Neuro Flashcards
what is MS
autoimmune disease causing CNS demyleination
CD4 mediated oligodendrocyte destruction + humoral response to myelin binding protein
mainly affects female 20-40yr
associated with HLA-DRB1 gene (+ absence of HLA-A)
what is radio + histological hallmark feature of MS
demyelination plaques in CNS - radiological
eventual axonal loss - pathological
what are the classifications of MS
primary progressive
relapsing-remitting -> secondary progressive
mostly relapsing remitting
progressive-relapsing
what is diagnostic criteria for MS
McDonalds criteria to diagnose
2+ relapses disseminated in time (by a month) and space (2+ hyper intense T2-weighted lesions on MRI)
if 1 ep of demyelination + clinical signs = clinically isolated syndrome
not diagnosed as MS as not disseminated in time+space
what are 2 phases of MS
early active phase neuroinflammation (disease activity):
macrophage myelin destruction, T cell infiltration, axonal damage, reactive astrocytes
new T2 lesions on MRI +/- clinical relapse (may be asymptomatic)
late chronic phase neurodegeneration:
myelin debris, axonal loss, activated microglia
more clinical markers (MRI, atrophy) but independent of relapse activity (occurs but symptoms don’t worsen)
what is pathophysiology of MS + effects on white/grey matter
only affects oligodendrocytes in CNS
causes multifocal neuroinflammation plaques within:
white matter - more apparent
grey matter (subcortical/cortical) - fewer T/B cells, causes cognitive impairment (late disease)
what immune cells cause MS
auto-CNS-reactive T cells (mostly CD8>CD4)
infiltrates CNS via endothelial adhesion molecules
APC reactive T cell so they release MMP that breakdown BBB
causes oligodendrocyte demyelination, axonopathy, gliosis
what occurs in first attack
MS usually presents with optic neuritis (first attack)
inflammatory processes occur long before
causes optic neuritis - loss of central vision, painful eye movements
MS is disseminated in time and space - so affects different nerves, causing different symptoms
how does early + late MS disease differ
early - re-myelination can resolve symptoms
late - re-myelination is incomplete, so symptoms don’t resolve
how does MS present
optic neuritis (first attack) - loss of central vision (central scotoma), painful eye movements, impaired colour vision
CN6 lesion - double vision, conjugate lateral gaze disorder
lesion in medial longitudinal fasciculus - internuclear opthalmoplegia
Horner syndrome, limb paralysis, incontinence
what are MS RF
20-40yr female, scandanavian
symptoms improve in pregnancy + postpartum
low VitD, UVB exposure, past EBV infection
obese, diabetes, smoker
genes: present HLA-DRB1, absent HLA-A
sarcoidosis, SLE
how is MS investigated
CSF shows oligoclonal bands, indicating ongoing inflammation
gold standard - MRI (shows hyper intense T2-weighted lesions disseminated in time + space)
lesions = inflammation, demyelination, axon damage, oedema
location: periventricular, juxtacortical, infratentorial, medullar
how does MS look micro + macroscopically
micro - initial perivascular/myelin swelling with BBB breakdown
early active phase (neuroinflammation) - T cell infiltration, macrophage myelin destruction, reactive astrocytes
late chronic phase (neurodegenration) - myelin debris, axonal loss, activated microglia
macro - global atrophy, hydrocephalus ex vacuo, thinned corpus callosum, periventricular/juxtacortical demyelination
how is acute MS attack managed
glucocorticoids = IV methylprednisolone 1g OD for 3/7
if not responding to steroids, give plasma exchange
how is relapsing-remitting MS chronically managed
DMART + symptom relief
DMART - reduce disease activity to induce long term remission (3months to reach full effectiveness)
symptom relief - physiotherapy, baclofen (for muscle spasm), anticholinergic (for incontinence), sildenafil (for erectile dysfunction)
what DMART are given for MS
injectable: B-interferon, glatiramer
oral: dimethyl fumarate, teriflunamide, fingolimod
biologic: natalizumab, alemtuzumab
what are neurological + cardiological causes of collapse
neuro - sieuzures, non-epileptic attack disorders
cardio - syncope
how do seizure + syncope differ
seizure = post-ictal confusion, syncope = no confusion
