Neuro Flashcards
myasthenia clinical features
Variable weakness
- not mental fatigue
- Worse with exertion, later in day
- ?ppt by infection, antibiotics
Pattern
- Ocular/ Facial‐ most!
- Bulbar
- Truncal
- Limbs
Would you discontinue AEDs if someone has not had a seizure in 2yrs - and if so - who would you not consider an ideal candidate for this?
- yes - if in remission for at least 2 yrs - 60% still in remission after 2 yrs
- unfavourable factors - previous unsuccessful withdrawal, abnormal EEG, syndrome (JME) seizure types -juvenile myoclonic epilepsy - cannot withdraw
What is Fampridine PR?
- drug used to improve walking speed in MS - medication for symptomatic management in MS and does not alter the disability progression - has been thought to cause seizures in some patients esp with incorrect dosing.
What is the evidence for warfarin in AF with stroke
Evidence for warfarin in primary/secondary prevention of
ischemic stroke in patients with AF:
- Warfarin is much better than placebo:
- SPAF, EAFT…
- Warfarin is much better than aspirin + clopidogrel:
- ACTIVE‐W
- Aspirin + clopidogrel is no better than aspirin:
- ACTIVE‐A
- Age alone does not alter the overall benefit of warfarin but
aspirin gets riskier for no benefit:
• BAFTA Lancet 2007 370:493‐503
What is PML?
- rare progressive demyelinating and potentially fatal infection of the brain - caused by opportunistic reactivation of JC-virus ( a polyoma virus) induced oligondendrolgliopathy - association of PML with 3 humanised monoclonal antibodies - Natalizumab, rituximab and other immunosupp MMF, MTX, aza
What is transverse myelitis?
- condition in which the spinal cord is inflamed
- inflam damages nerve fibres and causes them to lose their myelin coating leading to decreased electrical conductivity in CNS
- MOST common is idiopathic
- bimodal peak 10-19, 30-39 M=F
- presentation with cord syndromes - sensorimotor/autonomic evolving over hours/days - bilateral signs, limb weakness, stiffness, muscle spasm.
- urinary retention, constipation, autonomic dysreflexia
- preceding non specific viral illness is ocmmon - fever, nausea, myalgia
- clearly defined sensory level, progression to nadir of clinical deficits between 4hrs and 21days after symptom onset
what is juvenile myoclonic epilepsy of janz?
idiopathic primary generalized epilepsy
- age of onset – usually 12-17 yrs
- myoclonic seizures on waking (100%)
- +/- generalized tonic-clonic seizures (90%)
- plus ? absence seizuresi n 10-15%
- 90% will never remit – ie lifelong treatment
EEG:
- Generalised polyspike-wave-discharges 3-6Hz – 30-40% show photosensitivity
High heritability – two single gene causes identified – minority of cases – EFHC1 – unknown function and CLCN2 – voltage gated chloride channel
Treatment = Valproate, Lamotrigine
Carbamazepine worsens control
When is epilepsy surgery beneficial
- 1% of pts may be suitable – principally mesial temporal sclerosis and other focal temporal lobe lesions
- 75-85% pts are seizure free post surgery – with 10% having late relapse
- extratemporal and non-lesional resections do worse
- typical pathologies
- mesial temporal sclerosis
- cavernous haemangiomas – cavernomas
What is the oral treatment for MS?
Fingolimod - the FIRST tablet to be available on the PBS - it selectively retains circulating lymphocytes in lymphoid organs - acts on four of five sphingosine 1 phosphate receptors - on admin - rare cases of heart block in the first 6 hrs - do not administer with Beta blockers within first 2-4weeks. Can cause macular oedema in 1st 3 months. Superior to IFN B1a in relapse rate but not disability.
Treatment of MG
- control symptoms - Anti-cholinesterase inhibitors - Mestinon
- induce remission
- avoid relapse
- minimise side effects , avoid extreme temps, tirednesss
- prednisolone
- other immuno-supp - aza, cyclo, myco, cyclophos ?thymectomy
ivig plasma exchange
What causes a thunderclap headache when SAH and ICH excluded -
Consider reversible cerebral vasconstriction syndrome - esp in marijuana smokers
What is Alemtuzumab - lemtrada for MS?
anti CD52 antibody CD52 is a B and T cell antigen - but therapy depletes B cells more than T cells Monoclonal ab to CD52 - ablates circulating lymphocytes B cells recover fastest SE: increase in early infections esp HzV, VZV and pneumonia. a few cases of PML
What are the MS subtypes
1) RRMS - relapsing - remitting (most common, F/M 3:1 - most aggressive, relapses decrease after 1st 5 yrs 2) SPMS - secondary progressive MS - 1/3 have relapses 3)PPMS - 20% of males, behaves exactly like secondary progressive disease 4) progressive relapsing MS -
IV TPA contraindications expanded
Too mild, rapidly improving, too severe?
