Clinical outcome Measures, Trials

Clinical outcome Measures, Trials
By:Professor and Acting Chair of Neurology
Director, MS Comprehensive Care Center
SUNY at Stony Brook, New York


MS: Diagnostic Issues
* Diagnostic principles
* Misdiagnosis clues
* Differential diagnosis
* Case presentations

Diagnosis Of MS
Diagnosis Based On Schumacher Criteria
* Appropriate age (10-50 years)
* CNS white matter disease
* Lesions disseminated in time and space
* Objective abnormalities
* Consistent time course
* No better explanation
* Diagnosis by a competent clinician
(preferably neurologist)

MRI Dissemination In Space
MRI Dissemination In Time
Diagnostic Criteria
Diagnostic Criteria For Primary Progressive MS
Diagnosis Of MS: MRI
MRI Features Suggestive of MS
Diagnosis Of MS: CSF
Diagnosis Of MS: Blood And Ancillary Tests
Diagnosis Of MS: Evoked Potentials
Misdiagnosis of MS
* Clinical
* Neuroimaging
* Cerebrospinal fluid (CSF)

Clinical Clues
* Normal examination
* No dissemination over time and
space
* Onset before age 10 or after age 55
* Genetic "red flag”
+ positive family history
+ early age onset
+ unexplained non CNS disease
* Progressive course starting before age 35
* Localized disease
* Atypical features
+ prominent fever
+ prominent headache
+ abrupt hemiparesis
+ abrupt hearing loss
+ prominent pain (except trigeminal
neuralgia)
+ no optic nerve or ocular motility
disturbance
+ normal sensory and bladder function
+ progressive myelopathy without
bladder /bowel involvement
+ impaired level of consciousness
+ prominent uveitis
+ peripheral neuropathy
+ nonscotomatous field defects
+ gray matter features (prominent
early dementia, seizures, aphasia,
fasciculations, extrapyramidal
features)

Neuroimaging Clues
Brain
* Normal brain MRI
* Small lesions (< 3mm)
* Subcortical lesions (internal
capsule)
* Predominant infratentorial
involvement
* Prominent GM involvement (basal
ganglia)
Neuroimaging Clues
Brain
* Symmetric, confluent hemispheric
WM involvement
* Significant mass effect
* Hydrocephalus
* Severe cerebellar/ brainstem atrophy
* Absence of callosal or periventricular
lesions

Neuroimaging Clues
Spinal cord
* Lesion > 2 vertebral segments
* Severe swelling
* Full thickness lesions
CSF Clues
* Normal CSF
* Disappearance of oligoclonal bands;
normalization of intrathecal IgG production
* Cell count > 50 WBC /mm3
* Protein > 100 mg/dl

Differential Diagnosis of MS
* Genetic
* Infectious
* Inflammatory
* Metabolic
* Miscellaneous
* Neoplastic
* Psychiatric
* Structural
* Toxic
* Vascular
* Variants

Acute Leukoencephalopathy
Feature Disorders
Cranial neuropathies - Lyme disease, Sarcoidosis
Cortical blindness - multiple infarcts, PML,
Hearing loss - Cogan’s, Susac
Intracranial - hemorrhagic infarction, tumor,
hemorrhage venous infarction
Acute Leukoencephalopathy
Feature Disorders
Lockedin syndrome - CPM, infarction
Migraine - antiphospholipid syndrome,CADASIL, mitochondrial encephalopathy
Muscular rigidity - paraneoplastic brainstem encephalitis
Myoclonus - antiamphiphysin paraneoplastic syndrome, hashimoto’s
Papilledema - Gliomatosis, venous sinus thrombosis
Differential Diagnosis:
Variants
* Balo's concentric sclerosis
* Disseminated subpial demyelination
* Neuromyelitis optica (Devic's disease)
* Marburg variant
* Tumefactive MS
* Myelinoclastic diffuse sclerosis
(Schilder disease)
* Postinfectious encephalomyelitis
* Clinically isolated syndromes

CIS Issues
CIS Controversies
* What features define first attack MS
* What features predict subsequent course
* Who should be offered MS DMT

CIS Considerations
* Appropriate age
o excludes too young and too old
* Characteristic syndrome
* Other causes excluded
* Abnormal brain MRI
o with suggestive features
MS CIS Syndromes
* typically unilateral
* retrobulbar
* typically painful
* some recovery expected
* no retinal exudates or

Optic neuritis
MS CIS Syndromes
Myelitis
MS CIS Syndromes
MRI Dissemination in Space*
MRI Dissemination In Time
Diagnostic Criteria
CIS and MRI Predictors*
Role Of MRI In Suspected MS*
MS Differential Diagnosis
* Migraine
* Sarcoid
* Sjögren syndrome
* Stroke and ischemic
* Unidentified bright objects on MRI
* Vascular malformations
* Vasculitis (primary CNS or other)
* Vitamin deficiency (B12, E)
* Number and volume of brain MRI
CIS and Therapy
CIS: Conclusions
Cognitive Impairment In Minimal Disability MS*
Diagnostic Criteria For Primary Progressive MS
Neuromyelitis Optica (NMO)
NMO Differential
NMO: Clinical Features
Recent Pediatric Series ..........

Clinical outcome Measures, Trials.ppt