NEUROLOGY Flashcards
What is MS?
chronic and progressive condition that involves demyelination of the myelinated neurones in the central nervous system (affects the white matter of the brain and spinal cord).
Inflammatory process involving activation of the immune cells against myelin.
What type of hypersensitivity reaction is MS?
Type 4 - T cell mediated
When does MS present?
Young adults <50 years
Women
Which types of cells provide myelin?
Schwann cells (peripheral nervous system) Oligodendrocytes (central nervous system)
Which myelin producing cells are mostly affected in MS?
Oligodendrocytes
Name 5 causes of MS.
Genetic EBV Low vitamin D Smoking Obesity
When might MS symptoms improve?
Pregnancy
Postpartum period
How do you describe the frequency of MS symptoms?
Disseminated in time and space
Name five different ways that MS can present.
Optic neuritis Eye movement abnormalities Focal weakness Focal sensory symptoms Ataxia
How long does first-presentation of MS usually last?
Symptoms progress over 24 hours
Lasts days-weeks and then improves
What is the most common presentation of MS?
Optic neuritis (demyelination of the optic nerve)
Which cranial nerve is commonly affected in MS?
CN 6 - abducens
How does a CN6 lesion present?
Internuclear ophthalmoplegia
Conjugate lateral gaze disorder
Give some examples of focal weakness in MS.
Bell’s palsy
Horner’s syndrome
Limb paralysis
Incontinence
Give some examples of sensory symptoms in MS.
Trigeminal neuralgia
Numbness
Paraesthesia (pins and needles)
Lhermitte’s sign - electric shock sensation that travels down the spine when flexing the neck
What is Lhermitte’s sign?
Lhermitte’s sign is an electric shock sensation that travels down the spine and into the limbs when flexing the neck. It indicates disease in the cervical spinal cord in the dorsal column. It is caused by stretching the demyelinated dorsal column.
Name two types of ataxia that are seen in MS.
Sensory ataxia - loss of proprioceptive sense (results in positive Romberg’s test)
Cerebellar ataxia - suggests cerebellar lesions
Name four types of disease patten in MS.
Clinically isolated - may never progress to MS
Relapsing-remitting -
Secondary progressive
Primary progressive
Which is the most common disease patten seen in MS?
Relapsing-remitting
What is meant by active or not active MS?
Active = new symptoms or lesions are developing
Not active = no new symptoms or lesions are developing
What is meant by worsening or not worsening MS?
Worsening = overall disability is worsening over time
Not worsening = there is no worsening of disability over time
Describe the disease pattern seen in secondary progressive MS.
Initially relapsing-remitting.
Then progressive worsening of disability over time.
What is primary progressive MS?
The disease progressively worsens overtime without relapse or remission.
How does optic neuritis present?
Central scotoma
Pain on eye movement
Impaired colour vision
Relative afferent pupillary defect
Name 7 causes of optic neuritis.
Sardcoidosis SLE Diabetes Syphilis Measles Mumps Lymes disease
What is Uhthoff’s phenomenon?
Symptoms brought on by changes in temperature
What signs might be elicited in a patient with MS?
Reduced visual acuity
Weakness
Increased tone
Loss of proprioception
How is MS diagnosed?
Clinical picture - symptoms suggesting lesions change location
Other causes for the symptoms must be excluded
How is primary progressive MS diagnosed?
Symptoms must be progressive over a period of 1 year.
Which investigations can support the diagnosis?
MRI scans - demonstrate lesions
LP - oligoclonal bands
What type of MRI is requested in MS?
MRI contrast
FLAIR sequence can help distinguish non-specific white matter lesions.
How many lesions are expected to be seen on MRI investigating for MS?
One lesion per decade = normal
>1 lesions per decade = increased likelihood of MS
What investigation can be done to test nerve function in MS?
Evoked potential studies
What are the aims of MS treatment?
Induce remission - DMARDs
Treat relapses - methylprednisolone
How are relapses of MS treated?
Methylprednisolone 500mg for 5 days
1g IV for 3-5 days if oral treatment fails/relapse is severe
How are symptoms managed in MS?
