Flashcards in General neurology Deck (185):
What % of those with ALS have FTD?
What is the major genetic cause shared by ALS and FTD?
TDP-43 is found in which diseases?
FTD and ALS
What is Onuf's nucleus responsible for?
How do triptans work (in migraine)?
Activators of 5-HT receptors, 1B/1D/1F
What options are available for migraine prophylaxis?
Amitriptyline, nortriptyline, pizotifen, candesartan, propranolol, sodium valproate, topiramate, verapamil
Which nerves pass through the jugular foramen?
IX, X, XI
What passes through the cavernous sinus?
CN III, IV, V1, V2, VI
What causes autonomic dysreflexia?
Spinal cord injuries above T6.
- HTN and bradycardia
- Below T6 allows splanchnic innervation and therefore dilatation to bring down BP
What are the common side effects of phenytoin?
Gingival hyperplasia, hirsutism, rash, folic acid depletion, osteoporosis, cerebellar signs
What is the prognosis at diagnosis?
What does reinnervation look like on EMG?
High amplitude CMAPs
How is conduction block defined on Nerve Conduction Studies?
A reduction in CMAP area/amplitude of at least 20% compared with distal CMAP area/amplitude.
The duration of the proximal CMAP should not increase by >20% (see temporal dispersion)
Which antibody is multifocal motor neuropathy associated with?
How is primary lateral sclerosis distinguishable?
Affects upper motor neurons only
How is progressive muscular atrophy distinguishable?
Affects lower motor neurons only
What are the 2 most commonly found mutations in ALS?
C9orf72 and SOD1
How is EPHA4 implicated in prognosis in ALS?
Lower EPHA4 = longer survival
Which exposure is the strongest risk factor for ALS?
How does riluzole work in ALS?
Suppresses excessive motor neuronal firing
How does edaravone work in ALS?
Suppresses oxidative stress
What is the treatment for cluster headaches?
Acute: 100% O2, triptan
- Severe refractory => indomethacin or dihydroergotamine
Bridging: prednisone or occipital nerve block with methylpred
What is the genetic mutation responsible for Wilson's disease?
ATP7B mutation on chromosome 13 (autosomal recessive)
Which mutation is associated with the highest risk of multiple sclerosis?
Other risk = *0801
What is first line treatment in primary progressive MS and what is its mechanism of action?
Ocrelizumab - fully humanised anti-CD20 that suppresses B cell
What does downbeating nystagmus represent?
Lesion in the foramen magnum
What does upbeating nystagmus represent?
Lesion in the midbrain or floor of the fourth ventricle
How do you distinguish between myositis and myopathy on EMG?
Spontaneous firing in myositis, but not myopathy
What are the causes of predominantly sensory neuropathy?
Hereditary sensory and autonomic neuropathy
What are the causes of predominantly motor neuropathy?
Acute motor axonal neuropathy
Hereditary motor and sensory neuropathy
Multifocal motor neuropathy
Which antibodies may be positive in GBS?
GM1, GM2 and GD1
What is the triad found in Miller-Fisher and what is the antibody associated with it?
Ataxia, ophthalmoplegia and areflexia
What does CSF show in GBS and CIDP?
Albuminocytologic dissociation - high protein / low cells
What is the treatment for GBS?
IVIG or plasma exchange
What are the treatment options for CIDP?
IVIG or plasma exchange
Steroid-sparing agents: AZA or MMF (faster action)
In which variant of CIDP is asymmetry classic?
What is POEMS? Which serum level is diagnostic?
VEGF level is doagnostic
What pedal changes would be seen in Charcot-Marie-Tooth disease?
What is the mutation responsible for hereditary sensitivity to pressure palsies (HSPP)?
- Prolonged distal motor latencies
What does nerve biopsy show in Charcot-Marie-Tooth disease?
Where is a biopsy taken form for diagnosis of amyloidosis? What does it show?
Apple-green birefringence on congo red stain
What are the treatment options for diabetic neuropathy?
2 duloxetine or pregabalin or gabapentin
What are the features of Morvan Syndrome and which antibody is implicated?
- Caspr-2 => directed at Voltage-gated K channels
Which antibodies are implicated in 60% of cases of stiff person syndrome?
What antibodies are associated with myasthenia gravis?
