Intraoperative cortical stimulation mapping with laryngeal electromyography for the localization of human laryngeal motor cortex.

OBJECTIVE: The objectives of this study were to describe the authors' clinical methodology and outcomes for mapping the laryngeal motor cortex (LMC) and define localization of the LMC in a cohort of neurosurgical patients undergoing intraoperative brain mapping. Because of mapping variability across patients, the authors aimed to define the probabilistic distribution of cortical sites that evoke laryngeal movement, as well as adjacent cortical somatotopic representations for the face (mouth), tongue, and hand. METHODS: Thirty-six patients underwent left (n = 18) or right (n = 18) craniotomy with asleep motor mapping. For each patient, electromyography (EMG) electrodes were placed in the face, tongue, and hand; a nerve integrity monitor (NIM) endotracheal tube with surface electrodes detected EMG activity from the bilateral vocal folds. After dense cortical stimulation was delivered throughout the sensorimotor cortex, motor responses were then mapped onto a three-dimensional reconstruction of the patient's cortical surfaces for location characterization of the evoked responses. Finally, stimulation sites were transformed into a two-dimensional coordinate system for probabilistic mapping of the stimulation site relative to the central sulcus and sylvian fissure. RESULTS: The authors found that the LMC was predominantly localized to a mid precentral gyrus region, dorsal to face representation and surrounding a transverse sulcus ventral to the hand knob. In 14 of 36 patients, the authors identified additional laryngeal responses located ventral to all orofacial representations, providing evidence for dual LMC representations. CONCLUSIONS: The authors determined the probabilistic distribution of the LMC. Cortical stimulation mapping with an NIM endotracheal tube is an easy and effective method for mapping the LMC and is simply integrated into the current neuromonitoring methods for brain mapping.

A comparison of incidental and symptomatic unruptured brain arteriovenous malformations in children.

OBJECTIVE: Patients with unruptured brain arteriovenous malformations (AVMs) may present with headaches, seizures, and/or neurological deficits. A smaller number of cases may be discovered incidentally. These lesions remain incompletely understood due to their sparse reporting. Herein, the authors describe the largest series to date comparing the presentation, angioarchitecture, and management of incidental versus symptomatic unruptured AVMs in children. METHODS: The authors performed a retrospective analysis of patients who presented with brain AVMs from 1998 to 2022 at the University of California, San Francisco. Inclusion criteria were age ≤ 18 years at the time of presentation and an angiographically proven unruptured AVM that had been diagnosed postnatally. RESULTS: Of 76 children with unruptured AVMs, 66 (86.8%) presented with headaches, seizures, and/or neurological deficit. Ten AVMs (13.1%) were incidentally discovered through unrelated disease workup (50%), cranial trauma (40%), or research study participation (10%). Compared with patients with symptomatic unruptured AVMs, patients with incidental unruptured AVMs had a smaller mean ± SD maximum nidus diameter (2.82 ± 1.1 vs 3.98 ± 1.52 cm, p = 0.025) and fewer had deep venous drainage (20% of patients vs 61%, p = 0.036). They also presented at an earlier age (10 ± 5.2 vs 13.5 ± 4 years, p = 0.043) and with longer duration to first treatment (541 ± 922 vs 196 ± 448 days, p = 0.005). During the observation period, 1 patient developed recurring headaches and demonstrated AVM nidus growth. Four AVMs greater than 3 cm in size or in a deep location were treated with radiosurgery. Six other AVMs were treated with resection, with 2 receiving preoperative embolization. Eight AVMs (80%) were obliterated on last follow-up. Postprocedural complications included 2 transient neurological deficits after resection and 1 case of delayed seizure development after radiosurgery. The mean follow-up period was 5.7 ± 5.7 years without any hemorrhage episodes. CONCLUSIONS: A substantial proportion of pediatric patients with unruptured AVMs are discovered incidentally. With earlier presentation and more elementary angioarchitecture than symptomatic unruptured AVMs, these incidental lesions provide a snapshot into the natural history of AVM before symptom development or rupture.

