II. Epidemiology
- Top disabling condition of young adults (U.S.)
-
Prevalence
- Northern U.S.: 191 cases per 100,000 persons (Olmstead County, Minnesota)
- Southern U.S.: 40 cases per 100,000 persons (Lubbock, Texas)
- U.S. Total: 1 Million patients affected
- Howard (2016) Neurol Clin 34(4): 919-39 [PubMed]
III. Pathophysiology
- Acute attacks (relapsing remitting MS) are a result of inflammatory reaction
- Inflammatory cells (T Cells, B Cells and Macrophages) cross the blood-brain barrier at weakened vessel surfaces
- Immunoglobulins target the Myelin Sheath
- Macrophages damage the axons with free radical release
- Results
- Focal regions of inflammation and demyelination of white matter
- Periventricular and subpial white matter are particularly involved
- Gliosis
- Glial cell proliferation and activation
- Degeneration
- Axonal Loss
- Focal regions of inflammation and demyelination of white matter
IV. Risk Factors
- Race: White > Black
- Gender: Female > Male (2:1)
- High socioeconomic status
- Northern latitudes
- Environmental factors (toxins, viruses)
- Tobacco Abuse
- HLA histocompatible Antigens
- Vitamin D Deficiency (or less sunlight exposure)
V. Symptoms
- Sensory loss of vibration, proprioception or nociception (37%)
- Optic Neuritis (36%)
- Focal Weakness (35%)
- Paresthesias with numbness or tingling Sensation (24%)
- Diplopia (15%)
- Ataxia or Incoordination (11%)
- Vertigo (6%)
- Paroxysmal symptoms (4%)
- Urinary Incontinence (4%)
-
Lhermitte Sign (3%)
- Electrical Sensation down spine on neck flexion
-
Dementia (2%)
- Cognitive dysfunction is a late disease finding (consider alternative diagnosis if a concern at presentation)
- Findings may include Learning Difficulty, memory deficit, slowed processing speed
- Visual Loss (2%)
- Facial palsy (1%)
- Erectile Dysfunction or Sexual Dysfunction (1%)
- Myokymia (1%)
- Seizures (1%)
- Other findings
- Tremor
- Dysarthria
- Depressed mood
- Fatigue
- Hearing Loss or Tinnitus
- Heat intolerance
- Bowel Dsyfunction (e.g. Constipation)
VI. Signs
- Dysarthria
- Decreased pain, vibration and position sense
- Decreased coordination and balance
- Ataxia
- Difficult Tandem Walking
-
Eye Exam
- Visual Field Defects
- Decreased Visual Acuity
- Red color Perception
- Afferent Pupillary Defect
- Optic Nerve pallor (Optic Neuritis)
- Nystagmus (most commonly Horizontal Nystagmus)
- Bilateral Internuclear Ophthalmoplegia
- Nystagmus of abducting eye on lateral gaze
- Other eye with slow adduction
- Reflexes
- Deep Tendon Reflexes hyperactive
- Spasticity
- Abdominal reflexes lost
- Ankle Clonus present
- Babinski Reflex with up-going toes
-
Charcot's Triad
- Intention Tremor
- Nystagmus
- Scanning speech
- Hot Bath Test
- Hot bath exacerbates visual signs
VII. Diagnosis: General Criteria
- Overview
- Diagnosis Requires 2 episodes and 2 CNS areas
- Episodes (Attacks) are discrete events lasting >24 hours and not associated with fever or infection
- Specific Criteria
- Objective findings on exam consistent with history
- Long white matter tracts predominately involved
- Pyramidal
- Cerebellar
- Medial Longitudinal Fasciculus (MLF)
- Optic Nerve
- Posterior Columns
- Dissemination in space (DIS)
- Characteristic MS regions (periventricular, juxtacortical, infratemporal or spinal)
- Two CNS Areas or more are involved
- Dissemination in time (DIT)
- Two separate episodes of symptom clusters
- Involve different CNS areas
- Or Progression over at least 12 months
- Two separate episodes of symptom clusters
- No other explanation for CNS symptoms
- Not associated with fever or infection
- Age range 15 to 60 years
- Findings suggestive of alternative diagnosis (typically not due to Multiple Sclerosis)
- Abrupt or transient symptoms (<24 hours)
