Continuous Positive Airway Pressure (CPAP) for Fatigue in Patients With Multiple Sclerosis (MS) and Obstructive Sleep Apnea (OSA)

Multiple sclerosis (MS) is a demyelinating inflammatory disease that is one of the most
common neurological causes of disability in young adults. Besides physical disability,
fatigue is a very common symptom present in 76 to 92% of people with MS. The 1998 Multiple
Sclerosis Council for clinical practice guidelines published a consensus definition:
subjective lack of physical and/or mental energy that is perceived by the individual or
caregiver to interfere with the usual and desired activity. Although fatigue may be
difficult to differentiate from sleepiness, it is a clinically different symptom. Sleepiness
is the tendency to fall asleep or doze off. Some reports that the prevalence of moderate to
severe sleep problems in MS is significantly higher than in the general population 51.5% vs
33.1%. It has also been reported that poor sleep can correlate with depression in subject
with MS. Few studies have examined the effect of stimulants, amantadine or modafinil for
treatment of fatigue and have shown contradictory data as effective treatments in MS
patients.

Obstructive sleep apnea (OSA) has also been seen described in MS. Few case reports studies
have reported that MS patients with OSA treated with continuous positive airway pressure
(CPAP) had improvement in fatigue but not quality of life. Although the prevalence of OSA in
the MS population is unknown, it may as much as twice as common as in the general
population, which is 3 to 7%. Aside from the increased risk of daytime sleepiness, mood
disorders, cardiovascular risk factors and accidents, OSA has also been implicated in
increasing inflammatory markers like tumor necrosis factor (TNF-α). Elevation in TNF-α has
also been seen in MS patients complaining of fatigue, which is thought to play a role in
pathophysiology of fatigue in MS. The rational of this study is to determine if treatment of
OSA with CPAP in MS patients improves fatigue. If effective, CPAP may not only decrease the
risk of long term complications but may also improve the quality of life and daily living of
these patients.

Inclusion Criteria:

- 18-65 years old

- Diagnosis of clinical MS as defined by the 2010 McDonald criteria

- Have either relapsing remitting, primary progressive or secondary progressive forms
of MS

- expanded disability status scale ≤5

- Complaint of fatigue defined subjective lack of physical and/or mental energy that is
perceived by the individual or caregiver to interfere with the usual and desired
activity.

- Berlin questionnaire score of ≥2 35

- Mild to moderate OSA defined as Apnea hypopnea index (AHI) of ≥ 5 and < 30
events/hour on baseline ambulatory PSG

Exclusion Criteria:

- Prior diagnosis, past or current treatment for sleep related breathing disorder

- Severe sleep apnea defined as AHI ≥ 30 events/hour on baseline ambulatory PSG,

- Prior diagnosis of restless leg syndrome, parasomnias, insomnia, and narcolepsy

- Prior diagnosis of pulmonary disease: asthma, chronic obstructive pulmonary disease
and bronchiectasis

- Diagnosis of clinical depression or Center for epidemiologic studies-depression
scale(CES-D)score of ≥ 16 36,37

- An acute MS exacerbation in the last 3 months. If patient has an acute exacerbation
during the study, the patient will be excluded from the study as this can be a cause
fatigue

- Started on any disease modifying treatment (either primary or second line agents) or
have switched to a second therapy in the last 6 month poor sleep and fatigue can be
side effects.

- Current use of sedative-hypnotics medications, tricyclic, antidepressants, or
trazodone.

- Started or change in dose within the last 3 months of amantadine, modafinil,
armodafinil, or other stimulating agent for MS related fatigue

- Pregnancy

- Unstable medical or psychiatric condition