A case-control sleep study in children with polyarticular juvenile rheumatoid arthritis

OBJECTIVE: To investigate the relationship between clinical manifestations and sleep abnormalities in patients with juvenile rheumatoid arthritis (JRA). METHODS: Twenty-one patients with active polyarticular JRA and 20 healthy controls were enrolled consecutively. Pain and functional impairment were assessed with standardized, validated Brazilian questionnaires. Sleep evaluation was based on parent reporting of their child's sleep habits and polysomnography; subjects underwent an adaptation night in the sleep laboratory. Sleep architecture was analyzed and spectral analysis of non-rapid eye movement (REM) sleep was carried out by electroencephalography. RESULTS: Patients with JRA exhibited higher indexes of periodic leg movements (PLM; p = 0.02), isolated leg movements (LM), and arousals, as well as increases in alpha activity in non-REM sleep (all p < 0.01), in spite of similar frequency of sleep complaints in comparison to controls. Among JRA patients, greater alpha activity in non-REM sleep was observed in the participants with greater joint involvement assessed by the Escola Paulista de Medicina-Pediatric Range of Motion Scale (p = 0.03) or joint count (p = 0.02). Correlation was observed between morning stiffness and PLM and/or LM (rS = 0.75, Sr = 0.74, p < 0.001 for both), and between self-rating scores of pain and alpha activity in non-REM sleep (rS = 0.74, p < 0.001). CONCLUSION: Pain symptoms and disability are related to sleep fragmentation in patients with active polyarticular JRA.     

Cyclic alternating pattern: a new marker of sleep alteration in patients with fibromyalgia?

OBJECTIVE: In the dynamic organization of sleep, cyclic alternating pattern (CAP) expresses a condition of instability of the level of vigilance that manifests the brain's fatigue in preserving and regulating the macrostructure of sleep. We evaluated the presence of CAP in patients with fibromyalgia (FM) compared to healthy controls. METHODS: Forty-five patients with FM (42 women) were studied and compared with 38 healthy subjects (36 women) matched for age, sex, and body mass index. Entry criteria were diagnosis of FM according to 1990 American College of Rheumatology criteria; willingness to participate in the study; and having no other diagnosis of autoimmune, neoplastic, or other possible causes of secondary diffuse musculoskeletal pain. Patients in the study underwent polysomnography recordings and a sleep questionnaire. Hypersomnolence was evaluated according to the Epworth Sleepiness Scale. RESULTS: FM patients had less sleep efficiency (sleep time/time in bed) than controls (79 +/- 10 vs 89 +/- 6; p < 0.01), a higher proportion of stage 1 non-rapid eye movement (non-REM) sleep (20 +/- 5 vs 12 +/- 5; p < 0.001), and twice as many arousals per hour of sleep (9.7 +/- 3.3 vs 4.1 +/- 1.9; p < 0.01). The CAP rate (total CAP time/non-REM sleep time) was significantly increased in FM patients compared to controls (68 +/- 6% vs 45 +/- 11%; p < 0.001). CAP rate seemed to correlate with the severity of clinical symptoms in FM patients (tender points index; p < 0.01) and with less efficiency of sleep (p < 0.01). CONCLUSION: The increase of CAP rate indicates a worse quality of sleep in patients with FM. These data are strongly correlated to the severity of symptoms.     

The effects of cyclobenzaprine on sleep physiology and symptoms in patients with fibromyalgia

A double blind, placebo controlled, crossover design study examined overnight sleep physiology, pain, fatigue, and mood symptoms in 12 patients with fibromyalgia treated with cyclobenzaprine. Nine patients completed the study. Patients receiving cyclobenzaprine showed a decrease in evening fatigue (F = 4.7, p less than 0.05) and an increase in total sleep time (F = 4.4, p less than 0.05). Pain, including tender point count and dolorimetry, mood ratings, and alpha non-REM EEG sleep anomaly were unchanged by cyclobenzaprine.     

