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Different surgical approaches have been described for selective amygdalohippocampectomy in patients with pharmacoresistant temporal lobe epilepsy. The aim of this study was to report the results of the innovative anterior trans-superior temporal gyrus approach in a single-center series. Patients' characteristics, postoperative outcomes, and complications were reviewed in a series of 8 consecutive patients with temporal lobe epilepsy operated on using the anterior trans-superior temporal gyrus approach between November 2015 and April 2017. Over a mean 2.5-year follow-up, 7 of 8 patients (87.5%) remained seizure-free (Engel class I). Only 1 patient (12.5%) was not cured (Engel class III) with no clear explanation for treatment failure. Mean operative time was 237 minutes, which was 80 minutes shorter compared with the classic transsylvian approach. No perioperative deaths were recorded and there were no visual field defects or visual acuity impairments secondary to the approach. One patient experienced a left posterior thalamocapsular stroke. The anterior trans-superior temporal gyrus approach is feasible, fast, and safe for selective amygdalohippocampectomy in patients with drug-refractory temporal lobe epilepsy. This approach allows preservation of the optic radiation but cuts part of the uncinate fasciculus and potentially the anterior aspect of the anterior bundle of the middle longitudinal fasciculus.

Liver disease, occurring during pediatric or adult age, is often of undetermined cause. Some cases are probably related to undiagnosed inherited metabolic disorders. Hepatic disorders associated with fructose-1,6-bisphosphatase deficiency, a gluconeogenesis defect, are not reported in the literature. These symptoms are mainly described during acute crises, and many reports do not mention them because hypoglycemia and hyperlactatemia are more frequently in the forefront. Herein, the liver manifestations of 18 patients affected with fructose-1,6-bisphosphatase deficiency are described and the corresponding literature is reviewed. Interestingly, all 18 patients had liver abnormalities either during follow-up (hepatomegaly [n = 8/18], elevation of transaminases [n = 6/15], bright liver [n = 7/11]) or during acute crises (hepatomegaly [n = 10/17], elevation of transaminases [n = 13/16], acute liver failure [n = 6/14], bright liver [n = 4/14]). Initial reports described cases of liver steatosis, when liver biopsy was necessary to confirm the diagnosis by an enzymatic study. There is no clear pathophysiological basis for this fatty liver disease but we postulate that endoplasmic reticulum stress and de novo lipogenesis activation could be key factors, as observed in FBP1 knockout mice. Liver steatosis may expose patients to severe long-term liver complications. As hypoglycemia becomes less frequent with age, most adult patients are no longer monitored by hepatologist. Signs of fructose-1,6-bisphosphatase deficiency may be subtle and can be missed in childhood. We suggest that fructose-1,6-bisphosphatase deficiency should be considered as an etiology of hepatic steatosis, and a liver monitoring protocol should be set up for these patients, during lifelong follow-up.

Although seizures in neonates are common and often due to acute brain injury, 10-15% are unprovoked from congenital brain malformations. A better understanding of the risk of neonatal-onset epilepsy by the type of brain malformation is essential for counseling and monitoring. In this retrospective cohort study, we evaluated 132 neonates with congenital brain malformations and their risk of neonatal-onset epilepsy. Malformations were classified into one of five categories based on imaging patterns on prenatal or postnatal imaging. Infants were monitored with continuous video EEG (cEEG) for encephalopathy and paroxysmal events in addition to abnormal neuroimaging. Seventy-four of 132 (56%) neonates underwent EEG monitoring, and 18 of 132 (14%) were diagnosed with neonatal-onset epilepsy. The highest prevalence of epilepsy was in neonates with disorders of neuronal migration/organization (9/34, 26%; 95% confidence interval [CI] = 13-44%), followed by disorders of early prosencephalic development (6/38, 16%; 95% CI = 6-31%), complex total brain malformations (2/16, 13%; 95% CI = 2-38%), and disorders of midbrain/hindbrain malformations (1/30, 3%; 95% CI = 0-17%). Of neonates with epilepsy, 5 of 18 (28%) had only electrographic seizures, 13 of 18 (72%) required treatment with two or more antiseizure medicines (ASMs), and 7 of 18 (39%) died within the neonatal period. Our results demonstrate that disorders of neuronal migration/organization represent the highest-risk group for early-onset epilepsy. Seizures are frequently electrographic only, require treatment with multiple ASMs, and portend a high mortality rate. These results support American Clinical Neurophysiology Society recommendations for EEG monitoring during the neonatal period for infants with congenital brain malformations.

The role of neuroinflammation in epileptogenesis is extensively investigated, but short-term effects of seizures on established CNS pathologies are less studied and less predictable. We describe the case of a woman with previous recurrent episodes of focal cerebral haemorrhage of unknown cause who developed a pseudo-tumoural oedema triggered by provoked focal status epilepticus. A brain biopsy revealed that the underlying condition was primary angiitis of the CNS. Ictal-induced blood-brain barrier dysfunction allows the entry of water and inflammatory molecules that, in the context of CNS inflammatory diseases, may trigger a self-reinforcing process. Caution should be observed when tapering antiepileptic drugs in patients with such conditions.

