Corticospinal tract hyperintensity in patients with LGI1-antibody encephalitis and other central nervous system disorders with neuroglial antibodies.

The frequency of corticospinal tract (CST) T2/FLAIR hyperintensity in disorders with neuroglial antibodies is unclear. Herein, we retrospectively reviewed brain MRIs of 101 LGI1-antibody encephalitis patients, and observed CST hyperintensity in 30/101 (30%). It was mostly bilateral (93%), not associated with upper motor neuron signs/symptoms (7%), and frequently decreased over time (39%). In a systematic review including patients with other neuroglial antibodies, CST hyperintensity was reported in 110 with neuromyelitis optica (94%), myelin oligodendrocyte glycoprotein-associated disease (2%), Ma2-antibody (3%) and GAD65-antibody paraneoplastic neurological syndrome (1%). CST hyperintensity is not an infrequent finding in LGI1-Ab encephalitis and other disorders with neuroglial antibodies.

Comparative Study of Paraneoplastic and Nonparaneoplastic Autoimmune Encephalitis With GABABR Antibodies.

BACKGROUND AND OBJECTIVES: While patients with paraneoplastic autoimmune encephalitis (AE) with gamma-aminobutyric-acid B receptor antibodies (GABABR-AE) have poor functional outcomes and high mortality, the prognosis of nonparaneoplastic cases has not been well studied. METHODS: Patients with GABABR-AE from the French and the Dutch Paraneoplastic Neurologic Syndromes Reference Centers databases were retrospectively included and their data collected; the neurologic outcomes of paraneoplastic and nonparaneoplastic cases were compared. Immunoglobulin G (IgG) isotyping and human leukocyte antigen (HLA) genotyping were performed in patients with available samples. RESULTS: A total of 111 patients (44/111 [40%] women) were enrolled, including 84 of 111 (76%) paraneoplastic and 18 of 111 (16%) nonparaneoplastic cases (cancer status was undetermined for 9 patients). Patients presented with seizures (88/111 [79%]), cognitive impairment (54/111 [49%]), and/or behavioral disorders (34/111 [31%]), and 54 of 111 (50%) were admitted in intensive care unit (ICU). Nonparaneoplastic patients were significantly younger (median age 54 years [range 19-88] vs 67 years [range 50-85] for paraneoplastic cases, p < 0.001) and showed a different demographic distribution. Nonparaneoplastic patients more often had CSF pleocytosis (17/17 [100%] vs 58/78 [74%], p = 0.02), were almost never associated with KTCD16-abs (1/16 [6%] vs 61/70 [87%], p < 0.001), and were more frequently treated with second-line immunotherapy (11/18 [61%] vs 18/82 [22%], p = 0.003). However, no difference of IgG subclass or HLA association was observed, although sample size was small (10 and 26 patients, respectively). After treatment, neurologic outcome was favorable (mRS ≤2) for 13 of 16 (81%) nonparaneoplastic and 37 of 84 (48%) paraneoplastic cases (p = 0.03), while 3 of 18 (17%) and 42 of 83 (51%) patients had died at last follow-up (p = 0.008), respectively. Neurologic outcome no longer differed after adjustment for confounding factors but seemed to be negatively associated with increased age and ICU admission. A better survival was associated with nonparaneoplastic cases, a younger age, and the use of immunosuppressive drugs. DISCUSSION: Nonparaneoplastic GABABR-AE involved younger patients without associated KCTD16-abs and carried better neurologic and vital prognoses than paraneoplastic GABABR-AE, which might be due to a more intensive treatment strategy. A better understanding of immunologic mechanisms underlying both forms is needed.

How valid are proxy assessment of mental health and sleep comorbidities of patients with epilepsy using standardized questionnaires?

