Epidemiological features of meningiomas: a single Brazilian center's experience with 993 cases.

BACKGROUND: Meningiomas are the most frequent primary central nervous system (CNS) tumors. Their geographical and ethnic characteristics need to be known, in order to enable rational treatment. OBJECTIVE: To investigate clinical and epidemiological aspects in a series of patients with meningiomas. METHODS: Retrospective analysis on the demographic profile, location and histopathology of 993 patients with meningiomas (768 operated and 225 not operated). RESULTS: Meningiomas represented 43.8% of the primary CNS tumors; 6.8% were multiple tumors (14.7% with neurofibromatosis 2) and 0.6% were radiation-induced tumors. The mean ages were 53.0 and 63.9 years for operated and non-operated patients and the female/male ratios were 3.2:1 and 6.3:1. Diagnosis was made later among females. The peak incidences were in the 6th and 7th decades respectively for operated and non-operated patients. The incidence was low at early ages and higher among patients aged 70+ years. The meningiomas were intracranial in 96.5% and most were WHO grade I (88.9%) and transitional. In the spinal canal (3.5%), they occurred mainly in the dorsal region (all grade I; mostly transitional). The racial distribution was 1.0% in Asian-Brazilians, 87% in Caucasians and 12% in African-Brazilians. 83.4% and 51.6% of the patients were estimated to be recurrence-free at 10 and 20 years, and the mortality rate was 3%. CONCLUSIONS: Most of the demographic data were similar to what has been observed in other western centers. Differences were higher incidence of meningiomas, female and older predominance in non-operated patients, predominance in Caucasian, and higher association with neurofibromatosis 2.

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.

Modulation of NMDA receptor by miR-219 in the amygdala and hippocampus of patients with mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy with hippocampal sclerosis is the most frequent form of focal epilepsy in adults, and it is often refractory to drug treatment. Regardless of the efforts on developing new antiepileptic drugs for refractory cases, studies suggest a need for better understanding the molecular bases of epilepsy. The microRNAs have been progressively investigated as potential targets for both epilepsy mechanisms elucidation and treatment. Therefore, the goal of this study was to evaluate the differential expression of miR-219, miR-181b, and miR-195, previously described as regulators of the excitatory neurotransmitter receptors NMDA-R1 and AMPA-GluR2 and inhibitory neurotransmitter GABAA (α2, ß3, and γ2 subunits) in the amygdala and hippocampus of patients with mesial temporal lobe epilepsy. Based on genes and miRNAs' quantitative Polymerase Chain Reaction (qPCR) from 18 patients with epilepsy, our results showed an inverse relationship between miR-219 and NMDA-NR1 expression in both the amygdala and hippocampus in comparison to their expression in controls. NR1 and GluR2 were upregulated in the amygdala of epileptic patients. Low miR-195 expression was observed in the amygdala of patients with epilepsy. Our findings indicate that miR-219 has a possible regulatory role in excitatory neurotransmission in patients with epilepsy, contributing to the new avenue of miRNA biology in drug-resistant epilepsy, reserving huge potential for future applications and clinical interventions in conjunction with existing therapies.

Histological correlates of hippocampal magnetization transfer images in drug-resistant temporal lobe epilepsy patients.

OBJECTIVE: Temporal lobe epilepsy patients (TLE) often present with hippocampal atrophy, increased T2 relaxation, and reduced magnetization transfer ratio (MTR) in magnetic resonance images (MRI). The histological correlates of the reduced hippocampal MTR are so far unknown. Since MTR is dependent on the tissue's macromolecules, our aim was to evaluate the correlations between cellular populations, extracellular matrix molecules and the MTR in TLE patients. METHODS: Patients with TLE (n = 26) and voluntaries (=20) were scanned in a 3 Tesla MRI scanner, and MTR images were calculated from 3DT1 sequences with magnetization pulse on resonance. Immunohistochemistry for neurons, reactive astrocytes, activated microglia, and extracellular matrix chondroitin sulfate were performed in formalin fixed, paraffin embedded tissues of TLE and autopsy controls (n = 10). Results were considered significant with adjusted p < 0.05. RESULTS: Compared to the respective controls, TLE patients had reduced hippocampal MTR, increased reactive astrocytes and activated microglia, increased extracellular chondroitin sulfate, and reduced neuron density, compares to controls. MTR correlated positively with neuron density in CA3 and with chondroitin sulfate in CA3 and CA1. Multiple linear regressions reinforced the correlations between chondroitin sulfate and MTR. SIGNIFICANCE: Our data indicate that extracellular matrix molecules are the most significant histological correlates of magnetization transfer ratio in the hippocampus of TLE patients.

