Neurology Flashcards
What is a cerebrovascular accident?
Ischaemia or infarction of brain tissue secondary to inadequate blood supply
OR
Intracranial haemorrhage
What are the different types of cerebrovascular accidents?
Transient Ischaemic Attack(TIA)
Stroke:
Haemorrhagic
Ischaemic
What is a TIA?
Sudden onset focal neurological deficit.
Older definition:
symptoms of a stroke that resolve within 24 hours.
New definition:
transient neurological dysfunction secondary to ischaemia without infarction.
What is a crescendo TIA?
where there are two or more TIAs within a week. This carries a high risk of developing in to a stroke.
What are the risk factors for a TIA?
Increasing age
Hypertension
Smoking
Diabetes
Hypercholesterolaemia
Atrial fibrillation
HTN
VSD
Carotid stenosis
What are the causes of a TIA?
Thrombus formation or embolus (for example in patients with atrial fibrillation)
Atherosclerosis
Shock
Vasculitis
What artery is commonly the route of a TIA?
90% = ICA
10% = Vertebral
What are the symptoms of a TIA?
Depends on the site of the TIA:
ACA - weak/numb contralateral leg
MCA - weak/numb contralateral side of body, face drooping w/forehead spared, dysphasia (temporal)
PCA - Vision loss
Vertebral A - Cerebellar Syndrome
What would be the signs of a TIA in the Anterior Cerebral artery?
Weak/numb contralateral leg
What would be the signs of a TIA in the Middle Cerebral Artery?
weak/Numb contralateral side of body
Face drooping w/ forehead spared
Dysphasia
What would be the signs of a TIA in the Posterior Cerebral Artery?
Vision loss:
Contralateral homonymous hemianopia w/ macula sparing = occipital cortex affected.
What would be the signs of a TIA in the Vertebral Artery?
Cerebellar Syndrome: DANISH w/ +tve romberg test
What is Amaurosis Fugax?
a painless temporary loss of vision, usually in one eye
Due to occlusion/reduced blood flow to the retina through the ophthalmic, retinal or ciliary artery.
This is a bad sign as it often signals stroke is impending
What is the Primary investigation for a TIA?
Clinically made:
Usually TIA/Stroke is obvious
FAST campaign
ABCD^2
What is the FAST acronym?
FACE
ARMS
SPEECH
TIME
What is the ABCD^2 scoring system for TIA/Stroke?
No longer recommended by NICE
Age >60
BP >140/90
Clinical Sx
Duration 1hr +2 / <1hr
DM - Type 2
How can you distinguish between a TIA and a Stroke?
You cant until after recovery
TIA Sx resolve usually within/<24 hours
Stroke Sx last more than 24 hours
What is the management of a TIA?
Aspirin 300mg
Start secondary prevention of CVD:
Clopidogrel 75mg
Atorvastatin 80mg
What are the main complications of a TIA?
Increased risk of stroke
Increased risk of underlying CVD
What are the two types of stroke?
Ischaemic (85% of cases)
Haemorrhagic (15% of cases)
Define a stroke?
Focal neurological deficit that lasts for more than 24 hrs due to infarction
What is an Ischaemic Stroke?
Reduction in cerebral blood flow due to arterial occlusion or stenosis. Typically divided into thrombotic, embolic, and lacunar
What is a Haemorrhagic Stroke?
Ruptured blood vessel leading to reduced blood flow to the brain
What are the subtypes of haemorrhagic stroke?
Intracerebral: bleeding within the brain parenchyma
Subarachnoid: bleeding into the subarachnoid space
Intraventricular: bleeding within the ventricles; prematurity is a very strong risk factor in infants
What is the 3rd leading cause of mortality in the US and UK?
Stroke
What are the risk factors for stroke?
Hypertension - greatest RF
Increased age - 68-75 MC
Smoking
Diabetes
Hypercholesterolaemia
AF
FHx
Medication
What are the symptoms of stroke?
Focal neurological deficit based on site of the infarct.
What would be an extra finding in haemorrhagic stroke?
Increased intracranial pressure (ICP)
Causes midline shift
What is a Lacunar Stroke?
Very common type of ischaemic stroke of the lenticulostriate arteries.
These supply the deep brain structures (BG, IC, Thalamus, pons)
What are the clinical manifestations of a stroke in the anterior cerebral artery?
Contralateral hemiparesis and sensory loss with lower limbs > upper limbs
What are the clinical manifestations of a stroke in the Middle cerebral artery?
Contralateral hemiparesis and sensory loss with upper limbs > lower limbs
Homonymous hemianopia
Aphasia: if affecting the ‘dominant’ hemisphere (the left in 95% of right-handed people)
Hemineglect syndrome: if affecting the ‘non-dominant’ hemisphere
What are the clinical manifestations of a stroke in the Posterior cerebral artery?
Contralateral homonymous hemianopia with macular sparing
Visual agnosia
What are the clinical manifestations of a stroke in the Vertebrobasilar artery?
Cerebellar signs
Reduced consciousness
Quadriplegia or hemiplegia
What are the clinical manifestations of a stroke in Weber’s syndrome (midbrain infarct; branches of posterior cerebral artery)
Oculomotor palsy and contralateral hemiplegia
What are the clinical manifestations of a stroke in Lateral medullary syndrome (posterior inferior cerebellar artery occlusion)
Ipsilateral facial loss of pain and temperature
Ipsilateral Horner’s syndrome
Ipsilateral cerebellar signs
Contralateral loss of pain and temperature
What are the clinical manifestations of a stroke in the Basilar Artery?
Locked in syndrome
What are the primary investigations for a stroke?
NCCT Head:
Ischaemic - mostly normal
Haemorrhagic - Hyperdense blood
What is the management for an Ischaemic stroke?
immediate CT to exclude primary intracerebral haemorrhage
If presents within 4.5hrs:
Clot buster (thrombolysis) - IV Alteplase
Aspirin 300mg for 2 weeks
Prophylaxis - Lifelong clopidogrel (75mg)
What is the function of Alteplase?
Tissue plasminogen activator that rapidly breaks down clots and can reverse the effects of a stroke if given in time.
What is the management of a Haemorrhagic Stroke?
Neurosurgery referral
Iv mannitol for increased ICP
What type of stroke should be suspected if the patient is on oral anticoagulants?
Suspect Haemorrhagic until proven otherwise
What is the prophylactic prevention of secondary strokes?
Clopidogrel 75mg once daily (alternatively dipyridamole 200mg twice daily)
Atorvastatin 80mg should be started but not immediately
Carotid endarterectomy or stenting in patients with carotid artery disease
Treat modifiable risk factors such as hypertension and diabetes
What is a haematoma?
Describes a bleed that has mostly clotted and hardened
What is a Haemorrhage?
Describes an active ongoing bleed
Where can intracranial haemorrhages occur?
Extradural
Subdural
Subarachnoid
Intracerebral
What is an Extradural (Epidural) haemorrhage (EHD)?
Bleeding into the potential space between the skull and the dura mater.
The blood then collects in this space and is referred to as an extradural haematoma (EDH).
What are the causes of Extradural haemorrhage?
Usually Trauma (blunt trauma):
Arterial bleed - often middle meningeal artery
Venous bleed - often due to dural venous sinus
What is the most common blood vessel damaged to cause an extradural bleed?
Middle meningeal artery due to damage to the pterygoid bone
What are some rarer causes of an EDH?
Non-traumatic:
Haemorrhagic tumour
Coagulopathy
Infection
Vascular Malformation
What are the risk factors for an EDH?
Younger age (20-30)
Male
Anticoagulant usage
Why is an EDH less likely to occur in the elderly?
The Dura matter is more firmly adhered to the skull so blood is less likely to accumulate in this region.
What are the symptoms of an Extradural bleed?
Initial event / loss of consciousness
Lucid interval - “I feel fine”
Rapid Decline of neurological status due to raised ICP:
Dec GCS, Cushing Triad, N+V
Evidence of head injury:
Bleeding from ears
bruising/scalp haematoma
Death
What are the cushings triad signs of an extradural haemorrhage?
Hypertension
Bradycardia
Respiratory irregularity
Why is there an increased ICP in an EDH?
Haemorrhage - increased volume decreased pressure
old blood clots which can then take up water (osmotically active)
Will increase in volume and raise ICP
What are the primary investigations of an EDH?
NCCT head:
Lens shaped hyperdense bleed
Confined to suture lines
Midline shift
What is the management on an EDH?
Urgent Surgery
IV Mannitol to reduce ICP
What are the complications of an EDH?
Cerebral oedema
Raised intracranial pressure and herniation
Ischameia: can occur due to mass effect, herniation, hypoperfusion, vasospasm
Seizures
Infection
What is the Typical presentation of an EDH?
The typical history is a young patient with a traumatic head injury that has an ongoing headache.
