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Multiple Sclerosis Doug Symptom Presentation and Course
What Causes MS? Clues from epidemiology Autoimmune response or idiopathic degeneration? Neurobehavioral Manifestations Cognitive profile The role of fatigue Psychiatric symptoms
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Doug 35 y.o. married software engineer
Age 20 – 1st episode unexplained symptoms Bilateral lower extremity numbness, tingling, weakness, lack of coordination Resolved spontaneously at 3 mos. Played hockey senior year of college Age 26 – 2nd episode Visual blurring, diagnosed as optic neuritis MRI showed plaques characteristic of MS Ages – 3 exacerbations with full recovery Age 33 – exacerbation followed by persisting BLE weakness, fatigue & cognitive changes
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Doug Functional limitations Current complaints
severe difficulty concentrating, easily distracted poor memory for recent events severe fatigue Functional limitations left work 2 years ago limited multitasking (no complex recipes) extensive use of lists/cellphone 1-2 household chores/day sleeps hours/day, fewer with Adderal
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Multiple Sclerosis An immune-mediated process in which an abnormal response of the body’s immune system is directed against the central nervous system (brain, spinal cord and optic nerves). Immune system attacks the myelin and nerve fibers nerve impulses traveling to and from the brain and spinal cord are distorted or interrupted, producing a wide variety of symptoms.
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Most Common Presenting Symptoms
Frequency Sensory disturbance – limbs 30.7 Visual loss 15.9 Motor disturbance (gradual onset) 8.9 Double vision 6.8 Gait disturbance 4.8 Motor disturbance (sudden onset) 4.3 Balance problem 2.9 Sensory disturbance - face 2.8 Bobholz & Gremley, 2011
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Multiple Sclerosis Diagnostic Criteria
Establish dissemination of 2+ lesions in space and time Rule out other diagnoses Polman , 2011
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Progression of MS Lesions on MRI
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Signs and Symptoms Compston, 2008
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Epidemiology 80-90/100,000 in US ~400,000 in US/ 2.5 million worldwide
Female:Male ratio = 2.6:1 Onset (5% < 18 years) Slow course
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Subtypes by Course SYMPTOMS TIME Progressive Relapsing (~5-10%)
Secondary Progressive ( ~ 65%) SYMPTOMS Primary Progressive ( ~10%) Relapsing Remitting( ~15%) TIME Bobholz & Gremley, 2011
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Epidemiology Increased risk with affected family member
linkage to gene for immune molecule higher latitude of residence in childhood Ohio = 112.4/100,000 Texas = 42.8/100,000 later infection with Measles, Epstein-Barr virus
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Compston, 2008
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Compston, 2008
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Risk of MS by UV exposure and Gender
Orton, 2011
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Effect of Month of Birth and Latitude on MS Risk
All Samples Dobson, 2013
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Effect of Month of Birth and Latitude on MS Risk
All Samples Samples Living > 52° Latitude Dobson, 2012
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Effect of Month of Birth and Latitude on MS Risk
HI LO Pre-natal UV Exposure All Samples Samples Living > 52° Latitude Dobson, 2012
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Effect of Month of Birth and Latitude on MS Risk
Dobson, 2012
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Pathogenesis of MS Blood-brain barrier: abnormally activated lymphocytes disrupt BBB Autoimmune: lymphocytes enter brain, activate local immune response Inflammation: T- cell attacks on myelin triggers inflammatory processes
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Waxman, 1998
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Gray Matter Loss 1 year after 1st MS Episode
Raz, 2010
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Cognitive Function in MS
Common (40-50%) Predict vocational status Affect daily function Heterogeneous Emerge early in disease Deficits in verbal fluency, information processing, working memory, encoding and retrieval
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adapted from Benedict, 2011
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Effect of Exertion in MS
Claros-Salinas, 2012
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Effect of Exertion in MS
Claros-Salinas, 2012
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Prevalence of Neuropsychiatric Comorbidities
Condition Prevalence in MS* Major Depression 25-50% Anxiety Disorders 36% Pseudo-bulbar Affect 10% Euphoria Sclerotica 9% Bipolar Disorder 2% Psychosis 2.5-4% * all elevated compared to control population Feinstein, 2012; Korostil, 2007;Patten, 2005
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Doug’s Test Results WAIS-III SS Similarities 11 Premorbid IQ (HART)
Comprehension 13 Trail Making A 8 Matrix Reasoning 15 Trail Making B 1 Symbol Search 6 Phonemic Fluency Letter-Num Seq. Category Fluency Digit Span 5 Grooved Pegboard 10 WMS-III Imm. Memory Finger Tapping Delayed Memory CVLT Initial Learning 7 Intrusions – Cued Recall
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Self-reported Psychiatric Symptoms
Clinically Significant
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