- Seizures, Aphasia or other significant cortical findings
- Peripheral Neuropathy
- Non-neurologic involvement (e.g. cardiac)
- Family History of neurologic disorder other than MS that may explain findings
- Progressive Ataxia
- Cognitive dysfunction
- Nonspecific neurologic symptoms that are difficult to localize
VIII. Diagnosis: McDonald Criteria (2017)
- Definitive diagnosis: Relapsing Remitting
- Two or more attacks AND
- Two or more lesions or objective clinical evidence of one lesion and clear-cut historical evidence of prior attack
- Definitive diagnosis: Primary Progressive (PPMS)
- Insidious neurologic pregression of one year or more AND
- Additional criteria (2 of 3 required)
- One or more T2 lesion in characteristic MS regions (periventricular, juxtacortical, infratemporal or spinal)
- Two or more T2 lesions affecting the spinal cord
- Positive CSF findings (oligoclonal bands or elevated IgG Index)
- Presentations requiring a second attack for definitive diagnosis
- Dissemination in Time (DIT)
- Two or more attacks with objective evidence of one T2 lesion
- Lesion affects 2 of 4 characteristic MS regions (periventricular, juxtacortical, infratemporal or spinal)
- Dissemination in Space (DIS)
- One attack with objective evidence of two or more T2 lesions
- Simultaneous asymptomatic gadolinium-enhancing and nonenhancing lesions at a point in time OR
- New T2 or gadolinium-enhancing lesion on follow-up MRI OR
- Positive CSF-specific Oligoclonal Bands
- One attack with objective evidence of two or more T2 lesions
- One attack with objective evidence of one lesion
- Await additional attack with characteristics of one of the two presentations (DIT or DIS) as above
- Dissemination in Time (DIT)
- References
IX. Differential Diagnosis
- Degenerative disease
- Amyotrophic Lateral Sclerosis
- Huntington Disease
- Demyelinating disease
- Acute inflammatory demyelinating Polyneuropathy (Guillain Barre Syndrome)
- Chronic inflammatory demyelinating Polyneuropathy
- Neuromyelitis Optica
- Paraneoplastic Syndromes
-
CNS Infection
- Tertiary Lyme Disease
- Tertiary Syphilis (Neurosyphilis)
- Human Immunodeficiency Virus (HIV)
- Mycoplasma
- Progressive Multifocal Leukoencephalopathy (JC Virus Infection)
- CNS Inflammation
- CNS Vascular Disease
- Hypertension
- Diabetes Mellitus
- Cerebrovascular Accident
- Migraine Headache
- Vasculitis
- Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy (CADASIL)
- CNS mass or structural disease
- Cervical Spondylosis (or other Spinal Cord Syndromes)
- Cervical Disc Disease
- CNS neoplasm
- Arnold Chiari Malformation
- Arteriovenous Malformation
- Medications and recreational drugs
-
Vitamin Deficiency or Toxicity
- Vitamin B12 Deficiency
- Folate Deficiency
- Vitamin E deficiency
- Manganese Toxicity
- Psychiatric conditions
-
Genetic disorders
- Leukodystrophy
- Mitochondrial disease
- Miscellaneous
- References
X. Types: Course
- Relapsing Remitting MS (85 to 90% of cases)
- Discrete attacks evolve over days to weeks
- Recovery for weeks to months in which there is no neurologic worsening between attacks
- Recovery results from axonal changes, neuroplasty and remyelination
- Secondary progressive MS
- Starts as relapsing remitting (RRMS) and secondarily progresses in 50% of untreated RRMS cases
- Progresses to gradual neurologic deterioration outside of discrete, acute attacks
- Primary progressive (PPMS) and progressive relapsing (10-15% of cases)
- Steady functional decline from Multiple Sclerosis onset (and acute exacerbations may occur)
- Termed primary progressive if no attacks occur
- Termed progressive relapsing if attacks occur
- References
XI. Types: Diagnostic Surety
- Definite Multiple Sclerosis
- All criteria fulfilled
