Sleep characteristics in Goldenhar Syndrome.

OBJECTIVE: To examine the characteristics of sleep in patients with Goldenhar Syndrome. DESIGN: Retrospective review of all polysomnography studies conducted at the University of North Carolina Hospitals between 2003 and 2013 on patients carrying the diagnosis of Goldenhar's Syndrome. RESULTS: A preponderance of patients demonstrated severe obstructive sleep apnea and hypercapnia. CONCLUSIONS: Patients with Goldenhar Syndrome should be screened for sleep apnea and hypercapnia.

Heart period sensitivity to forced oscillations in ventilatory pressure.

Heart rate variability analysis is a dynamic method to estimate the autonomic control over the cardiac cycle. Although dysfunction in this control system may appear spontaneously, other deficits may require provocation of the system. In this article we describe a non-invasive method to perturb the autonomic influences on the cardiac cycle. We recorded the ECG and respiratory pressure of ten healthy volunteers while introducing a random forced oscillation pressure wave onto spontaneous respiration. The heart period time series was determined and the power spectra for the 0.05-0.15, 0.15-0.3 and 0.05-0.4 Hz bands were calculated. The random input did not alter mean heart rate. However, the segments with the forced oscillation input demonstrated, on average, a tenfold increase in spectral power averaged across all subjects, with a maximum observed effect of 100-fold increase in power. This increase in power correlated with the respiratory frequency. This study demonstrates that random noise ventilation, such as used in respiratory forced oscillation impedance estimates, significantly alters the autonomic input to cardiac cycle variability in wake subjects.

Treating obstructive sleep apnea in adults with epilepsy: a randomized pilot trial.

OBJECTIVE: Small uncontrolled series suggest that treatment of obstructive sleep apnea (OSA) in patients with epilepsy may improve seizure control. Prior to conducting a definitive randomized controlled trial, we addressed critical design issues in a pilot study. METHODS: We identified a cohort of adult patients with medically refractory epilepsy and coexisting OSA, documented by polysomnography (PSG). After an 8-week baseline period, subjects with OSA were randomized to therapeutic or sham continuous positive airway pressure (CPAP) for 10 weeks. Subjects maintained seizure calendars and antiepileptic drug dosages were held constant. RESULTS: Sixty-eight subjects with suspected OSA were enrolled and 35 subjects randomized to therapeutic CPAP (22 subjects) or sham (13 subjects) CPAP. Male gender and an elevated sleep apnea questionnaire score were predictive of OSA on PSG. Nineteen subjects in the therapeutic group and all 13 subjects in the sham group completed the trial. Baseline apnea-hypopnea index (AHI) and CPAP adherence were comparable between groups. A significant reduction in AHI was observed in the therapeutic CPAP group as compared to the sham group. Subjects, study coordinators, and principal investigators were unable to predict treatment allocation. CONCLUSIONS: This pilot study provided critical information related to study design and feasibility for planning a comprehensive trial to test the hypothesis that treating obstructive sleep apnea in patients with epilepsy improves seizure control.

Intraoperative methods for confirmation of correct placement of the vagus nerve stimulator.

Vagus nerve stimulation is a progressive therapy for intractable epilepsy. Variations in cervical anatomy can complicate localization of the vagus nerve and may lead to inappropriate placement of the stimulator leads. We have developed two intraoperative techniques that improve correct identification of the vagus nerve. Both of these techniques utilize the co-localization of the recurrent laryngeal nerve with the vagus nerve. For patients undergoing stimulator placement with regional and local anesthesia, the stimulator current intensity is increased until alteration of voice can be confirmed with a voice test. Patients undergoing general anesthesia can also be tested by direct stimulation of the isolated vagus nerve. Utilizing visualization of the larynx and vocal cords via fiberoptic endoscopy, direct stimulation of the vagus nerve will produce a contraction of the left lateral wall of the larynx and tightening of the left vocal cord. Neither of these procedures produce any untoward effects for the patients. We have found these methods improve our ability to confirm correct placement of the stimulator with minimal increase in operative time (with Video).

Periodic lateralized epileptiform discharges after complex partial status epilepticus associated with increased focal cerebral blood flow.

Periodic lateralized epileptiform discharges (PLEDs) are typically associated with encephalitis, cerebral abscess, cerebral infarct, and status epilepticus. There is considerable debate as to whether this pattern is ictal or interictal when seen in association with status epilepticus. We present a patient with complex partial status epilepticus who developed PLEDs and remained comatose despite optimal drug therapy. Technetium 99m single-photon emission computed tomography (SPECT) showed hyperperfusion that resolved with further aggressive antiepileptic drug therapy, indicating that this pattern may indeed be ictal. Further studies are needed to define the significance of PLEDs in patients with status epilepticus. The role of SPECT in differentiating PLEDs as an interictal or ictal pattern also requires further study.

