Geert-Jan Rutten

Language area localization with three-dimensional functional magnetic resonance imaging matches intrasulcal electrostimulation in Broca's area

In this study, intraoperative electrocortical stimulation mapping (ioESM), the current gold standard for the localization of critical language areas, is compared with functional magnetic resonance imaging (fMRI) in a 14‐year‐old girl with medically intractable epilepsy caused by a tumor in the region of Brocas area. Prior to the operation, four different fMRI tasks that target inferior frontal language areas were applied. Prior to the resection, ioESM as well as fMRI detected no language areas at the exposed cortical area. After removal of the tumor, a unique opportunity presented itself, where ioESM could be performed in the depth of a now exposed and intact gyrus. One specific locus that was indicated to be a critical language area by multiple‐task fMRI was targeted. IoESM selectively confirmed the location of this language area to within an estimated 3 mm. We propose that the combined use of different fMRI tasks increases the sensitivity and specificity for the detection of essential language areas.

The role of functional magnetic resonance imaging in brain surgery.

New functional neuroimaging techniques are changing our understanding of the human brain, and there is now convincing evidence to move away from the classic and clinical static concepts of functional topography. In a modern neurocognitive view, functions are thought to be represented in dynamic large-scale networks. The authors review the current (limited) role of functional MR imaging in brain surgery and the possibilities of new functional MR imaging techniques for research and neurosurgical practice. A critique of current clinical gold standard techniques (electrocortical stimulation and the Wada test) is given.

Activation of striate cortex in the absence of visual stimulation: An fMRI study of synesthesia.

It has been suggested that internally generated visual perception involves the primary visual cortex V1. To test this hypothesis, a functional MRI study was conducted with a female subject with orthographic color–word synesthesia. This subject was selected as she reported clear involuntary visualization of auditorily presented verbal material. Hearing a word resulted in seeing the word in a particular color. fMRI scans were acquired while the subject performed two verbal tasks (passive listening to words and verbal fluency). Significant activity was detected in primary visual cortex, in the absence of external visual stimulation. This finding provides evidence for a role of modulatory feedback connections between associative and primary visual areas in visual experience without direct visual stimulation.

Task and task‐free FMRI reproducibility comparison for motor network identification

Test‐retest reliability of individual functional magnetic resonance imaging (fMRI) results is of importance in clinical practice and longitudinal experiments. While several studies have investigated reliability of task‐induced motor network activation, less is known about the reliability of the task‐free motor network. Here, we investigate the reproducibility of task‐free fMRI, and compare it to motor task activity. Sixteen healthy subjects participated in this study with a test‐retest interval of seven weeks. The task‐free motor network was assessed with a univariate, seed‐voxel‐based correlation analysis. Reproducibility was tested by means of intraclass correlation (ICC) values and ratio of overlap. Higher ICC values and a better overlap were found for task fMRI as compared to task‐free fMRI. Furthermore, ratio of overlap improved for task fMRI at higher thresholds, while it decreased for task‐free fMRI, suggesting a less focal spatial pattern of the motor network during resting state. However, for both techniques the most active voxels were located in the primary motor cortex. This indicates that, just like task fMRI, task‐free fMRI can properly identify critical brain areas for motor task performance. Although both fMRI techniques are able to detect the motor network, resting‐state fMRI is less reliable than task fMRI. Hum Brain Mapp 35:340–352, 2014.

The impact of surgery in molecularly defined low-grade glioma: an integrated clinical, radiological, and molecular analysis

