Disrupting the epileptogenic network with stereoelectroencephalography-guided radiofrequency thermocoagulation.

Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) is a treatment option for focal drug-resistant epilepsy. In previous studies, this technique has shown seizure reduction by ≥50% in 50% of patients at 1 year. However, the relationship between the location of the ablation within the epileptogenic network and clinical outcomes remains poorly understood. Seizure outcomes were analyzed for patients who underwent SEEG-guided RF-TC and across subgroups depending on the location of the ablation within the epileptogenic network, defined as SEEG sites involved in seizure generation and spread. Eighteen patients who had SEEG-guided RF-TC were included. SEEG-guided seizure-onset zone ablation (SEEG-guided SOZA) was performed in 12 patients, and SEEG-guided partial seizure-onset zone ablation (SEEG-guided P-SOZA) in 6 patients. The early spread was ablated in three SEEG-guided SOZA patients. Five patients had ablation of a lesion. The seizure freedom rate in the cohort ranged between 22% and 50%, and the responder rate between 67% and 85%. SEEG-guided SOZA demonstrated superior results for both outcomes compared to SEEG-guided P-SOZA at 6 months (seizure freedom p = .294, responder rate p = .014). Adding the early spread ablation to SEEG-guided SOZA did not increase seizure freedom rates but exhibited comparable effectiveness regarding responder rates, indicating a potential network disruption.

Cold-Induced Reflex Epilepsy.

This case report describes a woman cold-induced reflex seizures.

Longitudinal Comparison of PNES spell and ASM reduction in PNES Patients with and without Epilepsy Discharged from an Epilepsy Monitoring Unit.

OBJECTIVE: To examine trends of Antiseizure Medication (ASM) reduction and discontinuation, as well as Psychogenic Non-Epileptic Seizure (PNES) spell reduction and resolution in patients with PNES, with and without comorbid epileptic seizures (ES). METHODS: A retrospective analysis was conducted on data from 145 patients with PNES, including 109 with PNES alone and 36 with PNES plus comorbid epilepsy. Patients were admitted to the Epilepsy Monitoring Unit (EMU) between May 2000 and April 2008, with follow-up clinical data collected until September 2015. Clinical records were thoroughly examined, encompassing the period preceding the PNES diagnosis until either loss to follow-up or September 2015. A subsequent chart review was conducted by two neurologists, covering the period following the diagnosis of PNES until either loss to follow-up or September 2015, which ever came first. RESULTS: Patients with PNES alone had higher rates of ASM reduction for all variables of ASM reduction measured compared to those with comorbid epilepsy (all at p < 001). Among patients with PNES alone, reductions in ASMs were observed after EMU discharge, but an uptick and plateau were seen in later follow-up years (100% of patients free of ASMs at years 2-3, 20% on at least one ASM by year 7). This pattern differs greatly in PNES + ES patients, in which the only time point at which any patient was able to discontinue all ASMs was at EMU discharge (4.5% of patients), with all patients taking at least one ASM for every other follow-up time point. Reductions in PNES spell frequency did not differ significantly between the two groups (for example PNES spells reduced at final FU 47.2% vs 42.9%, p = 0.65). In both groups, despite an initial drop in variables of PNES spell reduction and resolution in the early years post discharge, there is an eventual rebound and plateau (for example in PNES only patients, 33.9% of patients having no resolution in 1st year FU, which rises to 78% at years 4-5, and plateus around 52.8% at more than 7 years follow-up.) SIGNIFICANCE: This study contributes to the growing body of research focused on improving the current approach to management and prognostic outlook of PNES. Although PNES only patients had higher rates of ASM reduction, the uptick and plateau observed in later years highlights the challenges in managing PNES. Similarly, the continued persistence and rebound of PNES spells underline the continued poor prognostic outcomes associated with this condition.

Radiologic Classification of Hippocampal Sclerosis in Epilepsy.

