Demyelinating
Multiple Sclerosis
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Multiple Sclerosis
, MS
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]
Pathophysiology
Acute attacks (relapsing remitting MS) are a result of inflammatory reaction
Inflammatory cells (T Cells,
B Cell
s and
Macrophage
s) cross the blood-brain barrier at weakened vessel surfaces
Immunoglobulin
s target the
Myelin Sheath
Macrophage
s 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
Axon
al Loss
Risk Factors
Race: White > Black
Gender: Female > Male (2:1)
High socioeconomic status
Northern latitudes
Environmental factors (toxins, viruses)
Infectious Mononucleosis
Tobacco Abuse
HLA histocompatible
Antigen
s
Vitamin D Deficiency
(or less sunlight exposure)
Munger (2006) JAMA 296:2832-2838 [PubMed]
Symptoms
Sensory loss of vibration, proprioception or nociception (37%)
Optic Neuritis
(36%)
Focal Weakness (35%)
Paresthesia
s 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%)
Seizure
s (1%)
Other findings
Tremor
Dysarthria
Depressed mood
Fatigue
Hearing Loss
or
Tinnitus
Heat intolerance
Bowel
Dsyfunction (e.g.
Constipation
)
Signs
Dysarthria
Decreased pain, vibration and position sense
Decreased coordination and balance
Ataxia
Difficult
Tandem Walk
ing
Eye Exam
Visual Field Defect
s
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 Reflex
es 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
Diagnosis
Gene
ral 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 Column
s
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
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)
Seizure
s,
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
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 one lesion
Await additional attack with characteristics of one of the two presentations (DIT or DIS) as above
References
Polman (2011) Ann Neurol 69(2): 292-302 [PubMed]
Thompson (2018) Lancet Neurol 17(2): 162-73 [PubMed]
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
Sarcoidosis
Systemic Lupus Erythematosus
(SLE)
Sjogren Syndrome
Behcet Syndrome
Susac Syndrome
Granulomatosis with Polyangiitis
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 Syndrome
s)
Cervical Disc Disease
CNS neoplasm
Arnold
Chiari Malformation
Arteriovenous Malformation
Medications and recreational drugs
Alcohol Abuse
Cocaine Abuse
Methanol Poisoning
Isoniazid
Lithium
Penicillin
Phenytoin
(
Dilantin
)
Anticholinergic Toxicity
Biologic Agent
s
Etanercept
(
Enbrel
)
Infliximab
(
Remicade
)
Vitamin Deficiency
or Toxicity
Vitamin B12 Deficiency
Folate Deficiency
Vitamin E
deficiency
Manganese Toxicity
Psychiatric conditions
Anxiety Disorder
Conversion Disorder
Somatization
Gene
tic disorders
Leukodystrophy
Mitochondrial disease
Miscellaneous
Hypothyroidism
References
Miller (2008) Mult Scler 14(9): 1157-74 [PubMed]
Rolak (2007) Neurologist 13(2): 57-72 [PubMed]
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
Lublin (1996) Neurology 46(4): 907-11 [PubMed]
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
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
Evoked Potentials
Visual, auditory, somatosensory, and motor
Visually evoked potentials are most useful
One or more evoked potential abnormal in 80-90% of MS
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
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]
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-Cell
Lymph
otropic virus type I (HTLV-1)
Very Long chain
Fatty Acid
level (for Adrenoleukodystophy)
Management
Gene
ral
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 Supplement
ation may help prevent exacerbations
Tobacco Cessation
!
Disability
progression decreases with each year of being
Tobacco
free
Tanasescu (2018) Nicotine Tob Res 20(5): 589-95 [PubMed]
Risk of progression from RRMS to SPMS increases 4.7% per additional year of smoking after diagnosis
Ramanujam (2015) JAMA Neurol 72(10): 1117-23 [PubMed]
Management
Acute Episode or Relapse
Evaluate for provocative event
Acute Sinusitis
Acute Bronchitis
Urinary Tract Infection
Emotional stressors may also provoke an event
Corticosteroid
s:
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
Corticosteroid
s
Plasmapheresis
Indicated in cases refractory to
Corticosteroid
s
Plasma exchange performed every other day for 14 days
Brochet (2020) J Clin Apher 35(4): 281-9 [PubMed]
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 Vaccine
s (e.g.
