Multiple Sclerosis (Degeneration Of CNS) Flashcards
Definition
Acquired-immune mediated inflammatory condition of CNS = Type 4 hypersensitivity reaction against the myelin basic protein of oligodendrocytes (CNS myelinating cells) = demyelination of CNS neurones
resulting in areas of demyelination gliosis + secondary neurological damage throughout the CNS
Epidemiology
Young Adults
- non-traumatic cause of significant neurological disability in younger than 20-40 years
WOMEN
Risk factors (VAGINOS)
Vit D def
Autoimmune disease
Genetic factors - HLA-DRB1, HLA-DR2
Infection - EBV asssosciation
Northern latitudes
Obesity during adolescence
Smoking
Aetiology
The cause of MS is unknown
- thought that acute then chronic immune mediated inflammation is precipitated by an abnormal response to environmental triggers in people who are:
1. Multiple genes
2. EBV
3. Low Vit D
4. Smoking
5. Obesity
Pathophysiology
Demyelinating condition + axonal loss caused by autoimmune reaction against myelin and oligodendrocites. CD4 T cells mediate an attack on white matter oligodendrocites.
Antibodies to myelin basic protein seen early on in the disease. Normally, macrophages cannot easily cross BBB, but in Multiple Sclerosis, they exhibit glycoprotein α4 β1, allowing them to adhere to and cross the endothelium.
At the active lesions there are increased numbers of inflammatory cells = macrophages digest the myelin sheath. Also the macrophages produce nitric oxide which directly damages the axon.
Plaques can be found anywhere in the CNS, but particularly in the :
Optic nerves
Periventricular region
Corpus callosum
Brainstem and cerebellar connections
Cervical spinal cord:
Posterior columns
Corticospinal tracts
A characteristic feature of MS is that lesions vary in their location over time, meaning that different nerves are affected and symptoms change over time. The key expression to remember to describe the way MS lesions change location over time is that they are “disseminated in time and space”.
Types of MS
- RELAPSING & REMITTING
- Random attacks over a number of years
- Disabilities accumulate from one attack to the next
- Further classified into: Active, Not active, Worsening, Not Worsening
- CHRONIC PROGRESSIVE
- Slow decline in neurological function from disease onset
- PRIMARY – gradually worsens without relapsing
- SECONDARY – relapsing and remitting then gets worse
- Slow decline in neurological function from disease onset
- BENIGN
- Few relapses and little disability
Eye signs
Optic neuritis (MC) = Loss of vision in one eye
Eye movement abnormalities =
- sixth cranial nerve (abducens nerve) = double vision
- internuclear ophthalmoplegia
- conjugate lateral gaze disorder = affected eye will not be able to abduct
Focal weakness
Focal weakness
- Bells palsy
- Horners syndrome
- Limb paralysis
- Incontinence
Focal sensory symptoms
Trigeminal neuralgia
Numbness
Paraesthesia (pins and needles)
Lhermitte’s sign = electric shock sensation that travels down the spine and into the limbs when flexing the neck = cervical spinal cord disease in the dorsal column. It is caused by stretching the demyelinated dorsal column.
Ataxia signs
Ataxia is a problem with coordinated movement. It can be sensory or cerebellar:
- Sensory ataxia = loss of the proprioceptive sense (ability to sense the position of the joint e.g. is the joint flexed or extended) = +ve Romberg’s test and can cause pseudoathetosis.
- Cerebellar ataxia = coordinating movement.
Charcot neurological triad
Dysarthria
Nystagmus
Intention tremor
Symptoms (NUMBB)
Numbness, tingling and other strange sensations
- E.g. Paraesthesia
Uhthoff’s phenomenon = symptoms exacerbated by heat e.g. shower
Movement
- Ataxia
Bowel and bladder dysfunction
Blurred vision
+ Weakness
How the disease first presents
Symptoms usually progress over more than 24 hours. At the first presentation, symptoms tend to last days to weeks and then improve
MS cannot be diagnosed on one episode as the lesions have not been “disseminated in time and space”
Diagnosis + Criteria
MCDONALD CRITERIA = 2 < Attacks disseminated in time and space
Gold standard = MRI brain and cord w/ gadolinium contrast to see how long lesions have been present
- PERIVENTRICULAR LESIONS/PLAQUES
- high signal T2 lesions
- Dawson fingers: often seen on FLAIR images - hyperintense lesions penpendicular to the corpus callosum
- shows dissemination in SPACE + TIME
Lumbar puncture: OLIGOCLONAL BANDS found in the CSF and not in the serum (unmatched), increased IgG
Visual evoked potentials
Treatment
ACUTELY (in episodes) = IV METHYLPREDNISOLONE
Prophylaxis = DMARD biologics
- Glatiramer acetate (FIRST LINE) - safe in preggos
- B interferon
