Gamma amplitude is coupled to opposed hippocampal theta-phase states during the encoding and retrieval of episodic memories in humans.

Computational models and in vivo studies in rodents suggest that the emergence of gamma activity (40-140 Hz) during memory encoding and retrieval is coupled to opposed-phase states of the underlying hippocampal theta rhythm (4-9 Hz).1,2,3,4,5,6,7,8,9,10 However, direct evidence for whether human hippocampal gamma-modulated oscillatory activity in memory processes is coupled to opposed-phase states of the ongoing theta rhythm remains elusive. Here, we recorded local field potentials (LFPs) directly from the hippocampus of 10 patients with epilepsy, using depth electrodes. We used a memory encoding and retrieval task whereby trial unique sequences of pictures depicting real-life episodes were presented, and 24 h later, participants were asked to recall them upon the appearance of the first picture of the encoded episodic sequence. We found theta-to-gamma cross-frequency coupling that was specific to the hippocampus during both the encoding and retrieval of episodic memories. We also revealed that gamma was coupled to opposing theta phases during both encoding and recall processes. Additionally, we observed that the degree of theta-gamma phase opposition between encoding and recall was associated with participants' memory performance, so gamma power was modulated by theta phase for both remembered and forgotten trials, although only for remembered trials the dominant theta phase was different for encoding and recall trials. The current results offer direct empirical evidence in support of hippocampal theta-gamma phase opposition models in human long-term memory and provide fundamental insights into mechanistic predictions derived from computational and animal work, thereby contributing to establishing similarities and differences across species.

Daily resting-state intracranial EEG connectivity for seizure risk forecasts.

Forecasting seizure risk aims to detect proictal states in which seizures would be more likely to occur. Classical seizure prediction models are trained over long-term electroencephalographic (EEG) recordings to detect specific preictal changes for each seizure, independently of those induced by shifts in states of vigilance. A daily single measure-during a vigilance-controlled period-to estimate the risk of upcoming seizure(s) would be more convenient. Here, we evaluated whether intracranial EEG connectivity (phase-locking value), estimated from daily vigilance-controlled resting-state recordings, could allow distinguishing interictal (no seizure) from preictal (seizure within the next 24 h) states. We also assessed its relevance for daily forecasts of seizure risk using machine learning models. Connectivity in the theta band was found to provide the best prediction performances (area under the curve ≥ .7 in 80% of patients), with accurate daily and prospective probabilistic forecasts (mean Brier score and Brier skill score of .13 and .72, respectively). More efficient ambulatory clinical application could be considered using mobile EEG or chronic implanted devices.

Human periventricular nodular heterotopia shows several interictal epileptic patterns and hyperexcitability of neuronal firing.

Periventricular nodular heterotopia (PNH) is a malformation of cortical development that frequently causes drug-resistant epilepsy. The epileptogenicity of ectopic neurons in PNH as well as their role in generating interictal and ictal activity is still a matter of debate. We report the first in vivo microelectrode recording of heterotopic neurons in humans. Highly consistent interictal patterns (IPs) were identified within the nodules: (1) Periodic Discharges PLUS Fast activity (PD+F), (2) Sporadic discharges PLUS Fast activity (SD+F), and (3) epileptic spikes (ES). Neuronal firing rates were significantly modulated during all IPs, suggesting that multiple IPs were generated by the same local neuronal populations. Furthermore, firing rates closely followed IP morphologies. Among the different IPs, the SD+F pattern was found only in the three nodules that were actively involved in seizure generation but was never observed in the nodule that did not take part in ictal discharges. On the contrary, PD+F and ES were identified in all nodules. Units that were modulated during the IPs were also found to participate in seizures, increasing their firing rate at seizure onset and maintaining an elevated rate during the seizures. Together, nodules in PNH are highly epileptogenic and show several IPs that provide promising pathognomonic signatures of PNH. Furthermore, our results show that PNH nodules may well initiate seizures.

Older patients with COVID-19 and neuropsychiatric conditions: A study of risk factors for mortality.

