Presence Of Brain Lesions Research Articles

A lesion‐aware automated processing framework for clinical stroke magnetic resonance imaging

AbstractMagnetic resonance imaging (MRI) and MRI based computational modelling studies provide insights into severity and recovery of ischemic stroke patients. The presence of brain lesions, however, can heavily distort and impair state‐of‐the‐art processing frameworks due to abnormal intensity values and tissue distortions. In this study, we introduce and validate the novel “Lesion Aware automated Processing Pipeline (LeAPP).” LeAPP automatically processes clinical stroke MRI data while significantly reducing the impact of pathological artefacts on processing outputs such as structural and functional connectomes (SC, FC). This helps to advance the identification of biomarkers for recovery and mechanism‐based intervention planning using MRI as well as computational approaches. We extended existing frameworks, such as the Human Connectome Project (HCP) minimal processing pipeline, introducing correction steps, and implementing and modifying functional and diffusion processing to cope with MRI acquisition protocols more typical for the clinical context. A total of 51 participants (36 patients, 15 age‐matched controls) were processed across four time points for patients (3–5, 30–40, 85–95, 340–380 days after stroke onset) and one time point for controls. We validated performance using artificial lesioned brains (N = 81), derived from healthy brains and informed by real stroke lesions. The quality of reconstructing the ground truth was quantified on whole brain level and for lesion affected and unaffected regions‐of‐interest (ROIs) for brain parcellations and for SCs. Volume based agreement was evaluated using metrics such as dice coefficient, volume difference or ROI center‐of‐gravity distance while SC based agreement was defined as the difference in network metrics (e.g., node strength, clustering coefficient, or centrality). The observed deviations in reconstructed ground truth brain parcellations and structural connectomes from lesioned brains were significantly reduced for LeAPP, compared to the performance of existing pipelines such as HCP minimal processing pipeline. For instance, in the case of lesion affected ROIS we achieved a mean dice coefficient (where a value of one represents total agreement as defined by an exact overlap of both ROIs) of 0.81 with LeAPP, compared to 0.75 for HCP (p < .0001*). Additionally, the average measured ROI distance (where a value of zero represents no difference) for lesion ROIs was 0.87 for LeAPP in contrast to 1.7 for HCP (p < .0001*), indicating an overall superior performance of LeAPP. The pipeline generates standardized output files ready for brain network modelling for instance with The Virtual Brain software. This novel open‐source automated processing framework contributes to reproducible research and provides a robust framework for automated processing of clinical stroke MRI data, supporting the identification of brain network‐based biomarkers of stroke recovery.

Model predicting the onset of antiepileptic drug resistance in women of reproductive age with epilepsy: analytical study

Introduction. In attempt to find an answer regarding the possible scenarios of epilepsy evolution in women of reproductive age (e.g. worsening, remission, antiepileptic drug resistance, status epilepticus occurence), preferably - objective, based on simple, replicable, observable indicators that can be included in a mathematical probability estimation model, could significantly improve their quality of life and increase the effectiveness of prescribed treatments. Materials and methods. Bidirectional, cohort, descriptive-analytical study, conducted between 2016-2020. Primary data were collected in the Diomid Gherman Institute of Neurology and Neurosurgery, the State Hospital of Republic of Moldova and the Excellence Private Medical Institution. Out of 366 unique parameters, which were recorded in the 159 patients enrolled in the study at each visit (total, 4 documentation visits over 5 years period), 10 parameters were selected for multivariate analysis, considered relevant for predicting clinically significant outcomes. Criteria for parameter relevance were: reaching p≤0.1 in univariate analysis, easy documentation. Subsequently, testing for multicollinearity (calculation of variance inflation factor) and the contribution of each parameter in the formula was performed using the Akaike informativeness criteria. The performance of the developed predictive models was expressed by the area under the ROC curve, positive and negative prognostic power. Statistical analysis: GraphPad Prism, v. 9 trial (Graph Pad Software, Boston, USA). Results. Age at onset of the disease 14.0±6.3 years; age at first referral to specialist 24.0±7.2 years. The developed predictive model, based on 3 parameters (depressive state, annual frequency of seizures, presence of brain lesions on MRI) has a positive predictive value of 83%, negative of 62%, with an area under the ROC curve of 0.72 (95%CI = 0.56 to 0.88) and a probability of occurrence of 96%. Conclusions. Depressed patients with documented structural lesions on MRI and a high frequency of epileptic seizures have a progressive, significant risk (an OR of 5.3-24.0) of developing resistance to antiepileptic drugs.

