Clinical considerations on a right operculo-insular cavernous angioma: an illustrative case.

The insular cortex is considered one of the most complex regions of the brain, defined as the "hub" of somatosensory areas. Here, we examine the case of a surgically treated haemorrhagic cavernoma involving the middle and posterior insular cortex, presenting both sensory, gustative and speech symptoms. By reviewing the recent findings in humans' and primates' basic research, we illustrated clinical and radiological correlations of the reported case, confirming insular role in sensitive and gustatory functions.

Mapping the brain network of the phonological loop.

The cortical and subcortical neural correlates underlying item and order information in verbal short-term memory (STM) were investigated by means of digit span in 29 patients with direct electrical stimulation during awake surgery for removal of a neoplastic lesion. Stimulation of left Broca's area interfered with span, producing significantly more item than order errors, as compared to the stimulation of the supramarginal/angular gyrus, which also interfered with span but, conversely, produced more order than item errors. Similarly, stimulation of the third segment of the left superior longitudinal fasciculus (SLF-III), also known as anterior segment of the arcuate fascicle (AF), produced more order than item errors. Therefore, we obtained two crucial results: first, we were able to distinguish between content and order information storage. Second, we demonstrated that the SLF-III is involved in transferring order information from Geschwind's area to Broca's area. In a few patients, we demonstrated that also order information of nonverbal material was disrupted by left supramarginal gyrus stimulation. Order information is thus likely stored in the supramarginal gyrus, possibly independently from the nature of the material. Hum Brain Mapp 38:3011-3024, 2017. © 2017 Wiley Periodicals, Inc.

Value of Surgical Resection in Patients with Newly Diagnosed Grade III Glioma Treated in a Multimodal Approach: Surgery, Chemotherapy and Radiotherapy.

BACKGROUND: Current treatments in grade III gliomas include surgery, radiotherapy, and chemotherapy. The value of the entity of surgical resection remains an open question. The aim of this evaluation was to analyze the impact of extent of resection (EOR) and residual tumor volume (RTV) on progression-free survival (PFS) and overall survival (OS) in patients with newly diagnosed grade III gliomas. METHODS: Overall, 136 patients were included in this evaluation. EOR and RTV were defined in all patients on postoperative volumetric magnetic resonance imaging, with EOR being defined as the rate of surgical resection, and RTV as contrast-enhancing RTV (CE-RTV) and fluid-attenuated inversion recovery (FLAIR) RTV. A threshold of EOR and RTV was recorded using increments of 2 % and 1 cm(3). RESULTS: EOR and RTV were the only clinical variables influencing PFS and OS. The EOR cut-off value for conditioning survival was 76 %. For EOR ≥76 % or <76 %, the 5- to 10-year PFS was 57 % and 18 % versus 0 % (p = 0.03), and 5- to 10-year OS was 68 % and 42 % versus 0 % (p = 0.06), respectively. Additionally, the RTV cut-off value was 3 cm(3); for RTV <3 cm(3) or >3 cm(3), 5- to 10-year PFS was 64.3 % and 48.2 % versus 42 % and 0 % (p = 0.02), and 5- to 10-year OS was 66.8 % and 33.4 % versus 56 % and 0 % (p = 0.3), respectively. RTV was a more significant parameter conditioning PFS and OS than EOR (p = 0.04), and the presence of CE-RTV was an unfavorable prognostic factor compared with FLAIR-RTV. CONCLUSIONS: In heterogeneous lesions from a radiological point of view as WHO grade III gliomas if a complete removal is not possible, it would be advisable to maximize the removal of enhancing areas, possibly with an EOR >76 % and an RTV <3 cm(3).

The mirror neuron system and the strange case of Broca's area.

Mirror neurons, originally described in the monkey premotor area F5, are embedded in a frontoparietal network for action execution and observation. A similar Mirror Neuron System (MNS) exists in humans, including precentral gyrus, inferior parietal lobule, and superior temporal sulcus. Controversial is the inclusion of Broca's area, as homologous to F5, a relevant issue in light of the mirror hypothesis of language evolution, which postulates a key role of Broca's area in action/speech perception/production. We assess "mirror" properties of this area by combining neuroimaging and intraoperative neurophysiological techniques. Our results show that Broca's area is minimally involved in action observation and has no motor output on hand or phonoarticulatory muscles, challenging its inclusion in the MNS. The presence of these functions in premotor BA6 makes this area the likely homologue of F5 suggesting that the MNS may be involved in the representation of articulatory rather than semantic components of speech.

