Multiple scelorosis 222222222222222.pptx

multiple scelorosis description

1. Multiple sceloresis

2. 🧠 INDEX — Multiple Sclerosis (MS) Comprehensive Topics 🩺 1. General Overview 🧬 2. Pathogenesis (How MS develop) 🧩 3. Genetic and Immunologic Factors 🦠 4. Environmental and Viral Triggers 💫 5. Gender Differences 🧩 6. Clinical Features 🧠 7. Types of MS 🔬 8. Diagnosis 💊 9. Treatment

3. Multiple sceloresis Multiple sclerosis (MS) is an  autoimmune condition  that affects your brain and spinal cord central nervous system What are autoimmune diseases? Autoimmune diseases are health conditions that happen when your immune system attacks your body instead of defending it. What is the central nervous system? Your central nervous system (CNS) is part of your nervous system. It consists of your brain and spinal cord. Your CNS collects information from your sensory nerves to process and respond to them. It regulates everything your body does.

4. The neurons A neuron in the CNS (central nervous system) is the basic functional unit that processes and transmits information. The neuron consist of 1- body (soma), containing the nucleus and providing energy; dendrites, which receive signals from other neurons; and an axon, a long extension that transmits signals to other cells 2- The myelin sheath is a fatty, insulating layer that wraps around nerves, allowing electrical signals to travel quickly and efficiently along the nerve cell (axon).

5. The myelin sheath A fattty, insulating layer that wraps around the axons of nerve cells (neurons) in the brain, protecting them and enabling electrical impulses to travel quickly and efficiently Your myelin sheath isn’t one solid covering. It’s a lineup of individual sections of myelin, each separated from the next by a tiny gap —called introdes What happened when the myelin sheath is damage ? Myelin can be damaged when your body’s immune cells think that myelin is a foreign substance. Your body’s immune system produces inflammatory substances that damage myelin and eventually kill the cells (the oligodendrocytes and Schwann cells) that make myelin. The location where the myelin is attacked determines your symptoms. The destruction of the myelin sheath is called demyelination

6. What are the types of demyelinating diseases? Demyelinating diseases are disorders where the myelin sheath (the protective covering of nerve fibers) is damaged, leading to disrupted nerve signal conduction. Types of demyelinating diseases Multiple sclerosis (MS).
Neuromyelitis optica spectrum disorder (NMOSD).
Transverse myelitis (TM).
Acute disseminated encephalomyelitis (ADEM).
Progressive multifocal leukoencephalopathy (PML).
Central pontine myelinolysis

7. Is demyelinating disease always MS? No, there are several conditions that are classified as demyelinating diseases. MS is the one most common in North America. How common are demyelinating diseases? Multiple sclerosis is one of the most common demyelinating diseases. A study in 2019 estimated that there were nearly 1 million people in the United States living with MS.

8. Causes of Multiple Sclerosis (MS) 1 . Genetic Factors Genetic predisposition, especially with the HLA-DRB1*15:01 alleles Family history increases susceptibility. 2-Immune System Dysregulation Loss of immune tolerance leads to activation of autoreactive T and B cells.
Myelin is mistakenly recognized as a “foreign” antigen. 3. Environmental Triggers Vitamin D deficiency due to low sunlight exposure
Certain viral infections, particularly Epstein–Barr virus (EBV).

9. Causes of Multiple Sclerosis (MS) 4-Geographical Factors Higher prevalence in populations farther from the equator. 5. Blood–Brain Barrier Dysfunction Increased permeability of the BBB allows immune cells to infiltrate the CNS.

10. 1- genetics factors: Types of HLA in the Human Body HLA = Human Leukocyte Antigen These are genes on chromosome 6 that encode surface proteins helping the immune system distinguish self from non-self.
They are divided into two main classes: 1. HLA Class I Types: HLA-A, HLA-B, HLA-C
Location: expressed on almost all nucleated cells
Function: present intracellular peptides (e.g., from viruses or tumor cells) to CD8+ cytotoxic T cells
Role: defense against viral infections and cancer

11. 2. HLA Class II Types: HLA-DR, HLA-DQ, HLA-D
Location: expressed on antigen-presenting cells (APCs) like B cells, macrophages, dendritic cell
Function: present extracellular peptides to CD4+ helper T cell
Role: initiate and regulate adaptive immune responses

