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BACKGROUND: Meningiomas are often embolized preoperatively to reduce intraoperative blood loss and facilitate tumor resection. However, the procedure is controversial and its effects have not yet been reported. We evaluated preoperative embolization for meningiomas and its effect on postoperative outcome and recurrence. METHODS: We retrospectively reviewed the medical records of 186 patients with WHO grade I meningiomas who underwent surgical treatment at our hospital between January 2010 and December 2020. We used propensity score matching to generate embolization and no-embolization groups (42 patients each) to examine embolization effects. RESULTS: Preoperative embolization was performed in 71 patients (38.2%). In the propensity-matched analysis, the embolization group showed favorable recurrence-free survival (RFS) (mean 49.4 vs 24.1 months; Wilcoxon p=0.049). The embolization group had significantly less intraoperative blood loss (178±203 mL vs 221±165 mL; p=0.009) and shorter operation time (5.6±2.0 hours vs 6.8±2.8 hours; p=0.036). There were no significant differences in Simpson grade IV resection (33.3% vs 28.6%; p=0.637) or overall perioperative complications (21.4% vs 11.9%; p=0.241). Tumor embolization prolonged RFS in a subanalysis of cases who experienced recurrence (n=39) among the overall cases before variable control (mean RFS 33.2 vs 16.0 months; log-rank p=0.003). CONCLUSIONS: After controlling for variables, preoperative embolization for meningioma did not improve the Simpson grade or patient outcomes. However, it might have effects outside of surgical outcomes by prolonging RFS without increasing complications.
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Embolização Terapêutica , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Estudos Retrospectivos , Perda Sanguínea Cirúrgica , Procedimentos Neurocirúrgicos , Embolização Terapêutica/métodos , Resultado do Tratamento , Cuidados Pré-Operatórios , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/cirurgiaRESUMO
BACKGROUND AND OBJECTIVES: Insulo-opercular surgery can cause ischemic motor complications. A source of this is the arteries around the superior limiting sulcus (SLS), which reach the corona radiata, but the detailed anatomy remains unclear. To characterize arteries around the SLS including the long insular arteries (LIAs) and long medullary arteries, we classified them and examined their distribution in relation to the SLS, which helps reduce the risk of ischemia. METHODS: Twenty adult cadaveric hemispheres were studied. Coronal brain slices were created perpendicular to the SLS representing insular gyri (anterior short, middle short, posterior short, anterior long, and posterior long). The arteries within 10-mm proximity of the SLS that reached the corona radiata were excavated and classified by the entry point. RESULTS: A total of 122 arteries were identified. Sixty-three (52%), 20 (16%), and 39 (32%) arteries penetrated the insula (LIAs), peak of the SLS, and operculum (long medullary arteries), respectively. 100 and six (87%) arteries penetrated within 5 mm of the peak of the SLS. The arteries were distributed in the anterior short gyrus (19%), middle short gyrus (17%), posterior short gyrus (20%), anterior long gyrus (19%), and posterior long gyrus (25%). Seven arteries (5.7%) had anastomoses after they penetrated the parenchyma. CONCLUSION: Approximately 90% of the arteries that entered the parenchyma and reached the corona radiata were within a 5-mm radius of the SLS in both the insula and operculum side. This suggests that using the SLS as a landmark during insulo-opercular surgery can decrease the chance of ischemia.
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Encéfalo , Artéria Cerebral Média , Adulto , Humanos , Extremidade Superior , IsquemiaRESUMO
Sonic hedgehog (Shh) signaling pathways are known to play an important role in the morphological development of the hippocampus in vivo, but their actual roles in humans have not been clarified. Hypothalamic hamartoma (HH) is known to be associated with germline or somatic gene mutations of Shh signaling. We hypothesized that patients with HH and mutations of Shh-related genes also show hippocampal maldevelopment and an abnormal hippocampal infolding angle (HIA). We analyzed 45 patients (age: 1-37 years) with HH who underwent stereotactic radiofrequency thermocoagulation and found Shh-related gene mutations in 20 patients. In addition, 44 pediatric patients without HH (age: 2-25 years) who underwent magnetic resonance imaging (MRI) examinations under the same conditions during the same period were included in this study as a control group. HIA evaluated on MRI was compared between patients with gene mutations and the control group. The median HIA at the cerebral peduncle slice in patients with the gene mutation was 74.36° on the left and 76.11° on the right, and these values were significantly smaller than the corresponding values in the control group (80.46° and 80.56°, respectively, p < 0.01). Thus, mutations of Shh-related genes were correlated to incomplete hippocampal inversion. The HIA, particularly at the cerebral peduncle slice, is a potential indicator of abnormalities of the Shh-signaling pathway.