- Symptoms suggestive of SAH despite normal CT
- Seizure at onset
- BSL <2.7mmol/L
- BP >185/110
- Head trauma or prior stroke within 3 months
- Non‐compressible arterial puncture within 7 days
- Any history of previous intra‐cranial hemorrhage
- Evidence of active bleeding or acute trauma (fracture) on
examination
- If on anticoagulation: warfarin+INR>1.7/heparin w/ abnormal APTT
- Platelets <100
RELATIVE Contra‐indications
- Myocardial infarction within 3 months
- Gastrointestinal or genitourinary hemorrhage within 21 days
- Major surgery within 14 days
- CT >1/3 MCA hypodensity —> beyond our help
What about AEDs in the elderly
need to consider hepatic and renal function
drug interactions
- CBZ least tolerated - 31% ceased
- LTG best tolerated - 12% ceased
efficacy similar
For dx of MS what criteria are used
Mcdonald criteria - dissemination in space and time - so need minimum 2 lesions in 2+ regions in CNS - periventricular, juxtacortical, infratentorial and spinal cord
what is the clinical course of MG
- Untreated‐ spontaneous remission in 12‐ 21%
- Mildmoderate/severe over months
– Spread from eyes>face>bulbar>trunk, limbs
• Pure ocular MG
– ~50% generalised MG in < 2yrs
• GeneralisedMG
– Maximal worsening occurs in 1st 2‐3yrs
– Most of relapses, variability occurs in first 7 yrs
– Improvement less likely in more severe cases
What is the treatment for CIDP
Prednisolone‐ daily
IVIG‐ ~4 weekly
Plasma Exchange
IV Methyl Prednisolone – pulse
+/‐ Azathioprine
+/‐ Cyclosporin A, Mycophenolate, Rituximab
? (Cyclophosphamide +/‐IVMP +/‐ Plasma Exchange)
Tx for PML and MS
- stop immunosuppressant immediately 2. consider immune reconstitution - plasma exchange to remove antibodies 3. risk of severe immune reconstitution inflame syndrome (IRIS) with cerebral oedema and clinical deterioration can use mirtazepine (possible reduction of virus entry into cells) can use Mefloquine - some anti JCV activitis - trial ongoing IV methylpred - given at fire sign of IRIS - 7 day course
Ischaemic stroke classification 1
• Large artery thromboembolism
• Cortical infarction, >50% relevant large artery stenosis,
absence of cardiac source
• Cardiogenic embolism
• Cortical infarction, sometimes >1 vascular territory,
identifiable cardiac source (most often Afib), absence of
large artery disease
• Lacunar Infarction
• Subcortical infarction, absence of large artery or cardiac
source, clinical syndromes
Nerve conduciton studies in demyelinating neuropathy
Nerve conduction studies
Conduction velocity: Very slow (Upper extremity < 37 M/s)
Conduction block: Failure of impulse conduction along an anatomically intact axon
Dispersion of motor response
Prolonged distal latencies & F‐waves
EMG
Reduced motor unit recruitment (fast firing motor units) in clinically weak muscles
what are the first line drugs for genreralised epilepsy
- first line - valproate, ethosuximide
- new AEDs - lamotrigine, topiramate, levetiracetam
- second line - clonazepam/clobazam
what is the inflam response in MS
Bias towards Th1 and Th17 lymphocytes environment with T reg cell dysfunction secreted cytokines disrupt BBB and up-regulation of endothelium - hence T cells enter CNS
Define epilepsy
tendency to recurrent unprovoked seizures of primary cerebral origin (requires at least two unprovoked seizures
typically a clinical diagnosis, history is paramount
seizure – transient occurrence of signs and or/symptoms due to abnormal excessive activity in the brain.
What is Glatiramer acetate (cop axone) and when is it used?
- synthetic polypeptide containing myelin basic protein - promote proliferation of Th2 cytokines, alters macrophage function. Reduces interferon gamma. Induces Th1 –> Th2 Adverse - daily injection, rare reaction with palpitations, chest pain dyspnoea, pregnancy category B
What is Multiple sclerosis?
- autoimmune inflammatory disease - affects CNS - demyelination and axonal degeneration - 50% need walking stick at 15 yrs
drug induced neuropathy
What is the pharmacokinetic explanation for vaproate-dose-effect?
• Beta‐oxidation of VPA saturates at
approximately 800 mg/day.*
– Percentage of VPA excreted as glucuronide
increases:
• from 12.8% at 400 mg/day to 49.4% at 2000 mg/day.
– Glucuronide more reactive than products of betaoxidation. - doses above 1000mg are toxic
Where do motor tracts cross? ipsilateral or contralateral symptoms?