BACKGROUND: The study aimed to determine the level of agreement between patients with epilepsy and their proxies when assessing psychiatric comorbidities, sleep disorders, and medication adherence using standardized questionnaires. METHODS: This agreement study is an ancillary analysis of the PRERIES study, a matched case-control study exploring SUDEP risk factors. Controls aged 15 years and older, with active epilepsy or in remission for less than 5 years were recruited between 01/01/2011 and 03/31/2019. An interview was carried out by a trained psychologist on both the patient and a proxy-respondent. During these independent interviews, the following comorbidities were explored: psychiatric comorbidities using the MINI, the STAI- Y2 and NDDI-E scales, sleep disorders with the SDQ-SA and Epworth scales and medication adherence. Level of agreement between patient and their proxy was estimated using Gwet's AC1&2. RESULTS: Among the 107 patient-proxy dyads recruited, proxy respondents were mainly family members (65.4%) or spouses (30.8%). Exploration of present major depression showed excellent agreement at 0.81 [0.65;0.97], as well as exploration of dysthymia at 0.96 [0.61;1]. Suicidal risk evaluation had a lesser agreement at 0.77 [0.60;0.94]. Agreement on anxiety was moderate 0.5 [0.38;0.62]. For sleep disorder, SDQ-SA presented a better agreement than the Epworth questionnaire with respectively 0.73 [0.51;0.95] and 0.45 [0.26;0.63]. For medication adherence, the overall agreement rate was excellent (0.90 [0.78;1]). CONCLUSION: Exploration of potential risk factors through families can give valuable and relatively robust information, especially if the respondent lives with the patient, and should be retrieved, when possible, in usual clinical setting.

[Functional neurological disorders: A clinical anthology]. / Troubles neurologiques fonctionnels : une anthologie clinique.

Functional neurological disorders have a broad phenotypic spectrum and include different clinical syndromes, which are sometimes associated to each other or appear consecutively over the course of the disease. This clinical anthology provides details on the specific and sensitive positive signs that are to be sought in the context of a suspected functional neurological disorder. Beside these positive elements leading to the diagnosis of functional neurological disorder, we should keep in mind the possibility of an associated organic disorder as the combination of both organic and functional disorders is a relatively frequent situation in clinical practice. Here we describe the clinical characteristics of different functional neurological syndromes: motor deficits, abnormal hyperkinetic and hypokinetic movements, voice or speech disorders, sensory disorders, and functional dissociative seizures. The clinical examination and the identification of positive signs play a critical role in the diagnosis of functional neurological disorder. Knowledge of the specific signs associated with each phenotype render possible to make an early diagnosis. For that matter, it contributes to the improvement of patient care management. It allows to a better engagement in an appropriate care pathway, which influence their prognosis. Highlighting and discussing positive signs with patients can also be an interesting step in the process of explaining the disease and its management.

Intracerebral Correlates of Scalp EEG Ictal Discharges Based on Simultaneous Stereo-EEG Recordings.

BACKGROUND AND OBJECTIVES: It remains unknown to what extent ictal scalp EEG can accurately predict the localization of the intracerebral seizure onset in presurgical evaluation of drug-resistant epilepsies. In this study, we aimed to define homogeneous ictal scalp EEG profiles (based on their first ictal abnormality) and assess their localizing value using simultaneously recorded scalp EEG and stereo-EEG. METHODS: We retrospectively included consecutive patients with drug-resistant focal epilepsy who had simultaneous stereo-EEG and scalp EEG recordings of at least 1 seizure in the epileptology unit in Nancy, France. We analyzed 1 seizure per patient and used hierarchical cluster analysis to group similar seizure profiles on scalp EEG and then performed a descriptive analysis of their intracerebral correlates. RESULTS: We enrolled 129 patients in this study. The hierarchical cluster analysis showed 6 profiles on scalp EEG first modification. None were specific to a single intracerebral localization. The "normal EEG" and "blurred EEG" clusters (early muscle artifacts) comprised only 5 patients each and corresponded to no preferential intracerebral localization. The "temporal discharge" cluster (n = 46) was characterized by theta or delta discharges on ipsilateral anterior temporal scalp electrodes and corresponded to a preferential mesial temporal intracerebral localization. The "posterior discharge" cluster (n = 42) was characterized by posterior ipsilateral or contralateral rhythmic alpha discharges or slow waves on scalp and corresponded to a preferential temporal localization. However, this profile was the statistically most frequent scalp EEG correlate of occipital and parietal seizures. The "diffuse suppression" cluster (n = 9) was characterized by a bilateral and diffuse background activity suppression on scalp and corresponded to mesial, and particularly insulo-opercular, localization. Finally, the "frontal discharge" cluster (n = 22) was characterized by bilateral frontal rhythmic fast activity or preictal spike on scalp and corresponded to preferential ventrodorsal frontal intracerebral localizations. DISCUSSION: The hierarchical cluster analysis identified 6 seizure profiles regarding the first abnormality on scalp EEG. None of them were specific of a single intracerebral localization. Nevertheless, the strong relationships between the "temporal," "frontal," "diffuse suppression," and "posterior" profiles and intracerebral discharge localizations may contribute to hierarchize hypotheses derived from ictal scalp EEG analysis regarding intracerebral seizure onset.

