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Biomedical subjects

M W Mahowald

Publications and source records attributed to M W Mahowald.

At least 37 records · Page 2Linked to original sources
PubMed1998

Blood pressure effects of long-term stimulant use in disorders of hypersomnolence.

Untoward cardiovascular effects have been implicated as a deterrent to long-term central nervous system (CNS) stimulant use in disorders of hypersomnolence. In this study, we reviewed the relationship between blood pressure and long-term stimulant use. Medical records of 54 patients with narcolepsy and idiopathic CNS hypersomnolence (ICH) were reviewed. The overall mean number of months of follow-up for the entire group was 45.6 (95% CI: 42-49). Both simple linear regression and multiple regression utilizing generalized estimating equations were used to show relationships between blood pressure (BP), time and other covariates. In the simple linear regression model, the average slope of the line of systolic BP (SBP) on time for the entire group was 0.06 (95% CI: -0.09, 0.13) and the line of diastolic BP (DBP) on time was 0.01 (95% CI: -0.05, 0.07). Two multiple regression equations were fitted for the continuous response variables SBP and DBP. Covariates in the model included: time, hypertension, weight at baseline, weight, SBP baseline (SBPBL), DBP baseline (DBPBL), high vs. low dose stimulant therapy and age at starting treatment. For SBP, the covariates weight at baseline, weight and SBPBL were significant (P < 0.05) predictors. For DBP, covariates reaching statistical significance (P < 0.05) included weight and DBPBL. There was no significant change in SBP or DBP over time in either model. Two different statistical models support the conclusion that there was no significant change in SBP or DBP over time in this population.

Adult↗
PubMed1998

Analysis of polysomnographic events surrounding 252 slow-wave sleep arousals in thirty-eight adults with injurious sleepwalking and sleep terrors.

A systematic study of electrophysiologic events [eight-channel EEG, electrocardiogram, electromyogram (EMGs)] surrounding 252 arousals from slow-wave sleep (SWS) in adults with sleepwalking (SW) and sleep terrors (ST) is reported. Hospital-based, overnight polysomnographic monitoring was conducted in 38 adults presenting to a sleep disorders center with injurious SW, ST (21 males, 17 females; mean age 29 years, range 17-69 years). Before nonbehavioral or behavioral arousals from SWS, neither EEG "delta wave buildup," nor heart rate (HR) acceleration, nor tonic/phasic EMG activation was identified. The postarousal EEG demonstrated three patterns: (a) diffuse, rhythmic, delta activity with a typical frequency of 2.2 Hz, a typical amplitude of 85 microV, and a typical duration of 20 s; (b) diffuse delta and theta activity intermixed with alpha and beta activity; and (c) prominent alpha and beta activity. Multichannel, high-voltage, delta activity was observed in <2% of all prearousal periods. HR acceleration emerged abruptly with SWS arousals, with significant changes in mean pre- versus postarousal HR (p < .001). Macrostructural sleep parameters ("sleep architecture") were intact. Therefore, our findings in adults with SW, ST strongly support the classification of SW/ST as disorders of (abrupt) arousal.

Adult↗
PubMed1998

An analysis of a recent criminal trial involving sexual misconduct with a child, alcohol abuse and a successful sleepwalking defence: arguments supporting two proposed new forensic categories.

The final judgment from a recent criminal trial in the British Columbia (Canada) Supreme Court is summarized and discussed. The trial involved sexual misconduct with a child, excessive alcohol use, and a successful 'sleepwalking (SW) defence' (non-insane automatism). Our comments on this trial provide an opportunity to present our arguments buttressing two newly proposed forensic categories: (i) parasomnia with continuing danger as a non-insane automatism, which originally was proposed for cases involving recurrent, sleep-related violence, but which can also be applied to SW cases involving sleep-related sexual misconduct and alcohol abuse (and other high-risk self-abusive behaviours); (ii) (intermittent) state-dependent continuing danger, an intermediate category within the 'continuing danger' concept, with the core feature being that a person acquitted of a criminal charge on the basis of the 'SW defence' (or some other parasomnia defence), in which the SW episode was provoked by a high-risk behaviour (e.g. alcohol intoxication) should bear full legal culpability for any future episode that was provoked by a recurrence of the high-risk behaviour--provided that the individual had wilfully engaged in that behaviour.

