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Multiple sclerosis

Multiple Sclerosis (Demyelinating Disorder)
It is characterized by
  1. Relapsing – remitting or progressive course.Q
  2. Pathological triad of CNS inflammation, demyelination & gliosis.Q 
  3. It is a disease which is disseminated in time and space. 
Risk factors –
  1. Females are affected 2 times more. 
  2. Positive family history.
  3. Class II (HLA – D) region of MHC associated with it.
  4. Presence of Myelin Basic Protein (MBP) – reactive T cells.
  5. Auto antibodies against myelin oligodendrocyte glycoprotein (MOG). Q
  6. HHV type 6, chlamydia pneumoniae. Q
  7. Latitude: One proposed explanation for the latitude effect on MS is that there is a protective effect of sun exposure. Exposure of the skin to ultraviolet-B (UVB) radiation from the sun is essential for the biosynthesis of vitamin D, and this endogenous production is the most important source of vitamin D in most individuals. (Ref. Hari. 18th ed., page 3396)

The McDonald criteria are diagnostic criteria for multiple sclerosis (MS).


Currently, McDonald criteria is regarded as the Gold standard for MS diagnosis.


Clinical features –

  1. Weakness of limbs – Fatigue, gait disturbance
  2. Pyramidal signs (LQ 2012) – Increase tone, hyperreflexia, extensor plantar.
    (Treatment: Baclofen, Dantrolene, Tizanidine) 
  3. DTR may be lost (lesion at dorsal root entry zone).
  4. Optic neuritis (LQ 2012)–
    Usually symptoms are monocular, Periorbital pain.
    Decrease acuity, papillitis, optic atrophy.
    Diplopia due to inter nuclear ophthalmoplegia.
  5. Sensory symptoms – paresthesia, numbness.
  6. Impotency is a feature
  7. Ataxia – cerebellum or cerebellar pathway involvement.
  8. Bladder dysfunction – Urgency, hesitancy, incontinence
    (Treatment: Use oxybutynin or tolterodine if post micturition urine is present).
  9. Cognitive dysfunction – Memory loss, impaired attention.
  10. Depression – Upto 60% pts. Suicidal tendencies are more.
  11. Heat sensitivity (Uhthoff's phenomenon) – Appearance of new symptoms or the worsening of pre existing symptoms on exposure to heat. – Conduction block which may occur in response to increase temperature or metabolic derangements. (Negative conduction abnormalities Q
  12. Lhermitte’s symptom (Barber chair sign) – Generation of ectopic impulse giving rise to Lhermitte’s Sympt, paroxysmal symptoms or paresthesias. (Positive conduction abnormalities Q
  13. Paroxysmal symptoms – Brief and stereotypic. Tonic spasm, dysarthria, ataxia, diplopia, paresthesia, pain.
  14. Trigeminal neuralgia Q
  15. Facial myokymia
  16. Vertigo – of brain stem origin.

Extra Edge:

  1. Parkinsonism, Speech aphasia, & epilepsy are the not the feature of multiple sclerosis!!!.
  2. The Initial symptoms of MS are Sensory loss, Optic neuritis, Weakness & Paresthesias. (LQ 2012)
  3. Hydrocephalus is not a feature of multiple sclerosis (LQ 2012)
  4. Barber chair sign is also seen in:
    1. Vit B12 deficiency
    2. Cervical spondyloses.


  1. MRI – Increase in vascular permeability – earliest event
    1. Dawson’s finger sign – Lesion appear to extent from the ventricular surface,  corresponding to a pattern of perivenous demyelination.
    2. Lesion of ant corpus callosum are specific as this site is usually spared in cerebro vascular diseases.
  2. Evoked responses – To detect slowed or absent conduction in visual, auditory, somatosensory or motor pathways.
  3. CSF –
    1. Mononuclear pleocytosis, TLC usually < 20/cmm
    2. Increase IgGQ
    3. Oligoclonal bandingQ

Poor prognostic factor

  1. Older male
  2. Motor symptom present at onset
  3. Multiple relapses
  4. Early relapses
  5. Multiple lesion seen in MRI.

Treatment of Acute Attack (Ref. Hari. 18th ed., Pg- 3402)

  1. Glucocorticoid treatment - Pulse Methyl Prednisolone
  2. Plasma exchange

Prophylaxis Treatment (Disease modifying agent) for relapsing form of MS includes the following drugs–

  1. MethotrexateQ
  2. Cyclophosphamide
  3. Azathioprine

Recent Advances: New Drugs for prophylaxis:

  1. Glatiramer acetate Q
  2. Mitoxantrone (it is a doxorubicin analogue) Q
  3. IFN-Beta-1a, 1b
  4. Natalizumab
  5. Alemtuzumab (It is T cell killing monoclonal antibodies)

Recent Advances in the prophylaxes of MS (Ref. Hari. 18th ed., Pg- 3405)

  1. Fingolimod is a sphingosine-1-phosphate (S1P) inhibitor and it prevents the egress of lymphocytes from the secondary lymphoid organs such as the lymph nodes and spleen.
  2. Cladribine is a purine analog that inhibits DNA synthesis and repair, and acts as a general immunosuppressant.

Extra Edge: Clinical Variants of MS

  1. Acute MS (Marburg's variant) is a fulminant demyelinating process that in some cases progresses inexorably to death within 1–2 years. (Ref. Hari. 18th ed., Pg- 3408)
  2. Neuromyelitis optica (NMO), or Devic's syndrome, is an aggressive inflammatory disorder consisting most typically of attacks of acute ON and myelitis. Attacks of ON can be bilateral (rare in MS) or unilateral; myelitis can be severe and transverse (rare in MS) and is typically longitudinally extensive, involving three or more contiguous vertebral segments. (Ref. Hari. 18th ed., Pg- 3407)
Important Points: Uses of interferon:
  1. Interferon alpha
    1. Hepatitis B, Hepatitis C        
    2. Mucocutaneous manifestations of Beh|et’s syndrome
    3. Carcinoid syndrome                     
    4. CML
    5. Follicular lymphoma                     
    6. Malignant melanoma
    7. Essential thrombocytosis      
  2. Interferon Beta
    1. Multiple sclerosis
  3. Interferon γ
    1. Osteopetrosis                       
    2. Systemic sclerosis
    3. Idiopathic pulmonary fibrosis
    4. Chronic granulomatous disease leprosy, non tuberculosis mycobacteria & visceral leishmaniosis
    5. Multiple myeloma                        
    6. Renal cell carcinoma

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