Hypocretin-1/orexin-A, sleep and excessive daytime sleepiness in patients with nonconvulsive status epilepticus: A cross-sectional cohort study.

BACKGROUND AND OBJECTIVES: Nonconvulsive status epilepticus (NCSE) manifests as a change in mental status without a coma (NCSE proper) or comatose NCSE. Hypocretin-1/orexin-A (H/O) is involved in alertness and sleep maintenance. Sleep impairment and excessive daytime sleepiness (EDS) have a negative impact on cognitive functions and activities of daily living (ADL). METHODS: Patients meeting the NCSE criteria underwent cerebrospinal fluid and brain magnetic resonance imaging examinations, polysomnographies (PSG), multiple latency sleep tests (MSLT), and completed Epworth Sleepiness Scale (ESS). Montreal Cognitive Assessment was used to evaluate cognitive functions, and the Barthel Index was used to assess ADL in the acute phase (V1) and three months follow-up (V2). RESULTS: From May 2020 to May 2023, we enrolled 15 patients, eight (53.3 %) women, with a median age of 69 (14) years. The median H/O CSF concentration was 250 (63.6) pg/ml; however, only three CSF samples (20 %) decreased below the borderline concentration of 200 pg/ml. Fourteen out of 15 patients (93.3 %) completed the PSG study. The median of wakefulness after sleep onset was 167 (173.5) min, sleep efficiency (SE) was 62.9 (63) %, sleep latency (SL) was 6 (32) min, REM sleep was 2.85 (7.2) %, and REM first episode latency was 210.5 (196.5) minutes. The medians of the stages N1 NREM were 4.65 (15) %, N2 NREM 68.4 (29.9) %, and N3 NREM 21.8 (35.5) %. MSLT mean latency was 7.7 (12.6) minutes. A significant negative correlation exists between H/O CSF concentrations and the stage N1 NREM (rs = -0.612, p = 0.02), and the proportion of cumulative sleep time with oxygen saturation below 90 % in total sleep time (TST) t90 (rs = -0.57, p = 0.03). MSLT had significant negative correlation with TST (rs = -0.5369, p = 0.0478), with SE (rs = -0.5897, p = 0.0265), with apnea-hypopnea index (rs = -0.7631, p = 0.0002) and with deoxygenation index (rs = -0.8009, p = 0.0006). A positive correlation exists between MSLT and SL (rs = 0.6284, p = 0.0161) and between ESS and t90 (rs = 0.9014, p = 0.0004). The correlation between H/O CSF concentrations and EDS, cognitive performance, and ADL was not proved. CONCLUSIONS: Patients after NCSE exhibited sleep impairment and excessive daytime sleepiness. Hypocretin-1/orexin-A concentrations decreased only in 20 % of these cases.

The effects of COVID-19 on sleep and general health of Czech patients with epilepsy.

Objectives: To assess the impact of COVID-19 illness and pandemic era on sleep, general health, health care, and social status in patients with epilepsy in the Czech Republic. Methods: Our designed and approved questionnaire consisted of 23 questions. We focused on (1) patients' demographic and epidemiological data regarding COVID-19, (2) subjective assessment of sleep; (3) epilepsy, and (4) perception of general health during the first year of the COVID-19 pandemic in the Czech Republic from March 2020 to May 2021. We administered the questionnaires during outpatient visits or by phone calls in three major university Czech epilepsy centers (Ostrava, Brno, Pilsen). Results: We enrolled 227 (100%) patients. The mean age (±SD) was 41.2 ± 14.82 years (min 18, max 86 years), and 138 (61%) were women. COVID-19 was confirmed using the PCR test method in 57 (25.1%) patients. In the pre-pandemic era, 62 (27.3%) patients reported sleep disturbances. Insomnia in 46 (74.2%) and excessive daytime sleepiness in 6 (9.7%) were the most mentioned sleep abnormalities. Nocturnal seizures predispose to sleep impairment (p = 0.014) and vivid dreams and nightmares (p = 0.033). COVID-19 infection significantly increased the risk of vivid dreams and nightmares in patients with diurnal seizures (p = 0.006). Sleep quality impairment and seizure frequency worsening [(p < 0.001) and (p = 0.001), respectively] were the most significant risk factors to perform general health deterioration regardless of having COVID-19 (p = 0.559). The most affected age group was 51+ years (p = 0.033). The three centers provided adequate outpatient care during the first year of the pandemic. The employment and social status of the patients remained unchanged (p = 0.074). Conclusions: COVID- 19 infection significantly increased the occurrence of vivid dreams and nightmares in patients with diurnal seizures. Sleep quality deterioration and seizure frequency worsening significantly negatively impacted general health performance.

