Predictive Model for Estimating the Risk of Epilepsy After Aneurysmal Subarachnoid Hemorrhage: The RISE Score.

BACKGROUND AND OBJECTIVES: The occurrence of seizures after aneurysmal subarachnoid hemorrhage (aSAH) is associated with a poorer functional and cognitive prognosis and less favorable quality of life. It would be of value to promptly identify patients at risk of epilepsy to optimize follow-up protocols and design preventive strategies. Our aim was to develop a predictive score to help stratify epilepsy risk in patients with aSAH. METHODS: This is a retrospective, longitudinal study of all adults with aSAH admitted to our center (2012-2021). We collected demographic data, clinical and radiologic variables, data on early-onset seizures (EOSs), and data on development of epilepsy. Exclusion criteria were previous structural brain lesion, epilepsy, and ≤7 days' follow-up. Multiple Cox regression was used to evaluate factors independently associated with unprovoked remote seizures (i.e., epilepsy). The best fitting regression model was used to develop a predictive score. Performance was evaluated in an external validation cohort of 308 patients using receiver-operating characteristic curve analysis. RESULTS: From an initial database of 743 patients, 419 met the inclusion criteria and were included in the analysis. The mean age was 60 ± 14 years, 269 patients (64%) were women, and 50 (11.9%) developed epilepsy within a median follow-up of 4.2 years. Premorbid modified Rankin Score (mRS) (hazard ratio [HR] 4.74 [1.8-12.4], p = 0.001), VASOGRADE score (HR 2.45 [1.4-4.2], p = 0.001), surgical treatment (HR 2.77 [1.6-4.9], p = 0.001), and presence of EOSs (HR 1.84 [1.0-3.4], p = 0.05) were independently associated with epilepsy. The proposed scale, designated RISE, scores 1 point for premorbid mRS ≥ 2 (R), VASOGRADE-Yellow (I, Ischemia), surgical intervention (S), and history of EOSs (E) and 2 points for VASOGRADE-Red. RISE stratifies patients into 3 groups: low (0-1), moderate (2-3), and high (4-5) risk (2.9%, 20.8%, and 75.7% developed epilepsy, respectively). On validation in a cohort from a different tertiary care center (N = 308), the new scale yielded a similar risk distribution and good predictive power for epilepsy within 5 years after aSAH (area under the curve [AUC] 0.82; 95% CI 0.74-0.90). DISCUSSION: The RISE scale is a robust predictor of post-SAH epilepsy with immediate clinical applicability. In addition to facilitating personalized diagnosis and treatment, RISE may be of value for exploring future antiepileptogenesis strategies.

Real-life evidence about the use of intravenous brivaracetam in urgent seizures: The BRIV-IV study.

PURPOSE: Urgent seizures are a medical emergency for which new therapies are still needed. This study evaluated the use of intravenous brivaracetam (IV-BRV) in an emergency setting in clinical practice. METHODS: BRIV-IV was a retrospective, multicenter, observational study. It included patients ≥18 years old who were diagnosed with urgent seizures (including status epilepticus (SE), acute repetitive seizures, and high-risk seizures) and who were treated with IV-BRV according to clinical practice in 14 hospital centers. Information was extracted from clinical charts and included in an electronic database. Primary effectiveness endpoints included the rate of IV-BRV responder patients, the rate of patients with a sustained response without seizure relapse in 12 h, and the time between IV-BRV administration and clinical response. Primary safety endpoints were comprised the percentage of patients with adverse events and those with adverse events leading to discontinuation. RESULTS: A total of 156 patients were included in this study. The mean age was 57.7 ± 21.5 years old with a prior diagnosis of epilepsy for 57.1% of patients. The most frequent etiologies were brain tumor-related (18.1%) and vascular (11.2%) epilepsy. SE was diagnosed in 55.3% of patients. The median time from urgent seizure onset to IV treatment administration was 60.0 min (range: 15.0-360.0), and the median time from IV treatment to IV-BRV was 90.0 min (range: 30.0-2400.0). Regarding dosage, the mean bolus infusion was 163.0 ± 73.0 mg and the mean daily dosage was 195.0 ± 87.0 mg. A total of 77.6% of patients responded to IV-BRV (66.3% with SE vs. 91% other urgent seizures) with a median response time of 30.0 min (range: 10.0-60.0). A sustained response was achieved in 62.8% of patients. However, adverse events were reported in 14.7%, which were predominantly somnolence and fatigue, with 4.5% leading to discontinuation. Eighty-six percent of patients were discharged with oral brivaracetam. CONCLUSION: IV-BRV in emergency settings was effective, and tolerability was good for most patients. However, a larger series is needed to confirm the outcomes.

