Frontal Lobe Involvement Research Articles

Unveiling hierarchy and spatial distribution of O6-methylguanine-DNA methyltransferase promoter methylation in World Health Organization grade 2-3 gliomas.

This study investigated the role of O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation hierarchy and heterogeneity in grade 2-3 gliomas, focusing on variations in chemotherapy benefits and resection dependency. A cohort of 668 newly diagnosed grade 2-3 gliomas, with comprehensive clinical, radiological, and molecular data, formed the basis of this analysis. The extent of resection was categorized into gross total resection (GTR ≥100%), subtotal resection (STR >90%), and partial resection (PR ≤90%). MGMTp methylation levels were examined using quantitative pyrosequencing. Our findings highlighted the critical role of GTR in improving the prognosis for astrocytomas (IDH1/2-mutant and 1p/19q non-codeleted), contrasting with its lesser significance for oligodendrogliomas (IDH1/2 mutation and 1p/19q codeletion). Oligodendrogliomas demonstrated the highest average MGMTp methylation levels (median: 28%), with a predominant percentage of methylated cases (average methylation levels >20%). Astrocytomas were more common in the low-methylated group (10%-20%), while IDH wild-type gliomas were mostly unmethylated (<10%). Spatial distribution analysis revealed a decrement in frontal lobe involvement from methylated, low-methylated to unmethylated cases (72.8%, 59.3%, and 47.8%, respectively). In contrast, low-methylated and unmethylated cases were more likely to invade the temporal-insular region (19.7%, 34.3%, and 40.4%, respectively). Astrocytomas with intermediate MGMTp methylation were notably associated with temporal-insular involvement, potentially indicating a moderate response to temozolomide and underscoring the importance of aggressive resection strategies. In conclusion, our study elucidates the complex interplay of MGMTp methylation hierarchy and heterogeneity among grade 2-3 gliomas, providing insights into why astrocytomas and IDH wild-type lower-grade glioma might derive less benefit from chemotherapy.

Selective Impairment of Verb Tense in MazandaraniSpeaking Agrammatic Patients

Introduction: Among many grammatical problems affecting agrammatic patients, those of inflectional morphology, specifically tense, stand at the forefront. This study aimed to analyze tense properties in Mazandarani-speaking Broca patients to see which aspects of this inflectional system were more negatively affected. Materials and Methods: Utilizing inclusion/exclusion criteria, we chose 10 patients (mean age 47 years) in this descriptive-analytical research. To select our participants, some criteria including the results of the Persian aphasia test, monolingualism, and magnetic resonance imaging reports were considered which corroborated the involvement of the anterior frontal lobe, inferior anterior parietal lobe, Perisylvian, and Broca’s areas as well as inferior frontal gyrus. To monitor our patients’ performance in three separate tenses of present (progressive), future, and past (simple past, past perfect, and past continuous), we administered written sentence completion and sentence-to-picture matching tests. To investigate whether our patients’ performance in diverse verb tenses was significantly different, we utilized Wilcoxon statistics to analyze our data. Results: The results demonstrated a significant difference between the performance of the patients in past progressive tense compared to other tenses (P=0.02). Furthermore, a significant difference was observed between the mean responses to past tenses and present-future tenses. Conclusion: Mazandarani-speaking agrammatic demonstrated selective poor performance in the past tense inflection. Regarding the crucial role of tense properties in verbal communication, specifically past tense, to talk about past events and memories, more attention is needed by clinicians and speech therapists to reinforce tense properties enhancing agrammatic communication capabilities.

ETMR-30. CLINICAL AND MOLECULAR CHARACTERIZATION OFDICER-MUTANT CENTRAL NERVOUS SYSTEM SARCOMA

Abstract BACKGROUND Central nervous system (CNS) sarcomas are rare mesenchymal non-meningothelial tumors accounting for 0.2% of brain tumors. Due to their rarity, there is a lack of substantive clinical, histological and molecular data. METHODS Patients diagnosed with primary CNS sarcomas were identified through several international collaborations. DNA methylation profiles were generated using 850K microarray assays, followed by unsupervised hierarchical clustering and t-SNE analyses. Additionally, targeted DNA sequencing was employed to characterize the somatic landscape. Clinical data was collected and summarized using descriptive statistics, and survival estimates were calculated using the Kaplan-Meier method. RESULTS We analyzed DNA methylation data of 65 tumor samples. Clustering analyses demonstrated DICER-1 CNS sarcomas segregate into two distinct epigenetic subgroups. Copy number analysis demonstrated frequent CNV alterations and chromothripsis in 35% of the samples. DICER-1 mutations were present in 85% of cases and associated with frequent additional alterations in TP53 (65%) and KRAS (51%). The median age at diagnosis was 10.4 years (r: 0.4 - 71 y) and 52% (n=34) of subjects were male. Tumors were frequently (91%) located in the supratentorial compartment, frontal lobe involvement was noted in 62% of cases. Patients were treated with multimodal approaches including surgery, ICE chemotherapy, and focal radiation. At median follow-up time of 27.5 months, the 2-year progression-free and overall survival was 50.8% (r: 0.31-0.67) and 53.5% (r: 0.34-0.69) respectively. CONCLUSIONS DICER-1 CNS Sarcoma is an aggressive entity that segregates into two epigenetic subgroups, clinical and genotype correlations remain to be elucidated. Current multimodal approaches are only effective in a subset of patients. The identification of MAPK pathway alterations in most cases should be explored as a therapeutic avenue.

