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Abstract The progression of Parkinson’s disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts worldwide, to identify stage-specific profiles of white matter differences. Diffusion-weighted MRI data from 1654 participants diagnosed with PD (age: 20–89 years; 33% female) and 885 controls (age: 19–84 years; 47% female) were analyzed using the ENIGMA-DTI protocol to evaluate white matter microstructure. Skeletonized maps of fractional anisotropy (FA) and mean diffusivity (MD) were compared across Hoehn and Yahr (HY) disease groups and controls to reveal the profile of white matter alterations at different stages. We found an enhanced, more widespread pattern of microstructural alterations with each stage of PD, with eventually lower FA and higher MD in almost all regions of interest: Cohen’s d effect sizes reached d = −1.01 for FA differences in the fornix at PD HY Stage 4/5. The early PD signature in HY stage 1 included higher FA and lower MD across the entire white matter skeleton, in a direction opposite to that typical of other neurodegenerative diseases. FA and MD were associated with motor and non-motor clinical dysfunction. While overridden by degenerative changes in the later stages of PD, early PD is associated with paradoxically higher FA and lower MD in PD, consistent with early compensatory changes associated with the disorder.

Background Autoimmune encephalitis (AIE) is a group of inflammatory diseases characterized by the presence of antibodies against neuronal and glial antigens, leading to subacute psychiatric symptoms, memory complaints, and movement disorders. The patients are predominantly young, and delays in treatment are associated with worse prognosis.

The treatment of epilepsy has advanced over the past 30 years through the development of new antiseizure medications (ASMs). Unfortunately, not all of them have been approved yet in Brazil, and many are still underused. When comparing new ASMs to older ones, they are generally not more effective in treating epilepsy. However, they offer better tolerability, with fewer interactions and long-term side effects, especially for patients with comorbidities or those requiring polytherapy. Enzyme induction caused by older ASMs is associated with increased cholesterol levels, drug interactions with decreased effects of statins and other cardiovascular medications, anticoagulants, chemotherapy, immunosuppressors, anti-infective agents (including HIV treatment), antidepressants, and contraceptives. Additionally, they can reduce levels of vitamin D and sex hormones, as well as decrease bone density. The increasing concern about these effects during life, especially after prolonged exposure, has led most developed countries to change prescription patterns in favor of new ASMs, particularly levetiracetam and lamotrigine. Both are also considered the safest options for women of childbearing age. Regrettably, the prescription trends in Brazil have remained largely unchanged over time. This can be partially attributed to the slower approval process of ASM and the reluctance of general physicians and neurologists to embrace these new concepts. In this concise review, we highlight the various advantages linked to the new ASM, aiming to promote a shift in the prescription pattern for ASM. The selection of ASM should be customized according to individual characteristics, and practical suggestions for choosing ASMs are provided in this paper.

Abstract Sickle cell disease (SCD) patients are at higher risk of developing silent cerebral infarcts and overt stroke, which may reflect cognitive impairment, functional limitations, and worse quality of life. The cognitive function of Brazilian adult SCD patients (n = 124; 19–70 years; 56 men; 79 SS, 28 SC, 10 S/β0, 7 S/β+) was screened through Montreal Cognitive Assessment (MoCA) and correlated the results with possible predictive factors for test performance, including sociocultural, clinical, laboratory data and brain imaging. The Median MoCA score was 23 (8–30); 70% had a 25‐or‐less score, suggesting some level of cognitive impairment. There were no significant associations between MoCA results and any clinical or laboratory data in SS and SC patients; however, a significant correlation (P = 0.03) with stroke was found in HbS/β‐thalassemic patients. Correlations were further detected according to sociodemographic conditions, such as age (r = −0.316; P

Abstract Background Neuropsychiatric sequelae of COVID-19 have been widely documented in patients with severe neurological symptoms during the chronic or subacute phase of the disease. However, it remains unclear whether subclinical changes in brain metabolism can occur early in the acute phase of the disease. The aim of this study was to identify and quantify changes in brain metabolism in patients hospitalized for acute respiratory syndrome due to COVID-19 with no or mild neurological symptoms. Results Twenty-three non-intubated patients (13 women; mean age 55.5 ± 12.1 years) hospitalized with positive nasopharyngeal swab test (RT-PCR) for COVID-19, requiring supplemental oxygen and no or mild neurological symptoms were studied. Serum C-reactive protein measured at admission ranged from 6.43 to 189.0 mg/L (mean: 96.9 ± 54.2 mg/L). The mean supplemental oxygen demand was 2.9 ± 1.4 L/min. [18F]FDG PET/CT images were acquired with a median of 12 (4–20) days of symptoms. After visual interpretation of the images, semiquantitative analysis of [18F]FDG uptake in multiple brain regions was evaluated using dedicated software and the standard deviation (SD) of brain uptake in each region was automatically calculated in comparison with reference values of a normal database. Evolutionarily ancient structures showed positive SD mean values of [18F]FDG uptake. Lenticular nuclei were bilaterally hypermetabolic (> 2 SD) in 21/23 (91.3%) patients, and thalamus in 16/23 (69.6%), bilaterally in 11/23 (47.8%). About half of patients showed hypermetabolism in brainstems, 40% in hippocampi, and 30% in cerebellums. In contrast, neocortical regions (frontal, parietal, temporal and occipital lobes) presented negative SD mean values of [18F]FDG uptake and hypometabolism (

Abstract Stroke is one of the most common causes of acquired epilepsy, which can also result in disability and increased mortality rates particularly in elderly patients. No preventive treatment for post‐stroke epilepsy is currently available. Development of such treatments has been greatly limited by the lack of biomarkers to reliably identify high‐risk patients. The glymphatic system, including perivascular spaces (PVS), is the brain's waste clearance system, and enlargement or asymmetry of PVS (ePVS) is hypothesized to play a significant role in the pathogenesis of several neurological conditions. In this article, we discuss potential mechanisms for the role of perivascular spaces in the development of post‐stroke epilepsy. Using advanced MR‐imaging techniques, it has been shown that there is asymmetry and impairment of glymphatic function in the setting of ischemic stroke. Furthermore, studies have described a dysfunction of PVS in patients with different focal and generalized epilepsy syndromes. It is thought that inflammatory processes involving PVS and the blood–brain barrier, impairment of waste clearance, and sustained hypertension affecting the glymphatic system during a seizure may play a crucial role in epileptogenesis post‐stroke. We hypothesize that impairment of the glymphatic system and asymmetry and dynamics of ePVS in the course of a stroke contribute to the development of PSE. Automated ePVS detection in stroke patients might thus assist in the identification of high‐risk patients for post‐stroke epilepsy trials. Plain Language Summary Stroke often leads to epilepsy and is one of the main causes of epilepsy in elderly patients, with no preventative treatment available. The brain’s waste removal system, called the glymphatic system which consists of perivascular spaces, may be involved. Enlargement or asymmetry of perivascular spaces could play a role in this and can be visualised with advanced brain imaging after a stroke. Detecting enlarged perivascular spaces in stroke patients could help identify those at risk for post‐stroke epilepsy.

Abstract Although some studies have shown neuroimaging and neuropsychological alterations in post-COVID-19 patients, fewer combined neuroimaging and neuropsychology evaluations of individuals who presented a mild acute infection. Here we investigated cognitive dysfunction and brain changes in a group of mildly infected individuals. We conducted a cross-sectional study of 97 consecutive subjects (median age of 41 years) without current or history of psychiatric symptoms (including anxiety and depression) after a mild infection, with a median of 79 days (and mean of 97 days) after diagnosis of COVID-19. We performed semi-structured interviews, neurological examinations, 3T-MRI scans, and neuropsychological assessments. For MRI analyses, we included a group of non-infected 77 controls. The MRI study included white matter (WM) investigation with diffusion tensor images (DTI) and functional connectivity with resting-state functional MRI (RS-fMRI). The patients reported memory loss (36%), fatigue (31%) and headache (29%). The quantitative analyses confirmed symptoms of fatigue (83% of participants), excessive somnolence (35%), impaired phonemic verbal fluency (21%), impaired verbal categorical fluency (13%) and impaired logical memory immediate recall (16%). The WM analyses with DTI revealed higher axial diffusivity values in post-infected patients compared to controls. Compared to controls, there were no significant differences in the functional connectivity of the posterior cingulum cortex. There were no significant correlations between neuropsychological scores and neuroimaging features (including DTI and RS-fMRI). Our results suggest persistent cognitive impairment and subtle white matter abnormalities in individuals mildly infected without anxiety or depression symptoms. The longitudinal analyses will clarify whether these alterations are temporary or permanent.

