Evidence based noninvasive presurgical evaluation for patients with drug resistant epilepsies.

PURPOSE OF REVIEW: To review the current practices and evidence for the diagnostic accuracy and the benefits of presurgical evaluation. RECENT FINDINGS: Preoperative evaluation of patients with drug-resistant focal epilepsies and subsequent epilepsy surgery leads to a significant proportion of seizure-free patients. Even those who are not completely seizure free postoperatively often experience improved quality of life with better social integration. Systematic reviews and meta-analysis on the diagnostic accuracy are available for Video-electroencephalographic (EEG) monitoring, magnetic resonance imaging (MRI), electric and magnetic source imaging, and functional MRI for lateralization of language and memory. There are currently no evidence-based international guidelines for presurgical evaluation and epilepsy surgery. SUMMARY: Presurgical evaluation is a complex multidisciplinary and multiprofessional clinical pathway. We rely on limited consensus-based recommendations regarding the required staffing or methodological expertise in epilepsy centers.

Iatrogenic cerebral amyloid angiopathy: A multinational case series and individual patient data analysis of the literature.

BACKGROUND: The transmission of amyloid ß (Aß) in humans leading to iatrogenic cerebral amyloid angiopathy (iCAA) is a novel concept with analogies to prion diseases. However, the number of published cases is low, and larger international studies are missing. AIMS: We aimed to build a large multinational collaboration on iCAA to better understand the clinical spectrum of affected patients. METHODS: We collected clinical data on patients with iCAA from Austria, Croatia, Italy, Slovenia, and Spain. Patients were included if they met the proposed Queen Square diagnostic criteria (QSC) for iCAA. In addition, we pooled data on disease onset, latency, and cerebrospinal fluid (CSF) biomarkers from previously published iCAA cases based on a systematic literature review. RESULTS: Twenty-seven patients (22% women) were included in this study. Of these, 19 (70%) met the criteria for probable and 8 (30%) for possible iCAA. Prior neurosurgical procedures were performed in all patients (93% brain surgery, 7% spinal surgery) at median age of 8 (interquartile range (IQR) = 4-18, range = 0-26 years) years. The median symptom latency was 39 years (IQR = 34-41, range = 28-49). The median age at symptom onset was 49 years (IQR = 43-55, range = 32-70). Twenty-one patients (78%) presented with intracranial hemorrhage and 3 (11%) with seizures. CONCLUSIONS: Our large international case series of patients with iCAA confirms a wide age boundary for the diagnosis of iCAA. Dissemination of awareness of this rare condition will help to identify more affected patients.

Network topology in brain tumor patients with and without structural epilepsy: a prospective MEG study.

Background: It was proposed that network topology is altered in brain tumor patients. However, there is no consensus on the pattern of these changes and evidence on potential drivers is lacking. Objectives: We aimed to characterize neurooncological patients' network topology by analyzing glial brain tumors (GBTs) and brain metastases (BMs) with respect to the presence of structural epilepsy. Methods: Network topology derived from resting state magnetoencephalography was compared between (1) patients and controls, (2) GBTs and BMs, and (3) patients with (PSEs) and without structural epilepsy (PNSEs). Eligible patients were investigated from February 2019 to March 2021. We calculated whole brain (WB) connectivity in six frequency bands, network topological parameters (node degree, average shortest path length, local clustering coefficient) and performed a stratification, where differences in power were identified. For data analysis, we used Fieldtrip, Brain Connectivity MATLAB toolboxes, and in-house built scripts. Results: We included 41 patients (21 men), with a mean age of 60.1 years (range 23-82), of those were: GBTs (n = 23), BMs (n = 14), and other histologies (n = 4). Statistical analysis revealed a significantly decreased WB node degree in patients versus controls in every frequency range at the corrected level (p1-30Hz = 0.002, pγ = 0.002, pß = 0.002, pα = 0.002, pθ = 0.024, and pδ = 0.002). At the descriptive level, we found a significant augmentation for WB local clustering coefficient (p1-30Hz = 0.031, pδ = 0.013) in patients compared to controls, which did not persist the false discovery rate correction. No differences regarding networks of GBTs compared to BMs were identified. However, we found a significant increase in WB local clustering coefficient (pθ = 0.048) and decrease in WB node degree (pα = 0.039) in PSEs versus PNSEs at the uncorrected level. Conclusion: Our data suggest that network topology is altered in brain tumor patients. Histology per se might not, however, tumor-related epilepsy seems to influence the brain's functional network. Longitudinal studies and analysis of possible confounders are required to substantiate these findings.