Cerebral correlates of visuospatial neglect: a direct cerebral stimulation study.

OBJECTIVE: To assess the role of the superior longitudinal fascicle, the inferior fronto-occipital fascicle, and the posterior parietal lobe in visuospatial attention in humans during awake brain surgery. EXPERIMENTAL DESIGN: Seven patients with hemispheric gliomas (six in the right hemisphere) entered the study. During surgery in asleep/awake anesthesia, guided by Diffusion Tensor Imaging Fiber Tractography, visuospatial neglect was assessed during direct electrical stimulation by computerized line bisection. PRINCIPAL OBSERVATIONS: A rightward deviation, indicating left visuospatial neglect, was induced in six of seven patients by stimulation of the parietofrontal connections, in a location consistent with the trajectory of the second branch of the superior longitudinal fascicle. Stimulation of the medial and dorsal white matter of the superior parietal lobule (corresponding to the first branch of the superior longitudinal fascicle), of the ventral and lateral white matter of the supramarginal gyrus (corresponding to the third branch of the superior longitudinal fascicle), and of the inferior occipitofrontal fasciculus, was largely ineffective. Stimulation of the superior parietal lobule (Brodmann's area 7) caused a marked rightward deviation in all of the six assessed patients, while stimulation of Brodmann's areas 5 and 19 was ineffective. CONCLUSIONS: The parietofrontal connections of the dorso-lateral fibers of the superior longitudinal fascicle (i.e., the second branch of the fascicle), and the posterior superior parietal lobe (Brodmann's area 7) are involved in the orientation of spatial attention. Spatial neglect should be assessed systematically during awake brain surgery, particularly when the right parietal lobe may be involved by the neurosurgical procedure.

A novel method of neurophysiological brainstem mapping in neurosurgery.

BACKGROUND: Brainstem mapping with electrical stimulation allows functional identification of neural structures during resection of deep lesions. Single pulses or train of pulses are delivered to map cranial nerves and corticospinal tracts, respectively. NEW METHOD: We introduce a hybrid stimulation technique for mapping the brainstem. The stimulus consists of an electrical single pulse followed by a short train of 3-5 pulses at 500 Hz, at an interval of 60-75 ms. The responses to this stimulation pattern are recorded from appropriate cranial and limb muscles. RESULTS: Both the single pulse and the short train elicit electromyographic responses when motor fibers or motor nuclei of the cranial nerves are stimulated. Responses to the train but not to the preceding single pulse indicate activation of the descending motor tracts, in the mesencephalon and the pons. Conversely, in the medulla, limb responses to stimulation of the corticospinal tracts are elicited by a single pulse. Identification of the extra and intra-axial courses of the trigeminal motor and sensory fibers is possible by recording responses from the masseter and the tongue muscles. COMPARISON WITH EXISTING METHOD(S): To date, either a pulse or a train is delivered during brainstem mapping, switching from one to the other modality according to the expected target structure. This procedure can be time-consuming and may even lead to false negative responses to the stimulation, eventually leading to inaccurate neurosurgical procedures. CONCLUSIONS: The novel hybrid pulse-train technique enhances the advantage of brainstem mapping procedure, minimizing pitfalls and improving patient safety.

What is the role of the uncinate fasciculus? Surgical removal and proper name retrieval.

The functional role of the uncinate fasciculus is still a matter of debate. We examined 44 patients submitted to awake surgery for removal of a left frontal or temporal glioma. In 18 patients, the removal included the uncinate fasciculus. We compared patients with or without removal on a series of neuropsychological tasks, performed at different time intervals: pre-surgery, in the first week after surgery and 3 months after surgery. Functional magnetic resonance and diffusion tensor imaging, fibre-tracking techniques were performed before surgery. At the last examination, patients with uncinate removal were significantly impaired in naming of famous faces and objects as compared with patients without removal. We further divided patients according to the site of the tumour (either frontal or temporal). At the follow-up, patients with a temporal glioma who underwent uncinate removal had the worst loss of performance in famous face naming. In addition, on the same task, the group with a frontal glioma that underwent resection of the frontal part of the uncinate performed significantly worse than the group with a frontal glioma but without uncinate removal. In conclusion, the resection of the uncinate fasciculus, in its frontal or temporal part, has long-lasting consequences for famous face naming. We suggest that this fibre tract is part of a circuitry involved in the retrieval of word form for proper names. Retrieval of conceptual knowledge was intact.

