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Background and Purpose: Infections and vaccinations have been identified as potential immunological triggers of neuralgic amyotrophy (NA), but the exact type and frequency of the preceding agents is unknown., Methods: This was a multicentre, prospective, observational, matched case-control study. NA was diagnosed by neuromuscular experts according to validated clinical criteria and electrodiagnostic studies. Clinical data and biological samples of NA patients were collected within 90 days from disease onset between June 2018 and December 2023. All NA patients were asked about prior infection and vaccination in the month before disease onset. Serological tests for hepatitis E virus, human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, Epstein-Barr virus, cytomegalovirus, parvovirus B19, varicella-zoster virus, Borrelia burgdorferi, Mycoplasma pneumoniae and Bartonella henselae were performed in a central laboratory. Each case was matched with a healthy control for age, sex, place of residence and time of blood collection., Results: Fifty-seven patients and corresponding controls were included. The mean age was 45 years for both groups. NA onset was preceded by a symptomatic infectious trigger confirmed by microbiological tests in 15/57 (26.3%) patients. Coronavirus disease 2019 vaccination was considered a potential trigger in 7/57 (12.3%) subjects. An acute viral infection was associated with a bilateral involvement of the brachial plexus (p = 0.003, Cramèr's V = 0.43)., Conclusions: Confirmed immune triggers (infection or vaccination) preceded disease onset in 22/57 (38.6%) NA cases. We suggest to test NA patients in the acute phase for intracellular antigens, especially in the case of concomitant bilateral involvement and hepatitis., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Myasthenia gravis (MG) is an autoimmune disease characterized by fluctuating weakness of skeletal muscles. Despite current treatments, a significant percentage of patients remain symptomatic. This review explores new immunosuppressive therapies and ongoing clinical trials in MG, including depletion of B lymphocytes with agents such as rituximab and inebilizumab, as well as the use of eculizumab, efgartigimod, satralizumab, tocilizumab, and CAR-T (Chimeric Antigen Receptor-T) cell therapy. These advancements aim to improve disease control and patients' quality of life., Competing Interests: La Dre Marie Théaudin a reçu des honoraires pour sa participation à des advisory boards d’Alexion, Argenx et UCB ainsi que des frais de déplacement de la part d’Alexion. La Dre Agustina M. Lascano a reçu des honoraires de ADC therapeutics et d’Alexion pour sa participation à un advisory board et de Sanofi pour une présentation. Le Pr Patrice H. Lalive a reçu des honoraires pour des conférences et/ou des frais de déplacement de Biogen, Merck, Novartis et Roche, des honoraires de consultation de Biogen, GeNeuro, Merck, Novartis et Roche, et un soutien à la recherche de Roche et Novartis. Aucun n’était lié à ce travail. Les autres auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: Acute hepatitis E virus (HEV) infection has recently emerged as a potential trigger for acute dysimmune neuropathies, but prospective controlled studies are lacking., Aims: To compare the frequency of concomitant acute HEV infection in patients with neuralgic amyotrophy (NA), Guillain-Barré syndrome (GBS), and Bell's palsy with a matched control population., Methods: Swiss multicenter, prospective, observational, matched case-control study over 3 years (September 2019-October 2022). Neurological cases with NA, GBS, or Bell's palsy were recruited within 1 month of disease onset. Healthy controls were matched for age, sex, geographical location, and timing of blood collection. Diagnostic criteria for acute hepatitis E were reactive serum anti-HEV IgM and IgG assays (ELISA test) and/or HEV RNA detection in serum by real-time polymerase chain reaction (RT-PCR). RT-PCR was performed on sera to confirm IgM positivity., Results: We included 180 patients (59 GBS, 51 NA, 70 Bell's palsy cases) and corresponding matched controls (blood donors) with median age 51 years for both groups and equal gender distribution. Six IgM+ cases were detected in the NA, two in the GBS, and none in the Bell's palsy group. Two controls were anti-HEV IgM-positive. At disease onset, most cases with acute HEV infection had increased liver enzymes. A moderate association (p = 0.027, Fisher's exact test; Cramér's V = -0.25) was observed only between acute HEV infection and NA., Conclusion: This prospective observational study suggests an association between concomitant acute HEV infection and NA, but not with GBS or Bell's palsy., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Arterial spin-labeling is a noninvasive MR imaging technique allowing direct and quantitative measurement of brain perfusion. Arterial spin-labeling is well-established in clinics for investigating the overall cerebral perfusion, but it is still occasionally employed during tasks. The typical contrast for functional MR imaging is blood oxygen level-dependent (BOLD) imaging, whose specificity could be biased in neurologic patients due to altered neurovascular coupling. This work aimed to validate the use of functional ASL as a noninvasive tool for presurgical functional brain mapping. This is achieved by comparing the spatial accuracy of functional ASL with transcranial magnetic stimulation as the criterion standard., Materials and Methods: Twenty-eight healthy participants executed a motor task and received a somatosensory stimulation, while BOLD imaging and arterial spin-labeling were acquired simultaneously. Transcranial magnetic stimulation was subsequently used to define hand somatotopy., Results: Functional ASL was found more adjacent to transcranial magnetic stimulation than BOLD imaging, with a significant shift along the inferior-to-superior direction. With respect to BOLD imaging, functional ASL was localized significantly more laterally, anteriorly, and inferiorly during motor tasks and pneumatic stimulation., Conclusions: Our results confirm the specificity of functional ASL in targeting the regional neuronal excitability. Functional ASL could be considered as a valid supplementary technique to BOLD imaging for presurgical mapping when spatial accuracy is crucial for delineating eloquent cortex., (© 2023 by American Journal of Neuroradiology.)

