Surgical waiting lists and queue management in a Brazilian tertiary public hospital.

BACKGROUND: Centralized management of queues helps to reduce the surgical waiting time in the publicly funded healthcare system, but this is not a reality in the Brazilian Unified Healthcare System (BUHS). We describe the implementation of the "Patients with Surgical Indication" (PSI) in a Brazilian public tertiary hospital, the impact on waiting time, and its use in rationing oncological surgeries during the COVID-19 Pandemic. METHODS: Retrospective observational study of elective surgical requests (2016-2022) in a Brazilian general, public, tertiary university hospital. We recovered information regarding the inflows (indications), outflows and their reasons, the number of patients, and waiting time in queue. RESULTS: We enrolled 82,844 indications in the PSI (2016-2022). The waiting time (median and interquartile range) in days decreased from 98(48;168) in 2016 to 14(3;152) in 2022 (p < 0.01). The same occurred with the backlog that ranged from 6,884 in 2016 to 844 in 2022 (p < 001). During the Pandemic, there was a reduction in the number of non-oncological surgeries per month (95% confidence interval) of -10.9(-18.0;-3.8) during Phase I (January 2019-March 2020), maintenance in Phase II (April 2020-August 2021) 0.1(-10.0;10.4) and increment in Phase III (September 2021-December 2022) of 23.0(15.3;30.8). In the oncological conditions, these numbers were 0.6(-2.1;3.3) for Phase I, an increase of 3.2(0.7;5.6) in Phase II and 3.9(1,4;6,4) in Phase III. CONCLUSION: Implementing a centralized list of surgical indications and developing queue management principles proved feasible, with effective rationing. It unprecedentedly demonstrated the decrease in the median waiting time in Brazil.

The intellectual profile of pediatric patients with posterior cortex epilepsy.

BACKGROUND: Cognitive functioning in epileptic syndromes has been widely explored in patients with temporal lobe epilepsy (TLE), but few studies have investigated the neuropsychological profile in posterior cortex epilepsy (PCE). In this study, we investigated the presurgical intellectual profile of children and adolescents with drug-resistant PCE. METHODS: Children and adolescents diagnosed with PCE (n = 25) participated in this study. The data were obtained from medical records, with assessments carried out between the years 2003 and 2019. To compare the intellectual profile, we also included patients diagnosed with frontal (n = 26) and temporal lobe epilepsy (n = 40). The Wechsler Intelligence Scales were used for the assessment of general intelligence. RESULTS: There was an effect of the brain region on the Working Memory Index (p < 0.01), in which patients with TLE had significantly higher scores than groups with FLE (p < 0.01) and PCE (p < 0.05). We also demonstrated that patients with PCE tended to perform worse in the Processing Speed Index than patients with TLE (p = 0.055). The Full-Scale Intelligence Quotient, Verbal Comprehension, and Perceptual Reasoning indexes did not differ among the brain regions. CONCLUSIONS: Children and adolescents with PCE demonstrated significant impairment in working memory and processing speed. The pattern of cognitive dysfunction in PCE was similar to that observed in FLE, which expands the evidence of the involvement of frontoparietal networks on cognitive proficiency.

Drebrin expression patterns in patients with refractory temporal lobe epilepsy and hippocampal sclerosis.