ACh receptor Ab
- 80-90% sensitive
- positive in 40% of AChR-negative patients.
- more severe weakness, not affecting eyes or limbs
- not associated with thymic disease.
- mild-moderate disease
- not associated with thymic disease.
Anti-striated muscle Ab
- positive in 90% of thymomas
Ryanodine receptor Ab
- positive in 70% of thymomas with MG
- marker for severe disease
Titin Ab (in addition to ACh R Ab)
- thymoma and late-onset MG
- poor sensitivity but specific for MG
What should be specifically checked for on examination in myasthenia gravis?
- Sustained upward gaze - weakness of eyelid elevators and oculomotor muscles
- Peek sign - eyelids separate after 30sec of closing, and sclera is visible.
- Dysarthria - palate weakness
- Dysphonia on counting - bulbar weakness
- Smiling causes snarling expression
- Neck flexion weakness
- Flap 1 arm then test muscle strength together - asymmetrical due to fatigue of one arm
- Improvement of ptosis with ice cube application
What does EMG show in myaesthenia gravis?
Repetitive stimulation shows progressive decrease in amplitude of action potentials
Needle examination - motor unit potential variation and, sometimes, fibrillation potentials and myopathic changes
Single-fibre EMG - increased jitter (variable interpotential interval). 80% sensitive.
What other investigations should be performed in myaesthenia gravis?
Thymoma search - CXR, chest CT or MRI
Respiratory function tests - weakness in muscles of respiration
What is myasthenic crisis and how is it treated?
Crisis involves respiratory weakness causing respiratory failure. Often caused by an infection.
IVIG or plasma exchange
What is first line treatment for myaesthenia gravis?
Acetylcholinesterases - pyridostigmine
K supplements and K-sparing diuretics may improve symptoms but are rarely used
What if acetylcholinesterase inhibitors fail in myaesthenia gravis?
Steroids - may worsen symptoms and therefore should be monitored closely during initiation.
Immunosuppressants next line - azathioprine may be used as steroid-sparing agent, however should never be used as monotherapy.
Rituximab in desperate cases
What % of myasthenia gravis have isolated ocular signs?
Which antibodies are implicated in isolated ocular myasthenia gravis?
Acetylcholine and LRP4 (not MuSK)
What autoimmune diseases are often associated with myasthenia gravis?
Thyroiditis (most commonly)
SLE and RA
Kv1.4, ryanodine and titin antibodies in myasthenia gravis are associated with which coexisting cardiac condition?
What is the most effective cholinesterase inhibitor used in myasthenia gravis?
Which subpopulation is it less effective in?
Less effective in MuSK positive patients
What is second line Rx for myasthenia gravis?
2nd - Prednisone + AZA
3rd - Mycophenolate (mild) or rituximab (moderate)
4th - Methotrexate, cyclosporin, tacrolimus
How is myasthenic crisis treated?
IVIG or plasmapheresis
Which myasthenia patients should have a thymectomy?
- Those with thymomas
- Early-onset myasthenia gravis
- Generalised myasthenia gravis and ACh receptor Abs. 70% of these show improvement after thymectomy.
- Seronegative MG with generalised disease and biomarkers similar to early-onset MG
Not recommended in:
- MuSK or LRP4 Ab positive
- Ocular MG
- Seronegative MG
Which medications may precipitate a myasthenic crisis?
Calcium channel blockers
What side effects are associated with pyridostigmine?
Abdominal cramps, diarrhoea
Which features of Lambert-Eaton Myasthenic Syndrome distinguish it from myasthenia gravis?
- No ophthalmoparesis, facial weakness or bulbar involvement
- Poor response to cholinesterase inhibitors
- Autonomic symptoms
- Reduced deep tendon reflexes
- Increase in size of CMAP on repetitive nerve stimulation
Anti-Hu antibodies are associated most strongly with which cancer?
What paraneoplastic syndromes are they associated with?
- Lung cancer (mostly small cell)
- Encephalomyelitis, limbic encephalitis, brain stem encephalitis, cerebellar degeneration, multi-segmental myelitis, sensory neuronopathy, sensorimotor neuronopathy, autonomic neuronopathy
Anti-Yo antibodies are associated with which cancers?
Which paraneoplastic syndrome are they associated with?
- Ovarian and breast
- Subacute cerebellar degeneration
Anti-CRMP5 antibodies are associated with which cancers?
