The Reciprocal Relationship between Sleep and Epilepsy.

The relationship between sleep and epilepsy is bidirectional. Certain epilepsy syndromes predominantly or exclusively manifest during sleep, with seizures frequently originating from non-rapid eye movement (NREM) sleep. Interictal epileptiform discharges observed on electroencephalograms are most likely to be activated during the deep NREM sleep stage known as N3. Conversely, epileptiform discharges, anti-seizure medications (ASMs), as well as other anti-seizure therapies can exert detrimental effects on sleep architecture. Moreover, the co-occurrence of sleep disorders has the potential to exacerbate seizure control. Understating the relationship between sleep and epilepsy is crucial for healthcare providers. Addressing and managing sleep-related problems in individuals with epilepsy can potentially contribute to improved seizure control and overall well-being. At the same time, improving seizure control can improve sleep quality and quantity, thus further improving the health of individuals with epilepsy.

AWAreness during REsuscitation - II: A multi-center study of consciousness and awareness in cardiac arrest.

INTRODUCTION: Cognitive activity and awareness during cardiac arrest (CA) are reported but ill understood. This first of a kind study examined consciousness and its underlying electrocortical biomarkers during cardiopulmonary resuscitation (CPR). METHODS: In a prospective 25-site in-hospital study, we incorporated a) independent audiovisual testing of awareness, including explicit and implicit learning using a computer and headphones, with b) continuous real-time electroencephalography(EEG) and cerebral oxygenation(rSO2) monitoring into CPR during in-hospital CA (IHCA). Survivors underwent interviews to examine for recall of awareness and cognitive experiences. A complementary cross-sectional community CA study provided added insights regarding survivors' experiences. RESULTS: Of 567 IHCA, 53(9.3%) survived, 28 of these (52.8%) completed interviews, and 11(39.3%) reported CA memories/perceptions suggestive of consciousness. Four categories of experiences emerged: 1) emergence from coma during CPR (CPR-induced consciousness [CPRIC]) 2/28(7.1%), or 2) in the post-resuscitation period 2/28(7.1%), 3) dream-like experiences 3/28(10.7%), 4) transcendent recalled experience of death (RED) 6/28(21.4%). In the cross-sectional arm, 126 community CA survivors' experiences reinforced these categories and identified another: delusions (misattribution of medical events). Low survival limited the ability to examine for implicit learning. Nobody identified the visual image, 1/28(3.5%) identified the auditory stimulus. Despite marked cerebral ischemia (Mean rSO2 = 43%) normal EEG activity (delta, theta and alpha) consistent with consciousness emerged as long as 35-60 minutes into CPR. CONCLUSIONS: Consciousness. awareness and cognitive processes may occur during CA. The emergence of normal EEG may reflect a resumption of a network-level of cognitive activity, and a biomarker of consciousness, lucidity and RED (authentic "near-death" experiences).

Detection of Common Arrhythmias by the Watch-PAT: Expression of Electrical Arrhythmias by Pulse Recording.

Background: The WatchPAT (WP) device was shown to be accurate for the diagnosis of sleep apnea and is widely used worldwide as an ambulatory diagnostic tool. While it records peripheral arterial tone (PAT) and not electrocardiogram (ECG), the ability of it to detect arrhythmias is unknown and was not studied previously. Common arrhythmias such as atrial fibrillation (AF) or premature beats may be uniquely presented while recording PAT/pulse wave. Purpose: To examine the potential detection of common arrhythmias by analyzing the PAT amplitude and pulse rate/volume changes. Patients and Methods: Patients with suspected sleep disordered breathing (SDB) were recruited with preference for patients with previously diagnosed AF or congestive heart failure (CHF). They underwent simultaneous WP and PSG studies in 11 sleep centers. A novel algorithm was developed to detect arrhythmias while measuring PAT and was tested on these patients. Manual scoring of ECG channel (recorded as part of the PSG) was blinded to the automatically analyzed WP data. Results: A total of 84 patients aged 57±16 (54 males) participated in this study. Their BMI was 30±5.7Kg/m2. Of them, 41 had heart failure (49%) and 17 (20%) had AF. The sensitivity and specificity of the WP to detect AF segments (of at least 60 seconds) were 0.77 and 0.99, respectively. The correlation between the WP derived detection of premature beats (events/min) to that of the PSG one was 0.98 (p<0.001). Conclusion: The novel automatic algorithm of the WP can reasonably detect AF and premature beats. We suggest that when the algorithm raises a flag for arrhythmia, the patients should shortly undergo ECG and/or Holter ECG study.

