Neurology Flashcards
Define Alzheimer’s disease?
Alzheimer’s disease (AD) is a progressive degenerative disease of the brain accounting for the majority of dementia seen in the UK
What are the risk factors for Alzheimer’s disease?
Increasing age
Family history
Inherited autosomal trait
Apoprotein E allele E4
Caucasian ethnicity
Down syndrome
What autosomal dominant traits are associated with an increased risk of Alzheimer’s disease?
Mutations in:
- The amyloid precursor protein (chromosome 21)
- Presenilin 1 (chromosome 14)
- Presenilin 2 (chromosome 1) genes
What genetic condition is associated with an increased risk of Alzheimer’s disease?
Down syndrome
What macroscopic pathological changes are seen in Alzheimer’s disease?
Widespread cerebral atrophy, particularly involving the cortex and hippocampus
What microscopic pathological changes are seen in Alzheimer’s disease?
Cortical plaques due to deposition of type A-Beta-amyloid protein and intraneuronal neurofibrillary tangles caused by abnormal aggregation of the tau protein
Hyperphosphorylation of the tau protein has been linked to AD
What biochemical pathological changes are seen in Alzheimer’s disease?
There is a deficit of acetylcholine from damage to an ascending forebrain projection
What are some non-pharmacological managements of Alzheimer’s disease?
A range of activities to promote wellbeing that are tailored to the person’s preference
Group cognitive stimulation therapy for patients with mild and moderate dementia
Group reminiscence therapy and cognitive rehabilitation
What pharmacological management can be given for mild to moderate Alzheimer’s disease?
Donepezil, Galantamine and Rivastigmine
What types of drugs are donepezil, galantamine and rivastigmine?
Acetylcholinesterase inhibitors
What second line pharmacological management can be given for Alzheimer’s disease?
Memantine
What type of drug is memantine?
NMDA receptor antagonist
Under what conditions can the second line pharmacological management be used for Alzheimer’s disease?
For moderate Alzheimer’s who are intolerant of, or have a contraindication to, acetylcholinesterase inhibitors.
As an add-on drug to acetylcholinesterase inhibitors for patients with moderate or severe Alzheimer’s.
Monotherapy in severe Alzheimer’s
What feature would contraindicate use of donepezil?
Bradycardia
What is an adverse effect of donepezil?
Insomnia
List some causes of Parkinsonism?
Parkinson’s disease
Drug-induced e.g. antipsychotics, metoclopramide*
Progressive supranuclear palsy
Multiple system atrophy
Wilson’s disease
Post-encephalitis
Dementia pugilistica (secondary to chronic head trauma e.g. boxing)
Toxins: carbon monoxide, MPTP
What is the cause of parkinsonism?
Parkinson’s disease is a progressive neurodegenerative condition caused by degeneration of dopaminergic neurons in the substantia nigra.
What is the classic triad of parkinson’s disease?
The reduction in dopaminergic output results in a classical triad of features: bradykinesia, tremor and rigidity.
The symptoms of Parkinson’s disease are characteristically asymmetrical.
Describe the bradykinesia seen in Parkinson’s disease?
Poverty of movement also seen, sometimes referred to as hypokinesia
Short, shuffling steps with reduced arm swinging
Difficulty in initiating movement
Describe the tremor seen in Parkinson’s disease?
Most marked at rest, 3-5 Hz
Worse when stressed or tired, improves with voluntary movement
Typically ‘pill-rolling’, i.e. in the thumb and index finger
What are some other ‘axillary’ characteristics seen in Parkinson’s disease?
Mast-like facies
Flexed posture
Micro-graphia
Drooling of saliva
Impaired olfaction
REM sleep disturbance
Fatigue
Postural hypertension
What is the first line management for Parkinson’s disease if motor symptoms are affecting the quality of life?
Levodopa nearly always combined with a decarboxylase inhibitor (e.g. carbidopa or benserazide)
Why is levodopa combined with a decarboxylase inhibitor for Parkinson’s therapy?
This prevents the peripheral metabolism of levodopa to dopamine outside of the brain and hence can reduce side effects
List some common side effects of levodopa?
Dry mouth
Anorexia
Palpitations
Postural hypotension
Psychosis
What pharmacological agent can be given for excessive salivation in Parkinson’s disease?
Glycopyrronium bromide
What pharmacological agent should be considered if a patient with Parkinson’s disease develops orthostatic hypotension? What is the mechanism of this drug?
Midodrine - acts on peripheral alpha-adrenergic receptors to increase arterial resistance
What pharmacological agent should be considered if excessive daytime sleepiness occurs in a patient with Parkinson’s disease?
Modafinil
What is the first line management for Parkinson’s disease if motor symptoms are NOT affecting the quality of life?
Dopamine agonist (non-ergot derived - bromocriptine, cabergoline)
Levodopa
Monoamine oxidase B (MAO-B) inhibitor
List some dopamine receptor agonists that are used in the treatment of Parkinson’s disease?
Bromocriptine
Ropinirole
Cabergoline
Apomorphine
What investigations should be organised before prescribing ergot-derived dopamine receptor agonists?
Echocardiogram
ESR
Creatinine
Chest x-ray
Due to being associated with pulmonary, retroperitoneal and cardiac fibrosis
What class of Parkinson’s drugs have potential for impulse control disorders?
Dopamine receptor agonists
What is the mechanism of action of MAO-B inhibitors? Give an example of this class of drug?
Monoamine Oxidase-B inhibitors work by inhibiting the breakdown of dopamine secreted by the dopaminergic neurones.
Selegiline
Give some examples of COMT inhibitors for Parkinson’s disease?
Entacapone
Tolcapone
What is the mechanism of action of COMT inhibitors?
Catechol-O-Methyl Transferase inhibitors - an enzyme involved in the breakdown of dopamine, and hence may be used as an adjunct to levodopa therapy
What is ‘end-of-dose’ wearing off phenomenon in Parkinson’s disease management?