BACKGROUND: Little is known about risk factors for mortality in older patients with COVID-19 and neuropsychiatric conditions. METHODS: We conducted a multicentric retrospective observational study at Assistance Publique-Hôpitaux de Paris. We selected inpatients aged 70 years or older, with COVID-19 and preexisting neuropsychiatric comorbidities and/or new neuropsychiatric manifestations. We examined demographics, comorbidities, functional status, and presentation including neuropsychiatric symptoms and disorders, as well as paraclinical data. Cox survival analysis was conducted to determine risk factors for mortality at 40 days after the first symptoms of COVID-19. RESULTS: Out of 191 patients included (median age 80 [interquartile range 74-87]), 135 (71%) had neuropsychiatric comorbidities including cognitive impairment (39%), cerebrovascular disease (22%), Parkinsonism (6%), and brain tumors (6%). A total of 152 (79%) patients presented new-onset neuropsychiatric manifestations including sensory symptoms (6%), motor deficit (11%), behavioral (18%) and cognitive (23%) disturbances, gait impairment (11%), and impaired consciousness (18%). The mortality rate at 40 days was 19.4%. A history of brain tumor or Parkinsonism or the occurrence of impaired consciousness were neurological factors associated with a higher risk of mortality. A lower Activities of Daily Living score (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.58-0.82), a neutrophil-to-lymphocyte ratio ≥ 9.9 (HR 5.69, 95% CI 2.69-12.0), and thrombocytopenia (HR 5.70, 95% CI 2.75-11.8) independently increased the risk of mortality (all p < .001). CONCLUSION: Understanding mortality risk factors in older inpatients with COVID-19 and neuropsychiatric conditions may be helpful to neurologists and geriatricians who manage these patients in clinical practice.

Psychogenic non-epileptic seizures (PNES) in the COVID-19 pandemic era: A systematic review with individual patients' analysis.

OBJECTIVE: Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures but are not due to underlying epileptic activity and in some cases coexist alongside epilepsy. We described the clinical characteristics of patients with PNES as reported in the literature from the outbreak of the COVID-19 pandemic. We evaluated differences between patients with a diagnosis made immediately before the pandemic (pPNES) and those newly diagnosed during it (nPNES). METHODS: A systematic search with individual patient analysis of PNES cases published since the COVID-19 pandemic outbreak was performed. Differences between pPNES and nPNES were analyzed using Chi-square or Fisher exact test. RESULTS: Eleven articles were included, with 133 patients (106 pPNES and 27 nPNES). In the pPNES group, PNES frequency increased during the pandemic in 20/106 patients, whereas in 78/106, the frequency remained stable or decreased. nPNES was associated with higher risks of SARS-CoV-2 infection and epilepsy diagnosis, whereas psychiatric comorbidities were less frequent. CONCLUSIONS: During the pandemic, most patients with pPNES remained stable or improved, whereas nPNES was associated with a lower burden of psychiatric comorbidities. These intriguing findings suggest that, at least in some patients, the COVID-19 pandemic may not necessarily lead to worsening in the frequency of PNES and quality of life.

Semiology, EEG, and neuroimaging findings in temporal lobe epilepsies.

Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy. First descriptions of TLE date back in time and detailed portraits of epileptic seizures of temporal origin can be found in early medical reports as well as in the works of various artists and dramatists. Depending on the seizure onset zone, several subtypes of TLE have been identified, each one associated with peculiar ictal semiology. TLE can result from multiple etiological causes, ranging from genetic to lesional ones. While the diagnosis of TLE relies on detailed analysis of clinical as well as electroencephalographic (EEG) features, the lesions responsible for seizure generation can be highlighted by multiple brain imaging modalities or, in selected cases, by genetic investigations. TLE is the most common cause of refractory epilepsy and despite the great advances in diagnostic tools, no lesion is found in around one-third of patients. Surgical treatment is a safe and effective option, requiring presurgical investigations to accurately identify the seizure onset zone (SOZ). In selected cases, presurgical investigations need intracerebral investigations (such as stereoelectroencephalography) or dedicated metabolic imaging techniques (interictal PET and ictal SPECT) to correctly identify the brain structures to be removed.