Temporal lobe epilepsy is a common form of epilepsy that is often associated with hippocampal sclerosis (HS). Although HS is commonly considered a binary assessment in radiological evaluation, it is known that histopathological changes occur in distinct clusters. Some subtypes of HS only affect certain subfields, resulting in minimal changes to the overall volume of the hippocampus. This is likely a major reason why whole hippocampal volumetrics have underperformed versus expert readers. With recent advancements in MRI technology, it is now possible to characterize the substructure of the hippocampus more accurately. However, this is not consistently addressed in radiographic evaluations. The histological subtype of HS is critical for prognosis and treatment decision making, necessitating improved radiological classification of HS. The International League Against Epilepsy (ILAE) has issued a consensus classification scheme for subtyping HS histopathological changes. This review aims to explore how the ILAE subtypes of HS correlate with radiographic findings, introduce a grading system that integrates radiological and pathological reporting in HS, and outline an approach to detecting HS subtypes using MRI. This framework will not only benefit current clinical evaluations, but also enhance future studies involving high-resolution MRI in temporal lobe epilepsy.ABBREVIATIONS: CA = cornu ammonis; DG = dentate gyrus; HS = hippocampal sclerosis; ILAE = International League Against Epilepsy; SRLM = strata radiatum, lacunosum, and moleculare layers; TLE = temporal lobe epilepsy.

Management of patients with epilepsy and Intellectual disabilities in group homes vs. Family Homes: Insights into polypharmacy and seizure characteristics.

OBJECTIVES: This study aimed to investigate the differences in ASMs prescription, seizure characteristics and predictors of polypharmacy in patients with epilepsy and Intellectual disabilities (IDs) residing in group homes versus family homes. METHODS: This nine-year retrospective study analyzed patients with epilepsy and IDs who were admitted to the EMU, epilepsy clinics at LHSC and rehabilitation clinics for patients with IDs at Parkwood Institution. The study included individuals aged 16 years and older residing in either group homes or family homes. Data on demographics, epilepsy characteristics, and ASMs use were collected and analyzed using the Statistical Package for Social Sciences. The study utilized binary logistic regression to identify predictors of polypharmacy in patients with epilepsy and IDs. RESULTS: The study enrolled a total of 81 patients, of which 59.3 % resided in family homes. Group home residents were significantly older (41 vs. 24.5 years; p = 0.0001) and were prescribed more ASMs (3 vs. 2; p = 0.002). Specific ASMs were more common in group homes, including valproic acid (54.5 % vs. 25.0 %), lacosamide (54.5 % vs. 22.9 %), topiramate (33.3 % vs. 14.6 %), and phenytoin (30.3 % vs. 6.2 %). Admission to the EMU was more prevalent in group homes (93.9 % vs. 52.1 %; p = 0.0001). Living in a group home increased the risk of polypharmacy (OR = 10.293, p = 0.005), as did older epilepsy onset age (OR = 1.135, p = 0.031) and generalized or focal & generalized epilepsy (OR = 7.153, p = 0.032 and OR = 10.442, p = 0.025, respectively). SIGNIFICANCE: Our study identified notable differences in the demographic and clinical characteristics of patients with epilepsy and IDs living in group homes versus family homes. Age of epilepsy onset, EMU admissions, epilepsy types, and residency setting were significant predictors of polypharmacy. These findings highlight the need for personalized care strategies and increased awareness of the potential risks associated with polypharmacy.

Psychogenic non-epileptic seizures with and without epilepsy: Exploring the influence of co-existing psychiatric disorders on clinical characteristics and outcomes.

