RPA neurology Flashcards
mitochondrial epilepsy - what anti-epileptic to avoid
valproate - will worsen epilepsy
EEG right vs left vs central
right is even
left is odd
central is z
normal background rhythm EEG
8-13Hz in occipital leads
where is the faster activity in normal EEG
frontal central region “frontal central beater”
15-25 Hz
normal EEEG in drowsiness
neat looking EEG
opening and closing - slow rolloing eye movements
v waves in EEG
normal variant
moving into stage 1 sleep
pointing towards on another in Cz
k complex in EEG
followed by stage spindle
in stage II non REM sleep
REM sleep EEG
looks more like wakeful EEG
has rectus spikes - eyes are moving
intermittent generalised delta slowing in EEG
not specific
encephalopathy
postictal
intermittent theta slowing in EEG
4-7Hz
continuous generalised slowing in EEG
mild to mod encephalopathy
phase reversal in EEG
focal slowing
4Hz spike and wave
JME
triphasic waves
hepatic encephalopathy
but also present in other forms of encephalopathy
PLEDs in EEG
period lateralised epileptiform discharges
high risk of seizure but not seizure yet
?HSV
GPEDs in EEG
generalised periodic epileptiform dishcarges
bad
severe hypoxic brain injury/other bad insults
enzyme inducer p$%)
PHT PB Primidone CBZ OXC TPM
enzyme inducer p450
PHT PB Primidone CBZ OXC TPM
what synergises lamotrigine
valproate
drug resistant epilepsy def
failing after 2 drugs at all doses
carbamazepine and OCP
makes OCP uneffective
Carbamazepine and bones
increases bone loss by increased metabolism of vit D
perampanel MOA
noncompetitive AMPA receptor antagonism
competitive AMPA receptor antagonism
liver metabolised
?for generalised epilepsy syndromes
lacosamide
slow sodium channel blocker - prevents reactivation of the neuron
metabolised by the liver
good for focal status
CAN PROLONG PR
clobazam
benzo
structurally different to benzo
better antiepileptic but less sedating
good for drug resistant focal epilepsy
sleep related epilepsy
clustering
brivaracetam vs levetiracetam
SV2A protein action like keppra
but no ampa effect
so less neutropsychiatric syndromes theorectically unlike keppra
brivaracetam metabolised by the liver
which part of cannibis is used for epilepsy
CBD for epilepsy
THC is psychoactive component but in real life exacerbates seizures
Currently some data for use in lannox gastaut syndrome but not much for adult epilepsies
which part of cannibis is used for epilepsy
CBD for epilepsy
THC is psychoactive component but in real life exacerbates seizures
Currently some data for use in lannox gastaut syndrome but not much for adult epilepsies
risk of epilepsy to offsprings (Generally)
5-8%
targeted therapy for tuberous sclerosis
everolimus because it’s due to aberrant signalling mTOR pathway
HLA-B*15:02
carbamazepine SJS
lamotrigine levels in pregnancy
lamotrigine metabolism accelerated by oestrogen
need to do levels and probably need to increase dose in pregnancy and when on OCP
keppra levels in pregnancy
increased plasma volume in pregnancy so need to monitor levels and probbaly increase dose
painful eye movements MS
optic neuritis
MS typical lesions (Criteria for dissemination in space) - 5
periventricular juxtacortical infratentorial spinal cord cortical
high risk of CIS going onto MS
MRI brain lesions w MS features
greater number of T2 lesions is associated with a graeter risk
60-80% of MS within several years
CSF oligoclonal bands also increases risk of going onto MS
teriflunomide MOA
selectively inhibits DHOH - inhibits pyrimidine de novo synthesis
inhibits rapidly dividing cells - including activated T cells
tecfidera (dimethyl fumerate) MOA
protect oligodendrocytes from inflammatory and metabolic injury
but MOA not really know
fingolimod MOA
functional antagonist of S1P receptors on lymphocytes, fingolimod-phosphate blocks the capacity of lymphocytes to egress from lymph nodes, causing a redistribution, rather than depletion, of lymphocytes
fingolomod SE
macula oedema
lymphopenias
bradycardia/AV block
cladribine pros
oral dosing
minimal monitoring
cladribine MOA
As a purine analog, it is a synthetic chemotherapy agent that targets lymphocytes and selectively suppresses the immune system, its exact mechanism of action in MS is not clear.