Long latency responses in tongue muscle elicited by various stimulation sites in anesthetized humans - New insights into tongue-related brainstem reflexes.

BACKGROUND: Long Latency Responses (LLR) in tongue muscles are a scarcely described phenomenon, the physiology of which is uncertain. OBJECTIVES: The aim of this exploratory, observational study was to describe tongue-LLR elicited by direct trigeminal nerve (DTNS), dorsal column (DoColS), transcranial electric (TES) and peripheral median nerve (MNS) stimulation in a total of 93 patients undergoing neurosurgical procedures under general anesthesia. METHODS: Bilateral tongue responses were derived concurrently after each of the following stimulations: (1) DTNS applied with single monophasic or train-of-three pulses, ≤5 mA; (2) DoColS applied with a train-of-three pulses, ≤10 mA; (3) TES consisting of an anodal train-of-five stimulation, ≤250 mA; (4) MNS at wrist consisting of single or train-of-three monophasic pulses, ≤50 mA. Polyphasic tongue muscle responses exceeding the latencies of tongue compound muscle action potentials or motor evoked potentials were classified as LLR. RESULTS: Tongue-LLR were evoked from all stimulation sites, with latencies as follows: (1) DTNS: solely ipsilateral 20.2 ± 3.3 msec; (2) DoColS: ipsilateral 25.9 ± 1.6 msec, contralateral 25.1 ± 4.2 msec; (3) TES: contralateral 55.3 ± 10.2 msec, ipsilateral 54.9 ± 12.0 msec; (4) MNS: ipsilateral 37.8 ± 4.7 msec and contralateral 40.3 ± 3.5 msec. CONCLUSION: The tongue muscles are a common efferent in brainstem pathways targeted by trigeminal and cervical sensory fibers. DTNS can elicit the "trigemino-hypoglossal-reflex". For the MNS elicited tongue-LLR, we propose the term "somatosensory-evoked tongue-reflex". Although the origin of the TES related tongue-LLR remains unclear, these data will help to interpret intraoperative tongue recordings.

Intramedullary spinal cord tumors: the value of intraoperative neurophysiological monitoring in a series of 57 cases from two Italian centers.

BACKGROUND: Intramedullary spinal cord tumors are rare lesions of the central nervous system. Anatomical, molecular and radiological features are well defined, but correct management is still matter of debate. Pertinent literature has reported conflicting opinions regarding the use of intraoperative electrophysiological monitoring (IONM) in the surgical treatment of this kind of lesions, recently. We report a retrospective study from two Italian centers, in order to highlight the usefulness of IONM in the management of intramedullary lesions. METHODS: We performed a retrospective review of patients with intramedullary spinal tumor who underwent surgical resection from February 2011 to February 2018 in two different institutions. Clinical and radiological data, lesion features, timing of symptom onset and IONM findings were recorded. The IONM included somatosensory-evoked potentials (SSEP), motor-evoked potentials (MEP) and D-Wave whenever possible. We evaluated the outcome according to the Modified McCormick scale. We also evaluated the accuracy and relevance of surgical outcomes for each evoked potential (SSEP, MEP, D-Wave). RESULTS: A total of 57 patients were included. A gross total removal was achieved in 46 cases. Neurological follow-up was assessment at 3 days, and 3 and 6 months after surgery. Comparing the preoperative status and 6 months follow-up: the modified McCormick scale showed a neurological stability for 30 patients (52.63%), a worsening of neurological status for 7 patients (12.28%) and an improvement for 20 patients (35.08%). IONM presented high accuracy (sensibility of 100% and specificity of 95.65%) and significantly predicted postoperative permanent motor deficits (P<0.0001; AUC=0.978). D-Wave appeared to have significant greater predictive value than MEP and especially SSEP alone (0.967 vs 0.722 vs 0.542; P=0.044 and P<0.001 respectively). CONCLUSIONS: The gold standard in the intramedullary lesion treatment is maximal safe resection with good neurological outcome, as shown in our patients. The use of IONM is helpful in intramedullary tumors resection in order to minimize postoperative neurological deficits and our analysis suggests that the use of D-Wave presents a statistically significant higher accuracy for predicting postoperative deficits than SSEP and MEP alone.