- cross in the lower medulla
- originate from a long cortical strip - posterior frontal lobe
- compact in the internal capsule and in the spinal cord
- any lesion in the spinal cord will give ipsilateral problems
- anything in the brainstem or above will give contralateral problems
what is impaired consciousness in epilepsy
inability to encode new memories
inability to interact purposefully with environment – test by asking pt to obey commands
What is Dimethyl Fumarate - Tecfidera
it is an oral drug - also used for psoriasis and MS - activates NRF-2 pathway vs oxidative stress and causes mild neutropenia SE: flushing, GIT - but may settle in 1-3/12.
What does the lumbar puncture show in transverse myelitis?
demonstrates spinal cord inflammation - pleocytosis or elevated IgG index
IgG index is a measure of intrathecal synthesis of immunoglobulin
Classification of ICH
Deep
- Putamen, thalamus, brainstem, cerebellum
- Usually due to hypertension and rupture of deep penetrating arteries
Lobar
- Superficial
- Often secondary to amyloid angiopathy, tumour, arteriovenous malformation, venous sinus thrombosis
melanoma met bleeding most common
What is Natalizumab (Tysabri) and when used?
Monoclonal ab to alpha4 integrin (VCAM1) inhibits tissue migration of lymphocytes and monocytes into CNS In other words - binds to alpha4 intern (VLA-4) on lymphocytes stopping them from binding to endothelial VCAM1 and crossing BBB. Used as mono therapy for RELAPSING-REMITTING MS - given monthly IV- relapse risk reduction 67% LFT abnormalities can occur - transaminitis
What are the risk factors to develop PML
- duration of exposure > 2yrs 2. previous exposure to an immunosupp - methotrexate, aza, cycle 3. JCV serology positive
what is demyelinating neuropathy
- primary destruction of the myelin sheath leaving the axon intact
- secondary axonal degeneration common late in the disease course
- weakness - proximal and distal wasting
- tendon reflexes reduced
- many causes incl immune/inflammatory, drugs/toxins, metabolic,
What are the major SE of interferons
1) Flu like symptoms at commencement 2) Injection site reactions - ice skin before injection 3) LFT abnormalities are mild - screen at 1 and 6 months after starting treatment
What are the clinical features of PMS
Subacute onset progressive cortical symptoms/signs behaviours and neuropsych alteration hemiparesis
Where do dorsal columns cross over?
- dorsal columns responsible for joint position and vibration
- input from large sensory fibres in peripheral nerves
- cross in medulla
- cross over in lower brainstem
What is the primary tx for MS - first treatment available
Interferon B1 - avonex or 1FNB1b - betaferon It binds to receptors on immune cells - decreases antigen presentation and T cell proliferation, decreases cytokine and MMP expression Major reaction is flu like symptoms and injection site necrosis
what is primary lateral sclerosis
Primary lateral sclerosis
- 2‐3.7% of all patients with MND;
- pure UMN syndrome
- Slow rate of progression Pringe et al 1992
What is the link between AED and PCOS
- menstrual irregularities and polycystic ovaries more common -regardless of which AED
hyperandrogenism associated with VPA - avoid in child-bearing
PCOS prevalence 12.5-26% compared to 6.6% (seems to be associated with VPA)
WHAT ABOUT EPILEPSY AND CONTRACEPTION
Pregnancy and epilepsy
- proconvulsant effect of oestrogen vs progesterone
- background malformation rate – 2%
- roughly doubles on one AED
- valproate especially more than 1g a day and polypharmacy particularly teratogenic
- no agent known to be safe
Contraception
- combined OCPs – increased oestrogen metabolism with PHT, CBZ, PB, LTG levels lowered
- progesterone – anticonvulsant effect
what is the difference between simple partial and compex partial seizures
Simple partial – consciousness preserved
Motor or sensory incl special sensory
Autonomic
Psychic
Complex partial – consciousness impaired –not lost
Simple partial onset – aura
Or consciousness impaired from onset
Ix and diagnosis of PML
CTB - often normal - occasional areas of hypo density MRI brain - almost always abnormal - very often sub-cortical U fibers, large >3cm lesions, contrast enhancement in 41% with early PML (60-76% overall) Ix - serology 55% of normal adults have JCV antibodies DNA - JCV PCR of CSF - 74-93% sensitive, 92-100% specific. PCR of PBMC or urine not helpful, CNS biopsy still required frequently
What is chronic inflammatory demyelinating polyneuropathy (CIDP)
Symmetric motor & sensory deficits
- Proximal & distal weakness>wasting
- Absent or reflexes
- Distal LL>UL sensory loss ‐20% painful; autonomic/resp uncommon
Gradual onset over months‐years; progressive > 2M
10% acute onset
Natural history variable
Chronic progressive 60%
Relapsing ‐remitting 30%
Monophasic 10%
Spontaneous remission not uncommon but difficult to predict
M>F, all ages (mean 50yrs)
<10% children
What is subacute combined degeneration of spinal cord?