Value contribution of cenobamate for the treatment of Focal-Onset Seizures (FOS) in patients with drug-resistant epilepsy (DRE) in Spain through reflective Multi-Criteria Decision Analysis (MCDA).

INTRODUCTION: Epilepsy is one of the most common neurological conditions worldwide. The main goal of its treatment is to achieve seizure freedom without intolerable adverse effects. However, despite the availability of many anti-seizure medications, including the latest options, called third-generation anti-seizure medications (ASMs), approximately 40% of people with epilepsy present drug-resistant epilepsy (DRE). Cenobamate is the first ASM approved in Spain for the adjunctive treatment of Focal-Onset Seizures (FOS) in adult patients with DRE. In a chronic disease with a portfolio of available ASMs, the decision to introduce a new therapeutic alternative must follow a holistic evaluation of value provided. Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine the value contribution of a treatment in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders. PURPOSE: The aim of this study was to determine the relative value contribution of cenobamate in the treatment of FOS in patients with DRE compared with third-generation ASMs using reflective MCDA-based methodology. METHODS: A systematic literature review (combining biomedical databases and grey literature sources) was performed to populate the Evidence and Value: Impact on DEcisionMaking (EVIDEM) MCDA framework adapted to determine what represents value in the management of FOS in patients with DRE in Spain. The study was conducted in two phases. The first took place in 2021 with a multi-stakeholder group of eight participants. The second phase was conducted in 2022 with a multi-stakeholder group of 32 participants. Participants were trained in MCDA methodology and scored four evidence matrices (cenobamate vs. brivaracetam, vs. perampanel, vs. lacosamide and vs. eslicarbazepine acetate). Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology. RESULTS: DRE is considered a very severe condition associated with many important unmet needs, mainly with regard to the lack of more effective treatments to achieve the ultimate goal of treatment. Compared to third-generation ASMs, cenobamate is perceived to have a better efficacy profile based on improvements in responder rate and seizure freedom. Regarding safety, it is considered to have a similar profile to alternatives and a positive quality-of-life profile. Cenobamate results in lower direct medical costs (excluding pharmacological) and indirect costs. Overall, cenobamate is regarded as providing a high therapeutic impact and supported by high-quality evidence. CONCLUSIONS: Based on reflective MCDA methodology and stakeholders' experience in clinical management of epilepsy in Spain, cenobamate is perceived as a value-added option for the treatment of patients with DRE when compared with third-generation ASMs.

Eating-induced seizures: A semiological sign of the right temporal pole.

OBJECTIVE: Eating-induced seizures (EIS) are a rare form of reflex seizures. The objective of this study was to report a series of cases of EIS involving patients admitted to our epilepsy unit, and to analyze the clinical characteristics, etiology, and treatment response of this type of infrequent seizure. METHODS: We performed a single-center retrospective analysis of all consecutive patients diagnosed with epilepsy with eating-induced seizures between 2008 and 2020. RESULTS: We included eight patients (six women) with mean age 54.75 years (range: 40-79), and mean age at epilepsy onset 30.75 years (range: 9-58 years). EIS were triggered during a meal in 5/8 (at dinner 1/8, at breakfast in 1/8, and without time preference in 3/8), by a certain flavor in 1/8, by eating different textures or drinking soft drinks in 1/8, and by slicing food in 1/8. All patients suffered nonreflex seizures and 3/8 other types of reflex seizures. In 6/8 of patients, EIS originated in the right hemisphere. In 5/8, the EIS progressed to impaired awareness with oromandibular automatisms. In 6/8, the epilepsy was drug-resistant. Temporopolar encephalocele was the most frequent etiology, in 4/8. Three of the eight underwent surgical treatment, with Engel IA 1 year in 3/3. Three of the eight were treated with vagal stimulation therapy, with McHugh A 1 year in 2/3. SIGNIFICANCE: In our series, eating-induced seizures were observed in patients with focal epilepsy. It was frequently drug-resistant and started predominantly in the right hemisphere, due to temporal pole involvement in half of the patients.

Reward-based decision-making in mesial temporal lobe epilepsy patients with unilateral hippocampal sclerosis pre- and post-surgery.