Expression of MicroRNAs miR-145, miR-181c, miR-199a and miR-1183 in the Blood and Hippocampus of Patients with Mesial Temporal Lobe Epilepsy.

The aim of this study was to analyze the expression profiles of the microRNAs (miRNAs) miR-145, miR-181c, miR-199a and miR-1183 in the hippocampus and blood of patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and to investigate whether these can be used as diagnosis and prognosis biomarkers for epilepsy. Hippocampus and blood samples were collected from 20 patients with MTLE-HS, ten of whom had a favorable surgical outcome (Engel I) and ten with an unfavorable surgical outcome (Engel III-IV). Hippocampus samples from autopsied individuals with no neurological or psychiatric medical history (necropsy samples) and blood samples from healthy individuals were used as controls. Real-time quantitative PCR (RQ-PCR) was used to analyze miRNA expression. The results showed that the expressions of these miRNAs differed quantitatively in the hippocampus and blood of patients with MTLE-HS in comparison to the respective control. This difference was most pronounced for miR-145, which was hypo-expressed in the hippocampus and hyper-expressed in the blood of MTLE-HS patients. MiRNAs miR-145, miR-181c, miR-199a and miR-1183 were hyper-expressed in the blood of patients with MTLE-HS. No statistical differences in the levels of these miRNAs in the blood or hippocampus were found between Engel I patients and Engel III-IV patients. These results suggest that the analyzed microRNAs are potential circulating biomarkers for epilepsy diagnosis.

Manual Hippocampal Subfield Segmentation Using High-Field MRI: Impact of Different Subfields in Hippocampal Volume Loss of Temporal Lobe Epilepsy Patients.

In patients with temporal lobe epilepsy (TLE), presurgical magnetic resonance imaging (MRI) often reveals hippocampal atrophy, while neuropathological assessment indicates the different types of hippocampal sclerosis (HS). Different HS types are not discriminated in MRI so far. We aimed to define the volume of each hippocampal subfield on MRI manually and to compare automatic and manual segmentations for the discrimination of HS types. The T2-weighted images from 14 formalin-fixed age-matched control hippocampi were obtained with 4.7T MRI to evaluate the volume of each subfield at the anatomical level of the hippocampal head, body, and tail. Formalin-fixed coronal sections at the level of the body of 14 control cases, as well as tissue samples from 24 TLE patients, were imaged with a similar high-resolution sequence at 3T. Presurgical three-dimensional (3D) T1-weighted images from TLE went through a FreeSurfer 6.0 hippocampal subfield automatic assessment. The manual delineation with the 4.7T MRI was identified using Luxol Fast Blue stained 10-µm-thin microscopy slides, collected at every millimeter. An additional section at the level of the body from controls and TLE cases was submitted to NeuN immunohistochemistry for neuronal density estimation. All TLE cases were classified according to the International League Against Epilepsy's (ILAE's) HS classification. Manual volumetry in controls revealed that the dentate gyrus (DG)+CA4 region, CA1, and subiculum accounted for almost 90% of the hippocampal volume. The manual 3T volumetry showed that all TLE patients with type 1 HS (TLE-HS1) had lower volumes for DG+CA4, CA2, and CA1, whereas those TLE patients with HS type 2 (TLE-HS2) had lower volumes only in CA1 (p ≤ 0.038). Neuronal cell densities always decreased in CA4, CA3, CA2, and CA1 of TLE-HS1 but only in CA1 of TLE-HS2 (p ≤ 0.003). In addition, TLE-HS2 had a higher volume (p = 0.016) and higher neuronal density (p < 0.001) than the TLE-HS1 in DG + CA4. Automatic segmentation failed to match the manual or histological findings and was unable to differentiate TLE-HS1 from TLE-HS2. Total hippocampal volume correlated with DG+CA4 and CA1 volumes and neuronal density. For the first time, we also identified subfield-specific pathology patterns in the manual evaluation of volumetric MRI scans, showing the importance of manual segmentation to assess subfield-specific pathology patterns.

