Giovanni Raffa

Navigated transcranial magnetic stimulation for "somatotopic" tractography of the corticospinal tract.

BACKGROUND: Diffusion tensor imaging tractography provides 3-dimensional reconstruction of principal white matter tracts, but its spatial accuracy has been questioned. Navigated transcranial magnetic stimulation (nTMS) enables somatotopic mapping of the motor cortex. OBJECTIVE: We used motor maps to reconstruct the corticospinal tract (CST) by integrating elements of its somatotopic organization. We analyzed the accuracy of this method compared with a standard technique and verified its reliability with intraoperative subcortical stimulation. METHODS: We prospectively collected data from patients who underwent surgery between January 2012 and October 2013 for lesions involving the CST. nTMS-based diffusion tensor imaging tractography was compared with a standard technique. The reliability and accuracy between the 2 techniques were analyzed by comparing the number of fibers, the concordance in size, and the location of the cortical end of the CST and the motor area. The accuracy of the technique was assessed by using direct subcortical stimulation. RESULTS: Twenty patients were enrolled in the study. nTMS-based tractography provided a detailed somatotopic reconstruction of the CST. This nTMS-based reconstruction resulted in a decreased number of fibers (305.1 ± 231.7 vs 1024 ± 193, P < .001) and a significantly greater overlap between the motor cortex and the cortical end-region of the CST compared with the standard technique (90.5 ± 8.8% vs 58.3 ± 16.6%, P < .001). Direct subcortical stimulation confirmed the CST location and the somatotopic reconstruction in all cases. CONCLUSION: These results suggest that nTMS-based tractography of the CST is more accurate and less operator dependent than the standard technique and provides a reliable anatomic and functional characterization of the motor pathway. ABBREVIATIONS: CST, corticospinal tract DSS, direct subcortical stimulation DTI, diffusion tensor imaging DWI, diffusion-weighted imaging FDI, first dorsal interosseous FLAIR, fluid attenuated inversion recovery MEN, mentalis MEP, motor evoked potential nTMS, navigated transcranial magnetic stimulation RMT, resting motor threshold ROI, region of interest TA, tibialis anterior TE, echo time TMS, transcranial magnetic stimulation TR, repetition time

Preoperative functional mapping for rolandic brain tumor surgery

The resection of tumors within or close to eloquent motor areas is usually guided by the compromise between the maximal allowed resection and preservation of neurological functions. Navigated transcranial magnetic stimulation (nTMS) is an emerging technology that can be used for preoperative mapping of the motor cortex. We performed pre-surgical mapping by using nTMS in 17 patients with lesions in or close to the precentral gyrus. The study was conducted on consecutive patients scheduled for surgical treatment. nTMS allowed to exactly localize the motor cortex in 88.2% of cases. In 70.6% it provided the surgeon with new unexpected information about functional anatomy of the motor area, influencing the pre-operative planning. Moreover, in 29.4% these functional information had a clear impact on surgery, making necessary a change of surgical strategy to avoid damage to the motor cortex. Our results prove that nTMS has a large benefit in the treatment of rolandic brain tumors. It adds important information about spatial relationship between functional motor cortex and the tumor and reduces surgical-related post-operative motor deficits.

A Novel Technique for Region and Linguistic Specific nTMS-based DTI Fiber Tracking of Language Pathways in Brain Tumor Patients

Navigated transcranial magnetic stimulation (nTMS) has recently been introduced as a non-invasive tool for functional mapping of cortical language areas prior to surgery. It correlates well with intraoperative neurophysiological monitoring (IONM) findings, allowing defining the best surgical strategy to preserve cortical language areas during surgery for language-eloquent tumors. Nevertheless, nTMS allows only for cortical mapping and postoperative language deficits are often caused by injury to subcortical language pathways. Nowadays, the only way to preoperatively visualize language subcortical white matter tracts consists in DTI fiber tracking (DTI-FT). However, standard DTI-FT is based on anatomical landmarks that vary interindividually and can be obscured by the presence of the tumor itself. It has been demonstrated that combining nTMS with DTI-FT allows for a more reliable visualization of the motor pathway in brain tumor patients. Nevertheless, no description about such a combination has been reported for the language network. The aim of the present study is to describe and assess the feasibility and reliability of using cortical seeding areas defined by error type-specific nTMS language mapping (nTMS-positive spots) to perform DTI-FT in patients affected by language-eloquent brain tumors. We describe a novel technique for a nTMS-based DTI-FT to visualize the complex cortico-subcortical connections of the language network. We analyzed quantitative findings, such as fractional anisotropy values and ratios, and the number of visualized connections of nTMS-positive spots with subcortical pathways, and we compared them with results obtained by using the standard DTI-FT technique. We also analyzed the functional concordance between connected cortical nTMS-positive spots and subcortical pathways, and the likelihood of connection for nTMS-positive vs. nTMS-negative cortical spots. We demonstrated, that the nTMS-based approach, especially what we call the “single-spot” strategy, is able to provide a reliable and more detailed reconstruction of the complex cortico-subcortical language network as compared to the standard DTI-FT. We believe this technique represents a beneficial new strategy for customized preoperative planning in patients affected by tumors in presumed language eloquent location, providing anatomo-functional information to plan language-preserving surgery.