Symptoms often worsen towards the end of dosage interval. This results in a decline of motor activity
What is ‘on-off phenomenon’ in Parkinson’s disease management?
Large variations in motor performance, with normal function during the ‘on’ period, and weakness and restricted mobility during the ‘off’ period
What side-effects may be seen at peak dose of levadopa?
Dystonia, chorea and athetosis (involuntary writhing movements)
What is Huntington’s disease?
Huntington’s disease is an inherited neurodegenerative condition.
It is a progressive and incurable condition that typically results in death 20 years after the initial symptoms develop.
In what pattern is the gene for Huntington’s disease inherited?
Autosomal dominant fashion
What type of genetic disease is Huntington’s disease?
Trinucleotide repeat disorder: repeat expansion of CAG
As Huntington’s disease is a trinucleotide repeat disorder, the phenomenon of anticipation may be seen, where the disease is presented at an earlier age in successive generations
What is the genetic mechanism of Huntington’s disease?
Due to defect in huntingtin gene on chromosome 4
Results in degeneration of cholinergic and GABAergic neurons in the striatum of the basal ganglia
What are the classical features of Huntington’s disease?
Typically develop after 35 years old:
Chorea
Personality changes (e.g. irritability, apathy, depression and intellectual impairment)
Dystonia
Saccadic eye movements
What is motor neurone disease?
Motor neuron disease is a neurological condition of unknown cause which can present with both upper and lower motor neuron signs.
What are the main types of motor neurone disease?
Amyotrophic lateral sclerosis
Primary lateral sclerosis
Progressive muscular atrophy
Progressive bulbar palsy
In what motor neurone disease is there a potential genetic component and what chromosome does the gene in question reside on?
Amyotrophic lateral sclerosis - in familial cases the gene responsible lies on chromosome 21 and codes for superoxide dismutase
What does UMN sign mean?
Upper motor neurone (UMN) signs are a set of symptoms that can indicate a lesion in the brainstem, cerebral cortex, or spinal cord.
What does LMN sign mean?
Lower motor neurone (LMN) signs are a set of symptoms that can indicate a lesion in the lower (anterior horn cell, motor nerve roots or peripheral motor nerve) motor neurones.
List some classical UMN signs?
Disuse atrophy (minimal) or contractures
Increased tone (spasticity/rigidity) +/- ankle clonus
Pyramidal pattern of weakness (extensors weaker than flexors in arms, and vice versa in legs)
Hyperreflexia
Upgoing plantars (Babinski sign)
List some classical LMN signs?
Marked atrophy
Fasciculations
Reduced tone
Variable patterns of weakness
Reduced or absent reflexes
Downgoing plantars or absent response
What would the pattern of signs be in ALS?
LMN signs in arms and UMN signs in legs
What would the pattern of signs be in PLS?
UMN signs only
What would the pattern of signs be in PMA?
LMN signs only
Affects distal muscles before proximal
What would the pattern of signs be in PBP?
Palsy of the tongue
Muscles of chewing/swallowing and facial muscles due to loss of function of brainstem motor nuclei
Which subclass of motor neurone disease carries the worst and best prognosis?
Progressive muscular atrophy - best prognosis
Progressive bulbar palsy - worst prognosis
A motor neurone disease with mixed UMN and LMN signs would be which subtype?
Amyotrophic lateral sclerosis
A motor neurone disease with UMN signs only would be which subtype?
Primary lateral sclerosis
A motor neurone disease with LMN signs only and affects distal muscles before proximal ones would be which subtype?
Progressive muscular atrophy
Palsy of the tongue, muscles of chewing/swallowing and facial muscles due to loss of function of brainstem motor nuclei would be which motor neurone disease?
Progressive bulbar palsy
What symptoms are ‘spared’ in motor neurone disease?
Doesn’t affect external ocular muscles
No cerebellar signs
Abdominal reflexes are usually preserved
Sphincter dysfunction if present is a late feature
What is the pharmacological management for motor neurone disease?
Riluzole
Prolongs life for about 3 months
What is the mechanism of action of riluzole?
Prevents stimulation of glutamate receptors
What is the non-pharmacological management for motor neurone disease?
Non-invasive ventilation (usually BIPAP) is used at night (survival benefit - 7 months)
PEG tube for nutritional support
What is multiple sclerosis?
Multiple sclerosis is chronic cell-mediated autoimmune disorder characterised by demyelination in the central nervous system
What is relapsing-remitting multiple sclerosis?
Acute attacks (e.g. last 1-2 months) followed by periods of remission
Most common form (85%)
What is secondary progressive multiple sclerosis?
Describes relapsing-remitting patients who have deteriorated and have developed neurological signs and symptoms between relapses.
65% of patients with relapsing remitting will develop secondary progressive within 15 years of diagnosis
What is primary progressive multiple sclerosis?
Symptoms get progressively worse from diseaseonsetwithno periods of remission
10% of patients. More common in older people
What is progressive relapsing multiple sclerosis?
One constant attack but there are bouts superimposed during which the disability increases even faster
What are the visual features of multiple sclerosis?
Optic neuritis
Optic atrophy
Uhthoff’s phenomenon: worsening of vision following rise in body temperature
Internuclear ophthalmoplegia
What are the sensory features of multiple sclerosis?
Pins and needles
Numbness
Trigeminal neuralgia
Lhermitte’s syndrome: paraesthesiae in limbs on neck flexion
What are the motor features of multiple sclerosis?
Spastic weakness: most commonly seen in the legs
What are the cerebellar features of multiple sclerosis?
Ataxia: more often seen during an acute relapse than as a presenting symptom
Tremor
What are some other signs of multiple sclerosis?
Urinary incontinence
Sexual dysfunction
Intellectual deterioration
What would multiple sclerosis show on an MRI?
High signal T2 lesions
Periventricular plaques
Dawson fingers: often seen on FLAIR images - hyperintense lesions penpendicular to the corpus callosum
High signal T2 lesions, periventricular plaques and Dawson’s fingers on an MRI would indicate what?