C2 translaminar screw fixation in pediatric occipitocervical fusion.

PURPOSE: Rigid occipitocervical (O-C) instrumentation can reduce the anterior pathology and has a high fusion rate in children with craniovertebral instability. Typically, axis (C2) screw fixation utilizes C1-C2 transarticular screws or C2 pars screws. However, anatomic variation may preclude these screw types due to the size of fixation elements or by placing the vertebral artery at risk for injury. Pediatric C2 translaminar screw fixation has low risk of vertebral artery injury and may be used when the anatomy is otherwise unsuitable for C1-C2 transarticular screws or C2 pars screws. METHODS: We retrospectively reviewed a neurosurgical database at UCSF Benioff Children's Hospital Oakland for patients who had undergone a cervical spinal fusion that utilized translaminar screws for occipitocervical instrumentation between 2002 and 2020. We then reviewed the operative records to determine the parameters of C2 screw fixations performed. Demographic and all other relevant clinical data were then recorded. RESULTS: Twenty-five patients ranging from 2 to 18 years of age underwent O-C fusion, with a total of 43 translaminar screws at C2 placed. Twenty-three patients were fused (92%) after initial surgery with a mean follow-up of 43 months. Two patients, both with Down syndrome, had a nonunion. Another 2 patients had a superficial wound dehiscence that required wound revision. One patient died of unknown cause 7 months after surgery. One patient developed an adjacent-level kyphosis. CONCLUSION: When performing occipitocervical instrumentation in the pediatric population, C2 translaminar screw fixation is an effective option to other methods of C2 screw fixation dependent on anatomic feasibility.

Validation of the Ruptured Arteriovenous Malformation Grading Scale in a pediatric cohort.

OBJECTIVE: Pediatric brain arteriovenous malformations (AVMs) are the leading cause of spontaneous intracranial hemorrhage (SICH) in children. Although the incidence of SICH is low in pediatric populations, such events cause substantial morbidity. The recently created Ruptured Arteriovenous Malformation Grading Scale (RAGS) is proposed as a reliable and novel grading system to specifically serve as a predictor of clinical outcomes in patients following AVM rupture, similar to the Hunt and Hess (HH) grade for ruptured aneurysms. While these data are promising, pediatric patients were notably absent from the original study validating the RAGS. Therefore, correlation of the RAGS score with clinical outcomes following AVM rupture in individuals younger than 18 years of age using the RAGS score is needed. The objective of this study was to validate the RAGS in a cohort of pediatric patients with AVMs who presented with hemorrhage, thereby demonstrating the score's generalizability, and expanding its external validity. METHODS: A cohort of children with ruptured AVMs were retrospectively reviewed. Using disability, measured by the modified Rankin Scale (mRS), as the response variable, the area under the receiver operating characteristic curve (AUROC) was calculated for patients based on their RAGS scores for three time periods. The AUROC values were then compared with those generated by two commonly used clinical grading systems, the HH classification and Glasgow Coma Scale. RESULTS: A total of 81 children who presented with ruptured AVMs were included in the study, with a mean follow-up duration of 4 years. The RAGS score outperformed other clinical grading scales in predicting mRS scores, with AUROC values of 0.81, 0.82, and 0.81 at three distinct follow-up periods. CONCLUSIONS: The RAGS score correlated well with the clinical outcome after AVM rupture in pediatric patients. Additional validation studies across multiple treatment centers are needed to further demonstrate the generalizability of the scoring system.