CD4 preferentially depleted to CD8
cladribine administration
oral
Two treatment courses, twelve months apart
Tolosa-Hunt syndrome
It is characterized by painful ophthalmoplegia (weakness of the eye muscles) and is caused by an idiopathic granulomatous inflammation of the cavernous sinus
different in measuring CMAP vs SNAP amplitude
CMAP is onset to peak
SNAP is peak to peak
are reflexes lost in demyelination or axonal neuropathy
demyelinating due to the dispersion of nerve impulse transmission that is not sufficient to result in a reflex
e.g. GBS would have loss of reflexes but diabetics rarely do
IgM paraprotein in CIDP
bigger upper limb tremor
POEMS syndrome
Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes
all patients have peripheral neuropathy and a monoclonal plasma cell disorder, almost always of the lambda light chain type
CIDP IVIG vs methylpred
methylpred actually has decreased relapses but some people do not respond and there are more adverse effects
CIDP treatment options
IVIG, methylpred
Other immunosuppressive patients: aza, mycophenolate
rituximab
CMT1a
Most common subtype (40%) of charcot marie tooth
autosomal dominant inherited neuropathy
duplication of the PMP22 gene
Patients with point mutations usually have more prominent clinical manifestations. In these patients, PMP22 partially accumulates in the Schwann cells rather than being inserted in the myelin sheath, as occurs with gene duplication
histology: onion bulb formation (which is characteristic of all demyelination) but is uniform in this disease.
most common form of diabetic neuropathy
Distal symmetric polyneuropathy is the most common form of diabetic neuropathy. The proximate cause is a length-dependent “dying back” axonopathy, primarily involving the distal portions of the longest myelinated and unmyelinated sensory axons, with relative sparing of motor axons.
eye and neurology risks in gastric banding
B12 and thamine def -> peripheral neuropathy
Vit a def -> cataract and retinal changes
what is one of the only myopathies that start with distal weakness
myotonic dystrophy
inclusion body myositis muscles affected
forearm flexors and knee extensors
dermatomyositis biopsy
peripheral inflammation
dermatomyositis antibody
anti Jo1
what else to screen for in dermatomyositis
malignancies
brain, lung, breast
30%
often manifest after DM diagnosis
what antibody is assoc w cancer in dermatomyositis
anti-TIF1gamma
50% have cancer
inclusion body myositis pathology
rimmed vacuoles
characteristic inclusion bodies on EM
need multiple biopsies as the pathology is patchy
anti-HMG-CoA reductase antibodies
associated with autoimmune (immune-mediated) necrotizing myopathies
More than 60% of patients with anti-HMG-CoA reductase antibodies have current or previous exposure to statin therapy
late onset Pompe’s pathophysiology
glycogen storage disease type 2, acid maltase deficiency, alpha glucosidase deficiency
Pompe genetics
GAA ch 17
RYR1 gene
malignant hyperthermia exertional rhabdomylolysis myalgias periodic paralysis complex syndrome`
titin gene
causes muscle myopathies through sacomere something something
drugs that can worsen myasthenias
aminoglycosides, tetracyclines, botox, muscle relaxants
(high dose) pred, aza in the initial period
antibodies in myasthenia
anti musc
ACHR atibodies
ANti LRP4 antibodies
Titin antibodies (often present in ppl w thymoma)
anti-musc phenotype myasthenia
predominantly faciobulbar weakness
general endovascular clot retrieval time limit
6hr
with thrombolysis up to 4.5 hours
thrombolysis treatment time limit stroke
4.5hr (but guidelines worldwide say 6hr)
thrombolysis drug in stroke (in guidelines)
alteplase
however EXTEND-1A TNK campbell et al showed tenectaplase achieved greater rates of reperfusion
clot retrieval extended time frame
up to 24hr <70ml core
idarucizumab
antidote for dabigatran
fragmented antibody binds drug
risk factors for recurrence after TIA/stroke
multiple infarcts on imaging
large atherosclerotic region
ABCD2 6-7
best antihypertensives in stroke
calcium channel blockers
what antihypertensives to avoid in stroke (Except where it is indicated by other means)
beta-blocker
when to start rehab in strokes
after 24hr
lifetime prevalence of stroke
1:6
ICH blood pressure aim
uncertain
don’t go below 140
not too high
most common mimic of a stroke
seizure
definition of “minor stroke” for DAPT in minor strokes
NIHSS <3
prevention of DVT in stroke
enoxaparin (better than heparin and TED stockings are ineffective)
first imaging modality to perform in TIA
CTA
Lewy bodies pathology
alpha-synucleinopathy - accumulation of intraneuronal protein aggregates
affecting substantia nigra pars compacta - dopaminergic projects to the pallidum is depleted
dopamine agonists
pramipexole (D2/3), rotigotine (D3)
rasagiline
