Warning: Declaration of Custom_Menu_Wizard_Walker::walk($elements, $max_depth) should be compatible with Walker::walk($elements, $max_depth, ...$args) in /home/eviden14/public_html/wp-content/plugins/custom-menu-wizard/include/class.walker.php on line 1320

Warning: Declaration of Custom_Menu_Wizard_Sorter::walk($elements, $max_depth = 0) should be compatible with Walker::walk($elements, $max_depth, ...$args) in /home/eviden14/public_html/wp-content/plugins/custom-menu-wizard/include/class.sorter.php on line 73
Multiple Sclerosis – Evidence Reviewed

Multiple Sclerosis

Multiple Sclerosis 2018-01-30T16:37:11+08:00
  • Chronic inflammatory demyelinating disorder, primarily of young adults
  • Peak age of onset is 30 years, women more commonly affected than men
  • Clinical phenotypes
    • Relapsing-remitting (85%)
      • Approximately half go on to develop secondary progressive MS
    • Primary progressive or progressive-relapsing (15%)
  • Diagnostic criteria (MacDonald Criteria)
    • Dissemination in space (multiple areas of the CNS involved)
    • Dissemination in time (ongoing disease activity over time)

Relevant physical signs

  • General inspection
    • Spasticity
    • Walking aids
    • Feeding tubes
    • Lhermitte’s sign: tingling or shock-like sensation on neck flexion
    • Indwelling urinary catheter
    • Baclofen by the bedside
    • Presence of eye patch – binocular diplopia
    • Pronator drift
    • Rebound phenomenon
  • Eyes
    • Loss of direct light reflex with preservation of consensual light reflex (afferent pupillary defect)
    • Red desaturation
    • Central scotoma in acute, severe cases
    • Relative afferent pupillary defect in affected eye
    • Offer fundoscopy to look for pallor of the affected disc
      • May be normal as disease is retrobulbar in the majority of patients
    • Extra-ocular movements
      • Hypermetric saccades or hypometric saccades, broken pursuit
      • Internuclear ophthalmoplegia – failure of adduction of affected eye, with nystagmus on abduction of the contralateral eye
        • Document preservation of convergence
      • Nystagmus
  • Brainstem
    • Trigeminal neuralgia
    • Facial palsy
  • Cerebellar
    • Ataxic gait
    • Staccato speech
    • Intention tremor
    • Dysmetria
    • Dysdiadochokinesis
  • Limbs
    • Limbs are usually not wasted, unless there is substantial disuse atrophy
    • Increased tone
    • Hyperreflexia with upgoing plantars
    • Pyramidal weakness
    • Variable dorsal column loss
    • Spinothalamic tract may be affected, but this is very uncommon

 Differential diagnosis

  • Inflammatory
    • Acute disseminated encephalomyelitis
      • Monophasic demyelinating disorder
      • Often widespread, multifocal lesions (>50% of total white matter)
      • May follow vaccination or viral illness
    • Neuromyelitis optica (Devic’s disease)
      • Idiopathic inflammatory disease affecting optic nerves and spinal cord
      • Typically follows relapsing-remitting course
      • Seropositive for NMO antibodies (antibodies against IgG aquaporin-4)
    • Transverse myelitis
    • Systemic inflammatory disorders with central manifestations
      • Systemic lupus erythematosus
      • Sarcoidosis
      • Sjögren’s syndrome
      • Behçet’s syndrome
      • Polyarteritis nodosa
  • Hereditary spastic paraparesis (if mainly affecting lower limbs – MRI often normal)
  • Metabolic leukodystrophies
    • Severe B12 deficiency
    • Acute intermittent porphyria
  • Non-metabolic leukodystrophies
    • Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) – typical onset in fourth and fifth decade
  • Lysosomal storage diseases
    • Fabry disease, X-lined recessive; incomplete penetrance in female heterozygotes
    • Krabbe disease (adult-onset phenotype), autosomal recessive disorder causing demyelination
  • Mitochondrial disorders
    • Myoclonic epilepsy with lactic acidosis and stroke-like episodes (MELAS)
    • Myoclonic epilepsy with ragged red fibres (MERRAF)
    • Leber’s hereditary optic neuropathy

Investigations

  • Full blood count (anaemia of chronic disease)
  • Liver function, renal function prior to starting immunosuppression
  • Lumbar puncture looking for unmatched oligoclonal bands (>80% of patients with MS, but not specific)
  • Magnetic resonance imaging of the brain and spinal cord to look for lesions separated in space
    • Peri-ventricular white matter changes on FLAIR imaging, hyper-intense on T2
    • Hypo-intense T1 lesions reflecting axonal damage and gliosis
    • Gadolinium may differentiate between lesions disseminated in time – enhancing lesions are active, chronic lesions do not enhance
  • Visual evoked potentials looking for conduction delay (increased latency) or reduced amplitude
  • Consider aquaporin-4 IgG antibody for NMO, especially if brain MRI is normal