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Visuospatial impairments have long been reported in Severe Alcohol Use Disorder but remain poorly understood, notably regarding the involvement of magnocellular (MC) and parvocellular (PC) pathways. This empirical gap hampers the understanding of the implications of these visual changes, especially since the MC and PC pathways are thought to sustain central bottom-up and top-down processes during cognitive processing. They thus influ- ence our ability to efficiently monitor our environment and make the most effective decisions. To overcome this limitation, we measured PC-inferred spatial and MC-inferred temporal resolution in 35 individuals with SAUD and 30 healthy controls. We used Landolt circles displaying small apertures outside the sensitivity range of MC cells or flickering at a temporal frequency exceeding PC sensitivity. We found evidence of preserved PC spatial resolution combined with impaired MC temporal resolution in SAUD. We also measured how spatial and tem- poral sensitivity is influenced by the prior presentation of fearful faces – as emotional content could favor MC processing over PC one – but found no evidence of emotional modulation in either group. This spatio-temporal dissociation implies that individuals with SAUD may process visual details efficiently but perceive rapidly updating visual information at a slower pace. This deficit has implications for the tracking of rapidly changing stimuli in experimental tasks, but also for the decoding of crucial everyday visual incentives such as faces, whose micro-expressions vary continuously. Future studies should further specify the visual profile of individuals with SAUD to incorporate disparate findings within a theoretically grounded model of vision.

Visuo-perceptive deficits in severe alcohol use disorder (SAUD) remain little understood, notably regarding the respective involvement of the two main human visual streams, i.e., magnocellular (MC) and parvocellular (PC) pathways, in these deficits. Besides, in healthy populations, low-level visual perception can adapt depending on the nature of visual cues, among which emotional features, but this MC and PC pathway adaptation to emotional content is unexplored in SAUD. To assess MC and PC functioning as well as their emotional modulations in SAUD. We used sensitivity indices (d') and repeated-measures analyses of variance to compare orientation judgments of Gabor patches sampled at various MC- and PC-related spatial frequencies in 35 individuals with SAUD and 38 matched healthy controls. We then explored how emotional content modulated performances by introducing neutral or fearful face cues immediately before the Gabor patches and added the type of cue in the analyses. SAUD patients showed a general reduction in sensitivity across all spatial frequencies, indicating impoverished processing of both coarse and fine-scale visual content. However, we observed selective impairments depending on facial cues: individuals with SAUD processed intermediate spatial frequencies less efficiently than healthy controls following neutral faces, whereas group differences emerged for the highest spatial frequencies following fearful faces. Altogether, SAUD was associated with mixed MC and PC deficits that may vary according to emotional content, in line with a flexible but suboptimal use of low-level visual content. Such subtle alterations could have implications for everyday life's complex visual judgments.

Hemorrhage in the basal ganglia resulting to lenticulostriate artery aneurysm rupture is extremely rare. This distal micro-aneurysm of the perforating lenticulostriate arteries is called Charcot-Bouchard aneurysm. We wish to report a case of an hematoma in the basal ganglia due to a Charcot-Bouchard aneurysm demonstrated by Computed Tomography Angiograpy (CTA) and Magnetic Resonance Angiography (MRA) and confirmed by selective catheter angiography. Charcot-Bouchard aneurysm is a very rare distal micro-aneurysm of the perforating lenticulostriate arteries. Young patients who experience basal ganglia hemorrhage should have contrast-enhanced CT, especially if they don't have arterial hypertension and if subarachnoid hemorrhage is associated.

Consistent data highlight the presence and clinical significance of social cognition impairments in severe alcohol use disorder (SAUD). However, social perception and knowledge (i.e., the ability to interpret social situations and to identify latent social rules), an important social cognition component, has not yet been explored in this disorder. 35 patients with SAUD and 35 healthy controls (HC) completed the Social Perception and Knowledge test (PerSo), an experimental task requiring participants to comprehensively describe social situations and to identify the social rules illustrated in 8 pictures. We performed group and single-case analyses. Patients with SAUD, as a group, spontaneously identified less relevant "where"/"who"/"what" aspects of the social situations (social perception) than HC. They were however able to provide these elements when explicitly asked to. They were also less able to identify the social rules that subtended the situations (social knowledge). Single-case analyses revealed that 23 % of patients were significantly impaired for social perception, and 34 % for social knowledge. We provide novel evidence that SAUD is associated with social perception and knowledge impairments at the group level, and that these impairments strongly vary across patients. Such results should lead to the integration of social perception and knowledge impairments in the conceptualization and treatment of socio-affective difficulties in SAUD.

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Electroconvulsive therapy (ECT) is a highly effective treatment for depression but how it achieves its clinical effects remains unclear. We set out to study the brain's response to ECT from a large-scale brain-network perspective. Using a voxelwise analysis, we looked at resting-state functional connectivity before and after a course of ECT at the whole-brain and the between- and within-network levels in 17 patients with a depressive episode. Using a group-independent component analysis approach, we focused on four networks known to be affected in depression: the salience network (SN), the default mode network (DMN), the cognitive executive network (CEN), and a subcortical network (SCN). Our clinical measures included mood, cognition, and psychomotor symptoms. We found ECT to have increased the connectivity of the left CEN with the left angular gyrus and left middle frontal gyrus as well as its within-network connectivity. Both the right CEN and the SCN showed increased connectivity with the precuneus and the anterior DMN with the left amygdala. Finally, improvement of psychomotor retardation was positively correlated with an increase of within-posterior DMN connectivity. The limitations of our study include its small sample size and the lack of a control dataset to confirm our findings. Our voxelwise data demonstrate that ECT induces a significant increase of connectivity across the whole brain and at the within-network level. Furthermore, we provide the first evidence on the association between an increase of within-posterior DMN connectivity and an improvement of psychomotor retardation, a core symptom of depression.