Adult↗
PubMed1997

A parasomnia overlap disorder involving sleepwalking, sleep terrors, and REM sleep behavior disorder in 33 polysomnographically confirmed cases.

A series of 33 patients with combined (injurious) sleepwalking, sleep terrors, and rapid eye movement (REM) sleep behavior disorder (viz. "parasomnia overlap disorder") was gathered over an 8-year period. Patients underwent clinical and polysomnographic evaluations. Mean age was 34 +/- 14 (SD) years; mean age of parasomnia onset was 15 +/- 16 years (range 1-66); 70% (n = 23) were males. An idiopathic subgroup (n = 22) had a significantly earlier mean age of parasomnia onset (9 +/- 7 years) than a symptomatic subgroup (n = 11) (27 +/- 23 years, p = 0.002), whose parasomnia began with either of the following: neurologic disorders, n = 6 [congenital Mobius syndrome, narcolepsy, multiple sclerosis, brain tumor (and treatment), brain trauma, indeterminate disorder (exaggerated startle response/atypical cataplexy)]; nocturnal paroxysmal atrial fibrillation, n = 1; posttraumatic stress disorder/major depression, n = 1; chronic ethanol/amphetamine abuse and withdrawal, n = 1; or mixed disorders (schizophrenia, brain trauma, substance abuse), n = 2. The rate of DSM-III-R (Diagnostic and Statistical Manual, 3rd edition, revised) Axis 1 psychiatric disorders was not elevated; group scores on various psychometric tests were not elevated. Forty-five percent (n = 15) had previously received psychologic or psychiatric therapy for their parasomnia, without benefit. Treatment outcome was available for n = 20 patients; 90% (n = 18) had substantial parasomnia control with bedtime clonazepam (n = 13), alprazolam and/or carbamazepine (n = 4), or self-hypnosis (n = 1). Thus, "parasomnia overlap disorder" is a treatable condition that emerges in various clinical settings and can be understood within the context of current knowledge on parasomnias and motor control/dyscontrol during sleep.

Adult↗
PubMed1997

A controlled study of serum anti-locus ceruleus antibodies in REM sleep behavior disorder.

The newly identified association of human nonnarcoleptic rapid eye movement (REM) sleep behavior disorder (RBD) with human leukocyte antigen (HLA) DQw1 class II genes raises the possibility that RBD may arise from autoimmune mechanisms. Two recent case reports involving postmortem brain stem histochemical analyses in elderly males with RBD identified severe monoaminergic cell loss in the locus ceruleus (LC). Thus, we designed a study to detect anti-LC antibodies in RBD. Ten Caucasian males (mean age, 66 years) with polygraphically confirmed RBD (n = 5, idiopathic RBD: n = 5, RBD with Parkinson's disease), but without narcolepsy, idiopathic hypersomnia, or autoimmune disease, were recruited for this study, along with 10 Caucasian male controls (mean age, 63 years) without a history of sleep disorder or autoimmune disease. In a blinded design, sera from the RBD patients and their controls were tested against human LC and other brainstem neurons. Brainstem tissue was obtained from autopsies of neurologically normal individuals. The presence of anti-LC antibodies was examined using immunohistochemistry on brainstem sections. Sections incubated with sera from normal individuals and sera from patients with paraneoplastic antineuronal antibodies (anti-Hu and anti-Ri) were used as controls. No reactivity with LC or any other brainstem area was identified with sera from either RBD patients or their controls, or from the other group of normal individuals. In contrast, sera from patients with paraneoplastic anti-Hu and anti-Ri antibodies reacted strongly with nuclei of LC and other brainstem neurons, sparing the nucleoli, and reacted to a lesser extent with the cytoplasm of these neurons. Therefore, it is unlikely that human RBD is associated with anti-LC antibodies. However, an autoimmune process in RBD has not been excluded by this study.