[Anti-NMDAR encephalitis as a serious adverse event probably related to yellow fever vaccination].

We present a case of a 17-year-old female with anti-NMDAR encephalitis probably associated with vaccination against yellow fever. Her symptoms occurred 27 days after vaccination against yellow fever. Anti-NMDAR encephalitis manifested as acute psychosis, memory loss and catatonia following fever with complex partial epileptic seizures. Interictal electroencephalogram showed slow-wave delta background activity with "delta brushes". The diagnosis was confirmed by NMDAR antibody positivity in serum and cerebrospinal fluid. Since ovarian teratoma, as the most common cause of anti-NMDAR encephalitis, did not develop within five years from its onset, the association with vaccination against yellow fever seems to be highly probable.

New-Onset Refractory Status Epilepticus with Claustrum Damage: Definition of the Clinical and Neuroimaging Features.

New-onset refractory status epilepticus (NORSE) is a rare but challenging condition occurring in a previously healthy patient, often with no identifiable cause. We describe the electro-clinical features and outcomes in a group of patients with NORSE who all demonstrated a typical magnetic resonance imaging (MRI) sign characterized by bilateral lesions of the claustrum. The group includes 31 patients (12 personal and 19 previously published cases; 17 females; mean age of 25 years). Fever preceded status epilepticus (SE) in 28 patients, by a mean of 6 days. SE was refractory/super-refractory in 74% of the patients, requiring third-line agents and a median of 15 days staying in an intensive care unit. Focal motor and tonic-clonic seizures were observed in 90%, complex partial seizures in 14%, and myoclonic seizures in 14% of the cases. All patients showed T2/FLAIR hyperintense foci in bilateral claustrum, appearing on average 10 days after SE onset. Other limbic (hippocampus, insular) alterations were present in 53% of patients. Within the personal cases, extensive search for known autoantibodies was inconclusive, though 7 of 11 patients had cerebrospinal fluid lymphocytic pleocytosis and 3 cases had oligoclonal bands. Two subjects died during the acute phase, one in the chronic phase (probable sudden unexplained death in epilepsy), and one developed a persistent vegetative state. Among survivors, 80% developed drug-resistant epilepsy. Febrile illness-related SE associated with bilateral claustrum hyperintensity on MRI represents a condition with defined clinical features and a presumed but unidentified autoimmune etiology. A better characterization of de novo SE is mandatory for the search of specific etiologies.

Claustrum damage and refractory status epilepticus following febrile illness.