- Clinically Isolated Syndrome
- First episode of acute or subacute symptoms characteristic of MS, lasting at least 24 hours
- Does not yet meet diagnostic criteria of MS
- Abnormal MRI predicts 80% progression to MS in 20 years (contrast with 20% if MRI normal)
- Probable Multiple Sclerosis: All criteria fulfilled except
- Only 1 neurologic sign (2 Symptomatic episodes) or
- Neurologic signs unrelated to 1 Symptomatic episode
- At risk for Multiple Sclerosis: All criteria fulfilled except
- Only 1 episode and
- No neurologic signs on exam
- Radiologically Isolated Syndrome
- Absent clinical symptoms, but incidental radiologic findings of inflammatory demyelination suspicious for MS
- Progression to MS or Clinically Isolated Syndrome in 30 to 40% of patients
XII. Diagnostics
-
MRI Head (preferred first line study)
- Abnormal scan in >90% of Multiple Sclerosis patients
- Findings
- Plaque formation (Myelin Sheath loss)
- Spotty and irregular demyelination
- Distribution
- Involves Brainstem, Cerebellum, corpus callosum
- Other localized distribution
- Around ventricles
- Around gray-white junction
- Gadolinium enhancing if active inflammation
-
CT Head
- Not nearly as useful as MRI Head
- Indicated when MRI is contraindicated or unavailable
- Findings
- Ventricular enlargement
- Low density periventricular abnormalities
- Focal enhancement
- Not nearly as useful as MRI Head
- Evoked Potentials
- Visual, auditory, somatosensory, and motor
- Visually evoked potentials are most useful
- One or more evoked potential abnormal in 80-90% of MS
XIII. Labs: Multiple Sclerosis Findings
- Cerebrospinal Fluid
- CSF is primarily used to exclude other causes on the differential diagnosis (e.g. Meningitis or Encephalitis)
- However, Oligoclonal bands can be used in place of one imaging lesion for MS diagnosis (see below)
- CSF Pleocytosis (>5 cells/microliter)
- CSF IgG Increased (not specific for MS)
- Oligoclonal banding of CSF IgG by electrophoresis
- Oligoclonal bands >1 in 75-90% of MS patients
- CSF Myelin breakdown products present
- CSF is primarily used to exclude other causes on the differential diagnosis (e.g. Meningitis or Encephalitis)
- Serum titers predictive of Multiple Sclerosis
- Anti-Myelin oligodendrocyte Glycoprotein (anti-MOG)
- Anti-Myelin basic Protein (anti-MBP)
- Berger (2003) N Engl J Med 349:139-45 [PubMed]
XIV. Labs: Evaluation of differential diagnosis
- First-line tests
- Complete Blood Count
- Serum Vitamin B12 level
- Thyroid Stimulating Hormone (TSH)
- Erythrocyte Sedimentation Rate (ESR)
- C-Reactive Protein (C-RP)
- Lyme Disease titer (Borelia titer)
- Rapid Plasma Reagin (RPR)
- Antinuclear Antibody
- Consider autoimmune evaluation
- Additional tests if indicated
- Angiotensin Converting Enzyme level (ACE Level) for Sarcoidosis
- Autoantibody assays for Behcet Syndrome, Sjogren Syndrome, Systemic Lupus Erythematosus and Vasculitis
- Antineutrophil Cytoplasmic Antibody (ANCA)
- Anticariolipin Antibody
- Antiphospholipid Antibody
- Sjogren Syndrome Antibodies (Anti-SS-A Antibody, Anti-SS-B Antibody)
- Human Immunodeficiency Virus Screening (HIV Test)
- Human T-CellLymphotropic virus type I (HTLV-1)
- Very Long chain Fatty Acid level (for Adrenoleukodystophy)
XV. Management: General
- Involve a multidisciplinary team
- Neurologists (many tertiary centers have specialists in MS)
- Physical Therapy
- Occupational Therapy
- Speech and Language Therapy
- Mental Health providers
- Dietician
- Pharmacist
- Nonspecific supportive measures
- Keep Cool
- Regular Exercise
- Pursuit of wellness and positive attitude
- Education regarding the disease
- Support from family and MS support groups
- Vitamin D Supplementation may help prevent exacerbations
- Tobacco Cessation!