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This study investigated the effect of Mahjong, which is a table game played by three or four players and involves intellectual activity, on the intelligence quotient (IQ) of children. The participants were children between the age of 6 and 15 years, and their IQ was assessed immediately after enrolling in children's Mahjong classes and 1 year after the enrollment using the Wechsler Intelligence Scale for Children Fourth Edition (WISC-IV). Twenty children were included in the analysis. Their mean age at the time of the initial evaluation was 9 years and 6 months. In addition, we conducted a 1-year post-examination. The change in the IQ of this group was compared to that of a historical control group with a similar age range and test-retest interval. The mean overall full-scale IQ of the 20 children during the initial and post-1-year examinations was 106.05 and 113.75, respectively, and showed a statistically significant increase (p < 0.01). Based on the subscale index, the verbal comprehension index (VCI) and processing speed index (PSI) scores both showed a statistically significant increase from 100.6 to 106.75 and from 108.05 to 119.05 (p < 0.01), respectively. The PSI of the children included in the analysis showed a statistically significant increase compared to the historical control group. This study suggests that children who participate in Mahjong classes during their childhood have increased PSI scores of WISC-IV.
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OBJECTIVE: Intensive genetic analysis was performed to reveal comprehensive molecular insights into hypothalamic hamartoma (HH). METHODS: Thirty-eight individuals with HH were investigated by whole exome sequencing, target capture-based deep sequencing, or single nucleotide polymorphism (SNP) array using DNA extracted from blood leukocytes or HH samples. RESULTS: We identified a germline variant of KIAA0556, which encodes a ciliary protein, and 2 somatic variants of PTPN11, which forms part of the RAS/mitogen-activated protein kinase (MAPK) pathway, as well as variants in known genes associated with HH. An SNP array identified (among 3 patients) one germline copy-neutral loss of heterozygosity (cnLOH) at 6p22.3-p21.31 and 2 somatic cnLOH; one at 11q12.2-q25 that included DYNC2H1, which encodes a ciliary motor protein, and the other at 17p13.3-p11.2. A germline heterozygous variant and an identical somatic variant of DYNC2H1 arising from cnLOH at 11q12.2-q25 were confirmed in one patient (whose HH tissue, therefore, contains biallelic variants of DYNC2H1). Furthermore, a combination of a germline and a somatic DYNC2H1 variant was detected in another patient. CONCLUSIONS: Overall, our cohort identified germline/somatic alterations in 34% (13/38) of patients with HH. Disruption of the Shh signaling pathway associated with cilia or the RAS/MAPK pathway may lead to the development of HH.
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Dineínas do Citoplasma/genética , Hamartoma/genética , Doenças Hipotalâmicas/genética , Proteínas Associadas aos Microtúbulos/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Adolescente , Adulto , Criança , Pré-Escolar , Cílios , Epilepsias Parciais/fisiopatologia , Epilepsia Parcial Complexa/fisiopatologia , Feminino , Mutação em Linhagem Germinativa , Hamartoma/fisiopatologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Doenças Hipotalâmicas/fisiopatologia , Lactente , Recém-Nascido , Sistema de Sinalização das MAP Quinases , Masculino , Mutação , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Transdução de Sinais , Sequenciamento do Exoma , Adulto JovemRESUMO
OBJECTIVE: It is well-known that there is a correlation between the neuropathological grade of hippocampal sclerosis (HS) and neuroradiological atrophy of the hippocampus in mesial temporal lobe epilepsy (mTLE) patients. However, there is no strict definition or criterion regarding neuron loss and atrophy of the amygdala neighboring the hippocampus. We examined the relationship between HS and neuronal loss in the amygdala. MATERIALS AND METHODS: Nineteen mTLE patients with neuropathological proof of HS were assigned to Group A, while seven mTLE patients without HS were assigned to Group B. We used FreeSurfer software to measure amygdala volume automatically based on pre-operation magnetic resonance images. Neurons observed using Klüver-Barrera (KB) staining in resected amygdala tissue were counted. and the extent of immunostaining with stress marker antibodies was semiquantitatively evaluated. RESULTS: There was no significant difference in amygdala volume between the two groups (Group A: 1.41±0.24; Group B: 1.41±0.29cm3; p=0.98), nor in the neuron cellularity of resected amygdala specimens (Group A: 3.98±0.97; Group B: 3.67±0.67 10×-4 number of neurons/µm2; p=0.40). However, the HSP70 level, representing acute stress against epilepsy, in Group A patients was significantly larger than that in Group B. There was no significant difference in the level of Bcl-2, which is known as a protein that inhibits cell death, between the two groups. CONCLUSIONS: Neuronal loss and volume loss in the amygdala may not necessarily follow hippocampal sclerosis. From the analysis of stress proteins, epileptic attacks are as likely to damage the amygdala as the hippocampus but do not lead to neuronal death in the amygdala.