Associations between regional blood-brain barrier permeability, aging, and Alzheimer's disease biomarkers in cognitively normal older adults.

Increased blood-brain barrier permeability (BBBp) has been hypothesized as a feature of aging that may lead to the development of Alzheimer's disease (AD). We sought to identify the brain regions most vulnerable to greater BBBp during aging and examine their regional relationship with neuroimaging biomarkers of AD. We studied 31 cognitively normal older adults (OA) and 10 young adults (YA) from the Berkeley Aging Cohort Study (BACS). Both OA and YA received dynamic contrast-enhanced MRI (DCE-MRI) to quantify Ktrans values, as a measure of BBBp, in 37 brain regions across the cortex. The OA also received Pittsburgh compound B (PiB)-PET to create distribution volume ratios (DVR) images and flortaucipir (FTP)- PET to create partial volume corrected standardized uptake volume ratios (SUVR) images. Repeated measures ANOVA assessed the brain regions where OA showed greater BBBp than YA. In OA, Ktrans values were compared based on sex, Aβ positivity status, and APOE4 carrier status within a composite region across the areas susceptible to aging. We used linear models and sparse canonical correlation analysis (SCCA) to examine the relationship between Ktrans and AD biomarkers. OA showed greater BBBp than YA predominately in the temporal lobe, with some involvement of parietal, occipital and frontal lobes. Within an averaged ROI of affected regions, there was no difference in Ktrans values based on sex or Aβ positivity, but OA who were APOE4 carriers had significantly higher Ktrans values. There was no direct relationship between averaged Ktrans and global Aβ pathology, but there was a trend for an Ab status by tau interaction on Ktrans in this region. SCCA showed increased Ktrans was associated with increased PiB DVR, mainly in temporal and parietal brain regions. There was not a significant relationship between Ktrans and FTP SUVR. Our findings indicate that the BBB shows regional vulnerability during normal aging that overlaps considerably with the pattern of AD pathology. Greater BBBp in brain regions affected in aging is related to APOE genotype and may also be related to the pathological accumulation of Aβ.

Ictal Coprolalia: Three Cases with Nondominat Frontal Lobe Involvement and Review of the Literature.

Objective: Coprolalia is defined as the involuntary use of obscene, socially unacceptable, and derogatory words. Ictal coprolalia is a rare presentation of epilepsy. This study aimed to determine the localizing and lateralizing value and frequency of ictal coprolalia in epilepsy patients. Methods: Medical files, discharge summaries, and electroencephalography (EEG) reports of 2238 patients were reviewed retrospectively. We identified patients who suffered from ictal coprolalia. Electroencephalography reports, neuroimaging [brain magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET), single-photon emission computerized tomography (SPECT)] records, F-18 FDG fused on MRI images, and ictal SPECT fused on MRI images were evaluated. Also, original and review articles were identified through a systematic search of Pubmed, Scopus, and Clarivate Analytics. Results: Ictal coprolalia was detected in 3 male (0.15%) patients. In all patients, ictal semiology was extratemporal-frontal type, and potential/proven epileptic focus was non-dominant hemisphere frontal lobe. Topectomy was done in one of the patients, including the suspected dysplastic area plus the area where the electroencephalographic ictal and interictal changes occur, on the left frontal lobe, and the patient had an Engel's classification class IIA. The data depending on the published cases showed that ictal coprolalia was dominant in the male gender and the responsible epileptic area tended to be located in the non-dominant hemisphere frontotemporal region. Conclusion: The rate of ictal coprolalia in the Turkish population is lower compared to other series. Our results are consistent with previous studies in which reported that male preponderance for ictal coprolalia and involvement of non-dominant frontal lobe.

Anomia: Deciphering Functional Neuroanatomy in Primary Progressive Aphasia Variants.