Perampanel enhances the cardiovagal tone and heart rate variability (HRV) in patients with drug-resistant temporal lobe epilepsy.

OBJECTIVE: The temporal lobe plays a central role in the regulation of the "Central Autonomic Network" and cardiovascular functions. The blockade of glutamatergic pathways in the temporal lobe affects cardio-autonomic control. Perampanel (PER) is a non-competitive agonist of the AMPA receptor. This study evaluated PER effects on cardiac autonomic control in patients affected by drug-resistant TLE (DRTLE). METHODS: We enrolled 40 adults with DRTLE treated with PER as add-on therapy (PER group) and 32 DRTLE age, sex, and seizure-frequency matched controls treated with different additional anti-seizure medication (ASM) as add-on therapy (No-PER group). HRV analysis was performed on 5-minute EKG recording in resting state before and 6-months after the introduction of add-on ASM. Linear Mixed Models (LMM) were used to analyzed HRV variables according to time (baseline and 6-months follow-up) and groups. RESULTS: At baseline no differences were detected between PER group and No-PER group according to time-domain and frequency-domain HRV parameters. At the follow-up, in PER group a multiplicative effect for the interaction between treatment and time was observed for MeanRR (ms) (p=0.03), LnRMSSD (ms) (p=0.04), LnHF (ms2) (p<0.001), HF n.u. (p=0.001), HF% (p=0.002) with increased values, and for LnLF (ms2) (p=0.001), LF n.u. (p=0.001), LF% (p=0.01), and LF/HF (p<0.001) with reduced values. The change in seizure frequency after add-on therapy was comparable between the two groups (p=0.81) CONCLUSIONS: Our data support the notion that PER increases the vagal tone in DRTLE. This activity may exert a cardioprotective effect by reducing the risk of developing cardiac arrhythmias. Furthermore, given the correlations between HRV modifications and the occurrence of SUDEP, future studies will need to test the protective effects of PER on SUDEP.

A review of the natural history of Sturge-Weber syndrome through adulthood.

BACKGROUND: Sturge-Weber syndrome (SWS) is a neurocutaneous disorder caused by a somatic mutation in the GNAQ gene, leading to capillary venous malformations with neurological, ocular, and cutaneous abnormalities. Descriptions of adult and elderly patients with SWS are scarce compared to those of neonates or children. METHODS: We reviewed clinical, neuro-radiological and electroencephalographical findings of adult patients diagnosed with SWS, treated in our tertiary center for rare epilepsies. RESULTS: Ten adult patients were identified with a median age of 48 years at inclusion. All patients had seizures, with features of temporal lobe involvement for five patients. One patient presented typical drug-resistant mesial temporal seizures with ipsilateral hippocampal sclerosis and leptomeningeal enhancement, and was treated surgically. Other patients presented typical neurological and brain imaging features found in SWS. One patient without visible leptomeningeal angioma or brain calcifications presented neurological symptoms (tonic-clonic generalized seizures) for the first time at the age of 56. Two of the oldest patients in our cohort with supratentorial leptomeningeal angioma displayed contralateral cerebellar atrophy, consistent with crossed cerebellar diaschisis. Over 70 years of follow-up data were available for one patient whose epilepsy started at the age of 6 months, offering a vast overview of the course of SWS, in particular the onset of dementia and contralateral micro-bleeds in relation to the leptomeningeal angioma. CONCLUSION: The long follow-up of our cohort allows for a description of the course of SWS and a characterization of uncommon neurological features in adult and elderly patients.

Long-term deep intracerebral microelectrode recordings in patients with drug-resistant epilepsy: Proposed guidelines based on 10-year experience.