12. 2- immune dysregulation; Relationship Between HLA and Multiple Sclerosis (MS) Genetic predisposition strongly influences MS risk 🧩 Step 1: Presence of the HLA-DRB1*15:01 gene HLA-DRB1*15:01 is a Class II HLA allele, meaning it helps antigen-presenting cells (like macrophages and dendritic cells) display antigens to CD4⁺ T helper cells.
This specific version (15:01) has a slightly different peptide-binding groove structure, allowing it to bind more strongly to certain myelin-derived peptides, such as Myelin Basic Protein (MBP). ⚠️ Step 2: Increased T-cell reactivity People carrying HLA-DRB1*15:01 have hyper-reactive T cells — their T cells require a lower activation threshold.
This means that even weak signals from myelin antigens can trigger these T cells, leading to exaggerated immune activation.

13. 🔥 Step 3: Production of pro-inflammatory cytokines IFN-γ (Interferon-gamma)
TNF-α (Tumor necrosis factor-alpha)
IL-17 These molecules cause inflammation within the central nervous system (CNS) and recruit more immune cells, resulting in damage to the myelin sheath and formation of MS plaques. 🧠 Step 4: Strong binding to myelin antigens HLA-DRB1*15:01 has a high binding affinity for epitopes from Myelin Basic Protein (MBP) and other myelin components.
This strong binding makes it more likely for antigen-presenting cells to display self-myelin peptides to CD4⁺ T cells.
As a result, the immune system mistakenly identifies myelin as a foreign target — initiating an autoimmune attack against the myelin sheath.

14. ⚖️ Step 5: Protective HLA alleles Other HLA Class II alleles, such as DRB1*11 and DRB1*12, are thought to be protective.
They promote the activity of regulatory T cells (Tregs), which suppress excessive immune activation and help maintain self-tolerance — preventing the immune system from attacking its own tissues 🌍 Step 6: Ethnic and regional variations The distribution of HLA alleles varies among different ethnic groups:
In European populations, HLA-DRB1*15:01 is the major genetic risk factor for MS.
In the Middle East and North Africa (MENA) region, the same allele is present but less common.
Other alleles, such as HLA-DRB1*03, HLA-DRB1*13, and HLA-DQB1*06, have been linked to MS susceptibility in MENA populations.
This shows that the genetic background of MS is complex and influenced by both ethnic and environmental factors.

15. 3- environmental factors; Role of Epstein–Barr Virus (EBV) in MS Strong Epidemiological Link Almost all MS patients (>95%) have a history of EBV infection (usually in adolescence or early adulthood).
The risk of developing MS is much higher in people who had infectious mononucleosis (symptomatic EBV infection) . Molecular Mimicry EBV proteins (e.g., EBNA1) share structural similarity with myelin proteins (like MBP, MOG).
This “mimicry” may confuse the immune system → T cells and antibodies activated against EBV also attack myelin

16. 3.. B cell Infection and Reservoir EBV infects B cells and makes them persist as long-lived memory B cells.
In MS, these EBV-infected B cells can cross into the CNS, present autoantigens (via HLA class II), and drive chronic inflammation. 4 . Interaction with HLA Genes Certain HLA alleles (e.g., HLA-DRB1*15:01) make antigen presentation of EBV peptides more likely to trigger autoimmunity.
This explains why EBV + susceptible HLA type = much higher MS risk. 5. Evidence from Antibody Levels People who later develop MS usually have very high levels of anti-EBV antibodies years before diagnosis.

17. . 1- Activation in the periphery: T-cells become activated outside the brain (by a trigger such as a virus like EBV or another antigen that mimics myelin). 2. Expression of adhesion molecules: Activated T-cells express adhesion molecules (like integrins) and chemokine receptors.
Cells lining brain blood vessels (endothelial cells) also express matching receptors due to inflammatory signals.The inflamed brain releases chemokines — small signaling molecules.
These chemokines act like a chemical GPS, guiding T cells toward the brain’s blood vessels 3. Binding and entry: T-cells bind to the blood vessel wall, then squeeze through it (a process called diapedesis). Blood brain barrier dysfunction; How T-cells cross the BBB in MS:

18. 4.Adhesion to the Blood–Brain Barrier When T cells reach the BBB:
The inner cells of the blood vessels (endothelial cells) express adhesion moleculessuch as
VCAM-1 and ICAM-1.
The T cells carry matching receptors (VLA-4, LFA-1) that let them stick to the vessel wall. This makes them slow down and prepare to cross. 5- Diapedesis (Transmigration) After adhesion:
T cells release matrix metalloproteinases (MMPs), enzymes that open small gaps in the vessel wall.
They squeeze between endothelial cells and cross the basement membrane.
→ This process is called diapedesis. 6 -Reactivation inside CNS: Once inside the brain, T cells meet antigen-presenting cells (microglia, macrophages).
These cells show them myelin antigens, which reactivates the T cells.
Now the T cells start attacking myelin, forming MS plaques.