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To guide health care professionals in Belgium in selecting the appropriate antiepileptic drugs (AEDs) for their epilepsy patients, a group of Belgian epilepsy experts developed recommendations for AED treatment in adults and children (initial recommendations in 2008, updated in 2012). As new drugs have become available, others have been withdrawn, new indications have been approved and recommendations for pregnant women have changed, a new update was pertinent. A group of Belgian epilepsy experts (partly overlapping with the group in charge of the 2008/2012 recommendations) evaluated the most recent international guidelines and relevant literature for their applicability to the Belgian situation (registration status, reimbursement, clinical practice) and updated the recommendations for initial monotherapy in adults and children and add-on treatment in adults. Recommendations for add-on treatment in children were also included (not covered in the 2008/2012 publications). Like the 2008/2012 publications, the current update also covers other important aspects related to the management of epilepsy, including the importance of early referral in drug-resistant epilepsy, pharmacokinetic properties and tolerability of AEDs, comorbidities, specific considerations in elderly and pregnant patients, generic substitution and the rapidly evolving field of precision medicine.

Central nervous system adverse effects of cytarabine treatment include aseptic meningitis, myelopathy, and more rarely, encephalopathy, seizures, and cerebellar dysfunction. This case illustrates a cytarabine-induced encephalitis with predominant cerebellar involvement.

Purines are essential molecules that are components of vital biomolecules, such as nucleic acids, coenzymes, signaling molecules, as well as energy transfer molecules. The de novo biosynthesis pathway starts from phosphoribosylpyrophosphate (PRPP) and eventually leads to the synthesis of inosine monophosphate (IMP) by means of 10 sequential steps catalyzed by six different enzymes, three of which are bi-or tri-functional in nature. IMP is then converted into guanosine monophosphate (GMP) or adenosine monophosphate (AMP), which are further phosphorylated into nucleoside di- or tri-phosphates, such as GDP, GTP, ADP and ATP. This review provides an overview of inborn errors of metabolism pertaining to purine synthesis in humans, including either phosphoribosylpyrophosphate synthetase (PRS) overactivity or deficiency, as well as adenylosuccinate lyase (ADSL), 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC), phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), and adenylosuccinate synthetase (ADSS) deficiencies. ITPase deficiency is being described as well. The clinical spectrum of these disorders is broad, including neurological impairment, such as psychomotor retardation, epilepsy, hypotonia, or microcephaly; sensory involvement, such as deafness and visual disturbances; multiple malformations, as well as muscle presentations or consequences of hyperuricemia, such as gouty arthritis or kidney stones. Clinical signs are often nonspecific and, thus, overlooked. It is to be hoped that this is likely to be gradually overcome by using sensitive biochemical investigations and next-generation sequencing technologies.

Primary microcephaly (PM) is defined as a significant reduction in occipitofrontal circumference (OFC) of prenatal onset. Clinical and genetic heterogeneity of PM represents a diagnostic challenge. We performed detailed phenotypic and genomic analyses in a large cohort (n = 169) of patients referred for PM and could establish a molecular diagnosis in 38 patients. Pathogenic variants in ASPM and WDR62 were the most frequent causes in non-consanguineous patients in our cohort. In consanguineous patients, microarray and targeted gene panel analyses reached a diagnostic yield of 67%, which contrasts with a much lower rate in non-consanguineous patients (9%). Our series includes 11 novel pathogenic variants and we identify novel candidate genes including IGF2BP3 and DNAH2. We confirm the progression of microcephaly over time in affected children. Epilepsy was an important associated feature in our PM cohort, affecting 34% of patients with a molecular confirmation of the PM diagnosis, with various degrees of severity and seizure types. Our findings will help to prioritize genomic investigations, accelerate molecular diagnoses, and improve the management of PM patients.

Contrast-enhanced FLAIR images have unsurpassed value for the radiological depiction of hypertensive papilledema. FLAIR acquisition should therefore be performed after intravenous contrast, especially in the of work-up of intracranial hypertension and/or tumor.

Optimizing patient safety and quality improvement is increasingly important in surgery. Benchmarks and clinical quality registries are being developed to assess the best achievable results for several surgical procedures and reduce unwarranted variation between different centers. However, there is no clinical database from international centers for establishing standardized reference values of patients undergoing surgery for mesial temporal lobe epilepsy. The Enhancing Safety in Epilepsy Surgery (EASINESS) study is a retrospectively conducted, multicenter, open registry. All patients undergoing mesial temporal lobe epilepsy surgery in participating centers between January 2015 and December 2019 are included in this study. The patient characteristics, preoperative diagnostic tools, surgical data, postoperative complications, and long-term seizure outcomes are recorded. The collected data will be used for establishing standardized reference values ("benchmarks") for this type of surgical procedure. The primary endpoints include seizure outcomes according to the International League Against Epilepsy (ILAE) classification and defined postoperative complications. The EASINESS will define robust and standardized outcome references after amygdalohippocampectomy for temporal lobe epilepsy. After the successful definition of benchmarks from an international cohort of renowned centers, these data will serve as reference values for the evaluation of novel surgical techniques and comparisons among centers for future clinical trials. This study is indexed at clinicaltrials.gov (NT 04952298).

