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Multiple sclerosis
- 1. Multiple Sclerosis Name :Vihari Vichakshana Rajaguru Group No : 32 4th year 1st semester (2016) Kursk State Medical University
- 2. Introduction Transmission ofaction potentials along myelinated axons. An action potential “jumps” from node to node. Voltage-gated Na+ channels are present only at the nodes of Ranvier.
- 3. What is MS? a chronic, typically progressive disease involving damage to the sheaths of nerve cells in the brain and spinal cord. The immune system attacks the protective sheath (myelin) that covers nerve fibers and causes communication problems between your brain and the rest of your body. Eventually, the disease can cause the nerves themselves to deteriorate or become permanently damaged
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- 6. Etiology Cause ofMS is still not known, scientists believe that the interaction of several different factors may be involved. Immunologic Factors Environmental Factors Infectious Factors Genetic Factors
- 7. Path physiology Blood-brain barrier breakdown TheBBB prevent entrance of T cells into the nervous system. The blood–brain barrier is normally not permeable to these types of cells, unless triggered by infection or a virus, which decreases the integrity of the tight junctions. When the blood–brain barrier regains its integrity, usually after infection or virus has cleared, the T cells are trapped inside the brain. Autoimmunology The immune system attacks the nervous system, forming plaques or lesions. Commonly involves white matter. Destroys oligodendrocytes- causing demyelination Remyelination occurs in early phase but not completely. Repeated attacks lead to fewer remyelination. Inflammation T-cells attacks on myelin triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. Leaks form in the BBB cause swelling, activation of macrophages, and more activation of cytokines and other destructive proteins
- 12. CLASSIFICATION OF MULTIPLESCLEROS PRMS Progressive Relapsing MS SPMS Secondary Progressive MS PPMS Primary Progressive MS RRMS Relapsing/ Remitting MS Gradual progression of the disease from its onset with no relapses or remissions Unpredictable attacks which may or may not leave permanent deficits followed by periods of remission Initial RRMS that suddenly begins to decline without periods of remission and relapses. Steady decline since onset with super-imposed attacks.
- 13. Progressive Relapsing Mildinfrequent sensory exacerbations with full recovery. Secondary Progressive Condition of patients with relapsing/remitting disease begins to gradually worsen over time with resulting accumulation of neurological signs and symptoms. In this form of the disease, relapses become more severe while remissions are less complete, shorter in duration, and eventually non- existent. The course of MS becomes steadily progressive.
- 14. Primary Progressive Thereis no history of relapse in these patients. Disease begins with a slow progression of neurologic deficits. Problems appear and gradually worsen over time. Common problems include spastic paraparesis, cerebellar ataxia, urinary incontinence. Relapsing Remitting Multiple Sclerosis Episodes of exacerbations and remissions during which not all symptoms resolve completely. The patient may be left with permanent disability which may vary in severity. Relapses are often more severe than in the previous group. Relapses also become more severe with time.
- 15. The most common initialsymptoms • changes in sensation in the arms, legs or face : numbness (33%) • Optic neuritis (20%) • weakness (13%) • double vision- internuclear opthalmoplegia (7%) • unsteadiness when walking (5%) • and balance
- 16. sensory exam ◦ -ascending numbness starting in the feet; ◦ - bilateral hand numbness; ◦ - hemiparesthesia; ◦ - dysesthesia in one of the above distributions; ◦ - generalized heat intolerance Objectively the most common sensory findings in the"numb" areas are dorsal column signs, such as reduction of vibration, proprioception and stereognosis, rather than problems with spinothalamic tract.
- 17. Right internuclear ophthalmoplegia ina patient with multiple sclerosis. In the initial phase of leftward gaze (upper photograph), only the left eye is abducted. The right eye follows, after a delay (lower photograph).
