What are the diagnostic and clinical features of multiple sclerosis (MS)?

Diagnostic and Clinical Features of Multiple Sclerosis

Multiple sclerosis (MS) is diagnosed based on evidence of central nervous system lesions disseminated in both time and space, with no better explanation for the clinical and investigative findings. 1

Clinical Presentation

• MS typically presents in young adults (mean age 20-30 years) with neurological symptoms developing over several days, including unilateral optic neuritis, partial myelitis, sensory disturbances, or brainstem syndromes such as internuclear ophthalmoplegia 2
• Common symptoms include sensory disturbances, Lhermitte sign (electric-like sensation running down the spine with neck flexion), motor weakness, visual problems, impaired coordination, and fatigue 1, 3
• MS affects women more commonly than men with a female to male ratio of nearly 3:1 2
• The clinical course can be classified into four major types 4:
  • Relapsing-remitting MS (RRMS): most common type, characterized by relapses followed by periods of partial or complete remission
  • Primary progressive MS (PPMS): steadily increasing neurological disability from onset
  • Secondary progressive MS (SPMS): steadily increasing disability following an initial relapsing course
  • Progressive relapsing MS (PRMS): progressive disease from onset with acute relapses

Diagnostic Criteria

• The diagnosis of MS requires evidence of central nervous system lesions disseminated in both time and space 1
• MRI is the preferred imaging modality, showing characteristic T2 lesions and gadolinium-enhancing lesions 1
• The 2017 McDonald Criteria incorporate clinical presentation, MRI findings, and laboratory findings (e.g., cerebrospinal fluid-specific oligoclonal bands) 2
• For typical presentations, diagnosis applies best to individuals between 10 and 59 years of age 5
• In atypical presentations (e.g., dementia, epilepsy, aphasia) or progressive onset, additional evidence from CSF and visual evoked potentials (VEP) may help secure the diagnosis 5

Differential Diagnosis

• Several conditions may mimic MS and should be carefully considered 5:
  • Cerebrovascular disease: multifocal areas of cerebral ischemia or infarction in young adults (phospholipid antibody syndrome, lupus, CADASIL, Takayasu's disease, meningovascular syphilis, carotid dissection)
  • Infectious diseases: HTLV1, Lyme disease
  • Paraneoplastic disorders: cerebellar ataxia (may present with elevated IgG in CSF)
  • Monophasic demyelinating diseases: acute disseminated encephalomyelitis, postviral Devic's syndrome, acute transverse myelitis
  • Recurrent demyelinating diseases: neuromyelitis optica (Devic's syndrome), recurrent longitudinally extensive transverse myelitis
  • Genetic disorders of myelin: leukodystrophies (particularly in children and teenagers)

Diagnostic Workup

• MRI is essential for diagnosis, showing characteristic lesions in periventricular, juxtacortical, infratentorial, and spinal cord regions 1
• Cerebrospinal fluid analysis may reveal oligoclonal bands not present in serum, supporting the diagnosis 2
• Visual evoked potentials can demonstrate delayed conduction in visual pathways, even in patients without visual symptoms 1
• Diagnosis should be made by a specialist familiar with MS, its differential diagnoses, and interpretation of paraclinical assessments 5

Important Diagnostic Considerations

• Diagnosis should not be made in cases of monophasic demyelinating diseases unless new symptoms/signs or imaging abnormalities appear more than three months after clinical onset 5
• Sudden onset of focal neurologic symptoms (headache, confusion, diplopia, dysarthria, focal weakness, numbness) may indicate stroke rather than MS 1
• Bilateral sudden hearing loss may indicate a condition other than MS 1
• Regular MRI monitoring is recommended to assess disease activity and treatment response 1
• Biopsy is rarely needed but can confirm inflammatory demyelinating lesions; interpretation by neuropathologists experienced in demyelinating diseases is essential 5

Prognosis

• Overall life expectancy is reduced compared to the general population (75.9 vs 83.4 years) 2
• There is significant interpatient variability in prognosis 6
• Pregnancy reduces disease activity, but there is a higher risk of relapse in the postpartum period 6

Management Approach

• Disease-modifying therapies (DMTs) should be initiated early to forestall disease and preserve function 3
• Nine classes of DMTs are available for relapsing forms of MS, with efficacy rates ranging from 29-68% reduction in annualized relapse rates 2
• Corticosteroids (typically intravenous methylprednisolone for 3 days) are the treatment of choice for acute significant symptom exacerbations 3, 6
• Symptom management is crucial and may include treatment for spasticity, paresthesias, tremor, erectile dysfunction, depression, anxiety, fatigue, and pain 3
• Rehabilitation, including physical therapy, occupational therapy, and cognitive rehabilitation, plays a crucial role in maintaining function 1