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IntroductionNeuroworsening may be a sign of progressive brain injury and is a factor for treatment of traumatic brain injury (TBI) in intensive care settings. The implications of neuroworsening for clinical management and long-term sequelae of TBI in the emergency department (ED) require characterization.MethodsAdult TBI subjects from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study with ED admission and disposition Glasgow Coma Scale (GCS) scores were extracted. All patients received head computed tomography (CT) scan

ObjectivesSpine surgery is associated with early impairment of gastrointestinal motility, with postoperative ileus rates of 5-12%. A standardized postoperative medication regimen aimed at early restoration of bowel function can reduce morbidity and cost, and its study should be prioritized.MethodsA standardized postoperative bowel medication protocol was implemented for all elective spine surgeries performed by a single neurosurgeon from March 1, 2022 to June 30, 2022 at a metropolitan Veterans Affairs medical center. Daily bowel function was tracked and medications were advanced using the protocol. Clinical, surgical, and length of stay data are reported.ResultsAcross 20 consecutive surgeries in 19 patients, mean age was 68.9 years [standard deviation (SD) = 10; range 40-84]. Seventy-four percent reported preoperative constipation. Surgeries consisted of 45% fusion and 55% decompression; lumbar retroperitoneal approaches constituted 30% (10% anterior, 20% lateral). Two patients were discharged in good condition prior to bowel movement after meeting institutional discharge criteria; the other 18 cases all had return of bowel function by postoperative day (POD) 3 (mean = 1.8-days, SD = 0.7). There were no inpatient or 30-day complications. Mean discharge occurred 3.3-days post-surgery (SD = 1.5; range 1-6; home 95%, skilled nursing facility 5%). Estimated cumulative cost of the bowel regimen was $17 on POD 3.ConclusionsCareful monitoring of return of bowel function after elective spine surgery is important for preventing ileus, reducing healthcare cost, and ensuring quality. Our standardized postoperative bowel regimen was associated with return of bowel function within 3 days and low costs. These findings can be utilized in quality-of-care pathways.

BackgroundTraumatic subdural hematomas (SDH) can have devastating neurologic consequences. Acute-on-chronic SDHs are more frequent in the elderly, who have increased comorbidities and perioperative risks. The subdural evacuation port system (SEPS) procedure consists of a twist drill hole connected to a single drain on suction, which can be performed at bedside to evacuate SDHs without requiring general anesthesia. However, a single SEPS can be limited due to inability to evacuate across septations between SDHs of different ages.PurposeWe present to our knowledge the first case of using tandem SEPS to evacuate a multi-loculated SDH. We discuss the technical nuances of the procedure as a treatment option for complex SDHs.FindingsAn 86-year-old man with cognitive impairment and recurrent falls presented acutely after ground-level fall with worsening dysarthria and right hemiparesis. Computed tomography scan showed a 11 mm left holohemispheric mixed-density SDH with loculated acute and subacute/chronic components with 2 mm midline shift. Following two interval stability scans, the patient underwent drainage of a superficial chronic component, and a posterolateral acute/subacute component using two sequential SEPS drains at bedside in the intensive care unit. The patient's symptoms markedly improved, drains were removed, and the patient was discharged home with home health on post-procedure day 6.ConclusionsJudicious patient selection and pre-procedural planning can enable the use of tandem SEPS to evacuate multi-loculated SDHs under moderate sedation. Using multiple subdural ports to evacuate complex SDHs should be an option for proceduralists in settings where general anesthesia is not feasible.

BackgroundThe Centers for Medicare and Medicaid Services (CMS) hierarchical condition category (HCC) coding is a risk adjustment model that allows for the estimation of risk-and cost-associated with health care provision. Current models may not include key factors that fully delineate the risk associated with spine surgery.ObjectiveTo augment CMS HCC risk adjustment methodology with socioeconomic data to improve its predictive capabilities for spine surgery.MethodsThe National Inpatient Sample was queried for spinal fusion, and the data was merged with county-level coverage and socioeconomic status variables obtained from the Brookings Institute. We predicted outcomes (death, nonroutine discharge, length of stay [LOS], total charges, and perioperative complication) with pairs of hierarchical, mixed effects logistic regression models-one using CMS HCC score alone and another augmenting CMS HCC scores with demographic and socioeconomic status variables. Models were compared using receiver operating characteristic curves. Variable importance was assessed in conjunction with Wald testing for model optimization.ResultsWe analyzed 653 815 patients. Expanded models outperformed models using CMS HCC score alone for mortality, nonroutine discharge, LOS, total charges, and complications. For expanded models, variable importance analyses demonstrated that CMS HCC score was of chief importance for models of mortality, LOS, total charges, and complications. For the model of nonroutine discharge, age was the most important variable. For the model of total charges, unemployment rate was nearly as important as CMS HCC score.ConclusionThe addition of key demographic and socioeconomic characteristics substantially improves the CMS HCC risk-adjustment models when modeling spinal fusion outcomes. This finding may have important implications for payers, hospitals, and policymakers.