Connectivity constraints on cortical reorganization of neural circuits involved in object naming.

The brain's plasticity in response to sensory deprivation and other perturbations is well established. While the functional properties of the reorganized areas are under vigorous investigation, the factors that constrain cortical reorganization remain poorly understood. One factor constraining such reorganization may be long-distance subcortical connectivity between relevant cortical regions-reorganization attempts to preserve the functionality of subcortical connections. Here we provide human neurophysiological evidence for the role of the subcortical connections in shaping cortical reorganization of the networks involved in object naming following perturbation of normal function. We used direct electrical stimulation (DES) during surgical removal of gliomas to identify the sites that are involved in naming different categories of objects. The sites that were selectively inhibited in naming either living or non-living objects were displaced relative to those observed with other subject populations, possibly reflecting cortical reorganization due to slowly evolving brain damage. Subcortical DES applied to the white matter underlying these regions also led to category-specific naming deficits. The existence of these subcortical fiber pathways was confirmed using diffusion tensor tractography. These results constitute the first neurophysiological evidence for the critical role of subcortical pathways as part of the neural circuits that are involved in object naming; they also highlight the importance of subcortical connectivity in shaping cortical reorganization following perturbations of normal function.

Cerebellopontine Angle Surgery Assisted by Continuous Mapping of the Facial Nerve Via the Ultrasonic Aspirator.

BACKGROUND: Cerebellopontine angle (CPA) surgery carries the risk of lesioning the facial nerve. The goal of preserving the integrity of the facial nerve is usually pursued with intermittent electrical stimulation using a handheld probe that is alternated with the resection. We report our experience with continuous electrical stimulation delivered via the ultrasonic aspirator (UA) used for the resection of a series of vestibular schwannomas. METHODS: A total of 17 patients with vestibular schwannomas, operated on between 2010 and 2018, were included in this study. A constant-current stimulator was coupled to the UA used for the resection, delivering square-wave pulses throughout the resection. The muscle responses from upper and lower face muscles triggered by the electrical stimulation were displayed continuously on multichannel neurophysiologic equipment. The careful titration of the electrical stimulation delivered through the UA while tapering the current intensity with the progression of the resection was used as the main strategy. RESULTS: All operations were performed successfully, and facial nerve conduction was maintained in all patients except one, in whom a permanent lesion of the facial nerve followed a miscommunication to the neurosurgeon. CONCLUSION: The coupling of the electrical stimulation to the UA provided the neurosurgeon with an efficient and cost-effective tool and allowed a safe resection. Positive responses were obtained from the facial muscles with low current intensity (lowest intensity: 0.1 mA). The availability of a resection tool paired with a stimulator allowed the surgeon to improve the surgical workflow because fewer interruptions were necessary to stimulate the facial nerve via a handheld probe.

Intraoperative use of diffusion tensor imaging fiber tractography and subcortical mapping for resection of gliomas: technical considerations.

Resection of lesions involving motor or language areas or pathways requires the intraoperative identification of functional cortical and subcortical sites for effectively and safe guidance. Diffusion tensor (DT) imaging and fiber tractography are MR imaging techniques based on the concept of anisotropic water diffusion in myelinated fibers, which enable 3D reconstruction and visualization of white matter tracts and provide information about the relationship of these tracts to the tumor mass. The authors routinely used DT imaging fiber tractography to reconstruct various tracts involved in the motor and/or language system in a large series of patients with lesions involving the motor and/or language areas or pathways. The DT imaging fiber tractography data were loaded into the neuronavigational system and combined intraoperatively with those obtained from direct electrical stimulation applied at the subcortical level. In this paper the authors report the results of their experience, describing the findings for each tract and discussing technical aspects of the combined use as well as the pitfalls.

Intraoperative electrical stimulation in awake craniotomy: methodological aspects of current practice.

