Asymmetrical hippocampal connectivity in mesial temporal lobe epilepsy: evidence from resting state fMRI

<p>Abstract</p> <p>Background</p> <p>Mesial temporal lobe epilepsy (MTLE), the most common type of focal epilepsy in adults, is often caused by hippocampal sclerosis (HS). Patients with HS usually present memory dysfunction, which is material-specific according to the hemisphere involved and has been correlated to the degree of HS as measured by postoperative histopathology as well as by the degree of hippocampal atrophy on magnetic resonance imaging (MRI). Verbal memory is mostly affected by left-sided HS, whereas visuo-spatial memory is more affected by right HS. Some of these impairments may be related to abnormalities of the network in which individual hippocampus takes part. Functional connectivity can play an important role to understand how the hippocampi interact with other brain areas. It can be estimated via functional Magnetic Resonance Imaging (fMRI) resting state experiments by evaluating patterns of functional networks. In this study, we investigated the functional connectivity patterns of 9 control subjects, 9 patients with right MTLE and 9 patients with left MTLE.</p> <p>Results</p> <p>We detected differences in functional connectivity within and between hippocampi in patients with unilateral MTLE associated with ipsilateral HS by resting state fMRI. Functional connectivity resulted to be more impaired ipsilateral to the seizure focus in both patient groups when compared to control subjects. This effect was even more pronounced for the left MTLE group.</p> <p>Conclusions</p> <p>The findings presented here suggest that left HS causes more reduction of functional connectivity than right HS in subjects with left hemisphere dominance for language.</p

Long-term postoperative atrophy of contralateral hippocampus and cognitive function in unilateral refractory MTLE with unilateral hippocampal sclerosis

Objective: This study aimed to evaluate long-term atrophy in contralateral hippocampal volume after surgery for unilateral MTLE, as well as the cognitive outcome for patients submitted to either selective transsylvian amygdalohippocampectomy (SelAH) or anterior temporal lobe resection (ATL). Methods: We performed a longitudinal study of 47 patients with MRI signs of unilateral hippocampal sclerosis (23 patients with right-sided hippocampal sclerosis) who underwent surgical treatment for MTLE. They underwent preoperative/postoperative high-resolution MRI as well as neuropsychological assessment for memory and estimated IQ. To investigate possible changes in the contralateral hippocampus of patients, we included 28 controls who underwent two MRIs at long-term intervals. Results: The volumetry using preoperative MRI showed significant hippocampal atrophy ipsilateral to the side of surgery when compared with controls (p b 0.0001) but no differences in contralateral hippocampal volumes. The mean postoperative follow-up was 8.7 years (±2.5 SD; median = 8.0). Our patients were classified as Engel I (80%), Engel II (18.2%), and Engel III (1.8%). We observed a small but significant reduction in the contralateral hippocampus of patients but no volume changes in controls. Most of the patients presented small declines in both estimated IQ and memory, which were more pronounced in patients with left TLE and in those with persistent seizures. Different surgical approaches did not impose differences in seizure control or in cognitive outcome. Conclusions: We observed small declines in cognitive scores with most of these patients, which were worse in patients with left-sided resection and in those who continued to suffer from postoperative seizures. We also demonstrated that manual volumetry can reveal a reduction in volume in the contralateral hippocampus, although this change was mild and could not be detected by visual analysis. These new findings suggest that dynamic processes continue to act after the removal of the hippocampus, and further studies with larger groups may help in understanding the underlying mechanisms

New insights into Trypanosoma cruzi genetic diversity, and its influence on parasite biology and clinical outcomes