PURPOSE: Human neuronal activity, recorded in vivo from microelectrodes, may offer valuable insights into physiological mechanisms underlying human cognition and pathophysiological mechanisms of brain diseases, in particular epilepsy. Continuous and long-term recordings are necessary to monitor non predictable pathological and physiological activities like seizures or sleep. Because of their high impedance, microelectrodes are more sensitive to noise than macroelectrodes. Low noise levels are crucial to detect action potentials from background noise, and to further isolate single neuron activities. Therefore, long-term recordings of multi-unit activity remains a challenge. We shared here our experience with microelectrode recordings and our efforts to reduce noise levels in order to improve signal quality. We also provided detailed technical guidelines for the connection, recording, imaging and signal analysis of microelectrode recordings. RESULTS: During the last 10 years, we implanted 122 bundles of Behnke-Fried hybrid macro-microelectrodes, in 56 patients with pharmacoresistant focal epilepsy. Microbundles were implanted in the temporal lobe (74%), as well as frontal (15%), parietal (6%) and occipital (5%) lobes. Low noise levels depended on our technical setup. The noise reduction was mainly obtained after electrical insulation of the patient's recording room and the use of a reinforced microelectrode model, reaching median root mean square values of 5.8 µV. Seventy percent of the bundles could record multi-units activities (MUA), on around 3 out of 8 wires per bundle and for an average of 12 days. Seizures were recorded by microelectrodes in 91% of patients, when recorded continuously, and MUA were recorded during seizures for 75 % of the patients after the insulation of the room. Technical guidelines are proposed for (i) electrode tails manipulation and protection during surgical bandage and connection to both clinical and research amplifiers, (ii) electrical insulation of the patient's recording room and shielding, (iii) data acquisition and storage, and (iv) single-units activities analysis. CONCLUSIONS: We progressively improved our recording setup and are now able to record (i) microelectrode signals with low noise level up to 3 weeks duration, and (ii) MUA from an increased number of wires . We built a step by step procedure from electrode trajectory planning to recordings. All these delicate steps are essential for continuous long-term recording of units in order to advance in our understanding of both the pathophysiology of ictogenesis and the neuronal coding of cognitive and physiological functions.

Epilepsy related to focal neuronal lipofuscinosis: extra-frontal localization, EEG signatures and GABA involvement.

Focal neuronal lipofuscinosis (FNL) is an uncommon epileptic disorder related to an excess of lipofuscin accumulation within dysmorphic-appearing neurons (DANs), whose epileptogenic mechanisms are still poorly understood. It shares some clinical and neuroimaging similarities with focal cortical dysplasia of type IIb (FCDIIb), but it represents a different pathological entity. Here, we identified two patients with FNL among a 10-year cohort of 323 patients who underwent neurosurgery for a focal pharmacoresistant epilepsy. We describe the electroclinical, metabolic and neuropathological features of both patients with FNL who benefited from a comprehensive presurgical investigation. While the previous reports showed frontal lobe localization of the lesion, FNL was identified in the temporal lobe, in one of our patients. EEG investigations in both patients showed striking focal and rich interictal activity resembling that described in FCDIIb. Besides focal intraneuronal lipofuscin accumulation, the neuropathological analysis demonstrated that somata of DANs were surrounded by a large amount of GABAergic presynaptic buttons, suggesting the involvement of interneurons in the epileptogenicity of FNL. To further explore the role of GABAergic transmission in the generation of epileptiform activity in FNL, we performed in vitro multi-electrode array recordings on the post-surgery tissue from one patient. Spontaneous interictal-like discharges (IILDs) were identified only in the restricted area displaying the highest density of lipofuscin-containing DANs, suggesting a close correlation between the density of lipofuscin-containing neurons and epileptogenicity. Moreover, IILDs were blocked by the GABAA receptor antagonist gabazine. All together, these findings showed how GABA signaling may contribute to the generation of interictal-like activity in FNL tissue.

Neuron Specific Enolase, S100-beta protein and progranulin as diagnostic biomarkers of status epilepticus.

