The neuroscience and endocrinology of fibromyalgia.
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Fibromyalgia↗
Biomedical subjects
H Moldofsky
Publications and source records attributed to H Moldofsky.
Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy.
Seventy-five patients meeting international diagnostic criteria for narcolepsy enrolled in a 6-week, three-period, randomized, crossover, placebo-controlled trial. Patients received placebo, modafinil 200 mg, or modafinil 400 mg in divided doses (morning and noon). Evaluations occurred at baseline and at the end of each 2-week period. Compared with placebo, modafinil 200 and 400 mg significantly increased the mean sleep latency on the Maintenance of Wakefulness Test by 40% and 54%, with no significant difference between the two doses. Modafinil, 200 and 400 mg, also reduced the combined number of daytime sleep episodes and periods of severe sleepiness noted in sleep logs. The likelihood of falling asleep as measured by the Epworth Sleepiness Scale was equally reduced by both modafinil dose levels. There were no effects on nocturnal sleep initiation, maintenance, or architecture, nor were there any effects on sleep apnea or periodic leg movements. Neither dose interfered with the patients' ability to nap voluntarily during the day nor with their quantity or quality of nocturnal sleep. Modafinil produced no changes in blood pressure or heart rate in either normotensive or hypertensive patients. The only significant adverse effects were seen at the 400-mg dose, which was associated with more nausea and more nervousness than either placebo or the 200-mg dose. As little as a 200-mg daily dose of modafinil is therefore an effective and well-tolerated treatment of excessive daytime somnolence in narcoleptic persons.
Adult↗
Regional differences in technetium-99m-ECD clearance on brain SPECT in healthy subjects.
UNLABELLED: The aim of this study was to evaluate the in vivo stability of ECD brain SPECT. METHODS: Twenty normal volunteers (35.4 +/- 9.1 yr) each had six ECD scans at 30, 60, 120, 240, 360 and 480 min postinjection. Each scan was acquired for 24 min using a triple-head SPECT system. Average counts per pixel were measured from frontal, temporal, parietal, occipital, cerebellum, basal ganglia, thalamus and white matter regions. ECD clearance rates were calculated by fitting regional time activity data to a monoexponential equation. Regional gray-to-white matter (G/W) and gray-to-cerebellum (G/C) ratios were calculated for each scan. Analysis of variance was used to compare regional ECD clearance and ratio measurements. RESULTS: The average ECD clearance was 4.3%/hr. There was a significant regional variation in the ECD clearance, being higher for occipital (6.34%/hr) but lower for both white matter (2.39%/hr) and thalamus (2.45%/hr). Both G/W and G/C ratios showed a significant regional variation with time. The overall G/W ratio was 2.13 at 30 min and became progressively lower after 2 hr, reaching 1.78 at 8 hr. All regional G/W ratios declined with time except for thalamus where it remained constant at 2.15. The overall G/C ratio was 0.984 at 30 min but it declined after 4 hr, reaching 0.955 at 8 hr. All regional G/C ratios declined with time except for thalamus where it increased progressively from 0.955 to 1.120 at 8 hr. CONCLUSION: ECD clears from normal brain slowly and shows a significant regional variation. As a result, G/W contrast begins to decrease after 2 hr and the gray-matter activity pattern becomes significantly different after 4 hr. Therefore, the optimal imaging time may be between 30-120 min. However, images obtained up to 4 hr still maintain the initial gray-matter activity pattern.
Adult↗
Sleep, daytime symptoms, and cognitive performance in patients with fibromyalgia.