- Disability progression decreases with each year of being Tobacco free
- Risk of progression from RRMS to SPMS increases 4.7% per additional year of smoking after diagnosis
XVI. Management: Acute Episode or Relapse
- Evaluate for provocative event
- Acute Sinusitis
- Acute Bronchitis
- Urinary Tract Infection
- Emotional stressors may also provoke an event
-
Corticosteroids: Methylprednisolone
- Initial 3 day course of Methylprednisolone IV or Oral (similar efficacy for oral dosing)
- Methylprednisolone 1000 mg orally daily (or in divided doses) for 3 days OR
- Methylprednisolone 1000 mg in 500 ml D5W infused over 4 to 6 hours each morning for 3 days
- Next: Steroid Taper after first 3 days (examples only, dosing varies widely, consult neurology for local protocol)
- Methylprednisolone 500 mg daily IV or Oral for 3 days, then 250 mg daily IV or Oral for 3 days OR
- Prednisone 1 mg/kg/day orally daily for 14 days OR
- No further Corticosteroids
- Initial 3 day course of Methylprednisolone IV or Oral (similar efficacy for oral dosing)
- Plasmapheresis
- Indicated in cases refractory to Corticosteroids
- Plasma exchange performed every other day for 14 days
XVII. Management: Disease modifying agents for relapsing remitting Multiple Sclerosis
- Precautions
- All agents are very expensive, costing over $60,000 per year (except Mitoxantrone)
- Most disease modifying agents suppress T-cell Autoimmunity and have the potential for significant adverse effects
- Agents are typically selected, prescribed and monitored by neurologists with expertise in Multiple Sclerosis
- Drug selection is a balance of effectiveness versus adverse effects given the underlying disease burden
- Moderately effective agents (e.g. Glatiramer, Interferon) are used in new RRMS with minimal disease burden
- Highly effective agents (e.g. Alemtuzumab, Cladribine, Natalizumab) are used in new rapidly progressive RRMS
- Expect to continue disease modifying agents lifelong
- Consider switching to more effective agent if inadequate benefit after 6 month trial
- Consider changing to alternative medication if significant adverse effects
- Conditions in which disease modifying agents may be discontinued
- Secondary progressive MS in a non-ambulatory, significantly disabled patient without relapse in 2 years
- Preconception Counseling prior to intended pregnancy (risk of MS relapse is decreased in pregnancy)
- Vaccination
- Live Vaccines (e.g. Zostavax) should be administered >1 month before starting most of these MS agents
- Inactivated Vaccines may be given at any time
- Immunomodulatory agents: Interferon
- Longest track record (starting in 1993) of the disease modifying agents
- Adverse Effects
- Local injection site inflammation
- Influenza-like symptoms (decreases after first 3 months)
- Lab abnormalities include Leukopenia and increased liver transaminases
- Exacerbation of depressed mood (including increased Suicidality)
- Interferon Beta-1B (Betaseron, Extavia)
- Betaseron 0.25 mg SC every other day
- Modestly protects against exacerbation for 1 year
- Injection site reaction, Influenza-like symptoms, rare liver toxicity
- Generic Cost $6500 per month in 2022 (non-generic cost >$125,000/month)
- Filippini (2003) Lancet 361:545-52 [PubMed]
- Interferon Beta-1A (Avonex, Rebif)
