Incidence and risk factors for seizures associated with deep brain stimulation surgery.

OBJECTIVE: The objective of this study was to determine the incidence of seizures following deep brain stimulation (DBS) electrode implantation and to evaluate factors associated with postoperative seizures. METHODS: The authors performed a single-center retrospective case-control study. The outcome of interest was seizure associated with DBS implantation. Univariate analyses were performed using the Student t-test for parametric continuous outcomes. The authors used the Kruskal-Wallis test or Wilcoxon rank-sum test for nonparametric continuous outcomes, chi-square statistics for categorical outcomes, and multivariate logistic regression for binomial variables. RESULTS: A total of 814 DBS electrode implantations were performed in 645 patients (478 [58.7%] in men and 520 [63.9%] in patients with Parkinson's disease). In total, 22 (3.4%) patients who had undergone 23 (2.8%) placements experienced seizure. Of the 23 DBS implantation-related seizures, 21 were new-onset seizures (3.3% of 645 patients) and 2 were recurrence or worsening of a prior seizure disorder. Among the 23 cases with postimplantation-related seizure, epilepsy developed in 4 (17.4%) postoperatively; the risk of DBS-associated epilepsy was 0.50% per DBS electrode placement and 0.63% per patient. Nine (39.1%) implantation-related seizures had associated postoperative radiographic abnormalities. Multivariate analyses suggested that age at surgery conferred a modest increased risk for postoperative seizures (OR 1.06, 95% CI 1.02-1.10). Sex, primary diagnosis, electrode location and sidedness, and the number of trajectories were not significantly associated with seizures after DBS surgery. CONCLUSIONS: Seizures associated with DBS electrode placement are uncommon, typically occur early within the postoperative period, and seldom lead to epilepsy. This study suggests that patient characteristics, such as age, may play a greater role than perioperative variables in determining seizure risk. Multiinstitutional studies may help better define and mitigate the risk of seizures after DBS surgery.

Using the neutrophil-to-lymphocyte ratio to predict outcomes in pediatric patients with traumatic brain injury.

OBJECTIVE: The brain's inflammatory reaction to traumatic brain injury (TBI) generally peaks between 24 and 48 h after injury. This inflammatory cascade can be neuroprotective or may mediate secondary brain injury beyond the initial TBI. Therefore, circulating inflammatory markers may be useful for predicting outcomes in pediatric TBI. The goal of this study was to determine whether elevations in peripheral blood neutrophil-to-lymphocyte ratios (NLRs) are associated with adverse outcomes in pediatric TBI patients. PATIENTS AND METHODS: 188 pediatric patients (0-18 years) presenting to our institution with TBI from 2007 to 2017 were retrospectively reviewed. Absolute neutrophil and lymphocyte counts from a complete blood count (CBC) were used to calculate NLRs on admission (<12 h) and approximately 24, 48, and 72 h after injury. Data points included Glasgow Coma Scale (GCS) on admission, presence of post-traumatic amnesia (PTA), loss of consciousness (LOC), and Glasgow Outcome Scale Extended Pediatric Version (GOS-E Peds) with a median outcome span of 86 days. RESULTS: A one-way ANOVA demonstrated statistically significant differences in NLR at 24 h (p = 0.004) and 48 h (p=0.003) among patients stratified by GOS-E Peds. No significant differences in NLR were observed at any time point based on GCS or PTA. Patients who experienced LOC had a significantly higher NLR on admission (p=0.013) and at 24 h (p<0.001) than those who did not. CONCLUSION: In this study, relatively higher NLRs at 24 and 48 h post-TBI were associated with worse outcomes in pediatric patients. This suggests that NLR may be a useful and cost-effective outcome predictor in pediatric TBI as well as a possible future target for therapeutic intervention, warranting larger prospective trials.

Anterior two-thirds corpus callosotomy via stereotactic laser ablation.

Anterior two-thirds corpus callosotomy is a common palliative surgical intervention most commonly employed in patients with atonic or drop seizures. Recently, stereotactic laser ablation of the corpus callosum without a craniotomy has shown promise in achieving similar outcomes with fewer side effects and shorter hospitalizations. The authors demonstrate ablation of the anterior two-thirds corpus callosum in a patient with Lennox-Gastaut syndrome and drug-resistant drop seizures. Technical nuances of laser ablation with 3 laser fibers are described. Postoperatively, the patient showed a significant reduction in seizure frequency and severity over a 9-month follow-up period. The video can be found here: https://youtu.be/3-mMq5-PLiM .

