV considered if respiratory weakness is an use
Treatment of complications as per MS
What is the prognosis of MND?
Remission is not known
Death eventually from bronchopneumonia or ventilatory failure due to weakness of respiratory muscles
What is dementia?
A syndrome of acquired global impairment of higher cerebral function
What are the criteria for diagnosis of dementia?
Impairment of memory + one of: language impairment Apraxia Agnosia Impairment of executive functioning
Impairment of functioning
No other medical or psychiatric explanation
Present for at least 6 months
What is mild cognitive impairment?
Evidence of early memory decline on formal memory tests e.g. MMSE without clinical evidence of the other features of dementia
Describe the three phases of dementia
Early: short term memory loss, difficulty embracing change, repetition of questions, minor behavioural changes
Middle: Difficulty with daily tasks, need frequent prompting, failure to recognise people, hallucinations may develop
Increasing support required for daily life
Late: Incontinence, aggression, weight loss can all develop
What dementia symptoms occur from the frontal lobe?
Personality change: dulling of personality, social withdrawal
Disinhibition: with irresponsible behaviours
difficulties with reasoning and abstract thought
difficulty initiating actions e.g. speech
What dementia symptoms occur from the temporal lobe?
Difficulty with short-term memory
Difficulty holding attention on tasks
Poor speech production
What dementia symptoms occur from the parietal lobe?
Problems recognising faces and objects
Agnosia: cannot associate objects with their purpose
Difficulty carrying out a sequence of actions, e.g.making a cup of tea
clumsiness
What are the causes of dementia?
Degenerative disease:
alzheimer’s, frontotemporal dementia, Lewy body dementia, Parkinson’s, Huntington’s
Vascular: multi-infarct, cerebral infarct, Biswanger’s disease, systemic disease
Trauma: major head injuries, repetitive minor trauma e.g. boxing
Malignancy: Primary or secondary neoplasm
Hydrostatic: Hydrocephalus, normal-pressure hydrocephalus, intracranial haematomas
Toxic: alcohol related, heavy metal poisoning, including Wilson’s disease, drug related
Endocrine: hypothyroidism
Metabolic: B1, B12, folate deficiencies. Uraemia / liver failure
Infective: Tertiary syphilis, HIV, Creutzfeld-Jakob disease, cryptococcus
Psychiatric: Depressive pseudo dementia
What are the prevalences of each type of dementia?
Alzheimer's: 62% Vascular: 17% Mixed AD/Vascular: 10% Lewy Body: 4% Fronto-temporal: 2% Parkinson's: 2%
What are the history points for dementia?
Rule out mimics: delirium, depression
Assess for potentially reversible causes
Classify type of dementia and severity
What Ix should be done for dementia?
MMSE/MOCA
Bloods: FBC, U&E, LFT, ESR, Calcium, TFTs, glucose, lipids
syphilis serology / HIV If risk factors
CT/MRI head: all patients with suspected dementia - neuroimaging
ECG
What is the most common cause of dementia int the UK?
Alzheimer’s disease
How does Alzheimer’s disease cause dementia?
Protein plaques and tangles in cortical areas, lead to cell death
Progressive loss of the ability to learn, retain and process new information
Early, middle and late stages of symptoms as described above. In the later stages, behavioural changes develop
What are the sub-types of vascular dementia?
Post-stroke dementia
Cortical vascular dementia (multiple small infarcts in cerebral cortex)
Subcortical vascular dementia (affects subcortical areas only, associated with hypertension
What are the symptoms of vascular dementia?
Similar to AD, but certain features favour vascular disease;
step-wise progression of disease
personal history, family history, symptoms, signs of vascular disease
early gait disturbance, with unsteadiness and falls
For diagnosis, need radiological evidence of cerebrovascular disease
What is Lewy-Body Dementia?
Formation of Lewy bodies in the basal ganglia and cortex - leading to both cognitive and motor symptoms
Again, the main symptom is progressive cognitive decline, yet core / supportive symptoms favour a diagnosis of LBD
Where are the core features of Lewy body dementia?
Visual hallucinations
Fluctuating cognition
Features of Parkinsonism
What are the supportive features of Lewy body dementia?
