Transcript CIS = clinically isolated syndrome

Clinically Isolated
Syndrome
Emergency Lecture Series
By: Laurence Poliquin-Lasnier
Aug 7th 2013
CIS
 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)
Multiple Sclerosis
4 types:
1. RRMS (80-85%)
2. PPMS (10-15%)
3. SPMS (majority will develop eventually)
4. Progressive relapsing MS (? Truly different from
PPMS)
Definitions
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
Multiple sclerosis
 Mean age of onset 30yo (70% have onset between 2040 yo)
 Prevalence 3X higher in F>M
 Prevalence in Canada: 50/100 000 ( as opposed to
1:100,000 in equatorial regions)
What is an attack?
 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
Diagnosis
 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
What provides evidence for
DIS?
 ≥ 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
Positive CSF: Oligoclonal IgG bands in CSF (and not
serum) or elevated IgG index
Situations where VEP and
CSF may be useful in RRMS
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
Differential Dx
Vascular
Age, stroke, migraine, antiphospholip
Infectious
Lyme, HTLV-1, HIV, PML, Neurosyphilis, whipple,
chronic meningitis (TB, fungal)
Trauma/structural
Arnold-Chiari, syrinx, cavernous malformation,
disc herniation
Autoimmune/Inflammatory
SLE, Sjogren, Behcet, Susac, Sneddon, PAN,
ADEM, post-infectious myelitis, vasculitis
Graulomatous: sarcoidosis, wegener,
lymphomatoid granulomatosis
Metabolic
B12 deficiency, copper deficiency, celiac
Inherited
CADASIL, spastic paraparesis, Metachromatic or
adreno leukodystrophy,
Adrenomyeloleukodystrophy, Spinocerebellar
disorders, mitochondrial disorders
Neoplastic
Paraneoplastic encephalomyelopathies, brain or
spinal cord tumor, CNS or intravascular
lymphoma
Red flags
History
Exam
Investigations
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
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
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
Investigations
 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
Doctor, Do I have MS?
What is my risk of MS after a
transverse myelitis?
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
What is my risk of MS after an
optic neuritis?
Optic Neuritis Treatment Trial

5-year cumulative probability of MS:




16% with no brain MRI lesions
51% with three or more lesions
Probability of developing MS by 10 years




30% overall
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
Treatment
 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
References
 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