Exercise - maintain activity and strength
Neuropathic pain - amitriptyline/gabapentin
Depression - SSRIs
Urge incontinence - oxybutynin
Spasticity - baclofen, gabapentin
Which medication is used to treat fatigue in MS?
Amantadine
What is the management of optic neuritis?
Urgent referral to ophthalmology
Steroids
2-6 weeks recovery
50% of patients will develop MS in the next 15 years
What is GBS?
Acute paralytic polyneuropathy
Causes demyelination of the peripheral nervous system
Usually triggered by an infection
Which infections are associated with GBS?
Campylobacter jejuni
Cytomegalovirus
EBV
What is the pathophysiology of GBS?
Molecular mimicry: B cells target antibodies on the pathogen, which are similar to antigens on the myelin sheath of motor neurons.
How does GBS present?
Ascending symmetrical weakness
Reduced reflexes
Peripheral loss of sensation or neuropathic pain
May progress to facial nerves and cause facial weakness
When do patients present with GBS?
4 weeks after preceding infection
How long is the recovery period for GBS?
Months - years
How long is the recovery period for GBS?
Months - years
How is GBS diagnosed?
Clinically: Brighton criteria
Which investigations support the diagnosis of GBS?
Nerve conduction studies
Lumbar puncture
What might be seen on a LP in GBS?
Raised protein, normal cell count
What is the management of GBS?
IV IG
Plasma exchange
Supportive care
VTE prophylaxis
What is the leading cause of death in GBS?
PE
Respiratory failure
What is the prognosis in GBS?
80% fully recover
15% left with some neurological disability
5% will die
Name some differentials for degenerative myelopathy.
Compressive myelopathy (cancer, trauma) Peripheral neuropathy (diabetes) Infectious myelitis Anterior spinal artery occlusion = sensory, motor Posterior spinal artery occlusion = proprioception, vibration
How do patients present with myelopathy?
Neck pain
Loss of motor function (digital dexterity)
Loss of sensory function
Loss of autonomic function (urinary or faecal incontinence and/or impotence)
Hoffman’s sign
What is Hoffman’s sign?
Hoffman’s sign: is a reflex test to assess for cervical myelopathy. It is performed by gently flicking one finger on a patient’s hand. A positive test results in reflex twitching of the other fingers on the same hand in response to the flick.
What investigation is needed for myelopathy?
MRI cervical spine
What is the management of myelopathy?
Spinal decompression surgery: laminectomy
What is a seizure?
Transient episodes of abnormal electrical activity in the brain.
Name 6 different types of seizure.
Tonic-clonic Focal seizures Absence Atonic Myoclonic Infantile spasms
Where do focal seizures typically start?
Temporal lobes
Name 5 differentials for epileptic seizures.
Syncope: - Vaso-vagal - Cardiac - Orthostatic Non-epileptic seizures: - Psychogenic - Hypoglycaemic
When do generalised seizures usually present?
< 30 years
How do clonic-tonic seizures present?
Loss of consciousness
Tonic (muscle tensing)
Clinic (muscle jerking)
Typically the tonic phase comes before the clonic phase
There may be associated tongue biting, incontinence, groaing and irregular breathing
What is a post-ictal period? What symptoms are experienced?
Confusion, drowsy, irritable or depressed
How can focal seizures present?
Temporal - deja-vu, lip-smacking, auditary hallucinations
Parietal - sensory changes
Occipital - visual
Frontal - jacksonian march
What are simple and complex focal seizures?
Simple = with consciousness Complex = without consciousness
How do absence seizures present?
Blank, staring into space
Typically present in children
Last 10-20 seconds
How do atonic seizures present?
‘Drop attacks’
< 3 minutes
May be indicative of Lennox-Gastaut syndrome
How do myoclonic seizures present?
Sudden brief muscle contractions
Remains conscious
Typically in juvenile myoclonic epilepsy
What is West syndrome?
Infantile spasms
Starts around 6 months of age
Clusters of full body spasms
Poor prognosis (1/3 die by age of 25)
What investigations can help support a diagnosis of epilepsy?