BACKGROUND AND OBJECTIVES: Psychogenic non-epileptic seizures (PNES) are commonly associated with co-existing psychiatric disorders. The relationship between psychiatric factors and PNES episodes with and without epilepsy remains understudied. We reviewed co-existing psychiatric disorders in PNES-only, PNES with epilepsy aiming to examine whether these co-existing disorders associated with PNES clinical presentation and long-term outcomes. METHODS: We conducted a retrospective, longitudinal cohort study of patients with PNES diagnosed at our EMU from May 2000 to April 2008, with follow-up clinical data until September 2015. We categorized patients into three groups: PNES-only, PNES+ definite epilepsy, and PNES+ possible/probable epilepsy. RESULTS: In total, 271 patients with PNES were identified: 194 had PNES-only, 30 had PNES+ possible or probable epilepsy, and 47 had PNES+ definite epilepsy. No significant differences were observed in the prevalence of depression, anxiety, post-traumatic stress disorder (PTSD), substance abuse, or suicidal thoughts among the three groups. Similarly, no differences in co-existing psychiatric disorders characteristics were discovered among patients grouped by various durations and frequencies of PNES episodes. At EMU admission, for PNES-only patients total of 130/194 patients (67%) were on ASMs, and 64/194 (32.9%) were not. PNES-only not on ASM were the most likely to report at least two of the three main psychiatric disorders (depression, anxiety, and PTSD; p = 0.01). At the final follow-up, 68/130 (52.3%) and 92/130 (70.8%) patients were able to discontinue or reduce their ASM intake, respectively, with no significant differences in co-existing psychiatric disorders among them (p < 0.001). Overall, 51.6% or 31.3% of patients reported reduced or resolved PNES episodes, respectively. Further, this reduction and resolution of PNES episode were not affected by any psychological variable. CONCLUSIONS: Co-existing psychiatric disorders prevalence did not differ between patients with PNES-only and those with coexisting epilepsy. Further, co-existing psychiatric disorders characteristics did not reliably predict PNES episode duration, frequency, reduction, or resolution. For patients with PNES-only, the presence of co-existing psychiatric disorders did not predict the rate at which ASMs could be reduced or discontinued.

Lack of spontaneous typical seizures during intracranial monitoring with stereo-electroencephalography.

OBJECTIVE: In the presurgical evaluation of patients with drug-resistant epilepsy (DRE), occasionally, patients do not experience spontaneous typical seizures (STS) during a stereo-electroencephalography (SEEG) study, which limits its effectiveness. We sought to identify risk factors for patients who did not have STS during SEEG and to analyze the clinical outcomes for this particular set of patients. METHODS: We conducted a retrospective analysis of all patients with DRE who underwent depth electrode implantation and SEEG recordings between January 2013 and December 2018. RESULTS: SEEG was performed in 155 cases during this period. 11 (7.2%) did not experience any clinical seizures (non-STS group), while 143 experienced at least one patient-typical seizure during admission (STS group). No significant differences were found between STS and non-STS groups in terms of patient demographics, lesional/non-lesional epilepsy ratio, pre-SEEG seizure frequency, number of ASMs used, electrographic seizures or postoperative seizure outcome in those who underwent resective surgery. Statistically significant differences were found in the average number of electrodes implanted (7.0 in the non-STS group vs. 10.2 in STS), days in Epilepsy Monitoring Unit (21.8 vs. 12.8 days) and the number of cases that underwent resective surgery following SEEG (27.3% vs. 60.8%), respectively. The three non-STS patients (30%) who underwent surgery, all had their typical seizures triggered during ECS studies. Three cases were found to have psychogenic non-epileptic seizures. None of the patients in the non-STS group were offered neurostimulation devices. Five of the non-STS patients experienced transient seizure improvement following SEEG. SIGNIFICANCE: We were unable to identify any factors that predicted lack of seizures during SEEG recordings. Resective surgery was only offered in cases where ECS studies replicated patient-typical seizures. Larger datasets are required to be able to identify factors that predict which patients will fail to develop seizures during SEEG.

Involvement of the posterior cingulate gyrus in temporal lobe epilepsy: A study using stereo-EEG.

OBJECTIVE: To analyze the involvement of the posterior cingulate gyrus (PCG) during mesial temporal lobe seizures (MTLS). METHODS: We retrospectively reviewed the stereo-EEG (SEEG) recordings of patients with MTLS performed in our institution from February 2013 to December 2020. Only patients who had electrode implantation in the PCG were included. Patients with lesions that could potentially alter the seizure spread pathways were excluded. We assessed the propagation patterns of MTLS with respect to the different structures sampled. RESULTS: Nine of 97 patients who had at least one seizure originating in the mesial temporal region met the inclusion criteria. A total of 174 seizures were analyzed. The PCG was the first site of propagation in most of the cases (8/9 patients and 77.5% of seizures, and 7/8 patients and 65.6% of seizures after excluding an outlier patient). The fastest propagation times were towards the contralateral mesial temporal region and ipsilateral PCG. Seven patients underwent standard anterior temporal lobectomy and, of these, all but one were Engel 1 at last follow up. CONCLUSION: We found the PCG to be the first propagation site of MTLS in this group of patients. These results outline the relevance of the PCG in SEEG planning strategies. Further investigations are needed to corroborate whether fast propagation to the PCG predicts a good surgical outcome.