They have a period of improved neurological symptoms and consciousness followed by a rapid decline over hours as the haematoma gets large enough to compress the intracranial contents.
What is a Subdural Haemorrhage?
When blood accumulates in between the dura and arachnoid matter
What are the causes of a Subdural haemorrhage?
Often due to the rupture of a bridging vein caused by trauma:
Shearing deceleration injury
Abused children (shaken baby sydrome)
What are the risk factors for a subdural haemorrhage?
Increased age
alcoholics
Trauma
Cortical atrophy (due to age/dementia)
Child abuse
What are the symptoms of a subdural haemorrhage?
Often gradual symptom onset with a latent period.
Progressive confusion and cognitive deficit
Headaches and vomiting
Focal neurological deficit, e.g. weakness or fixed dilated pupil
What are the clinical signs of a subdural haemorrhage?
Raised ICP
Cushing Triad - HTN, Bradycardia,
Resp irregularity
Fluctuating GSC
What are the primary investigations of a subdural haemorrhage?
NCCT Head:
Banana/Crescent shaped dense region.
Not confined to suture lines.
May have midline shift
If acute - Hyperdense (bright)
If Subacute - Isodense
If Chronic - Hypodense (darker than brain
What is the treatment for a subdural haemorrhage?
IV mannitol - reduce ICP
Burr hole / Craniotomy to relieve pressure
What is a subarachnoid haemorrhage (SAH)?
Subarachnoid haemorrhage involves bleeding in to the subarachnoid space, where the cerebrospinal fluid is located, between the pia mater and the arachnoid membrane.
This is usually the result of a ruptured cerebral aneurysm.
What are the possible causes of an SAH?
Trauma
Non-Trauma: (spontaneous)
Berry Aneurysm from circle of willis- MC of spontaneous SAH
AVM
Where do berry aneurysms often occur?
Usually at junctions of arteries within the circle of Willis.
Often communicating junctions
What is the most common artery affected in an SAH?
Circle of Willis:
Anterior communicating artery
ACA junction
What are the risk factors for a SAH?
What are some strong associations with SAH?
Increased age - >50yrs
HTN
PKD
Trauma
FHx
Smoking
Alcohol excess
Strong associations with Cocaine Use and Sickle Cell
What are the symptoms of a SAH?
Occipital Thunderclap Headache
Meningism (mimics meningitis)
Reduced GSC
Nerve palsies - 3rd / 6th
What are the characteristics of the headache experienced in an SAH?
Occipital Thunderclap Headache
Sudden onset
Worst headache of their life (0-10 instantly)
May have a sentinel headache preceding this
Why may you get nerve palsies in SAH?
3rd nerve palsy:
An aneurysm arising from the posterior communicating artery will press on the 3rd nerve, causing a palsy with a fixed dilated pupil
6th nerve palsy:
A non-specific sign which indicates raised intracranial pressure
What are the primary investigations in a SAH?
CT Head - diagnostic with 100% sensitivity if performed within 6 hrs.
If Negative:
Lumbar Puncture (performed after 12hrs)
will show xanthochromia / yellowish CSF due to RBC haemolysis
Angiography (CT or MRI) can be used once a subarachnoid haemorrhage is confirmed to locate the source of the bleeding.
Who do SAHs more commonly affect?
Black patients
Female patients
Age 45-70
What is the Glasgow Coma Scale (GCS)?
Tool for assessing consciousness:
Based on Eyes, verbal and motor response.
Normal - 15/15
Comatose - 8/15
Unresponsive - 3/15
Eyes:
Spontaneous = 4
Speech = 3
Pain = 2
None = 1
Verbal response:
Orientated = 5
Confused conversation = 4
Inappropriate words = 3
Incomprehensible sounds = 2
None = 1
Motor response:
Obeys commands = 6
Localises pain = 5
Normal flexion = 4
Abnormal flexion = 3
Extends = 2
None = 1
What are important differential diagnoses of SAH?
Meningitis - no thunderclap headache in this
Migraine - no meningism/thundercap headache in this
What is the treatment for an SAH?
1st line:
Neurosurgery:
1st - Endovascular coiling
2nd - Surgical clipping
Give immediate Nimodipine (CCB) 60mg - prevents vasospasm
What is an Intracerebral haemorrhage?
Intracerebral haemorrhage involves bleeding into the brain tissue. It presents similarly to an ischaemic stroke.
Often has a headache/come and signs of raised ICP
Define Meningitis?
Inflammation of the meninges
This is a notifiable condition to PHE
What are the different causes of Meningitis?
Viral:
Enterovirus (coxsackie)
HSV2
VZV
Bacterial:
N. Meningitidis
S. pneumonia
What is the most common cause of meningitis?
Viral cause
What organism is the most common cause of viral and bacterial meningitis?
Viral - Enterovirus (coxsackie)
Bacterial - S. pneumoniae
Which is a more severe form of meningitis?
Bacterial is more severe
What are the main risk factors for meningitis?
Extremes of age (Infant/elderly)
Immunocompromised
Crowded environment - barracks/uni
Non-vaccinated
What is the most common bacterial cause of meningitis in neonates (0-3 months)?
Group B Strep (S. agalactiae)
Due to the colonisation of mothers vagina which can cause infection in neonate at birth.
Also E.coli and Listeria
What is the most common bacterial cause of Meningitis in Infants?
N. meningitidis
S. pneumoniae
H. Influenzae (now rare due to vaccine)
Why is Haemophilus influenzae now a less common cause of meningitis?
Due to vaccination
What are the common bacterial causes of meningitis in adults?
S. pneumoniae
N. Meningitidis
What are the most common bacterial causes of meningitis in the elderly?
S. pneumoniae
N. meningitidis
Listeria
What are the most common bacterial causes of meningitis in the immunocompromised?
Listeria monocytogenes
M. Tuberculosis
What vaccines are available for meningitis coverage?
N. Meningitidis - Men B + Men C + Men ACWY
S. pneumoniae - PCV Vaccine
What is meningococcal Septicaemia?
N. meningitidis infection in the blood.
This causes a non-blanching purpuric rash
This is due to Disseminated intravascular coagulopathy (DIC) and subcutaneous haemorrhages
What are the symptoms of Meningitis?
Meningism:
Headache, Photophobia, Neck stiffness
Fever
Nausea + Vomiting
Seizures
What are the clinical signs of meningitis?
Kernig’s Sign:
When the hip is flexed and the knee is at 90°, extension of the knee results in pain
Brudzinski Sign:
severe neck stiffness causes the hips and knees to flex when the neck is flexed
What are the primary investigations in meningitis?
Lumbar Puncture (LP) + CSF Analysis
FBC - raised WCC
CRP - raised
Blood glucose - compared with CSF
Blood culture
What are some contraindications for a lumbar puncture?
Raised ICP
GCS <9
Focal Neurological signs
Where is a lumbar puncture usually taken from?
Between L3/L4
What would the results of an LP CSF sample analysis look like in bacterial meningitis?
CSF:
Appearance - Cloudy
WCC - High neutrophils
Protein High
Glucose - Low
Culture - bacterial organism
bacteria swimming in the CSF (cloudy) will release proteins (high) and use up the glucose (low). Immune response to bacteria is neutrophils
What would the results of an LP CSF sample analysis look like in Viral meningitis?
CSF:
Appearance - Clear
WCC - High Lymphocytes
Protein - Normal/Mildly raised
Glucose - Normal
Culture - Negative
Viruses cant be seen (clear) don’t use glucose (normal) but may release a small amount of protein (normal/mild inc). Immune response to viruses are lymphocytes
What is the treatment for viral Meningitis?
Usually milder and so Supportive Tx
If HSV/VZV infection then Acyclovir
What is the treatment for bacterial meningitis in a hospital?
Under 3 months:
Cefotaxime + Amoxicillin to cover listeria (from pregnancy)
Over 3 months: Ceftriaxone
What is the treatment for suspected meningitis w/ non-blanching rash present in the community?
Urgent/immediate IM Benzylpenicillin
Prior to immediate transfer to a hospital
What are some complications of meningitis?
Hearing loss is a key complication
Seizures and epilepsy
Cognitive impairment and learning disability
Memory loss
Cerebral palsy, with focal neurological deficits such as limb weakness or spasticity
What are some specific complications related to meningococcal meningitis?
Risk of DIC
Risk of Waterhouse Friedrichsen Syndrome
What is Waterhouse Friedrichsen Syndrome?
Adrenal insufficiency caused by intra-adrenal haemorrhage as a result of meningococcal DIC
What is the most common cause of fungal meningitis?
Cryptococcus Neoformans
Candida
Very rarely affects immune competent people
What is Encephalitis?
infection of the brain leading to inflammation of the brain parenchyma
What are the causes of Encephalitis?
Viral (most common)
Also bacterial, fungal, parasitic, paraneoplastic
What is the most common cause of encephalitis?
HSV-1
Accounts for 95% of the cases
Also CMV, EBV, HIV
What are the risk factors of encephalitis?