Metabolic connectivity is associated with seizure outcome in surgically treated temporal lobe epilepsies: A 18F-FDG PET seed correlation analysis.

18F-FDG PET provides high sensitivity for the pre-surgical assessment of drug-resistant temporal lobe epilepsy (TLE). However, little is known about the metabolic connectivity of epileptogenic networks involved. This study therefore aimed to evaluate the association between metabolic connectivity and seizure outcome in surgically treated TLE. METHODS: The study included 107 right-handed patients that had undergone a presurgical interictal 18F-FDG PET assessment followed by an anterior temporal lobectomy and were classified according to seizure outcome 2 years after surgery. Metabolic connectivity was evaluated by seed correlation analysis in left and right epilepsy patients with a Class Engel IA or > IA outcome and compared to age-, sex- and handedness-matched healthy controls. RESULTS: Increased metabolic connectivity was observed in the >IA compared to the IA group within the operated temporal lobe (respective clusters of 7.5 vs 3.3 cm3 and 2.6 cm3 vs 2.2 cm3 in left and right TLE), and to a lower extent with the contralateral temporal lobe (1.2 vs 0.7 cm3 and 1.7 cm3 vs 0.7 cm3 in left and right TLE). Seed correlations provided added value for the estimated individual performance of seizure outcome over the group comparisons in left TLE (AUC of 0.74 vs 0.67). CONCLUSION: Metabolic connectivity is associated with outcome in surgically treated TLE with a strengthened epileptogenic connectome in patients with non-free-seizure outcomes. The added value of seed correlation analysis in left TLE underlines the importance of evaluating metabolic connectivity in network related diseases.

Case Report: Atonic PNES Capture in fMRI.

Psychogenic Non-Epileptic Seizures (PNES) are a misunderstood and disabling pathology, characterized by a paroxysmal occurrence of clinical signs without the epileptic activity. Resting-state functional MRI (fMRI) studies in patients with PNES have shown abnormal functional connectivity of the resting-state networks, especially in the limbic and motor systems, and in the precuneus. However, the transient nature of PNES episodes prevents us from elucidating the underlying mechanisms of seizures. Here, we report the case of a patient who presented an atonic episode of PNES during a 3T fMRI session. The patient is a 23-year-old woman, suffering from post-traumatic stress disorder, with no neurological comorbidities. The preprocessing of the fMRI images involved realignment, co-registration, segmentation, normalization, denoising (PhysIO toolbox), and smoothing. The time boundary of the seizure was defined according to the patient's reports, and the seizure period was contrasted with the resting state period before the seizure. A whole-brain analysis showed significant activations (left inferior temporal gyrus, left temporo-occipital junction) and deactivations (right precuneus, right superior parietal lobule, right postcentral gyrus, bilateral lingual gyri, inferior occipital gyri, and cerebellar lobules; right insula in a sub-thresholded analysis). Activations and deactivations occurred in four cerebral networks: emotional processing, agency, self-perception, and dissociation. To our knowledge, this report is the first published case of functional MRI during PNES. These results could confirm the emotional and dissociative hypothesis of the physiopathology of PNES and highlight future targets for neuromodulation.

Functional MRI-based study of emotional experience in patients with psychogenic non-epileptic seizures: Protocol for an observational case-control study-EMOCRISES study.

BACKGROUND: Psychogenic non epileptic seizures (PNES) are a frequent, disabling and costly disorder for which there is no consensual caring. They are considered as a dissociative disorder and they share many common characteristics with post-traumatic stress disorder (PTSD). Nevertheless, their pathophysiology is still unclear. In this study, we plan to obtain new data comparing functional brain activity of participants suffering from PNES, from PTSD and healthy controls via functional brain MRI during resting state and under emotional visual stimulation. The protocol presented hereunder describes an observational study with no direct treatment implication. Nevertheless, it could lead to a better understanding of PNES and to identifying targets for specialised cares of post-traumatic or dissociative disorders, like repetitive transcranial magnetic stimulation. METHODS & ANALYSIS: This is a prospective, single-centre, interventional, non-randomized, open, controlled and exploratory clinical study. It will involve 75 adult French, right-handed women in 3 groups, either suffering from PNES or PTSD, or healthy controls. An informed consent will be signed by each participant. All of them will be given psychiatric tests to assess dissociation and alexithymia, psychopathological profile and history, and emotional recognition. Each participant will undergo a functional brain MRI. We will record anatomical images and five functional imaging sequences including emotional periodic oscillatory stimulation, standard emotional stimulation, Go / No Go task under emotional stimulation, and resting state. Analysis will include a descriptive analysis of all participants and the treatment for functional magnetic resonance imaging images of each sequence. REGISTRATION, ETHICS & DISSEMINATION: This study was approved the regional Protection of Persons Committee under the reference 16.10.01 and by the French National Medical Security Agency under the reference 2016-A01295-46. The protocol and results will be published in peer-reviewed academic medical journals and disseminated to research teams, databases, specialised media and concerned patients' organisations.

