The hypothalamic link between arousal and sleep homeostasis in mice

Sleep and wakefulness are not simple, homogenous all-or-none states but represent a spectrum of substates, distinguished by behavior, levels of arousal, and brain activity at the local and global levels. Until now, the role of the hypothalamic circuitry in sleep–wake control was studied primarily with respect to its contribution to rapid state transitions. In contrast, whether the hypothalamus modulates within-state dynamics (state “quality”) and the functional significance thereof remains unexplored. Here, we show that photoactivation of inhibitory neurons in the lateral preoptic area (LPO) of the hypothalamus of adult male and female laboratory mice does not merely trigger awakening from sleep, but the resulting awake state is also characterized by an activated electroencephalogram (EEG) pattern, suggesting increased levels of arousal. This was associated with a faster build-up of sleep pressure, as reflected in higher EEG slow-wave activity (SWA) during subsequent sleep. In contrast, photoinhibition of inhibitory LPO neurons did not result in changes in vigilance states but was associated with persistently increased EEG SWA during spontaneous sleep. These findings suggest a role of the LPO in regulating arousal levels, which we propose as a key variable shaping the daily architecture of sleep–wake states.

Background frequency can enhance the prognostication power of EEG patterns categories in comatose cardiac arrest survivors: a prospective, multicenter, observational cohort study

Background We assessed the prognostic accuracy of the standardized electroencephalography (EEG) patterns (“highly malignant,” “malignant,” and “benign”) according to the EEG timing (early vs. late) and investigated the EEG features to enhance the predictive power for poor neurologic outcome at 1 month after cardiac arrest. Methods This prospective, multicenter, observational, cohort study using data from Korean Hypothermia Network prospective registry included adult patients with out-of-hospital cardiac arrest (OHCA) treated with targeted temperature management (TTM) and underwent standard EEG within 7 days after cardiac arrest from 14 university-affiliated teaching hospitals in South Korea between October 2015 and December 2018. Early EEG was defined as EEG performed within 72 h after cardiac arrest. The primary outcome was poor neurological outcome (Cerebral Performance Category score 3–5) at 1 month. Results Among 489 comatose OHCA survivors with a median EEG time of 46.6 h, the “highly malignant” pattern (40.7%) was most prevalent, followed by the “benign” (33.9%) and “malignant” (25.4%) patterns. All patients with the highly malignant EEG pattern had poor neurologic outcomes, with 100% specificity in both groups but 59.3% and 56.1% sensitivity in the early and late EEG groups, respectively. However, for patients with “malignant” patterns, 84.8% sensitivity, 77.0% specificity, and 89.5% positive predictive value for poor neurologic outcome were observed. Only 3.5% (9/256) of patients with background EEG frequency of predominant delta waves or undetermined had good neurologic survival. The combination of “highly malignant” or “malignant” EEG pattern with background frequency of delta waves or undetermined increased specificity and positive predictive value, respectively, to up to 98.0% and 98.7%. Conclusions The “highly malignant” patterns predicted poor neurologic outcome with a high specificity regardless of EEG measurement time. The assessment of predominant background frequency in addition to EEG patterns can increase the prognostic value of OHCA survivors. Trial registration KORHN-PRO, NCT02827422. Registered 11 September 2016—Retrospectively registered.

Abstract 12398: Cardiopulmonary Resuscitation Duration Determines Phenotype of Post-Arrest Brain Injury

Introduction: Patients resuscitated from out-of-hospital cardiac arrest (OHCA) have variable severity of brain injury. Signatures of severe injury on brain imaging and EEG including diffuse cerebral edema and burst suppression with identical bursts (BSIB). Current therapies for these patterns of injury are inadequate and patient outcomes are poor. Hypothesis: We hypothesize distinct phenotypes of brain injury are associated with increasing CPR duration. Methods: We identified from our prospective registry OHCA patients treated between January 2010 to July 2019. We abstracted CPR duration, best neurological examination < 6 hours from OHCA, initial brain CT grey-to-white ratio (GWR), and initial EEG pattern. We defined cerebral edema as GWR <1.20. We defined BSIB according to American Clinical Neurophysiology Society guidelines. We considered four phenotypes on presentation: awake; comatose with neither BSIB nor cerebral edema; BSIB; and cerebral edema. BSIB and cerebral edema were considered as non-mutually exclusive outcomes. We compared duration of CPR across groups using Kruskal-Wallis tests with Bonferroni correction for multiple hypothesis testing. We report the probability of presenting phenotype at the median CPR duration for each group using local regression. Results: We included 2,721 patients, of whom 582 (21%) were awake, 1,428 (52%) had coma without BSIB or edema, 372 (14%) had BSIB and 356 (13%) had cerebral edema. Only 47 (2%) had both BSIB and edema. Median CPR duration was 16 [IQR 8-28] minutes overall. Median CPR duration increased in a stepwise manner across groups: awake 6 [3-12] minutes; comatose without BSIB or edema 16 [9-27] minutes; BSIB 21 [14-30] minutes; cerebral edema 32 [22-46] minutes (all P <0.001). The probability of observing each phenotype at the median CPR duration for each was: awake (0.42); comatose without BSIB or edema (0.72); BSIB (0.34); cerebral edema (0.29). Conclusions: The brain injury phenotype is related to CPR duration, which is a surrogate for severity of ischemic injury. The sequence of most likely brain injury phenotype with progressively longer CPR duration is awake, coma without BSIB or edema, BSIB, and finally cerebral edema.