BACKGROUND: Correct functioning of the reward processing system is critical for optimizing decision-making as well as preventing the development of addictions and/or neuropsychiatric symptoms such as depression, apathy, and anhedonia. Consequently, patients with mesial temporal lobe epilepsy due to unilateral hippocampal sclerosis (mTLE-UHS) represent an excellent opportunity to study the brain networks involved in this system. OBJECTIVE: The aim of the current study was to evaluate decision-making and the electrophysiological correlates of feedback processing in a sample of mTLE-UHS patients, compared to healthy controls. In addition, we assessed the impact of mesial temporal lobe surgical resection on these processes, as well as general, neuropsychological functioning. METHOD: 17 mTLE-UHS patients and 17 matched healthy controls completed: [1] a computerized version of the Game of Dice Task, [2] a Standard Iowa Gambling Task, and [3] a modified ERP version of a probabilistic gambling task coupled with multichannel electroencephalography. Neuropsychological scores were also obtained both pre- and post-surgery. RESULTS: Behavioral analyses showed a pattern of increased risk for the mTLE-UHS group in decision-making under ambiguity compared to the control group. A decrease in the amplitude of the Feedback Related Negativity (FRN), a weaker effect of valence on delta power, and a general reduction of delta and theta power in the mTLE-UHS group, as compared to the control group, were also found. The beta-gamma activity associated with the delivery of positive reward was similar in both groups. Behavioral performance and electrophysiological measures did not worsen post-surgery. CONCLUSIONS: Patients with mTLE-UHS showed impairments in decision-making under ambiguity, particularly when they had to make decisions based on the outcomes of their choices, but not in decision-making under risk. No group differences were observed in decision-making when feedbacks were random. These results might be explained by the abnormal feedback processing seen in the EEG activity of patients with mTLE-UHS, and by concomitant impairments in working memory, and memory. These impairments may be linked to the disruption of mesial temporal lobe networks. Finally, feedback processing and decision-making under ambiguity were already affected in mTLE-UHS patients pre-surgery and did not show evidence of clear worsening post-surgery.

Outcomes from a Spanish Expanded Access Program on cannabidiol treatment in pediatric and adult patients with epilepsy.

AIM: To evaluate the effectiveness and tolerability of cannabidiol (CBD) in patients with developmental and epileptic encephalopathies, including Dravet syndrome (DS), and Lennox-Gastaut syndrome (LGS), in a Spanish Expanded Access Program (EAP). METHODS: This was a multicenter, retrospective, observational study of patients treated with purified CBD in 14 hospitals across Spain. Patients with (1) written informed consent and (2) at least 6 months follow-up before the closure of the database were included. Primary effectiveness endpoints included reductions (100 %, ≥75 %, ≥50 %, ≥25 %, or 0 %) or worsening in seizure frequency (all seizure types and most disabling seizures) at 1-, 3-, 6-, and 12-month visits and at the last visit, and median relative seizure reduction between baseline and last visit. Secondary effectiveness endpoints included retention rate, reduction in seizure severity, status epilepticus, healthcare utilization, and quality of life. Primary safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation. RESULTS: One hundred and two patients (DS 12 %; LGS 59 %; other epilepsy syndromes 29 %) with a mean age of 15.9 years were enrolled. Patients were highly refractory to antiseizure medications (ASMs); mean number of prior failed ASMs was 7.5 (SD 3.7). The mean CBD dose was 13.0 mg/kg/day at the last visit. The proportion of patients with ≥50 % reduction in the total number of seizures from baseline was 44.9 % at 6 months and 38.9 % at 12 months. The median number of total seizures per month reduced by 47.6 % from baseline to the last visit. At 12 months, seizure severity was lower in 33/54 patients (61.1 %) and unchanged in 17/54 patients (31.5 %). Quality of life, based on the CAVE scale, increased from a mean score of 17.9 ± 4.7 (n = 54) at baseline to 21.7 ± 5.5 (n = 51) at the last patient visit (21.2 % improvement). The mean treatment retention time was 10.3 months. There were no statistically significant changes in the number of status epilepticus episodes, but lower healthcare utilization was observed. Adverse events occurred in sixty-eight patients (66.7 %), and the most common were somnolence (34.3 %) and diarrhea (12.7 %). Cannabidiol was discontinued exclusively due to AEs in 7.8 % of patients, increasing to 25.5 % when both lack of efficacy and AEs were considered together. CONCLUSIONS: Cannabidiol demonstrated promising effectiveness and tolerability in patients with developmental and epileptic encephalopathies taking part in a Spanish EAP.

Verbal Learning and Longitudinal Hippocampal Network Connectivity in Temporal Lobe Epilepsy Surgery.

