Demyelinating Disease Flashcards
Where are the lesions typically distributed in MS?
Perivenous white matter
What is the pathology of acute lesions in MS?
Myelin destruction with relative axon sparing
Mononuclear cell and lymphocyte infiltration with interstitial oedema
Breakdown of the BBB
How do acute lesions progress in MS after initial inflammation?
Astrocyte proliferation
Old lesions are acellular, clearly demarcated and bare axons surrounded by astrocytes; increasing axonal loss accounts for increasing disability
Is there a prodrome to MS?
Sometimes - vague, non-specific e.g. Headaches, lethargy, aches
What should be considered the underlying diagnosis in a young adult presenting with paroxysmal facial pain?
Trigeminal neuralgia - MS presentation
What is Lhermitte’s sign?
Shock-like sensation in limbs on neck flexion due to cervical posterior column/spinothalamic plaques
What does loss of all sensory modalities at a given spinal level in MS suggest about the location of the lesion?
Dorsal root entry zone
What are the most common motor presentation distributions in MS?
Monoparesis or paraparesis
Much less commonly hemiparesis or quadraparesis
What reflex is lost in UMNL?
Abdominal reflex
What would a plaque of demyelination at the anterior horn cell root cause?
A mixed UMNL and LMNL picture
What are the symptoms of optic neuritis?
Visual loss with central scotoma
Pain on eye movement may occur due to irritation of dural membrane surrounding optic nerve
What might a mild optic neuritis cause isolated loss of?
Colour vision
What does bilateral optic neuritis suggest in terms of differential diagnosis?
MS less likely
Neuromyelitis optica
Leber’s hereditary optic neuropathy (mitochondrial)
What is Uhthoff’s phenomenon?
Visual Sx of MS (or demyelinating disease generally) worsening following hot bath or exercise
What does fundoscopy show in optic neuritis?
Papillitis
2 investigations for optic neuritis?
HRCT/MRI - exclude optic nerve tumour and possibly identify plaques
Delayed VERs/VEPs
What does an optic disc with previous optic neuritis look like?
Atrophic with a pale, punched out temporal margin
What is internuclear ophthalmoplegia? Where is the lesion?
Medial longitudinal fasciculus lesion pathognomonic of MS in young people
Causes a failure of adduction on the affected side and a side-by-side diplopia
When does primary progressive MS more commonly occur?
If it presents after that age of 45 or so
What process do unmatched oligoclonal CSF bands indicate?
Intrathecal antibody production
What MRI modality best highlights demyelination?
T2 - demyelination shows increased signal
What MRI modality is best for showing acute demyelinating lesions?
GAD
What does GAD highlight in demyelinating disease?
Acute lesions
What criteria is used to diagnose MS with a single clinical episode?
McDonald Criteria
What does the McDonald criteria require for a diagnosis of MS?
At least one clinical episode
At least 2 episodes attributable to demyelination at least 30 days apart
Exclusion of alternative pathologies
When can PPMS be diagnosed?
After 1 year of progressive deficit with MRI plaques and mismatched CSF oligoclonal bands
7 differentials for unmatched CSF oligoclonal bands?
MS HIV Lyme disease Syphilis Chronic meningitis Neurosarcoidosis Subacute sclerosing panencephalitis
How are MS relapses treated?
3d IV methylpred
How does NMO usually present visually?
Rapid bilateral visual loss
What is the usual progression of Sx in NMO?
Rapid bilateral visual loss
Transverse myelitis with back pain, girdle pain, lower limb paraesthesia and urinary retention
Occasionally ascending sensorimotor loss
What antibody is commonly implicated in NMO?
Anti-aquaporin 4 Ab
What disease does the presence of anti-aquaporin 4 Ab suggest?
NMO
What may differentiate MS from NMO on CSF analysis?
NMO does not have unmatched oligoclonal bands
What might you consider in a presumed MS patient without unmatched oligoclonal CSF bands?
NMO
What is acute disseminated encephalomyelitis otherwise known as?
Post-infectious encephalomyelitis
What 4 things does ADEM usually follow?
Measles
VZV
Occasionally URTIs or GI infections
Live or attenuated vaccines
How does ADEM present?
Days-weeks after a viral infection resolves, fever headache n+v develop
Progressing on to meningism, drowsiness, multifocal neuro signs and symptoms and myoclonus
What is the imaging modality of choice for ADEM?
MRI - shows small focal white matter changes which simultaneously enhance with contrast (same degree of acuteness unlike MS)
CT will be normal
What suggests ADEM over acute MS?
Fever, meningism
What does ADEM with raised intracranial pressure and bloodstained CSF suggest?
Acute haemorrhagic leukoencephalitis
Over what time period does PML occur?
3-6m
What relapse related side effect is associated with alemtuzumab therapy for MS?
Pseudo-relapses - repeats of previous relapses
What drug is associated with pseudo relapses in MS?
Alemtuzumab
What is tecfedira otherwise known as?
Dimethyl fumerate
What is dimethyl fumerate otherwise known as?
Tecfedira
What is tysabri?
Natalizumab
What is Natalizumab otherwise known as?
Tysabri
What is Campath?
Alemtuzumab
What is Alemtuzumab otherwise known as?
Campath
What are the 2 first line drugs for relapse prevention in MS?
B interferon and capaxone
How is B interferon delivered?
Injection
What is a rough guideline for need to start relapse prevention therapy in RRMS?
2 attacks in 2 years
How much do capaxone and B interferon lower relapse rate in RRMS?
Roughly 35%
What are the 2 second line drugs for RRMS?
Fingolomod
Dimethyl fumerate
How are fingolomod and Dimethyl fumerate delivered?
Oral
By how much do Dimethyl fumerate and fingolomod lower relapse rate in RRMS?
Roughly 50%
What are the major risks associated with Alemtuzumab therapy?
Autoimmunity - Goodpastures, thyroid (either way), ITP
Pseudo relapses
What is the major risk associated with Natalizumab?
PML
What drug for RRMS is most associated with PML?
Natalizumab
How does ocrelizumab work?
CD19 inhibitor
What radiological signs suggest PML?
Multifocal white matter lesions
Leading edge on DWI
Scalloping of cortex
What two viruses are mostly associated with PML?
JC virus
BK virus
What are anti-MOG antibodies? What diseases are they associated with?
Anti-Myelin Oligodendrocyte Glycoprotein
May have a role in seroneg NMO, optic neuritis and ADEM
Also adrenoleukodystrophy and vanishing white matter disease
What is the owls eye sign and what can it be seen in?
Spinal cord - e.g. In long term NMO, chronic ischaemic change in anterior horn cells
If NMO patient is AQP4 positive, what does it suggest about their disease course?
Relapsing remitting