NCMP-23. EVALUATION OF IMMUNOTHERAPY EFFECTS IN CANCER PATIENTS ON EPILEPTIFORM ACTIVITY

Abstract BACKGROUND/OBJECTIVE Immune checkpoint inhibitors are associated with increased risk of autoimmune neurologic conditions, both in the peripheral and central nervous system. Increased activation of the immune system can lower seizure threshold, potentially increasing a patient’s risk of seizures. We hypothesize that patients treated with immune checkpoint inhibitors have a higher rate of seizures. METHODS We retrospectively reviewed 465 cancer patients undergoing electroencephalography (EEG) monitoring performed at Memorial Sloan Kettering Cancer Center from January 2022 to March 2023. Data was gathered from an EEG RedCap database containing patient demographic and seizure data. Patients were separated based on whether they had received immune checkpoint inhibitors (+ICI) prior to seizure occurrence or were never exposed to immune checkpoint inhibitors (-ICI) and had a seizure. Patient cancer type and presence of brain lesions (primary or metastases) were also reviewed. RESULTS Out of 465 patients, 109 received immune checkpoint inhibitors (+ICI) during their treatment. Seven of those patients were reported to have had at least one seizure (7/109, 6.42%) following treatment with ICI. The remaining 356 patients did not undergo immune checkpoint inhibitor treatment (-ICI), of which 30 were reported to have had at least one seizure (30/356, 8.43%). Of the +ICI patients who were experiencing seizures, 5 of them had brain lesions; 4 had primary brain tumors and 1 had brain metastases. Of –ICI patients, 21 patients had brain lesions; 15 had primary brain tumors and 6 had brain metastases. DISCUSSION Although immune checkpoint therapy may lead to increased activation of the immune system, our data did not reveal a higher incidence of seizures. Limitations to our study include its retrospective design, low number of patients, and low overall number of seizures captured on EEG.

Clinical and MRI characteristics of multiple sclerosis in Iranian Children and Adolescents.

To determine the clinical and MRI characteristics of multiple sclerosis (MS) in the children and adolescents. In this cross-sectional study, information of 95 MS patients was obtained from the Iranian MS registry. Disease characteristics and imaging data were collected using medical records. Ninety-five patients including 64 female and 31 male subjects with mean age of 13.97±2.4 years (range, 8-18) years were enrolled. The most frequent signs and symptoms were ophthalmic symptoms (n=61, 64.2%), brainstem signs (n=44, 46.3%), cerebellar signs (n=32, 33.6%) and pyramidal signs (n=26, 27.3%). Blurred vision (n=21, 34.4%) was the most common ophthalmic symptom and ataxia (n=24, 75%) the most prevalent cerebellar sign. The most common brainstem signs/symptoms were motor symptoms and vertigo (each n=14, 31.8%) and the most common pyramidal sign/symptom was right upper monoparesis (n=14, 23.3%). Active demyelinating lesions were reported in brain MRI of all patients, mostly appeared as periventricular (n=91, 95.8%) and pericallosal (n=55, 57.9%) lesions. Acute demyelinating spinal lesions were presented in 38 patients (51.3%) with a prominent involvement of the cervical spine (n=33, 86.8%). In our study, the most frequent signs and symptoms were eye symptoms, brainstem signs, cerebellar signs and pyramidal signs, respectively. Moreover, our results showed that MRI plays a critical role in the diagnostic evaluation of MS in children with presence of brain lesions in all patients and spinal lesion in a considerable portion of patients.