- also known as Lichteim’s disease
- refers to degeneration of pos and lateral columns of spinal cord
- 2* to Vit B12 deficiency - most common
- other causes - vitamin E deficiency, copper deficiency
- presents with patchy loss of myelin in dorsal and lateral columns - weakness of legs, arms, trunk, tingling, and numbness that progressively wrosens
- made worse with nitric oxide in those with B12 deficiency
- can precipitate copper def if taking zinc - displaces zinc
What is the classic basilar occlusion?
- unconscious collapse and decreased GCS at presentation without cardio/resp arrest
- preceding hx helps
- Quadriparesis with upgoing plantars
- check the eyes - loss of VOR - the vestibulo-ocular reflex
- pupillary changes, ptosis
- CT angiogram if NCCT excludes brainstem and large hemispheric ICH
Which artery supplies most of the spinal cord - hence if it is a spinal cord infarct what aa is likely?
- ant spinal aa supplies most of the spine
- the pos spine supplied by various arteries - so if infarct then ant spine
what are the key important facts about monitoring phenytoin and other drug levels? would you measure valproate levels?
- suitable drugs have narrow therapeutic index
- close relation of plasma levels to therapeutic/toxic effects
- wide inter-individual variation in metabolism
- must monitor phenytoin (zero order kinetics)
- useful to monitor carbamazepine +- phenobar, ? lamotrigine
- valproate levels only useful for monitoring compliance
- trough levels important if half life is short – carbamazepine, not phenobarb
where does the spinothalamic tract cross?
- responsible for pain and temperature
- input from small sensory fibres in the peripheral nerves
- cross in spinal cord just above site of entry
what are automatisms in seizures?
typically seen during complex partial seizures
stereotyped automatisms
- lip smacking/chewing (operculum)
- limb postures – as above
reactive automatisms
- semi-purposeful interaction with environment – planned actions do not occur
What are the most common causes of axonopathy?
Diabetes
Alcohol
Uraemia
Toxic / drugs
Paraneoplastic (some)
Nutritional
What is pharmcoresistant epilepsy?
- on 2 drugs
still not achieved remissed –> refer for surgery if appropriate candidates
important facts about old AEDs
Phenytoin (PHT) - Saturable – zero order kinetics
Causes purple glove syndrome and phosphenytoin
Carbamazepine (CBZ)
Stevens-johnson syndrome in East Asians – 8% carry HLA B*1502
Hyponatramia common – but more so with valproate
Valproate
Teratogenicity especially at doses above 800mg day
IV form available
Lamotrigine
Danger of SJS – must start slowly – (12.5-25mg daily)
Half life halved by CBZ, PHT, doubled by VPA)
What is brown-sequard syndrome?
- damage to half of the spinal cord
- results in paralysis and loss of proprioception on the same (ipsilateral side of the injury)
- loss of pain and temperature on the opposite (contra-lateral) side as the lesion
- affects dorsal-column-medial lemniscus tract, corticospinal tract, contralateral- - affects spinothalamic.
Pure Brown-Séquard syndrome is associated with the following:
Interruption of the lateral corticospinal tracts:
- Ipsilateral spastic paralysis below the level of the lesion
- Babinski sign ipsilateral to lesion
- Abnormal reflexes and Babinski sign may not be present in acute injury.
Interruption of posterior white column:
- Ipsilateral loss of tactile discrimination, vibratory, and position sensation below the level of the lesion
Interruption of lateral spinothalamic tracts:
- Contralateral loss of pain and temperature sensation. This usually occurs 2-3 segments below the level of the lesion.
what are the emg findings for CIDP
NCS‐ Segmental Demyelination
Motor slowing,
Conduction block, dispersion
Long distal/F‐wave latencies
Absent/low ampl. SNAPs (UL>LL)
CSF protein elevated; <10 cells/mm
MRI
- Nerve root hypertrophy , enhancement
Nerve biopsy‐
- inflammation + atrophy
- segmental demyelination /remyelination
What are the indications for carotid endarterectomy and % of stenosis - ? use in total occlusion
Symptomatic stenosis 70‐99% ‐ strong evidence of benefit
(NASCET, ECST) NB not if already severely disabled
• Symptomatic stenosis 50‐70% ‐ benefit if low surgical
morbidity and good life expectancy
• Carotid occlusion/trickle flow – low risk of recurrent stroke,
generally not suitable for surgery
• Asymptomatic carotid stenosis – surgery rarely indicated
– risk of stroke on optimal medical therapy (antiplatelet,
statin, antihypertensives) estimated ~0.5%pa
• Carotid stenting currently has a higher risk of stroke than
endarterectomy (possible role in patients aged <70?)
what is ALS - amyotropic lateral sclerosis? umn or lmn? involvement?
Amyotrophic lateral sclerosis
- Most common form
- Mixed UMN & LMN
- Limbs & Bulbar involvement
What AEDs to use with contraception
enzyme inducing AEDs promote oestrogen and progestin metabolism (CBZ, PHT, PHB, PRM)
high dose depot is effective
implanon not effective
progestin IUD has acceptable failure rate
EMG and nerve conduction studies in axonopathy?
