EHR525 Week 13 Lecture 1 - Pathophysiology of Multiple Sclerosis (Charles Sturt University) PDF

WARNING This material has been reproduced and communicated to you by or on behalf of Charles Sturt University in accordance with section 113P of the Copyright Act 1968 (Act). The material in this com...

WARNING This material has been reproduced and communicated to you by or on behalf of Charles Sturt University in accordance with section 113P of the Copyright Act 1968 (Act). The material in this communication may be subject to copyright under the Act. Any further reproduction or communication of this material by you may be the subject of copyright protection under the Act. Do not remove this notice School of Allied Health, Exercise Science and Sports Sciences 1 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 1  EHR525 EXERCISE FOR NEUROLOGICAL AND NEUROMUSCULAR CONDITIONS Lecture: Pathophysiology of Multiple Sclerosis Presenter: Jack Cannon School of Allied Health, Exercise Science and Sports Sciences 2 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 2 What We Will Cover: Introduction to MS. MS statistics in Australia. Pathophysiology of MS and its effect on nerve communication. Common sites for MS lesions and associated signs and symptoms. General risk factors for MS. Diagnosis of MS. Clinical course of MS. Treatment of MS. School of Allied Health, Exercise Science and Sports Sciences 3 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 3 Introduction Multiple Sclerosis (MS): Is a chronic, inflammatory disease of the CNS characterised by disseminated demyelination of nerve fibres in the brain and spinal cord. Most common cause of neurological impairment in young adults in Australia and worldwide. Impact of MS can be enormous because the disease course is unpredictable and the symptoms can change. No known cure and progresses to disability in the majority of cases but treatments are available to slow progression. School of Allied Health, Exercise Science and Sports Sciences 4 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 4 MULTIPLE SCLEROSIS STATISTICS More than 23,000 people are diagnosed with MS in Australia. A further 1,000 people are diagnosed every year. Age of onset ranges from 20-50 years in 85% of cases. Average age of diagnosis is between 25-35 years old. 75% of people diagnosed are women. Palmer A. (2011). Economic Impact of MS in 2010 Australian MS Longitudinal Study. School of Allied Health, Exercise Science and Sports Sciences 5 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 5 Economic Impact of Multiple Sclerosis Total cost of MS in Australia is $1.04 billion per year. $500 million due to lost productivity. 50-80% of people with MS cease work full-time within 10 years of diagnosis. Replacement cost of informal care provided to Australians with MS is $125 million. Australians with MS pay $78m per year out of their own pockets. Palmer A. (2011). Economic Impact of MS in 2010 Australian MS Longitudinal Study. School of Allied Health, Exercise Science and Sports Sciences 6 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 6 PATHOPHYSIOLOGY OF MULTIPLE SCLEROSIS Considered an inflammatory autoimmune disease of the CNS. Characterised by random nerve axon demyelination. Axons are spared from disease processes, but inflammation may damage nerves. Results in multiple areas of scarring (sclerosis) and formation of plaques that eventually slow or blocks nerve conduction. Can potentially occur anywhere within the white matter of CNS. School of Allied Health, Exercise Science and Sports Sciences 7 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 7  Nerve Cell Structure And Function School of Allied Health, Exercise Science and Sports Sciences 8 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 8 Oligodrenocytes Oligodendrocytes: Myelinating cells of the CNS. Composed of 80% lipid and 20% protein. Each cell may support up to 40 neurons. Myelin supports saltatory conduction and efficient neural communication. School of Allied Health, Exercise Science and Sports Sciences 9 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 9 Electrical Characteristics Of Demyelinated Nerve Fibres Increased leakage of current and reduced capacitance: □ Impaired depolarisation. □ Longer to reach threshold. □ Conduction block. Hyperexcitability: □ Spontaneous discharge and mechanical stimulation. □ Ephapthic impulse transmission. Increased temperature sensitivity: □ Current flows too fast to excite adjacent node. School of Allied Health, Exercise Science and Sports Sciences 10 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 10  Saltatory Nerve Conduction Myelin prevents the local current from leaking across the membrane allowing it to flow farther along the axon. Voltage-gated Na+ channels are present only at the nodes of Ranvier. Generation of active, voltage-gated currents only occur at unmyelinated regions. Result is a greatly enhanced velocity of action potential conduction. School of Allied Health, Exercise Science and Sports Sciences 11 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 11 Role of Autoimmune Dysfunction Although the exact cause of MS is still unknown. Believed that an