19. Disease formation; Plaques formation in MS After B-cells enter the CNS and attack myelin:
1. Antibody production: B-cells become plasma cells and start producing antibodies against myelin proteins (like myelin basic protein, MBP). 2. Complement activation: These antibodies bind to the myelin sheath → activate the complement system → causes further damage to myelin and oligodendrocytes.

20. 3. Macrophage recruitment: The immune reaction attracts macrophages that phagocytose (eat) the damaged myelin debris .Inflammation amplifies:
Cytokines (like TNF-α, IFN-γ, IL-1β) released by T and B cells increase inflammation, breaking down more myelin. 5. Axonal injury: Without myelin, axons are exposed and vulnerable, leading to slowed or blocked nerve conduction, and sometimes axon degeneration. 6. Plaque formation: Over time, the damaged area becomes filled with glial scar tissue (gliosis).
This chronic lesion is called an MS plaque, visible on MRI as a bright spot in white matter

21. W hy lack of Vitamin D increases the risk of Multiple Sclerosis (MS): ☀️ 1. Vitamin D and the immune system Vitamin D isn’t just for bones — it’s also a powerful immune regulator.
It helps keep the immune system balanced, preventing it from becoming overactive.
When Vitamin D levels are low, the immune system becomes more likely to attack the body’s own tissues — in MS, this means attacking the myelin sheath (the protective covering around nerve fibers). 🧠 2. How it relates to MS MS is an autoimmune disease, where the body’s immune cells (T cells and B cells) mistakenly attack myelin in the brain and spinal cord.

22. Vitamin D normally: Inhibits pro-inflammatory T cells (like Th1 and Th17).
Stimulates regulatory T cells (Tregs) that calm down immune attacks.
So, if you have Vitamin D deficiency, these regulatory effects are weaker → inflammation increases → more myelin damage → higher MS risk or worse progression. 🌍 3. Geographic link (sunlight exposure) MS is more common in countries farther from the equator, where people get less sunlight, which means less natural Vitamin D production in the skin.
Studies show that people who grow up in low-sunlight regions have a much higher risk of developing MS later in life.

23. How MS Is Diagnosed 🧠 Diagnosis of Multiple Sclerosis (MS) There is no single test that confirms MS — instead, doctors combine clinical signs, MRI findings, and laboratory tests to make the diagnosis. The key idea is to prove that :
1. There is damage in at least two separate areas of the central nervous system (CNS).
2. The damage happened at different times.
This is called:
➡️ Dissemination in space and time

24. 🩺 1. Clinical Evaluation The neurologist first looks for neurological symptoms that suggest demyelination, such as: Optic neuritis (pain and vision loss in one eye). ,Weakness or numbness in limbs. ,Loss of balance or coordination. ,Bladder problems.,These must not be explained by another disease (like infection or stroke). 🧲 2. MRI Scan (Magnetic Resonance Imaging ). MRI is the main tool for diagnosing MS. Findings : White matter plaques (lesions) in typical MS areas:
Periventricular (around brain ventricles) ,,Juxtacortical (near the cortex),, Infratentorial (brainstem, cerebellum) ,,,Spinal cord Dissemination in space: lesions in different parts of CNS. Dissemination in time: New and old lesions appearing at different times …….. Gadolinium enhancement shows active inflammation (new plaques)series of MRI images are taken without gadolinium. Then the patient is taken out of the MRI machine and gadolinium contrast agent is administered intravenously. The patient is then put back in the MRI and a new set of pictures are taken with the gadolinium contract agent. The gadolinium contrast agent highlights inflamed legions showing current disease activity.