Simvastatin Administration Ameliorates Neurobehavioral Consequences of Subarachnoid Hemorrhage in the Rat

In the present study we assessed the neuroprotective effects of simvastatin in a rodent model of experimental subarachnoid hemorrhage (SAH). Based on recent data showing the role of statins not only in lowering the level of cholesterol but also in preventing cardiac and cerebrovascular damage in risk population, and in decreasing vasospasm and delayed ischemia after aneurysmal SAH, we investigated the neuroprotective effects of intraperitoneal administration of simvastatin (40 mg/kg/day for 5 consecutive days) in Sprague-Dawley rats 30 min after SAH, as compared to vehicle-treated SAH animals. We employed a battery of well-characterized tests to assess memory, learning, motivational, balance, and behavioral performances. On days 1-4 post-SAH, simvastatin-treated rats have significantly improved beam balance scores (days 1-2, p<0.001; days 3-4, p<0.01), beam balance times (days 1-4, p<0.01), and latency to traverse the beam (days 1-3, p<0.01; day 2, p<0.005; day 4, p<0.0001) in comparison with control groups that, conversely, were not protected against SAH-related body weight changes. These results demonstrate that the administration of simvastatin may represent a beneficial therapeutic approach able to reduce post-SAH cognitive dysfunction.

Intraoperative neurophysiological mapping and monitoring in spinal tumor surgery: sirens or indispensable tools?

Spinal tumor (ST) surgery carries the risk of new neurological deficits in the postoperative period. Intraoperative neurophysiological monitoring and mapping (IONM) represents an effective method of identifying and monitoring in real time the functional integrity of both the spinal cord (SC) and the nerve roots (NRs). Despite consensus favoring the use of IONM in ST surgery, in this era of evidence-based medicine, there is still a need to demonstrate the effective role of IONM in ST surgery in achieving an oncological cure, optimizing patient safety, and considering medicolegal aspects. Thus, neurosurgeons are asked to establish which techniques are considered indispensable. In the present study, the authors focused on the rationale for and the accuracy (sensitivity, specificity, and positive and negative predictive values) of IONM in ST surgery in light of more recent evidence in the literature, with specific emphasis on the role of IONM in reducing the incidence of postoperative neurological deficits. This review confirms the role of IONM as a useful tool in the workup for ST surgery. Individual monitoring and mapping techniques are clearly not sufficient to account for the complex function of the SC and NRs. Conversely, multimodal IONM is highly sensitive and specific for anticipating neurological injury during ST surgery and represents an important tool for preserving neuronal structures and achieving an optimal postoperative functional outcome.

The Impact of Diffusion Tensor Imaging Fiber Tracking of the Corticospinal Tract Based on Navigated Transcranial Magnetic Stimulation on Surgery of Motor-Eloquent Brain Lesions

BACKGROUND Navigated transcranial magnetic stimulation (nTMS) enables preoperative mapping of the motor cortex (M1). The combination of nTMS with diffusion tensor imaging fiber tracking (DTI-FT) of the corticospinal tract (CST) has been described; however, its impact on surgery of motor-eloquent lesions has not been addressed. OBJECTIVE To analyze the impact of nTMS-based mapping on surgery of motor-eloquent lesions. METHODS In this retrospective case-control study, we reviewed the data of patients operated for suspected motor-eloquent lesions between 2012 and 2015. The patients underwent nTMS mapping of M1 and, from 2014, nTMS-based DTI-FT of the CST. The impact on the preoperative risk/benefit analysis, surgical strategy, craniotomy size, extent of resection (EOR), and outcome were compared with a control group. RESULTS We included 35 patients who underwent nTMS mapping of M1 (group A), 35 patients who also underwent nTMS-based DTI-FT of the CST (group B), and a control group composed of 35 patients treated without nTMS (group C). The patients in groups A and B received smaller craniotomies (P = .01; P = .001), had less postoperative seizures (P = .02), and a better postoperative motor performance (P = .04) and Karnofsky Performance Status (P = .009) than the controls. Group B exhibited an improved risk/benefit analysis (P = .006), an increased EOR of nTMS-negative lesions in absence of preoperative motor deficits (P = .01), and less motor and Karnofsky Performance Status worsening in case of preoperative motor deficits (P = .02, P = .03) than group A. CONCLUSION nTMS-based mapping enables a tailored surgical approach for motor-eloquent lesions. It may improve the risk/benefit analysis, EOR and outcome, particularly when nTMS-based DTI-FT is performed.

