Multiple Sclerosis Flashcards
Histopathology of MS lesions:
- perivascular cuffing and parenchymal infiltration with T lymphocytes and macrophages
- loss of oligodendrocytes –> primary demyelination
- axonal transection, axonal degeneration –> gliosis (secondary demyelination)
What is the difference between primary and secondary demyelination?
Primary demyelination: demyelination by damage to oligodendrocytes, but axon remains intact.
As axons cannot regenerate but myelin can, this means there is potential for improvement / recovery.
Secondary demyelination: transection of axon –> axon distal to transaction degenerates, as does myelin sheath –> gliosis (scarring).
Both processes can occur in MS.
Typical sites of MS lesions:
- Cerebrum:
- Periventricular (juxtacortical)
- Corpus callosum
- Juxtacortical - Brainstem
- Cerebellum
- Optic nerve
- Spinal cord
RR-MS: lesions tend to be in white matter, periventricular
PP-MS: lesions tend to affect cerebral and cerebellar cortices
MS is a CNA chronic inflammatory demyelinating disease.
Pathogenesis remains uncertain and is probably multifactorial.
Features that suggest implicate primary autoimmunity are:
- HLA association
- DRB11501
- DQA10102
- DQB1*0602 - Increased occurrence of other AI diseases in MS patients / families
- similarities with animal model (EAE experimental autoimmune encephalomyelitis)
- MS patients have increased T-cell reactivity to myelin antigens
- Increased anti-myelin and anti-ganglioside Abs
- Response to high-dose corticosteroids and immunotherapy
Temporal profile of MS:
Relapsing remitting
Primary progressive
Secondary progressive
Relapsing remitting:
Typical attack - time from onset to maximum deficit is days to weeks.
Primary progressive
Secondary progressive
Pathogenesis of MS - how would EBV contribute to the development of MS?
Postulated that EBV infection is a prerequisite for the development of MS.
Autoimmune genes (→ ↓CD8 cells that regulate EBV) \+ Genetic predisposition (eg. HLA-DR15) \+ Late EBV infection ↓ MS
Mechanism: EBV → infects autoreactive
B cells → seed CNS → pathogenic autoantibodies and provide survival signals to autoreactive T cells.
Pathophysiology of MS:
Explain conduction block:
Loss of myelin → loss of saltatory conduction → leak / dissipation of electrical signal → conduction block.
If occurring in enough fibres in a nerve → will see effect on function
(eg. optic nerve: visual loss)
Pathophysiology of MS:
Explain why conduction block can increase with increased body temperature.
Reduction current generated at each node of Ranvier with increasing temperature due to shortening of action potential (all people).
In demyelination the decreased current may not be sufficient to allow conduction → conduction block.
With cooling function may improve.
Known as Uhtoff’s phenomenon in MS.
Pathophysiology of MS: Mechanisms of recovery from conduction block
Conduction block occurs when nerve fibre conduction is halted due to demyelination (impulses dissipate due to lack of insulation).
Over time:
1. Redistribution of Na+ channels along axon (instead of only at nodes of Ranvier) → conduction occurs, but slowly
- Remyelination can occur → recovery of saltatory conduction and normal function.
Symptoms and signs of optic neuritis (common in MS):
Optic neuritis:
- pain with EOM
- reduced VA
- desaturation of colour vision
- RAPD (Marcus Gunn pupil)
- scotoma
Symptoms and signs of MS:
Optic neuritis
SC involvement:
- UMN deficits of limbs
- sensory deficits of limbs
- bladder and bowel dysfunction
Brainstem involvement:
- CN symptoms: diplopia, vertigo, facial weakness, facial pain
- Long tract signs - sensory and motor
- Cerebellar signs
Cerebellar involvement:
- ataxia
- nystagmus
- dysarthria
Cerebral involvement:
- hemiparesis (eg. internal capsular lesion)
- epilepsy
- cognitive impairment (multiple lesions)
Diagnosis of MS:
Dissemination of CNS lesions (that are typical of MS) in time and space.
- clinical
- MRI
Exclude other causes.
LP is not usually required in diagnosis of MS, but can be used in difficult cases. What would be seen in MS?
Abnormal IgG bands in CSF but not in serum.
Oligoclonal B cell expansion in CSF.
Typical of MS but DDx: subacute sclerosing panencephalitis, neuro-berylliosis
Visual evoked responses - when to perform:
- If looking for second lesion (separated in space) - will show slowing of conduction in optic pathway, suggestive of demyelination.
But need to exclude ocular or retinal pathology before attributing to demyelination.
- If visual symptoms suspected to be functional (ie. to rule out optic neuritis)
Neuromyelitis optica (NMO) / Devic’s disease is a variant of MS. What are the diagnostic criteria?
- Transverse myelitis and optic neuritis
- At least 2 of:
- Brain MRI non-Dx for MS
- SC lesion extending ≥3 vertebral segments
- seropositive for NMO IgG
(directed against aquaporin 4 water channel - affects atsrocytes that form BBB)