There is increasing evidence that the extent of tumor removal in low-grade glioma surgery is related to patient survival time. Thus, the goal of resecting the largest amount of tumor possible without leading to permanent neurological sequelae is a challenge for the neurosurgeon. Electrical stimulation of the brain to detect cortical and axonal areas involved in motor, language, and cognitive function and located within the tumor or along its boundaries has become an essential tool in combination with awake craniotomy. Based on a literature review, discussions within the European Low-Grade Glioma Group, and illustrative clinical experience, the authors of this paper provide an overview for neurosurgeons, neurophysiologists, linguists, and anesthesiologists as well as those new to the field about the stimulation techniques currently being used for mapping sensorimotor, language, and cognitive function in awake surgery for low-grade glioma. The paper is intended to help the understanding of these techniques and facilitate a comparison of results between users.

Holmes tremor: a delayed complication after resection of brainstem cavernomas.

OBJECTIVE: In this paper, the authors aimed to illustrate how Holmes tremor (HT) can occur as a delayed complication after brainstem cavernoma resection despite strict adherence to the safe entry zones (SEZs). METHODS: After operating on 2 patients with brainstem cavernoma at the Great Metropolitan Hospital Niguarda in Milan and noticing a similar pathological pattern postoperatively, the authors asked 10 different neurosurgery centers around the world to identify similar cases, and a total of 20 were gathered from among 1274 cases of brainstem cavernomas. They evaluated the tremor, cavernoma location, surgical approach, and SEZ for every case. For the 2 cases at their center, they also performed electromyographic and accelerometric recordings of the tremor and evaluated the post-operative tractographic representation of the neuronal pathways involved in the tremorigenesis. After gathering data on all 1274 brainstem cavernomas, they performed a statistical analysis to determine if the location of the cavernoma is a potential predicting factor for the onset of HT. RESULTS: From the analysis of all 20 cases with HT, it emerged that this highly debilitating tremor can occur as a delayed complication in patients whose postoperative clinical course has been excellent and in whom surgical access has strictly adhered to the SEZs. Three of the patients were subsequently effectively treated with deep brain stimulation (DBS), which resulted in complete or almost complete tremor regression. From the statistical analysis of all 1274 brainstem cavernomas, it was determined that a cavernoma location in the midbrain was significantly associated with the onset of HT (p < 0.0005). CONCLUSIONS: Despite strict adherence to SEZs, the use of intraoperative neurophysiological monitoring, and the immediate success of a resective surgery, HT, a severe neurological disorder, can occur as a delayed complication after resection of brainstem cavernomas. A cavernoma location in the midbrain is a significant predictive factor for the onset of HT. Further anatomical and neurophysiological studies will be necessary to find clues to prevent this complication.

Intraoperative mapping and monitoring of brain functions for the resection of low-grade gliomas: technical considerations.

Low-grade gliomas ([LGGs] WHO Grade II) are slow-growing intrinsic cerebral lesions that diffusely infiltrate the brain parenchyma along white matter tracts and almost invariably show a progression toward malignancy. The treatment of these tumors forces the neurosurgeon to face uncommon difficulties and is still a subject of debate. At the authors' institution, resection is the first option in the treatment of LGGs. It requires the combined efforts of a multidisciplinary team of neurosurgeons, neuroradiologists, neuropsychologists, and neurophysiologists, who together contribute to the definition of the location, extension, and extent of functional involvement that a specific lesion has caused in a particular patient. In fact, each tumor induces specific modifications of the brain functional network, with high interindividual variability. This requires that each treatment plan is tailored to the characteristics of the tumor and of the patient. Consequently, surgery is performed according to functional and anatomical boundaries to achieve the maximal resection with maximal functional preservation. The identification of eloquent cerebral areas, which are involved in motor, language, memory, and visuospatial functions and have to be preserved during surgery, is performed through the intraoperative use of brain mapping techniques. The use of these techniques extends surgical indications and improves the extent of resection, while minimizing the postoperative morbidity and safeguarding the patient's quality of life. In this paper the authors present their paradigm for the surgical treatment of LGGs, focusing on the intraoperative neurophysiological monitoring protocol as well as on the brain mapping technique. They briefly discuss the results that have been obtained at their institution since 2005 as well as the main critical points they have encountered when using this approach.

Assessment of the praxis circuit in glioma surgery to reduce the incidence of postoperative and long-term apraxia: a new intraoperative test.