- Small cell lung cancer, thymoma
Anti-Ma2 antibodies are associated with which cancers?
- Testicular cancer
Anti-Ri antibodies are associated with which cancers? Which syndrome is most associated with it?
- Breast, ovarian, SCLC
- Associated with opsoclonus-myoclonus syndrome
Anti-amphiphysin antibodies are associated with which cancers?
Which paraneoplastic syndrome are they associated with?
- Breast, SCLC
- Limbic encephalitis, stiff person syndrome
Lhermitte's sign is suggestive of a lesion in which part of the nervous system?
Dorsal columns of C-spine or caudal medulla
Which antibodies in neuromyelitis optica are associated moreso with optic neuritis than myelitis?
- Also found in ADEM
What is the order of progression in multiple sclerosis medications?
1. Glatiramer acetate, beta-interferon
2. Daclizumab, teriflunomide
3. Fingolimod, dimethyl fumarate
4. Natalizumab, alemtuzumab
5. Autologous HSCT
What is the mechanism of action of fingolimod?
- S1P receptor agonist. Causes
- Prevention of lymphocytes from migrating out of lymph nodes
What side effects are associated with alemtuzumab?
Autoimmune thyroid disease
Immune thrombotic thrombocytopenia
Membranous GN and anti-GBM disease
What does CADASIL stand for and what is the mutation responsible for it?
CADASIL = Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy
Notch 3 mutation - chromosome 19q12
Which 2 areas of the brain are classically involved in CADASIL?
Anterior temporal lobes
What is the mechanism of action of glatiramer?
- Competition with myelin antigens for binding to T cells
- Induction of Th2 suppressor cells that downregulate inflammation
What is the mechanism of action of alemtuzumab?
CD52 mAb - stimulates antigen dependent cell-mediated cytotoxicity
What side effects of dimethyl fumarate should be monitored for?
What side effects are associated with fingolimod?
What are the 3 main clinical presentations associated with neuromyelitis optica? What are 3 less common presentations?
- Optic neuritis
- Longitudinally extensive transverse myelitis
- Area postrema syndrome (nausea/vomiting/hiccups)
- Other brainstem lesion
- Narcolepsy or diencephalic syndrome with MRI lesion
- Symptomatic cerebral syndrome with MRI lesion
What is the treatment for neuromyelitis optica?
What does dimethyl fumarate act on to down-regulate inflammation?
How does teriflunomide act?
Inhibition of DHODH, which is necessary for pyimidine synthesis in prolferating lymphocytes.
What are the risk factors for Sudden Unexplained Death in EPilepsy (SUDEP)?
Long duration of therapy
Early onset epilepsy
What is the approximate incidence of SUDEP in epileptic adults?
1 in 1000
What is the most common genetic generalised epilepsy?
What are the typical features of it?
Juvenile myoclonic epilepsy
- Typical absence seizures, usually precede myoclonic jerks by 1-9 years
- Myoclonic jerks on wakening
- Generalised tonic clonic seizures develop months to years after myoclonic jerks
- Very sensitive to EtOH and sleep deprivation
- Autosomal dominant
What is first line treatment for juvenile myoclonic epilepsy?
What is the most commonly affected area in temporal lobe epilepsy?
Mesial temporal lobe (hippocampus) - 65%
During which period of sleep do sleep-related hypermotor epileptic seizures usually occur?
What is the classic finding in GLUT1 deficiency and how is it treated?
Low CSF glucose
Treat with ketogenic diet
What is the classic finding in GLUT 2 deficiency?
Paroxysmal exercise-induced dystonia
Which 2 HLA genes are associated with Stevens Johnson Syndrome?
HLA-A*3101: Europeans and Japanese
Which form of epilepsy is anti-GAD antibody associated with?
Temporal lobe epilepsy
What does levetiracetam bind to?
Where do gabapentin and pregabalin act on?
Post-synaptic calcium channels
What are the 2 sites of action of lacosamide?
CRMP-2 pathway (pre-synaptic)
Na channel inactivation (pre-synaptic)
What is the primary site of lamotrigine?
Which antiepileptic is 1st line in absence seizures?
What % of patients become seizure-free after their first antiepileptic agent?
What happens in coadministration of COCP and lamotrigine?
