Multiple sclerosis

Question 1

epidemiology and etiology of MS? (genetic and environment)

Answer 1

common in females between 20-40 years especially living far from equator.

genetic predisposition: HLA-DRB1*15 also common if first degree relatives are affected

environment risks: vit. D deficiency, EBV, HHV6 (roseola), smoking

Question 2

define:
MS exacerbation/flare/attack
MS remission
Radiologically-isolated MS
clinically-isolated MS

Answer 2

MS flare: new symptoms or worsening symptoms due to CNS demyelination lasting at least 24 hours not accompanied by fever or infections.

MS remission: recovery after exacerbation during which clinical symptoms resolve completely or partially

RIMS: the presence of demyelinating lesions specific to MS in an asymptomatic individual (not phenotype, can progress to MS)

CIMS: single episode of symptoms due to CNS demyelination. second episode will make it more likely to be MS (meet diagnostic criteria)

Question 3

clinical patterns? and pathophysiology?

Answer 3

1. relapsing remitting (exacerbations with partial or complete remission in between)
2. 2ndary progressive (RR-MS that leads to progressively worse neurologic function)
3. primary progressive (progressively worse neurologic function from the first onset)

pathophysiology: autoimmune inflammation, demyelination, and axonal degradation. Activation of T-cells -> inflammation -> focal demyelination -> loss of axons and atrophy of oligodendrocytes -> gliosis and inadequate remyelination. B-cells also play a role to produce igG

Question 4

ALL clinical features?

Answer 4

optic neuritis: most often the earliest sign and unilateral. painful eye movements, impaired vision, color blindness, RAPD. NORMAL FUNDOSCOPY (retrobulbar neuritis)

internuclear ophthalmoplegia due to lesion in medial longitudinal fasciculus: ipsilateral medial rectus weakness (fail to adduct) with contralateral lateral nystagmus

Spinal cord tracts involvement:
Lhermitte’s sign: neck flexion causes shooting electric pain along the spine

dorsal column: loss of vibration, proprioception, numbness

pyramidal tract: UMN weakness (hypertonia, hyperreflexia, babinski)

cerebellum: impaired gait, charcot neurological triad of scanning speech (slow with paauses between sylabuls and words), nystagmus, intention tremor

cranial nerve palsies: facial palsy, diplopia, trigeminal neuralgia,

autonomic dysfunction: urinary/fecal incontinence, sexual dysfunction

fatigue, headache, depression

uhthoff phenomenon: reversible flare following increase body T by fever, warm bath or physical exertion

transverse myelitis: paraplegia, sensory loss, bladder dysfunction

neuropathic pain

Question 5

which diagnostic criteria used for MS? diagnostic modalities?

Answer 5

McDonald criteria: dissemination in time and space
time: occurrence of lesions over time confirmed clinically or with imaging
space: occurrence of lesions in multiple regions of CNS confirmed clinically or with imaging

1. MRI showing multiple sclerotic plaques due to demyelination and gliosis (commonly in periventricular, juxtacortical, infratentorial, and spinal cord)
   ENHANCED: SHOW ACTIVE LESIONS
   NON ENHANCED: SHOW ALL LESIONS but cannot tell which is active
2. oligoclonal bands on CSF (means high igG) not in blood. Lymphocytic pleocytosis
3. prolonged evoked potentials (delayed)
4. to rule out other DDx: CBC, TSH, ANA, and specific autoantibodies

Question 6

treatment for acute attack and long term?

Answer 6

acute attack: IV/PO steroid OR plasmapheresis

disease-modifying:
1. interferon beta (suppress T-cell activity)
2. natalizumab/ocrelizumab (monoclonal antibodies)
ALWAYS check JC virus serology bcz they may activate the virus and cause progressive multifocal leukoencephalopathy
3. glatiramer acetate (acts as decoy for Tcells instead of myelin)
4. dimethyl fumerate (antinflammatiory)
5. fingolimod/siponimod (sphingosine receptor agonists)

physiotherapy, stop smoking, vitamin d

Question 7

prognosis?

Answer 7

good: female, young, sensory and optic involvement only

bad: male, motor or cerebellar involvement

Question 8

DDx?

Answer 8

1.neuromyelitis optica spectrum disorders
define: autoimmune inflammation of optic nerve and SC
pathophysiology: anti-aquaporin 4
symptoms: bilateral optic neuritis (impaired vision, retrobulbar pain), transverse myelitis, area postrema syndrome (N/V/hiccups)
diagnosis: evidence of aquaporin-4 antibody and clinical
Tx: steroid, plasmapheresis

2. acute disseminated encephalomyelitis
   define: autoimmune demyelinating CNS dx due to infections or after vaccination
   symptoms: motor, sensory, cranial nerve, brainstem impairment, optic neuritis
   diagnosis: LP show lymphocytic pleocytosis, high protein, MRI
   tx: steroid, IV IG, acyclovir

vasculitis: SLE, polyarteritis nodosa, bahcet, sarcoid