Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults.

More than half of adults with epilepsy undergoing resective epilepsy surgery achieve long-term seizure freedom and might consider withdrawing antiseizure medications. We aimed to identify predictors of seizure recurrence after starting postoperative antiseizure medication withdrawal and develop and validate predictive models. We performed an international multicentre observational cohort study in nine tertiary epilepsy referral centres. We included 850 adults who started antiseizure medication withdrawal following resective epilepsy surgery and were free of seizures other than focal non-motor aware seizures before starting antiseizure medication withdrawal. We developed a model predicting recurrent seizures, other than focal non-motor aware seizures, using Cox proportional hazards regression in a derivation cohort (n = 231). Independent predictors of seizure recurrence, other than focal non-motor aware seizures, following the start of antiseizure medication withdrawal were focal non-motor aware seizures after surgery and before withdrawal [adjusted hazard ratio (aHR) 5.5, 95% confidence interval (CI) 2.7-11.1], history of focal to bilateral tonic-clonic seizures before surgery (aHR 1.6, 95% CI 0.9-2.8), time from surgery to the start of antiseizure medication withdrawal (aHR 0.9, 95% CI 0.8-0.9) and number of antiseizure medications at time of surgery (aHR 1.2, 95% CI 0.9-1.6). Model discrimination showed a concordance statistic of 0.67 (95% CI 0.63-0.71) in the external validation cohorts (n = 500). A secondary model predicting recurrence of any seizures (including focal non-motor aware seizures) was developed and validated in a subgroup that did not have focal non-motor aware seizures before withdrawal (n = 639), showing a concordance statistic of 0.68 (95% CI 0.64-0.72). Calibration plots indicated high agreement of predicted and observed outcomes for both models. We show that simple algorithms, available as graphical nomograms and online tools (predictepilepsy.github.io), can provide probabilities of seizure outcomes after starting postoperative antiseizure medication withdrawal. These multicentre-validated models may assist clinicians when discussing antiseizure medication withdrawal after surgery with their patients.

Histopathological characterization of cerebral small vessel disease in epilepsy patients with temporal lobe epilepsy submitted to surgery: A case-control study.

BACKGROUND: Cerebrovascular disease (CVD) is a major contributor to epilepsy; however, patients with epilepsy also have a significantly increased risk of stroke. The way in which epilepsy contributes to the increased risk of stroke is still uncertain and is ill-characterized in neuropathological studies. A neuropathological characterization of cerebral small vessel disease (cSVD) in patients with chronic epilepsy was performed. METHODS: Thirty-three patients with refractory epilepsy and hippocampal sclerosis (HS) submitted to epilepsy surgery from a reference center were selected between 2010 and 2020 and compared with 19 autopsy controls. Five randomly selected arterioles from each patient were analyzed using a previously validated scale for cSVD. The presence of CVD disease imaging markers in pre-surgical brain magnetic resonance imaging (MRI) was studied. RESULTS: There were no differences in age (43.8 vs. 41.6 years; p = 0.547) or gender distribution (female gender 60.6% vs. male gender 52.6%; p = 0.575) between groups. Most CVD findings in brain MRI were mild. Patients had a mean time between the epilepsy onset and surgery of 26 ± 14.7 years and were medicated with a median number of three antiseizure medication (ASMs) [IQR 2-3]. Patients had higher median scores in arteriolosclerosis (3 vs. 1; p < 0.0001), microhemorrhages (4 vs. 1; p < 0.0001) and total score value (12 vs. 8.9; p = 0.031) in comparison with controls. No correlation was found between age, number of years until surgery, number of ASMs or cumulative defined daily dosage of ASM. CONCLUSION: The present study provides evidence supporting the increased burden of cSVD in the neuropathological samples of patients with chronic epilepsy.

Seizures after Ischemic Stroke: A Matched Multicenter Study.