EEG
MRI - structural pathology
What investigations can help exclude other causes of seizures?
ECG
Bloods - FBC, BMs, serum prolactin (true seizure)
Which patients require imaging following a seizure?
Over 25 and new onset
Focal
What is the aim of treatment for epilepsy?
To be seizure free on the minimum dose of anti-epileptic dose
What is the management for a first-time unprovoked seizure?
No treatment needed
What is the management for a second unprovoked seizure (tonic-clonic)?
Anti-convulsive monotherapy: sodium valproate (1st line)
Second line: lamotrigine or carbamazepine
What is the management of focal seizures?
First-line: carbamazepine or lamotrigine
Second-line: sodium valproate or levetiracetam
What is the management of absence seizures?
Typically stop in adulthood
First-line: sodium valproate or ethosuximide
What is the management of atonic seizures?
First-line: sodium valproate
Second-line: lamotrigine
What is the management of myoclonic seizures?
First-line: sodium valproate
Second-line: lamotrigine, levetiracetam or topiramate
What is the management of infantile spasms?
Prednisolone
Vigabatrin
What is the mechanism of action of sodium valproate?
Increasing GABA activity
What are the side effects of sodium valproate?
Teratogenic - advise about contraception
Liver damage
Hair loss
Tremor
What is the mechanism of action of carbamazepine?
Sodium channel blocker
What are the side effects of carbamazepine?
Hyponatraemia
Agranulocytosis
Aplastic anaemia
What is cubital tunnel syndrome?
Compression of the ulnar nerve causing paraesthesia in the 4th and 5th fingers
What is the first-line treatment for restless leg syndrome?
Ropinirole
Which type of dementia is associated with MND?
frontotemporal dementia
What is the treatment for Bell’s palsy?
PO Prednisolone within 72 hours
Artificial tears
No improvement within 3 weeks = urgent referral to ENT
Give 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 first-line treatment for a low pressure headache following LP?
Caffeine & fluids
What is seen on EEG in absence seizures?
EEG: bilateral, symmetrical 3Hz spike and wave pattern
Give two causes of bitemporal hemianopia
upper quadrant defect > lower quadrant defect = inferior chiasmal compression, commonly a pituitary tumour
lower quadrant defect > upper quadrant defect = superior chiasmal compression, commonly a craniopharyngioma
What are the 5 MRC grades?
Grade 0 = no movement Grade 1 = flicker of movement Grade 2 = movement when gravity is removed Grade 3 = movement against gravity Grade 4 = movement against resistance Grade 5 = full power
What triad of symptoms is seen in CJD?
Rapidly progressive dementia
Myoclonus
Rigidity
What is the gold standard test for diagnosing a venous sinus thrombosis?
MR venogram
Where do brain metastases most commonly spread from?
Lung
Which anti epileptic drug is most associated with weight gain?
Sodium valproate
Which scale is used to assess disability following a stroke?
Barthel index
What are the characteristic features of CJD?
Rapidly progressive dementia
Myoclonus
Which spinal tract is affected by Syringomyelia?
SPinoThalamic - pain & temperature
Syringomyelia = Superman - “cape-like” distribution of loss in shoulders and upper limbs
What is Parkinson’s?
Progressive neurodegeneration of dopaminergic neurones in the basal ganglia
Results in movement disorders
Where in the brain is dopamine produced?
Substantia nigra
Give 7 causes of Parkinsonism.
Parkinson's disease Parkinson's plus conditions (4) Drug-induced parkinsonism Toxins - CO/MPTP Wilson's Post-encephalitis Dementia pugilistica
What is dementia pugilistica?
A form of chronic traumatic encephalopathy
How does bradykinesia present in Parkinson’s disease?
• Shuffling gait
• Micrographia (handwriting gets smaller)
• Difficulty initiating movement
- Hypomimia (reduced facial expression)
What is the triad of symptoms seen in Parkinson’s? Name some other symptoms outside of the triad.
Bradykinesia
Rigidity
Tremor
Depression, postural instability, anosmia, insomnia, cognitive impairment
Describe the features of a tremor seen in Parkinsons.
