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Multiple
Sclerosis

Multiple Sclerosis (MS) is a chronic disease where the immune system attacks the central nervous system (brain and spinal cord), damaging the protective myelin around nerves. This disrupts nerve signals, causing symptoms like fatigue, vision problems, muscle weakness, numbness, and balance issues.

The severity and progression of MS vary, and while the exact cause is unknown, genetic, environmental, and immune factors are involved. Though there is no cure, treatments can manage symptoms, reduce relapses, and slow the disease, improving quality of life.

Variants of MS​

Clinically Isolated Syndrome (CIS): A single episode of neurological symptoms lasting at least 24 hours. May develop into MS.

  1. Relapsing-Remitting MS (RRMS): The most common form, characterized by episodes of new or worsening symptoms (relapses) followed by periods of partial or full recovery (remissions).

  2. Secondary Progressive MS (SPMS): Initially starts as RRMS but transitions into a steady progression of symptoms with fewer or no relapses.

  3. Primary Progressive MS (PPMS): Gradual worsening of symptoms from the start without distinct relapses or remissions.

Treatments

There is no cure for MS, but treatments aim to manage symptoms, reduce relapses, and slow disease progression:

  1. Disease-Modifying Therapies (DMTs):

    • Reduce relapse frequency and delay progression.

    • Common DMTs:

      • Injectables: Interferons (e.g., Avonex, Rebif), Glatiramer acetate (Copaxone).

      • Oral medications: Fingolimod (Gilenya), Dimethyl fumarate (Tecfidera), Siponimod (Mayzent).

      • Infusions: Natalizumab (Tysabri), Ocrelizumab (Ocrevus), Alemtuzumab (Lemtrada).

  2. Relapse Management:

    • High-dose corticosteroids (e.g., methylprednisolone) to reduce inflammation during acute relapses.

  3. Symptom Management:

    • Medications for fatigue, spasticity, pain, or depression.

    • Physical and occupational therapy for mobility and strength.

  4. Lifestyle Modifications:

    • Regular exercise, balanced nutrition, stress management, and smoking cessation can improve overall health.

  5. Emerging Treatments:

    • Stem cell therapy (HSCT) is being explored for aggressive MS.

    • Remyelination therapies and novel DMTs are under clinical trials.

Early diagnosis and treatment are key to improving long-term outcomes.

Symptoms

  • Fatigue

  • Muscle weakness or spasticity

  • Vision problems (e.g., optic neuritis)

  • Cognitive difficulties

  • Numbness or tingling

  • Balance and coordination issues

  • Bladder and bowel dysfunction

Guideline for Investigating and Managing Multiple Sclerosis (MS) and Its Variants

​

1. Diagnosis and Investigation

  • Clinical Evaluation:

    • History of relapses/remissions or progressive neurological symptoms.

    • Comprehensive neurological examination.

  • Key Diagnostic Tools:

    • Magnetic Resonance Imaging (MRI):

      • Detects demyelinating lesions in the CNS.

      • Use contrast (gadolinium) to identify active inflammation.

    • Lumbar Puncture:

      • Analysis of cerebrospinal fluid (CSF) for oligoclonal bands.

    • Evoked Potentials:

      • Visual, auditory, or somatosensory evoked potentials to assess electrical conduction in the CNS.

    • Blood Tests:

      • Rule out differential diagnoses (e.g., B12 deficiency, infections, vasculitis).

 

2. Classification of MS

  • Clinically Isolated Syndrome (CIS):

    • Single neurological episode; may progress to MS.

  • Relapsing-Remitting MS (RRMS):

    • Episodes of neurological dysfunction followed by remission.

  • Primary Progressive MS (PPMS):

    • Gradual worsening of neurological function without relapses.

  • Secondary Progressive MS (SPMS):

    • Initial relapsing-remitting course transitioning to progressive worsening.

  • Variants (e.g., Neuromyelitis Optica Spectrum Disorder):

    • Require differentiation for appropriate treatment.

 

3. Treatment Strategies

 
A. Disease-Modifying Therapies (DMTs)

  • For RRMS:

    • Interferon-beta (e.g., Avonex, Rebif):

      • Dose: 30 mcg IM weekly or 22–44 mcg SC 3 times/week.

    • Glatiramer Acetate (e.g., Copaxone):

      • Dose: 20 mg SC daily or 40 mg SC 3 times/week.

    • Fingolimod (e.g., Gilenya):

      • Dose: 0.5 mg orally once daily.

    • Dimethyl Fumarate (e.g., Tecfidera):

      • Dose: 120 mg orally twice daily for 7 days, then 240 mg twice daily.

    • Natalizumab (e.g., Tysabri):

      • Dose: 300 mg IV infusion every 4 weeks.

    • Ocrelizumab (e.g., Ocrevus):

      • Dose: 600 mg IV infusion every 6 months after initial loading dose (300 mg IV x 2, separated by 2 weeks).