OBJECTIVE: To assess sleep, daytime symptoms, and cognitive performance in patients with fibromyalgia (FM). METHODS: Ten female patients with FM (mean age 32 yrs) and a matched, noncomplaintive comparison group (n = 9; mean age 30 yrs) spent 2 nights in the sleep laboratory. After the 2nd night, subjects completed a computerized 20 min battery of self-assessment and performance tests at hourly intervals from 07:00 to 20:00 h. RESULTS: Patients with FM spent more time in stage 1 sleep; however, there were no group differences on any other sleep measures. They reported greater sleepiness, more fatigue, more pain, more negative mood, and lower accuracy on performance tasks across a 14 h day. The FM group was slower in speed, but not impaired in accuracy, on performance of complex tasks, i.e., grammatical reasoning, serial addition/subtraction, and a simulated multi-task office procedure. CONCLUSION: Patients with FM have diurnal impairment in speed of performance on complex cognitive tasks, which accompany light stage 1 electroencephalographic (EEG) sleep and their experience of diffuse pain and nonrestorative sleep symptoms of sleepiness, fatigue, and negative mood.
Adult↗
The clinical course of musculoskeletal pain in empirically derived groupings of injured workers.
The purpose of this paper is to examine the clinical course of musculoskeletal, soft tissue, work-related injury. An analysis of empirically derived sub-groupings of workers based on prognostically important pain and disability variables assessed on enrollment into the study is described. Multidimensional time-dependent profiles are used to characterize stages in the development of pain, impairment, disability and handicap. The clinical course over the 18 months of study of the three subgroups is examined. The conceptual model, used to examine the workers' changing responses over time, is based on the World Health Organization Classification of Impairments, Disabilities and Handicaps (1980). Methodologically, the study employed a prospective longitudinal design. A randomly selected cohort of workers who had not returned to work by 3 months post-injury were identified from the files of the Workers' Compensation Board of Ontario. The workers were interviewed and examined on enrollment into the study at 3 months and subsequently at 9 months, 15 months and 21 months after injury. The outcomes were return to work or continued work disability. The results are based on those 104 workers who attended all four assessment periods. K means clustering was used to identify homogenous subgroups of workers. Repeated measures ANOVAs were used to characterize the stages of development of pain, impairment, disability and handicap. Duncan's multiple range test was used to compare pairs of means at each assessment period. Cluster groupings, based on three prognostically important clinical variables, number of pain sites, pain behavior and functional disability, obtained at the initial assessment were valid predictors of the number of days to return to work and total number of days on work disability. Prognostic stratification can enhance confidence in predictive decisions of clinical practice and improve clinical trials of therapy.
Adult↗
Periodic K-alpha sleep EEG activity and periodic limb movements during sleep: comparisons of clinical features and sleep parameters.
The K-alpha sleep electroencephalographic (EEG) phenomenon is characterized by periodic (approximately 20-40 seconds) K-complexes, immediately followed by alpha-EEG activity (7.5-11 Hz) of 0.5- to 5.0-second duration. A group of 14 subjects with the periodic K-alpha anomaly was found to have a similar distribution pattern of interevent intervals as compared with previously published data for sleep-related periodic limb movements during sleep (PLMS). Sleep parameters and somatic symptoms of 30 patients with K-alpha were compared with 30 patients with PLMS. The periodic K-alpha group was predominantly female, younger, exhibiting more slow-wave sleep, gastrointestinal symptoms and muscular complaints and fewer movement arousals on overnight polysomnography. The K-alpha group presented uniformly with complaints of unrefreshing sleep, often associated with fibromyalgia and chronic fatigue syndrome. The PLMS group was predominantly male, showed greater sleep disruption and presented with a variety of sleep-related symptoms.
Adult↗
The effects of bright light treatment on the symptoms of fibromyalgia.
OBJECTIVE: To investigate the effects of bright light treatment on the symptoms of pain, mood, and sleep in patients with fibromyalgia (FM) reporting seasonality of symptoms on the Seasonal Pattern Assessment Questionnaire (SPAQ). METHODS: A randomized 10 week crossover study compared the effects of 4 weeks of "visible electromagnetic fields" (EMF) (light condition; mean 4750 lux, SD 2337 lux) to 4 weeks of "nonvisible EMF" (no light condition) in 14 patients with FM having a minimum SPAQ score of 11. The light visor system (Bio-Brite) was fitted with an opaque filter for the "nonvisible EMF" control condition. RESULTS: No significant differences were found between treatment conditions on tenderness measured with dolorimetry, self-ratings of sleep, pain, mood, and global measures. Mood was not related to pain or sleep. There was significant reduction in depression scores and subjective pain, but increased tenderness and nocturnal awakenings related to time. CONCLUSION: The were no significant differences between the light and no light conditions on pain, mood, or sleep in patients with FM reporting seasonality of symptoms. No relationship was found between mood and the symptoms of FM (i.e., pain, sleep, and fatigue).