Introduction: We present a case of a 10-month-old girl undergoing repetitive TMS (rTMS) for the treatment of drug-resistant epilepsy. Case report: A 10-month-old girl, later diagnosed with pathogenic POLG1 mutations, presented to our institution with chronic progressive EPC (epilepsia partialis continua) manifesting as a frequent, left-sided, synchronous continuous jerking of the arms and legs. The seizures were drug-resistant to multiple antiseizure medications and epilepsy surgery, responding only to continuous anesthesia. rTMS therapy was attempted to interrupt seizures. Results: rTMS therapy, using an activating protocol to introduce a temporary lesion effect, was used to interrupt persistent, ongoing seizures. Conclusion: rTMS can be safely used to abort seizures in patients as young as 10 months old.

ObjectiveGliomas are intrinsic brain tumors with the hallmark of diffuse white matter infiltration, resulting in short- and long-range network dysfunction. Preoperative magnetoencephalography (MEG) can assist in maximizing the extent of resection while minimizing morbidity. While MEG has been validated in motor mapping, its role in speech mapping remains less well studied. The authors assessed how the resection of intraoperative electrical stimulation (IES)-negative, high functional connectivity (HFC) network sites, as identified by MEG, impacts language performance.MethodsResting-state, whole-brain MEG recordings were obtained from 26 patients who underwent perioperative language evaluation and glioma resection that was guided by awake language and IES mapping. The functional connectivity of an individual voxel was determined by the imaginary coherence between the index voxel and the rest of the brain, referenced to its contralesional pair. The percentage of resected HFC voxels was correlated with postoperative language outcomes in tasks of increasing complexity: text reading, 4-syllable repetition, picture naming, syntax (SYN), and auditory stimulus naming (AN).ResultsOverall, 70% of patients (14/20) in whom any HFC tissue was resected developed an early postoperative language deficit (mean 2.3 days, range 1-8 days), compared to 33% of patients (2/6) in whom no HFC tissue was resected (p = 0.16). When bifurcated by the amount of HFC tissue that was resected, 100% of patients (3/3) with an HFC resection > 25% displayed deficits in AN, compared to 30% of patients (6/20) with an HFC resection < 25% (p = 0.04). Furthermore, there was a linear correlation between the severity of AN and SYN decline with percentage of HFC sites resected (p = 0.02 and p = 0.04, respectively). By 2.2 months postoperatively (range 1-6 months), the correlation between HFC resection and both AN and SYN decline had resolved (p = 0.94 and p = 1.00, respectively) in all patients (9/9) except two who experienced early postoperative tumor progression or stroke involving inferior frontooccipital fasciculus.ConclusionsImaginary coherence measures of functional connectivity using MEG are able to identify HFC network sites within and around low- and high-grade gliomas. Removal of IES-negative HFC sites results in early transient postoperative decline in AN and SYN, which resolved by 3 months in all patients without stroke or early tumor progression. Measures of functional connectivity may therefore be a useful means of counseling patients about postoperative risk and assist with preoperative surgical planning.

