What is Multiple Sclerosis (MS) ?
Multiple Sclerosis (MS) is an autoimmune disease that produces antibodies against components of the myelin sheath that surrounds that nerve fibers causing demyelination, causes communication problems between your brain and the rest of your body. Eventually, the disease can cause permanent damage or deterioration of the nerves.
There are four clinical subtypes of multiple sclerosis (MS):
Clinically isolated syndrome (CIS): a patient’s initial symptom characteristic of CNS demyelination that may be due to MS but does not fulfill the criteria of dissemination in time. Approximately 60% of individuals diagnosed with CIS will later relapse and be diagnosed with MS.
Relapsing-remitting multiple sclerosis (RRMS): episodic flare-ups occurring over days to weeks between periods of neurologic stability. During attacks, new symptoms may present, whereas previous symptoms may worsen.
Secondary progressive multiple sclerosis (SPMS): a gradual decline in disease status after an initial relapsing-remitting disease course. Progressive phase may be associated with acute exacerbations. SPMS is often diagnosed retrospectively.
Primary progressive multiple sclerosis (PPMS): a progressive decline in disease status and accumulation of disability from onset of disease without an initial relapsing-remitting disease course.
MS is a complex condition that is multifactorial, and although advances in genomics and immunology have increased our understanding of the disease process, much is yet to be discovered. It most often affects Caucasian women in their 2nd and 3rd generations of life and is more common in those with first-degree relatives with the disease.
Women (worldwide): 3.6 cases/100,000 person-years
Men (worldwide): 2.0 cases/100,000 person-years.
- T-cells and B-cells are excessively produced against the myelin sheath.
- Dysregulation and mistaken antigen identity lead CD4 T-cells to cross the blood–brain barrier and recognize proteins on the surface of the myelin sheath.
- Cytokines, interferon-γ, and tumor necrosis factor-α are subsequently released, and activation of macrophages and B-cells leads to myelin destruction.
- Age: peak incidence ages 15 to 45 years, mean age 28 to 31 years (slightly earlier in women than men)
- Race: Caucasian > African Caribbean > East-Asian
- Gender: 2 to 3 times more common in women
- Infectious: prior infections with Epstein-Barr virus and history of infectious mononucleosis
- Gait disturbance
- Foot drop
- Hyperesthesia or paresthesia
- Cerebellar dysarthria (scanning speech)
- Spasticity (especially in lower extremities)
- Uhthoff phenomenon: Symptoms worsen with exposure to higher than usual temperature.
- Lhermitte sign: electric-like shocks extending down the spine caused by neck movement, especially flexion
- MRI of head/spine: Periventricular and callosal lesions are relatively specific for MS.
- Lumbar puncture: Cerebrospinal fluid can reveal elevated or normal total protein levels. Oligoclonal immunoglobulin G bands are seen in approximately 90% of MS but may be absent early in the disease process. Positive findings are not diagnostic for MS but may be beneficial if other diagnostic criteria are equivocal.
- Blood tests: Antinuclear antibody, antineutrophil cytoplasmic antibody, anti–double-stranded DNA antibody, extractable nuclear antigen, antiphospholipid antibody, compliment, erythrocyte sedimentation rate, immunoglobulin G, immunoglobulin M, rheumatoid factor, and Lyme disease antibody can be used to rule out alternative diagnosis.
Acute relapse treatment of Multiple Sclerosis
Methylprednisolone 0.5 g PO daily for 5 days or 1 g IV daily for 3 to 5 days; without subsequent oral tapering; a second course may be given.
Side effects: increased infection risk, adrenal insufficiency, Cushing syndrome, fluid retention, hypokalemia, GI disturbances, headache, emotional lability
Disease-modifying treatment of Multiple Sclerosis
1) IFN-β1a, 30 μg IM weekly
2) IFN-β1a, 22 or 44 μg SC 3 times per week
3) IFN-β1b, 250 μg SC every other day
Monitoring: CBC, LFTs, TSH
Side effects: flu-like symptoms, depression, skin site reactions, thyroid dysfunction, liver enzyme abnormalities
4) Glatiramer acetate, 20 mg SC daily
Side effects: skin site reactions, immediate post injection reaction, lipoatrophy
5) Dimethyl fumarate, 120 to 240 mg PO twice daily
Side effects: diarrhea, cramps, LFT elevation, nausea, flushing
6) Teriflunomide, 7 to 14 mg PO daily
Monitoring: CBC, LFTs, UA
Side effects: nasopharyngitis, headache, diarrhea, fatigue, back pain, influenza, hair thinning, LFT elevation, nausea, UTI
7) Natalizumab, 300 mg IV every 28 days
Monitoring: CBC, LFTs
Side effects: headache, fatigue, UTI, hypersensitivity reaction
8) Alemtuzumab, 12 to 24 mg IV for 5 days than 3 days 12 months after initial treatment
Monitoring: CBC, LFTs, TSH
Side effects: immune thrombocytopenic purpura, autoimmune thyroid related problems, headaches, flushing
9) Fingolimod, 0.5 mg PO daily
Monitoring: ECG, CBC, LFTs, eye exam
Side effects: first-degree AV block, bradycardia, macular edema, shingles, worsening pulmonary function, skin cancer, back pain
Symptomatic therapies of Multiple Sclerosis
Spasticity: baclofen, dantrolene, diazepam, tizanidine, cannabis extract, botulinum toxin, physiotherapy
Pain: amitriptyline, pregabalin, gabapentin, cannabis extract (nabiximols)
Bladder dysfunction: oxybutynin, tolterodine, cannabis extract (nabiximols), catheterization, intravesical botulinum toxin
Constipation: natural or other laxatives, stool softeners, bulk-producing agents
Erectile dysfunction: sildenafil
Fatigue: amantadine, modafinil
Tremors: clonazepam, primidone, β-blockers
Depression: SSRI (citalopram), SSNRI (venlafaxine), TCA (amitriptyline)