Lamotrigine metabolism increased by COCP - dose must be increased
What is the main teratogenic risk involved with sodium valproate and carbamazepine?
What side effects are associated with sodium valproate?
What side effects are associated with carbamazepine?
What side effects are associated with phenytoin?
Coarsening of facial features
What side effects are associated with topiramate?
What is the most effective treatment in mesial temporal lobe epilepsy?
What are the first line antidepressants for epileptics?
Citalopram and sertraline
What are the 2 main genetic forms of Parkinson's Disease?
Parkin, DJ-1 (recessive) also PINK1
Lrrk2, SNCA (Dominant)
Name the 3 main synucleinopathies?
Lewy Body Dementia
Multiple System Atrophy
What is the main part of the brain affected in Parkinson's Disease?
Substantia nigra pars compacta
Which receptors do pramiprexole and ropinirole act on?
Which receptor does rotigotine act on?
Which population are they useful in?
Useful in dysphagia
What are the ergot-derived dopamine agonists and which receptors do they act on?
What are the MAO-B inhibitors used in Parkinson's Disease?
Rasagiline and selegiline
- Reserved for late disease
What is the mechanism of action of apomorphine?
D2 receptor agonist
What is amantadine used for?
Dyskinesias in Parkinson's Disease
Which part of the brain is deep brain stimulation targeted at?
Globus pallidus internus
Which antipsychotic has evidence supporting treatment of psychosis in Parkinson's Disease?
Trial reduction in anti-PD meds first
What is the first line treatment for depression in Parkinson's Disease?
What are the approved treatments for dementia in Parkinson's Disease?
Donepezil may be useful for hallucinations and cognitive impairment
What are the treatment options for REM sleep behaviour disorder?
How do Parkinsonian tremor and essential tremor differ from each other?
PD - Rest tremor, 5Hz, asymmetrical
Essential tremor - Postural tremor, 10Hz, symmetrical
What is the putaminal slit sign specific for?
MSA Parkinsonian type
What is the classic pontine finding in multiple system atrophy - cerebellar type?
Hot cross bun type
How does midodrine act?
What is the mechanism of action of mirabegron?
What is a side effect of levodopa in MSA?
Exacerbation of orthostatic hypotension
What is the first eye movement to be affected in Progressive Supranuclear Palsy?
What is the MRI brain classic finding in PSP?
Hummingbird sign - midbrain atrophy
What are the treatment options in PSP?
Levodopa and amantadine
Which Parkinsonian condition demonstrates myoclonus and limb apraxia?
Which of the Parkinsonian syndromes has the worst median survival from diagnosis?
What can be used to treat dystonias in corticobasal degeneration?
Botox if painful
What is the genetic mutation responsible for Huntington's disease?
When does it become symptomatic?
CAG triplet repeat disorder of the huntingtin gene on chromosome 4.
Symptomatic at >37 repeats
Which neurons are affected in Huntingtin's Disease?
Which part of the brain may show atrophy in Huntington's Disease?
What is the treatment for tardive dyskinesia?
Which brain structure is damaged in hemibalism?
How does Brown-Sequard syndrome present and what is it caused by?
- Ipsilateral paralysis
- Ipsilateral vibration, proprioception and light touch discrimination
- Contralateral pain and temperature
Caused by cord hemisection.
What is the genetic mutation responsible for Wilson's Disease? What is its mode of inheritance?
How is Wilson's Disease diagnosed?
High urinary copper
High copper levels on liver biopsy
What are the treatment options in Wilson's Disease?
Trientene if intolerant of penicillamine
What is the genetic mutation responsible for Fragile X-associated tremor/ataxia syndrome (FXTAS)? What is the mode of inheritance?
CGG triplet repeat 55-200 in FMR1 gene
What is the classic MRI sign found in FXTAS?
Middle cerebellar peduncle sign
Name 3 dopamine receptor agonists approved for restless legs syndrome
Pramipexole, ropinirole, rotigotine
Name 5 causes of restless legs syndrome
Drug induced - metoclopramide
What ar the windows for IV thrombolysis and IA thrombectomy?
thrombolysis - 4.5 hours
thrombectomy - 6 hours
What is the mechanism of action of idaracizumab?
Monoclonal antibody that competitively inhibits dabigatran (competes with FIIa)
In cervical artery dissection, is anticoagulation or antiplatelet therapy more effective?