Single versus dual operative spine fractures in ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis, the most common spondyloarthritis, fuses individual spinal vertebrae into long segments. The unique biomechanics of the ankylosed spine places patients at unusually high risk for unstable fractures secondary to low-impact mechanisms. These injuries are unique within the spine trauma population and necessitate thoughtful management. Therefore, the authors aimed to present a richly annotated data set of operative AS spine fractures with a significant portion of patients with simultaneous dual noncontiguous fractures. METHODS: Patients with ankylosing spondylitis with acute fractures who received operative management between 2012 and 2020 were reviewed. Demographic, admission, surgical, and outcome parameters were retrospectively collected and reviewed. RESULTS: In total, 29 patients were identified across 30 different admissions. At admission, the mean age was 71.7 ± 11.8 years. The mechanism of injury in 77% of the admissions was a ground-level fall; 30% also presented with polytrauma. Of admissions, 50% were patient transfers from outside hospitals, whereas the other half presented primarily to our emergency departments. Fifty percent of patients sustained a spinal cord injury, and 35 operative fractures were identified and treated in 32 surgeries. The majority of fractures clustered around the cervicothoracic (C4-T1, 48.6%) and thoracolumbar (T8-L3, 37.11%) junctions. Five patients (17.2%) had simultaneous dual noncontiguous operative fractures; these patients were more likely to have presented with a higher-energy mechanism of injury such as a bicycle or motor vehicle accident compared with patients with a single operative fracture (60% vs 8%, p = 0.024). On preoperative MRI, 56.3% of the fractures had epidural hematomas (EDHs); 25% were compressive of the underlying neural elements, which dictated the number of laminectomy levels performed (no EDH, 2.1 ± 2.36; noncompressive EDH, 2.1 ± 1.85; and compressive EDH, 7.4 ± 4 [p = 0.003]). The mean difference in instrumented levels was 8.7 ± 2.6 with a mean estimated blood loss (EBL) of 1183 ± 1779.5 mL. Patients on a regimen of antiplatelet therapy had a significantly higher EBL (2635.7 mL vs 759.4 mL, p = 0.015). Overall, patients had a mean hospital length of stay of 15.2 ± 18.5 days; 5 patients died during the same admission or after transfer to an outside hospital. Nine of 29 patients (31%) had died by the last follow-up (the mean follow-up was 596.3 ± 878.9 days). CONCLUSIONS: Patients with AS who have been found to have unstable spine fractures warrant a thorough diagnostic evaluation to identify secondary fractures as well as compressive EDHs. These patients experienced prolonged inpatient hospitalizations with significant morbidity and mortality.

Multiple Tumor-Associated Intracranial Aneurysms Adjacent to a Suprasellar Germ Cell Tumor: Case Report and Review of Literature.

INTRODUCTION: Tumor-associated intracranial aneurysms are rare and not well understood. CASE PRESENTATION: We describe a 4-year-old female with multiple intracranial aneurysms intimately associated with a suprasellar germ cell tumor (GCT). We provide the clinical history, medical, and surgical treatment course, as well as a comprehensive and concise synthesis of the literature on tumor-associated aneurysms. DISCUSSION: We discuss mechanisms for aneurysm formation with relevance to the current case, including cellular and paracrine signaling pertinent to suprasellar GCTs and possible molecular pathways involved. We review the complex multidisciplinary treatment required for complex tumor and cerebrovascular interactions.

Cerebrovascular complications of coccidioidomycosis meningitis: Case report and systematic review.

Coccidioidomycosis exposure is common in the southwest United States and northern Mexico. Dissemination to the meninges is the most severe form of progression. Although ischemic strokes are well-reported in these patients, other cerebrovascular complications of coccidioidomycosis meningitis (CM), as well as their treatment options and outcomes, have not been systematically studied. We present a uniquely severe case of CM with several cerebrovascular complications. We also systematically queried PubMed and EMBASE databases, including articles published before April 2020 reporting human patients with CM-induced cerebrovascular pathology other than ischemic infarcts. Sixteen articles met inclusion criteria, which describe 6 patients with aneurysmal hemorrhage, 10 with non-aneurysmal hemorrhage, one with vasospasm, and one with transient ischemic attacks. CM-associated aneurysms invariably presented with hemorrhage. These were universally fatal until the past decade, when advances in surgical clipping and/or combined surgical and endovascular treatment have improved outcomes. We found that non-aneurysmal intracranial hemorrhages were limited to male patients, involved a diverse set of intracranial vasculature, and had a mortality rate surpassing 80%. Vasospasm was reported once, and was treated with percutaneous transluminal angioplasty. Transient ischemic attacks were reported once, and were successfully treated with fluconazole and dexamethasone. This review suggests that CM can present with a wide array of cerebrovascular complications, including ischemic infarcts, aneurysmogenesis, non-aneurysmal intracranial hemorrhage, vasospasm, and transient ischemic attacks. Mortality has improved over time due to advances in surgical and endovascular treatment modalities. The exception is non-aneurysmal intracranial hemorrhage, which remains associated with high mortality rates and few targeted therapeutic options.