Introduction: Learning new verbal information can be impaired in 20-40% of patients after mesial temporal lobe resection. In recent years, understanding epilepsy as a brain network disease, and investigating the relationship between large-scale resting networks and cognition has led to several advances. Aligned studies suggest that it is the integrity of the hippocampal connectivity with these large-scale networks what is relevant for cognition, with evidence showing a functional and structural heterogeneity along the long axis hippocampus bilaterally. Objective: Our aim is to examine whether pre-operative resting-state connectivity along the long hippocampal axis is associated with verbal learning decline after anterior temporal lobe resection. Methods: Thirty-one patients with epilepsy who underwent an anterior temporal lobe resection were pre-surgically scanned at 3-tesla, and pre/post-surgery evaluated for learning deficits using the Rey Auditory Verbal Learning Task (RAVLT). Eighteen controls matched by age, gender and handedness were also scanned and evaluated with the RAVLT. We studied the functional connectivity along the (anterior/posterior) long axis hippocampal subregions and resting-state functionally-defined brain networks involved in learning [executive (EXE), dorsal attention (DAN) and default-mode (DMN) networks]. Functional connectivity differences between the two groups of patients (learning intact or with learning decline) and controls were investigated with MANOVA and discriminant analysis. Results: There were significant differences in the pattern of hippocampal connectivity among the groups. Regarding the anterior connectivity hippocampal pattern, our data showed an increase of connectivity in the pathological side with the DAN (p = 0.011) and the EXE (p = 0.008) when comparing learning-decline vs. learning-intact patients. Moreover, the non-pathological side showed an increase in the anterior connectivity pattern with the DAN (p = 0.027) between learning-decline vs. learning-intact patients. In contrast, the posterior hippocampus showed a reduction of connectivity in the learning-decline patients with the DMN, both in the pathological (p = 0.004) and the non-pathological sides (p = 0.036). Finally, the discriminant analysis based on the pre-operative connectivity pattern significantly differentiated the learning-decline patients from the other groups (p = 0.019). Conclusion: Our findings reveal bilateral connectivity disruptions along the longitudinal axis of the hippocampi with resting-state networks, which could be key to identify those patients at risk of verbal learning decline after epilepsy surgery.

The contribution of fenfluramine to the treatment of Dravet syndrome in Spain through Multi-Criteria Decision Analysis.

INTRODUCTION: Dravet Syndrome (DS) is a severe, developmental epileptic encephalopathy (DEE) that begins in infancy and is characterized by pharmaco-resistant epilepsy and neurodevelopmental delay. Despite available antiseizure medications (ASMs), there is a need for new therapeutic options with greater efficacy in reducing seizure frequency and with adequate safety and tolerability profiles. Fenfluramine is a new ASM for the treatment of seizures associated with DS as add-on therapy to other ASMs for patients aged 2 years and older. Fenfluramine decreases seizure frequency, prolongs periods of seizure freedom potentially helping to reduce risk of Sudden Unexpected Death in Epilepsy (SUDEP) and improves patient cognitive abilities positively impacting on patients' Quality of Life (QoL). Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine what represents value in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders. The aim of this study was to determine the relative value contribution of fenfluramine for the treatment of DS in Spain using MCDA. METHOD: A literature review was performed to populate an adapted a MCDA framework for orphan-drug evaluation in Spain. A panel of ten Spanish experts, including neurologists, hospital pharmacists, patient representatives and decision-makers, scored four comparative evidence matrices. Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology. RESULTS: Dravet syndrome is considered a severe, rare disease with significant unmet needs. Fenfluramine is perceived to have a higher efficacy profile than all available alternatives, with a better safety profile than stiripentol and topiramate and to provide improved QoL versus studied alternatives. Fenfluramine results in lower other medical costs in comparison with stiripentol and clobazam. Participants perceived that fenfluramine could lead to indirect costs savings compared to available alternatives due to its efficacy in controlling seizures. Overall, fenfluramine's therapeutic impact on patients with DS is considered high and supported by high-quality evidence. CONCLUSIONS: Based on reflective MCDA, fenfluramine is considered to add greater benefit in terms of efficacy, safety and QoL when compared with available ASMs.

New-onset non-lesional aphasic status epilepticus. Clinical description, diagnostic clues, and treatment algorithm.