Immunocompromised
Extremes of age
Transfusion/Transplantation
Why can close contact with cats be a risk factor for encephalitis?
Risk of toxoplasmosis infection
What are the symptoms of encephalitis?
Fever
Headache
Focal Neurological deficit
Encephalopathy:
Behavioural changes
psychotic behaviour
mood changes
Confusion
Seizures
What are the clinical signs of encephalitis?
Pyrexia
Reduced GCS
Focal neurological deficit:
Aphasia
Hemiparesis
Cerebellar signs
What is the most common place to be affected by encephalitis?
Temporal and inferior frontal lobe
What are the primary investigations for encephalitis?
CT/MRI Head:
Shows evidence of unilateral encephalitis
CSF analysis:
Viraemia - increased lymphocytes
Consider PCR for confirmation
What is the treatment of encephalitis?
Acyclovir
What is multiple sclerosis?
Chronic progressive autoimmune, T-cell mediated inflammatory disorder
of the CNS
against the myelin basic protein of oligodendrocytes
causing demyelination of CNS neurons
What type of reaction is MS?
Type 4 Hypersensitivity Reaction:
T-Cell mediated
What are the risk factors for MS?
Females
20-40
Autoimmune disease
FHx
EBV
What is the pathophysiology of MS?
T4 Hypersensitivity Rxn
T-cells cause inflammation and damage against the myelin basic protein of oligodendrocytes.
The inflammation also damages the myelin on neurons in the CNS leading to demyelination
What are the types of MS?
Relapse - Remitting:
The most common pattern (85% of cases)
Episodic flare-ups (may last days, weeks or months), separated by periods of remission
Secondary Progressive:
Starts with relapse remitting
Gets progressively worse w/o remission
Primary Progressive:
Symptoms get progressively worse from disease onset with no periods of remission
What percentage of MS patients progress from relapse remitting to secondary progressive MS?
60-75% progress within 15 years
What are the causes of MS?
Unclear cause for demyelination but:
Multiple genes
Epstein–Barr virus (EBV)
Low vitamin D
Smoking
Obesity
combination of these have an influence
What is the presentation of MS?
Variable presentation
Sx progress over 24 hrs and can last days-weeks and then Improve
What are the symptoms of MS?
Blurred Vision
Numbness and tingling
Weakness
Fatigue
Bowel and bladder dysfunctions
Uhtoff’s Phenomenon
What is Uhtoff’s Phenomenon?
worsening of MS symptoms following a rise in temperature, such as a hot bath or shower
What are the clinical signs of MS?
Optic Neuritis - inflamed optic nerve and inability to see red (properly)
Internuclear Ophthalmoplegia - impaired 6th nerve and therefore one eye doesnt abduct in one direction but fine in other
Sensory loss - demyelination of spinothalamic and DCML pathways
Cerebellar signs - Ataxia and tremor
UMN signs - Spastic paraparesis
Lhermitte Phenomenon - Electric shock sensation on neck flexion
Charcot Neurological Triad: Dysarthria, Nystagmus, Intention tremor
What are the primary investigations for MS?
Clinical Dx (using McDonald criteria) and Sx progression/remission
MRI of Brain and spinal cord:
Used to support Dx by identification of demyelinating plaques
LP - may show oligoclonal bands in CSF
What is the McDonald Criteria?
Criteria used to diagnose MS:
Uses symptoms/signs which demonstrate dissemination in space (i.e. different parts of the CNS affected) and time.
What would the results of the McDonald Criteria be to diagnose MS?
2 or more relapses
AND EITHER
Objective clinical evidence of 2 or more lesions
OR
Objective clinical evidence of one lesion WITH a reasonable history of a previous relapse
(Objective evidence’ is defined as an abnormality on neurological exam, MRI or visual evoked potential)
Who manages MS?
MDT:
including neurologists, specialist nurses, physiotherapy, occupational therapy and others.
How can MS be treated long term?
Disease modifying treatments such as beta-interferon and monoclonal antibodies
How can acute relapses of MS be treated?
Steroids:
IV Methylprednisolone
+ Sx treatment of Complications:
Depression - SSRIs
Neuropathic pain - Gabapentin
Exercise - maintain strength
What is Guillain Barre Syndrome?
Guillain-Barré syndrome (GBS) is an autoimmune, rapidly progressive demyelinating condition of the peripheral nervous system, often triggered by infection
“Equivalent to MS for the PNS”
What are the causes of Guillain Barre Syndrome?
Usually triggered post infection (6 weeks) and strongly associated with:
Campylobacter jejuni (most common)
CMV
EBV
What is the most common cause of Guillain Barre Syndrome?
Post C. jejuni infection
Who is typically affected by Guillain Barre syndrome?
Males
Age peak (15-30 & 50-70)
Hx of recent infection (typically GI or Respiratory)
What is the most common type of Guillain Barre Syndrome?
Acute demyelinating inflammatory polyneuropathy (ADIP) in 90% of cases
What is the pathophysiology of Guillain Barre Syndrome?
Molecular Mimicry:
A pathogenic antigen (e.g. Campylobacter jejuni) resembles myelin gangliosides in the peripheral nervous system
The immune system targets the antigen of pathogen and subsequently and attacks the similar antigen of the myelin sheath of sensory and motor nerves
This autoimmune process involves the production of anti-ganglioside antibodies (anti-GMI is positive in 25% of patients)
The demyelination causes polyneuropathy
What are the symptoms of Guillain Barre syndrome?
Recent Hx of Infection (GI/URTI)
Glove/stocking numbness
Ascending symmetrical muscle weakness and paralysis
Back and leg pain
SOB - can progress to resp failure
What are the clinical signs of Guillain Barre Syndrome?
Reduced sensation in limbs
Symmetrical weakness - lower extremities first (proximal then distal)
Loss of deep tendon reflexes (hyporeflexia)
Autonomic dysfunction - Tachycardia, HTN, postural hypotension etc.
Respiratory distress - RF in 35% of patients
What are the primary investigations for Guillain Barre syndrome?
Clinical Dx of Hx of recent infection with progressive weakness and areflexia
Ix to exclude other causes:
TFTs - Hypothyroidism for cause of weakness
U&Es - Electrolytes for neuropathic issues
Spirometry - measure lung function
What investigations can aid to confirm the diagnosis of Guillain Barre?
Nerve conduction studies:
Conduction velocity reduced/blocked
LP - Raised protein + normal WCC = inflammation but no infection
What is the management of Guillain Barre syndrone?
First line:
IV Ig for 5 days
+ Plasma exchange
What is the prognosis of Guillain Barre?
Good prognosis
85% make a full recovery
When may Ig treatment for Guillain Barre be contraindicated?
If patient is IgA deficient
May cause an allergic reaction
What is Huntington’s Chorea (HD)?
Autosomal dominant genetic condition that causes progressive deterioration of the nervous system.
What is the penetrance of HD?
Full penetrance:
All genotypes of Huntington’s will express the phenotype
What are the genetics related to HD?
Huntington’s chorea is a “trinucleotide repeat disorder” that involves a genetic mutation in the HTT gene on chromosome 4.
CAG repeats affecting HTT gene
What is a common feature of tri-nucleotide repeat disorders in terms of prevalence?
They Show anticipation:
where successive generations have more repeats in the gene, resulting in:
Earlier age of onset
Increased severity of disease
When do symptoms of HD usually present?
Often ASx in patients under 30 yrs
Sx present between 30-50 yrs
People with HD will have more severe symptoms typically around 60+ yrs
What are the symptoms of HD?
Insidious progressive worsening:
Starts with cognitive, psychiatric and mood problems.
Then can progress to:
Chorea (involuntary, abnormal movements)
Eye movement disorders
dysarthria
dysphagia
How is a Diagnosis of HD made?
Clinical diagnosis with FHx HD and subsequent generations showing anticipation.
Genetic testing - >35 CAG repeats on chromosome 4
What is the treatment of HD?
No Tx to stop or progress HD
Provide Extensive counselling and support
Can provide Sx treatment for chorea:
Antipsychotics (olanzapine)
Benzodiazepines (diazepam)
Dopamine-depleting agents (tetrabenazine)
What is the prognosis of HD?
Progressive uncurable condition
Life expectancy of 15-20 years post diagnosis
High rate of suicide
What is a possible explanation of the chorea in HD?
Lack of GABA
Excessive Nigrostriatal pathway
What is Parkinson’s Disease (PD)?
A neurodegenerative disorder characterised by loss of dopaminergic neurones within the substantia nigra pars compacta (SNPC) of the basal ganglia (nigrostriatal pathway).
What is the prevalence of PD?
The second most common neurodegenerative disorder after dementia
What are the risk factors for PD?
Increased age
Male
FHx
What is the peak age of onset for PD?
55-65 yrs
What are the causes of PD?