RESUMO A Covid-19 é uma doença multissistêmica e consequências funcionais e tardias estão em estudo. Sequelas psicológicas e neurocognitivas podem comprometer a Capacidade para o Trabalho (CT) dos trabalhadores. Objetivou-se investigar a CT de pessoas previamente infectadas pelo Sars-CoV-2, correlacionando-a com avaliação da sonolência, ansiedade, depressão e fadiga. Estudo transversal, com trabalhadores diagnosticados com Covid-19 e em acompanhamento no Serviço de Neurologia da Universidade Estadual de Campinas (Unicamp). Aplicou-se o instrumento Índice de Capacidade para o Trabalho (ICT), um formulário com dados sociodemográficos e ocupacionais, bem como escalas de sonolência, ansiedade, depressão e fadiga. Dos 119 trabalhadores que participaram do estudo, mais da metade apresentaram comprometimento da CT (52,9%). Distúrbio emocional foi o agravo relatado mais frequente (31,9%). A regressão logística múltipla mostrou que a interação entre ansiedade e sonolência esteve associada ao comprometimento da CT (OR=4,50 com p=0,002). Ansiedade e sonolência foram alterações tardias da Covid-19 e associadas ao comprometimento da CT dos trabalhadores avaliados. Este estudo demonstra a necessidade de que todos os trabalhadores com teste positivo por Covid-19 tenham sua CT avaliada por ocasião do retorno ao trabalho. Ações de promoção à saúde, reabilitação funcional e adaptação do trabalho de acordo com as sequelas apresentadas pelos trabalhadores.

Abstract Objective To investigate how the presence/side of hippocampal sclerosis (HS) are related to the white matter structure of cingulum bundle (CB), arcuate fasciculus (AF), and inferior longitudinal fasciculus (ILF) in mesial temporal lobe epilepsy (MTLE). Methods We acquired diffusion‐weighted magnetic resonance imaging (MRI) from 86 healthy and 71 individuals with MTLE (22 righ‐HS; right‐HS, 34 left‐HS; left‐HS, and 15 nonlesional MTLE). We utilized two‐tensor tractography and fiber clustering to compare fractional anisotropy (FA) of each side/tract between groups. Additionally, we examined the association between FA and nonverbal (WMS‐R) and verbal (WMS‐R, RAVLT codification) memory performance for MTLE individuals. Results White matter abnormalities depended on the side and presence of HS. The left‐HS demonstrated widespread abnormalities for all tracts, the right‐HS showed lower FA for ipsilateral tracts and the nonlesional MTLE group did not differ from healthy individuals. Results indicate no differences in verbal/nonverbal memory performance between the groups, but trend‐level associations between higher FA of visual memory and the left CB (r = 0.286, P = 0.018), verbal memory (RAVLT) and ‐left CB (r = 0.335, P = 0.005), ‐right CB (r = 0.286, P = 0.016), and ‐left AF (r = 0.287, P = 0.017). Significance Our results highlight that the presence and side of HS are crucial to understand the pathophysiology of MTLE. Specifically, left‐sided HS seems to be related to widespread bilateral white matter abnormalities. Future longitudinal studies should focus on developing diagnostic and treatment strategies dependent on HS's presence/side.

Abstract Focal cortical dysplasia (FCD) is a brain malformation that causes medically refractory epilepsy. FCD is classified into three categories based on structural and cellular abnormalities, with FCD type II being the most common and characterized by disrupted organization of the cortex and abnormal neuronal development. In this study, we employed cell-type deconvolution and single-cell signatures to analyze bulk RNA-seq from multiple transcriptomic studies, aiming to characterize the cellular composition of brain lesions in patients with FCD IIa and IIb subtypes. Our deconvolution analyses revealed specific cellular changes in FCD IIb, including neuronal loss and an increase in reactive astrocytes (astrogliosis) when compared to FCD IIa. Astrogliosis in FCD IIb was further supported by a gene signature analysis and histologically confirmed by glial fibrillary acidic protein (GFAP) immunostaining. Overall, our findings demonstrate that FCD II subtypes exhibit differential neuronal and glial compositions, with astrogliosis emerging as a hallmark of FCD IIb. These observations, validated in independent patient cohorts and confirmed using immunohistochemistry, offer novel insights into the involvement of glial cells in FCD type II pathophysiology and may contribute to the development of targeted therapies for this condition.

Abstract Objective Typical aging is associated with gradual cognitive decline and changes in brain structure. The observation that cognitive performance in mesial temporal lobe epilepsy (TLE) patients diverges from controls early in life with subsequent decline running in parallel would suggest an initial insult but does not support accelerated decline secondary to seizures. Whether TLE patients demonstrate similar trajectories of age‐related gray (GM) and white matter (WM) changes as compared to healthy controls remains uncertain. Methods 3D T1‐weighted and diffusion tensor images were acquired at a single site in 170 TLE patients (aged 23–74 years) with MRI signs of unilateral hippocampal sclerosis (HS, 77 right) and 111 healthy controls (aged 26–80 years). Global brain (GM, WM, total brain, and cerebrospinal fluid) and regional volumes (ipsi‐ and contralateral hippocampi), and fractional anisotropy (FA) of 10 tracts (three portions of corpus callosum, inferior longitudinal, inferior fronto‐occipital and uncinate fasciculi, body of fornix, dorsal and parahippocampal‐cingulum, and corticospinal tract) were compared between groups as a function of age. Results There were significant reductions of global brain and hippocampi volumes (greatest ipsilateral to HS), and FA of all 10 tracts in TLE versus controls. For TLE patients, regression lines run in parallel to those from controls for brain volumes and FA (for all tracts except the parahippocampal‐cingulum and corticospinal tract) versus age across the adult lifespan. Interpretation These results imply a developmental hindrance occurring earlier in life (likely in childhood/neurodevelopmental stages) rather than accelerated atrophy/degeneration of most brain structures herein analyzed in patients with TLE.

Introduction Despite significant advances in managing acute stroke and reducing stroke mortality, preventing complications like post-stroke epilepsy (PSE) has seen limited progress. PSE research has been scattered worldwide with varying methodologies and data reporting. To address this, we established the International Post-stroke Epilepsy Research Consortium (IPSERC) to integrate global PSE research efforts. This protocol outlines an individual patient data meta-analysis (IPD-MA) to determine outcomes in patients with post-stroke seizures (PSS) and develop/validate PSE prediction models, comparing them with existing models. This protocol informs about creating the International Post-stroke Epilepsy Research Repository (IPSERR) to support future collaborative research.Methods and analysis We utilised a comprehensive search strategy and searched MEDLINE, Embase, PsycInfo, Cochrane, and Web of Science databases until 30 January 2023. We extracted observational studies of stroke patients aged ≥18 years, presenting early or late PSS with data on patient outcome measures, and conducted the risk of bias assessment. We did not apply any restriction based on the date or language of publication. We will invite these study authors and the IPSERC collaborators to contribute IPD to IPSERR. We will review the IPD lodged within IPSERR to identify patients who developed epileptic seizures and those who did not. We will merge the IPD files of individual data and standardise the variables where possible for consistency. We will conduct an IPD-MA to estimate the prognostic value of clinical characteristics in predicting PSE.Ethics and dissemination Ethics approval is not required for this study. The results will be published in peer-reviewed journals. This study will contribute to IPSERR, which will be available to researchers for future PSE research projects. It will also serve as a platform to anchor future clinical trials.Trial registration number NCT06108102

BackgroundThe expression of serine protease granzyme-B (GzmB) by circulating CD8+ T lymphocytes has been recently suggested as a biomarker for poor immunotherapy response and severe disability in patients with Neuromyelitis Optica spectrum disorders (NMOSD). In parallel, venous thromboembolism (VTE) has been reported mainly in NMOSD patients exhibiting transverse myelitis.Case presentationHere, we describe an Aquaporin-4 positive (AQP4-positive) NMOSD patient who showed short myelitis (SM) and experienced a fatal pulmonary thromboembolism/lower extremity deep vein thrombosis during anti-CD20 treatment. Flow cytometry analyses from the peripheral blood revealed an enhanced cytotoxic behavior through circulating CD8+GzmB+ T, CD4+GzmB+ T lymphocytes, and residual CD19+GzmB+ B cells.ConclusionsFatal VTE may be a rare outcome, particularly in patients exhibiting SM, and may share poorly understood immunological mechanisms with AQP4-positive NMOSD severity.

