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Haoxuan Lu, Jiaji Lin, Yongqin Xiong, Linlin Deng, Xiaoyu Wang, Dekang Zhang, Xiangbing Bian, Jiayou Zhou, Longsheng Pan, and Xin Lou

OBJECTIVE

Although magnetic resonance–guided focused ultrasound (MRgFUS) at the ventral intermediate (VIM) thalamic nucleus is a novel and effective treatment for medication-refractory essential tremor (ET), it is unclear how the ablation lesion affects functional activity. The current study sought to evaluate the functional impact of MRgFUS thalamotomy in patients with ET, as well as to investigate the relationship between neuronal activity changes and tremor control.

METHODS

This study included 30 patients with ET who underwent MRgFUS thalamotomy with a 6-month follow-up involving MRI and clinical tremor rating. Additional sex- and age-matched healthy people were recruited for the healthy control group. The fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity were used to identify functional alteration regions of interest (ROIs). To investigate changes after treatment, ROI- and seed-based functional connectivity (FC) analyses were performed.

RESULTS

Patients with ET had significantly increased fALFF in the right postcentral gyrus (PoCG; ROI 1), regional homogeneity in the left PoCG (ROI 2), and regional homogeneity in the right PoCG (ROI 3, cluster-level p value family-wise error [pFWE] < 0.05), which were recovered and normalized at 6 months after MRgFUS thalamotomy. FCs between ROI 2 and the right supramarginal gyrus, ROI 2 and the right superior parietal gyrus, and ROI 3 and the left precentral gyrus were also found to be increased after treatment (cluster-level pFWE < 0.05). Furthermore, changes in fALFF, regional homogeneity, and FC values were significantly correlated with tremor relief (p < 0.05). Preoperative FC strengths were found to be inversely related to the postoperative tremor control ratio (p < 0.05).

CONCLUSIONS

In patients with ET, the VIM lesion of MRgFUS thalamotomy resulted in symptom-related regional functional recovery associated with sensorimotor and attention networks. Preoperative FC strengths may reflect the postoperative tremor control ratio, implying that this metric could be a useful neuroimaging biomarker for predicting symptom relief in patients with ET following thalamotomy.

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Carlos Bennett, Matías González, Gisella Tapia, Rodrigo Riveros, Francisco Torres, Nicole Loyola, Alejandro Veloz, and Stéren Chabert

OBJECTIVE

Noninvasive brain mapping with functional MRI (fMRI) and mapping with direct electrical stimulation (DES) are important tools in glioma surgery, but the evidence is inconclusive regarding the sensitivity and specificity of fMRI. The Human Connectome Project (HCP) proposed a new cortical parcellation that has not been thoroughly tested in a clinical setting. The main goal of this study was to evaluate the correlation of fMRI and DES mapping with HCP areas in a clinical setting, and to evaluate the performance of fMRI mapping in motor and language tasks in patients with glioma, using DES as the gold standard.

METHODS

Forty patients with supratentorial gliomas were examined using preoperative fMRI and underwent awake craniotomy with DES. Functional activation maps were visualized on a 3D representation of the cortex, classified according to HCP areas, and compared with surgical mapping.

RESULTS

Functional MRI was successful in identifying language and motor HCP areas in most cases, including novel areas such as 55b and the superior longitudinal fasciculus (SLF). Functional MRI had a sensitivity and specificity of 100% and 71%, respectively, for motor function in HCP area 4. Sensitivity and specificity were different according to the area and fMRI protocol; i.e., semantic protocols performed better in Brodmann area (BA) 55b/peri-sylvian language areas with 100% sensitivity and 20% specificity, and word production protocols in BAs 44 and 45 with 70% sensitivity and 80% specificity. Some compensation patterns could be observed, such as motor activation of the postcentral gyrus in precentral gliomas.

CONCLUSIONS

HCP areas can be detected in clinical scenarios of glioma surgery. These areas appear relatively stable across patients, but compensation patterns seem to differ, allowing occasional resection of activating areas. Newly described areas such as 55b and SLF can act as critical areas in language networks. Surgical planning should account for these parcellations.

