Electrophysiological markers of memory consolidation in the human brain when memories are reactivated during sleep.

Human accomplishments depend on learning, and effective learning depends on consolidation. Consolidation is the process whereby new memories are gradually stored in an enduring way in the brain so that they can be available when needed. For factual or event knowledge, consolidation is thought to progress during sleep as well as during waking states and to be mediated by interactions between hippocampal and neocortical networks. However, consolidation is difficult to observe directly but rather is inferred through behavioral observations. Here, we investigated overnight memory change by measuring electrical activity in and near the hippocampus. Electroencephalographic (EEG) recordings were made in five patients from electrodes implanted to determine whether a surgical treatment could relieve their seizure disorders. One night, while each patient slept in a hospital monitoring room, we recorded electrophysiological responses to 10 to 20 specific sounds that were presented very quietly, to avoid arousal. Half of the sounds had been associated with objects and their precise spatial locations that patients learned before sleep. After sleep, we found systematic improvements in spatial recall, replicating prior results. We assume that when the sounds were presented during sleep, they reactivated and strengthened corresponding spatial memories. Notably, the sounds also elicited oscillatory intracranial EEG activity, including increases in theta, sigma, and gamma EEG bands. Gamma responses, in particular, were consistently associated with the degree of improvement in spatial memory exhibited after sleep. We thus conclude that this electrophysiological activity in the hippocampus and adjacent medial temporal cortex reflects sleep-based enhancement of memory storage.

Depth versus surface: A critical review of subdural and depth electrodes in intracranial electroencephalographic studies.

Intracranial electroencephalographic (IEEG) recording, using subdural electrodes (SDEs) and stereoelectroencephalography (SEEG), plays a pivotal role in localizing the epileptogenic zone (EZ). SDEs, employed for superficial cortical seizure foci localization, provide information on two-dimensional seizure onset and propagation. In contrast, SEEG, with its three-dimensional sampling, allows exploration of deep brain structures, sulcal folds, and bihemispheric networks. SEEG offers the advantages of fewer complications, better tolerability, and coverage of sulci. Although both modalities allow electrical stimulation, SDE mapping can tessellate cortical gyri, providing the opportunity for a tailored resection. With SEEG, both superficial gyri and deep sulci can be stimulated, and there is a lower risk of afterdischarges and stimulation-induced seizures. Most systematic reviews and meta-analyses have addressed the comparative effectiveness of SDEs and SEEG in localizing the EZ and achieving seizure freedom, although discrepancies persist in the literature. The combination of SDEs and SEEG could potentially overcome the limitations inherent to each technique individually, better delineating seizure foci. This review describes the strengths and limitations of SDE and SEEG recordings, highlighting their unique indications in seizure localization, as evidenced by recent publications. Addressing controversies in the perceived usefulness of the two techniques offers insights that can aid in selecting the most suitable IEEG in clinical practice.

ATP6V0C variants impair V-ATPase function causing a neurodevelopmental disorder often associated with epilepsy.

The vacuolar H+-ATPase is an enzymatic complex that functions in an ATP-dependent manner to pump protons across membranes and acidify organelles, thereby creating the proton/pH gradient required for membrane trafficking by several different types of transporters. We describe heterozygous point variants in ATP6V0C, encoding the c-subunit in the membrane bound integral domain of the vacuolar H+-ATPase, in 27 patients with neurodevelopmental abnormalities with or without epilepsy. Corpus callosum hypoplasia and cardiac abnormalities were also present in some patients. In silico modelling suggested that the patient variants interfere with the interactions between the ATP6V0C and ATP6V0A subunits during ATP hydrolysis. Consistent with decreased vacuolar H+-ATPase activity, functional analyses conducted in Saccharomyces cerevisiae revealed reduced LysoSensor fluorescence and reduced growth in media containing varying concentrations of CaCl2. Knockdown of ATP6V0C in Drosophila resulted in increased duration of seizure-like behaviour, and the expression of selected patient variants in Caenorhabditis elegans led to reduced growth, motor dysfunction and reduced lifespan. In summary, this study establishes ATP6V0C as an important disease gene, describes the clinical features of the associated neurodevelopmental disorder and provides insight into disease mechanisms.

Putative roles for homeostatic plasticity in epileptogenesis.