OBJECTIVES: De novo aphasic status epilepticus (ASE) in patients without a previous history of epilepsy and without cerebral lesions (aphasic NOSE) is rare. The aim of the study is to describe its clinical characteristics, etiologies, and outcome. MATERIALS & METHODS: Single-center study including consecutive patients presenting to the emergency department between 2011 and 2019 with acute aphasia, which was finally diagnosed as aphasic NOSE. Subsequent episodes of aphasia (>5 min) were recorded and divided into confirmed ASE and postictal aphasic episodes (non-ASE). Clinical characteristics of the two types of episodes were compared. RESULTS: Nineteen patients were included, suffering fifty episodes of epileptic aphasia, episodes per patient 2.6 (range 1-7). Fifteen patients (71.4%) were women, mean age at ASE onset was 66.05 years old (SD 6.3). Nine (47%) patients died, 6 of them (66.7%) during the aphasic episode. Ictal EEG was available in 37 episodes, confirming the diagnosis of ASE in 12 episodes; in 8 episodes, the EEG fulfilled the criteria of possible ASE. The most frequent etiologies were inflammatory and vascular. Comparing ASE with non-ASE episodes, ASE was longer than non-ASE (225 vs 65 h, p .024) and was treated more frequently with BZD (76 vs 24%, p .001) but with a longer delay (22.2 vs 1.5 h, p .06). CONCLUSIONS: ASE is a treatable, highly relapsing emergency, with the subsequent relapses ASE or postictal aphasia. EEG is diagnostic in half of the patients, while in others imaging techniques are also useful. Benzodiazepines should be administered. Persistent aphasia, of more than 65 hours' duration, is highly suggestive of ASE.

Mapping connectivity fingerprints for presurgical evaluation of temporal lobe epilepsy.

BACKGROUND: Surgery may render temporal lobe epilepsy (TLE) patients seizure-free. However, TLE is a heterogenous entity and surgical prognosis varies between patients. Network-based biomarkers have been shown to be altered in TLE patients and hold promise for classifying TLE subtypes and improving pre-surgical prognosis. The aim of the present study is to investigate a network-based biomarker, the weighted degree of connectivity (wDC), on an individual level, and its relation to TLE subtypes and surgical prognosis. METHODS: Thirty unilateral TLE patients undergoing the same surgical procedure (anterior temporal resection) and 18 healthy controls were included. All patients were followed-up in the same center for a mean time of 6.85 years and classified as seizure-free (SF) and non seizure-free (non-SF). Using pre-surgical resting state functional MRI, whole brain wDC values for patients and controls were calculated. Then, we divided both temporal lobes in three Regions-of-interest (ROIs) -mesial, pole and lateral- as these areas are known to behave differently in seizure onset and propagation, delimiting different TLE profiles. The wDC values for the defined ROIs of each individual patient were compared with the healthy group. RESULTS: After surgery, 14 TLE patients remained SF. As a group, patients had higher wDC than controls in both the temporal pole (p < 0.05) as well as in the mesial regions (p < 0.002) of the to-be-resected temporal lobe. When comparing between SF and non-SF patients, a step-wise binary logistic regression model including all the ROIs, showed that having an increased wDC of the temporal pole (p < 0.05) and the mesial area (p < 0.05) of the to-be-resected temporal lobe was associated with seizure freedom long-term after surgery. CONCLUSIONS: This study provides a network-based presurgical biomarker that could pave the way towards personalized prediction. In patients with TLE undergoing anterior temporal resections, having an increased wDC at rest could be a signature of the epileptogenic area, and could help identifying those patients who would benefit most from surgery.

Risk of Developing Epilepsy after Autoimmune Encephalitis.

BACKGROUND: Acute symptomatic seizures (ASS) are a common manifestation of autoimmune encephalitis (AE), but the risk of developing epilepsy as a sequela of AE remains unknown, and factors predisposing the development of epilepsy have not been fully identified. OBJECTIVE: To assess the risk of developing epilepsy in AE and study related risk factors. MATERIALS AND METHODS: This was a retrospective single centre study including patients diagnosed with AE according to criteria described by Graus et al., with a minimum follow-up of 12 months after AE resolution. The sample was divided according to whether patients developed epilepsy or not. RESULTS: A total of 19 patients were included; 3 (15.8%) had AE with intracellular antibodies, 9 (47.4%) with extracellular antibodies, and 7 (36.8%) were seronegative. During follow-up, 3 patients (15.8%) died, 4 (21.1%) presented relapses of AE, and 11 (57.89%) developed epilepsy. There was a significant association between the development of epilepsy and the presence of hippocampal atrophy in control brain magnetic resonance imaging (MRI) (p = 0.037), interictal epileptiform discharges (IED) on control electroencephalogram (EEG) (p = 0.045), and immunotherapy delay (p = 0.016). CONCLUSIONS: Hippocampal atrophy in neuroimaging, IED on EEG during follow-up, and immunotherapy delay could be predictors of the development of epilepsy in patients with AE.

Functional neuroimaging in nonepileptiform electroencephalographic patterns in status epilepticus.