Aged↗
PubMed1996

HLA class II genes associated with REM sleep behavior disorder.

Twenty-five white men with rapid eye movements (REM) sleep behavior disorder, but without narcolepsy, underwent HLA class II antigen typing: 84% (N=21) were DQwl (DQB1*05,06) positive (28% [N=7] were DR2 positive); DQB1*0501 (N=9) and DQB1*0602 (N=7) were the most common phenotypes. The 84% DQwl rate in men with REM sleep behavior disorder was significantly greater (p=0.015) than the 56% DQwl rate found in a local white comparison group (N=66), and was greater than the 39 to 66% DQwl rates published for 12 white groups (N=40-418/group). Thus, another disorder of REM sleep dysregulation (besides narcolepsy) appears to be strongly associated with specific HLA class II genes.

Electromyography↗
PubMed1996

Long-term, nightly benzodiazepine treatment of injurious parasomnias and other disorders of disrupted nocturnal sleep in 170 adults.

PURPOSE: To assess the efficacy, dose stability, safety, and abuse potential of long-term, nightly benzodiazepine treatment of chronic disorders of disrupted nocturnal sleep. PATIENTS AND METHODS: During a 12-year period, one author evaluated and treated 170 adult referrals for > or = 6 months with nightly benzodiazepine therapy for longstanding, sleep-disruptive disorders: injurious sleepwalking and sleep terrors (69); rapid eye movement sleep behavior disorder (52); chronic, severe insomnia (25); and restless legs syndrome/periodic limb movement disorder (24). RESULTS: Complete/substantial control of the sleep disorders was achieved by 146 patients (86%); 8% had adverse effects requiring medication changes; 2% had relapses of alcohol or chemical abuse requiring hospitalization; another 2% at times misused their medications. A total of 136 patients received clonazepam nightly for a mean 3.5 (+/- 2.4) years, with no significant difference in inital versus final mean dose: 0.77 mg (+/- 0.46) versus 1.10 mg (+/- 0.96). Similar results were obtained with chronic alprazolam treatment and with other benzodiazepine treatments. CONCLUSION: Long-term, nightly benzodiazepine treatment of injurious parasomnias and other disorders of disrupted nocturnal sleep resulted in sustained efficacy in most cases, with low risk of dosage tolerance, adverse effects, or abuse. Data from this study on the treatment of chronic, severe insomnia (a small subset of all insomnia) are not generalizable to the typical insomnia patient.

Adult↗
PubMed1996

Diagnostic testing. Sleep disorders.

Sleep/wake complaints are very prevalent and may be associated with severe personal distress, with personal and societal socioeconomic consequences. A through clinical evaluation, coupled with judicious use of laboratory studies, usually reveals a specific and treatable underlying condition.

Circadian Rhythm↗
PubMed1996

NREM sleep parasomnias.

The three states of mammalian being--wakefulness, REM sleep, and NREM sleep--are not mutually exclusive and may occur simultaneously, oscillate rapidly, or appear in dissociated or incomplete form to produce primary sleep parasomnias. Dysfunctions of a wide variety of organ systems may take advantage of the sleeping state to declare themselves, resulting in the secondary sleep parasomnias. Contrary to popular opinion, most of these often bizarre and frightening experiences are not the manifestation of underlying psychological or psychiatric conditions. Formal study in an experienced sleep disorders center usually reveals a diagnosable and treatable condition. Various parasomnias may result in injurious or violent behavior. The forensic science implications are beyond the scope of this article but have been reviewed extensively elsewhere. Continued study of unusual sleep-related events undoubtedly will reveal more fascinating conditions, expanding our knowledge of sleep physiology and strengthening the bonds between clinicians and basic science sleep researchers.

Bruxism↗
PubMed1996

REM sleep parasomnias.

This article focuses primarily on REM sleep behavior disorder, a recently identified syndrome with a corresponding animal model. Diagnostic methods and criteria, treatment, and the world literature are reviewed, and the experience of the authors' institution--The Minnesota Regional Sleep Disorders Center (Minneapolis, MN)--is summarized. Other REM parasomnias, including nightmares, REM sleep-related sinus arrest, and sleep-related painful erections, are discussed briefly.