Management of sleep disorders in fibromyalgia

In summary, the treatment of patients with FM requires a proper assessment of the reason for the unrefreshing sleep, which is an important component of the FM syndrome. Sleep laboratory investigations provides a suitable rationale for management where a specific primary sleep disorder is determined. Nonspecific treatments include various behavioral approaches to improve sleep hygiene, fitness, and regular proper nutrition that serve to regularize disturbances in circadian sleep-wake rhythms. As yet, no medication is known to improve the EEG sleep arousal disorders that include phasic (alpha-delta), tonic alpha non-REM sleep disorders, or the periodic K alpha cycling alternating pattern disorder. Traditional hypnotic agents, while helpful in initiating and maintaining sleep and reducing daytime tiredness, do not provide restorative sleep or reduce pain. Tricyclic drugs, such as amitriptyline and cyclobenzaprine, may provide long term benefit for improving sleep but may not have a continuing benefit beyond one month for reducing pain. The use of a biologic agent that facilitates sleep-related neuroendocrine functions, for example growth hormone, is reported to improve symptoms but the need for injection and high cost restrict its use. No systematic studies have been reported on the use of remedial measures for the management of PLMS/restless legs syndrome and sleep apnea that occur in some patients with FM.     

Sleep-Related Autonomic Disturbances in Symptom Subgroups of Women with Irritable Bowel Syndrome

The objective was to investigate whether predominant symptom patterns in women with irritable bowel syndrome (IBS) affect autonomic activity during sleep. Seventy-five women with IBS underwent a polysomnographic sleep study. Twenty-two of the IBS patients were diarrhea-predominant (IBS-D), 33 were constipation-predominant (IBS-C), and 20 patients had alternating symptoms (IBS-A). Autonomic activity was measured by heart rate variability. The IBS-D group had significant vagal withdrawal compared to the IBS-A group during REM and non-REM sleep (P < 0.05). The IBS-D symptom subgroup had significantly (P < 0.05) greater sympathetic dominance during non-REM than IBS-A patients. Lower abdominal pain correlated with sympathetic dominance during sleep in the IBS-D group (r=0.54, P < 0.01). The IBS-D patients were physiologically distinct with regard to autonomic functioning during sleep compared to the alternating patients, but not the constipated patients. Sleep appears to unmask differences in autonomic activity that may distinguish IBS patients.     

Fatigue in systemic lupus erythematosus: contributions of disordered sleep, sleepiness, and depression

OBJECTIVE: To clarify the role of sleep disorders, sleepiness, and depression in patients with systemic lupus erythematosus (SLE) who complain of disabling tiredness. METHODS: Patients with SLE (31 women, 4 men) with disabling tiredness were evaluated with the Epworth Sleepiness Scale (ESS) and overnight polysomnography, followed by daytime multiple sleep latency tests (MSLT) and the Beck Depression Inventory (BDI). Their polysomnography was compared with 17 healthy, asymptomatic controls. RESULTS: Polysomnography of the patients in comparison with healthy controls showed impaired sleep efficiency (p < 0.02), high arousal frequencies (p < 0.01), increased stage 1 sleep (p < 0.02), decreased stage 3/4 slow-wave sleep (p < 0.02), and a high percentage (77% of patients) with increased alpha-EEG non-REM sleep. In 23% of patients periodic limb movement (PLM) disorder was observed (mean PLM index 31.1 +/- 15); 26% of patients had obstructive sleep apnea (mean apnea/hypopnea index 19.3 +/- 10), and one patient had narcolepsy-cataplexy. Remarkably, 51% of patients were excessively sleepy on both the ESS and MSLT (mean sleep latency < 10 min). This excessive daytime sleepiness was not related to sleep restriction. There was no association between sleepiness and SLE disease features such as neuropsychiatric SLE, medications, fibromyalgia, or disease activity. As a whole, the study group reported mild to moderate depression (mean BDI = 15.8 +/- 9.9). Within the group, the sleepy patients had lower BDI scores than the non-sleepy patients (p < 0.02), and fewer of the sleepy patients were depressed (p < 0.04). CONCLUSION: Primary sleep disorders, sleepiness, and depression are common in tired SLE patients. Tiredness in SLE that is the result of excessive daytime sleepiness can be distinguished from tiredness of depression. Such distinctions will help identify appropriate treatment for tired patients with SLE.     