- 18. Lhermitte's sign (25-40%) is anelectrical sensation that runs down the back and into the limbs and is produced by bending the neck forwards. The sign suggests a lesion of the dorsal columns of the cervical cord or of the caudal Uhthoff's phenomenon is the worsening of neurologic symptoms in multiple sclerosis and other neurological, demyelinating conditions when the body gets overheated from hot weather,
- 19. Ongoing Symptoms and Signs Motor system: ◦ -weakness (variable severity mono- and paraparesis, hemiparesis, quadriparesis) ◦ -increased spasticity resulting in spastic gait ◦ -pathologic signs (Babinski's, Chaddock's, Hoffmann, Oppenheim's, etc.) -dysarthria Cerebellar signs: ◦ -incoordination (dysdiadochokinesia, problems with heel-to-shin test) ◦ -slowing of rapid repeating movements ◦ -cerebellar ataxia (ataxic gait) ◦ -scanning speech
- 20. INVESTIGATION CSF oligoclonal bands,abnormal colloidal gold curve, elevated γ- globulin IgG, mild mononuclear pleocytosis (<40 cells/mL), myelin debris, normal or slightly elevated protein. (Myelin basic Protein) Blood test •B-12 and folate levels or antinuclear antibody (ANA) titers. •Antiphospholipid antibody syndrome must be undertaken in patients with evidence of blood dyscrasia and in women with unexplained miscarriages or history of deep venous thrombosis. •elevated erythrocyte sedimentation rate (ESR) and positive titers of rheumatoid factor (RF) should help identify the presence of a vasculitic disorder that may be mimicking MS. MRI MRI of the head and spine (more sensitive than CT): May show many plaques. MRI reveals multiple lesions with high T2 signal intensity and one large white matter lesion. These demyelinating lesions may sometimes mimic brain tumors because of the associated edema and inflammation.
- 25. Diagnostic Criteria Clinical PresentationAdditional Data Needed * 2 or more attacks (relapses) * 2 or more objective clinical lesions None; clinical evidence will suffice (additional evidence desirable but must be consistent with MS) * 2 or more attacks * 1 objective clinical lesion Dissemination in space, demonstrated by: * MRI * or a positive (cerebrospinal fluid) CSF and 2 or more MRI lesions consistent with MS * or further clinical attack involving different site Diagnosis is based on McDonald’s Criteria (Revised 2010)
- 26. * 1 attack *2 or more objective clinical lesions Dissemination in time, demonstrated by: * MRI * or second clinical attack * 1 attack * 1 objective clinical lesion (monosymptomatic presentation) Dissemination in space demonstrated by: * MRI * or positive CSF and 2 or more MRI lesions consistent with MS and Dissemination in time demonstrated by: * MRI * or second clinical attack Insidious neurological progression suggestive of MS (primary progressive MS) One year of disease progression (retrospectively or prospectively determined) andTwo of the following: a. Positive brain MRI (nine T2 lesions or four or more T2 lesions with positive VEP)b. Positive spinal cord MRI (two focal T2 lesions)c. Positive CSF
- 27. Treatment As of2011, six treatments have been approved by FDA 1. Interferon beta 1a (Avonex, CinnoVex,ReciGen and Rebif) 2. Interferon beta-1b (Betaseron ) 3. Glatiramer acetate (Copaxone), a non- steroidalimmunomodulator. 4. Mitoxantrone, is an immunosuppressant 5. Natalizumab (Tysabri) Steroids: methylprednisolone (MP) 500–1,000 mg/d IV for 5 days followed by tapered oral prednisone or MP 1 g/d IV for 3 days ± oral taper
- 28. MANAGEMENT Spasticity Baclofen 5mg PO 1–3 t.i.d. and increase as needed Diazepam 2–5 mg PO at bedtime Pain NSAIDs Gabapentin effective vs. MS pain syndromes at 300 mg/d PO, may increase to 1,800 mg/d within 1 week, max dose 3,600 mg/d Bladder dysfunction Propantheline 7.5 mg PO q3–4h to start, increase to 15 mg t.i.d. to q.i.d. plus 15–30 mg at bedtime Oxybutynin chloride 5 mg PO t.i.d.–q.i.d. Prophylactic antibiotics for urinary infections Self-catheterizations for inadequate bladder emptying Constipation: Stool softeners, bulk-producing agents, laxative suppositories Incoordination or tremors: Incoordination or tremors: Depression and emotional lability Antidepressant agents such as SSRIs. Psychotherapy and support Paranoia or mania Haloperidol lithium or atypical antipsychotic Hemifacial and dysesthesias Carbamazepine 100–200 mg PO once or twice a day to start; increase to total daily dosage of 600–1,600 mg t.i.d.–q.i.d. Must monitor serum levels
- 29. Other regime Amain focus for MS patients is intake of foods that lower inflammation, not aggravate it. • Polyphenols (including flavonoids and nonflavonoids) and carotenoids: vegetables, fruits, wine, spices, and herbs • Polyunsaturated fats , omega-3 fatty acids and DHA: olive oil, oily fish, fish oil. ◦ Limiting saturated fats of animal origin ◦ limit caffeine consumption to decrease bone mineralization loss
- 30. Vitamin B12deficits is associated with demyelination of nerve fibers so supplementation of Vitamin B12 and Vitamin B complex assists in prevention. Calcium supplementation is important as the incidence of osteoporosis , related to decreased mobility, is higher in MS patients. vitamin D, selenium, and zinc have all been found to decrease the production of inflammatory molecules associated with MS as well.
