Multiple Sclerosis

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/