Hypersomnolence in fibromyalgia syndrome

OBJECTIVE: To evaluate hypersomnolence in patients affected by fibromyalgia syndrome. METHODS: Thirty consecutive patients affected by fibromyalgia syndrome (FMS) (28 F) completed a sleep questionnaire and underwent the following evaluations: lung function tests; polysomnography; the Epworth sleepiness scale (ESS), which measures sleep complaints and daytime hypersomnolence; and the visual analogical scale (VAS) to detect subjective pain, fatigue, anxiety and depression. RESULTS: The FMS patients were divided into two groups based on their ESS score. Patients complaining of daytime hypersomnolence had a higher number of tender points (15 +/- 2 vs. 12 +/- 1, p < 0.01), a higher subjective pain score (72 +/- 15 vs. 52 +/- 13, p < 0.05), and more fatigue (p < 0.05). The diffusing capacity of the lung (Tlco) was more impaired and the occurrence of periodic breathing was higher. FMS patients complaining of daytime somnolence had significantly less efficient sleep than the FMS patients with no daytime somnolence (p < 0.05), i.e. a lower proportion of stage 3 sleep (5 +/- 2% vs. 12 +/- 3%; p < 0.001), stage 4 sleep (1 +/- 0.5% vs. 4 +/- 1%; p < 0.001), and twice as many arousals per hour of sleep (p < 0.01). The respiratory pattern of FMS patients with hypersomnolence showed a higher occurrence of periodic breathing (p < 0.05). The short length of apneas and hypopnoeas did not affect the apnea/hypopnea index (5.1 +/- 3 vs. 7 +/- 4; ns), but FMS patients with daytime hypersomnolence had a greater number of desaturations per hour of sleep (11 +/- 6 vs. 6 +/- 5; p < 0.05). Pulmonary volumes did not differ between the two groups. The EES score was significantly correlated in FMS patients, and even more markedly in the FMS patients with hypersomnolence, TLco, A/I, and disease duration. The ESS score was correlated significantly with the number of tender points only in FMS patients with daytime hypersomnolence. CONCLUSION: The occurrence of daytime hypersomnolence in FMS patients is linked to a greater severity of fibromyalgia symptoms and to more severe polysomnographic alterations.     

Endogenous excitatory drive modulating respiratory muscle activity across sleep-wake states

RATIONALE: The concept of a tonic drive activating respiratory muscle in wakefulness but not sleep has been an important and enduring notion in respiratory medicine, not least because it is useful in modeling sleep effects on breathing and understanding the pathogenesis of sleep-related breathing disorders such as obstructive sleep apnea. However, a neurotransmitter substrate mediating respiratory muscle activation across sleep-wake states has not been identified. OBJECTIVES: We determined if alpha1 receptor antagonism at the hypoglossal motor nucleus (HMN) decreases genioglossus (GG) activity consistent with a role for an endogenous noradrenergic drive contributing to GG activation across sleep-wake states. We also determined if alpha1 receptor stimulation could counteract reduced endogenous noradrenergic drive and increase sleeping GG activity. METHODS: Thirty-five rats were implanted with electroencephalogram and neck electrodes to record sleep-wake states and GG and diaphragm electrodes for respiratory muscle recordings. Microdialysis probes were inserted into the HMN. MEASUREMENTS AND MAIN RESULTS: Microdialysis perfusion of the alpha1 receptor antagonist terazosin into the HMN significantly decreased GG activity in wakefulness and nonrapid eye movement (non-REM) sleep but not REM sleep. The alpha1 receptor agonist phenylephrine increased GG activity in wakefulness and sleep, but periods of motor inactivity persisted in REM sleep; there was no potentiating effect of combined alpha1 and 5-HT2 receptor stimulation. CONCLUSIONS: Identification of an endogenous noradrenergic drive contributing to GG activation in wakefulness and non-REM sleep, but not REM sleep, is important given the prevalence and clinical significance of sleep-induced hypoventilation and obstructive sleep apnea in humans and the potential for pharmacologic treatment.     