Idiopathic condition but potentially related to genetics
There are secondary causes of parkinsonism:
Drugs
Wilsons disease
What are the genetic factors related to PD?
Mutation in Parkin Gene
Mutation in alpha-Synuclein gene
What is the pathogenesis of PD?
Progressive degeneration of dopamine neurons from SNpc that project to the Striatum (Str)
Therefore loss of Str inhibition which will subsequently increase activation of the subthalamic nucleus (STN)
This will activate the GPi/SNr which will increase inhibition on the Thalamus.
Therefore an inhibited thalamus will not signal to the MC making it harder to initiate movement resulting in parkinsonism.
What are the typical Parkinsonism Symptoms?
Bradykinesia
Resting Tremor
Rigidity
What are the symptoms of PD?
Parkinsonism
Anosmia - early sign
Constipation
Postural instability
Sleep disturbances
Cognitive/memory problems
Depression
What are the clinical signs of PD?
Signs are often Asymmetrical (unilateral)
Pin rolling tremor of thumb
Lead pipe arm (reduced arm swing)
Shuffling gait
Cogwheel movement
What makes up a diagnosis of PD?
Clinical Dx based on Sx and Examination.
Bradykinesia + 1 or more other Cardinal Sx
What is the treatment for PD?
No cure so Sx management
Levodopa (synthetic Dopamine) to increase levels
+ Benserazide or Carbidopa
(Often combined with a peripheral decarboxylase inhibitor to prevent breakdown of dopamine)
Combination therapies:
Benyldopa (Levodopa + Benserazide)
Carledopa (Levodopa + Carbidopa)
What is the issue with using levodopa to treat PD?
Initially works well but soon the Px becomes resistant to it and the effects wear off.
Therefore want to only use it when Sx are bad enough to prevent early resistance.
What is an important differential diagnosis to PD?
Lewy body dementia (often associated with parkinsonism)
Parkinson Sx then Dementia = Parkinson dementia
Dementia then Parkinson Sx = Lewy body dementia w/ Parkinsonsim.
What is dementia?
A syndrome caused by neurodegeneration of various causes resulting in progressive reduction of cognition and difficulty with ADLs
What is the commonest cause of dementia?
Alzheimer’s Disease (AD)
Accounts for 60-75% of all dementias
What is the epidemiology of AD?
Rarely affects under 65yrs
(otherwise EOAD which accounts for 3% of cases)
Affects more females than males
Prevalence significantly rises with age
What is the pathophysiology of AD?
Accumulation of Beta amyloid plaques (Ab plaques) and Tau Neurofibrillary tangles (NFT) in the cerebral cortex.
This leads to cortical scarring and brain atrophy
Additionally, damage to ACh neurons leading to poor neurotransmission
What is the APP protein?
Amyloid Precursor protein that is pathologically cleaved into Beta Amyloid plaques that accumulate in the brain (AD) and other tissues (in amyloidosis)
What are the risk factors for AD?
Increasing age
Downs Syndrome
APP gene mutation
APOE4 allele for familial AD (linked to EOAD)
What are the symptoms of AD?
Agnosia - cant recognise things
Apraxia - Cant do basic motor skills
Aphasia - Speech difficulties
What is the progression of cognitive decline like in AD?
Steady progressive decline
What is the second most common cause of dementia?
Vascular Dementia
Accounts for roughly 20% of cases
What is Vascular Dementia?
Cognitive decline that occurs in a stepwise manner due to a Hx of cerebrovascular events.
What is the pathophysiology of Vascular dementia?
Hx of cerebrovascular events leads to infarction and loss of brain cells/damaged tissue.
Neurons cannot regenerate so the neurodegeneration is permanent.
Increased risk of secondary cerebrovascular events can lead to further brain damage and cognitive decline.
What are the symptoms of vascular dementia?
Signs of vascular pathology:
Raised BP
Hx of cerebrovascular events
Focal CNS signs
General cognitive decline in a stepwise manner
What is Lewy Body Dementia?
3rd most common form of dementia
Alpha-Synuclein and Ubiquiting aggregates accumulate in the cerebral cortex
Results in cognitive decline.
What are the symptoms of Lewy Body Dementia?
Cognitive decline
+ Parkinsonism
What is Frontotemporal dementia?
An uncommon form of dementia (5% of cases)
Specific degeneration of frontotemporal lobes often causing speech and language deterioration and Thinking/memory problems
What are the risk factors for Frontotemporal dementia?
FHx
Autosomal dominant mutation in Tau protein (chromosome 17)
FHx of MND (TDP-43)
What is the Diagnostic test for dementia?
Mini Mental State Exam (MMSE) /30
>25 = normal
18-25 = impaired
<17 = severely impaired
Brain MRI - May show cortical atrophy
What is the treatment for dementia?
Mostly Conservative:
Social stimulation/interaction
Exercise
What pharmacological treatment can be given to aid Alzheimer’s Disease?
Sx management:
First line: AChE inhibitors (rivastigmine, neostigmine)
NMDA antagonist - memantine
SSRIs - treat BPSD (behaviour and psychological Sx of dementia)
What Pharmacological therapy can be given to aid vascular dementia?
Antihypertensives - Ramipril
To reduce risk of subsequent cerebrovascular events
What are the primary headaches?
No underlying cause relevant to headache:
Migraine
Cluster
Tension
(Trigeminal Neuralgia)
What are the secondary Headaches?
Due to underlying conditions:
GCA
Infection
SAH
Trauma
Cerebrovascular disease
Eye, Ear Sinus pathology
Drug overdose
Define a Migraine?
Recurrent throbbing headache often preceded by an aura and associated
with nausea, vomiting and visual changes
What is the epidemiology of a Migraine?
Most common cause of episodic (recurrent) headaches
More common in females
90% onset in under 40 yrs
(if onset > 50 yrs then think pathological)
What happens to Migraine severity with age?
Severity of Migraine typically decreases with advancing age
What are the potential triggers of a migraine?
CHOCOLATE:
- Chocolate
- Hangovers
- Orgasms
- Cheese
- Oral contraceptives
- Lie-ins
- Alcohol
- Tumult - loud noise
- Exercise
What are the different Types of migraine?
Migraine without aura
Migraine with aura
Silent migraine (migraine with aura but without a headache)
Hemiplegic migraine
What is the typical progression of migraines?
Occur in attacks that tend to follow a typical pattern:
Prodrome
Aura
Throbbing headache
Resolution
Post-dromal/recovery
Explain the progression of a Migraine?
Prodrome: Days prior to attack
Mood changes
Aura: last for 60mins
Vision changes minutes before attack (attack follows soon after)
ZigZag lines
Throbbing Headache: 4-72hrs
(Hemiplegic in some cases)
Resolution:
Headache fades away slowly
Recovery
What is the Clinical Dx of a migraine?
2 or more of:
Unilateral pain
Throbbing
Motion Sickness
Mood severely intense
PLUS
1 or more of:
Nausea
Vomiting
Photophobia/Phonophobia
W/ A NORMAL NEURO EXAM
How are migraines diagnosed?
Clinical Dx unless pathology is suspected
What are the treatments for Migraines?
Acute Mx:
Paracetamol
NSAIDs - ibuprofen
Triptans - sumatriptan
Anti-emetics - metoclopramide
Prophylaxis:
Avoid triggers
Propranolol (decrease BP)
Amitriptyline
What is the mechanism of action of Triptans?
Why are they used for migraines?
5-HT receptor agonists (serotonin) that are used to abort migraines when they start to develop
What are cluster headaches?
Severe unilateral headaches often periorbital that come in clusters of attacks
How long can a cluster headache last for?
Clusters of attacks may last for weeks/months before a pain free period follows which may last for years
What is the primary feature of a cluster headache?
Periorbital unilateral pain
Extremely painful (most disabling of primary headaches)
Who typically presents with Cluster headaches?
Males
30-50 yrs old
What are the risk factors for cluster headaches?
Male
Smokers
30-50yrs old
Genetics (autosomal dominant link)
What are the symptoms of cluster headaches?
Abrupt onset - last 15-60 mins
Crescendo excruciating headaches
Unilateral periorbital
Autonomic features:
Bloodshot eye/lacrimation
Ptosis
Rhinorrhoea
What is the diagnosis of cluster headaches?
Clinical Dx
5 or more similar attacks fulfilling criteria
What is the treatment of cluster headaches?
Acute Mx:
Triptans - Sumatriptan
High flow 100% oxygen
Prophylaxis:
Verapamil (CCB)
What are Tension Headaches?
The most common form of a primary headache which has a characteristic rubber band feeling around the head.
What is the headache like in a tension headache?
Mild generalised headache
Bilateral
Tight rubber band around head
Can be felt in neck/trapezius too
What is the diagnosis for a tension headache?
Clinical Diagnosis from Hx
What is the treatment for a Tension headache?
Simple analgesia:
Aspirin/Paracetamol
What is the main risk factor/trigger for a tension headache?