Defective vascular signaling & prospective therapeutic targets in brain arteriovenous malformations.

The neurovascular unit is composed of endothelial cells, vascular smooth muscle cells, pericytes, astrocytes and neurons. Through tightly regulated multi-directional cell signaling, the neurovascular unit is responsible for the numerous functionalities of the cerebrovasculature - including the regulation of molecular and cellular transport across the blood-brain barrier, angiogenesis, blood flow responses to brain activation and neuroinflammation. Historically, the study of the brain vasculature focused on endothelial cells; however, recent work has demonstrated that pericytes and vascular smooth muscle cells - collectively known as mural cells - play critical roles in many of these functions. Given this emerging data, a more complete mechanistic understanding of the cellular basis of brain vascular malformations is needed. In this review, we examine the integrated functions and signaling within the neurovascular unit necessary for normal cerebrovascular structure and function. We then describe the role of aberrant cell signaling within the neurovascular unit in brain arteriovenous malformations and identify how these pathways may be targeted therapeutically to eradicate or stabilize these lesions.

National trends in cerebral bypass surgery in the United States, 2002-2014.

OBJECTIVECerebral bypass procedures are microsurgical techniques to augment or restore cerebral blood flow when treating a number of brain vascular diseases including moyamoya disease, occlusive vascular disease, and cerebral aneurysms. With advances in endovascular therapy and evolving evidence-based guidelines, it has been suggested that cerebral bypass procedures are in a state of decline. Here, the authors characterize the national trends in cerebral bypass surgery in the United States from 2002 to 2014.METHODSUsing the National (Nationwide) Inpatient Sample, the authors extracted for analysis the data on all adult patients who had undergone cerebral bypass as indicated by ICD-9-CM procedure code 34.28. Indications for bypass procedures, patient demographics, healthcare costs, and regional variations are described. Results were stratified by indication for cerebral bypass including moyamoya disease, occlusive vascular disease, and cerebral aneurysms. Predictors of inpatient complications and death were evaluated using multivariable logistic regression analysis.RESULTSFrom 2002 to 2014, there was an increase in the annual number of cerebral bypass surgeries performed in the United States. This increase reflected a growth in the number of cerebral bypass procedures performed for adult moyamoya disease, whereas cases performed for occlusive vascular disease or cerebral aneurysms declined. Inpatient complication rates for cerebral bypass performed for moyamoya disease, vascular occlusive disease, and cerebral aneurysm were 13.2%, 25.1%, and 56.3%, respectively. Rates of iatrogenic stroke ranged from 3.8% to 20.4%, and mortality rates were 0.3%, 1.4%, and 7.8% for moyamoya disease, occlusive vascular disease, and cerebral aneurysms, respectively. Multivariate logistic regression confirmed that cerebral bypass for vascular occlusive disease or cerebral aneurysm is a statistically significant predictor of inpatient complications and death. Mean healthcare costs of cerebral bypass remained unchanged from 2002 to 20014 and varied with treatment indication: moyamoya disease $38,406 ± $483, vascular occlusive disease $46,618 ± $774, and aneurysm $111,753 ± $2381.CONCLUSIONSThe number of cerebral bypass surgeries performed for adult revascularization has increased in the United States from 2002 to 2014. Rising rates of surgical bypass reflect a greater proportion of surgeries performed for moyamoya disease, whereas bypasses performed for vascular occlusive disease and aneurysms are decreasing. Despite evolving indications, cerebral bypass remains an important surgical tool in the modern endovascular era and may be increasing in use. Stagnant complication rates highlight the need for continued interest in advancing available bypass techniques or technologies to improve patient outcomes.