Transcranial Electrical Stimulation generates electric fields in deep human brain structures.

BACKGROUND: Transcranial electrical stimulation (TES) efficiency is related to the electric field (EF) magnitude delivered on the target. Very few studies (n = 4) have estimated the in-vivo intracerebral electric fields in humans. They have relied mainly on electrocorticographic recordings, which require a craniotomy impacting EF distribution, and did not investigate deep brain structures. OBJECTIVE: To measure the electric field in deep brain structures during TES in humans in-vivo. Additionally, to investigate the effects of TES frequencies, intensities, and montages on the intracerebral EF. METHODS: Simultaneous bipolar transcranial alternating current stimulation and intracerebral recordings (SEEG) were performed in 8 drug-resistant epileptic patients. TES was applied using small high-definition (HD) electrodes. Seven frequencies, two intensities and 15 montages were applied on one, six and one patients, respectively. RESULTS: At 1 mA intensity, we found mean EF magnitudes of 0.21, 0.17 and 0.07 V·m-1 in the amygdala, hippocampus, and cingulate gyrus, respectively. An average of 0.14 ± 0.07 V·m-1 was measured in these deep brain structures. Mean EF magnitudes in these structures at 1Hz were 11% higher than at 300Hz (+0.03 V·m-1). The EF was correlated with the TES intensities. The TES montages that yielded the maximum EF in the amygdalae were T7-T8 and in the cingulate gyri were C3-FT10 and T7-C4. CONCLUSION: TES at low intensities and with small HD electrodes can generate an EF in deep brain structures, irrespective of stimulation frequency. EF magnitude is correlated to the stimulation intensity and depends upon the stimulation montage.

Epilepsy in Early Onset Alzheimer's Disease.

BACKGROUND: Epilepsy seems to be an important comorbidity in patients with early onset Alzheimer's disease (EOAD). Currently, seizures are still underestimated in this population. However, seizures may interact with AD evolution with possible acceleration of cognitive decline. OBJECTIVE: To better define the epileptic disorders observed in patients with EOAD. METHODS: All patients diagnosed as EOAD in our hospital between 2013 and 2019 with positive CSF biomarkers for AD were selected. The usual follow-up was extended with a 3-h EEG and a consultation with an epilepsy expert. Information on epilepsy and AD were collected and analyzed. RESULTS: Among the 25 included patients, 10 (40%) were classified as epileptic. Seizure types were tonic-clonic (25%), typical temporal seizures (25%), myoclonus (25%), focal extra-temporal seizures (8%), and other seizure types (17%). AD-E patients had a significant lower MMSE (15.3±8.4 AD-E versus 22.1±5.1 AD-NE, p = 0.036) and a lower autonomy (IADL 4.1±2.7 AD-E versus 6.4±1.9 AD-NE, p = 0.046) at AD diagnosis with comparable ages between AD-E and AD-NE. Epileptic patients seemed to present a faster cognitive decline ([ΔMMSE per year 1.7±1.3 AD-E versus 0.9±1.4 AD-NE; p = 0.09). All patients with severe cognitive impairment (MMSE ≤ 10) had an epileptic comorbidity. CONCLUSION: Epilepsy is a frequent comorbidity in EOAD patients, with a percentage of 40%in our study. This comorbidity may be associated with a severe form of EOAD. The role of epilepsy in the acceleration of cognitive decline and the positive impact of antiepileptic drugs on cognition need further research.

Tutor-Student Partnership in Practice OSCE to Enhance Medical Education.

