Neuronal nicotinic acetylcholine receptor antibodies in autoimmune central nervous system disorders

BackgroundNeuronal nicotinic acetylcholine receptors (nAChRs) are abundant in the central nervous system (CNS), playing critical roles in brain function. Antigenicity of nAChRs has been well demonstrated with antibodies to ganglionic AChR subtypes (i.e., subunit α3 of α3β4-nAChR) and muscle AChR autoantibodies, thus making nAChRs candidate autoantigens in autoimmune CNS disorders. Antibodies to several membrane receptors, like NMDAR, have been identified in autoimmune encephalitis syndromes (AES), but many AES patients have yet to be unidentified for autoantibodies. This study aimed to develop of a cell-based assay (CBA) that selectively detects potentially pathogenic antibodies to subunits of the major nAChR subtypes (α4β2- and α7-nAChRs) and its use for the identification of such antibodies in “orphan” AES cases.MethodsThe study involved screening of sera derived from 1752 patients from Greece, Turkey and Italy, who requested testing for AES-associated antibodies, and from 1203 “control” patients with other neuropsychiatric diseases, from the same countries or from Germany. A sensitive live-CBA with α4β2-or α7-nAChR–transfected cells was developed to detect antibodies against extracellular domains of nAChR major subunits. Flow cytometry (FACS) was performed to confirm the CBA findings and indirect immunohistochemistry (IHC) to investigate serum autoantibodies’ binding to rat brain tissue.ResultsThree patients were found to be positive for serum antibodies against nAChR α4 subunit by CBA and the presence of the specific antibodies was quantitatively confirmed by FACS. We detected specific binding of patient‐derived serum anti‐nAChR α4 subunit antibodies to rat cerebellum and hippocampus tissue. No serum antibodies bound to the α7-nAChR-transfected or control-transfected cells, and no control serum antibodies bound to the transfected cells. All patients positive for serum anti‐nAChRs α4 subunit antibodies were negative for other AES-associated antibodies. All three of the anti‐nAChR α4 subunit serum antibody-positive patients fall into the AES spectrum, with one having Rasmussen encephalitis, another autoimmune meningoencephalomyelitis and another being diagnosed with possible autoimmune encephalitis.ConclusionThis study lends credence to the hypothesis that the major nAChR subunits are autoimmune targets in some cases of AES and establishes a sensitive live-CBA for the identification of such patients