Free-floating adult human brain-derived slice cultures as a model to study the neuronal impact of Alzheimer's disease-associated Aß oligomers.

BACKGROUND: Slice cultures have been prepared from several organs. With respect to the brain, advantages of slice cultures over dissociated cell cultures include maintenance of the cytoarchitecture and neuronal connectivity. Slice cultures from adult human brain have been reported and constitute a promising method to study neurological diseases. Despite this potential, few studies have characterized in detail cell survival and function along time in short-term, free-floating cultures. NEW METHOD: We used tissue from adult human brain cortex from patients undergoing temporal lobectomy to prepare 200 µm-thick slices. Along the period in culture, we evaluated neuronal survival, histological modifications, and neurotransmitter release. The toxicity of Alzheimer's-associated Aß oligomers (AßOs) to cultured slices was also analyzed. RESULTS: Neurons in human brain slices remain viable and neurochemically active for at least four days in vitro, which allowed detection of binding of AßOs. We further found that slices exposed to AßOs presented elevated levels of hyperphosphorylated Tau, a hallmark of Alzheimer's disease. COMPARISON WITH EXISTING METHOD(S): Although slice cultures from adult human brain have been previously prepared, this is the first report to analyze cell viability and neuronal activity in short-term free-floating cultures as a function of days in vitro. CONCLUSIONS: Once surgical tissue is available, the current protocol is easy to perform and produces functional slices from adult human brain. These slice cultures may represent a preferred model for translational studies of neurodegenerative disorders when long term culturing in not required, as in investigations on AßO neurotoxicity.

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.

Correction: Increased Metallothionein I/II Expression in Patients with Temporal Lobe Epilepsy.

[This corrects the article DOI: 10.1371/journal.pone.0044709.].

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.

Mesial temporal lobe epilepsy with psychiatric comorbidities: a place for differential neuroinflammatory interplay.

BACKGROUND: Despite the strong association between epilepsy and psychiatric comorbidities, few biological substrates are currently described. We have previously reported neuropathological alterations in mesial temporal lobe epilepsy (MTLE) patients with major depression and psychosis that suggest a morphological and neurochemical basis for psychopathological symptoms. Neuroinflammatory-related structures and molecules might be part of the altered neurochemical milieu underlying the association between epilepsy and psychiatric comorbidities, and such features have not been previously investigated in humans. METHODS: MTLE hippocampi of subjects without psychiatric history (MTLEW), MTLE + major depression (MTLE + D), and MTLE + interictal psychosis (MTLE + P) derived from epilepsy surgery and control necropsies were investigated for reactive astrocytes (glial fibrillary acidic protein (GFAP)), activated microglia (human leukocyte antigen, MHC class II (HLA-DR)), glial metallothionein-I/II (MT-I/II), and aquaporin 4 (AQP4) immunohistochemistry. RESULTS: We found an increased GFAP immunoreactive area in the molecular layers, granule cell layer, and cornus ammonis region 2 (CA2) and cornus ammonis region 1 (CA1) of MTLEW and MTLE + P, respectively, compared to MTLE + D. HLA-DR immunoreactive area was higher in cornus ammonis region 3 (CA3) of MTLE + P, compared to MTLE + D and MTLEW, and in the hilus, when compared to MTLEW. MTLEW cases showed increased MT-I/II area in the granule cell layer and CA1, compared to MTLE + P, and in the parasubiculum, when compared to MTLE + D and MTLE + P. Differences between MTLE and control, such as astrogliosis, microgliosis, increased MT-I/II, and decreased perivascular AQP4 in the epileptogenic hippocampus, were in agreement to what is currently described in the literature. CONCLUSIONS: Neuroinflammatory-related molecules in MTLE hippocampus show a distinct pattern of expression when patients present with a comorbid psychiatric diagnosis, similar to what is found in the pure forms of schizophrenia and major depression. Future studies focusing on inflammatory characteristics of MTLE with psychiatric comorbidities might help in the design of better therapeutic strategies.