Unilateral
4-6hz
Resting (improves with intentional movement)
Pill-rolling
What are the key differences between essential tremor and Parkinson’s tremor?
Parkinson's: • Asymmetric/unilateral • 4-6hz • Resting • Not improved by alcohol
Essential: • Bilateral • 5-8hz • Intention - Improved by alcohol
How can you differentiate between essential tremor and Parkinson’s tremor?
Clinical features
SPECT if uncertainty
Give another name for a SPECT? What is it used for?
DaTScan - also used to diagnose LBD
Name 4 Parkinson’s plus syndromes.
- Multiple system atrophy
- Lewy-body dementia
- Progressive supranuclear palsy
- Corticobasal degeneration
What are the features of multiple system atrophy?
Parkinsonism
Autonomic dysfunction = ED, loss of bladder control, postural hypotension
Cerebellar dysfunction = ataxia
What are the features of LBD?
Parkinsonism
Dementia
Visual hallucinations/delusions
Fluctuating consciousness
What are the features of progressive supranuclear palsy?
Vertical diplopia
Poor response to L-dopa
Cognitive impairment
How is Parkinson’s diagnosed?
Clinically
UK Parkinson’s Disease Society Brain Bank Criteria
What is the first-line management for Parkinson’s disease?
Movement affecting life = levodopa
Movement not affecting life = dopamine agonist
What is levodopa?
Dopamine precursor
Often combined with peripheral carboxylase inhibitor to prevent breakdown before reaching the brain = co-benyldopa, co-carledopa
Loses effect overtime - 2 years
Give two examples of peripheral carboxylase inhibitors.
Carbidopa
Benserazide
What is the second-line treatment of Parkinson’s disease?
If symptoms persist after L-dope/dopamine agonist:
Combination: [L-dopa + peripheral carboxylase inhibitor] AND [MOA-inhibitor, dopamine agonist, COMT inhibitor]
What is the purpose of using COMT inhibitors and MAO-inhibitors in Parkinson’s disease? Give examples
Extends the effective duration of levodopa by preventing breakdown
Entacapone = COMT inhibitor
Selegiline, rasagiline = MOA-inhibitor
What is the purpose of using dopamine agonists in Parkinson’s disease? Give an example.
Delay the need for leva-dopa
Cabergoline
Bromocriptine
Pergolide
Why should Parkinson’s medication not be stopped?
Can cause neuromalignant syndrome
If patient cannot tolerate oral medication or has vomiting/diarrhoea = use transdermal patch
What are impulse control disorders?
Disinhibited behavioural change caused by dopamine-agonists e.g. gambling
What drug can be used to treat daytime sleepiness in Parkinson’s disease?
Midodrine
What drug can be used to treat hypersalivation in Parkinson’s?
Glycopyronium bromide
What is neuroleptic induced Parkinsonism?
Parkinsonism caused by anti-psychotics
How is orthostatic hypotension treated in Parkinson’s?
Medication review
Lifestyle - ^fluids, ^salt
Fludrocortisone
Which Parkinson’s medications might cause pulmonary fibrosis?
Dopamine agonists
What is myasthenia gravis?
autoimmune condition that causes muscle weakness that gets progressively worse with activity and improves with rest
Which conditions are associated with MG?
Pernicious anaemia
RA
SLE
When does MG present?
Women < 40 years
Men > 60 years
Which antibodies are seen in MG?
- ACh receptor antibodies (85%)
- MuSK - Muscle-specific tyrosine kinase antibodies
- LDR4 - Low-density lipoprotein receptor-related protein 4
What is the pathophysiology of MG?
Autoantibodies act on NMJ to prevent the effective contraction of muscles:
1. Anti-Ach receptor = block and damage receptor cells, activate complement system
Anti-MuSK and Anti-LDR4 = prevent rebuilding/organisation of Ach receptors
Which drugs are likely to exacerbate MG?
Penicillamine Quinidine, procainamide Beta-blockers Lithium Phenytoin Antibiotics: gentamicin, macrolides, quinolones, tetracyclines
What is the hallmark feature of MG?
Fatiguability
Which muscle groups are most affected in MG?