Factors that affect the number of tender points in fibromyalgia and chronic widespread pain patients who did not meet the ACR 1990 criteria for fibromyalgia: are tender points a reflection of neuropathic pain?

OBJECTIVE: This study aims to compare fibromyalgia (FM) and chronic widespread pain (CWP) patients who do not fulfill the criteria for tender points (TP). METHODS: We included 150 patients diagnosed with FM according to ACR 1990 criteria and 42 patients with CWP who did not fulfill TP criteria for FM into the study. The clinical features of the patients were recorded, and the TP count was determined. By means of a visual analog scale (VAS), all patients were questioned about the severity of pain and FM-related symptoms. In addition, the patients were administered the Duke Anxiety Depression (Duke-AD) scale and somatization symptom questionnaire. Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale was used to determine the neuropathic pain score. RESULTS: According to VAS, the severity of pain, sleep disturbance, the number of somatization symptoms, LANSS, and Duke-AD scores were significantly higher in FM patients than in patients with CWP (all P values <0.05). The number of TP correlated with severity of pain (r = 0.32, P < 0.001), the number of somatization symptoms (r = 0.26, P = 0.01), sleep disturbance (r = 0.18, P = 0.01), and LANSS score (r = 0.4, P < 0.001). Multiple logistic regression analysis revealed that independent factors that affected the presence of > or =11 TP were the severity of pain on VAS (OR: 1.03, 95% CI: 1.01-1.06, P = 0.045) and LANSS score (OR: 1.36, 95% CI: 1.12-1.62, P = 0.001). CONCLUSIONS: CWP patients have symptoms similar to FM patients, though less severe. The most important factor that affects the criteria for fulfilling the number TP in CWP patients is the neuropathic pain score, which suggests that FM is primarily a neuropathic pain syndrome.     

Upper airway muscle activation is augmented in patients with obstructive sleep apnea compared with that in normal subjects

Although phasic electromyographic (EMG) activity of upper airway muscles in patients with obstructive sleep apnea (OSA) decreases at apnea onset, the presence of phasic activity in normal subjects has not been studied and compared with that in patients. We consequently compared the percentage of total sleep time in which phasic activity of the genioglossal EMG activity was present in 8 adult patients with OSA and 3 control groups without OSA, one consisting of 6 young, normal subjects, one matched for age, and one matched for age and obesity. From wakefulness to sleep, genioglossal EMG phasic activity time increased in patients but not in control subjects. Patients with OSA had more phasic genioglossal group EMG activity during non-REM sleep than did control subjects. At apnea onset, phasic EMG activity decreased in patients but remained greater than zero. In many control subjects, phasic activity was not detected, yet their pharyngeal airway remained patent. We conclude that phasic genioglossal group EMG activity occurs more frequently during sleep in patients with OSA than in control subjects, suggesting that it is a compensatory mechanism that occurs when patency of the pharyngeal airway is precarious.     