BACKGROUND: The diagnosis of nonconvulsive status epilepticus (NCSE) in patients with nonepileptiform EEG patterns remains a challenge. OBJECTIVE: To evaluate the usefulness of single photon emission computerized tomography (SPECT) and its quantification (QtSPECT) in the diagnosis of NCSE. METHODS: We retrospectively reviewed patients admitted with clinical suspicion of NCSE who underwent an HMPAO-SPECT simultaneously with scalp EEG showing nonepileptiform patterns, in a 5-year period. After a complete diagnostic workup, treatment, and clinical evolution, disregarding the SPECT results, patients were classified into confirmed NCSE (n = 11) and non-NCSE (n = 8). Then, we compared the EEG and SPECT results in both groups. RESULTS: Lateralized rhythmic delta activity (LRDA) was predominant in the NCSE group (45.4%, p = .045), while lateralized irregular slowing was observed equally in both groups. Patients with NCSE showed significant hyperperfusion compared with non-NCSE patients (p = .026). QtSPECT correctly classified 91% of patients in NCSE and 75% patients with non-NCSE (p = .006). CONCLUSIONS: Regional cerebral blood flow measured with SPECT could be useful in the diagnosis of NCSE in cases of an EEG pattern with lateralized slow activity and high clinical suspicion.

Relationship between sleep quality and cognitive performance in patients with epilepsy.

PURPOSE: To investigate the relationship between self-reported sleep quality and cognitive function in patients with epilepsy (PWE), as well as anxiety and depressive symptoms and patient quality of life (QoL). METHODS: This multicenter cross-sectional study included PWE aged ≥12 years who were receiving ≥1 anti-seizure medication (ASM) and had not been diagnosed with a sleep disorder. Patients completed the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Montreal Cognitive Assessment test (MoCA), the Hospital Anxiety and Depression Scale (HADS), and the Quality of Life in Epilepsy Inventory-10 (QOLIE-10). RESULTS: The study enrolled 150 patients aged 16-83 years, mean age (standard deviation [SD]) 40.6 (15.2) years; 58.7% were female and 75.3% had focal epilepsy. Mean (SD) PSQI score was 4.71 (3.08), 44.4% of patients had impaired sleep quality (PSQI score ≥5), 19.9% had pathologic excessive daytime sleepiness (ESS score >12), and 32.7% had mild cognitive impairment (MoCA score <26). Within the PSQI, sleep disturbance (P = 0.036) and use of sleep medication (P = 0.006) scores were significantly higher in patients with mild cognitive impairment. Multiple regression analysis showed older age (regression coefficient [B], -0.086; 95% confidence interval [CI], -0.127, -0.045; P < 0.001) and the use of sleep medication component of the PSQI [B, -1.157; 95% CI, -2.064, -0.220; P = 0.013) were independently associated with lower MoCA score. Poor sleep quality was associated with probable anxiety and depression symptoms, and directly correlated with reduced QoL. CONCLUSIONS: In PWE, sleep quality was not significantly independently associated with mild cognitive impairment, although poor sleep quality had a negative effect on mood and QoL.

Brain FDG-PET findings in glutamic acid decarboxylase antibody-associated epilepsy.

BACKGROUND AND PURPOSE: Glutamic acid decarboxylase antibodies (GAD-Ab) are sometimes associated with chronic drug-resistant focal epilepsy. Clinically, it may manifest as mesial temporal lobe epilepsy (mTLE), with GAD-Ab patients difficult to distinguish. Therefore, the aim of this study is to compare brain metabolism of patients with mTLE and high serum titers of GAD-Ab (>2000 UI/ml) to those with mTLE and hippocampal sclerosis (HS) and confirmed GAD-ab negativity. METHODS: Images from PET studies were normalized to an SPM 12 template. Voxel to voxel comparisons were made using a two-sample one-tailed t-test. RESULTS: In both patients with GAD-Ab and controls (mTLE-HS), hypometabolism in mesial temporal lobe areas was observed. When comparing the two groups, GAD-Ab patients had statistically significant reduced metabolism in both insulae and medial inferior frontal-hypothalamus area (p < 0.001). CONCLUSIONS: Hypometabolism in mesial temporal lobe areas together with hypometabolism in insulae and medial inferior frontal-hypothalamus may be characteristic of patients with epilepsy and GAD-ab. This PET pattern could be a useful diagnostic tool to identify GAD-Ab patients.

Vagus nerve stimulation as a potential modulator of periictal psychotic episodes: A report of four cases.

