Activation by selegiline (Eldepryle) of REM sleep behavior disorder in parkinsonism.

Abnormal sleep-wake organization is frequently seen in idiopathic parkinsonism (PD) and other parkinsonism syndromes. A 1993 article in The Annals of Neurology first described the high rate of REM behavior disorder (RBD) in non-demented PD patients (1). In this article, we present the case reports of three non-demented PD patients who manifested RBD while on recommended doses of selegiline (Eldepryle). None of them had problems severe enough to suggest RBD while they were being treated with varying doses of other dopaminergic agents (carbidopa/L-dopa, pergolide) unaccompanied by selegiline.

Experimental evidence of penile erections during paradoxical sleep in the rat.

We have developed a new technique to chronically monitor penile erections in the rat across behavioural states. This technique, involving chronic erectile tissue pressure monitoring and simultaneous ischiocavernosus and bulbospongiosus (IC-BS) muscle electromyography, demonstrates for the first time that rats exhibit penile erections during paradoxical sleep (PS). No erectile events were observed during slow wave sleep. These PS-related erectile events were similar to visually confirmed, waking state, erections in that they were associated with an increase in baseline erectile tissue pressure and, with IC-BS muscle bursts, dramatic suprasystolic penile pressure peaks often greater than 1000 mmHg. PS-related erections were 11 +/- 7 s in duration and were observed in 28.5% of all PS episodes. This method of chronic penile erection monitoring in the rat provides a new animal model for investigating neural mechanisms of sleep-related erections.

The ischiocavernosus and bulbospongiosus muscles in mammalian penile rigidity.

The role of the perineal muscles in erection physiology is currently controversial. Specifically, confusion persists as to the function, if any, the ischiocavernosus (IC) and bulbospongiosus (BS) muscles possess in nonejaculatory erections. An extensive review of the evidence for and against such an erectile role across five orders of mammalian species indicates that the IC muscles create rigidity by producing suprasystolic intracavernous pressures. The BS muscles, on the other hand, are primarily involved in expelling semen during ejaculation. Beckett and coworkers were the first to demonstrate a clear relationship between IC muscle contractions, suprasystolic intracavernous pressures and rigidity. This Beckett model is used to differentiate an erect phase from a rigid erect phase in the erection cycle. The involvement of these muscles in sleep-related erection physiology is also reviewed. Clinical implications and directions for future research are discussed.

An exploration of central dysregulation of erectile function as a contributing cause of diabetic impotence.

Diabetic impotence is generally presumed to be secondary to peripheral abnormalities of the vascular or autonomic nervous system, although central nervous control of the autonomic nervous system has not previously been studied. Measures of rapid eye movement (REM) sleep as potential indicators of central autonomic dysfunction were studied along with sleep-related tumescence for 10 impotent diabetics, nine psychogenically impotent men, and 10 men whose impotence was secondary to pelvic trauma. Low REM density was found in the diabetics with REM density correlating with measures of tumescence. These results suggest that central autonomic dysfunction may be a contributing factor in the impotence of diabetic men. A metabolic disturbance in the central nervous system of diabetics which might alter both sleep and autonomic nervous system activity is proposed to explain these results and may help in the understanding of other observed abnormalities in both the sleep and autonomic dysfunction of diabetics.

Short REM latency in impotence without depression.

In a retrospective study, the presence of depression was studied in a group of 14 impotent patients who were selected on the basis of the similarity between their electroencephalographic (EEG) sleep patterns and those of patients with endogenous depression. Specifically, the value of rapid eye movement (REM) latency plus age less than 100 was used as a selection criterion. Sleep continuity disturbances, increased REM time, and increased REM% were noted in the short REM latency impotent group. On the basis of MMPI and psychiatric history and interview, only one of these impotent patients showed major depression. The authors conclude that impotent patients with a short REM latency are not, as a group, depressed and that the incidence of depression in impotent men should be determined irrespective of EEG sleep findings.