Multiple sclerosis
What would analysis of CSF in multiple sclerosis show?
Oligoclonal bands (and not in serum)
Increased intrathecal synthesis of IgG
Oligoclonal bands (and not in serum) and increased intrathecal synthesis of IgG in CSF would indicate what pathology?
Multiple sclerosis
What is the management for multiple sclerosis during an acute relapse?
High-dose steroids (e.g. oral or IV methylprednisolone) may be given for 5 days to shorten the length of an acute relapse.
Shorten length of relapse but do not alter degree of recovery.
What disease modifying drugs should be used first-line in patients with multiple sclerosis?
Natalizumab
Ocrelizumab
Fingolimod
What is the mechanism of action of natalizumab?
A recombinant monoclonal antibody that antagonises alpha-4 beta-1-integrin found on the surface of leucocytes inhibit migration of leucocytes across the endothelium across the blood-brain barrier
What is the mechanism of action of fingolimod?
Sphingosine 1-phosphate (S1P) receptor modulator prevents lymphocytes from leaving lymph nodes
What is the management for fatigue in multiple sclerosis?
Rule out other causes e.g. anaemia, thyroid, depression
Trial of amantadine
What is the management for spasticity in multiple sclerosis?
Baclofen and gabapentin are first-line.
Other options include diazepam, dantrolene and tizanidine
What is the management for oscillopsia in multiple sclerosis?
Gabapentin
What are the indications for disease modifying drugs in relapsing remitting multiple sclerosis?
2 relapses in past 2 years + able to walk 100m unaided
What are the indications for disease modifying drugs in secondary progressive multiple sclerosis?
2 relapses in past 2 years + able to walk 10m (aided or unaided)
What is the pattern of inheritance of Duchenne muscular dystrophy?
X-linked recessive inherited disorder in the dystrophin genes required for normal muscular function.
What are the classical features of Duchenne muscular dystrophy?
Progressive proximal muscle weakness from 5 years
Calf pseudohypertrophy
Gower’s sign: child uses arms to stand up from a squatted position
30% of patients have intellectual impairment
What are the investigations for Duchenne muscular dystrophy?
Raised creatinine kinase
Genetic testing is GOLD STANDARD
What is bulbar palsy?
A unilateral lower motor neurone lesion of cranial nerves IX, X, XI and XII, and it’s caused by a lesion in the medulla that affects the nucleus ambiguus and the hypoglossal nucleus.
What are the classical features of bulbar palsy?
Characterised by weakness or paralysis of muscles innervated by the cranial nerves located in the brainstem.
These cranial nerves control functions such as swallowing, speech, facial movements and respiratory functions
Symptoms specifically depends on the affects cranial nerves
What is chronic fatigue syndrome (myalgic encephalomyelitis)?
Diagnosed after at least 3 months of disabling fatigue affecting mental and physical function more than 50% of the time in the absence of other disease which may explain symptoms
What is narcolepsy?
Narcolepsy is a chronic sleep boundary disorder that affects the control of sleep and wakefulness with rapid eye movement sleep (REM) intrusion into the wake state
What gene and protein is narcolepsy associated with?
HLA-DR2 is the gene
Low levels of orexin (hypocretin), a protein which is responsible for controlling appetite and sleep patterns
What is the management for narcolepsy?
Daytime stimulants - modafinil
Nightime sodium oxybate
What is normal pressure hydrocephalus? What is it thought to be caused by?
Normal pressure hydrocephalus is a reversible cause of dementia seen in elderly patients. It is thought to be secondary to reduced CSF absorption at the arachnoid villi.
What is the classic triad of features seen in normal pressure hydrocephalus?
Urinary incontinence
Dementia and bradyphrenia
Gait abnormality (may be similar to Parkinson’s disease)
What would the triad of urinary incontinence, dementia and bradyphrenia, gait abnormality (may be similar to Parkinson’s disease) suggest?
Normal pressure hydrocephalus
What would normal pressure hydrocephalus present with on imaging?
Hydrocephalus with ventriculomegaly in the absence of, or out of proportion to, sulcal enlargement
Ventriculomegaly without sulcal enlargement on imaging of the brain would indicate what?
Normal pressure hydrocephalus
What is the management of normal pressure hydrocephalus?
Ventriculoperitoneal shunting
What are the complications of ventriculoperitoneal shunting?
Around 10% of patients who have shunts experience significant complications such as seizures, infection and intracerebral haemorrhages
What is Meniere’s disease?
Meniere’s disease is a disorder of the inner ear of unknown cause.
It is characterised by excessive pressure and progressive dilation of the endolymphatic system.
What are the classical features of Meniere’s disease?
Recurrent episodes of vertigo, tinnitus and hearing loss (sensorineural).
Aural fullness or pressure
Nystagmus and positive Romberg’s test
Symptoms are typically unilateral
What is the management for acute attacks of Meniere’s disease?
Buccal or intramuscular prochlorperazine
What is the prevention management for Meniere’s disease?
Betahistine and vestibular rehabilitation exercises may be of benefit
What is the classic triad of Wernicke’s encephalopathy?
Confusion
Ataxia
Nystagmus/ophthalmoplegia
What is Wernicke’s encephalopathy?
Wernicke’s encephalopathy is a neuropsychiatric disorder caused by thiamine deficiency which is most commonly seen in alcoholics
What is the classic pentad of Korsakoff syndrome?
Confusion
Ataxia
Nystagmus/ophthalmoplegia
Amnesia (retrograde and anterograde)
Confabulation
What is the management for Wernicke’s encephalopathy?
Pabrinex (IV B/C vitamins)
Replacement of thiamine
What mnemonic can be used for features of Wernicke’s encephalopathy?
A useful mnemonic to remember the features of Wernicke’s encephalopathy is CAN OPEN
Confusion
Ataxia
Nystagmus
Ophthamoplegia
PEripheral
Neuropathy
What is temporal arteritis?
