Left-sided epileptiform activity influences language lateralization in right mesial temporal sclerosis.

OBJECTIVE: To investigate the association between left epileptiform activity and language laterality indices (LI) in patients with right mesial temporal sclerosis (MTS). METHODS: Twenty-two patients with right MTS and 22 healthy subjects underwent fMRI scanning while performing a language task. LI was calculated in multiple regions of interest (ROI). Data on the presence of left epileptiform abnormalities were obtained during prolonged video-EEG monitoring. RESULTS: After correction for multiple comparisons, LI was reduced in the middle temporal gyrus in the left interictal epileptiform discharges (IED+) group, compared with the left IED- group (p < 0.05). SIGNIFICANCE: Using a responsive reading naming fMRI paradigm, right MTS patients who presented left temporal interictal epileptiform abnormalities on video-EEG showed decreased LI in the middle temporal gyrus, indicating decreased left middle temporal gyrus activation, increased right middle temporal gyrus activation or a combination of both, demonstrative of language network reorganization, specially in the MTG, in this patient population. PLAIN LANGUAGE SUMMARY: This research studied 22 patients with right mesial temporal sclerosis (a specific type of epilepsy) comparing them to 22 healthy individuals. Participants were asked to perform a language task while undergoing a special brain imaging technique (fMRI). The findings showed that patients with epilepsy displayed a change in the area of the brain typically responsible for language processing. This suggests that their brains may have adapted due to their condition, altering the way language is processed.

Clinical, cerebrospinal fluid, and neuroimaging findings in COVID-19 encephalopathy: a case series.

OBJECTIVE: To describe the clinical, neurological, neuroimaging, and cerebrospinal fluid (CSF) findings associated with encephalopathy in patients admitted to a COVID-19 tertiary reference center. METHODS: We retrospectively reviewed records of consecutive patients with COVID-19 evaluated by a consulting neurology team from March 30, 2020 through May 15, 2020. RESULTS: Fifty-five patients with confirmed SARS-CoV-2 were included, 43 of whom showed encephalopathy, and were further divided into mild, moderate, and severe encephalopathy groups. Nineteen patients (44%) had undergone mechanical ventilation and received intravenous sedatives. Eleven (26%) patients were on dialysis. Laboratory markers of COVID-19 severity were very common in encephalopathy patients, but did not correlate with the severity of encephalopathy. Thirty-nine patients underwent neuroimaging studies, which showed mostly non-specific changes. One patient showed lesions possibly related to CNS demyelination. Four had suffered an acute stroke. SARS-CoV-2 was detected by RT-PCR in only one of 21 CSF samples. Two CSF samples showed elevated white blood cell count and all were negative for oligoclonal bands. In our case series, the severity of encephalopathy correlated with higher probability of death during hospitalization (OR = 5.5 for each increment in the degree of encephalopathy, from absent (0) to mild (1), moderate (2), or severe (3), p < 0.001). CONCLUSION: In our consecutive series with 43 encephalopathy cases, neuroimaging and CSF analysis did not support the role of direct viral CNS invasion or CNS inflammation as the cause of encephalopathy.

Acute Disseminated Encephalomyelitis in COVID-19: presentation of two cases and review of the literature.

BACKGROUND: Neurological manifestations of COVID-19 are still incompletely understood. Neurological manifestations may be due to direct viral effect on neurons and glial cells, to an immune-mediated response to the virus, or to a hypercoagulable state and associated endothelial damage, as well as to severe systemic disease with prolonged intensive care unit stay. OBJECTIVE: To describe two patients with severe SARS-CoV-2 infection and delayed recovery of consciousness after sedation withdrawal, in whom MRI disclosed multifocal white matter brain lesions, compatible with the diagnosis of acute disseminated encephalomyelitis. METHODS: Observational report of two cases of severe COVID-19 infection in patients from two tertiary hospitals in São Paulo, Brazil. RESULTS: These patients underwent neurologic and systemic evaluation for delayed awakening after sedation withdrawal. MRI displayed multifocal centrum semiovale lesions, suggestive of demyelinating inflammation. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for SARS-CoV-2 was negative in both cases. CONCLUSION: A recurrent pattern of multifocal white matter lesions can occur in COVID-19 patients, possibly associated with delayed awakening. Additional studies are necessary to elucidate the role of the viral infection and of inflammatory and immune-mediated associated changes in neurological manifestations of COVID-19.