Introduction: Guillain-Barré syndrome (GBS) is an immune-mediated poly(radiculo)neuropathy with a variable clinical outcome. Identifying patients who are at risk of suffering from long-term disabilities is a great challenge. Biomarkers are useful to confirm diagnosis, monitor disease progression, and predict outcome., Areas Covered: The authors provide an overview of the diagnostic and prognostic biomarkers for GBS, which are useful for establishing early treatment strategies and follow-up care plans., Expert Opinion: Detecting patients at risk of developing a severe outcome may improve management of disease progression and limit potential complications. Several clinical factors are associated with poor prognosis: higher age, presence of diarrhea within 4 weeks of symptom onset, rapid and severe weakness progression, dysautonomia, decreased vital capacity and facial, bulbar, and neck weakness. Biological, neurophysiological and imaging measures of unfavorable outcome include multiple anti-ganglioside antibodies elevation, increased serum and CSF neurofilaments light (NfL) and heavy chain, decreased NfL CSF/serum ratio, hypoalbuminemia, nerve conduction study with early signs of demyelination or axonal loss and enlargement of nerve cross-sectional area on ultrasound. Depicting prognostic biomarkers aims at predicting short-term mortality and need for cardio-pulmonary support, long-term patient functional outcome, guiding treatment decisions and monitoring therapeutic responses in future clinical trials.

Objective: To validate the prognostic value of multimodal evoked potentials (mmEP) in primary progressive multiple sclerosis (PPMS) and to determine the most predictive EP-modalities., Methods: Thirty-nine patients with PPMS (expanded disability status scale (EDSS): 2.0-6.5; mean clinical follow-up: 2.8 years) had visual (VEP), upper and lower limb somatosensory (SEP) and motor EP (MEP) at baseline. Quantitative EP-scores for single (qVEP, qSEP, qMEP) and combined modalities were correlated to EDSS and compared to previously published data of 21 PPMS patients. Predictors of EDSS-change were analyzed in pooled data by linear regression., Results: Samples were comparable. Except qVEP, all EP-scores were correlated to EDSS at baseline (Rho: 0.45-0.69; p < 0.01) and follow-up (Rho: 0.59-0.80; p < 0.001). Combined EP-modalities significantly predicted EDSS-change (R 2 adj : 0.24), while EDSS and age did not. Tibial qSEP (R 2 adj : 0.22) and qMEP (R 2 adj : 0.26) were the best single modality predictors, outperformed by their combination (R 2 adj : 0.32)., Conclusions: Quantitative EP-scores predict up to 32% of EDSS-change over three years. Modalities representing motor and long tract function carry the main prognostic information., Significance: Replication of previous results corroborates the use of mmEP as a prognostic biomarker candidate in PPMS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: To determine whether CSF interleukin 8 (IL-8) concentration can help to distinguish Guillain-Barré syndrome (GBS) from chronic inflammatory demyelinating polyneuropathy (CIDP) at the initial stage of the disease., Methods: We performed retrospective immunoassay of IL-8 in CSF, collected at the University Hospitals of Geneva between 2010 and 2018, from patients diagnosed with GBS (n = 45) and with CIDP (n = 30) according to the Brighton and European Federation of Neurological Societies/Peripheral Nerve Society criteria by a physician blinded to biological results., Results: CSF IL-8 was higher in GBS (median: 83.9 pg/mL) than in CIDP (41.0 pg/mL) ( p < 0.001). Receiver operating characteristic analyses indicated that the optimal IL-8 cutoff was 70 pg/mL. Above this value, patients were more likely to present GBS than CIDP (specificity 96.7%, sensitivity 64.4%, positive predictive value [PPV] 96.7%, and negative predictive value [NPV] 64.4%). Among GBS subcategories, IL-8 was higher in acute inflammatory demyelinating polyneuropathy (AIDP, median: 101.8 pg/mL) than in other GBS variants (median: 53.7 pg/mL). In addition, with CSF IL-8 above 70 pg/mL, patients were more likely to present AIDP than acute-onset CIDP ( p < 0.001; specificity 100%, sensitivity 78.8%, PPV 100%, and NPV 46.2%) or other CIDP with nonacute presentation ( p < 0.0001; specificity 95.8%, sensitivity 78.8%, PPV 96.3%, and NPV 76.7%)., Conclusion: CSF IL-8 levels can help to differentiate AIDP variant of GBS from CIDP, including acute-onset CIDP, with high specificity and PPV. This may improve early and appropriate treatment., Classification of Evidence: This study provides Class II evidence that CSF IL-8 levels accurately distinguish patients with GBS from those with CIDP., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: No studies assessing rabies vaccine (RV) tolerability in persons with multiple sclerosis (MS) have been conducted. Given the lack of safety data, RV is recommended essentially only for post-exposure prophylaxis, which is difficult to administer effectively in many rabies-endemic countries. We sought to determine whether RV administration as pre-exposure prophylaxis was associated with MS relapse., Methods: This retrospective cohort study compared the clinical courses of MS patients in the year before and after rabies vaccination. The year before vaccination was defined as the pre-exposure risk period, the three months thereafter as the exposure-risk period, and the following nine months as the post-risk period. All adult MS patients immunized with RV between 2014 and 2018 and with available medical records in the two-year window were included. The primary outcome was the incidence of symptomatic MS relapse in the exposure-risk period versus the pre-exposure period., Results: Fifty-five patients received at least one dose of RV. Most (38/55, 69%) were female; mean age was 38.5 years (SD ±9.2). While 21 (38%) patients experienced 24 relapses in the year before vaccination, only three (5%) experienced one relapse each in the post-vaccination exposure-risk period; three others (5%) experienced a total of four relapses in the subsequent post-risk period. The annualized relapse rates in the pre-exposure, exposure-risk, and post-risk periods were 0.44, 0.22, and 0.10, respectively (rate ratio for exposure-risk to pre-exposure periods, 0.509 [95% CI 0.098-1.677])., Conclusions: In this cohort, rabies vaccination was not associated with clinical MS relapse. Larger, prospective studies are needed to confirm these results., Competing Interests: Declaration of Competing Interest Dr P. H. Lalive received honoraria for speaking from Biogen-Idec, CSL Bering, Merck Serono, Novartis, Sanofi-Aventis, Teva, Roche; consulting fees from Biogen-Idec, Geneuro, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva; and research grants from Biogen-Idec, Merck Serono, and Novartis. All other authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