monoamine oxidase B inhibitors
can increase dyskinesias
safinamide
MAO B inhibitor + glutamate release inhibitor
shown to increase on time but prevents increase in dyskinesias
entacapone
inhibitor of catechol-O-methyltransferase (COMT). It is used in combination with levodopa and carbidopa (Sinemet) to treat the end-of-dose ‘wearing-off’ symptoms of Parkinson’s disease
used together with levadopa/carbidopa
apomorphine
apomine/movapo
Potent parenteral dopamine agonist, is an effective rescue therapy for sudden “off” periods, for early-morning “off” states, and as a bridge to shorten the “wearing off” effect between scheduled levodopa doses. Prior to regular self-administration, the effective dose for a patient is established by test administration in the office or at home with a specially trained health care professional
best antipsychotic for parkinson’s
clopazine
D1/2 and noradrenergic antagonist
but in real life quetiapine
depression in parkinson’s
nortriptyline
pramipexole
parkinson’s dementia tx
tivastigmine
donepezil
not much evidence
parkinson’s dementia REM sleep
clonazepam
amitriptyline
lewy body dementia vs parkinsons
cognitive problems for 1 year before other parkinson’s symptoms
lewy body vs parkinson’s pathology
lewy body predominantly cortex (but also substantia nigra)
essential tremor frequency
4-12Hz (Parkinson;’s 4-6Hz)
essential tremor characteristics clinical
action tremor
symmetrical
improves w alcohol
can have head tremor
essential tremor plus
classic tremor +
mild neurological signs e.g. cognitive, dystonia etc
or have action + resting tremor
treatment essential tremor
propanolol 1st line
primidone 2nd line (MOA unknown but probably to do with sodium channels - also used as antiepileptic)
other:
- DBS
- focus ultrasound thalamotomy
MSA subtypes
parkinsonian vs cerebellar
MSA characteristics
autonomic dysfunction stridor, sleep apnoea, sleep disturbance JERKY tremor pyramidal signs (brisk reflexes; not present in other parkinsonian conditions) antecollis (head foward) camptocormia (bend forward at hips) Pisa (lean to 1 side) REM sleep disturbance mood instability
young age of onset
MSA pathology
alpha synucleinopathy in glial cells
nigrostriatal or olivoponticerebellar
MSA on MRI
parkinson’s type - putaminal rim
cerebellar type - hot cross bun
MSA treatment
levodopa but can excerbate orthostatic hypotension
treat orthostatic hypotension
manage urinary dysfunction w oxybutinin
PSP gaze palsy
restricted vertical eye movements but overcome w doll’s head manoeuvre
initially presenting with slow vertical saccades
PSP characteristics
vertical palsy
axial rigidity
postural instability
see slides
PSP pathology
tauopathy
PSP MRI
Hummingbird sign - midbrain atrophy
PSP treatment
usually poor response but..
levodopa amantadine (can help w balance)
movement disorder with long halting speech, dysgraphaesthesia, limb apraxia
corticobasal degeneration
corticobasal degeneration pathology
tauopathy
corticobasal degeneration MRI
cortical atrophy
what parkinson like syndromes are tauopathies
CBD
PSP
impersistence of tongue protrusion + depression + occular movement dysfuction
huntington’s
huntington’s pathology
caudate atrophy
gabaergic neurons
huntington’s treatment
chorea - tetrabenazine, antipsychotics
parkisonian features - levodopa
antidepressants
antipsychotics and mood stabilisers
tx for tardive dyskinesias
tetrabenazine
unilateral violent flinging movements of the limbs
hemiballismus
lesions usually in contralateral subthalamic nucleus
but can also happen in caudate nucleus
what liver disease can cause movement disorders
wilson’s disease
presents after hepatic
ATP7B gene
intention tremor + ataxia
+/- parkinsonian sx, peripheral neuropathy
fragile X assoc tremor/ataxia syndrome
fragile X genetic defect
CGG repeat 55-200 is tremor/ataxia syndrome
>200 is just fragile X
X-linked dominant inheritance
fragile X assoc tremor/ataxia syndrome pathology
neuronal and astrocytic inclusions
fragile X assoc tremor/ataxia syndrome MRI
middle cerebellar peduncle signs
restless legs syndrome secondary causes
peripheral neuropathy iron deficiency ESRD pregnancy antiepileptics
treatment for restless legs syndrome
dopamine agonist
levodopa
pregabalin, gabapentin
brachioradialis reflex nerve root
c6
medial thigh and below knee sensory deficit
L3 nerve root compression
headache worse on bending over
increased ICP
pure alexia without agraphia in stroke presentation
dominant occipital love with the involvement of the splenium of the corpus callosum
what causes mollaret’s
HSV2
recurrent meningitis
what else to give pneumococcus
ceft, vanc, dex 10mg IV
Pupil-sparing 3rd nerve lesions
ischemic lesions such as diabetes, hypertension, or arteriosclerotic disease.
acoustic neuroma sx
not discrete episodes
slowly progressive
ear fullness + vertigo
meniere’s