Chagas disease, caused by Trypanosoma cruzi, remains a serious public health problem worldwide. The parasite was subdivided into six distinct genetic groups, called “discrete typing units” (DTUs), from TcI to TcVI. Several studies have indicated that the heterogeneity of T. cruzi species directly affects the diversity of clinical manifestations of Chagas disease, control, diagnosis performance, and susceptibility to treatment. Thus, this review aims to describe how T. cruzi genetic diversity influences the biology of the parasite and/or clinical parameters in humans. Regarding the geographic dispersion of T. cruzi, evident differences were observed in the distribution of DTUs in distinct areas. For example, TcII is the main DTU detected in Brazilian patients from the central and southeastern regions, where there are also registers of TcVI as a secondary T. cruzi DTU. An important aspect observed in previous studies is that the genetic variability of T. cruzi can impact parasite infectivity, reproduction, and differentiation in the vectors. It has been proposed that T. cruzi DTU influences the host immune response and affects disease progression. Genetic aspects of the parasite play an important role in determining which host tissues will be infected, thus heavily influencing Chagas disease’s pathogenesis. Several teams have investigated the correlation between T. cruzi DTU and the reactivation of Chagas disease. In agreement with these data, it is reasonable to suppose that the immunological condition of the patient, whether or not associated with the reactivation of the T. cruzi infection and the parasite strain, may have an important role in the pathogenesis of Chagas disease. In this context, understanding the genetics of T. cruzi and its biological and clinical implications will provide new knowledge that may contribute to additional strategies in the diagnosis and clinical outcome follow-up of patients with Chagas disease, in addition to the reactivation of immunocompromised patients infected with T. cruzi

Long-term postoperative atrophy of contralateral hippocampus and cognitive function in unilateral refractory MTLE with unilateral hippocampal sclerosis