Objective: The adult brain's potential for plastic reorganization is an important mechanism for the preservation and restoration of function in patients with primary glial neoplasm. Patients with recurrent brain tumors requiring multiple interventions over time present an opportunity to examine brain reorganization. Magnetoencephalography (MEG) is a noninvasive imaging modality that can be used for motor cortical network mapping which, when performed at regular intervals, offers insight into this process of reorganization. Utilizing MEG-based motor mapping, we sought to characterize the reorganization of motor cortical networks over time in a cohort of 78 patients with recurrent glioma. Methods: MEG-based motor cortical maps were obtained by measuring event-related desynchronization (ERD) in ß-band frequency during unilateral index finger flexion. Each patient presented at our Department at least on two occasions for tumor resection due to tumor recurrence, and MEG-based motor mapping was performed as part of preoperative assessment before each surgical resection. Whole-brain activation patterns from first to second MEG scan (obtained before first and second surgery) were compared. Additionally, we calculated distances of activation peaks, which represent the location of the primary motor cortex (MC), to determine the magnitude of movement in motor eloquent areas between the first and second MEG scan. We also explored which demographic, anatomic, and pathological factors influence these shifts. Results: The whole-brain activation motor maps showed a subtle movement of the primary MC from first to second timepoint, as was confirmed by the determination of motor activation peaks. The shift of ipsilesional MC was directly correlated with a frontal-parietal tumor location (p < 0.001), presence of motor deficits (p = 0.021), and with a longer period between MEG scans (p = 0.048). Also, a disengagement of wide areas in the contralesional (ipsilateral to finger movement) hemisphere at the second time point was observed. Conclusions: MEG imaging is a sensitive method for depicting the plasticity of the motor cortical network. Although the location of the primary MC undergoes only subtle changes, appreciable shifts can occur in the setting of a stronger and longer impairment of the tumor on the MC. The ipsilateral hemisphere may serve as a reservoir for functional recovery.

In patients with gliomas, changes in hemispheric specialization for language determined by magnetoencephalography (MEG) were analyzed to elucidate the impact of treatment and tumor recurrence on language networks. Demonstration of reorganization of language networks in these patients has significant implications on the prevention of postoperative functional loss and recovery. Whole-brain activity during an auditory verb generation task was estimated from MEG recordings in a group of 73 patients with recurrent gliomas. Hemisphere of language dominance was estimated using the language laterality index (LI), a measure derived from the task. The initial scan was performed prior to resection; patients subsequently underwent surgery and adjuvant treatment. A second scan was performed upon recurrence prior to repeat resection. The relationship between the shift in LI between scans and demographics, anatomic location, pathology, and adjuvant treatment was analyzed. Laterality shifts were observed between scans; the median percent change was 29.1% across all patients. Laterality shift magnitude and relative direction were associated with the initial position of language dominance; patients with increased lateralization experienced greater shifts than those presenting more bilateral representation. A change in LI from left or right to bilateral (or vice versa) occurred in 23.3% of patients; complete switch occurred in 5.5% of patients. Patients with tumors within the language-dominant hemisphere experienced significantly greater shifts than those with contralateral tumors. The majority of patients with glioma experience shifts in language network organization over time which correlate with the relative position of language lateralization and tumor location.

IntroductionThe apolipoprotein E (APOE) ε4 allele associates with memory impairment in neurodegenerative diseases. Its association with memory after mild traumatic brain injury (mTBI) is unclear.MethodsmTBI patients (Glasgow Coma Scale score 13-15, no neurosurgical intervention, extracranial Abbreviated Injury Scale score ≤1) aged ≥18 years with APOE genotyping results were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study. Cohorts determined by APOE-ε4(+/-) were assessed for associations with 6-month verbal memory, measured by California Verbal Learning Test, Second Edition (CVLT-II) subscales: Immediate Recall Trials 1-5 (IRT), Short-Delay Free Recall (SDFR), Short-Delay Cued Recall (SDCR), Long-Delay Free Recall (LDFR), and Long-Delay Cued Recall (LDCR). Multivariable regression controlled for demographic factors, seizure history, loss of consciousness, posttraumatic amnesia, and acute intracranial pathology on computed tomography (CT).ResultsIn 114 mTBI patients (APOE-ε4(-)=79; APOE-ε4(+)=35), ApoE-ε4(+) was associated with long-delay verbal memory deficits (LDFR: B = -1.17 points, 95% CI [-2.33, -0.01], p = .049; LDCR: B = -1.58 [-2.63, -0.52], p = .004), and a marginal decrease on SDCR (B = -1.02 [-2.05, 0.00], p = .050). CT pathology was the strongest predictor of decreased verbal memory (IRT: B = -8.49, SDFR: B = -2.50, SDCR: B = -1.85, LDFR: B = -2.61, LDCR: B = -2.60; p

