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.

This quiz covers the basics of multiple sclerosis, an autoimmune disease affecting the central nervous system, including its characteristics, course, and effects on the CNS.