OBJECTIVE: The purpose of this study was to identify risk factors for acute symptomatic seizures and post-stroke epilepsy after acute ischemic stroke and evaluate the effects of reperfusion treatment. METHODS: We assessed the risk factors for post-stroke seizures using logistic or Cox regression in a multicenter study, including adults from 8 European referral centers with neuroimaging-confirmed ischemic stroke. We compared the risk of post-stroke seizures between participants with or without reperfusion treatment following propensity score matching to reduce confounding due to treatment selection. RESULTS: In the overall cohort of 4,229 participants (mean age 71 years, 57% men), a higher risk of acute symptomatic seizures was observed in those with more severe strokes, infarcts located in the posterior cerebral artery territory, and strokes caused by large-artery atherosclerosis. Strokes caused by small-vessel occlusion carried a small risk of acute symptomatic seizures. 6% developed post-stroke epilepsy. Risk factors for post-stroke epilepsy were acute symptomatic seizures, more severe strokes, infarcts involving the cerebral cortex, and strokes caused by large-artery atherosclerosis. Electroencephalography findings within 7 days of stroke onset were not independently associated with the risk of post-stroke epilepsy. There was no association between reperfusion treatments in general or only intravenous thrombolysis or mechanical thrombectomy with the time to post-stroke epilepsy or the risk of acute symptomatic seizures. INTERPRETATION: Post-stroke seizures are related to stroke severity, etiology, and location, whereas an early electroencephalogram was not predictive of epilepsy. We did not find an association of reperfusion treatment with risks of acute symptomatic seizures or post-stroke epilepsy. ANN NEUROL 2021;90:808-820.

Anterior Nucleus of Thalamus Deep Brain Stimulation: A Clinical-Based Analysis of the Ideal Target in Drug-Resistant Epilepsy.

INTRODUCTION: Deep brain stimulation of the anterior nucleus of thalamus (ANT-DBS) is an approved procedure for drug-resistant epilepsy. However, the preferred location inside ANT is not well known. In this study, we investigated the relationship between stereotactical coordinates of stimulated contacts and clinical improvement, in order to define the ideal target for ANT-DBS. METHODS: Individual contact's coordinates were obtained in the Montreal Neurological Institute (MNI) 152 space, with the utilization of advanced normalization tools and co-registration of pre- and postoperative MRI and CT images in open-source toolbox lead-DBS with the "Atlas of the Human Thalamus." Each contact's pair was either classified as a responder (≥50% seizure reduction and absence of intolerable adverse effects) or nonresponder, with a minimum follow-up of 11 continuous months of stimulation. RESULTS: A total of 19 contacts' pairs were tested in 14 patients. The responder rate was 9 out of 14 patients (64.3%). In 4 patients, a change in contacts' pairs was needed to achieve this result. A highly encouraging location inside ANT (HELIA) was delimited in MNI space, corresponding to an area in the anterior and inferior portion of the anteroventral (AV) nucleus, medially to the endpoint of the mammillothalamic tract (ANT-mtt junction) (x [3.8; 5.85], y [-2.1; -6.35] and z [6.2; 10.1] in MNI space). Statistically significant difference was observed between responders and nonresponders, in terms of the number of coordinates inside this volume. Seven responders and two nonresponders had at least 5 of 6 coordinates (2 electrodes) inside HELIA (77.8% sensitivity and 80% specificity). In 3 patients, changing to contacts that were better placed inside HELIA changed the status from nonresponder to responder. CONCLUSIONS: A relationship between stimulated contacts' coordinates and responder status was observed in drug-resistant epilepsy. The possibility to target different locations inside HELIA may help surpass anatomical variations and eventually obtain increased clinical benefit.

Amygdalohippocampotomy for mesial temporal lobe sclerosis: Epilepsy outcome 5 years after surgery.