A vasculitis of unknown cause that affects medium and large-sized vessels arteries.
It occurs in those over 50 years old, with a peak incidence in patients who are in their 70s.
What are the classic features of temporal arteritis?
Headache
Jaw claudication
Ocular complications
What is the normal age of a patient with temporal arteritis?
Over 50 years old with peak incidence at 70s
What is the main ocular complication seen in temporal arteritis?
Anterior ischemic optic neuropathy accounts for the majority of ocular complications.
It results from occlusion of the posterior ciliary artery (a branch of the ophthalmic artery) → ischaemia of the optic nerve head.
What would fundoscopy show in a patient with temporal arteritis?
Swollen pale disc and blurred margins
Swollen pale disc and blurred margins on fundoscopy would indicate what?
Anterior ischemic optic neuropathy - temporal arteritis
What would the management of temporal arteritis be if there is no visual loss?
High-dose prednisolone
What would the management of temporal arteritis be if there is evolving visual loss?
IV methylprednisolone is usually given prior to starting high-dose prednisolone
Aside from high-dose glucocorticoids, what else should be prescribed in temporal arteritis?
Alendronate (bisphosphonates)
Define stroke?
A stroke (also known as cerebrovascular accident, CVA) represents a sudden interruption in the vascular supply of the brain.
What about the metabolism of neural tissue means that strokes are devastating?
Neural tissue is completely dependent on aerobic metabolism so any problem with oxygen supply can quickly lead to irreversible damage.
What are the two types of stroke?
Ischeamic - 85% - ‘Blockage’ in the blood vessel stops blood flow
Haemorrhagic - 15% - Blood vessel ‘bursts’ leading to reduction in blood flow
What is the difference between a stroke and TIA?
TIA describes the sudden onset of a focal neurologic symptom and/or sign lasting typically less than an hour, brought on by a transient decrease in blood flow. A stroke on the other had will cause permanent damage.
What are the subtypes of ischaemic stroke?
Thrombotic stroke - thrombosis from large vessel
Embolic stroke - blood clot, fat, air, bacteria
What are the subtypes of haemorrhagic stroke?
Intracerebral haemorrhage - bleeding within the brain
Subarachnoid haemorrhage - bleeding on the surface of the brain
What would the symptoms of a cerebral hemisphere infarct be?
Contralateral hemiplegia: Initially flaccid then spastic
Contralateral sensory loss
Homonymous hemianopia
Dysphasia
What would the symptoms of a brainstem infarct be?
May result in more severe symptoms including quadriplegia and lock-in-syndrome
What would the symptoms of a lacunar infarct be?
May result in pure motor, pure sensory, mixed motor and sensory signs or ataxia
What classification system is used to classify strokes based on the initial symptoms?
Oxford stroke classification (also known as the Bamford classification)
What is the Oxford stroke classification (Bamford classification) used for?
Used to classify strokes based on the initial symptoms
What criteria are assessed in the Oxford stroke classification (Bamford classification)?
- Unilateral hemiparesis and/or hemisensory loss of the face, arm & leg
- Homonymous hemianopia
- Higher cognitive dysfunction e.g. dysphasia
How would a total anterior circulation infarct present and what arteries would be involved?
All three of the Oxford stroke classification (Bamford classification)
Involves the middle and anterior cerebral arteries
How would a partial anterior circulation infarct present and what arteries would be involved?
2/3 of the Oxford stroke classification (Bamford classification)
Involves the smaller arteries of anterior circulation e.g. upper and lower division of the middle cerebral arteries
How would a lacunar infarct present and what arteries would be present?
1 of the following:
- Unilateral weakness (and/or sensory deficit) of face and arm, arm and leg or all three.
- Pure sensory stroke.
- Ataxic hemiparesis
How would a posterior circulation infarct present and what arteries would be involved?
Presents with 1 of the following:
- cerebellar or brainstem syndromes
- loss of consciousness
- isolated homonymous hemianopia
Involves the vertebrobasilar arteries
What symptoms may be useful to differentiate between a ischaemic or haemorrhagic stroke?
Haemorrhagic stroke patients are more likely to have:
Decreased level of consciousness.
Headache
Nausea and vomiting
Seizures
What is the first line investigation for a stroke?
Non contrast CT of the head
MRI can also be used
What is the first line management for an ischaemic stroke?
300mg aspirin*
*only if a haemorrhagic stroke has been excluded with brain imaging
Cholesterol >3.5 mmol/l then give statin
What is the criteria for thrombolysis for stroke?
Administered within 4.5 hours of onset of stroke symptoms
Haemorrhagic stroke has been excluded
Blood pressure to be lowered to 185/110 mmHg
What pharmacological agents are given for thrombolysis in stroke?
Alteplase
Tenecteplase
What is the secondary prevention pharmacological agent for stroke?
Clopidogrel
Aspirin + modified-release (MR) dipyridamole if contraindicated
What is the immediate management for TIA with symptoms that have resolved and are awaiting specialist review in 24 hours?
300mg Aspirin
What is the management for TIA when reviewed by a specialist and at high risk for further events?
Aspirin 300mg then 75mg OD until diagnosis confirmed
Then
Clopidogrel 300mg then 75mg OD
What is the long term secondary prevention for TIA?
Clopidogrel 75mg OD
Define subarachnoid haemorrhage?
An intracranial haemorrhage that is defined as the presence of blood within the subarachnoid space
What is the most common cause of subarachnoid haemorrhage?
Trauma to the head - called traumatic SAH
List some causes of spontaneous SAH?
Intercranial (berry) aneurysm (85%)
Ateriovenous malformation
Pituitary apoplexy
Mycotic (infective aneurysms)
What are some conditions associated with berry aneurysms?
Hypertension
Polycystic kidney disease
Ehlers-Danlos syndome
Coarctation of the aorta
What are the investigations for SAH?