Adult↗
The effect of zolpidem in patients with fibromyalgia: a dose ranging, double blind, placebo controlled, modified crossover study.
OBJECTIVE: This dose ranging, double blind, placebo controlled, modified crossover study examined whether zolpidem would improve the disturbed sleep, fatigue, mood and pain symptoms in patients with fibromyalgia (FM). METHODS: All symptoms were rated over 4 nights and 4 conditions for 16 consecutive nights during which 19 patients (mean age 42 years) randomly received placebo or zolpidem 5 mg, 10 mg, or 15 mg at bedtime. RESULTS: The 16 patients who completed the study reported no significant differences in ratings of pain, number of tender points, mood, sleep quality, morning fatigue, morning sleepiness or ability to concentrate. Compared to the placebo group, patients treated with zolpidem recorded significantly reduced time to fall asleep, increased sleep time, reduced awakenings, overall improvement in sleep and daytime energy, but a lower rating for evening energy. Zolpidem at the 10 mg dose was rated most acceptable for sleep. Adverse incidence rates were highest in the placebo group and lowest in the zolpidem 10 mg group. One person withdrew because of migraine while taking zolpidem 10 mg. CONCLUSION: Short term treatment with zolpidem (5 to 15 mg) does not affect the pain of FM, but is useful for sleep and daytime energy in this patient population.
Adult↗
Sleep and the immune system.
Recent animal and human studies show that the immune-neuroendocrine-thermal operations of the body are intimately linked to the sleeping-waking brain. In humans, the diurnal pattern of aspects of both peripheral cellular immune functions, e.g. natural killer cell cytotoxicity, and of cytokines, e.g. interleukin-1, are related to sleep. The harmonious interrelationships of the circadian patterns of the immune, neuroendocrine, thermal and brain functional activities are important for the cause and function of sleep. Disorganization or loss of the sleep-wake system is accompanied by alteration of the immunological, neuroendocrine and thermal functions of the body, and contributes to pathological processes such as infectious disease.
Animals↗
Sleep, neuroimmune and neuroendocrine functions in fibromyalgia and chronic fatigue syndrome.
The justification for disordered chronobiology for fibromyalgia and chronic fatigue syndrome (CFS) is based on the following evidence: The studies on disordered sleep physiology and the symptoms of fibromyalgia and CFS; the experimental studies that draw a link between interleukin-1 (IL-1), immune-neuroendocrine-thermal systems and the sleep-wake cycle; studies and preliminary data of the inter-relationships of sleep-wakefulness, IL-1, and aspects of peripheral immune and neuroendocrine functions in healthy men and in women during differing phases of the menstrual cycle; and the observations of alterations in the immune-neuroendocrine functions of patients with fibromyalgia and CFS (Moldofsky, 1993b, d). Time series analyses of measures of the circadian pattern of the sleep-wake behavioural system, immune, neuroendocrine and temperature functions in patients with fibromyalgia and CFS should determine whether alterations of aspects of the neuro-immune-endocrine systems that accompany disordered sleep physiology result in nonrestorative sleep, pain, fatigue, cognitive and mood symptoms in patients with fibromyalgia and CFS.
Animals↗
Sleep-related violence.
