Definition and Overview
Multiple sclerosis (MS) is a chronic autoimmune disease in which the immune system attacks the myelin sheath of central nervous system (CNS) neurons, causing demyelination, axonal damage, and progressive neurological disability [1].
MS affects approximately 2.8 million people worldwide with a 3:1 female-to-male ratio. Peak onset is between ages 20-40. Relapsing-remitting MS (RRMS) accounts for 85% of initial presentations [1].
Pathophysiology
Autoreactive T cells cross the blood-brain barrier and initiate inflammatory cascades targeting myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP). B cells contribute through antibody production and antigen presentation [2].
Demyelination disrupts saltatory conduction, producing neurological symptoms. Progressive axonal loss leads to irreversible disability over time.
Classification
- RRMS (relapsing-remitting): 85% of cases; discrete relapses with full or partial recovery
- SPMS (secondary progressive): gradual progression after initial RRMS course
- PPMS (primary progressive): progressive decline from onset without discrete relapses
- CIS (clinically isolated syndrome): first episode suggesting MS
Symptoms
Symptoms depend on lesion location and include optic neuritis (visual loss), limb weakness, sensory symptoms (numbness, tingling), cerebellar ataxia, and Lhermitte's sign (electrical sensation down the spine with neck flexion) [3].
Autonomic dysfunction affects up to 80% of MS patients: bladder dysfunction (urgency, frequency, retention), bowel problems (constipation), cardiovascular dysregulation, sexual dysfunction, and thermoregulatory impairment [4].
Fatigue is the most common symptom (75-95%), often the most disabling. Cognitive impairment affects 40-70% of patients.
Diagnosis
McDonald criteria (2017 revision) require dissemination in space (DIS) and time (DIT). MRI shows periventricular, juxtacortical, infratentorial, and spinal cord T2/FLAIR lesions with gadolinium-enhancing lesions. CSF oligoclonal bands support the diagnosis [5].
Treatment
Disease-modifying therapies (DMTs) reduce relapse rates and slow disability progression. Options range from injectable therapies (interferon-beta, glatiramer acetate) to oral agents (dimethyl fumarate, fingolimod, teriflunomide) and high-efficacy infusions (natalizumab, ocrelizumab, alemtuzumab) [3].
Acute relapses are treated with high-dose IV methylprednisolone (1g/day for 3-5 days). Symptomatic management addresses spasticity, fatigue, pain, bladder dysfunction, and depression.