Patients with psychogenic nonepileptic seizures and suspected epilepsy: An antiseizure medication reduction study.

OBJECTIVE: To examine predictors of ASM reduction/discontinuation and PNES reduction/resolution in patients with PNES with a confirmed or strong suspicion of comorbid ES. METHODS: A retrospective analysis of 271 newly diagnosed Patients with PNESs admitted to the EMU between May 2000 and April 2008, with follow-up clinical data collected until September 2015. Forty-seven patients met our criteria of PNES with either confirmed or probable ES. RESULTS: Patients with PNES reduction were significantly more likely to have come off all ASMs by the time of final follow-up (21.7 vs. 0.0%, p = 0.018), while documented generalized (i.e. epileptic) seizures were much more common in patients with no reduction in PNES frequency (47.8 vs 8.7%, p = 0.003). When comparing patients that reduced their ASMs (n = 18) with those that did not (n = 27), the former were more likely to have neurological comorbid disorders (p = 0.004). When comparing patients with PNES resolution (n = 12) vs not (n = 34), those with PNES resolution were more likely to have a neurological comorbid disorder (p = 0.027), had a younger age at EMU admission (29.8 vs 37.4, p = 0.05) and a greater proportion of patients with ASMs reduced in EMU (66.7% vs 30.3%, p = 0.028). Similarly, those with ASM reduction had more unknown (non-generalized, non-focal) seizures (33.3 vs 3.7%, p = 0.029). On hierarchical regression analysis, a higher level of education and absence of generalized epilepsy remain as positive predictors of PNES reduction (p = 0.042, 0.015), while the presence of some other neurological disorder besides epilepsy (p = 0.04) and being on more ASMs at EMU admission (p = 0.03) were positive predictors of ASM reduction by final follow-up. SIGNIFICANCE: Patients with PNES and epilepsy have distinct demographic predictors of PNES frequency and ASM reduction by final follow-up. Patients with PNES reduction and resolution had higher level education, less generalized epileptic seizures, younger age at EMU admission, more likely to have presence of a neurological disorder besides epilepsy, and a greater proportion of patients had a reduction in the number of ASMs in the EMU. Similarly, patients with ASM reduction and discontinuation were on more ASMs at initial EMU admission and also were more likely to have a neurological disorder besides epilepsy. The positive relationship between reduction in psychogenic nonepileptic seizure frequency and discontinuation of ASMs at final follow-up elucidates that tapering medication in a safe environment may reinforce psychogenic nonepileptic seizure diagnosis. This can be reassuring to both patients and clinicians, resulting in the observed improvements at the final follow-up.

Paroxysmal slow-wave discharges in a model of absence seizure are coupled to gamma oscillations in the thalamocortical and limbic systems.

OBJECTIVE: Using the gamma-butyrolactone (GBL) model of absence seizures in Long-Evans rats, this study investigated if gamma (30-160 Hz) activity were cross-frequency modulated by the 2-6 Hz slow-wave discharges induced by GBL in the limbic system. We hypothesized that inactivation of the nucleus reuniens (RE), which projects to frontal cortex (FC) and hippocampus, would affect the cross-frequency coupling of gamma (γ) in different brain regions. METHODS: Local field potentials were recorded by electrodes implanted in the FC, ventrolateral thalamus (TH), basolateral amygdala (BLA), nucleus accumbens (NAC), and dorsal hippocampus (CA1) of behaving rats. At each electrode, the coupling between the γ amplitude envelope to the phase of the 2-6 Hz slow-waves (SW) was measured by modulation index (MI) or cross-frequency coherence (CFC) of γ amplitude with SW. In separate experiments, the RE was infused with saline or GABAA receptor agonist, muscimol, before the injection of GBL. RESULTS: Following GBL injection, an increase in MI and CFC of SW to γ1 (30-58 Hz), γ2 (62-100 Hz) and γ3 (100-160 Hz) bands was observed at the FC, hippocampus and BLA, with significant increase in SW-γ1 and SW-γ3 coupling at TH, and increase in peak SW-γ1 CFC at NAC. Strong SW-γ modulation was also found during baseline immobility high-voltage spindles. Muscimol inactivation of RE, as compared to saline infusion, significantly decreased SW-γ1 CFC in the FC, and peak frequency of the SW-γ1 CFC in the thalamus, but did not significantly alter SW-γ CFCs in the hippocampus, BLA or NAC. SIGNIFICANCE: The paroxysmal 2-6 Hz SW discharges, a hallmark of absence seizure, significantly modulate γ activity in the hippocampus, BLA and NAC, suggesting a modulation of limbic functions. RE inactivation disrupted the SW modulation of FC and TH, partly supporting our hypothesis that RE participates in the modulation of SW discharges.

