Bioelectronics goes 3D: new trends in cell-chip interface engineering.

Bioelectronic platforms can be used for electrophysiology, monitoring and stimulating specific cellular functions. While planar electroactive materials have been extensively used, in the past decade new approaches have focused on engineering the interface with pseudo-3D micro and nanostructures and, more recently, on 3D geometries (i.e. scaffold-like). Here, we present an overview of this transition from 2D to 3D bioelectronic platforms and our recent achievements of characterizing the interface between the cells and the device.

Improvement of sleep architecture in PD with subthalamic nucleus stimulation.

High-frequency stimulation of the subthalamic nucleus (STN) was used to investigate the relationship of sleep disorders with motor handicap in PD. In 10 insomniac patients with PD, stimulation reduced nighttime akinesia by 60% and completely suppressed axial and early morning dystonia, but did not alleviate periodic leg movements (n = 3) or REM sleep behavior disorders (n = 5). Total sleep time increased by 47%; wakefulness after sleep onset decreased by 51 minutes. Insomnia in patients with PD may predominantly result from nighttime motor disability.

Linkage of hiccup with heartbeat.

We explored a possible link between the cardiac cycle and the timing of recurrent hiccups in 10 patients with chronic, intractable hiccups. Recordings made during daytime naps in a sleep laboratory included sleep state; electrocardiogram; and respiration by means of a thermistor to detect airflow, bands around the rib cage and abdomen to assess expansion, and a bipolar surface electrode electromyogram over parasternal intercostal muscles. Hiccups could be detected on the abdominal bands and the parasternal electromyogram. The time of occurrence of each hiccup and each R wave in a continuous tracing of 100 or more hiccups were recorded and analyzed together with semiquantitive estimates of the phase of hiccup respiration. Whereas the hiccup rate ranged from approximately one-third to one-eighth of heart rate and was more variable than heart rate, hiccups showed a tendency, stronger in some subjects than others, to occur in midsystole. Variation in R-wave-R-wave (R-R) interval in association with hiccups was found in five patients. In three of these patients, hiccups were synchronized with respiration so that the cyclic change in R-R interval posthiccup could be explained as sinus arrhythmia, but, in two patients, the hiccups were not synchronized with respiration, so that hiccups are most likely responsible for the variation in heart rate. Also, the variation of R-R interval with hiccups suggests that there is some phasic autonomic efferent activity associated with hiccups.

Effect of low and high frequency thalamic stimulation on sleep in patients with Parkinson's disease and essential tremor.

Continuous high frequency stimulation of the ventral intermediate nucleus of the thalamus (Vim), delivered through surgically implanted quadripolar electrodes, alleviates tremor in Parkinson's disease (PD) and essential tremor (ET). The Vim is adjacent to the thalamic reticular nuclei, where sleep spindles originate according to animal models. In order to determine whether Vim stimulation affects sleep spindles, six patients (4 PD, 2 ET), aged 60-69 years, were recorded on a control night and a stimulation night (130 Hz, 2-3 V; right stimulation in five patients and bilateral stimulation in one patient). Stimulation did not modify sleep quality or architecture. Sleep spindles were present and symmetrical in five out of six patients under stimulation. However, in one patient with a sustained 'thalamotomy-like effect' that abolished tremor, spindles were asymmetrical even without stimulation. In each patient, spindle density was similar on both nights (mean+/- SEM: 2.25+/-0. 61 spindles per min of stage 2 sleep vs. 1.84+/-0.31). In an attempt to promote sleep two different patterns of stimulation were applied in the region of ventrooralis posterior and reticularis nuclei in five patients in the awake state. Continuous low frequency stimulation (5 Hz, 0.1 V), and repeated trains of 15 Hz for 1 s every 15 s mimicking the pattern of physiological spindles, each failed to induce sleep or cortical synchronization. We conclude that Vim stimulation, unlike thalamotomy, selectively reduces tremor without altering sleep or sleep spindles. Our results also suggest that low frequency stimulation applied in the region of the reticular nuclei does not induce sleep.

Sleep disorders and diaphragmatic function in patients with amyotrophic lateral sclerosis.