seizure:
sudden onset, with limb jerk/tongue bite/incontinence
usually last <5min
pt is confused after (post-ictal confusion) and may have Todd paresis (residual focal neurological deficit)
syncope:
there is no confusion after fall
vasovagal (neurocardiogenic) - sweating, light-headed, narrowing of vision, lower themself to floor
arrhythmogenic syncope (stokes adams attack) - abrupt onset, no warning
what is status epileptics
seizure lasting 30min+, or multiple seizures over 30min with incomplete resolution
assume status epileptics at 5min
what are 4 stages of status epileptics management
premonitory 0-10min
early status 0-30min
established status 0-60min
refractory 30-90min
how is status epileptics immediately managed
premonitory 0-10min
rectal diazepam 10-20mg
repeat (or buccal midazolam 10mg) once 15min later if status continues
if seizures continue (in hospital), IV lorazepam and if needed repeat once 15min after
what is monitored during status epileptics
O2 sats + glucose (as they are common and rapidly reversible causes of seizures)
if history of alcohol abuse, give parbinex before glucose - to prevent wernicke encephalopathy
how are epileptic syndromes categorised
focal + generalised
focal - usually temporal lobe:
simple
complex - consciousness impaired, loose consciousness after an aura/seizure onset
secondary generalised - initially focal, then become bilateral seizure (usually tonic clonic - convulsive seizure)
generalised:
absence - common in children, lasting <10sec
tonic-clonic - pt looses consciousness with post-ictal confusion, limbs stiffen (tonic) then jerks (clonic)
myoclonic - sudden jerking of limb/trunk/face
atonic seizure - pt falls due to sudden loss of muscle tone, pt retains consciousness
what are features of specific focal seizures
temporal lobe - most common:
hallucinations - auditory/olfactatory/gustatory, automatism (lip smacking)
frontal lobe:
motor features = dysphasia, Todd paresis (residual focal neurological deficit),
Jacksonian (only on 1 side, progressing from 1 muscle group to nearby ones quickly)
parietal lobe: sensory symptoms (tingling/numbness)
occipital lobe: visual symptoms (spots/lines in field)
how are focal seizures treated
1 - lamotrigine or levetiracetam
then consider carbamazepine, orxcabenzapine
lacosamide
how are general seizures treated
absence = sodium valproate (avoid carbamazepine as worsens seizure)
tonic-clonic = sodium valproate or lamotrigine
myoclonic = sodium valproate, unless women of child-bearing age then use levetiracetam/topiramate (avoid carbamazepine as worsens seizure)
atonic = sodium valproate or lamotrigine
what triggers seizures + what are complications
triggers: poor sleep, alcohol/drug (+ withdrawal), stroke, SOL, intracranial haemorrhage
complications:
status epilepticus (5+min of continuous seizures - 30min of seizure or incomplete resolution of multiple seizures) = rectal/IV lorazepam -> repeat/buccal midazolam -> IV phenytoin
depression, suicide, sudden death
what is an ideal AED (anti-epileptic drug) for women of child bearing age
lamotrigine
as sodium valproate is highly teratogenic so risks neural tube defects
what are the guidelines for epilepsy+driving if:
one off seizure
multiple seizures
seizure after changing medication
one-off seizure = reapply in 6 months
multiple = reapply in 1yr
after changing medication = reapply if seizure more than 6 months ago, OR back on previous med for 6+ months
what are RF for subarachnoid haemorrhage (SAH)
SAH due to ruptured berry aneurysm
HTN, APCKD - autosomal dominant inheritance
alcohol excess, smoking
how does SAH present
sudden onset occipital headache ‘thunderclap’
worst headache of their life
physical exertion before onset
on exam - reduced GCS, meningism (neck stiffness), focal neurological signs
how is SAH investigated
CT head - berry aneurysm in circle of willis (base of skull)
if CT head doesn’t confirm diagnosis, LP done (ideally 12hr after symptom onset)
shows xanthochromia
how is SAH managed
medical - nimodipine (CCB to prevent vasospasm to prevent subsequent ischaemic damage), don’t treat HTN
surgical - EVAR for coiling/stenting SAH bleed, surgical clipping of vessel
what is main neuromodulator + neuropeptide in pain
modulator - 5HT