Priapism associated with lumbar stenosis: case report and literature review.

Lumbar spinal stenosis (LSS) is characterized by narrowing of the central canal, lateral recesses, or foramina leading to compression of neural tissue. The clinical syndrome associated with LSS is usually neurogenic claudication, which often presents as lower back and extremity pain, numbness, and tingling upon ambulation. Autonomic dysfunction is rarely observed in patients with LSS; however, a subset of male patients has been reported to experience intermittent priapism associated with the onset of neurogenic claudication symptoms. We present the case of a 33-year-old male who was diagnosed with LSS associated with neurogenic claudication and priapism who underwent minimally invasive decompressive surgery. Complete resolution of claudication and priapism was observed at the 6-week follow-up visit. This case report highlights minimally invasive lumbar decompression as an effective treatment for the rarely observed presentation of priapism associated with LSS.

Cerebrospinal fluid untargeted metabolomic profiling of aneurysmal subarachnoid hemorrhage: an exploratory study.

INTRODUCTION: Despite advancements in medical and surgical therapies, clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH) continue to be poor. Currently, aSAH pathophysiology remains poorly understood. No aSAH biomarkers are commonly used in the clinical setting. This exploratory study used metabolomics profiling to identify global metabolic changes and metabolite predictors of long-term outcome using cerebrospinal fluid (CSF) samples of aSAH patients. METHODS AND METHODS: Gas chromatography time-of-flight mass spectrometry was applied to CSF samples collected from 15 consecutive high-grade aSAH patients (modified Fisher grade 3 or 4). Collected CSF samples were analyzed at two time points (admission and the anticipated vasospasm timeframe). Metabolite levels at both time points were compared and correlated with vasospasm status and Glasgow Outcome Scale (GOS) of patients at 1 year post-aSAH. Significance level was defined as p < 0.05 with false discovery rate correction for multiple comparisons. RESULTS: Of 97 metabolites identified, 16 metabolites, primarily free amino acids, significantly changed between the two time points. These changes were magnified in modified Fisher grade 4 compared with grade 3. Six metabolites (2-hydroxyglutarate, tryptophan, glycine, proline, isoleucine, and alanine) correlated with GOS at 1 year post-aSAH independent of vasospasm status. When predicting patients who had low disability (GOS 5 vs. GOS ≤4), 2-hydroxyglutarate had a sensitivity and specificity of 0.89 and 0.83 respectively. CONCLUSIONS: Our preliminary study suggests that specific metabolite changes occur in the brain during the course of aSAH and that quantification of specific CSF metabolites may be used to predict long-term outcome in patients with aSAH. This is the first study to implicate 2-hydroxyglutarate, a known marker of tissue hypoxia, in aSAH pathogenesis.

Novel biomarker identification using metabolomic profiling to differentiate radiation necrosis and recurrent tumor following Gamma Knife radiosurgery.