Objective: This study aimed to evaluate long-term atrophy in contralateral hippocampal volume after surgery for unilateral MTLE, as well as the cognitive outcome for patients submitted to either selective transsylvian amygdalohippocampectomy (SelAH) or anterior temporal lobe resection (ATL). Methods: We performed a longitudinal study of 47 patients with MRI signs of unilateral hippocampal sclerosis (23 patients with right-sided hippocampal sclerosis) who underwent surgical treatment for MTLE. They underwent preoperative/postoperative high-resolution MRI as well as neuropsychological assessment for memory and estimated IQ. To investigate possible changes in the contralateral hippocampus of patients, we included 28 controls who underwent two MRIs at long-term intervals. Results: The volumetry using preoperative MRI showed significant hippocampal atrophy ipsilateral to the side of surgery when compared with controls (p. <. 0.0001) but no differences in contralateral hippocampal volumes. The mean postoperative follow-up was 8.7. years (±. 2.5 SD; median = 8.0). Our patients were classified as Engel I (80%), Engel II (18.2%), and Engel III (1.8%). We observed a small but significant reduction in the contralateral hippocampus of patients but no volume changes in controls. Most of the patients presented small declines in both estimated IQ and memory, which were more pronounced in patients with left TLE and in those with persistent seizures. Different surgical approaches did not impose differences in seizure control or in cognitive outcome. Conclusions: We observed small declines in cognitive scores with most of these patients, which were worse in patients with left-sided resection and in those who continued to suffer from postoperative seizures. We also demonstrated that manual volumetry can reveal a reduction in volume in the contralateral hippocampus, although this change was mild and could not be detected by visual analysis. These new findings suggest that dynamic processes continue to act after the removal of the hippocampus, and further studies with larger groups may help in understanding the underlying mechanisms. © 2014 Elsevier Inc.This study aimed to evaluate long-term atrophy in contralateral hippocampal volume after surgery for unilateral MTLE, as well as the cognitive outcome for patients submitted to either selective transsylvian amygdalohippocampectomy (SelAH) or anterior temp36108114FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2010/02492-0Hauser, W.A., Annegers, J.F., Rocca, W.A., Descriptive epidemiology of epilepsy - contributions of population-based studies from Rochester, Minnesota (1996) Mayo Clinic Proceedings, 71, pp. 576-586Yasuda, C.L., Tedeschi, H., Oliveira, E.L., Ribas, G.C., Costa, A.L., Cardoso, T.A., Comparison of short-term outcome between surgical and clinical treatment in temporal lobe epilepsy: a prospective study (2006) Seizure, 15, pp. 35-40. , [S1059-1311(05)00209-8 [pii]]Wiebe, S., Blume, W.T., Girvin, J.P., Eliasziw, M., A randomized, controlled trial of surgery for temporal-lobe epilepsy (2001) N Engl J Med, 345, pp. 311-318Helmstaedter, C., Neuropsychological aspects of epilepsy surgery (2004) Epilepsy Behav, 5 (SUPPL. 1), pp. S45-S55. , [S1525505003003196 [pii]]Sherman, E.M., Wiebe, S., Fay-McClymont, T.B., Tellez-Zenteno, J., Metcalfe, A., Hernandez-Ronquillo, L., Neuropsychological outcomes after epilepsy surgery: systematic review and pooled estimates (2011) Epilepsia, 52, pp. 857-869Andersson-Roswall, L., Engman, E., Samuelsson, H., Malmgren, K., Cognitive outcome 10years after temporal lobe epilepsy surgery: a prospective controlled study (2010) Neurology, 74, pp. 1977-1985. , [74/24/1977 [pii]]Baxendale, S., Thompson, P.J., Duncan, J.S., Neuropsychological function in patients who have had epilepsy surgery: a long-term follow-up (2012) Epilepsy Behav, 23, pp. 24-29. , [S1525-5050(11)00619-6 [pii]]Helmstaedter, C., Kurthen, M., Lux, S., Reuber, M., Elger, C.E., Chronic epilepsy and cognition: a longitudinal study in temporal lobe epilepsy (2003) Ann Neurol, 54, pp. 425-432Grammaldo, L.G., Di Gennaro, G., Giampà, T., De Risi, M., Meldolesi, G.N., Mascia, A., Memory outcome 2 years after anterior temporal lobectomy in patients with drug-resistant epilepsy (2009) Seizure, 18 (2), pp. 139-144Kuang, Y., Yang, T., Gu, J., Kong, B., Cheng, L., Comparison of therapeutic effects between selective amygdalohippocampectomy and anterior temporal lobectomy for the treatment of temporal lobe epilepsy: A meta-analysis (2013) Br J Neurosurg., 7, pp. 1-4Tanriverdi, T., Olivier, A., Poulin, N., Andermann, F., Dubeau, F., Long-term seizure outcome after