- Falls / syncope - as per Parkinson’s, there is autonomic dysfunction and postural hypotension
- Sensitivity to neuroleptics: patients rapidly develop EPSEs and in extreme cases, neuroleptic malignant syndrome
- REM sleep behaviour disturbance: during periods of REM sleep, the person will move, gesture and/or speak
Describe the presentation of Parkinson’s disease dementia?
Prevalence in Parkinson’s disease is around 30%
Classic Parkinson’s disease with initial unilateral symptoms present for a few years and then subsequent decline in cognitive function would favour PDD
What is fronto-temporal dementia?
Heterogenous condition
age of onset before 65 years
normally +ve FH
Behaviour changes: emotional bunting, loss of inhibitions, decline in personal hygeine / grooming, hyperorality
Language difficulties: difficulty finding words and reduction in amount of speech, progressing o echolalia and complete aphasia
Early loss of insight and on examination, primitive reflexes may be present e.g. grasp
What is Creutzfeldt-Jakob disease?
Prion disease - ?contaminated beef
Certain inheritable forms
Classical CJD presents in middle age with dementia associated with visual disturbance and upper motor neurone signs in teh limbs
EEG Is diagnostic, showing characteristic abnormalities
What is the mode of inheritance of Huntington’s disease?
Autosomal dominant inheritance of the Huntington’s gene
Show’s ‘anticipation’ with symptoms getting more severe in each generation
“trinucleotide repeat disorder” that involves a genetic mutation in the HTT gene on chromosome 4.
Progressive dementia and chorea develop in middle age
What is delirium?
Acute confusional state
Change in cognition that develops over a short period of time, typified by a disturbance of attention or arousal
There is a tendency for symptoms to fluctuate during the course of the day with disturbance of the sleep-wake cycle
Name the different types of delirium
Hypoactive (40%)
apathy, withdrawal, lethargy and reduced motor activity
Hyperactive (25%) increased motor activity and associated agitation, hallucinations and challenging behaviour
Mixed (35%) mixed picture with fluctuation throughout the day
What is the management of delirium?
Treat the underlying cause
Promote orientation, maintain hydration and nutrition
pain controlled, but use of sedative drugs kept to a minimum
Prevention of complications
Patient and relative explanation
What is the prognosis for delirium?
Although rapid onset, delirium is often slow to resolve
40% cases persist at 2 weeks, 33% at one month and 25% at 3 months
20% never recover
Describe the differentiation between delirium, dementia depression
Delirium: acute onset, fluctuating course, hours-weeks in duration, altered consciousness, impaired attention, increased or decreased psychomotor and is reversible
Dementia: Insidious onset, progressive course, lasts months to years and consciousness ok. Attention and psychomotor normal. Irreversible
Depression: acute or insidious, may be chronic, months to years duration, attention decreased, psychomotor may be slowed.
Usually reversible
How is dementia managed?
MDT
Social care needs
Reduce vascular risks: BP, lipid profile, glycemic control
Cognitive stiualtion therapy may slow decline
Mild-moderate AD/LBD: AChE inhibitors, donezepil, galantamine, rivastigmine
Severe AD/LBD or intolerance to AChE inhibitors: NMDA receptor antagonists - memantin
Manage behavioural and psychological symptoms of dementia
What is a radiculopathy?
Process affecting nerve roots
What is a neuropathy?
Pathological process affecting a peripheral nerve/nerves
What is a mononeuropathy?
process affecting a single nerve
What is a mono neuritis multiplex?
Process affecting several individual nerves
What is a polyneuropathy / peripheral neuropathy?
Diffuse, symmetrical disease, usually beginning peripherally
Can be motor, sensory, autonomic or combinations of these
can be broadly classified into demyelinating and axonal types
widespread loss of tendon reflexes is usual, as well as ‘glove and stocking’ sensory loss
What are the causes of polyneuropathy / peripheral neuropathy?
