Sleep, Circadian Rhythms, and Epilepsy.

PURPOSE OF REVIEW: There is a known interrelationship between sleep and epilepsy. This review highlights the recent findings regarding interactions between sleep and circadian rhythms and the manifestations of epilepsy and surgical treatments for refractory epilepsy. RECENT FINDINGS: CLOCK gene expression may be reduced within the epileptogenic focus in patients with refractory epilepsy. Interictal epileptiform discharges during NREM and especially REM sleep may lateralize to the epileptogenic hemisphere. Intracranial video EEG monitoring and EEG from implanted responsive neurostimulator devices confirm scalp video EEG findings of a nocturnal peak for interictal epileptiform discharges. Successful epilepsy surgery may improve sleep macrostructure and quality. Sleep outcomes in people with epilepsy undergoing epilepsy surgery and neurostimulator implantation may provide innovative understandings into the associations between sleep and epilepsy. These associations may then provide novel therapeutic options targeting sleep and circadian pathways to improve seizure control and improve the quality of life for patients with this debilitating disorder.

Surface EMG activity during REM sleep in Parkinson's disease correlates with disease severity.

OBJECTIVES: Over 40% of individuals with Parkinson's disease (PD) have rapid eye movement sleep behavior disorder (RBD). This is associated with excessive sustained (tonic) or intermittent (phasic) muscle activity instead of the muscle atonia normally seen during REM sleep. We examined characteristics of manually-quantitated surface EMG activity in PD to ascertain whether the extent of muscle activity during REM sleep is associated with specific clinical features and measures of disease severity. METHODS: In a convenience sample of outpatients with idiopathic PD, REM sleep behavior disorder was diagnosed based on clinical history and polysomnogram, and severity was measured using the RBD sleep questionnaire. Surface EMG activity in the mentalis, extensor muscle group of the forearms, and anterior tibialis was manually quantitated. Percentage of REM time with excessive tonic or phasic muscle activity was calculated and compared across PD and RBD characteristics. RESULTS: Among 65 patients, 31 had confirmed RBD. In univariate analyses, higher amounts of surface EMG activity were associated with longer PD disease duration (srho = 0.34; p = 0.006) and greater disease severity (p < 0.001). In a multivariate regression model, surface EMG activity was significantly associated with RBD severity (p < 0.001) after adjustment for age, PD disease duration, PD severity and co-morbid sleep abnormalities. CONCLUSION: Surface EMG activity during REM sleep was associated with severity of both PD and RBD. This measure may be useful as a PD biomarker and, if confirmed, may aid in determining which PD patients warrant treatment for their dream enactment to reduce risk of injury.

Association between dopaminergic medications and nocturnal sleep in early-stage Parkinson's disease.

BACKGROUND: Poor nocturnal sleep is common in Parkinson's disease (PD) and negatively impacts quality of life. There is little data on how dopaminergic drugs influence nocturnal sleep in PD, particularly in relation to medication timing. We examined the association between dopaminergic medications and subjective and objective nocturnal sleep in PD. METHODS: Individuals with PD were recruited from the outpatient clinic. Demographics and disease information were collected. Patients underwent one-night polysomnography and responded to SCOPA-SLEEP, a self-administered questionnaire which includes a section on nighttime sleep and an overall measure of sleep quality; higher scores indicate worse sleep. Medication intake, including medication timing in relation to bedtime, was obtained and converted to levodopa equivalents. RESULTS: 41 Males and 21 females, median age 63.9 years, participated. Median disease duration was 5 years. After adjusting for age, sex, disease severity, and disease duration, greater total levodopa equivalent intake within 4 h of sleep was associated with higher total SCOPA-nighttime score (p = 0.009) and greater wake time after sleep onset (p = 0.049). Greater dopaminergic medication intake prior to sleep was also associated with less rapid eye movement (REM) sleep as a percent of total sleep time (p = 0.004). CONCLUSIONS: Higher amounts of dopaminergic medications taken prior to sleep were associated with poor sleep quality and less REM sleep. Although poor nocturnal sleep in PD is likely multi-factorial in etiology, our findings suggest that timing and dose of medications prior to sleep need to be considered in its management.

Questionnaire-based diagnosis of REM sleep behavior disorder in Parkinson's disease.