Epilepsy is a brain network disorder with associated genetic risk factors. Here, the authors show that spatial patterns of transcriptomic vulnerability co-vary with structural brain network alterations in focal and generalized epilepsy.

IntroductionFocal cortical dysplasia (FCD) is a common cause of pharmacoresistant epilepsy. According to the 2022 International League Against Epilepsy classification, FCD type II is characterized by dysmorphic neurons (IIa and IIb) and may be associated with balloon cells (IIb). We present a multicentric study to evaluate the transcriptomes of the gray and white matters of surgical FCD type II specimens. We aimed to contribute to pathophysiology and tissue characterization.MethodsWe investigated FCD II (a and b) and control samples by performing RNA-sequencing followed by immunohistochemical validation employing digital analyses.ResultsWe found 342 and 399 transcripts differentially expressed in the gray matter of IIa and IIb lesions compared to controls, respectively. Cholesterol biosynthesis was among the main enriched cellular pathways in both IIa and IIb gray matter. Particularly, the genes HMGCS1, HMGCR, and SQLE were upregulated in both type II groups. We also found 12 differentially expressed genes when comparing transcriptomes of IIa and IIb lesions. Only 1 transcript (MTRNR2L12) was significantly upregulated in FCD IIa. The white matter in IIa and IIb lesions showed 2 and 24 transcripts differentially expressed, respectively, compared to controls. No enriched cellular pathways were detected. GPNMB, not previously described in FCD samples, was upregulated in IIb compared to IIa and control groups. Upregulations of cholesterol biosynthesis enzymes and GPNMB genes in FCD groups were immunohistochemically validated. Such enzymes were mainly detected in both dysmorphic and normal neurons, whereas GPNMB was observed only in balloon cells.DiscussionOverall, our study contributed to identifying cortical enrichment of cholesterol biosynthesis in FCD type II, which may correspond to a neuroprotective response to seizures. Moreover, specific analyses in either the gray or the white matter revealed upregulations of MTRNR2L12 and GPNMB, which might be potential neuropathological biomarkers of a cortex chronically exposed to seizures and of balloon cells, respectively.

Abstract Objectives We compared the proteomic signatures of the hippocampal lesion induced in three different animal models of mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS): the systemic pilocarpine model (PILO), the intracerebroventricular kainic acid model (KA), and the perforant pathway stimulation model (PPS). Methods We used shotgun proteomics to analyze the proteomes and find enriched biological pathways of the dorsal and ventral dentate gyrus (DG) isolated from the hippocampi of the three animal models. We also compared the proteomes obtained in the animal models to that from the DG of patients with pharmacoresistant MTLE+HS. Results We found that each animal model presents specific profiles of proteomic changes. The PILO model showed responses predominantly related to neuronal excitatory imbalance. The KA model revealed alterations mainly in synaptic activity. The PPS model displayed abnormalities in metabolism and oxidative stress. We also identified common biological pathways enriched in all three models, such as inflammation and immune response, which were also observed in tissue from patients. However, none of the models could recapitulate the profile of molecular changes observed in tissue from patients. Significance Our results indicate that each model has its own set of biological responses leading to epilepsy. Thus, it seems that only using a combination of the three models may one replicate more closely the mechanisms underlying MTLE+HS as seen in patients.

Abstract The causes of the neurodegenerative processes in Alzheimer's disease (AD) are not completely known. Recent studies have shown that white matter (WM) damage could be more severe and widespread than whole‐brain cortical atrophy and that such damage may appear even before the damage to the gray matter (GM). In AD, Amyloid‐beta (Aβ42) and tau proteins could directly affect WM, spreading across brain networks. Since hippocampal atrophy is common in the early phase of disease, it is reasonable to expect that hippocampal volume (HV) might be also related to WM integrity. Our study aimed to evaluate the integrity of the whole‐brain WM, through diffusion tensor imaging (DTI) parameters, in mild AD and amnestic mild cognitive impairment (aMCI) due to AD (with Aβ42 alteration in cerebrospinal fluid [CSF]) in relation to controls; and possible correlations between those measures and the CSF levels of Aβ42, phosphorylated tau protein (p‐Tau) and total tau (t‐Tau). We found a widespread WM alteration in the groups, and we also observed correlations between p‐Tau and t‐Tau with tracts directly linked to mesial temporal lobe (MTL) structures (fornix and hippocampal cingulum). However, linear regressions showed that the HV better explained the variation found in the DTI measures (with weak to moderate effect sizes, explaining from 9% to 31%) than did CSF proteins. In conclusion, we found widespread alterations in WM integrity, particularly in regions commonly affected by the disease in our group of early‐stage disease and patients with Alzheimer's disease. Nonetheless, in the statistical models, the HV better predicted the integrity of the MTL tracts than the biomarkers in CSF.

Abstract Objective To assess and validate the performance of a new tool developed for segmenting and characterizing lacunas in postoperative MR images of epilepsy patients. Methods A MATLAB‐based pipeline was implemented using SPM12 to produce the 3D mask of the surgical lacuna and estimate its volume. To validate its performance, we compared the manual and automatic lacuna segmentations obtained from 51 MRI scans of epilepsy patients who underwent temporal lobe resections. Results The code is consolidated as a tool named ResectVol, which can be run via a graphical user interface or command line. The automatic and manual segmentation comparison resulted in a median Dice similarity coefficient of 0.77 (interquartile range: 0.71‐0.81). Significance Epilepsy surgery is the treatment of choice for pharmacoresistant focal epilepsies, and despite the extensive literature on the subject, we still cannot predict surgical outcomes accurately. As the volume and location of the resected tissue are fundamentally relevant to this prediction, researchers commonly perform a manual segmentation of the lacuna, which presents human bias and does not provide detailed information about the structures removed. In this study, we introduce ResectVol, a user‐friendly, fully automatic tool to accomplish these tasks. This capability enables more advanced analytical techniques applied to surgical outcomes prediction, such as machine‐learning algorithms, by facilitating coregistration of the resected area and preoperative findings with other imaging modalities such as PET, SPECT, and functional MRI ResectVol is freely available at https://www.lniunicamp.com/resectvol.