In amyotrophic lateral sclerosis (ALS), the progressive loss of upper and lower motor neurons leads to respiratory failure, often with predominant diaphragm dysfunction, and death. Because the diaphragm is the only active inspiratory muscle during rapid eye movement (REM) sleep, there is a high theoretical risk of respiratory disorders during REM sleep in patients with ALS. To assess this hypothesis, we studied sleep characteristics (polysomnography) in 21 patients with ALS, stratified according to the presence or absence of diaphragmatic dysfunction. Diaphragmatic dysfunction was defined as an absent or delayed diaphragm response to cervical or cortical magnetic stimulation, abdominal paradox, or respiratory pulse (Group 1, 13 patients). These patients did not differ in age, clinical course, or form (bulbar or spinal) from the eight others, who did not have diaphragmatic dysfunction (Group 2). REM sleep was reduced in Group 1 (7 +/- 7% of total sleep time; mean +/- SD) and normal in Group 2 (18 +/- 6%, p = 0.004). Apneas or hypopneas were rare in both groups. In Group 1, REM sleep was absent or minimal (less than 3 min) in five patients. An unusual and remarkable preservation of phasic inspiratory sternomastoid activation during REM was associated with longer REM sleep duration in six of the other patients with diaphragmatic dysfunction. Median survival time was dramatically shorter (217 d) in Group 1 than in Group 2 (619 d, p = 0.015).

Modafinil in obstructive sleep apnea-hypopnea syndrome: a pilot study in 6 patients.

We studied the effects of modafinil, a vigilance-enhancing drug, on excessive daytime sleepiness, memory, night sleep and respiration in 6 patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) using a double-blind random cross-over design with 24-hour polysomnography, verbal memory test and a 5-week sleep-wake diary kept by the patients. There were two 2-week treatment periods in which either modafinil or placebo was used; they were separated by a 1-week wash-out period. Our results show that modafinil reduces daytime sleep duration, lengthens the duration of subjective daytime vigilance and improves long-term memory in patients with OSAHS without modifying night sleep and respiration events.

Chronic hiccups and sleep.

To explore the effect of sleep on hiccups, we studied eight patients aged 20-81 years, all males with chronic hiccups lasting 7 days to 7 years, by means of overnight polysomnography. The incidence of new bouts of hiccups and the likelihood of hiccups being present were both highest in wakefulness and became progressively lower through stages I-IV of slow wave sleep (SWS) to rapid eye movement sleep (REMS). There was a significant tendency for hiccups to disappear at sleep onset and REMS onset. Of all 21 bouts of hiccups that were observed to stop, 10/21 did so during an apnea or hypopnea. Frequency of hiccups within a bout slowed progressively from wakefulness through the stages of SWS to REMS. For the whole group, mean frequency decreased significantly from wakefulness [(25.6 +/- 12.1), (mean +/- SD)] to sleep onset or stage I (22.3 +/- 12.2). Sleep latency was increased from 8 +/- 16.3 minutes when hiccups were absent to 16.35 +/- 19.9 minutes when it was present. Sleep efficiency was poor because of long waking periods, and there were deficiencies of both SWS and REMS. Hiccups themselves were not responsible for any arousals or awakenings. We conclude that neural mechanisms responsible for hiccups are strongly influenced by sleep state and that hiccups disrupt sleep onset but not established sleep.

[Narcolepsy disclosing neurosarcoidosis]. / Narcolepsie révélatrice d'une neurosarcoïdose.

A 37-year-old man developed excessive daytime sleepiness, sleep attacks and cataplexy revealing an hypothalamic tumour. Multiple Sleep Latency Tests (MSLT) were characteristics of narcolepsy. Tissue typing was positive for HLA DR2 and DQ1. Most cases of narcolepsy are idiopathic without any evidence of brain pathology. Although symptomatic narcolepsy may occur occasionally with diencephalic lesions. The relationship between narcolepsy with diencephalic lesions is unsettled and will be discussed.

Non-pharmacological approaches to the treatment of narcolepsy.

A way of evaluating the part played by non-drug treatments is to study cases of patients who discontinued stimulant medications but still came back for follow-up visits. Out of 40 patients with narcolepsy-cataplexy, three refused medication because their work was compatible with a regimen of naps (follow-up 1 year), and 10 stopped taking drugs when they could adapt nap therapy to a new life-style (follow-up 6.9 +/- 5 years). Three interrelated levels of non-pharmacological treatments of narcolepsy were examined: 1) Behavioral management, which includes: (A) structured sleep schedules: literature shows that a single long afternoon nap proffered greatest performance benefits in reaction time, significantly increased over a no-nap control condition, with no evidence of sleep inertia. The placement of this nap might yield better results if scheduled 1 hour before that of a normal subject. (B) Dietary factors: little is known about the effects of diet in narcoleptics; however, avoiding simple sugars will improve alertness in some patients. 2) Medical and psychiatric aspects of care. 3) Social factors as an interface between the patients and their environment.

Factors related to sleep apnea syndrome in sleep clinic patients.