Acute Disseminated Encephalomyelitis in COVID-19: presentation of two cases and review of the literature / Encefalomielite disseminada aguda associada a COVID-19: relato de dois casos e revisão de literatura

ABSTRACT Background: Neurological manifestations of COVID-19 are still incompletely understood. Neurological manifestations may be due to direct viral effect on neurons and glial cells, to an immune-mediated response to the virus, or to a hypercoagulable state and associated endothelial damage, as well as to severe systemic disease with prolonged intensive care unit stay. Objective: To describe two patients with severe SARS-CoV-2 infection and delayed recovery of consciousness after sedation withdrawal, in whom MRI disclosed multifocal white matter brain lesions, compatible with the diagnosis of acute disseminated encephalomyelitis. Methods: Observational report of two cases of severe COVID-19 infection in patients from two tertiary hospitals in São Paulo, Brazil. Results: These patients underwent neurologic and systemic evaluation for delayed awakening after sedation withdrawal. MRI displayed multifocal centrum semiovale lesions, suggestive of demyelinating inflammation. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for SARS-CoV-2 was negative in both cases. Conclusion: A recurrent pattern of multifocal white matter lesions can occur in COVID-19 patients, possibly associated with delayed awakening. Additional studies are necessary to elucidate the role of the viral infection and of inflammatory and immune-mediated associated changes in neurological manifestations of COVID-19.

RESUMO Introdução: As manifestações neurológicas causadas pela COVID-19 ainda não estão completamente elucidadas. O comprometimento neurológico pode decorrer de um efeito viral direto em neurônios ou em células gliais, a efeito imunomediado em resposta à infecção viral, ou de um efeito secundário a estados de hipercoagulabilidade e danos endoteliais, assim como decorrente de complicações sistêmicas graves relacionadas a cuidados intensivos prolongados na unidade de terapia intensiva. Objetivo: Descrever dois pacientes com recuperação tardia do nível de consciência após a retirada da sedação associados à infecção grave pelo SARS-CoV-2, que apresentaram lesões multifocais de substância branca, compatíveis com o diagnóstico de encefalomielite disseminada aguda. Métodos: Estudo observacional, com relato de dois casos de infecção grave pela COVID-19, em dois hospitais terciários na cidade de São Paulo, Brasil. Resultados: Os pacientes foram submetidos à investigação sistêmica e neurológica para avaliação de estado alterado de consciência após retirada de sedação. A ressonância magnética de crânio evidenciou lesões multifocais no centro semioval, sugestivos de processo inflamatório desmielinizante. Análise liquórica evidenciou PCR negativo para SARS-CoV-2 em ambos os casos. Conclusão: Lesões multifocais de substância branca podem ocorrer em pacientes com COVID-19, possivelmente associadas a estados alterados de consciência. Estudos adicionais são necessários para determinar o processo fisiopatológico da infecção viral e dos estados inflamatórios e imunomediados na gênese das manifestações neurológicas causadas pela COVID-19.

Analysis of fractional anisotropy and mean diffusivity in refractory and non-refractory idiopathic generalized epilepsies.