Status epilepticus (SE) is a life-threatening prolonged epileptic seizure. A rapid diagnosis is fundamental to initiate antiepileptic treatment and to prevent the development of neurological sequels. Several serum and cerebrospinal fluid biomarkers have been proposed to help in the diagnosis of SE. Nevertheless, previous studies were conducted on too small patient cohorts, precluding the utilization of interesting biomarkers for the SE diagnosis. Here, we aimed to assess the ability of Neuron Specific Enolase (NSE), S100-beta protein (S100B) and progranulin to help in the diagnosis of SE in a large cohort of patients (36 control patients, 56 patients with pharmacoresistant epilepsy and 82 SE patients). Blood NSE, S100B and progranulin levels were higher in SE patients when compared with control patients or patients with pharmacoresistant epilepsy. Both NSE and progranulin levels were higher in cerebrospinal fluid from SE patients when compared with control patients. The receiver-operating characteristics curves revealed good accuracy at detecting SE for serum S100B (AUC 0.748) and plasma progranulin (AUC 0.756). The performances were lower for serum NSE (AUC 0.624). Eighty-four percent of patients with serum S100B levels above 0.09 ng/mL presented with a SE, whereas 90% of patients without SE had serum S100B levels lower than 0.09 ng/mL. Serum S100B levels were not significantly different according to SE etiology, SE semiology or SE refractoriness. Our results confirm that NSE, S100B and progranulin levels are increased after SE. We suggest that serum S100B levels might be added to clinical evaluation and electroencephalogram to identify difficult-to-diagnose form of SE.

Heart rate variability is reduced during the menstrual phase in women with catamenial C1-type temporal lobe epilepsy.

INTRODUCTION: Temporal lobe epilepsy (TLE) is the most frequent focal epilepsy in adulthood. Catamenial C1-type TLE, is characterized by a cyclic seizure exacerbation during the menstrual phase. The heart rate variability (HRV) analysis assesses cardiac autonomic control and may represent a biomarker for Sudden Unexpected Death in Epilepsy (SUDEP). It is plausible that female sex hormones can influence HRV. These changes might be more pronounced in patients suffering from catamenial C1-type TLE where hormonal changes also increase seizure susceptibility. To that aim, we evaluated HRV changes during the menstrual phase of women suffering from catamenial C1-type TLE. METHODS: We enrolled 12 adults with a diagnosis of catamenial C1-type TLE (Catamenial Group) and 12 age-, and seizure-frequency-matched controls with TLE (Non-Catamenial Group). Each patient underwent a 20-minute EEG + EKG recording in resting state during the menstrual phase. HRV parameters were calculated with a short-lasting analysis of EKG records. Time domain-related, frequency domain-related, as well as non-linear analysis parameters, were compared between the two groups. RESULT: Compared to the Non-Catamenial Group, the Catamenial Group showed significant reductions in SDNN (p-value = 0.01), RMSSD (p-value = 0.04), pNN50 (p-value = 0.001), LnLF ms2 (p-value = 0.05), LnHF ms2 (p-value = 0.007), SD1 (p-value = 0.02), and SD2 (p-value = 0.01). These results were independent from age, disease duration, numbers of ASM, and seizure etiology. CONCLUSION: Our data provide experimental evidence that vagal output is reduced during the menstrual phase in patients with catamenial C1-type TLE. These results indicate that, during the menstrual phase, patients with catamenial C1-type TLE may be at a higher risk of developing cardiac dysfunctions and SUDEP.

Coffee consumption and seizure frequency in patients with drug-resistant focal epilepsy.

