Multiple sclerosis Flashcards
Definition
- Autoimmune
- Inflammatory
- Demyelinating
- Neurodegenerative
Disease affecting the CNS
Leads to;
- Destruction of blood brain barriers
- Axonal damage
- Gliosis
- Formation of scleortic plaques in white/ grey matter.
Classifications
Clinically isolated syndrome (CIS)
- attack suggestive of demyelination but does not fulfill MS
Radiologically isolated syndrome (RIS)
Relapsing-remitting MS (most common)
- Unpredictable relapses, followed by remission
Secondary progressive MS
- Initial relapsing-remitting
- Develop progressive neurological decline between attack without definite periods of remission
- Most common time to conversion is 19 years
Primary progressive MS
- No remission after initial symptoms
Epidemiology
- Age
- Ethnicity
- Sex
- Geography
Onset usually younger adults
- 20-40
- Rarely in <10
Affects white, northern europeans mainly
Risk if 2x higher in females
- 5 million global prevalence
- 100K UK prevalence
- More common in colder climates
Aetiology
- Genetics
- Infection
Genetics
- HLA association on chromosome 6: HLA DRB1*1501
- Non HLA, IL genes: IL7RA, IL2RA
- Familial risk: 20% pattern, risk decreases with successive relatives.
Viral aetiology
- 40% associated with viral infection, 10% show relapse after infection
- Risk increases with onset of infection for measles, EBV, rubella and mumps
- EBV infection in young adulthood= 8x risk
Diagnosis
Core diagnosis based on evidence of dissemination
- In space (DIS)
- In time (DIT)
Evidence showing that it affects at least 2 different parts of the CNS at different points in time
Stratified by the McDonald criteria
DIS
Dissemination in space
Criteria >1 T2 lesions in at least 2 of these areas in CNS: - Periventricular - Juxtacortical - Infratentorial - spinal cord
DIT
Dissemination in time
Criteria
- A new T2 and/ gadolinum-enhancing lesions on follow MRI with reference to baseline scan
- Simultaneous presence of asymptomatic gadolinium enhancing and non-enhancing lesions at any time
Differential for CIS
Conditions that produce relapsing-remitting disease confined to one focal area of CNS
- Tumour
- Sarcoidosis
- Behcet’s disease
- Leber’s optic atrophy
- Glioblastoma
- Lyme disease
Positive sensory features
Lhermitte’s
- Electric shock sensation on bending neck
Uhtoff’s
- Symptoms are worse after exertion
Symptoms brought on by increased body temperature
Pathophysiology
CD4 mediated destruction of oligodendrocytes
- Leads to demyelination and eventual neuronal death.
Predictors of long-term disability
First inter-attack interval
- The shorter the interval, the quicker the onset of disability
Number of attacks in first 2 years
- Higher number= more disability
Trend with increased number of lesions and disability
- although very variable
Location of lesion
- >2 infratentorial lesion= worse outcome of disability
Grey matter atrophy
- Correlated with disability
Volume of lesion and prognosis
Rate of lesion growth is 3x higher in those who develop secondary-progressive, from relapsing-remittiing
Lesion volume increases in those with relapse onset
Clinical features
- Sensory
- Motor
- eyes
- Bowl
- Cerebellum
Sensory
- Paraesthesia, dysesthesia
- Decreased vibration sensation
- Trigeminal neuralgia
Eye
- Visual disturbance in one eye (graying, blurring, pain, loss of colour discrimination)
- Optic neuritis: pain, loss of vision, blurred vision
Motor
- Spasticity, increased tone
- Increased deep tendon reflexes
- foot dragging
Bowel dysfunction
- Constipation
Cerebellum
- Imbalance and incoordination: wide based gait, limb ataxia
CIS
Clinically isolated syndrome
- Syndrome of clinical features that suggests acute attack due to demyelination
Features
- Optic neuritis
- Brainstem/ cerebellar dysfunction
- Partial myelitis
Can progress to relapsing-remitting MS
Relapsing- remitting MS
Acute attacks followed by periods of no sign of disease
- The acute attack may leave injury
Requires MRI evidence of DIS and DIT