PURPOSE: To compare white matter bundles and fiber tract changes in seizure-free and non-seizure-free idiopathic generalized epilepsy (IGE) patients. METHOD: Forty adult patients with IGE underwent a 3 T brain MRI with DTI sequences. According to seizure control status, eighteen patients were classified as refractory (R) if they had presented at least one incapacitating seizure in the previous six months, while on appropriate antiepileptic drug treatment. Twenty two seizure-free patients with adequate seizure control were considered non-refractory (NR). We compared fractional anisotropy (FA) and mean diffusivity (MD) values in sixteen white matter tracts in the R and NR groups, and in twenty healthy subjects. RESULTS: R and NR groups did not differ in gender, age and education. We found decreased FA in two tracts in the R group (forceps major and right uncinate fasciculus) and approaching statistical significance in two tracts in the NR group (right cingulate gyrus and right uncinate fasciculus) group, as well as increased MD in six tracts in the R group (forceps minor, left thalamic anterior radiation, right inferior longitudinal fasciculus, right longitudinal superior parietal and temporal fasciculi, and right cingulate gyrus) and in five tracts in the NR group (forceps minor, left thalamic anterior radiation, right inferior longitudinal fasciculus, right longitudinal superior parietal and temporal fasciculi), compared to controls. No differences were noted comparing FA and MD values between R and NR groups. CONCLUSIONS: In our patient population, refractory IGE patients on adequate antiepileptic drug treatment did not present more severe white matter tract involvement compared to non-refractory patients.

Corpus callosum diffusion abnormalities in refractory epilepsy associated with hippocampal sclerosis.

OBJECTIVES: To detect by diffusion tensor imaging (DTI) the extent of microstructural integrity changes of the corpus callosum (CC) in patients with hippocampal sclerosis (HS) and to evaluate possible association with clinical characteristics. METHODS: Fourty-two patients with temporal lobe epilepsy (TLE) and HS and 30 control subjects were studied with DTI. We grouped patients according to lesion side (left or right) HS. Mean diffusivity (MD), fractional anisotropy (FA), radial (RD) and axial diffusivity (AD) were extracted from five segments in CC midsagittal section obtained by automatic segmentation. CC DTI findings were compared between groups. We also evaluated association of DTI changes and clinical characteristics. RESULTS: HS patients displayed decreased FA and increased MD and RD in the anterior, mid-posterior and posterior CC segments, compared to controls. No differences were observed in AD. Patients reporting febrile seizure as the initial precipitating event presented more intense diffusion changes. No differences were seen comparing left and right HS. Age at epilepsy onset, disease duration and seizure frequency were not associated with DTI findings. CONCLUSIONS: This is one of the largest series of TLE-HS patients evaluating CC white matter fiber integrity by DTI, which allowed us to study how some clinical characteristics, such as seizure frequency, disease duration and lesion side, are related to CC integrity. Occurrence of febrile seizure was the only factor that had significant impact on tract integrity. Diffusion changes were not restricted to the posterior part of the CC; we observed the same changes for the anterior part of the CC. Diffusion changes were characterized by an increase in RD, while the AD remained intact for all regions of the CC.

Contralateral interictal and ictal EEG epileptiform activity accentuate memory impairment in unilateral mesial temporal sclerosis patients.

OBJECTIVE: Memory impairment is a recognized complication of mesial temporal sclerosis (MTS). Epileptiform activity may negatively impact on cognition. We evaluated the impact of contralateral EEG involvement on memory in unilateral MTS (uMTS) patients. METHOD: Retrospective review of 121 right-handed uMTS patients (69 left) evaluated with prolonged video-EEG and verbal and nonverbal memory tests (Rey Auditory Verbal Learning Test and Rey-Osterrieth Complex figure), with additional very delayed trials. Patients were classified according to ictal/interictal EEG findings and MTS side as left or right concordant or discordant. Thirty-nine normal individuals who underwent the same neuropsychological battery served as controls. RESULTS: Demographic, disease, and treatment features did not differ among groups. On the 7-day verbal memory free recall, left discordant performed significantly worse than controls and right concordant, recognized fewer words, and had more recognition errors than all other groups, including left concordant. For nonverbal memory, right discordant performed significantly worse than controls on delayed recall, and attained lower scores than other groups on immediate and 7-day recall, but this difference did not reach statistical significance. Left discordant had higher scores of memory complaints than controls and disclosed a trend toward accentuated memory impairment compared with the other groups over time. CONCLUSIONS: Our results suggest that contralateral electrographic involvement in uMTS was associated with more pronounced memory impairment for verbal material in left discordant patients, and to a lesser extent, for nonverbal material in right discordant patients. Left discordant group also had increased memory complaints. (PsycINFO Database Record

