Multiple Sclerosis Latest Update Already Passed

Multiple Sclerosis Latest Update Already Passed Multiple Sclerosis autoimmune disease directed against CNS myelin and oligodendrocytes; leading cause of progressive neurologic disability in young adults with a worldwide prevalence of 2.5 million MS population females effect 2:1 to males median age = 30 years age range = 20-50 years most prevalent in Caucasians of northern European descent Characteristic degeneration in MS T-cell perivascular inflammation Demyelination Axonal loss Gliosis Multiple plaques/ lesions throughout brain and spinal cord Myelin damage in MS inflammatory response of myelin (called an attack) leads to indiscriminate destruction of brain; leads to the destruction of oligodendrocytes and impairs function of nearby neurons Effects of myelin damage in MS loss of vision, sensory problems, massive degradation anywhere in CNS depends on where the lesion or set of lesions are located that determine what function is damaged Functional recovery follows attacks and may include: restored function of non-affected neurons development of new neuronal pathways and connections remyelination of remaining oligdendrocytes Consequences of repeated attacks fewer remyelinations build up of hardened "sclerotic" tissue blocks the formation of new myelin axonal transection Lesion location in MS most frequently in periventricular and pericallosal areas of the brain also in optic nerves, brain stem, spinal cord, corpus callosum, cerebellar WM and corticospinal tracts Atrophy in MS Axonal (WM) degeneration Neural (GM) degeneration Apoptosis (remaining neurons become overworked) Neurotoxic effects Early symptoms of MS acute/sub-acute onset: numbness paresis/spasticity (motor neuron dysfunction) optic neuritis (blurred/lost vision) Later symptoms of MS cerebellar signs (poor coordination) sensory symptoms (decrease vibratory sense and dysesthetic pain) significant cognitive changes Genetic links twin studies concordance rate= 20-30% 20% risk with at least one affected relative increased risk in children greater susceptibility for Anglosaxon, Nordic, German persons Environmental factors those living closer to the equator have lower risk sunlight & ultraviolet radiation vitamin D over-exposure early viral exposure (modifies expression of later viral exposure) Immunological factors higher female prevalence onset before 4 is rare disease suppressed during pregnancy higher frequency of myelin-reactive T-cell clones Blood-brain barrier and MS T-cells, in response to myelin andogens, get through blood brain barrier and attack antibodies Diagnosing MS made one the basis of findings of attacks Ancillary tests used for supporting evidence exclusion of other conditions which produce similar looking attacks all criteria must be fulfilled for a definite MS diagnosis MS attacks last > 24 hours, must be able to rule out other cases, must be > 30 days between the onset of separate attacks MRI evidence of MS T2 hyperintensities and T1 enhancing lesions dissemination in time and space important criteria Cerebrospinal fluid increased immunoglobin G (IgG) in 90-95% people with MS; indicates abnormal autoimmune response but is also present in other diseases Visual evoked potentials test the conduction and efficiency of optic nerves; optic nerve most compromised in MS and may be used to help diagnose MS with substantial amount of other evidence Clinical presentation for definitive diagnosis >/= 2 attacks; >/= 2 lesions; 1 lesion plus reasonable evidence of prior attack Disease course in MS relapsing-remitting, secondary progressive, primary progressive, progressive-relapsing Clinically-isolated syndrome single clinical episode that is indicative of, but not diagnostic of, MS (i.e. optic neuritis, transverse myelitis, etc) can evolve to MS where MRI T2 lesion load is high or CSF reflects inflammation Relapsing-remitting 85-90% patients; characterised by unpredictable periods attacks followed by periods (months to years) of appearing relatively symptom free with no new symptoms; symptoms may resolve or be permanent Secondary-progressive 80% of those initially diagnosed with RRMS; neurological decline between acute attacks with no definitive remission; can include the worsening of cognitive function, new neurological symptoms and other deficits presents the greatest amount of disability Primary-progressive 10% diagnosed; no remission after the initial MS symptoms, decline is progressive and continuous with no clear attacks tends to affect people who are older at disease onset Progressive-relapsing very uncommon, very debilitating; steady neurological decline from the onset of disease with the potential to suffer superimposed attacks Expanded disability status scale neurological examination determining the degree of disability of an MS sufferer Treatment for relapsing/remitting MS immunomodulatory drugs immunosuppressants monoclonal antibodies Interferon beta, Glatiramer acetate immunomodulatory drugs that are a first line treatment for MS; decrease