Metabolic: diabetes, B12, folate, thiamine deficiency, uraemia
Toxic: alcohol, chronic liver disease, lead, radiation
Autoimmune: RA, CTDs, myoedema
Inflammatory: Guillian-Barre syndrome, chronic inflammatory demyelinating polyneuropathy
Drugs: amiodarone, statins, hydralazine, phenytoin, antibiotics
Infective: syphilis, HIV
Vascular: vasculitis
Neoplastic: Myeloma, paraneoplastic syndromes
Inherited: Charcot-Marie-Tooth
Freidrich’s ataxia
What are the most common causes of polymyopathy?
Diabetes mellitus, carcinomatous neuropathy, B vitamin deficiency and drugs
How are demyelinating and axonal neuropathies differentiated?
Nerve conduction studies:
Describe the difference between demyelinating and axonal neuropathies
Demyelinating: damage spares axons but affects Schwann cells, more common in immune mediated disease such as GBS
Inferred by decreased conduction velocity
Schwann cells can regrow, so will improve with treatment
Axonal: nerve cell bodies are unable to maintain long axonal process, leading to degeneration that starts at the periphery, progressing up towards the neuronal cell
Inferred by reduced amplitude of nerve impulses
axons cannot regrow, so treatment outcomes are poor
What are the other patterns of nerve damage?
Wallerian degeneration: seen following nerve section or microinfarction
Compression neuropathy: leading to focal demyelination
Nerve infiltration: malignancy of granulomatous infiltration e.g. sarcoid
What investigations should be done for peripheral neuropathy?
Bloods: FBC, U&Es, LFTs, HbA1c, B12/folate, ANCA, VDRL, autoantibodies
Nerve conduction studies
LP - raised protein in GBS, CIDP
Peripheral nerve biopsy: if diagnosis uncertain
What is the mot common acute polyneuropathy?
Guillain barre syndrome (GBS)
acute paralytic polyneuropathy that affects the peripheral nervous system.
It causes acute, symmetrical, ascending weakness and can also cause sensory symptoms
What is the cause of GBS?
molecular mimicry. The B cells of the immune system create antibodies against the antigens on the pathogen that causes the preceding infection. These antibodies also match proteins on the nerve cells. They may target proteins on the myelin sheath of the motor nerve cell or the nerve axon
demyelinating: ?autoallergic
Infection: campylobacter jejuni, cytomegalovirus and Epstein-Barr virus.
What is the presentation of GBS?
1-3 after infection: paralysis
Symmetrical ascending weakness (starting at the feet and moving up the body)
Reduced reflexes
There may be peripheral loss of sensation or neuropathic pain
It may progress to the cranial nerves and cause facial nerve weakness
Other complications: VTE, autonomic involvement leading to blood pressure lability / arrhythmias
How is GBS diagnosed?
A diagnosis of Guillain-Barré syndrome is made clinically. The Brighton criteria can be used for diagnosis.
Diagnosis can be supported by investigations:
Nerve conduction studies (reduced signal through the nerves)
Lumbar puncture for CSF (raised protein with a normal cell count and glucose)
What is the management of GBS?
HDU
IV immunoglobulins
Plasma exchange (alternative to IV IG)
Supportive care
VTE prophylaxis (pulmonary embolism is a leading cause of death)
In severe cases with respiratory failure patients may need intubation, ventilation and admission to the intensive care unit.
What is the prognosis of GBS?
In mild cases, little disability before spontaneous recovery
Complete recovery occurs over months in 80-90%
May get residual weakness
Mortality is high in acute phase
80% will fully recover
15% will be left with some neurological disability
5% will die
What is shingles?
Re-activation of varicella-zoster infection within the dorsal root ganglion
Most commonly occurs in lower thoracic dermatomes
What are the symptoms of shingles?
Erythema and dermatomal eruption of vesicles
Increased burning and itching
Vesicles become pustular 2-3 days later and may separate 3 weeks later
What is ophthalmic herpes?
Infection of the first division of the fifth nerve - uveitis, corneal scarring and secondary panophthalmitis
What is Ramsey-hunt syndrome?
Infection of the geniculate ganglion
Clinical features: facial palsy (often severe and irreversible) with facial / ear pain and vesicles in the ear canal, pinna and soft palate
May be sensorineual deafness and vertigo, and neuropathy of nerves 5, 9, 10
What is the managent of Ramsey-hunt?