Rapidly Progressive Dementia: Prevalence and Causes in a Neurologic Unit of a Tertiary Hospital in Brazil.

BACKGROUND: Rapidly progressive dementia (RPD) is usually associated with Creutzfeldt-Jakob disease, a fatal condition. Current advances in the understanding of immune-mediated diseases allow the diagnosis of previously unrecognized treatable RPDs. OBJECTIVE OF THE STUDY: The objective of the study was to describe the prevalence and causes of RPD in a neurology service, identifying potentially reversible causes. METHODS: We carried out a cross-sectional evaluation of all patients admitted to the neurology unit of a tertiary hospital in Brazil between March 2012 and February 2015. We included patients who had progressed to moderate or severe dementia within a few months or up to 2 years at the time of hospitalization, and used multivariable logistic regression analysis to identify factors associated with a favorable outcome. RESULTS: We identified 61 RPD (3.7%) cases among 1648 inpatients. Mean RPD patients' age was 48 years, and median time to progression was 6.4 months. Immune-mediated diseases represented the most commonly observed disease group in this series (45.9% of cases). Creutzfeldt-Jakob disease (11.5%) and nonprion neurodegenerative diseases (8.2%) were less common in this series. Outcome was favorable in 36/61 (59.0%) RPD cases and in 28/31 (89.3%) of immune-mediated cases. Favorable outcome was associated with shorter time from symptom onset to diagnosis and abnormal cerebrospinal fluid findings. CONCLUSIONS: Immune-mediated diseases were the most common cause of RPD in this series. Timely evaluation and diagnosis along with institution of appropriate therapy are required in RPD, especially in view of potentially reversible causes.

Contralateral ictal electrographic involvement is associated with decreased memory performance in unilateral mesial temporal sclerosis.

PURPOSE: To evaluate the effect of contralateral electrographic involvement on memory performance (measured by neuropsychological and Wada memory testing) in patients with epilepsy associated with unilateral mesial temporal sclerosis (MTS). METHODS: We studied 51 patients with medically-refractory epilepsy associated with unilateral MTS (27 women, 30/51, left MTS) submitted to prolonged non-invasive video-EEG monitoring and bilateral Wada testing. According to ictal electrographic involvement, patients were classified as: Contralateral ictal involvement, when one or more seizures evolved with rhythmic activity in the temporal region contralateral to the MTS or exclusive ipsilateral ictal involvement if all seizures showed ictal EEG activity exclusively on the MTS side. Wada testing involved a twelve-item memory paradigm. Wada memory asymmetry score was calculated for each patient subtracting the number of recalled items after injection on the lesion side from the number of recalled items after contralateral injection. Expected asymmetry (EA) was considered if Wada memory asymmetry>0, and Symmetrical or Reversed memory asymmetry (S-RA) when ≤ 0. Neuropsychological testing was applied in the 51 patients and in 40 healthy controls. Verbal Memory was evaluated with the Rey Auditory Verbal Learning Test (RAVLT), considering the number of recalled items on immediate recall after the initial five consecutive encoding trials (RAVLT 6), a post-interference delayed (30 min) recall (RAVLT 7), and recall after 7 days. Nonverbal memory was tested with Wechsler Memory Scale-III (WMS-III) Faces subtests 1 e 2. RESULTS: Groups did not differ in demographic, clinical and video-EEG monitoring variables. S-RA was observed more frequently in the group with contralateral ictal involvement (57.2% vs. 27.0%; p: 0.03). Logistic regression analysis considering demographic, clinical, hippocampal volume and video-EEG monitoring variables showed contralateral ictal involvement as the only independent variable associated with S-RA (coefficient=1.32, p=0.029, odds ratio 3.77; 95% CI 1.1-12.47). Additionally, the patient group with contralateral ictal EEG involvement displayed worse verbal and nonverbal memory scores compared to healthy controls. CONCLUSION: In this cohort of unilateral MTS patients, contralateral ictal involvement was associated with decreased memory performance on Wada and on neuropsychological testing.