Naming decline is one of the most common symptoms of primary progressive aphasia (PPA). Most studies on anomia in PPA are performed without taking into account PPA variants, especially for action naming. Only limited data are available for the neuroanatomical basis of anomia considering differences in the pathogenesis of PPAs. The aim of our study is to investigate the associations between anomia severity for both noun and verb naming and gray matter (GM) atrophy, as well as accompanying functional connectivity (FC) changes in three PPA variants. A total of 17 patients with non-fluent (nfvPPA), 11 with semantic (svPPA), and 9 with logopenic (lvPPA) PPA variants were included in the study and underwent cognitive/naming assessments and brain MRIs. Voxel-based morphometry was performed to evaluate GM volume. A resting-state functional MRI was applied to investigate FC changes in the identified GM areas. The study shows that different brain regions are involved in naming decline in each PPA variant with a predominantly temporal lobe involvement in svPPA, parietal lobe involvement in lvPPA, and frontal lobe involvement in nfvPPA. Separate data for object and action naming in PPA variants are provided. The obtained results mainly correspond to the current understanding of language processing and indicate that the evaluation of language impairments is preferable for each PPA variant separately. A further analysis of larger cohorts of patients is necessary to confirm these preliminary results.

Semantic processing during continuous speech production: an analysis from eye movements and EEG.

Speech production involves neurological planning and articulatory execution. How speakers prepare for articulation is a significant aspect of speech production research. Previous studies have focused on isolated words or short phrases to explore speech planning mechanisms linked to articulatory behaviors, including investigating the eye-voice span (EVS) during text reading. However, these experimental paradigms lack real-world speech process replication. Additionally, our understanding of the neurological dimension of speech planning remains limited. This study examines speech planning mechanisms during continuous speech production by analyzing behavioral (eye movement and speech) and neurophysiological (EEG) data within a continuous speech production task. The study specifically investigates the influence of semantic consistency on speech planning and the occurrence of "look ahead" behavior. The outcomes reveal the pivotal role of semantic coherence in facilitating fluent speech production. Speakers access lexical representations and phonological information before initiating speech, emphasizing the significance of semantic processing in speech planning. Behaviorally, the EVS decreases progressively during continuous reading of regular sentences, with a slight increase for non-regular sentences. Moreover, eye movement pattern analysis identifies two distinct speech production modes, highlighting the importance of semantic comprehension and prediction in higher-level lexical processing. Neurologically, the dual pathway model of speech production is supported, indicating a dorsal information flow and frontal lobe involvement. The brain network linked to semantic understanding exhibits a negative correlation with semantic coherence, with significant activation during semantic incoherence and suppression in regular sentences. The study's findings enhance comprehension of speech planning mechanisms and offer insights into the role of semantic coherence in continuous speech production. Furthermore, the research methodology establishes a valuable framework for future investigations in this domain.

Initial frontal lobe involvement in adult cerebral X-linked adrenoleukodystrophy.

Adult cerebral X-linked adrenoleukodystrophy (ACALD) with initial frontal lobe involvement is a rare genetic disease that is easily misdiagnosed and underdiagnosed. We sought to improve the early identification of such diseases. We present three cases of adult X-linked adrenoleukodystrophy (ALD) with initial frontal lobe involvement and identify an additional 13 cases from the database. The clinical and imaging characteristics of the overall sixteen cases were analyzed. The average age of onset was 37years, with 15 male and 1 female patient. A total of 12 patients (75%) developed a decline in cerebral executive and cognitive functions. Brain trauma is the possible trigger for the onset of ALD in five patients (31%). An elevated level of very-long-chain fatty acids (VLCFA) was observed in all 15 patients on whom a plasma VLCFA was performed.10 patients with gene tests showed different mutation sites in the ABCD1 gene. Brain MRI of six patients (46%) were characterized by frontal lobe "butterfly wings"-like lesions with peripheral rim enhancement. Four patients underwent brain biopsies (patients 1, 3, 15, and 13), and five patients (31%) were initially misdiagnosed (patients 1, 2, 3, 11, and 15). Nine of the patients with follow-up records experienced poor prognoses, and five of them, unfortunately, died (56%). ACALD patients with anterior patterns tend to be misdiagnosed. The early clinical manifestation is a decline in cerebral executive and cognitive function. Brain trauma may be a trigger for this pattern. Brain MRI findings are characterized by frontal lobe "butterfly wing"-like lesions with peripheral rim enhancement. The determination of the VLCFA levels and the genetic detection of the causative mutations are required to confirm the diagnosis.