Zostavax
) should be administered >1 month before starting most of these MS agents
Inactivated
Vaccine
s 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
Gene
ric 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
Palpitation
s
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 Acid
s found in myelin basic
Protein
Specifically, the
Amino Acid
s are
Glutamic Acid
,
Lysine
,
Alanine
, and
Tyrosine
Good track record of safety and greater efficacy than
Interferon
Gene
ric Cost $4700 to $6000 per month in 2022 (non-generic costs >$22,000/month)
Oral
Immunosuppressant
s
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
,
Macula
r 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 Test
s)
Teratogen
ic and requires reliable
Contraception
Dose: 7 to 14 mg orally daily
Dimethyl Fumarate
(
Tecfidera
)
Gene
ric 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
Teratogen
ic! (requires
Pregnancy Test
ing before each course of medication)
Progressive Multifocal Leukoencephalopathy
(PML)
Malignancy risk
Nausea
,
Headache
, flu-like symptoms, severe lymphopenia,
Shingles
,
Tuberculosis
Parenteral
Immunosuppressant
s 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 Test
s)
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 Cell
s
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
Parenteral
Immunosuppressant
s 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
Other interventions
Hematopoietic Stem Cell Transplant
(experimental in 2022)
Burt (2019) JAMA 321(2): 165-74 [PubMed]
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
Cannabinoid
s
Non-pharmacologic Management
Physical therapy or Physiotherapy
Transcutaneous Nerve Stimulation
Transcranial Magnetic Stimulation
Structured
Exercise
Program
Hydrotherapy
Castro-Sanchez (2012) Evid Based Compliment Alternat Med 2012: 473963 [PubMed]
Ataxia
Baclofen
Tizanidine
Dantrolene
Threonine
Cannabinoid
s
Vestibular Rehabilitation
Deep Brain Stimulation
Ambulatory Dysfunction
Dalfampridine XR
(
Ampyra
)
Physiotherapy
Occupational Therapy
Supervised
Resistance Training
Tremor
Onabotulinum Toxin A
(local
Tremor
s)
Beta Blocker
s
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]
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
)
Cannabinoid
s
Clean intermittent self cathetrization
Neurogenic bowel
Constipation
: Manage aggressively
Docusate
Sodium
(
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
Muscle
s
Planned toilet times
Fecal Incontinence
Fiber
supplementation
Consider short-term anti-
Diarrhea
l agent
Colostomy has been used in refractory cases
Fatigue
(90% of patients)
Evaluate for comorbid
Major Depression
, sleep disorder,
Thyroid
disease,
Anemia
, and
Vitamin B12 Deficiency
Amantadine
100 mg orally twice daily
Peuckmann (2010) Cochrane Database Syst Rev (11): CD006788 [PubMed]
Modafinil
(
Provigil
) 100 to 200 mg orally each morning
Variable efficacy
Brown (2010) Ann Pharmacother 44(6): 1098-103 [PubMed]
Other agents to consider
Selective Serotonin Reuptake Inhibitor
or
SSRI
(e.g.
Escitalopram
,
Fluoxetine
,
Sertraline
)
Dextroamphetamine
Methylphenidate
(
Ritalin
)
Other non-pharmacologic therapy
Aerobic
Exercise
Avoid excessive heat, over-exertion and stress
Mindfulness
Training
Major Depression
or Emotional Lability
Selective Serotonin Reuptake Inhibitor
or
SSRI
(e.g.
Escitalopram
,
Fluoxetine
,
Sertraline
)
Serotonin Norepinephrine Reuptake Inhibitor
or
SNRI
(e.g.
Venlafaxine
,
Duloxetine
)
Bupropion
(
Wellbutrin
)
Cognitive Behavioral Therapy
Sexual Dysfunction
Affects >50% of men and >40% of women
Men
See
Erectile Dysfunction
Phosphodiesterase Inhibitor
s (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
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)
Resources
National Multiple Sclerosis Society
http://www.nmss.org
NIH Multiple Sclerosis
http://www.ninds.nih.gov/disorders/multiple_sclerosis/multiple_sclerosis.htm
Multiple Sclerosis Association of America (MSAA)
http://www.mymsaa.org/
Multiple Sclerosis Foundation
http://www.msfocus.org/
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]
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