Multiple Sclerosis

Diagnosis (Solomon 2019)

1. Identification of a typical MS syndrome (i.e. optic neuritis, internuclear ophthalmoplegia, cerebellar syndromes, transverse myelitis)
2. Objective evidence of CNS involvement (i.e. afferent pupillary defect suggestive of optic neuritis)
3. Demonstration of dissemination in SPACE (periventricular, cortical / juxtacortical, infratentorial brain, spinal cord)
4. Demonstration of dissemination in TIME (MRI or CSF)
5. No better explanation other than MS (atypical characteristics of MS may include hyperacute onset, vascular territory signs, age >50, isolated trigeminal neuralgia, fluctuating ocular/bulbar weakness, nonremitting, fever, meningism)

Imaging

• FLAIR:
  • lesions are hyperintense
  • Dawson's fingers are characteristic perpendicularly extending lesions from the lateral ventricules
• T1:
  • lesions are iso- or hypointense
  • thinned corpus callosum
• T1 + contrast:
  • active lesions show enhancement
  • open ring sign - incomplete enhancement around periphery

Symptomatic treatment

Fatigue occurs in up to 80% of patients with MS, often described as the symptom most affecting their quality of life (Feinstein, Freeman, and Lo, 2015)

- Limited efficacy in relapsing remitting and progressive MS, studies of amantadine, carnitine, energy conservation program, aerobic exercise training, and progressive resistance training yielded equivocal results (Feinstein, Freeman, and Lo, 2015)

- Some benefit from yoga was found in fatigue though due to mostly low power of studies data was considered inadequate to draw meaningful conclusions (Cramer et al, 2014)

- Lisdexamfetamine did not show improvement in fatigue as a secondary outcome in a study on cognition (Morrow et al, 2013)

Cognitive dysfunction occurs in up to 40% of relapsing remitting and 60% of primary progressive MS, most frequent affected domains include processing speed, memory, and executive function (Feinstein, Freeman, and Lo, 2015)

- Manage factors that impact cognition (mood, anxiety, fatigue, sleep) (Feinstein et al, 2019)

- Chronic anticholinergic medications, such as those used to treat bladder dysfunction, can significantly reduce processing speed (Kalb et al, 2018)

- Cannabis use leads to more cognitive impairment, especially processing speed and memory. A study of chronic (smoked) cannabis users that stopped use revealed significant improvement across cognitive domains (processing speed, executive function, learning and memory both verbal and visual) (Feinstein et al, 2019).

- Donepezil study without benefit (Feinstein, Freeman, and Lo, 2015)

- Studies of cognitive retraining and exercise with positive results (Feinstein, Freeman, and Lo, 2015; Kalb et al, 2018)

- Some benefits in secondary outcomes for L-amphetamine (Feinstein, Freeman, and Lo, 2015)

- Improvement on some measures of processing speed in a phase II study of lisdexamfetamine (up to 70mg QD), though patients reported no subjective improvement (Morrow et al, 2013)

Depression a third to a half of patients with MS will develop major depressive episode during their lives (Feinstein, Freeman, and Lo, 2015)

- Limited efficacy with pharmacologic treatment with mixed efficacy in studies of desipramine and paroxetine (Feinstein, Freeman, and Lo, 2015)

- Studies of cognitive behavioral therapy for depression in MS yielded good results

Pseudobulbar affect present in up to 10% of MS patients, mainly in secondary progressive MS patients (Feinstein, Freeman, and Lo, 2015)

- Dextromethorphan plus quinidine helpful and endorsed by American Academy of Neurology

References

Cramer, H., Lauche, R., Azizi, H., Dobos, G. & Langhorst, J. Yoga for Multiple Sclerosis: A Systematic Review and Meta-Analysis. PLoS ONE 9, e112414 (2014). https://pubmed.ncbi.nlm.nih.gov/25390344/

Feinstein, A., Freeman, J. & Lo, A. C. Treatment of progressive multiple sclerosis: what works, what does not, and what is needed. Lancet Neurol. 14, 194–207 (2015). https://pubmed.ncbi.nlm.nih.gov/25772898/

Feinstein, A., Meza, C., Stefan, C. & Staines, R. W. Coming off cannabis: a cognitive and magnetic resonance imaging study in patients with multiple sclerosis. Brain 142, 2800–2812 (2019). https://pubmed.ncbi.nlm.nih.gov/31363742/

Kalb, R. et al. Recommendations for cognitive screening and management in multiple sclerosis care. Mult. Scler. J. 24, 1665–1680 (2018). https://pubmed.ncbi.nlm.nih.gov/30303036/

Morrow, S. A. et al. Lisdexamfetamine dimesylate improves processing speed and memory in cognitively impaired MS patients: a phase II study. J. Neurol. 260, 489–497 (2013). https://pubmed.ncbi.nlm.nih.gov/23001556/

Solomon AJ. Diagnosis, differential diagnosis, and misdiagnosis of multiple sclerosis. Continuum. 2019. Jun;25(3):611-635. https://pubmed.ncbi.nlm.nih.gov/31162308/