Subpial resection of epileptogenic tubers: operative nuances and lessons learned.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder. Tubers of the central nervous system are a hallmark of the disorder and often cause epilepsy. Many TSC patients fail to achieve seizure control with medication alone. Several case series have demonstrated high seizure freedom rates after resective surgery. However, the technique for the resection of epileptogenic tubers has largely been unreported. Here the authors present 2 cases to illustrate their multistage approach for localizing and resecting the seizure onset zone in patients with TSC. At their institution, they have excellent seizure outcomes and a low complication rate with this technique. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2411.

Disruption of neural periodicity predicts clinical response after deep brain stimulation for obsessive-compulsive disorder.

Recent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy ( NCT05915741 ). We developed our neurobehavioral models based on continuous neural recordings in the region of the ventral striatum in an initial cohort of five patients and tested and validated them in a held-out cohort of seven additional patients. Before DBS activation, in the most symptomatic state, theta/alpha (9 Hz) power evidenced a prominent circadian pattern and a high degree of predictability. In patients with persistent symptoms (non-responders), predictability of the neural data remained consistently high. On the other hand, in patients who improved symptomatically (responders), predictability of the neural data was significantly diminished. This neural feature accurately classified clinical status even in patients with limited duration recordings, indicating generalizability that could facilitate therapeutic decision-making.

Stereo-EEG-guided network modulation for psychiatric disorders: Surgical considerations.

BACKGROUND: Deep brain stimulation (DBS) and other neuromodulatory techniques are being increasingly utilized to treat refractory neurologic and psychiatric disorders. OBJECTIVE: /Hypothesis: To better understand the circuit-level pathophysiology of treatment-resistant depression (TRD) and treat the network-level dysfunction inherent to this challenging disorder, we adopted an approach of inpatient intracranial monitoring borrowed from the epilepsy surgery field. METHODS: We implanted 3 patients with 4 DBS leads (bilateral pair in both the ventral capsule/ventral striatum and subcallosal cingulate) and 10 stereo-electroencephalography (sEEG) electrodes targeting depression-relevant network regions. For surgical planning, we used an interactive, holographic visualization platform to appreciate the 3D anatomy and connectivity. In the initial surgery, we placed the DBS leads and sEEG electrodes using robotic stereotaxy. Subjects were then admitted to an inpatient monitoring unit for depression-specific neurophysiological assessments. Following these investigations, subjects returned to the OR to remove the sEEG electrodes and internalize the DBS leads to implanted pulse generators. RESULTS: Intraoperative testing revealed positive valence responses in all 3 subjects that helped verify targeting. Given the importance of the network-based hypotheses we were testing, we required accurate adherence to the surgical plan (to engage DBS and sEEG targets) and stability of DBS lead rotational position (to ensure that stimulation field estimates of the directional leads used during inpatient monitoring were relevant chronically), both of which we confirmed (mean radial error 1.2±0.9 mm; mean rotation 3.6±2.6°). CONCLUSION: This novel hybrid sEEG-DBS approach allows detailed study of the neurophysiological substrates of complex neuropsychiatric disorders.

Robot-Assisted Deep Brain Stimulation: High Accuracy and Streamlined Workflow.

BACKGROUND: A number of stereotactic platforms are available for performing deep brain stimulation (DBS) lead implantation. Robot-assisted stereotaxy has emerged more recently demonstrating comparable accuracy and shorter operating room times compared with conventional frame-based systems. OBJECTIVE: To compare the accuracy of our streamlined robotic DBS workflow with data in the literature from frame-based and frameless systems. METHODS: We retrospectively reviewed 126 consecutive DBS lead placement procedures using a robotic stereotactic platform. Indications included Parkinson disease (n = 94), essential tremor (n = 21), obsessive compulsive disorder (n = 7), and dystonia (n = 4). Procedures were performed using a stereotactic frame for fixation and the frame pins as skull fiducials for robot registration. We used intraoperative fluoroscopic computed tomography for registration and postplacement verification. RESULTS: The mean radial error for the target point was 1.06 mm (SD: 0.55 mm, range 0.04-2.80 mm) on intraoperative fluoroscopic computed tomography. The mean operative time for an asleep, bilateral implant without implantable pulse generator placement was 238 minutes (SD: 52 minutes), and skin-to-skin procedure time was 116 minutes (SD: 42 minutes). CONCLUSION: We describe a streamlined workflow for DBS lead placement using robot-assisted stereotaxy with a comparable accuracy profile. Obviating the need for checking and switching coordinates, as is standard for frame-based DBS, also reduces the chance for human error and facilitates training.

