Multiple sclerosis (MS) is an autoimmune disease of the CNS characterized by:
- Chronic inflammation
- Gliosis (scarring)
- Neuronal loss.
- Activated T cells disrupt blood brain barrier (type 4 hypersensitivity)
- Some B cells form myelin-specific autoantibodiies, causing demyelination (hallmark of MS).
Site of involvement (demyelination):
The classical 4 locations of MS lesions are :
- Infratentorial and
- Spinal cord.
Classical of MS is dissemination in space & time:
- Dissemination in space: Lesions in different locations
- Dissemination in time: Lesions at different stages of activity, i.e. (old + new) lesions.
- Earliest symptom: Sensory loss → Heat sensitivity (Uhthoff ’s symptom)
- Uhthoff’s phenomenon is the worsening of neurologic symptoms in multiple sclerosis and other demyelinating conditions when the body gets overheated.
- Retrobulbar neuritis:
- Gradual painful loss of vision
- Optic disc margin is normal as the inflammation is behind the eyeball
- Pain on attempted elevation (SR) / adduction (MR).
According to Harrison 20th, there are 3 types:
- A. Relapsing MS (RMS)
- B. Secondary progressive MS (SPMS)
- C. Primary progressive MS (PPMS).
- MAGNIMS imaging diagnostic criteria
- Defined locations characteristic for MS:
- Periventricular (minimum 3 lesions)
- Spinal cord
- Optic neuritis.
B. CSF: Oligoclonal bands on liquid chromatograph: assesses intrathecal production of IgG.
- Dawson’s fingers: Areas of demyelination perpendicular to the sagittal surface of ventricle
- Open ring sign: It is a relatively specific sign for demyelination.
Severity grading: Expanded Disability Status Scale (EDSS)
- DOC of acute attack: Methylprednisolone
- Diesase modifying agents:
- Interferon β
- Glatiramer Acetate
- Fingolimod (sphingosine-1-phosphate [S1P] inhibitor)
- Natalizumab (Highly Effective): Humanized monoclonal antibody directed against the α4 subunit of α4β1 integrin, a cellular adhesion molecule expressed on the surface of lymphocytes. The major concern with long-term treatment is risk of PML, which increases in subsequent years of treatment.
- Ocrelizumab (humanized monoclonal antibody directed against the CD20 molecule present on the surface of mature B cells)
- Teriflunomide (inhibits the mitochondrial enzyme dihydro-orotate dehydrogenase, which is a key part of the pathway for de novo pyrimidine biosynthesis; thus limiting the proliferation of rapidly dividing T and B cells)
- Alemtuzumab (humanized monoclonal antibody directed against the CD52 antigen that is expressed on both monocytes and lymphocytes)
- Mitoxantrone (risk of cardiotoxicity & acute leukemia, rarely used now).
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