Special Considerations in the Management of Women with Epilepsy in Reproductive Years.

Anti-seizure medications (ASMs) fail to prevent seizure recurrence in more than 30% of patients with epilepsy. The treatment is more difficult in premenopausal women with epilepsy (WWE) because changes in plasma estrogen and progesterone concentrations during the menstrual cycle often affect seizure frequency and intensity. Interactions between enzyme-inducin ASMs and hormonal contraceptives can lead to both a loss of seizure control and failure of contraception. Significant changes in the function of the liver and kidneys during pregnancy can accelerate metabolism and elimination of ASMs, causing breakthrough seizures. In addition, the teratogenic, cognitive, and psychological effects of ASMs on potential offspring have to be considered when choosing the best ASM regimen. Therefore, aspecialized approach is necessary for the treatment of premenopausal WWE.

Watch-PAT is Useful in the Diagnosis of Sleep Apnea in Patients with Atrial Fibrillation.

BACKGROUND: Early diagnosis and treatment of sleep apnea in patients with atrial fibrillation (AF) is critical. The WatchPAT (WP) device was shown to be accurate for the diagnosis of sleep apnea; however, studies using the WatchPAT device have thus far excluded patients with arrhythmias due to the potential effect of arrhythmias on the peripheral arterial tonometry (PAT) amplitude and pulse rate changes. PURPOSE: To examine the accuracy of the WP in detecting sleep apnea in patients with AF. PATIENTS AND METHODS: Patients with AF underwent simultaneous WP and PSG studies in 11 sleep centers. PSG scoring was blinded to the automatically analyzed WP data. RESULTS: A total of 101 patients with AF (70 males) were recruited. Forty-six had AF episodes during the overnight sleep study. A significant correlation was found between the PSG-derived AHI and the WP- derived AHI (r=0.80, p<0.0001). There was a good agreement between PSG-derived AHI and WP-derived AHI (mean difference of AHI: -0.02±13.2). Using a threshold of AHI ≥15 per hour of sleep, the sensitivity and specificity of the WP were 0.88 and 0.63, respectively. The overall accuracy in sleep staging between WP and PSG was 62% with Kappa agreement of 0.42. CONCLUSION: WP can detect sleep apnea events in patients with AF. AF should not be an exclusion criterion for using the device. This finding may be of even greater importance in the era of the COVID19 epidemic, when sleep labs were closed and most studies were home based.

Are we responding effectively to bone mineral density loss and fracture risks in people with epilepsy?

OBJECTIVE: A 2007 study performed at Montefiore Medical Center (Bronx, NY) identified high prevalence of reduced bone density in an urban population of patients with epilepsy and suggested that bone mineralization screenings should be regularly performed for these patients. We conducted a long-term follow-up study to determine whether bone mineral density (BMD) loss, osteoporosis, and fractures have been successfully treated or prevented. METHODS: In the current study, patients from the 2007 study who had two dual-energy absorptiometry (DXA) scans performed at least 5 years apart were analyzed. The World Health Organization (WHO) criteria to diagnose patients with osteopenia or osteoporosis were used, and each patient's probability of developing fractures was calculated with the Fracture Risk Assessment Tool (FRAX). RESULTS: The median time between the first and second DXA scans for the 81 patients analyzed was 9.4 years (range 5-14.7). The median age at the first DXA scan was 41 years (range 22-77). Based on WHO criteria, 79.0% of patients did not have worsening of bone density, while 21.0% had new osteopenia or osteoporosis; many patients were prescribed treatment for bone loss. Older age, increased duration of anti-epileptic drug (AED) usage, and low body mass index (BMI) were risk factors for abnormal BMDs. Based on the first DXA scan, the FRAX calculator estimated that none of the patients in this study had a 10-year risk of more than 20% for developing major osteoporotic fracture (hip, spine, wrist, or humeral fracture). However, in this population, 11 patients (13.6%) sustained a major osteoporotic fracture after their first DXA scan. SIGNIFICANCE: Despite being routinely screened and frequently treated for bone mineral density loss and fracture prevention, many patients with epilepsy suffered new major osteoporotic fractures. This observation is especially important as persons with epilepsy are at high risk for falls and traumas.

Principles of Epilepsy Management for Women in Their Reproductive Years.