Management

  • Multidisciplinary team approach
  • Occupational and physiotherapy to preserve and maximize function
  • Walking aids / visual aids as necessary
  • Acute attacks
    • Intravenous methylprednisolone 1g/day for 3 – 5 days
    • If symptoms persistent, consider second cycle of methylprednisolone, up to 2g/day for 5 days
    • Plasma exchange may also be considered for relapses refractory to second cycle
  • Disease modifying treatment
    • Start with basic treatment and escalate in treatment non-responders (monitor with MRI or clinically)
      • ≥1 relapse per year
      • Incomplete recovery from relapses
      • MRI progression with or without clinical signs
    • Interferon-β (Avonex, Betaferon, etc.)
      • Reduces relapse rate by 30%
      • Improves quality of life, inflammatory changes on MRI
      • Generally well-tolerated, but may cause malaise and flu-like symptoms in up to 60%
      • Patients may develop neutralizing antibodies, limiting the effectiveness of IFN-β
    • Glatiramer acetate
      • Mixture of polymers of four amino acids, antigenically similar to myelin basic protein
      • Reduces relapse rate by 30%
      • Usually well-tolerated, but administered as daily subcutaneous injection
    • Natalizumab
      • Humanized monoclonal anti-α4-integrin antibody
      • Blocks leukocytes from traversing the blood-brain barrier
      • Reduces relapse rate by two-thirds
      • Complications: progressive multifocal leukoencephalopathy secondary to JC virus infection
    • Fingolimod
      • Immunomodulatory and immunosuppressive oral drug
      • Binds to spingosine-1-phosphate receptors, inhibits B and T cells from egressing lymph node
      • Reduces relapse rate by 50% compared to IFN-β01a (Avonex)
      • Adverse effects: cardiac arrhythmia, macular edema, mainly at the start of therapy
    • Mitoxantrone
      • Immunosuppressive anthracenedione derivative
      • Reduces relapse rate by 65%
      • Limited to cumulative total life dose of 140mg/m2 due to cardiotoxicity
      • Adverse effects: cardiotoxicity, therapy-related acute leukaemia
    • Alemtuzumab
      • Humanized anti-CD52 resulting in long-lasting depletion of circulating T and B lymphocytes
      • Reduces relapse rate by 30%
      • Adverse effect: secondary autoimmune thyroid and immune thrombocytopaenia
  • Symptomatic treatment
    • Spasticity: baclofen, gabapentin, tizanidine, dantrolene
    • Depression: selective serotonin re-uptake inhibitors, tricyclic antidepressants
    • Fatigue: amantadine
    • Neuropathic pain: TCAs, pregabalin, gabapentin, carbamazepine
    • Bladder dysfunction: intermittent self-catheterization, α1-antagoinists, anti-cholinergic agents

Summary

Sir, this patient has a right relative afferent pupillary defect and red desaturation. This is associated with a right internuclear ophthalmoplegia and multidirectional nystagmus. There is bilateral cerebellar ataxia, dysmetria, intention tremor, dysdiadochokinesis and staccato speech. In the limbs, there is hyperreflexia with spastic pyramidal weakness and upgoing plantars. There is dorsal column loss with sparing of pain and temperature. The most likely unifying diagnosis is a demyelinating disorder such as multiple sclerosis. Possible differentials include neuromyelitis optica, although the internuclear ophthalmoplegia and cerebellar signs are unusual, transverse myelitis, central manifestations of inflammatory disease such as SLE, sarcoidosis, Behçet’s syndrome or polyarteritis nodosa, severe B12 deficiency or lysosomal storage disorders such as Fabry disease or an adult-onset variant of Krabbe disease.

Multiple Sclerosis

This Is A Custom Widget

This Sliding Bar can be switched on or off in theme options, and can take any widget you throw at it or even fill it with your custom HTML Code. Its perfect for grabbing the attention of your viewers. Choose between 1, 2, 3 or 4 columns, set the background color, widget divider color, activate transparency, a top border or fully disable it on desktop and mobile.

This Is A Custom Widget

This Sliding Bar can be switched on or off in theme options, and can take any widget you throw at it or even fill it with your custom HTML Code. Its perfect for grabbing the attention of your viewers. Choose between 1, 2, 3 or 4 columns, set the background color, widget divider color, activate transparency, a top border or fully disable it on desktop and mobile.