Leukoencephalopathy resolution after atypical mycobacterial treatment: a case report.

BACKGROUND: Association of leukoencephalopathy and atypical mycobacteriosis has been rarely reported. We present a case that is relevant for its unusual presentation and because it may shed further light on the pathogenic mechanisms underlying reversible encephalopathies. CASE REPORT: We report the case of a Hispanic 64-year-old woman with cognitive decline and extensive leukoencephalopathy. Magnetic resonance imaging revealed white-matter lesions with increased water diffusivity, without blood-brain-barrier disruption. Brain biopsy showed tissue rarefaction with vacuolation, mild inflammation, few reactive astrocytes and decreased aquaporin water-channel expression in the lesions. Six months later, she was diagnosed with atypical mycobacterial pulmonary infection. Brain lesions resolved after antimycobacterial treatment. CONCLUSION: We hypothesize leukoencephalopathic changes and vasogenic edema were associated with decreased aquaporin expression. Further studies should clarify if reversible leukoencephalopathy has a causal relationship with decreased aquaporin expression and atypical mycobacterial infection, and mechanisms underlying leukoencephalopathy resolution after antimycobacterial treatment. This article may contribute to the understanding of pathogenic mechanisms underlying magnetic resonance imaging subcortical lesions and edema, which remain incompletely understood.

The intracarotid etomidate Wada test: a 54-patient series.

Hemispheric language dominance and isolated hemispheric memory function evaluation can be undertaken with the intracarotid injection of a general anesthetic agent (Wada test). Amobarbital has been traditionally used as the anesthetic agent, but legal and commercial constraints limit its use. We evaluated the use of etomidate as an alternative agent for the Wada test in a series of 54 consecutive adult patients with mesial temporal sclerosis undergoing presurgical evaluation for epilepsy surgery. Language lateralization and hemispheric memory function evaluation were successfully achieved in all cases. Side effects (somnolence, tremor, and dystonia) were infrequent, minor, and transient and did not require interruption of the procedure. Etomidate appears to be a safe and effective alternative agent to amobarbital in the Wada test. Similarly to the amobarbital Wada test, the ability of the etomidate Wada test to predict postoperative memory decline remains unclear.

Small calcified lesions suggestive of neurocysticercosis are associated with mesial temporal sclerosis.

UNLABELLED: Recent studies have suggested a possible relationship between temporal lobe epilepsy with mesial temporal sclerosis (MTS) and neurocysticercosis (NC). We performed a case-control study to evaluate the association of NC and MTS. METHOD: We randomly selected patients with different epilepsy types, including: MTS, primary generalized epilepsy (PGE) and focal symptomatic epilepsy (FSE). Patients underwent a structured interview, followed by head computed tomography (CT). A neuroradiologist evaluated the scan for presence of calcified lesions suggestive of NC. CT results were matched with patients' data. RESULTS: More patients in the MTS group displayed calcified lesions suggestive of NC than patients in the other groups (p=0.002). On multivariate analysis, MTS was found to be an independent predictor of one or more calcified NC lesions (p=0.033). CONCLUSION: After controlling for confounding factors, we found an independent association between NC calcified lesions and MTS.