BackgroundAlthough several studies have emphasized the association between epilepsy and psychiatric disorders, fewer have investigated the impact of epilepsy on caregivers' emotional status, mainly in adult people with epilepsy (PWE). Here we investigated depressive symptoms, suicidal ideation, and anxiety symptoms in a large group of adult PWE and their caregivers.MethodsWe analyzed symptoms of depression [with the Beck Depression Inventory-II (BDI-II)], suicidal ideation (with BDI-II item 9), and anxiety symptoms (with the Beck Anxiety Inventory) in a large group of adult PWE [N = 548 (60% women; median age 41)] and caregivers [N = 191 (72% women; median age 47)] from a Brazilian tertiary center, considering sociodemographic and clinical aspects. We also applied the Liverpool Adverse Events Profile to assess anti-seizure drugs adverse events.ResultsWhile the presence (p = 0.026) (and intensity, p = 0.007) of depressive symptoms and suicidal ideation (p = 0.02) were higher in PWE compared to caregivers, the proportion of clinical anxiety symptoms (p = 0.32) (and the intensity, p = 0.13) was similar in both groups. Although the rates of suicidal ideation were higher in focal epilepsy (20%), both generalized genetic epilepsy and caregivers also presented elevated frequencies (11%) of suicidal ideation. The analyses of 120 patient-caregiver dyads revealed that the intensity of depressive symptoms in PWE (but not anxiety) correlated with the intensity of depressive (r = 0.35; p < 0.001) and anxiety (r = 0.25; p = 0.01) symptoms in their caregivers. In the multivariate analyses of PWE, focal epilepsy (compared to GGE) was associated with clinical depressive symptoms (odds ratio, OR 2.1) and suicidal ideation (OR 3.2), while recurrent seizures (compared to the seizure-free group) were associated with suicidal ideation (OR 2.6) and anxiety symptoms (OR 2.1). Also, caregivers with anxiety symptoms were 8 times more likely to exhibit depressive symptoms, and those with depressive symptoms were 8 times more likely to present anxiety symptoms.ConclusionOur study suggests that specific attention for the caregivers' mental health is as essential as PWE. There is an urgent need for more studies involving caregivers to identify their emotional distress and provide adequate treatment.

Background and purpose Thrombotic microangiopathy (TMA) is a group of microvascular occlusive disorders that presents with neurological involvement in up to 87% of the cases. Although the central nervous system (CNS) is an important target organ in TMA, the role of neurological manifestations in the disease clinical course is not well established. In this study, we described the neurological manifestations and CNS radiological aspects in patients with a first, acute TMA event. We also examined the association between severe neurological involvement and adverse clinical outcomes in TMA. Methods A cohort of patients diagnosed with a first TMA event between 1995 and 2016 was included, their medical charts and imaging tests were retrospectively evaluated. Results A total of 49 patients were included, 85.7% were women and the mean age was 36.5 years-old (SD 13.0). Neurological manifestations were described in 85.7% of the patients, most of them (88%) were considered severe and consisted of confusion, compromised sensorimotor function, stupor, seizures, and personality change. Imaging tests were performed in 62% of the patients with neurological manifestations and detected acute CNS lesions, such as posterior reversible encephalopathy syndrome, hemorrhagic and ischemic stroke were observed, in 7 (27%) of them. While the need for intensive care unit admission was greater and longer among patients with severe neurological manifestations, the number of plasma exchange sessions, the total duration of hospitalization and in-hospital death were similar between groups. Conclusions Severe neurological manifestations are common in first TMA events and are responsible for a worse disease presentation at admission. While the effect of neurological manifestations on acute TMA clinical course seems to be modest, these manifestations may have an important impact on the development of chronic cognitive impairment, which highlights the need for proper diagnosis and treatment.

Central nervous system (CNS) involvement in childhood-onset systemic lupus erythematosus (cSLE) occurs in more than 50% of patients. Structural magnetic resonance imaging (MRI) has identified global cerebral atrophy, as well as the involvement of the corpus callosum and hippocampus, which is associated with cognitive impairment. In this cross-sectional study we included 71 cSLE (mean age 24.7 years (SD 4.6) patients and a disease duration of 11.8 years (SD 4.8) and two control groups: (1) 49 adult-onset SLE (aSLE) patients (mean age of 33.2 (SD 3.7) with a similar disease duration and (2) 58 healthy control patients (mean age of 29.9 years (DP 4.1)) of a similar age. All of the individuals were evaluated on the day of the MRI scan (Phillips 3T scanner). We reviewed medical charts to obtain the clinical and immunological features and treatment history of the SLE patients. Segmentation of the corpus callosum was performed through an automated segmentation method. Patients with cSLE had a similar mid-sagittal area of the corpus callosum in comparison to the aSLE patients. When compared to the control groups, cSLE and aSLE had a significant reduction in the mid-sagittal area in the posterior region of the corpus callosum. We observed significantly lower FA values and significantly higher MD, RD, and AD values in the total area of the corpus callosum and in the parcels B, C, D, and E in cSLE patients when compared to the aSLE patients. Low complement, the presence of anticardiolipin antibodies, and cognitive impairment were associated with microstructural changes. In conclusion, we observed greater microstructural changes in the corpus callosum in adults with cSLE when compared to those with aSLE. Longitudinal studies are necessary to follow these changes, however they may explain the worse cognitive function and disability observed in adults with cSLE when compared to aSLE.

Introduction: 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.Design: 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.Outcomes: 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.Discussion: 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.Clinical trial registration: This study is indexed at clinicaltrials.gov (NT 04952298).

Hippocampal sclerosis (HS) is a common cause of pharmacoresistant focal epilepsy. Here, we (1) performed a histological approach to the anterior temporal pole of patients with HS to evaluate cortical and white matter (WM) cell populations, alteration of myelin integrity and markers of neuronal activity, and (2) correlated microscopic data with magnetic resonance imaging (MRI) findings. Our aim was to contribute with the understanding of neuroimaging and pathophysiological mechanisms of temporal lobe epilepsy (TLE) associated with HS. We examined MRIs and surgical specimens from the anterior temporal pole from TLE-HS patients (n = 9) and compared them with 10 autopsy controls. MRIs from healthy volunteers (n = 13) were used as neuroimaging controls. Histological techniques were performed to assess oligodendrocytes, heterotopic neurons, cellular proliferative index, and myeloarchitecture integrity of the WM, as well as markers of acute (c-fos) and chronic (ΔFosB) activities of neocortical neurons. Microscopic data were compared with neuroimaging findings, including T2-weighted/FLAIR MRI temporopolar blurring and values of fractional anisotropy (FA) from diffusion-weighed imaging (DWI). We found a significant increase in WM oligodendrocyte number, both in hematoxylin and eosin, and in Olig2-stained sections. The frequencies of oligodendrocytes in perivascular spaces and around heterotopic neurons were significantly higher in patients with TLE–HS compared with controls. The percentage of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase; a marker of myeloarchitecture integrity) immunopositive area in the WM was significantly higher in TLE-HS, as well as the numbers of c-fos- and ΔFosB-immunostained neocortical neurons. Additionally, we demonstrated a decrease in axonal bundle integrity on neuroimaging, with a significant reduction in the FA in the anterior temporal pole. No differences were detected between individuals with and without temporopolar blurring on visual MRI analysis, considering the number of oligodendroglial cells and percentage of WM CNPase-positive areas. Also, there was no relationship between T2 relaxometry and oligodendrocyte count. In conclusion, our histopathological data support the following: (1) the hypothesis that repetitive neocortical neuronal activity could induce changes in the WM cellular constitution and myelin remodeling in the anterior temporal pole from patients with TLE-HS, (2) that oligodendroglial hyperplasia is not related to temporal blurring or T2 signal intensity on MRI, and (3) that reduced FA is a marker of increase in Olig2-immunopositive cells in superficial temporopolar WM from patients with TLE-HS.

Carotid artery stenosis (CAS) is a common vascular disease with long-term consequences for the brain. Although CAS is strongly associated with impaired cerebral hemodynamics and neurodegeneration, the mechanisms underlying hemodynamic impairment in the microvasculature remain unknown. In this work, we employed functional near-infrared spectroscopy (fNIRS) to introduce a methodological approach for quantifying the temporal delay of the evoked hemodynamic response. The method was validated during a vasodilatory task (breath-holding) in 50 CAS patients and 20 controls. Our results suggest that the hemodynamic response to breath-holding can be delayed by up to 6 s in the most severe patients, a significant increase from the median 4 s measured for the control group (p = 0.01). In addition, the fraction of brain regions that responded to the task decreased as the CAS severity increased, from a median of 90% in controls to 73% in the most severe CAS group (p = 0.04). The presence of collateral circulation increases the response to breath-holding and decreases the average time delays across the brain, although the number of communicating arteries alone cannot predict these fNIRS-based hemodynamic variables (p > 0.09). Overall, this work proposes a method to quantitatively assess impaired cerebral hemodynamics in CAS patients.