BACKGROUND: Rapid eye movement (REM) sleep behavior disorder (RBD) is present in around 40% of Parkinson's disease (PD) patients. Definitive diagnosis requires a polysomnogram, but that is costly, time intensive, and not practical for large-scale studies. Therefore, we assessed using a questionnaire-based diagnostic approach. METHODS: The patient-administered RBD questionnaire and bed-partner-administered question 1 of the Mayo questionnaire were prospectively validated. RESULTS: Seventy-five PD patients (51 male, 68 Hoehn and Yahr stages I and II) participated. Forty-eight had a clinical history of RBD. Sensitivity was 100% (95% CI, 86.3%-100%) when a combination of both questionnaires was compared with the gold standard of polysomnogram-confirmed RBD. Among those who achieved REM sleep (n=65), specificity was highest for the patient questionnaire used alone, at 82.4% (95% CI, 64.8%-92.6%). CONCLUSIONS: A combination of patient and bed-partner questionnaires is a useful tool to detect RBD.

Sleep-disordered breathing.

PURPOSE OF REVIEW: This article introduces readers to the clinical presentation, diagnosis, and treatment of sleep-disordered breathing and reviews the associated risk factors and health consequences. RECENT FINDINGS: Sleep-disordered breathing is associated with significant impairments in daytime alertness and cognitive function as well as adverse health outcomes. The initial treatment of choice is positive airway pressure. Improvements in technology and mask delivery systems have helped to make this treatment more comfortable and convenient for many patients. SUMMARY: Sleep-disordered breathing, particularly in the form of obstructive sleep apnea, is highly prevalent in the general population and has important implications for neurology patients. Sleep-disordered breathing is characterized by repetitive periods of cessation in breathing, termed apneas, or reductions in the amplitude of a breath, known as hypopneas, that occur during sleep. These events are frequently associated with fragmentation of sleep, declines in oxygen saturation, and sympathetic nervous system activation with heart rate and blood pressure elevation. Obstructive sleep apnea, which represents cessation of airflow, develops because of factors such as anatomic obstruction of the upper airway related to obesity, excess tissue bulk in the pharynx, and changes in muscle tone and nerve activity during sleep. Central sleep apnea represents cessation of airflow along with absence or significant reduction in respiratory effort during sleep and is more commonly found in the setting of congestive heart failure, neurologic disorders, or cardiopulmonary disease.

Prolonged assessment of sleep and daytime sleepiness in unrestrained Macaca mulatta.

STUDY OBJECTIVE: To establish a method for the prolonged recording of electrophysiologic variables of sleep in freely moving nonhuman primates. To establish and validate means for scoring nocturnal sleep and quantifying daytime alertness in these subjects. DESIGN: Four animals (M. mulatta) were permanently instrumented for the recording of electroencephalograms, electrooculograms, and electromyograms. A telemetry unit housed in a backpack transmitted these variables for several overnight periods to establish normal sleep. During the day, a modified Multiple Sleep Latency Test protocol was followed to quantify daytime alertness. High-quality recordings were maintained from a minimum of 8 months to a maximum of 5.5 years. MEASUREMENTS AND RESULTS: Across 6 to 7 nights per animal, average total sleep time was 522 minutes, with a sleep latency of 20 minutes. The proportion of total sleep spent in the various stages of sleep was 10.8%, stage 1; 56.4%, stage 2; 20.0%, stages 3-4; and 12.7%, rapid eye movement sleep. Mean sleep latency across testing sessions for each monkey was 12.5 minutes, 20 minutes (no daytime sleep), 14.6 minutes, and 8.6 minutes for animals 1 to 4, respectively. Intrarater and interrater reliabilities were high and similar to those obtained when the same scorers evaluated human sleep and Multiple Sleep Latency Tests. CONCLUSIONS: Similarities in sleep architecture between M. mulatta and humans make this an excellent animal model for investigations of normal and pathologic human sleep. This study confirms and extends previous findings in nonhuman primates. Stable, high-quality data were obtained for months to years using a telemetric system capable of long-term data collection.

Autonomic and vascular responses to reduced limb perfusion.