OBJECTIVE: Drebrins are crucial for synaptic function and dendritic spine development, remodeling, and maintenance. In temporal lobe epilepsy (TLE) patients, a significant hippocampal synaptic reorganization occurs, and synaptic reorganization has been associated with hippocampal hyperexcitability. This study aimed to evaluate, in TLE patients, the hippocampal expression of drebrin using immunohistochemistry with DAS2 or M2F6 antibodies that recognize adult (drebrin A) or adult and embryonic (pan-drebrin) isoforms, respectively. METHODS: Hippocampal sections from drug-resistant TLE patients with hippocampal sclerosis (HS; TLE, n = 33), of whom 31 presented with type 1 HS and two with type 2 HS, and autopsy control cases (n = 20) were assayed by immunohistochemistry and evaluated for neuron density, and drebrin A and pan-drebrin expression. Double-labeling immunofluorescences were performed to localize drebrin A-positive spines in dendrites (MAP2), and to evaluate whether drebrin colocalizes with inhibitory (GAD65) and excitatory (VGlut1) presynaptic markers. RESULTS: Compared to controls, TLE patients had increased pan-drebrin in all hippocampal subfields and increased drebrin A-immunopositive area in all hippocampal subfields but CA1. Drebrin-positive spine density followed the same pattern as total drebrin quantification. Confocal microscopy indicated juxtaposition of drebrin-positive spines with VGlut1-positive puncta, but not with GAD65-positive puncta. Drebrin expression in the dentate gyrus of TLE cases was associated negatively with seizure frequency and positively with verbal memory. TLE patients with lower drebrin-immunopositive area in inner molecular layer (IML) than in outer molecular layer (OML) had a lower seizure frequency than those with higher or comparable drebrin-immunopositive area in IML compared with OML. SIGNIFICANCE: Our results suggest that changes in drebrin-positive spines and drebrin expression in the dentate gyrus of TLE patients are associated with lower seizure frequency, more preserved verbal memory, and a better postsurgical outcome.

Two-Dimensional Temporal Clustering Analysis for Patients with Epilepsy: Detecting Epilepsy-Related Information in EEG-fMRI Concordant, Discordant and Spike-Less Patients.

EEG acquired simultaneously with fMRI (EEG-fMRI) is a multimodal method that has shown promise in mapping the seizure onset zone in patients with focal epilepsy. However, there are many instances when this method is unsuccessful or not applicable, and other data driven fMRI methods may be utilized. One such method is the two-dimensional temporal clustering analysis (2dTCA). In this study we compared the classic EEG-fMRI and 2dTCA performance in mapping regions related to the seizure onset region in 18 focal epilepsy patients (12 presenting interictal epileptiform discharges (IEDs), during EEG-fMRI acquisition) with Engel I or II surgical outcome. Activation maps of both 2dTCA timing outputs (positive and negative histograms) and EEG detected IEDs were computed and compared to the region of epilepsy surgical resection. Patients were evaluated in three categories based on frequency of EEG detected spiking during the MRI. EEG-fMRI maps were concordant to the epilepsy region in 5/12 subjects, four with frequent IEDs on EEG. The 2dTCA was successful in mapping 13/18 patients including 3/6 with no IEDs detected (10/12 with IEDs detected). The epilepsy-related activities were successfully mapped by both methods in only 4/12 patients. This work suggests that the epilepsy-related information detected by each method may be different: while EEG-fMRI is more accurate in patients with high rather than lower numbers of EEG detected IEDs; 2dTCA can be useful in evaluating patients even when no concurrent EEG spikes are detected or EEG-fMRI is not effective. Therefore, our results support that 2dTCA might be an alternative for mapping epilepsy-related BOLD activity in negative EEG-fMRI (6/7 patients) and spike-less patients.

Individual hippocampal subfield assessment indicates that matrix macromolecules and gliosis are key elements for the increased T2 relaxation time seen in temporal lobe epilepsy.