relapse rate and reduce new and enlarging T2 lesions do not prevent development or progression in the long term Mitoxantrone immunosuppressant; causes damage to DNA or T- and B-cells and inhibits the secretion of molecules promoting inflammation unclear long-term safety profile Tysabri monoclonal antibody; locks onto lymphocytes thus preventing their migration across the blood-brain barrier risk of progressive multifocal leukoencephalopathy Progressive multifocal leukoencephalopathy rare and unusual viral disease causing progressive damage and inflammation to WM; immunosuppressive drugs prevent the immune system from combating it Treatment for secondary-progressive MS anti-inflammatory/immunomodulatory treatments high dose, high frequency interferons Mitoxantrone Methotrexate Treatment for primary-progressive MS no treatment proven to modify course; potential for stem cell transplantation investigated presently Treatment for CIS immunomodulatory drugs delay the conversion to cogntive deficit MS Optic neuritis initial clinical manifestation of MS in >15%, major symptoms in >90% patients includes decreased colour vision and contrast sensitivity, visual field loss Uveitis inflammation of the uvea causing blurred vision, floaters, mild/strong pain, light sensitivity increases chances for visual loss, raised eye pressure and cataracts treated with corticosteroids Nystagmus failure of gaze-holding network Jerk: slow drift, downbeating saccade, periodic alternative saccades Pendular: back and forth, retinal slip severly disrupting vision treated with corticosteroids Motor symptoms of MS paresis, plegia, spasticity, tremor, dysarthria (slurred speech), muscle atrophy, spasms and cramps, hypotonia (posture problems) Paresis partial/mild paralysis during voluntary muscle contraction or holding posture plegia/paralysis= total loss of strength Spasticity involuntary contraction of complementary muscles; caused by lesions to the cerebellum or WM tracts that connect the peripheral motor and sensory nerves Myonclonus sudden, uncontrollable jerks of muscle or groups of muscles Myokymia successive, involuntary, small muscle contractions or tics affecting bundle of muscles Sensory symptoms of MS paraesthesia, anaesthesa, pain, proprioceptive dysfunction (loss of awareness of body location) Paraesthesia abnormal sensations (i.e. tingling, prickling, skin burning or crawling); may present in band around trunk Pain in MS neuropathic (misdirected nerve signals) musculoskeletal (result of spasticity, immobility, gait changes associated with MS) paroxysmal Ataxia lack of ability to voluntarily direct muscles not resulting from muscular weakness; dysfunction in processing of sensory nerve inputs and motor nerve outputs may be cerebellar, vestibular or proprioceptive Bladder and bowel dysfunction bladder dysfunction occures in >80% MS sufferers; commonly results from spinal cord lesions; bladder spasticity and flaccid bladder bowel dysfunction in 45-68% Neuropsychological syndromes of MS decreased information processing speed decreased WM speed perceptual deficits less fluency and control of language LTM retrieval problems sustained/divided attentional deficits Neuropsychiatric problems of MS anxiety and mood disorders depressive disorders (reactive to diagnosis? organic from demyelination? medicational SE?) emotional liability and increased irritability mood swings increased incidence of suicide, manic episodes, panic attacks and OCD symptoms Fatigue manifests clinically as mental and physical exhaustion, loss of energy and increase somnolence; unprovoked fatigue; activity and heat typically exacerbate symptoms Impaired thermoregulation inappropriate increase/decrease in body temperature; effects nerve conduction velocity which can enhance symptoms or bring on new ones Early overt MS symptoms unexplained fatigue; uncharacteristic clumsiness; unexplained limb weakness; impaired language; slurred speech; inability to concentrate; incontinence; visual disturbances; disinhibition Life expectancy MS is not a fatal disease, it's symptoms do not lead to death; 90-95% sufferers have normal life expectancy MS effects quality of life substantially, but not length Cognitive dysfunction 40-65% MS sufferers; memory, complex attention, information- processing speed and executive functions are most commonly involved; studies have shown cognitive dysfunction in even CIS patients, implicating it as a precursor to the onset of the disorder Functional impact of cognitive dysfunction domain-specific deficits, not a global decline; high societal cost because it is the biggest risk factor for high unemployment in MS Executive functioning deficits abstract reasoning, problem solving, planning, monitoring, cognitive estimation and verbal fluency on both semantic and phonemic stimuli all substantially affected Methodological limitations of MS studies based on selected clinical series with limited sample size; high attrition rates; brief follow-up series; practice effects; patient's treatment may affect cognition