- reduced/absent sensory potentials lower>>upper limbs
- low amplitude distal motor responses, mildly delayed F-waves
- conduction velocities: mildly reduced consistent with loss of large myelinated nerve fibres
- EMG - neurogenic distal >> proximal muscles
- motor units: high amplitude, long duration, polyphasic, rapid firing
- fibrillations, positive sharp waves
MG diagnosis
History & Exam
Fatigue, variability, pure motor.
Serology‐AChRAb, MuSK Ab
_ Electrophysiolog_y
Repetitive stimulation
Single fibre EMG - most sensitive
_ Pharmacology‐AChEsteras_e
Inhibitors
Tensilon test
Trial of neo/pyridostigmine
antibiodies sensitive but not specific
endovascular clot retrieval and indications
most trial pts were pre-treated with alteplase
indications in 2015 - <6hrs from onset, good non contrast CT scan (small core infarct), ICA, basilar or prox MCA occlusion (M1 or M2)
what is the commonest familial metabolic cause of rhabdo
- CPTII deficiency
- carnitine palmitoyl transferase assay
- muscle bx - moth eaten fibres, Type IIb fibre atrophy and moderate lipid stasis
what is the risk of sudden death in epilepsy?
20-30x higher in young epileptics
total death rate
- increases by 3 or more in young epileptics – depends on syndrome
? caused by cardiac arrhythmias or apnoea
related to frequency and types of seizures
1 = 2/year, absences –> no increase
needs to be raised when discussing treatment and compliance
what are the treatment guidelines for epilepsy?
Provoked seizures – avoid the provoking stimulus – DUH
Generalised seizures – valproate à lamotrigine/topiramate/levetiractam
Absence seizures à valproate/lamotrigine/ethosuximide/levetiracetam (avoid carbamazepine/tiagabine)
Partial seizures à carbamazepine à levetiracetam, topiramate, gabapentin, oxcarbazepine, valproate, tiagabine
Phenytoin still used as IV form – but levetiracetam and valproate also IV forms
What is motor neuron disease?
- protein accumulation in nerve cells
- usually involves uml and lmn
- progressive degeneratio of motor neurons -
- Amyotrophic muscle atrophy, weakness, fasiculation (LMN)
- lateral sclerosis: gliosis post degeneration of corticospinal tracts (UMN)
Oxfordshire stroke classification
Total Anterior Cerebral Infarct (TACI)
– Large infarct, poor prognosis
– Hemiparesis, hemianopia, cortical signs
Partial Anterior Cerebral Infarct (PACI)
– Smaller, better prognosis, risk of recurrence
– 2 of 3 TACI symptoms
• Hemiparesis, cortical signs, hemianopia
Lacunar Infarct (LACI)
– No cortical signs, relatively good prognosis
– Pure motor hemiparesis, pure sensory stroke, sensorimotor stroke, ataxic
hemiparesis, dysarthria‐clumsy hand
Posterior Cerebral Infarct (POCI)
– Stroke with brainstem and/or cerebellar features
– Variable prognosis
– Ataxia, ophthalmoplegia, quadriparesis, crossed signs
What is pharmacoresistant epilepsy?
on 2 meds and still have not acheived remission –> refer for surgery if suitable
What was the Interact2 trial?
It was about BP lowering in ICH
- aggressive BP lowering vs standard care
- showed no increase in serious adverse events
multiple secondary outcomes improved
treat BP aggressively to <140/90 early - some benefit
Treat BP aggressively long term - <130/80
What is progressive bulbar palsy ?
Progressive bulbar palsy
- Presenting sx in ~20% of all px
- Most commonly seen and worst prognosis in in menopausal women
- Lower cervical‐thoracic area
rarely confined to bulbar region only
what is myasthenia pathology?
- disorder of synapse antibody blockade, defect of synapse
- antibody production against NMJ - AChr or MUSK - ? LRP4, Agrin
- thymic hyperplasia
- Ab and immune complexes at NMJ
- ? associated wiht auto-immune disease - organ specific +- FH
- graves, hashimoto’s thyroiditis, pernicious anaemia, vitilligo, diabetes, pemphigus, chronic active hepatitis
- thymoma 15% - invasive rare
- chronic myopathy - long standing/untreated
AEDs and congential malformations - things to know
AEDs are bad, in a dose‐ dependent manner
- Valproate is worst
- Polytherapy is bad
- Folate supplementation is good
- No AED exposure ~3%
- Monotherapy ~6%
- High‐dose valproate ~10%
- Conflicting data on polytherapy
- Levetiracetam low risk
- No proof for folate supplementation
Define stroke and TIA
The classic epidemiological definition…
– Stroke is the rapid onset of focal (or global,
as in subarachnoid haemorrhage) cerebral
deficit, lasting >24 hrs or leading to death,
with no apparent cause other than a
vascular one
– TIAs are the same phenomenon <24 hours = DEBUNKED
- HOWEVER - modern definition -TIAs that last than 1hr usually only a few mins, pt with symptoms have stroke.