BACKGROUND: The goal of the present study is the evaluation of the long-term clinical outcome of epilepsy in patients with mesial temporal lobe sclerosis (MTLS) submitted to amygdalohippocampotomy (AHCo). AHCo consists of the lateral ablation of the amygdala and the peri-hippocampal disconnection instead of amygdalohippocampectomy (AHC), which involves the removal of both structures. We previously reported the short-term results of AHCo, so we here present the long-term results (> 5 years of follow-up) of the patients operated on with AHCo. METHOD: Since 2007, 35 patients (22 females) aged 20-61 years (mean: 42 years) were operated on with the AHCo technique, 17 patients on the left side and 18 on the right. Of these patients, 21 (14 females) have been followed up > 5 years (5 to 7.5 years, mean 6.5 years). We compare the present results with those observed shortly after surgery and with the patients operated on with AHC. FINDINGS: In all 21 cases, the diagnosis was mesial temporal lobe sclerosis (histology confirmed in 20), 11 on the left side and 10 on the right. Epilepsy results after 5 years were good/very good in 18 patients (85.7%), with Engel class IA-B in 15 (71.4%) and II in 3 (14.3%), and bad in 3 patients, with Engel Class III in 2 (9.5%) and class IV in 1 (4.8%). Concerning morbidity, one patient had hemiparesis (hypertensive capsular hemorrhage 24 h after surgery), two verbal memory worsening, two quadrantanopia and three late depression that was reversed with medication. Comparatively, the AHC long-term results were 87% Engel class I, 8% Engel class II and 5% Engel class III-IV. The morbidity was equally small. CONCLUSIONS: The good/very good results of AHCo 5 years after surgery are 86%, which is not distinct from the AHC results. So AHCo seems to be effective and potentially safer than AHC in long-term follow-up.

Molecular characterization of the circadian clock in patients with Parkinson's disease-CLOCK4PD Study protocol.

INTRODUCTION: Circadian rhythms (CRs) orchestrate intrinsic 24-hour oscillations which synchronize an organism's physiology and behaviour with respect to daily cycles. CR disruptions have been linked to Parkinson's Disease (PD), the second most prevalent neurodegenerative disorder globally, and are associated to several PD-symptoms such as sleep disturbances. Studying molecular changes of CR offers a potential avenue for unravelling novel insights into the PD progression, symptoms, and can be further used for optimization of treatment strategies. Yet, a comprehensive characterization of the alterations at the molecular expression level for core-clock and clock-controlled genes in PD is still missing. METHODS AND ANALYSIS: The proposed study protocol will be used to characterize expression profiles of circadian genes obtained from saliva samples in PD patients and controls. For this purpose, 20 healthy controls and 70 PD patients will be recruited. Data from clinical assessment, questionnaires, actigraphy tracking and polysomnography will be collected and clinical evaluations will be repeated as a follow-up in one-year time. We plan to carry out sub-group analyses considering several clinical factors (e.g., biological sex, treatment dosages, or fluctuation of symptoms), and to correlate reflected changes in CR of measured genes with distinct PD phenotypes (diffuse malignant and mild/motor-predominant). Additionally, using NanoStringⓇ multiplex technology on a subset of samples, we aim to further explore potential CR alterations in hundreds of genes involved in neuropathology pathways. DISCUSSION: CLOCK4PD is a mono-centric, non-interventional observational study aiming at the molecular characterization of CR alterations in PD. We further plan to determine physiological modifications in sleep and activity patterns, and clinical factors correlating with the observed CR changes. Our study may provide valuable insights into the intricate interplay between CR and PD with a potential to be used as a predictor of circadian alterations reflecting distinct disease phenotypes, symptoms, and progression outcomes.

Automated algorithms for seizure forecast: a systematic review and meta-analysis.

This study aims to review the proposed methodologies and reported performances of automated algorithms for seizure forecast. A systematic review was conducted on studies reported up to May 10, 2024. Four databases and registers were searched, and studies were included when they proposed an original algorithm for automatic human epileptic seizure forecast that was patient specific, based on intraindividual cyclic distribution of events and/or surrogate measures of the preictal state and provided an evaluation of the performance. Two meta-analyses were performed, one evaluating area under the ROC curve (AUC) and another Brier Skill Score (BSS). Eighteen studies met the eligibility criteria, totaling 43 included algorithms. A total of 419 patients participated in the studies, and 19442 seizures were reported across studies. Of the analyzed algorithms, 23 were eligible for the meta-analysis with AUC and 12 with BSS. The overall mean AUC was 0.71, which was similar between the studies that relied solely on surrogate measures of the preictal state, on cyclic distributions of events, and on a combination of these. BSS was also similar for the three types of input data, with an overall mean BSS of 0.13. This study provides a characterization of the state of the art in seizure forecast algorithms along with their performances, setting a benchmark for future developments. It identified a considerable lack of standardization across study design and evaluation, leading to the proposal of guidelines for the design of seizure forecast solutions.

Acute symptomatic seizures in patients with recurrent ischemic stroke: A multicentric study.