A superficial siderosis-related transient focal neurological episode in a patient with Marfan syndrome.

Sagittal computed tomography of lumbal spine showing dural ectasia and Tarlow Cyst (red arrows) (A). Magnetic resonance imaging (MRI) axial slice, susceptibility-weighted imaging (SWI) sequences showing siderosis in cerebellar sulci (red arrows) and in the inset uncharacteristic iron deposition in dental nuclei, more pronounced on the left side (red arrows) (B, inset). MRI, SWI, axial slice, showing numerous foci of superficial siderosis (C).

Immunomodulatory Aspects of Therapeutic Plasma Exchange in Neurological Disorders-A Pilot Study.

Therapeutic plasma exchange (TPE) is used for drug-resistant neuroimmunological disorders, but its mechanism of action remains poorly understood. We therefore prospectively explored changes in soluble, humoral, and cellular immune components associated with TPE. We included ten patients with neurological autoimmune disorders that underwent TPE and assessed a panel of clinically relevant pathogen-specific antibodies, total serum immunoglobulin (Ig) levels, interleukin-6 (IL-6, pg/mL), C-reactive protein (CRP, mg/dL), procalcitonin (PCT, µg/L) and major lymphocyte subpopulations (cells/µL). Blood was collected prior to TPE (pre-TPE, baseline), immediately after TPE (post-TPE), as well as five weeks (follow-up1) and 130 days (follow-up2) following TPE. Pathogen-specific antibody levels were reduced by -86% (p < 0.05) post-TPE and recovered to 55% (follow-up1) and 101% (follow-up2). Ig subclasses were reduced by -70-89% (p < 0.0001) post-TPE with subsequent complete (IgM/IgA) and incomplete (IgG) recovery throughout the follow-ups. Mean IL-6 and CRP concentrations increased by a factor of 3-4 at post-TPE (p > 0.05) while PCT remained unaffected. We found no alterations in B- and T-cell populations. No adverse events related to TPE occurred. TPE induced a profound but transient reduction in circulating antibodies, while the investigated soluble immune components were not washed out. Future studies should explore the effects of TPE on particular cytokines and assess inflammatory lymphocyte lineages to illuminate the mode of action of TPE beyond autoantibody removal.

Perampanel in Brain Tumor-Related Epilepsy: A Systematic Review.

Brain tumor-related epilepsy (BTRE) is a common comorbidity in patients with brain neoplasms and it may be either the first symptom or develop after the tumor diagnosis. Increasing evidence suggests that brain tumors and BTRE share common pathophysiological mechanisms. Glutamatergic mechanisms can play a central role in promoting both primary brain tumor growth and epileptogenesis. Perampanel (PER), which acts as a selective antagonist of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, may play a role both in the reduction in tumor growth and the control of epileptiform activity. This systematic review aimed to summarize the pre-clinical and clinical evidence about the antitumor properties, antiseizure effects and tolerability of PER in BTRE. Eight pre-clinical and eight clinical studies were identified. The currently available evidence suggests that PER can be an effective and generally well-tolerated therapeutic option in patients with BTRE. In vitro studies demonstrated promising antitumor activity of PER, while no role in slowing tumor progression has been demonstrated in rat models; clinical data on the potential antitumor activity of PER are scarce. Additional studies are needed to explore further the effects of PER on tumor progression and fully characterize its potentialities in patients with BTRE.

Physicians' beliefs about brain surgery for drug-resistant epilepsy: A global survey.