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Nathan K. Leclair, William Lambert, Kimberley Roche, Eileen Gillan, Joanna J. Gell, Ching C. Lau, Gregory Wrubel, Joshua Knopf, Shirali Amin, Megan Anderson, Jonathan E. Martin, Markus J. Bookland, and David S. Hersh

OBJECTIVE

Pediatric low-grade gliomas (pLGGs) frequently exhibit dysregulation of the mitogen-activated protein kinase (MAPK) pathway. Targeted therapies, including mutant BRAF inhibitors (dabrafenib) and MEK inhibitors (trametinib), have shown promise in patients in whom conventional chemotherapy has failed. However, few studies have investigated the use of targeted therapy as a first-line treatment for pLGG. Here, the authors reviewed their institutional experience with using a personalized medicine approach to patients with newly diagnosed pLGGs.

METHODS

All pediatric patients at the authors’ institution who had been treated with dabrafenib or trametinib for pLGG without first receiving conventional chemotherapy or radiation were retrospectively reviewed. Demographic, clinical, and radiological data were collected.

RESULTS

Eight patients underwent targeted therapy as a first-line treatment for pLGG. Five patients had a BRAF alteration (1 with a BRAF V600E mutation, 4 with a KIAA1549:BRAF fusion), and 3 patients had an NF1 mutation. One of the 8 patients was initially treated with dabrafenib, and trametinib was added later. Seven patients were initially treated with trametinib; of these, 2 later transitioned to dual therapy, whereas 5 continued with trametinib monotherapy. Six patients (75%) demonstrated a partial response to therapy during their treatment course, whereas stable disease was identified in the remaining 2 patients (25%). One patient experienced mild disease progression after completing a course of trametinib monotherapy, but ultimately stabilized after a period of close observation. Another patient experienced tumor progression while on dabrafenib, but subsequently responded to dual therapy with dabrafenib and trametinib. The most common adverse reactions to targeted therapy were cutaneous toxicity (100%) and diarrhea (50%).

CONCLUSIONS

Targeted therapies have the potential to become a standard treatment option for pLGG due to their favorable toxicity profile and oral route of administration. This case series provides preliminary evidence that targeted therapies can induce an early disease response as a first-line adjuvant treatment; however, large-scale studies are required to assess long-term durability and safety.

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Sehan Park, Jae Woo Park, Jin Hoon Park, Choon Sung Lee, Dong-Ho Lee, Chang Ju Hwang, Jae Jun Yang, and Jae Hwan Cho

OBJECTIVE

Metastatic epidural spinal cord compression (MESCC) causes neurological deficits that may hinder ambulation. Understanding the prognostic factors associated with increased neurological recovery and regaining ambulatory functions is important for surgical planning in MESCC patients with neurological deficits. The present study was conducted to elucidate prognostic factors of neurological recovery in MESCC patients.

METHODS

A total of 192 patients who had surgery for MESCC due to preoperative neurological deficits were reviewed. A motor recovery rate ≥ 50% and ambulatory function restoration were defined as the primary favorable endpoints. Factors associated with a motor recovery rate ≥ 50%, regaining ambulatory function, and patient survival were analyzed.

RESULTS

About one-half (48.4%) of the patients had a motor recovery rate ≥ 50%, and 24.4% of patients who were not able to walk due to MESCC before the surgery were able to walk after the operation. The factors “involvement of the thoracic spine” (p = 0.015) and “delayed operation” (p = 0.041) were associated with poor neurological recovery. Low preoperative muscle function grade was associated with a low likelihood of regaining ambulatory functions (p = 0.002). Furthermore, performing the operation ≥ 72 hours after the onset of the neurological deficit significantly decreased the likelihood of regaining ambulatory functions (p = 0.020). Postoperative ambulatory function significantly improved patient survival (p = 0.048).