Small fiber neuropathy (SFN) causes damage to small-calibre nerve fibers (unmyelinated C fibers and myelinated A-delta fibers). The symptoms of SFN usually are sensitive including paresthesia, dysesthesia or burning pain, and protopathic deficits, sometimes associated with dysautonomia. The causes of SFN can be classified in six main groups: idiopathic, toxic, metabolic, immunological, infectious and hereditary. In this article, we present the diagnostic approach to SFN, the most common autoimmune aetiologies, as well as elements of their therapeutic management., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction. Immunosuppressive treatments are part of the therapeutic armamentarium in MG. Long-term systemic steroid administration carry considerable risks and adverse events. Consequently, steroid-free immunosuppressive therapy is necessary to reduce the dose or discontinue steroids. First immunosuppressive drug trials in MG were performed in the mid-60s using standard and nonspecific immunosuppression. Since then, only few randomized controlled clinical trials were conducted in MG and assesed drug efficacy in terms of its steroid-sparing capacity and the ability to reduce myasthenic signs and symptoms. Treatment strategy in MG is quite challenging, mainly due to the disease heterogeneity in terms of clinical presentation, immunopathogenesis and drug response. To solve this dilemma, emerging treatment are based on biological drugs and use new targets of the immune pathway., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Tandem spinal stenosis (TSS) is an entity which refers to spinal canal diameter narrowing in at least two distinct regions of the spine. When symptomatic, management of TSS is controversial. In this study, we present a consecutive series of patients with symptomatic TSS and report diagnostic and surgical challenges. We retrospectively reviewed a consecutive series of N = 8 patients with symptomatic TSS who underwent surgical treatment in at least one region of the spine. Patients presented with multiple complaints, including neurogenic claudication, progressive gait disturbances, and signs of radiculopathy and/or myelopathy, among others. Modified Japanese Orthopedic Association (mJOA) and Oswestry Low Back Pain Disability Questionnaire (ODI) were obtained in pre- and postoperative period. Electroneurophysiological examinations were limited to patients whose clinical and radiological signs were not sufficient to determine which region was more affected. From 2015 to 2018, we included N = 8 consecutive patients with TSS who underwent surgery by a staged approach. The stenosis was localized in the cervical and lumbar region in six patients (75%) and in the cervical, dorsal, and lumbar level (triple TSS) in two patients (25%). Four patients (50%) underwent cervical and lumbar surgery, two (25%) underwent cervical surgery alone, and two (25%) were operated in all three involved regions. Surgical treatment allowed an improvement of the mean mJOA score (from 12.5/17 to 15/17) and mean ODI score (from 41 to 28%). TSS represents a clinical, diagnostic, and surgical challenge. We recommend to systematically obtain electrophysiological and radiological examinations and then to perform a staged surgery, beginning at the most symptomatic region.

Objective: To determine whether live-attenuated yellow fever vaccine (YFV) was associated with MS relapse, we evaluated the clinical courses of 23 patients in the year before and the year after immunization at the university hospital of Geneva, Switzerland., Methods: This self-controlled retrospective cohort included adult patients with MS receiving YFV between 2014 and 2018 and defined the year before vaccination, the 3 months thereafter, and the 9 months following as the pre-exposure (PEP), exposure-risk (ERP), and postrisk (PRP) periods, respectively. The primary outcome was the relative incidence of relapse in the ERP vs the PEP. Secondary end points included the presence of new T2-weighted (T2) or T1-weighted gadolinium-positive (T1Gd+) MRI lesions., Results: Of 23 patients with MS receiving YFV (20 relapsing MS and 3 primary progressive MS), 17 (74%) were women; mean age was 34 years (SD ±10); and 10 of 23 (40%) were treated with disease-modifying therapies (DMTs). Although 9 patients experienced 12 relapses in the PEP, only one experienced a relapse in the ERP; 3 other patients experienced one relapse each in the PRP. None of the 8 patients receiving natalizumab at the time of vaccination experienced relapse thereafter. In the PEP, ERP, and PRP, 18, 2, and 9 patients had new brain and/or spinal cord lesions on T2 or T1Gd + MRI, respectively., Conclusions: In this cohort, YF vaccination was associated with neither an increase in MS relapse nor emergence of brain and/or spinal lesions. Further studies are warranted to confirm these findings., Classification of Evidence: This study provides Class IV evidence that for persons with MS, YFV may not increase relapse risk., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