Neurotrophin receptors expression in mesial temporal lobe epilepsy with and without psychiatric comorbidities and their relation with seizure type and surgical outcome.

Epilepsy and psychiatric comorbidities are frequently associated, but their common biological substrate is unknown. We have previously reported altered structural elements and neurotrophins (NTs) expression in mesial temporal lobe epilepsy (MTLE) patients with psychiatric comorbidities. NTs receptors can regulate neurotransmission and promote neuroplasticity, being important candidates in the regulation and manifestation of psychopatological states and seizure-related events. MTLE hippocampi of subjects without psychiatric history, MTLE + major depression, MTLE + interictal psychosis derived from epilepsy surgery, and control necropsies were investigated for p75(NTR), TrkB, TrkA, and TrkC immunohistochemistry. Increased expression of p75(NTR), decreased TrkA, unaltered TrkC, and complex alterations involving TrkB expression were seen in MTLE groups. Increased TrkB expression in patients without complete seizure remission and in those with secondarily generalized seizures was seen. Decreased p75(NTR) expression associated with interictal psychosis, and increased TrkB in those with psychosis or major depression was also reported, although their p75(NTR)/TrkB ratios were lower than in MTLE without psychiatric comorbidities. Our results provide evidence of alterations in expression of NTs receptors in the epileptogenic hippocampus that are differentially modulated in presence of psychiatric comorbidities. As already explored in animal models, even in chronic human MTLE increased TrkB expression, among other NT receptors alterations, may play a major role in seizure type, frequency and surgery outcome.

Neurotrophins in mesial temporal lobe epilepsy with and without psychiatric comorbidities.

Despite the strong association between epilepsy and psychiatric comorbidities, data on clinicopathologic correlations are scant. We previously reported differential mossy fiber sprouting (MFS) in mesial temporal lobe epilepsy (MTLE) patients with psychosis (MTLE + P) and major depression (MTLE + D). Because neurotrophins (NTs) can promote MFS, here, we investigated MFS, neuronal density and immunoreactivity for the NT nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) in hippocampi of 14 MTLE patients without a psychiatric history, 13 MTLE + D, 13 MTLE + P, and 10 control necropsies. Mossy fiber sprouting correlated with granular layer NGF immunoreactivity and seizure frequency. Patients with secondarily generalized seizures exhibited less NGF immunoreactivity versus patients with complex partial seizures. There was greater NT immunoreactivity in MTLE versus control groups but lesser NT immunoreactivity in MTLE + P versus MTLE patients; these findings correlated with neuropsychologic scores. Patients with MTLE + D taking fluoxetine showed greater BDNF immunoreactivity than those not taking fluoxetine; MTLE + P patients taking haloperidol had decreased neuronal density and immunoreactivity for NGF and BDNF in specific subfields versus those not taking haloperidol. There were no differences in NT3 immunoreactivity among the groups. These findings support a close association between MFS and NT expression in the hippocampi of MTLE patients and suggest that distinct structural and neurochemical milieu may contribute to the genesis or maintenance of psychiatric comorbidities in MTLE.

Microtubule-associated proteins in mesial temporal lobe epilepsy with and without psychiatric comorbidities and their relation with granular cell layer dispersion.

BACKGROUND: Despite strong association between epilepsy and psychiatric comorbidities, biological substrates are unknown. We have previously reported decreased mossy fiber sprouting in mesial temporal lobe epilepsy (MTLE) patients with psychosis and increased in those with major depression. Microtubule associated proteins (MAPs) are essentially involved in dendritic and synaptic sprouting. METHODS: MTLE hippocampi of subjects without psychiatric history, MTLE + major depression, and MTLE + interictal psychosis derived from epilepsy surgery and control necropsies were investigated for neuronal density, granular layer dispersion, and MAP2 and tau immunohistochemistry. RESULTS: Altered MAP2 and tau expression in MTLE and decreased tau expression in MTLE with psychosis were found. Granular layer dispersion correlated inversely with verbal memory scores, and with MAP2 and tau expression in the entorhinal cortex. Patients taking fluoxetine showed increased neuronal density in the granular layer and those taking haloperidol decreased neuronal density in CA3 and subiculum. CONCLUSIONS: Our results indicate relations between MAPs, granular layer dispersion, and memory that have not been previously investigated. Differential MAPs expression in human MTLE hippocampi with and without psychiatric comorbidities suggests that psychopathological states in MTLE rely on differential morphological and possibly neurochemical backgrounds. This clinical study was approved by our institution's Research Ethics Board (HC-FMRP no. 1270/2008) and is registered under the Brazilian National System of Information on Ethics in Human Research (SISNEP) no. 0423.0.004.000-07.