Homeostatic plasticity allows neural circuits to maintain an average activity level while preserving the ability to learn new associations and efficiently transmit information. This dynamic process usually protects the brain from excessive activity, like seizures. However, in certain contexts, homeostatic plasticity might produce seizures, either in response to an acute provocation or more chronically as a driver of epileptogenesis. Here, we review three seizure conditions in which homeostatic plasticity likely plays an important role: acute drug withdrawal seizures, posttraumatic or disconnection epilepsy, and cyclic seizures. Identifying the homeostatic mechanisms active at different stages of development and in different circuits could allow better targeting of therapies, including determining when neuromodulation might be most effective, proposing ways to prevent epileptogenesis, and determining how to disrupt the cycle of recurring seizure clusters.

Seizure onset patterns predict outcome after stereo-electroencephalography-guided laser amygdalohippocampotomy.

OBJECTIVE: Stereotactic laser amygdalohippocampotomy (SLAH) is an appealing option for patients with temporal lobe epilepsy, who often require intracranial monitoring to confirm mesial temporal seizure onset. However, given limited spatial sampling, it is possible that stereotactic electroencephalography (stereo-EEG) may miss seizure onset elsewhere. We hypothesized that stereo-EEG seizure onset patterns (SOPs) may differentiate between primary onset and secondary spread and predict postoperative seizure control. In this study, we characterized the 2-year outcomes of patients who underwent single-fiber SLAH after stereo-EEG and evaluated whether stereo-EEG SOPs predict postoperative seizure freedom. METHODS: This retrospective five-center study included patients with or without mesial temporal sclerosis (MTS) who underwent stereo-EEG followed by single-fiber SLAH between August 2014 and January 2022. Patients with causative hippocampal lesions apart from MTS or for whom the SLAH was considered palliative were excluded. An SOP catalogue was developed based on literature review. The dominant pattern for each patient was used for survival analysis. The primary outcome was 2-year Engel I classification or recurrent seizures before then, stratified by SOP category. RESULTS: Fifty-eight patients were included, with a mean follow-up duration of 39 ± 12 months after SLAH. Overall 1-, 2-, and 3-year Engel I seizure freedom probability was 54%, 36%, and 33%, respectively. Patients with SOPs, including low-voltage fast activity or low-frequency repetitive spiking, had a 46% 2-year seizure freedom probability, compared to 0% for patients with alpha or theta frequency repetitive spiking or theta or delta frequency rhythmic slowing (log-rank test, p = .00015). SIGNIFICANCE: Patients who underwent SLAH after stereo-EEG had a low probability of seizure freedom at 2 years, but SOPs successfully predicted seizure recurrence in a subset of patients. This study provides proof of concept that SOPs distinguish between hippocampal seizure onset and spread and supports using SOPs to improve selection of SLAH candidates.

Visual cortex responds to sound onset and offset during passive listening.

Sounds enhance our ability to detect, localize, and respond to co-occurring visual targets. Research suggests that sounds improve visual processing by resetting the phase of ongoing oscillations in visual cortex. However, it remains unclear what information is relayed from the auditory system to visual areas and if sounds modulate visual activity even in the absence of visual stimuli (e.g., during passive listening). Using intracranial electroencephalography (iEEG) in humans, we examined the sensitivity of visual cortex to three forms of auditory information during a passive listening task: auditory onset responses, auditory offset responses, and rhythmic entrainment to sounds. Because some auditory neurons respond to both sound onsets and offsets, visual timing and duration processing may benefit from each. In addition, if auditory entrainment information is relayed to visual cortex, it could support the processing of complex stimulus dynamics that are aligned between auditory and visual stimuli. Results demonstrate that in visual cortex, amplitude-modulated sounds elicited transient onset and offset responses in multiple areas, but no entrainment to sound modulation frequencies. These findings suggest that activity in visual cortex (as measured with iEEG in response to auditory stimuli) may not be affected by temporally fine-grained auditory stimulus dynamics during passive listening (though it remains possible that this signal may be observable with simultaneous auditory-visual stimuli). Moreover, auditory responses were maximal in low-level visual cortex, potentially implicating a direct pathway for rapid interactions between auditory and visual cortices. This mechanism may facilitate perception by time-locking visual computations to environmental events marked by auditory discontinuities.NEW & NOTEWORTHY Using intracranial electroencephalography (iEEG) in humans during a passive listening task, we demonstrate that sounds modulate activity in visual cortex at both the onset and offset of sounds, which likely supports visual timing and duration processing. However, more complex auditory rate information did not affect visual activity. These findings are based on one of the largest multisensory iEEG studies to date and reveal the type of information transmitted between auditory and visual regions.