OBJECTIVE: Epileptic seizures occur frequently after stroke due to changes in brain function and structure, and up to around 10% of stroke patients experience stroke recurrence in the first year. We aimed to establish the risk of acute symptomatic seizures in patients with recurrent stroke. METHODS: Retrospective cohort study including consecutive admissions to a Stroke Unit due to acute ischemic stroke, during a 5-year period. Additional inclusion of patients admitted to two centers in different countries to corroborate findings (confirmatory cohort). We aimed to compare acute symptomatic seizure incidence in patients with and without previous stroke. Patients with history of epilepsy were excluded. Logistic regression modeling was performed to identify predictors in middle cerebral artery (MCA) stroke. RESULTS: We included 1473 patients (1085 with MCA stroke), of which 117 had a recurrent ischemic stroke (84 with MCA stroke). Patients with recurrent stroke had a seizure risk during hospital stay similar to that of patients with a first-ever stroke (5.1% vs. 4.5%, OR 1.15, 95% CI .48-2.71, p = .75). Risk of acute symptomatic seizures was also similar (5.0% vs. 4.1, OR 1.22, 95% CI .29-5.27, p = .78). Older age, female sex, and hemorrhagic transformation were predictors of seizures in patients with a first MCA ischemic stroke, but not in recurrent stroke patients. Electrographic characteristics were similar between the two groups in patients who had an electroencephalogram (46 with first stroke, 5 with recurrent stroke). The low rate of seizures (1.5%) in the confirmatory cohort (n = 198) precluded full comparison with the initial cohort. Nevertheless, the rate of seizures was not higher in stroke recurrence. SIGNIFICANCE: History of previous stroke was not associated with an increased risk of acute symptomatic seizures during hospital stay. Larger, prospective studies, with prospective electrophysiological evaluation, are needed to explore the impact of stroke recurrence on seizure risk.

PreEpiSeizures: description and outcomes of physiological data acquisition using wearable devices during video-EEG monitoring in people with epilepsy.

The PreEpiSeizures project was created to better understand epilepsy and seizures through wearable technologies. The motivation was to capture physiological information related to epileptic seizures, besides Electroencephalography (EEG) during video-EEG monitorings. If other physiological signals have reliable information of epileptic seizures, unobtrusive wearable technology could be used to monitor epilepsy in daily life. The development of wearable solutions for epilepsy is limited by the nonexistence of datasets which could validate these solutions. Three different form factors were developed and deployed, and the signal quality was assessed for all acquired biosignals. The wearable data acquisition was performed during the video-EEG of patients with epilepsy. The results achieved so far include 59 patients from 2 hospitals totaling 2,721 h of wearable data and 348 seizures. Besides the wearable data, the Electrocardiogram of the hospital is also useable, totalling 5,838 h of hospital data. The quality ECG signals collected with the proposed wearable is equated with the hospital system, and all other biosignals also achieved state-of-the-art quality. During the data acquisition, 18 challenges were identified, and are presented alongside their possible solutions. Though this is an ongoing work, there were many lessons learned which could help to predict possible problems in wearable data collections and also contribute to the epilepsy community with new physiological information. This work contributes with original wearable data and results relevant to epilepsy research, and discusses relevant challenges that impact wearable health monitoring.

Association of Mortality and Risk of Epilepsy With Type of Acute Symptomatic Seizure After Ischemic Stroke and an Updated Prognostic Model.

