Multiple Sclerosis Flashcards
What is MS
Multiple sclerosis (MS) is an acquired, chronic, immune-mediated, inflammatory condition of the central nervous system (CNS) that can affect the brain, brainstem, and spinal cord.
The inflammatory process causes areas of demyelination (damage to white matter), gliosis (scarring), and neuronal damage throughout the CNS.
What is myelin
Several layers of cytoplasmic membrane wrapped around axons.
Oligodendrocytes (central) or scwann cell (motor/peripheral)
What is demyelination
Loss of myelin disrupting neuronal function resulting in loss of function or hyper-excitable
describe pathology of MS
Results in plaques (areas of scarring).
Can occur in a number of different locations in the cns and different times.
common locations of plaques
- optic tract
- spinal cord
- brain stem
- basal ganglia
HOW
Supporting diagnosis and monitoring
MRI - to identify plaques
symptoms of MS
Methyl prednisolone works for noone
very common: pain, numbness, walking difficulty, muscle spasms, fatigue,
common: Depression, headache, dizziness, cognitive impairment
less common: visual problems, itching, tremor
rare: seizures, hearing problems, breathing difficulty
general
MS risk factors
Genetic + enviromental factors
Age: 25-40
obesity: alter inflamatory response
sex: higher risk in females (hormonal, not chromosome related)
enviromental
MS risk factors
Epstein-barr virus
smoking
latitude
vitamin D
Development of MS
Genetics/enviroment
>
Peripheral immune response with
activation and proliferation of self-reactive T-cells
>
Interaction with adhesion molecules on brain endothelial cells leads to crossing of the blood brain barrier (BBB)
>
Reactivation within the CNS leading to pro-inflammatory environment recruitment of more B cells, macrophages, microglia resulting in autoimmune demyelination
Relapsing/remitting MS (RRMS)
Periods of disability (relapse) with a stable periods of recovery (remission)
Secondary progressive MS (SPMS)
RMPS often (~50%) followed by slowly progressive clinical course known as Secondary Progressive (SP-MS)
* No longer have relapses
Benign form of MS
relapsing/remitting pattern but will make a full recovery from each episode
Primary progressive MS (PPMS)
Around 10% of patients will have steady progress over time Primary Progressive multiple sclerosis (PP-MS)
* Won’t have relapses early in disease course
Relapse periods
-symptoms arrise because myelin and oligodendrocytes are destroyed resluting in blocked/slowed nerve transmission
- The location of the plaques will determine the symptoms of MS
Remission periods
the limited ability of the CNS to repair or replace damage but more a reflection of the CNS redirecting signals through alternate routes
D
Diagnosis of MS
- no specific tests available
- neurologist
- 2 or more relapses in the last 2 years
- 2 or more clinically defined lesions
- mri supports diagnosis
Diagnosis of MS
supporting eveidence
- MRI to locate/identify lesions
- evoked potentials (neuronal stimulation to test transmition speed/strength)
- lumbar puncture
treatment of acute relapses
Oral/IV corticosteroids used to shorten the duration of relapse
1. Oral methylprenisolone: 0.5g for Five days as close to start of relapse as possible. no less than 0.5g
2. IV methylprednisolone: 1g DAILY for 3-5 days. in those whom oral corticosteroids have failed / not tolerated and hospital admission required
side effects:anxiety, insomnia, restlesness, depression, psychosis or euphoria
RAID
Disease modifying therapies (DMT)
- Drugs that will effect or modify the course of MS
- surpress the inflamatory responses and immune reponses against myelein at range of sites
- NOT A CURE but can reduce the number and severity of attacks
Reduce relapse and prolong remission
NICE guidlines on: glatiramer acetate and interferon beta
Can no longer be reccomended but should stay on treatment until a suitable alternative is identified for those already started on these drugs.
DMT drugs
- Dimethyl fumurate: for RRMS but not active or rapidly progressing
- Significantly reduced the annulized relapse rate and GD enhanced lesions.
- Alemtuzumab: for treating adults with RRMS
Mechanisms and effectivness of dmt for ms
F
Flingolimod: used in treatment of highly active RRMS in adults if an unchanged or increased relapse rate or ongoing sever relapses compared to the previous year despite beta interferon treatment.
Mechanisms and effectivness of dmt for ms
N A C O
- Natalizumab - for the treatment of only rapidly evolving severe MS. Reduces ARR by 60% and gd lesions by 80%
- Alemtuzumab - for treating adults with active RRMS. upto 78% of patients were relapse free for 2 years
- Cladribine - targets lymphocytes and surpresses the immune system (SPMS)
- Ocrelizumab - targets B lymphocytes and acts as immunosupressive drug (PPMS)
