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OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy ameliorates symptoms in patients with essential tremor (ET). How this treatment affects canonical brain networks has not been elucidated. The purpose of this study was to clarify changes of brain networks after MRgFUS thalamotomy in ET patients by analyzing resting-state networks (RSNs). METHODS: Fifteen patients with ET were included in this study. Left MRgFUS thalamotomy was performed in all cases, and MR images, including resting-state functional MRI (rsfMRI), were taken before and after surgery. MR images of 15 age- and sex-matched healthy controls (HCs) were also used for analysis. Using rsfMRI data, canonical RSNs were extracted by performing dual regression analysis, and the functional connectivity (FC) within respective networks was compared among pre-MRgFUS patients, post-MRgFUS patients, and HCs. The severity of tremor was evaluated using the Clinical Rating Scale for Tremor (CRST) score pre- and postoperatively, and its correlation with RSNs was examined. RESULTS: Preoperatively, ET patients showed a significant decrease in FC in the sensorimotor network (SMN), primary visual network (VN), and visuospatial network (VSN) compared with HCs. The decrease in FC in the SMN correlated with the severity of tremor. After MRgFUS thalamotomy, ET patients still exhibited a significant decrease in FC in a small area of the SMN, but they exhibited an increase in the cerebellar network (CN). In comparison between pre- and post-MRgFUS patients, the FC in the SMN and the VSN significantly increased after treatment. Quantitative evaluation of the FCs in these three groups showed that the SMN and VSN increased postoperatively and demonstrated a trend toward those of HCs. CONCLUSIONS: The SMN and CN, which are considered to be associated with the cerebello-thalamo-cortical loop, exhibited increased connectivity after MRgFUS thalamotomy. In addition, the FC of the visual network, which declined in ET patients compared with HCs, tended to normalize postoperatively. This could be related to the hypothesis that visual feedback is involved in tremor severity in ET patients. Overall, the analysis of the RSNs by rsfMRI reflected the pathophysiology with the intervention of MRgFUS thalamotomy in ET patients and demonstrated a possibility of a biomarker for successful treatment.
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Tremor Essencial , Humanos , Tremor Essencial/diagnóstico por imagem , Tremor Essencial/cirurgia , Tremor , Tálamo/diagnóstico por imagem , Tálamo/cirurgia , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância MagnéticaRESUMO
OBJECTIVE: The efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) ablation for essential tremor (ET) is well known; however, no prognostic factors have been established. The authors aimed to retrospectively investigate MRgFUS ablation outcomes and associated factors and to define the cutoff values for each prognostic factor. METHODS: Sixty-four Japanese patients who underwent unilateral ventral intermediate nucleus thalamotomy with MRgFUS for ET were included. Follow-up evaluations were performed at 1 week and 1, 3, 6, 12, and 24 months postoperatively. Tremor suppression was evaluated using the Clinical Rating Scale for Tremor (CRST), and adverse effects were recorded postoperatively. Outcome-associated factors were examined preoperatively, intraoperatively, and postoperatively using multivariate analyses. The cutoff values for the prognostic factors were calculated using receiver operating characteristics. RESULTS: Percentage improvements in the CRST scores of the affected upper limb were 82.4%, 72.2%, 68.6%, and 65.9% at 1, 3, 6, and 12 months, respectively. Preoperatively, a high skull density ratio (SDR) (p ≤ 0.047), low CRST part B score (used to assess tremors during several tasks) (cutoff value 25, p ≤ 0.041), and nonoccurrence of resting tremors (p = 0.027) were significantly associated with improved tremor control. An intraoperatively high maximum mean temperature (cutoff value 52.5°C, p ≤ 0.047), postoperatively large lesion (cutoff value 3.9 mm in the anterior-posterior direction, p ≤ 0.002; cutoff value 5.0-5.55 mm in the superior-inferior direction, p ≤ 0.026), and small transducer focus correction (p ≤ 0.015) were also associated with improved tremor control. No valid cutoff value was found for SDR. Adverse effects (limb weakness, sensory disturbance, ataxia/walking disturbance, dysgeusia, dysarthria, and facial swelling) occurred transiently and were associated with high SDR, high temperature, high number of sonication sessions, large lesion, and occurrence of resting tremor. Patients who developed leg weakness experienced greater percentage improvement in tremors at 3 months postoperatively than those who did not. CONCLUSIONS: MRgFUS ablation could be used to achieve good tremor control with acceptable adverse effects in Japanese patients with ET. The relatively low SDR in Asian ethnic groups as compared with that of Western populations makes treatment difficult; however, the cutoff values obtained in this study may be useful for achieving good treatment outcomes even in such patients. Clinical trial registration no.: UMIN000026952 (University Hospital Medical Information Network). ABBREVIATIONS: ACPC = anterior commissure-posterior commissure; AP = anterior to posterior; CRST = Clinical Rating Scale for Tremor; ET = essential tremor; MRgFUS = magnetic resonance-guided focused ultrasound; PC = posterior commissure; PSA = posterior subthalamic area; RL = right to left; ROC = receiver operating characteristic; SDR = skull density ratio; SI = superior to inferior; T2WI = T2-weighted imaging; VIM = ventral intermediate nucleus.