- 31. Prognostic Factors inPatients with Multiple Sclerosis Good prognosis Optic Neuritis Isolated sensory symptoms Long interval to second relapse No evidence of disability after 5 years Female gender Poor Prognosis ‘Multifocal’ Clinically Isolated Syndrome Efferent (motor/cerebellar) systems High relapse rate in 5 years Substantial disability after 5 years Abnormal MRI with
- 32. Mortality Rates forMultiple Sclerosis The average life span of an individual with MS is 25-35 years after initial diagnosis. Most MS patients live into the 7th decade Studies have shown that individuals with MS die around 10 years earlier than the general population Studies have indicated that MS is not a cause of death, whereas deaths occur as a result of other chronic complications resulting from immobility, chronic urinary tract infections, dypsnea, dysphagia, aspiration & bacterial pneumonia
Editor's Notes
- #3 SaltatoryConduction Inward Na currents through the voltage-gated Na+ channels cause an action potential It regenerates the passive current to flow through the next segment of myelinated axon.
- #4 The damaged myelin forms scar tissue (sclerosis) In MS, immune system T cells pass from the bloodstream into the central nervous system to attack the myelin coating around nerve fibers. Autoimmune attack (of T cells and B cells) against oligodendrocytes
- #5 No 01 : Normal axon No 02 : Demylinated axon No 03 : Degenerated axon Results of demylination : slower conduction time along the affected nerve When any part of the myelin sheath or nerve fiber is damaged or destroyed, nerve impulses traveling to and from the brain and spinal cord are distorted or interrupted, producing a wide variety of symptoms.
- #6 Affects mainly Caucasians (N. Europe) Most common neurodegenerative disease of young adults (1 per 400) Average age at onset 28(f)/30(m) years. Female : male ratio = 2:1 MS appears to be more prevalent in temperate regions of the world than in the tropics leading to research on the effects of exposure to sunlight and vitamin D
- #7 In MS, an abnormal immune-mediated response attacks the myelin coating around nerve fibers in the central nervous system, as well as the nerve fibers themselves. In recent years, researchers have been able to identify which immune cells are mounting the attack, some of the factors that cause them to attack, and some of the sites (receptors) on the attacking cells that appear to be attracted to the myelin to begin the destructive process. Ongoing efforts to learn more about the immune-mediated process in MS — what sets it in motion, how it works, and how to slow or stop it — are bringing us closer to understanding the cause of MS. MS is known to occur more frequently in areas that are farther from the equator.Growing evidence suggests that vitamin D plays an important role. People who live closer to the equator are exposed to greater amounts of sunlight year-round. As a result, they tend to have higher levels of naturally-produced vitamin D, which is thought to support the immune function and may help protect against immune-mediated diseases like MS. The possible relationship between MS and sunlight exposure is currently being looked at in a Society-funded epidemiological study in Australia. The evidence is also growing that smoking plays an important role in MS. Studies have shown that smoking increases a person’s risk of developing MS and is associated with more severe disease and more rapid disease progression. Since initial exposure to numerous viruses, bacteria and other microbes occurs during childhood, and since viruses are well-recognized as causes of demyelination and inflammation, it is possible that a virus or other infectious agent is the triggering factor in MS. More than a dozen viruses and bacteria — including measles, canine distemper, human herpes virus-6, Epstein-Barr, and Chlamydia pneumonia — have been or are being investigated to determine if they are involved in the development of MS, but none have been definitively proven to trigger MS. While MS is not hereditary, having a first-degree relative such as a parent or sibling with MS does significantly increase an individual's risk of developing the disease. Studies have shown that there is a higher prevalence of certain genes in populations with higher rates of MS. Common genetic factors have also been found in some families where there is more than one person with MS. Some researchers theorize that MS develops because a person is born with a genetic predisposition to react to some environmental agent that, upon exposure, triggers an immune-mediated response. If you have a parent or sibling with MS there’s 1-3% of you developing MS. If you are a twin it’s 30%.