In the United States, there are over one million women with epilepsy (WWE) in their childbearing years. Pregnancy can be challenging for this population. A number of international registries have documented that children born to these women are at increased risk for major congenital malformations (MCM), lower intelligence quotient scores and neurodevelopmental disorders, when the mother is managed on antiseizure medications (ASMs). To prevent poor neonatal outcomes for this population, safe and thoughtful management strategies are necessary. We propose to divide these management strategies into five principles. These include (I) choosing suitable ASMs for the patient's seizure type, (II) choosing an ASM with the least teratogenic and cognitive side effects, (III) dosing at the lowest possible effective dosage, (IV) selecting the best ASM regimen as promptly as possible, even before a woman has her first menses, and (V) supplementing these patients with folic acid in order to try to enhance cognition and reduce neural tube defects.

Detecting central sleep apnea in adult patients using WatchPAT-a multicenter validation study.

STUDY OBJECTIVES: To assess the accuracy of WatchPAT (WP-Itamar-Medical, Caesarea, Israel) enhanced with a novel systolic upstroke analysis coupled with respiratory movement analysis derived from a dedicated snoring and body position (SBP) sensor, to enable automated algorithmic differentiation between central sleep apnea (CSA) and obstructive sleep apnea (OSA) compared with simultaneous in-lab sleep studies with polysomnography (PSG). METHODS: Eighty-four patients with suspected sleep-disordered breathing (SDB) underwent simultaneous WP and PSG studies in 11 sleep centers. PSG scoring was blinded to the automatically analyzed WP data. RESULTS: Overall WP apnea-hypopnea index (AHI; mean ± SD) was 25.2 ± 21.3 (range 0.2-101) versus PSG AHI 24.4 ± 21.2 (range 0-110) (p = 0.514), and correlation was 0.87 (p < 0.001). Using a threshold of AHI ≥ 15, the sensitivity and specificity of WP versus PSG for diagnosing sleep apnea were 85% and 70% respectively and agreement was 79% (kappa = 0.867). WP central AHI (AHIc) was 4.2 ± 7.7 (range 0-38) versus PSG AHIc 5.9 ± 11.8 (range 0-63) (p = 0.034), while correlation was 0.90 (p < 0.001). Using a threshold of AHI ≥ 15, the sensitivity and specificity of WP versus PSG for diagnosing CSA were 67% and 100% respectively with agreement of 95% (kappa = 0.774), and receiver operator characteristic (ROC) area under the curve of 0.866, (p < 0.01). Using a threshold of AHI ≥ 10 showed comparable overall sleep apnea and CSA diagnostic accuracies. CONCLUSIONS: These findings show that WP can accurately detect overall AHI and effectively differentiate between CSA and OSA.

Associations between mother-preschooler attachment and maternal depression symptoms: A systematic review and meta-analysis.

The current study aimed to systematically review and meta-analyze concurrent and longitudinal associations between maternal depression symptoms and mother-child attachment during the preschool period (aged 2 to 7 years) as assessed using the coding systems by Cassidy and Marvin (1992) and Main and Cassidy (1988). The review was pre-registered with PROSPERO (International Prospective Register of Systematic Reviews; Registration number CRD42017073417) and was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 7,969 records were screened and 18 articles were deemed as eligible for inclusion in the review. Studies were reviewed using qualitative synthesis techniques and, where appropriate, meta-analysis. Qualitative synthesis indicated that mothers of disorganized/controlling children most consistently reported the highest levels of depressive symptoms, both concurrently and longitudinally. The association between disorganized/controlling child attachment and concurrent maternal depressive symptoms was significant (n = 1,787; g = 0.27, 95% CI [0.13,0.40]), and was not moderated by sample type, child gender, or risk of bias. Findings of a relationship between child attachment insecurity and maternal depressive symptoms must be qualified due to significant within-study heterogeneity and publication bias. Results suggest that maternal depressive symptoms may confer risk for disorganized/controlling attachment during the preschool period.

Monitoring the Relationship Between Changes in Cerebral Oxygenation and Electroencephalography Patterns During Cardiopulmonary Resuscitation: A Feasibility Study.