STRESS
What is Trigeminal Neuralgia?
A chronic, debilitating condition resulting in intense and extreme episodes of pain
What are the risk factors for Trigeminal Neuralgia?
Increased age
MS
Female
Who is typically affected by Trigeminal Neuralgia?
Females
50-60 yrs
What is the headache like in Trigeminal Neuralgia?
Electric Shock Pain that lasts for seconds to minutes across the face
90% unilateral
10% bilateral
What is the diagnostic criteria for trigeminal neuralgia?
Clinical Dx
3 or more attacks with characteristic Symptoms
What are the treatment options for trigeminal neuralgia?
First Line:
Carbamazepine (anticonvulsant)
Surgery possible to decompress/intentially damage nerve
Where do berry aneurysms often occur?
Usually at junctions of arteries within the circle of Willis.
Often communicating junctions
Where do berry aneurysms often occur?
Usually at junctions of arteries within the circle of Willis.
Often communicating junctions
Define a Seizure?
A paroxysmal alteration of neurological function as a result of excessive, hypersynchronous discharge of neurons within the brain
Define Epilepsy?
A neurological disorder characterised by an increased tendency to have recurrent seizures that are idiopathic and unprovoked.
(>2 episodes more than 24hrs apart)
What are the different causes of seizures?
VITAMIN DE:
Vascular
Infection
Trauma
Autoimmune - SLE
Metabolic - Hypocalcaemia
Idiopathic - Epilepsy
Neoplasms
Dementia + Drugs (cocaine)
Eclampsia + everything else
What are the risk factors for developing epilepsy?
Familial inherited
Dementia (10x more likely)
Drug use
Cerebrovascular events
What is the epidemiology of epilepsy?
One of the most common neurological disorders
Highest prevalence at extremes of life (<20yr or >60yrs)
What is the pathophysiology of seizures?
Disrupted neurological function resulting in an imbalance between inhibition and excitation of neurons.
Balance of GABA and Glutamate shifts towards glutamate
Therefore more excitatory stimulation
What are the different types of seizures?
Epileptic vs Non-Epileptic:
Generalised
Focal
What are the subtypes of generalised seizures?
Tonic Clonic
Absence
Toni
Myoclonic
Atonic
What are the subtypes of Focal Seizures?
Simple focal
complex focal
How are Seizures classified?
Where the seizures began
Level of awareness during the seizure
Other features of the seizure e.g. motor
What are generalised seizures?
A seizure that starts within both hemispheres of the brain at onset.
They are bilateral
ALWAYS a loss of consciousness
What are Focal Seizures?
Seizures that originate within one side of the brain and are usually confined to one region.
They may progress to secondary lobes (Focal-bilateral seizures)
What is the clinical progression of an epileptic seizure?
Prodrome: (days before)
Mood changes
Pre-Ictal: (minutes before)
Aura
Seizure trigger
Automatisms - lip smacking/rapid blinking
Ictal Event: The Seizure
Post-Ictal Period: (30 mins after)
Headaches
Confusion / reduced GCS
Todd’s Paralysis
Amnesia
Sore tongue
What are the features of a Tonic Clonic seizure?
No aura
Loss of consciousness
Tonic phase - rigidity/muscle tensing (fall to floor)
Clonic phase - Jerking of limbs/muscles
Upgazing open eyes
Incontinence
Tongue bitten
What is the management of a Tonic Clonic Seizure?
First line: sodium valproate
Second line: lamotrigine or carbamazepine
What is an Absence Seizure?
Typically in children:
Px stares blankly into space (seconds to mins)
Unaware of surrounds and will not respond.
Will then carry on as normal after the seizure.
What is a tonic seizure?
A seizure where there is just rigidity/muscle tensing
What is a Myoclonic seizure?
A seizure where there is just jerking limbs
What is an Atonic Seizure?
Sudden floppy limbs and muscles
They may be indicative of Lennox-Gastaut syndrome
What is a febrile convulsion?
Seizures that occur in children whilst they have a fever.
They are not caused by epilepsy or underlying pathology.
What parts of the brain are affected in a generalised Seizure?
All the cortex and deep brain structures bilaterally affected.
What parts of the brain are affected in a simple focal seizure?
The Focal region of cortex
NO basal ganglia/thalamus involvement
What parts of the brain are affected in a complex focal seizure?
The focal region of cortex
Basal ganglia and thalamus are involved.
What is a Simple Focal Seizure?
No Loss of consciousness
The patient is awake and aware
Will have uncontrollable muscle jerking and may be unable to speak
What is a Complex Focal Seizure?
There is loss of Consciousness
Patient is unaware
What are the symptoms of Focal seizures?
Dependent on where the focal deficit is located
What is the most common region affected in a focal seizure?
Temporal lobe
What are the features of a Temporal focal seizure?
Oral automatism: lip smacking, chewing, swallowing
Manual automatisms: picking, fumbling
Automatic behaviour: running, walking
Auras: déjà vu, feeling of fear, unpleasant smells
Auditory: buzzing, ringing, vertigo
What are the features of a Frontal focal seizure?
Predominantly motor symptoms: pelvic thrusting, bicycling, tonic posturing
Sexual automatisms
Bizarre behaviour
Vocalisations
What are the features of a Parietal focal seizure?
Parasthesias
Visual hallucinations
Visual illusions
More subjective and difficult to diagnose than other areas
What are the features of a Occipital focal seizure?
Visual hallucinations
Transient blindness
Rapid and forced blinking
Movement of head or eyes to the opposite side
What is required for a diagnosis of Epilepsy?
Must have had 2 or more seizures MORE THAN 24 hrs apart to be considered:
CT/MRI head - Examine HIPPOCAMPUS, check for bleeds and trauma
EEG: 3H2 wave in absence
Bloods: rule out metabolic/infection
What is the Treatment for epilepsy and seizures?
Sodium Valporate for generalised epilepsy
Carbamazepine for focal seizures
Surgical resection possible
What is a contraindication for using Sodium Valporate?
All females of childbearing age (15-45)
Sodium Valporate is Teratogenic
Instead use Lamotrigine
What is a complication of Epilepsy?
Status Epilepticus (NEURO EMERGENCY)
Epileptic seizures without a break back to back
OR
Seizure lasting >5 minutes
What is the treatment for Status Epilepticus?
Benzodiazepines:
Lorazepam 4mg IV
If not worked then Lorazepam again.
Then Phenytoin if second dose doesnt work.
What are the differences between an epileptic and non-epileptic seizure?
Epileptic Seizures have:
Eyes OPEN
Synchronous Movements
Can occur in sleep
What is the length of the spinal cord?
From C1-L1/2
Where is the conus medullaris and cauda equina?
At L3
Define Hemiplegia?
Paralysis to one side of the body
(usually due to a brain lesion)
Define Paraplegia?
Paralysis of both legs/lower body
(usually due to a spinal cord lesion)
What does the DCML tract convey information for?
Ascending tract for fine touch, 2pt discrimination and proprioception.
What is the pathway for the DCML
Travels in dorsal route
(Fasciculus Gracilis/Cuneatus)
Decussates in the medulla
What does the spinothalamic tract convey information for?
Ventral: Coarse Touch and pressure
Lateral: Pain and temperature
What is the pathway for the spinothalamic tract?
Ascending:
Enters at spinal level of nerve
ascends 1-2 spinal levels and then decussates
What information does the corticospinal tract convey?
Upper motor neurons for movement.
Decussates at the medulla
What are the nerve routes for the Knee jerk reflex?
L3/4
What are the nerve routes for the Big toe reflex?
L5
What are the nerve routes for the ankle Jerk reflex?
S1/2
What are the commonest causes of spinal cord injury?
Trauma
Vertebral compression fractures
Intervertebral disc disease - prolapse/herniation
Tumours
Infection
What are the common vertebral body neoplasms that can cause spinal compression?
Mets from:
Lungs
Breast
RCC
Melanoma
What are the different types of spinal cord compression?
Complete SC injury
Anterior SC injury
Posterior SC injury
Central SC injury
Brown-Sequard Syndrome
What is Spinal Cord Compression?
Compression of the spinal cord resulting in upper neurone signs and specific symptoms dependent on where compression is
What is the commonest cause of acute spinal cord compression?
Vertebral body neoplasms
What are the symptoms of spinal cord compression?
Sx depend on level of cord compression:
Progressive leg weakness
UMN signs - hyperreflexia, +tve babinski reflex and spasticity
Sensory loss below the lesion
What is the concern if there is sphincter involvement in spinal cord compression
This is a late and bad sign signalling a poorer prognosis
What would be the features of a complete spinal cord compression?
All motor and sensory function below the SCI level
What would be the features of an anterior spinal cord compression?
Disruption of anterior spinal cord or anterior spinal artery
Loss of motor function below the level
Loss of pain and temperature sensation (anterior column)
Preservation of fine touch and proprioception (posterior column)
What would be the features of a posterior spinal cord compression?