The prevalence of neuropsychiatric disorders following traumatic brain injury (TBI) is 20%-50%, and disorders of mood and cognition may remain even after recovery of neurologic function is achieved. Selective serotonin reuptake inhibitors (SSRI) block the reuptake of serotonin in presynaptic cells to lead to increased serotonergic activity in the synaptic cleft, constituting first-line treatment for a variety of neurocognitive and neuropsychiatric disorders. This review investigates the utility of SSRIs in treating post-TBI disorders. In total, 37 unique reports were consolidated from the Cochrane Central Register and PubMed (eight randomized-controlled trials (RCTs), nine open-label studies, 11 case reports, nine review articles). SSRIs are associated with improvement of depressive but not cognitive symptoms. Pooled analysis using the Hamilton Depression Rating Scale demonstrate a significant mean decrease of depression severity following sertraline compared to placebo-a result supported by several other RCTs with similar endpoints. Evidence from smaller studies demonstrates mood improvement following SSRI administration with absent or negative effects on cognitive and functional recovery. Notably, studies on SSRI treatment effects for post-traumatic stress disorder after TBI remain absent, and this represents an important direction of future research. Furthermore, placebo-controlled studies with extended follow-up periods and concurrent biomarker, neuroimaging and behavioral data are necessary to delineate the attributable pharmacological effects of SSRIs in the TBI population.

Mild traumatic brain injury (mTBI) results in variable clinical trajectories and outcomes. The source of variability remains unclear, but may involve genetic variations, such as single nucleotide polymorphisms (SNPs). A SNP in catechol-o-methyltransferase (COMT) is suggested to influence development of post-traumatic stress disorder (PTSD), but its role in TBI remains unclear. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val158Met polymorphism is associated with PTSD and global functional outcome as measured by the PTSD Checklist - Civilian Version and Glasgow Outcome Scale Extended (GOSE), respectively. Results in 93 predominately Caucasian subjects with mTBI show that the COMT Met158 allele is associated with lower incidence of PTSD (univariate odds ratio (OR) of 0.25, 95% CI [0.09-0.69]) and higher GOSE scores (univariate OR 2.87, 95% CI [1.20-6.86]) 6-months following injury. The COMT Val158Met genotype and PTSD association persists after controlling for race (multivariable OR of 0.29, 95% CI [0.10-0.83]) and pre-existing psychiatric disorders/substance abuse (multivariable OR of 0.32, 95% CI [0.11-0.97]). PTSD emerged as a strong predictor of poorer outcome on GOSE (multivariable OR 0.09, 95% CI [0.03-0.26]), which persists after controlling for age, GCS, and race. When accounting for PTSD in multivariable analysis, the association of COMT genotype and GOSE did not remain significant (multivariable OR 1.73, 95% CI [0.69-4.35]). Whether COMT genotype indirectly influences global functional outcome through PTSD remains to be determined and larger studies in more diverse populations are needed to confirm these findings.

Traumatic brain injury (TBI) often leads to heterogeneous clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism (SNP) in the dopamine D2 receptor (DRD2) may influence cognitive deficits following TBI. However, part of the association with DRD2 has been attributed to genetic variability within the adjacent ankyrin repeat and kinase domain containing 1 protein (ANKK1). Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether a novel DRD2 C957T polymorphism (rs6277) influences outcome on a cognitive battery at 6 months following TBI-California Verbal Learning Test (CVLT-II), Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), and Trail Making Test (TMT). Results in 128 Caucasian subjects show that the rs6277 T-allele associates with better verbal learning and recall on CVLT-II Trials 1-5 (T-allele carrier 52.8 ± 1.3 points, C/C 47.9 ± 1.7 points; mean increase 4.9 points, 95% confidence interval [0.9 to 8.8]; p = 0.018), Short-Delay Free Recall (T-carrier 10.9 ± 0.4 points, C/C 9.7 ± 0.5 points; mean increase 1.2 points [0.1 to 2.5]; p = 0.046), and Long-Delay Free Recall (T-carrier 11.5 ± 0.4 points, C/C 10.2 ± 0.5 points; mean increase 1.3 points [0.1 to 2.5]; p = 0.041) after adjusting for age, education years, Glasgow Coma Scale, presence of acute intracranial pathology on head computed tomography scan, and genotype of the ANKK1 SNP rs1800497 using multivariable regression. No association was found between DRD2 C947T and non-verbal processing speed (WAIS-PSI) or mental flexibility (TMT) at 6 months. Hence, DRD2 C947T (rs6277) may be associated with better performance on select cognitive domains independent of ANKK1 following TBI.