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Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/patologia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/patologia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/patologia , Adolescente , Adulto , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/cirurgia , Contagem de Células , Criança , Epilepsia Resistente a Medicamentos/metabolismo , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/cirurgia , Feminino , Proteínas de Choque Térmico HSP70/metabolismo , Hipocampo/diagnóstico por imagem , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/cirurgia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neurônios/metabolismo , Neurônios/patologia , Tamanho do Órgão , Esclerose/diagnóstico por imagem , Esclerose/metabolismo , Esclerose/patologia , Esclerose/cirurgia , Software , Adulto JovemRESUMO
OBJECTIVE: We aimed to validate the usefulness of gradient magnetic-field topography (GMFT) for analysis of ictal magnetoencephalography (MEG) in patients with neocortical epilepsy. METHODS: We identified 13 patients presenting with an ictal event during preoperative MEG. We applied equivalent current dipole (ECD) estimation and GMFT to detect and localize the ictal MEG onset, and compared these methods with the ictal onset zone (IOZ) derived from chronic intracranial electroencephalography. The surgical resection areas and outcomes were also evaluated. RESULTS: GMFT detected and localized the ictal MEG onset in all patients, whereas ECD estimation showed localized ECDs in only 2. The delineation of GMFT was concordant with the IOZ at the gyral-unit level in 10 of 12 patients (83.3%). The detectability and precision of delineation of ictal MEG activity by GMFT were significantly superior to those of ECD (p<0.05 and p<0.01, respectively). Complete resection of the IOZ in the concordant group provided seizure freedom in 3 patients, whereas seizures remained in 9 patients who had incomplete resections. CONCLUSIONS: Because of its higher spatial resolution, GMFT of ictal MEG is superior to conventional ECD estimation in patients with neocortical epilepsy. SIGNIFICANCE: Ictal MEG study is a useful tool to estimate the seizure onset in patients with neocortical epilepsy.
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Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Magnetoencefalografia/métodos , Neocórtex/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Epilepsia/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neocórtex/cirurgia , Estudos Retrospectivos , Adulto JovemRESUMO
Objectives There are three conceivable reasons for the failure of resective surgery for intractable epilepsy: incomplete resection of the epileptogenic zone including or overlapping with eloquent area (group A); incorrect determination of the epileptogenic zone prior to the first surgery (group B); and the development of a new epileptic focus after the first surgery (group C). We examined the relationship between the reason for failure of initial surgery and patient outcomes after repeated surgical resection. Methods The study included 18 patients (5.1%) underwent additional surgery after failure of the initial operation. Post-operative outcomes, complications and other clinical data were collected by retrospective chart review. Results Four patients (22.2%) were assigned to group A, 13 (72.2%) were assigned to group B, and 1 patient was assigned to group C (5.6%). Six patients (40.0%) were seizure-free for 2 or more years after additional surgery. In group B, 11 patients underwent additional resection of the cortex adjacent to the previously resected area and 2 underwent re-operation involving a site distant from the previously resected area; notably, the latter 2 patients did not achieve seizure-free status post-surgery. After the first operation, only one patient (group A) experienced transient paresis; after additional surgery, 10 of 18 patients (56%; 3 group A, 6 group B, and 1 group C) experienced various complications. Discussion Although additional resective surgery provided freedom from seizures in about 40% of the patients, it is important to weigh a high risk of complications against possible benefits when considering additional surgery.