mesial temporal lobe epilepsy surgery: corticalamygdalohippocampectomy versus selective amygdalohippocampectomy (2008) J Neurosurg, 108, pp. 517-524von, R.B., Nelles, M., Urbach, H., von, L.M., Schramm, J., Helmstaedter, C., Neuropsychological outcome after selective amygdalohippocampectomy: subtemporal versus transsylvian approach (2012) J Neurol Neurosurg Psychiatry, 83, pp. 887-893. , [jnnp-2011-302025 [pii]]Baxendale, S., Thompson, P.J., Duncan, J.S., Neuropsychological function in patients who have had epilepsy surgery: a long-term follow-up (2011) Epilepsy Behav, , [S1525-5050(11)00619-6 [pii]]Chapin, J.S., Busch, R.M., Silveira, D.C., Wehner, T., Naugle, R.I., Ferguson, L., Memory performance in older adults before and after temporal lobectomy for pharmacoresistant epilepsy (2013) Clin Neuropsychol, 27, pp. 1316-1327Engel, J., A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology (2001) Epilepsia, 42, pp. 796-803. , [epi10401 [pii]]Yasuda, C.L., Valise, C., Saude, A.V., Pereira, A.R., Pereira, F.R., Ferreira Costa, A.L., Dynamic changes in white and gray matter volume are associated with outcome of surgical treatment in temporal lobe epilepsy (2010) Neuroimage, 49, pp. 71-79. , [S1053-8119(09)00891-X [pii]]Bonilha, L., Kobayashi, E., Cendes, F., Min, L.L., Protocol for volumetric segmentation of medial temporal structures using high-resolution 3-D magnetic resonance imaging (2004) Hum Brain Mapp, 22, pp. 145-154Strauss, E., Sherman, E.M.S., Spreen, O., (2006) A compendium of neuropsychological test, , OXFORD University Press, New YorkMalloy-Diniz, L.F., Lasmar, V.A., Gazinelli, L.S., Fuentes, D., Salgado, J.V., The Rey Auditory-Verbal Learning Test: applicability for the Brazilian elderly population (2007) Rev Bras Psiquiatr, 29, pp. 324-329. , [S1516-44462006005000053 [pii]]de, T.J., Bell, G.S., Peacock, J.L., McEvoy, A.W., Harkness, W.F., Sander, J.W., The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study (2011) Lancet, 378, pp. 1388-1395. , [S0140-6736(11)60890-8 [pii]]Noulhiane, M., Samson, S., Clemenceau, S., Dormont, D., Baulac, M., Hasboun, D., A volumetric MRI study of the hippocampus and the parahippocampal region after unilateral medial temporal lobe resection (2006) J Neurosci Methods, 156, pp. 293-304. , [S0165-0270(06)00135-X [pii]]Bonilha, L., Edwards, J.C., Kinsman, S.L., Morgan, P.S., Fridriksson, J., Rorden, C., Extrahippocampal gray matter loss and hippocampal deafferentation in patients with temporal lobe epilepsy (2010) Epilepsia, 51, pp. 519-528. , [EPI2506 [pii]]Andersson, D., Wilhelmsson, U., Nilsson, M., Kubista, M., Stahlberg, A., Pekna, M., Plasticity response in the contralesional hemisphere after subtle neurotrauma: gene expression profiling after partial deafferentation of the hippocampus (2013) PLoS One, 8, pp. e70699. , [PONE-D-13-15506 [pii]]Baxendale, S., The impact of epilepsy surgery on cognition and behavior (2008) Epilepsy Behav, 12, pp. 592-599. , [S1525-5050(07)00479-9 [pii]]Rausch, R., Kraemer, S., Pietras, C.J., Le, M., Vickrey, B.G., Passaro, E.A., Early and late cognitive changes following temporal lobe surgery for epilepsy (2003) Neurology, 60, pp. 951-959Alpherts, W.C., Vermeulen, J., van Rijen, P.C., da Silva, F.H., van Veelen, C.W., Verbal memory decline after temporal epilepsy surgery?: a 6-year multiple assessments follow-up study (2006) Neurology, 67, pp. 626-631. , [67/4/626 [pii]]Sattler, J.M., (1988) Assessment of children, p. 995. , Jerome M. Sattler, Publisher, San DiegoHelmstaedter, C., Cognitive outcomes of different surgical approaches in temporal lobe epilepsy (2013) Epileptic Disord, 15, pp. 221-239. , [epd.2013.0587 [pii]]Paglioli, E., Palmini, A., Portuguez, M., Paglioli, E., Azambuja, N., da Costa, J.C., Seizure and memory outcome following temporal lobe surgery: selective compared with nonselective approaches for hippocampal sclerosis (2006) J Neurosurg, 104, pp. 70-78Clusmann, H., Schramm, J., Kral, T., Helmstaedter, C., Ostertun, B., Fimmers, R., Prognostic factors and outcome after different types of resection for temporal lobe epilepsy (2002) J Neurosurg, 97, pp. 1131-1141Helmstaedter, C., Richter, S., Roske, S., Oltmanns, F., Schramm, J., Lehmann, T.N., Differential effects of temporal pole resection with amygdalohippocampectomy versus selective amygdalohippocampectomy on material-specific memory in patients with mesial temporal lobe epilepsy (2008) Epilepsia, 49, pp. 88-97. , [EPI1386 [pii]]Sagher, O., Thawani, J.P., Etame, A.B., Gomez-Hassan, D.M., Seizure outcomes and mesial resection volumes following selective amygdalohippocampectomy and temporal lobectomy (2012) Neurosurg Focus, 32, pp. E