OBJECTIVE: Increased T2 relaxation time is often seen in temporal lobe epilepsy (TLE) with hippocampal sclerosis. Water content directly affects the effective T2 in a voxel. Our aim was to evaluate the relation between T2 values and two molecules associated with brain water homeostasis aquaporin 4 (AQP4) and chondroitin sulfate proteoglycan (CSPG), as well as cellular populations in the hippocampal region of patients with TLE. METHODS: Hippocampal T2 imaging and diffusion tensor imaging (DTI) were obtained from 42 drug-resistant patients with TLE and 20 healthy volunteers (radiologic controls, RCs). A similar protocol (ex vivo) was applied to hippocampal sections from the same TLE cases and 14 autopsy control hippocampi (histologic and radiologic controls, HRCs), and each hippocampal subfield was evaluated. Hippocampal sections from TLE cases and HRC controls were submitted to immunohistochemistry for neurons (neuron nuclei [NeuN]), reactive astrocytes (glial fibrillary acidic protein [GFAP]), activated microglia (human leukocyte antigen-D-related [HLA-DR]), polarized AQP4, and CSPG. RESULTS: Patients with TLE had higher in vivo and ex vivo hippocampal T2 relaxation time. Hippocampi from epilepsy cases had lower neuron density, higher gliosis, decreased AQP4 polarization, and increased CSPG immunoreactive area. In vivo relaxation correlated with astrogliosis in the subiculum and extracellular CSPG in the hilus. Ex vivo T2 relaxation time correlated with astrogliosis in the hilus, CA4, and subiculum, and with microgliosis in CA1. The difference between in vivo and ex vivo relaxation ratio correlated with mean diffusivity and with the immunopositive area for CSPG in the hilus. SIGNIFICANCE: Our data indicate that astrogliosis, microgliosis, and CSPG expression correlate with the increased T2 relaxation time seen in the hippocampi of patients with TLE.

Understanding the association of neurocysticercosis and mesial temporal lobe epilepsy and its impact on the surgical treatment of patients with drug-resistant epilepsy.

Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) is one of the most common types of focal epilepsies. This is an epileptic syndrome commonly associated with treatment-resistant seizures, being also the most prevalent form of drug-resistant epilepsy which is treated surgically in most epilepsy surgery centers. Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system, and one of the most common etiological agents of focal epilepsy, affecting millions of patients worldwide. Recently, researchers reported a curious association between MTLE-HS with NCC, but this association remains poorly understood. Some argue that calcified NCC lesions in MTLE-HS patients is only a coincidental finding, since both disorders are prevalent worldwide. However, others suppose there might exist a pathogenic relationship between both disorders and some even suspect that NCC, by acting as an initial precipitating injury (IPI), might cause hippocampal damage and, eventually, MTLE-HS. In this review, we discuss the various reports that examine this association, and suggest possible explanations for why calcified NCC lesions are also observed in patients with MTLE-HS. We also propose mechanisms by which NCC could lead to MTLE-HS. Finally, we discuss the implications of NCC for the treatment of pharmacologically-resistant focal epilepsies in patients with calcified NCC or in patients with MTLE-HS and calcified NCC lesions. We believe that investigations in the relationship between NCC and MTLE-HS might offer further insights into how NCC may trigger epilepsy, and into how MTLE-HS originates. Moreover, observations in patients with drug-resistant epilepsy with both NCC and hippocampal sclerosis may not only aid in the understanding and treatment of patients with MTLE-HS, but also of patients with other forms of dual pathologies aside from NCC. This article is part of a Special Issue titled Neurocysticercosis and Epilepsy.

Everyday memory impairment in patients with temporal lobe epilepsy caused by hippocampal sclerosis.

OBJECTIVE: Patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) have episodic memory impairment. Memory has rarely been evaluated using an ecologic measure, even though performance on these tests is more related to patients' memory complaints. We aimed to measure everyday memory of patients with TLE-HS to age- and gender-matched controls. METHODS: We evaluated 31 patients with TLE-HS and 34 healthy controls, without epilepsy and psychiatric disorders, using the Rivermead Behavioral Memory Test (RBMT), Visual Reproduction (WMS-III) and Logical Memory (WMS-III). We evaluated the impact of clinical variables such as the age of onset, epilepsy duration, AED use, history of status epilepticus, and seizure frequency on everyday memory. Statistical analyses were performed using MANCOVA with years of education as a confounding factor. RESULTS: Patients showed worse performance than controls on traditional memory tests and in the overall score of RBMT. Patients had more difficulties to recall names, a hidden belonging, to deliver a message, object recognition, to remember a story full of details, a previously presented short route, and in time and space orientation. Clinical epilepsy variables were not associated with RBMT performance. Memory span and working memory were correlated with worse performance on RBMT. SIGNIFICANCE: Patients with TLE-HS demonstrated deficits in everyday memory functions. A standard neuropsychological battery, designed to assess episodic memory, would not evaluate these impairments. Impairment in recalling names, routes, stories, messages, and space/time disorientation can adversely impact social adaptation, and we must consider these ecologic measures with greater attention in the neuropsychological evaluation of patients with memory complaints.