Seizures are the most common neurological emergency in the neonatal period and in contrast to those in infancy and childhood, are often provoked seizures with an acute cause and may be electrographic-only. Hence, neonatal seizures may not fit easily into classification schemes for seizures and epilepsies primarily developed for older children and adults. A Neonatal Seizures Task Force was established by the International League Against Epilepsy (ILAE) to develop a modification of the 2017 ILAE Classification of Seizures and Epilepsies, relevant to neonates. The neonatal classification framework emphasizes the role of electroencephalography (EEG) in the diagnosis of seizures in the neonate and includes a classification of seizure types relevant to this age group. The seizure type is determined by the predominant clinical feature. Many neonatal seizures are electrographic-only with no evident clinical features; therefore, these are included in the proposed classification. Clinical events without an EEG correlate are not included. Because seizures in the neonatal period have been shown to have a focal onset, a division into focal and generalized is unnecessary. Seizures can have a motor (automatisms, clonic, epileptic spasms, myoclonic, tonic), non-motor (autonomic, behavior arrest), or sequential presentation. The classification allows the user to choose the level of detail when classifying seizures in this age group.

OBJECTIVE: We aimed to delineate the phenotypic spectrum and long-term outcome of individuals with KCNB1 encephalopathy. METHODS: We collected genetic, clinical, electroencephalographic, and imaging data of individuals with KCNB1 pathogenic variants recruited through an international collaboration, with the support of the family association "KCNB1 France." Patients were classified as having developmental and epileptic encephalopathy (DEE) or developmental encephalopathy (DE). In addition, we reviewed published cases and provided the long-term outcome in patients older than 12 years from our series and from literature. RESULTS: Our series included 36 patients (21 males, median age = 10 years, range = 1.6 months-34 years). Twenty patients (56%) had DEE with infantile onset seizures (seizure onset = 10 months, range = 10 days-3.5 years), whereas 16 (33%) had DE with late onset epilepsy in 10 (seizure onset = 5 years, range = 18 months-25 years) and without epilepsy in six. Cognitive impairment was more severe in individuals with DEE compared to those with DE. Analysis of 73 individuals with KCNB1 pathogenic variants (36 from our series and 37 published individuals in nine reports) showed developmental delay in all with severe to profound intellectual disability in 67% (n = 41/61) and autistic features in 56% (n = 32/57). Long-term outcome in 22 individuals older than 12 years (14 in our series and eight published individuals) showed poor cognitive, psychiatric, and behavioral outcome. Epilepsy course was variable. Missense variants were associated with more frequent and more severe epilepsy compared to truncating variants. SIGNIFICANCE: Our study describes the phenotypic spectrum of KCNB1 encephalopathy, which varies from severe DEE to DE with or without epilepsy. Although cognitive impairment is worse in patients with DEE, long-term outcome is poor for most and missense variants are associated with more severe epilepsy outcome. Further understanding of disease mechani

Early diagnosis of Alzheimer's disease (with the announcement of the diagnosis). The number of patients consulting to find out if they have Alzheimer's disease continues to grow. Reasons to consult most often include anxiety about being affected by this disease, confidence in medical and therapeutic advances relayed in the media and the desire to plan for the future, taking into account a possible deterioration. Advances in the knowledge of the natural history of the disease and the technical progress currently allow an early diagnosis, before the stage of dementia. Although the clinical use of biomarkers is justified in patients who have attended a Memory Clinic, ethical issues remain. The disclosure of the diagnosis of Alzheimer's disease to the person who is not yet suffering from dementia remains a sensitive subject. In this context, it seems appropriate at this stage to restrict the use of these methods to centers specializing in early diagnosis.

OBJECTIVE: To assess nonparoxysmal movement disorders in ATP1A3 mutation-positive patients with alternating hemiplegia of childhood (AHC). METHODS: Twenty-eight patients underwent neurologic examination with particular focus on movement phenomenology by a specialist in movement disorders. Video recordings were reviewed by another movement disorders specialist and data were correlated with patients' characteristics. RESULTS: Ten patients were diagnosed with chorea, 16 with dystonia (nonparoxysmal), 4 with myoclonus, and 2 with ataxia. Nine patients had more than one movement disorder and 8 patients had none. The degree of movement disorder was moderate to severe in 12/28 patients. At inclusion, dystonic patients (n = 16) were older (p = 0.007) than nondystonic patients. Moreover, patients (n = 18) with dystonia or chorea, or both, had earlier disease onset (p = 0.042) and more severe neurologic impairment (p = 0.012), but this did not correlate with genotype. All patients presented with hypotonia, which was characterized as moderate or severe in 16/28. Patients with dystonia or chorea (n = 18) had more pronounced hypotonia (p = 0.011). Bradykinesia (n = 16) was associated with an early age at assessment (p < 0.01). Significant dysarthria was diagnosed in 11/25 cases. A history of acute neurologic deterioration and further regression of motor function, typically after a stressful event, was reported in 7 patients. CONCLUSIONS: Despite the relatively limited number of patients and the cross-sectional nature of the study, this detailed categorization of movement disorders in patients with AHC offers valuable insight into their precise characterization. Further longitudinal studies on this topic are needed.

