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Hidetoshi Matsukawa, Hiroyasu Kamiyama, Takanori Miyazaki, Yu Kinoshita, Nakao Ota, Kosumo Noda, Takaharu Shonai, Osamu Takahashi, Sadahisa Tokuda and Rokuya Tanikawa

OBJECTIVE

Perforator territory infarction (PTI) is still a major problem needing to be solved to achieve good outcomes in aneurysm surgery. However, details and risk factors of PTI diagnosed on postoperative MRI remain unknown. The authors aimed to investigate the details of PTI on postoperative diffusion-weighted imaging (DWI) in patients with surgically treated unruptured intracranial saccular aneurysms (UISAs).

METHODS

The data of 848 patients with 1047 UISAs were retrospectively evaluated. PTI was diagnosed on DWI, which was performed the day after aneurysm surgery. Clinical and radiological characteristics were compared between UISAs with and without PTI. Poor outcome was defined as an increase in 1 or more modified Rankin Scale scores at 12 months after aneurysm surgery.

RESULTS

Postoperative DWI was performed in all cases, and it revealed PTI in 56 UISA cases (5.3%). Forty-three PTIs occurred without direct injury and occlusion of perforators (43 of 56, 77%). Poor outcome was more frequently observed in the PTI group (17 of 56, 30%) than the non-PTI group (57 of 1047, 5.4%) (p < 0.0001). Thalamotuberal arteries (p < 0.01), lateral striate arteries (p < 0.01), Heubner’s artery (p < 0.01), anterior median commissural artery (p < 0.05), terminal internal carotid artery perforators (p < 0 0.01), and basilar artery perforator (p < 0 0.01) infarctions were related to poor outcome by adjusted residual analysis. On multivariate analysis, statin use (OR 10, 95% CI, 3.3–31; p < 0.0001), specific aneurysm locations (posterior communicating artery [OR 4.1, 95% CI 2.1–8.1; p < 0.0001] and basilar artery [OR 3.1, 95% CI 1.1–8.9; p = 0.031]), larger aneurysm size (OR 1.1, 95% CI 1.1–1.2; p = 0.043), and permanent decrease of motor evoked potential (OR 38, 95% CI 3.1–468; p = 0.0045) were related to PTI.

CONCLUSIONS

Despite efforts to avoid PTI, it occurred even without direct injury, occlusion of perforators, or evoked potential abnormality. Therefore, surgical treatment of UISAs, especially with the aforementioned risk factors of PTI, should be more carefully considered. The evaluation of PTI in the territory of the above-mentioned perforators could be useful in helping predict the clinical course in patients after aneurysm surgery.

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Saman Shabani, Mayank Kaushal, Matthew Budde and Shekar N. Kurpad

OBJECTIVE

Conventional MRI is routinely used to demonstrate the anatomical site of spinal cord injury (SCI). However, quantitative and qualitative imaging parameters have limited use in predicting neurological outcomes. Currently, there are no reliable neuroimaging biomarkers to predict short- and long-term outcome after SCI.

METHODS

A prospective cohort of 23 patients with SCI (19 with cervical SCI [CSCI] and 4 with thoracic SCI [TSCI]) treated between 2007 and 2014 was included in the study. The American Spinal Injury Association (ASIA) score was determined at the time of arrival and at 1-year follow-up. Only 15 patients (12 with CSCI and 3 with TSCI) had 1-year follow-up. Whole-cord fractional anisotropy (FA) was determined at C1–2, following which C1–2 was divided into upper, middle, and lower segments and the corresponding FA value at each of these segments was calculated. Correlation analysis was performed between FA and ASIA score at time of arrival and 1-year follow-up.

RESULTS

Correlation analysis showed a positive but nonsignificant correlation (p = 0.095) between FA and ASIA score for all patients (CSCI and TCSI) at the time of arrival. Additional regression analysis consisting of only patients with CSCI showed a significant correlation (p = 0.008) between FA and ASIA score at time of arrival as well as at 1-year follow-up (p = 0.025). Furthermore, in case of patients with CSCI, a significant correlation between FA value at each of the segments (upper, middle, and lower) of C1–2 and ASIA score at time of arrival was found (p = 0.017, p = 0.015, and p = 0.002, respectively).