Small calcified lesions suggestive of neurocysticercosis are associated with mesial temporal sclerosis / Pequenas lesões calcificadas sugestivas de neurocisticercose e estão associadas com esclerose mesial temporal

Recent studies have suggested a possible relationship between temporal lobe epilepsy with mesial temporal sclerosis (MTS) and neurocysticercosis (NC). We performed a case-control study to evaluate the association of NC and MTS. Method: We randomly selected patients with different epilepsy types, including: MTS, primary generalized epilepsy (PGE) and focal symptomatic epilepsy (FSE). Patients underwent a structured interview, followed by head computed tomography (CT). A neuroradiologist evaluated the scan for presence of calcified lesions suggestive of NC. CT results were matched with patients’ data. Results: More patients in the MTS group displayed calcified lesions suggestive of NC than patients in the other groups (p=0.002). On multivariate analysis, MTS was found to be an independent predictor of one or more calcified NC lesions (p=0.033). Conclusion: After controlling for confounding factors, we found an independent association between NC calcified lesions and MTS. .

Estudos recentes têm sugerido possível relação entre epilepsia do lobo temporal com esclerose mesial temporal (MTS) e neurocisticercose (NC). Conduzimos um estudo caso-controle para avaliar a associação de NC e MTS. Método: Selecionamos randomicamente pacientes com diferentes tipos de epilepsia, incluindo: MTS, epilepsia primariamente generalizada (PGE) e epilepsia focal sintomática (FSE). Pacientes foram submetidos a uma entrevista estruturada, seguida por uma tomografia computadorizada de crânio (CT). Um neuroradiologista avaliou as imagens quanto à presença de lesões calcificadas sugestivas de NC. Resultados das CT foram comparados com os dados dos pacientes. Resultados: Mais pacientes do grupo MTS apresentaram lesões calcificadas sugestivas de NC que de outros grupos (p=0,002). Na análise multivariável, MTS foi um preditor independente de uma ou mais calcificações sugestivas de NC (p=0,033). Conclusão: Após controlar para fatores confusionais, encontramos uma associação independente entre lesões calcificadas de NC e MTS. .

Comorbid epilepsy and psychogenic non-epileptic seizures: how well do patients and caregivers distinguish between the two.

PURPOSE: To determine whether patients with comorbid epilepsy and psychogenic nonepileptic seizure (PNES) and their caregivers can distinguish between these two events at least one year after initial diagnosis, and to investigate factors associated with correct identification. METHODS: Adult patients with at least a one year diagnosis of both epilepsy and PNES, confirmed through video-electroencephalography (VEEG), were selected. Patients and a caregiver of their choice were interviewed and shown videos containing the patients' epileptic and PNES events. Variables associated with correct identification of events by patients and their caregivers were evaluated. RESULTS: Twenty-four patients participated in the study. Mean time between VEEG diagnosis and enrollment in the study was 26.8 months (±12.4). Six of patients correctly distinguished between the events shown. Factors associated with correct identification were the absence of intellectual disability, unremitted PNES, and a degree of preserved awareness during the PNES event. Twelve caregivers correctly distinguished between the events shown. Factors associated with correct identification among caregivers were the presentation of only one epileptic seizure type in the patient, and the participation of the caregiver during VEEG monitoring and communication of PNES diagnosis to the patient. CONCLUSION: A significant proportion of patients with epilepsy and PNES and their caregivers seem to be unable to discriminate between these events a year after diagnosis. These findings have implications for both clinical follow-up and research involving this population. Future research should further investigate methods that would allow patients and their caregivers to better distinguish between these two events.

Low prevalence but high specificity of material-specific memory impairment in epilepsy associated with hippocampal sclerosis.