Magnetic resonance imaging brain yield in developmental delay: A developing country perspective

BackgroundDevelopmental delay (DD) is an important neuro-morbidity in children affecting the quality of life. MRI plays a crucial role by delineating the underlying structural, metabolic, and genetic abnormalities. AimTo determine the yield of MRI brain in delineating the various underlying abnormalities and etiological factors in children with DD and to correlate these findings with the clinical presentation. MethodsThis cross-sectional study enrolled 50 children with the developmental delay between 6 months to 6 years of age. Outcomes and resultsThe mean age was 31.32 ± 20.56 months. The sensitivity of MRI was 72%. 81.3% of the children with microcephaly had abnormal MRI. The most common underlying etiology was hypoxic-ischemic encephalopathy (42%), followed by congenital/developmental defects and metabolic diseases (10% each). The most commonly involved region of the cerebral cortex was the occipital lobe (44%) because of the high occurrence of coexisting hypoglycemic brain injury, which is extremely common in developing countries and rare in developed countries, with 80% of them having visual abnormalities. Frontal lobe involvement was significantly more in children with abnormal motor findings and behavioral changes. Cortical grey matter abnormalities were significantly more in children with seizures. Conclusion and implicationsIt is to be emphasized that children with developmental delays should be evaluated with MRI whenever possible. Apart from hypoxic-ischemic encephalopathy, other etiologies should also be looked for.

Frontal lobe epilepsy and mild malformation with oligodendroglial hyperplasia: Further observations on electroclinical and imaging phenotypes, and surgical perspectives.

Mild malformation with oligodendroglial hyperplasia (MOGHE) is a recently described clinicopathologic entity, associated with drug-resistant epilepsy and extensive epileptogenic networks. Knowledge is accumulating about particular electroclinical phenotypes, correlations with imaging, and potential prognostic significance for surgical outcomes. The study adds relevant information by documenting the presence of a hyperkinetic frontal lobe seizure phenotype in adolescents and an epileptic encephalopathy phenotype in young children. Five cases were subjected to a structured presurgical evaluation protocol, including EEG-FMRI, chronic and acute invasive EEG, subjected to frontal lobe surgery with postoperative follow-up between 15 months and 7 years. In the two adult cases, surface EEG demonstrated lateralized widespread frontal lobe epileptogenicity and hyperkinetic semiological features. MRI demonstrated cortical white matter blurring and deeper white matter abnormalities. EEG-FMRI suggested concordant frontal lobe involvement. iEEG demonstrated a widespread frontal lobe epilepsy network. The three young children demonstrated a diffuse epileptic encephalopathy phenotype, with nonlocalizing, nonlateralizing surface EEG, and "spasms" as the main seizure type. MRI demonstrated extensive frontal lobe subcortical gray and white matter abnormalities, consistent with MOGHE literature for this age, while EEG-FMRI, in 2/3, demonstrated concordant frontal lobe involvement. They did not undergo chronic iEEG, and the resection was assisted by acute intraoperative ECoG. All cases were subjected to extensive frontal lobectomies with Engel class IA (2/5), IB (1/5), and IIB (2/5) outcomes. The study confirms the presence of frontal lobe epilepsy and epileptic encephalopathy phenotypes, in accordance with epilepsy phenotypes already described in MOGHE literature. Presurgical evaluation studies, including EEG-FMRI, can provide strong lateralizing and localizing evidence of the epileptogenic networks involved. All responded favorably to extensive frontal lobe resections, despite widespread epileptic activity recorded by surface and intracranial EEG pre- and postoperatively; an epileptic encephalopathy phenotype, in the first years of life, should not discourage such a resection.

Use of Thalamus L-Sign to Differentiate Periventricular Leukomalacia From Neurometabolic Disorders.

To assess the diagnostic value of the thalamus L-sign on magnetic resonance imaging (MRI) in distinguishing between periventricular leukomalacia and neurometabolic disorders in pediatric patients. In this retrospective study, clinical and imaging information was collected from 50 children with periventricular leukomalacia and 52 children with neurometabolic disorders. MRI was used to evaluate the L-sign of the thalamus (ie, injury to the posterolateral thalamus) and the lobar distribution of signal intensity changes. Age, sex, gestational age, and level of Gross Motor Function Classification System (only for periventricular leukomalacia) constituted the clinical parameters. Statistical evaluation of group differences for imaging and clinical variables were conducted using univariable statistical methods. The intra- and inter-observer agreement was evaluated using Cohen's kappa. Univariable or multivariable logistic regression was employed for selection of variables, determining independent predictors, and modeling. The thalamus L-sign was observed in 70% (35/50) of patients in the periventricular leukomalacia group, but in none of the patients with neurometabolic disorder (P < .001). The gestational age between groups varied significantly (P < .001). Involvement of frontal, parietal, and occipital lobes differed significantly between groups (P < .001). In the logistic regression, the best model included negative thalamus L-sign and gestational age, yielding an area under the curve, accuracy, sensitivity, specificity, and precision values of 0.995, 96.1%, 96%, 96.2%, and 96%, respectively. Both the lack of thalamus L-sign and gestational age were independent predictors (P < .001). The thalamus L-sign and gestational age may be useful in distinguishing between periventricular leukomalacia and neurometabolic disorders.