We hypothesized that sleep-related violent behavior associated with parasomnias occurs as the result of a diathesis and is precipitated by stressors and mediated by disturbed nonrapid eye movement (NREM) sleep physiology. Sixty-four consecutive adult patients (mean age 30 years) who were investigated for sleepwalking or sleep terrors were categorized according to clinical history into three groups: serious violence during sleep to other people or to property or self (n = 26); harmful, but not destructive behavior (n = 12); and nonviolent behavior (n = 26). Log linear analysis showed that a diathesis (childhood parasomnia and/or family history of parasomnia) and a stressor (psychologic distress, substance abuse and sleep schedule disorder) predicted the presence of sleepwalking or night terror. Serious violent acts were more likely to occur with males (p < 0.004) who showed sleep schedule disorder (p < 0.03). Both harmful and serious violent sleep behavior occurred with drug abuse (p < 0.009). In comparison to all other groups, those who were violent to other people were males who experienced more stressors (p < 0.02), drank excessive caffeinated beverages, abused drugs (p < 0.03) and showed less stage 4 sleep (p < 0.02) and less alpha (7.5-11 Hz) electroencephalogram NREM sleep (p < 0.02) on polysomnography. Being male and having < 2% stage 4 sleep provided 89% sensitivity, 80% specificity and 81% diagnostic accuracy for individuals who were violent to others. The forensic implications of these findings are discussed.
Adolescent↗
Diurnal sleep/wake-related immune functions during the menstrual cycle of healthy young women.
Animal and human studies have related the sleeping/waking brain to the immune system. Because women are more susceptible to certain immunological illnesses, and sex steroids regulate immune functions, it was investigated whether the diurnal sleep/wake pattern of aspects of cellular immune functions and interleukin-1 (IL-1) and IL-2-like activities differed during low and high progesterone phases of the menstrual cycle. Eleven healthy women, mean age 24 y, were assessed over 24 h with serial venous blood samples. Peripheral blood monocytes were assayed for mitogen responses, i.e. phytohemagglutin (PHA) and pokeweed (PWM) and natural killer (NK) cell activities. Plasma was assayed for IL-1 and IL-2-like activities, cortisol and progesterone. Data were standardized by Z transformation and analysed by repeated-measures analysis of variance by comparing high (N = 5) vs. low (N = 6) progesterone phases. During the high progesterone phase, delayed slow-wave sleep (SWS) onset time and reduced amount of SWS was accompanied by a delay in the decline of NK cell activity, but rise in PHA activity following sleep onset. With the low progesterone phase, the pattern was similar to men with an early sleep decline in NK cell and late sleep rise in PHA activities. PWM rose during the night and plasma IL-1-like activity peaked during midday and during nocturnal sleep irrespective of the amount of progesterone. Slow-wave sleep and sleep-related NK cell and PHA activities differed over the menstrual cycle, but not PWM response. Increases in plasma IL-1 functions during midday and night are consistent with predisposition to sleepiness during these times.
Journal Article↗
Fibromyalgia and disability. Report of the Moss International Working Group on medico-legal aspects of chronic widespread musculoskeletal pain complaints and fibromyalgia.
The present article is the result of a working group conference held in Moss, Norway, in June 1993, financed by the Royal Norwegian Ministry of Health and Social Affairs. Its purpose was to review and focus upon problems and needs related to the medico-legal aspects of fibromyalgia and chronic widespread musculoskeletal complaints: thus to define directions for future work on issues which have generally not been addressed within the medical community. Our report describes specific problems in this area in regard to definition, evaluation and recommendation, and in currently available work and disability statistics. We have recommended international efforts to establish research programs through organizations such as the International Social Security Association and the World Health Organization. While our recommendations call for research into medico-legal interactions, causes and pathogenic mechanisms, prevention and treatment are also key and relevant concerns in the medico-legal setting.
Chronic Disease↗
The probability of recovery and return to work from work disability as a function of time.