We aimed to investigate the role of interleukin-1 beta (IL-1β) in the mechanisms underlying mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS). We assessed a cohort of 194 patients with MTLE+HS and 199 healthy controls. Patients were divided into those with positive and negative antecedent febrile seizures (FS). We used a multidimensional approach, including (i) genetic association with single nucleotide polymorphisms (SNPs) in the IL1B gene; (ii) quantification of the IL1B transcript in the hippocampal tissue of patients with refractory seizures; and (iii) quantification of the IL-1β protein in the plasma. We found a genetic association signal for two SNPs, rs2708928 and rs3730364*C in the IL1B gene, regardless of the presence of FS (adjusted p = 9.62e–11 and 5.14e–07, respectively). We found no difference between IL1B transcript levels when comparing sclerotic hippocampal tissue from patients with MTLE+HS, without FS, and hippocampi from autopsy controls (p > 0.05). Nevertheless, we found increased IL-1β in the plasma of patients with MTLE+HS with FS compared with controls (p = 0.0195). Our results support the hypothesis of a genetic association between MTLE+HS and the IL1B gene

Genetic generalized epilepsies (GGEs) include well-established epilepsy syndromes with generalized onset seizures: childhood absence epilepsy, juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), myoclonic absence epilepsy, epilepsy with eyelid myoclonia (Jeavons syndrome), generalized tonic–clonic seizures, and generalized tonic–clonic seizures alone. Genome-wide association studies (GWASs) and exome sequencing have identified 48 single-nucleotide polymorphisms (SNPs) associated with GGE. However, these studies were mainly based on non-admixed, European, and Asian populations. Thus, it remains unclear whether these results apply to patients of other origins. This study aims to evaluate whether these previous results could be replicated in a cohort of admixed Brazilian patients with GGE. We obtained SNP-array data from 87 patients with GGE, compared with 340 controls from the BIPMed public dataset. We could directly access genotypes of 17 candidate SNPs, available in the SNP array, and the remaining 31 SNPs were imputed using the BEAGLE v5.1 software. We performed an association test by logistic regression analysis, including the first five principal components as covariates. Furthermore, to expand the analysis of the candidate regions, we also interrogated 14,047 SNPs that flank the candidate SNPs (1 Mb). The statistical power was evaluated in terms of odds ratio and minor allele frequency (MAF) by the genpwr package. Differences in SNP frequencies between Brazilian and Europeans, sub-Saharan African, and Native Americans were evaluated by a two-proportion Z-test. We identified nine flanking SNPs, located on eight candidate regions, which presented association signals that passed the Bonferroni correction (rs12726617; rs9428842; rs1915992; rs1464634; rs6459526; rs2510087; rs9551042; rs9888879; and rs8133217; p-values

Abstract Neurocysticercosis is a frequent cause of seizures in endemic countries. It is caused by the larvae of the tapeworm Taenia solium. The larvae once hosted in the cerebral parenchyma evolve into viable cysts, called the vesicular stage (with little or no inflammatory reaction), and may remain at this stage for years, or may enter in an inflammatory‐degenerative process (colloidal phase) that ends with calcified nodules. Edema and MRI contrast enhancement associated with these calcifications have been described, suggesting that it may be associated with seizures. However, most of these reports were either cross‐sectional case‐control series or case reports with a single time point MRI. Therefore, the clinical significance of recurring perilesional edema and contrast enhancement around calcified lesions is still uncertain. Here, we describe repeated MRIs of a patient with calcified neurocysticercosis over 4 years. The seizures were associated with edema and contrast enhancement that disappeared in the seizure‐free periods, occurring only around one calcified nodule that coincided with the EEG findings and seizure semiology, although he had three additional calcifications. These findings support the association between pericalcification contrast enhancement and edema with recent seizures. This MRI finding may be a marker to define the epileptogenic focus in epilepsies with calcified neurocysticercosis.

Artificial intelligence has recently gained popularity across different medical fields to aid in the detection of diseases based on pathology samples or medical imaging findings. Brain magnetic resonance imaging (MRI) is a key assessment tool for patients with temporal lobe epilepsy (TLE). The role of machine learning and artificial intelligence to increase detection of brain abnormalities in TLE remains inconclusive. We used support vector machine (SV) and deep learning (DL) models based on region of interest (ROI-based) structural (n = 336) and diffusion (n = 863) brain MRI data from patients with TLE with (“lesional”) and without (“non-lesional”) radiographic features suggestive of underlying hippocampal sclerosis from the multinational (multi-center) ENIGMA-Epilepsy consortium. Our data showed that models to identify TLE performed better or similar (68–75%) compared to models to lateralize the side of TLE (56–73%, except structural-based) based on diffusion data with the opposite pattern seen for structural data (67–75% to diagnose vs. 83% to lateralize). In other aspects, structural and diffusion-based models showed similar classification accuracies. Our classification models for patients with hippocampal sclerosis were more accurate (68–76%) than models that stratified non-lesional patients (53–62%). Overall, SV and DL models performed similarly with several instances in which SV mildly outperformed DL. We discuss the relative performance of these models with ROI-level data and the implications for future applications of machine learning and artificial intelligence in epilepsy care.

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A major challenge in the clinical management of patients with mesial temporal lobe epilepsy (MTLE) is identifying those who do not respond to antiseizure medication (ASM), allowing for the timely pursuit of alternative treatments such as epilepsy surgery. Here, we investigated changes in plasma metabolites as biomarkers of disease in patients with MTLE. Furthermore, we used the metabolomics data to gain insights into the mechanisms underlying MTLE and response to ASM. We performed an untargeted metabolomic method using magnetic resonance spectroscopy and multi- and univariate statistical analyses to compare data obtained from plasma samples of 28 patients with MTLE compared to 28 controls. The patients were further divided according to response to ASM for a supplementary and preliminary comparison: 20 patients were refractory to treatment, and eight were responsive to ASM. We only included patients using carbamazepine in combination with clobazam. We analyzed the group of patients and controls and found that the profiles of glucose (p = 0.01), saturated lipids (p = 0.0002), isoleucine (p = 0.0001), β-hydroxybutyrate (p = 0.0003), and proline (p = 0.02) were different in patients compared to controls (p < 0.05). In addition, we found some suggestive metabolites (without enough predictability) by multivariate analysis (VIP scores > 2), such as lipoproteins, lactate, glucose, unsaturated lipids, isoleucine, and proline, that might be relevant to the process of pharmacoresistance in the comparison between patients with refractory and responsive MTLE. The identified metabolites for the comparison between MTLE patients and controls were linked to different biological pathways related to cell-energy metabolism and pathways related to inflammatory processes and the modulation of neurotransmitter release and activity in MTLE. In conclusion, in addition to insights into the mechanisms underlying MTLE, our results suggest that plasma metabolites may be used as disease biomarkers. These findings warrant further studies exploring the clinical use of metabolites to assist in decision-making when treating patients with MTLE.

Human language can convey a broad range of entities and relationships through processes that are highly complex and structured. All of these processes are happening somewhere inside our brains, and one way of precising these locations is through the usage of the functional magnetic resonance imaging. The great obstacle when experimenting with complex processes, however, is the need to control them while still having data that are representative of reality. When it comes to language, an interactional phenomenon in its nature, and that integrates a wide range of processes, a question emerges concerning how compatible it is with the current experimental methodology, and how much of it is lost in order to fit the controlled experimental environment. Because of its particularities, the fMRI technique imposes several limitations to the expression of language during experimentation. This paper discusses the different conceptions of language as a research object, the hardships of combining this object with the requirements of fMRI, and what are the current perspectives for this field of research.