CONCLUSIONS

In patients with CSCI, the measurement of diffusion anisotropy of the high cervical cord (C1–2) correlates significantly with injury severity and long-term follow-up. However, this correlation is not seen in patients with TSCI. Therefore, FA can be used as an imaging biomarker for evaluating neural injury and monitoring recovery in patients with CSCI.

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Sérgio A. F. Dantas, Eduardo J. L. Alho, Juliano J. da Silva, Nilson N. Mendes Neto, Erich Talamoni Fonoff and Clement Hamani

Hypothalamic deep brain stimulation (DBS) has been used for more than a decade to treat cluster headache (CH) but its mechanisms remain poorly understood. The authors have successfully treated a patient with CH using hypothalamic DBS and found that the contact used for chronic stimulation was located in a white matter region posterior to the mammillary bodies. Fiber tracts crossing that region were the medial forebrain bundle and those interconnecting the hypothalamus and brainstem, including the dorsal longitudinal fasciculus. Because the stimulation of axons is an important mechanism of DBS, some of its clinical effects in CH may be related to the stimulation of fibers interconnecting the hypothalamus and brainstem.

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Wataru Ishida, Joshua Casaos, Arun Chandra, Adam D’Sa, Seba Ramhmdani, Alexander Perdomo-Pantoja, Nicholas Theodore, George Jallo, Ziya L. Gokaslan, Jean-Paul Wolinsky, Daniel M. Sciubba, Ali Bydon, Timothy F. Witham and Sheng-Fu L. Lo

OBJECTIVE

With the advent of intraoperative electrophysiological neuromonitoring (IONM), surgical outcomes of various neurosurgical pathologies, such as brain tumors and spinal deformities, have improved. However, its diagnostic and therapeutic value in resecting intradural extramedullary (ID-EM) spinal tumors has not been well documented in the literature. The objective of this study was to summarize the clinical results of IONM in patients with ID-EM spinal tumors.

METHODS

A retrospective patient database review identified 103 patients with ID-EM spinal tumors who underwent tumor resection with IONM (motor evoked potentials, somatosensory evoked potentials, and free-running electromyography) from January 2010 to December 2015. Patients were classified as those without any new neurological deficits at the 6-month follow-up (group A; n = 86) and those with new deficits (group B; n = 17). Baseline characteristics, clinical outcomes, and IONM findings were collected and statistically analyzed. In addition, a meta-analysis in compliance with the PRISMA guidelines was performed to estimate the overall pooled diagnostic accuracy of IONM in ID-EM spinal tumor resection.

RESULTS

No intergroup differences were discovered between the groups regarding baseline characteristics and operative data. In multivariate analysis, significant IONM changes (p < 0.001) and tumor location (thoracic vs others, p = 0.018) were associated with new neurological deficits at the 6-month follow-up. In predicting these changes, IONM yielded a sensitivity of 82.4% (14/17), specificity of 90.7% (78/86), positive predictive value (PPV) of 63.6% (14/22), negative predictive value (NPV) of 96.3% (78/81), and area under the curve (AUC) of 0.893. The diagnostic value slightly decreased in patients with schwannomas (AUC = 0.875) and thoracic tumors (AUC = 0.842). Among 81 patients who did not demonstrate significant IONM changes at the end of surgery, 19 patients (23.5%) exhibited temporary intraoperative exacerbation of IONM signals, which were recovered by interruption of surgical maneuvers; none of these patients developed new neurological deficits postoperatively. Including the present study, 5 articles encompassing 323 patients were eligible for this meta-analysis, and the overall pooled diagnostic value of IONM was a sensitivity of 77.9%, a specificity of 91.1%, PPV of 56.7%, and NPV of 95.7%.

CONCLUSIONS

IONM for the resection of ID-EM spinal tumors is a reasonable modality to predict new postoperative neurological deficits at the 6-month follow-up. Future prospective studies are warranted to further elucidate its diagnostic and therapeutic utility.