- Avonex 30 mcg IM once weekly (cost $7200 per month in 2022)
- Similar adverse effects to Interferon Beta-1B
- Rebif 22 to 44 mcg SC three times per week (cost $35,000 per month in 2022)
- Peginterferon Beta-1A (Plegridy) 125 mcg SQ every 2 weeks
- Immunomodulatory agents: Non-Interferon agents
- Glatiramer (Copaxone)
- Adverse effects include local injection site inflammation, facial Flushing
- May also experience chest tightness, Dyspnea and Palpitations
- Dose: 20 mg/ml SQ daily or 40 mg/ml SQ three times weekly
- Copolymer 1 that cross reacts with myelin basic Protein and may act as a decoy for immune response
- Contains random length peptide chains with 4 Amino Acids found in myelin basic Protein
- Specifically, the Amino Acids are Glutamic Acid, Lysine, Alanine, and Tyrosine
- Good track record of safety and greater efficacy than Interferon
- Generic Cost $4700 to $6000 per month in 2022 (non-generic costs >$22,000/month)
- Glatiramer (Copaxone)
- Oral Immunosuppressants
- Fingolimod (Gilenya)
- Sphingosine-1-phosphate receptor blocker
- Costs $10,000 per month in 2022
- Adverse effects include Bradycardia, Hypertension, QTc Prolongation, elevated liver transaminases
- Other adverse effects include Melanoma, Macular edema, HSV Encephalitis
- Dose: 0.5 mg orally daily
- Bradycardia risk (may present with Dizziness or Fatigue)
- Observe for 6 hours after first dose
- Avoid in those with known Arrhythmia or other heart disorder
- Avoid concurrent use with Digoxin, Diltiazem or Beta Blocker
- Siponimod (Mayzent)
- Released in 2020 and similar to Fingolimod
- Dose 2 mg orally once daily
- Ozanimod (Zeposia)
- Released in 2020 and similar to Fingolimod
- Dose 0.92 mg orally once daily
- Ponesimod (Ponvory)
- Released in 2021 and similar to Fingolimod
- Dose 20 mg orally once daily ($8300 per month in 2022)
- Teriflunomide (Aubagio)
- Adverse effects include Alopecia, Diarrhea, Nausea, Leukopenia, elevated liver transaminases, Peripheral Neuropathy
- FDA Black Box warning for hepatotoxicity (monitor Liver Function Tests)
- Teratogenic and requires reliable Contraception
- Dose: 7 to 14 mg orally daily
- Dimethyl Fumarate (Tecfidera)
- Generic in 2020 ($130 per month in 2022)
- Adverse effects include Abdominal Pain, Diarrhea, Nausea, lymphocytopenia, elevated liver transaminases
- Flushing is common, and decreases over time (consider taking Aspirin 30 min before dose)
- Monitor Complete Blood Count
- Dose: 120 to 240 mg orally twice daily
- Monomethyl Fumarate (Bafiertam)
- Released in 2020 and similar to Dimethyl Fumarate
- Dose: 190 mg orally twice daily
- Diroximel Fumarate (Vumerity)
- Released in 2020 and similar to Dimethyl Fumarate
- Dose 231 mg orally twice daily
- Similar adverse effects to Dimethyl Fumarate
- Cladribine (Mavenclad)
- Dose: 1.75 mg/kg orally twice yearly (over 2 year treatment course with dosing cycles)
- Indicated in refractory cases and not first line
- Similar efficacy to Dimethyl Fumarate
- Adverse Effects
- Teratogenic! (requires Pregnancy Testing before each course of medication)
- Progressive Multifocal Leukoencephalopathy (PML)
- Malignancy risk
- Nausea, Headache, flu-like symptoms, severe lymphopenia, Shingles, Tuberculosis
- Fingolimod (Gilenya)
- Parenteral Immunosuppressants for refractory disease: Monoclonal Antibodies
- Alemtuzumab (Lemtrada)