Sleep electroencephalography and the clinical response to amitriptyline in patients with fibromyalgia

Objective. To determine the prevalence and clinical correlations of an anomaly consisting of electroencephalographic (EEG) waves within the alpha frequency band during non–rapid eye movement (NREM) sleep in patients with fibromyalgia, and to evaluate the alpha NREM sleep anomaly as a predictor of response to amitriptyline. Methods. Twenty-two patients with fibromyalgia were studied in a 2-month, double-blind, crossover trial of amitriptyline (25 mg/day) versus placebo. Nocturnal EEGs were conducted on 2 consecutive nights at baseline and at the end of each 2-month treatment period. Results. Six patients (27%) had a clinical response to amitriptyline, while none responded to placebo (P = 0.02). Treatment with amitriptyline or placebo did not result in any changes in the alpha ratings during NREM sleep. Only 8 patients (36%) exhibited the alpha NREM sleep anomaly at baseline. Those patients reported more sleep difficulty, but otherwise were clinically indistinguishable from those without this EEG sleep anomaly. Lower baseline alpha NREM sleep ratings were seen in responders to amitriptyline than in nonresponders, but these differences did not reach statistical significance. Conclusion. The alpha NREM sleep anomaly is present in only a small proportion of patients with fibromyalgia. It does not correlate with disease severity nor is it affected by treatment with amitriptyline. A larger sample size will be needed to adequately assess the value of this sleep anomaly in predicting the response to amitriptyline.     

Central sympathetic inhibition augments sleep-related ultradian rhythm of parasympathetic tone in patients with chronic heart failure.

BACKGROUND: Abnormal sleep dynamics in patients with heart failure is one of the mechanisms for the relative predominance of central sympathetic outflow over parasympathetic tone. This study was designed to examine whether central sympathoinhibition could improve the sympathovagal imbalance related to rapid-eye-movement (REM)/non-REM ultradian sleep rhythm in these patients. METHODS AND RESULTS: Beat-by-beat RR intervals of overnight electrocardiogram were serially subject to power spectral analysis in 14 patients with chronic heart failure and 13 age-matched subjects with normal cardiac function. To assess autonomic sleep dynamics, the ultradian rhythm was extracted from all-night consecutive high-frequency (HF) components of heart rate variability (HRV) before and after administration of an (alpha2)-adrenergic agonist, guanfacine. Night-time HRV in heart failure was characterized by an attenuated ultradian rhythm of HF-components with a concomitant reduction in averaged HF power. Guanfacine reduced blood pressure, heart rate, and plasma norepinephrine concentrations by 7%, 8%, and 34% (p < 0.01), respectively. After guanfacine, HF power rose by 154% (p < 0.01) with a prominent augmentation of the all-night ultradian rhythm (+361%, p < 0.01). CONCLUSIONS: Central sympathoinhibition augments a sleep-related ultradian rhythm of parasympathetic tone, suggesting a potential benefit to autonomic balancing and sleep quality in patients with chronic heart failure.     

Pain and fatigue in patients with rheumatic disorders

Summary The purpose of the study was to investigate whether fibromyalgia patients (n=50) differed from patients with rheumatoid arthritis (n=22) and ankylosing spondylitis (n=31) with respect to pain experience, pain coping and fatigue. A high general pain intensity level was recorded by the McGill Pain Questionnaire (p<0.01) and the visual analogue scale (p<0.01) in the fibromyalgia group compared to the other groups. The pain was of continuous duration in the fibromyalgia patients while the rheumatoid arthritis and ankylosing spondylitis patients experienced intermittent pain. A high correlation between sensory and affective pain rating indexes was determined in all patient groups (p<0.01). No statistically significant difference between the groups in pain coping was recorded. A high frequency of reported gastrointestinal problems (p<0.01) and high intensity of fatigue (p<0.01) were seen in the fibromyalgia group compared to the other groups. In the fibromyalgia group there was no correlation between the sleep problems and fatigue intensity. Thus, the fibromyalgia patients differed from the other groups in reporting frequently shoulder and upper arm pain, continuous pain, higher levels of fatigue and pain intensities as well as high frequency of gastrointestinal problems.     

