Multiple Sclerosis
Definition: Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS), characterized by inflammation, demyelination, axonal damage, and neurodegeneration.
Etiology (Causes & Risk Factors)
1.Autoimmune reaction (loss of tolerance to myelin antigens)
2.Genetic predisposition (e.g., HLA-DRB1*15:01 allele)
3.Environmental triggers: Low vitamin D levels, Epstein-Barr Virus (EBV) infection, Smoking, Living in higher latitudes (less sun exposure), Gender: More common in women (2–3x)
Pathogenesis
1.Autoimmune Activation: CD4+ T cells become autoreactive to myelin antigens (e.g., MBP – myelin basic protein).
2.Blood-Brain Barrier Breakdown: Immune cells (T-cells, B-cells, macrophages) infiltrate the CNS.
3.Demyelination: Immune attack causes destruction of oligodendrocytes and myelin sheath → slowing or blocking nerve conduction.
4.Axonal Injury & Neurodegeneration: Persistent inflammation → irreversible damage to axons.
5.Plaque Formation: Sclerotic plaques (gliotic scars) form in white matter (especially periventricular areas, spinal cord, optic nerves).
Clinical Types
1.Relapsing-Remitting MS (RRMS) (most common): Attacks (relapses) followed by recovery
2.Secondary Progressive MS: Initial RRMS → gradual progression
3.Primary Progressive MS: Progressive disability from onset
Clinical Manifestations
Relapsing-remitting pattern in ~85% of patients
Symptoms vary depending on lesion location, but classic signs include:
Mnemonic: "MS WINS"
M – Motor weakness (limbs, spasticity)
S – Sensory symptoms (numbness, tingling)
W – Vision problems (optic neuritis – blurry or painful vision)
I – Incoordination (ataxia, balance problems)
N – Neurogenic bladder/bowel (urgency, retention)
S – Speech or cognitive changes (fatigue, memory loss)
Characteristic Signs
1.Internuclear Ophthalmoplegia (INO): Due to lesion of the medial longitudinal fasciculus (MLF).
- Findings: Impaired adduction of one eye. Nystagmus of the abducting eye
2.Lhermitte Sign: Electric shock sensation down the spine on neck flexion.
3.Uhthoff Phenomenon: Worsening of symptoms with heat or exercise.
Examination Findings
- Motor: Spasticity. Hyperreflexia. Babinski sign
- Sensory: Impaired vibration/proprioception. Paresthesias.
- Cerebellar: Ataxia. Intention tremor
- Visual: Reduced visual acuity. Optic disc pallor (late)
Diagnosis
- MRI (most important)
- Shows multiple demyelinating plaques: Periventricular lesions. Juxtacortical lesions. Brainstem lesions. Spinal cord lesions
- CSF: Oligoclonal IgG bands. Increased IgG index
- Evoked Potentials: Delayed conduction (especially visual evoked potentials)
Differential Diagnosis
1. Neuromyelitis Optica (NMO): Severe optic neuritis + myelitis. Aquaporin-4 antibodies positive
2. Acute Disseminated Encephalomyelitis (ADEM): Usually post-infectious. Monophasic course
3. Vitamin B12 Deficiency: Posterior column signs. No demyelinating plaques
4. CNS Vasculitis: Multifocal neurological deficits
Treatment
- Acute Relapse: High-dose IV corticosteroids
- Disease-Modifying Therapy: Interferon beta. Glatiramer acetate. Monoclonal antibodies and newer agents
- Symptomatic Treatment: Antispasticity drugs. Bladder management. Physiotherapy