25. 3 . Lumbar Puncture (CSF analysis) Used when MRI isn’t clear. Findings: . White blood cells. I f you have multiple sclerosis, then the number of white cells in your cerebrospinal fluid is usually up to seven times higher than normal. If the count is even higher than this, it is probably due to an infection of some sort, such as Lyme disease, and not MS. Neurofilaments . These are fragments of the structural support that normally surrounds your nerve axons. If neurofilaments are found in the CSF, then this is evidence that your myelin is under attack. If you have a subsequent lumbar puncture and fewer neurofilaments are found than before, this could be evidence that your disease-modifying drugs are effectively protecting the nerves. Oligoclonal bands . The immune system produces antibodies to fight infection. In MS, antibodies cross the blood-brain barrier and attack the myelin surrounding nerves. As a result, the level of antibodies in the cerebrospinal fluid of someone with MS is higher than it should be. It will also be higher than the level in the blood, so a blood sample will usually be analysed at the same time for comparison.
The test that shows the presence of antibodies is called electrophoresis.

26. 4 _ Evoked potential E voked potential tests Evoked potential tests measure the electrical activity in areas of your brain and spinal cord in response to certain stimuli. The tests involve electrodes placed on specific parts of your scalp and/or other parts of your body and delivery of a stimulus (such as images, sounds or electrical pulses). The electrodes “catch” your brain’s and nerves’ electrical signal responses to the stimulus. Evoked potential tests record how quickly and completely nerve signals reach your brain. They can find damage along nerve and brain pathways that are too subtle to show up during a neurological examination. The damage also may not yet be noticeable to the person.

27. 5. Blood Tests (to exclude other diseases) MS has no specific blood marker, but tests are done to rule out:
Infections (e.g. Lyme disease, syphilis)
Autoimmune diseases (e.g. L upus, sarcoidosis)
Vitamin B12 deficiency 6. McDonald Criteria (most used) Doctors use the McDonald criteria to confirm MS diagnosis:
✅ Evidence of dissemination in space
✅ Evidence of dissemination in time
✅ No better alternative explanation
The criteria combine MRI + clinical + CSF findings to make the diagnosis faster and more accurate.

28. The Four Stages of Multiple Sclerosis 1. Clinically Isolated Syndrome (CIS) What happens: The person experiences their first neurological episode that lasts more than 24 hours. Typical symptoms : N numbness or tingling in one area of the body Blurred or double vision Muscle weakness Problems with balance or coordination Some people fully recover, while others may have another attack and progress to RRMS

29. 2. Relapsing-Remitting MS (RRMS)What happens The disease goes through relapses (attacks) where symptoms appear or get worse Followed by remissions where symptoms improve or disappear. During relapses : Vision problems (optic neuritis — pain and blurred vision)Muscle weakness or stiffness Numbness or tingling in limbs Fatigue (extreme tiredness)Difficulty walking or loss of balance During remission :The immune attack stops, inflammation decrease Some or all symptoms improve. No disease progression during this time.

30. 3. Secondary Progressive MS (SPMS) What happens After years of RRMS, the disease becomes steadily progressive.
Damage accumulates in the nervous system even without obvious relapses. Symptoms: Gradual worsening of mobility — walking becomes harder
Muscle stiffness and spasms
Increased weakness and fatigue
Cognitive (memory and concentration) problems may appear
Relapses may still occur, but recovery becomes less complete each time.

31. 4. Primary Progressive MS (PPMS) What happens: From the start, symptoms steadily worsen over time without relapses or remissions.
Typical symptoms:
Slow but constant weakness in legs or arms
Problems with walking and balance
Muscle stiffness and spasticity
Fatigue
Bladder or bowel problems
Sometimes mild sensory symptoms (numbness, tingling)
No clear “attacks” — just continuous progression.

32. Treatment for MS There is no cure for multiple sclerosis. Treatment typically focuses on speeding recovery from attacks, reducing relapses, slowing the progression of the disease and managing MS symptoms. Some people have such mild symptoms that no treatment is necessary. ⚡ 1. Treatment of Acute Attacks (Relapse Manageme nt) When a patient experiences a sudden relapse or worsening of symptoms, the goal is to reduce inflammation quickly.
The main treatment is high-dose corticosteroids, such as methylprednisolone given intravenously for 3–5 days.
Steroids help decrease inflammation in the brain and spinal cord and shorten the duration of the attack.
If corticosteroids don’t work or the relapse is very severe, plasma exchange (plasmapheresis ) can be used. This process removes harmful antibodies from the blood and reduces immune system activity.