PURPOSE: Material-specific memory impairment is used as a lateralizing tool in the evaluation of temporal lobe epilepsy. Lateralizing ability of material-specific memory deficits in temporal lobe epilepsy remains controversial. METHODS: We studied memory impairment profiles of verbal and nonverbal memory deficits with eight memory subtests of four neuropsychological instruments (two verbal and two nonverbal) in 87 right-handed patients with epilepsy associated with unilateral mesial temporal sclerosis (MTS; 44 right - R, 43 left - L) and 42 controls, with an IQ >70, at least 8 years of education, and without comorbidities. KEY FINDINGS: Selective verbal memory impairment was noted in 11 of 43 or 25.6% of left MTS cases, with 82.2% specificity, whereas selective nonverbal memory impairment was noted in 11 of 42 or 26.2% of right MTS cases, with 92% specificity. Nonlateralizing profiles of memory performance were seen in the remaining 65 of 87 patients. Approximately half (46/87 or 52.9%) of the patients had intact memory function in both modalities, equally distributed between patients with right MTS (23/44) and left MTS (23/43). Global impairment of both memory types was seen in 12 of 87 or 13.8% of patients, equally distributed between the two groups (7/43 left and 5/44 right). SIGNIFICANCE: Lateralizing profiles of selective verbal and nonverbal memory deficits are highly specific for left and right MTS, although infrequently encountered in our patients. Nonlateralizing profiles predominated in this population. These findings suggest hemispheric asymmetry memory function, with complex functional interaction of the hippocampi, and possible compensatory mechanisms in the setting of a unilateral lesion.

Factors associated with treatment non-adherence in patients with epilepsy in Brazil.

PURPOSE: To investigate factors associated with treatment non-adherence in Brazilian patients with epilepsy. METHODS: Prospective cross-sectional study. We evaluated 385 epilepsy outpatients in a tertiary referral center, 18 years or older, literate, without cognitive impairment or active psychiatric disorders, who were independent in daily living activities. Data were analyzed with correlation tests and conjoint analysis using multivariate logistic regression. RESULTS: Non-adherence rate, measured by the Morisky-Green Test, was 66.2%, a moderate-to-low adherence level. Non-adherence was higher in men, in younger patients and in patients with uncontrolled seizures. Increasing treatment complexity was also associated with decreased treatment adherence. CONCLUSION: Strategies designed to improve treatment adherence should address peculiarities associated with younger ages and male gender. Physicians should be made aware that prescription of less complex treatment regimens may result in better treatment adherence, and, therefore, better seizure control. The challenge in adjusting AED treatment in this population is to minimize treatment complexity, thus increasing chances for treatment adherence.

Hippocampal CA3 transcriptome signature correlates with initial precipitating injury in refractory mesial temporal lobe epilepsy.

BACKGROUND: Prolonged febrile seizures constitute an initial precipitating injury (IPI) commonly associated with refractory mesial temporal lobe epilepsy (RMTLE). In order to investigate IPI influence on the transcriptional phenotype underlying RMTLE we comparatively analyzed the transcriptomic signatures of CA3 explants surgically obtained from RMTLE patients with (FS) or without (NFS) febrile seizure history. Texture analyses on MRI images of dentate gyrus were conducted in a subset of surgically removed sclerotic hippocampi for identifying IPI-associated histo-radiological alterations. METHODOLOGY/PRINCIPAL FINDINGS: DNA microarray analysis revealed that CA3 global gene expression differed significantly between FS and NFS subgroups. An integrative functional genomics methodology was used for characterizing the relations between GO biological processes themes and constructing transcriptional interaction networks defining the FS and NFS transcriptomic signatures and its major gene-gene links (hubs). Co-expression network analysis showed that: i) CA3 transcriptomic profiles differ according to the IPI; ii) FS distinctive hubs are mostly linked to glutamatergic signalization while NFS hubs predominantly involve GABAergic pathways and neurotransmission modulation. Both networks have relevant hubs related to nervous system development, what is consistent with cell genesis activity in the hippocampus of RMTLE patients. Moreover, two candidate genes for therapeutic targeting came out from this analysis: SSTR1, a relevant common hub in febrile and afebrile transcriptomes, and CHRM3, due to its putative role in epilepsy susceptibility development. MRI texture analysis allowed an overall accuracy of 90% for pixels correctly classified as belonging to FS or NFS groups. Histological examination revealed that granule cell loss was significantly higher in FS hippocampi. CONCLUSIONS/SIGNIFICANCE: CA3 transcriptional signatures and dentate gyrus morphology fairly correlate with IPI in RMTLE, indicating that FS-RMTLE represents a distinct phenotype. These findings may shed light on the molecular mechanisms underlying refractory epilepsy phenotypes and contribute to the discovery of novel specific drug targets for therapeutic interventions.