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Epilepsia Resistente a Medicamentos/cirurgia , Procedimentos Neurocirúrgicos , Reoperação , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Criança , Pré-Escolar , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Complicações Pós-Operatórias , Convulsões/diagnóstico por imagem , Convulsões/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
Gradient magnetic-field topography (GMFT) is one method for analyzing magnetoencephalography (MEG) and representing the spatiotemporal dynamics of activity on the brain surface. In contrast to spatial filters, GMFT does not include a process reconstructing sources by mixing sensor signals with adequate weighting. Consequently, noisy sensors have localized and limited effects on the results, and GMFT can handle MEG recordings with low signal-to-noise ratio. This property is derived from the principle of the planar-type gradiometer, which obtains maximum gradient magnetic-field signals just above the electrical current source. We assumed that this characteristic allows GMFT to represent even faint changes in brain activities that cannot be achieved with conventional equivalent current dipole analysis or spatial filters. GMFT is thus hypothesized to represent brain surface activities from onset to propagation of epileptic discharges. This study aimed to validate the spatiotemporal accuracy of GMFT by analyzing epileptic activities using simultaneous MEG and intracranial electroencephalography (iEEG) recordings. Participants in this study comprised 12 patients with intractable epilepsy. Epileptic spikes simultaneously detected on both MEG and iEEG were analyzed by GMFT and voltage topography (VT), respectively. Discrepancies in spatial distribution between GMFT and VT were evaluated for each epileptic spike. On the lateral cortices, areas of GMFT activity onset were almost concordant with VT activities arising at the gyral unit level (concordance rate, 66.7-100%). Median time lag between GMFT and VT at onset in each patient was 11.0-42.0 ms. On the temporal base, VT represented basal activities, whereas GMFT failed but instead represented propagated activities of the lateral temporal cortices. Activities limited to within the basal temporal or deep brain region were not reflected on GMFT. In conclusion, GMFT appears to accurately represent brain activities of the lateral cortices at the gyral unit level. The slight time lag between GMFT and VT is likely attributable to differences in the detection principles underlying MEG and iEEG. GMFT has great potential for investigating the spatiotemporal dynamics of lateral brain surface activities.
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Epilepsia Resistente a Medicamentos/fisiopatologia , Eletrocorticografia/métodos , Magnetoencefalografia/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Eletrocorticografia/normas , Feminino , Humanos , Magnetoencefalografia/normas , Masculino , Adulto JovemRESUMO
OBJECTIVE: Hypothalamic hamartoma (HH) is a congenital anomalous brain tumor. Although most HHs are found without any other systemic features, HH is observed in syndromic disorders such as Pallister-Hall syndrome (PHS) and oral-facial-digital syndrome (OFD). Here, we explore the possible involvement of somatic mutations in HH. METHODS: We analyzed paired blood and hamartoma samples from 18 individuals, including three with digital anomalies, by whole-exome sequencing. Detected somatic mutations were validated by Sanger sequencing and deep sequencing of target amplicons. The effect of GLI3 mutations on its transcriptional properties was evaluated by luciferase assays using reporters containing eight copies of the GLI-binding site and a mutated control sequence disrupting GLI binding. RESULTS: We found hamartoma-specific somatic truncation mutations in GLI3 and OFD1, known regulators of sonic hedgehog (Shh) signaling, in two and three individuals, respectively. Deep sequencing of amplicons covering the mutations showed mutant allele rates of 7-54%. Somatic mutations in OFD1 at Xp22 were found only in male individuals. Potential pathogenic somatic mutations in UBR5 and ZNF263 were also identified in each individual. Germline nonsense mutations in GLI3 and OFD1 were identified in each individual with PHS and OFD type I in our series, respectively. The truncated GLI3 showed stronger repressor activity than the wild-type protein. We did not detect somatic mutations in the remaining 9 individuals. INTERPRETATION: Our data indicate that a spectrum of human disorders can be caused by lesion-specific somatic mutations, and suggest that impaired Shh signaling is one of the pathomechanisms of HH.