Multiple Sclerosis (Neurology)

Multiple Sclerosis (MS)

• Chronic autoimmune disease of the central nervous system (CNS)
• Characterized by chronic inflammation, demyelination, gliosis, and neuronal loss
• Course may be relapsing-remitting or progressive in nature
• Lesions in the CNS occur at different times and in different locations, known as "disseminated in time and space"

Disease Course

• Relapsing-remitting (RR): 70-80% of MS patients, with initial onset characterized by relapses
• Primary progressive (PP): 15-20% of patients, with gradual deterioration from the onset and no relapses
• Secondary progressive (SP): characterized by gradual neurologic deterioration after an initial RR course
• Clinically isolated syndrome (CIS): often classified as a single episode of inflammatory CNS demyelination

Etiology

• Exact etiology unknown
• Factors involved in pathogenesis group into three categories:
  • Immune factors: autoimmune attack on the CNS
  • Environmental factors: latitudinal gradients, vitamin D deficiency, and infections (e.g., Epstein Barr virus)
  • Genetic associations

Epidemiology

• Approximately 400,000 individuals in the US and 2.5 million individuals worldwide have MS
• Disease is three-fold more common in females than males
• Age of onset usually between 20-40 years, but can present at any age
• Almost 10% of cases present before the age of 18

Pathogenesis

• Pathophysiology limited to the primary CNS
• Two main processes: focal inflammation resulting in plaques and injury to the blood-brain barrier, and neurodegeneration with microscopic injury involving different components of the CNS

Clinical Presentations

• Vision symptoms: vision loss, double vision, optic neuritis
• Vestibular symptoms: vertigo, gait imbalance
• Bulbar dysfunction: dysarthria, dysphagia
• Motor: weakness, tremor, spasticity, fatigue
• Sensory: loss of sensation, paresthesia, dysesthesias
• Urinary and bowel symptoms: incontinence, retention, urgency, constipation, diarrhea, reflux
• Cognitive symptoms: memory impairment, impairment of executive functions, trouble concentrating
• Psychiatric symptoms: depression, anxiety

MS Relapse

• RR course characterized by exacerbation and relapses of neurological symptoms with stability between episodes
• Features of RR course: new or recurrent neurological symptoms, symptoms developing over days and weeks, and symptoms lasting 24-48 hours

Diagnosis

• Dissemination in space (DIS) and dissemination in time (DIT) are two hallmarks of accurate diagnosis
• DIT demonstrated by new lesions on a follow-up MRI, new clinical relapse, or presence of oligoclonal bands in CSF
• DIS established by noting at least one T2 lesion in two of the four CNS sites: spinal cord, infratentorial, juxtacortical, and periventricular regions

Investigations

• MRI brain and spinal cord with contrast
• CSF analysis
• Evoked potentials (optional)
• Blood studies: CBC, TSH, vitamin B12, sedimentation rate, and ANA

MRI Picture

• Lesions are T2 hyperintense (white), T1 isointense/hypointense
• Lesions are classically oval
• High predilection for periventricular white matter
• Lesions are perpendicular to the ependymal surface (Dawson's fingers)
• Contrast enhancement with active lesions noted as classically diffuse or rim enhancement
• Cord lesions classically involve the cervical or thoracic cord

CSF Findings

• Elevated protein
• Leukocytes less than 50 (occasionally seen, and typically mononuclear cells)
• Increased total IgG index, oligoclonal bands

Differential Diagnosis

• Other demyelinating or inflammatory CNS syndromes (e.g., optic neuritis, acute disseminated encephalomyelitis, neuromyelitis optica)
• General inflammatory and autoimmune syndromes (e.g., systemic lupus erythematosus)
• Infectious etiologies (e.g., Lyme disease, HIV, herpes viruses)
• Vascular etiologies (e.g., migraine headaches, vascular malformations, and emboli)
• Metabolic causes (e.g., vitamin deficiencies, thyroid disease)
• Neoplastic causes (e.g., primary CNS malignancies or metastasis)

Prognosis and Treatment

• Prognosis and severity vary between patients
• High-dose steroids for treating relapses
• Disease-modifying therapies are the mainstay of treatment for relapsing-remitting MS
• Treatment usually continues for life
• Many options are available, including injectables (e.g., interferon-beta preparations, glatiramer acetate), oral medications (e.g., dimethyl fumarate, fingolimod), and others.