TIAs have very high short term risk of stroke - upto 20% within 3 months, HIGHEST risk in first 48hrs!!!
what are the endocrine abnormalities of AEDs on fertility
Endocrine abnormalities (effect of AEDs)
– Increased SHBG levels
– Hyperandrogenism
– Polycystic ovaries
– Menstrual irregularities
– Anovulatory cycles
– Obesity
– Insulin resistance
What is the commonest neuropathy type and the major causes?
Axonopathy! - most common aeitology is diabetes, alcohol, uraemia, toxic/drugs, nutritonal and occs paraneoplastic
they account for 75% of peripheral nerve pathology.
what are the first line drugs for focal seizures?
- First line —> carbamazepine, phenytoin or valproate
- New AEDs - any
- third line - clonazepam/clobazam
The 2007 lancet study on first AED selection - what were the outcomes
CBZ vs LTG, TPM, GBP, OXC: LTG best tolerated;
CBZ and LTG most efficacious
VPA vs TPM, LTG: VPA better tolerated than TPM
and more efficacious than LTG
spinal cord
best treatment for CIS in MS?
Tx with interferons (avonex) with Glatiramer acetate AND Terifluonomide - delays onset of clinically defined MS and reduces MRI activity markedly. not pubs approved
What is the anatomy of cervical roots?
Cervical spine: vertebrae C1-C7, roots C1-C8.
Cervical roots emerge above
• i.e. C6 emerges at C5/6
Thoracic & lumbar roots emerge below
• i.e. L5 emerges at L5/S1
What is HIV neuropathy
Distal symmetric polyneuropathy
Lumbosacral polyradiculopathy (caudaequina syndrome; CMV)
Inflammatory demyelinating polyradiculoneuropathy
Sensory neuronopathy
HIV treatment neuropathies eg. ddI, ddC,d4T, lamivudine etc
What are the main cells involved in MS - pathogenesis?
Oligodendrocytes! - responsible for myelination, one cell can myelinated many fibres in CNS. Patho: 1) inflammation - focal + global infiltration with T cells - CD3, CD4, CD8 and macrophages 2) Demyelination - loss of oligodendrocytes 3) axonal loss - apoptosis and neuronal die-back
What is syrinx syndrome?
lesion with selective, disassociative sensory loss - think central cord lesion
with syrinx can have lower moter neuro signs a well as it spreads out
Def: A syrinx is a rare, fluid-filled neuroglial cavity within the spinal cord
What is the relationship between AEDs and fractures
Study of Osteoporotic Fractures
– Accelerated bone loss in patients on AEDs (phenytoin)
– Increased risk of hip fracture OR ~2
– Not due to seizures
Epilepsy and/or AED use fracture risk OR ~2
– Risk increases with cumulative AED exposure, regardless of
type
potential mechanisms - balance, bone density, vit D metabolism, calcium absorption, bone modelling
need to take measures for bone health - ie smoking cessation, calcium, vit D levels, DEXA
HOT topic - what is benign MS?
A joke! Benign MS is not benign high chance of further disease activity if not treated. truly benign MS can only be diagnosed after 20yrs and in retrospect
what is progressive muscular atrophy?
Progressive muscular atrophy
- Only develop LMN signs without UMN signs;
- Older males more commonly
- Improved survival median 48 months cf 36months
What is dissemination in time?
This is for MS - so you need 2+ relapses at least 1 month apart - i.e. new lesion on follow-up MRI brain or simultaneous non enhancing and contrast enhancing lesions
What are the neuromyelitis optical spectrum disorders?
disorders that are like MS but need to be differentiated from them - need to have +ve anti-aquaporin4 (AQP4) igG and 1 core clinical feature - like optic neuritis, acute myelitis. usually bilaterally.
what are the most commonest type of seizures
- focal - 60%
then eneralised tonic clonic 35%
Characteristics
Epileptic seizures rarely exceed 2 minutes
Eyes open, slowing of bilaterally synchronous clonic movements
Lateral tongue biting is fairly specific
what is flail-arm syndrome
Flail‐arm syndrome
• Symmetric proximal and distal bi‐brachial wasting positive babinski sign
Hu et al 1998
- ~ 10% of patients; M:F 9:1 flail arm group
- Trend toward improved survival in flail‐arm group 57 months cf 39months
What is the TIA to Stroke risk score?
ABCD2 – a prognostic score
- Age ≥60 years = 1
- BP (systolic >140 and/or diastolic ≥90) = 1
- Clinical features
- unilat weakness =2; speech =1; other =0
- Duration
- >60 mins =2; 10-59 =1; <10 =0
- Diabetes
2 day ABCD2 risk:
1% if = 0-3
- 1% if = 4-5
- 1% if = 6-7
Although ignores carotid stenosis and AF
what is the management of status epilepticus?