PURPOSE: To investigate the opinions of physicians about brain surgery for drug-resistant epilepsy worldwide. METHODS: Practicing neurologists, psychiatrists, and neurosurgeons from around the world were invited to participate in an online survey. The survey anonymously collected data about demographics, years in clinical practice, discipline, nation, work setting, and answers to the questions about beliefs and attitudes about brain surgery for drug-resistant epilepsy. RESULTS: In total, 1410 physicians from 20 countries and different world regions participated. The propensity to discuss brain surgery with patients, who have drug-resistant seizures, was higher among men (versus women) [Odds Ratio (OR) 1.67, 95% CI 1.20-2.31; p = 0.002]. In comparison to neurologists, psychiatrists were less likely (OR 0.28, 95% CI 0.17-0.47; p < 0.001) and neurosurgeons were more likely (OR 2.00, 95% CI 1.08-3.72; p = 0.028) to discuss about it. Survey participants working in Africa, Asia, the Middle East, and the Former Union of Soviet Socialist Republics showed a lower propensity to discuss epilepsy surgery with patients. CONCLUSION: This study showed that on an international level, there is still a knowledge gap concerning epilepsy surgery and much needs to be done to identify and overcome barriers to epilepsy surgery for patients with drug-resistant seizures worldwide.

Allergy-induced systemic inflammation impairs tendon quality.

BACKGROUND: Treatment of degenerating tendons still presents a major challenge, since the aetiology of tendinopathies remains poorly understood. Besides mechanical overuse, further known predisposing factors include rheumatoid arthritis, diabetes, obesity or smoking all of which combine with a systemic inflammation. METHODS: To determine whether the systemic inflammation accompanying these conditions contributes to the onset of tendinopathy, we studied the effect of a systemic inflammation induced by an allergic episode on tendon properties. To this end, we induced an allergic response in mice by exposing them to a timothy grass pollen allergen and subsequently analysed both their flexor and Achilles tendons. Additionally, we analysed data from a health survey comprising data from more than 10.000 persons for an association between the occurrence of an allergy and tendinopathy. FINDINGS: Biomechanical testing and histological analysis revealed that tendons from allergic mice not only showed a significant reduction of both elastic modulus and tensile stress, but also alterations of the tendon matrix. Moreover, treatment of 3D tendon-like constructs with sera from allergic mice resulted in a matrix-remodelling expression profile and the expression of macrophage-associated markers and matrix metalloproteinase 2 (MMP2) was increased in allergic Achilles tendons. Data from the human health study revealed that persons suffering from an allergy have an increased propensity to develop a tendinopathy. INTERPRETATION: Our study demonstrates that the presence of a systemic inflammation accompanying an allergic condition negatively impacts on tendon structure and function. FUNDING: This study was financially supported by the Fund for the Advancement of Scientific Research at Paracelsus Medical University (PMU-FFF E-15/22/115-LEK), by the Land Salzburg, the Salzburger Landeskliniken (SALK, the Health Care Provider of the University Hospitals Landeskrankenhaus and Christian Doppler Klinik), the Paracelsus Medical University, Salzburg and by unrestricted grants from Bayer, AstraZeneca, Sanofi-Aventis, Boehringer-Ingelheim.

Diagnostic value of MRI in the presurgical evaluation of patients with epilepsy: influence of field strength and sequence selection: a systematic review and meta-analysis from the E-PILEPSY Consortium.

MRI is a cornerstone in presurgical evaluation of epilepsy. Despite guidelines, clinical practice varies. In light of the E-PILEPSY pilot reference network, we conducted a systematic review and meta-analysis on the diagnostic value of MRI in the presurgical evaluation of epilepsy patients. We included original research articles on diagnostic value of higher MRI field strength and guideline-recommended and additional MRI sequences in detecting an epileptogenic lesion in adult or paediatric epilepsy surgery candidates. Lesion detection rate was used as a metric in meta-analysis. Eighteen studies were included for MRI field strength and 25 for MRI sequences, none were free from bias. In patients with normal MRI at lower-field strength, 3T improved lesion detection rate by 18% and 7T by 23%. Field strengths higher than 1.5T did not have higher lesion detection rates in patients with hippocampal sclerosis (HS). The lesion detection rate of epilepsy-specific MRI protocols was 83% for temporal lobe epilepsy (TLE) patients. Dedicated MRI protocols and evaluation by an experienced epilepsy neuroradiologist increased lesion detection. For HS, 3DT1, T2, and FLAIR each had a lesion detection rate at around 90%. Apparent diffusion coefficient indices had a lateralizing value of 33% for TLE. DTI fractional anisotropy and mean diffusivity had a localizing value of 8% and 34%. A dedicated MRI protocol and expert evaluation benefits lesion detection rate in epilepsy surgery candidates. If patients remain MRI negative, imaging at higher-field strength may reveal lesions. In HS, apparent diffusion coefficient indices may aid lateralization and localization more than increasing field strength. DTI can add further diagnostic information. For other additional sequences, the quality and number of studies is insufficient to draw solid conclusions. Our findings may be used as evidence base for developing new high-quality MRI studies and clinical guidelines.