Visual speech differentially modulates beta, theta, and high gamma bands in auditory cortex.

Speech perception is a central component of social communication. Although principally an auditory process, accurate speech perception in everyday settings is supported by meaningful information extracted from visual cues. Visual speech modulates activity in cortical areas subserving auditory speech perception including the superior temporal gyrus (STG). However, it is unknown whether visual modulation of auditory processing is a unitary phenomenon or, rather, consists of multiple functionally distinct processes. To explore this question, we examined neural responses to audiovisual speech measured from intracranially implanted electrodes in 21 patients with epilepsy. We found that visual speech modulated auditory processes in the STG in multiple ways, eliciting temporally and spatially distinct patterns of activity that differed across frequency bands. In the theta band, visual speech suppressed the auditory response from before auditory speech onset to after auditory speech onset (-93 to 500 ms) most strongly in the posterior STG. In the beta band, suppression was seen in the anterior STG from -311 to -195 ms before auditory speech onset and in the middle STG from -195 to 235 ms after speech onset. In high gamma, visual speech enhanced the auditory response from -45 to 24 ms only in the posterior STG. We interpret the visual-induced changes prior to speech onset as reflecting crossmodal prediction of speech signals. In contrast, modulations after sound onset may reflect a decrease in sustained feedforward auditory activity. These results are consistent with models that posit multiple distinct mechanisms supporting audiovisual speech perception.

Stereotactic laser anterior corpus callosotomy for Lennox-Gastaut syndrome.

OBJECTIVE: Corpus callosotomy is an effective palliative treatment for drug-resistant Lennox-Gastaut syndrome (LGS). Laser interstitial thermal therapy has been increasingly used in the treatment of epilepsy. Here, we assess the safety and effectiveness of minimally invasive stereotactic laser anterior corpus callosotomy (SLACC) for drop attacks in LGS. METHODS: We reviewed sequential cases of patients with medically intractable LGS who underwent SLACC using a two-cannula technique between November 2014 and July 2019. Pre- and postoperative magnetic resonance imaging was used to measure the anteroposterior length of callosal ablation (contrast-enhancing lesion) and estimated disconnection (gap in tract projections on diffusion tensor imaging). Patients were followed longitudinally to assess clinical outcomes. RESULTS: Ten patients were included in this study. The median age was 33 (range = 11-52) years, median duration of epilepsy was 26 (range = 10-49) years, and median duration of postoperative follow-up was 19 (range = 6-40) months. In the anteroposterior direction, 53 ± 7% (mean ± SD) of the corpus callosum was ablated and 62 ± 19% of the corpus callosum was estimated to be disconnected. Six (60%) of 10 patients achieved >80% seizure reduction, two (20%) of whom became seizure-free. Eight (80%) patients had >80% reduction in drop attacks, five (50%) of whom became free of drop attacks. Three patients subsequently underwent laser posterior callosotomy with further improvement in drop attacks and/or overall seizure frequency. One patient had an asymptomatic intracerebral hemorrhage along the cannula tract. One patient developed significant aggression after becoming seizure-free. SIGNIFICANCE: Seizure outcomes following SLACC were comparable to previously reported outcomes of open callosotomy, with reasonable safety profile. SLACC appears to be an effective alternative to open anterior corpus callosotomy with minimal postoperative discomfort and a short recovery period.

Stereotactic laser interstitial thermal therapy for epilepsy associated with solitary and multiple cerebral cavernous malformations.