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Resting-state functional MRI (rs-fMRI) has been utilized to visualize large-scale brain networks. We evaluated the usefulness of multitier network analysis using rs-fMRI in patients with focal epilepsy. Structural and rs-fMRI data were retrospectively evaluated in 20 cases with medically refractory focal epilepsy, who subsequently underwent surgery. First, structural changes were examined using voxel-based morphometry analysis. Second, alterations in large-scale networks were evaluated using dual-regression analysis. Third, changes in cortical hubs were analyzed and the relationship between aberrant hubs and the epileptogenic zone (EZ) was evaluated. Finally, the relationship between the hubs and the default mode network (DMN) was examined using spectral dynamic causal modeling (spDCM). Dual-regression analysis revealed significant decrease in functional connectivity in several networks including DMN in patients, although no structural difference was seen between groups. Aberrant cortical hubs were observed in and around the EZ (EZ hubs) in 85% of the patients, and a strong degree of EZ hubs correlated to good seizure outcomes postoperatively. In spDCM analysis, facilitation was often seen from the EZ hub to the contralateral side, while inhibition was seen from the EZ hub to nodes of the DMN. Some cognition-related networks were impaired in patients with focal epilepsy. The EZ hub appeared in the vicinity of EZ facilitating connections to distant regions in the early phase, which may eventually generate secondary focus, while inhibiting connections to the DMN, which may cause cognitive deterioration. Our results demonstrate pathological network alterations in epilepsy and suggest that earlier surgical intervention may be more effective.
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Epilepsia Resistente a Medicamentos , Epilepsia , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Mapeamento Encefálico , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Humanos , Imageamento por Ressonância Magnética , Estudos RetrospectivosRESUMO
Magnetic resonance (MR)-guided focused ultrasound surgery (MRgFUS) is the latest minimally invasive stereotactic procedure, and thalamotomy using this novel modality has demonstrated its effectiveness and safety, especially for patients with essential tremor (ET) and Parkinson's disease (PD). In Japan, the application of MRgFUS to treat ET and PD has recently been covered by health insurance. Technically, the transducer with 1024 elements emits ultrasound beams, which are then focused on the target with a phase control, resulting in optimal ablation by thermal coagulation. The technical advantages of MRgFUS are continuous intraoperative monitoring of clinical symptoms and MR images and fine adjustment of the target by the steering function. Postoperative tremor control is compatible with other modalities, although long-term follow-up is necessary. The adverse effects are usually transient and acceptable. Prognostic factors for good tremor control include high temperature and large lesion size. A high skull density ratio is a factor to achieve high temperature and large lesioning, but it may not be necessary and sufficient for clinical outcomes. For patients with advanced symptoms such as bilateral tremor or head/neck tremor, deep brain stimulation may be recommended because of the adjustability of stimulation and the possibility of bilateral treatment. Patients have high expectations of MRgFUS because of its non-invasiveness. To perform this treatment safely and effectively, physicians need to understand the technological aspects, the physiological principles. To choose the appropriate modality, physicians also should recognize the clinical advantages and disadvantages of MRgFUS compared to other modalities.