Trapped ventricle after laser ablation of a subependymal giant cell astrocytoma complicated by intraventricular gadolinium extravasation: case report.

Magnetic resonance imaging-guided stereotactic laser ablation of intracranial targets, including brain tumors, has expanded dramatically over the past decade, but there have been few reports of complications, especially those occurring in a delayed fashion. Laser ablation of subependymal giant cell astrocytomas (SEGAs) is an attractive alternative to maintenance immunotherapy in some children with tuberous sclerosis complex (TSC); however, the effect of treatment on disease progression and the nature and frequency of potential complications remains largely unknown. The authors report the case of a 5-year-old boy with TSC who underwent stereotactic laser ablation of a SEGA at the right foramen of Monro on 2 separate occasions. After the second ablation, immediate posttreatment MRI revealed gadolinium extravasation from the tumor into the lateral ventricle. Nine months later, the patient presented with papilledema and delayed obstructive hydrocephalus secondary to intraventricular adhesions causing a trapped right lateral ventricle. This was successfully treated with endoscopic septostomy. The authors discuss the potential cause and clinical management of a delayed complication not previously reported after a relatively novel surgical therapy.

Intracranial Anatomical Triangles: A Comprehensive Illustrated Review.

There are multiple anatomical triangles of the skull base. However, to our knowledge, there has been no comprehensive review of these geometric landmarks. To allow for a safe and consistent approach to lesions of the skull base such as those near the internal carotid artery, internal acoustic meatus, and cavernous sinus, a comprehensive review of the variations with illustrations is required. This article provides an overview of the anatomical borders, dimensions, and surgical implications as well as illustrations of the major skull base triangles.

The Relationship of Electrophysiologic Subthalamic Nucleus Length as a Predictor of Outcomes in Deep Brain Stimulation for Parkinson Disease.

BACKGROUND: Intraoperative measurement of subthalamic nucleus (STN) width through microelectrode recording (MER) is a common proxy for optimal electrode location during deep brain stimulation (DBS) surgery for Parkinson disease. We assessed whether the MER-determined STN width is a predictor of postoperative Unified Parkinson Disease Rating Scale (UPDRS) improvement. METHODS: Records were reviewed for patients who underwent single-sided STN DBS placement for Parkinson disease between 2005 and 2010 at the UAB Medical Center. Reviews of preoperative and 3-month postoperative UPDRS part III, intraoperative MER records, and postoperative MRI scans were conducted. RESULTS: The final cohort consisted of 73 patients (mean age 59 ± 9.7 years, length of disease 13 ± 9.7 years). STN widths were defined as depths associated with increased background activity and motor-driven, spiking action potentials on MER. The mean contralateral UPDRS improvement was 58% (± 24). The mean STN width was 5.1 mm (± 1.6, min = 0.0, max = 8.7). No significant relationship between STN width and UPDRS improvement was found, with and without AC-PC normalization (R2 < 0.05). CONCLUSION: This analysis raises questions about seeking the maximal electrophysiological width of STN as a proxy for optimal outcome in DBS for PD. We suggest this strategy for DBS placement in Parkinson disease be subject to more robust prospective investigation.

Surveillance survey of family history in children with neural tube defects.