Post-stroke Epilepsy and its Association with Stroke Location - Meta-analysis (P3-1.004)

<h3>Objective:</h3> The objective of this study was to review the association between stroke location and post-stroke epilepsy (PSE). <h3>Background:</h3> There have been several meta-analytic studies that investigated potential risk factors for PSE^1,2. Cortical location is known to be associated with increased risk of PSE. However, relationship between the involvement of specific lobe with stroke and PSE has not been evaluated in a meta-analysis due to availability of relevant data. To the best of our knowledge, this is the first meta-analysis on this subject matter. <h3>Design/Methods:</h3> The PubMed and Embase databases were comprehensively assessed and searched for studies that evaluated the association between the involvement of different lobes with PSE. Studies that evaluated post-stroke epilepsy or recurrent post-stroke seizure were included, and acute symptomatic seizure was excluded. Following search strategy was used, “post-stroke” OR “stroke” OR “intracerebral hemorrhage” AND “epilepsy” OR “seizure” AND “lobe” OR “territory” OR “location”. A random effects model was used to estimate pooled odds ratio of the selected outcomes with 95 percent confidence intervals (CIs), and the study heterogeneity was analyzed. <h3>Results:</h3> Nine studies^3–11 were identified with 1328 stroke patients. 9/9 studies showed association of frontal lobe involvement with higher likelihood of PSE (OR=2.10, 95% CI=1.37–3.21, p-value=0.0007). All studies showed association of parietal stroke with increased likelihood of PSE (OR=2.85, 95% CI=1.93–4.22, p-value &lt;0.00001). Previous temporal lobe stroke was associated with increased risk of PSE (OR=3.55, 95% CI=1.95–6.45, p-value &lt;0.00001). In contrast, association between occipital lobe involvement and PSE was not statistically significant (OR=1.37, 95% CI=0.95–1.96, p-value &lt;0.09). <h3>Conclusions:</h3> Our meta-analysis shows that PSE is associated with frontal, parietal, and temporal involvement of previous stroke. There was no statistically significant association between occipital lobe involvement and PSE. Further high quality studies are needed to investigate if stroke in one lobe/territory can be more epileptogenic than those in others. <b>Disclosure:</b> Dr. Park has nothing to disclose. Dr. Esengul has nothing to disclose. Dr. Sheikh has nothing to disclose. Dr. Gharaibeh has nothing to disclose.

FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures overlaying anti-N-methyl-D-aspartate receptor encephalitis: a case report and literature review

FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) has been identified increasingly frequently in recent years. However, this rare MOG antibody disease may coexist with anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARe), in an overlap syndrome with unknown clinical features and prognosis. We report a new case of this overlap syndrome and present a systematic review of similar cases in the literature to provide information on the clinical presentation, MRI features, EGG abnormalities, treatment, and prognosis of patients with this rare syndrome. A total of 12 patients were analyzed in the study. The most common clinical manifestations of FLAMES overlaid with anti-NMDARe were epilepsy (12/12), headache (11/12), and fever (10/12). Increases in intracranial pressure (median: 262.5 mmH2O, range: 150-380 mmH2O), cerebrospinal fluid (CSF) leukocyte count (median: 128×106/L, range: 1-610×106/L), and protein level (median: 0.48 g/L) were also observed. The median CSF anti-NMDAR antibody titer was 1:10 (1:1-1:32), while the median serum MOG antibody titer was 1:32 (1:10-1:1024). Seven cases exhibited unilateral cortical FLAIR hyperintensity, and five cases (42%) had bilateral cortical FLAIR hyperintensity, including four cases involving the bilateral medial frontal lobes. Of the 12 patients, five showed lesions at other sites (e.g., the brainstem, corpus callosum, or frontal orbital gyrus) before or after the development of cortical encephalitis. EEG showed slow waves in four cases, spike-slow waves in two cases, an epileptiform pattern in one case, and normal waves in two cases. The median number of relapses was two. Over a mean follow-up period of 18.5 months, only one patient experienced residual visual impairment, while the remaining 11 patients had good prognoses. FLAMES alone is difficult to distinguish from overlap syndrome based on clinical features. However, FLAMES with bilateral medial frontal lobe involvement suggests the presence of the overlap syndrome.