Development and Validation of the 5-SENSE Score to Predict Focality of the Seizure-Onset Zone as Assessed by Stereoelectroencephalography.

Importance: Stereoelectroencephalography (SEEG) has become the criterion standard in case of inconclusive noninvasive presurgical epilepsy workup. However, up to 40% of patients are subsequently not offered surgery because the seizure-onset zone is less focal than expected or cannot be identified. Objective: To predict focality of the seizure-onset zone in SEEG, the 5-point 5-SENSE score was developed and validated. Design, Setting, and Participants: This was a monocentric cohort study for score development followed by multicenter validation with patient selection intervals between February 2002 to October 2018 and May 2002 to December 2019. The minimum follow-up period was 1 year. Patients with drug-resistant epilepsy undergoing SEEG at the Montreal Neurological Institute were analyzed to identify a focal seizure-onset zone. Selection criteria were 2 or more seizures in electroencephalography and availability of complete neuropsychological and neuroimaging data sets. For validation, patients from 9 epilepsy centers meeting these criteria were included. Analysis took place between May and July 2021. Main Outcomes and Measures: Based on SEEG, patients were grouped as focal and nonfocal seizure-onset zone. Demographic, clinical, electroencephalography, neuroimaging, and neuropsychology data were analyzed, and a multiple logistic regression model for developing a score to predict SEEG focality was created and validated in an independent sample. Results: A total of 128 patients (57 women [44.5%]; median [range] age, 31 [13-58] years) were analyzed for score development and 207 patients (97 women [46.9%]; median [range] age, 32 [16-70] years) were analyzed for validation. The score comprised the following 5 predictive variables: focal lesion on structural magnetic resonance imaging, absence of bilateral independent spikes in scalp electroencephalography, localizing neuropsychological deficit, strongly localizing semiology, and regional ictal scalp electroencephalography onset. The 5-SENSE score had an optimal mean (SD) probability cutoff for identifying a focal seizure-onset zone of 37.6 (3.5). Area under the curve, specificity, and sensitivity were 0.83, 76.3% (95% CI, 66.7-85.8), and 83.3% (95% CI, 72.30-94.1), respectively. Validation showed 76.0% (95% CI, 67.5-84.0) specificity and 52.3% (95% CI, 43.0-61.5) sensitivity. Conclusions and Relevance: High specificity in score development and validation confirms that the 5-SENSE score predicts patients where SEEG is unlikely to identify a focal seizure-onset zone. It is a simple and useful tool for assisting clinicians to reduce unnecessary invasive diagnostic burden on patients and overutilization of limited health care resources.

Unraveling the enigma of new-onset refractory status epilepticus: a systematic review of aetiologies.