The approach to patients with psychogenic nonepileptic seizures in epilepsy surgery centers regarding diagnosis, treatment, and education.

Previous studies, using surveys, provided an understanding about how health-care providers address patients with PNES. To date, there is limited information on the management of patients with PNES by tertiary referral centers for epilepsy. In this study, we surveyed 11 Brazilian epilepsy center directors about diagnosis, treatment, education and research on PNES. Respondents reported that patients with PNES represented 10-20% of all adult patients recorded by video-EEG (VEEG). All respondents recognized VEEG as the method to confirm the diagnosis, and 81.8% used this approach for confirmation. Most centers had a standard protocol for diagnosis. None of the centers had a particular protocol to treat PNES, but 90.9% had a uniform treatment approach including therapy and educational measures. Psychotherapy was not easily obtained in nine centers (81.8%). Seven (63.3%) centers reported ongoing research projects with PNES. Five centers referred to an educational PNES program discussing diagnosis, but only one reported an educational program for treatment. This study showed a commitment to PNES diagnosis; however, some gaps remain regarding treatment and training, namely implementing a psychotherapy approach for patients and providing educational curricula for clinicians.

Towards motion insensitive EEG-fMRI: Correcting motion-induced voltages and gradient artefact instability in EEG using an fMRI prospective motion correction (PMC) system.

The simultaneous acquisition of electroencephalography and functional magnetic resonance imaging (EEG-fMRI) is a multimodal technique extensively applied for mapping the human brain. However, the quality of EEG data obtained within the MRI environment is strongly affected by subject motion due to the induction of voltages in addition to artefacts caused by the scanning gradients and the heartbeat. This has limited its application in populations such as paediatric patients or to study epileptic seizure onset. Recent work has used a Moiré-phase grating and a MR-compatible camera to prospectively update image acquisition and improve fMRI quality (prospective motion correction: PMC). In this study, we use this technology to retrospectively reduce the spurious voltages induced by motion in the EEG data acquired inside the MRI scanner, with and without fMRI acquisitions. This was achieved by modelling induced voltages from the tracking system motion parameters; position and angles, their first derivative (velocities) and the velocity squared. This model was used to remove the voltages related to the detected motion via a linear regression. Since EEG quality during fMRI relies on a temporally stable gradient artefact (GA) template (calculated from averaging EEG epochs matched to scan volume or slice acquisition), this was evaluated in sessions both with and without motion contamination, and with and without PMC. We demonstrate that our approach is capable of significantly reducing motion-related artefact with a magnitude of up to 10mm of translation, 6° of rotation and velocities of 50mm/s, while preserving physiological information. We also demonstrate that the EEG-GA variance is not increased by the gradient direction changes associated with PMC. Provided a scan slice-based GA template is used (rather than a scan volume GA template) we demonstrate that EEG variance during motion can be supressed towards levels found when subjects are still. In summary, we show that PMC can be used to dramatically improve EEG quality during large amplitude movements, while benefiting from previously reported improvements in fMRI quality, and does not affect EEG data quality in the absence of large amplitude movements.

Decision-making in patients with temporal lobe epilepsy: Delay gratification ability is not impaired in patients with hippocampal sclerosis.