Good surgical outcome in discordant ictal EEG-MRI unilateral mesial temporal sclerosis patients.

PURPOSE: Video electroencephalography (vEEG) monitoring of patients with unilateral mesial temporal sclerosis (uMTS) may show concordant or discordant seizure onset in relation to magnetic resonance imaging (MRI) evidence of MTS. Contralateral seizure usually leads to an indication of invasive monitoring. Contralateral seizure onset on invasive monitoring may contraindicate surgery. We evaluated long-term outcome after anteromesial temporal lobectomy (AMTL) in a consecutive series of uMTS patients with concordant and discordant vEEG findings, uniformly submitted to AMTL on the MRI evidence of MTS side without invasive monitoring. METHODS: We compared surgical outcome of all uMTS patients undergoing vEEG monitoring between January 1999 and April 2005 in our service. Discordant cases were defined by at least one seizure onset contralateral to the MRI evidence of MTS. Good surgical outcome was considered as Engel's class I. We also evaluated ictal SPECT concordance to ictal EEG and surgical outcome. RESULTS: Fifty-four patients had concordant (C) and 22 had discordant (D) scalp EEG and MRI. Surgical outcome was similar in both groups (C = 74% versus D = 86%). Duration of follow-up was comparable in both groups: C = 56.1 +/- 20.7 months versus D = 59.8 +/- 21.2 months (p = 0.83, nonsignificant). Discordant single-photon emission computed tomography (SPECT) results did not influence surgical outcome. DISCUSSION: Surgical outcome was not influenced by contralateral vEEG seizure onset or contralateral increased flow on ictal SPECT. Although vEEG monitoring should still be performed in these patients, to rule out psychogenic seizures and extratemporal seizure onset, a potentially risky procedure such as invasive monitoring may not only not be indicated in this patient population, but may also lead to patients erroneously being denied surgery.

Prospective memory and mesial temporal epilepsy associated with hippocampal sclerosis.

Episodic memory impairment is commonly observed in patients with epilepsy associated with mesial temporal sclerosis (MTS). Prospective memory (PM) is a set cognitive abilities that allow future performance of a present intention, in response to time- or event-based evocation cues, that trigger the intended action at the appropriate time. PM has not been evaluated in mesial temporal sclerosis. We evaluated the role of right and left hippocampal lesions on performance in both the retrospective and prospective PM components in patients with epilepsy secondary to mesial temporal sclerosis and correlated with performance in traditional neuropsychological tests, as well as with self-perception of memory impairment. We tested the hypotheses that a hippocampal lesion impacts on the prospective components of PM, and that a left-sided lesion had a greater impact on performance in the prospective component of PM than a right-sided lesion. We evaluated PM in 26 patients with right MTS, 22 left MTS patients, and 26 age-gender and education matched controls. The prospective component of PM was impaired in both patient groups, with both a lesion (patients performed significantly worse in the PM battery) and laterality effect (left MTS patients performed significantly worse than right MTS patients in the PM battery). Performance in the prospective component of the PM battery correlated with long-term delay performance in episodic verbal memory and self-perception of memory impairment in the left MTS group. The retrospective component was impaired in left MTS patients. Impaired performance was not accounted for solely by depression, anxiety or an antiepileptic drug effect. We conclude that mesial temporal lobe structures, including the hippocampus, play an important role in both the prospective and retrospective components of PM processes in tasks involving long delay intervals.