Videoendoscopic determination of the mechanism of obstruction in obstructive sleep apnea.

Six patients with obstructive sleep apnea were studied with our system of simultaneous video recording of the polysomnographic record and the endoscopic image from the pharyngeal airway. Preoperative and postoperative recordings were made during sleep in each patient. Tracheotomized patients recreated their preoperative laryngeal inlet obstruction and its immediate cessation by alternately opening and closing the tracheotomy tube. This demonstration coupled with the physical examination findings of "disproportionate anatomy," leads to the determination that the mechanism of obstructive sleep apnea is twofold: (1) an underlying CNS propensity to hypotonia of pharyngeal musculature during sleep and (2) either an isolated obstructive upper airway lesion or a combination of alterations in normal relationships within the upper airway that cause a passive narrowing of the upper airway. This combination of altered relationships is collectively referred to as "disproportionate anatomy."

L-tryptophan in the treatment of impaired respiration in sleep.

15 subjects (mean age: 48.2 yr; 13 males, 2 females) with sleep apnea (12 obstructive, 3 central) were treated with an average dose of 2500 mg L-tryptophan (L-T) at bedtime. Comparison of pre- and post-drug polysomnograms showed significant improvement in obstructive sleep apnea but not with central sleep apnea. Most dramatic improvement is seen in subjects with obstructive sleep apnea in non-REM sleep only, but severity of apnea appears to be the most important factor determining improvement. L-T increased REM time and shortened REM latency but had no other significant effects on sleep architecture. Serotoninergic activity with a defect in feedback control of tryptophan-serotonin metabolism is postulated as a potential mechanism in the pathophysiology of obstructive sleep apnea. The enhanced usefulness of L-T in combination with protriptyline is predicted based on early preliminary work at the OSU Sleep Center. The Potential influence of dietary intake on respiratory automaticity is reviewed.

Anthropometric characteristics, cardiac abnormalities and adrenergic activity in patients with primary disorders of sleep.

Sixty-one patients (pts) with sleep apnea (SA), 35 with narcolepsy (N) and 24 with idiopathic hypersomnolence (H) were studied in the Clinical Research Center. The height to body weight ratio was less than normal in SA pts (0.32 +/- 0.01 vs 0.45 +/- 0.01, p less than 0.01), but normal in N and H pts (0.45 +/- 0.02 and 0.45 +/- 0.01, respectively). Twenty-four hour urinary epinephrine (E) plus norepinephrine (NE) was greater than normal (p less than 0.01), but not different among SA, N and H pts. The incidence of mitral valve prolapse (MVP) was greater in N (49%) and H (58%) compared to SA (20%) (p less than 0.01). The ratio of the pre-ejection period to the left ventricular ejection time (PEP/LVET) was abnormal (greater than 0.42) in 36% of the pts with SA and only in one pt with N and H (p = 0.02). The % shortening of the echocardiographic internal diameter (% delta D) was abnormal (less than 28%) in 28% of pts with SA and normal in all pts with N and H (p = 0.02). The incidence of malignant ventricular dysrhythmias (24 hour Holter) was 26% in SA, 3% in N and 4% in H (p = 0.04). Thus, pts with impaired alertness have high adrenergic tone despite evidence for a role of catecholamines in wakefulness. Left ventricular dysfunction, malignant dysrhythmias and obesity are common findings in SA, while MVP is very common in N and H.

Significance of impaired penile tumescence and associated polysomnographic abnormalities in the impotent patient.

Of 15 consecutive patients with secondary impotence 7 (46 per cent) had varied degrees of abnormal nocturnal penile tumescence and 1 or more of the following sleep-associated events: frequent apnea and hypoventilation, myoclonus and a slow but remarkably stable heart rate even during episodes of respiratory impairment. All nocturnal penile tumescence measurements, except circumference change at the glans, were significantly lower than in patients with psychogenic impotence or normal subjects. These findings, not described previously, suggest probable central nervous system etiology of organic impotence in some patients. Skilled nocturnal penile tumescence assessment in conjunction with a comprehensive polysomnographic study is an essential diagnostic procedure in the evaluation of the impotent patient.

