Musculoskeletal Symptoms and Non-REM Sleep Disturbance in Patients with "Fibrositis Syndrome" and Healthy Subjects HARVEY MOLDOFSKY, MD, PHILLIP SCARISBRICK, BS ROBERT ENGLAND, BA, AND HUGH SMYTHE, MD

In sleep studies of (a) patients with the "fibrositis syndrome" and (b) healthy subjects undergoing stage 4 sleep deprivation, we observed in both groups the anomalous presence of alpharhythms in the non-rapid-eye-movement (NREM) sleep EEG. This phenomenon has been termed alpha-del ta sleep. In the healthy subjects stage 4 deprivation was accompanied by the temporary appearance of musculoskeletal and mood symptoms comparable to the symptoms seen chronically in the patients. It is suggested that the external arousing stimulus, which induced alphadelta sleep in the subjects, is paralleled in the patients by an internal arousing mechanism. Such a mechanism, acting in competition with the NREM sleep system, would impair the presumed restorative function of NREM sleep and lead to the development of symptoms. It is proposed that the "fibrositis" symptom complex be considered a "non-restorative sleep syndrome." Evidence from the literature is presented in support of the hypothesis that a disorder of serotonin metabolism serves as a basis for both the EEG sleep disturbance and the symptoms.

INTRODUCTION

Since its introduction in 1904, the diagnosis of "fibrositis'' (1) has been applied to an amorphous group of painful disorders of the locomotor system. It is responsible for about half of all work absenteeism due to rheumatic disease (2), and forms the bulk of rheumatic complaints (3). Unlike many musculoskeletal conditions, definitive physical pathology has not been found to be associated with the localised areas of nonarticular pain and stiffness characteristic of the disorder (4). CurFrom the Department of Clinical Neurophysiology, The Clarke Institute of Psychiatry, and The Rheumatic Diseases Unit, The Wellesley Hospital, Toronto, Ontario, Canada. This research was supported by Ontario Mental Health Foundation Grants Nos. 229 and 446, and by National Health and Welfare Research Grant No. 605-7-621. Address reprint requests to: H. Moldofsky, The Clarke Institute of Psychiatry, 250 College Street, Toronto, Ontario, Canada M5T1R8. Received for publication September 25,1974; revision received January 6, 1975.

rently, the etiological hypothesis most widely accepted is that muscle tension and pain are related in a vicious cycle (5). However, Kraft et al. (5), by means of EMG recordings obtained from 16 patients, have demonstrated a lack of physiological evidence for "involuntary muscle spasm." In the absence of organic findings, some authors (4,6) have suggested that the pain is primarily of psychopathological origin, hence the term "psychogenic rheumatism." However, psychosomatic studies to date have been restricted to a general assessment of personality disturbances (7). No known psychophysiological studies have been carried out. A variety of treatment approaches have been employed, but generally the disorder has been found unresponsive to most medical and psychiatric therapies. The course of the illness is variable, but the trend is to functional disability and chronicity (8). The major source of investigative difficulty has been the vagueness of the clinical picture. We have noted that patients with "fibrositis syndrome" un-

Psychosomatic Medicine Vol. 37, No. 4 (July-August 1975) Copyright ° 1975 by the American Psychosomatic Society, Inc. Published by American Elsevier Publishing Company, Inc.

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iformly complain of sleep disturbance and intensification of pain and stiffness upon awakening. Traditionally, it has been assumed that the pain causes the sleep disturbance. In this paper we wish to report on a specific pattern of EEG sleep disturbance and its relationship to musculoskeletal and mood symptoms, both in patients who conform to predesignated criteria for the "fibrositis syndrome" and in screened healthy subjects undergoing stage 4 EEG sleep deprivation. METHOD

(range 37-64) and mean duration of illness was 5.9 years (range 1-25). Following a drug-free period of approximately 2 weeks, subjects slept for two or three nights in a sound-attenuated, electrically shielded room. A Grass Model 7 polygraph was used to obtain all-night EEG (fromC3 /A2andC4 /Al derivations), submental EMG, and EOG recordings. Paper speed was 15mm/sec, and all records were scored in 40 sec epochs according to the recognized criteria (9). Subjects were requested not to sleep outside the laboratory during the study period, and not to drink coffee or tea in the 6 hr period before sleep was to be recorded. To allow for accommodation to the experimental situation, the first night results were discarded. The following procedures were carried out on a presleep (1 hr or less before retiring) and postsleep (within 30 min of arousal) basis:

(1) Measurements of musculoskeletal tenderness were obtained using a 20 pound pressure dolorimeter applied to 13 pairs of bilaterally symmetrical sites in the musculoskeletal system. This instrument was described by McCarty et al. (10,11) and has been used successfully in the study of rheumatoid arthritis (12). All the measurements from each subject were obtained by a single observer. The following surfaceStudy 1 anatomical sites were selected: 2 cm below the occipiIn this study subjects were 10 patients (7 women, 3 tal crest; the mid-upper border of the trapezius; the men) who conformed to our criteria for the "fibrositis mid-bicep; the erector spinae, 2 cm lateral to C8, T8, syndrome" (Table 1). Mean age was 51.9 years LI, and L5; the lumbar triangle; the third intercostal

The studies described below were approved in advance by the Human Experimentation Committee of the Office of Research Administration of the University of Toronto. An informed consent was obtained from all subjects.

TABLE 1. Criteria for the "Fibrositis Syndrome"

CLINICAL OBSERVATIONS 1. Local Point Tenderness

SUBJECTIVE COMPLAINTS 1. Subjective Aching and Stiffness for More than 3 Months

2. Absence of Muscle Induration 3. Unrestricted Range of Musculo-Skeletal Motion on Objective Testing

2. Chronic Fatigue and Poor Work Tolerance for More than 3 Months 3. Sleep Disturbance for More than 3 Months

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4 Emotional Distress - Depression Anxiety, Irritability

4. Morning Aching and Stiffness

5. Dermatographia

5. Weather Effect

6. Normal Skeletal X-Rays, and Normal ESR, SGOT, CPK. Latex Fixation Test and ANF

6. Temporary Relief with Heat 7. Poor Appetite

Psychosomatic M e d i c i n e V o l . 3 7 , N o . 4 (July-August 1975)

MUSCULOSKELETAL SYMPTOMS AND NON-REM SLEEP space, 3 cm lateral to the sternal border over the pectoralis major; the anterior superior spine; the mid gluteus maximus; the mid-lateral thigh; the medial knee, 3 cm superior to the adductor tubercle. These sites sample the regions commonly affected in patients with the "fibrositis syndrome." (2) Subjective reports of the presence and intensity of symptoms (regional musculoskeletal pain and stiffness, appetitive, and gastrointestinal) were obtained. Subjects were requested to scale the intensity of any symptoms reported from 1 (barely perceptible) to 6 (severe). (3) Without their knowledge, the subjects' mood (as perceived by the investigator) was rated using a 27 item adjective checklist derived by Moldofsky and Chester (12) from Nowlis and Nowlis (13). Each adjective was assigned a score from 0 (not at all) to 6 (extremely). Adjectives previously found by cluster analysis to load on factors identified in a rheumatological population were combined. These factors, angry-submissive, anxious-calm, and sluggish-energetic, were examined for evidence of overnight change. For four subjects one night of EEG was recorded on magnetic tape using a Hewlett-Packard 3960 FM tape recorder. Frequency spectrum analysis was later carried out on a Digital Equipment Corporation Linc-8 computer programmed to digitize the EEG data and perform a Fast Fourier Transform (by the CooleyTukey algorithm) over a 2 sec epoch. Longer periods of analysis were achieved by averaging together successive 2 sec epochs. Frequency resolution was 0.5 cps over the range 0-32 cps. In Fig. 1 spectra have been plotted only from 0-20 cps, no significant frequency content being observed above this range.

Study 2 In this study we investigated the hypothesis that stage 4 sleep deprivation would be associated with the appearance of musculoskeletal and mood symptoms. Subjects were six paid volunteers. They were males, nonathletes, and between 19 and 24 years old. Selection was carried out by interview, the Cornell Medical Index, and the Eysenck Personality Inventory in order to minimize the possibility of any confounding medical or emotional variables. The subjects were instructed to refrain during the study from taking any drugs or alcohol, and to avoid drinking coffee or tea after 5.00 PM. They were also told not to sleep outside the laboratory but otherwise to maintain their usual regimen of physical and mental activity. The sleep records and frequency spectra

were obtained by the methods described in study 1. The pre-and postsleep procedures (l)and (2) above were also employed on every laboratory night. Procedure (3) was omitted since no rater who was blind to the experimental design was consistently available. The design of the study called for two nights of undisturbed sleep to allow for accommodation to the laboratory and to establish a baseline. This was followed by three nights of stage 4 sleep deprivation and two further nights of undisturbed sleep. Deprivation was effected by means of a variety of auditorystimuli of up to 90 db against a background of 55 db. One of these was delivered whenever four delta waves ( s 75 uV, *£ 2 cps) appeared in one 40 sec epoch of record. The tone was delivered in anticipation of the emergence of stage 4 sleep. Stimulation was maintained until the polygraph record showed clear signs of a movement arousal or a shift to stage 1 or 2. Awakening the subject was avoided whenever possible.