OBJECTIVES: To date, no studies have examined real-time electroencephalography and cerebral oximetry monitoring during cardiopulmonary resuscitation as markers of the magnitude of global ischemia. We therefore sought to assess the feasibility of combining cerebral oximetry and electroencephalography in patients undergoing cardiopulmonary resuscitation and further to evaluate the electroencephalography patterns during cardiopulmonary resuscitation and their relationship with cerebral oxygenation as measured by cerebral oximetry. DESIGN: Extended case series of in-hospital and out-of-hospital cardiac arrest subjects. SETTING: Tertiary Medical Center. PATIENTS: Inclusion criteria: Convenience sample of 16 patients undergoing cardiopulmonary resuscitation during working hours between March 2014 and March 2015, greater than or equal to 18 years. A portable electroencephalography (Legacy; SedLine, Masimo, Irvine, CA) and cerebral oximetry (Equanox 7600; Nonin Medical, Plymouth, MN) system was used to measure cerebral resuscitation quality. INTERVENTIONS: Real-time regional cerebral oxygen saturation and electroencephalography readings were observed during cardiopulmonary resuscitation. The regional cerebral oxygen saturation values and electroencephalography patterns were not used to manage patients by clinical staff. MEASUREMENTS AND MAIN RESULTS: In total, 428 electroencephalography images from 16 subjects were gathered; 40.7% (n = 174/428) were artifactual, therefore 59.3% (n = 254/428) were interpretable. All 16 subjects had interpretable images. Interpretable versus noninterpretable images were not related to a function of time or duration of cardiopulmonary resuscitation but to artifacts that were introduced to the raw data such as diaphoresis, muscle movement, or electrical interference. Interpretable data were able to be obtained immediately after application of the electrode strip. Seven distinct electroencephalography patterns were identified. Voltage suppression was commonest and seen during 78% of overall cardiopulmonary resuscitation time and in 15 of 16 subjects at some point during their cardiopulmonary resuscitation. Other observed patterns and their relative prevalence in relation to overall cardiopulmonary resuscitation time were theta background activity 8%, delta background activity 5%, bi frontotemporal periodic discharge 4%, burst suppression 2%, spike and wave 2%, and rhythmic delta activity 1%. Eight of 16 subjects had greater than one interpretable pattern. At regional cerebral oxygen saturation levels less than or equal to 19%, the observed electroencephalography pattern was exclusively voltage suppression. Delta background activity was only observed at regional cerebral oxygen saturation levels greater than 40%. The remaining patterns were observed throughout regional cerebral oxygen saturation categories above a threshold of 20%. CONCLUSIONS: Real-time monitoring of cerebral oxygenation and function during cardiac arrest resuscitation is feasible. Although voltage suppression is the commonest electroencephalography pattern, other distinct patterns exist that may correlate with the quality of cerebral resuscitation and oxygen delivery.

Treatment of Kleine-Levin syndrome with acetazolamide.

Kleine-Levin syndrome (KLS) is a rare and disabling disorder characterized by recurrent episodes of hypersomnia as well as cognitive and behavioral abnormalities. Sadly, the treatment options are very limited and often ineffective. To our knowledge, there have been no reports in the literature for the use of acetazolamide as a treatment for this disorder. We report the case of a 26-year-old female patient with KLS in whom acetazolamide was used to treat recurrent hypersomnia and cognitive abnormalities. The patient had a dramatic improvement on acetazolamide in both the frequency and severity of her symptoms. The symptoms recurred when acetazolamide was stopped on two occasions and improved with resumption of the drug, leading us to conclude that its therapeutic effect was significant.

Value of routine screening for bone demineralization in an urban population of patients with epilepsy.

BACKGROUND: Reduced bone mineral density (BMD) is increasingly recognized in patients receiving antiepileptic drug therapy. The precise prevalence is not known due to variability across populations studied. We set out to characterize the prevalence of abnormal BMD in an urban population of patients with epilepsy with the intent to determine the value of routine BMD screening. METHODS: We performed a cross-sectional study of 130 consecutive patients seen thorough our Comprehensive Epilepsy Center. BMD was measured using dual X-ray absorptiometry and was reported as T-score and Z-score. Additional information collected for each patient included age, race, gender, current and prior AEDs, ambulatory state, menopausal state, concomitant medications potentially associated with reduced bone mineralization, and comorbid illness potentially associated with reduced bone mineralization. Associations between reduced bone mineralization and variables were tested for significance using Fisher's exact test, Student's t-test, and Wilcoxon rank sum test. RESULTS: The average age of the entire study population was 43.5 (+/-12.5) years. Fifty-five percent of patients had T-score less than or equal to -1, the WHO criterion for osteopenia in postmenopausal women. The prevalence of Z-scores less than -2.0 was 15%, which is more than sixfold greater than expected. The markers for decreased BMD included older age or menopause in women, longer duration of therapy, and a history of use of phenytoin or phenobarbital. Assisted ambulation was also associated with low BMD. CONCLUSION: Our results indicate that reduced bone mineralization is prevalent and a significant health concern in an urban population of patients with epilepsy. Because of the high prevalence of reduced bone mineralization reported in numerous studies including this study, routinely screening for reduced bone mineralization is warranted in patients receiving anticonvulsant therapy.