Parasomnias--an update.

Primary parasomnias are a group of sleep-related clinical disorders that occur in otherwise healthy children, which may be provoked by a variety of physical, psychosocial, and environmental stimuli. In typical cases, additional investigations are not necessary, and treatment should be instituted with the aim of reducing the frequency and adverse consequences of the parasomnia. In patients with co-existing clinical disorders, parasomnias need to be distinguished from symptoms of the underlying disorder. This article provides a brief review of the recent literature regarding parasomnias, and a clinically oriented approach to the management of parasomnias in patients with co-existing clinical disorders.

Heart period variability during vagal nerve stimulation.

Vagal nerve stimulation is an emerging therapy for epilepsy, yet little is known regarding the effects of this stimulation on heart period variability. We selected 10 patients (two female, eight male) who were receiving high-frequency, high-intensity left vagal nerve stimulation for intractable epilepsy. Electrocardiogram data were recorded for a 7 min baseline, 2.5 min of stimulation and a 7 min post-stimulation period. We found no significant changes in average heart period, instantaneous changes of successive R-to-R intervals greater than 50 ms or fractal dimension. We also found no significant changes in the total power in the 0.0-0.04 Hz, 0.04-0.12 Hz and 0.2-0.4 Hz bands with stimulation of the left vagus nerve. This study suggests that left vagal nerve stimulation has little acute effect on the cardiac rhythm or heart period variability.

Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial.

OBJECTIVE: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. BACKGROUND: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. METHODS: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. RESULTS: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. CONCLUSIONS: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.

Seizures in lung transplant recipients.

PURPOSE: We wished to assess organ transplant recipients, who incur a significant risk for seizures. METHOD: We reviewed 85 lung transplants performed in 81 patients at the University of North Carolina hospitals between 1991 and 1994. All patients were reviewed for age, reason for transplant, detailed description of seizures, neurological examination, medications, and laboratory results, including cyclosporine level, EEG, and brain imaging. RESULTS: Eighteen of 81 (22%) patients experienced seizures. Patients aged < 25 years had the greatest risk of seizures and 15 of the 18 patients had cystic fibrosis. Sixteen of the 18 (89%) patients, by history, had partial-onset seizures. Eleven of the 18 (61%) patients had seizures < or = 10 days after initiation of intravenous methylprednisolone for allograft rejection. Two patients had seizures associated with sustained hypertension: 1 of these patients was simultaneously being treated for rejection. Four patients had strokes (1 before transplant) and seizures. Two patients were receiving imipenem. Magnetic resonance imaging (MRI) of the brain demonstrated areas of increased T2 signal in 8 of 9 patients. CONCLUSIONS: Our findings demonstrate multiple etiologies for seizures in our transplant recipients. However, we believe that patients, especially those aged < 25 years, being treated with intravenous methylprednisolone for rejection may be at increased risk of seizures. We hypothesize that the focal loss of blood-brain barrier (BBB) may play a significant role in the development of partial seizures in lung transplant recipients.

Similarities of EEG and seizures in del(1q) and benign rolandic epilepsy.

We studied the seizure disorders manifested by three previously reported children with "de novo" terminal deletions of the long arm of chromosome 1 (46,XX,del(1)(q43)) and similar clinical phenotypes. In late infancy, two of these children developed partial seizures characterized by tonic-clonic movements of the ipsilateral face and arm with occasional involvement of the leg. In both children, the seizure frequency decreased with increasing age. Electroencephalograms of these two children demonstrated centrotemporal spike discharges morphologically similar to rolandic spikes. Although these cases present significant similarities to benign rolandic epilepsy, they also express many manifestations not detected in benign rolandic epilepsy that may reflect the extensive deletion of chromosome 1. Based on the seizure semiology and centrotemporal epileptiform discharges, we suggest that the distal portion of the long arm of chromosome 1 is a potential site for a candidate gene for benign rolandic epilepsy.

Improvement of epileptic seizure control with treatment of obstructive sleep apnoea.

Sleep deprivation increases the risk of recurrent seizures in epileptic patients. We identified 10 patients with recurrent seizures and sleep disruption related to obstructive sleep apnoea. Two patients were treated with positional therapy and the remaining eight patients were treated with continuous positive airway pressure. Three of the patients became seizure free and a fourth patient had a greater than 95% reduction in seizure frequency following only the initiation of therapy for the sleep apnoea. Three of these four patients responding to therapy, had a state-dependent seizure pattern. Two of the four responders did not exhibit the typical body habitus for obstructive sleep apnoea. Three additional patients improved in seizure frequency with change in anticonvulsant medication and treatment of the obstructive sleep apnoea. The remaining three patients had less than 50% reduction in seizure frequency with treatment of the obstructive sleep apnoea. These results indicate sleep disruption caused by sleep apnoea may increase the seizure frequency in some epileptic patients. Regardless of body habitus, epilepsy patients should be questioned carefully for a history of sleep disturbance and state dependence to their seizures. Treatment of sleep disorders in this population may lower the frequency of recurrent seizures.