OBJECTIVE: The authors sought to perform a preliminary assessment of the safety and effectiveness of stereotactic laser interstitial thermal therapy (LITT) for patients with cerebral cavernous malformation (CCM)-related epilepsy. METHODS: The authors retrospectively analyzed 6 patients with CCM-related epilepsy who underwent LITT. Pre-, intra-, and postoperative brain MRI studies were used to characterize preoperative CCM volume, ablation volume, and postablation hemosiderin volume. Clinical outcomes were assessed postoperatively during clinic follow-up visits or phone interviews. RESULTS: LITT was performed in 7 CCMs in 6 patients. Two patients had familial CCM disease with multifocal lesions. Four treated CCMs were extratemporal, and 3 were in or near the visual pathways. The median follow-up was 25 (range 12-39) months. Five of 6 (83%) patients achieved seizure freedom (Engel I classification), of whom 4 (67%) were Engel IA and 1 was Engel IC after a single seizure on postoperative day 4. The remaining patient had rare seizures (Engel II). One patient had a nondisabling visual field deficit. There were no hemorrhagic complications. All patients were discharged within 24 hours postablation. MRI 3-11 months after ablation demonstrated expected focal necrosis and trace hemosiderin-related T2 hypointensity measuring 9%-44% (median 24%) of the original lesion volume, with significant (p = 0.04) volume reduction. CONCLUSIONS: LITT is a minimally invasive option for treating CCM-related epilepsy with seizure outcomes comparable to those achieved with open lesionectomy. The precision of LITT allows for the obliteration of eloquent, deep, small, and multifocal lesions with low complication rates, minimal postoperative discomfort, and short hospital stays. In this study the feasibility and benefits of this method were demonstrated in 2 patients with multifocal lesions.

Stereotactic EEG-guided laser interstitial thermal therapy for mesial temporal lobe epilepsy.

OBJECTIVE: To determine the outcomes of combined stereo-electroencephalography-guided and MRI-guided stereotactic laser interstitial thermal therapy (LITT) in the treatment of patients with drug-resistant mesial temporal lobe epilepsy (mTLE). METHODS: We prospectively assessed the surgical and neuropsychological outcomes in 21 patients with medically refractory mTLE who underwent LITT at the University of Chicago Medical Center. We further compared the surgical outcomes in patients with and without mesial temporal sclerosis (MTS). RESULTS: Of the 21 patients, 19 (90%) underwent Invasive EEG study and 11 (52%) achieved freedom from disabling seizures with a mean duration of postoperative follow-up of 24±11 months after LITT. Eight (73%) of 11 patients with MTS achieved freedom from disabling seizures, whereas 3 (30 %) of 10 patients without MTS achieved freedom from disabling seizures. Patients with MTS were significantly more likely to become seizure-free, as compared with those without MTS (P=0.002). There was no significant difference in total ablation volume and the percentage of the ablated amygdalohippocampal complex between seizure-free and non-seizure-free patients. Presurgical and postsurgical neuropsychological assessments were obtained in 10 of 21 patients. While there was no group decline in any neuropsychological assessment, a significant postoperative decline in verbal memory and confrontational naming was observed in individual patients. CONCLUSIONS: MRI-guided LITT is a safe and effective alternative to selective amygdalohippocampectomy and anterior temporal lobectomy for mTLE with MTS. Nevertheless, its efficacy in those without MTS seems modest. Large multicentre and prospective studies are warranted to further determine the efficacy and safety of LITT.

Antiglutamic acid decarboxylase 65 (GAD65) antibody-associated epilepsy.

Glutamic acid decarboxylase (GAD) antibody-associated encephalitis causes both acute seizures and chronic epilepsy with predominantly temporal lobe onset. This condition is challenging in diagnosis and management, and the incidence of GAD antibody (Ab)-related epilepsy could be much higher than commonly believed. Imaging and CSF evidence of inflammation along with typical clinical presentations, such as adult onset temporal lobe epilepsy (TLE) with unexplained etiology, should prompt testing for the diagnostic antibodies. High serum GAD Ab titer (≥2000U/mL or ≥20nmol/L) and evidence of intrathecal anti-GAD Ab synthesis support the diagnosis. Unlike other immune-mediated epilepsies, antiglutamic acid decarboxylase 65 (GAD65) antibody-mediated epilepsy is often poorly responsive to antiepileptic drugs (AEDs) and only moderately responsive to immune therapy with steroids, intravenous immunoglobulin (IVIG), or plasma exchange (PLEX). Long-term treatment with more aggressive immunosuppressants such as rituximab (RTX) and/or cyclophosphamide is often necessary and may be more effective than current immunosuppressive approaches. The aim of this review is to review the physiology, pathology, clinical presentation, related ancillary tests, and management of GAD Ab-associated autoimmune epilepsy by searching the keywords and to promote the recognition and the initiation of proper therapy for this condition.