BACKGROUND AND PURPOSE: New-onset refractory status epilepticus (NORSE) is a clinical presentation, neither a specific diagnosis nor a clinical entity. It refers to a patient without active epilepsy or other pre-existing relevant neurological disorder, with a NORSE without a clear acute or active structural, toxic or metabolic cause. This study reviews the currently available evidence about the aetiology of patients presenting with NORSE and NORSE-related conditions. METHODS: A systematic search was carried out for clinical trials, observational studies, case series and case reports including patients who presented with NORSE, febrile-infection-related epilepsy syndrome or the infantile hemiconvulsion-hemiplegia and epilepsy syndrome. RESULTS: Four hundred and fifty records were initially identified, of which 197 were included in the review. The selected studies were retrospective case-control (n = 11), case series (n = 83) and case reports (n = 103) and overall described 1334 patients both of paediatric and adult age. Aetiology remains unexplained in about half of the cases, representing the so-called 'cryptogenic NORSE'. Amongst adult patients without cryptogenic NORSE, the most often identified cause is autoimmune encephalitis, either non-paraneoplastic or paraneoplastic. Infections are the prevalent aetiology of paediatric non-cryptogenic NORSE. Genetic and congenital disorders can have a causative role in NORSE, and toxic, vascular and degenerative conditions have also been described. CONCLUSIONS: Far from being a unitary condition, NORSE is a heterogeneous and clinically challenging presentation. The development and dissemination of protocols and guidelines to standardize diagnostic work-up and guide therapeutic approaches should be implemented. Global cooperation and multicentre research represent priorities to improve the understanding of NORSE.

Update on treatment strategies for vasculitis affecting the central nervous system.

Vasculitis affecting the nervous system is a rare disease that can not only present with nonspecific initial symptoms, but also run a severe course without accurate treatment. Although improvements have been achieved, diagnosis of vasculitis remains challenging, because many classification criteria are unspecific or inconclusive with regard to central nervous system (CNS) manifestations. Currently, beside an isolated primary CNS vasculitis, several systemic types of vasculitis are known to affect the nervous system. In this review, we provide an overview of the pathophysiology, current therapeutic guidelines, and highlight novel treatment strategies for CNS vasculitis.

The CXCL13/CXCR5-chemokine axis in neuroinflammation: evidence of CXCR5+CD4 T cell recruitment to CSF.

BACKGROUND: C-X-C chemokine ligand 13 (CXCL13) is frequently elevated in cerebrospinal fluid (CSF) in a variety of inflammatory central nervous system (CNS) diseases, has been detected in meningeal B cell aggregates in brain tissues of multiple sclerosis patients, and proposedly recruits B cells into the inflamed CNS. Besides B cells also follicular helper T (Tfh) cells express the cognate receptor C-X-C chemokine receptor type 5 (CXCR5) and follow CXCL13 gradients in lymphoid tissues. These highly specialized B cell helper T cells are indispensable for B cell responses to infection and vaccination and involved in autoimmune diseases. Phenotypically and functionally related circulating CXCR5+CD4 T cells occur in blood. Their co-recruitment to the inflamed CSF is feasible but unresolved. METHODS: We approached this question with a retrospective study including data of all patients between 2017 and 2019 of whom immune phenotyping data of CXCR5 expression and CSF CXCL13 concentrations were available. Discharge diagnoses and CSF laboratory parameters were retrieved from records. Patients were categorized as pyogenic/aseptic meningoencephalitis (ME, n = 29), neuroimmunological diseases (NIMM, n = 22), and non-inflammatory neurological diseases (NIND, n = 6). ANOVA models and Spearman's Rank-Order correlation were used for group comparisons and associations of CXCL13 levels with immune phenotyping data. RESULTS: In fact, intrathecal CXCL13 elevations strongly correlated with CXCR5+CD4 T cell frequencies in the total cohort (p < 0.0001, r = 0.59), and ME (p = 0.003, r = 0.54) and NIMM (p = 0.043, r = 0.44) patients. Moreover, the ratio of CSF-to-peripheral blood (CSF/PB) frequencies of CXCR5+CD4 T cells strongly correlated with CXCL13 levels both in the total cohort (p = 0.001, r = 0.45) and ME subgroup (p = 0.005, r = 0.50), indicating selective accumulation. ME, NIMM and NIND groups differed with regard to CSF cell counts, albumin quotient, intrathecal IgG, CXCL13 elevations and CXCR5+CD4 T cells, which were higher in inflammatory subgroups. CONCLUSION: The observed link between intrathecal CXCL13 elevations and CXCR5+CD4 T cell frequencies does not prove but suggests recruitment of possible professional B cell helpers to the inflamed CSF. This highlights CSF CXCR5+CD4 T cells a key target and potential missing link to the poorly understood phenomenon of intrathecal B cell and antibody responses with relevance for infection control, chronic inflammation and CNS autoimmunity.

Epileptic aphasia - A critical appraisal.