    • Alemtuzumab (e.g., Lemtrada):

      • Dose: 12 mg/day IV infusion for 5 days (year 1), 3 days (year 2).

  • For PPMS:

    • Ocrelizumab (e.g., Ocrevus):

      • As noted above.

  • For SPMS:

    • Siponimod (e.g., Mayzent):

      • Dose: Titration from 0.25 mg daily to maintenance dose of 2 mg orally daily.

B. Acute Relapse Management

  • High-dose Corticosteroids:

    • Methylprednisolone: 500–1000 mg IV daily for 3–5 days.

    • Oral prednisone taper may follow if required.

C. Symptomatic Management

  • Spasticity: Baclofen (5–20 mg orally TID) or tizanidine (2–8 mg orally TID).

  • Fatigue: Amantadine (100 mg BID) or modafinil (100–200 mg daily).

  • Pain/Neuropathy: Gabapentin (300–1200 mg daily in divided doses) or pregabalin (150–600 mg daily in divided doses).

  • Bladder Dysfunction: Oxybutynin (5 mg BID) or mirabegron (25–50 mg daily).

D. Supportive Therapies

  • Physical and occupational therapy.

  • Cognitive therapy for memory and processing deficits.

  • Mental health support for depression and anxiety.

4. Monitoring

  • Regular MRI scans (annual or biannual) to monitor disease progression.

  • Routine blood tests for medication side effects.

  • Neurological exams every 6–12 months or as clinically indicated.

5. Patient Education and Support

  • Provide education on disease progression and treatment goals.

  • Emphasize adherence to therapy and follow-up.

  • Encourage a healthy lifestyle: balanced diet, exercise, and smoking cessation.

6. Emerging Therapies​

Neuromyelitis Optica Spectrum Disorder (NMOSD)

1. Diagnosis

  • Clinical Features:

    • Recurrent optic neuritis (ON): Sudden vision loss or pain in one or both eyes.

    • Longitudinally extensive transverse myelitis (LETM): Spinal cord inflammation spanning ≥3 vertebral segments.

    • Area postrema syndrome: Intractable hiccups, nausea, or vomiting due to medullary involvement.

    • Brainstem or hypothalamic symptoms.

  • Diagnostic Criteria (2023 Update):

    1. Core Clinical Characteristics: Optic neuritis, myelitis, or area postrema syndrome.

    2. AQP4-IgG Antibody Testing:

      • Positive aquaporin-4 (AQP4) antibodies confirm NMOSD.

    3. MRI Findings:

      • Lesions specific to NMOSD (e.g., optic nerve, spinal cord, or area postrema involvement).

    4. Exclude Differential Diagnoses:

      • Exclude multiple sclerosis (MS), systemic autoimmune diseases, and infections.

  • Other Tests:

    • Myelin oligodendrocyte glycoprotein (MOG) antibody testing to distinguish MOG-associated disease.

    • CSF analysis (less commonly oligoclonal bands compared to MS).

 

2. Management

A. Acute Relapse Treatment

  • High-Dose Corticosteroids:

    • Methylprednisolone: 1000 mg IV daily for 3–5 days.

    • Followed by an oral prednisone taper over weeks.

  • Plasma Exchange (PLEX):

    • Indicated for severe or steroid-refractory relapses.

    • Typical dose: 5–7 sessions, every other day.

 
B. Long-Term Maintenance Therapy

Aimed at preventing relapses and minimizing disability.

  1. FDA-Approved Therapies for AQP4-IgG Positive NMOSD:

    • Eculizumab (Soliris):

      • Dose: 900 mg IV weekly for 4 weeks, then 1200 mg IV every 2 weeks.

      • Complement inhibitor; requires meningococcal vaccination prior to use.

    • Inebilizumab (Uplizna):

      • Dose: 300 mg IV on day 1 and day 15, then 300 mg IV every 6 months.

      • Anti-CD19 monoclonal antibody.

    • Satralizumab (Enspryng):

      • Dose: 120 mg SC at weeks 0, 2, and 4, then 120 mg SC every 4 weeks.

      • IL-6 receptor inhibitor.

  2. Off-Label Therapies:

    • Rituximab:

      • Dose: 375 mg/m² IV weekly for 4 weeks or 1000 mg IV every 6 months.

      • Anti-CD20 monoclonal antibody; effective in relapse prevention.

    • Azathioprine:

      • Dose: 2–3 mg/kg/day orally.

      • Requires monitoring for bone marrow suppression and liver toxicity.

    • Mycophenolate Mofetil (CellCept):

      • Dose: 1–3 g/day orally in divided doses.

      • Immunosuppressive; requires monitoring for infection risk.

 
C. Symptomatic Management

  • Neuropathic Pain: Gabapentin (300–1200 mg/day) or pregabalin (150–600 mg/day).

  • Spasticity: Baclofen (5–20 mg orally TID) or tizanidine (2–8 mg TID).

  • Bladder Dysfunction: Oxybutynin (5 mg BID) or mirabegron (25–50 mg daily).