AIM: The intensity of the most appropriate exercise to use in depressed youth is unclear due to differences in methodology and the lack of evidence documenting the effect of physical activity in children. Therefore, the authors of this study attempted to document the effectiveness of different training intensities to reduce symptoms of depression and anxiety in pre-teens. METHODS: The study included twenty-seven, randomly selected pre-adolescents (aged between 9-11 years of age) all of whom had Primary education. The participants were enrolled and, over a 5-week period, were subject to either intensive or low-to-moderate exercise programs four times a week. Psychological self-reports, as well as physical examinations, were conducted before and after such programs in blinded assessments. Psychological effects were considered the primary outcome, whilst physical condition was secondary. RESULTS: Four subjects were lost and twenty-three were analyzed. General linear model with 2 criteria revealed significant changes (p = 0.05) in trait anxiety symptoms over time in the low-to-moderate intensity group (LMIG). Within group changes followed a significant decrease in levels of anxiety (38.82 ± 2.20 to 33.36 ± 2.83, p = 0.004) and depression (10.36 ± 2.83 to 6.73 ± 1.88, p = 0.006) related symptoms amongst those in the LMIG. INTERPRETATION: This study indicated that depression and anxiety symptoms were reduced amongst a non-clinical sample of Primary educated pre-adolescents when they were subject to a low-to-moderate exercise program. The program focused on associating movement with pleasure, encouraged positive and non-competitive interactions between participants. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT02970825, autumn 2016, updated May 7, 2018 (https://clinicaltrials.gov/ct2/show/NCT02970825).

A 90-year-old female patient was brought to our hospital by ambulance after her husband found her somnolent and mute upon waking. Upon arrival, neurological and physical examinations showed spastic flexion of the right arm and deviation of gaze to the left. A so-called ‘wake-up stroke procedure’ was triggered and brain magnetic resonance imaging (MRI), including fluid-attenuation inversionrecovery (FLAIR) and diffusion weighted imaging (DWI) acquisitions, was immediately performed (Figure 1). Axial FLAIR images showed only leukoaraiosis (Figure 1A). DWI demonstrated high signal intensity in the territory of left middle cerebral artery (MCA) at high b-value (Figure 1B) with decreased apparent diffusion coefficient values. MRangiography was precluded by patient’s movements. Non-contrast CT (NCCT), CT-angiography (CTA), and CT-perfusion (CTP) were thereafter performed for angiographic assessment including carotid arteries, circle of Willis, and intracranial collateral circulation (Figure 2).

Introduction: Since we recently showed in behavioural tasks that the top-down cognitive control was specifically altered in tinnitus sufferers, here we wanted to establish the link between this impaired executive function and brain alterations in the frontal cortex in tinnitus patients Method: Using functional magnetic resonance imaging (fMRI), we monitored the brain activity changes in sixteen tinnitus patients (TP) and their control subjects (CS) while they were performing a spatial Stroop task, both in audition and vision. Results: We observed that TP differed from CS in their functional recruitment of the dorsolateral prefrontal cortex (dlPFC, BA46), the cingulate gyrus and the ventromedial prefrontal cortex (vmPFC, BA10). This recruitment was higher during interference conditions in tinnitus participants than in controls, whatever the sensory modality. Furthermore, the brain activity level in the right dlPFC and vmPFC correlated with the performance in the Stroop task in TP. Conclusion: Due to the direct link between poor executive functions and prefrontal cortex alterations in TP, we postulate that a lack of inhibitory modulation following an impaired top-down cognitive control may maintain tinnitus by hampering habituation mechanisms. This deficit in executive functions caused by prefrontal cortex alterations would be a key-factor in the generation and persistence of tinnitus.

Hearing a beat recruits a wide neural network that involves the auditory cortex and motor planning regions. Perceiving a beat can potentially be achieved via vision or even touch, but it is currently not clear whether a common neural network underlies beat processing. Here, we used functional magnetic resonance imaging (fMRI) to test to what extent the neural network involved in beat processing is supramodal, that is, is the same in the different sensory modalities. Brain activity changes in 27 healthy volunteers were monitored while they were attending to the same rhythmic sequences (with and without a beat) in audition, vision and the vibrotactile modality. We found a common neural network for beat detection in the three modalities that involved parts of the auditory dorsal pathway. Within this network, only the putamen and the supplementary motor area (SMA) showed specificity to the beat, while the brain activity in the putamen covariated with the beat detection speed. These results highlighted the implication of the auditory dorsal stream in beat detection, confirmed the important role played by the putamen in beat detection and indicated that the neural network for beat detection is mostly supramodal. This constitutes a new example of convergence of the same functional attributes into one centralized representation in the brain.

Background: Emotional and interpersonal impairments have been largely reported in alcohol-dependence, and their role in its development and maintenance is widely established. However, earlier studies have exclusively focused on group comparisons between healthy controls and alcohol-dependent individuals, considering them as a homogeneous population. The variability of socio-emotional profiles in this disorder thus remains totally unexplored. The present study used a cluster analytic approach to explore the heterogeneity of affective and social disorders in alcohol-dependent individuals. Methods: 296 recently-detoxified alcohol-dependent patients were first compared with 246 matched healthy controls regarding self-reported emotional (i.e. alexithymia) and social (i.e. interpersonal problems) difficulties. Then, a cluster analysis was performed, focusing on the alcohol-dependent sample, to explore the presence of differential patterns of socio-emotional deficits and their links with demographic, psychopathological and alcohol-related variables. Results: The group comparison between alcohol-dependent individuals and controls clearly confirmed that emotional and interpersonal difficulties constitute a key factor in alcohol-dependence. However, the cluster analysis identified five subgroups of alcohol-dependent individuals, presenting distinct combinations of alexithymia and interpersonal problems ranging from a total absence of reported impairment to generalized socio-emotional difficulties. Conclusions: Alcohol-dependent individuals should no more be considered as constituting a unitary group regarding their affective and interpersonal difficulties, but rather as a population encompassing a wide variety of socio-emotional profiles. Future experimental studies on emotional and social variables should thus go beyond mere group comparisons to explore this heterogeneity, and prevention programs proposing an individualized evaluation and rehabilitation of these deficits sho