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Tremor Essencial , Tremor , Tremor Essencial/diagnóstico por imagem , Tremor Essencial/cirurgia , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Tálamo/diagnóstico por imagem , Tálamo/cirurgia , Resultado do Tratamento , Tremor/terapiaRESUMO
Magnetic resonance(MR)-guided focused ultrasound ablation(FUS)is a minimally invasive technique for targeted tissue thermo-ablation and is promising for neuromodulation in various neurological disorders. The effectiveness and safety of this technique have been recognized worldwide. In Japan, the applications of FUS for the treatment of essential tremors and Parkinson's disease have recently been covered under health insurance. The FUS system is composed of a phased-array transducer with 1024 elements, with a beam of ultrasound emerging from each element. The phase and amplitude of the beam are computed and controlled to focus on the target with the calculation of computed tomography(CT)profiles, resulting in optimal thermo-ablation. To utilize FUS safely and effectively, a deep understanding of the physics of this technology is necessary. Furthermore, the technique should be compared with other options including deep brain stimulation(DBS)and radiofrequency thermo-ablation. Although FUS has received attention because of minimally invasive characteristics and a possibility of procedural target refinement, DBS has some advantages on bilateral implantation, a potential of postoperative adjustment, and control of head/leg tremors. In this article, we first reviewed the physics of FUS and demonstrated the typical treatment protocols. Second, we reviewed the outcomes from the existing literature, and revealed the advantages and disadvantages of this procedure, with the evaluation of the optimal condition for FUS.
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Ablação por Ultrassom Focalizado de Alta Intensidade , Doença de Parkinson , Humanos , Japão , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância MagnéticaRESUMO
Deep-seated epileptic focus estimation using magnetoencephalography is challenging because of its low signal-to-noise ratio and the ambiguity of current sources estimated by interictal epileptiform discharge (IED). We developed a distributed source (DS) analysis method using a volume head model as the source space of the forward model and standardized low-resolution brain electromagnetic tomography combined with statistical methods (permutation tests between IEDs and baselines and false discovery rate between voxels to reduce variation). We aimed to evaluate the efficacy of the combined DS (cDS) analysis in surgical cases. In total, 19 surgical cases with adult and pediatric focal epilepsy were evaluated. Both cDS and equivalent current dipole (ECD) analyses were performed in all cases. The concordance rates of the two methods with surgically identified epileptic foci were calculated and compared with surgical outcomes. Concordance rates from the cDS analysis were significantly higher than those from the ECD analysis (68.4% vs. 26.3%), especially in cases with deep-seated lesions, such as in the interhemispheric, fronto-temporal base, and mesial temporal structures (81.8% vs. 9.1%). Furthermore, the concordance rate correlated well with surgical outcomes. In conclusion, cDS analysis has better diagnostic performance in focal epilepsy, especially with deep-seated epileptic focus, and potentially leads to good surgical outcomes.
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Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsias Parciais/diagnóstico por imagem , Cabeça , Magnetoencefalografia/métodos , Neuroimagem/métodos , Imagens de Fantasmas , Cuidados Pré-Operatórios/métodos , Adolescente , Adulto , Criança , Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia , Epilepsias Parciais/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Speech disorders are among the most common adverse effects after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients. However, longitudinal speech changes after STN-DBS are not fully understood. OBJECTIVE: We performed a two-year prospective study on PD patients who underwent STN-DBS and analyzed changes in speech function to clarify factors predicting for speech deterioration. METHODS: Twenty-five PD patients were assessed before and up to two years after STN implantation. Speech function was evaluated in the on-stimulation condition and 30âmin after stimulation cessation using auditory-perceptual assessment. Patients who experienced overall worsening in speech intelligibility or naturalness ≥1 point during follow-up were classified into a deteriorated group (nâ=â16), with the remaining subjects being classified into a stable group (nâ=â9). Cognitive and motor functions were also assessed. RESULTS: The stable group had significantly better values of low volume, monoloudness, and asthenic voice subscores of the auditory-perceptual assessment in the on-stimulation condition compared with the off-stimulation condition. Imprecise consonants, excess loudness variation, and strained voice subscores were improved via cessation of stimulation in both groups. Before surgery, the deteriorated group had significantly lower scores in the Stroop Color-Word Test and Digit Span compared to the stable group. CONCLUSIONS: During follow-up, some subscores showed significant worsening in the on-stimulation condition in both groups. However, beneficial effects of STN-DBS on speech appeared to counterbalance negative effects of STN-DBS on speech function only in the stable group. Worse cognitive function may be a potential predictor for speech deterioration after STN-DBS in PD patients.