Paracetemol and amitryptiline for pain
5-7 days oral acyclovir
What is post-herpetic neuralgia?
Pain in previous shingles zone, occurring in 10%
Burning, continuous pain that responds poorly to analgesia
Amitryptiline is commonly used, plus topical capsaicin
Associated with depression
Gradual recovery over around 2 years
Describe the pathology of Myasthenia graves?
autoimmune condition that causes muscle weakness that gets progressively worse with activity and improves with rest.
Generation of IgG autoantibodies to the ACh receptor location the post-synaptic membrane of the motor end plates
Blocks synaptic transmission at the NMJ
Associated with other autoimmune pathology e.g. thymoma in the thyroid (25%)
What is the presentation of MG?
Weakness and fatiguability that gets worse throughout the day
Classically affects proximal limb muscles, extra-ocular muscles, bulbar muscles and muscles of facial expression
Fluctuating proximal weakness, more common in the upper limb
Extraocular muscle weakness causing double vision (diplopia)
Eyelid weakness causing drooping of the eyelids (ptosis)
Weakness in facial movements
Difficulty with swallowing
Fatigue in the jaw when chewing
Slurred speech
Progressive weakness with repetitive movements
How is MG diagnosed?
Serum anti-AchR antibody titre: raised in 90%
Single fibre electromyography
TFTs and CT for thymoma
Endrophonium tests: now rarely used due to risk of arrhythmia.
IV injection of edrophonium produces improvement in features
What is the management of MG?
Reversible acetylcholinesterase inhibitors (usually pyridostigmine or neostigmine) increases the amount of acetylcholine in the neuromuscular junction and improve symptoms
Immunosuppression (e.g. prednisolone or azathioprine) suppresses the production of antibodies
Thymectomy can improve symptoms even in patients without a thymoma
Monoclonal antibodies
Rituximab is a monoclonal antibody that targets B cells and reduces the production of antibodies. It is available on the NHS if standard treatment is not effective and certain criteria are met.
What is the prognosis of MG?
May never progress beyond ophthalmoplegia and periods of remission for up to 3 years can occur
Outlook is poor if there is respiratory muscle involvement
What are the three types of muscular disease?
Muscular dystrophies: genetically determined diseases that result in progressive deterioration
Myopathies: diverse group of conditions that are grouped due toothier predominant effect on muscle
Neurogenic disease: disease of peripheral nerves or motor neurones that causes secondary skeletal muscle atrophy
What is the inheritance of Duchenne Muscular Dystrophy?
X-linked recessive
30% spontaneous mutations
What is the cause of DMD?
mutation in dystrophin gene, making muscle fibres liable to break down with repeated contraction
What is the presentation of DMD?
Onset in early childhood:
Global muscle weakness
Calf pseudo hypertrophy: due to fatty replacement of muscles
Gower’s sign: use of hands to climb up to standing
Investigations show raised CK
Genetic testing / mm biopsy can confirm diagnosis
Prognosis is poor with individuals dying in their late teens due to respiratory failure and cardiomyopathy
What is Beck’s muscular dystrophy?
Less common: producing partially functioning dystrophin
Symptoms are milder and prognosis better than DMD
Patients tend to survive until mid-40s
What is myotonic dystrophy?
autosomal dominant condition caused by Cl- channelopthy
Shows ‘anticipation’ with symptoms more severe in each generation
due to expansion of a CTG repeat
characterised by muscle weakness and myotonia. inability to relax muscles
What are the other associations of myotonic dystrophy?
Cataracts, frontal baldness, mental impairment and cardiac abnormalities
What serum muscle enzyme is checked in muscular disorders?
CK
raised in muscular dystrophies and inflammatory muscle disorders
normal in MG
Electromyography: classical trace for myopathy, denervation, myotonic discharges and in MG
Muscle biopsy: can differentiate between denervation and muscular disease
How Is spasticity managed?
Physical management: physiotherapy, gait retraining, removal of exacerbating stimuli
Surgical management: tendon lengthening, releases for fixed deformities
Medical: baclofen, dantrolene, benzodiazepines, botilinium toxin injections
How are contractures managed?
Aim to prevent development with good management of spasticity
orthopaedic referral
physiotherapy and aids