CONCLUSIONS

Delayed operation and the involvement of the thoracic spine were poor prognostic factors for neurological recovery after MESCC surgery. Furthermore, a more severe preoperative neurological deficit was associated with a lesser likelihood of regaining ambulatory functions postoperatively. Earlier detection of motor weaknesses and expeditious surgical interventions are necessary, not only to improve patient functional status and quality of life but also to enhance survival.

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Howard Colman, Susan M. Chang, Michael Vogelbaum, and Priscilla Brastianos

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Shuaihua Song, Peng Qiu, Haoran Wang, Di Zhang, Qianjin Qi, and Li Feng

OBJECTIVE

In other specialties, malnutrition has been shown to be closely linked to postoperative complications. However, there is no research on the relationship between nutritional parameters and the complications of transsphenoidal pituitary surgery. This study was designed to identify the relationship between preoperative nutritional markers and postoperative complications in nonfunctioning pituitary adenomas.

METHODS

This observational study included 429 patients whose first transsphenoidal surgery was performed in Shandong Provincial Hospital between January 2015 and July 2020. Preoperative prealbumin, retinol-binding protein (RBP), the prognostic nutritional index, clinicopathological data, and postoperative complication data were collected to investigate outcomes.

RESULTS

After multivariable adjustment, preoperative prealbumin and RBP were inversely associated with risk of complication (p value for trend = 0.006, 0.021). The increase of preoperative serum prealbumin and RBP concentration may decrease the risk of postoperative intracranial infection and hyponatremia (both OR per SD increment, < 1; p < 0.05). The increase of preoperative prealbumin may also decrease the risk of diabetes insipidus (OR per SD increment, 0.591; p = 0.001), but similar results were not obtained for the RBP (p > 0.05). Prealbumin and RBP are both useful in predicting overall complications (area under the receiver operating characteristic curve [AUC] 0.749, 0.678), especially in intracranial infection (AUC 0.794, 0.738). However, the predictive value of prealbumin was better than that of RBP.

CONCLUSIONS

Low preoperative prealbumin or RBP concentrations may be associated with higher surgical risk, especially for intracranial infection. This study emphasizes the suggestion that preoperative prealbumin and RBP concentrations may be vital factors in predicting operative complications of nonfunctioning pituitary adenomas.

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Sandro M. Krieg, Denise Bernhard, Sebastian Ille, Bernhard Meyer, Stephanie Combs, Alexander Rotenberg, and Michael C. Frühwald

OBJECTIVE

In adult patients, an increasing group of neurosurgeons specialize entirely in the treatment of highly eloquent tumors, particularly gliomas. In contrast, extensive perioperative neurophysiological workup for pediatric cases has been limited essentially to epilepsy surgery.

METHODS

The authors discuss radio-oncological and general oncological considerations based on the current literature and their personal experience.

RESULTS

While several functional mapping modalities facilitate preoperative identification of cortically and subcortically located eloquent areas, not all are suited for children. Direct cortical intraoperative stimulation is impractical in many young patients due to the reduced excitability of the immature cortex. Behavioral requirements also limit the utility of functional MRI and magnetoencephalography in children. In contrast, MRI-derived tractography and navigated transcranial magnetic stimulation are available across ages. Herein, the authors review the oncological rationale of function-guided resection in pediatric gliomas including technical implications such as personalized perioperative neurophysiology, surgical strategies, and limitations.

CONCLUSIONS

Taken together, these techniques, despite the limitations of some, facilitate the identification of eloquent areas prior to tumor surgery and radiotherapy as well as during follow-up of residual tumors.

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Zhijie Pei, Yi Fang, Shuwen Mu, Jun Li, Tianshun Feng, Kunzhe Lin, and Shousen Wang

OBJECTIVE

Perioperative adenohypophyseal hormone assessment can improve therapeutic strategies and be used to evaluate the prognosis of pituitary adenomas. An individual hormone level does not entirely reflect the pituitary gland. Thus, this study aimed to analyze perioperative hormonal changes and propose a normalized method to facilitate overall assessment of the adenohypophysis.