OBJECTIVE: To assess the relation between coffee consumption and seizure frequency in patients with drug-resistant focal epilepsy. METHODS: Cross-sectional analysis of data collected in the SAVE study, which included patients with drug-resistant focal epilepsy during long-term EEG monitoring. Patients in whom both coffee consumption and data about seizure frequency, including focal to bilateral tonic-clonic seizures (FBTCS), were available were selected. Coffee consumption was collected using a standardized self-report questionnaire and classified into four groups: none, rare (from less than 1 cup/week to up 3 cups/week), moderate (from 4 cups/week to 3 cups/day), and high (more than 4 cups/day). RESULTS: Six hundred and nineteen patients were included. There was no relation between coffee consumption and total seizure frequency (p = 0.902). In contrast, the number of FBTCS reported over the past year was significantly associated with usual coffee consumption (p = 0.029). Specifically, number of FBCTS in patients who reported moderate coffee consumption was lower than in others. In comparison with patients with moderate coffee consumption, the odds ratio (95%CI) for reporting at least 1 FBTCS per year was 1.6 (1.03-2.49) in patients who never take coffee, 1.62 (1.02-2.57) in those with rare consumption and 2.05 (1.24-3.4) in those with high consumption. Multiple ordinal logistic regression showed a trend toward an association between coffee consumption and number of FBTCS (p = 0.08). CONCLUSIONS AND RELEVANCE: Our data suggest that effect of coffee consumption on seizures might depend on dose with potential benefits on FBTCS frequency at moderate doses. These results will have to be confirmed by prospective studies.

Seizures in autoimmune encephalitis: specific features based on a systematic comparative study.

OBJECTIVE: To highlight specific characteristics of seizure semiology and EEG features associated with different subtypes of autoimmune encephalitis (AE). METHODS: We systematically reviewed the seizure semiology and all the EEG recordings from patients with AE managed in a tertiary referral centre for epilepsy and a neuro-intensive care unit. Each characteristic across the different subtypes of AE was compared by post hoc analysis. RESULTS: We identified 66 patients with anti-neuronal antibody-mediated AE or Rasmussen's encephalitis (RE) experiencing seizures, which were the most frequent symptom at onset. Anti-NMDAR and anti-LGI1 AE accounted for the majority of patients; 41% and 24%, respectively. We isolated specific semiological features, such as early tonic-clonic seizures (TCS) in anti-NMDAR AE, early mesial temporal lobe seizures with emotional symptoms in anti-GAD AE, somatosensory seizures in RE, and a lower frequency of TCS in anti-LGI1 AE. EEG analysis also provided additional insights into distinguishing the subtypes based on: (1) generalized rhythmic delta activity, which was more sensitive than extreme delta brush in identifying anti-NMDAR AE among all subtypes; and (2) temporal interictal epileptiform activity and temporal seizures on EEG in anti-GAD AE. We identified a new EEG pattern consisting of temporal low-voltage and periodic spikes associated with ipsilateral hippocampal abnormalities on MRI, which could be a sign of inflammatory mesial temporal involvement. SIGNIFICANCE: Specific clinical and EEG features can be useful in guiding the diagnosis of a subtype of AE with acute symptomatic seizures, particularly before the results of anti-neuronal antibody testing are available.

A self-supervised learning strategy for postoperative brain cavity segmentation simulating resections.

PURPOSE: Accurate segmentation of brain resection cavities (RCs) aids in postoperative analysis and determining follow-up treatment. Convolutional neural networks (CNNs) are the state-of-the-art image segmentation technique, but require large annotated datasets for training. Annotation of 3D medical images is time-consuming, requires highly trained raters and may suffer from high inter-rater variability. Self-supervised learning strategies can leverage unlabeled data for training. METHODS: We developed an algorithm to simulate resections from preoperative magnetic resonance images (MRIs). We performed self-supervised training of a 3D CNN for RC segmentation using our simulation method. We curated EPISURG, a dataset comprising 430 postoperative and 268 preoperative MRIs from 430 refractory epilepsy patients who underwent resective neurosurgery. We fine-tuned our model on three small annotated datasets from different institutions and on the annotated images in EPISURG, comprising 20, 33, 19 and 133 subjects. RESULTS: The model trained on data with simulated resections obtained median (interquartile range) Dice score coefficients (DSCs) of 81.7 (16.4), 82.4 (36.4), 74.9 (24.2) and 80.5 (18.7) for each of the four datasets. After fine-tuning, DSCs were 89.2 (13.3), 84.1 (19.8), 80.2 (20.1) and 85.2 (10.8). For comparison, inter-rater agreement between human annotators from our previous study was 84.0 (9.9). CONCLUSION: We present a self-supervised learning strategy for 3D CNNs using simulated RCs to accurately segment real RCs on postoperative MRI. Our method generalizes well to data from different institutions, pathologies and modalities. Source code, segmentation models and the EPISURG dataset are available at https://github.com/fepegar/resseg-ijcars .