Apnea duration and hypoxemia during REM sleep in patients with obstructive sleep apnea

Nocturnal sleep studies of 12 patients with obstructive sleep apnea and a matched control group of 12 subjects without the sleep apnea syndrome were analyzed to compare arterial oxyhemoglobin saturation (SaO2) during REM and non-REM sleep. Mean percentage of total sleep time spent in REM sleep was not significantly different in patients with obstructive sleep apnea and in subjects without significant apnea (14.2 +/- SEM 2.2 percent in patients vs 12.0 +/- 2.2 percent in nonapnea subjects). Apneas were longer during REM than non-REM sleep in all 12 patients (p less than 0.01). Oxyhemoglobin desaturations were more frequent during REM than non-REM sleep in both apnea patients and the control subjects. In addition, there was a greater mean fall in SaO2 per desaturation episode in both the apnea patients and non-apnea subjects. We conclude: 1) sleep apneas are longer during REM sleep than non-REM sleep in patients with obstructive sleep apnea; 2) hypoxemia is greater during REM sleep than non-REM sleep in subjects with and without the sleep apnea syndrome.     

Fibromyalgia and headache: an epidemiological study supporting migraine as part of the fibromyalgia syndrome

Fibromyalgia is defined by widespread body pain, tenderness to palpation of tender point areas, and constitutional symptoms. The literature reports headache in about half of fibromyalgia patients. The current epidemiological study was designed to determine the prevalence and characteristics of headache in fibromyalgia patients. Treatment-seeking fibromyalgia patients were evaluated with measures for fibromyalgia, chronic headache, quality of life, and psychological distress. Multivariate analysis of variance (MANOVA) and t-tests were used to identify significant differences, as appropriate. A total of 100 fibromyalgia patients were screened (24 fibromyalgia without headache and 76 fibromyalgia with headache). International Headache Society diagnoses included: migraine alone (n=15 with aura, n=17 without aura), tension-type alone (n=18), combined migraine and tension-type (n=16), post-traumatic (n=4), and probable analgesic overuse headache (n=6). Fibromyalgia tender point scores and counts and most measures of pain severity, sleep disruption, or psychological distress were not significantly different between fibromyalgia patients with and without headache. As expected, the fibromyalgia patients with headache scored higher on the Headache Impact Test (HIT-6) (62.1±0.9 vs 48.3±1.6, p<0.001). HIT-6 scores were >60 in 80% of fibromyalgia plus headache patients, representing severe impact from headache, and 56–58 in 4%, representing substantial impact. In summary, chronic headache was endorsed by 76% of treatment-seeking fibromyalgia patients, with 84% reporting substantial or severe impact from their headaches. Migraine was diagnosed in 63% of fibromyalgia plus headache patients, with probable analgesic overuse headache in only 8%. General measures of pain, pain-related disability, sleep quality, and psychological distress were similar in fibromyalgia patients with and without headache. Therefore, fibromyalgia patients with headache do not appear to represent a significantly different subgroup compared to fibromyalgia patients without headache. The high prevalence and significant impact associated with chronic headache in fibromyalgia patients, however, warrants inclusion of a headache assessment as part of the routine evaluation of fibromyalgia patients.     