- #10 Plaques were demonstrated to occur anywhere within the white matter of the CNS, but the most frequently affected sites are the optic nerves, the brainstem, the cerebellum and the spinal cord. Lesions in these locations often correlate with clinical symptoms. In the cerebral hemispheres periventricular distribution of plaques is often seen. When plaques are adjacent to the cortex, subcortical myelinated fibers are often spared. Plaques located nearby the gray matter may rarely spread into the gray matter, including deep nuclei and the cortex. There often is axon sparing within the plaque.
- #11 Whatever route the pathological process takes from inflammation to demyelination, the effects of loss of myelin by the nerve fibers are quite dramatic. Saltatory conduction is much more energy efficient than nerve impulses transmitted along the entire length of the nerve fiber. Loss of myelin results in one or all of the following: conduction block at the site of lesion slower conduction time along the affected nerve increased subjective feeling of fatigue secondary to compensation for neurologic deficits
- #16 Multiple Sclerosis most often is characterized by episodes of neurological dysfunction followed by periods of stabilization or partial to complete remission of symptoms. These symptoms (relapses or exacerbations) can appear over a few hours or days, can be gradually worsening over a period of a few weeks, or sometimes can present themselves acutely. Depending on a course and a subtype of the disease, these symptoms will either persist or slowly resolve over weeks or months and may even culminate as a complete remissions. A relapsing-remitting pattern is the most common and is characteristic for this disease.
- #17 sensory exam is the most difficult one to perform reliably and accurately in evaluation of patients with neurologic complaints. However, certain distributions of sensory problems can be suspicious for early MS. Optic Neuritis is a frequent presenting symptom of MS. It is characterized by blurred vision, a change in color perception, visual field defect i.e.,. Central scotoma, and possible headaches and retro-orbital pain precipitated by eye movements. These symptoms may require neuro-ophthalmologic evaluation, MRI imaging and Visual Evoked Potential studies to establish a degree of optic nerve function.
- #19 Motor weakness often is accompanied by upper motor neuron signs, such as mild spasticity, hyperreflexia, and pathologic signs. The most common initial presentation is paraparesis, but weakness can be also found in just one extremity (monoparesis) or all four extremities (quadriparesis).
- #20 And all other symptoms that we discussed above in the picture.
- #25 Evoked potentials studies can be helpful in providing evidence of separation of lesions in space. An abnormal slowing of electrical impulses is used to assess this separation. The most commonly used evoked potentials in patients with MS are Visual Evoked Responses (VER), Brain stem Auditory Evoked Responses (BAER), and Somatosensory Evoked Responses (SSER). Approximately 75% of MS patients exhibit abnormal VER regardless of whether a patient does or does not have a history of clinically apparent optic neuritis. In a latter case, abnormal visual evoked response can be used to identify a para clinical second lesion and confirm the diagnosis of MS. The BAER is harder to interpret and only 30% of patients exhibit abnormal response from the central hearing areas in the brain stem. The SSEP is technically the most challenging study to perform, but is found to be abnormal in more than 80% of patients with definite MS. This study can help identify slowed conduction in the central sensory pathways, and help distinguish peripheral lesions from central ones.
- #28 The interferons (side effects include flulike symptoms, injection-site reactions, mild liver dysfunction) and glatiramer acetate are delivered by frequent injections, varying from once-per-day for glatiramer acetate to once-per-week (but intra-muscular) for Avonex. Natalizumab and mitoxantrone are given by IV infusion at monthly intervals.
- #31 Multiple sclerosis has a profound impact on patients’ social roles and the well-being of their families. Varying degrees of functional decline typically accompany MS. Because the onset is usually at about 30 years of age, the loss in productivity of people with MS can be substantial.