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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

Tailoring neurophysiological strategies with clinical context enhances resection and safety and expands indications in gliomas involving motor pathways.

BACKGROUND: Resection of motor pathway gliomas requires the intraoperative recognition of essential cortical-subcortical motor structures. The degree of involvement of motor structures is variable, and increases as result of treatments patients are submitted to. Intraoperative neurophysiology offers various stimulation modalities, which efficiency is based on the ability to recognize essential sites with the highest possible resolution in most clinical conditions. Two stimulation paradigms evolved for intraoperative guidance of motor tumors removal: the 60 Hz-technique [low frequency (LF)] and the pulse-technique [high frequency-(HF)], delivered by bipolar or monopolar probe respectively. Most surgical teams rely on to either of the 2 techniques. The key point is the integration of the choice of the stimulation modality with the clinical context. METHODS: In 591 tumors involving the corticospinal tract, the use of HF and LF was tailored to the clinical context defined by patient clinical history and tumor features (by imaging). The effect was evaluated on the feasibility of mapping, the impact on immediate and permanent morbidity, the extent of resection, and the number of patients treated. RESULTS: By integrating the choice of the probe and the stimulation protocol with patient clinical history and tumor characteristics, the best probe-frequency match was identified for the different sets of clinical conditions. This integrative approach allows increasing the extent of resection and patient functional integrity, and greatly expands the number of patients who could benefit from surgery. CONCLUSIONS: The integration of stimulation modalities with clinical context enhances the extent and safety of resection and expands the population of patients who could benefit from surgical treatment.

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.

Intraoperative forces and moments analysis on patient head clamp during awake brain surgery.

In brain surgery procedures, such as deep brain stimulation, drug-resistant epilepsy and tumour surgery, the patient is intentionally awakened to map functional neural bases via electrophysiological assessment. This assessment can involve patient's body movements; thus, increasing the mechanical load on the head-restraint systems used for keeping the skull still during the surgery. The loads exchanged between the head and the restraining device can potentially result into skin and bone damage. The aim of this work is to assess such loads for laying down the requirements of a surgical robotics system for dynamic head movements compensation by fast moving arms and by an active restraint able to damp such actions. A Mayfield(®) head clamp was tracked and instrumented with strain gages (SGs). SG locations were chosen according to finite element analyses. During an actual brain surgery, displacements and strains were measured and clustered according to events that generated them. Loads were inferred from strain data. The greatest force components were exerted vertically (median 5.5 N, maximum 151.87 N) with frequencies up to 1.5 Hz. Maximum measured displacement and velocity were 9 mm and 60 mm/s, with frequencies up to 2.8 Hz. The analysis of loads and displacements allowed to identify the surgery steps causing maximal loads on the head-restraint device.

Role of diffusion tensor magnetic resonance tractography in predicting the extent of resection in glioma surgery.

Diffusion tensor imaging (DTI) tractography enables the in vivo visualization of the course of white matter tracts inside or around a tumor, and it provides the surgeon with important information in resection planning. This study is aimed at assessing the ability of preoperative DTI tractography in predicting the extent of the resection achievable in surgical removal of gliomas. Patients with low-grade gliomas (LGGs; 46) and high-grade gliomas (HGGs; 27) were studied using a 3T scanner according to a protocol including a morphological study (T2, fluid-attenuated inversion-recovery, T1 sequences) and DTI acquisitions (b = 1000 s/mm(2), 32 gradient directions). Preoperative tractography was performed off-line on the basis of a streamline algorithm, by reconstructing the inferior fronto-occipital (IFO), the superior longitudinal fascicle (SLF), and the corticospinal tract (CST). For each patient, the relationship between each bundle reconstructed and the lesion was analyzed. Initial and residual tumor volumes were measured on preoperative and postoperative 3D fluid-attenuated inversion-recovery images for LGGs and postcontrast T1-weighted scans for HGGs. The presence of intact fascicles was predictive of a better surgical outcome, because these cases showed a higher probability of total resection than did subtotal and partial resection. The presence of infiltrated or displaced CST or infiltrated IFO was predictive of a lower probability of total resection, especially for tumors with preoperative volume <100 cm(3). DTI tractography can thus be considered to be a promising tool for estimating preoperatively the degree of radicality to be reached by surgical resection. This information will aid clinicians in identifying patients who will mostly benefit from surgery.