Determinants of sleep quality in women with systemic lupus erythematosus

OBJECTIVE: To characterize sleep complaints in women with systemic lupus erythematosus (SLE) and to identify correlates of sleep quality. METHODS: Sleep quality in 100 women with SLE was assessed using the Pittsburgh Sleep Quality Index (PSQI). Participants completed standardized questionnaires assessing depressed mood, leisure time physical activity, functional disability, and pain severity. A clinical examination determined disease activity, cumulative damage, and whether patients fulfilled the American College of Rheumatology criteria for fibromyalgia. A series of hierarchical multiple regressions were computed. RESULTS: The mean +/- SD global PSQI score was 6.98 +/- 4.03, with moderate to severe sleep impairment reported by 56% of the sample. The first model testing the importance of demographic factors was not statistically significant. In the disease-related model, the use of prednisone and functional disability both contributed to poor sleep quality (P < 0.001). The addition of level of exercise participation to the demographic set significantly added to the model (P = 0.001). Depression significantly added to the demographic set, explaining 29% of the variance (P < 0.0001). When these variables, along with disease related variables, were simultaneously regressed on the PSQI Global Score, only depressed mood appeared as a significant independent determinant of global sleep quality (P < 0.001). However, the point estimates for the Beta coefficients were consistent with effects for lack of exercise and prednisone use. CONCLUSION: A significant proportion of women with SLE suffer from poor sleep quality. The findings suggest that depressed mood, prednisone use, and lack of exercise contribute to decreased overall sleep quality.     

Impact of fibromyalgia pain on health-related quality of life before and after treatment with tramadol/acetaminophen

OBJECTIVE: To assess health-related quality of life (HRQOL) in patients with moderate-to-severe fibromyalgia pain compared with the general population, and to assess the relationship between pain severity and HRQOL before and after treatment with an analgesic. METHODS: Data were obtained from a randomized, double-blind study of patients with moderate-to-severe fibromyalgia pain. Patients received either tramadol/acetaminophen or placebo 4 times/day as needed for 91 days. HRQOL was measured with the Short Form 36 Health Survey (SF-36) and the Fibromyalgia Impact Questionnaire (FIQ). Baseline HRQOL scores were compared with a national sample of noninstitutionalized adults and a sample of patients with impaired HRQOL due to congestive heart failure. Patients with fibromyalgia were divided into tertiles by change in pain severity, and SF-36 scores were compared across the tertiles. Mean changes in SF-36 and FIQ scores were compared between treatment groups. RESULTS: Patients with fibromyalgia scored lower than the US norm on all SF-36 scales (P < 0.0001) and lower than patients with congestive heart failure on most scales. More severe pain was associated with greater impairment of HRQOL compared with less severe pain (P < 0.0001). Patients in the highest tertile for improved pain severity had greater improvement in HRQOL scores than patients in the lower tertiles. Compared with patients who received placebo (n = 157), patients treated with tramadol/acetaminophen (n = 156) showed greater improvement on SF-36 physical functioning, role physical, bodily pain, and physical summary scales, as well as FIQ scales for ability to do job, pain, and stiffness (P < 0.01). CONCLUSION: Moderate-to-severe fibromyalgia pain significantly impairs HRQOL, and effective pain relief in these patients significantly increases HRQOL.     

Cold-induced vasospasm in patients with fibromyalgia and chronic low back pain in comparison to healthy subjects

Summary Using capillary videomicroscopy of the nail fold, the frequency of cold-induced vasospasm and capillary hemodynamic parameters were studied after application of cold in 50 patients with primary fibromyalgia, 50 patients with chronic low back pain, and 50 healthy controls. Cold-induced vasospasm was detected in 38% of the patients with fibromyalgia. In this group it was significantly more frequent than in the patients with chronic low back pain (20%, p<0.05) and healthy subjects (8%, p<0.001). In the fibromyalgia group, the magnitude of vasospasm as measured by the capillary blood flow deceleration after cold application correlated negatively with the pain intensity as measured by pain score (r=–0.3839, p<0.01). No differences in clinical appearance were found between patients with and without cold-induced vasospasm in both the fibromyalgia and low back pain group.     

Sleep and duodenal motor activity in patients with severe non-ulcer dyspepsia.