Agitation and Dementia: Prevention and Treatment Strategies in Acute and Chronic Conditions.

Agitation is a behavioral syndrome characterized by increased, often undirected, motor activity, restlessness, aggressiveness, and emotional distress. According to several observations, agitation prevalence ranges from 30 to 50% in Alzheimer's disease, 30% in dementia with Lewy bodies, 40% in frontotemporal dementia, and 40% in vascular dementia (VaD). With an overall prevalence of about 30%, agitation is the third most common neuropsychiatric symptoms (NPS) in dementia, after apathy and depression, and it is even more frequent (80%) in residents of nursing homes. The pathophysiological mechanism underlying agitation is represented by a frontal lobe dysfunction, mostly involving the anterior cingulate cortex (ACC) and the orbitofrontal cortex (OFC), respectively, meaningful in selecting the salient stimuli and subsequent decision-making and behavioral reactions. Furthermore, increased sensitivity to noradrenergic signaling has been observed, possibly due to a frontal lobe up-regulation of adrenergic receptors, as a reaction to the depletion of noradrenergic neurons within the locus coeruleus (LC). Indeed, LC neurons mainly project toward the OFC and ACC. These observations may explain the abnormal reactivity to weak stimuli and the global arousal found in many patients who have dementia. Furthermore, agitation can be precipitated by several factors, e.g., the sunset or low lighted environments as in the sundown syndrome, hospitalization, the admission to nursing residencies, or changes in pharmacological regimens. In recent days, the global pandemic has increased agitation incidence among dementia patients and generated higher distress levels in patients and caregivers. Hence, given the increasing presence of this condition and its related burden on society and the health system, the present point of view aims at providing an extensive guide to facilitate the identification, prevention, and management of acute and chronic agitation in dementia patients.

Sleep scoring based on video-electroencephalography monitoring in an Epileptology Unit: Comparison with polysomnography.

The aim of the study was to compare the performance of video- electroencephalography (EEG) monitoring and standard polysomnography for sleep scoring in an Epileptology Unit. We calculated the level of agreement between two methods of sleep scoring, using either 27-electrode video-EEG or polysomnography for 1 night in 22 patients admitted to our Epileptology Unit. Independent experts manually scored sleep using the American Academy of Sleep Medicine 2017 guidelines. We evaluated the number of sleep cycles and their distribution on hypnogram, total sleep time, sleep efficiency, sleep and rapid eye movement sleep-onset latency, wake after sleep-onset, and sleep stages. We then extracted sub-samples of recordings to examine the agreement in microarousal and rapid eye movement scoring. We used Bland and Altman plots and Cohen's kappa test to measure agreement. Bland and Altman plots showed at least 95% agreement for all studied sleep parameters with the exception of wake after sleep onset, where there was an 11 min difference. Cohen's kappa test showed an agreement for the recognition of microarousal (0.89) and of rapid eye movements (0.96) in sub-samples. Video-EEG represents an acceptable alternative tool for sleep architecture study in patients admitted to an Epileptology Unit.

Association of Clinical, Biological, and Brain Magnetic Resonance Imaging Findings With Electroencephalographic Findings for Patients With COVID-19.