OBJECTIVE Although there are known risk factors for the development of neural tube defects (NTDs), little is known regarding the role of family history. The authors' goal in this study is to describe the family history in their population of patients with NTDs. METHODS Surveys were completed for 254 patients who were accompanied by their biological mother during their annual visit to the multidisciplinary Spina Bifida Clinic at Children's of Alabama. An NTD has been diagnosed in all patients who are seen in this clinic (myelomeningocele, lipomeningocele, split cord malformation, and congenital dermal sinus tract). Each mother answered questions regarding known NTD risk factors and their pregnancy, as well as the family history of NTDs, other CNS disorders, and birth defects. RESULTS The overall prevalence of family history of NTDs in children with an NTD was 16.9% (n = 43), of which 3.1% (n = 8) were in first-degree relatives. In patients with myelomeningocele, 17.7% (n = 37) had a positive family history for NTDs, with 3.8% in first-degree relatives. Family history in the paternal lineage for all NTDs was 8.7% versus 10.6% in the maternal lineage. Twenty-two patients (8.7%) had a family history of other congenital CNS disorders. Fifteen (5.9%) had a family history of Down syndrome, 12 (4.7%) had a family history of cerebral palsy, and 13 (5.1%) patients had a family history of clubfoot. Fourteen (5.5%) had a family history of cardiac defect, and 13 (5.1%) had a family history of cleft lip or palate. CONCLUSIONS The family history of NTDs was 16.9% in children with NTD without a difference between maternal and paternal lineage. This high rate of positive family history suggests that genetics and epigenetics may play a larger role in the pathogenesis of NTD in the modern era of widespread folate supplementation.

Design of a Phase I Clinical Trial to Evaluate M032, a Genetically Engineered HSV-1 Expressing IL-12, in Patients with Recurrent/Progressive Glioblastoma Multiforme, Anaplastic Astrocytoma, or Gliosarcoma.

M032 is a second-generation oncolytic herpes simplex virus (oHSV) that selectively replicates in tumor cells. M032 kills tumor cells directly through oncolytic replication and then proceeds to infect tumor cells in proximity, continuing the process of tumor destruction. In addition to this direct oncolytic activity, the virus carries a therapeutic payload-thus acting as a gene therapy vector-and causes the tumor cell to synthesize and secrete the immunity-stimulating protein interleukin-12 (IL-12) before cell death. (1) Human IL-12 is expressed and promotes an immune response against surviving tumor cells, increasing the antitumor effect of the therapy. IL-12 also produces an antiangiogenic effect, by interfering with the production of new tumor blood vessels necessary for tumor growth. Thus, M032 oHSV exerts antitumor effects through three distinct potential mechanisms. The virus has also been genetically engineered to minimize toxic effects for the patient. Preclinical animal models support the safety of intracranial inoculation with M032 in two relevant species (mouse and nonhuman primate). This clinical protocol outlines the dose-escalating phase I study for evaluation of M032 in patients with recurrent or progressive malignant glioma.

Sleep-disordered breathing in patients with myelomeningocele.

OBJECT A paucity of literature examines sleep apnea in patients with myelomeningocele, Chiari malformation Type II (CM-II), and related hydrocephalus. Even less is known about the effect of hydrocephalus treatment or CM-II decompression on sleep hygiene. This study is an exploratory analysis of sleep-disordered breathing in patients with myelomeningocele and the effects of neurosurgical treatments, in particular CM-II decompression and hydrocephalus management, on sleep organization. METHODS The authors performed a retrospective review of all patients seen in their multidisciplinary spina bifida clinic (approximately 435 patients with myelomeningocele) to evaluate polysomnographs obtained between March 1999 and July 2013. They analyzed symptoms prompting evaluation, results, and recommended interventions by using descriptive statistics. They also conducted a subset analysis of 9 children who had undergone polysomnography both before and after neurosurgical intervention. RESULTS Fifty-two patients had polysomnographs available for review. Sleep apnea was diagnosed in 81% of these patients. The most common presenting symptom was "breathing difficulties" (18 cases [43%]). Mild sleep apnea was present in 26 cases (50%), moderate in 10 (19%), and severe in 6 (12%). Among the 42 patients with abnormal sleep architecture, 30 had predominantly obstructive apneas and 12 had predominantly central apneas. The most common pulmonology-recommended intervention was adjustment of peripheral oxygen supplementation (24 cases [57%]), followed by initiation of peripheral oxygen (10 cases [24%]). In a subset analysis of 9 patients who had sleep studies before and after neurosurgical intervention, there was a trend toward a decrease in the mean number of respiratory events (from 34.8 to 15.9, p = 0.098), obstructive events (from 14.7 to 13.9, p = 0.85), and central events (from 20.1 to 2.25, p = 0.15) and in the apnea-hypopnea index (from 5.05 to 2.03, p = 0.038, not significant when corrected for multiple measures). CONCLUSIONS A large proportion of patients with myelomeningocele who had undergone polysomnography showed evidence of disordered sleep on an initial study. Furthermore, 31% of patients had moderate or severe obstructive sleep apnea. Myelomeningocele patients with an abnormal sleep structure who had undergone nonoperative treatment with peripheral oxygen supplementation showed improvement in the apnea-hypopnea index. Results in this study suggested that polysomnography in patients with myelomeningocele may present an opportunity to detect and classify sleep apnea, identify low-risk interventions, and prevent future implications of sleep-disordered breathing.