Brain Plasticity For Verbal And Visual Memories In Patients With Mesial Temporal Lobe Epilepsy And Hippocampal Sclerosis: An Fmri Study.

We aimed to identify the brain areas involved in verbal and visual memory processing in normal controls and patients with unilateral mesial temporal lobe epilepsy (MTLE) associated with unilateral hippocampal sclerosis (HS) by means of functional magnetic resonance imaging (fMRI). The sample comprised nine normal controls, eight patients with right MTLE, and nine patients with left MTLE. All subjects underwent fMRI with verbal and visual memory paradigms, consisting of encoding and immediate recall of 17 abstract words and 17 abstract drawings. A complex network including parietal, temporal, and frontal cortices seems to be involved in verbal memory encoding and retrieval in normal controls. Although similar areas of activation were identified in both patient groups, the extension of such activations was larger in the left-HS group. Patients with left HS also tended to exhibit more bilateral or right lateralized encoding related activations. This finding suggests a functional reorganization of verbal memory processing areas in these patients due to the failure of left MTL system. As regards visual memory encoding and retrieval, our findings support the hypothesis of a more diffuse and bilateral representation of this cognitive function in the brain. Compared to normal controls, encoding in the left-HS group recruited more widespread cortical areas, which were even more widespread in the right-HS group probably to compensate for their right mesial temporal dysfunction. In contrast, the right-HS group exhibited fewer activated areas during immediate recall than the other two groups, probably related to their greater difficulty in dealing with visual memory content.34186-9

Who is who at the ILRI Addis campus

<p>(A) Overall reactivity profile of sera samples at late stage of single (TcI/COL, n = 29; TcVI/CL, n = 29 and TcII/Y, n = 35) and dual (TcI/COL+TcVI/CL, n = 28; TcVI/CL+TcII/Y, n = 43 and TcI/COL+TcII/Y, n = 36) <i>T</i>. <i>cruzi</i> infections with distinct genotypes. The IgG2a reactivity was evaluated along the titration curve with each target-antigens amastigote (AMA = green), trypomastigote (TRYPO = red) and epimastigote (EPI = yellow) from TcI, TcVI and TcII genotypes of <i>T</i>. <i>cruzi</i>. The results are shown on radar charts and expressed as mean of percentage of positive fluorescent parasites (PPFP). (B) Titration curves were assessed at eight serum dilutions (1:500 to 1:64,000) using target-antigens AI, AVI and AII; TI, TVI and TII along with EI, EVI and EI at late stage of single [TcI/COL (triangle), TcVI/CL (square), TcII/Y (circle)] and dual [TcI/COL+TcVI/CL (cross), TcVI/CL+TcII/Y (dash), TcI/COL+TcII/Y (asterisk)] <i>T</i>. <i>cruzi</i> infections.</p

Selection of attributes for Chagas-Flow ATE-IgG2a to discriminate single and dual <i>T</i>. <i>cruzi</i> infections at early and late stages.

<p>(A) Comparative analysis of IgG2a reactivity at early stage of single (n = 50) and dual (n = 60) <i>T</i>. <i>cruzi</i> infections, using pre-selected pairs of attributes, including: AI 1,000; AVI 8,000; AII 2,000; TI 2,000; TVI 2,000; TII 8,000; EI 2,000; EVI 2,000 and EII 1,000. (B) Comparative analysis of IgG2a reactivity at late stage of single (n = 93) and dual (n = 107) <i>T</i>. <i>cruzi</i> infections, using pre-selected pairs of attributes, including: AI 500; AVI 500; AII 32,000; TI 8,000; TVI 4,000; TII 16,000; EI 4,000; EVI 2,000 and EII 4,000. The results are expressed as median of PPFP values in box plot format with the outliers showed by shaded dots. Comparative analyses were performed by the Kruskal-Wallis/Dunn’s post test. Significant differences were considered at p<0.05 and highlighted by connecting lines. The light gray background highlights the pairs of attributes (“target antigen and serum dilution”) with the higher performance to discriminate single and dual <i>T</i>. <i>cruzi</i> infections at early and late stages. Decision trees were constructed using the sets of attributes (“target-antigen and serum dilution/cut-off”) to create algorithms (root and branches) to classify individual samples from single and dual <i>T</i>. <i>cruzi</i> infections at (C) early and (D) late stages. Global accuracy and leave-one-out-cross-validation-LOOCV are provided in the Figure.</p

Selection of attributes for genotype-specific Chagas-Flow ATE-IgG2a at late stage of single and dual <i>T</i>. <i>cruzi</i> infections.