Study of imaging, hormonological and neurophychology

Introduction: The basic aim during the monitoring of the epileptic patients is controling their seizures and minimizing the adverse efffects of the anti-epileptic drugs (AED). As a result of this practice is that less obvious consequences of epilepsy or AED are not being perceptible. The cognitive functions and the hormonal status of the patients are two parameters that can be affected by the nature of epilepsy and by the AED and they can affect the quality of life of the patients. Aim: The basic aim of the study was the evaluation of patients using neuropsychological tests and screening their levels of sex-hormones in order to investigate whether these can be additional factors that can aid at the classification of the patients, that can affect the quality of life and that possibly can help in better screening of chronic epileptic patients. Patients-Methods: For the evaluation of sex-hormones 78 chronic epileptic patients (38 men and 40 women) were included in the study. The patients were divided to subgroups according to their epileptic syndromes based on ILAE criteria. The clinical parameters that were taken into consideration were the duration of the disease, the seizure frequency and the anti-epileptic treatment. The hormones LH, FSH, PRL, T, Pg, E2 were evaluated using the IRMA method. The hormone levels were compared with age and sex-matched controls (n=42, 11 men and 32 women). For the neuropsychological assessment 40 patients were included in the study (20 men and 20 women). The patients were categorized based on their epileptic syndrome. The parameters that were taken into consideration were the duration of the disease, the seizure frequency, the anti-epileptic treatment and the years of education. The levels of AED were within therapeutic limits The patients had IQ<70 and all patients with depression were excluded from the study. The evaluation was performed at the beginning of the study and at 1-year follow-up using the following tests: Rey-Osterrieth Figure Test, Digit Span, WAIS III, Word List Learning Test, Verbal Fluency Test, Trail Making Test, Stroop test. 20 healthy sex, age and education-matched individuals were used as controls. For the statistical analysis SPSS (v.15 and v.17) were used. Values p<0.05 were statistical significant.Εισαγωγή : Βασικός στόχος στην παρακολούθηση των ασθενών με επιληψία είναι η ρύθμιση των κρίσεων με έλεγχο των κύριων ανεπιθύμητων ενεργειών των ΑΕΦ. Αποτέλεσμα αυτής της πρακτικής είναι πολλές φορές οι λιγότερο εμφανείς συνέπειες της επιληψίας ή των ΑΕΦ, να μην γίνονται αντιληπτές. Η γνωστικές λειτουργίες όπως και η ορμονική κατάσταση αυτών των ασθενών είναι δύο παράμετροι που μπορούν να επηρεαστούν από την επιληψία και τα ΑΕΦ και ταυτόχρονα μπορούν να επηρεάσουν την ποιότητα ζωής τους. Σκοπός : Κύριος στόχος ήταν η εκτίμηση αυτών των ασθενών με νευροψυχολογικές δοκιμασίες και με τα επίπεδα των ορμονών φύλου, προκειμένου να διερευνηθεί εάν προκύπτουν επιπλέον στοιχεία σε σχέση με την επιληψία και τα ΑΕΦ που ενισχύουν την ταξινόμηση των ασθενών, επηρεάζουν την ποιότητα ζωής των ασθενών και που πιθανώς βοηθούν στην καλύτερη παρακολούθηση των χρόνιων επιληπτικών ασθενών. Ασθενείς – μέθοδος : Στην εκτίμηση των ορμονών φύλου 78 χρόνιοι ασθενείς με επιληψία (38 άνδρες και 40 γυναίκες) συμπεριλήφθησαν. Σύμφωνα με τα κριτήρια της ILAE διαχωρίστηκαν σε επιληπτικά σύνδρομα. Οι κλινικές παράμετροι της νόσου οι οποίες ελήφθησαν υπόψη ήταν οι εξής : η διάρκεια νόσου, η συχνότητα κρίσεων, η αντιεπιληπτική θεραπεία. Οι LH, FSH, PRL, T, Pg, E2 μετρήθηκαν με τη μέθοδο IRMA.Τα αποτελέσματα των ορμονών συγκρίθηκαν με τα επίπεδα ορμονών υγιών ίδιου φύλου και ηλικίας (n=42, 11 άνδρες και 31 γυναίκες). Στην εκτίμηση της νευροψυχολογικής κατάστασης 40 ασθενείς συμπεριλήφθησαν (20 άνδρες και 20 γυναίκες). Οι ασθενείς ταξινομήθηκαν σύμφωνα με το επιληπτικό τους σύμδρομο. Οι παράμετροι που ελήφθησαν υπόψη ήταν : η διάρκεια νόσου, η συχνότητα κρίσεων, η αντιεπιληπτική αγωγή, τα χρόνια εκπαίδευσης. Τα επίπεδα των ΑΕΦ ήταν σε θεραπευτικά όρια, οι ασθενείς με IQ ˂ 70 και οι ασθενείς με κατάθλιψη αποκλείστηκαν από τη μελέτη. Η εκτίμηση έγινε στην αρχή της μελέτης και στον πρώτο χρόνο παρακολούθησης με τις εξής δοκιμασίες : Rey-Osterrieth Figure Test, μνημονικό πεδίο ψηφίων (Digit Span, WAIS III), δοκιμασία μάθησης λέξεων (Word List Learning Test), δοκιμασία λεκτικής ροής (Verbal Fluency Test), δοκιμασία οπτικο-νοητικής ιχνηλάτησης (Trail Making Test), Stroop test. Ομάδα ελέγχου αποτέλεσαν 20 υγιείς ίδιας ηλικίας, φύλου, εκπαιδευτικού επιπέδου με τους ασθενείς

EEG-Neurofeedback as a Potential Therapeutic Approach for Cognitive Deficits in Patients with Dementia, Multiple Sclerosis, Stroke and Traumatic Brain Injury