BACKGROUND: Decision-making abilities have rarely been examined in patients with temporal lobe epilepsy related to hippocampal sclerosis (TLE-HS). We aimed to investigate the ability to delay gratification, a decision-making subdomain, in patients with intractable TLE-HS and to verify the association of delay gratification performance and cool executive function tests. METHODS: We evaluated 27 patients with TLE-HS (mean age: 35.46 [±13.31] years; 7 males) and their cognitive performance was compared with that of 27 age- and gender-matched healthy controls (mean age: 35.33 [±12.05] years; 7 males), without epilepsy and psychiatric disorders. Patients were assessed using the delay discounting task (DDT) and tests of attention, shifting, inhibitory control, and concept formation. Results were correlated with clinical epilepsy variables such as age of onset, epilepsy duration, AED use, history of status epilepticus, febrile seizures, and the presence of generalized seizures. Statistical analysis was performed using one-way ANCOVA with years of education as a confounding factor. RESULTS: Patients and controls demonstrated similar performance on DDT, showing similar discount rate (p=0.935) and probability rate (p=0.585). Delay gratification was not related to cool executive function tests (Digit Span, Stroop Color Test, Trail Making Test, Wisconsin Card Sorting Test, and Connors' CPT). History of status epilepticus, presence of generalized seizures and higher seizure frequency, age at onset, and epilepsy duration had a significant impact on DDT. CONCLUSION: Patients with intractable TLE-HS showed unimpaired delay gratification abilities, being able to accept a higher delay and a lower amount of chance for receiving a higher reward in the future. Clinical variables related to the epilepsy severity impacted the performance on delay gratification. Impairment on cool aspects of executive function was unrelated to this decision-making domain.

Temporal lobe epilepsy patients with severe hippocampal neuron loss but normal hippocampal volume: Extracellular matrix molecules are important for the maintenance of hippocampal volume.

OBJECTIVE: Hippocampal sclerosis is a common finding in patients with temporal lobe epilepsy (TLE), and magnetic resonance imaging (MRI) studies associate the reduction of hippocampal volume with the neuron loss seen on histologic evaluation. Astrogliosis and increased levels of chondroitin sulfate, a major component of brain extracellular matrix, are also seen in hippocampal sclerosis. Our aim was to evaluate the association between hippocampal volume and chondroitin sulfate, as well as neuronal and astroglial populations in the hippocampus of patients with TLE. METHODS: Patients with drug-resistant TLE were subdivided, according to hippocampal volume measured by MRI, into two groups: hippocampal atrophy (HA) or normal volume (NV) cases. Hippocampi from TLE patients and age-matched controls were submitted to immunohistochemistry to evaluate neuronal population, astroglial population, and chondroitin sulfate expression with antibodies against neuron nuclei protein (NeuN), glial fibrillary acidic protein (GFAP), and chondroitin sulfate (CS-56) antigens, respectively. RESULTS: Both TLE groups were clinically similar. NV cases had higher hippocampal volume, both ipsilateral and contralateral, when compared to HA. Compared to controls, NV and HA patients had reduced neuron density, and increased GFAP and CS-56 immunopositive area. There was no statistical difference between NV and HA groups in neuron density or immunopositive areas for GFAP and CS-56. Hippocampal volume correlated positively with neuron density in CA1 and prosubiculum, and with immunopositive areas for CS-56 in CA1, and negatively with immunopositive area for GFAP in CA1. Multiple linear regression analysis indicated that both neuron density and CS-56 immunopositive area in CA1 were statistically significant predictors of hippocampal volume. SIGNIFICANCE: Our findings indicate that neuron density and chondroitin sulfate immunopositive area in the CA1 subfield are crucial for the hippocampal volume, and that chondroitin sulfate is important for the maintenance of a normal hippocampal volume in some cases with severe neuron loss.

Using network dynamic fMRI for detection of epileptogenic foci.