Fully Endoscopic Freehand Evacuation of Spontaneous Supratentorial Intraparenchymal Hemorrhage

OBJECTIVE A modification of other reported endoscopic techniques for intracerebral clot evacuation is described and illustrated. METHODS From January 2014 to December 2014, we operated on 6 patients harboring a spontaneous supratentorial intracerebral hemorrhage using a fully endoscopic freehand technique. Clinical chart and surgical videos were analyzed. Volumetric evaluation of the clot preoperatively and the residual hematoma postoperatively was performed. Clinical outcome was measured using the modified Rankin Scale and Glasgow Outcome Scale. RESULTS The mean operative time was 96 minutes (range, 72-125 minutes). Clot evacuation was >90% in all patients. No patient experienced rebleeding after surgery. Two patients died. The Glasgow Outcome Scale score at 6 months was 4 in 2 patients, 3 in 2 patients, and 1 (death) in 2 patients. The modified Rankin Scale score at 6 months was 6 (death) in 2 patients, 4 in 2 patients, 3 in 1 patient and 2 in 1 patient. CONCLUSIONS The proposed minimally invasive technique allows a good rate of hematoma evacuation and intraoperative bleeding control. Further studies in large series are needed to confirm the role of this freehand endoscopic technique.

Resting-state fMR evidence of network reorganization induced by navigated transcranial magnetic repetitive stimulation in phantom limb pain

Abstract Objectives Repetitive transcranial magnetic stimulation (rTMS) is a promising tool for treatment of chronic pain. We describe the use of navigated rTMS to treat a patient affected by phantom limb pain (PLP) and to modulate brain functional connectivity. We reviewed the literature on the use of rTMS as a tool for relieving central pain by promoting brain plasticity. Methods A 69-year-old patient came to our observation blaming severe pain (Visual Analog scale, VAS, score 9) to a phantom right lower limb. We mapped left primary motor area (PMA) by navigated TMS and assessed connectivity with resting-state functional MR (rsfMR). The patient underwent 30-days navigated rTMS treatment. We applied low-frequency stimulation (1 Hz) over the primary somatosensory area (PSA) and high-frequency stimulation (10 Hz) over PMA and dorsolateral prefrontal cortex (DLPFC) of the left hemisphere. Results This strategy allowed a pain relief with a reduction of 5 points of the VAS score after 1 month. Post-treatment rsfMR showed increased connectivity, mainly in the sensory-motor network and the unaffected hemisphere (P < 0.05). Discussion This report represents a proof-of-concept that navigated rTMS can be effectively used to stimulate selected brain areas in PLP patients in order to promote brain connectivity, and that rsfMR is a useful tool able to analyze functional results. In the literature, we found data supporting the assumption that, in patients affected by PLP, a reduced connectivity in interhemispherical and sensory-motor network plays a role in generating pain and that rTMS has the potential to restore impaired connectivity.

nTMS-Based DTI Fiber Tracking of Motor Pathways

DTI fiber tracking allows for the 3D reconstruction of main white matter fascicles, including the corticospinal tract (CST). Nevertheless, standard diffusion tensor imaging fiber tracking (DTI FT) is limited by the fact that it is based on the selection of anatomical landmarks as seeding regions of interest (ROIs) for tract computation. This reduces the reliability and reproducibility of DTI FT results, especially in brain tumor patients, in which the neural plasticity induced by the tumor itself causes a reorganization of the motor network, resulting in a mismatch between anatomical and functional landmarks. The nTMS technique provides a reliable mapping of the functional organization of the motor cortex that can be successfully used as seeding ROI for the DTI computation of the CST. This improves the reliability and accuracy of the DTI FT of the CST compared to the standard DTI technique. Moreover, it provides the somatotopic organization of the CST, especially improving the visualization of fiber bundles connected to the motor cortical representation of arm and face muscles.

Intraoperative Neurophysiological Monitoring in Spine Surgery: A Significant Tool for Neuronal Protection and Functional Restoration.

Although there is recent evidence for the role of intraoperative neurophysiological monitoring (IONM) in spine surgery, there are no uniform opinions on the optimal combination of the different tools. At our institution, multimodal IONM (mIONM) approach in spine surgery involves the evaluation of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) with electrical transcranial stimulation, including the use of a multipulse technique with multiple myomeric registration of responses from limbs, and a single-pulse technique with D-wave registration through epi- and intradural recording, and free running and evoked electromyography (frEMG and eEMG) with bilateral recording from segmental target muscles. We analyzed the impact of the mIONM on the preservation of neuronal structures and on functional restoration in a prospective series of patients who underwent spine surgery. We observed an improvement of neurological status in 50 % of the patients. The D-wave registration was the most useful intraoperative tool, especially when MEP and SEP responses were absent or poorly recordable. Our preliminary data confirm that mIONM plays a fundamental role in the identification and functional preservation of the spinal cord and nerve roots. It is highly sensitive and specific for detecting and avoiding neurological injury during spine surgery and represents a helpful tool for achieving optimal postoperative functional outcome.