Carbamazepine as a treatment for cataplexy.

Cataplexy is a common symptom associated with narcolepsy. We evaluated a 51-year-old female who developed symptoms of progressive daytime sleepiness with cataplexy. The diagnosis of narcolepsy was confirmed by overnight polysomnogram and was consistent with results of a multiple sleep latency study, and episodes of cataplexy were documented by video-EEG-EMG monitoring. Examination during a catapletic episode was significant for areflexia and paralysis. The frequency of cataplexy increased with fluoxetine, protriptyline and sertraline and the patient developed frank choreiform movements with protriptyline and sertraline. The cataplexy resolved following treatment with carbamazepine. We feel carbamazepine is a potential treatment for patients with refractory cataplexy.

Heart period variability in sleep.

Analysis of heart period variability is a dynamic noninvasive technique to quantify the autonomic control over the heart period. We recorded electroencephalographic, electro-oculographic, electromyographic and electrocardiographic data from 10 normal subjects during sleep using an ambulatory polysomnographic monitor. R-R intervals were determined for 10 min segments of electrocardiographic data from wakefulness, stage 2 sleep, slow wave sleep and REM sleep. Average heart period, instantaneous changes greater than 50 msec and fractal dimension were calculated and the time domain and phase plots were depicted. The R-R interval time domain plots were subsequently analyzed using the discrete Fourier transform. We found sleep stage specific, time domain and frequency domain changes in heart period variability, particularly using spectral analysis of heart period. Increased power in the 0.2-0.4 Hz band was associated with stage 2 sleep when compared to awake and slow wave sleep states. Power in the 0.0-0.04 and 0.04-0.12 Hz bands was increased in association with REM sleep when compared to non-REM sleep, and slow wave sleep had diminished power in all frequency bands. Our results support other investigations demonstrating stage 2 sleep is associated with increased parasympathetic influences and REM sleep is associated with increased sympathetic and neurohumoral influences. We feel that spectral analysis of heart period variability is an effective noninvasive method to quantify changes in the autonomic influences over the heart during sleep.

Symptomatic cataplexy in pontomedullary lesions.

Cataplexy is a cardinal manifestation of the narcolepsy syndrome. Although symptomatic narcolepsy is well described, isolated cataplexy is extremely rare. We reviewed clinical and radiologic data in two patients with isolated symptomatic cataplexy and associated CNS disease. In an HLA-DR2-positive patient with chronic progressive MS, we confirmed cataplexy by observation of reported spells. MRI revealed diffuse white-matter lesions involving the medial medulla, pons, and subcortical white matter; protriptyline provided symptomatic relief. A second patient with a pontomedullary pilocytic astrocytoma developed infrequent but recurrent cataplectic attacks in association with sleep fragmentation due to nocturnal cough and nausea. MRI revealed an enhancing lesion involving the dorsal pons and medulla. Genetic predisposition and sleep fragmentation may precipitate symptomatic cataplexy in patients with structural pontomedullary lesions.

Localization of methadone in the brain of young rats by computer-assisted autoradiography.

The distribution of systemically administered [14C]methadone in the brain of 21-day-old rats was examined by computer-assisted autoradiography. Methadone binding differed 2.5-fold across the more than 90 neural structures examined, with the dentate nucleus having the highest levels and lamina I of the anterior parietal cortex the lowest. Since a full normal probability plot demonstrated that the binding was distributed normally across brain structures (r = 0.99), binding classes were defined in terms of 0.5 standard deviation units from the mean. In addition to marked binding differences between neuronal structures, there were prominent laminar differences in the cerebral cortex, hippocampus, superior colliculus and cerebellar cortex. These highly specific patterns of methadone localization were specifically related to the opioid receptor because naloxone blocked the antinociceptive effects of methadone on the hot-plate test and abolished the distribution of methadone binding in the central nervous system. The relatively high levels of methadone binding in layers III and V of neocortex, sensory relay nuclei, inferior olive, pontine nuclei, cerebellar nuclei and cerebellar molecular layer suggest that the constellation of physiological and neurobehavioral sequelae of perinatal opioid exposure result from specific binding at multiple sites involved in sensory, motor and integrative information processing.