<p>(A) Comparative analysis of IgG2a reactivity at late stage of single infection with distinct <i>T</i>. <i>cruzi</i> genotypes (TcI/COL, n = 29; TcVI/CL, n = 29 and TcII/Y, n = 35) using pre-selected pairs of attributes, including: AI 2,000; AVI 1,000; AII 1,000; TI 4,000; TVI 1,000; TII 16,000; EI 2,000; EVI 1,000 and EII 4,000. (B) Comparative analysis of IgG2a reactivity at late stage of dual infection with distinct <i>T</i>. <i>cruzi</i> genotypes (TcI/COL+TcVI/CL, n = 28; TcVI/CL+TcII/Y, n = 43 and TcI/COL+TcII/Y, n = 36) using pre-selected pairs of attributes, including: AI 2,000; AVI 500; AII 1,000; TI 64,000; TVI 16,000; TII 64,000; EI 4,000; EVI 16,000 and EII 4,000. The results are expressed as median PPFP values in box plot format with the outliers showed by shaded dots. Comparative analyses were performed by the Kruskal-Wallis/Dunn’s post test. Significant differences were considered at p<0.05 and highlighted by connecting lines. The light gray background highlights the pairs of attributes (“target antigen and serum dilution”) with the higher performance for the genotype-specific diagnosis at late stage of single and dual <i>T</i>. <i>cruzi</i> infections. Decision trees were constructed using the sets of attributes (“target-antigen and serum dilution/cut-off”) to create algorithms (root and branches) to classify at late stage, individual samples from (C) single and (D) dual <i>T</i>. <i>cruzi</i> infections. Global accuracy and leave-one-out-cross-validation-LOOCV are provided in the Figure.</p

Overall Chagas-Flow ATE-IgG2a reactivity at early and late stages of single and dual <i>T</i>. <i>cruzi</i> infections.

<p>(A) Panoramic reactivity profile of sera samples at early stage of single (Triangle, n = 50) and dual (Cross, n = 60) as well as at late stage of single (Square, n = 93) and dual (Asterisk, n = 107) <i>T</i>. <i>cruzi</i> infections. The IgG2a reactivity was evaluated along the titration curve with each target-antigens amastigote (AMA = green), trypomastigote (TRYPO = red) and epimastigote (EPI = yellow) from TcI, TcVI and TcII genotypes of <i>T</i>. <i>cruzi</i>. The results are shown in radar charts and expressed as mean of percentage of positive fluorescent parasites (PPFP). (B) Titration curves at eight serum dilutions (1:500 to 1:64,000) using target-antigens AI, AVI and AII; TI, TVI and TII and EI, EVI and EII were assessed at early and late stages of single and dual <i>T</i>. <i>cruzi</i> infections.</p

Selection of attributes for genotype-specific Chagas-Flow ATE-IgG2a at early stage of single and dual <i>T</i>. <i>cruzi</i> infections.

<p>(A) Comparative analysis of IgG2a reactivity at early stage of single infection with distinct <i>T</i>. <i>cruzi</i> genotypes (TcI/COL, n = 16; TcVI/CL, n = 15 and TcII/Y, n = 19) using pre-selected pairs of attributes, including: AI 1,000; AVI 500; AII 500; TI 4,000; TVI 500; TII 1,000; EI 1,000; EVI 500 and EII 500. (B) Comparative analysis of IgG2a reactivity at early stage of dual infection with distinct <i>T</i>. <i>cruzi</i> genotypes (TcI/COL+TcVI/CL, n = 16; TcVI/CL+TcII/Y, n = 24 and TcI/COL+TcII/Y, n = 20) using pre-selected pairs of attributes, including: AI 500; AVI 1,000; AII 2,000; TI 16,000; TVI 500; TII 8,000; EI 2,000; EVI 2,000 and EII 2,000. The results are expressed as median PPFP values in box plot format with the outliers showed by shaded dots. Comparative analyses were performed by the Kruskal-Wallis/Dunn’s post test. Significant differences were considered at p<0.05 and highlighted by connecting lines. The light gray background highlights the pairs of attributes (“target antigen and serum dilution”) with the higher performance for the genotype-specific diagnosis at early stage of single and dual <i>T</i>. <i>cruzi</i> infections. Decision trees were constructed using the sets of attributes (“target-antigen and serum dilution/cut-off”) to create algorithms (root and branches) to classify at early stage, individual samples from (C) single and (D) dual <i>T</i>. <i>cruzi</i> infections. Global accuracy and leave-one-out-cross-validation-LOOCV are provided in the Figure.</p