L’année 2016 a été marquée en neurochirurgie par la publication de nos résultats de l’application intervertébrale de greffes ostéodifférenciées à partir de cellules souches adipeuses reconstituées en structure tridimensionnelle. Trois patients souffrant de spondylodiscarthrose dégénérative ont bénéficié d’un abord minimal invasif transforaminal (MI-TLIF) pour la réalisation d’une fusion vertébrale intersomatique. Pour un d’entre eux, deux niveaux ont été opérés en même temps, portant le nombre total de niveaux opérés à quatre. Les trois patients ont eu un prélèvement de graisse abdominale par liposuccion pour une culture et transformation en cellules souches au laboratoire de banque des tissus. Après une ostéodifférenciation des cellules souches et reconstitution en matrice 3D, une implantation a été réalisée au cours de la chirurgie. Les patients ont ensuite bénéficié d’un suivi radiologique et clinique jusqu’à 12 mois en postopératoire. Au terme de la période d’observation, le score de la douleur VAS (visual analog score) s’est amélioré de 8,3 à 2 et le score d’ODI (Oswestry Disability Index) est passé de 47 à 31 %. Sur le plan radiologique, une fusion de grade 3 a été observée sur 2 des 4 niveaux opérés. Aucune complication n’a été déplorée. Au total, la greffe 3D reconstituée à partir de cellules souches mésenchymateuses constitue une alternative nouvelle et intéressante pour la fusion vertébrale et offre l’avantage d’être une source autologue sans les inconvénients des prélèvements de greffes autologues comme celles de la crête iliaque. Des études étendues sont encore nécessaires pour confirmer l’efficacité de cette nouvelle technologie.

Over the last decade, functional brain imaging has provided insight to the maturation processes and has helped elucidate the pathophysiological mechanisms involved in brain plasticity in the absence of vision. In case of congenital blindness, drastic changes occur within the deafferented "visual" cortex that starts receiving and processing non visual inputs, including olfactory stimuli. This functional reorganization of the occipital cortex gives rise to compensatory perceptual and cognitive mechanisms that help blind persons achieve perceptual tasks, leading to superior olfactory abilities in these subjects. This view receives support from psychophysical testing, volumetric measurements and functional brain imaging studies in humans, which are presented here.

Early blindness results in both structural and functional changes of the brain. However, these changes have rarely been studied in relation to each other. We measured alterations in cortical thickness caused by early visual deprivation and their relationship with cortical activity. Structural and functional magnetic resonance imaging was performed in 12 early blind humans (EB) and 12 sighted controls (SC). Experimental conditions included one-back tasks for auditory localization and pitch identification, as well as a simple sound-detection task. Structural and functional data were analyzed in a whole-brain approach and within anatomically-defined regions of interest in sensory areas of the spared (auditory) and deprived (visual) modalities. Functional activation during sound-localization or pitch-identification tasks correlated negatively with cortical thickness in occipital areas of EB (calcarine sulcus, lingual gyrus, superior and middle occipital gyri, and cuneus) and in nonprimary auditory areas of SC. These results suggest a link between cortical thickness and activation and demonstrate that the relationship between cortical structure and function depends on sensory experience, probably via selective pruning of exuberant connections. Activity-dependent effects of early sensory deprivation and long-term practice are superimposed on normal maturation and aging. Together these processes shape the relationship between brain structure and function over the lifespan.

Purpose: Tinnitus is the perception of a sound in the absence of external stimulus. Currently, the pathophysiology of tinnitus is not fully understood, but recent studies indicate that alterations in the brain involve non-auditory areas, including the prefrontal cortex. Here, we hypothesize that these brain alterations affect top-down cognitive control mechanisms that play a role in the regulation of sensations, emotions and attention resources. Methods: The efficiency of the executive control as well as simple reaction speed and processing speed were evaluated in tinnitus participants (TP) and matched control subjects (CS) in both the auditory and the visual modalities using a spatial Stroop paradigm. Results: TP were slower and less accurate than CS during both the auditory and the visual spatial Stroop tasks, while simple reaction speed and stimulus processing speed were affected in TP in the auditory modality only. Conclusions: Tinnitus is associated both with modality-specific deficits along the auditory processing system and an impairment of cognitive control mechanisms that are involved both in vision and audition (i.e. that are supra-modal). We postulate that this deficit in the top-down cognitive control is a key-factor in the development and maintenance of tinnitus and may also explain some of the cognitive difficulties reported by tinnitus sufferers.

Objective: To evaluate our technique of implanting subdural grids by linear craniectomy under computer-assisted navigation for invasive electroencephalography in medically refractory epilepsy. Material and method: We report results from our first 38 consecutive patients with medically refractory epilepsy who underwent subdural grids implantation by linear craniectomy. For each case, a preoperative MRI was performed for navigation followed by a postoperative MRI for localization control of the intracranial electrode contacts. A linear skin incision, adapted to the depth and type of subdural electrode (strip or grid) and compatible with possible subsequent therapeutic surgery, was carried out. One or two linear craniectomies (maximal length 6. cm, width 1. cm) were then drilled with a bevel. The dura mater was incised under microscopic guidance to avoid opening the arachnoid. The required subdural electrodes were then slipped subdurally through each linear craniectomy (letter-box technique). Results: Forty-one invasive electroencephalographies were performed with 28 (68%) bilateral. For all invasive electroencephalographies, at least one subdural grid was implanted. Sixty-one subdural grids were implanted in total, 52 with 20contacts and nine with 32contacts. No cerebrospinal fluid leakage, no infection, no neurological deficit and no permanent complications were observed. Three subdural grids (5%) were not positioned exactly as planned but this had no consequence for the invasive electroencephalography analysis. Conclusion: The implantation of 61 consecutive subdural grids for invasive electroencephalography through linear craniectomies was associated with no transient or permanent complications in this population. This letter-box technique appears to be practical and safe without limiting explorative efficacy

