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.

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.

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.

Evidence of acute ischemic tissue change in transient global amnesia in magnetic resonance imaging: case report and literature review.

Transient global amnesia is a benign syndrome of sudden-onset alteration of behavior with temporary dysfunction of anterograde and recent retrograde memory. Its neural substrates remain uncertain. Possible causes include ischemia, migraine, and epilepsy. The authors report a case of a 62-year-old man with a transient attack of memory disturbance, suggestive of transient global amnesia, in which magnetic resonance imaging performed 48 hours after onset showed left mesial temporal lobe signal changes on diffusion-weighted imaging and fluid-attenuated inversion recovery images. The findings and a literature review lend further support to the ischemic pathogenesis of transient global amnesia as a possible etiology, and underscore the role of diffusion-weighted imaging in the diagnosis of this condition.

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.

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.

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. .