Multiple Sclerosis Flashcards
Clinical Menifestations
Blurred vision, diplpia
Ataxia, vertigo, nystagmus
Urinary incontinence, sexual disorders
Reduced strength and activity, weak muscles, spasms
Sensory changes, hypesthesia, progressive sensroy loss
General and Prevelance
First cause of non-traumatic disability in young adults of North America and Europe.
Prevelance in Northern Europe, Canada and US
340 cses/100 000 population
14,000 people in Alberta
Average onset is about 30s but really can happen whenever.
Pediatric MS: 6% in total. 3-10% of MS patients onset before age 18
Prevelenace is increasing. 3:1 now from 2:1 for females to males.
Multiple scars-clinical symptoms are tip of iceberg. Demyelination, remyelination, axonal transection.
Disease Course
Graph-peaks and troughs-gradual increase
Clinically isolated syndrome, relapsing-remitting (80%). Seondary progressive (75%-80% of relapsing-remitting)
Primary progressive (10-15%)
Diagnosis
Clinical record, reflexes, sensitivity, spinal tap, lab blood, evoked potentials and imagiing.
Demylination-ventricles close to cortex, paraventricular lesions.
decreased axonal density in MS plaques
Corpus callosum reduced in density and volume
Neurodegeneration
Process of neuronal, myelin or tissue breakdown, the degradative products of which evoke a reaction of phagocytosis and cellular astrogliosis
Characteristics of Neurodegenerative Disease
Specific parts of functional systems of NS
Insidius beginning-period of normal NS function and pursue a gradually progressive course.
CSF shows minimal changes-mild increase in proteins
Imagiing shows either no change or only a volumetric reduction (atrophy)
Oligoclonal bands in CSF-present is abnormal. Shows aminoglobulins.
Causes
Genes, infections, environement, salt.
Disease of Immune Dysfunction
Initiating etiological factors unknown-destruction within the CNS is thought to be immune-mediated
- many nflammatory cell types are localized to tension sites in CNS
- activity of several inflammatory cell types is dysregulated.
- levels of several inflammatory cytokines are increased in the serum, CSF and CNS of patients with MS
Genetics
DRB*15:01
Immune Priviledge
Allogenic skin grafts placede heterotopically in anterior chamber of the eye and into the brains of rabbits.
Survive for prolonged and sometimes indefinite periods of time.
Eye: cornea, anterior chamber, vitreous cavity and subretinal space.
Brain: ventricles and striatum
Pregnant uterus
Ovary and Testis
Adrenal Cortex
Hair follicles
EAE can be produced in animals by myelin specific T-cells.
Immunology of EAE-mylin antigen-tolerance then break tolerance by injectory protein.
Proliferate and ctivated. look for antigen
Central Nervous System
Transmigrate BBB-induce damage-local inflammation due to damaging axon or killing myelin
Peri-vascular Inflammation in MS Plaques
Damage
Axonal Transection in Acute MS Lesions
Staining shows block
Pathology of MS
Axonal-gradual Myelin-more relapse. Brain Atrophy. Type I: majority-cortical demylination-local TypeII: diverse cortical Type III: full cortical
Target and Treatment
Inflammation, neurodegeneration/demylination, failure to repair/gliosis.
- Therapeutic Options: injections, oral, monoclonal antibodies, chemotherapies, autologous stem cell transplant and clinical trials
- Traditional-interferon, IFNB1a, Glatiraner Acetate (GA)
GA is presented as an antigen and generates GA-specific T-cells of TH2 bias.
-GA peptide—GA specific TH2cells.
Interfeuron-B acts through the interferon-B receptor and inhibits antigen presentation and T-cell activation.
Reduced activation AF autoreactive Tcells.
decreases pro-inflammtory TH1 cytokines.