The influence of occupation type and complexity on cognitive performance in older adults

Sociodemographic factors, such as education and occupation, may influence the individual's cognitive reserve. We explored the extent to which the type and complexity of previous work activities influence cognitive performance (evaluated with Mini-Mental State Examination, MMSE, and the Animal Naming Test, ANT) in 799 older people with or without brain damage. The presence of cortical/subcortical ischemic brain lesions and right/left hippocampal atrophy was derived from magnetic resonance imaging. We found that individuals who had done intellectual work had better MMSE and ANT scores than their counterparts in the presence of brain lesions or hippocampal atrophy. Among the manual workers there were significant differences between the MMSE scores of individuals with and without brain damage (mean MMSE difference (2.09 [SD: 0.68], p=0.01), but not among the intellectuals (0.19 [SD: 0.29], p=0.36) nor the service providers (1.67 [SD: 0.55], p=0.21). Occupations involving more complex dealings with people were associated with better MMSE scores in the presence of brain lesions [β=-0.41, 95%CI: -0.72,-0.09] and hippocampal atrophy [β=-0.29, 95%CI:-0.58,-0.001]. These results indicate that in more cognitively stimulating work with greater social interaction may help older individuals preserve cognitive functions, even in the presence of brain damage.

Factors associated with comorbid epilepsy in patients with psychogenic nonepileptic seizures: A large cohort study

ObjectiveComorbid epilepsy and psychogenic nonepileptic seizures (PNES) occur in 12–22% of cases and the diagnosis of both simultaneous disorders is challenging. We aimed to identify baseline characteristics that may help distinguish patients with PNES-only from those with comorbid epilepsy. MethodsWe performed a longitudinal cohort study on those patients diagnosed with PNES in our epilepsy monitoring unit (EMU) between May 2001 and February 2011, prospectively followed up until September 2016. Patients were classified into PNES-only, PNES + possible or probable epilepsy, and PNES + definite epilepsy based on the clinical, vEEG, and neuroimaging data. Demographic and basal clinical data were obtained from chart review. Multiple regression models were performed to identify significant predictors of PNES + definite epilepsy, excluding patients with only possible or probable epilepsy for this specific analysis. ResultsOne-hundred and ninety four patients with PNES-only, 30 with PNES + possible or probable epilepsy and 47 with PNES + definite epilepsy were included. 73.8% were female and the mean age at EMU admission was 37.4 ± standard deviation 13.5 years.Patients with PNES + definite epilepsy most likely had never worked, had history of febrile seizures, structural brain lesions, developmental disabilities, and maximum reported seizure duration between 0.5 and 2 min.Patients with PNES-only were on fewer anti-seizure medications (ASM), reported more frequently an initial minor head trauma, seizures longer than 10 min, and a higher number of neurological and medical illnesses – being migraine (18.1%), other types of headaches (18.5%), and asthma (15.5%) the most prevalent ones. All p < 0.05.On the hierarchical regression analysis, history of febrile seizures, developmental disabilities, brain lesions, longest reported seizure duration between 0.5 and 2 min, and lack of neurological comorbidity, remained as significant predictors of PNES + epilepsy. The model's performance of a 5-fold cross-validation analysis showed an overall accuracy of 84.7% to classify patients correctly. ConclusionsSome demographic and clinical characteristics may support the presence of comorbid epilepsy in patients with PNES, being unemployment, the presence of brain lesions, developmental disabilities, history of febrile seizures, seizure duration and lack of comorbid headaches the most relevant ones.

Convolutional Neural Networks Enable Robust Automatic Segmentation of the Rat Hippocampus in MRI After Traumatic Brain Injury.