Pearls & Oy-sters: Salt and Pepper Sign, PLNTY for Drug-Resistant Epilepsy.

Drug-resistant epilepsy, defined as the failure of 2 or more antiseizure medications to achieve seizure freedom, is responsible for 2/3 of epilepsy cases. Tumors are responsible for up to 15% of all adult onset and up to 6% of childhood onset epilepsies. Among these tumors, commonly known subtypes DNET, ganglioglioma, and low-grade astrocytoma are often suspected. New advances in tumor classification have been made, with genetics playing a key role in tumor classification. Polymorphic low-grade neuroepithelial tumor of the young (PLNTY) is a highly epileptogenic subtype of tumors that may mimic low-grade gliomas but offer pathologic and genetic clues: oligodendroglioma-like cellular components and infiltration patterns and strong CD34-immunopositive stain. In addition, a key finding is radiologic: a unifocal abnormality best seen on MRI brain in FLAIR sequence as the "salt and pepper sign" and calcifications appreciated on CT head.

Roles of fMRI and Wada tests in the presurgical evaluation of language functions in temporal lobe epilepsy.

Surgical treatment of pharmacoresistant temporal lobe epilepsy (TLE) carries risks for language function that can significantly affect the quality of life. Predicting the risks of decline in language functions before surgery is, consequently, just as important as predicting the chances of becoming seizure-free. The intracarotid amobarbital test, generally known as the Wada test (WT), has been traditionally used to determine language lateralization and to estimate their potential decline after surgery. However, the test is invasive and it does not localize the language functions. Therefore, other noninvasive methods have been proposed, of which functional magnetic resonance (fMRI) has the greatest potential. Functional MRI allows localization of language areas. It has good concordance with the WT for language lateralization, and it is of predictive value for postsurgical naming outcomes. Consequently, fMRI has progressively replaced WT for presurgical language evaluation. The objective of this manuscript is to review the most relevant aspects of language functions in TLE and the current role of fMRI and WT in the presurgical evaluation of language. First, we will provide context by revising the language network distribution and the effects of TLE on them. Then, we will assess the functional outcomes following various forms of TLE surgery and measures to reduce postoperative language decline. Finally, we will discuss the current indications for WT and fMRI and the potential usefulness of the resting-state fMRI technique.

The role of the temporal pole in temporal lobe epilepsy: A diffusion kurtosis imaging study.

This study aimed to evaluate the use of diffusion kurtosis imaging (DKI) to detect microstructural abnormalities within the temporal pole (TP) and its temporopolar cortex in temporal lobe epilepsy (TLE) patients. DKI quantitative maps were obtained from fourteen lesional TLE and ten non-lesional TLE patients, along with twenty-three healthy controls. Data collected included mean (MK); radial (RK) and axial kurtosis (AK); mean diffusivity (MD) and axonal water fraction (AWF). Automated fiber quantification (AFQ) was used to quantify DKI measurements along the inferior longitudinal (ILF) and uncinate fasciculus (Unc). ILF and Unc tract profiles were compared between groups and tested for correlation with disease duration. To characterize temporopolar cortex microstructure, DKI maps were sampled at varying depths from superficial white matter (WM) towards the pial surface. Patients were separated according to the temporal lobe ipsilateral to seizure onset and their AFQ results were used as input for statistical analyses. Significant differences were observed between lesional TLE and controls, towards the most temporopolar segment of ILF and Unc proximal to the TP within the ipsilateral temporal lobe in left TLE patients for MK, RK, AWF and MD. No significant changes were observed with DKI maps in the non-lesional TLE group. DKI measurements correlated with disease duration, mostly towards the temporopolar segments of the WM bundles. Stronger differences in MK, RK and AWF within the temporopolar cortex were observed in the lesional TLE and noticeable differences (except for MD) in non-lesional TLE groups compared to controls. This study demonstrates that DKI has potential to detect subtle microstructural alterations within the temporopolar segments of the ILF and Unc and the connected temporopolar cortex in TLE patients including non-lesional TLE subjects. This could aid our understanding of the extrahippocampal areas, more specifically the temporal pole role in seizure generation in TLE and might inform surgical planning, leading to better seizure outcomes.