Importance: Acute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk. Objective: To compare mortality and risk of epilepsy following different types of acute symptomatic seizures. Design, Setting, and Participants: This cohort study analyzed data acquired from 2002 to 2019 from 9 tertiary referral centers. The derivation cohort included adults from 7 cohorts and 2 case-control studies with neuroimaging-confirmed ischemic stroke and without a history of seizures. Replication in 3 separate cohorts included adults with acute symptomatic status epilepticus after neuroimaging-confirmed ischemic stroke. The final data analysis was performed in July 2022. Exposures: Type of acute symptomatic seizure. Main Outcomes and Measures: All-cause mortality and epilepsy (at least 1 unprovoked seizure presenting >7 days after stroke). Results: A total of 4552 adults were included in the derivation cohort (2547 male participants [56%]; 2005 female [44%]; median age, 73 years [IQR, 62-81]). Acute symptomatic seizures occurred in 226 individuals (5%), of whom 8 (0.2%) presented with status epilepticus. In patients with acute symptomatic status epilepticus, 10-year mortality was 79% compared with 30% in those with short acute symptomatic seizures and 11% in those without seizures. The 10-year risk of epilepsy in stroke survivors with acute symptomatic status epilepticus was 81%, compared with 40% in survivors with short acute symptomatic seizures and 13% in survivors without seizures. In a replication cohort of 39 individuals with acute symptomatic status epilepticus after ischemic stroke (24 female; median age, 78 years), the 10-year risk of mortality and epilepsy was 76% and 88%, respectively. We updated a previously described prognostic model (SeLECT 2.0) with the type of acute symptomatic seizures as a covariate. SeLECT 2.0 successfully captured cases at high risk of poststroke epilepsy. Conclusions and Relevance: In this study, individuals with stroke and acute symptomatic seizures presenting as status epilepticus had a higher mortality and risk of epilepsy compared with those with short acute symptomatic seizures or no seizures. The SeLECT 2.0 prognostic model adequately reflected the risk of epilepsy in high-risk cases and may inform decisions on the continuation of antiseizure medication treatment and the methods and frequency of follow-up.

Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Drug-Resistant Epilepsy in the MORE Multicenter Patient Registry.

BACKGROUND AND OBJECTIVES: The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice. METHODS: MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes. RESULTS: Of the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years (p < 0.0001) with 32.3% RR. In the subgroup of 47 patients who completed 5 years of follow-up, the median monthly SF decreased by 55.1% from 16 at baseline to 7.9 at 5 years (p < 0.0001) with 53.2% RR. High-volume centers (>10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported. DISCUSSION: The MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy. TRIAL REGISTRATION INFORMATION: MORE ClinicalTrials.gov Identifier: NCT01521754, first posted on January 31, 2012.

Frequency of epileptic seizures in patients undergoing decompressive craniectomy after ischemic stroke.

BACKGROUND: Decompressive surgery has proven to be lifesaving in patients with a malignant anterior circulation ischemic stroke. Recently, some studies have shown a high frequency of epileptic seizures in patients undergoing this procedure. However, the quantification of this risk and its associated factors have not been extensively investigated. OBJECTIVE: To determine the frequency of epileptic seizures and epilepsy in patients with an anterior circulation ischemic stroke admitted to our Stroke Unit from January 2006 to March 2019 that have been submitted to craniectomy and to study their associated demographic, clinical, imagiological and neurophysiological features. METHODS: Retrospective observational study of 56 consecutive patients with an anterior circulation ischemic stroke that have undergone craniectomy. The frequency of seizures was both clinically and neurophysiologically assessed after reviewing clinical records, discharge or death reports and all EEGs performed during the hospital admission. Bivariate analysis was used to compare patients with and without seizures. RESULTS: Sixteen patients (28,6%) had epileptic seizures. Bivariate analysis showed an association between the occurrence of unprovoked seizures and the median ASPECTS from the first CT performed. CONCLUSIONS: In this study, the frequency of epileptic seizures after a malignant stroke submitted to craniectomy was high, albeit lower than that reported in previous studies. The size of infarction at hospital admission appears to be a risk factor for the occurrence of epilepsy in this group of patients.

Etiology and Clinical Impact of Interictal Periodic Discharges on the Routine Outpatient Scalp EEG.

PURPOSE: Periodic discharges (PDs) are common in acute structural or metabolic brain lesions, but their occurrence during follow-up of epileptic patients in an outpatient setting is rare. Aim of this article was to study whether PDs on the routine outpatient scalp EEG of patients with epilepsy, as compared with nonperiodic epileptiform discharges, are associated with drug refractoriness and the decompensation of epilepsy and particular etiologies. METHODS: A retrospective case-control study. EEG reports were screened for PDs and their variants. The inclusion criteria were as follows: a diagnosis of epilepsy, epileptogenic lesion on imaging, or a normal 3-T MRI. Inpatient EEGs or EEGs performed in patients with acute cerebral lesions were excluded. Age- and sex-matched controls presenting with other epileptiform EEG abnormalities were selected, and similar selection criteria were applied. RESULTS: Forty-one patients with PDs and 82 controls were selected. There were no significant differences between the cases and controls in the rates of epilepsy decompensation at the time of EEG collection or drug refractoriness. Stroke, hippocampal sclerosis, and malformations of cortical development were the most frequent etiologies, without significant differences between the groups. CONCLUSIONS: By performing a case-control study, the authors have shown that PDs are not a marker of epilepsy decompensation and drug refractoriness and that the finding of PDs is not suggestive of particular epilepsy etiologies, when compared with other epileptiform abnormalities.