OBJECTIVE Following an initial response of brain metastases to Gamma Knife radiosurgery, regrowth of the enhancing lesion as detected on MRI may represent either radiation necrosis (a treatment-related inflammatory change) or recurrent tumor. Differentiation of radiation necrosis from tumor is vital for management decision making but remains difficult by imaging alone. In this study, gas chromatography with time-of-flight mass spectrometry (GC-TOF) was used to identify differential metabolite profiles of the 2 tissue types obtained by surgical biopsy to find potential targets for noninvasive imaging. METHODS Specimens of pure radiation necrosis and pure tumor obtained from patient brain biopsies were flash-frozen and validated histologically. These formalin-free tissue samples were then analyzed using GC-TOF. The metabolite profiles of radiation necrosis and tumor samples were compared using multivariate and univariate statistical analysis. Statistical significance was defined as p ≤ 0.05. RESULTS For the metabolic profiling, GC-TOF was performed on 7 samples of radiation necrosis and 7 samples of tumor. Of the 141 metabolites identified, 17 (12.1%) were found to be statistically significantly different between comparison groups. Of these metabolites, 6 were increased in tumor, and 11 were increased in radiation necrosis. An unsupervised hierarchical clustering analysis found that tumor had elevated levels of metabolites associated with energy metabolism, whereas radiation necrosis had elevated levels of metabolites that were fatty acids and antioxidants/cofactors. CONCLUSIONS To the authors' knowledge, this is the first tissue-based metabolomics study of radiation necrosis and tumor. Radiation necrosis and recurrent tumor following Gamma Knife radiosurgery for brain metastases have unique metabolite profiles that may be targeted in the future to develop noninvasive metabolic imaging techniques.

Demonstration of differential radiosensitivity based upon mutation profile in metastatic melanoma treated with stereotactic radiosurgery.

BACKGROUND: Metastatic melanoma often involves the brain. Radiotherapy is an important treatment of melanoma brain metastases, although melanoma radiosensitivity is considered heterogeneous. Thus, identifying subsets with differential radiosensitivity is essential. MATERIALS AND METHODS: Patients with metastatic melanoma were identified in a prospective stereotactic radiosurgery (SRS) database. Tumor were tested for alterations in B-RAF, N-RAS, and c-KIT. Standardized imaging following SRS was reviewed for recurrence. Differences in local and distant failure were determined using modified Cox proportional hazards models. RESULTS: 102 patients and 1,028 brain metastases were included. N-RAS mutated patients were significantly less likely to develop local recurrence after SRS than wild type patients (HR 0.17, 95% CI 0.04-0.72, p=0.017). B-RAF and c-KIT mutations were not associated with altered rates of local recurrence. Lower local recurrence rates for N-RAS mutated tumors persisted on multivariate analysis (HR 0.18, 95% CI 0.04-0.84p=0.029). CONCLUSIONS: N-RAS mutation is associated with improved local control following SRS. Local recurrence is more common in wild type patients and those with B-RAF or c-KIT mutations. Further research is needed to validate these findings and integrate into practice.

Hemifacial spasm and neurovascular compression.

Hemifacial spasm (HFS) is characterized by involuntary unilateral contractions of the muscles innervated by the ipsilateral facial nerve, usually starting around the eyes before progressing inferiorly to the cheek, mouth, and neck. Its prevalence is 9.8 per 100,000 persons with an average age of onset of 44 years. The accepted pathophysiology of HFS suggests that it is a disease process of the nerve root entry zone of the facial nerve. HFS can be divided into two types: primary and secondary. Primary HFS is triggered by vascular compression whereas secondary HFS comprises all other causes of facial nerve damage. Clinical examination and imaging modalities such as electromyography (EMG) and magnetic resonance imaging (MRI) are useful to differentiate HFS from other facial movement disorders and for intraoperative planning. The standard medical management for HFS is botulinum neurotoxin (BoNT) injections, which provides low-risk but limited symptomatic relief. The only curative treatment for HFS is microvascular decompression (MVD), a surgical intervention that provides lasting symptomatic relief by reducing compression of the facial nerve root. With a low rate of complications such as hearing loss, MVD remains the treatment of choice for HFS patients as intraoperative technique and monitoring continue to improve.

Intra-arterial treatment of acute ischemic stroke: the continued evolution.

OPINION STATEMENT: The devastation caused by acute ischemic strokes is evident in every intensive care unit across the world. Although there is no doubt that progress has been made in treatment, it has been slow to come. With the emergence of new technologies in imaging, thrombolysis and endovascular intervention, the treatment modalities of acute ischemic stroke will enter a new era. In this review, we present the concept of the seven evolutionary phases in the treatment of acute ischemic stroke to date.