Non-contrast CT of the head
More than 6 hours from symptoms = Also lumbar puncture, but this should be done after 12 hours
What are the subsequent investigations for spontaneous SAH?
CT intracranial angiogram - to identify vascular lesion
+/- digital subtraction angiogram (catheter angiogram)
What pattern of bleeding would a SAH show on CT?
Hyperdense/bright tissue typically distributed in the basal cisterns, sulci and in severe cases the ventricular system.
Hyperdense/bright tissue typically distributed in the basal cisterns, sulci and in severe cases the ventricular system would suggest what pathology?
Subarachnoid haemorrhage
What is the management for confirmed aneurysmal SAH?
Bed rest
Analgesia
Venous thromboembolism prophylaxis
Discontinuation of antithrombotics (reversal of anticoagulation if present)
What are the complications of aneurysmal SAH?
Re-bleeding - repeat CT
Hydrocephalus - external ventricular drain
Vasospasm
Hyponatraemia
Seizures
How is vasospasm in subarachnoid haemorrhage prevented?
Nimodipine
What would the characteristic shape of a subdural haemorrhage be on a head CT?
Follow the contour of the brain and form a crescent-shape and cross suture lines.
What would the characteristic shape of a extradural haemorrhage be on a head CT?
Don’t cross suture lines and they push on the brain forming a biconvex shape (lemon).
What is vascular dementia?
It is not a single disease but a group of syndromes of cognitive impairment caused by different mechanisms causing ischaemia or haemorrhage secondary to cerebrovascular disease.
What is the second most common form of dementia?
Vascular dementia
What are the subtypes of vascular dementia?
Stroke-related VD
Subcortical VD
Mixed dementia
What is stroke-related VD?
Vascular dementia caused by a multi-infarct or single-infarct dementia
What is subcortical VD?
Vascular dementia caused by small vessel disease.
What is mixed dementia?
The presence of both VD and Alzheimer’s disease
What are the risk factors for vascular dementia?
History of stroke or transient ischaemic attack (TIA)
Atrial fibrillation
Hypertension
Diabetes mellitus
Hyperlipidaemia
Smoking
Obesity
Coronary heart disease
A family history of stroke or cardiovascular
In what disease would vascular dementia be inherited?
CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopath)
What is the typical presentation of vascular dementia?
Several months or several years of a history of a sudden or STEPWISE DETERIORATION of cognitive function.
What may some features of vascualr dementia be?
Focal neurological abnormalities e.g. visual disturbance, sensory or motor symptoms
The difficulty with attention and concentration
Seizures
Memory disturbance
Gait disturbance
Speech disturbance
Emotional disturbance
What criteria is used to diagnose vascular dementia?
NINDS-AIREN criteria
The NINDS-AIREN criteria is used for what?
For a diagnosis of vascular dementia
Outline the NINDS-AIREN criteria?
Presence of cognitive decline that interferes with activities of daily living, not due to secondary effects of the cerebrovascular event
Cerebrovascular disease defined by neurological signs and/or brain imaging
A relationship between the above two disorders inferred by:
- The onset of dementia within three months following a recognised stroke
- An abrupt deterioration in cognitive functions
fluctuating, stepwise
- Progression of cognitive deficits
What is the management for vascular dementia?
Include: cognitive stimulation programmes, multisensory stimulation, music and art therapy, animal-assisted therapy
What is the surgical management for a brain abscess?
A craniotomy is performed and the abscess cavity debrided
What is the antibacterial management of a brain abscess?
IV 3rd generation cephalosporin + metronidazole
What pharmacological agent can be given for intercranial pressure management in a brain abscess?
Dexamethasone
What anticonvulsant can be given for brain abscess’?
Levetiracetam
Give some examples of 3rd generation cephalosporins?
Ceftriaxone
Ceftazidime
Cefotaxime
What tumours most commonly spread to the brain?
Lung (most common)
Breast
Bowel
Skin (melanoma)
Kidney
What is the inheritance pattern of neurofibromatosis?
NF1 and NF2 are both are inherited in an autosomal dominant fashion
On which chromosome is the gene mutation for NF1?
Chromosome 17 which encodes neurofibromin
On which chromosome is the gene mutation for NF2?
Gene mutation on chromosome 22
What are the classical features of NF1?
Cafe-au-lait spots (>= 6, 15 mm in diameter)
Axillary/groin freckles
Peripheral neurofibromas
Iris hamatomas (Lisch nodules) in > 90%
Scoliosis
Pheochromocytomas
What are the classical features of NF2?
Bilateral vestibular schwannomas
Multiple intracranial schwannomas, mengiomas and ependymomas
What is the classical history of vestibular schwannoma (acoustic neuroma)?
Combination of:
Vertigo,
Hearing loss,
Tinnitus,
Absent corneal reflex.
If cranial nerve VIII was affected in an acoustic neuroma, what would the features be?
Vertigo
Unilateral sensorineural hearing loss
Unilateral tinnitus
If cranial nerve V was affected in an acoustic neuroma, what would the features be?
Absent corneal reflex
If cranial nerve VII was affected in an acoustic neuroma, what would the features be?
Facial palsy
In what disease may you see bilateral vestibular schwannomas?
Neurofibromatosis type 2
What is the management for essential tremor?
Propanolol is first line
Primidone is alternative
What is Guillain-Barre syndrome?
An immune-mediated demyelination of the peripheral nervous system often triggered by an infection (classically Campylobacter jejuni)
What antibodies may be seen in up to 25% of patients in Guillain-Barre syndrome?
anti-GM1
What is classically the initial symptom of Guillain-Barre syndrome?
Around 65% of patients experience back/leg pain in the initial stages of the illness
What is the characteristic feature of Guillain-Barre syndrome?
Progressive, ascending symmetrical weakness of all the limbs with reduced or absent reflexes and preserved sensory signs
Worsening lower limb weakness following gastroenteritis would make you suspect which pathology?