Registration-based methods are commonly used in the automatic segmentation of magnetic resonance (MR) brain images. However, these methods are not robust to the presence of gross pathologies that can alter the brain anatomy and affect the alignment of the atlas image with the target image. In this work, we develop a robust algorithm, MU-Net-R, for automatic segmentation of the normal and injured rat hippocampus based on an ensemble of U-net-like Convolutional Neural Networks (CNNs). MU-Net-R was trained on manually segmented MR images of sham-operated rats and rats with traumatic brain injury (TBI) by lateral fluid percussion. The performance of MU-Net-R was quantitatively compared with methods based on single and multi-atlas registration using MR images from two large preclinical cohorts. Automatic segmentations using MU-Net-R and multi-atlas registration were of excellent quality, achieving cross-validated Dice scores above 0.90 despite the presence of brain lesions, atrophy, and ventricular enlargement. In contrast, the performance of single-atlas segmentation was unsatisfactory (cross-validated Dice scores below 0.85). Interestingly, the registration-based methods were better at segmenting the contralateral than the ipsilateral hippocampus, whereas MU-Net-R segmented the contralateral and ipsilateral hippocampus equally well. We assessed the progression of hippocampal damage after TBI by using our automatic segmentation tool. Our data show that the presence of TBI, time after TBI, and whether the hippocampus was ipsilateral or contralateral to the injury were the parameters that explained hippocampal volume.

Tumefactive multiple sclerosis

Tumefactive multiple sclerosis is a rare variant of multiple sclerosis, characterized by the presence of brain lesions that may be solitary or multiple. Considering that these lesions have a pseudotumoral appearance, it is a challenge to differentiate them from central nervous system neoplasms through neuroimaging. Many cases are associated with the administration of monoclonal antibodies, and due to an increase in the incidence of cancer globally, it is expected that secondary to chemotherapeutic treatments, more and more cases may appear. Taking into account the above, the objective of this review is to review aspects of usefulness in clinical practice, on the diagnosis and approach of this pathological condition

Development of a Prognostic Model for Predicting Multiple Sclerosis After Optic Neuritis: A Secondary Analysis of Data From the Optic Neuritis Treatment Trial.

Optic neuritis can be the initial manifestation of multiple sclerosis (MS). The purpose of this study was to develop a prognostic model for predicting the risk of MS development among patients with optic neuritis. The data from 388 patients with optic neuritis were retrieved from the Optic Neuritis Treatment Trial (ONTT). Cox proportional hazards regression analysis was used to develop a prognostic model. The performance of the model was assessed by using Harrell's C-index and calibration curves. The rates of MS development were estimated using the Kaplan-Meier method. Among the enrolled subjects, a total of 154 (39.7%) patients developed clinically definite MS during a median follow-up period of 15.8 years (interquartile range, 7.2-16.9 years). The factors associated with the development of MS were the presence of brain lesions as on baseline MRI, previous nonspecific neurologic symptoms, commencing low-dose corticosteroids treatment, ocular pain, and absence of optic disc/peripapillary hemorrhage. After incorporating these 5 factors into the prognostic model, a C-index of 0.72 (95% confidence interval [CI], 0.69-0.76) and good calibration curves were obtained. The C-index of the model was significantly higher than the C-indexes of any single factor (P < 0.001 in all cases). The model was able to stratify the ONTT patient cohort into 3 risk groups with significantly different intergroup rates of developing MS (rates for developing MS within a 15-year period: high-risk group, 75.7% [95% CI, 65.6%-82.9%], intermediate-risk group, 44.7% [95% CI, 31.4%-55.4%]; and low-risk group, 20.8% [95% CI, 14.2%-26.8%]; log-rank P < 0.001). This prognostic model had a better prediction ability when compared with the standard practice that relies solely on using brain lesions on MRI. It can, therefore, help guide decision-making to initiate earlier disease-modifying therapy for patients with optic neuritis at risk of developing MS.

Neurodevelopmental Outcomes after Congenital Heart Disease Surgery in Infancy: A 2-Year Serial Follow-Up.