Background Extensive resections in low-grade glioma (LGG) are associated with improved overall survival (OS). However, World Health Organization (WHO) classification of gliomas has been completely revised and is now predominantly based on molecular criteria. This requires reevaluation of the impact of surgery in molecularly defined LGG subtypes. Methods We included 228 adults who underwent surgery since 2003 for a supratentorial LGG. Pre- and postoperative tumor volumes were assessed with semiautomatic software on T2-weighted images. Targeted next-generation sequencing was used to classify samples according to current WHO classification. Impact of postoperative volume on OS, corrected for molecular profile, was assessed using a Cox proportional hazards model. Results Median follow-up was 5.79 years. In 39 (17.1%) histopathologically classified gliomas, the subtype was revised after molecular analysis. Complete resection was achieved in 35 patients (15.4%), and in 54 patients (23.7%) only small residue (0.1-5.0 cm3) remained. In multivariable analysis, postoperative volume was associated with OS, with a hazard ratio of 1.01 (95% CI: 1.002-1.02; P = 0.016) per cm3 increase in volume. The impact of postoperative volume was particularly strong in isocitrate dehydrogenase (IDH) mutated astrocytoma patients, where even very small postoperative volumes (0.1-5.0 cm) already negatively affected OS. Conclusion Our data provide the necessary reevaluation of the impact of surgery in molecularly defined LGG and support maximal resection as first-line treatment for molecularly defined LGG. Importantly, in IDH mutated astrocytoma, even small postoperative volumes have negative impact on OS, which argues for a second-look operation in this subtype to remove minor residues if safely possible.

Effects of Insula Resection on Autonomic Nervous System Activity.

Background: The insula is an essential component of the central autonomic network and plays a critical role in autonomic regulation in response to environmental stressors. The role of the insula in human autonomic regulation has been primarily investigated following cerebrovascular accidents, but interpretation of these findings is complicated by lack of control over time-related processes preceding and following cerebrovascular accidents. Surgical resection of tumors in the insula provides unique information about the neural circuits of autonomic dysregulation and subsequent cardiac arrhythmias. Methods: This study examined autonomic modulation in 2 unique cases during tumor resection of the right and left insula, respectively (WHO grade II low-grade astrocytoma). The patients were monitored for changes in heart rate variability and cardiac arrhythmias before and during tumor resection. Results: Right insular tumor resection was accompanied by significantly increased parasympathetic activity followed by bradyarrhythmias. Removal of the left insula did not change autonomic indices. Conclusions: These findings suggest that the right insula plays a critical role in parasympathetic autonomic modulation and subsequent cardiac arrhythmias. Additional research is needed to establish the long-term effects of right versus left insula resection as related to autonomic dysregulation and adverse brain-heart interactions, particularly in patients at risk of cardiac arrhythmias.

Cognitive functioning in meningioma patients: a systematic review.

This systematic review evaluates relevant findings and methodologic aspects of studies on cognitive functioning in meningioma patients prior to and/or following surgery with or without adjuvant radiotherapy. PubMed and Web of Science electronic databases were searched until December 2015. From 1012 initially identified articles, 11 met the inclusion criteria for this review. Multiple methodological limitations were identified which include the lack of pre-treatment assessments, variations in the number and types of neuropsychological tests used, the normative data used to identify patients with cognitive deficits, and the variety of definitions for cognitive impairment. Study results suggest that most of meningioma patients are faced with cognitive deficits in several cognitive domains prior to surgery. Following surgery, most of these patients seem to improve in cognitive functioning. However, they still have impairments in a wide range of cognitive functions compared to healthy controls. Suggestions are given for future research. Adequate diagnosis and treatment of cognitive deficits may ultimately lead to improved outcome and quality of life in meningioma patients.

Does early resection of presumed low-grade glioma improve survival? A clinical perspective

Early resection is standard of care for presumed low-grade gliomas. This is based on studies including only tumors that were post-surgically confirmed as low-grade glioma. Unfortunately this does not represent the clinicians’ situation wherein he/she has to deal with a lesion on MRI that is suspect for low-grade glioma (i.e. without prior knowledge on the histological diagnosis). We therefore aimed to determine the optimal initial strategy for patients with a lesion suspect for low-grade glioma, but not histologically proven yet. We retrospectively identified 150 patients with a resectable presumed low-grade-glioma and who were otherwise in good clinical condition. In this cohort we compared overall survival between three types of initital treatment strategy: a wait-and-scan approach (n = 38), early resection (n = 83), or biopsy for histopathological verification (n = 29). In multivariate analysis, no difference was observed in overall survival for early resection compared to wait-and-scan: hazard ratio of 0.92 (95% CI 0.43–2.01; p = 0.85). However, biopsy strategy showed a shorter overall survival compared to wait-and-scan: hazard ratio of 2.69 (95% CI 1.19–6.06; p = 0.02). In this cohort we failed to confirm superiority of early resection over a wait-and-scan approach in terms of overall survival, though longer follow-up is required for final conclusion. Biopsy was associated with shorter overall survival.