Association of sleep with sudden unexpected death in epilepsy.

OBJECTIVE: The objective of this study was to determine the association of sleep with sudden unexpected death in epilepsy (SUDEP). METHODS: We conducted a systematic review and meta-analysis based on literature search from databases PubMed, Web of Science, and Scopus using keywords "SUDEP", or "sudden unexpected death in epilepsy", or "sudden unexplained death in epilepsy". Sudden unexpected death in epilepsy was considered to occur during sleep if the patient was found in bed, if the SUDEP cases were documented as in sleep, or if the patient was found at bedside on the bedroom floor. RESULTS: Circadian pattern was documented in 880 of the 1025 SUDEP cases in 67 studies meeting the inclusion and exclusion criteria. Of the 880 SUDEP cases, 69.3% occurred during sleep and 30.7% occurred during wakefulness. Sudden unexpected death in epilepsy was significantly associated with sleep as compared to wakefulness (P<0.001). In the subgroup of 272 cases in which circadian pattern and age were documented, patients 40years old or younger were more likely to die in sleep than those older than 40years (OR: 2.0; 95% CI=1.0, 3.8; P=0.05). In the subgroup of 114 cases in which both circadian pattern and body position at the time of death were documented, 87.6% (95% CI=81.1%, 94.2%) of patients who died during sleep were in the prone position, whereas 52.9% (95% CI=24.7%, 81.1%) of patients who died during wakefulness were in the prone position. Patients with nocturnal seizures were 6.3 times more likely to die in a prone position than those with diurnal seizures (OR: 6.3; 95% CI=2.0, 19.5; P=0.002). CONCLUSIONS: There is a strong association of SUDEP with sleep, suggesting that sleep is a significant risk factor for SUDEP. Although the risks of SUDEP associated with sleep are unknown and likely multifactorial, the prone position might be an important contributory factor.

Impact of periictal nurse interventions on postictal generalized EEG suppression in generalized convulsive seizures.

OBJECTIVES: The objective of this study was to determine the impact of periictal nurse interventions on postictal generalized EEG suppression (PGES) in generalized convulsive seizures (GCS). METHODS: We retrospectively reviewed the video-EEG recordings of patients during long-term video-EEG monitoring. We compared the duration of seizures, seizure phases (tonic, clonic, and tonic-clonic phases), and the occurrence and duration of postictal generalized EEG suppression (PGES) in patients with and without periictal interventions (e.g., oxygen administration, suctioning, and repositioning). Statistical analyses were performed to determine the association between the seizure-related variables and the periictal interventions. RESULTS: A total of 109 patients with 150 GCS were included in the study. Periictal interventions were provided in 122 GCS, of which, ictal administration of oxygen was provided in 29 GCS. The duration of PGES was significantly shortened in GCS with interventions when compared with those without interventions (p=0.003). However, the ictal administration of oxygen, assessed as an independent variable, did not influence the occurrence or duration of PGES. CONCLUSION: Periictal interventions significantly shortened the duration of PGES, and may, as a consequence, reduce the risk of SUDEP. However, ictal administration of oxygen did not influence the occurrence or duration of PGES.

Paraneoplastic epilepsy.

Epilepsy can be a manifestation of paraneoplastic syndromes which are the consequence of an immune reaction to neuronal elements driven by an underlying malignancy affecting other organs and tissues. The antibodies commonly found in paraneoplastic encephalitis can be divided into two main groups depending on the target antigen: 1) antibodies against neuronal cell surface antigens, such as against neurotransmitter (N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), gamma-aminobutyric acid (GABA)) receptors, ion channels (voltage-gated potassium channel (VGKC)), and channel-complex proteins (leucine rich, glioma inactivated-1 glycoprotein (LGI1) and contactin-associated protein-2 (CASPR2)) and 2) antibodies against intracellular neuronal antigens (Hu/antineuronal nuclear antibody-1 (ANNA-1), Ma2/Ta, glutamate decarboxylase 65 (GAD65), less frequently to CV2/collapsin response mediator protein 5 (CRMP5)). In this review, we provide a comprehensive survey of the current literature on paraneoplastic epilepsy indexed by the associated onconeuronal antibodies. While a range of seizure types can be seen with paraneoplastic syndromes, temporal lobe epilepsy is the most common because of the association with limbic encephalitis. Early treatment of the paraneoplastic syndrome with immune modulation/suppression may prevent the more serious potential consequences of paraneoplastic epilepsy.