BACKGROUND: Epilepsy is one of the most prevalent neurological disorders. It remains medically intractable for about one-third of patients with focal epilepsy, for whom precise localization of the epileptogenic zone responsible for seizure initiation may be critical for successful surgery. Existing fMRI literature points to widespread network disturbances in functional connectivity. Per previous scalp and intracranial EEG studies and consistent with excessive local synchronization during interictal discharges, we hypothesized that, relative to same regions in healthy controls, epileptogenic foci would exhibit less chaotic dynamics, identifiable via entropic analyses of resting state fMRI time series. METHODS: In order to first validate this hypothesis on a cohort of patients with known ground truth, here we test individuals with well-defined epileptogenic foci (left mesial temporal lobe epilepsy). We analyzed voxel-wise resting-state fMRI time-series using the autocorrelation function (ACF), an entropic measure of regulation and feedback, and performed follow-up seed-to-voxel functional connectivity analysis. Disruptions in connectivity of the region exhibiting abnormal dynamics were examined in relation to duration of epilepsy and patients' cognitive performance using a delayed verbal memory recall task. RESULTS: ACF analysis revealed constrained (less chaotic) functional dynamics in left temporal lobe epilepsy patients, primarily localized to ipsilateral temporal pole, proximal to presumed focal points. Autocorrelation decay rates differentiated, with 100 % accuracy, between patients and healthy controls on a subject-by-subject basis within a leave-one-subject out classification framework. Regions identified via ACF analysis formed a less efficient network in patients, as compared to controls. Constrained dynamics were linked with locally increased and long-range decreased connectivity that, in turn, correlated significantly with impaired memory (local left temporal connectivity) and epilepsy duration (left temporal - posterior cingulate cortex connectivity). CONCLUSIONS: Our current results suggest that data driven functional MRI methods that target network dynamics hold promise in providing clinically valuable tools for identification of epileptic regions.

A Comparison of Independent Component Analysis (ICA) of fMRI and Electrical Source Imaging (ESI) in Focal Epilepsy Reveals Misclassification Using a Classifier.

Interictal epileptiform discharges (IEDs) can produce haemodynamic responses that can be detected by electroencephalography-functional magnetic resonance imaging (EEG-fMRI) using different analysis methods such as the general linear model (GLM) of IEDs or independent component analysis (ICA). The IEDs can also be mapped by electrical source imaging (ESI) which has been demonstrated to be useful in presurgical evaluation in a high proportion of cases with focal IEDs. ICA advantageously does not require IEDs or a model of haemodynamic responses but its use in EEG-fMRI of epilepsy has been limited by its ability to separate and select epileptic components. Here, we evaluated the performance of a classifier that aims to filter all non-BOLD responses and we compared the spatial and temporal features of the selected independent components (ICs). The components selected by the classifier were compared to those components selected by a strong spatial correlation with ESI maps of IED sources. Both sets of ICs were subsequently compared to a temporal model derived from the convolution of the IEDs (derived from the simultaneously acquired EEG) with a standard haemodynamic response. Selected ICs were compared to the patients' clinical information in 13 patients with focal epilepsy. We found that the misclassified ICs clearly related to IED in 16/25 cases. We also found that the classifier failed predominantly due to the increased spectral range of fMRIs temporal responses to IEDs. In conclusion, we show that ICA can be an efficient approach to separate responses related to epilepsy but that contemporary classifiers need to be retrained for epilepsy data. Our findings indicate that, for ICA to contribute to the analysis of data without IEDs to improve its sensitivity, classification strategies based on data features other than IC time course frequency is required.

Looking for complexity in quantitative semiology of frontal and temporal lobe seizures using neuroethology and graph theory.