Introduction: Subtraction of ictal-interictal SPECT co-registered to MRI (SISCOM) is a quantification tool that can improve the sensitivity and specificity of the epileptogenic zone (EZ) localization. Commercially available image analysis software packages for SISCOM are costly, and Statistical Parametric Mapping (SPM) could be an alternative free software for the definition of the EZ. There are only a few studies that compare SISCOM using SPM (SISCOM-SPM) with visual analysis.Aim: To compare SISCOM-SPM vs. visual analysis for localization of the EZ in patients with pharmacoresistant focal epilepsies.Materials and methods: We evaluated all our patients with focal epilepsies that underwent ictal and interictal SPECT. We defined the reference standard to locate the EZ by pathology and follow-up (in patients submitted to surgery), or seizure semiology, serial EEG, long-term video-EEG, 18F-FDG PET/CT, and MRI (in patients who were not operated). We compared the location of the EZ by visual analysis of SPECT images and by SISCOM-SPM to the reference standard and classified as concordant, discordant, or partially concordant.Results: We included 23 patients. Visual analysis was concordant with the EZ reference standard in only 13 patients (56.5%), while SISCOM-SPM was concordant in 18 cases (78.3%), providing a 21.8% increase in the location of EZ. However, this difference was not significant due to the small sample size (p = 0.0856).Conclusion: Our preliminary results demonstrate that, in clinical practice, SISCOM-SPM has the potential to add information that might help localize the EZ compared to visual analysis. SISCOM-SPM has a lower cost than other commercially available SISCOM software packages, which is an advantage for developing countries. Studies with more patients are necessary to confirm our findings.

Resumo Contexto A espectroscopia próxima ao infravermelho (NIRS) é uma técnica não invasiva que detecta as alterações hemodinâmicas teciduais. A NIRS pode monitorar de forma contínua as informações fisiológicas vasculares intracranianas. Por ser portátil, ela pode ser utilizada à beira do leito e no centro cirúrgico. Objetivos Avaliar as possíveis alterações hemodinâmicas cerebrais durante a endarterectomia em pacientes com estenoses maiores que 70% utilizando NIRS. Métodos Foram avaliados 10 voluntários portadores de doença carotídea aterosclerótica com indicação de endarterectomia. Após a seleção dos pacientes, que responderam um questionário com dados epidemiológicos e informações referentes à presença de comorbidades, a doença foi confirmada por métodos diagnósticos. No procedimento cirúrgico, utilizou-se a NIRS para monitorização. Foram avaliadas as variáveis saturação de oxigênio (SatO2), hemoglobina total (HbT), hemoglobina reduzida (HbR) e hemoglobina oxigenada (HbO) nos três tempos cirúrgicos pré-, trans e pós-clampeamento carotídeo. Utilizou-se p < 0,05 como nível de significância. Resultados A avaliação dos resultados obtidos por meio das medidas registradas pela NIRS permite afirmar que HbR e SatO2 variam ao longo das etapas da cirurgia. Durante o clampeamento, a variável HbR mostra valores mais elevados que nas outras duas etapas da cirurgia. Por outro lado, a variável SatO2 mostra redução durante o clampeamento. Conclusões A NIRS é um método viável e aplicável de monitorização intracerebral, não invasivo e em tempo real, durante a endarterectomia carotídea, capaz de medir de forma precisa as mudanças das condições hemodinâmicas capilares intracerebrais.

Background The clinical aspects of sickle cell anemia (SCA) are heterogeneous, and different patients may present significantly different clinical evolutions. Almost all organs can be affected, particularly the central nervous system. Transient ischemic events, infarcts, and cerebral hemorrhage can be observed and affect ≈25% of the patients with SCA. Differences in the expression of molecules produced by endothelial cells may be associated with the clinical heterogeneity of patients affected by vascular diseases. In this study, we investigated the differential expression of genes involved in endothelial cell biology in SCA patients with and without stroke. Methods and Results Endothelial progenitor cells from 4 SCA patients with stroke and 6 SCA patients without stroke were evaluated through the polymerase chain reaction array technique. The analysis of gene expression profiling identified 29 differentially expressed genes. Eleven of these genes were upregulated, and most were associated with angiogenesis (55%), inflammatory response (18%), and coagulation (18%) pathways. Downregulated expression was observed in 18 genes, with the majority associated with angiogenesis (28%), apoptosis (28%), and cell adhesion (22%) pathways. Remarkable overexpression of the MMP1 (matrix metalloproteinase 1) gene in the endothelial progenitor cells of all SCA patients with stroke (fold change: 204.64; P=0.0004) was observed. Conclusions Our results strongly suggest that angiogenesis is an important process in sickle cell stroke, and differences in the gene expression profile of endothelial cell biology, especially MMP1, may be related to stroke in SCA patients.

The User-Friendly Functional Connectivity (UF2C) software provides researchers with a platform to analyze functional magnetic resonance neuroimages from the initial preprocessing steps to the generation of manuscript-quality figures. UF2C is implemented in Matlab language and falls within the FreeBSD license. Our toolbox builds on a combination of existing methods to increase the user’s power to perform different types of resting-state functional connectivity, event-related, and task activation analyses. To keep up with ongoing advances in this field, UF2C is regularly updated to reflect these advances and incorporate user demands.

Background: Major Depressive Disorder (MDD) is highly prevalent in patients with mesial temporal lobe epilepsy (MTLE), especially in women, carrying significant morbidity. This study aimed to investigate the cortical thickness (CT) abnormalities associated with MDD in women with MTLE and hippocampal atrophy (HA). Also, we investigated the impact of MDD upon the volumes of the hippocampus and amygdala in these patients.Methods: We included 50 women with MTLE and HA (20 left, LMTLE; 30 right, RMTLE), 41 healthy women in the control group, and 15 women with MDD without epilepsy. MTLE patients were subdivided into three groups: MTLE-without-MDD (23 MTLE patients without MDD), MTLE-mild-MDD (nine MTLE patients with mild symptoms of MDD), and MTLE-severe-MDD (18 MTLE patients with moderate to severe symptoms of MDD). The five groups were balanced for age (p = 0.56). All participants had high-resolution 3D T1-weighted images in a 3T scanner. We used FreeSurfer 6.0 for volumetry and CT parcellation. All participants were submitted to a clinical psychological evaluation through the Structured Clinical Interview for DSM-IV (SCID-IV) and completed the Beck Depression Inventory (BDI-II).Results: We identified a smaller ipsilateral amygdala volume (p = 0.04) in the MTLE-severe-MDD group when compared to the control group. Our results presented a reduced ipsilateral lateral orbitofrontal cortex (p = 0.02) in the MTLE-severe-MDD in comparison to the MTLE-mild-MDD group. We also identified a thinner ipsilateral fusiform gyrus (p < 0.01) in the MTLE-severe-MDD compared to both MTLE-without-MDD and control groups. A reduced CT of the contralateral superior frontal gyrus (p = 0.02) was observed in the MTLE-severe-MDD in comparison to the MTLE-mild-MDD group.Conclusions: The identification of areas with reduced CT and atrophy of the ipsilateral amygdala in women with MTLE and MDD suggest that the cortical thinning in the network of the paralimbic system is related to the co-occurrence and intensity of depressive symptoms in this group.