The incidence of peri-ictal prone position in patients with generalized convulsive seizures.

OBJECTIVE: The objectives of this study were to determine the incidence of peri-ictal prone position in patients with generalized convulsive seizures (GCS) and to further assess the risk of sudden unexpected death in epilepsy (SUDEP) associated with the prone position. METHOD: We retrospectively reviewed the video-EEG data of 308 GCS in 193 patients who underwent long-term video-EEG monitoring in two epilepsy centers. We determined the peri-ictal (preictal, ictal, and/or postictal) body positions. RESULTS: A peri-ictal prone position was observed in 12 (6.2%) of 193 patients and 13 (4.2%) of 308 GCS. In 5 (1.6%) of 308 GCS, patients in nonprone positions at seizure onset turned into the prone position during versive seizures. In 8 (2.6%) of 308 GCS, patients were sleeping prone at seizure onset. Peri-ictal intervention with body repositioning was provided in 11 of 12 patients and 12 of the 13 GCS. Repositioning was not provided during the remaining seizure; the patient died in the prone position. In the subset of 96 GCS without ictal intervention, patients in a supine position at seizure onset remained in the supine position at seizure termination in 57 (98.3%) of 58 GCS. Patients sleeping prone at seizure onset remained in the prone position at seizure termination in 4 (80%) of 5 GCS. CONCLUSION: Our data suggest that the incidence of peri-ictal prone position in patients with GCS is low. Both prone sleeping and forced ictal version may result in postictal prone position. Although avoiding prone sleeping may reduce the SUDEP risk, influencing forced ictal version may be difficult in the absence of supervision.

Impact of intracranial subclinical seizures on seizure outcomes after SLAH in patients with mesial temporal lobe epilepsy.

OBJECTIVE: To investigate the association between subclinical seizures detected on intracranial electroencephalographic (i-SCSs)recordings and mesial temporal sclerosis (MTS), as well as their impact on surgical outcomes of stereotactic laser amygdalohippocampotomy (SLAH). METHODS: A retrospective review was conducted on 27 patients with drug-resistant mesial temporal lobe epilepsy (MTLE) who underwent SLAH. The number of seizures detected on scalp EEG and iEEG was assessed. Patients were followed for a minimum of 3 years after SLAH. RESULTS: Of the 1715 seizures recorded from mesial temporal regions, 1640 were identified as i-SCSs. Patients with MTS were associated with favorable short- and long-term surgical outcomes. Patients with MTS had a higher number of i-SCSs compared to patients without MTS. The numbers of i-SCSs were higher in patients with Engel I-II outcomes, but no significant statistical difference was found. However, it was observed that patients with MTS who achieved Engel I-II classification had higher numbers of i-SCSs than patients without MTS (P < 0.05). CONCLUSION: Patients with MTS exhibited favorable short-term and long-term surgical outcome after SLAH. A higher number of i-SCSs was significantly associated with MTS in patients with MTLE. The number of i-SCSs tended to be higher in patients with Engel Ⅰ-Ⅱ surgical outcomes. SIGNIFICANCE: The association between i-SCSs, MTS, and surgical outcomes in MTLE patients undergoing SLAH has significant implications for understanding the underlying mechanisms and identifying potential therapeutic targets to enhance surgical outcomes.

Tonic phase of a generalized convulsive seizure is an independent predictor of postictal generalized EEG suppression.