INTRODUCTION: Aphasic and other language disturbances occur in patients with epilepsy during and after epileptic seizures. Moreover, the interictal language profile in these patients is heterogeneous, varying from normal language profile to impairment in different language functions. The aim of this paper was to critically review the terms and concepts of ictal language alterations. MATERIAL AND METHOD: For this review we performed an extensive literature search on the term "epileptic aphasia" and analyzed the semiology and terminology indicating language-associated seizure symptoms. In addition, we give an overview on EEG, etiology, and brain imaging findings and ictal language disorders. RESULTS: In the literature, a plethora of terms indicates language-associated seizure symptoms. Simultaneous Video-EEG monitoring represents the gold standard to correctly classify ictal versus postictal language disturbances and to differentiate aphasic symptoms from speech automatisms. Different rhythmic and periodic EEG patterns associated with ictal language disturbances are recognized. Cerebral magnetic resonance imaging (cMRI) is essential in the diagnosis of seizures and epilepsy. Brain tumors and acute or remote cerebrovascular lesions are the most frequently reported structural etiologies underlying ictal language alterations. However, it has to be recognized that brain imaging may show alterations being the consequence of seizures itself rather than its cause. Functional brain imaging might be informative in patients with inconclusive EEG and MRI findings. Overall, seizure-associated aphasia is reported to have good lateralizing significance. CONCLUSION: Various language disturbances are caused by different types of seizures, epilepsies and underlying etiologies. In the clinical context, simultaneous Video-EEG monitoring facilitates precise classification of ictal versus postictal language alterations and differentiation of aphasic symptoms from speech automatisms.

[Epilepsy in the aged : Challenges in diagnostics and treatment]. / Altersepilepsie : Herausforderungen in Diagnostik und Therapie.

Epilepsy is the third most frequent neurological disorder in aged patients after stroke and dementia. The incidence of epilepsy increases with age with the highest rates in patients ≥ 65 years old. Due to demographic changes the number of aged patients with epilepsy is expected to increase further in the coming years. The leading cause of new onset epilepsy in aged patients is cerebrovascular disease followed by dementia. The recognition of seizures in aged patients is often delayed. Status epilepticus occurs more frequently in aged patients and is associated with a high mortality and morbidity. Antiepileptic drug (AED) treatment of aged patients is complicated by comorbidities and polypharmacy and AEDs with a low interaction profile and high tolerability should be selected. Levetiracetam and lamotrigine are the AEDs of choice due to low interactions and good tolerability.

VarioGuide® frameless neuronavigation-guided stereoelectroencephalography in adult epilepsy patients: technique, accuracy and clinical experience.

BACKGROUND: Stereoelectroencephalography (SEEG) allows the identification of deep-seated seizure foci and determination of the epileptogenic zone (EZ) in drug-resistant epilepsy (DRE) patients. We evaluated the accuracy and treatment-associated morbidity of frameless VarioGuide® (VG) neuronavigation-guided depth electrode (DE) implantations. METHODS: We retrospectively identified all consecutive adult DRE patients, who underwent VG-neuronavigation DE implantations, between March 2013 and April 2019. Clinical data were extracted from the electronic patient charts. An interdisciplinary team agreed upon all treatment decisions. We performed trajectory planning with iPlan® Cranial software and DE implantations with the VG system. Each electrode's accuracy was assessed at the entry (EP), the centre (CP) and the target point (TP). We conducted correlation analyses to identify factors associated with accuracy. RESULTS: The study population comprised 17 patients (10 women) with a median age of 32.0 years (range 21.0-54.0). In total, 220 DEs (median length 49.3 mm, range 25.1-93.8) were implanted in 21 SEEG procedures (range 3-16 DEs/surgery). Adequate signals for postoperative SEEG were detected for all but one implanted DEs (99.5%); in 15/17 (88.2%) patients, the EZ was identified and 8/17 (47.1%) eventually underwent focus resection. The mean deviations were 3.2 ± 2.4 mm for EP, 3.0 ± 2.2 mm for CP and 2.7 ± 2.0 mm for TP. One patient suffered from postoperative SEEG-associated morbidity (i.e. conservatively treated delayed bacterial meningitis). No mortality or new neurological deficits were recorded. CONCLUSIONS: The accuracy of VG-SEEG proved sufficient to identify EZ in DRE patients and associated with a good risk-profile. It is a viable and safe alternative to frame-based or robotic systems.

