Treatable Causes of Fatigue in Patients with MS

If MS fatigue can be figured out and treated then with just the most miniscule amount of stroke leadership we can find the solution to stroke fatigue. This is so fucking simple, assign a team of your employees to find this and tell them not to come back until they succeed. My fatigue was so bad while in the hospital that with only 10 minutes between therapy sessions I would fall asleep.
http://www.medpagetoday.com/resource-center/MS-Resource-Center/MS-Fatigue/a/56243?

By Candy Gulko
Reviewed by Aaron Miller, MD, Professor of Neurology, Icahn School of Medicine at Mount Sinai and Medical Director at the Corinne Goldsmith Dickinson Center for Multiple Sclerosis, New York, NY

Take Note

• Fatigue is one of the most common symptoms of MS and one of the most disturbing to patients. It negatively impacts employment and quality of life.
• Since fatigue has been shown to affect up to 90% of patients with MS at some point during the course of their disease, it’s understandable that most clinicians don’t look for other causes.
• There’s mounting evidence that not all fatigue is disease-related. It may be a symptom of a secondary, treatable condition--such as a sleep disturbance possibly related to depression, pain, spasticity, medication, or frequent urination--or a primary sleep disorder, such as obstructive sleep apnea.

A growing body of evidence demonstrates that fatigue, a hallmark and difficult-to-treat symptom of multiple sclerosis (MS), may often be due to a treatable, secondary cause. Studies have implicated sleep disturbances, often related to frequent urination, pain, spasticity, depression, or medications, and primary sleep disorders, such as obstructive sleep apnea (OSA), as common, treatable causes of fatigue in patients with MS. Much of the evidence related to poor sleep comes from studies conducted by research teams at the University of Michigan.
“Collectively, our recent work^1-3 suggests that MS patients are at an increased risk for OSA and other sleep disturbances; that MS patients with evidence of brainstem lesions may be vulnerable to more severe forms of sleep apnea; and that sleep disturbances, and OSA in particular, may be highly prevalent yet underrecognized contributors to fatigue in persons with MS,” says Tiffany J. Braley, MD, MS, lead author of these studies and Assistant Professor of Neurology at the University of Michigan Medical School in Ann Arbor.
In a recently published study¹ using the STOP-Bang screening questionnaire for OSA, the University of Michigan team found that 56% of 195 MS patients were at increased risk for OSA but only 21% had been diagnosed with the condition, leading the investigators to suggest that OSA may be underrecognized in patients with MS—much as it is in the general population. While noting that cross-sectional studies can’t establish cause and effect, Dr. Braley says that, “Clinically speaking, this suggests that providers caring for MS patients should maintain a low threshold to screen these patients for sleep disorders, such as OSA, and endeavor to identify underlying nocturnal symptoms that could affect sleep quality and contribute to daytime fatigue.”
Subanalysis of another one of this team’s studies² suggested that brainstem dysfunction due to MS plaque formation might contribute to both obstructive and central sleep apnea in MS patients. In this cross-sectional, overnight polysomnography (PSG) study, MS patients with clinical or radiographic evidence of brainstem involvement showed a mean apnea-hypopnea index (AHI) of 21, nearly double the AHI of 11 in MS patients without brainstem involvement.²
The link between poor sleep efficiency and fatigue in MS patients was demonstrated in another University of Michigan study.⁴ In a nocturnal PSG study of 30 patients with MS and 30 matched controls, decreased sleep efficiency demonstrated on PSG correlated with fatigue, tiredness, and lack of energy in MS patients (Spearman correlation P=.002, .029, and .048, respectively) but not with sleepiness or any symptom among controls.
A recently published study by an Oregon-based team⁵ similarly demonstrated a relationship between fatigue and sleep quality, this time in 121 patients with MS and cognitive impairment. Fatigue, assessed with the Modified Fatigue Impact Scale (MFIS) and the Fatigue Severity Scale (FSS), was significantly associated with decreased sleep quality, as assessed with the Pittsburgh Sleep Quality Index (PSQI), and greater disability (MFIS: F=15.60, P<.01; FSS: F=12.09, P<.01).