This paper describes a prospective longitudinal cohort study of musculoskeletal soft tissue pain impairment following a work related injury. It focuses on specific, univariate prognostic factors indicated in previous research studies that might affect the likelihood that injured workers will return to work or remain on work disability at any point in time. These factors include gender, age, return to work attempts and site of injury. Life table analysis was used to model the probability of work disability. The results showed that different disability and return to work patterns emerged for males and females. Males were more likely to return to work; however, females had a higher probability than males of remaining at work once they returned to work. Older workers had the highest probability of being off work any given number of days after injury; were less likely to return to work, and if they did, had a higher probability of becoming disabled again. Efforts to return early to work contributed to a decrease in overall work disability. Workers with low back injuries had a greater likelihood of recurrence compared to injuries at other body sites.
Adolescent↗
Chronobiological influences on fibromyalgia syndrome: theoretical and therapeutic implications.
A review of the evidence from diurnal physiological, seasonal environmental and prospective studies of social-behavioural functions suggest that a chronobiological theoretical model provides a comprehensive basis for the dynamics of central nervous system mechanisms, the assessment and the management of patients with fibromyalgia. The chronobiological model stresses the importance of temporal variation and the factors that influence and govern recurrent patterns of biological functions and behaviour that determine health and illness. Finally, the theory allows for an integrated study of brain, behaviour and somatic functions over time and emphasizes that such a comprehensive approach is core to any therapeutic intervention.
Chronobiology Phenomena↗
Central nervous system and peripheral immune functions and the sleep-wake system.
This paper reviews the relationship of aspects of the immune system to the sleep-wake system in animals and humans. In addition to the influence of certain cytokines such as interleukin-1 (IL-1) on the sleeping-waking brain, circadian measures of plasma IL-1 and peripheral immune cellular functions, for example, natural killer cell activities and cortisol are related to the sleep-wake system in humans. Changes in the circadian patterns of immune functions over the menstrual cycle are associated with the amount of progesterone and slow wave sleep. The harmonious inter-relationship of the circadian pattern of the immune, endocrine and sleep-wake systems may be important in the cause and functions of sleep.
Animals↗
Fibromyalgia, sleep disorder and chronic fatigue syndrome.
Various research studies show that the amalgam of disordered sleep physiology, chronic fatigue, diffuse myalgia, and cognitive and behavioural symptoms constitutes a non-restorative sleep syndrome that may follow a febrile illness, as in the chronic fatigue syndrome. Where rheumatic complaints are prominent such a constellation of disturbed sleep physiology and symptoms also characterizes the fibromyalgia disorder. In contrast to the chronic fatigue syndrome, fibromyalgia is associated with a variety of initiating or perpetuating factors such as psychologically distressing events, primary sleep disorders (e.g. sleep apnoea, periodic limb movement disorder) and inflammatory rheumatic disease, as well as an acute febrile illness. The chronic fatigue syndrome and fibromyalgia have similar disordered sleep physiology, namely an alpha rhythm disturbance (7.5-11 Hz) in the electroencephalogram (EEG) within non-rapid eye movement (NREM) sleep that accompanies increased nocturnal vigilance and light, unrefreshing sleep. Aspects of cytokine and cellular immune functions are shown to be related to the sleep-wake system. The evidence suggests a reciprocal relationship of the immune and sleep-wake systems. Interference either with the immune system (e.g. by a viral agent or by cytokines such as alpha-interferon or interleukin 2) or with the sleeping-waking brain system (e.g. by sleep deprivation) has effects on the other system and will be accompanied by the symptoms of the chronic fatigue syndrome.
Behavior↗
Litigation, sleep, symptoms and disabilities in postaccident pain (fibromyalgia)
Twenty-four patients with chronic postaccident pain were studied with self-rating symptom checklists, polysomnography and disability questionnaires. All except one had fibromyalgia. Eight had litigation resolved (R) while 16 had medicolegal claims still unresolved (UR). Patients from the R group were older, with a longer duration of symptoms and more occupation handicap compared to those from the UR group. There were no significant differences between the 2 groups in other demographic data, nature of accident, symptoms, polysomnographic findings and disability. Medicolegal claim status in these patients did not differentiate the outcome of their symptoms. Implications for litigation, treatment and further studies are discussed.
Accidents↗