OBJECTIVEApraxia is a cognitive-motor deficit affecting the execution of skilled movements, termed praxis gestures, in the absence of primary sensory or motor disorders. In patients affected by stroke, apraxia is associated with lesions of the lateral parietofrontal stream, connecting the posterior parietal areas with the ventrolateral premotor area and subserving sensory-motor integration for the hand movements. In the neurosurgical literature to date, there are few reports regarding the incidence of apraxia after glioma surgery. A retrospective analysis of patients who harbored a glioma around the central sulcus and close to the parietofrontal circuits in depth showed a high incidence of long-term postoperative hand apraxia, impairing the patients' quality of life. To avoid the occurrence of postoperative apraxia, the authors sought to develop an innovative intraoperative hand manipulation task (HMt) that can be used in association with the brain mapping technique to identify and preserve the cortical and subcortical structures belonging to the praxis network.METHODSThe intraoperative efficacy of the HMt was investigated by comparing the incidence of postoperative ideomotor apraxia between patients undergoing mapping with (n = 79) and without (n = 41) the HMt. Patient groups were balanced for all demographic and clinical features.RESULTSIn patients with lesions in the dominant hemisphere, the HMt dramatically reduced the incidence of apraxia, with a higher sensitivity for the ideomotor than for the constructional abilities; patients with lesions in the nondominant hemisphere benefitted from the HMt for both ideomotor and constructional abilities. The administration of the test did not reduce the extent of resection.CONCLUSIONSThe HMt is a safe and feasible intraoperative tool that allowed surgeons to prevent the occurrence of long-term hand apraxia while attaining resection goals for the surgical treatment of glioma.

Monopolar high-frequency language mapping: can it help in the surgical management of gliomas? A comparative clinical study.

OBJECT Intraoperative language mapping is traditionally performed with low-frequency bipolar stimulation (LFBS). High-frequency train-of-five stimulation delivered by a monopolar probe (HFMS) is an alternative technique for motor mapping, with a lower reported seizure incidence. The application of HFMS in language mapping is still limited. Authors of this study assessed the efficacy and safety of HFMS for language mapping during awake surgery, exploring its clinical impact compared with that of LFBS. METHODS Fifty-nine patients underwent awake surgery with neuropsychological testing, and LFBS and HFMS were compared. Frequency, type, and site of evoked interference were recorded. Language was scored preoperatively and 1 week and 3 months after surgery. Extent of resection was calculated as well. RESULTS High-frequency monopolar stimulation induced a language disturbance when the repetition rate was set at 3 Hz. Interference with counting (p = 0.17) and naming (p = 0.228) did not vary between HFMS and LFBS. These results held true when preoperative tumor volume, lesion site, histology, and recurrent surgery were considered. Intraoperative responses (1603) in all patients were compared. The error rate for both modalities differed from baseline values (p < 0.001) but not with one another (p = 0.06). Low-frequency bipolar stimulation sensitivity (0.458) and precision (0.665) were slightly higher than the HFMS counterparts (0.367 and 0.582, respectively). The error rate across the 3 types of language errors (articulatory, anomia, paraphasia) did not differ between the 2 stimulation methods (p = 0.279). CONCLUSIONS With proper setting adjustments, HFMS is a safe and effective technique for language mapping.

Specific disgust processing in the left insula: New evidence from direct electrical stimulation.

Neuropsychological and neuroimaging studies yielded controversial results concerning the specific role of the insula in recognizing the facial expression of disgust. To verify whether the insula has a selective role in facial disgust processing, emotion recognition was studied in thirteen patients during intraoperative stimulation of the insula in awake surgery performed for removal of a glioma close to this structure. Direct electrical stimulation of the left insula produced a general decrease in emotion recognition but only in the case of disgust there was a statistically significant detrimental effect (p=0.004). Happiness and anger were the best and the worst recognized emotion, respectively. The worst baseline performance with anger and, partly, fear could be explained with the involvement of the left temporal regions, striatum, and the connection between the striatum and the frontal lobe, as suggested in previous studies. Therefore, upon these intra-operative evidences, we argue for a selective role of the left insula in disgust recognition, although a (non significant) decrease in the recognition of other negative emotions was found. However, additional networks can develop, as demonstrated by the fact that disgust recognition was not impaired after surgery even in patients with insular resection in the current as in previous studies.