This pilot study was designed to compare the levels of interleukin-8 (IL-8), a pro-inflammatory chemokine, in the cerebrospinal fluid (CSF) of patients with Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), non-inflammatory polyneuropathy (PNP), and other non-inflammatory neurological diseases (functional syndrome or migraine). The results show elevated CSF IL-8 levels in GBS compared to the other groups (p < 0.05). IL-8 could be considered a potential biomarker to differentiate GBS from CIDP. This distinction could be relevant in terms of therapeutic decisions and functional prognosis.

Background: Fingolimod is the first approved oral disease-modifying treatment for relapsing-remitting multiple sclerosis. Fingolimod targets lymphocytes, exerting a modulator effect on cell-surface sphingosine-1-phosphate receptors and thus blocking lymphocytes egression from secondary lymphoid organs. Recent reports describe fingolimod cessation being followed by severe or pseudo-tumoral relapse, but it usually does not happen on continuous long-term treatment., Case Presentation: Here we present the case of a patient on continuous long-term fingolimod treatment who presented with fulminant atypical multifocal relapse involving over 30 new and active lesions., Conclusion: This case is unique since this fulminant multifocal relapse occurred in a patient with grade 3 lymphopenia and irreproachable adherence. This observation should be known as a possible side effect of fingolimod treatment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Autoimmune encephalitis (AE) refers to a central nervous system (CNS) antibody-mediated entity characterized by a rapid onset behavioural and cognitive decline that can be associated with movement disorders, epileptic and dysautonomic features. Interestingly, it is thought to be as common as its infectious disease counterpart and can share some clinical, radiological, and laboratory findings., Objectives: The aim is to describe the main clinical features of AE caused by antibodies targeting cell-surface neuronal agents and the diagnostic means to identify them. Paraneoplastic syndromes, associated with intracellular antibodies, will not be tackled in this review., Sources: PubMed/MEDLINE were the sources., Content: According to a recent population-based study, autoimmunity is one of the most frequent cause of encephalitis after infectious agents. Its diagnosis lies upon 'classic' clinical features, which are dominated by neuropsychiatric symptoms and epileptic seizures. Cerebral spinal fluid (CSF) and serum autoantibody testing can confirm AE. Complementary examination with magnetic resonance imaging (MRI) and electroencephalogram (EEG) may be helpful for excluding other causes and managing seizures. In addition, exclusion of infectious and other origins must be considered., Implications: AE misdiagnosis can lead to a delay in treatment onset and, thus, clinical worsening. In this sense, identifying the causative agent is of utmost importance. However, the absence of CSF or serum antibody detection does not exclude the diagnosis of AE. Despite extensive testing, many encephalitis cases remain of unknown origin. It is obvious that some autoantibodies have not yet been identified in AE. Since radiological and biological examinations are not always contributive, early symptom recognition might help to hasten the diagnostic process., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We report the case of a patient affected by systemic sclerosis (SSc) who developed autoimmune limbic encephalitis, which improved under immunosuppressant agents and high-dose intravenous immunoglobulins. In our patient the autoimmune encephalitis occurred during apparently quiescent SSc, though concomitantly with novel arthritis. Moreover, our patient showed auto-antibodies directed against SSA antigen but the panel of auto-antibodies associated with autoimmune encephalitis was negative. We discuss the potential for immunopathogenic inflammatory events affecting the central nervous system in SSc then favoring the occurrence of autoimmune encephalitic disorders. The possibility of a "neuro-scleroderma" may have important consequences in terms of therapeutic approaches., (Copyright © 2018. Published by Elsevier B.V.)

Evoked potentials (EPs) are a powerful and cost-effective tool for evaluating the integrity and function of the central nervous system. Although imaging techniques, such as MRI, have recently become increasingly important in the diagnosis of neurological diseases, over the past 30 years, many neurologists have continued to employ EPs in specific clinical applications. This review presents an overview of the recent evolution of 'classical' clinical applications of EPs in terms of early diagnosis and disease monitoring and is an extension of a previous review published in this journal in 2005 by Walsh and collaborators. We also provide an update on emerging EPs based on gustatory, olfactory and pain stimulation that may be used as clinically relevant markers of neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and cortical or peripheral impaired pain perception. EPs based on multichannel electroencephalography recordings, known as high-density EPs, help to better differentiate between healthy subjects and patients and, moreover, they provide valuable spatial information regarding the site of the lesion. EPs are reliable disease-progression biomarkers of several neurological diseases, such as multiple sclerosis and other demyelinating disorders. Overall, EPs are excellent neurophysiological tools that will expand standard clinical practice in modern neurology., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