“Fatigue has a very big impact on quality of life in MS, clearly diminishing the patient’s ability to participate in many activities,” says the study’s lead author, Michelle H. Cameron, MD, PT, Assistant Professor of Neurology at Oregon Health & Science University in Portland and at the Portland Veterans Affairs Medical Center. She adds that the take-home point of their study is this: “Don’t assume all fatigue is due to MS. There are lots of secondary causes, including sleep dysfunction and depression, which we can treat.”
Across the Atlantic, a Norwegian team⁶ used the PSQI to compare 90 MS patients to 108 sex-and-age-matched controls. The team reported that 67.1% of MS patients were identified as poor sleepers compared to 43.9% of controls (P=.002). Risk factors identified for poor sleep were female gender, pain, fatigue, immunotherapy, moderate depression, and antidepressant medication.
Hanne Marie Bøe Lunde, MD, a neurologist at The Norwegian Multiple Sclerosis Competence Center, Haukeland University Hospital, in Bergen, Norway, and the study’s lead author, cites several clinical implications for their study. “Sleep disorders in MS are a potential treatable condition and by revealing possible risk factors associated with poor sleep, one could earlier intervene and treat this condition,” she says.
Noting that 80% of the MS patients in their study had pain, which may have contributed to their poor sleep, Dr. Lunde says, “There are numerous agents that can be used to treat pain in MS. Some of these agents have a beneficial effect on sleep and others may in fact worsen a pre-existing sleep disorder.”
Commenting on the association between poor sleep and immunotherapy, Dr. Lunde adds that, “Although the results from our study revealed no causality between use of immunotherapy and poor sleep, we believe our findings are sufficiently suggestive to introduce a possible theory on the relationship between timing of immunomodulatory drugs and impact on sleep.” Immunomodulatory drugs, especially interferon, are generally given at night to offset side effects, but Dr. Lunde’s team has switched some patients with sleep disturbances to morning doses.
Poor sleep associated with depression was also demonstrated in this study. There was a threefold higher prevalence of depressive symptoms in MS patients compared to controls, and all patients classified as having moderate depression and all patients on antidepressant medications in this study suffered from poor sleep.⁶ The authors also point out the high psychological burden of MS that was associated with poor sleep.
How should neurologists approach the management of fatigue in the MS patient? “I think it’s often the case that treatable conditions are overlooked in MS patients, as it’s assumed that fatigue is due to MS directly,” says John R. Corboy, MD, Professor, Department of Neurology, University of Colorado School of Medicine, Aurora, and Co-Director, Rocky Mountain Multiple Sclerosis Center at Anschutz Medical Campus.
“To me, this is almost a diagnosis of exclusion,” Dr. Corboy says. “You need to ask about and pursue all potential causes of fatigue in an MS patient. If a primary sleep disorder is suspected, refer to a qualified sleep center for a complete sleep study. If you identify a secondary sleep issue, such as frequent awakenings to urinate, pain, depression, or medication, treat the primary cause.”

Published: 02/17/2016
References:

1. Braley TJ, Segal BM, Chervin RD. Obstructive sleep apnea and fatigue in patients with multiple sclerosis. J Clin Sleep Med. 2014;10:155-162.
2. Braley TJ, Segal BM, Chervin RD. Sleep-disordered breathing in multiple sclerosis. Neurology. 2012;79:929-936.
3. Braley TJ, Chervin RD, Segal BM. Fatigue, tiredness, lack of energy, and sleepiness in multiple sclerosis patients referred for clinical polysomnography. Mult Scler Int. 2012;2012:673936.
4. Braley TJ, Chervin RD. Fatigue in multiple sclerosis: mechanisms, evaluation, and treatment. Sleep. 2010;33:1061-1067.
5. Cameron MH, Peterson V, Boudreau EA, et al. Fatigue is associated with poor sleep in people with multiple sclerosis and cognitive impairment. Mult Scler Int. 2014;2014:872732.
6. Bøe Lunde HM, Aae TF, Indrevåg W, et al. Poor sleep in patients with multiple sclerosis. PLoS One. 2012;7:e49996.