What are the clinical features and management of Multiple Sclerosis (MS)?

Clinical Features of Multiple Sclerosis

Multiple sclerosis presents with acute-onset neurological symptoms that develop over hours to days, typically stabilize, and often resolve spontaneously, with the most common initial pattern being relapsing-remitting disease affecting approximately 85% of patients. 1

Disease Subtypes and Patterns

Relapsing-Remitting MS (RRMS) - the predominant form:

• Affects approximately 85% of patients at onset 2
• Characterized by acute inflammatory episodes (relapses) followed by periods of remission 1
• Nerve conduction may be affected during acute phases but tends to improve during remission 2
• Over time, relapses cause cumulative myelin damage with progressive neuronal loss 2

Primary Progressive MS (PPMS):

• Affects approximately 15% of patients 2, 3
• Presents with steadily increasing neurological disability from onset without distinct relapses 1
• Often manifests as progressive myelopathy 1
• Characterized by progressive neurological damage rather than relapse-remission cycles 2

Typical Clinical Presentations

Common neurological symptoms include:

• Optic neuritis - visual impairment, scotoma, red-green desaturation, pain with eye movement 2
• Sensory disturbances - paresthesias, numbness 2, 4
• Motor symptoms - paraparesis, weakness, spasticity 2, 5
• Diplopia (double vision) 2
• Myelopathy (spinal cord dysfunction) 2
• Balance and gait dysfunction - affecting 50-80% of patients, with coordination and imbalance issues 5
• Bladder dysfunction 5, 6
• Fatigue and heat sensitivity 5, 6

Temporal characteristics of MS relapses:

• Symptoms develop over hours to days (acute onset) 2, 1
• Episodes typically stabilize 2, 1
• Often resolve spontaneously even without therapy 2
• True relapses last at least 24 hours with new inflammatory demyelinating activity 1

Red Flags Suggesting Alternative Diagnoses

Atypical features requiring additional investigation:

• Subacute onset over weeks (suggests PML rather than MS) 2
• Progressive evolution without stabilization (PML pattern) 2
• Dementia, epilepsy, or aphasia as presenting features 1
• Bilateral sudden hearing loss - requires prompt evaluation for alternative diagnosis 4
• Sudden focal symptoms with headache, confusion - may indicate stroke 4

PML (Progressive Multifocal Leukoencephalopathy) presents distinctly:

• Aphasia, behavioral/neuropsychological changes, retrochiasmal visual deficits, hemiparesis, seizures 2
• Progressive course over weeks without stabilization 2
• This is a critical differential in immunosuppressed patients, particularly those on natalizumab 2, 7

MRI Characteristics

Classic MS lesion features:

• Focal, periventricular location 2
• Lesions in corpus callosum and spinal cord 2
• Sharp edges, ovoid/flame-shaped (especially periventricular) 2, 1
• Orientation perpendicular to ventricles 1
• Homogeneous T2 hyperintensity 2
• Acute lesions may show mass effect 2
• Three or more periventricular lesions are required to demonstrate dissemination in space 2

Additional diagnostic locations:

• Juxtacortical, infratentorial, and spinal cord regions 1
• Optic nerve involvement (documented clinically or via imaging) 2
• Cortical lesions detected in >30% of CIS patients using specialized sequences 2

Age-Specific Considerations

Typical diagnostic age range:

• Best applies to individuals between 10-59 years 4

Pediatric cases (under age 11):

• Require special diagnostic care 4
• Presence of at least one "black hole" (T1 hypointense lesion) plus one periventricular lesion helps distinguish MS from monophasic demyelination 4
• Single periventricular lesion is highly significant in children 2

Older patients (>50 years) or those with vascular risk factors:

• Apply more stringent criteria (higher number of periventricular lesions required) 4

Associated Features

Nutritional and systemic manifestations:

• Weight loss, malnutrition, and cachexia are well-recognized 2
• Causes include reduced mobility, fatigue, dysphagia, poor appetite, physical difficulty eating/drinking, reduced cognition 2

Falls and mobility:

• Over 50% of patients fall at least once yearly 5
• Balance dysfunction conceptualized as decreased positional stability, limited movement toward stability limits, and delayed postural responses 5

Diagnostic Essentials

Core diagnostic requirements:

• Evidence of CNS lesions disseminated in both time and space 4, 1
• At least one clinical event consistent with acute demyelination 4
• Diagnosis should not be made solely on MRI findings 4
• Must exclude alternative diagnoses that can mimic MS 4

Supportive paraclinical findings:

• Oligoclonal bands specific to CSF (often present) 1, 8
• Visual evoked potentials showing delayed conduction 2, 8
• Tibbling & Link IgG index, isoelectrofocusing for oligoclonal bands 8

Critical differential diagnoses to exclude:

• Neuromyelitis optica spectrum disorder (NMOSD) 4
• Cerebrovascular disease (multifocal ischemia/infarction in young adults) 4
• Infectious diseases (HTLV1, Lyme disease) 4
• Paraneoplastic disorders 4
• Monophasic demyelinating diseases 4

Diagnosis should be made by a specialist familiar with MS, its differential diagnoses, and interpretation of paraclinical assessments. 4