Guillain-Barre syndrome
What are the investigations for Guillain-Barre syndrome?
Lumbar puncture - increased protein, normal WBC
Nerve conduction studies:
Decreased motor nerve conduction velocity (due to demyelination)
Prolonged distal motor latency
Increased F wave latency
Define encephalitis?
Encephalitis describes inflammation of the brain parenchyma. It mostly affects frontal and temporal lobes
What pathogen typically causes encephalitis in adults?
Herpes simplex 1 (95%)
CMV and VZV can also be a cause
What is the management for encephalitis?
IV acyclovir in HSV and VZV
Ganciclovir in CMV
What is the pathogen which causes malaria?
Plasmodium protozoa:
Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
How is Malaria spread?
Female Anopheles mosquito
Which species of plasmodium is responsible for severe malaria?
Plasmodium falciparum causes nearly all episodes of severe malaria. The other three types, of which Plasmodium vivax is the most common, cause ‘benign’ malaria.
What are some protective diseases against malaria?
Sickle cell disease
G6PD deficiency
HLA-B53
Absence of Duffy antigen
What is the classic triad of falciparum malaria infection?
Paroxysms of fever - cyclical (48 hours)
Chills
Sweating
What is the first line management for falciparum malaria?
Artemisinin-based combination therapies (ACTs)
What is the management for non-falciparum malaria?
Chloroquine, if ineffective then ACTs.
Also give primaquine to destroy destroy liver hypnozoites and prevent relapse.
What pathogen is responsible for singles?
Reactivation of the varicella-zoster virus (VZV) aka herpes-zoster infection
What disease is caused by the reactivation of the varicella-zoster virus (VZV)?
Shingles (Herpes Zoster)
Where does the virus lie dormant in shingles?
The virus lies dormant in the dorsal root or cranial nerve ganglia.
What are the most commonly affected dermatomes in shingles?
The most commonly affected dermatomes are T1-L2.
What is the prodromal period in shingles?
Burning pain over the affected dermatome for 2-3 days
Pain may be severe and interfere with sleep
20% of patients will experience fever, headache, lethargy
Describe the rash seen in shingles?
Initially erythematous, macular rash over the affected dermatome which quickly becomes vesicular
Characteristically is well demarcated by the dermatome but can ‘bleed’ into adjacent areas
When are individuals with shingles no longer infectious and who should they avoid in particular?
Infectious until the vesicles have crusted over, usually 5-7 days following onset
Avoid pregnant women and immunocompromised patients
What is the management for shingles?
Paracetamol and NSAIDs are first line
Neuropathic agents - amitriptyline can be considered
Oral corticosteroids can be used in first 2 weeks
Antivirals in first 72 hours
What antivirals can be used in shingles infection, what patient group can they not be used in?
Aciclovir
Famciclovir
Valaciclovir
Should not be used in over 50 year olds.
Define Horner’s syndrome?
Horner syndrome is a neurological condition that results from a lesion of the sympathetic chain supplying the eye
What is the characteristic triad of Horner’s syndrome?
Ptosis (drooping eyelid)
Anhidrosis (lack of sweating)
Miosis (constricted pupils) on the ipsilateral side.
What are the different central lesions that may cause Horner’s syndrome? How would they present differently to pre-ganglionic and post-ganglionic lesions?
4 S’s:
Stroke
Multiple Sclerosis
Swelling
Syringomyelia (cyst in the spinal cord)
Anhidrosis of the face, arms, and trunk
What are the different pre-ganglionic lesions that may cause Horner’s syndrome? How would they present differently to central and post-ganglionic lesions?
4 T’s:
Tumour (Pancoast tumour)
Trauma
Thyroidectomy
Top rib → a cervical rib growing above the first rib and clavicle)
Anhidrosis of the face
What are the different post-ganglionic lesions that may cause Horner’s syndrome? How would they present differently to central and pre-ganglionic lesions?
4 C’s:
Carotid artery dissection
Carotid aneurysm
Cavernous sinus thrombosis
Cluster headache
No anhidrosis seen
What is myasthenia gravis?
Myasthenia gravis is an autoimmune disorder resulting in insufficient functioning acetylcholine receptors
What is the classical feature of myasthenia gravis?
Muscle fatigability - muscles become progressively weaker during periods of activity and slowly improve after periods of rest
What are the investigations for myasthenia gravis?
Single fibre electromyography
Antibodies for acetylcholine receptors
What is the management for myasthenia gravis?
Pyridostigmine
Immunosuppression - Prednisolone
What is the mechanism of action of pyridostigmine?
Long-acting acetylcholinesterase inhibitor that reduces the breakdown of acetylcholine in the neuromuscular junction
What is the management for a myasthenic crisis?
Plasmapheresis
Intravenous immunoglobulins
What drugs may exacerbate myasthenia gravis?
Penicillamine
Quinidine, procainamide
Beta-blockers
Lithium
Phenytoin
Antibiotics: gentamicin, macrolides, quinolones, tetracyclines
What are the classical features of a migraine?
A severe, unilateral, throbbing headache associated with nausea, photophobia and phonophobia
May be precipitated by aura
What is the first line management for migraine?
Offer combination therapy with:
an oral triptan and an NSAID, OR
an oral triptan and paracetamol
What formulation of triptan should be used in young people?
Nasal and not oral
What are the prophylaxis management options for migraines?
Propranolol
Topiramate
Amitriptyline
In what demographic of patient should topiramate be avoided for prophylactic management of migraines?
Should be avoided in women of childbearing age as it may be teratogenic and it can reduce the effectiveness of hormonal contraceptives
What are the rules surrounding migraines with aura and COC pill?
If patients have migraine with aura then the COC is absolutely contraindicated due to an increased risk of stroke
What is a cluster headache?
Headaches that typically occur in clusters lasting several weeks, with the clusters themselves typically once a year
What are the classical features of cluster headaches?