Distinct increased metabotropic glutamate receptor type 5 (mGluR5) in temporal lobe epilepsy with and without hippocampal sclerosis.

Metabotropic glutamate receptor type 5 (mGluR5) upregulation in temporal lobe epilepsy (TLE) and the correlation of its expression with features of hippocampal sclerosis (HS) remains unclear. Here we characterized mGluR5 immunoreactivity in hippocampus, entorhinal cortex (EC), and subiculum of TLE specimens with confirmed HS, with neocortical TLE (non-HS) and necropsy controls. We correlated mGluR5 immunoreactivity with neuronal density, mossy fiber sprouting, astrogliosis (GFAP), and dendritic alterations (MAP2). TLE specimens showed increased mGluR5 expression, which was most pronounced in the EC, subiculum, CA2, and dentate gyrus outer molecular layer. Increased mGluR5 expression was seen in hippocampal head and body segments and was independent of neuronal density, astrogliosis, or dendritic alterations. Positive correlation between mGluR5 expression with mossy fiber sprouting and with MAP2 in CA3 and CA1 was found only in HS specimens. Negative correlation between mGluR5 expression with seizure frequency and epilepsy duration was found only in non-HS cases. Specimens from HS patients without previous history of febrile seizure (FS) showed higher mGluR5 and MAP2 expression in CA2. Our study suggests that mGluR5 upregulation is part of a repertoire of post-synaptic adaptations that might control overexcitation and excessive glutamate release rather than a dysfunction that leads to seizure facilitation. That would explain why non-HS cases, on which seizures are likely to originate outside the hippocampal formation, also exhibit upregulated mGluR5. On the other hand, lower mGluR5 expression was related to increased seizure frequency. In addition to its role in hyperexcitability, mGluR5 upregulation could play a role in counterbalance mechanisms along the hyperexcitable circuitry uniquely altered in sclerotic hippocampal formation. Inefficient post-synaptic compensatory morphological (dendritic branching) and glutamatergic (mGluR5 expression) mechanisms in CA2 subfield could potentially underlie the association of FS with HS and TLE.

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.

Results of microsurgical treatment of paraclinoid carotid aneurysms.

The term "paraclinoid aneurysms", has been used for aneurysms of the internal carotid artery (ICA) between the cavernous sinus and the posterior communicating artery. Due to their complex anatomical relationship at the skull base and because they are frequently large/giant, their surgical treatment remains a challenge. Ninety-five patients harboring 106 paraclinoid aneurysms underwent surgery (1990-2010). Age, 11-72 years old. Sex, 74:21 female/male. Follow-up; 1-192 months (mean = 51.7 months). Eighty-six patients had single and 9 had multiple paraclinoid aneurysms. Sixty-six were ophthalmic, 14 were in the ICA superior wall, 13 in the inferior, 10 in the medial, and 3 in the ICA lateral wall. Eleven were giant, 29 were large, and 66 were small. Sixty-three patients had ruptured and 32 had unruptured aneurysms. Two patients with bilateral aneurysms had bilateral approaches, totaling 97 procedures. A total of 98.2% of aneurysms were clipped (complete exclusion in 93.8%). ICA occlusion occurred in 10 (5.6%). There was no patient rebleeding during the follow-up period. A good outcome was achieved in 76.8%, with better results for unruptured aneurysms, worse results for patients with vasospasm, and with no difference according to size. Thirty-six (37.9%) patients had transient/permanent postoperative neurological deficits (25.4% ruptured vs. 62.5% unruptured aneurysms). The most frequent deficits were visual impairment and third cranial nerve palsies. Operative mortality was 11.6%, all in patients presenting with ruptured aneurysms. Despite relatively high morbidity/mortality, especially for patients with ruptured aneurysms, microsurgical treatment of paraclinoid aneurysm has high efficacy, with better outcome for unruptured aneurysms and worse outcome for patients with vasospasm.