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Spyridon Komaitis, Georgios P. Skandalakis, Aristotelis V. Kalyvas, Evangelos Drosos, Evgenia Lani, John Emelifeonwu, Faidon Liakos, Maria Piagkou, Theodosis Kalamatianos, George Stranjalis and Christos Koutsarnakis

OBJECTIVE

The aim of this study was to investigate the anatomical consistency, morphology, axonal connectivity, and correlative topography of the dorsal component of the superior longitudinal fasciculus (SLF-I) since the current literature is limited and ambiguous.

METHODS

Fifteen normal, adult, formalin-fixed cerebral hemispheres were studied through a medial to lateral fiber microdissection technique. In 5 specimens, the authors performed stepwise focused dissections of the lateral cerebral aspect to delineate the correlative anatomy between the SLF-I and the other two SLF subcomponents, namely the SLF-II and SLF-III.

RESULTS

The SLF-I was readily identified as a distinct fiber tract running within the cingulate or paracingulate gyrus and connecting the anterior cingulate cortex, the medial aspect of the superior frontal gyrus, the pre–supplementary motor area (pre-SMA), the SMA proper, the paracentral lobule, and the precuneus. With regard to the morphology of the SLF-I, two discrete segments were consistently recorded: an anterior and a posterior segment. A clear cleavage plane could be developed between the SLF-I and the cingulum, thus proving their structural integrity. Interestingly, no anatomical connection was revealed between the SLF-I and the SLF-II/SLF-III complex.

CONCLUSIONS

Study results provide novel and robust anatomical evidence on the topography, morphology, and subcortical architecture of the SLF-I. This fiber tract was consistently recorded as a distinct anatomical entity of the medial cerebral aspect, participating in the axonal connectivity of high-order paralimbic areas.

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Shanmukha Srinivas, Arvin R. Wali and Martin H. Pham

OBJECTIVE

Riluzole is a glutamatergic modulator that has recently shown potential for neuroprotection after spinal cord injury (SCI). While the effects of riluzole are extensively documented in animal models of SCI, there remains heterogeneity in findings. Moreover, there is a paucity of data on the pharmacology of riluzole and its effects in humans. For the present study, the authors systematically reviewed the literature to provide a comprehensive understanding of the effects of riluzole in SCI.

METHODS

The PubMed database was queried from 1996 to September 2018 to identify animal studies and clinical trials involving riluzole administration for SCI. Once articles were identified, they were processed for year of publication, study design, subject type, injury model, number of subjects in experimental and control groups, dose, timing/route of administration, and outcomes.

RESULTS

A total of 37 studies were included in this study. Three placebo-controlled clinical trials were included with a total of 73 patients with a mean age of 39.1 years (range 18–70 years). For the clinical trials included within this study, the American Spinal Injury Association Impairment Scale distributions for SCI were 42.6% grade A, 25% grade B, 26.6% grade C, and 6.2% grade D. Key findings from studies in humans included decreased nociception, improved motor function, and attenuated spastic reflexes. Twenty-six animal studies (24 in vivo, 1 in vitro, and 1 including both in vivo and in vitro) were included. A total of 520 animals/in vitro specimens were exposed to riluzole and 515 animals/in vitro specimens underwent other treatment for comparison. The average dose of riluzole for intraperitoneal, in vivo studies was 6.5 mg/kg (range 1–10 mg/kg). Key findings from animal studies included behavioral improvement, histopathological tissue sparing, and modified electrophysiology after SCI. Eight studies examined the pharmacology of riluzole in SCI. Key findings from pharmacological studies included riluzole dose-dependent effects on glutamate uptake and its modified bioavailability after SCI in both animal and clinical models.

CONCLUSIONS

SCI has many negative sequelae requiring neuroprotective intervention. While still relatively new in its applications for SCI, both animal and human studies demonstrate riluzole to be a promising pharmacological intervention to attenuate the devastating effects of this condition.

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Joshua D. Burks, Katie L. Gant, James D. Guest, Aria G. Jamshidi, Efrem M. Cox, Kim D. Anderson, W. Dalton Dietrich, Mary Bartlett Bunge, Barth A. Green, Aisha Khan, Damien D. Pearse, Efrat Saraf-Lavi and Allan D. Levi

OBJECTIVE

In cell transplantation trials for spinal cord injury (SCI), quantifiable imaging criteria that serve as inclusion criteria are important in trial design. The authors’ institutional experience has demonstrated an overall high rate of screen failures. The authors examined the causes for trial exclusion in a phase I, open-lab clinical trial examining the role of autologous Schwann cell intramedullary transplantation. Specifically, they reviewed the imaging characteristics in people with chronic SCI that excluded applicants from the trial, as this was a common cause of screening failures in their study.