Disruption of posterior spinal cord or posterior spinal artery (rare)
Loss of fine touch and proprioception (posterior column)
Preservation of pain and temperature sensation (anterior column)
What would be the features of brown-Sequard syndrome?
Hemi-section of the spinal cord:
Ipsilateral spastic paralysis
Ipsilateral loss of vibration and proprioception
Contralateral loss of pain and temperature sensation
What is the primary investigation if suspecting a Spinal cord compression?
MRI Spinal cord ASAP:
(risk of permanent damage)
CT CAP - if malignancy suspected
What is the treatment for spinal cord compression?
Neurosurgery to decompress cord
Dexamethasone to reduce inflammation
What is Sciatica?
Sciatica refers to the symptoms associated with irritation of the sciatic nerve.
What spinal nerves form the sciatic nerve?
L4-S3 spinal roots
What is the innervation of the sciatic nerve?
The sciatic nerve supplies sensation to the lateral lower leg and the foot.
It supplies motor function to the posterior thigh, lower leg and foot.
What nerves are branches of the sciatic nerve?
Common peroneal nerve
Tibial nerve
What are the symptoms of Sciatica?
unilateral pain from the buttock radiating down the back of the thigh to below the knee or feet
paraesthesia (pins and needles), numbness and motor weakness
Reflexes may be affected depending on spinal root affected
What are the main causes of Sciatica?
Intervertebral Herniated/prolapsed disc
Tumours
Piriformis Syndrome
Spondylolisthesis
Spinal stenosis
What is Bilateral sciatica a red flag for?
Cauda Equina syndrome
What is the Socrates mnemonic for?
Assessing pain
S – Site
O – Onset
C – Character
R – Radiation
A – Associations
T – Timing
E – Exacerbating and relieving factors
S – Severity
What are the diagnostic investigations for sciatica?
Clinical Dx generally:
Can’t Do straight leg raise test without pain
May have:
XR
CT
MRI - if cauda equina suspected
What is the main treatment for sciatica?
Physiotherapy + Analgesia:
Amitriptyline
Duloxetine
What is Cauda Equina Syndrome (CES)?
surgical emergency where the nerve roots of the cauda equina at the bottom of the spine are compressed below the conus medullaris (L3)
What do the nerves of the cauda equina supply?
Sensation to the lower limbs, perineum, bladder and rectum
Motor innervation to the lower limbs and the anal and urethral sphincters
Parasympathetic innervation of the bladder and rectum
What are the main causes of CES?
Herniated disc (the most common cause)
Tumours, particularly metastasis
Spondylolisthesis (anterior displacement of a
vertebra out of line with the one below)
Abscess (infection)
Trauma
What is the most common cause of CES?
Lumber Herniation l4/5 or L5/S1
What are the main symptoms of CES?
Leg weakness w/ LMN signs (ipsilateral hypotonia, fasciculations, hyporeflexia)
Saddle anaesthesia - perianal numbmess
Bladder/Bowel dysfunction + sphincter involvement
What is the diagnostic investigation for CES?
MRI spinal cord (diagnostic)
Testing nerve roots/reflexes
What is the treatment for CES?
Neurosurgical input to consider lumbar decompression surgery
What is Brown-Sequard Syndrome
Hemi-section of the spinal cord (sagitally):
Presents with :
Ipsilateral UMN weakness/spastic paralysis
Ipsilateral loss of Vibration and proprioception due to DCML
Contralateral loss of pain and temperature due to spinothalamic
What cranial nerves arise from the brainstem?
CN3-CN12
What is the causes of Cranial nerve lesions?
Damage to the brainstem:
- Tumour
- MS
- Trauma
- Aneurysm
- Vertebral artery dissection resulting in infarction
- Infection - cerebellar abscess from ear
What are the symptoms of a CN3 palsy?
Ptosis
Down and out eye
Fixed and dilated pupil
Why do you get a down and out eye in a CN3 palsy?
Unopposed action of the Trochlear (CN4) and Abducens (CN6) cranial nerves
Why do you get a fixed and dilated pupil in a CN3 palsy?
Loss of parasympathetic outflow from the Edinger-Westphal nucleus supplying the pupillary sphincter and ciliary bodies.
What are the causes of a CN3 palsy?
- Raised ICP
- Diabetes
- Hypertension
- Giant cell arteritis
What are the symptoms of a CN4 palsy?
Diplopia (double vision) when looking down
“walking down stairs”
What are the causes of a CN4 palsy?
Rare:
Due to trauma of the orbit
What are the symptoms of a CN5 palsy?
- Jaw deviates to side of lesion
- Loss of corneal reflex
What are the causes of a CN5 Palsy?
Trigeminal Neuralgia (pain but no sensory loss)
VZV
nasopharyngeal cancer
What are the symptoms of a CN6 palsy?
Adducted eye
What are the causes of a CN6 palsy?
Raised ICP
MS
Wernicke’s Encephalopathy
Pontine Stroke
What are the symptoms of a combined CN3,4,6 palsy?
Non-Functional Eye
What are the causes of a combined CN3,4,6 palsy?
- Stroke
- Tumours
- Wernicke’s encephalopathy
What are the signs of a CN7 palsy?
unilateral facial weakness (motor component), altered taste (sensory component), and a dry mouth (parasympathetic component).
What are the causes of a CN7 palsy?
Bells Palsy
Fractures to pteroid bone
Parotic inflammation
Otitis Media
What is Bells Palsy?
Neurological condition that presents with a rapid onset of unilateral facial paralysis
What is clinically relevant about the control of the facial muscles?
The lower half of the faces only has contralateral innervation
Top half has bilateral. forehead sparing
How can you tell if a bells palsy is an UMN or LMN lesion?
UMN injured, lower half on contralateral side is weak but forehead is not as it has contralateral and ipsilateral innervation (bilateral)
LMN - weakness of all the muscles on the ipsilateral side of the face
How do you determine the level of CN7 lesion?
Proximal to pons - loss of all function (lacrimation, salivation, taste, facial weakness)
Lesion above chorda tympani (same as previous but does have lacrimation)
Distal Lesion to the stylomastoid foramen (facial weakness only)
How do you determine the level of CN7 lesion?
Proximal to pons - loss of all function (lacrimation, salivation, taste, facial weakness)
Lesion above chorda tympani (same as previous but does have lacrimation)
Distal Lesion to the stylomastoid foramen (facial weakness only)
What are the symptoms of a CN8 palsy?
Hearing impairment
Vertigo
Loss of balance
What are the causes of a CN8 palsy?
Skull fracture
Otitis Media
Tumours
Compression
What are the symptoms of a CN9 and CN10 palsy?
- Gag reflex issues
- Swallowing issues
- Vocal issues - hoarse voce
What are the causes of a CN9/CN10 palsy?
Jugular foramen lesion
What are the symptoms of a CN11 palsy?
Can’t shrug shoulders/turn head against resistance
What are the symptoms of a CN12 palsy?
Tongue deviation towards the side of the lesion
What is Motor Neuron Disease (MND)
Progressive neurodegenerative disease where both upper and lower motor neurons stop functioning but there is no effect on the sensory neurons.
What is the most common form of MND?
Amyotrophic Lateral Sclerosis (ALS)
Accounts for 50% of cases
What are the risk factors of MND?
Increased age >60 yrs
Male
FHx
Smoking
RUGBY
What genetic mutation is linked with MND?
SOD-1 mutation
What is the main motor tract in the body?
Corticospinal tract
UMN from precentral gyrus
Anterior (10% - no decussation)
Lateral (90% - Decussation in Medullary pyramids)
What are the different types of MND?
Amyotrophic Lateral Sclerosis (ALS)
Progressive Muscular Atrophy (PMA)
Primary Lateral Sclerosis (PLS)
Progressive Bulbar Palsy (PBP)
What are the signs of ALS?
UMN and LMN signs
What are the signs of PMA?
LMN only
Has best prognosis
What are the signs of PLS?
UMN signs only
What are the signs of PBP?
CN9-12 affected
Speech and swallowing issues
Worst prognosis
What are the signs of an Upper motor neuron (UMN) lesion?
Hypertonia
Rigidity + spasticity
Hyperreflexia
Babinski Reflex Positive
Power:
Arms - Flexors > Extensors
Legs - Flexors < Extensors
What are the signs of a Lower Motor Neuron (LMN) Lesion?
Hypotonia
Flaccidity + muscle wasting
Hyporeflexia
Fasciculations
Babinski Reflex Negative
Generally loss of power
What should you think if you see a patient with mixed Upper and lower motor neuron signs?
MND!!
Where is an UMN lesion?
Anywhere on a motor nerve between the pre-central gyrus to the anterior spinal cord
Where is a LMN lesion?
Anywhere on a motor nerve between the anterior spinal cord and the innervated muscle
What is NEVER affected in MND?
