Multiple Sclerosis Overview

Study Notes

Unknown cause.
Genetic factors include HLA alleles, IL2RA, and IL7RA.
Environmental factors such as viruses, geography, diet, and smoking may play a role.
Risk increases with distance from the equator, particularly during the first 15 years of life.
Multiple immune mechanisms (B and T lymphocytes, innate) are involved in the disease process.
No definitive autoantigen, autoantibody, or infectious agent has been identified.
Over 200 genetic variations influence MS risk.

Focal demyelination is common, frequently centered around blood vessels.
Axonal damage and neuronal degeneration accompany demyelination.
Lesions appear in both white and gray matter of the brain and spinal cord, as well as in the optic nerve.
Reactive gliosis occurs.

Most common initial symptom is paresthesia (numbness).
Other common symptoms include gait problems, lower/upper extremity weakness, vision loss, diplopia (double vision).
Signs (physical exam findings) include absent abdominal reflexes, hyperreflexia, lower extremity ataxia, extensor plantar responses, impaired alternating movements, impaired vibratory and position senses, optic neuropathy, nystagmus, and intention tremor.
Bilateral hand numbness is least common initial symptom. A young patient with non-localized symptoms should raise concern.
Upper motor neuron involvement (UMN): defined by hyperreflexia, spasticity, Babinski, and absent abdominal reflexes, are common in this disease.

Relapsing-remitting (RRMS): most common form (85% of patients), characterized by attacks followed by partial or complete recovery.
Secondary progressive (SPMS): approximately 75% of RRMS cases will transition, characterized by gradual worsening after initial period of attacks and remissions. There is worsening of the disease without attacks.
Primary progressive (PPMS): slow, continuous progression of symptoms from onset without clear attacks or remissions.
Progressive-relapsing (PRMS): from onset, disease progresses with clear attacks.

Symptoms develop over a few hours to several days
Symptoms are highly variable depending on affected areas.
Optic neuritis is evidenced by decreased visual acuity, central scotoma (blind spot), reduced color vision; Marcus-Gunn pupil and relative afferent pupillary defect (RAPD), paradoxical pupil dilation.
Other features include depression and Uthoff's phenomenon.
Lhermitte's sign and neurological pathologies (e.g.,. Abscesses) can also be present.

Clinical criteria: typical symptom presentation and neurological findings plus one or more characteristic locations on MRI.
MRI: for evidence of CNS lesions (typically periventricular, juxtacortical). Important to confirm active lesions.
CSF (cerebrospinal fluid analysis): increased white blood cells, proteins. Oligoclonal bands suggest CNS immune response. Increased IgG index (CSF IgG/serum IgG)/(CSF albumin/serum albumin) > 0.7 indicates dissemination in time.
Evoked potentials: to confirm neurological demyelination (Visual, Somatosensory, auditory)
McDonald Criteria (2017): diagnostic criteria for MS, including 1 year of disability progression with 2 or more supporting factors.

Early-onset and female sex can be indicators of better outcomes.
Optic neuritis or sensory symptoms as initial presentation often correlates with a better outcome.
Recovery after attacks and minimal dysfunction at 5 years are indicators of favorable outcomes.
Conversely, male sex, later age of onset, and other initial symptoms (e.g., cerebellar or motor dysfunction) may indicate a poorer prognosis.
Long-term outcome assessment depends on MRI loading.

Acute attacks: high-dose steroids (e.g., methylprednisolone).
Relapse prevention: disease-modifying therapies such as interferon, glatiramer acetate, fingolimod, etc. or monoclonal antibodies such as natalizumab and ocrelizumab .