BACKGROUND: Training of examiners is essential to ensure the quality of objective structured clinical examination (OSCE). We aimed to study a perceived effectiveness of tutor-student partnership in a practice OSCE module by novice OSCE tutors and medical students. METHOD: We implemented a practice OSCE at a medical faculty in France with novice tutors and third year medical students as partners. Each tutor (n = 44) served as a partner for the group of 5 students in the conception of the scenario and as an evaluator of the tutored station. Students (n = 303) were involved in the conception of a case and the roles of a physician, evaluator and a simulated patient. Data were obtained through self-assessment questionnaires. Descriptive statistics were used to analyze items of the questionnaires. Free-form answers were coded and analyzed thematically. RESULTS: A total of 36 tutors (82%) and 185 students (61%) responded to the questionnaires. The intervention was well perceived. Thirty-two percent of the tutors reported some difficulties in the assessment of student performance and were disposed to receive further training. Fifty-five percent of the students considered the participation in the OSCE case development appropriate to their level of knowledge, and 70% perceived it as beneficial allowing them to set their learning goals. CONCLUSION: This initiative provides a relevant method beneficial to OSCE tutors, medical students, and the faculty. Tutors learn how to assess student performance according to expected achievement levels. It allows students to be engaged as partners in co-creation of learning and teaching. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01421-9.

Past Trauma Is Associated With a Higher Risk of Experiencing an Epileptic Seizure as Traumatic in Patients With Pharmacoresistant Focal Epilepsy.

Objective: The present study aimed to evaluate the prevalence of traumatic experienced seizures (TES) and of postepileptic seizure PTSD (PS-PTSD) in patients with pharmacoresistant focal epilepsy and to explore the determining factors of TES. Methods: We conducted an observational study enrolling 107 adult refractory epilepsy patients. We used the DSM-5 criteria of traumatic events and PTSD to define TES and PS-PTSD. We assessed all traumatic life events unrelated to epilepsy, general and specific psychiatric comorbidities, and quality of life. Results: Nearly half (n = 48) of the 107 participants reported at least one TES (44.85%). Among these, one-third (n = 16) developed PS-PTSD. The TES group was more likely to experience traumatic events unrelated to epilepsy (p < 0.001), to have generalized anxiety disorder (p = 0.019), and to have specific psychiatric comorbidities [e.g., interictal dysphoric disorder (p = 0.024) or anticipatory anxiety of seizures (p = 0.005)]. They reported a severe impact of epilepsy on their life (p = 0.01). The determining factors of TES according to the multifactorial model were the experience of trauma (p = 0.008), a history of at least one psychiatric disorder (p = 0.03), and a strong tendency toward dissociation (p = 0.03). Significance: Epileptic seizures may be a traumatic experience in some patients who suffer from pharmacoresistant epilepsy and may be the source of the development of PS-PTSD. Previous trauma unrelated to epilepsy and psychiatric history are determining factors of TES. These clinical entities should be explored systematically.

Brain 18F-FDG PET for the diagnosis of autoimmune encephalitis: a systematic review and a meta-analysis.

OBJECTIVE: To consolidate current understanding of detection sensitivity of brain 18F-FDG PET scans in the diagnosis of autoimmune encephalitis and to define specific metabolic imaging patterns for the most frequently occurring autoantibodies. METHODS: A systematic and exhaustive search of data available in the literature was performed by querying the PubMed/MEDLINE and Cochrane databases for the search terms: ((PET) OR (positron emission tomography)) AND ((FDG) OR (fluorodeoxyglucose)) AND ((encephalitis) OR (brain inflammation)). Studies had to satisfy the following criteria: (i) include at least ten pediatric or adult patients suspected or diagnosed with autoimmune encephalitis according to the current recommendations, (ii) specifically present 18F-FDG PET and/or morphologic imaging findings. The diagnostic 18F-FDG PET detection sensitivity in autoimmune encephalitis was determined for all cases reported in this systematic review, according to a meta-analysis following the PRISMA method, and selected publication quality was assessed with the QUADAS-2 tool. RESULTS: The search strategy identified 626 articles including references from publications. The detection sensitivity of 18F-FDG PET was 87% (80-92%) based on 21 publications and 444 patients included in the meta-analysis. We also report specific brain 18F-FDG PET imaging patterns for the main encephalitis autoantibody subtypes. CONCLUSION AND RELEVANCE: Brain 18F-FDG PET has a high detection sensitivity and should be included in future diagnostic autoimmune encephalitis recommendations. Specific metabolic 18F-FDG PET patterns corresponding to the main autoimmune encephalitis autoantibody subtypes further enhance the value of this diagnostic.