Drug resistant epilepsy (DRE) has been associated with a high incidence of psychotic disorders. Patients can develop psychosis after starting a new antiseizure medication, after undergoing resective surgery, or after implantation of a vagus nerve stimulation (VNS) system. The aim of this study was to investigate the modulation effect of VNS on psychotic episodes in DRE patients with a pre-existing history of periictal psychotic episodes (PPE). We retrospectively report the outcome of four patients from a single tertiary center with PPE prior to implantation. None of the implanted patients developed de novo PPE after VNS therapy. Regarding seizure outcome, all patients demonstrated a response to VNS with two who experienced who status epilepticus and three patients wtih a change in semiology with after VNS implantation. PPE disappeared in all the study patients, two of them at 6 months post-implantation and in the others after 2 and 3 years, respectively. 18F-FDG-PET results showed hypermetabolism in both anterior insular and medial frontal lobes which disappeared in the 18F -FDG-PET 4 years post-implantation. Based on the results of this series of cases we suggest that VNS therapy may be useful to modulatet PPE in patients with DRE, though effectiveness may be time-dependent.

Theta rhythm supports hippocampus-dependent integrative encoding in schematic/semantic memory networks.

Integrating new information into existing schematic/semantic structures of knowledge is the basis of learning in our everyday life as it enables structured representation of information and goal-directed behaviour in an ever-changing environment. However, how schematic/semantic mnemonic structures aid the integration of novel elements remains poorly understood. Here, we showed that the ability to integrate novel picture information into learned structures of picture associations that overlapped by the same picture scene (i.e., simple network) or by a conceptually related picture scene (i.e., schematic/semantic network) is hippocampus-dependent, as patients with lesions at the medial temporal lobe (including the hippocampus) were impaired in inferring novel relations between pictures within these memory networks. We also found more persistent and widespread scalp EEG theta oscillations (3-5 Hz) while participants integrated novel pictures into schematic/semantic memory networks than into simple networks. On the other hand, greater neural similarity was observed between EEG patterns elicited by novel and related events within simple networks than between novel and related events within schematic/semantic memory networks. These findings have important implications for our understanding of the neural mechanisms that support the development and organization of structures of knowledge.

Seizures and epilepsy of autoimmune origin: A long-term prospective study.

OBJECTIVE: To follow prospectively a group of patients with seizures or epilepsy and suggestive clinical features of autoimmune aetiology and find out how many are finally diagnosed with acute symptomatic seizures (ASS) secondary to autoimmune encephalitis or autoimmune-related epilepsy, and how many develop epilepsy. METHODS: Consecutive patients meeting the inclusion criteria from 2010 to 2018 were identified. Patients were classified as confirmed, probable autoimmune, non-autoimmune, or unknown. RESULTS: One-hundred and nine patients were included, 64 (48.7 %) women, mean age 55.2 years (SD 17.9). ASS were reported by 61 patients (56 %), while 48 presented epilepsy (44 %). During follow-up 18 patients died (16.5 %). Final diagnosis was autoimmune-relatedepilepsy (confirmed + probable) in 22 cases and ASS secondary to autoimmune encephalitis (confirmed or probable) in 27, non-autoimmune aetiologies or other diagnosis in 49 (44 %), and unknown aetiology in 11 (10.2 %). Neuronal antibodies (ab) were found in 27 patients (24.7 %). T-lymphocyte infiltration in temporal lobes was observed in 2/8 patients (20 %). Neuronal ab were more frequent in the autoimmune groups: 17 patients (29.8 %) vs 1(2.3 %), p:0.001, and they suffered more autoimmune diseases: 37 (75.5 %) vs 12 (24.48 %), p:0.0001, and 34 (69 %) vs 22 (44.9 %) p:0.027, respectively. All patients with GAD ab 17/17 (100 %) evolved to chronic disease. Four patients (29 %) with ASS secondary to autoimmune encephalitis developed epilepsy. SIGNIFICANCE: ASS secondary to autoimmune encephalitis or autoimmune-related epilepsy will be diagnosed in nearly half of patients who have been suspected of it. The only diagnostic clue is neuronal ab. Patients who have suffered ASS secondary to autoimmune encephalitis may develop epilepsy over time.

Hippocampal microstructural architecture and surgical outcome: Hippocampal diffusivity could predict seizure relapse.

PURPOSE: Our aim was to study the microstructural architecture of the contralateral hippocampus to the affected side in patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and its relation with surgical outcome. METHOD: We included 33 consecutive patients evaluated in our epilepsy surgery program during a five-year period. They underwent a presurgical MRI with volumetric T1 and diffusion weighted sequences. 22 patients with TLE-HS (13 women, 12 right TLE-HS) were finally selected. Median follow-up after surgery was 6.25 years (4.5-8.83 years). We segmented the hippocampal subfields of the contralateral hippocampus using FreeSurfer and calculated the fractional anisotropy (FA) and the mean diffusivity (MD) of each subfield. We also scanned 18 healthy age-matched controls. RESULTS: After surgery, 50 % of the patients (n = 11) remained seizure-free (SF) following surgery. Comparing non-SF to SF patients, the MD showed increased values of the CA1 (p = 0.035), the molecular layer (p = 0.010) and the dentate gyrus (p = 0.041) in the healthy hippocampus. Using a cut-off point for a survival analysis, we found that patients with lower values of MD of the molecular layer and the CA1 remained SF during long-term post-operative follow-up (p < 0.0001). CONCLUSIONS: The contralateral hippocampal internal microstructure may have be implicated in post-surgery seizure freedom in patients with TLE-HS.