We examined 129 patients recruited from two sleep clinics to study the sleep apnea syndrome (SAS), defined by the apnea-hypopnea index (AHI) > or = 10. Information was registered from a self-administered questionnaire, basal physical measurements, and polysomnography. In 68 subjects recorded for two consecutive nights, a high correlation was found between first- and second-night AHIs (r = 0.89). Habitual loud snoring and breathing arrests during sleep were associated with AHI > or = 10. A model including these two variables, sex, age, and body mass index was created in order to predict AHI > or = 10 and with which it was possible to successfully classify almost three of four patients. Among subjective sleep questionnaire items, only daytime sleepiness was related to drops of transcutaneous oxygen tension. These discrepancies in the observed relationship between sleep parameters and subjective sleep items reduce the questionnaire value in epidemiologic settings where it aimed to detect SAS, as defined solely by the AHI value.

[Insomnia therapy and withdrawal of hypnotics]. / Traitement de l'insomnie et sevrage des hypnotiques.

The aim of this study is to evaluate the efficiency of a treatment prescribed, in the course of an hospital consultation for sleep pathology, to patients suffering from chronic insomnia not improved by longstanding and sustained medication with hypnotic drugs. The basis of the treatment is a progressive but total withdrawal of hypnotics in so far taken regularly. The withdrawal of hypnotics was prescribed to 79 patients: 33 aged 17 to 39 years (group 1, mean age 30) and 46 aged 40 to 70 years (group 2, mean age 51). 41 showed primary psychophysiological insomnia and 28 showed insomnia associated with psychiatric disorders. In patients of group 1, the average durations were 8 years for insomnia and 3 years for sustained hypnotic use; these durations were 15 and 5 years respectively in patients of group 2. Hypnotic drug withdrawal was achieved without placebos in 3 months in group 1 patients and 5 months in group 2 patients. 65 patients completely stopped the continual use of hypnotics. Subjective improvement of insomnia was reported by 51 of these patients (as well as by 6 patients who were given simultaneous antidepressant therapy). 16 of the 51 improved patients have resorted to hypnotics occasionally (at intervals of 10 days or more). After complete withdrawal, patients went on consulting for various lengths of time: 5 months average for group 1, 14 months average for group 2. This study of a fairly large group of insomniacs shows the frequent ineffectiveness of a sustained use of currently available hypnotics. It also shows that two times out of three the complete stop of sustained hypnotic medication proved beneficial to the patient.

[Age and insomnia: the number and length of waking periods (author's transl)]. / Age et insomnie: parts respectives du nombre et de la durée des éveils.

The role and importance of the number of awakenings and their duration in relation to increasing intervening wakefulness were investigated. The data were collected from a group of 38 subjects suffering from chronic primary insomnia, aged 17-70 years, polygraphically recorded; the analysis was made on the second night. With age, the total quantity of intervening wakefulness increases more quickly than the total number of awakenings. The amount of wakefulness due to awakenings lasting greater than or equal to 3 min increases with age. Older insomniacs wake up somewhat more often but, above all, they go back to sleep less quickly. Our hypothesis is that in old patients insomnia is linked to an increase in stability of wakefulness.

[Nocturnal awakenings as a function of age in insomniacs (author's transl)]. / Les éveils nocturnes chez le sujet insomniaque en fonction de l'age.

The effect of ageing on the sleep of insomniacs was studied by comparing objective insomnia characteristics from polygraphic recordings made during two successive nights in two groups of different ages : 14 patients aged 19 to 39 years (mean 31 years) and 11 aged 42 to 65 years (mean 50 years). All of them had severe insomnia causing them to request consultation for sleep disorders. Their only clinical symptom was chronic primary insomnia, persisting following withdrawal of hypnotics, no other physical (particularly no sleep apnea) or psychological disorder being present. Parameters studied during the first and the second night were the number and duration of intra-sleep awakenings, and the proportions of the sleep and wakefulness periods.

[Night sleep patterns in post-operative intensive care patients (author's transl)]. / Organisation du sommeil de nuit chez des malades en réanimation chirurgicale.

5 patients admitted to intensive care following post-operative complications had EEG recordings on 2 consecutive nights some time after their operations. Study of the different sleep stages showed a marked increase in deep slow wave sleep and waking but asignificant reduction in light slow wave sleep and paradoxical sleep. The appearance of the sleep cycles through the night was unusual with respect to the maximum occurrence of the various stages and their evolution. Finally certain characteristics of paradoxical sleep, the rhythm and duration of the phases and the number and frequency of ocular movements were also modified. Comparison of these findings with those previously reported show that these abnormalities, rather than suggesting sleep deprivation resemble more closely the fidings in shift workers when they resume night sleep after a period of day sleep. The also resemble the changes seen in people whose circadian rhythm has been displaced by 12 hours.