Non-convulsive status epilepticus induced by acute thalamic lesions: A report of three cases.

The thalamocortical network appears to play a pivotal role in ictogenesis. We herein present three cases of non-convulsive status epilepticus (SE), in adult patients without previous history of epilepsy or seizures, precipitated by acute thalamic vascular and metabolic-induced lesions. In all cases the EEG showed patterns consistent with generalized SE confirmed either by a fast and complete clinical and EEG response to anti-seizure medication or definitive subtle motor signs consistent with SE. We argue that the subcortical disruption of thalamocortical networks due to the thalamic lesion predisposed to the occurrence of non-convulsive SE. In patients with thalamic disorders and unexplained mental status changes EEG evaluation should always be considered.

A Computational Analysis in a Cohort of Parkinson's Disease Patients and Clock-Modified Colorectal Cancer Cells Reveals Common Expression Alterations in Clock-Regulated Genes.

Increasing evidence suggests a role for circadian dysregulation in prompting disease-related phenotypes in mammals. Cancer and neurodegenerative disorders are two aging related diseases reported to be associated with circadian disruption. In this study, we investigated a possible effect of circadian disruption in Parkinson's disease (PD) and colorectal cancer (CRC). We used high-throughput data sets retrieved from whole blood of idiopathic PD (IPD) patients and time course data sets derived from an in vitro model of CRC including the wildtype and three core-clock knockout (KO) cell lines. Several gene expression alterations in IPD patients resembled the expression profiles in the core-clock KO cells. These include expression changes in DBP, GBA, TEF, SNCA, SERPINA1 and TGFB1. Notably, our results pointed to alterations in the core-clock network in IPD patients when compared to healthy controls and revealed variations in the expression profile of PD-associated genes (e.g., HRAS and GBA) upon disruption of the core-clock genes. Our study characterizes changes at the transcriptomic level following circadian clock disruption on common cellular pathways associated with cancer and neurodegeneration (e.g., immune system, energy metabolism and RNA processing), and it points to a significant influence on the overall survival of colon cancer patients for several genes resulting from our analysis (e.g., TUBB6, PAK6, SLC11A1).

Complex sleep-disordered breathing after vagus nerve stimulation: broadening the spectrum of adverse events of special interest.

Two young males with refractory epilepsy of unknown aetiology were referred for vagus nerve stimulation (VNS). Sleep disturbances emerged following VNS parameter changes. In Patient 1, video-polysomnogram (PSG) disclosed snoring and catathrenia in non-REM sleep. Central apnoea also occurred, but more rarely. In Patient 2, video-PSG showed mixed apnoea with desaturation and episodes of stridor followed by a catathrenia-like sound. A drug-induced sleep endoscopy (DISE) revealed, during VNS OFF time, glossoptosis, "trap door" of the epiglottis, and paresis of the left side of the larynx and ipsilateral vocal cords. During ON time, there were periods of pharyngeal collapse, in which video-PSG revealed patterns suggestive of both obstructive and central sleep apnoea. All these sleep-related phenomena were coincident with VNS ON time. In the first patient, VNS parameter adjustment was sufficient to successfully reverse all the symptoms, whereas the other patient required concomitant treatment with continuous positive airway pressure. The data broaden our knowledge about sleep disorders related to VNS, in particular stridor and catathrenia. We suggest that central sleep apnoea may be associated with laryngeal occlusion. DISE may be considered in selected cases as a valuable clinical tool to evaluate, in a single session, the effectiveness of multiple VNS parameter changes on respiration and laryngeal side effects. [Published with video sequences].

Gelastic seizures: a retrospective study in five tertiary hospital centres.