PURPOSE: To determine the incidence, duration, risk factors for, and clinical correlates of postictal generalized electroencephalography (EEG) suppression (PGES), and to further delineate the significance of PGES in the pathogenesis of sudden unexpected death in epilepsy (SUDEP). METHODS: We retrospectively reviewed the video-EEG studies of 109 consecutive patients with 151 generalized convulsive seizures (GCS) during video-EEG monitoring. We determined the incidence, duration, and clinical correlates of PGES. We also investigated whether factors such as age, sex, seizure type, total seizure duration, and duration of tonic and clonic phases influenced PGES. KEY FINDINGS: PGES was observed in 64 (58.7%) of 109 patients and in 98 (64.9%) of 151 GCS. Average duration of PGES was 42.4 ± 19.1 s. Statistical analysis showed that patients with PGES had no difference in age, gender, total seizure duration, total convulsive duration, clonic phase, seizure type, and seizure termination, as compared to those without PGES. However, tonic phase was significantly prolonged in patients with PGES than in those without PGES (p = 0.00086). A 1 s increase in tonic phase duration was associated with a 0.06 increase in log odds of PGES (odds ratio = 1.1, p = 0.00055). Clinically, 95.3% patients were unresponsive or immobile during PGES, whereas only 26.7% patients without PGES were unresponsive or immobile immediately after seizure termination. SIGNIFICANCE: PGES is a common EEG pattern of GCS. Tonic phase of GCS is an independent predictor of PGES, which is well correlated with postictal unresponsiveness or immobile, and may play a significant role in the mechanism of SUDEP.

Periictal autonomic dysfunction and generalized postictal EEG suppression in convulsive seizures arising from sleep and wakefulness.

Sleep appears to be an independent risk factor of sudden unexpected death in epilepsy (SUDEP). We retrospectively determined the periictal electrophysiological characteristics of nocturnal and diurnal generalized convulsive seizures (GCSs) in 109 patients. Our data showed that preictal heart rate (HR) was significantly lower in 46 patients with nocturnal GCSs than in 63 patients with diurnal GCSs (p=0.002). However, there was no significant difference in postictal HR and respiratory rate (RR), total seizure duration, total convulsive phase, tonic phase, and clonic phase. Meanwhile, postictal generalized EEG suppression (PGES) was observed in 52.4% of the patients with diurnal GCSs and 67.4% of the patients with nocturnal GCSs. Duration of PGES was 38.2±17.3s in patients with diurnal GCSs and 49.5±21.7s in patients with nocturnal GCSs. There was also no significant difference in the prevalence (p=0.118) and duration (p=0.044, Bonferroni-corrected significant level: α=0.00625) of PGES in the two patient groups. Therefore, there is no clear evidence to attribute the SUDEP risk associated with sleep to postictal autonomic dysfunction and PGES, as compared to wakefulness.

Clinical features and brain MRI volumetric changes in anti-mGluR5 encephalitis.

BACKGROUND: Anti-metabotropic glutamate receptor 5 (mGluR5) encephalitis is a rare and under-recognized autoimmune encephalitis. This study is conducted to characterize its clinical and neuroimaging features. METHODS: Twenty-nine patients with anti-mGluR5 encephalitis (15 new cases identified in this study and 14 previously reported cases) were included in this study and their clinical features were characterized. Brain MRI volumetric analysis using FreeSurfer software was performed in 9 new patients and compared with 25 healthy controls at both early (≤6 months of onset) and chronic (>1 year of onset) disease stages. RESULTS: The common clinical manifestations of anti-mGluR5 encephalitis included cognitive deficits (n = 21, 72.4%), behavioral and mood disturbances (n = 20, 69%), seizures (n = 16, 55.2%), and sleep disorder (n = 13, 44.8%). Tumors were observed in 7 patients. Brain MRI T2/FLAIR signal hyperintensities were observed predominantly in mesiotemporal and subcortical regions in 75.9% patients. MRI volumetric analysis demonstrated significant amygdala enlargement in both early and chronic disease stages compared to healthy controls (P < 0.001). Twenty-six patients had complete or partial recovery, one remained stable, one died and one was lost to follow-up. CONCLUSION: Our findings demonstrated that cognitive impairment, behavioral disturbance, seizures, and sleep disorder are the prominent clinical manifestations of anti-mGluR5 encephalitis. Most patients showed a good prognosis with full recovery, even in the paraneoplastic disease variants. The amygdala enlargement in the early and chronic disease stages is a distinct MRI feature, which exploratively offer a valuable perspective for the study of the disease processes.