OBJECTIVE: To characterize the clinical, EEG, and brain imaging findings in an adult case series of patients with de novo refractory status epilepticus (SE) occurring after a febrile illness. METHODS: A retrospective study (2010-2013) was undertaken with the following inclusion criteria: (1) previously healthy adults with refractory SE; (2) seizure onset 0-21 days after a febrile illness; (3) lacking evidence of infectious agents in CSF; (4) no history of seizures (febrile or afebrile) or previous or concomitant neurologic disorder. RESULTS: Among 155 refractory SE cases observed in the study period, 6 patients (17-35 years old) fulfilled the inclusion criteria. Confusion and stupor were the most common symptoms at disease onset, followed after a few days by acute repeated seizures that were uncountable in all but one. Seizures consisted of focal motor/myoclonic phenomena with subsequent generalization. Antiepileptic drugs failed in every patient to control seizures, with all participants requiring intensive care unit admission. Barbiturate coma with burst-suppression pattern was applied in 4 out of 6 patients for 5-14 days. One participant died in the acute phase. In each patient, we observed a reversible bilateral claustrum MRI hyperintensity on T2-weighted sequences, without restricted diffusion, time-related with SE. All patients had negative multiple neural antibodies testing. Four out of 5 surviving patients developed chronic epilepsy. CONCLUSIONS: This is a hypothesis-generating study of a preliminary nature supporting the role of the claustrum in postfebrile de novo SE; future prospective studies are needed to delineate the specificity of this condition, its pathogenesis, and the etiology.

Narcolepsy and pregnancy: a retrospective European evaluation of 249 pregnancies.

In a retrospective cohort study undertaken in 12 European countries, 249 female narcoleptic patients with cataplexy (n = 216) and without cataplexy (n = 33) completed a self-administrated questionnaire regarding pregnancy and childbirth. The cohort was divided further into patients whose symptoms of narcolepsy started before or during pregnancy (308 pregnancies) and those in whom the first symptoms of narcolepsy appeared after delivery (106 pregnancies). Patients with narcolepsy during pregnancy were older during their first pregnancy (P < 0.001) and had a higher body mass index (BMI) prior to pregnancy (P < 0.01). Weight gain during pregnancy was higher in narcoleptic patients with cataplexy (P < 0.01). More patients with narcolepsy-cataplexy during pregnancy had impaired glucose metabolism and anaemia. Three patients experienced cataplexy during delivery. The rate of caesarean sections was higher in the narcolepsy-cataplexy group compared to the narcolepsy group (P < 0.05). The mean birth weight and gestational age of neonates were within the normal range and did not differ across groups. Neonatal care was affected adversely by symptoms of narcolepsy in 60.1% of those with narcolepsy during pregnancy. This study reports more obstetric complications in patients with narcolepsy-cataplexy during pregnancy; however, these were not severe. This group also had a higher BMI and higher incidence of impaired glucose metabolism during pregnancy. Caesarian section was conducted more frequently in narcolepsy-cataplexy patients, despite cataplexy being a rare event during delivery. Furthermore, symptoms of narcolepsy may render care of the infant more difficult.

Assessment of pregnancy outcomes in Czech and Slovak women with narcolepsy.

BACKGROUND: Narcolepsy is associated with altered metabolic functions. We sought to investigate the effect of narcolepsy on pregnancy and newborns. MATERIAL/METHODS: A retrospective cohort study of patients in whom the first symptoms of narcolepsy appeared before or after pregnancy. Our study included 54 women, mothers of a total of 110 children (37 with symptoms of narcolepsy before and during pregnancy, 17 developed the narcolepsy syndrome only after childbirth). With only 1 exception, none of the patients were treated with drugs during pregnancy. RESULTS: We did not find any significant differences between the 2 groups in the registered parameters of: age of mothers at delivery, history of spontaneous abortion, alcohol and nicotine consumption, medication, complications during pregnancy, symptoms of narcolepsy, weight gain during pregnancy, length of pregnancy and delivery, complications during delivery, and weight and length of the newborn. The women experiencing symptoms of narcolepsy before or during pregnancy were found to have a significantly higher total number of pregnancy complications (35.8%) than those with later onset of symptoms (9.1%), although the complications were not clinically significant. More patients in the symptomatic group tended to have impaired glucose tolerance or type 2 diabetes, compared to the asymptomatic group. CONCLUSIONS: The study revealed no clinically relevant adverse effects of narcolepsy on pregnancy, childbirth or the newborn.