Importance: There is evidence of central nervous system impairments associated with coronavirus disease 2019 (COVID-19) infection, including encephalopathy. Multimodal monitoring of patients with COVID-19 may delineate the specific features of COVID-19-related encephalopathy and guide clinical management. Objectives: To investigate clinical, biological, and brain magnetic resonance imaging (MRI) findings in association with electroencephalographic (EEG) features for patients with COVID-19, and to better refine the features of COVID-19-related encephalopathy. Design, Setting, and Participants: This retrospective cohort study conducted in Pitié-Salpêtrière Hospital, Paris, France, enrolled 78 hospitalized adults who received a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) and underwent EEG between March 30 and June 11, 2020. Exposures: Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription-polymerase chain reaction assay or, in the case of associated pneumonia, on a computed tomography scan of the chest. Main Outcomes and Measures: Data on the clinical and paraclinical features of the 78 patients with COVID-19 were retrieved from electronic patient records. Results: Of 644 patients who were hospitalized for COVID-19, 78 (57 men [73%]; mean [SD] age, 61 [12] years) underwent EEG. The main indications for EEG were delirium, seizure-like events, and delayed awakening in the intensive care unit after stopping treatment with sedatives. Sixty-nine patients showed pathologic EEG findings, including metabolic-toxic encephalopathy features, frontal abnormalities, periodic discharges, and epileptic activities. Of 57 patients who underwent brain MRI, 41 showed abnormalities, including perfusion abnormalities, acute ischemic lesions, multiple microhemorrhages, and white matter-enhancing lesions. Fifty-five patients showed biological abnormalities, including dysnatremia, kidney failure, and liver dysfunction, the same day as the EEG. The results of cerebrospinal fluid analysis were negative for SARS-Cov-2 for all tested patients. Nine patients who had no identifiable cause of brain injury outside COVID-19 were further isolated; their brain injury was defined as COVID-19-related encephalopathy. They represented 1% (9 of 644) of patients with COVID-19 requiring hospitalization. Six of these 9 patients had movement disorders, 7 had frontal syndrome, 4 had brainstem impairment, 4 had periodic EEG discharges, and 3 had MRI white matter-enhancing lesions. Conclusions and Relevance: The results from this cohort of patients hospitalized with COVID-19 suggest there are clinical, EEG, and MRI patterns that could delineate specific COVID-19-related encephalopathy and guide treatment strategy.

Disturbances of brain cholesterol metabolism: A new excitotoxic process associated with status epilepticus.

The understanding of the excitotoxic processes associated with a severe status epilepticus (SE) is of major importance. Changes of brain cholesterol homeostasis is an emerging candidate for excitotoxicity. We conducted an overall analysis of the cholesterol homeostasis both (i) in fluids and tissues from patients with SE: blood (n = 63, n = 87 controls), CSF (n = 32, n = 60 controls), and post-mortem brain tissues (n = 8, n = 8 controls) and (ii) in a mouse model of SE induced by an intrahippocampal injection of kainic acid. 24-hydroxycholesterol levels were decreased in kainic acid mouse hippocampus and in human plasma and post-mortem brain tissues of patients with SE when compared with controls. The decrease of 24-hydroxycholesterol levels was followed by increased cholesterol levels and by an increase of the cholesterol synthesis. Desmosterol levels were higher in human CSF and in mice and human hippocampus after SE. Lanosterol and dihydrolanosterol levels were higher in plasma from SE patients. Our results suggest that a CYP46A1 inhibition could occur after SE and is followed by a brain cholesterol accumulation. The excess of cholesterol is known to be excitotoxic for neuronal cells and may participate to neurological sequelae observed after SE. This study highlights a new pathophysiological pathway involved in SE excitotoxicity.

Autonomic Status Epilepticus in a Patient with Parasellar Meningioma: A Case Report.

Autonomic status epilepticus (Aut SE) is a condition characterized by ongoing focal autonomic seizure lasting for >30 min. Aut SE can show a variety of clinical manifestations including vomiting, nausea, changes in heart rate, piloerection, pupillary abnormalities, and visual abnormalities. Although Aut SE is a common finding in childhood in the context of Panayiotopoulos syndrome, few reports have described this condition during adulthood. In the present report, we describe a case of Aut SE in an adult patient with parasellar meningioma and bilateral frontotemporal epileptiform activity on EEG record.