Intense sharp, stabbing pain around one eye
Episodes last 15 mins - 2 hours
Cluster typically lasts 4-12 weeks
What is the acute management for cluster headaches?
100% oxygen (80% response rate within 15 minutes)
Subcutaneous triptan (75% response rate within 15 minutes)
What is the prophylactic management of cluster headaches?
Verapamil
What is the classical presentation of a tension headache?
Often described as a ‘tight band’ around the head or a pressure sensation.
Symptoms tend to be bilateral
What is the management for tension type headaches?
Aspirin, paracetamol or an NSAID are first-line
What is a medication overuse headache?
A headache that is present for 15 days or more per month AND
Has developed or worsened whilst taking regular symptomatic medication
What patients are at most risk of medication overuse headaches?
Patients using opioids and triptans
What is the management for medication overuse headaches?
Simple analgesics and triptans should be withdrawn abruptly (may initially worsen headaches)
Opioid analgesics should be gradually withdrawn
Define cerebral palsy?
A disorder of movement and posture due to a non-progressive lesion of the motor pathways in the developing brain
What are the causes of ceberal palsy?
Antenatal (80%)
Intrapartum (10%)
Post-natal (10%)
What are the classifications of cerebral palsy?
Spastic (70%)
Dyskinetic
Ataxic
Mixed
What are the associated non-motor problems with cerebral palsy?
Learning difficulties (60%)
Epilepsy (30%)
Squints (30%)
Hearing impairment (20%)
What are the subtypes of spastic cerebral palsy?
Hemiplegia
Diplegia
Quadriplegia
Where is the damage located in spastic cerebral palsy?
Increased tone resulting from damage to upper motor neurons
Where is the damage located in dyskinetic cerebral palsy?
Damage to the basal ganglia and the substantia nigra
Where is the damage located in ataxic cerebral palsy?
Damage to the cerebellum with typical cerebellar signs
What is the management for hypoxic ischaemic encephalopathy?
Therapeutic hypothermia - involves actively cooling the core temperature of the baby according to a strict protocol.
Reduces the inflammation and neuronal loss after the acute hypoxic injury. It reduces the risk of cerebral palsy, developmental delay, learning disability, blindness and death.
What is Cauda equina syndrome?
A rare but serious condition in which the lumbosacral nerve roots that extend below the spinal cord are compressed.
What is the most common cause of Cauda equina syndrome?
Central disc prolapse typically occuring at L4/5 or L5/S1
What are some possible features of Cauda equina syndrome?
Low back pain
Bilateral sciatica (50%)
Saddle numbness
Decreased anal tone
Urinary dysfunction
What is the investigation and management for cauda equina syndrome?
Urgent MRI
Surgical decompression
What is incomplete spinal cord injury?
Still have some feeling, function and muscle control below the site of their injury due to the ability of the neurons in the spinal cord still being able to communicate to and from the brain.
What is complete spinal cord injury?
No muscle control, sensation or function below the site of injury to the no nerve communication below the injury site to the brain
What is the first line investigation for spinal cord injury?
High-resolution CT whole spine
Outline a C1-C3 spinal cord injury?
Usually results in paralysis of both upper and lower limbs, affecting the muscles that control breathing. Assistance with breathing (ventilator) may be required.
Outline a C4 spinal cord injury?
Quadriplegia with some shoulder and neck movement. Requires assistance for daily activities.
Outline a C5 spinal cord injury?
Quadriplegia with improved shoulder and some elbow movement. May be able to perform limited self-care tasks.
Outline a C6 spinal cord injury?
Limited hand and wrist movement. Some independence in daily activities, including feeding and grooming.
Outline a T1-T5 spinal cord injury?
Paraplegia with upper extremity mobility. Limited trunk control.
Outline a T6-T12 spinal cord injury?
Paraplegia with improved trunk control. Increased independence in mobility.
Outline a L1-L2 spinal cord injury?
Paraplegia with hip flexor weakness. Requires assistive devices for mobility.
Outline a L3-L4 spinal cord injury?
Paraplegia with improved hip and knee flexion. Better ambulation potential with braces or assistive devices.
Outline a S1-S2 spinal cord injury?
Bowel and bladder dysfunction
What are cranial mononeuropathies?
Relates to the 12 paired nerves arising from the brain and brain stem
What are upper limb mononeuropathies?
Relates to the peripheral nerves involved in upper limb function
What are lower limb mononeuropathies?
Relates to the peripheral nerves involved in lower limb function
What are the main organisms that cause meningitis in 6-60 year olds?
Neisseria meningitidis
Streptococcus pneumoniae
What are the main organisms that cause meningitis in >60 year olds?
Streptococcus pneumoniae
Neisseria meningitidis
Listeria monocytogenes
What is the main organism that causes meningitis in immunocompromised patients?
Listeria monocytogenes
What type of organism is Neisseria meningitidis?
Gram negative diplococci
What type of organism is Streptococcus pneumoniae?
Gram positive diplococci/chain
What type of organism is Listeria monocytogenes?
Gram positive rod
What type of organism is Haemophillus influenzae?
Gram negative coccobacilli
What type of organism is E. coli?
Gram negative rod
What are the main features of meningitis?
Headache
Fever
Nausea/vomiting
Photophobia
Drowsiness
Seizures
Neck stiffness
Purpuric rash
What are the findings in CSF fluid for bacterial meningitis?
Cloudy
Low glucose (< 1/2 plasma)
High protein
10-5,000 polymorphs/mm³
What are the findings in CSF fluid for viral meningitis?
Clear/cloudy
60-80% of plasma glucose
Normal/raised protein
15-1,000 lymphocytes/mm³
What are the findings in CSF for tuberculosis meningitis?
Slight cloudy, fibrin web
Low glucose (< 1/2 plasma)
High protein
10-1,000 lymphocytes/mm³
CSF fluid for suspected meningitis:
Cloudy
Low glucose (< 1/2 plasma)
High protein
10-5,000 polymorphs/mm³
What type of pathogen is involved?