What is the prefered class of antihypertensives in ischaemic stroke?
- Calcium channel blockers
- Beta blockers may increase risk of ischaemic stroke, however are indicated in concurrent ischaemic heart disease
When should patients be mobilised after an ischaemic stroke?
After 24 hours
What is the mechanism of action of evolocumab?
- PCSK9 inhibitor - increases hepatocyte LDL receptors available to degrade LDL
- PCSK9 degrades LDL receptors
How does amyloid angiopathy present and in which population?
Lobar, juxta-cortical haemorrhages in the elderly
Where do hypertensive intracerebral haemorrhages tend to present?
Putamen, thalamus, pons
Which levels of the Modified Rankin Scale qualify for thrombolysis?
Which medication should be used for DVT prophylaxis post-ischaemic stroke?
Enoxaparin (more effective than heparin in this population)
Which patiets with an ischaemic stroke would benefit from hemicraniectomy?
Large ischaemic MCA stroke and age<60
When should a NOAC be commenced post-stroke in non-valvular AF?
small stroke - day 3
moderate stroke - day 6
large stroke - day 12
When is TIA or stroke recurrence highest?
3 weeks to 3 months
What consitutes valvular atrial fibrillation
AF with the absence of mitral stenosis or mechanical heart valve
Which patients should have carotid endarterectomies and within what time frame?
- Treat SYMPTOMATIC carotid artery stenosis 70-99%.
- Carotid endarterectomy within 2 weeks of event
When should patent foramen ovale be closed?
1. PFO + atrial septal aneurysm + large shunt
2. Young patient with ambolic ischaemic stroke and no other cause identified for stroke
How does the OCP affect stroke risk?
Elevated risk with oestrogen but not progesterone
What are the 4 clinical features associated with Creutzfeldt-Jakob Disease?
Visual or cerebellar disturbance
Which tumour are NMDA receptor antibodies associated with?
What should be tested for in hypokalaemic periodic paralysis?
Alexia without agraphia is specific for which arterial territory?
What are the 4 types of Creutzfeldt-Jakob Disease?
Sporadic - most common (85%)
Iatrogenic - from dural grafts, etc
Variant - from bovine spongiform encephalopathy
What is the classic MRI finding in CJD?
FLAIR and DWI: Cortical ribboning and basal ganglia hyperintensity
What is necessary to diagnose CJD?
- Brain biopsy showing PrPsc
- PRNP gene testing must be performed to exclude familial CJD
What might CSF show in CJD?
- Pleocytosis (lymphocytes)
- Elevated protein
- 14-3-3 protein
Which muscles are affected in a deep peroneal nerve palsy? Which sensory distribution?
- Tibialis anterior: ankle dorsiflexion, foot eversion
- Extensor hallucis: big toe extension
- Extensor digitorum longus: lateral 4 toes extension
- Extensor digitorum brevis: big toe and medial 3 toes extension
Sensory: first dorsal webspace
How can an L5 nerve palsy be distinguished from common peroneal nerve palsy?
L5: Foot inversion and hip abduction affected, unlike peroneal nerve
How might CSF help distinguish between multiple sclerosis and neuromyelitis optica?
MS: oligoclonal bands
NMO: NO oligoclonal bands
What is the treatment for neuromyelitis optica?
Rituximab and MMF
A lesion in which vascular territory is responsible for the syndrome of alexia without agraphia?
What is the mechanism of action of pimavanserin and what is it used for?
Inverse agonist of 5-HT2A receptor.
Used for psychosis in Parkinson's Disease.
What are the first and second line treatments for trigeminal neuralgia?
What are the first and second line treatments for greater occipital neuralgia?
1. Occipital nerve block
2. Gabapentin or pregabalin
Which nerves are most likely to be affected by a cerebellopontine angle tumour?
V, VII, VIII
Which muscle flexes the distal interphalangeal joints in the fingers?
Flexor digitorum profundus
What is the mechanism of action of benztropine in Parkinson's Disease?
Atypical competitive inhibitor of dopamine reuptake
How can central retinal artery occlusion and central retinal vein occlusion be differentiated on fundoscopy?
- Grossly swollen and pale retina
- Prominent fovea (cherry red spot)
- Disc is massively swollen with splotches of haemorrhage and cotton wool spots