autoimmune response that is influenced by a combination of environmental, infectious, and genetic factors. Process likely initiated by autoreactive T cells: □ Cross blood–brain barrier and begin myelin damage. □ Antibodies and white blood cells attack proteins in the myelin sheath. School of Allied Health, Exercise Science and Sports Sciences 12 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 12 New Sodium Channels And Myelin Repair New sodium channels may develop in demyelinated node but conduction is unreliable. Remyelination can occur following acute demyelination: □ Remyelination is always thinner that original myelin sheath. □ Nodal length is reduced. □ Impaired conduction velocity. In older lesions macrophages and astrocytes proliferate and remove debris and lay down a scar of fibrous tissue (sclerosis) on the axon. □ No potential for recovery. School of Allied Health, Exercise Science and Sports Sciences 13 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 13 SIGNS/SYMPTOMS OF MULTIPLE SCLEROSIS A number of signs and symptoms may be associated with MS. Common early indicators: □ Visual impairments. □ Motor function difficulties. □ Paresthesia. May affect any CNS function: □ Motor system. □ Sensory system. All symptoms can □ Vision. be exacerbated by □ Cognition. heat. □ Emotion. School of Allied Health, Exercise Science and Sports Sciences 14 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 14 Common Impairments Muscle weakness. Muscle spasticity. Symptomatic fatigue. Mobility impairments. Balance problems. Coordination difficulties. Impairments in cognitive function. School of Allied Health, Exercise Science and Sports Sciences 15 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 15 Location Of Lesions Most frequent lesion sites: □ Spinal cord: Approximately 55-75% of clients with MS have spinal cord lesions at some point during the course of the disease. □ Optic nerve: Approximately 20% of clients with MS present with optic neuritis as a first demyelinating event and 40% may experience this during the course of their disease. □ Other sites: Brainstem and Cerebellum. Location of lesions directly correlate with signs and symptoms. □ Poor correlation between lesion size and area and function/disability. School of Allied Health, Exercise Science and Sports Sciences 16 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 16 MRI Of Spinal Cord School of Allied Health, Exercise Science and Sports Sciences 17 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 17 MRI Of Optic Nerve School of Allied Health, Exercise Science and Sports Sciences 18 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 18 MRI Of Cerebellum School of Allied Health, Exercise Science and Sports Sciences 19 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 19 MRI Of Cerebral Hemispheres School of Allied Health, Exercise Science and Sports Sciences 20 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 20 Signs/Symptoms Of Multiple Sclerosis The Kurtzke Functional Systems classification tool: □ Used to assess and quantify neurological impairment in MS. □ Evaluates seven key functional systems: Pyramidal (motor functions). Bowel and bladder control. Cerebellar (coordination and balance). Visual function (blurred vision, double vision, etc). Brainstem (eye movements, speech, and swallowing). Cerebral or mental functions (cognition and behaviour). Sensory (pain, touch, and proprioception). □ Each system is scored based on the severity of impairment, from 0 (normal) to 5 or 6 (severe dysfunction). □ Help clinicians monitor disease progression and treatment effectiveness. □ Can also assist in determining exercise capabilities. School of Allied Health, Exercise Science and Sports Sciences 21 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 21  The Expanded Disability Status Scale (EDSS): □ Extension of the Kurtzke Functional Systems (FS) classification. □ Provides a more comprehensive measure of functional disability. □ EDSS combines scores from the seven functional systems assessed in the original FS classification with ambulation ability, giving greater weight to mobility and walking capacity. □ Scale ranges from 0 (normal neurological function) to 10 (death due to MS) with increments of 0.5 points. reflecting varying levels of disability. □ Stronger focus on walking (4.0 to 7.5). School of Allied Health, Exercise Science and Sports Sciences 22 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 22 Risk Factors For Multiple Sclerosis Age (15-60 years). Sex (females). Family history (genetic component). Infections (Epstein-Barr virus and infectious mononucleosis). Race (Northern European descent). Climate (temperate zones; sun exposure?). School of Allied Health, Exercise Science and Sports Sciences 23 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 23 Risk Factors For Multiple Sclerosis School of Allied Health, Exercise Science and Sports Sciences 24 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 24 DIAGNOSIS OF MULTIPLE SCLEROSIS Based on presenting signs/symptoms in combination with medical imaging and laboratory testing. Typical diagnostic tests include: □ Medical history: Assess past and present