10: Multiple Sclerosis Flashcards
MS: Relapse
• new symptoms/return of old symptoms, absence of infection or change in body temperature
• duration of symptoms at least 24h
• at least 30 days since last relapse
MS: Neurodegeneration
• Inflammation and Regeneration decrease
• Neurodegeneration increase
MS: Symptoms
• Sensibility
• Visual system
• Gait
• Paresis
• Vertigo
• Incontinence
• Fine motor skills
• Fatigue
• Psychologic
-> no MS specific symptom
MS: Disease course
• Onset btw 20 - 40 years
• Relapsing (inflammatory) phase avg. 15 years (1 to >30 years).
• After 15 years, 50% of patients still walk
• Time from moderate disability to loss of ability to walk (degenerative phase): 11 years avg.
• Highly active (aggressive) and benign (mild) courses of MS exist
• Prodropmalphase (tired, head aches,….) silent
MS: Diagnosis
3 pillars / diagnostic principles:
1. Typical symptoms
2. Dissemination in time and space
3. Exclusion of other differential diagnoses
Diagnostic tools:
• Medical history
• Neurostatus
• MRI (brain / spinal cord)
• Cerebrospinal fluid (CSF) diagnostics
• Electrophysiology (e.g. visual-evoked potentials, VEP)
Dissemination in space (DIS)
≥1 T2-lesion in at least 2 out of 4 following regions:
1. Periventricular
2. Cortical/Juxtacortical
3. Infratentorial
4. Spinal
Dissemination in time (DIT)
• Simultaneous presence of gadolinium-enhancing and non-enhancing lesions at any time
OR
• A new T2 or gadolinium enhancing lesion on a follow-up MRI with reference to a baseline scan
OR
• CSF-specific OCBs (≥2) can substitute MRI criteria for DIT
Typical CSF findings
- more cells in CSF
- activated lymphocytes & plasma cells
- specific oligoclonal bands
- M,R,Z positive reaction
CSF specific OCB = high Sensitivity (haben fast alle mit MS) aber low Specificity (kommt auch ohne MS oft vor)
Positive MRZ reaction = low Sensitivity (haben nicht alle mit MS), aber high Specificity (wenn man das hat, dann ziemlich sicher auch MS)
Visual evoked potential (VEP) testing
• electrical signals generated by the visual cortex in response to visual stimulation
• visual evoked potentials are delayed as a sign of demyelination
• prolonged conduction time in the optic nerve
MS: Therapy
• steroids (suppress immune reaction)
• If doesnt work -> Plasmapheresis (wash blood)
• Drugs act on decreasing T/B-cells
«Stepwise treatment escalation» vs. «early intensive treatment»:
• Early intense therapy better than escalation strategy
• Better protection from secondary progression (SPMS) with an early intensive treatment vs. slow stepwise treatment escalation
Major unmet needs in MS therapy
• prevention of progression
• neuroprotection
• remyelination
MS risk factors
• complex polygenetic disease/environmental factors (infections, Vit D, smoking, genes)
• Pathology: inflammatory demyelination, axonal/neuronal tissue damage
• Hygiene hypothesis: better hygiene -> worse immunesystem
Infections in childhood -> Decrease risk of MS
Infection in adolescence -> Increase risk of MS
• prevalence increases with socioeconomic status
• Diet (microbiota)
• Genetic riskfactors: >230 genes, DR15 haplotype = most significant genetic risk factor
Pathology
Meningeal ectopic lymphoid structures:
• Ectopic lymphoid structures heterogeneously distributed throughout brain
• Meningeal ectopic lymphoid structures found in ca. 30% MS patients
• These follicles predominantly found in deep cerebral sulci
Cortical lesions in multiple sclerosis:
• actively demyelinating cortical lesions are frequent in early MS
• associate with meningeal inflammation
Pathophysiology
• loss in immunotolerance -> attack own cells
• But no antibodys yet found!
Molecular mimicry
• possibility that sequence similarities between foreign and self- peptides are sufficient to result in the cross-activation of autoreactive T/B cells by pathogen-derived peptides
-> self-antigen mimics pathogen antigen