Background: The aim of this study is to assess the neurodevelopmental status of infant patients who underwent cardiac surgery in infancy and to investigate the factors affecting the neurodevelopmental status. Methods: This retrospective study included 108 patients who underwent cardiac surgery before the age of one. We used the Bayley Scales of Infant Development II to evaluate the neurodevelopmental status. All patients were analyzed according to the presence of the syndrome. Patients without the syndrome were analyzed according to the presence of brain lesions. Results: The mean mental developmental index (MDI) and the mean psychomotor developmental index (PDI) were 76.11 ± 20.17 and 65.95 ± 18.34, respectively, in the first evaluation, and 73.98 ± 22.53 and 69.48 ± 20.86, respectively, in the second evaluation. In the subgroup analysis, no significant difference was observed between the first evaluation and the second evaluation. Conclusions: No significant difference was observed in the degree of development of the patients in the two evaluation periods. Although the presence of syndrome, brain lesion, or gestational age affected the degree of developmental delay, more than half of the patients had developmental delay in the two evaluation periods in any of the subgroup. Therefore, the necessity of early screening and early rehabilitation intervention is emphasized.

Neonatal stroke in premature neonates

There are many neuro-imaging studies on the presence of brain lesions in the preterm infant, using cranial ultrasound (cUS) and/or term equivalent age MRI (TEA-MRI). These studies however tend to focus on germinal matrix-intraventricular hemorrhage (GMH-IVH) and white matter injury. Data about perinatal arterial ischemic stroke (PAIS) or cerebral sinovenous thrombosis (CSVT) in the preterm infant are very limited. In fact, several large cohort studies on neuro-imaging in preterm infants do not even mention neonatal stroke.1-4 Most studies about PAIS exclude preterm infants.5 The aim of this review was to provide an update on neonatal stroke in the preterm infant, with a focus on neuro-imaging findings.

Early neurodevelopmental characterization in children with cobalamin C/defect.

Cobalamin C (cblC) defect is the most common inherited disorder of cobalamin metabolism. Developmental delay, behavioral problems, and maculopathy are common, but they have not been systematically investigated. The aim of this study was to define early neurodevelopment in cblC patients and the possible contribution of different factors, such as mode of diagnosis, age at diagnosis, presence of brain lesions and epilepsy. Children up to the age of 4 years with a visual acuity ≥1/10 were evaluated using the Griffiths' Mental Development Scales. Eighteen children were enrolled (age range 12-48 months). Four were diagnosed by newborn screening (NBS); in the others mean age at diagnosis was 3.5 months (range 0.3-18 months). Eight had seizures: three in the first year, and five after the second year of life. Fourteen had brain lesions on magnetic resonance imaging (MRI). Neurovisual assessment evidenced low visual acuity (<3/10) in 4/18. NBS diagnosed patients had higher general and subquotients neurodevelopmental scores, normal brain MRI, and no epilepsy. The others showed a progressive reduction of the developmental quotient with age and language impairment, which was evident after 24 months of age. Our findings showed a progressive neurodevelopmental deterioration and a specific fall in language development after 24 months in cblC defect. The presence of brain lesions and epilepsy was associated with a worst neurodevelopmental outcome. NBS, avoiding major disease-related events and allowing an earlier treatment initiation, appeared to have a protective effect on the development of brain lesions and to promote a more favorable neurodevelopment.

The Impact of Artificial Sweeteners on Insulin, Body Composition and Drink Choice in Mice

The average American consumes almost 42 gallons of artificially sweetened beverages per year and about 66 pounds of sucrose. Although the USFDA supports that aspartame and stevia are safe for consumption, both nutritive and non‐nutritive sweeteners have been shown to negatively impact health. Sucrose causes addictive behaviors as well as excessive release of dopamine. Our study was designed to determine the behaviors and physiological changes in mice associated with consumption of aspartame and stevia when compared with sucrose. We exposed mice to untainted water or water containing 0.2% aspartame, 0.2% stevia, or 0.2% sucrose for 8 weeks, then provided the animals with a two‐bottle, treated and untreated, choice test for an additional week. After 9 weeks of treatment, mice were sacrificed and body composition, blood glucose, and serum insulin were determined. Stevia animals gained significantly more body weight than all other groups (p&lt;0.05) and consumed significantly more food than controls (p&lt;0.05). All treatment animals consumed significantly more fluid than control animals (p&lt;0.05). When provided with the two‐bottle choice, the treated animals chose the sweetened drink significantly more than untreated water (p&lt;0.05), while the control animals consumed water equally from both bottles. Aspartame treated animals had significantly heavier relative heart weights (p&lt;0.05). We found no significant difference in relative liver weights, blood glucose or serum insulin concentrations in this short term test. These results are consistent with previous studies reporting addictive behavior with sucrose consumption. Current work is focused on the presence of brain lesions and dopamine release with exposure to sugar versus substitutes.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Brain regional volume estimations with NeuroQuant and FIRST: a study in patients with a clinically isolated syndrome.