Adverse events associated with deep brain stimulation for movement disorders: analysis of 510 consecutive cases.

BACKGROUND: Although numerous studies have focused on the efficacy of deep brain stimulation (DBS) for movement disorders, less is known about surgical adverse events, especially over longer time intervals. OBJECTIVE: Here, we analyze adverse events in 510 consecutive cases from a tertiary movement disorders center at up to 10 years postoperatively. METHODS: We conducted a retrospective review of adverse events from craniotomies between January 2003 and March 2013. The adverse events were categorized into 2 broad categories--immediate perioperative and time-dependent postoperative events. RESULTS: Across all targets, perioperative mental status change occurred in 18 (3.5%) cases, and symptomatic intracranial hemorrhage occurred in 4 (0.78%) cases. The most common hardware-related event was skin erosion in 13 (2.5%) cases. The most frequent stimulation-related event was speech disturbance in 16 (3.1%) cases. There were no significant differences among surgical targets with respect to the incidence of these events. Time-dependent postoperative events leading to the revision of a given DBS electrode for any reason occurred in 4.7% ± 1.0%, 9.3% ± 1.4%, and 12.4% ± 1.5% of electrodes at 1, 4, and 7 years postoperatively, respectively. Staged bilateral DBS was associated with approximately twice the risk of repeat surgery for electrode replacement vs unilateral surgery (P = .020). CONCLUSION: These data provide low incidences for adverse events in a large series of DBS surgeries for movement disorders at up to 10 years follow-up. Accurate estimates of adverse events will better inform patients and caregivers about the potential risks and benefits of surgery and provide normative data for process improvement.

Hemispherectomy for treatment of refractory epilepsy in the pediatric age group: a systematic review.

OBJECT: Evidence in support of hemispherectomy stems from a multitude of retrospective studies illustrating individual institutions' experience. A systematic review of this topic, however, is lacking in the literature. METHODS: A systematic review of hemispherectomy for the treatment of refractory epilepsy available up to October 2013 was performed using the following inclusion criteria: reports of a total of 10 or more patients in the pediatric age group (≤ 20 years) undergoing hemispherectomy, seizure outcome reported after a minimum follow-up of 1 year after the initial procedure, and description of the type of hemispherectomy. Only the most recent paper from institutions that published multiple papers with overlapping study periods was included. Two reviewers independently applied the inclusion criteria and extracted all the data. RESULTS: Twenty-nine studies with a total of 1161 patients met the inclusion criteria. Seizure outcome was available for 1102 patients, and the overall rate of seizure freedom at the last follow-up was 73.4%. Sixteen studies (55.2%) exclusively reported seizure outcomes of a single type of hemispherectomy. There was no statistically significant difference in seizure outcome and type of hemispherectomy (p = 0.737). Underlying etiology was reported for 85.4% of patients with documented seizure outcome, and the overall distribution of acquired, developmental, and progressive etiologies was 30.5%, 40.7%, and 28.8%, respectively. Acquired and progressive etiologies were associated with significantly higher seizure-free rates than developmental etiologies (p < 0.001). Twenty of the 29 studies (69%) reported complications. The overall rate of hydrocephalus requiring CSF diversion was 14%. Mortality within 30 days was 2.2% and was not statistically different between types of hemispherectomy (p = 0.787). CONCLUSIONS: Hemispherectomy is highly effective for treating refractory epilepsy in the pediatric age group, particularly for acquired and progressive etiologies. While the type of hemispherectomy does not have any influence on seizure outcome, hemispherotomy procedures are associated with a more favorable complication profile.

The nonsurgical nature of patients with subarachnoid or intraparenchymal hemorrhage associated with mild traumatic brain injury.