33. 2-💊 2. Disease-Modifying Therapies (DMTs) These are long-term treatments that aim to reduce the number of relapses and slow the progression of disability.
They don’t cure MS but they can change the course of the disease by controlling the immune system. There are three main types of DMTs: Injectable therapies , such as interferon beta-1a, interferon beta-1b, and glatiramer acetate.
These drugs calm the immune system and reduce inflammation in the brain and spinal cord. Oral therapies , such as fingolimod, dimethyl fumarate, and teriflunomide.
These medications redu ce immune cell activity and prevent immune cells from attacking the myelin. Infusion (IV) therapies, s uch as natalizumab, ocrelizumab, and alemtuzumab.
These drugs block the entry of immune cells into the central nervous system or destroy overactive immune cells.
The choice of drug depends on the patient’s MS type, severity, and tolerance to side effects.
Patients need regular blood tests and MRI scans to monitor their response and safety.

34. 🌿 3. Symptomatic Treatment This part of therapy focuses on controlling daily symptoms and improving comfort. Fatigue can be managed with medications like amantadine, regular light exercise, and energy-saving strategies. Muscle stiffness or spasms are treated with baclofen, tizanidine, or physical therapy. Pain may respond to nerve pain medicines such as gabapentin or pregabalin. Bladde r problems can be managed with drugs like oxybutynin or intermittent catheter use. Depression or anxiety are treated with antidepressants, counseling, or stress management techniques. Mobility and balance problems can be improved through physiotherapy and assistive devices.

35. 🧬 Experimental & Emerging Therapies for MS 🧫 1. Stem Cell Therapy (HSCT – Hematopoietic Stem Cell Transplantation) Idea: “Reset” the immune system so it stops attacking the body’s own myelin. How it works: 1. The patient’s stem cells are collected from their blood.
2. Then strong chemotherapy destroys the faulty immune system.
3. The patient’s own stem cells are re-infused to rebuild a new immune system.
Effect: Can greatly reduce relapses and MRI activity, especially in aggressive relapsing forms of MS.
Limitations: Serious side effects, risk of infection, and not suitable for progressive MS in most cases.

36. 🧪 2. Remyelination and Neuroprotection Therapies These treatments aim to repair the damaged myelin sheath and protect neurons from degeneration.
Some promising approaches include: Anti-LINGO-1 antibodies (opicinumab): encourage oligodendrocytes to make new myelin. Clemastine fumarate (an antihistamine ): showed partial remyelination effects in trials. Biotin (high-dose vitamin B7 ): may improve energy metabolism and support nerve repair in progressive MS. Ibudilast : has anti-inflammatory and neuroprotective properties, slowing brain atrophy.

37. 🎯 3. BTK Inhibitors (Bruton’s Tyrosine Kinase Inhibitors) Mechanism: block BTK enzyme in B cells and microglia, reducing harmful immune activity in the brain.
Examples: Tolebrutinib, Evobrutinib, Fenebrutinib.
Advantage: can cross the blood–brain barrier and target immune cells inside the CNS — something current DMTs don’t fully do.
Status: Phase III clinical trials — showing promise for both relapsing and progressive MS.

38. Reference 📚 Textbook References 1. Jameson, J. L., Fauci, A. S., Kasper, D. L., Hauser, S. L., & Loscalzo, J. (2022). Harrison’s Principles of Internal Medicine (21st ed.). McGraw-Hill Education.
2. Ropper, A. H., Samuels, M. A., Klein, J. P., & Prasad, S. (2021). Adams and Victor’s Principles of Neurology (12th ed.). McGraw-Hill Education.
3. Snell, R. S. (2020). Clinical Neuroanatomy (9th ed.). Wolters Kluwer.
4. Filippi, M., Rocca, M. A., & Ciccarelli, O. (2023). Multiple Sclerosis and Related Disorders. 🔬 Research Article References
1. Hauser, S. L., & Cree, B. A. C. (2020). Treatment of Multiple Sclerosis: A Review. New England Journal of Medicine, 383(17), 1690–1701.
2. International Multiple Sclerosis Genetics Consortium (IMSGC). (2019). Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science, 365(6460), eaav7188.
3. Ascherio, A., & Munger, K. L. (2016). Epidemiology of Multiple Sclerosis: From Risk Factors to Prevention. Seminars in Neurology, 36(2), 103–114.