signs/symptoms. □ Neurological exam: Assess health of nervous system. □ MRI: Can determine spatial and temporal distribution of lesions. □ Evoked potential response: Measure electrical response to sensory stimulation (visual, auditory, somatosensory). □ Cerebrospinal fluid analysis: Assess for immunoglobulin level and oligoclonal bands. □ Blood tests: To rule out other diseases. School of Allied Health, Exercise Science and Sports Sciences 25 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 25 CLINICAL COURSE OF MULTIPLE SCLEROSIS Relapsing remitting MS (RRMS; 85%): Characterised by periodic exacerbations followed by full or partial recovery of deficits. Primary progressive MS (PPMS; 10%): Characterised by continuous disease progression from onset with little or no plateaus or improvements. Secondary progressive MS (PPMS; ??%): Initially characterised by relapsing-remitting course followed by primary-progressive course. Progressive relapsing MS (PRMS; 5%): Characterised by a progression from onset with distinct relapses superimposed on the steady progression. School of Allied Health, Exercise Science and Sports Sciences 26 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 26 Clinical Course And Prognosis Of Multiple Sclerosis Extent of disability is related to clinical course. Life expectancy is minimally reduced in MS. Most people with MS die from many of the same conditions as non-MS peers (e.g. cancer and heart disease). School of Allied Health, Exercise Science and Sports Sciences 27 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 27 Clinical Course And Prognosis Of Multiple Sclerosis Around two thirds of people diagnosed with MS are able to walk without a wheelchair two decades after their diagnosis. Some people will need crutches or a cane to remain ambulatory. Others use an electric scooter or wheelchair to help them cope with fatigue, balance or gait difficulties. 70% disabled within 10 years of diagnosis. School of Allied Health, Exercise Science and Sports Sciences 28 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 28 Disability Expectancy School of Allied Health, Exercise Science and Sports Sciences Kister. (2013). Neurology, 80(11); 18-24. 29 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 29 Multiple Sclerosis And Employment Restrictions Employment restrictions are significant for people with MS. 62.5% of persons with MS are restricted in their employment. Assistive/mobility devices: □ Canes. □ Crutches. □ Orthoses. □ Wheel chairs. School of Allied Health, Exercise Science and Sports Sciences 30 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 30 COMORBIDITY IN MULTIPLE SCLEROSIS Comorbidities are a concern throughout the MS course. Comorbidity is associated with: □ A longer delay between symptom onset and diagnosis. □ More severe disability at diagnosis. □ Greater disability progression. □ Increased health-care. □ Higher mortality. Marie, (2016). (In J MS care, 18(6); 271-272. School of Allied Health, Exercise Science and Sports Sciences 31 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 31 Comorbidity In Multiple Sclerosis Most common comorbidities: At the time of diagnosis: □ Depression. □ 19% have sought care for □ Anxiety. depression. □ Hypertension. □ 11.1% have sought care for □ Hyperlipidemia. anxiety. □ Chronic lung disease. □ Diabetes. □ Ischemic heart disease. □ Fibromyalgia. □ Inflammatory bowel disease Marie, (2016). In J MS care, 18(6); 271-272. School of Allied Health, Exercise Science and Sports Sciences 32 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 32 TREATMENT No cure for MS. Goal is to reduce or slow effects of MS and treat symptoms. Interferon 1-beta (Betaseron) or 1-alpha (Avonex), Copaxone (copolymer-1): □ Useful for relapsing-remitting, not stable or progressive. □ Prevention of T-cell activation and decreases relapse rate. Immunotherapy with corticosteroids: □ Suppress inflammatory response. □ Decrease severity/duration of exacerbations. □ Inhibit demyelinating process. Exercise is important for symptom management and maintaining daily function and quality of life. School of Allied Health, Exercise Science and Sports Sciences 33 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 33 Medications And Potential Side-Effects School of Allied Health, Exercise Science and Sports Sciences 34 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 34 Summary MS is a chronic, progressive demyelinating disease of the CNS. MS has significant economic costs for individuals and the health care system. Location of MS lesions is random and cannot be accurately predicted. MS is associated with many signs/symptoms that may influence sensory-motor, cognitive, and/or emotional functioning. General risk factors for developing MS include age, sex, family history, exposure to infection, race, and climate. The diagnosis of MS may involve a range of electrophysiological and neuroimaging techniques as well as a physical exam. Treatment of MS aims to slow progression through anti-inflammatory agents, such as interferon and corticosteroids, and reduce symptoms. School of Allied Health, Exercise Science and Sports Sciences 35 SCHOOL OF EXERCISE SCIENCE, SPORT & HEALTH 35