Memory deficits are common in patients with dementia, such as Alzheimer’s disease, but also in patients with other neurological and psychiatric disorders, such as brain injury, multiple sclerosis, ischemic stroke and schizophrenia. Memory loss affects patients’ functionality and, by extension, their quality of life. Non-invasive brain training methods, such as EEG neurofeedback, are used to address cognitive deficits and behavioral changes in dementia and other neurological disorders by training patients to alter their brain activity via operant activity. In this review paper, we analyze various protocols of EEG neurofeedback in memory rehabilitation in patients with dementia, multiple sclerosis, strokes and traumatic brain injury. The results from the studies show the effectiveness of the ΕΕG-NFB method in improving at least one cognitive domain, regardless of the number of sessions or the type of protocol applied. In future research, it is important to address methodological weaknesses in the application of the method, its long-term effects as well as ethical issues

EEG-Neurofeedback as a Potential Therapeutic Approach for Cognitive Deficits in Patients with Dementia, Multiple Sclerosis, Stroke and Traumatic Brain Injury

Memory deficits are common in patients with dementia, such as Alzheimer&rsquo;s disease, but also in patients with other neurological and psychiatric disorders, such as brain injury, multiple sclerosis, ischemic stroke and schizophrenia. Memory loss affects patients&rsquo; functionality and, by extension, their quality of life. Non-invasive brain training methods, such as EEG neurofeedback, are used to address cognitive deficits and behavioral changes in dementia and other neurological disorders by training patients to alter their brain activity via operant activity. In this review paper, we analyze various protocols of EEG neurofeedback in memory rehabilitation in patients with dementia, multiple sclerosis, strokes and traumatic brain injury. The results from the studies show the effectiveness of the &Epsilon;&Epsilon;G-NFB method in improving at least one cognitive domain, regardless of the number of sessions or the type of protocol applied. In future research, it is important to address methodological weaknesses in the application of the method, its long-term effects as well as ethical issues

Acute Finger Paralysis: A Case Report of Cortical Ischemic Stroke

Somatotopic distribution of motor cortex and sensory fibers is theoretically fully understood. We present a case of stroke, mimicking peripheral palsy, with finger paralysis attributed to cortical lesion. The patient’s brain MRI may be useful to further understand the somatotopic representation of fingers in precentral and postcentral gyrus

Aγγειῒτιδα Churg-Strauss σε 64χρονη γυναίκα με διαταραχή βάδισης

Peripheral neuropathy is often a feature of systemic diseases. We report a case of a 64-year-old woman with gait difficulty due to multifocal sensorimotor polyneuropathy which was diagnosed as Churg-Strauss syndrome and presented clinical improvement after oral prednisolone administration. The clinical suspicion of this condition is crucial to early and correct diagnosis.Η περιφερική πολυνευροπάθεια αποτελεί συχνά εύρημα συστηματικών παθήσεων. Παρουσιάζουμε περιστατικό μιας 64χρονης γυναίκας με διαταραχή βάδισης λόγω πολυεστιακής αισθητικοκινητικής πολυνευροπάθειας που διεγνώσθη ως σύνδρομο Churg-Strauss και παρουσίασε βελτίωση μετά την από του στόματος χορήγηση πρεδνιζολόνης. Η κλινική υποψία του συνδρόμου αυτού είναι κρίσιμη για την έγκαιρη διάγνωση και την σωστή θεραπεία του

Estimating Everyday Neuropsychological Functioning in Multiple Sclerosis: Reliability and Validity of the Greek Multiple Sclerosis Neuropsychological Questionnaire

The Multiple Sclerosis Neuropsychological Questionnaire is a brief screening questionnaire for the assessment of everyday neuropsychological competence of patients with Multiple Sclerosis. The aim of the present study was to examine psychometric properties of the Greek version of the instrument. One hundred and three MS patients and 60 informants participated in the present study and completed the questionnaire. From the initial patient sample, 51 participants completed broadly used neuropsychological tests and measures estimating cognitive failures and depression. Moreover, after a six-month interval the MSNQ was administered to 58 patients from the initial sample in order to explore test-retest reliability. Cronbach's α was 0.92 and 0.93 for patient and informant forms, respectively. The patient form was correlated significantly with measures of cognitive failures and depression. Low correlations were found between the informant form and performance on cognitive tests. In regard to the patient form, significant correlation was observed between repeated administrations and, psychometrically, the three-factor structure was preferable than the one-factor structure. The present study confirms the already established pattern of correlations among the two MSNQ forms, neuropsychological test performance and depression measurements. Additional research is needed in order to define a cut-off score for the MSNQ-I providing further information about the diagnostic interpretability of the instrument