Stereoelectroencephalographic language mapping of the basal temporal cortex predicts postoperative naming outcome.

OBJECTIVE: In drug-resistant temporal lobe epilepsy (TLE) patients, the authors evaluated early and late outcomes for decline in visual object naming after dominant temporal lobe resection (TLR) according to the resection status of the basal temporal language area (BTLA) identified by cortical stimulation during stereoelectroencephalography (SEEG). METHODS: Twenty patients who underwent SEEG for drug-resistant TLE met the inclusion criteria. During language mapping, a site was considered positive when stimulation of two contiguous contacts elicited at least one naming impairment during two remote sessions. After TLR ipsilateral to their BTLA, patients were classified as BTLA+ when at least one positive language site was resected and as BTLA- when all positive language sites were preserved. Outcomes in naming and verbal fluency tests were assessed using pre- and postoperative (means of 7 and 25 months after surgery) scores at the group level and reliable change indices (RCIs) for clinically meaningful changes at the individual level. RESULTS: BTLA+ patients (n = 7) had significantly worse naming scores than BTLA- patients (n = 13) within 1 year after surgery but not at the long-term evaluation. No difference in verbal fluency tests was observed. When RCIs were used, 5 of 18 patients (28%) had naming decline within 1 year postoperatively (corresponding to 57% of BTLA+ and 9% of BTLA- patients). A significant correlation was found between BTLA resection and naming decline. CONCLUSIONS: BTLA resection is associated with a specific and early naming decline. Even if this decline is transient, naming scores in BTLA+ patients tend to remain lower compared to their baseline. SEEG mapping helps to predict postoperative language outcome after dominant TLR.

Recurrent seizures of autoimmune origin: emerging phenotypes.

OBJECTIVE: Recurrent seizures of autoimmune origin (AEp) are one of the most frequent causes of recurrent seizures or suspected epilepsy of unknown cause. The aim of this study was to identify specific phenotypes corresponding to AEp. METHODS: We retrospectively reviewed features of patients with recurrent seizures of unknown cause and investigated for suspected AEp (January 2015-May 2018). Patients were separated in: (1) AEpAb+: AEp with positive autoantibodies; (2) AEpAb-: suspected AEp (inflammatory central nervous system (CNS) profile) without autoantibodies; (3) NAEp: epilepsy without CNS inflammation. RESULTS: Eighty-nine epileptic patients underwent a CSF antibody detection. From the remaining 57 epileptic patients (32 excluded for a differential diagnosis), 61.4% were considered as AEp. 21% were AEpAb+ (4 NMDAR, 2 GABAbR, 3 GAD-Ab, 2 LGi1, 1 CASPR2), 40.4% AEpAb-, and 38.6% NAE. AE (AEpAb+ and AEpAb-) was significantly associated with antibody prevalence in epilepsy (APE) score ≥ 4 (80%), encephalitic phase (71.4%), psychiatric involvement (64.7%), cognitive impairment (50%), and status epilepticus (41.2%). Within the group of 29 patients without encephalitic phase and with chronic epilepsy (NEPp), 34.5% were defined as AEp. 10.4% were AEpAb+ (2 GAD, 1 CASPR2) and 24.1% were AEpAb-. NEP AEp was associated with non-cerebral autoimmune disorders, short epileptic disease duration, and cognitive impairment. CONCLUSIONS: Autoimmune cause (AEp) should be assessed in patient suffering from recurrent seizures of unknown cause. Acute encephalitis is clearly the main AEp phenotype. AEp was also defined in more than one-third of chronic epilepsy patients (NEP) of unknown cause. Then, AEp may be combined with other autoimmune comorbidities, a shorter evolution of recurrent seizures, and cognitive impairment.

Anticipatory anxiety of epileptic seizures: An overlooked dimension linked to trauma history.