IntroductionThe Glasgow Coma Scale (GCS) score is the primary method of assessing consciousness after traumatic brain injury (TBI), and the clinical standard for classifying TBI severity. There is scant literature discerning the influence of circadian rhythms or emergency department (ED) arrival hour on this important clinical tool.MethodsRetrospective cohort analysis of adult patients suffering blunt TBI using the National Sample Program of the National Trauma Data Bank, years 2003-2006. ED arrival GCS score was characterized by midday (10 a.m.-4 p.m.) and midnight (12 a.m.-6 a.m.) cohorts (N=24548). Proportions and standard errors are reported for descriptive data. Multivariable regressions using odds ratios (OR), mean differences (B), and their associated 95% confidence intervals [CI] were performed to assess associations between ED arrival hour and GCS score. Statistical significance was assessed at p

Tuberculum sellae meningiomas frequently produce visual loss by direct compression from tumor, constriction of the optic nerve (ON) under the falciform ligament, and/or ON ischemia. The authors hypothesized that changes in visual function after tumor removal may be related to changes in blood supply to the ON that might be seen in the pial circulation at surgery. Indocyanine green (ICG) angiography was used to attempt to document these changes at surgery. The first patient in whom the technique was used had a left-sided, 1.4-cm, tuberculum meningioma. Time-lapse comparison of images was done postsurgery, and the comparison of video images revealed both faster initial filling and earlier complete filling of the ON pial circulation, suggesting improved pial blood flow after surgical decompression. In follow-up the patient had significant improvements in both visual acuity and visual fields function. Intraoperative ICG angiography of the ON can demonstrate measurable changes in pial vascular flow that may be predictive of postoperative visual outcome. The predictive value of this technique during neurosurgical procedures around the optic apparatus warrants further investigation in a larger cohort.

ObjectiveAsymmetric large-amplitude slow activity is sometimes observed on interictal electroencephalography (EEG) in epilepsy. However, few studies have examined slowing during magnetoencephalography (MEG) recordings, which are performed primarily to localize interictal spikes. Also, no prior investigations have compared the sensitivity of MEG to scalp EEG in detecting slow rhythms.MethodsWe performed a retrospective cohort study of focal epilepsy patients who received MEG followed by surgical resection at our institution. We examined MEG, simultaneous EEG, and long-term EEG recordings for prominent asymmetric slow activity (delta-range, 1-4 Hz), and evaluated post-operative seizure outcomes.ResultsWe studied 132 patients with ≥ 1 year post-operative follow-up (mean, 3.6 years). Mean age was 27 (range, 3-68) years, and 55% of patients were male. Asymmetric large-amplitude slow wave activity was observed on interictal MEG in 21 of 132 (16%) patients. Interictal slowing lateralized to the hemisphere of resection in all but one (95%) patient. Among the 21 patients with interictal MEG slowing, 11 (52%) individuals had similarly lateralized EEG slowing, 7 patients had no EEG slowing, and 3 had bilateral symmetric EEG slowing. Meanwhile, none of the 111 patients without lateralized MEG slowing had asymmetric EEG slowing, suggesting significantly higher sensitivity of MEG versus EEG in detecting asymmetric slowing (χ(2)=63.4, p

IntroductionPreoperative mapping of motor areas with navigated transcranial magnetic stimulation (nTMS) has been shown to improve surgical outcomes for peri-Rolandic lesions and, in particular, for gliomas. However, the impact of this technique on surgical outcomes for peri-Rolandic metastatic lesions is yet unknown.ObjectiveTo investigate the impact of nTMS on surgical outcomes for peri-Rolandic metastatic lesions, various clinical parameters were analyzed in our international study group.MethodsTwo prospectively enrolled cohorts were compared by investigating patients receiving preoperative nTMS (2010-2015; 120 patients) and patients who did not receive preoperative nTMS (2006-2015; 130 patients). Tumor location, pathology, size, and preoperative deficits were comparable.ResultsThe nTMS group showed a lower rate of residual tumor on postoperative magnetic resonance imaging (odds ratio 0.3025; 95% confidence interval 0.1356-0.6749). On long-term follow-up, surgery-related paresis was decreased in the nTMS group (nTMS vs. non-nTMS; improved: 30.8 vs. 13.1%, unchanged: 65.8 vs. 73.8%, worse: 3.4 vs. 13.1% of patients; p = 0.0002). Moreover, the nTMS group received smaller craniotomies (nTMS: 16.7 ± 8.6 cm2 vs. non-nTMS: 25.0 ± 17.1 cm2; p