Cognitive Impairment in MRI-Negative Epilepsy: Relationship between Neurophysiological and Neuropsychological Measures

Background: Epileptic patients frequently encounter cognitive impairment. Functions that are mostly affected involve memory, attention, and executive function; however, this is mainly dependent on the location of the epileptic activity. The aim of the present study is to assess cognitive functions in MRI-negative epilepsy patients by means of neurophysiological and neuropsychological measures, as well as study the concept of transient cognitive impairment in patients with epileptiform discharges during EEG acquisition. Methods: The patients were enrolled from an outpatient Epilepsy/Clinical Neurophysiology clinic over a time period of 6 months. The study sample comprised 20 MRI-negative epilepsy patients (mean age ± standard deviation (SD), 30.3 ± 12.56 years; age range, 16–60 years; average disease duration, 13.95 years) and 10 age-matched controls (mean age ± SD, 24.22 ± 15.39 years), who were also education-matched (p > 0.05). Patients with epileptogenic lesions were excluded from the study. Informed consent was obtained from all subjects involved in the study. Auditory ERPs and the cognitive screening tool EpiTrack were administered to all subjects. Results: Latencies of P300 and slow waves were prolonged in patients compared to controls (p < 0.05). The ASM load and patients’ performance in the EpiTrack maze subtest were the most significant predictors of P300 latency. A decline in the memory, attention, and speed of information processing was observed in patients with cryptogenic epilepsy compared to age-matched controls, as reflected by P300 latency and EpiTrack scores

EEG Window Length Evaluation for the Detection of Alzheimer’s Disease over Different Brain Regions

Alzheimer&#8217;s Disease (AD) is a neurogenerative disorder and the most common type of dementia with a rapidly increasing world prevalence. In this paper, the ability of several statistical and spectral features to detect AD from electroencephalographic (EEG) recordings is evaluated. For this purpose, clinical EEG recordings from 14 patients with AD (8 with mild AD and 6 with moderate AD) and 10 healthy, age-matched individuals are analyzed. The EEG signals are initially segmented in nonoverlapping epochs of different lengths ranging from 5 s to 12 s. Then, a group of statistical and spectral features calculated for each EEG rhythm (&#948;, &#952;, &#945;, &#946;, and &#947;) are extracted, forming the feature vector that trained and tested a Random Forests classifier. Six classification problems are addressed, including the discrimination from whole-brain dynamics and separately from specific brain regions in order to highlight any alterations of the cortical regions. The results indicated a high accuracy ranging from 88.79% to 96.78% for whole-brain classification. Also, the classification accuracy was higher at the posterior and central regions than at the frontal area and the right side of temporal lobe for all classification problems

A Dataset of Scalp EEG Recordings of Alzheimer’s Disease, Frontotemporal Dementia and Healthy Subjects from Routine EEG

Recently, there has been a growing research interest in utilizing the electroencephalogram (EEG) as a non-invasive diagnostic tool for neurodegenerative diseases. This article provides a detailed description of a resting-state EEG dataset of individuals with Alzheimer’s disease and frontotemporal dementia, and healthy controls. The dataset was collected using a clinical EEG system with 19 scalp electrodes while participants were in a resting state with their eyes closed. The data collection process included rigorous quality control measures to ensure data accuracy and consistency. The dataset contains recordings of 36 Alzheimer’s patients, 23 frontotemporal dementia patients, and 29 healthy age-matched subjects. For each subject, the Mini-Mental State Examination score is reported. A monopolar montage was used to collect the signals. A raw and preprocessed EEG is included in the standard BIDS format. For the preprocessed signals, established methods such as artifact subspace reconstruction and an independent component analysis have been employed for denoising. The dataset has significant reuse potential since Alzheimer’s EEG Machine Learning studies are increasing in popularity and there is a lack of publicly available EEG datasets. The resting-state EEG data can be used to explore alterations in brain activity and connectivity in these conditions, and to develop new diagnostic and treatment approaches. Additionally, the dataset can be used to compare EEG characteristics between different types of dementia, which could provide insights into the underlying mechanisms of these conditions