Brain volume estimates from magnetic resonance images (MRIs) are of great interest in multiple sclerosis, and several automated tools have been developed for this purpose. The goal of this study was to assess the agreement between two tools, NeuroQuant® (NQ) and FMRIB's Integrated Registration Segmentation Tool (FIRST), for estimating overall and regional brain volume in a cohort of patients with a clinically isolated syndrome (CIS). In addition, white matter lesion volume was estimated with NQ and the Lesion Segmentation Toolbox (LST). One hundred fifteen CIS patients were analysed. Structural images were acquired on a 3.0-T system. The volume agreement between methods (by estimation of the intraclass correlation coefficient) was calculated for the right and left thalamus, caudate, putamen, pallidum, hippocampus, and amygdala, as well as for the total intracranial volume and white matter lesion volume. In general, the estimated volumes were larger by NQ than FIRST, except for the pallidum. Agreement was low (ICC < 0.40) for the smaller structures (amygdala and pallidum) and fair to good (ICC > 0.40) for the remaining ones. Agreement was fair for lesion volume (ICC = 0.61), with NQ estimates lower than LST. Agreement between NQ and FIRST brain volume estimates depends on the size of the structure of interest, with larger volumes achieving better agreement. In addition, concordance between the two tools does seem to be dependent on the presence of brain lesions.

Brain Metastases from Biliary Tract Cancer: A Monocentric Retrospective Analysis of 450 Patients

Objective: Brain metastases (BMs) from biliary tract cancer (BTC) are extremely rare. The aim of our study was to report the incidence of BMs in patients with BTC. Methods: We retrospectively analyzed a series of 450 patients with BTC. Presence of brain lesions was investigated only when symptoms were evident. Cumulative incidence, median overall survival (OS) from detection of BMs, median OS from cancer diagnosis, and median time from cancer diagnosis to detection of BMs were evaluated. Results: In our series, 6 patients developed BMs with an incidence of about 1.4%. Median OS from detection of BMs and from cancer diagnosis was, respectively, 3.7 (0.9-17.8) and 23 (9.9-57.6) months. Median time between cancer diagnosis and detection of BMs was 13.6 (7.3-52.8) months. Moreover, we observed a significant association between BMs and bone metastases (particularly vertebral lesions). Discussion: Despite the retrospective design, this is the first study evaluating the incidence of BMs among patients with BTC in Western countries. BMs from BTC remain atypical, although their incidence is probably a little higher than previously assumed. Patients with BMs had poor prognosis. Unpredictably, bone involvement occurred in 5 out of 6 patients.

An abnormal periventricular magnetization transfer ratio gradient occurs early in multiple sclerosis.