Mild traumatic brain injury (mTBI) results in variable clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism in catechol-o-methyltransferase (COMT), an enzyme which degrades catecholamine neurotransmitters, may influence cognitive deficits following moderate and/or severe head trauma. However, this has been disputed, and its role in mTBI has not been studied. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val (158) Met polymorphism influences outcome on a cognitive battery 6 months following mTBI--Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), Trail Making Test (TMT) Trail B minus Trail A time, and California Verbal Learning Test, Second Edition Trial 1-5 Standard Score (CVLT-II). All patients had an emergency department Glasgow Coma Scale (GCS) of 13-15, no acute intracranial pathology on head CT, and no polytrauma as defined by an Abbreviated Injury Scale (AIS) score of ≥3 in any extracranial region. Results in 100 subjects aged 40.9 (SD 15.2) years (COMT Met (158) /Met (158) 29 %, Met (158) /Val (158) 47 %, Val (158) /Val (158) 24 %) show that the COMT Met (158) allele (mean 101.6 ± SE 2.1) associates with higher nonverbal processing speed on the WAIS-PSI when compared to Val (158) /Val (158) homozygotes (93.8 ± SE 3.0) after controlling for demographics and injury severity (mean increase 7.9 points, 95 % CI [1.4 to 14.3], p = 0.017). The COMT Val (158) Met polymorphism did not associate with mental flexibility on the TMT or with verbal learning on the CVLT-II. Hence, COMT Val (158) Met may preferentially modulate nonverbal cognition following uncomplicated mTBI.Registry: ClinicalTrials.gov Identifier NCT01565551.

Intractable focal epilepsy is a devastating disorder with profound effects on cognition and quality of life. Epilepsy surgery can lead to seizure freedom in patients with focal epilepsy; however, sometimes it fails due to an incomplete delineation of the epileptogenic zone. Brain networks in epilepsy can be studied with resting-state functional connectivity analysis, yet previous investigations using functional magnetic resonance imaging or electrocorticography have produced inconsistent results. Magnetoencephalography allows non-invasive whole-brain recordings, and can be used to study both long-range network disturbances in focal epilepsy and regional connectivity at the epileptogenic zone. In magnetoencephalography recordings from presurgical epilepsy patients, we examined: (i) global functional connectivity maps in patients versus controls; and (ii) regional functional connectivity maps at the region of resection, compared to the homotopic non-epileptogenic region in the contralateral hemisphere. Sixty-one patients were studied, including 30 with mesial temporal lobe epilepsy and 31 with focal neocortical epilepsy. Compared with a group of 31 controls, patients with epilepsy had decreased resting-state functional connectivity in widespread regions, including perisylvian, posterior temporo-parietal, and orbitofrontal cortices (P < 0.01, t-test). Decreased mean global connectivity was related to longer duration of epilepsy and higher frequency of consciousness-impairing seizures (P < 0.01, linear regression). Furthermore, patients with increased regional connectivity within the resection site (n = 24) were more likely to achieve seizure postoperative seizure freedom (87.5% with Engel I outcome) than those with neutral (n = 15, 64.3% seizure free) or decreased (n = 23, 47.8% seizure free) regional connectivity (P < 0.02, chi-square). Widespread global decreases in functional connectivity are observed in patients with focal epilepsy, and may reflect deleterious long-term effects of recurrent seizures. Furthermore, enhanced regional functional connectivity at the area of resection may help predict seizure outcome and aid surgical planning.