The purpose of this study was to examine hemodynamic responses to graded muscle reflex engagement in human subjects. We studied seven healthy human volunteers [24 +/- 2 (SE) yr old; 4 men, 3 women] performing rhythmic handgrip exercise [40% maximal voluntary contraction (MVC)] during ambient and positive pressure exercise (+10 to +50 mmHg in 10-mmHg increments every minute). Muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP), and mean blood velocity were recorded. Plasma lactate, hydrogen ion concentration, and oxyhemoglobin saturation were measured from venous blood. Ischemic exercise resulted in a greater rise in both MSNA and MAP vs. nonischemic exercise. These heightened autonomic responses were noted at +40 and +50 mmHg. Each level of positive pressure was associated with an immediate fall in flow velocity and forearm perfusion pressure. However, during each minute, perfusion pressure increased progressively. For positive pressure of +10 to +40 mmHg, this was associated with restoration of flow velocity. However, at +50 mmHg, flow was not restored. This inability to restore flow was seen at a time when the muscle reflex was clearly engaged (increased MSNA). We believe that these findings are consistent with the hypothesis that before the muscle reflex is clearly engaged, flow to muscle is enhanced by a process that raises perfusion pressure. Once the muscle reflex is clearly engaged and MSNA is augmented, flow to muscle is no longer restored by a similar rise in perfusion pressure, suggesting that active vasoconstriction within muscle is occurring at +50 mmHg.

Aging and the exercise pressor reflex in humans.

BACKGROUND: Blood flow limitation to exercising muscles engages the muscle reflex during exercise, evoking an increase in heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA). METHODS AND RESULTS: In the current study, we examined forearm flow and autonomic responses to ischemic handgrip in young and older subjects. We studied 6 younger subjects (mean age 23.5+/-2.2 years) and 7 older subjects (mean age 65.0+/-2.4 years). Subjects performed rhythmic handgrip (thirty 1-sec contractions/min) at 30% maximal voluntary contraction during six 1-minute stages: freely perfused exercise (E1) and exercise with forearm pressure of +10, +20, +30, +40, and +50 mm Hg (E2 through E6). We measured HR, BP, MSNA, forearm flow velocity, forearm venous oxygen saturation, H(+), and lactate. Compared with E1, ischemic exercise (E2 through E6) increased HR, BP, and MSNA, reduced forearm velocity, lowered venous oxygen saturation, and raised venous lactate and H(+). Compared with the younger subjects, the older subjects had attenuated BP at E6, attenuated MSNA indices (%(Delta)bursts, bursts/100 heart beats and signal averaged MSNA), attenuated H(+) at E6, a trend toward higher levels of oxygen saturation, and similar forearm velocity and HR responses. CONCLUSIONS: Aging attenuates the muscle reflex.

Venous plasma potassium is not associated with maintenance of the exercise pressor reflex in humans.

Increases in the concentration of interstitial potassium concentration during exercise may play a role in the modulation of the cardiovascular response to exercise. However, it is not known if changes in potassium correlate with indexes of muscle reflex engagement. Eight healthy subjects performed dynamic [rhythmic handgrip (RHG)] and static handgrip (SHG) exercise at 40% of maximal voluntary contraction. Forearm circulatory arrest was performed to assess the metaboreceptor component of the exercise pressor reflex. Mean arterial pressure (MAP) and muscle sympathetic nerve activity (MSNA) were measured during each exercise paradigm. Venous plasma potassium concentrations ([K(+)](V)) were measured and used as a surrogate marker for interstitial potassium. [K(+)](V) were measured at baseline and at 1-min intervals during dynamic handgrip. During SHG, [K(+)](V) were measured at baseline, 30 and 90 s of exercise, and twice during forearm circulatory arrest. Mean [K(+)](V) was 3.6 mmol/l at rest before both paradigms. During RHG, [K(+)](V) rose by approximately 1.0 mmol/l by min 2 and remained constant throughout the rest of handgrip. During SHG, [K(+)](V) rose significantly at 30 s and rose an additional approximately 1.0 mmol/l by peak exercise. MAP and MSNA rose during both exercise paradigms. During posthandgrip circulatory arrest (PHG-CA), MSNA and blood pressure remained above baseline. [K(+)](V) and MSNA did not correlate during either exercise paradigm. Moreover, during PHG-CA, there was clear dissociation of MSNA from [K(+)](V). These data suggest that potassium does not play a direct role in the maintenance of the exercise pressor reflex.