In established multiple sclerosis, tissue abnormality-as assessed using magnetization transfer ratio-increases close to the lateral ventricles. We aimed to determine whether or not (i) these changes are present from the earliest clinical stages of multiple sclerosis; (ii) they occur independent of white matter lesions; and (iii) they are associated with subsequent conversion to clinically definite multiple sclerosis and disability. Seventy-one subjects had MRI scanning a median of 4.6 months after a clinically isolated optic neuritis (49 females, mean age 33.5 years) and were followed up clinically 2 and 5 years later. Thirty-seven healthy controls (25 females, mean age 34.4 years) were also scanned. In normal-appearing white matter, magnetization transfer ratio gradients were measured 1-5 mm and 6-10 mm from the lateral ventricles. In control subjects, magnetization transfer ratio was highest adjacent to the ventricles and decreased with distance from them; in optic neuritis, normal-appearing white matter magnetization transfer ratio was lowest adjacent to the ventricles, increased over the first 5 mm, and then paralleled control values. The magnetization transfer ratio gradient over 1-5 mm differed significantly between the optic neuritis and control groups [+0.059 percentage units/mm (pu/mm) versus -0.033 pu/mm, P = 0.010], and was significantly steeper in those developing clinically definite multiple sclerosis within 2 years compared to those who did not (0.132 pu/mm versus 0.016 pu/mm, P = 0.020). In multivariate binary logistic regression the magnetization transfer ratio gradient was independently associated with the development of clinically definite multiple sclerosis within 2 years (magnetization transfer ratio gradient odds ratio 61.708, P = 0.023; presence of T2 lesions odds ratio 8.500, P = 0.071). At 5 years, lesional measures overtook magnetization transfer ratio gradients as significant predictors of conversion to multiple sclerosis. The magnetization transfer ratio gradient was not significantly affected by the presence of brain lesions [T2 lesions (P = 0.918), periventricular T2 lesions (P = 0.580) or gadolinium-enhancing T1 lesions (P = 0.724)]. The magnetization transfer ratio gradient also correlated with Expanded Disability Status Scale score 5 years later (Spearman r = 0.313, P = 0.027). An abnormal periventricular magnetization transfer ratio gradient occurs early in multiple sclerosis, is clinically relevant, and may arise from one or more mechanisms that are at least partly independent of lesion formation.

Cognitive and Behavioral Functioning in Childhood Acquired Demyelinating Syndromes.

The aim of this study was to describe cognitive, academic, and psychosocial outcomes after an incident demyelinating event (acquired demyelinating syndromes, ADS) in childhood and to investigate the contribution of brain lesions and confirmed MS diagnosis on outcome. Thirty-six patients with ADS (mean age=12.2 years, SD=2.7, range: 7-16 years) underwent brain MRI scans at presentation and at 6-months follow-up. T2-weighted lesions on MRI were assessed using a binary classification. At 6-months follow-up, patients underwent neuropsychological evaluation and were compared with 42 healthy controls. Cognitive, academic, and behavioral outcomes did not differ between the patients with ADS and controls. Three of 36 patients (8.3%) were identified with cognitive impairment, as determined by performance falling ≤1.5 SD below normative values on more than four independent tests in the battery. Poor performance on a visuomotor integration task was most common, observed among 6/32 patients, but this did not differ significantly from controls. Twelve of 36 patients received a diagnosis of MS within 3 years post-ADS. Patients with MS did not differ from children with monophasic ADS in terms of cognitive performance at the 6-months follow-up. Fatigue symptoms were reported in 50% of patients, irrespective of MS diagnosis. Presence of brain lesions at onset and 6 months post-incident demyelinating event did not associate with cognitive outcome. Children with ADS experience a favorable short-term neurocognitive outcome, even those confirmed to have MS. Longitudinal evaluations of children with monophasic ADS and MS are required to determine the possibility of late-emerging sequelae and their time course. (JINS, 2016, 22, 1050-1060).

Acute influenza virus-associated encephalitis and encephalopathy in adults: a challenging diagnosis

Background: Acute influenza-associated encephalopathy/encephalitis (IAE) in adults is a rare but well-known complication of influenza virus infection. The diagnosis is difficult to make due to the absence of distinctive clinical symptoms and validated diagnostic criteria. We present an illustrative case and a case review on acute IAE in adults.Methods: We performed a Medline search of the English literature using the terms influenz*, encephal* and adult, and constructed a database of detailed descriptions of patients with influenza virus infection with influenza-like symptoms at the onset of neurological symptoms.Results: A total of 44 patients were included. Confusion and seizures were the most prevalent neurological symptoms, present in 12 (27 %) and 10 (23 %) patients, respectively. Magnetic resonance imaging (MRI) was performed in 21 patients and anomalies were found in 13 (62 %), with lesions located throughout the brain. Influenza virus RNA was detected in cerebrospinal fluid (CSF) in 5 (16 %) of 32 patients. Eight (18 %) of the forty-four patients died. The benefits of antiviral and immunomodulatory therapy have not been well studied.Discussion: Our results show that many different neurological symptoms can be present in patients with acute onset IAE. Therefore, the diagnosis should be considered in patients with fever and neurological symptoms, especially during the influenza season. Laboratory diagnosis consists of demonstration of influenza virus RNA in brain tissue, CSF or respiratory samples, and demonstration of intrathecal antibody production against influenza virus. The presence of brain lesions in MRI and influenza virus in CSF appear to be of prognostic value.