Risk factors for comorbid epilepsy in patients with psychogenic non-epileptic seizures. Dataset of a large cohort study.

Psychogenic non-epileptic seizures (PNES) are the main differential diagnosis of pharmacorresistant epilepsy. Achieving the certainty in the diagnosis of PNES may be challenging, especially in the 10-22% of cases in which PNES and epilepsy co-exist. This difficulty hampers the management of these patients. Unfortunately, published series with this combined pathology are scarce and small in size. This article presents the dataset of our article "Factors associated with comorbid epilepsy in patients with psychogenic non-epileptic seizures: a large cohort study" (Massot-Tarrús et al. 2022). It is composed by a detailed demographic and clinical data of 271 consecutive patients diagnosed with PNES in our epilepsy monitoring unit (EMU) between May 2001 and February 2011, and followed until September 2016. Based on the clinical, neuroimaging and vEEG findings, 47 of these patients were diagnosed with definite comorbid epilepsy, and 30 with possible or probable comorbid epilepsy. All data was collected retrospectively from chart review. The cohort is depicted by means of demographic variables; age at PNES onset; years with PNES; frequency of PNES; duration of longest PNES seizure; self-reported history of minor head trauma (not associated with an increased risk of epilepsy) immediately preceding the first PNES; history of substance abuse; past or present history of active suicidal ideation; neuropsychological evaluation with the Minnesota Multiphasic Personality Inventory test; number and nature of risk factors for epilepsy; co-morbid degenerative brain disease or other neurological or psychiatric medical conditions; semiology of the seizures and triggers; EEG findings; type of epilepsy; number of past EMU admissions and epilepsy clinic visits and re-referrals; number of Anti-Seizure Medications (ASM) at EMU admission and discharge; and the outcome of the spells and ASM after the EMU discharge. Those ASM prescribed for reasons other than the treatment of the seizures (e.g., psychiatric disorders, migraine, pain syndromes, etc.) were not counted. The presented baseline data can be used in studies evaluating the characteristics of patients with PNES and comorbid epilepsy, and in the creation of algorithms to identify them. It could facilitate the prioritization of this subgroup of patients for prolonged video-EEG monitorization to confirm the co-existence of both types of seizures and treat them accordingly.

Stereo-Encephalographic Presurgical Evaluation of Temporal Lobe Epilepsy: An Evolving Science.

Drug-resistant epilepsy is present in nearly 30% of patients. Resection of the epileptogenic zone has been found to be the most effective in achieving seizure freedom. The study of temporal lobe epilepsy for surgical treatment is extensive and complex. It involves a multidisciplinary team in decision-making with initial non-invasive studies (Phase I), providing 70% of the required information to elaborate a hypothesis and treatment plans. Select cases present more complexity involving bilateral clinical or electrographic manifestations, have contradicting information, or may involve deeper structures as a part of the epileptogenic zone. These cases are discussed by a multidisciplinary team of experts with a hypothesis for invasive methods of study. Subdural electrodes were once the mainstay of invasive presurgical evaluation and in later years most Comprehensive Epilepsy Centers have shifted to intracranial recordings. The intracranial recording follows original concepts since its development by Bancaud and Talairach, but great advances have been made in the field. Stereo-electroencephalography is a growing field of study, treatment, and establishment of seizure pattern complexities. In this comprehensive review, we explore the indications, usefulness, discoveries in interictal and ictal findings, pitfalls, and advances in the science of presurgical stereo-encephalography for temporal lobe epilepsy.

Waveform detection by deep learning reveals multi-area spindles that are selectively modulated by memory load.