Proximal muscles
Muscles of the head and neck
What symptoms are seen in MG?
Proximal muscles - difficulty getting up
Muscles of the head and neck - diplopia, ptosis, facial droop, dysphagia, dysarthria
How can you elicit fatiguability during examination in MG?
Blink
Should abduction
What signs might you see on examination in MG?
Thymectomy scar
Ptosis
Facial droop
Which investigations should be done in MG?
- Single fibre electromyography
- Bloods:
- antibody tests: anti-Ach, anti-MuSK, anti-LDR4
- CK = normal - CXR - thymoma
- Tensilon test (edrophonium test) - not commonly used due to arrythmia risk
How can you distinguish MG from statin induced myopathy?
CK = normal
What is the Tensilon test?
Give neostigmine and measure response - positive if improvement of symptoms
Why should you order an CXR for patients with newly diagnosed myasthenia gravis?
Thymoma
What is the 1st line treatment for MG? What is second line?
- Pyrostigmine
2. Immunosuppressants - prednisolone, then azathioprine
What can be used if there is poor response to immunosuppression?
Monoclonal antibodies
Which monoclonal antibodies are used in MG?
Rituximab - B cells
Eculizumab (not NICE approved) - complement
What is a myasthenic crisis? What can cause it?
Acute worsening of symptoms –> resp failure
Triggered by infection
How do you manage a myasthenic crisis?
- A–>E (include bedside FVC)
- BiPAP –> intubation
- IVIG
What is motor neurone disease?
Cluster if degenerative diseases due to axonal degeneration of neurones in the motor cortex, CN nuclei and anterior horn cells.
What is the pattern of motor function seen in MND?
Mixed upper and lower motor neurone (if only one, polyneuropathy).
Which differential is considered more likely if there is sensory disturbance in suspected MND?
MS
Which differential is considered more likely if there is eye involvement in suspected MND?
MG
What is the prevalence of MND?
1 in 350
What percentage of MND cases are considered to be familial? What is the most common gene that causes MND?
10%
SOD1 - CX21
What are the different classifications of MND? Which is most common?
Amyotrophic lateral sclerosis - 50%
Progressive muscular atrophy
Progressive bulbar palsy
Primary lateral sclerosis
What are the features of ALS?
LMN signs in the arms, UMN signs in the legs
SOD1 (CX21)
What are the features of primary lateral sclerosis?
UMN signs only
Loss of Betz cells in the motor cortex
Pseudobulbar palsy
What are the features of progressive muscular atrophy?
LMN signs only (anterior horn cell lesions) - affects distal before proximal
Better prognosis
What are the features of progressive bulbar palsy?
Palsy of the tongue, muscles of chewing/swallowing
How is MND diagnosed?
Clinically - need to rule out other causes.
Which investigations should be ordered? What are the expected results?
MRI spine (rule out structural cause e.g. myelopathy)
LP (rule out inflammatory cause)
Nerve conduction studies - normal
What can be seen on electromyography in MND?
Reduced number of action potentials with increased amplitude
What is the management of MND?
Riluzole - can slow progression and extend survival by a few months
NIV can be used to assist breathing at night
End of life care planning - advanced directives
What is the most common cause of death from MND?
Respiratory failure
Pneumonia
What is the mechanism of action of riluzole?
Prevents the stimulation of glutamate receptors
What causes polio?
RNA virus - affects anterior horn cells
What other symptoms might be seen during a polio infection?
Sore throat
Myalgia
Fever
What is the most common cause of death due to polio?
Respiratory failure - muscle paralysis
Is there any sensory involvement in polio?
no
Is there any sensory involvement in polio?
no
What is the pattern of motor function seen in polio?
Asymmetric LMN paralysis
Where does the spinal cord end?
Between L1 and L2
What is the blood supply to the spinal cord?
3 longitudinal blood vessels:
• 2 posterior - supplies dorsal 1/3
• 1 anterior - supplies anterior 2/3
Longitudinal veins drain into extradural plexus.
Name two tracts that contain upper motor neurons.