ObjectiveLesion-based mapping of speech pathways has been possible only during invasive neurosurgical procedures using direct cortical stimulation (DCS). However, navigated transcranial magnetic stimulation (nTMS) may allow for lesion-based interrogation of language pathways noninvasively. Although not lesion-based, magnetoencephalographic imaging (MEGI) is another noninvasive modality for language mapping. In this study, we compare the accuracy of nTMS and MEGI with DCS.MethodsSubjects with lesions around cortical language areas underwent preoperative nTMS and MEGI for language mapping. nTMS maps were generated using a repetitive TMS protocol to deliver trains of stimulations during a picture naming task. MEGI activation maps were derived from adaptive spatial filtering of beta-band power decreases prior to overt speech during picture naming and verb generation tasks. The subjects subsequently underwent awake language mapping via intraoperative DCS. The language maps obtained from each of the 3 modalities were recorded and compared.ResultsnTMS and MEGI were performed on 12 subjects. nTMS yielded 21 positive language disruption sites (11 speech arrest, 5 anomia, and 5 other) while DCS yielded 10 positive sites (2 speech arrest, 5 anomia, and 3 other). MEGI isolated 32 sites of peak activation with language tasks. Positive language sites were most commonly found in the pars opercularis for all three modalities. In 9 instances the positive DCS site corresponded to a positive nTMS site, while in 1 instance it did not. In 4 instances, a positive nTMS site corresponded to a negative DCS site, while 169 instances of negative nTMS and DCS were recorded. The sensitivity of nTMS was therefore 90%, specificity was 98%, the positive predictive value was 69% and the negative predictive value was 99% as compared with intraoperative DCS. MEGI language sites for verb generation and object naming correlated with nTMS sites in 5 subjects, and with DCS sites in 2 subjects.ConclusionMaps of language function generated with nTMS correlate well with those generated by DCS. Negative nTMS mapping also correlates with negative DCS mapping. In our study, MEGI lacks the same level of correlation with intraoperative mapping; nevertheless it provides useful adjunct information in some cases. nTMS may offer a lesion-based method for noninvasively interrogating language pathways and be valuable in managing patients with peri-eloquent lesions.

PurposePrognostic factors affecting outcomes in pediatric spinal cord ependymomas are limited. We sought to investigate potential associations between extent of resection and histologic grade on progression-free survival (PFS) and overall survival (OS).MethodsA comprehensive literature search was performed to identify pediatric patients who underwent surgical resection for spinal cord ependymomas. Only manuscripts with clearly defined age, tumor grade, extent of resection, and clinical follow-up were included.ResultsA total of 80 patients were identified with a histologic distribution as follows: 36 % myxopapillary (grade I), 54 % classical (grade II), and 10 % anaplastic (grade III). There was no association between tumor grade and PFS. The only factor associated with improved PFS was gross total resection (GTR), which remained significant in a multivariate model (hazard ratio (HR) = 0.248, p = 0.022). Moreover, older age (HR = 0.818, p = 0.026), GTR (HR = 0.042, p = 0.013), and anaplastic grade (HR = 19.847, p = 0.008) demonstrated a significant association with OS in a multivariate model.ConclusionsAmong pediatric patients with spinal cord ependymomas, PFS did not differ across histologic grades but was prolonged among patients who underwent GTR. Age, extent of resection, and tumor grade were all significantly associated with survival.

Although the World Health Organization (WHO) categorizes spinal ependymomas into three histological grades, difference in surgical outcomes between WHO grades I and II tumors are unclear. For these benign tumors, prognosis may be best determined by factors other than tumor grade alone, such as extent of resection. To analyze the effects of the extent of resection on different grades of spinal ependymomas, we performed a comprehensive literature review to identify adult spinal ependymoma patients who received surgical resection with a clearly identifiable WHO grade. A total of 175 patients were identified. While grade III tumors carried the worst prognosis as expected (p