Congenital hydrocephalus in three sheep: Clinical, electroencephalographic and pathological features

The clinical, electroencephalographic and neuro-pathological features of three cases (cases 1, 2 and 3) of congenital hydrocephalus in sheep were described. The observed neurological signs reflected damage in the telencephalon and brain stem. The electroencephalogram performed in case 1 and case 2 showed different patterns: symmetric and synchronous high-voltage slow-activity in case 1, and low-voltage slow-activity in case 2. By the post-mortem examination, in all the animals, dilatation of the ventricular system, especially of the lateral ventricles, associated with a glial reaction surrounding the dilated ventricles was observed. Only in case 3, a monolateral meningeal thickening at the left cerebellopontine angle seemed to be responsible for the obstructive hydrocephalus. In the other two brains (case 1 and 2), no potential anatomical cause for the hydrocephalus were detected, even if, in case 2, a compensatory form was not excluded due to the moderate hypoplasia of the cerebrum and the presence of the non-suppurative inflammation. The results of this work provide a contribution to the EEG characterisation in ovine hydrocephalus cases; nevertheless further multidisciplinary studies of a larger number of sheep could permit to better characterise the EEG pattern in ovine hydrocephalus cases.

The Regional EEG Pattern of the Sleep Onset Process in Older Adults

Healthy aging is characterized by macrostructural sleep changes and alterations of regional electroencephalographic (EEG) sleep features. However, the spatiotemporal EEG pattern of the wake-sleep transition has never been described in the elderly. The present study aimed to assess the topographical and temporal features of the EEG during the sleep onset (SO) in a group of 36 older participants (59–81 years). The topography of the 1 Hz bins’ EEG power and the time course of the EEG frequency bands were assessed. Moreover, we compared the delta activity and delta/beta ratio between the older participants and a group of young adults. The results point to several peculiarities in the elderly: (a) the generalized post-SO power increase in the slowest frequencies did not include the 7 Hz bin; (b) the alpha power revealed a frequency-specific pattern of post-SO modifications; (c) the sigma activity exhibited only a slight post-SO increase, and its highest bins showed a frontotemporal power decrease. Older adults showed a generalized reduction of delta power and delta/beta ratio in both pre- and post-SO intervals compared to young adults. From a clinical standpoint, the regional EEG activity may represent a target for brain stimulation techniques to reduce SO latency and sleep fragmentation.

Electroclinical Features in MECP2 Duplication Syndrome: Pediatric Case Series

Objective: MECP2 duplication syndrome (MECP2DS) is an x-linked recessive syndrome characterized by infantile hypotonia, severe neurodevelopmental delay, intellectual disability, progressive spasticity, recurrent infections, and seizures. More than 50% of cases have been associated with epilepsy. Seizure semiology and electroencephalogram (EEG) findings in these patients are poorly described. Methods: In this case series, the authors describe the electroclinical features of children with MECP2DS presenting to their institution. In addition, they reviewed seizure types and therapies used. Results: Eight out of 9 patients with MECP2DS developed epilepsy, with 56% having normal initial EEG. Generalized slowing with generalized and focal/multifocal discharges was the most common EEG pattern which is consistent with prior studies. Atonic seizure was the most common semiology. Majority were pharmacoresistant (63%). Conclusion: The goal of this case series is to better define the clinical and electrophysiological aspects of the epilepsy associated with MECP2 duplication syndrome and provide practical guidance regarding management.

Electroencephalography: Experience at Abakaliki Nigeria

BACKGROUND: Electroencephalography (EEG) remains the most important investigative modality in the evaluation of individuals with epilepsy and other neurological disorders. The pattern of EEG done in a tertiary hospital at Abakaliki Nigeria is not known. It is against this background that we embarked on this retrospective observational study on the EEG pattern and patient characteristics in Neurophysiology laboratory at Abakaliki Nigeria. METHOD: This is a retrospective observational hospital based study where the attendance register of the Neurophysiology laboratory was used to extract information on the demography, clinical characteristics and EEG reports of patients seen at the Laboratory from November 2018 to April 2021. RESULTS: A total of 125 (Male- 69, Female- 56) persons did EEG over the study period, and 75.2% had epileptiform waves (generalized- 16.8%, focal- 57.6%).&nbsp; CONCLUSION: EEG services are been utilized at Abakaliki in evaluation of seizure disorder and other paroxysmal neurological events with more prevalent focal epileptiform waves.