A first seizure is a life-changing event with physical and psychological consequences. We aimed to assess the role of early comprehensive patient care after a first unprovoked seizure to improve diagnostic accuracy and follow-up adherence. From April 2011 to March 2012, patients presenting a first unprovoked epileptic seizure received standard patient care (SPC), i.e., a consultation in the ED, an EEG and a CT scan. The patients were notified of the follow-ups. We compared this protocol to subsequently acquired "early comprehensive patient care" (ECPC), which included a consultation by an epileptologist in the emergency department (ED), a routine or long-term monitoring electroencephalogram (LTM-EEG), magnetic resonance imaging and three follow-up consultations (3 weeks, 3 months, 12 months). 183 patients were included (113 ECPC, 70 SPC). LTM-EEG and MRI were performed in 51 and 85 %, respectively, of the patients in the ECPC group vs in 7 and 52 % of the patients in the SPC group (p < 0.001). A final diagnosis was obtained in 64 vs 43 % of the patients in the ECPC vs SPC group (p < 0.01). Patient attendance at 3-month was 84 % in the ECPC group vs 44 % in the SPC group (p < 0.001). At 12-month follow-up, the delay until the first recurrence was longer in the ECPC group (p = 0.008). An early epileptologist-driven protocol is associated with clinical benefit in terms of diagnostic accuracy, follow-up adherence and recurrence. This study highlights the need for epilepsy experts in the early assessment of a first epileptic seizure, starting already in the ED.

Despite intensive research activity leading to many important discoveries, the pathophysiological mechanisms underlying seizures and epilepsy remain poorly understood. An important number of specific gene defects have been related to various forms of epilepsies, and autoimmunity and epilepsy have been associated for a long time. Certain central nervous system proteins have been involved in epilepsy or acute neurological diseases with seizures either due to underlying gene defects or immune dysfunction. Here, we focus on 2 of them that have been the object of particular attention and in-depth research over the past years: the N-methyl-D-aspartate receptor and the leucin-rich glioma-inactivated protein 1 (LGI1). We also describe illustrative examples of situations in which genetics and immunology meet in the complex pathways that underlie seizures and epilepsy.

Objective: Preoperative workup aims at localizing the epileptogenic focus to achieve postoperative seizure-freedom. We studied the predictive value of non-invasive techniques, i.e. structural magnetic resonance imaging [MRI], high-density electric source imaging [HD-ESI] and metabolic imaging (positron emission tomography [PET]; single-photon emission computed tomography [SPECT]), in surgically treated patients., Methods: A prospective study of 190 epileptic operated patients, with >12 months follow-up and analyzed with state-of-the-art algorithms. 58 patients underwent all techniques. We computed sensitivity, specificity, predictive value and diagnostic odds ratio (OR) in relation to postoperative outcome., Results: Of 190 patients, 148 (77.9%) were seizure-free at follow-up. Resection of the epileptogenic focus was associated with favorable postsurgical outcome (p<0.05). Among 58 patients who underwent all tests, only MRI and HD-ESI were favorable outcome predictors (MRI: OR 10.9, p=0.004; HD-ESI: OR 13.1, p=0.004). Patients with concordant structural MRI and HD-ESI results had 92.3% (24/26) probability of favorable outcome. When both results were negative, probability was 0% (0/5); and when they disagreed, it was 63.0% (17/27)., Conclusions: Combination of MRI and HD-ESI offered the highest predictive value for postoperative seizure-freedom., Significance: This finding highlights the added value of HD-ESI in the presurgical workup, in particular in combination with an informative MRI., (Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background/aims: The monitoring of interictal epileptiform discharge rates (IEDRs) all along anterior temporal lobe resections (ATLRs) has never been reported. Here the effect of ATLR on continuous IEDR monitoring is described., Methods: IEDRs computed automatically during entire interventions were recorded in 34 patients (38.2%, 13/34 depth; 61.8%, 21/34 scalp electrodes only). Monitorings were invalidated when burst suppression occurred or if initial IEDRs were <5., Results: Monitoring was successful for 69.2% (9/13) of the patients with depth recordings and for 4.8% (1/21) of the patients with scalp recordings. Burst suppressions precluded it in 30.8% (4/13) of the depth and in 57.1% (12/21) of the scalp recordings. Initial IEDRs were <5 for 38.1% (8/21) of the scalp recordings. Significant IEDR decreases were observed in 8/10 patients with successful monitoring. These decreases started with resection of the superior temporal gyrus. IEDRs decreased further with amygdalohippocampectomy in 3/5 patients. At the 12-month follow-up, all patients with IEDR decreases remained seizure free; both patients without did not., Conclusion: IEDR monitoring was possible with depth, but not with scalp electrodes. IEDR decreases started with resection of the superior temporal gyrus. A larger patient cohort is necessary to confirm the high predictive values of IEDR monitoring that could become a tool for surgery customization., (© 2016 S. Karger AG, Basel.)