Sleep is generally considered to be a state of large-scale synchrony across thalamus and neocortex; however, recent work has challenged this idea by reporting isolated sleep rhythms such as slow oscillations and spindles. What is the spatial scale of sleep rhythms? To answer this question, we adapted deep learning algorithms initially developed for detecting earthquakes and gravitational waves in high-noise settings for analysis of neural recordings in sleep. We then studied sleep spindles in non-human primate electrocorticography (ECoG), human electroencephalogram (EEG), and clinical intracranial electroencephalogram (iEEG) recordings in the human. Within each recording type, we find widespread spindles occur much more frequently than previously reported. We then analyzed the spatiotemporal patterns of these large-scale, multi-area spindles and, in the EEG recordings, how spindle patterns change following a visual memory task. Our results reveal a potential role for widespread, multi-area spindles in consolidation of memories in networks widely distributed across primate cortex.

The brain processes memories as we sleep, generating rhythms of electrical activity called 'sleep spindles'. Sleep spindles were long thought to be a state where the entire brain was fully synchronized by this rhythm. This was based on EEG recordings, short for electroencephalogram, a technique that uses electrodes on the scalp to measure electrical activity in the outermost layer of the brain, the cortex. But more recent intracranial recordings of people undergoing brain surgery have challenged this idea and suggested that sleep spindles may not be a state of global brain synchronization, but rather localised to specific areas. Mofrad et al. sought to clarify the extent to which spindles co-occur at multiple sites in the brain, which could shed light on how networks of neurons coordinate memory storage during sleep. To analyse highly variable brain wave recordings, Mofrad et al. adapted deep learning algorithms initially developed for detecting earthquakes and gravitational waves. The resulting algorithm, designed to more sensitively detect spindles amongst other brain activity, was then applied to a range of sleep recordings from humans and macaque monkeys. The analyses revealed that widespread and complex patterns of spindle rhythms, spanning multiple areas in the cortex of the brain, actually appear much more frequently than previously thought. This finding was consistent across all the recordings analysed, even recordings under the skull, which provide the clearest window into brain circuits. Further analyses found that these multi-area spindles occurred more often in sleep after people had completed tasks that required holding many visual scenes in memory, as opposed to control conditions with fewer visual scenes. In summary, Mofrad et al. show that neuroscientists had previously not appreciated the complex and dynamic patterns in this sleep rhythm. These patterns in sleep spindles may be able to adapt based on the demands needed for memory storage, and this will be the subject of future work. Moreover, the findings support the idea that sleep spindles help coordinate the consolidation of memories in brain circuits that stretch across the cortex. Understanding this mechanism may provide insights into how memory falters in aging and sleep-related diseases, such as Alzheimer's disease. Lastly, the algorithm developed by Mofrad et al. stands to be a useful tool for analysing other rhythmic waveforms in noisy recordings.

Factors associated with comorbid epilepsy in patients with psychogenic nonepileptic seizures: A large cohort study.

OBJECTIVE: Comorbid epilepsy and psychogenic nonepileptic seizures (PNES) occur in 12-22% of cases and the diagnosis of both simultaneous disorders is challenging. We aimed to identify baseline characteristics that may help distinguish patients with PNES-only from those with comorbid epilepsy. METHODS: We performed a longitudinal cohort study on those patients diagnosed with PNES in our epilepsy monitoring unit (EMU) between May 2001 and February 2011, prospectively followed up until September 2016. Patients were classified into PNES-only, PNES + possible or probable epilepsy, and PNES + definite epilepsy based on the clinical, vEEG, and neuroimaging data. Demographic and basal clinical data were obtained from chart review. Multiple regression models were performed to identify significant predictors of PNES + definite epilepsy, excluding patients with only possible or probable epilepsy for this specific analysis. RESULTS: One-hundred and ninety four patients with PNES-only, 30 with PNES + possible or probable epilepsy and 47 with PNES + definite epilepsy were included. 73.8% were female and the mean age at EMU admission was 37.4 ±â€¯standard deviation 13.5 years. Patients with PNES + definite epilepsy most likely had never worked, had history of febrile seizures, structural brain lesions, developmental disabilities, and maximum reported seizure duration between 0.5 and 2 min. Patients with PNES-only were on fewer anti-seizure medications (ASM), reported more frequently an initial minor head trauma, seizures longer than 10 min, and a higher number of neurological and medical illnesses - being migraine (18.1%), other types of headaches (18.5%), and asthma (15.5%) the most prevalent ones. All p < 0.05. On the hierarchical regression analysis, history of febrile seizures, developmental disabilities, brain lesions, longest reported seizure duration between 0.5 and 2 min, and lack of neurological comorbidity, remained as significant predictors of PNES + epilepsy. The model's performance of a 5-fold cross-validation analysis showed an overall accuracy of 84.7% to classify patients correctly. CONCLUSIONS: Some demographic and clinical characteristics may support the presence of comorbid epilepsy in patients with PNES, being unemployment, the presence of brain lesions, developmental disabilities, history of febrile seizures, seizure duration and lack of comorbid headaches the most relevant ones.