peptide - CGRP calcitonin gene related peptide
what brainstem nuclei are involved in pain processing
trigeminocervical complex
superior salivary nucleus - ANS
locus coreulus - NA
dorsal raphe nucleus - 5HT
hypothalamus - orexin
what are 3 main primary headaches
migraine
tension type
trigeminal autonomic cephalgia
how is migraine diagnosed
recurrent headaches 5+
lasting 4-72hr
at least 2 of:
unilateral
pulsating
moderate severity
worse with activity
additional:
photo + phono-phobia
nausea/vomit
aura (may or may not occur) - zigzag lines, visual fortification, dysphasia, sensory disturbance (+ve and -ve symptoms)
what are the different types of migraine
migraine
migraine w aura
silent migraine (migraine w aura but no headache)
hemiplegic migraine - stroke mimic
what is pathophysiology of migraine
interaction between hypothalamus, thalamus, brainstem nuclei (involves 5HT dorsal raphe, NA from LC)
causes large amounts of extracellular K + glutamate secretion
triggers CSD release (cortical spreading depression - suppresses brain activity)
what is given for migraine prophylaxis
topiramate, amitriptyline, propranolol
stops CSD release
by interrupting interaction between hypo/thalamus, brainstem nuclei
what are the 5HT + DA pathways and how do they contribute
5HT = pain, DA = bothersome symptoms
low 5HT causes migraine
high 5HT1AA (5HT metabolite) seen in CSF/urine suggesting high 5HT turnover
DA hypersensitivity causes additional symptoms of nausea/vomit, yawning
what is role of CRGP in different nerve fibres + vessels
C fibre - release CRGP
A delta - contain CRGP receptors
CRGP is released from C fibre and acts on A-delta
modulating pain transmission
blood vessel - CRGP receptors
CRGP is released from C fibre, causing vasodilation
causes protein release, leading to neurogenic inflammation
this activates A-delta
which transmits signal to brainstem
how to manage an acute migraine attack
PO sumatriptan - decrease CRGP release (contraindicated in asthma)
+ NSAID - decrease prostaglandin
+ metclopramide - decrease DA (anti-emetic)
conservative - avoid trigger
hydration, good sleep hygiene
reduce alcohol/coffee
what is MOA of triptan
5HT agonist, decrease CRGP release
vasconstricts arteries smooth muscle
reduces CNS activity, inhibits peripheral pain receptors
why does photophobia occur during migraine
thalamocortical pathway is modulated by inputs from retina
what are RF for migraine
20-55yr female
on COCP
alcohol, caffeine, chocolate, cheese
dehydration
trigger - stress, bright lights
around menstruation or menopause as low oestrogen (as E2 increases 5HT)
what hormone is linked to E2
5HT
as E2 increases, more 5HT released
how do migraine differ to headaches
migraine - lasts 4-74hr
unilateral
pulsating
moderate severity
worse with activity
additional: photo+phono phobia, nausea/vomit
treat = prophylaxis - topiramate, propranolol, amitryptilline
acute - sumatriptan + paracetamol, NSAID
tension headache - female:
gradual onset
bilateral - tight band around forehead, mild ache
treat = analgesia according to WHO step ladder
cluster headache - 20-40yr male smoker:
sudden onset, pain <4hr
unilateral, around eye (red, swollen, ptosis/meiosis, sweating)
severe group of attacks then pain-free
treat = prophylaxis - verapamil
acute - O2, sumatriptan
trigeminal neuralgia (compressed CN5):
unilateral
short, stabbing pain in V2 + V3 distribution
triggered by cold wind, touching, brushing teeth
treat = medical - carbamazepine (phenytoin, lamotrigine, gabapentin)
surgical - microvascular decompression
what are red-flag symptoms in headache
meningitis = fever, neck stiffness, photophobia
stroke = new neurological symptoms
SAH = sudden onset occipital, thunderclap
glaucoma/GCA = temporary monocular blindness (treat with high dose steroids)
raised ICP (hydrocephalus, SOL - tumour/haemorrhage) = better after vomiting
worse when bending down, in morning
medication over-use = check DH
what are RF for idiopathic intracranial HTN
female, obese, PCOS
excess 11B-HSD1 causes:
cytokines (chronic inflammation), adipokines, excess androgen
treat with weight loss
what investigations done for headache
CT scan to diagnose SOL for raised ICP
MRI to exclude secondary causes
fundoscopy for papilloedema - IIH, raised ICP