Objective: We investigated the contribution of electrocortical stimulation (ECS), induced high gamma electrocorticography (hgECoG) and functional magnetic resonance imaging (fMRI) for the localization of somatosensory and language cortex., Methods: 23 Epileptic patients with subdural electrodes underwent a protocol of somatosensory stimulation and/or an auditory semantic decision task. 14 Patients did the same protocol with fMRI prior to implantation., Results: ECS resulted in the identification of thumb somatosensory cortex in 12/16 patients. Taking ECS as a gold standard, hgECoG and fMRI identified 53.6/33% of true positive and 4/12% of false positive contacts, respectively. The hgECoG false positive sites were all found in the hand area of the post-central gyrus. ECS localized language-related sites in 7/12 patients with hgECoG and fMRI showing 50/64% of true positive and 8/23% of false positive contacts, respectively. All but one of the hgECoG/fMRI false positive contacts were located in plausible language areas. Four patients showed post-surgical impairments: the resection included the sites positively indicated by ECS, hgECoG and fMRI in 3 patients and a positive hgECoG site in one patient., Conclusions: HgECoG and fMRI provide additional localization information in patients who cannot sufficiently collaborate during ECS., Significance: HgECoG and fMRI make the cortical mapping procedure more flexible not only by identifying priority cortical sites for ECS or when ECS is not feasible, but also when ECS does not provide any result., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Resection of abnormal brain tissue lying near the sensorimotor cortex entails precise localization of the central sulcus. Mapping of this area is achieved by applying invasive direct cortical electrical stimulation. However, noninvasive methods, particularly functional magnetic resonance imaging (fMRI), are also used. As a supplement to fMRI, localization of somatosensory-evoked potentials (SEPs) recorded with an electroencephalogram (EEG) has been proposed, but has not found its place in clinical practice., Objective: To assess localization accuracy of the hand somatosensory cortex with SEP source imaging., Methods: We applied electrical source imaging in 49 subjects, recorded with high-density EEG (256 channels). We compared it with fMRI in 18 participants and with direct cortical electrical stimulation in 6 epileptic patients., Results: Comparison of SEP source imaging with fMRI indicated differences of 3 to 8 mm, with the exception of the mesial-distal orientation, where variances of up to 20 mm were found. This discrepancy is explained by the fact that the source maximum of the first SEP peak is localized deep in the central sulcus (area 3b), where information initially arrives. Conversely, fMRI showed maximal signal change on the lateral surface of the postcentral gyrus (area 1), where sensory information is integrated later in time. Electrical source imaging and fMRI showed mean Euclidean distances of 13 and 14 mm, respectively, from the contacts where electrocorticography elicited sensory phenomena of the contralateral upper limb., Conclusion: SEP source imaging, based on high-density EEG, reliably identifies the depth of the central sulcus. Moreover, it is a simple, flexible, and relatively inexpensive alternative to fMRI.

Purpose: Patients with tuberous sclerosis complex (TSC) often suffer from medically refractory epilepsy. Despite the multifocality of the disease, resection of the most epileptogenic tuber can lead to major improvement of seizure control. Therefore, non-invasive imaging methods are needed for detecting epileptogenic sources. We assessed the utility of electric source imaging (ESI) in the presurgical work-up of TSC patients and its combination with Positron Emission Tomography (PET) and ictal/interictal Single Photon Emission Computed Tomography (SISCOM)., Methods: Thirteen patients underwent high density ESI (8/13) and/or low density ESI (13/13). We investigated the concordance between ESI, PET, SISCOM and the resection area in the 11 operated patients (nine seizure-free)., Results: High resolution ESI was partially or completely concordant with the resected area in 5/5 seizure free patients. Low resolution ESI was partially or completely concordant in 7/9 seizure free patients. PET and SPECT were concordant (partially or completely) in 8/9 and 6/9 cases, respectively. We found multifocal ESI sources in 2/9 seizure free patients, marked multifocal PET hypometabolism in 3/9 and multifocal SISCOM in 4/9. The region of concordant ESI and PET accurately predicted the dominant epileptogenic source in 6/9 patients. The same was true for concordant ESI and SISCOM in 4/9 patients, whereas the coregistration of only PET and SISCOM was insufficient in 3/9 successfully operated cases. The combination of all three imaging modalities could successfully identify the resection area in all but one patient with a favorable post-operation outcome., Conclusion: ESI is an important tool for the pre-surgical evaluation of TSC patients. It complements PET and SPECT results and can improve the management of candidates for surgery when integrated with electro-clinical information., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Traditionally, subcortical structures such as the cerebellum are supposed to exert a modulatory effect on epileptic seizures, rather than being the primary seizure generator. We report a 14-month old girl presenting, since birth, with seizures symptomatic of a right cerebellar dysplasia, manifested as paroxystic contralateral hemifacial spasm and ipsilateral facial weakness. Multimodal imaging was used to investigate both anatomical landmarks related to the cerebellar lesion and mechanisms underlying seizure generation. Electric source imaging (ESI) supported the hypothesis of a right cerebellar epileptogenic generator in concordance with nuclear imaging findings; subsequently validated by intra-operative intralesional recordings. Diffusion spectrum imaging-related tractography (DSI) showed severe cerebellar structural abnormalities confirmed by histological examination. We suggest that hemispheric cerebellar lesions in cases like this are likely to cause epilepsy via an effect on the facial nuclei through ipsilateral and contralateral aberrant connections., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Stroke lesions induce not only loss of local neural function, but disruptions in spatially distributed areas. However, it is unknown whether they affect the synchrony of electrical oscillations in neural networks and if changes in network coherence are associated with neurological deficits. This study assessed these questions in a population of patients with subacute, unilateral, ischemic stroke. Spontaneous cortical oscillations were reconstructed from high-resolution electroencephalograms (EEG) with adaptive spatial filters. Maps of functional connectivity (FC) between brain areas were created and correlated with patient performance in motor and cognitive scores. In comparison to age matched healthy controls, stroke patients showed a selective disruption of FC in the alpha frequency range. The spatial distribution of alpha band FC reflected the pattern of motor and cognitive deficits of the individual patient: network nodes that participate normally in the affected functions showed local decreases in FC with the rest of the brain. Interregional FC in the alpha band, but not in delta, theta, or beta frequencies, was highly correlated with motor and cognitive performance. In contrast, FC between contralesional areas and the rest of the brain was negatively associated with patient performance. Alpha oscillation synchrony at rest is a unique and specific marker of network function and linearly associated with behavioral performance. Maps of alpha synchrony computed from a single resting-state EEG recording provide a robust and convenient window into the functionality and organization of cortical networks with numerous potential applications., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Electroencephalography is mandatory to determine the epilepsy syndrome. However, for the precise localization of the irritative zone in patients with focal epilepsy, costly and sometimes cumbersome imaging techniques are used. Recent small studies using electric source imaging suggest that electroencephalography itself could be used to localize the focus. However, a large prospective validation study is missing. This study presents a cohort of 152 operated patients where electric source imaging was applied as part of the pre-surgical work-up allowing a comparison with the results from other methods. Patients (n = 152) with >1 year postoperative follow-up were studied prospectively. The sensitivity and specificity of each imaging method was defined by comparing the localization of the source maximum with the resected zone and surgical outcome. Electric source imaging had a sensitivity of 84% and a specificity of 88% if the electroencephalogram was recorded with a large number of electrodes (128-256 channels) and the individual magnetic resonance image was used as head model. These values compared favourably with those of structural magnetic resonance imaging (76% sensitivity, 53% specificity), positron emission tomography (69% sensitivity, 44% specificity) and ictal/interictal single-photon emission-computed tomography (58% sensitivity, 47% specificity). The sensitivity and specificity of electric source imaging decreased to 57% and 59%, respectively, with low number of electrodes (<32 channels) and a template head model. This study demonstrated the validity and clinical utility of electric source imaging in a large prospective study. Given the low cost and high flexibility of electroencephalographic systems even with high channel counts, we conclude that electric source imaging is a highly valuable tool in pre-surgical epilepsy evaluation.