MEDICAL EMERGENCY
- Death rate 10% - depends on underlying cause – encephalitis or tumour
- > 1 seizure with incomplete recover between or continuous or recurrent seizures for > 30mins (> 5mins medically observed) is a good predictor of CSE development – so TREAT it
- ABC – remove danger
- Stop seizures – benzo/IV/PR/oral/GEL
- Keep seizures stopped – IV phenytoin/levetiracetam/valproate
- Transfer to ICU
How to diagnose MS
MRI is gold standard as noted But can do CSF - oligoclonal bands but not in serum - indicates clonal B cells behind BBB Beware if any polymorphs Can do VERs/VEP - visual pattern evoked afferent volleys to occipital cortex - shows optic nerve demyelination
what causes foot drop after THR under spinal?
Peroneal @ knee vs sciatic @ hip vs L5
usually sciatic nerve - may lose ankle jerk-tibial nerve
What are the birth defects associated with AEDs?
- General increase in most types of birth defect
- Specific associations
– Neural tube defects and hypospadias (VPA, CBZ)
– Congenital heart defects (PHT, VPA, PB)
– Craniofacial abnormalities (PHT, VPA, PB, PRM)
– Genitourinary defects (PHT,
How safe is Terifluonomide in pregnancy
Not safe - although no proper clinical studies - but in rats - demonstrated teratogenicity
What is Terifluonomide - how does it work
active metabolite of leflunomide - approved to treat RA - selective reversible dihydroorotate -interferes with lymphocyte proliferation by inhibiting pyrimidine synthesis in lymphocytes -reducing tyrosine kinase activity - may prevent interaction of lymphocytes and antigen-presenting cells
What is commonest neuropathy?
- Axonopathy - is the commonest
- usually chronic - weeks to months
- predilection for large diameter, long nerve fibres
- distal symmetric pattern
- sensory>motor areflexia
- routine nerve conduciton studies only test for large nerve fibres
What is the approach to suspected acute stroke and contraindications for therapy?
- Consider all <4.5 hrs eligible for alteplase and clot retrieval
- Rapidly improving deficit may indicate good collaterals rather
than reperfusion – high chance of later worsening
• Non‐contrast CT brain + CT angiogram +/‐ CT perfusion
• Key eligibility:
- ischaemic stroke, <4.5 hr, CT excludes ICH
- Are there exclusion criteria for thrombolysis?
- Key exclusions: uncontrolled BP >185/110 at presentation,
recent ischaemic stroke, ICH, current anticoagulation,
excess bleeding risk
What is inclusion body myositis?
Progressive inflammatory vs degenerative myopathy
Most common inflamm disease in older popn
– Onset >60 yrs, ?1/100,000
– Disabling but not fatal
– Wheelchair dep’t in 5‐10yrs
– Auto‐immune disease in 15%
• Proximal & distal weakness
– Selective pattern ? Asymmetrical
– espQuads, Iliopsoas, FDP
– also triceps, biceps, Tibialis ant.
– Depressed reflexes
– Dysphagia in up to 40%
What is Guillian Barre syndrome?
- Most common cause of flaccid paralysis in the developed world
- occurs at all ages, peaks in young adulthood and late life
- slight male predominance
- increase of 20% with every 10 year rise in age after the first decade
- Clinical
- ascending, bilateral symmetric weakness progressing over 12hrs to 28days before plateau is reached
- variable degree of sensory involvement
- generalized hyporeflexia or areflexia – 10% have normal or brisk reflexes
- cranial n involvement, bulbar involvement
The most common precipitating illness leading to Guillain-Barre syndrome? – CAMPYLOBACTER JEJUNI GASTROENTERITIS
What is the antecedent event in GBS ?
- 3 days to 6 weeks before onset
- 30% of infections attributed to C.jejuni and incidence of GBS is estimated to be 0.25-0.65 per 1000 cases of c.jejuni.
- associated with acute motor axonal neurppathy
- may be secondary to presence of molecular mimicry between gangliosides and antecedent infectious agents – lipooligosaccharide on bacteria mimic gangliosides.
- Flu like respiratory illness – in EBV, CMV, VzV, mycoplasma pneumonia
what is the natural hx and prognosis of GBS
- progression upto 1-3 weeks after symptom onset
- recovery over weeks to months
- resp insufficiency in 25% patients
- mortality 1-2.5% 2* to pulmonary Cx
- 85% full functional recovery
- 15% permanent deficit
What is miller fischer syndrome?
- more common in eastern asia
- clinically – opthalmoplegia, ataxia, areflexia
- often distal paresthesia
- strong link to GQ!b IgG autoantibodies
- disease peaks 1 week – improvement in 2 weeks
- excellent prognosis – full recovery by 6 months
- likely to make recovery without treatment - IVIG but not plasmapharesis -_> slight hastening of recovery from opthalmoplegia or ataxia à but time to complete recovery same.
