Lecture 9 - Multiple Sclerosis and related disorders

1. Describe the natural history of multiple sclerosis in terms of
a. Percentages who progress to significant disability
Most patients will (see below). Only 5% have a benign clinical course.
b. Percentages who require ambulatory assistance after 10 years
50% will require a cane to ambulate, and 15% will require a wheelchair
c. Percentages who develop secondary progressive MS
50% within 10 years. 85-90% within 25 years.

2. Describe four characteristics that predict a severe course of MS.
Severe course
Males have a more severe course than females
Motor and cerebellar symptoms
Disability after the first attack
Short time interval between attacks
Numerous relapses within the first year
Burden of disease on MRI – >10 lesions on MRI at diagnosis indicates walking with a cane within 14 years
Change in lesion load within the first year

Less severe course
Sensory symptoms
Infrequent attacks,
Full neurological recovery after an attack
Low level of disability after 5-7 years
Burden of disease on MRI – No lesions on MRI at diagnosis indicates no significant disease within 14 years

3. Given the presentation of a patient with MS, characterize whether the patient has clinically isolated MS syndrome, relapsing remitting MS, secondarily progressive MS, or primary progressive MS.
Clinically isolated MS syndrome – one symptom or abnormality on clinical exam, w/o evidence of the classic adage “lesions in time and space” – a.k.a., there is clinical evidence of a single demyelinating lesion. May then progress to RRMS, especially if patient has additional clinically silent lesions on MRI.
Relapsing remitting MS – 85% – patients have relapses or exacerbations during the course of their disease comprised of symptoms such as visual blurring (optic neuritis), diplopia, vertigo, numbness, parasthesias, and weakness (myelopathy). Between attacks most patients have incomplete recovery, showing slight residual symptoms that lead to cumulative disability.
Secondarily progressive MS – 85% of RRMS, w/o treatment – characterized by more pronounced, steady, progressive decline in function +/– superimposed relapses. Most common symptoms are myelopathic ones – ambulation difficulties, bladder, bowel, and sexual dysfunction.
Primary progressive MS – 10-15% - gradual decline from the onset, typically with myelopathic features.
Progressive relapsing MS – 1% total – a subset of PPMS w/ rare relapses superimposed upon a slow progression.

Differentiating relapse from symptom exacerbation…
Relapse – due to production of a new lesion, or reactivation of an old lesion
Increase in size of lesion on MRI
Renewed gadolinium enhancement on MRI
Symptoms are persistent >1-2 days
Exacerbation – an old, quiescent lesion gets worse – due to heat, fatigue, infection (UTI, URI)
Symptoms may fluctuate over the course of the day
New gadolinium enhancement on MRI
Symptoms should resolve w/I 1-2 days of the inciting factor removal/treatment

4. Given a clinical presentation and an MRI of the head, be able to diagnose MS.
Clinical presentation – Need evidence of “multiple lesions in time and space”
Optic neuritis
Transverse myelitis
Intranuclear ophthalmoplegia
Spasticity
Fatigue
Urinary sphincter dysfunction
Incoordination
Nystagmus
NOT seizures (he says this is almost exclusionary for the dx) or cognitive decline
Spinal tap – positive oligoclonal bands and elevated IgG index and synthesis rate
May see mild lymphocytic pleiocytosis

MRI findings
Dawson’s fingers: Periventricular, perpendicular, ovoid lesions either in the cerebral hemispheres or infratentorially. Best seen on flair images (dark CSF).
Cervical cord lesions – cigar-shaped, typically span 1-2 segments, predilection for cervical cord. Best seen on proton density and T2 images (bright CSF).
Deep white matter and juxtacortical lesions (not specific)
Lesions often enhance with gadolinium contrast – distinguishes active inflammation from chronic lesions.

5. Given a patient presenting with signs and symptoms of MS, recognize Lhermittes sign, intranuclear ophthalmoplegia, optic neuritis, and transverse myelitis.
Lhermittes sign – sensation of “electrical shock” down the spinal column provoked by neck flexion
Intranuclear ophthalmoplegia
· Intact abduction with slowed or absent adduction of contralateral eye
· Often bilateral
· Due to destruction of the medial longitudinal fasciculus

Optic neuritis – inflammation and demyelination of the optic nerve
· Unilateral loss of acuity or color detection, occasionally blindness
· Concomitant pain w/ ocular movement
· Central or centrocecal defect (can’t see center part of visual field), a quadrantoanopia, a horizontal altitudinal defect, or enlargement of the blind spot
· Marcus Gunn pupil – afferent papillary defect – pupil constricts less (appears to dilate) in response to light
· Optic disc may have anterior swelling and edema leading to pallor over time
Transverse myelitis
· Predilection for posterior columns
· Loss of vibratory and proprioceptive senses
· Sensory ataxia
· Lower extremity spasticity
· Sphincter and sexual dysfunction
· May be related to Lhermitte’s sign

-CV

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