Increased metallothionein I/II expression in patients with temporal lobe epilepsy.

In the central nervous system, zinc is released along with glutamate during neurotransmission and, in excess, can promote neuronal death. Experimental studies have shown that metallothioneins I/II (MT-I/II), which chelate free zinc, can affect seizures and reduce neuronal death after status epilepticus. Our aim was to evaluate the expression of MT-I/II in the hippocampus of patients with temporal lobe epilepsy (TLE). Hippocampi from patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) and patients with TLE associated with tumor or dysplasia (TLE-TD) were evaluated for expression of MT-I/II, for the vesicular zinc levels, and for neuronal, astroglial, and microglial populations. Compared to control cases, MTLE group displayed widespread increase in MT-I/II expression, astrogliosis, microgliosis and reduced neuronal population. In TLE-TD, the same changes were observed, except that were mainly confined to fascia dentata. Increased vesicular zinc was observed only in the inner molecular layer of MTLE patients, when compared to control cases. Correlation and linear regression analyses indicated an association between increased MT-I/II and increased astrogliosis in TLE. MT-I/II levels did not correlate with any clinical variables, but MTLE patients with secondary generalized seizures (SGS) had less MT-I/II than MTLE patients without SGS. In conclusion, MT-I/II expression was increased in hippocampi from TLE patients and our data suggest that it is associated with astrogliosis and may be associated with different seizure spread patterns.

Validation of the Subjective Handicap of Epilepsy (SHE) in Brazilian patients with epilepsy.

The objectives of the study were to translate and adapt the Subjective Handicap of Epilepsy (SHE) instrument to Brazilian Portuguese and to determine its psychometric properties for the evaluation of quality of life in patients with epilepsy. A sample of 448 adult patients with epilepsy with different clinical profiles (investigation, preoperative period, postoperative period, and drug treatment follow-up) was evaluated with the SHE and the Epilepsy Surgery Inventory (ESI-55). Exploratory factorial analysis demonstrated that four factors explained 60.47% of the variance and were sensitive to discriminate the different clinical groups, with the preoperative group having the poorest quality of life. Internal consistency ranged from 0.92 to 0.96, and concurrent validity with the ESI-55 was moderate/strong (0.32-0.70). Test-retest reliability was confirmed, with an ICC value of 0.54 (2 days), 0.91 (7 days), and 0.97 (30 days). The SHE had satisfactory psychometric qualities for use in the Brazilian population, similar to those of the original version. The instrument seems to be more adequate in psychometric terms for the postoperative and drug treatment follow-up groups, and its use should be encouraged.

Differential aberrant sprouting in temporal lobe epilepsy with psychiatric co-morbidities.

Psychiatric co-morbidities in epilepsy are common in patients with temporal lobe epilepsy (TLE). Pathological alterations in TLE are well characterised; however, neuropathologic data are relatively scale regarding the association between psychiatric diseases and epilepsy. Our objective was to evaluate the clinical data of 46 adult TLE patients with and without psychiatric co-morbidities and to correlate the data with hippocampal neuronal density and mossy fiber sprouting. Accordingly, patients were grouped as follows: TLE patients without history of psychiatric disorder (TLE, n=16), TLE patients with interictal psychosis (TLE+P, n=14), and TLE patients with major depression (TLE+D, n=16). Hippocampi from autopsies served as non-epileptic controls (n=10). TLE+P exhibited significantly diminished mossy fiber sprouting and decreased neuronal density in the entorhinal cortex when compared with TLE. TLE+P showed significantly poorer results in verbal memory tasks. TLE+D exhibited significantly increased mossy fiber sprouting length when compared with TLE and TLE+P. Further, a higher proportion of TLE+D and TLE+P presented secondarily generalised seizures than did TLE. Our results indicate that TLE patients with psychiatric disorders have distinct features when compared with TLE patients without psychiatric co-morbidities and that these changes may be involved in either the manifestation or the maintenance of psychiatric co-morbidities in epilepsy.