Eye muscles:
Affected in MS and MG
Sensory Function and Sphincters:
Affected in MS and Polyneuropathies
What are the symptoms of MND?
Progressive weakness
Falls
Speech and swallowing issues (in PBP)
What is split hand sign?
Disproportionate wasting of the thenar muscles compared to the hypothenar muscles
What are the clinical signs of MND?
Mixed UMN and LMN signs
Dysarthria / Dysphagia
Fasciculations
Split Hand Sign
What is the primary investigation for MND?
Clinical Dx due to mixed UMN/LMN picture
EMG - fibrillation potentials
What is the management of MND?
No cure - progressive
Supportive therapy:
Physiotherapy
Breathing support if needed
Pharmacological Tx:
Riluzole - anti-glutaminergic
What are the complications of MND?
Aspiration pneumonia
Respiratory failure
What is Myasthenia Gravis (MG)?
Autoimmune condition characterised by Autoantibodies against the nAChR at the neuromuscular Junction.
What type of Hypersensitivity reaction is Myasthenia Gravis?
Type 2
What are the risk factors for MG?
Females
FHx
Autoimmunity
Thymoma/ Thymic Hyperplasia
What is the prevalence of MG?
Generally more common in Females
Female peak (20-30yrs) - associated with autoimmune disease
Male peak (50-60yrs) - associated with Thymoma
What is the pathophysiology of MG?
85% Anti-nACh Receptors:
- Bind to post synaptic receptor and competitively inhibit ACh binding.
- ACh cannot bind during exertion and therefore there is progressive weakness of muscles
- Auto-ABs Will also bind to complement and cause NMJ destruction
15% Anti MuSK:
Inhibit MuSK from synthesising ACh Receptors so there is reduced expression on post synaptic membrane.
What are the symptoms of MG?
Lethargy
Muscle weakness that starts at head/neck and moves downwards
Weak eye muscles - diplopia
Ptosis
Jaw fatiguability - slurred speech
Swallowing difficult
What is the progression of weakness like in MG?
Worse during the day/with exertion
Better with rest
Due to more AChRs being required in exertion and therefore greater inhibiton
What are the clinical signs of MG?
ptosis
Head drop
Myasthenic Snarl - difficulty smiling
What is the primary investigation for MG?
Serology - Ab testing:
Anti-nACh-R Abs (85%)
Anti-MuSK Abs (15%)
Edrophonium Test
CT/MRI - look for Thymoma
What is the Edrophonium Test?
Give Edrophonium (neostigmine) and AChE inhibitor to increase ACh
Will give brief/temporary relief of Sx and increase muscle power
What is the first line treatment for MG?
1st Line: Reversible AChE inhibitors:
Rivastigmine, Neostigmine Pyridostigmine
2nd Line: Immunosuppressants
Prednisolone/Azathioprine
Potentially Monoclonal Abs (Rituximab)
What is the main complication of MG?
Myasthenic Crisis:
Severe acute worsening of Sx
Often Triggered by another illness (URTI)
Severe Respiratory weakness
What is the Treatment for Myasthenic Crisis?
Non-invasive ventilation:
BiPAP for Resp failure
IV Ig and plasma Exchange
What is a differential Diagnosis of Myasthenia Gravis?
Lambert Eaton Syndrome
What is Lambert Eaton Syndrome?
A NMJ syndrome which has similar Sx to MG.
Autoimmunity against VG-Ca channels thereby reducing ACh release at the NMJ causing muscle weakness.
What is the cause of Lambert Eaton Syndrome?
Unclear but typically occurs in Px with Small Cell Lung Cancer (SCLC)
What is the presentation of Lambert Eaton Syndrome?
Proximal muscle weakness that develops more slowly
Sx start at extremities and progress towards the head
Shares most of same Sx with MG
What is the difference between MG and Lambert Eaton Syndrome clinically?
Lambert Eaton Syndrome symptoms tend to improve following a period of strong muscle contraction.
Post Tetanic Potentiation
What is the Treatment for Lambert Eaton Syndrome?
Dx and Tx underlying condition (often SCLC)
Amifampridine - blocks K+ channels and increases ACh release
+ Steroids and Immunosuppressants
What is Syncope?
Transient loss of consciousness due to transient global reduction in cerebral perfusion with complete and rapid recovery
What are the classifications of the causes of syncope?
Neurally mediated: Vasovagal
Orthostatic (postural) syncope
Cardiac syncope
Structural
Arrythmias
What is vasovagal syncope?
Vagus nerve receives a strong signal:
Emotion, pain, temperature change
Activates Parasympathetic NS
Dilates blood vessels reducing cerebral perfusion
causing hypoperfusion of the brain leading to collapse
What is the prodrome of syncope?
Hot or clammy
Sweaty
Heavy
Dizzy or lightheaded
Vision going blurry or dark
Headache
What are the causes of primary syncope?
Dehydration
Missed meals
Extended standing in a warm environment, such as a school assembly
A vasovagal response to a stimuli, such as sudden surprise, pain or the sight of blood
What are the causes of secondary syncope?
Hypoglycaemia
Dehydration
Anaemia
Infection
Anaphylaxis
Arrhythmias
Valvular heart disease
Hypertrophic obstructive cardiomyopathy
What is Orthostatic syncope?
Syncope due to postural change (standing from sitting)
Occurs due to:
Upon standing blood pools in the lower limbs/lower abdomen → venous return decreases → transient ↓cardiac output
Sympathetic activation increases SV. reduction of Parasympathetic stimulation further increases HR and CO.
Failure of these mechanisms leads to orthostatic syncope
What are the primary investigations for syncope?
Clinical Hx and examination
Ix to rule out pathological causes:
Bloods - infection
FBC - anaemia
ECG- arrythmia
Glucose - Hypoglycaemia
B-hCG - ectopic pregnancy
What is the management of Syncope?
Confirm Dx to exclude underlying pathology
Avoid Dehydration
Avoid missing meals
Avoid standing still
What is a mononeuropathy?
A process of nerve damage that affects a single nerve
What is polyneuropathy?
Disorders of peripheral or cranial nerves, whose distribution is
usually symmetrical and widespread
What is Mononeuritis Multiplex?
A type of peripheral neuropathy where there is damage to several individual nerves due to systemic causes.
What are the causes of Mononeuritis Multiplex?
WARDS PLC:
- Wegener’s granulomatosis
- Aids/Amyloid
- Rheumatoid arthritis
- Diabetes mellitus
- Sarcoidosis
- Polyarteritis nodosa
- Leprosy
- Carcinoma
What is Peripheral Neuropathy?
Nerve pathology outside of the CNS that affects the peripheral nerves
What is the most common Mononeuropathy?
Carpal Tunnel Syndrome
What is the pathophysiology of Carpal Tunnel Syndrome?
Compression/pressure of the Median Nerve as it passes through the Flexor Retinaculum “carpal tunnel”
What are the causes of Carpal Tunnel Syndrome?
Mostly Idiopathic
Also:
Hypothyroidism
Acromegaly
Rheumatoid Arthritis
Obesity
Diabetes
Pregnancy
Repetitive Strain Injury
What are the mechanisms of Peripheral Neuropathy?
Demyelination
Axonal Damage - Nerve cut
Nerve Compression
Vasa Nervorum Infarction
Wallerian Degeneration (Nerve lesion and distal end dies)
What are the causes of Peripheral Neuropathy?
ABCDE:
A – Alcohol
B – B12 deficiency
C – Cancer and Chronic Kidney Disease
D – Diabetes and Drugs (e.g. isoniazid, amiodarone and cisplatin)
E – Every vasculitis
Who is more likely affected by Carpal Tunnel Syndrome?
Females due to narrower wrists so more likely to have compression
Over 30s
What is the presentation of Carpal Tunnel Syndrome?
Gradual Onset of Sx
Start off as intermittent Sx
Worse at night
What are the Symptoms of Carpal Tunnel Syndrome?
Sensory Symptoms: Palmer aspects and full fingertips of:
Thumb
Index and middle finger
The lateral half of ring finger
Motor Symptoms: Thenar Muscles
Flexor Pollicis Brevis
Abductor Pollicis
Opponens Pollicis
What are the sensory symptoms of Carpal Tunnel Syndrome?
Numbness
Paraesthesia (pins and needles or tingling)
Burning sensation
Pain
What are the motor symptoms of Carpal Tunnel Syndrome?
Weakness of thumb movements
Weakness of grip strength
Difficulty with fine movements involving the thumb
Wasting of the thenar muscles (muscle atrophy)
What nerve is affected in Carpal Tunnel Syndrome?
Which branch is involved for the sensory symptoms?
MEDIAN Nerve
Sensory Sx: Palmer Digital Cutaneous Branch
What are the tests to diagnose Carpal Tunnel Syndrome?
Phalen Test
Tinel Test
What is the Phalen Test?
