Hallmarks of Multiple Sclerosis (MS)
The hallmarks of Multiple Sclerosis include focal demyelinating lesions in cerebral white and grey matter, brain atrophy, dissemination of lesions in space and time, and characteristic clinical presentations including optic neuritis, partial myelitis, sensory disturbances, and brainstem syndromes. 1, 2
Pathological Features
- Focal demyelinating lesions: The primary pathological hallmark of MS is the presence of multiple focal demyelinating lesions in both cerebral white and grey matter 1
- Brain atrophy: Substantial brain volume loss can occur even in early stages of MS and advances over the disease course 1
- Inflammatory activity: Active inflammation is evidenced by contrast-enhancing lesions on MRI 1, 2
- Axonal transection: Neurodegeneration occurs alongside inflammatory demyelination 3
Diagnostic MRI Features
Core Lesion Characteristics
- Periventricular lesions: Abutting the lateral ventricles without intervening white matter, often perpendicular to the corpus callosum ("Dawson's fingers") 1
- Juxtacortical lesions: Touching or within the cortex 1
- Infratentorial lesions: Located in brainstem, cerebellar peduncles, and cerebellar hemispheres 1
- Spinal cord lesions: Multiple discrete focal lesions, typically cigar-shaped on sagittal views and wedge-shaped on axial views, usually less than 2 vertebral segments in length 1
- Gadolinium-enhancing lesions: Nodular, open-ring, or closed-ring enhancement patterns indicating active inflammation 1
Green Flags (Supportive of MS Diagnosis)
- Periventricular lesions perpendicular to the corpus callosum ("Dawson's fingers") 1
- T2 hyperintense lesions in at least two characteristic regions 2
Red Flags (Suggestive of Alternative Diagnoses)
- Extensive posterior corpus callosum involvement with bilateral diencephalic hyperintense lesions (suggestive of neuromyelitis optica spectrum disorders) 1
- Longitudinal extensive transverse myelitis affecting ≥3 vertebral segments (suggestive of NMOSD) 1
Clinical Presentation
- Typical age of onset: 20-30 years 3
- Sex distribution: Female to male ratio of nearly 3:1 3
- Common presenting symptoms:
Disease Course Patterns
- Relapsing-remitting MS (RRMS): Characterized by relapses at onset with stable neurologic disability between episodes (approximately 85% of cases) 1, 3
- Primary-progressive MS (PPMS): Characterized by progressive neurological damage rather than relapses and remissions (approximately 15% of cases) 1
- Secondary progressive MS: Steadily increasing neurologic disability following an initial relapsing course 3
Diagnostic Criteria
The McDonald criteria require evidence of:
- Dissemination in space: Evidence of damage in different parts of the nervous system
- Dissemination in time: Evidence of damage occurring at different times
- No better explanation for the clinical presentation 2
Laboratory Findings
- Cerebrospinal fluid: Presence of oligoclonal IgG bands different from any bands in serum, elevated IgG index, and lymphocytic pleocytosis less than 50/mm³ 2
- Visual evoked potentials: Delayed but well-preserved waveform typical of MS 2
Common Complications
- Physical disability: Weakness, spasticity, and fatigue 5
- Cognitive impairment: Affecting quality of life 3
- Balance and gait dysfunction: Leading to falls in over 50% of patients annually 5
- Visual disorders: Including internuclear ophthalmoplegia (failure of ipsilateral eye adduction and contralateral eye abduction nystagmus) 4
Prognosis
- Life expectancy: Reduced compared to the general population (75.9 vs 83.4 years) 3
- Disease progression: Most long-term disability results from progressive disease rather than relapses 6
Understanding these hallmarks is crucial for early diagnosis and treatment, as current disease-modifying therapies can reduce annual relapse rates by 29-68% compared to placebo or active comparators 3.