Autobiographical memory in epileptic patients after temporal lobe resection or bitemporal hippocampal sclerosis.

The human hippocampus is believed to be a crucial node in the neural network supporting autobiographical memory retrieval. Structural mesial temporal damage associated with temporal lobe epilepsy (TLE) provides an opportunity to systematically investigate and better understand the local and distal functional consequences of mesial temporal damage in the engagement of the autobiographical memory network. We examined 19 TLE patients (49.21 ± 11.55 years; 12 females) with unilateral mesial TLE (MTLE; 12 with anterior temporal lobe resection: 6 right MTLE, 6 left MTLE) or bilateral mesial TLE (7 BMTLE) and 18 matched healthy subjects. We used functional MRI (fMRI) with an adapted autobiographical memory paradigm and a specific neuropsychological test (Autobiographical Memory Interview, AMI). While engaged in the fMRI autobiographical memory paradigm, all groups activated a large fronto-temporo-parietal network. However, while this network was left lateralized for healthy participants and right MTLE patients, left MTLE and patients with BMTLE also showed strong activation in right temporal and frontal regions. Moreover, BMTLE and left MTLE patients also showed significant mild deficits in episodic autobiographical memory performance measured with the AMI test. The right temporal and extra-temporal fMRI activation, along with the impairment in autobiographical memory retrieval found in left MTLE and BMTLE patients suggest that alternate brain areas-other than the hippocampus-may also support this process, possibly due to neuroplastic effects.

Usefulness of HMPAO-SPECT in the diagnosis of nonconvulsive status epilepticus.

BACKGROUND: The diagnosis of nonconvulsive status epilepticus (NCSE) can pose a challenge. Electroencephalogram (EEG) patterns can be difficult to interpret, and the absence of an EEG correlate does not rule out the diagnosis of NCSE. In this setting, neuroimaging tools to help in the diagnosis are crucial. Our aim was to evaluate the role of 99mTc-hexamethyl propyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) and quantitative HMPAO-SPECT (QtSPECT) in patients with clinical suspicion of NCSE, and to evaluate their value in the final diagnosis of NCSE. METHODS: We recruited consecutive patients admitted in our center with suspicion of NCSE, and selected those who underwent an HMPAO-SPECT. All patients were admitted to the neurology ward and underwent an EEG. We divided the patients into those who were finally with diagnosed NCSE (NCSE-p) and those who were not (non-NCSE) according to the Salzburg Diagnostic EEG criteria. Sensitivity and specificity of the diagnostic tools were calculated. The SPECTs were acquired in a Skylight SPECT (Philips Healthcare, Amsterdam). The injections were done during the clinical episode suspected of being an NCSE. The HMPAO-SPECT was analyzed by two experts and was also quantified. All data were normalized to the SPM SPECT template. We used an external healthy normal database to obtain a Z-score map for each individual versus the normal database. The Z-score maximum (Zmax) was extracted from each region of the AAL atlas as was the percentage of voxels with a Z-score higher than 2.5 (N(%)). A logistic regression combining the Zmax, N(%), and the effect of patient age was fitted to predict the final NCSE diagnosis. A receiver operator characteristic (ROC) curve and the area under the curve (AUC) were obtained to evaluate the classification performance. RESULTS: We included 55 patients, 21 of them women (38.9%), with a median age of 62.1 years old (range 25-84). Thirty-six patients were with diagnosed NCSE (62.9%). Initial EEG had a sensitivity of 61.1% and a specificity of 89%. Most of the patients were critically ill with diagnostic difficulties, and it could be one of the main reasons to find low sensitivity of the Salzburg diagnostic EEG criteria. The Zmax and N(%) were significantly higher in NCSE-p than in non-NCSE (p = 0.005 and p < 0.001, respectively). The HMPAO-SPECT qualitative analysis had a sensitivity of 80.5% and specificity of 89.5% while QtSPECT had a sensitivity of 82% and specificity of 81%. CONCLUSION: Both 99mTc-HMPAO-SPECT and QtSPECT can be useful in the diagnosis of NCSE. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".