METHODS

The authors retrospectively analyzed 89 male patients with nonfunctioning pituitary adenoma (NFPA) who underwent transsphenoidal surgery. Preoperative clinical data, imaging data, and perioperative hormone levels of the anterior pituitary gland were evaluated. Hormone values were rescaled using minimum-maximum normalization. The sum of the normalized hormone levels was defined as the total hormonal rate (THR).

RESULTS

Preoperative findings indicated correlations among different adenohypophyseal hormones. Luteinizing hormone (p = 0.62) and adrenocorticotropic hormone (p = 0.89) showed no significant changes after surgery, but growth hormone levels increased (p < 0.001). On the contrary, the levels of thyroid-stimulating hormone (p < 0.001), follicle-stimulating hormone (p = 0.02), and prolactin (p < 0.001) decreased. THR indicated a significant postoperative reduction in adenohypophyseal function (p = 0.04). Patients with postoperative hypopituitarism had significantly lower THR than those without (p = 0.003), with an area under the curve of 0.66. For NFPAs that presented with normal preoperative hormone levels, THR was a good clinical predictor of immediate postoperative hypopituitarism, with an area under the curve of 0.74.

CONCLUSIONS

The normalized synthesis index of hormones is a novel and clinically valuable method used to reflect adenohypophyseal secretion. Compared with individual hormones, these results indicated that THR can facilitate the analysis of general hormone levels despite various fluctuations in adenohypophyseal hormones. THR may also contribute to the effective prediction of short-term surgery-induced hypopituitarism.

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Giovanni Raffa, Giuseppina Marzano, Antonello Curcio, Shervin Espahbodinea, Antonino Germanò, and Filippo Flavio Angileri

OBJECTIVE

Awake surgery represents the gold standard for resection of brain tumors close to the language network. However, in some cases patients may be considered not eligible for awake craniotomy. In these cases, a personalized brain mapping of the language network may be achieved by navigated transcranial magnetic stimulation (nTMS), which can guide resection in patients under general anesthesia. Here the authors describe their tailored nTMS-based strategy and analyze its impact on the extent of tumor resection (EOR) and language outcome in a series of patients not eligible for awake surgery.

METHODS

The authors reviewed data from all patients harboring a brain tumor in or close to the language network who were considered not eligible for awake surgery and were operated on during asleep surgery between January 2017 and July 2022, under the intraoperative guidance of nTMS data. The authors analyzed the effectiveness of nTMS-based mapping data in relation to 1) the ability of the nTMS-based mapping to stratify patients according to surgical risks, 2) the occurrence of postoperative language deficits, and 3) the EOR.

RESULTS

A total of 176 patients underwent preoperative nTMS cortical language mapping and nTMS-based tractography of language fascicles. According to the nTMS-based mapping, tumors in 115 patients (65.3%) were identified as true-eloquent tumors because of a close spatial relationship with the language network. Conversely, tumors in 61 patients (34.7%) for which the nTMS mapping disclosed a location at a safer distance from the network were identified as false-eloquent tumors. At 3 months postsurgery, a permanent language deficit was present in 13 patients (7.3%). In particular, a permanent deficit was observed in 12 of 115 patients (10.4%) with true-eloquent tumors and in 1 of 61 patients (1.6%) with false-eloquent lesions. With nTMS-based mapping, neurosurgeons were able to distinguish true-eloquent from false-eloquent tumors in a significant number of cases based on the occurrence of deficits at discharge (p < 0.0008) and after 3 months from surgery (OR 6.99, p = 0.03). Gross-total resection was achieved in 80.1% of patients overall and in 69.5% of patients with true-eloquent lesions and 100% of patients with false-eloquent tumors.

CONCLUSIONS

nTMS-based mapping allows for reliable preoperative mapping of the language network that may be used to stratify patients according to surgical risks. nTMS-guided asleep surgery should be considered a good alternative for personalized preoperative brain mapping of the language network that may increase the possibility of safe and effective resection of brain tumors in the dominant hemisphere whenever awake mapping is not feasible.