This study aimed to characterize, clinically and neurophysiologically, a series of patients with gelastic seizures (GS), including both adults and children. We retrospectively collected patients with GS from epilepsy clinics of five tertiary hospital centres within a single country. Patients were selected through relatives'/caregivers' descriptions, home video and/or video-EEG monitoring. GS were identified through ictal semiology. Thirty-five patients were enrolled; 62.9% had initial GS in infancy, 14.3% in adolescence and 22.8% at adult age. Twenty-six had abnormal MRI: eight presented with hypothalamic hamartoma (HH) and 16 non-HH lesions that included different structural aetiologies and genetic, metabolic and immune aetiologies. All patients with HH had their first GS in infancy or adolescence. For the remaining aetiologies, GS started in infancy in 59.3%, in adolescence in 11.1% and at adult age in 29.6%. Video-EEG data was available for analysis in 11 patients, including seven patients with a non-HH MRI lesion. The ictal onset topography on scalp video-EEG was usually concordant with the MRI lesion (in 6/7 patients) and the most frequent ictal onset was fronto-temporal. In two patients, both video-EEG and MRI suggested a parietal and occipital epileptogenic zone. Aetiologies and patterns of affected topography unrelated to HH are common in patients with GS, and all age groups may manifest with this type of ictal semiology. This ictal manifestation has no lateralizing value and, despite a clear preponderance for hypothalamic, frontal and temporal lobe origins, other brain areas, namely the parietal and occipital lobes, should be considered.

Men and women with chronic insomnia disorder and OSAS: Different responses to CPAP.

OBJECTIVE: To evaluate the response to CPAP in patients with chronic insomnia disorder (CID) with OSAS in an unselected patient population including all OSAS severity groups. As a secondary objective, we also wanted to evaluate the differences between patients that improve insomnia symptoms with CPAP and patients that do not improve, specifically evaluating possible gender differences. METHODS: Retrospective study of patients with a diagnosis of OSAS treated with CPAP and CID at the first clinical visit, selected from a database of an outpatient sleep clinic of University Hospital. RESULTS: From a database of total of 827 patient, 90 patients were identified with OSAS and CID (53.3% women). Middle / moderate OSAS was diagnosed in 68.9% and severe OSA in 31.1%. Most patients (61.1%) improved insomnia symptoms after CPAP therapy. In the responders group, 58.2% had initial insomnia, 63.6% middle insomnia and 12.7% late insomnia. Responders to CPAP were more frequently women (women 61.8%, men 38.2%, p = 0.035) and there was no other difference between responders and non-responders. On subgroup analysis, this difference was significant only in severe OSAS (women 88.9%, men 31.6%, p = 0.013). CONCLUSION: In most patients with CID and OSA, there is a consistent reduction of insomnia symptoms with the CPAP use. This factor emphasizes the importance of performing PSG in CID. Insomnia in men with severe OSAS responds less frequently to CPAP suggesting that in these cases the insomnia phenotype is less dependent on the respiratory symptoms.

Hypothyroidism and cerebral vein thrombosis--a possible association.

BACKGROUND: There are many systemic illnesses that constitute risk factors for cerebral vein thrombosis (CVT). Hypothyroidism was never associated with CVT, despite growing evidence supporting a possible etiopathogenic link. We report two patients with CVT in whom hypothyroidism was concomitantly diagnosed. CLINICAL CASES: Cases were women 21 and 52 years old. They both presented with intracranial hypertension syndrome and symptomatic focal epilepsy. CVT was diagnosed with MRI and MR venography. Hypothyroidism was diagnosed in the acute phase of CVT. Both had an autoimmune thyroiditis. None of the patients had diffuse goitre. Other risk factors for CVT were oral contraceptives and elevated homocysteine in one and hormonal replacement therapy in the other. Both were treated with anticoagulation, anti-epileptic drugs and thyroid replacement therapy, with good clinical outcome. CONCLUSIONS: The association found between untreated hypothyroidism and CVT in these patients may result from chance. However, several haemostatic and fibrinolytic parameters have been demonstrated to be disturbed in hypothyroidism suggesting a possible role of this disease in CVT pathogenesis. In addition, indirect evidence also supports possible endothelial dysfunction and venous stasis in hypothyroidism, further emphasizing the physiopathological link between the two conditions. More research is needed to determine a possible causal role of hypothyroidism on CVT. We suggest that thyroid function should be included in the usual workup of CVT patients.