OBJECTIVE: Fear of having a seizure called anticipatory anxiety of epileptic seizure (AAS), constitutes a daily life burden but has been rarely studied. Our aim was to assess the prevalence and the determining factors of AAS in patients with drug-resistant focal epilepsy, a dimension that has not been thoroughly investigated before. METHODS: We conducted an observational, prospective study enrolling patients with drug-resistant focal epilepsy. The psychiatric assessment aimed to evaluate psychiatric comorbidities, trauma history, and quality of life using hetero-evaluation and self-assessment tools. Dimensions of anxiety specifically related to epilepsy (peri-and-inter-ictal) were explored as exhaustively as possible. RESULTS: AAS was found in 53 % of the 87 patients. We compared the two groups of patients: with or without AAS. Patients with AAS had a significantly shorter duration of epilepsy (p = 0.04). There was no difference between groups with respect to psychiatric disorders, except for cannabis dependence, more frequent in patients with AAS (p = 0.02). Compared to patients without AAS, those with AAS presented more subjective ictal anxiety (p = 0.0003) and postictal anxiety (p = 0.02), were more likely to avoid outdoor social situations due to seizure fear (p = 0.001), and had a poorer quality of life (QOLIE emotional well-being; p = 0.03). Additionally, they had experienced more traumatic events in their lifetime (p = 0.005) and reported more frequently a feeling of being unsafe during their seizures (p = 0.00002). SIGNIFICANCE: AAS is a specific dimension of anxiety, possibly linked to trauma history. AAS is strongly linked to subjective ictal anxiety but not to the objective severity of seizures or frequency.

Expanding the clinical spectrum of STIP1 homology and U-box containing protein 1-associated ataxia.

BACKGROUND: STUB1 has been first associated with autosomal recessive (SCAR16, MIM# 615768) and later with dominant forms of ataxia (SCA48, MIM# 618093). Pathogenic variations in STUB1 are now considered a frequent cause of cerebellar ataxia. OBJECTIVE: We aimed to improve the clinical, radiological, and molecular delineation of SCAR16 and SCA48. METHODS: Retrospective collection of patients with SCAR16 or SCA48 diagnosed in three French genetic centers (Montpellier, Strasbourg and Nancy). RESULTS: Here, we report four SCAR16 and nine SCA48 patients from two SCAR16 and five SCA48 unrelated French families. All presented with slowly progressive cerebellar ataxia. Additional findings included cognitive decline, dystonia, parkinsonism and swallowing difficulties. The age at onset was highly variable, ranging from 14 to 76 years. Brain MRI showed marked cerebellar atrophy in all patients. Phenotypic findings associated with STUB1 pathogenic variations cover a broad spectrum, ranging from isolated slowly progressive ataxia to severe encephalopathy, and include extrapyramidal features. We described five new pathogenic variations, two previously reported pathogenic variations, and two rare variants of unknown significance in association with STUB1-related disorders. We also report the first pathogenic variation associated with both dominant and recessive forms of inheritance (SCAR16 and SCA48). CONCLUSION: Even though differences are observed between the recessive and dominant forms, it appears that a continuum exists between these two entities. While adding new symptoms associated with STUB1 pathogenic variations, we insist on the difficulty of genetic counselling in STUB1-related pathologies. Finally, we underscore the usefulness of DAT-scan as an additional clue for diagnosis.

Short-term risk of relapse after a first unprovoked seizure in an adult population.

OBJECTIVE: To evaluate the incidence of short-term recurrence (<1 month) after a first unprovoked seizure (FUS) and the associated risk factors. METHODS: This is a prospective monocentric one-year observational study on all consecutive adult patients admitted to the Emergency Department (ED) and diagnosed as FUS. Patients underwent neurological consultation at one and three months after the FUS. Demographic information, clinical examination and seizure features, seizure recurrence at 1 and 3 months, electroencephalogram (EEG), brain imaging, precipitating factors, seizure type, and prescribed antiepileptic drugs (AED) were prospectively collected. RESULTS: Among 140 patients diagnosed as FUS, 109 patients attended the neurological consultation at 1 month. FUS diagnosis was confirmed in 80/109 cases. Nine patients (11.2%) had seizure recurrence before the consultation at 1 month. Identified specific risk factors of short-term recurrence were focal seizure (P=0.015) and abnormal EEG in the first 48hours (P=0.048). In the group of patients followed for three months (38 patients), the risk of seizure relapse was 15.7%. CONCLUSION: Most patients with FUS diagnosed in the ED did not present seizure recurrence within the first month, especially if no specific risk factors were present (focal seizure, abnormal EEG within first 48hours). The systematic use of prophylactic AED (benzodiazepines) is not recommended in the ED in the clinical setting of FUS. A specialized consultation within a one-month period is safe and adequate for FUS follow-up.