Adrenergic hyperactivity and cardiac abnormality in primary disorders of sleep.

Symptoms suggesting autonomic instability and increased adrenergic effect were identified in 53 patients with primary disorders of impaired wakefulness. Urine and plasma catecholamine concentrations were significantly increased in patients with sleep apnea. Excessive increases in heart rate during isoproterenol infusions suggested adrenergic hyperresponsiveness as an alternative explanation for symptoms of catecholamine excess in some individuals. Twenty-two patients demonstrated mitral valve prolapse (MVP), implicating primary neurologic disturbances as potential factors in the fatigue and lassitude often associated with MVP. The catecholamine abnormalities may explain some of the difficulties frequently encountered in using stimulants to treat sleep disorders.

Sleep-induced ventilatory dysfunction in Down's syndrome.

Three patients with Down's syndrome demonstrated severe sleep-induced ventilatory failure characterized by Cheyne-Stokes respiration with superimposed obstruction of the upper airway. Anatomic otolaryngologic factors were present in two of the three patients, implicating both mechanical and CNS factors in the pathogenesis of this phenomenon. Administration of protriptyline hydrochloride elicited considerable improvement in one case. Occult sleep-related ventilatory failure may account for the previously unexplained tendency for pulmonary hypertension to develop in patients with Down's syndrome.

Sleep apnea: treatment with protriptyline.

Fourteen patients with an average of more than 60 episodes of upper airway obstruction during night sleep were treated with a nonsedating tricyclic antidepressant, protriptyline. Frequency and duration of recorded apneas decreased in 11 cases, and satisfactory control of sleep apnea was maintained with medical therapy alone in 8 of these 11 patients for 7 to 15 months. Potential adverse effects of protriptyline, particularly on the cardiovascular system, limit its use in this illness. These results indicate the possibility of pharmacologic reversal of sleep-induced incoordination of the upper airway.

Disordered growth hormone and prolactin secretion in primary disorders of sleep.

Growth hormone (GH) and prolactin (PR) secretion were evaluated in 28 patients who had sleep apnea or narcolepsy but no other primary neurologic or endocrine disorders. Eighty-one percent of subjects with impaired alertness failed to demonstrate serum GH concentrations in excess of 5 ng per milliliter following oral administration of L-DOPA, 500 mg. Diminished GH responses to sleep and intravenous arginine were observed in 57 percent and 44 percent, respectively, of patients tested. Sleep-related PRL release was less than normal in women with narcolepsy, with or without sleep apnea. All patients had at least one abnormality in GH or PRL secretion.

Reversal of chronic diabetes insipidus during treatment with protriptyline.

We have described a 13-year-old white boy with Ondine's curse, sleep apnea and cataplexy who simultaneously developed progressive hypothalamic neuroendocrine deficiencies requiring replacement therapy. The patient was treated with protriptyline, a nonsedating tricyclic antidepressant, for control of the sleep-related symptoms. An unexpected result was the apparent reversal of his chronic diabetes insipidus by protriptyline, necessitating discontinuation of lysine-vasopressin. Some possible mechanisms of action were discussed.

Protriptyline: an effective agent in the treatment of the narcolepsy-cataplexy syndrome and hypersomnia.

The authors present five case reports illustrating that 10-20 mg of protriptyline in a single dose at bedtime can effectively control arousal dysfunction (sleep drunkenness and hypersomnia) and the narcolepsycataplexy syndrome without the apparent development of tolerance and without the side effects that are frequent complications of treatment with other agents. Although protriptyline was efficacious in controlling symptoms, it was found to have relatively poor REM sleep-suppressing properties.