Epileptic syndromes and seizures are the expression of complex brain systems. Because no analysis of complexity has been applied to epileptic seizure semiology, our goal was to apply neuroethology and graph analysis to the study of the complexity of behavioral manifestations of epileptic seizures in human frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE). We analyzed the video recordings of 120 seizures of 18 patients with FLE and 28 seizures of 28 patients with TLE. All patients were seizure-free >1 year after surgery (Engel Class I). All patients' behavioral sequences were analyzed by means of a glossary containing all behaviors and analyzed for neuroethology (Ethomatic software). The same series were used for graph analysis (CYTOSCAPE). Behaviors, displayed as nodes, were connected by edges to other nodes according to their temporal sequence of appearance. Using neuroethology analysis, we confirmed data in the literature such as in FLE: brief/frequent seizures, complex motor behaviors, head and eye version, unilateral/bilateral tonic posturing, speech arrest, vocalization, and rapid postictal recovery and in the case of TLE: presence of epigastric aura, lateralized dystonias, impairment of consciousness/speech during ictal and postictal periods, and development of secondary generalization. Using graph analysis metrics of FLE and TLE confirmed data from flowcharts. However, because of the algorithms we used, they highlighted more powerfully the connectivity and complex associations among behaviors in a quite selective manner, depending on the origin of the seizures. The algorithms we used are commonly employed to track brain connectivity from EEG and MRI sources, which makes our study very promising for future studies of complexity in this field.

Prnp gene and cerebellum volume in patients with refractory mesial temporal lobe epilepsy.

The cellular prion protein, encoded by Prnp gene, is involved in neuroprotection, neuroplasticity and neurodevelopment. The variant allele Valine at codon 129 of the Prnp was associated with decreased brain volume in healthy volunteers and schizophrenic patients. We investigate the association between the cerebellum volume and the presence of variant allele Valine at codon 129 of the Prnp gene in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS). The Prnp coding sequence was determined in 41 refractory MTLE-HS patients. The cerebellum volume corrected by the intracranial volume of patients with the normal Prnp genotypes was compared with that of patients presenting the variant alleles at codon 129. Twenty patients showed the Met129Met genotype, 16 showed Met129Val, and 5 had Val129Val. There were no association among clinical, demographic, electrophysiological, antiepileptic drugs used, and the presence of the Prnp variant alleles. The presence of Prnp variant allele at codon 129 was not associated with the analyzed cerebellum volume. Prnp variant alleles at codon 129 are not associated with cerebellum volume in patients with refractory MTLE-HS.

Hemispheric dysplasia and hemimegalencephaly: imaging definitions.

BACKGROUND AND PURPOSE: Hemispheric dysplasia (HD) and hemimegalencephaly (HME) are both brain malformations with early clinical manifestation including developmental delay and intractable epilepsy. Sometimes the differentiation of these conditions is not simple. HME is an anomaly of cortical development caused by a combination of neural proliferation and cell migration dysfunction, showing lobar or hemispheric enlargement. On the other hand, HD shows no brain hypertrophy, and even brain atrophy, eventually. PATIENTS AND METHODS: To compare both conditions, we reviewed clinical, MRI, and histopathology of 23 patients with developmental delay and refractory epilepsy treated with hemispheric surgery. RESULTS: Histologically, both groups presented polymicrogyria, focal cortical dysplasia, gray matter (GM) heterotopia, pachygyria, and agyria. The white matter (WM) showed different degrees of gliosis and myelin impairment. Even though with no specificity in histopathology, the degree of lesion was more impressive on HME. The combination of WM dysmyelination and hypertrophy leads to the so called hamartomatous appearing. Although not all HME showed brain enlargement and some HD might show no size changes or atrophy, the size of affected hemisphere and the hamartomatous appearance of the WM were the more relevant signs to differentiate both conditions. CONCLUSION: Brain MRI was the best diagnostic tolls because it allowed together high contrast resolution, whole brain coverage and spatial distribution analysis. HD and HMD showed brain asymmetry tendency, but in opposite directions. The size of affected hemisphere and the hamartomatous appearance of the WM were the more relevant signs to differentiate both conditions.

Atypical neuropsychological profiles and cognitive outcome in mesial temporal lobe epilepsy.

