How does a patient with multiple sclerosis typically present (age 20‑40, female predominance) regarding initial symptoms such as unilateral painful optic neuritis, sensory disturbances, motor weakness, ataxia, Lhermitte’s sign, fatigue, bladder dysfunction, and cognitive changes?

Clinical Presentation of Multiple Sclerosis

Typical Patient Demographics

Multiple sclerosis most commonly presents in young adults aged 20-30 years, with a nearly 3:1 female predominance, though diagnosis can occur between ages 10-59 years. 1, 2

• Women are affected approximately 3 times more frequently than men across all age groups 1
• Mean age of onset is 20-30 years, though the disease is most prevalent between ages 40-60 years 1, 2
• Less than 3% of cases occur before age 18 years 1
• Late-onset MS (after age 50) accounts for approximately 5% of cases 3

Initial Clinical Presentations

Most Common Presenting Symptoms

The hallmark presentation involves acute neurological symptoms developing over hours to days, typically including unilateral optic neuritis, sensory disturbances, motor weakness, or brainstem syndromes. 4, 2

Relapsing-remitting pattern is the most common initial presentation (approximately 80% of cases), characterized by acute onset of neurological symptoms that stabilize and resolve spontaneously. 4, 5

Optic Neuritis

• Unilateral painful vision loss is a classic presenting feature 2
• Develops over several days 2
• May be the sole initial manifestation 5

Sensory Disturbances

• Numbness, tingling, or abnormal sensations are common initial symptoms 5, 6, 7
• Can present as partial myelitis 2
• Sensory problems range from 5-94% in various presentations 3

Motor Symptoms

• Weakness affecting limbs is a frequent presentation 5, 7
• Motor dysfunction is particularly common in late-onset MS (35.4-100% of cases) 3
• Impaired gait and incoordination are typical 5, 7

Brainstem Syndromes

• Internuclear ophthalmoplegia is a characteristic brainstem presentation 2
• Brainstem dysfunction occurs in 12.3-25% of cases 3
• Diplopia may be present 1

Additional Common Symptoms

Patients frequently experience Lhermitte's sign (electric shock sensation down the spine with neck flexion), fatigue, bladder dysfunction, heat sensitivity, and cognitive changes. 5, 6, 7

• Lhermitte sign: Electric shock-like sensation radiating down the spine with neck flexion 7
• Fatigue: One of the most common and disabling symptoms 5, 6
• Bladder dysfunction: Urinary urgency, frequency, or retention 5, 6, 7
• Cognitive changes: Memory problems, impaired concentration, and dysregulated mood 5
• Heat sensitivity: Worsening of symptoms with elevated body temperature 5, 6
• Ataxia and imbalance: Incoordination and gait disturbances 5, 6
• Tremor: Movement disorders may develop 5, 7

Clinical Course Patterns

Relapsing-Remitting MS (Most Common)

• Accounts for approximately 80% of cases at onset 5
• Discrete episodes (attacks or relapses) of neurological symptoms 6
• Symptoms develop over hours to days 4
• Episodes typically stabilize and resolve spontaneously 4
• Patients remain stable between relapses 6
• Does not affect life expectancy 5

Primary Progressive MS

• Steadily increasing neurological disability from onset 4
• No distinct relapses or remissions 4
• Often presents as progressive myelopathy 4
• More common in late-onset MS (predominant phenotype in some studies) 3

True Relapse Characteristics

A true MS relapse must involve new or worsening neurological symptoms lasting at least 24 hours, with new inflammatory demyelinating activity. 4

• Symptoms must persist for minimum 24 hours to qualify as a relapse 8, 4
• Often shows new or enhancing lesions on MRI 4
• Subacute onset evolving over weeks (rather than hours-to-days) should raise concern for MS mimics 8

Age-Specific Presentation Differences

Late-Onset MS (After Age 50)

• Motor dysfunction is the most prevalent first presentation (35.4-100%), unlike typical adult-onset MS 3
• Progressive form is more common than in younger patients 3
• Female predominance persists but male cases increase with aging (57.7-70.2% female) 3
• Spinal cord involvement occurs in 65% of cases 3
• Relapsing-remitting form still occurs in approximately 50% 3

Pediatric MS (Under Age 11)

• Special diagnostic care is needed 1
• At least one black hole (T1 hypointense lesion) and one periventricular lesion helps distinguish MS from monophasic demyelination 8, 1

Red Flags Suggesting Alternative Diagnoses

Certain presentations should prompt consideration of MS mimics rather than typical MS. 8, 4

Clinical Red Flags

• Dementia, epilepsy, or aphasia as presenting features 8, 4
• Bilateral sudden hearing loss 8, 1
• Sudden onset of focal symptoms suggesting stroke (headache, confusion, diplopia, dysarthria, focal weakness, numbness) 8, 1
• Subacute onset evolving over weeks rather than hours-to-days 8
• Progressive evolution without stabilization 8
• Symptoms failing to meet 24-hour minimum duration 8
• Onset before age 10 or after age 59 requires more stringent diagnostic criteria 8, 1

Diagnostic Workup Essentials

Diagnosis requires evidence of CNS lesions disseminated in both time and space, based on clinical history, neurologic examination, MRI findings, and exclusion of alternative diagnoses. 1, 4, 2

Core Diagnostic Elements

• At least one clinical event consistent with acute demyelination is required 8, 1
• MRI showing characteristic T2 lesions in periventricular, juxtacortical, infratentorial, and spinal cord regions 4, 2
• Diagnosis cannot be made on MRI findings alone 8, 1
• Objective clinical findings are required—symptoms alone are insufficient 1

Additional Testing When Indicated

• Lumbar puncture for CSF analysis (including oligoclonal bands) is essential in atypical presentations, progressive onset, or diagnostic uncertainty 8, 1
• Oligoclonal bands specific to CSF are often present (46-98% in various studies) 4, 3
• Visual evoked potentials may be useful in suspected optic nerve involvement or when MRI access is limited 8, 1
• Aquaporin-4 IgG antibody testing to exclude neuromyelitis optica spectrum disorders 8
• ANA and antiphospholipid antibodies should be considered if clinically indicated to exclude mimics 8, 1

Critical Diagnostic Pitfalls

• Diagnosis should be made by a specialist familiar with MS and its mimics 8, 1
• Alternative diagnoses must be excluded, including cerebrovascular disease, infectious diseases (HTLV1, Lyme), paraneoplastic disorders, and NMOSD 8, 1, 4
• In patients over 50 years or with vascular risk factors, apply higher diagnostic thresholds 8, 1
• A positive test for a putative MS mimic does not automatically exclude MS diagnosis 6