A logistic binary Jaya optimization-based channel selection scheme for motor-imagery classification in brain-computer interface

BCI systems use motor imagery to allow users to control external devices through their brain activity. They extract neural signals from the brain using a large number of EEG channels. However, high-dimensional data from multichannel BCI systems increases the computational burden, leading to slower processing and higher costs. In this study, we proposed a Logistic S-shaped Binary Jaya Optimization Algorithm (LS-BJOA), which combines a logistic map with the Jaya optimization algorithm to alleviate the computational burden caused by many channels. The logistic map introduces stochasticity to better simulate the chaotic behavior of brain signals and improve predictive accuracy. Our method initializes a set of three electrodes as a candidate solution and subsequently determines the most relevant channels iteratively. We used a bi-objective fitness function to evaluate the significance of the selected channels, which involves maximizing classification accuracy and minimizing the length of the channel subset. Initially, a fifth-order bandpass filter with Independent Component Analysis (ICA) was applied to filter MI signals and artifacts reduction, respectively. The Regularized Common Spatial Pattern (RCSP) was used to extract spatiotemporal features from the selected channels. Finally, the three classifiers: (1) Support Vector Machine (SVM), (2) Naïve Bayes (NB), and (3) Linear Discriminant Analysis (LDA) were used to determine maximum classification accuracy. The experiment is validated on three public EEG datasets (BCI Competition IV- 2008 – IIA, BCI Competition IV- dataset 1, BCI competition III – dataset IVa). Our method achieved superior classification accuracy (83.59%, 82.09%, and 89.02% on datasets 1, 2, and 3 respectively) with fewer channels than baseline methods. Additionally, computation time was significantly reduced without compromising accuracy. Topographical mapping revealed frontal lobe involvement in MI tasks during physical activities. Topographical mapping of the selected channels showed that the frontal lobe executes various MI tasks during physical activities.

CAR t-cell therapy in BOlogNa-NEUrotoxicity TReatment and Assessment in Lymphoma (CARBON-NEUTRAL): proposed protocol and results from an Italian study.

To investigate neurotoxicity clinical and instrumental features, incidence, risk factors, and early and long-term prognosis in lymphoma patients who received CAR T-cell therapy. In this prospective study, consecutive refractory B-cell non-Hodgkin lymphoma patients who received CAR T-cell therapy were included. Patients were comprehensively evaluated (neurological examination, EEG, brain MRI, and neuropsychological test) before and after (two and twelve months) CAR T-cells. From the day of CAR T-cells infusion, patients underwent daily neurological examinations to monitor the development of neurotoxicity. Forty-six patients were included in the study. The median age was 56.5years, and 13 (28%) were females. Seventeen patients (37%) developed neurotoxicity, characterized by encephalopathy frequently associated with language disturbances (65%) and frontal lobe dysfunction (65%). EEG and brain FDG-PET findings also supported a predominant frontal lobe involvement. The median time at onset and duration were five and eight days, respectively. Baseline EEG abnormalities predicted ICANS development in the multivariable analysis (OR 4.771; CI 1.081-21.048; p = 0.039). Notably, CRS was invariably present before or concomitant with neurotoxicity, and all patients who exhibited severe CRS (grade ≥ 3) developed neurotoxicity. Serum inflammatory markers were significantly higher in patients who developed neurotoxicity. A complete neurological resolution following corticosteroids and anti-cytokines monoclonal antibodies was reached in all patients treated, except for one patient developing a fatal fulminant cerebral edema. All surviving patients completed the 1-year follow-up, and no long-term neurotoxicity was observed. In the first prospective Italian real-life study, we presented novel clinical and investigative insights into ICANS diagnosis, predictive factors, and prognosis.

Seizure in geriatric population - An unheeded integer.

Epilepsy is one of the most prevalent neurological conditions among the elderly. Age-related epileptogenic disorders as well as the ageing itself pose a risk for seizures in the elderly. The lack of witnesses, non-specific symptoms, and transient symptoms make the diagnosis challenging in the elderly. This study aimed to assess the various presentation and aetiology for the seizure disorder in the elderly population. A total of 125 elderly patients ≥60 years with new onset seizure were included in the study. Demographic data, co-morbidities, and clinical presentation of seizure were elicited. Hemogram, liver and renal function tests, random blood sugar, electrolytes, and serum calcium were analysed. Computed tomography (CT), magnetic resonance imaging (MRI) brain, and electroencephalogram (EEG) were performed. Seizure was seen predominantly in the males with age group of 60-70 years. Generalized tonic-clonic seizure was the commonest presentation, followed by focal seizures. The leading causes of seizures were cerebral vascular accidents, metabolic conditions, and alcohol. CT brain was abnormal in 49%, and 73% of the patients showed abnormality in MRI brain. EEG was abnormal in 17.3% of patients. Temporal lobe infarction was the commonest, trailed by parieto-temporal and frontal lobe involvement. Seizures in the elderly have varied clinical signs and aetiology. An awareness about these atypical presentation and aetiology is essential for the early diagnosis and management to prevent morbidity.