Tinnitus is the perception of sound in the absence of external stimulus. Currently, the pathophysiology of tinnitus is not fully understood, but recent studies indicate that alterations in the brain involve non-auditory areas, including the prefrontal cortex. In experiment 1, we used a go/no-go paradigm to evaluate the target detection speed and the inhibitory control in tinnitus participants (TP) and control subjects (CS), both in unimodal and bimodal conditions in the auditory and visual modalities. We also tested whether the sound frequency used for target and distractors affected the performance. We observed that TP were slower and made more false alarms than CS in all unimodal auditory conditions. TP were also slower than CS in the bimodal conditions. In addition, when comparing the response times in bimodal and auditory unimodal conditions, the expected gain in bimodal conditions was present in CS, but not in TP when tinnitus-matched frequency sounds were used as targets. In experiment 2, we tested the sensitivity to cross-modal interference in TP during auditory and visual go/no-go tasks where each stimulus was preceded by an irrelevant pre-stimulus in the untested modality (e.g. high frequency auditory pre-stimulus in visual no/no-go condition). We observed that TP had longer response times than CS and made more false alarms in all conditions. In addition, the highest false alarm rate occurred in TP when tinnitus-matched/high frequency sounds were used as pre-stimulus. We conclude that the inhibitory control is altered in TP and that TP are abnormally sensitive to cross-modal interference, reflecting difficulties to ignore irrelevant stimuli. The fact that the strongest interference effect was caused by tinnitus-like auditory stimulation is consistent with the hypothesis according to which such stimulations generate emotional responses that affect cognitive processing in TP. We postulate that executive functions deficits play a key-role in the perception and

Tinnitus can be defined as the perception of noxious disabling internal sounds in the absence of external stimulation. While most individuals with tinnitus show some habituation to these internal sounds, many of them experience significant daily life impairments. There is now convincing evidence that impairment in attentional processes may be involved in tinnitus, particularly by hampering the habituation mechanism related to the prefrontal cortex activity. However, it is thus still unclear whether this deficit is an alteration of alerting and orienting attentional abilities, or the consequence of more general alteration in the executive control of attention. In the present study, 20 tinnitus patients were compared to 20 matched healthy controls using the Attention Network Test, to clarify which attentional networks, among alerting, orienting, and executive networks, show differences between the groups. The results showed that patients with tinnitus do not present a general attentional deficit but rather a specific deficit for top-down executive control of attention. This deficit was highly correlated with patient characteristics of years of tinnitus duration and the frequency of coping strategies employed to alleviate tinnitus distress in daily life. These findings are discussed in terms of recent neurobiological models suggesting that prefrontal cortex activity might especially be related to tinnitus habituation. Therapeutic perspectives focusing both on rehabilitation of the executive control of attention and neuromodulation are also discussed.

The "neural Darwinism" theory predicts that when one sensory modality is lacking, as in congenital blindness, the target structures are taken over by the afferent inputs from other senses that will promote and control their functional maturation (Edelman, 1993). This view receives support from both cross-modal plasticity experiments in animal models and functional imaging studies in man, which are presented here.

Although early blind (EB) individuals are thought to have a better musical sense than sighted subjects, no study has investigated the musical rhythm and beat processing abilities in EB individuals. Using an adaptive 'up and down' procedure, we measured the beat asynchrony detection threshold and the duration discrimination threshold, in the auditory and vibrotactile modalities in both EB and sighted control (SC) subjects matched for age, gender, and musical experience. We observed that EB subjects were better than SC in the beat asynchrony detection task; that is, they showed lower thresholds than SC, both in the auditory and in the vibrotactile modalities. In addition, EB subjects had a lower threshold than SC for duration discrimination in the vibrotactile modality only. These improved beat asynchrony detection abilities may contribute to the known excellent musical abilities often observed in many blind subjects.

La stimulation du nerf vague est un traitement non pharmacologique de l’épilepsie pharmaco résistante. Plusieurs études ont démontré une efficacité clinique chez environ un tiers des patients implantés (> 50% moins de crises). Les mécanismes d’actions ne sont pas encore tout à fait élucidés. Presque tous les types d’épilepsie pharmaco résistantes sont susceptibles d’être améliorés. Une meilleure connaissance des mécanismes antiépileptiques mis en jeu, permettrait de mieux sélectionner les patients potentiellement répondeurs, Epilepsy is a chronic neurological disorder that is characterized by recurrent epileptic seizures. Its prevalence is estimated at 0.5 to 1[%] of the population. About 30[%] of epileptic patients are considered refractory, meaning that they do not respond to anti-epileptic drugs. For these patients, alternative treatment modalities such as epilepsy surgery or vagus nerve stimulation (VNS) may be useful. However, there are no predictive factors that enable us to identify VNS responders at an early stage. VNS is generally considered to be cost-efficient, and advancements in VNS technologies are developing rapidly.