Put the backs of their hands together in front of them with the wrists bent inwards at 90 degrees.
The test is positive when this position triggers the sensory symptoms of carpal tunnel, with numbness and paraesthesia in the median nerve distribution.
What is the Tinel Test?
Tapping Median nerve in carpal tunnel causes sensory Sx
(Tinels = Tapping)
What is the management for Carpal Tunnel Syndrome?
Wrist splints that maintain a neutral position
Steroid injections
Surgery - decompression (last resort)
What are the nerve roots for the Median Nerve?
C6-T1
What can lead to compression of the Median Nerve to cause Carpal Tunnel Syndrome?
Swelling of contents within Carpal Tunnel
Narrowing of the Carpal Tunnel
What is the nerve roots of the radial nerve?
C5-T1
What is the classical presentation of a radial nerve palsy?
Wrist drop
(with elbow flexed and arm pronated
What muscles are innervated by the Radial Nerve?
BEST:
Brachioradialis
Extensors of forearm
Supinator
Triceps
What muscles are innervated by the Median Nerve?
2LOAF:
- 2 Lumbricals
- Opponens pollicis
- Abductor pollicis brevis
- Flexor pollicis brevis
What can cause wrist drop?
Damage to the radial nerve
Compression of the radial nerve at the humerus
What is the nerve roots of the Ulnar Nerve?
C8-T1
What is the classical presentation of an ulnar nerve palsy?
Claw hand (4th/5th fingers claw up)
What is the treatment of Wrist drop and Claw hand?
Splint
Analgesia
What are the nerve roots for the common peroneal nerve?
L4-S1
(Branch off the Sciatic nerve)
What is the sign of a Sciatic/Common peroneal nerve Palsy?
Foot drop
What Drugs can cause peripheral Neuropathy?
amiodarone
isoniazid
vincristine
nitrofurantoin
metronidazole
What are the main symptoms of peripheral neuropathy?
numbness and tingling in the feet or hands
burning, stabbing or shooting pain in affected areas
loss of balance and co-ordination
muscle weakness, especially in the feet
What is Charcot-Marie-Tooth Syndrome?
Inherited sensory and motor peripheral neuropathy disease caused by an autosomal dominant mutation in PUP22 gene on chromosome17
What are the genetics of Charcot-Marie-Tooth Syndrome?
Mutation in PUP22 gene
Chromosome 17
+ multiple others
What is the pathophysiology of Charcot-Marie-Tooth Syndrome?
Generally mutations cause dysfunction of the myelin or axons leading to neuropathy
Different mutations in different genes have different pathophysiology’s.
When do symptoms onset in Charcot-Marie-Tooth Syndrome?
Usually before the age of 10.
May appear after 40yrs
What are the classical features of Charcot-Marie-Tooth Syndrome?
Foot Drop (common peroneal palsy)
Distal muscle wasting (stork legs)
Hammer Toes (toes always curled up)
Pes Cavus (high foot arches)
Peripheral sensory loss
Reduce tendon reflexes
What is the Diagnostic investigation for Charcot-Marie-Tooth Syndrome?
Clinical Dx
Nerve biopsy
Genetic Testing
What is the treatment for Charcot-Marie-Tooth Syndrome?
Supportive Tx:
Physiotherapists
Orthopaedics
Occupational Therapists
What is Duchenne Muscular Dystrophy (DMD)?
X-Linked recessive condition caused by a mutation in the Dystrophin Gene
Who presents with DMD?
Boys Exclusively:
Age of onset is around 3-5 years old
Explain the genetics of DMD?
X linked Recessive condition.
Therefore mother with 1 faulty gene:
Daughters - 50% chance of being carrier
Sons - 50% chance of being affected
What is the pathophysiology of DMD?
Lack of Dystrophin gene (vital part of muscle fibre) means that the muscles are not protected from being broken down by enzymes
Therefore in DMD you get progressive wasting and weakness of muscle as they are broken down.
The muscle tissue is then replaced by fibrofatty tissue
Most Px in wheelchair by teenage years
What cardiovascular condition is associated with DMD?
DCM
Dystrophin gene in heart muscle not present which is normally involved in membrane stability.
Therefore in DMD there is damage to the cellular mechanisms causing dilation of
ventricles due to wasting of the cardiac muscle causing cardiomyopathy
What are the symptoms of DMD?
Child struggles to get up from lying down
(GOWER’S sign)
Skeletal deformities - scoliosis
What are the diagnostic tests for DMD?
Prenatal tests and DNA genetic testing
What is Gower’s Sign?
Children with proximal muscle wasting stand up in a specific way:
They get onto their hands and knees, then push their hips up and backwards like the “downward dog” yoga pose.
They then shift their weight backwards and transfer their hands to their knees.
Whilst keeping their legs mostly straight they walk their hands up their legs to get their upper body erect
What is the treatment for DMD?
Purely Supportive: No cure
Physiotherapy
Occupational Therapy
Medical appliances - Wheelchairs
Tx of complications - Scoliosis/DCM
What is the life expectancy of a child with DMD?
25-35 years
What may be used to slow DMD muscular progression?
Oral steroids have been shown to delay progression by 2 years.
Creatine Supplements may improve some strength
What is Wernicke’s Encephalopathy?
Reversible severe cognitive decline due to severe Vitamin B1 (thiamine) deficiency.
What is the cause of Wernicke’s Encephalopathy?
Alcohol abuse
Alcohol massively decreases Thiamine levels leading to deficiency
What is the classic triad of Wernicke’s Encephalopathy?
Ataxia
Confusion
Ophthalmoplegia
How is Wernicke’s Encephalopathy Diagnosed?
Clinically Recognised
Macrocytic Anaemia
Deranged LFTs
What is the treatment of Wernicke’s Encephalopathy?
Parenteral PABRNEX (Vit B1) for 5 days.
Oral thiamine Prophylactically
What is the main complication of Wernicke’s Encephalopathy?
Korsakoff Syndrome:
Caused when WE left for too long without Tx
Leads to Sx with disproportionate memory loss and irreversible damage.
What bacteria causes Tetanus?
Clostridium Tetani (Gram +tve Bacillus)
Inoculation from dirty soil
What is the Pathophysiology of Tetanus?
Tetanospasmin Toxin produced.
Travels up axons
Blocks the release of the inhibitory neurotransmitters GABA and glycine
resulting in continuous motor neuron activity → continuous muscle contraction →
lockjaw and respiratory paralysis
What is the Treatment for Tetanus?
Primary Vaccine
What is Creutzfeldt-Jakub disease?
Prion disease “Mad cow Disease”
Idiopathic misfolded proteins deposited in the cerebrum and cerebellum
This leads to severe cerebellar Dysfunction.
There is NO Tx
What is the affect of Botulinum toxin?
Blocks acetylcholine (ACh) release leading to flaccid paralysis
What are the main Primary Brian tumours?
Astrocytoma
Oligodendrocytoma
Meningioma
Schwannoma
What is the most common Primary brain tumour?
Astrocytoma (90% of Primary brain tumours)
2nd Most common Paediatric cancer
What are the common causes of secondary brain tumours?
Metastases from:
Non-Small Cell Lung Cancer (NSCLC)
Breast
Small Cell Lung Cancer (SCLC)
Melanoma
RCC
Gastric Cancer
What is the most common cause of a brain tumour?
Secondary brain tumour from a NSCLC
What is the treatment for Secondary brain tumours?
Often Palliative Care (due to being mets from high grade tumours)
Chemotherapy
What is the grading for an astrocytoma?
Graded 1-4
1 = Benign
4 = Glioblastoma
What is a Glioma?
A tumour made arising from the Glial cells:
Astrocytoma (glioblastoma multiforme is the most common)
Oligodendroglioma
Ependymoma
What are the symptoms of a brain tumour?
Often ASx when small:
Focal neurological Sx as they develop
Will often RAISE ICP
Papilledema (due to raised ICP)
Cushing Triad (Increased PP, Bradycardia, Irregular Breathing)
Epileptic Seizures
Lethargy
Weight Loss
What is papilloedema?
Swelling of the optic disc that occurs secondary to a raised ICP.
This is often picked up on Fundoscopy
What is a Glioblastoma multiforme?
Glioblastoma (GBM), also referred to as a grade IV astrocytoma, is a fast-growing and aggressive brain tumour
Often fatal within 1 year of Dx
What are the investigations for a brain tumour?
MRI head - locate tumour
Biopsy - determine grade
Fundoscopy - Papilloedema due to raised ICP
What are the investigations for a brain tumour?
MRI head - locate tumour
Biopsy - determine grade
Fundoscopy - Papilloedema due to raised ICP
NO LP as this is CI in raised ICP
What is the management of brain tumours?
Depends on type and Grade:
Surgical removal if possible/reduce ICP
Chemotherapy/Radiotherapy Before/during/after surgery.
Palliative Care