The thalamus is crucial for sleep regulation and the pathophysiology of idiopathic generalised epilepsy (IGE), and may serve as the underlying basis for the links between the two. We investigated this using EEG-fMRI and a specific emphasis on the role and functional connectivity (FC) of the thalamus. We defined three types of thalamic FC: thalamocortical, inter-hemispheric thalamic, and intra-hemispheric thalamic. Patients and controls differed in all three measures, and during wakefulness and sleep, indicating disorder-dependent and state-dependent modification of thalamic FC. Inter-hemispheric thalamic FC differed between patients and controls in somatosensory regions during wakefulness, and occipital regions during sleep. Intra-hemispheric thalamic FC was significantly higher in patients than controls following sleep onset, and disorder-dependent alterations to FC were seen in several thalamic regions always involving somatomotor and occipital regions. As interactions between thalamic sub-regions are indirect and mediated by the inhibitory thalamic reticular nucleus (TRN), the results suggest abnormal TRN function in patients with IGE, with a regional distribution which could suggest a link with the thalamocortical networks involved in the generation of alpha rhythms. Intra-thalamic FC could be a more widely applicable marker beyond patients with IGE. Keywords: Functional connectivity, Generalised epilepsy, Sleep, Thalamic reticular nucleus thalamus

Neurocysticercosis (NC) is the most common parasitic infection of the central nervous system (CNS). Several studies have reported an association between NC and mesial temporal lobe epilepsy (MTLE). We intended to evaluate the frequency of hippocampal atrophy (HA), clinical evolution and imaging findings in patients with calcified neurocysticercotic lesions (CNLs).Methods: One hundred and eighty-one subjects (70 cases and 111 controls) were evaluated for the presence or absence of HA. We assessed the imaging findings, and the evolution of patients with NC treated or not with anthelmintics for NC.Results: Hippocampal volumes were different between cases and controls (p < 0.001). Seventy percent of the cases presented HA. 52.2% of the patients without a history of anthelmintic treatment for NC had reports of epileptic seizures. There was an association between non-treatment and the later occurrence of epileptic seizures (p = 0.006). There was an association between perilesional edema on MRI and the presence of uncontrolled epileptic seizures (p = 0.004).Conclusions: Hippocampal atrophy is frequent in patients with NCC. There was an association between no anthelmintic treatment in the acute phase of NC, perilesional edema, more pronounced hippocampal atrophy, and the occurrence of refractory seizures.

Epilepsy is a common neurologic disorder with diverse etiologies. Appropriate MRI investigation has an important role in the assessment of epilepsy. Specific protocols are required for recognition of epileptogenic lesions, particularly for recognition of subtle lesions. In patients with refractory epilepsy and “normal MRI,” multimodal imaging techniques are crucial in the definition of epilepsy etiology, including those that combine metabolic and functional investigation, such as fluorodeoxyglucose positron emission tomography (FDG-PET), single-photonemission computed tomography (SPECT), diffusion MRI and magnetic resonance spectroscopy (MRS). Familiarity with various protocols of imaging studies is required for optimized investigation of seizure etiology. Main features found in MRIs of patients with focal epilepsies are discussed in the present review, as are alternative protocols and techniques of imaging that may optimize neuroimaging investigation in patients with epilepsy. The findings described have a direct impact on treatment and prognosis counseling of patients with focal epilepsies.

Objectives: To assess white matter abnormalities in Parkinson's disease (PD).Methods: A hundred and thirty-two patients with PD (mean age 60.93 years; average disease duration 7.8 years) and 137 healthy controls (HC; mean age 57.8 years) underwent the same MRI protocol. Patients were assessed by clinical scales and a complete neurological evaluation. We performed a TBSS analysis to compare patients and controls, and we divided patients into early PD, moderate PD, and severe PD and performed an ROI analysis using tractography.Results: With TBSS we found lower FA in patients in corpus callosum, internal and external capsule, corona radiata, thalamic radiation, sagittal stratum, cingulum and superior longitudinal fasciculus. Increased AD was found in the corpus callosum, fornix, corticospinal tract, superior cerebellar peduncle, cerebral peduncle, internal and external capsules, corona radiata, thalamic radiation and sagittal stratum and increased RD were seen in the corpus callosum, internal and external capsules, corona radiata, sagittal stratum, fornix, and cingulum. Regarding the ROIs, a GLM analysis showed abnormalities in all tracts, mainly in the severe group, when compared to HC, mild PD and moderate PD.Conclusions: Since major abnormalities were found in the severe PD group, we believe DTI analysis might not be the best tool to assess early alterations in PD, and probably, functional and other structural analysis might suit this purpose better. However it can be used to differentiate disease stages, and as a surrogate marker to assess disease progression, being an important measure that could be used in clinical trials.HIGHLIGHTSDTI is not the best tool to identify early PDDTI can differentiate disease stagesDTI analysis may be a useful marker for disease progression

Autism spectrum disorders (ASD) represent a complex group of neurodevelopmental conditions characterized by deficits in communication and social behaviors. We examined the functional connectivity (FC) of the default mode network (DMN) and its relation to multimodal morphometry to investigate superregional, system-level alterations in a group of 22 adolescents and young adults with high-functioning autism compared to age-, and intelligence quotient-matched 29 healthy controls. The main findings were that ASD patients had gray matter (GM) reduction, decreased cortical thickness and larger cortical surface areas in several brain regions, including the cingulate, temporal lobes, and amygdala, as well as increased gyrification in regions associated with encoding visual memories and areas of the sensorimotor component of the DMN, more pronounced in the left hemisphere. Moreover, patients with ASD had decreased connectivity between the posterior cingulate cortex, and areas of the executive control component of the DMN and increased FC between the anteromedial prefrontal cortex and areas of the sensorimotor component of the DMN. Reduced cortical thickness in the right inferior frontal lobe correlated with higher social impairment according to the scores of the Autism Diagnostic Interview-Revised (ADI-R). Reduced cortical thickness in left frontal regions, as well as an increased cortical thickness in the right temporal pole and posterior cingulate, were associated with worse scores on the communication domain of the ADI-R. We found no association between scores on the restrictive and repetitive behaviors domain of ADI-R with structural measures or FC. The combination of these structural and connectivity abnormalities may help to explain some of the core behaviors in high-functioning ASD and need to be investigated further.

Objectives To assess depressive disorders in patients with mesial temporal lobe epilepsy (MTLE) refractory to medical treatment. Methods Adult patients with refractory MTLE completed two questionnaires (Mini International Neuropsychiatric Interview (MINI) and the Beck Depression Inventory (BDI) had a semi-structured psychiatric interview and a high resolution MRI scan. For complete neuropsychiatric diagnosis, as per International Classification of Diseases (ICD-10), the results were combined with clinical history and additional information from the patients’ family. Results Of the 40 patients identified for this case series study which took place from 2008–2012, 31 (77.5%) had a depressive disorder: 14 had dysthymia, 11 had recurrent depressive disorder and 6 had bipolar disorder. Of the nine patients without a firm diagnosis of mood disorder, seven had isolated symptoms of depression or anxiety and two presented with mixed depression/anxiety symptoms. Only 8/31 (25.8%) patients were receiving antidepressant treatment. There was no association between BDI scores and seizure frequency. No significant difference was found between patients with and without depression and the presence or laterality of HA. Conclusions Depressive disorders are common, underdiagnosed and undertreated in patients with refractory MTLE.

Aims: The objective of the present study was to assess the skeletal maturation by means of three-dimensional models of the cervical vertebrae generated through segmentation of the magnetic resonance (MR) images by using medical software. Methods: Twenty MR images of the skull of male and female individuals aged between 8 and 22 years old were selected. Assessment of the images was performed by using the ITK-SNAP software, consisting of three steps: 1) vertebral segmentation; 2) three-dimensional reconstruction; and 3) classification of skeletal maturation. Two specialists in orthodontics and two specialists in dentomaxillofacial radiology assessed the images. Results: Analysis of reproducibility and repeatability were performed by using the RR method, with paired t-test also being applied to the repeatability factor together with Lin’s concordance coefficient. The significance level was set at 5%. It was found that there was no difference in the inter-rater reliability (P-value = 0.625), but without statistical repeatability. Conclusions: New tools, as 3D reconstruction software, enabled us to build an effective and friendly 3D-reconstruction system for classification of the skeletal maturation stages of cervical vertebrae.

