Emergency Lecture Series
By: Laurence Poliquin-Lasnier
Aug 7th 2013


Definition: a first clinical episode characteristic of an
MS attack (typically, optic neuritis, myelitis or a brainstem syndrome) without the requisite features of dissemination in time (DIT) or dissemination in space
(DIS)

4 types:
1.
RRMS (80-85%)
2.
PPMS (10-15%)
3.
SPMS (majority will develop eventually)
4.
Progressive relapsing MS (? Truly different from
PPMS)

1.
RRMS : repeated, clearly defined acute attacks of neurologic symptoms and signs lasting >24 hours (relapses), each usually followed by full or partial recovery and a lack of disease progression between attacks
2.
PPMS : progressive disease from the onset; can have occasional plateaus or minor improvements, but the overall trend is toward progressive disability
3.
SPMS : progressive course that follows an initial period (often many years) of RRMS
4.
Progressive relapsing MS : disease progression from onset with distinct acute relapses. The natural history is similar to that of PPMS


Mean age of onset 30yo (70% have onset between 20-
40 yo)

Prevalence 3X higher in F>M
 Prevalence in Canada: 50/100 000 ( as opposed to
1:100,000 in equatorial regions)


Neurological disturbance typical for MS

Subjective report or objective observation

At least 24 hours duration in absence of fever or infection

Excludes pseudoattacks or single paroxysmal symptoms
(multiple episodes of paroxysmal sx occurring over 24 hours or more are acceptable as evidence)

Some historical events with symptoms and pattern typical for
MS can provide reasonable evidence of previous demyelinating event(s), even in absence of objective findings

Time Between Attacks : 30 days between onset of event 1 and onset of event 2


History and physical exam

Paraclinical tests:

MRI

CSF

VEP

Revised 2010 McDonald Criteria

These criteria should only be applied in patients who have experienced a typical CIS

It is now possible to diagnose MS at the time of the CIS presentation
 CSF OCB no longer has a role in facilitating dx of RRMS but may be used to exclude other diagnoses

Revised 2010 McDonald Criteria

Revised 2010 McDonald Criteria

 ≥ 1 T2 lesion in at least two out of four areas of the
CNS: periventricular, juxtacortical, infratentorial, or spinal cord
 Gadolinium enhancement of lesions is not required for
DIS

If a subject has a brainstem or spinal cord syndrome, the symptomatic lesions are excluded and do not contribute to lesion count

Revised 2010 McDonald Criteria
or

1. Pts >50 yrs or with vascular risk factors: brain MRI lesions can be present on the basis of age and/or ischemia.
In addition to evidence from spinal cord MRI, where non-MS lesions are uncommon, presence or absence of OCB in
CSF and/or abnormally prolonged latencies on VEP may aid in dx
2. Migraine: WM lesions frequently seen on brain MRI-> spinal cord, CSF and VEP may help
3. Pts with vague, non-specific symptoms such as dizziness, fleeting sensory phenomena, fatigue, subjective weakness, or cognitive issues. In addition to paraclinical tests, there is no substitute for repeat assessments over time (clinical and imaging) to come to a conclusive dx (MS or not MS).
4. When MRI access is limited or delayed

VITAMIN
Vascular
Infectious
Trauma/structural
Autoimmune/Inflammatory
Metabolic
Inherited
Neoplastic
Differential Dx
Age, stroke, migraine, antiphospholip
Lyme, HTLV-1, HIV, PML, Neurosyphilis, whipple, chronic meningitis (TB, fungal)
Arnold-Chiari, syrinx, cavernous malformation, disc herniation
SLE , Sjogren, Behcet, Susac, Sneddon, PAN,
ADEM, post-infectious myelitis, vasculitis
Graulomatous: sarcoidosis , wegener, lymphomatoid granulomatosis
B12 deficiency, copper deficiency, celiac
CADASIL, spastic paraparesis, Metachromatic or adreno leukodystrophy,
Adrenomyeloleukodystrophy, Spinocerebellar disorders, mitochondrial disorders
Paraneoplastic encephalomyelopathies, brain or spinal cord tumor, CNS or intravascular lymphoma

History
Positive family hx, fever, night sweats & wt loss, arthropathy, rash, mucocutaneous ulcers, dry mouth and eyes
(sicca syndrome), ocular disease (uveitis, retinitis), severe and persistent
H/A, stroke-like events, seizures, malabsorption syndrome
Exam
Encephalopathy, meningismus, movement disorders
(dystonia, myorrhythmia), LMN findings, findings confined to vascular territory, livedo reticularis, symmetric involvement, myopathy, neuropathy, renal dysfunction, diabetes insipidus, hypothalamic involvement, sensorineural hearing loss, pure cerebellar syndrome
Investigations
Significantly increased
ESR or CRP, positive serology, abnormal
CXR, CSF pleocytosis
(WBC count
>50/HPF) , very high protein (>0.7 g/L), absent
OCB in CSF, normal
MRI brain/ cord, atypical MRI


MS is a dx of exclusion (*to consider dept on clinical presentation):
 CBC, electrolytes, TSH, LFT
 ANA, ENA, RF, C3, C4, ESR, CRP

VitB12, *VitE, *Copper, *Zinc

VDRL, HIV, Lyme, *HTLV1-2, *APLA, *ACLA
(thrombophilia), Beta2M, *LDH, *Lactate
 *Chest imaging, ACE, *Calcium

Acute complete TM
 Risk of MS of only 5% to 10%
Partial or incomplete myelitis

Abnormal brain MRI : 60% to 90% dx with MS at 3-5 yrs

Normal brain MRI: 10% to 30% dx MS

Optic Neuritis Treatment Trial

5-year cumulative probability of MS:
 30% overall
 16% with no brain MRI lesions
 51% with three or more lesions

Probability of developing MS by 10 years
 38% overall
 22% with no lesions
 56% with 1 or more typical MS lesions
 Probability of developing MS by 15 years

50% overall cumulative probability

25% with no lesions on baseline brain MRI
 72% with 1 or more lesions on MRI
 Risk of developing MS highest in first 5 years
Probability of new MS dx at yr 15 in MS-free pts at
10-year
• 32% if 1 or more baseline lesions
• 2% if no baseline lesions

 Acute:

Solumedrol 1G IV qd X 3-5 days

Faster recovery

Does not change final outcome (based on ONTT)

Long term:

RCT in pts with CIS have shown that early treatment with beta interferons or copaxone can delay conversion to clinically definite MS

However, it is unknown whether such treatments prevent or delay long-term disability

Figure Recommended algorithm for diagnosis of inflammatory demyelinating diseaseADEM = acute disseminated encephalomyelitis; CIS = clinically isolated syndrome; DIS = dissemination in space; DIT = dissemination in time; MS = multiple sclerosis; NMO = neuromyelitis optica.
Selchen D et al. Neurology 2012;79:S1-S15
© 2013 American Academy of Neurology


Selchen et al. MS, MRI, and the 2010 McDonald criteria. A Canadian expert commentary. Neurology. Vol
79, number 23, supplement 2, Dec 2012
 Bradley
 Up to date