Although brain structures involved in central nervous olfactory processing in humans have been well identified with functional neuroimaging, little is known about the temporal sequence of their activation. We recorded olfactory event-related potentials (ERP) to H(2)S stimuli presented to the left and right nostril in 12 healthy subjects. Topographic and source analysis identified four distinct processing steps between 200 and 1000 ms. Activation started ipsilateral to the stimulated nostril in the mesial and lateral temporal cortex (amygdala, parahippocampal gyrus, superior temporal gyrus, insula). Subsequently, the corresponding structures on the contralateral side became involved, followed by frontal structures at the end of the activation period. Thus, based on EEG-related data, current results suggest that olfactory information in humans is processed first ipsilaterally to the stimulated nostril and then activates the major relays in olfactory information processing in both hemispheres. Most importantly, the currently described techniques allow the investigation of the spatial processing of olfactory information at a high temporal resolution., (Copyright 2010 IBRO. All rights reserved.)

Purpose: Patients with magnetic resonance (MR)-negative focal epilepsy (MRN-E) have less favorable surgical outcomes (between 40% and 70%) compared to those in whom an MRI lesion guides the site of surgical intervention (60-90%). Patients with extratemporal MRN-E have the worst outcome (around 50% chance of seizure freedom). We studied whether electroencephalography (EEG) source imaging (ESI) of interictal epileptic activity can contribute to the identification of the epileptic focus in patients with normal MRI., Methods: We carried out ESI in 10 operated patients with nonlesional MRI and a postsurgical follow-up of at least 1 year. Five of the 10 patients had extratemporal lobe epilepsy. Evaluation comprised surface and intracranial EEG monitoring of ictal and interictal events, structural MRI, [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET), ictal and interictal perfusion single photon emission computed tomography (SPECT) scans. Eight of the 10 patients also underwent intracranial monitoring., Results: ESI correctly localized the epileptic focus within the resection margins in 8 of 10 patients, 9 of whom experienced favorable postsurgical outcomes., Discussion: The results highlight the diagnostic value of ESI and encourage broadening its application to patients with MRN-E. If the surface EEG contains fairly localized spikes, ESI contributes to the presurgical decision process.

Objective: To test the accuracy of EEG source imaging in epilepsy patients with large cerebral lesions. It is hypothesized that lesions are most likely to change conductivity properties and to significantly impair the accuracy of electromagnetic source imaging (ESI) based on the EEG. This has, however, not been tested in patients' EEG., Methods: Fourteen patients with focal epilepsy and large cerebral lesions underwent high-resolution (128-256 channels) interictal EEG recordings. Thirteen patients were operated, leading to seizure freedom in 12. The spike sources were localized with a distributed linear inverse solution (LAURA) and compared to the post-operative MRI or the results of other invasive or non-invasive exams., Results: In 12 patients ESI indicated the maximum source of the epileptic activity to be located within the epileptogenic zone (85%). One of the remaining cases was not seizure free after surgery. According to the ESI result, however, the focus was incompletely removed., Conclusion: High resolution ESI constrained to the individual anatomy identifies the epileptogenic focus in patients with volume relevant brain lesions with excellent accuracy, comparable to that of other non-invasive methods., Significance: Our results are of particular clinical importance, as they show that ESI can be extended to patients with large inhomogeneous lesions.