OBJECT: Mild traumatic brain injury (mTBI), as defined by Glasgow Coma Scale (GCS) score of 13 or higher, is a common problem in the United States and worldwide, estimated to affect more than 1 million patients yearly. When associated with intracranial hemorrhage, it is a common reason for neurosurgical consultation and transfer to tertiary care centers. The authors set out to investigate the clinical implications of subarachnoid hemorrhage (SAH) and/or intraparenchymal hemorrhage (IPH) associated with mTBI in hopes of standardization of mTBI clinical care and optimization of resource allocation. METHODS: The authors performed a retrospective review of 500 consecutively treated patients with mTBI and SAH and/or IPH admitted to a Level I trauma center in Alabama between May 2003 and May 2013. They performed a review of medical records to confirm the diagnosis, determine neurological condition at admission, and assess for episodes of neurological decline or brain injury-related complications including altered mental status, seizures, and hyponatremia. RESULTS: Of the 500 patients for whom data were reviewed, 304 (60.8%) were male and 196 (39.2%) were female. Average age was 46.3 years. Overall, 63 patients (12.6%) had isolated IPH, 411 (82.2%) had isolated SAH, and 26 (5.2%) had radiographic evidence of both IPH and SAH. One hundred forty-five patients (29%) were transferred an average distance of 64.5 miles. The authors identified no patients who experienced neurological worsening during their hospital course. Two patients experienced hyponatremia that required treatment with sodium supplementation. CONCLUSIONS: Patients with the constellation of SAH and/or IPH and mTBI do not require neurosurgical consultation, and these findings should not be used as the sole criteria to justify transfer to tertiary referral centers.

Fast-sequence MRI studies for surveillance imaging in pediatric hydrocephalus.

OBJECT: Surveillance imaging of the cerebral ventricles can be valuable in following up children with shunt-treated hydrocephalus. There also, however, has been recent increased awareness and concern over the potential risk associated with imaging-related radiation exposure in children. Magnetic resonance imaging represents an imaging alternative that does not use ionizing radiation; however, its practical utility has been limited due to the near-uniform requirement for sedation or general anesthesia in children. Magnetic resonance imaging without sedation is often futile because of the movement artifact produced by the nonsedated pediatric patient. Some studies have demonstrated the feasibility of using fast-sequence MRI (fsMRI), but the reported experiences are limited. The authors have incorporated fsMRI into their routine shunt surveillance imaging paradigms and report here a 5-year experience with this modality. METHODS: The authors initially started using fsMRI for routine surveillance in a single clinic in 2008 and have gradually increased their institutional utilization of this modality as experience has accumulated and protocols have been refined. Imaging sequences obtained for each child include an axial T2-weighted half-Fourier acquisition single-shot turbo spin-echo (HASTE), coronal T2-weighted HASTE, and sagittal T2-weighted HASTE images. The authors conducted a retrospective chart and imaging review. They rated each fsMR image according to 5 visibility parameters: 1) ventricle size, 2) ventricle configuration, 3) presence or absence of transependymal flow, 4) presence or absence of motion artifact, and 5) visualization of the ventricular catheter. Each parameter was graded as 1 (present) or 0 (absent). Thus, the maximum value assigned to each scan could be 5 and the minimum value assigned to each scan could be 0. Interrater reliability between pairs of observers was calculated using the Kendall's tau-b and intraclass coefficients. RESULTS: Two hundred patients underwent fsMRI. No child required sedation. The average duration of examinations was approximately 3.37 minutes, and mean age of the patients was 5.7 years. Clinically useful images were attained in all cases. Overall quality of the fsMRI studies based on the 5 different visibility parameters showed that 169 images (84.5%) included 4 or 5 parameters (score ≥ 4) and had statistically significant excellent quality. The Kendall's tau-b for the overall fsMRI ratings was 0.82 (p = 0.002) and the intraclass coefficient was 0.87 (p < 0.0001). CONCLUSIONS: In the present cohort of 200 patients, fsMRI studies were shown to have an excellent overall quality and a statistically significant high degree of interrater reliability. Consequently, the authors propose that fsMRI is a sufficiently effective modality that eliminates the need for sedation and the use of ionizing radiation and that it should supplant CT for routine surveillance imaging in hydrocephalic patients.