Bacterial meningitis
CSF fluid for suspected meningitis:
Clear/cloudy
60-80% of plasma glucose
Normal/raised protein
15-1,000 lymphocytes/mm³
What type of pathogen is involved?
Viral meningitis
CSF fluid for suspected meningitis:
Slight cloudy, fibrin web
Low glucose (< 1/2 plasma)
High protein
10-1,000 lymphocytes/mm³
What type of pathogen is involved?
Tuberculosis meningitis
What is contraindicated in meningococcal septicaemia?
Lumbar puncture
Suspected bacterial meningitis: an LP should be done before IV antibiotics, unless?
Cannot be done within 1 hour
Signs of severe sepsis or a rapidly evolving rash
Significant bleeding risk
Signs of raised intracranial pressure
What is the management for meningitis in 3 months - 50 year olds when an LP cannot be performed?
IV cefotaxime (or ceftriaxone)
What is the management for meningitis in > 50 year olds when an LP cannot be performed?
IV cefotaxime (or ceftriaxone) + amoxicillin (or ampicillin)
What is the management for meningococcal meningitis?
IV benzylpenicillin or cefotaxime (or ceftriaxone)
What is the management for pneumococcal meningitis?
IV cefotaxime (or ceftriaxone)
What is the management for meningitis caused by Haemophilus influenzae?
IV cefotaxime (or ceftriaxone)
What is the management for meningitis caused by Listeria?
IV amoxicillin (or ampicillin) + gentamicin
Who should be offered prophylaxis for meningitis?
Offered to households and close contacts of patients affected with meningococcal meningitis
What is the prophylactic management for meningococcal meningitis?
Oral ciprofloxacin or rifampicin
What other pharmacological agent should be given for meningitis management aside from antibiotics? When would you not give this?
IV dexamethasone
Avoid dexamethasone in:
Septic shock
Meningococcal septicaemia
Immunocompromised
Meningitis following surgery
What is the management for viral meningitis?
Ceftriaxone and aciclovir intravenously
What is the most common cause of viral meningitis in adults?
Non-polio enteroviruses e.g. coxsackie virus, echovirus
What is the management of meningococcal meningitis in primary care?
IM benzylpenicillin
What antibiotic should be used for meningitis is a patient has a penicillin- or cephalosporin-allergy?
Chloramphenicol
What is the most common complication of meningitis?
Sensorineural hearing loss
Define Bell’s palsy?
An acute, unilateral, idiopathic, facial nerve paralysis.
What is the management of Bell’s palsy?
Oral prednisolone within 72 hours of onset of Bell’s palsy
Define trigeminal neuralgia?
Trigeminal neuralgia is a pain syndrome characterised by severe unilateral pain of the face
What things may evoke pain in trigeminal neuralgia?
The pain is commonly evoked by light touch, including washing, shaving, smoking, talking, and brushing the teeth (trigger factors), and frequently occurs spontaneously
What is the management for trigeminal neuralgia?
Carbamazepine is first-line
Define epilepsy?
Epilepsy is a common neurological condition characterised by recurrent seizures
How is a seizure classified?
- Where seizures begin in the brain
- Level of awareness during a seizure
- Other features of seizures
What is a focal seizure?
Start in a specific area, on one side of the brain.
The level of awareness can vary in focal seizures.
Can also be either motor or non-motor.
What is a generalised seizure?
Involve networks on both sides of the brain at the onset.
Consciousness lost immediately.
Can be further subdivided into motor (e.g. tonic-clonic) and non-motor (e.g. absence)
What are the different types of generalised seizures?
Tonic-clonic (grand mal)
Tonic
Clonic
Typical absence (petit mal)
Myoclonic
Atonic
What is a focal to bilateral seizure?
Starts on one side of the brain in a specific area before spreading to both lobes
What is a postictal phase in a seizure?
Where the person is confused, drowsy and feels irritable or depressed for around 15 minutes
What is a tonic seizure?
The muscles become stiff and flexed, which can cause the patient to fall, usually backwards
What is an atonic seizure?
Aka drop attacks. The muscles suddenly relax and become floppy, which can cause the patient to fall, usually forward.
What is a clonic seizure?
Clonic seizures: violent muscle contractions (convulsions)
What is a tonic-clonic seizure?
There is loss of consciousness andtonic(muscle tensing) andclonic(muscle jerking) episodes. Typically the tonic phase comes before the clonic phase.
What is a myoclonic seizure?
Short muscle twitches. The patient usually remains awake during the episode.
Typically happen in children as part ofjuvenile myoclonic epilepsy.
What is an absence seizure?
Aka petit mal seizures, impaired awareness or responsiveness. Patient becomes blank and stares into space before returning to normal.
What are the main investigations following a seizure?
Following their first seizure patients generally have both an electroencephalogram (EEG) and neuroimaging (usually a MRI)
What is the management for generalised tonic-clonic seizures in males?
Sodium valproate
What is the management for generalised tonic-clonic seizures in females?
Lamotrigine or levetiracetam
Girls aged under 10 years and who are unlikely to need treatment when they are old enough to have children or women who are unable to have children may be offered sodium valproate first-line
What is the first line management for focal seizures?
Lamotrigine or levetiracetam
What is the second line management for focal seizures?
Carbamazepine, oxcarbazepine or zonisamide
What is the first line management for absence (petit mal) seizures?
Ethosuximide
What is the second line management for absence (petit mal) seizures in males?
Sodium valproate
What is the second line management for absence (petit mal) seizures in females?
Lamotrigine or levetiracetam
What drug may exacerbate absence seizures?
Carbamazepine
What is the management for myoclonic seizures in males?
Sodium valproate
What is the management for myoclonic seizures in females?
Levetiracetam
What is the management for tonic or atonic seizures in males?
Sodium valproate
What is the management for tonic or atonic seizures in females?
Lamotrigine