Human functional imaging studies are increasingly focusing on the identification of large-scale neuronal networks, their temporal properties, their development, and their plasticity and recovery after brain lesions. A method targeting large-scale networks in rodents would open the possibility to investigate their neuronal and molecular basis in detail. We here present a method to study such networks in mice with minimal invasiveness, based on the simultaneous recording of epicranial EEG from 32 electrodes regularly distributed over the head surface. Spatiotemporal analysis of the electrical potential maps similar to human EEG imaging studies allows quantifying the dynamics of the global neuronal activation with sub-millisecond resolution. We tested the feasibility, stability and reproducibility of the method by recording the electrical activity evoked by mechanical stimulation of the mystacial vibrissae. We found a series of potential maps with different spatial configurations that suggested the activation of a large-scale network with generators in several somatosensory and motor areas of both hemispheres. The spatiotemporal activation pattern was stable both across mice and in the same mouse across time. We also performed 16-channel intracortical recordings of the local field potential across cortical layers in different brain areas and found tight spatiotemporal concordance with the generators estimated from the epicranial maps. Epicranial EEG mapping thus allows assessing sensory processing by large-scale neuronal networks in living mice with minimal invasiveness, complementing existing approaches to study the neurophysiological mechanisms of interaction within the network in detail and to characterize their developmental, experience-dependent and lesion-induced plasticity in normal and transgenic animals.

The aim of this study was to evaluate the capability of Levamisole to stimulate delayed tuberculin cutaneous hypersensitivity in malnourished and eutrophic infants who in spite of having been given BCG at birth, repeatedly failed to react to Mantoux intradermo-reaction. Leucocyte, lymphocyte and RFC counts, and blast cell transformation tests with PHA, BCG and AT were carried out at the beginning of the study, and every 4 weeks over a 4 month period. Tuberculin conversion occurred in 60% of the well-nourished and in 58% of the malnourished infants. Between the second to fourth months of treatment, 64% of the cases of PCM reached normal nutritional conditions, while 18% showed only fair recovery. The restoration of BCG-BCTT and AT-BCTT occurred before or during the cutaneous tuberculin reaction in both malnourished and well-nourished infants. Confirmation of the new chemical agent as being directly responsible for tuberculin conversion is difficult with the methods currently available. The positive reactions may be a consequence of the improvement observed in the weight-height parameters.

Three groups of infants were formed according to the type of feeding: I-breast milk from mothers without any kind of elimination diet, II-cow's milk-based formula, and III-breast milk till 2 months of age and after that, cow's milk formula. CD4 and CD8 were determined by monoclonal antibodies technique, IgE by ELISA and prick test with either intact or enzymatically digested cow's milk antigens. The average age of onset of the atopic disease in the first group was 2m 10d +/- 15d, in the second: 3m 4d +/- 14d, and in the third: 2m 11d +/- 1m 18d. The number of CD4 in group II was the lowest while in group III was the highest. CD8 value in the second group was higher than in the others. Ratio between CD4 and CD8 in cow's milk-fed infants was the lowest. Total serum IgE level in group II was the lowest although the mean values of the three groups were significantly increased. Prick tests, with at least one antigen, were positive in 75%, 50% and 48% in group I, II and III respectively. It is suggested that the behaviour of the parameters studied would be related to the dose of cow's milk proteins received through breast milk in breast-fed infants; to the relatively great amount of cow's milk antigens and to the lack of breast-feeding in infants fed on cow's milk formula; and to the interaction of such factors in infants fed with both cow's milk and breast milk.

1. Sera of 22 children with cow's milk clinical hypersensitivity were studied to demonstrate the presence of substances immunologically related with milk. They were compared with 23 controls. The infants of both groups were feed with bovine milk. The immunogenic capacity of cow's milk and their major proteins were experimentally investigated. 2. Specific rabbit antisera were obtained by injection of antigens with incomplete Freund adjuvant. Double difussion gel, passive hemagglutination and ultramicromethod for the determination of antigen antibody precipitated were performed. 3. Immunogenicity was proved by precipitation and hemagglutination methods. by precipitation cow's milk antigens were present in 5 of 22 sera of antigenic patients, in 3 of them ALA antigens were present and in only 1 of them, caseina were present. By hemagglutination, 12 of 22 allergic infants showed ALA and BLG and 11 caseine (C). In 2 of 7 controls, beta lactoglobuline (BLG) was present and in an other one C. It was possible to detect incomplete antigens related with ALA, BLG, and C in allergic infants as well as controls. A significative difference was found for BLG (P less than 0.01) and it was highest (P less than 0.003) in infants with protein calorie malnutrition. 4. It is concluded that sensitization depends not only on stimulation of incomplete or complete antigens, as were observed in this study but on the host's capacity to form citrotropic antibody in humoral hypersensitivity or to stimulate lymphocytes in cellular immunity field.