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Percepção Auditiva , Disfunção Cognitiva/fisiopatologia , Estimulação Encefálica Profunda/efeitos adversos , Neuroestimuladores Implantáveis/efeitos adversos , Doença de Parkinson/terapia , Distúrbios da Fala/etiologia , Distúrbios da Fala/fisiopatologia , Inteligibilidade da Fala , Núcleo Subtalâmico , Idoso , Percepção Auditiva/fisiologia , Disfunção Cognitiva/etiologia , Disartria/etiologia , Disartria/fisiopatologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Estudos Prospectivos , Inteligibilidade da Fala/fisiologia , Núcleo Subtalâmico/cirurgiaRESUMO
â¢A drug-resistant epilepsy case showed hypermotor seizures and amygdala enlargement.â¢Seizure onset zone was the hippocampus, not amygdala, as revealed by SEEG.â¢The enlarged amygdala pathology was classified as FCD type I.â¢Selective amygdalohippocampectomy led to good outcomes.
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Introduction Preliminary results of stereotactic radiotherapy (SRT) for spinal arteriovenous malformation (AVM) in five cases are presented. Methods Two cases were male and three were female. Their median age was 32 years (range: 23 to 54 years). The spinal intramedullary AVMs were located in the cervical spine in three and in the thoracic spine in two. SRT with 20 Gy in four fractions was delivered to the nidus in every case. Results At the end of the median follow-up period of 5.5 years (range: 3 to 8.5 years), the neurological symptoms and signs were improved or unchanged as compared with before treatment, although a temporary adverse effect developed between a half year and one year after SRT in one case. The nidi were obliterated five and a half years after SRT in one case and three years after SRT in one. In the other three cases, the nidi were unchanged. Conclusion SRT with 20 Gy in four fractions was thought to be a safe treatment, though this study dealt with only a small number of patients with a short-term follow-up period.
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Epilepsy surgery aims to control epilepsy by resecting the epileptogenic region while preserving function. In some patients with epileptogenic foci in and around functionally eloquent areas, awake surgery is implemented. We analyzed the surgical outcomes of such patients and discuss the clinical application of awake surgery for epilepsy. We examined five consecutive patients, in whom we performed lesionectomy for epilepsy with awake craniotomy, with postoperative follow-up > 2 years. All patients showed clear lesions on magnetic resonance imaging (MRI) in the right frontal (n = 1), left temporal (n = 1), and left parietal lobe (n = 3). Intraoperatively, under awake conditions, sensorimotor mapping was performed; primary motor and/or sensory areas were successfully identified in four cases, but not in one case of temporal craniotomy. Language mapping was performed in four cases, and language areas were identified in three cases. In one case with a left parietal arteriovenous malformation (AVM) scar, language centers were not identified, probably because of a functional shift. Electrocorticograms (ECoGs) were recorded in all cases, before and after resection. ECoG information changed surgical strategy during surgery in two of five cases. Postoperatively, no patient demonstrated neurological deterioration. Seizure disappeared in four of five cases (Engel class 1), but recurred after 2 years in the remaining patient due to tumor recurrence. Thus, for patients with epileptogenic foci in and around functionally eloquent areas, awake surgery allows maximal resection of the foci; intraoperative ECoG evaluation and functional mapping allow functional preservation. This leads to improved seizure control and functional outcomes.