Neuropsychiatric symptoms in Alzheimer’s disease (AD) are prevalent, however their relationship with patterns of cortical atrophy is not fully known. Objectives To compare cortical atrophy’s patterns between AD patients and healthy controls; to verify correlations between neuropsychiatric syndromes and cortical atrophy. Method 33 AD patients were examined by Neuropsychiatric Inventory (NPI). Patients and 29 controls underwent a 3T MRI scanning. We considered four NPI syndromes: affective, apathy, hyperactivity and psychosis. Correlations between structural imaging and neuropsychiatric scores were performed by Freesurfer. Results were significant with a p-value < 0.05, corrected for multiple comparisons. Results Patients exhibited atrophy in entorhinal cortices, left inferior and middle temporal gyri, and precuneus bilaterally. There was correlation between affective syndrome and cortical thickness in right frontal structures, insula and temporal pole. Conclusion Cortical thickness measures revealed atrophy in mild AD. Depression and anxiety symptoms were associated with atrophy of right frontal, temporal and insular cortices.

Objective Patients with mesial temporal lobe epilepsy (MTLE) may present unstable pattern of seizures. We aimed to evaluate the occurrence of relapse-remitting seizures in MTLE with (MTLE-HS) and without (MTLE-NL) hippocampal sclerosis. Method We evaluated 172 patients with MTLE-HS (122) or MTLE-NL (50). Relapse-remitting pattern was defined as periods longer than two years of seizure-freedom intercalated with seizure recurrence. “Infrequent seizures” was considered as up to three seizures per year and “frequent seizures” as any period of seizures higher than that. Results Thirty-seven (30%) MTLE-HS and 18 (36%) MTLE-NL patients had relapse-remitting pattern (X2, p = 0.470). This was more common in those with infrequent seizures (X2, p < 0.001). Twelve MTLE-HS and one MTLE-NL patients had prolonged seizure remission between the first and second decade of life (X2, p = 0.06). Conclusion Similar proportion of MTLE-HS or MTLE-NL patients present relapse-remitting seizures and this occurs more often in those with infrequent seizures.

AimsTo assess the validity of an online method to quantitatively evaluate cerebral hypometabolism in patients with pharmacoresistant focal epilepsy as a complement to the visual analysis of the 18F-FDG positron emission tomography (PET)/CT exam.MethodsA total of 39 patients with pharmacoresistant epilepsy and probable focal cortical dysplasia [22 patients with frontal lobe epilepsy (FLE) and 17 with temporal lobe epilepsy (TLE)] underwent a presurgical evaluation including EEG, video-EEG, MRI, and 18F-FDG PET/CT. We conducted the automated quantification of their 18F-FDG PET/CT data and compared the results with those of the visual-PET analysis conducted by experienced nuclear medicine physicians. For each patient group, we calculated Cohen’s Kappa coefficient for the visual and quantitative analyses, as well as each method’s sensitivity, specificity, and positive and negative predictive values.ResultsFor the TLE group, both the visual and quantitative analyses showed high agreement. Thus, although the quantitative analysis could be used as a complement, the visual analysis on its own was consistent and precise. For the FLE group, on the other hand, the visual analysis categorized almost half of the cases as normal, revealing very low agreement. For those patients, the quantitative analysis proved critical to identify the focal hypometabolism characteristic of the epileptogenic zone. Our results suggest that the quantitative analysis of 18F-FDG PET/CT data is critical for patients with extratemporal epilepsies, and especially those with subtle MRI findings. Furthermore, it can easily be used during the routine clinical evaluation of 18F-FDG PET/CT exams.SignificanceOur results show that quantification of 18F-FDG PET is an informative complementary method that can be added to the routine visual evaluation of patients with subtle lesions, particularly those in the frontal lobes.

Epilepsy is misdiagnosed in up to 25% of patients, leading to serious and long-lasting consequences. Recently, circulating microRNAs have emerged as potential biomarkers in a number of clinical scenarios. The purpose of this study was to identify and to validate circulating microRNAs that could be used as biomarkers in the diagnosis of epilepsy. Quantitative real-time PCR was used to measure plasma levels of three candidate microRNAs in two phases of study: an initial discovery phase with 14 patients with mesial temporal lobe epilepsy (MTLE), 13 with focal cortical dysplasia (FCD) and 16 controls; and a validation cohort constituted of an independent cohort of 65 patients with MTLE and 83 controls. We found hsa-miR-134 downregulated in patients with MTLE (p = 0.018) but not in patients with FCD, when compared to controls. Furthermore, hsa-miR-134 expression could be used to discriminate MTLE patients with an area under the curve (AUC) of 0.75. To further assess the robustness of hsa-miR-134 as a biomarker for MTLE, we studied an independent cohort of 65 patients with MTLE, 27 of whom MTLE patients were responsive to pharmacotherapy, and 38 patients were pharmacoresistant and 83 controls. We confirmed that hsa-miR-134 was significantly downregulated in the plasma of patients with MTLE when compared with controls (p < 0.001). In addition, hsa-miR-134 identified patients with MTLE regardless of their response to pharmacotherapy or the presence of MRI signs of hippocampal sclerosis. We revealed that decreased expression of hsa-miR-134 could be a potential non-invasive biomarker to support the diagnosis of patients with MTLE.

Our goal was to investigate the cortical thickness and subcortical volume in subjects with craniocervical dystonia and its subgroups.We studied 49 subjects, 17 with cervical dystonia, 18 with blepharospasm or oromandibular dystonia, and 79 healthy controls. We performed a whole group analysis, followed by a subgroup analysis. We used Freesurfer software to measure cortical thickness, subcortical volume and to perform a primary exploratory analysis in the craniocervical dystonia group, complemented by a region of interest analysis. We also performed a secondary analysis, with data generated from Freesurfer for subgroups, corrected by false discovery rate. We then performed an exploratory generalized linear model with significant areas for the previous steps using clinical features as independent variables.The primary exploratory analysis demonstrated atrophy in visual processing regions in craniocervical dystonia. The secondary analysis demonstrated atrophy in motor, sensory, and visual regions in blepharospasm or oromandibular dystonia, as well as in limbic regions in cervical dystonia. Cervical dystonia patients also had greater cortical thickness than blepharospasm or oromandibular dystonia patients in frontal pole and medial orbitofrontal regions. Finally, we observed an association between precuneus, age of onset of dystonia and age at the MRI exam, in craniocervical dystonia; between motor and limbic regions and age at the exam, clinical score and time on botulinum toxin in cervical dystonia and sensory regions and age of onset and time on botulinum toxin in blepharospasm or oromandibular dystonia.We detected involvement of visual processing regions in craniocervical dystonia, and a pattern of involvement in cervical dystonia and blepharospasm or oromandibular dystonia, including motor, sensory and limbic areas. We also showed an association of cortical thickness atrophy and younger onset age, older age at the MRI exam, higher clinical score and an uncertain association with longer time on botulinum toxin.

Epilepsy is more than seizures and includes a high risk of comorbidities and psychological disorders, leading to poor quality of life (QOL). Earlier studies have showed a sedentary lifestyle in people with epilepsy (PWE), which could contribute to poorer health and psychological problems. The purpose of the present study was to compare habits of physical activity (PA), aerobic capacity, and QOL between PWE and healthy controls in order to identify the necessity of intervention of habits and information on physical exercise (PE) and to better understand the importance of PE for PWE. The study included 38 patients with temporal lobe epilepsy and 20 normal controls. Both groups answered the WHOQOL-Bref, which assesses the level of QOL, and IPAQ to evaluate the level of PA. In addition, they were submitted to a treadmill maximal cardiopulmonary effort test to identify physical capacity. The continuous variables were compared between groups by t-test and a general linear model, and the frequencies were compared by Chi-Square test through SPSS software. There was no difference in the level of PA between groups by questionnaire evaluation. However, there were significant differences in overall QOL, physical health, and level of PA in relation to work and physical capacity between groups; controls demonstrated better scores than PWE. Controls presented better physical capacity than PWE by cardiopulmonary effort test. According to intra-group analyses, PWE who were physically active had better QOL than inactive PWE. The study concluded that questionnaires about PE may not be the best instrument of evaluation, as demonstrated by the discrepancy of results compared to the validated objective cardiopulmonary evaluation of level of PA and physical capacity in this study.