Multiple sclerosis (MS) is a chronic autoimmune disease that damages the protective myelin sheath surrounding nerve fibers in the central nervous system. Common symptoms include vision problems, difficulty walking, numbness, and tingling sensations. While the exact cause is unknown, it is believed to involve an interaction between genetic and environmental factors. Treatment focuses on reducing inflammation and immune system activity through medications like corticosteroids, beta-interferons, glatiramer, and mitoxantrone. Managing relapses and preventing disability progression long-term are important goals in MS treatment and management.

1. Multiple Sclerosis
(MS)
By
Isma’il Abdullahi

2. Contents
• Introduction
• Clinical Features
• Etiology
• Pathophysiology
• Morphology
• Types
• Treatment
• Summary

3. Multiple Sclerosis
• Multiple sclerosis (MS) is a chronic inflammatory autoimmune demyelinating disease of the central
nervous system characterized by distinct episodes of neurologic deficits, separated in time,
attributable to white matter lesions that are separated in space.
• Women = 2X males
• Relapse followed by episode of remission
Clinical Features
Optic neuritis – Blurred vision, Blindness
Difficulty in walking, urination
Sexual impairment
Paresthesia – Numbness, tingling sensation.
Depression
Etc

9. Types of MS

10. Management of Multiple Sclerosis
ACUTE MANAGEMENT OF MS
• Corticosteroids
• Cyclophosphamide
• Plasmapheresis
DISEASE MODIFYING DRUGS (DMT)
• β-Interferon
• Glatiramer
• Fingolimod
• Natalizumab*
• Mitoxantrone
• Teriflunomide
• Alemtuzumab*

11. Progressive forms of multiple sclerosis (MS).

12. Cyclophosphamide
MOA:
• It is converted to active metabolites in liver (aldophosphamide, phosphoramide mustard) which cross-
links DNA to prevent cell replication.
• It suppresses T cell and B cell function by 30-40%
SEs:
• Hemorrhagic cystitis – acrolein (metabolite)
• Alopecia – kills fast growing normal cells (hair cells)
• Leukopenia – myelosuppression

13. β-interferon
MOA:
Binds to its receptor in immune cells and;
• Reduces antigen presentation and T cell proliferation
• Alters cytokine and matrix metalloproteinases (MMP) expression
• Restore the suppressor function
SEs:
• Depression
• Flu-like symptoms
• Increased hepatic enzymes
• Headache
• Muscle ache
• Chills or Fever

14. Glatiramer
MOA:
• It have similar structure as myelin-sheath and thus blocks myelin-damaging T cells (attaches to and
kill the immune cells)
• It also reduces inflammation
SEs:
• Flushing
• Anxiety
• Chest pain
• Palpitation
• Skin rash
• Arthralgia

15. Fingolimod
MOA:
• It sticks to B and T cells and stops them from leaving lymph nodes where they are made.
• It might directly stops nerves from being damaged or help repair them.
SEs:
Common
• Increase susceptibility to infections: Flu, sinusitis
• Diarrhea
• Back pain
Serious
• Heart – Irregular heart beat
• Infections – Cold sores or Shingles
• Eye – Macular edema
• Brain – Progressive Multifocal Leukoencephalopathy (PML)

16. Natalizumab (ANTI-INTEGRIN THERAPHY)
- It is humanized IgG4 monoclonal antibody
MOA:
It blocks several integrins on circulating inflammatory cells and thus prevents binding to the vascular
adhesion molecule and subsequent sequestration into surrounding tissues.
SEs:
• Increase susceptibility to infections
• Progressive Multifocal Leukoencephalopathy (PML) – JC virus
• Dysmenorrhea
• Hypersensitivity reaction
USES:
-Crohn’s disease
-Multiple Sclerosis

17. Mitoxantrone
MOA:
It binds to DNA to produce strand breakage and inhibits both DNA and RNA synthesis (Cytotoxic drug).
SEs:
• Myelosuppression – Leukopenia, thrombocytopenia and anemia
• Increase susceptibility to infection
• Alopecia (Hair loss)
• Nausea and vomiting
• Mucositis
• Cardiac toxicity
• Blue discoloration of the finger nails, sclera and urine (2dys after administration)
USES
• Cancer (Prostate cancer, NHL, Breast cancer and AML)
• Multiple Sclerosis

18. Teriflunomide (Effectiveness – moderate)
MOA:
It inhibits the proliferation of T cells and reduce inflammation.
SEs:
• Increase susceptibility to infections (viral)
• Hair thinning
• Flu (Flu-like symptoms)
• UTIs or cystitis
• Bronchitis
• Diarrhea
• Tooth infection
• Fungal infections

19. Alemtuzumab
MOA:
It kills immune cells before they get to the brain and spinal cord and reset immune system for good.
SEs:
Common side effects
• Less serious infections: throat, UT and sinuses.
• Leukopenia
Serious Infections
• VZV infections: shingles, chickenpox, encephalitis
• Pneumonia
• Genital warts: HPV
• Tuberculosis
• Appendicitis
• Increase risk of thyroid, blood or skin cancer.

20. Summary:

21. Reactivation of JC virus – Present in latent form in 80% of adults.