The prevalence of sleep disturbances was studied in patients with severe non-ulcer dyspepsia. It was also considered if the change in sleep pattern was associated with changes in the rhythmic fasting motor activity of the gastrointestinal tract, and if motor events correlate with the patient's symptoms. Motor activity in the duodenum was monitored over a 24 hour period under freely ambulatory conditions in 10 healthy controls and in 10 patients with severe non-ulcer dyspepsia using a transnasally placed catheter with six solid state pressure transducers connected to a digital data logging device. Symptoms and sleep disturbance were assessed by questionnaire and diary. Based on their symptoms, the patients were separated into two groups: those with dyspepsia symptoms only (non-ulcer dyspepsia; n = 5) and those with dyspepsia and additional functional symptoms thought to arise from the lower gastrointestinal tract (non-ulcer dyspepsia+irritable bowel syndrome; n = 5). When compared with either the control or the non-ulcer dyspepsia+irritable bowel syndrome group, non-ulcer dyspepsia patients had a considerably decreased number of migrating motor complexes during the nocturnal period (0.7 v 4.6), a decreased percentage of nocturnal phase I (5.2% v 78.0%), and an increased percentage of the nocturnal period in phase II (94% v 15.4%). Patients with non-ulcer dyspepsia+irritable bowel syndrome were not different from normal controls. Four of the non-ulcer dyspepsia patients and all of the non-ulcer dyspepsia+irritable bowel syndrome patients reported difficulties with sleep. Clusters of high amplitude tonic and phasic activity, not accompanied by subjective reports of discomfort were noted in several patients in both groups during the study. In eight of 10 patients, abdominal pain was reported during normal motor activity, while in one patient, pain correlated with phase III of the migrating motor complex. In contrast with previous reports in patients with irritable bowel syndrome, our findings suggest an abnormality of diurnal rhythmicity--shown in changed sleep and changed rhythmic duodenal motor activity--in patients with chronic abdominal pain thought to arise from the upper gastrointestinal tract.     

Effect of pregabalin on sleep in patients with fibromyalgia and sleep maintenance disturbance: a randomized, placebo-controlled, 2-way crossover polysomnography study

Objective

To assess the effect of pregabalin on polysomnographic (PSG) measures of sleep and patient‐rated sleep, tiredness, and pain in fibromyalgia patients.

Methods

We performed a randomized, double‐blind, placebo‐controlled, 2‐period crossover PSG study. Patients ages ≥18 years with fibromyalgia satisfied subjective and objective sleep disturbance criteria prior to randomization. Eligible patients were randomized (1:1) to pregabalin (300–450 mg/day) or placebo for crossover period 1, and vice versa for period 2. Each crossover period comprised a dose‐adjustment and dose‐maintenance phase, with a 2‐week taper/washout between periods. In‐laboratory PSGs were recorded during 2 consecutive nights at screening and at the end of each crossover period. The primary end point was the difference in sleep maintenance defined by PSG‐recorded wake after sleep onset (WASO; minutes) between 4 weeks of treatment with pregabalin and with placebo. Other PSG measures; patient‐rated sleep, tiredness, and pain; and tolerability were assessed.

Results

Of 119 patients randomized (103 women [86.6%], mean age 48.4 years), 102 (85.7%) completed both periods. Patients treated with pregabalin showed a reduction in PSG‐determined WASO versus treatment with placebo (week 4 difference: ?19.2 minutes [95% confidence interval (95% CI) ?26.7, ?11.6]; P < 0.0001). Pain score improved (decreased) with pregabalin versus placebo treatment at all 4 weeks (week 4 difference: ?0.52 [95% CI ?0.90, ?0.14]; P = 0.0084). Modest (ρ = <0.3) but significant correlations were found between PSG sleep assessments and ratings of pain and sleep quality. Frequently reported all‐causality adverse events (pregabalin versus placebo) were: dizziness (30.4% versus 9.9%), somnolence (20.5% versus 4.5%), and headache (8.9% versus 8.1%).

Conclusion

Patients with fibromyalgia treated with pregabalin had statistically significant and meaningful improvements in sleep, as assessed by PSG. Patients with fibromyalgia also reported decreased daily pain. Pregabalin was well tolerated.