- Monoclonal Antibody dosed IV 12 mg/day for 5 days (then, in 12 months, repeat 12 mg/day for 3 days)
- Risk of infusion reaction, infection risk, Thyroid disorder, renal dysfunction
- Also risk of Venous Thromboembolism, immune Thrombocytopenia
- Daclizumab (Zinbryta)
- Monoclonal Antibody dosed SQ once monthly
- Hepatotoxicity risk (monitor Liver Function Tests)
- Natalizumab (Tysabri, Antegren)
- Monoclonal Antibody dosed 300 mg IV once every 4 weeks
- Adverse effects include Hypersensitivity, infusion reaction, Headache, Fatigue
- Risk of Progressive Multifocal Leukoencephalopathy
- Blocks CNS entry of immune response to Nerve Cells
- Reduces relapse rate by >60%
- (2004) Neurology 62:2038 [PubMed]
- Ocrelizumab (Ocrevus)
- First-line only in primary progresive MS (only one FDA approved in primary progressive MS)
- Dosed 600 mg IV once every 6 months (administered over 3.5 hours)
- Pretreatment with Methylprednisolone and Diphenhydramine
- Adverse effects: Severe infusion reactions, herpetic infection, PML, malignancy risk
- Ofatumumab (Kesimpta)
- Monoclonal Antibody to CD20
- Dose 20 mg SQ at week 0, 1 and 2, then as of week 4, start 20 mg per month
- Adverse effects include liver injury, PML, infection risk
- Alemtuzumab (Lemtrada)
- Parenteral Immunosuppressants for refractory disease: Miscellaneous Agents
- Mitoxantrone (Novantrone)
- Adverse effects include myelosuppression, elevated liver transaminases, CHF and Leukemia
- Dose: 5 to 12 mg/m2 IV every 3 months
- Costs $900/year
- Mitoxantrone (Novantrone)
- Other interventions
- Hematopoietic Stem Cell Transplant (experimental in 2022)
XVIII. Management: Symptom-specific control
- Spasticity (70 to 80% of patients)
- Baclofen 10 to 40 mg orally three times daily
- Baclofen Intrathecal Pump may be preferred due to less sedation and greater effect
- Tizanidine 2 to 8 mg orally three times daily
- Gabapentin (Neurontin) 300 to 900 mg orally three times daily
- Onabotulinumtoxin A (Botox) injection
- Cannabinoids
- Non-pharmacologic Management
- Physical therapy or Physiotherapy
- Transcutaneous Nerve Stimulation
- Transcranial Magnetic Stimulation
- Structured Exercise Program
- Hydrotherapy
- Baclofen 10 to 40 mg orally three times daily
-
Ataxia
- Baclofen
- Tizanidine
- Dantrolene
- Threonine
- Cannabinoids
- Vestibular Rehabilitation
- Deep Brain Stimulation
- Ambulatory Dysfunction
- Dalfampridine XR (Ampyra)
- Physiotherapy
- Occupational Therapy
- Supervised Resistance Training
-
Tremor
- Onabotulinum Toxin A (local Tremors)
- Beta Blockers
- Diazepam
- Isoniazid
- Visual Problems (Oscillopsia)
- Gabapentin (Neurontin, first-line)
- Memantine (Namenda, second-line)
- Vestibular rehabilitation
- Paroxysmal pain and other syndromes (85% of patients)
- Trigeminal Neuralgia
- Treat as with Trigeminal Neuralgia in non-Multiple Sclerosis patients
- First-Line
- Carbamazepine 100 to 600 mg orally three times daily
- Oxcarbazepine (Trileptal)
- Second-Line
- Baclofen (Lioresal) 10 to 80 mg/day
- Gabapentin
- Lamotrigine (Lamictal)
- Dysesthetic limb pain or Neuropathic Pain
- Hydrotherapy (see spasticity above)
- Amitriptyline or Nortriptyline
- Gabapentin 300 to 900 mg orally three times daily
- Pregabalin (Lyrica)
- Venlafaxine (second-line)
- Sativex (Available in Canada, not in U.S.)
