What is the physiological presentation of Multiple Sclerosis (MS)?

Physiological Presentation of Multiple Sclerosis

Multiple sclerosis presents with neurological symptoms that develop over hours to days due to inflammatory demyelination in the central nervous system, most commonly manifesting as unilateral optic neuritis, sensory disturbances, motor weakness, diplopia, balance dysfunction, or partial myelitis in young adults aged 20-30 years. 1, 2

Core Pathophysiology

• MS is an autoimmune-mediated neurodegenerative disease characterized by inflammatory demyelination with axonal transection affecting the brain, spinal cord, and optic nerves 2
• The disease causes focal demyelinating lesions in myelin-rich white matter, with increasing recognition of gray matter involvement even during earliest disease phases 3
• Neurodegeneration occurs through both direct and indirect neuroimmune interactions, with oxidative stress and mitochondrial dysfunction playing key roles in disease progression 3

Clinical Presentation Patterns

Relapsing-Remitting MS (85% of cases at onset)

• Acute neurological symptoms develop over hours to days, typically stabilize, and often resolve spontaneously 1, 2
• True relapses last at least 24 hours with new inflammatory demyelinating activity 1
• Nerve conduction is affected during acute phases but tends to improve during remission, though cumulative myelin damage and progressive neuronal loss occur over time 1

Primary Progressive MS (15% of cases)

• Steadily increasing neurological disability from onset without distinct relapses 1, 4
• Often presents as progressive myelopathy 4

Common Neurological Manifestations

Visual Symptoms

• Unilateral optic neuritis with visual impairment, scotoma, red-green desaturation, and pain with ocular movement 5, 1
• Impaired vision or diplopia 3, 6

Motor Symptoms

• Motor weakness, tremor, and spasticity 6, 7
• Weakness and paralysis in advanced cases 3

Sensory Disturbances

• Abnormal sensations including Lhermitte sign (electric shock sensation down spine with neck flexion) 7
• Sensory disturbances affecting various body regions 1, 2

Coordination and Balance

• Balance dysfunction conceptualized as three interrelated problems: decreased ability to maintain position, limited and slowed movement towards limits of stability, and delayed responses to postural displacements 8
• Impaired coordination and gait dysfunction affecting 50-80% of patients 8
• Over 50% of patients fall at least once yearly 8

Brainstem Syndromes

• Internuclear ophthalmoplegia and diplopia 1, 2
• Partial myelitis 4, 2

Other Manifestations

• Fatigue (extremely common) 3, 6, 7
• Dysregulated mood and depression 3, 6
• Cognitive impairment 2, 3
• Bladder and bowel dysfunction 6, 7
• Heat sensitivity 6
• Sexual dysfunction 7

Structural Changes on Imaging

• Focal T2 hyperintense lesions with sharp edges, ovoid/flame-shaped, oriented perpendicular to ventricles 1, 4
• Periventricular location (≥3 lesions required for diagnosis) 5, 1
• Lesions in corpus callosum, juxtacortical regions, infratentorial areas, and spinal cord 1, 4
• Gadolinium-enhancing lesions indicate active inflammation 4, 2
• Progressive brain volume loss over time reflecting neurodegeneration, with increasing ventricular and subarachnoid spaces 5

Disease Course Variability

• The course of disease is highly variable and largely unpredictable 3, 7
• Symptoms can affect balance, impaired vision or speech, weakness, paralysis, fatigue, depression, and cognitive impairment 3
• Patients accumulate physical and cognitive disabilities over time despite periods of remission 1, 6
• Life expectancy is reduced compared to general population (75.9 vs 83.4 years) 2

Red Flags for Alternative Diagnoses

• Subacute onset over weeks rather than hours to days 1
• Progressive evolution without stabilization 1
• Dementia, epilepsy, or aphasia as presenting features 1
• Bilateral sudden hearing loss 9, 1
• Sudden onset of focal symptoms with headache suggesting stroke 9

Age and Demographic Considerations

• Typical age of onset is 20-30 years, with diagnostic criteria applying best to ages 10-59 years 9, 1, 2
• More commonly affects women with female to male ratio of nearly 3:1 2
• Pediatric cases (under age 11) require special diagnostic care 9, 1
• Patients older than 50 years or with vascular risk factors require more stringent diagnostic criteria 9, 1