- immune trigger
- autoantigens bind to myelin – activation of complement and MAC – macrophages remove myelin debris
GM1 and GD1a antigens for axonal neuropathy – nodes of ranvier – abs – then directed against these antigens – disappearance of sodium channels – nerve conduction failure and degeneration.
What is CIDP
- preceding illness less common than in GBS
- evolution > 4 weeks, progression over at 2 months
- relapsing remitting – more common in young
- relatively symmetric upper and lower limbs
- usually distal and proximal weakness – if only distal – then think other etiologies
- usually sensorimotor – numbness or tingling – sometimes pain
- reduced absent reflexes
- postural or action tremor
What is the pathogenesis and nerve conduction studies pattern in CIDP
- immune mediated demyelination
- T cell activation is predominant factor
- Macrophages and humoral factors are also important
Nerve conduction studies
- most important investigation tool
- conduction block most common abnormality
- slow conduction velocities
- temporal dispersion
- increased distal motor latencies
- proximal stimulation increases Dx yield
- most have some “axonal change”
What is the treatment of CIPD
IV immunoglobulins
- improvement in 60%
- better earlier response than methylpred – relapse higher
- variable maintenance treatment
plasma exchange
- improvement in 80%
- used for pts who are very weak or experience a relapse on another therapy
- can be considered as long term therapy
steroids
- often avoided
- traditionally 60-100mg oral pred taken daily or alt day then taper
- pulsed cortico similar results with less side effects
What is lambert/eaton syndrome
- auto-antibodies block VGCC and decrease calcium influx during depolarization of pre synaptic membrane which required for release of acetylcholine from pre-synaptic motor nerve terminals
- rare condition
- M:F 5-1
- 50% have underlying malignancy
- may precede tumour by months-years
- usually small cell lung cancer
- other paraneoplastic syndromes may exist
- HLA- 88, -DR3 asssociated – same as MG
clincial features of lambert/eaton syndrome
- difficulty walking is initial symptoms in most
- bulbar and ocular muscles spared or mildly affected – e.g ptosis
- strength improves immediately after exercise
- autonomic dysfunction – dry mout, postural hypotension, erective dysfunction - - ie increasing ACH – increasing calcium release.
- Unlike MG – symptoms typically out of proportion to degree of weakness on examination
- Tendon refelexes absent or reduced – can be increased by brief activation of appropriate muscles or tapping the tendon
VGCC auto antibodies - 85-90% positive
define parkinson’s disease - diagnostic criteria
- accumulation of alpha synuclein
- cytoplasmic lewy bodies
- diagnostic criteria - UK brain bank
- bradykinesia and one of – rigidity, 4-6Hz rest remor, postural instability not due to other cause.
- Supportive criteria (3 criteria) required – unilateral onset, rest tremor, persistent asymmetry, progressive course more than 10yrs, L-dopa response - should be excellent (70-100%), severe L-dopa induced chorea or if response lasts more than 5 yrs – all support parkinsons
What are the pre parkinson’s disease symptoms
- REM sleep behavior disorder – act out their dreams – vivid nightmares, 50% at 10+ years - can use clonazepam or small dose melatonin for tx
- Impaired olfaction
- Constipation - ? GIT disease pre
- Depression
- Parkinsons start in Dorsal motor nucleus in the vagus – or gut, olfactory bulb, to brainstem à limbic à cortex
What are the common problems with non l dopa based strategies for PD
direct dopamine agonists
- ergot-derived – cabergoline - problem with fibrosis – cardiac, pulmonary, retroperitoneal
- non ergot derived – sifrol – pramipexole - behavior – OCD, gamble, shopaholics, sexual behaviours
what are the dx criteria for PSP
Diagnostic criteria
All of – onset age over 40, progressive course, bradykinesia, supranuclear gaze palsy
+ Any three of – dysarthria, dysphagia, minimal/absent tremor, neck/flex worse than extremities rigidity, frequent falls/gait disturbance early
And none of – early/prominent ataxia, unexplained neuropathy, prominent dysautonomia – isolated postural BP allowed
what are the dx criteria for multisystem atrophy
autonomic failure – urinary incontinence, + erectile dysfunction in men
and poorly L-dopa responsive parkinsonism – bradykinesia + 1 other of rigidity, tremor or postural instability
OR cerebellar syndrome
what are the dx criteria for corticobasal syndrome
- probable CBS – greater one yr duration, greater than 50yrs of age, insidious onset/gradual progression
- asymmetric presentation of 2 of :
- limb rigidity or akinesia
- limb dystonia
- limb myoclonus
- plus 2 of
- orobuccal or limb apraxia
- alient limb – not just limb elevation
- cortical sensory deficit
- CBD may also present as non-fluent aphasia