RESULTS

All significance levels quoted are twotailed. Study 1 All subjects reported that major stressful life situations had occurred at the time of onset of their sleep disturbance and musculoskeletal and mood symptoms. Typically, they had experienced a frightening but minor automobile or industrial accident or they had become helplessly involved in insoluble domestic difficulties. All subjects showed overnight increase in dolorimeter scores (P < 0.002, sign test [14]) and coincident non-rapideyemovement (NREM) EEG sleep disturbance. Seven subjects had NREM stages 2, 3, or 4 contaminated by an intercurrent alpha rhythm. This phenomenon closely approximates what Hauri and Hawkins (15) have termed alpha-delta sleep. The three subjects who failed to show this pattern had no stage 4 sleep and no, or very

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Fig. 1. Frequency spectra and raw EEG from (A) NREM (stage 4) sleep in a healthy 25-year-old subject. The spectrum shows that most amplitude is concentrated at 1 cps (delta); (B) NREM sleep in a 42-year-old "fibrositis" patient. The spectrum shows amplitude at both 1 cps (delta) and 8-10 cps (alpha); (C) NREM sleep of a healthy 21-year-old subject during stage 4 sleep deprivation. In the EEG there is a clear association between external arousal (auditory stimulation) and alpha onset. Again the frequency spectrum (obtained by 10 sec analysis from stimulus onset) shows amplitude concentrated in the delta and alpha bands.

little, stage 3. The sleep data summarized in Table 2 are based on the recognized criteria (9) and do not take into account the presence of alpha rhythms during sleep. Although the alpha contamination we have observed is clearly a phenomenon of NREM sleep, it does not seem to be associated with one particular sleep stage. Most commonly it appears throughout 344

NREM sleep stages 2, 3, and 4 (four subjects). However, within our sample there are two subjects in whom the alpha is confined to stages 2 and 3, disappearing with the development of normal stage 4, and one subject in whom stage 2 is normal, the alpha appearing only with the development of stages 3 and 4. See Fig. 1 (B) for an example of sleep EEG and associated

Psychosomatic Medicine Vol. 37, No. 4 (July-August 1975)

MUSCULOSKELETAL SYMPTOMS AND NON-REM SLEEP TABLE 2. EEG Sleep Data from Study 1—Drug-Free Sleep Characteristics of 10 Patients with the "Fibrositis Syndrome"

Sleep Variable

Statistic

Time (mins)

Mean S.D.

368 91.4

Sleep Latency (mins)

Mean S.D.

29.3 29.5

REM Latency (mins)

Mean S.D.

6a 4 ia7

Number of Arousals

Mean S.D.

5.5 4.2

% Movement Time

Mean S.D.

1.2 0.9

% Stage W

Mean S.D.

10.7 13.1

% Stage 1

Mean S.D.

9.8 4.1

% Stage 2

Mean S.D.

48.1 13.1

% Stage 3

Mean S.D.

6.0 43

% Stage 4

Mean S.D.

5.5 7.1

% Stage REM

Mean S.D.

1&6 5.1

Total Sleep

frequency spectrum from a subject with continuous NREM alpha contamination. For comparison see Fig. 1 (A) for EEG and frequency spectrum from normal delta sleep in a healthy subject. In the absence of sleep data from an age-matched group of healthy subjects of our own, we have made comparisons, where possible, with the data of Williams et al. (16) on a group of 41—46 year olds. Their use of differing criteria for delta sleep makes comparison impossible for stage 2, 3, and 4. Tests were made on both

raw (absolute time) and percentage data for stages W (awake), 1, and REM. Logarithmic (base 10) transformations were necessary on stage Wand stage 1 data (both raw and percentage) in order to attain homogeneity of variance. The only significant difference between the groups was in the amount of time spent in stage 1, our subjects spending about twice as long in this stage (raw data:F[l,18] = 4.68.P < 0.05; percentage data: F[l,18] = 7.37, P < 0.02). Inhomogeneity of variance between the groups in total sleep time (F [9,9] = 6.57,P

Musculosketal symptoms and non-REM sleep disturbance in patients with "fibrositis syndrome" and healthy subjects.

Musculoskeletal Symptoms and Non-REM Sleep Disturbance in Patients with "Fibrositis Syndrome" and Healthy Subjects HARVEY MOLDOFSKY, MD, PHILLIP SCARI...
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