Can emotional stress trigger the onset of epilepsy?

The aim of this study was to investigate the potential role of an acute adverse stress as "trigger" for the onset of epilepsy. Among 4618 consecutive patients, twenty-two reported a major life event within three months before the onset of epilepsy. All patients had focal epilepsy except one with idiopathic generalized epilepsy. The temporal lobe was involved in 90% of patients with focal epilepsy. More precisely, 13 patients (62% of patients with focal epilepsy) had medial temporal lobe epilepsy (MTLE), two had lateral temporal lobe epilepsy, four had temporoparietooccipital junction epilepsy, and two patients had central lobe epilepsy. The mean age and the median age at onset of epilepsy for patients with MTLE were both 38 years (range: 9.5-65 years). Ten patients had right and three had left MTLE. Among patients with focal epilepsy, MRI was abnormal in 7 (33%) with hippocampal sclerosis in four, periventricular nodular heterotopia in two, and complex cortical dysgenesis in one. The mean age at onset of epilepsy for patients with brain lesions was 26 years (range: 9.5-49). Twelve patients (54%) reported a death as a triggering factor for the onset of their epilepsy. Seven patients (32%) reported that a relationship of trust had been broken. Three patients (14%) had been subjects of violence. No patient reported sexual abuse as a triggering factor. This study provides evidence that some patients (5/1000 patients) began their seizures in the wake of significant life events. The average age at onset of epilepsy is quite late, around age 30, even in the presence of brain lesions. These patients are emotionally and affectively more prone to have consequences of a stressful life event. The recognition and management of such situations may bring significant relief with improvement of the control of epilepsy.

Clinical, pathological, and immunohistochemical findings in bald eagles (Haliaeetus leucocephalus) and golden eagles (Aquila chrysaetos) naturally infected with West Nile virus.

Fifteen bald eagles (Haliaeetus leucocephalus) and 3 golden eagles (Aquila chrysaetos) were diagnosed with West Nile disease based on 1) presence of lesions in brain, eyes, and heart, 2) viral antigen detection in brain, eyes, heart, kidney, and/or liver by immunohistochemical staining, 3) detection of viral RNA in tissue samples and/or cerebrospinal fluid (CSF) by polymerase chain reaction, and/or 4) detection of West Nile virus (WNV)-specific antibodies in CSF by serum neutralization assay. West Nile virus-associated gross lesions included cerebral pan-necrosis with hydrocephalus ex vacuo (7/15 bald eagles), fibrin exudation into the fundus in 1 golden eagle, retinal scarring in 1 bald eagle, and myocardial pallor and rounded heart apex in 4 bald eagles. Histologic lesions included lymphoplasmacytic encephalitis, most prominently in the cerebrum (17 eagles), lymphoplasmacytic pectenitis and choroiditis (15 and 8 eagles, respectively), and myocarditis (12 eagles). West Nile virus antigen was detected in the majority of the eagles in neurons of the brain (cerebrum and cerebellum), and less commonly present in neurons of the retina, tubular epithelial cells of the kidney, and cardiomyocytes. West Nile disease was diagnosed in 2 bald eagles based on the presence of cerebral pan-necrosis and WNV-specific antibodies in the CSF despite lacking viral antigen and RNA. In conclusion, WNV infection causes a fatal disease in bald and golden eagles. A variety of gross and histologic lesions are highly suggestive of WN disease in most eagles. A combination of detection of viral antigen and/or RNA or virus-specific antibodies proved useful in confirming the diagnosis.