METHODS

The authors reviewed MRI records from 152 people with chronic (> 1 year) SCI who volunteered for intralesional Schwann cell transplantation but were deemed ineligible by prospectively defined criteria. Rostral-caudal injury lesion length was measured along the long axis of the spinal cord in the sagittal plane on T2-weighted MRI. Other lesion characteristics, specifically those pertaining to lesion cavity structure resulting in trial exclusion, were recorded.

RESULTS

Imaging records from 152 potential participants with chronic SCI were reviewed, 42 with thoracic-level SCI and 110 with cervical-level SCI. Twenty-three individuals (55%) with thoracic SCI and 70 (64%) with cervical SCI were not enrolled in the trial based on imaging characteristics. For potential participants with thoracic injuries who did not meet the screening criteria for enrollment, the average rostral-caudal sagittal lesion length was 50 mm (SD 41 mm). In applicants with cervical injuries who did not meet the screening criteria for enrollment, the average sagittal lesion length was 34 mm (SD 21 mm).

CONCLUSIONS

While screening people with SCI for participation in a cell transplantation clinical trial, lesion length or volume can exclude potential subjects who appear appropriate candidates based on neurological eligibility criteria. In planning future cell-based therapy trials, the limitations incurred by lesion size should be considered early due to the screening burden and impact on candidate selection.

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Joseph P. Antonios, Ghassan J. Farah, Daniel R. Cleary, Joel R. Martin, Joseph D. Ciacci and Martin H. Pham

Spinal cord injury (SCI) has been associated with a dismal prognosis—recovery is not expected, and the most standard interventions have been temporizing measures that do little to mitigate the extent of damage. While advances in surgical and medical techniques have certainly improved this outlook, limitations in functional recovery continue to impede clinically significant improvements. These limitations are dependent on evolving immunological mechanisms that shape the cellular environment at the site of SCI. In this review, we examine these mechanisms, identify relevant cellular components, and discuss emerging treatments in stem cell grafts and adjuvant immunosuppressants that target these pathways. As the field advances, we expect that stem cell grafts and these adjuvant treatments will significantly shift therapeutic approaches to acute SCI with the potential for more promising outcomes.

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Paolo Belardinelli, Ramin Azodi-Avval, Erick Ortiz, Georgios Naros, Florian Grimm, Daniel Weiss and Alireza Gharabaghi

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for symptomatic Parkinson’s disease (PD); the clinical benefit may not only mirror modulation of local STN activity but also reflect consecutive network effects on cortical oscillatory activity. Moreover, STN-DBS selectively suppresses spatially and spectrally distinct patterns of synchronous oscillatory activity within cortical-subcortical loops. These STN-cortical circuits have been described in PD patients using magnetoencephalography after surgery. This network information, however, is currently not available during surgery to inform the implantation strategy.

The authors recorded spontaneous brain activity in 3 awake patients with PD (mean age 67 ± 14 years; mean disease duration 13 ± 7 years) during implantation of DBS electrodes into the STN after overnight withdrawal of dopaminergic medication. Intraoperative propofol was discontinued at least 30 minutes prior to the electrophysiological recordings. The authors used a novel approach for performing simultaneous recordings of STN local field potentials (LFPs) and multichannel electroencephalography (EEG) at rest. Coherent oscillations between LFP and EEG sensors were computed, and subsequent dynamic imaging of coherent sources was performed.

The authors identified coherent activity in the upper beta range (21–35 Hz) between the STN and the ipsilateral mesial (pre)motor area. Coherence in the theta range (4–6 Hz) was detected in the ipsilateral prefrontal area.

These findings demonstrate the feasibility of detecting frequency-specific and spatially distinct synchronization between the STN and cortex during DBS surgery. Mapping the STN with this technique may disentangle different functional loops relevant for refined targeting during DBS implantation.