Cognitive deficits in patients with trigeminal neuralgia: opportunities to improve care and quality of life

Cognitive impairments can often be found in patients with chronic pain disorders, in particular when attentional capacity, processing speed, or psychomotor speed are measured [1–3]. These impairments have been shown to affect therapy adherence, personal relationships, daily functioning, capacity for work, leisure activities, mood, and quality of life [4, 5]. Surprisingly, no prior studies have investigated cognitive functioning in patients with trigeminal neuralgia (TN). In particular, the subset of patients that are candidates for microvascular decompression (MVD) seem at high risk for cognitive impairments, because of severe, long-standing and medically intractable pain. In this study we examined whether patients with TN that were candidates for MVD showed cognitive deficits. Cognitive functionwas assessed in 32 patients 1 day prior to surgery, and compared with two control groups of healthy subjects: a normative American control group (n=1,069), and a Dutch control group (n=20). Subjects were administered a computerized neurocognitive test battery (i.e., CNS Vital Sign, www. cnsvs.com) [6]. This battery takes half an hour to administer, examines a wide range of cognitive functions, and generates automatic scores and an immediate report that provides insight into possible cognitive deficits. Patients with TN scored significantly below healthy controls from the normative sample on composite memory, psychomotor speed, reaction time, complex attention, cognitive flexibility, and general cognitive functioning. Comparisons between patients and a control group of Dutch subjects revealed a similar pattern, with the exception of reaction time where no impairment was found. These results resemble those of patients with chronic pain conditions [1–3]. In line with recent studies in the literature, we estimated the proportion of patients with clinically relevant cognitive impairment by using a z-score of 11⁄2 or more SDs below the normative mean (by CNS Vital Signs) [7]. When this was taken as criterion, 35 % of patients had deficits on psychomotor speed, 32 % on reaction time, 25 % on complex attention and cognitive flexibility, 19 % on composite memory, and 13 % on general cognitive functioning. This study is obviously confounded by the fact that the majority of TN patients were on anti-convulsant medication or opioids. It is well known that these drugs can interfere with cognitive functions. We are therefore unable to answer the question of what the precise cause or causes of cognitive impairments in TN patients is or are. Clearly, follow-up research is needed to study the possible contribution of drug side effects and mood (e.g., depression and anxiety). Despite these methodological drawbacks, we can conclude that TN patients are at risk for cognitive deficits, and that clinicians should be aware of this risk and the subsequent negative impact on normal socioprofessional life. As mild or moderate cognitive impairments are insufficiently detected with routine medical examinations, we propose that TN patients are routinely evaluated with neuropsychological testing [8]. For this purpose, a brief computerized neuropsychological assessment can be a practical alternative for traditional neuropsychological testing that takes several hours. As MVD generally provides pain relief in many TN patients, and medication can frequently be tapered off after surgery, we hypothesize that MVD is a means to improve cognitive impairments. We plan to follow-up on our operated TN patients to address this hypothesis in a future study. I. Meskal :M. E. Salden :M. M. Sitskoorn Department of Cognitive Neuropsychology, Tilburg University, Tilburg, The Netherlands

Volume rendering for neurosurgical planning

A volume rendering library is presented to interactively analyze volume data from modalities like CT, MR, PET, SPECT< and fMRI for the planning of nuerosurgical procedures. Current applications are logging of Penfield procedures, fMRI visualization, blood vessel visualization and interactive localization of EEG electrodes implanted in the subdural space of a patient with epilepsy.