- Cannabis extract (THC) in oral spray form
- Rapid onset or relief
- FDA considers as Schedule I (illegal to import)
- Wade (2004) Mult Scler 10:434-41 [PubMed]
- Trigeminal Neuralgia
- Neurogenic Bladder
- Evaluate with post-void residual testing to distinguish failure to store from failure to empty
- Failure to store (detrusor spasm)
- Avoid spicy or acidic foods, Caffeine and Alcohol
- Bladder Training
- Sacral neuromodulation
- Detrol LA (Tolterodine LA) 2 to 4 mg orally daily
- Ditropan XL or Oxytrol XR (Oxybutynin XR) 5 to 10 to 30 mg orally daily
- Onabotulinumtoxin A (Botox) injection has been used in refractory cases
- Nocturia
- Intranasal Desmopressin
- Failure to empty (outlet disorder)
- Trial on alpha adrenergic blocker (e.g. Prazosin or Terazosin)
- Cannabinoids
- Clean intermittent self cathetrization
- Neurogenic bowel
- Constipation: Manage aggressively
- DocusateSodium (Colace)
- Bisacodyl (Dulcolax)
- Magnesium Citrate or Magnesium Oxide
- Polyethylene Glycol (Miralax)
- Hydration and fiber supplementation (e.g. Psyllium)
- Rectal stimulants and enemas as needed
- Lubiprostone (Amitiza)
- Other measures
- Abdominal massage
- Biofeedback or electrostimulation of abdominal Muscles
- Planned toilet times
- Fecal Incontinence
- Constipation: Manage aggressively
-
Fatigue (90% of patients)
- Evaluate for comorbid Major Depression, sleep disorder, Thyroid disease, Anemia, and Vitamin B12 Deficiency
- Amantadine 100 mg orally twice daily
- Modafinil (Provigil) 100 to 200 mg orally each morning
- Variable efficacy
- Brown (2010) Ann Pharmacother 44(6): 1098-103 [PubMed]
- Other agents to consider
- Other non-pharmacologic therapy
- Aerobic Exercise
- Avoid excessive heat, over-exertion and stress
- Mindfulness Training
- Major Depression or Emotional Lability
-
Sexual Dysfunction
- Affects >50% of men and >40% of women
- Men
- See Erectile Dysfunction
- Phosphodiesterase Inhibitors (e.g. Sildenafil or Viagra)
- Intercavernous Vasodilator
- Women
- See Female Sexual Dysfunction
- Duloxetine
- Vaginal lubrication, clitoral vibratory stimulation
-
Cognitive Impairment or Dementia
- Donepezil (Aricept)
- Other agents have not shown benefit (e.g. Rivastigmine, ginkgo, Amantadine)
- Consider neuropsych rehabilitation
- Consider occupational therapy
XIX. Prognosis
- Relapse and remission cycles after first episode: 90%
- Benign course (1-2 relapses, then recovery): 20%
- Progressive course after 5 years of MS: 60-90%
- Progressive course from onset (10%)
- Rapidly progressive course from onset (very rare, Marburg Type)
- Overall decreased Life Expectancy by 7 to 8 years in women diagnosed at a young age (e.g. 35 years old)
XX. Resources
- National Multiple Sclerosis Society
- NIH Multiple Sclerosis
- Multiple Sclerosis Association of America (MSAA)
- Multiple Sclerosis Foundation
XXI. References
- (2017) Presc Lett 24(9): 53
- (2020) Presc Lett 27(11): 65
- Pirko in Goetz (2003) Clinical Neurology, p. 1060-76
- Wilson (1991) Harrison's IM, p. 657-8
- (1995) Neurology 45:1268-76, 1277-85 [PubMed]
- Calabresi (2004) Am Fam Physician 70:1935-44 [PubMed]
- Frohman (2003) Med Clin North Am 87:867-97 [PubMed]
- Hauser (2020) Am J Med 133(12): 1380-90 [PubMed]
- Hawker (2004) Prim Care 31:201-26 [PubMed]
- OConnor (2002) Neurology 59:s1-33 [PubMed]
- Saguil (2014) Am Fam Physician 90(9): 644-52 [PubMed]
- Saguil (2022) Am Fam Physician 106(2): 173-83 [PubMed]