Recent studies reported an involvement of motor/premotor brain areas during the perception of rhythm and beat in audition. However, little is known about the neural network of beat perception through non-auditory modalities. Here we used functional magnetic resonance imaging with auditory, vibro-tactile and visual rhythmic sequences in order to highlight the modality-specific areas involved in beat perception. We contrasted the brain activity changes in 20 healthy volunteers exposed to rhythmic sequences with a beat and control sequences without a beat. Results showed a recruitment of premotor cortex, supplementary motor area (SMA) and basal ganglia during beat sequences compared to rest in all three modalities. Beat sequences compared to no-beat sequences elicited the selective recruitment of the putamen and the SMA in the three sensory modalities, although to a lesser extent in vision. We conclude that the putamen and the SMA play a role in the prediction ability of a regular temporal pattern, although this seems less pronounced in vision compared to audition and to the vibro-tactile sensory modality.

In number comparison tasks, the performance is better when the distance between the numbers to compare increases. It has been shown that this so-called numerical distance effect (NDE) decreases with age but the neuroanatomical correlates of these age-related changes are poorly known. Using functional magnetic resonance imaging (fMRI), we recorded the brain activity changes in children aged from 8 to 14 years while they performed a number comparison task on pairs of Arabic digits and a control color comparison task on non-numerical symbols. On the one hand, we observed developmental changes in the recruitment of frontal regions and the left intraparietal sulcus (IPS), with lower activation as age increased. On the other hand, we found that a behavioral index of selective sensitivity to the NDE was positively correlated with higher brain activity in a right lateralized occipito-temporo-parietal network including the IPS. This leads us to propose that the left IPS would be engaged in the refinement of cognitive processes involved in number comparison during development, while the right IPS would underlie the semantic representation of numbers and its activation would be mainly affected by the numerical proximity between them.

Mutations in STXBP1 have been identified in a subset of patients with early onset epileptic encephalopathy (EE), but the full phenotypic spectrum remains to be delineated. Therefore, we screened a cohort of 160 patients with an unexplained EE, including patients with early myoclonic encephalopathy (EME), Ohtahara syndrome, West syndrome, nonsyndromic EE with onset in the first year, and Lennox-Gastaut syndrome (LGS). We found six de novo mutations in six patients presenting as Ohtahara syndrome (2/6, 33%), West syndrome (1/65, 2%), and nonsyndromic early onset EE (3/64, 5%). No mutations were found in LGS or EME. Only two of four mutation carriers with neonatal seizures had Ohtahara syndrome. Epileptic spasms were present in five of six patients. One patient with normal magnetic resonance imaging (MRI) but focal seizures underwent epilepsy surgery and seizure frequency dropped drastically. Neuropathology showed a focal cortical dysplasia type 1a. There is a need for additional neuropathologic studies to explore whether STXBP1 mutations can lead to structural brain abnormalities.

We report a case of Takotsubo syndrome after epilepsy, and review the literature. We identified 59 cases of Takotsubo syndrome after focal or generalised epilepsy. As in Takotsubo syndrome in general, the patients were mostly female (84%), with a mean age of 63 years, and the evolution was generally favourable. There was one death and one stroke, and 4 cases were of relapsing Takotsubo after a new seizure. Takotsubo syndrome may induce cardiac arrhythmias. A near-SUDEP (sudden unexplained death in epilepsy) was reported in one patient. Animal models of SUDEP have shown similar cardiac lesions to those seen in Takotsubo syndrome, and strengthen the hypothesis of a link between these conditions. Takotsubo syndrome after epilepsy may be relatively common; we suggest measurement of serum troponin levels in high-risk patients and cardiac follow-up. © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

It has been shown that the volume of the olfactory bulb (OB) changes with function. The aim of this study was to investigate whether the OB volume and the olfactory function in early blind (EB) subjects increase compared with controls. Psychophysical testing of olfactory performances and OB volumetric measurements assessed by an MRI scan were studied. Quantitative olfactory function expressed in the odor discrimination and odor-free identification scores was higher in EB subjects compared with controls. The mean of right, left and total OB volume was 65.40, 75.48, and 140.89 mm, respectively for the EB subjects and 54.47, 52.11, and 106.60 mm, respectively for the controls, with these differences being significant. EB subjects have superior olfactory abilities and presented with significantly higher OB volume than the sighted controls. OB plasticity may explain this compensatory mechanism between visual deprivation and enhanced olfactory perception.

Considering the putative neuroprotective role of the vasoactive intestinal peptide (VIP) and the pituitary adenylyl cyclase-activating polypeptide (PACAP), we investigated the acute modulation of glial glutamate uptake by the structurally related peptide histidine isoleucine (PHI). Using cultures of cortical astrocytes, we demonstrated that a 6 min treatment with 1 mumol/L PHI strongly increased the d-[(3)H]-aspartate uptake velocity from 24.3 +/- 1.9 to 46.8 +/- 3.5 nmol/mg prot/min. This effect was found to reflect an increase in the activity of the GLAST, the predominant functional glutamate transporter in these cultures. The combination of protein kinase A and C inhibitors was effective in blocking the effect of PHI and the use of peptide antagonists contributed to demonstrate the implication of the VIP/PACAP type 2 receptor (VPAC(2)). Accordingly, G-protein activation measures and gene reporter assays revealed the expression of functional PHI-sensitive receptors in cultured astrocytes. Biotinylation/immunoblotting studies indicated that PHI significantly increased the cell surface expression of the GLAST (by 34.24 +/- 8.74 and 43.00 +/- 6.36%, when considering the 72 and 55 kDa immunoreactive proteins, respectively). Such cross-talk between PHI and glutamate transmission systems in glial cells opens attractive perspectives in neuropharmacology.