Emotional Recognition in Patients With Mesial Temporal Epilepsy Associated With Enlarged Amygdala.

BACKGROUND: Amygdalae play a central role in emotional processing by interconnecting frontal cortex and other brain structures. Unilateral amygdala enlargement (AE) is associated with mesial temporal lobe epilepsy (mTLE). In a relatively large sample of patients with mTLE and AE, we aimed to evaluate functional integration of AE in emotion processing and to determine possible associations between fMRI activation patterns in amygdala and deficits in emotion recognition as assessed by neuropsychological testing. METHODS: Twenty-two patients with drug resistant unilateral mTLE due to ipsilateral AE were prospectively recruited in a large epilepsy unit and compared with 17 healthy control subjects in terms of amygdala volume, fMRI activation patterns and performance in emotion recognition as assessed by comprehensive affect testing system (CATS) and Ekman faces. All patients underwent structural and functional 1.5 Tesla MRI, electro-clinical assessment and neuropsychological testing. RESULTS: We observed BOLD signal ipsilateral to AE (n = 7; group PAT1); contralateral to AE (n = 6; group PAT2) and no activation (n = 9; group PAT3). In the region of interest (ROI) analysis, beta estimates for fearful face > landscape contrast in the left amygdala region did not differ significantly in patients with left TLE vs. patients with right TLE [T (16) = -1.481; p = 0.158]. However, beta estimates for fearful face > landscape contrast in the right amygdala region were significantly reduced in patients with right TLE vs. patients with left TLE [T (16) = -2,922; p = 0.010]. Patients showed significantly lower total scores in CATS and Ekman faces compared to healthy controls. CONCLUSION: In our cohort, patients with unilateral mesial TLE and ipsilateral AE, an amygdala could display either functional integration in emotion recognition or dysfunction as demonstrated by fMRI. Perception and recognition of emotions were impaired more in right-sided mTLE as compared to left-sided mTLE. Neuropsychological tests showed deficits in emotion recognition in patients as compared to healthy controls.

Epileptic seizures of suspected autoimmune origin: a multicentre retrospective study.

OBJECTIVE: To analyse autoantibody status in a well-defined European multicentre cohort of patients with epilepsy of unknown aetiology and to validate the recently proposed Antibody Prevalence in Epilepsy (APE2) and Response to ImmunoTherapy in Epilepsy (RITE2) scores. METHODS: We retrospectively collected clinical and paraclinical data of 92 patients referred to the Neurology Units of Verona and Salzburg between January 2014 and July 2019 with new-onset epilepsy, status epilepticus or chronic epilepsy of unknown aetiology. Fixed and live cell-based assays, tissue-based assays, immunoblot, and live rat hippocampal cell cultures were performed in paired serum/cerebrospinal fluid (CSF) to detect antineuronal and antiglial antibodies. The APE2 and RITE2 scores were then calculated and compared with clinical and laboratory data. RESULTS: Autoantibodies were detected in 29/92 patients (31.5%), with multiple positivity observed in 6/29 cases. The APE2 score (median 5, range 1-15) significantly correlated with antibody positivity (p=0.014), especially for the presence of neuropsychiatric symptoms (p<0.01), movement disorders (p<0.01), dysautonomia (p=0.03), faciobrachial dyskinesias (p=0.03) and cancer history (p<0.01). Status epilepticus was significantly more frequent in antibody-negative patients (p<0.01). Among the items of the RITE2 score, early initiation of immunotherapy correlated with a good treatment response (p=0.001), whereas a cancer history was significantly more common among non-responders (p<0.01). Persistence of neuropsychiatric symptoms and seizures correlated with antiepileptic maintenance after at least 1 year. CONCLUSIONS: This is the first study that independently validates the APE2 and RITE2 scores and includes the largest cohort of patients whose paired serum and CSF samples have been tested for autoantibodies possibly associated with autoimmune epilepsy.