Corticospinal = cortex --> spine (voluntary movement of skeletal muscle) Corticobulbar = cortex --> brainstem (voluntary movement of head/neck)
Where do UMNs of the corticospinal tract synapse with LMNs?
Anterior grey horn of spinal cord
Where do UMNs of the corticobulbar tract synapse with LMNs?
Cranial nerve nuclei:
- CN V = muscles of mastication
- CN VII = muscles of facial expression
- Nucleus ambiguous = CNIX, CNX & CNXI = swallowing, speech, uvula
- CNXII = muscles of the tongue
What is bulbar palsy?
LMN lesions affecting cranial nerves
What is pseudobulbar palsy?
UMN affecting corticobulbar tract
Give 3 causes of UMN lesions.
- Stroke
- De-myelination: MS, Freidrich’s ataxia, B12
- MND
Give 4 causes of LMN lesions.
- Anterior horn cell damage: polio, SMA
- Cauda equine (cord compression)
- DM neuropathy
- MND
What signs are seen in UMN lesions?
Mass: decrease (15%) Strength: spastic paralysis Tone: increased Fasciculations: absent Babinski: positive Pronator drift: positive Hoffman's sign: positive
What signs are seen in LMN lesions?
Mass: decrease (80%) Strength: flaccid paralysis Tone: decreased Fasciculations: present Babinski: absent Pronator drift: absent Hoffman's sign: absent
What are the two broad types of spinal cord injury?
Incomplete
Complete
Name 5 types of incomplete spinal cord injury.
Anterior horn lesion Central cord syndrome Posterior cord syndrome Anterior cord syndrome Brown-sequard
What signs/symptoms are seen in anterior horn injury?
LMN at the level of injury
What causes anterior horn injury?
Polio
SMA (spinal muscular atrophy)
MND
What signs/symptoms are seen in central cord syndrome?
Anterior horn lesion = LMN @ level of injury
Lateral corticospinal tract lesion = UMN below level of injury (upper limbs>lower limbs)
Spinothalamic decussation lesion = loss of pain, temp, crude touch below level of injury - cape sign
What is cape sign?
Loss of pain, temperature and crude touch sensation in shoulders and upper limbs
Often seen in central cord syndrome due to lesion in spinothalamic tracts
Common cause is syringomyelia
Give two causes of central cord syndrome.
- Hyperextension injury (RTA or minor (OA))
2. Syringomyelia
What symptoms are seen in posterior cord syndrome?
- Demyelination:
- MS
- B12
- Freidrich’s ataxia
What symptoms/signs are seen in anterior cord syndrome?
- Corticospinal tract = UMN below level of injury
- Anterior horn cells = LMN @ level of injury
- Spinothalamic tract = loss of pain & temperature & crude touch below level of injury
Only thing that stays intact = DCML = fine touch, vibration, proprioception
What can cause anterior cord syndrome?
Thrombus
Hyperflexion injury
What signs/symptoms are seen in Brown-Sequard syndrome?
DCML = IPSILATERAL loss of vibration & proprioception below injury
Corticospinal tract = IPSILATERAL UMN signs below injury
Anterior horn cells = IPSILATERAL LMN @ level of injury
Spinothalamic tract = CONTRALATERAL loss of pain, temperature and crude touch below injury
Give two causes of Brown-Sequard syndrome.
Trauma
Tumour
What are the signs/symptoms of a complete spinal cord injury?
- Paralysis (cervical = quadriplegia; thoracic = paraplegia): flaccid –> spastic overtime
- Complete loss of sensation below lesion
- Autonomic dysfunction:
- Faecal/urine incontinence (test using bulbocavernosus reflex)
- If above T6 –> sympathetic dysfunction –> bradycardia & hypotension
What might be seen in spinal cord injury above T6?
Neurogenic shock (bradycardia & hypotension) due to loss of sympathetic nerve supply to the heart and great vessels
What is the most common cause of complete spinal cord injury?
Trauma
What are the key differences in symptoms of lesions above and below L1/L2?
Above spinal cord = UMN signs
Below spinal cord = no UMN signs
What is the management for a symptomatic chronic subdural haematoma?
burr hole craniotomy