ObjectTraumatic brain injury (TBI) is one of the leading causes of morbidity worldwide. One mechanism by which blunt head trauma may disrupt normal cognition and behavior is through alteration of functional connectivity between brain regions. In this pilot study, the authors applied a rapid automated resting state magnetoencephalography (MEG) imaging technique suitable for routine clinical use to test the hypothesis that there is decreased functional connectivity in patients with TBI compared with matched controls, even in cases of mild TBI. Furthermore, they posit that these abnormal reductions in MEG functional connectivity can be detected even in TBI patients without specific evidence of traumatic lesions on 3-T MR images. Finally, they hypothesize that the reductions of functional connectivity can improve over time across serial MEG scans during recovery from TBI.MethodsMagnetoencephalography maps of functional connectivity in the alpha (8- to 12-Hz) band from 21 patients who sustained a TBI were compared with those from 18 age- and sex-matched controls. Regions of altered functional connectivity in each patient were detected in automated fashion through atlas-based registration to the control database. The extent of reduced functional connectivity in the patient group was tested for correlations with clinical characteristics of the injury as well as with findings on 3-T MRI. Finally, the authors compared initial connectivity maps with 2-year follow-up functional connectivity in a subgroup of 5 patients with TBI.ResultsFourteen male and 7 female patients (17-53 years old, median 29 years) were enrolled. By Glasgow Coma Scale (GCS) criteria, 11 patients had mild, 1 had moderate, and 3 had severe TBI, and 6 had no GCS score recorded. On 3-T MRI, 16 patients had abnormal findings attributable to the trauma and 5 had findings in the normal range. As a group, the patients with TBI had significantly lower functional connectivity than controls (p < 0.01). Three of the 5 patients with normal findings on 3-T MRI showed regions of abnormally reduced MEG functional connectivity. No significant correlations were seen between extent of functional disconnection and injury severity or posttraumatic symptoms (p > 0.05). In the subgroup undergoing 2-year follow-up, the second MEG scan demonstrated a significantly lower percentage of voxels with decreased connectivity (p < 0.05) than the initial MEG scan.ConclusionsA rapid automated resting-state MEG imaging technique demonstrates abnormally decreased functional connectivity that may persist for years after TBI, including cases classified as "mild" by GCS criteria. Disrupted MEG connectivity can be detected even in some patients with normal findings on 3-T MRI. Analysis of follow-up MEG scans in a subgroup of patients shows that, over time, the abnormally reduced connectivity can improve, suggesting neuroplasticity during the recovery from TBI. Resting state MEG deserves further investigation as a prognostic and predictive biomarker for TBI.

BackgroundThe removal of brain tumors in perieloquent or eloquent cortex risks causing new neurological deficits in patients. The assessment of the functionality of perilesional tissue is essential to avoid postoperative neurological morbidity.ObjectiveTo evaluate preoperative magnetoencephalography-based functional connectivity as a predictor of short- and medium-term neurological outcome after removal of gliomas in perieloquent and eloquent areas.MethodsResting-state whole-brain magnetoencephalography recordings were obtained from 79 consecutive subjects with focal brain gliomas near or within motor, sensory, or language areas. Neural activity was estimated using adaptive spatial filtering. The mean imaginary coherence between voxels in and around brain tumors was compared with contralesional voxels and used as an index of their functional connectivity with the rest of the brain. The connectivity values of the tissue resected during surgery were correlated with the early (1 week postoperatively) and medium-term (6 months postoperatively) neurological morbidity.ResultsPatients undergoing resection of tumors with decreased functional connectivity had a 29% rate of a new neurological deficit 1 week after surgery and a 0% rate at 6-month follow-up. Patients undergoing resection of tumors with increased functional connectivity had a 60% rate of a new deficit at 1 week and a 25% rate at 6 months.ConclusionMagnetoencephalography connectivity analysis gives a valuable preoperative evaluation of the functionality of the tissue surrounding tumors in perieloquent and eloquent areas. These data may be used to optimize preoperative patient counseling and surgical strategy.

ObjectDirect cortical stimulation (DCS) is the gold-standard technique for motor mapping during craniotomy. However, preoperative noninvasive motor mapping is becoming increasingly accurate. Two such noninvasive modalities are navigated transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) imaging. While MEG imaging has already been extensively validated as an accurate modality of noninvasive motor mapping, TMS is less well studied. In this study, the authors compared the accuracy of TMS to both DCS and MEG imaging.MethodsPatients with tumors in proximity to primary motor cortex underwent preoperative TMS and MEG imaging for motor mapping. The patients subsequently underwent motor mapping via intraoperative DCS. The loci of maximal response were recorded from each modality and compared. Motor strength was assessed at 3 months postoperatively.ResultsTranscranial magnetic stimulation and MEG imaging were performed on 24 patients. Intraoperative DCS yielded 8 positive motor sites in 5 patients. The median distance ± SEM between TMS and DCS motor sites was 2.13 ± 0.29 mm, and between TMS and MEG imaging motor sites was 4.71 ± 1.08 mm. In no patients did DCS motor mapping reveal a motor site that was unrecognized by TMS. Three of 24 patients developed new, early neurological deficit in the form of upper-extremity paresis. At the 3-month follow-up evaluation, 2 of these patients were significantly improved, experiencing difficulty only with fine motor tasks; the remaining patient had improvement to 4/5 strength. There were no deaths over the course of the study.ConclusionsMaps of the motor system generated with TMS correlate well with those generated by both MEG imaging and DCS. Negative TMS mapping also correlates with negative DCS mapping. Navigated TMS is an accurate modality for noninvasively generating preoperative motor maps.