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ABSTRACT. Objective. To determine the effects of bedtime very low dose (VLD) cyclobenzaprine (CBP) on symptoms and sleep physiology of patients with fibromyalgia (FM), unrefreshing sleep, and the α-nonREM sleep electroencephalographic (EEG) anomaly at screening. Methods. Of 37 patients with FM in the screened population, 36 were randomized and treated in this 8-week, double-blind, placebo-controlled, dose-escalating study of VLD CBP 1-4 mg at bedtime. We evaluated changes in subjective symptoms including pain, tenderness, fatigue, mood [Hospital Anxiety and Depression Scale (HAD)], and objective EEG sleep physiology (at screening, baseline, and Weeks 2, 4, and 8). Results. In the VLD CBP-treated group (n = 18) over 8 weeks, musculoskeletal pain and fatigue decreased, tenderness improved; total HAD score and the HAD depression subscore decreased; patient-rated and clinician-rated fatigue improved. In the placebo-treated group (n = 18), none of these outcome measures changed significantly. Compared to placebo at 8 weeks, VLD CBP significantly improved pain, tenderness, and the HAD Depression subscore. Analysis of cyclic alternating pattern (CAP) sleep EEG revealed that significantly more subjects in the VLD CBP group than the placebo group had increased nights of restorative sleep in which CAP A2+A3 /CAP A1+A2+A3 = CAP A2+A3(Norm) ≤ 33%. For VLD CBP-treated subjects, the increase in nights with CAP A2+A3(Norm) ≤ 33% was correlated to improvements in fatigue, total HAD score, and HAD depression score. Fibromyalgia syndrome (FM) is a common, chronic musculoskeletal pain disorder, diagnosed predominantly in women, that is characterized by widespread pain, increased sensitivity to pain (or tenderness) at multiple tender points, fatigue, unrefreshing sleep, and depressed mood 1 . Cyclobenzaprine (CBP) has been studied in FM in a number of randomized trials employing doses of 10-40 mg per day, with mixed result

Sleep assessment in a population-based study of chronic fatigue syndrome

BACKGROUND: Chronic fatigue syndrome (CFS) is a disabling condition that affects approximately 800,000 adult Americans. The pathophysiology remains unknown and there are no diagnostic markers or characteristic physical signs or laboratory abnormalities. Most CFS patients complain of unrefreshing sleep and many of the postulated etiologies of CFS affect sleep. Conversely, many sleep disorders present similarly to CFS. Few studies characterizing sleep in unselected CFS subjects have been published and none have been performed in cases identified from population-based studies. METHODS: The study included 339 subjects (mean age 45.8 years, 77% female, 94.1% white) identified through telephone screen in a previously described population-based study of CFS in Wichita, Kansas. They completed questionnaires to assess fatigue and wellness and 2 self-administered sleep questionnaires. Scores for five of the six sleep factors (insomnia/hypersomnia, non-restorative sleep, excessive daytime somnolence, sleep apnea, and restlessness) in the Centre for Sleep and Chronobiology's Sleep Assessment Questionnaire(© )(SAQ(©)) were dichotomized based on threshold. The Epworth Sleepiness Scale score was used as a continuous variable. RESULTS: 81.4% of subjects had an abnormality in at least one SAQ(© )sleep factor. Subjects with sleep factor abnormalities had significantly lower wellness scores but statistically unchanged fatigue severity scores compared to those without SAQ(© )abnormality. CFS subjects had significantly increased risk of abnormal scores in the non-restorative (adjusted odds ratio [OR] = 28.1; 95% confidence interval [CI]= 7.4–107.0) and restlessness (OR = 16.0; 95% CI = 4.2–61.6) SAQ(© )factors compared to non-fatigued, but not for factors of sleep apnea or excessive daytime somnolence. This is consistent with studies finding that, while fatigued, CFS subjects are not sleepy. A strong correlation (0.78) of Epworth score was found only for the excessive daytime somnolence factor. CONCLUSIONS: SAQ(© )factors describe sleep abnormalities associated with CFS and provide more information than the Epworth score. Validation of these promising results will require formal polysomnographic sleep studies

Tourette syndrome and neuropsychological performance

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65659/1/j.1600-0447.1991.tb03131.x.pd

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ABSTRACT. Objective. To determine the effects of sodium oxybate (SXB) on sleep physiology and sleep/wakerelated symptoms in patients with fibromyalgia syndrome (F

Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study

<p>Abstract</p> <p>Background</p> <p>The long term adverse effects of Severe Acute Respiratory Syndrome (SARS), a viral disease, are poorly understood.</p> <p>Methods</p> <p>Sleep physiology, somatic and mood symptoms of 22 Toronto subjects, 21 of whom were healthcare workers, (19 females, 3 males, mean age 46.29 yrs.+/- 11.02) who remained unable to return to their former occupation (mean 19.8 months, range: 13 to 36 months following SARS) were compared to 7 healthy female subjects. Because of their clinical similarities to patients with fibromyalgia syndrome (FMS) these post-SARS subjects were similarly compared to 21 drug free female patients, (mean age 42.4 +/- 11.8 yrs.) who fulfilled criteria for fibromyalgia.</p> <p>Results</p> <p>Chronic post-SARS is characterized by persistent fatigue, diffuse myalgia, weakness, depression, and nonrestorative sleep with associated REM-related apneas/hypopneas, an elevated sleep EEG cyclical alternating pattern, and alpha EEG sleep anomaly. Post- SARS patients had symptoms of pre and post-sleep fatigue and post sleep sleepiness that were similar to the symptoms of patients with FMS, and similar to symptoms of patients with chronic fatigue syndrome. Both post-SARS and FMS groups had sleep instability as indicated by the high sleep EEG cyclical alternating pattern rate. The post-SARS group had a lower rating of the alpha EEG sleep anomaly as compared to the FMS patients. The post-SARS group also reported less pre-sleep and post-sleep musculoskeletal pain symptoms.</p> <p>Conclusions</p> <p>The clinical and sleep features of chronic post-SARS form a syndrome of chronic fatigue, pain, weakness, depression and sleep disturbance, which overlaps with the clinical and sleep features of FMS and chronic fatigue syndrome.</p