Clinical characteristics and associated factors of pediatric acute disseminated encephalomyelitis patients with MOG antibodies: a retrospective study in Hangzhou, China

BackgroundTo explore the clinical characteristics and related factors of children with acute disseminated encephalomyelitis (ADEM) with positive anti-myelin oligodendrocyte glycoprotein (MOG) antibody.MethodsA retrospective study was conducted and enrolled pediatric ADEM patients who underwent serum MOG antibody detection from May 2017 to August 2020. The patients were divided into two groups: MOG- immunoglobulin G (IgG) positive (n = 35) and MOG-IgG negative (n = 50). We analyzed the clinical characteristics of MOG-IgG-positive ADEM pediatric patients and conducted a comparative analysis between the two groups.ResultsThirty-five patients (21 males and 14 females) in the MOG-IgG-positive group with encephalopathy, multifocal neurological symptoms, and typical magnetic resonance imaging (MRI) abnormalities were enrolled. They usually had a favorable outcome, while some suffered from relapse. Compared to the MOG-IgG-negative group, MOG-IgG-positive ADEM patients had a longer disease duration (median: 10 vs. 6 days), more meningeal involvement (31.4% vs. 8%) and frontal lobe involvement (82.8% vs. 68%), higher relapse rates (14.3% vs. 2%), lower serum tumor necrosis factor (1–12.4 pg/ml, median 1.7 vs. 1–34 pg/ml, median 2.2) and interferon-gamma (1–9.4 pg/ml, median 1.3 vs. 1–64 pg/ml, median 3) (P < 0.05, respectively). Multivariate logistic regression analysis showed that the longer disease duration, meningeal involvement and frontal lobe involvement were the correlated factors of patients with ADEM with MOG antibody (P < 0.05).ConclusionsOur findings provide clinical evidence that MOG-IgG positivity is associated with longer disease duration, meningeal involvement, and frontal lobe involvement.

A Novel Radiographic and Clinical Assessment Scoring Tool for Seizure Risk Stratification in the Acute Phase of Cerebral Venous Sinus Thrombosis: A Systematic Review and Meta-Analysis

Background: Nearly 40% of cerebral venous sinus thrombosis (CVST) cases experience a seizure. A plethora of problems may arise from seizures. Many of these are well recognized in literature as well as in clinical practice. These include the risk for acute respiratory failure, acute renal injury, demand ischemia of myocardium, aspiration pneumonia, and a variety of musculoskeletal injury. Given the lack of a validated tool to predict seizure in the acute phase of CVST, the use of prophylactic anti-epileptic drugs (AEDs) is controversial. A systematic review and meta-analysis of observational studies was conducted to identify risk factors to construct a clinical prediction tool for seizure in acute CVST. Methods: Systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Observational studies that investigated the risk factors for seizure in acute CVST were retrieved from MEDLINE, EBSCO, Web of Science, and Pro-Quest. The summary odds ratios (ORs) were calculated from the pool of data under the random effects model. A point value of 1, 2, or 3 was assigned to each risk factor based on their β-coefficient in the predictive model. Discriminative ability of this model was evaluated on the receiver operating characteristic curve. Results: Initial literature search revealed 1,046 articles discussing seizure as a complication of acute CVST. Through a robust systematic review process with two independent reviewers, 14 studies fully meeting the inclusion criteria were selected. Data elements extracted from the studies were analyzed and re-synthesized. Anatomical involvement of frontal lobe (OR: 4.85; 95% confidence interval (CI): 3.52 - 6.68), parietal lobe (OR: 2.52, 95% CI: 1.41 - 4.52), cortical vein thrombosis (OR: 3.16, 95% CI: 2.18 - 4.58), hemorrhagic venous ischemia (OR: 3.85; 95% CI: 3.20 - 4.64), and clinical presentation of motor deficit (OR: 3.07; 95% CI: 2.66 - 3.55) or confusion (OR: 2.15; 95% CI: 1.57 - 2.94) showed a strong association with increased risk for seizure in the setting of acute CVST. We developed a novel Radiographic and Clinical Assessment (RC) scoring system, consisting of the significant six risk factors. RC score yielded a calculated area under the curve of 0.89, with probabilities for seizure ranging from 40% with a score of 0 to 92% for score of 6. Conclusions: RC scoring tool can be used to stratify the seizure risk based on radiographic findings and the clinical presentation in the acute phase of CVST. This predictive tool may be helpful in identifying patients whose seizure risk is high and can potentially further be used as a clinical decision support tool for prophylactic AED treatment. J Neurol Res. 2022;12(3):114-120 doi: https://doi.org/10.14740/jnr731