Animals↗
PubMed1996

Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder.

We report longitudinal data on a group of 29 male patients 50 years of age or older who were initially diagnosed as having idiopathic REM sleep behavior disorder (RBD) after extensive polysomnographic and neurologic evaluations. Thirty-eight percent (11/29) were eventually diagnosed as having a parkinsonian disorder (presumably Parkinson's disease) at a mean interval of 3.7 +/- 1.4 (SD) years after the diagnosis of RBD+, and at a mean interval of 12.7 +/- 7.3 years after the onset of RBD. To date, only 7% (2/29) of patients have developed any other neurologic disorder. At the time of RBD diagnosis, data from the RBD group with eventual Parkinson's disease (n = 11) and the current idiopathic RBD group (n = 16) were indistinguishable, with two exceptions: the RBD-Parkinson's disease group had a significantly elevated hourly index of periodic limb movements of non-REM sleep and an elevated REM sleep percentage. RBD was fully or substantially controlled with nightly clonazepam treatment in 89% (24/27) of patients in both groups. Thus, RBD can be the heralding manifestation of Parkinson's disease in a substantial subgroup of older male RBD patients. However, a number of presumed Parkinson's disease patients may eventually be diagnosed with multiple system atrophy (striatonigral degeneration subtype). Our findings indicate the importance of serial neurologic evaluations after RBD is diagnosed and implicate the pedunculopontine nucleus as a likely site of pathology in combined RBD-Parkinson's disease, based on experimental and theoretical considerations rather than on autopsy data.

Brain↗
PubMed1995

A polysomnographically documented case of adult somnambulism with long-distance automobile driving and frequent nocturnal violence: parasomnia with continuing danger as a noninsane automatism?

A case of childhood-onset somnambulism is reported in which a 43-year-old man presented with repeated sleep-related injuries incurred during violent nocturnal activity, which included frenzied running, throwing punches and wielding knives. He had also driven an automobile a long distance during a presumed somnambulistic state. His wife had been repeatedly injured, and she felt that her life was threatened by his nocturnal violence 2-3 times yearly. Polysomnography (PSG) documented multiple episodes of complex and violent behaviors arising exclusively from stage 3/4 sleep, thus confirming the diagnosis of somnambulism. Other causes of sleep-related violence were excluded. The patient responded promptly to treatment with bedtime clonazepam, and benefit was maintained at 5-year follow-up. Although this strictly clinical case did not have any legal repercussions, it does carry forensic implications, particularly when placed in the context of the published medical literature on PSG-documented parasomnias (somnambulism, rapid eye movement sleep behavior disorder) containing explicit examples of recurrent violence, at times life-threatening, directed toward the bed partner and others. Thus, a new medical-legal concept is proposed, consisting of "parasomnia with continuing danger" as a noninsane automatism. Treatment guidelines, within the context of forensic medicine, are presented.

Adult↗
PubMed1995

The Breuer-Hering reflex in humans. Effects of pulmonary denervation and hypocapnia.

Passive lung inflation in humans causes reflex expiratory prolongation that is abolished by vagal blockade. We have studied two aspects of this classic Breuer-Hering reflex in humans: the effect of pulmonary denervation from bilateral lung transplantation, and the effect of alveolar hypocapnia. Lung inflations were performed in six normal subjects and four lung transplant patients during triazolam-induced sleep using a negative pressure body box. Lung inflation with isocapnic gas in normal subjects resulted in expiratory prolongation lasting up to 60 s and occurring at a volume threshold of 40 to 60% of inspiratory capacity (1.1 to 1.7 L). Expiratory prolongation increased in a graded fashion as volume of lung inflation increased. Inhibition of inspiration at any given inflation volume was prolonged by inflations with air as compared with inflations with isocapnic gas. In lung transplant patients lung inflations of up to 2 L caused no prolongation of expiration. We conclude that bilateral lung transplantation abolished expression of the reflex in humans, and that in normal intact humans the duration of expiratory prolongation with lung inflation is prolonged by alveolar hypocapnia.

Adult↗