Autonomic pain responses during sleep: a study of heart rate variability

The autonomic nervous system (ANS) reacts to nociceptive stimulation during sleep, but whether this reaction is contingent to cortical arousal, and whether one of the autonomic arms (sympathetic/parasympathetic) predominates over the other remains unknown. We assessed ANS reactivity to nociceptive stimulation during all sleep stages through heart rate variability, and correlated the results with the presence of cortical arousal measured in concomitant 32-channel EEG. Fourteen healthy volunteers underwent whole-night polysomnography during which nociceptive laser stimuli were applied over the hand. RR intervals (RR) and spectral analysis by wavelet transform were performed to assess parasympathetic (HF(WV)) and sympathetic (LF(WV) and LF(WV)/HF(WV) ratio) reactivity. During all sleep stages, RR significantly decreased in reaction to nociceptive stimulations, reaching a level similar to that of wakefulness, at the 3rd beat post-stimulus and returning to baseline after seven beats. This RR decrease was associated with an increase in sympathetic LF(WV) and LF(WV)/HF(WV) ratio without any parasympathetic HF(WV) change. Albeit RR decrease existed even in the absence of arousals, it was significantly higher when an arousal followed the noxious stimulus. These results suggest that the sympathetic-dependent cardiac activation induced by nociceptive stimuli is modulated by a sleep dependent phenomenon related to cortical activation and not by sleep itself, since it reaches a same intensity whatever the state of vigilance

Mitochondrial myopathy presenting as fibromyalgia: a case report

<p>Abstract</p> <p>Introduction</p> <p>To the best of our knowledge, we describe for the first time the case of a woman who met the diagnostic criteria for fibromyalgia, did not respond to therapy for that disorder, and was subsequently diagnosed by biochemical and genetic studies with a mitochondrial myopathy. Treatment of the mitochondrial myopathy resulted in resolution of symptoms. This case demonstrates that mitochondrial myopathy may present in an adult with a symptom complex consistent with fibromyalgia.</p> <p>Case presentation</p> <p>Our patient was a 41-year-old Caucasian woman with symptoms of fatigue, exercise intolerance, headache, and multiple trigger points. Treatment for fibromyalgia with a wide spectrum of medications including non-steroidal anti-inflammatory drugs, antidepressants, gabapentin and pregabalin had no impact on her symptoms. A six-minute walk study demonstrated an elevated lactic acid level (5 mmol/L; normal < 2 mmol/L). Biochemical and genetic studies from a muscle biopsy revealed a mitochondrial myopathy. Our patient was started on a compound of coenzyme Q10 (ubiquinone) 200 mg, creatine 1000 mg, carnitine 200 mg and folic acid 1 mg to be taken four times a day. She gradually showed significant improvement in her symptoms over a course of several months.</p> <p>Conclusions</p> <p>This case demonstrates that adults diagnosed with fibromyalgia may have their symptom complex related to an adult onset mitochondrial myopathy. This is an important finding since treatment of mitochondrial myopathy resulted in resolution of symptoms.</p

Identification of symptom and functional domains that fibromyalgia patients would like to see improved: a cluster analysis

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to determine whether some of the clinical features of fibromyalgia (FM) that patients would like to see improved aggregate into definable clusters.</p> <p>Methods</p> <p>Seven hundred and eighty-eight patients with clinically confirmed FM and baseline pain ≥40 mm on a 100 mm visual analogue scale ranked 5 FM clinical features that the subjects would most like to see improved after treatment (one for each priority quintile) from a list of 20 developed during focus groups. For each subject, clinical features were transformed into vectors with rankings assigned values 1-5 (lowest to highest ranking). Logistic analysis was used to create a distance matrix and hierarchical cluster analysis was applied to identify cluster structure. The frequency of cluster selection was determined, and cluster importance was ranked using cluster scores derived from rankings of the clinical features. Multidimensional scaling was used to visualize and conceptualize cluster relationships.</p> <p>Results</p> <p>Six clinical features clusters were identified and named based on their key characteristics. In order of selection frequency, the clusters were Pain (90%; 4 clinical features), Fatigue (89%; 4 clinical features), Domestic (42%; 4 clinical features), Impairment (29%; 3 functions), Affective (21%; 3 clinical features), and Social (9%; 2 functional). The "Pain Cluster" was ranked of greatest importance by 54% of subjects, followed by Fatigue, which was given the highest ranking by 28% of subjects. Multidimensional scaling mapped these clusters to two dimensions: Status (bounded by Physical and Emotional domains), and Setting (bounded by Individual and Group interactions).</p> <p>Conclusion</p> <p>Common clinical features of FM could be grouped into 6 clusters (Pain, Fatigue, Domestic, Impairment, Affective, and Social) based on patient perception of relevance to treatment. Furthermore, these 6 clusters could be charted in the 2 dimensions of Status and Setting, thus providing a unique perspective for interpretation of FM symptomatology.</p