P03.11.A Potential role of pre-radiotherapy MRI for target delineation in high-grade gliomas: a multicenter retro-prospective cohort study

Abstract Background The optimal timing for target identification in high-grade glioma (HGG) remains unclear due to variability in the hyper-signal T2/FLAIR between MRI performed at diagnosis, post-surgery and at radiotherapy (RT) start. The aim of this study was to retrospectively confirm that RT planned on delayed MRI might allow to spare more normal tissue without decreasing local tumour control, in order to prospectively evaluate the best standard and advanced MRI and metabolic imaging sequences for clinical tumor volume (CTV) adaptation. Material and Methods We analyzed a retrospective cohort of consecutive patients with HGG treated from 2017 to 2020. All patients had a diagnostic MRI and another performed immediately post-surgery or pre-RT. Target volumes were contoured, based on T2/FLAIR, on diagnostic and post-surgery MRI in group A, while in group B on pre-RT MRI. We analyzed GTV and CTV volume, and the percentage increase between them. Moreover, we compared the two groups in terms of clinical-pathological characteristics and progression-free survival (PFS) and overall survival (OS). A prospective study, started on January 2022, has enrolled patients with HGG evaluated by advanced sequences MRI at diagnosis, post-surgery and pre-RT. In addition, some selected patients have undergone diagnostic DOPA-PET and pre-RT DOPA-PET. 2 MRI-guided contours have been performed for each patient: adapted on T2/FLAIR post-surgery and CTV-adapt on pre-RT, to assess study objectives. Results In retrospective cohort we analyzed 54 patients (25 group A, 29 group B). The median age of patients was 61 years (IQR 17,75), 93% had an ECOG PS of 0 or 1, 51 were symptomatic at diagnosis. Patients in group B had more frequently MGMT methylation (59 % vs. 28%, p=0.01) while less frequently frontal lobe involvement (60% vs. 24%, p=0.01). The median percentage increase between GTV and CTV was higher in group A than B: 431% (range 62%-7335%) vs 385% (range 53%-3174%), respectively. No significant difference in the pattern of relapse was observed, since &amp;gt;90% of disease recurrences were in-field in both groups. Median PFS and OS of the overall population were 9.5 months (95% CI 7 - 12) and 18.5 months (95% CI 16 - 24), respectively. Patients in group B had a significant better PFS as compared to those in group A (p=0.03), but similar OS. Nevertheless, imbalance in MTMT methylation status between the two groups was a major driver for PFS. Overall, 37 out of 51 patients had improvement in neurological symptoms (p&amp;lt;0.001), with no difference between the two groups (p=0.54). Conclusion Our data suggest that CTV adaptation to pre-RT T2/FLAIR may allow reducing RT volume, without affecting symptoms relieving and disease control. Results from the prospective study will help identifying the best adaptation of CTV guided by T2/FLAIR, advanced MRI sequences and metabolic imaging, in order to optimize efficacy and safety of treatment planning.

I'm looking through you: Mentalizing in frontotemporal dementia and progressive supranuclear palsy

Mentalizing and emotion recognition are impaired in behavioral variant frontotemporal dementia (bvFTD). It is not clear whether these abilities are also disturbed in other conditions with prominent frontal lobe involvement, such as progressive supranuclear palsy (PSP). Our aim was to investigate social cognition (facial emotion recognition, recognition of social norms violation and mentalizing) in bvFTD and PSP. The neural basis of these functions in PSP and bvFTD groups, by analysis of structural neuroimaging, were also investigated. Twenty-three bvFTD patients, 21 PSP patients and 23 healthy controls were included. All participants underwent 3T brain MRI and a full cognitive exam including the short version of Social and Emotional Assessment (Mini-SEA), which is composed of a facial emotion recognition test (FERT) and the faux pas test. Two components of the faux pas test were distinguished: a score assessing the recognition of social norms violation and a score assessing mentalizing. Compared to controls, bvFTD and PSP patients had significantly reduced scores in all tests of social cognition but did not differ on these measures. PSP and bvFTD had cerebral atrophy in critical regions for social cognition processes, when compared to controls. The cortical correlates of emotion recognition partially overlapped in bvFTD and PSP, with correlations retrieved within the frontal medial cortex, cingulate, insula and limbic structures. PSP and bvFTD patients also displayed similar patterns of brain correlations for the composite score of social norms, with a significant cluster in anterior temporal lobes. Mentalizing scores were associated with frontal and temporal poles bilaterally, in both bvFTD and PSP. These findings support previous observations that PSP patients exhibit impairment in complex cognitive abilities, such as mentalizing. Moreover, these data extend previous findings showing that PSP and bvFTD share key clinical, cognitive and neuroimaging features.