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Epilepsia/cirurgia , Vigília , Adulto , Mapeamento Encefálico , Estudos de Coortes , Eletrocorticografia , Epilepsia/etiologia , Epilepsia/fisiopatologia , Feminino , Humanos , Masculino , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Pancreatic cysts are related to the presence of ductal adenocarcinomas elsewhere in the pancreas, and are also associated with an increased risk of pancreatic adenocarcinoma in the future. Most of the previous studies that investigated the prevalence of pancreatic cysts focused on patients within a hospital or out-patient setting, which may not be representative of the general population. We investigated the prevalence and predictive factors for the presence of pancreatic cysts within a large number of subjects via general health examination. METHODS: Between December 2007 and December 2013, a total of 5198 subjects were enrolled that underwent ultrasonography (US) on general health examination. We established a scoring system for predicting the presence of one or more pancreatic cysts using a split-sample method. RESULTS: Among the enrolled subjects, the prevalence of a pancreatic cyst was 3.5 %. In multivariate analysis, the prevalence was significantly increased with older age, female sex, and the presence of gall bladder adenomyomatosis (GB-ADM). Based on multivariate analysis in the training sample (n = 2,599), we established the scoring system consisting of age, sex, and the presence of GB-ADM to predict the presence of pancreatic cysts. This scoring system was validated in the testing sample (n = 2,599) and produced an area under the curve of 0.711. CONCLUSIONS: The prevalence of pancreatic cyst detected by US was 3.5 % in the general population, and increased with age, female sex, and the presence of GB-ADM. A new scoring system developed in the present study may help to identify better candidates for further examination when the pancreas is not visible by US.
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Cisto Pancreático/diagnóstico por imagem , Adulto , Fatores Etários , Idoso , Feminino , Doenças da Vesícula Biliar/epidemiologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Cisto Pancreático/epidemiologia , Cisto Pancreático/patologia , Prevalência , Curva ROC , Medição de Risco/métodos , Fatores de Risco , Fatores Sexuais , UltrassonografiaRESUMO
Porcine neuromedin U-8 (X-Asn-NH(2), X=H-Tyr-Phe-Leu-Phe-Arg-Pro-Arg) is occasionally unstable in the biological fluids used for bioassay as well as in the acidic solutions used for purification of synthetic peptides. In this study, HPLC examination of an incubate solution of X-Asn-NH(2) revealed that the main decomposition products in Tyrode's solution (pH 7.4) were either alpha- or beta-monocarboxylic acid analogs (X-Asn-OH or X-Asp-NH(2)), and that no dicarboxylic acid analog (X-Asp-OH) was produced. Further investigation, employing a model peptide (Y-Asn-NH(2), Y=Benzoyl-Pro-Arg) incubated in a 0.1 M sodium bicarbonate solution at 60 degrees C, revealed that the decomposition of C-terminal Asn-NH(2) occurred through the formation of an aminosuccinimide intermediate (Y-Asu), at a rate faster than that of Y-Asn-Ser peptide but slower than that of Y-Asn-Gly peptide. Mild acid hydrolysis of X-Asn-NH(2) examined in a 1 M HCl solution at 60 degrees C yielded X-Asn-OH and X-Asp-NH(2), which further decomposed to yield X-Asp-OH. The C-terminal degradation of X-Asn-NH(2) resulted in reduced biological and immunochemical binding activities.
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Asparagina/química , Neuropeptídeos/química , Ácidos , Álcalis , Sequência de Aminoácidos , Animais , Galinhas , Cromatografia Líquida de Alta Pressão , Meia-Vida , Imuno-Histoquímica , Técnicas In Vitro , Dados de Sequência Molecular , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Peptídeos/síntese química , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Espectrofotometria Ultravioleta , Relação Estrutura-Atividade , Succinimidas/química , SuínosRESUMO
The stomatitis accompanying chemotherapy reduces a patient's QOL. Many reports have suggested that some kinds of gargling agents for oral mucositis shorten the duration and severity of symptoms. This study tested the prevention and efficacy against stomatitis of a herbal medicine (Syousaikotou) as a gargling agent for patients receiving chemotherapy. Compared to gargling with providone-iodine and amphotericin B, the Syousaikotou gargle showed a significantly decreased incidence of stomatitis, and a painkilling effect. Stomatitis occurred in about 17.4% among 23 chemotherapy cycles with the Syousaikotou gargle, against about 40.8% among 71 chemotherapy cycles without the Syousaikotou gargle. Among the patients suffering stomatitis pain after 22 chemotherapy cycles, the painkilling effect was seen to be 76.2%, and continues for about 2 hours. Critical side effects were not seen, but in 4 cases there were complaints about foul smells, such as oil and grass smells. Syousaikotou gargle was considered to be one of the useful methods against the stomatitis prevention and sharp pain mitigation from the chemotherapy.