EEG and MRI Abnormalities in Patients With Psychogenic Nonepileptic Seizures.

OBJECTIVE: To compare the rate of EEG and MRI abnormalities in psychogenic nonepileptic seizures (PNES) patients with and without suspected epilepsy. Patients were also compared in terms of their demographic and clinical profiles. METHODS: A retrospective analysis of 271 newly diagnosed PNES patients admitted to the epilepsy monitoring unit between May 2000 and April 2008, with follow-up clinical data collected until September 2015. RESULTS: One hundred ninety-four patients were determined to have PNES alone, 16 PNES plus possible epilepsy, 14 PNES plus probable epilepsy, and 47 PNES plus confirmed epilepsy. Fifty-seven of the 77 patients (74.0%) with possible, probable, or definite epilepsy exhibited epileptiform activity on EEG, versus only 16 of the 194 patients (8.2%) in whom epilepsy was excluded. Twenty-four of these 194 patients (12.4%) had MRI abnormalities. Three of 38 patients (7.9%) with both EEG and MRI abnormalities were confirmed not to have epilepsy. In PNES patients with EEG or MRI abnormalities compared with those without, patients with abnormalities were more likely to have epilepsy risk factors, such as central nervous system structural abnormalities, and less likely to report minor head trauma. The presence of EEG abnormalities in PNES-only patients did not influence antiseizure medication reduction, whereas those with MRI abnormalities were less likely to have their antiseizure medications reduced. CONCLUSIONS: Psychogenic nonepileptic seizure patients without MRI or EEG abnormalities are less likely to have associated epilepsy, risk factors for epilepsy, and had different demographic profiles. There is a higher-than-expected level of EEG and MRI abnormalities in PNES patients without epilepsy.

Auditory verbal hallucinations as ictal phenomena in a patient with drug-resistant epilepsy.

PURPOSE: The presence of verbal auditory hallucinations is often associated with psychotic disorders and rarely is considered as an ictal phenomena. The aim of this paper is to describe the anatomical structures involved in the genesis of this ictal symptom during epileptic seizures and direct cortical stimulation using stereo encephalography (SEEG). METHOD: The case is of a 31-year-old right-handed female, bilateral speech representation, schizophrenia and with drug-resistant epilepsy and focal aware sensory seizures characterized by ictal verbal auditory hallucinations. She was implanted with depth electrodes, and she was monitored using SEEG recordings. RESULTS: She had focal aware sensory seizures characterized by verbal auditory hallucinations, with the following features: hearing numerous voices (both male and/or female), talking at the same time (not able to distinguish how many). The voices were inside her head, consisted of negative content, and lasted up to two minutes. Some of her focal aware sensory seizures evolved to focal motor seizures and rarely progressed to bilateral tonic clonic seizures. Her neurological examination, her brain MRI and her interictal SPECT were unremarkable. Her PET scan identified mild hypo metabolism over the right temporal and right frontal lobes. Her neuropsychological evaluation showed language laterality undetermined but her functional MRI showed bilateral language representation. On her video-EEG, three seizures were captured with a right posterior temporal onset. A subsequent SEEG showed thirteen typical seizures originating from the posterior temporal neocortical region. The cortical stimulation of the right posterior temporo-parietal neocortical region and right amygdala triggered her typical phenomena, which was multiple voices, inside her head, speaking in the second person, negative content, unable to identify gender, in English, and no side lateralization. CONCLUSION: Verbal auditory hallucinations should be analyzed carefully because they can be part of the seizure presentation. Our case supports the localization of these hallucinations in the right posterior neocortical temporal regions.