  • Depression/Anxiety: SSRIs or counseling.

 

3. Monitoring and Follow-Up

  • Frequency: Every 3–6 months or as clinically needed.

  • MRI:

    • Annual or relapse-based imaging of the brain and spinal cord.

  • Laboratory Tests:

    • Monitor for therapy-related side effects (e.g., CBC, liver function tests, infection screening).

  • AQP4-IgG Titers:

    • Not typically used to monitor disease activity but may assist in understanding relapse risk.

 

4. Patient Education and Support

  • Explain NMOSD as a relapsing disease distinct from MS.

  • Stress the importance of adherence to maintenance therapy to prevent relapses.

  • Address psychosocial aspects, including mental health and quality of life.

Would you like more detail on any specific therapy or aspect of NMOSD management?

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): Diagnosis and Management

 

1. Overview

MOGAD is an autoimmune neurological disorder caused by antibodies targeting myelin oligodendrocyte glycoprotein (MOG). It is distinct from multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD).

 

2. Clinical Features

  • Optic Neuritis (ON):

    • Often bilateral.

    • Severe visual loss with recovery over weeks to months.

  • Acute Disseminated Encephalomyelitis (ADEM):

    • Typically in children.

    • Fever, encephalopathy, and multifocal neurological symptoms.

  • Transverse Myelitis:

    • May involve both gray and white matter of the spinal cord.

    • Often longitudinally extensive (≥3 vertebral segments).

  • Brainstem Encephalitis:

    • Symptoms include nausea, vomiting, ataxia, and cranial neuropathies.

  • Cortical Encephalitis (Rare):

    • Seizures, focal deficits, or encephalopathy.

 

3. Diagnosis

  • MOG-IgG Antibody Testing:

    • Confirmed through cell-based assays (high specificity).

  • MRI Findings:

    • Brain:

      • ADEM-like lesions in children, large and fluffy lesions in the brainstem or cerebral cortex.

    • Spinal Cord:

      • Longitudinally extensive lesions involving gray matter.

    • Optic Nerves:

      • Bilateral involvement; edema of the optic nerve.

  • CSF Analysis:

    • Normal or mild pleocytosis.

    • Oligoclonal bands are uncommon (differentiating from MS).

 

4. Management

 
A. Acute Relapse Treatment

  • High-Dose Corticosteroids:

    • Methylprednisolone: 1000 mg IV daily for 3–5 days.

    • Oral prednisone taper over weeks.

  • Plasma Exchange (PLEX):

    • Consider for severe or steroid-refractory relapses.

    • Typical regimen: 5–7 sessions every other day.

  • Intravenous Immunoglobulin (IVIG):

    • Dose: 2 g/kg divided over 2–5 days for severe or relapsing cases.

B. Long-Term Maintenance Therapy

Aimed at reducing relapse frequency and severity.

  1. First-Line Therapies:

    • Rituximab:

      • Dose: 375 mg/m² IV weekly for 4 weeks or 1000 mg IV every 6 months.

      • Anti-CD20 therapy; effective for relapse prevention.

    • Azathioprine:

      • Dose: 2–3 mg/kg/day orally.

      • Immunosuppressive therapy requiring liver and CBC monitoring.

    • Mycophenolate Mofetil (CellCept):

      • Dose: 1–3 g/day orally in divided doses.

      • Effective with tolerable side effects.

  2. Second-Line Therapies:

    • IVIG:

      • Maintenance: 0.4–1 g/kg every 4 weeks.

      • Well-tolerated and effective, especially in children.

    • Tocilizumab:

      • Dose: 8 mg/kg IV every 4 weeks.

      • IL-6 receptor blockade, especially in refractory cases.

C. Symptomatic Management

  • Pain: Gabapentin (300–1200 mg/day) or pregabalin (150–600 mg/day).

  • Spasticity: Baclofen (5–20 mg TID) or tizanidine (2–8 mg TID).

  • Fatigue: Amantadine (100 mg BID) or modafinil (100–200 mg daily).

 

5. Prognosis

  • MOGAD generally has a monophasic or relapsing course.

  • Recovery from relapses is often better than NMOSD but may leave residual deficits.

  • Relapse risk is higher without maintenance immunotherapy.

 

6. Monitoring

  • Frequency: Every 3–6 months or as clinically indicated.

  • MRI:

    • Monitor for new lesions or relapses.

  • MOG-IgG Titers:

    • May assist in prognosis but not routinely used to guide treatment.

  • Laboratory Tests:

    • Monitor therapy-related side effects (e.g., CBC, liver function tests).

7. Patient Education and Support

  • Explain the relapsing nature of the disease and the importance of adherence to therapy.

  • Provide psychosocial support for coping with vision loss or neurological deficits.

  • Encourage healthy lifestyle habits: regular exercise, balanced diet, and mental health support.

​

CONTACT INFORMATION

604 841 3398
gurwantg@gmail.com

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