Patients with left mesial temporal lobe epilepsy (MTLE) have deficits in verbal memory processes, while patients with right MTLE have visuospatial memory impairment. However, atypical cognitive phenotypes among patients with MTLE may occur. In this study, we analyzed preoperative memory deficits in a cohort of 426 right-handed patients with unilateral MTLE. We also evaluated the cognitive outcome after anterior temporal lobectomy (ATL) of patients with atypical profiles in comparison with those with typical memory profile. We found that 25% of our patients had a typical cognitive profile, with verbal memory deficits associated with left side hippocampal sclerosis (HS) and visuospatial memory deficits associated with right side HS. However, 75% of our patients had atypical memory profiles. Despite these atypical profiles, patients submitted to right ATL had no significant cognitive deficit after surgery. In patients submitted to left ATL, the higher the presurgical scores on verbal memory and naming tests, the higher the cognitive decline after surgery.

Opercular myoclonic-anarthric status epilepticus due to glutamic acid decarboxylase antibody-associated encephalitis.

We report a patient who was diagnosed with opercular myoclonic-anarthric status epilepticus and found to have glutamic acid decarboxylase antibody (GADA)-associated encephalitis, a previously unrecognised aetiology of this condition. The patient was a 23-year-old female admitted for investigation of focal myoclonic status epilepticus in the right side of the face and glossopharyngeal area. Intravenous corticosteroid was administered and improvement was observed in seizure activity and overall general health. A video sequence of opercular myoclonia is included. Due to the presence of inflammatory elements based on brain MRI and CSF studies, a decision to investigate autoimmune encephalitis was undertaken. Anti-GAD65 radioimmunoassay was markedly positive. This case study highlights the need for awareness of the clinical presentation of GADA-associated encephalitis. [Published with video sequences].

Executive functioning in children with posterior cortex epilepsy compared to temporal and frontal lobe epilepsies.

OBJECTIVE: People with epilepsy are at an increased risk of experiencing executive dysfunction, particularly those with frontal lobe epilepsy (FLE). The literature has also demonstrated alterations in executive functioning (EF) in patients with temporal lobe epilepsy (TLE). However, few studies have examined the neuropsychological profile of posterior cortex epilepsy (PCE), and little attention has been given to cognitive impairments in the pediatric population with PCE. This study aims to investigate EF performance in children with drug-resistant PCE compared to patients with FLE and TLE. METHODS: We analyzed neuropsychological data from 217 patients aged 6-18 years who underwent preoperative evaluation for epilepsy surgery. The EF of patients with PCE was compared to patients with FLE and TLE. RESULTS: There was no significant difference in Full-Scale Intelligence Quotient (FSIQ) means between groups. However, we found a significant effect of brain region on the Coding task, in which patients with PCE and FLE performed worse than those with TLE (p = 0.034). We also observed performance differences between groups on the Stroop test (p = 0.005), with patients with PCE and FLE performing worse than the TLE group. SIGNIFICANCE: These findings suggest that children with PCE have alterations in their EF that are similar to the deficits found in FLE compared to patients with TLE. This emphasizes the importance of understanding the neuroanatomy of executive functions and the model of neural networks extending beyond the prefrontal cortex.

Amygdala gene expression of NMDA and GABA(A) receptors in patients with mesial temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common form of partial epilepsy and affects 40% of the patients. Seizures arising from the mesial temporal lobe structures (i.e., amygdala and hippocampus) are common, whereas neocortical seizures are rare. In recent years, many studies aimed to identify the pattern of gene expression of neurotransmitters involved in molecular mechanisms of epilepsy. We used real-time PCR to quantify the expression of GABA(A) (subunits α1, ß1, ß2) and NMDA (subunits NR1, NR2A, and NR2B) receptor genes in amygdalae of 27 patients with TLE and 14 amygdalae from autopsy controls. The NR1 subunit was increased in patients with epilepsy when compared with controls. No differences were found in expression of NMDA subunits NR2A and NR2B or in α1, ß1, and ß2 subunits of GABA(A) receptors. Our results suggest that the NR1 subunit of NMDA receptors is involved in the amygdala hyperexcitability in some of the patients with TLE.