Targeting the Tumor Microenvironment in Brain Metastasis.

Dynamic interplay between cancer cells and the surrounding microenvironment is a feature of the metastatic process. Successful metastatic brain colonization requires complex mechanisms that ultimately allow tumor cells to adapt to the unique microenvironment of the central nervous system, evade immune destruction, survive, and grow. Accumulating evidence suggests that components of the brain tumor microenvironment (TME) play a vital role in the metastatic cascade. In this review, the authors summarize the contribution of the TME to the development and progression of brain metastasis. They also highlight opportunities for TME-directed targeted therapy.

Natural history of high-grade pediatric arteriovenous malformations: implications for management options.

PURPOSE: Cerebral arteriovenous malformations are a common cause of pediatric intracranial hemorrhage. Often, small, superficial, lesions are treated surgically; however, more complex, deeper, eloquently located lesions portend higher-risk features and suffer from limitations in treatment. We sought to examine our institution's experience with the natural history of these high-grade arteriovenous malformations to explore outcomes with conservative treatment. METHODS: A retrospective chart review was performed to identify all pediatric cases of intracranial arteriovenous malformations seen at our institution from 2005 to 2018. Subjects with Spetzler-Martin grade IV or V lesions, treated conservatively, were examined for primary outcomes including rupture rate, progression, and functional outcomes. RESULTS: A total of 14 patients were included in the study, of which, 78.57% were classified as Spetzler-Martin grade IV and 21.43% Spetzler-Martin grade V. All patients in this study were treated conservatively, with surveillance, followed for a mean of 32.17 months (range 9.43-79.10). 7.14% experienced delayed hemorrhage or re-rupture, 7.14% had hydrocephalus, and 14.29% had seizures. Neurological sequelae included weakness, visual impairment, speech impairment, sensory changes, and dystonia; functionally independent outcomes, defined as modified Rankin Score of 0-2, were seen in 85.71% of patients. CONCLUSION: Our experience suggests that patients with large, deep lesions have significant morbidity with high rates of rupture and subsequent neurologic deficits. However, intervention of these lesions may carry high risk, and the literature suggests such lesions may have less favorable outcomes when treated. We propose conservative treatment for high-grade arteriovenous malformations as a viable option with good functional outcomes in a cohort often without good options for conventional treatment.

Pediatric intracranial arteriovenous malformations: Examining rehabilitation outcomes.

PURPOSE: Arteriovenous malformation (AVM) rupture in children can cause debilitating neurological injury. Rehabilitation is key to recovery, though literature details little regarding rehabilitation outcomes. We examined a single-center experience with pediatric AVMs as related to acute inpatient rehabilitation outcomes. METHODS: At our institution, a retrospective chart review was completed examining all cases of intracranial AVMs in patients age 18 and younger who completed our acute inpatient rehabilitation program between 2012-2018. Patient characteristics, clinical data, treatment modality, and functional outcomes were reviewed. RESULTS: 14 patients with AVMs underwent acute inpatient rehabilitation; nine (64.3%) treated surgically at our institution, two (14.3%) non-surgically at our institution, and three (21.4%) surgically at an outside facility prior to transitioning care at our institution. Eight (57.1%) were male, seven (50.0%) Caucasian, and seven (50.0%) Hispanic. Seven (50.0%) presented with AVM rupture; six (42.9%) were found incidentally on imaging. Clinical courses, treatment outcomes, and post-treatment complications varied. Several patients underwent repeat treatment or additional procedures. Neurological deficits identified included hemiparesis, dystonia, spasticity, epilepsy, hydrocephalus, and ataxia. Inpatient rehabilitation unit length of stay was on average 21 days (SD 9.02, range 9-41). Functional Independence Measure for Children (WeeFIM®) scores, including self-care, mobility, and cognition, demonstrated improvement upon discharge. The mean total change was 36.7 points in those treated surgically, 16.5 in those treated non-surgically, and 25.7 in those treated surgically at another facility. CONCLUSION: We found that all pediatric patients with intracranial AVMs, across all treatment modalities, demonstrated improved outcomes across all functional domains after an acute inpatient rehabilitation program.

Accuracy and Workflow Improvements for Responsive Neurostimulation Hippocampal Depth Electrode Placement Using Robotic Stereotaxy.

Background: Robotic stereotaxy is increasingly common in epilepsy surgery for the implantation of stereo-electroencephalography (sEEG) electrodes for intracranial seizure monitoring. The use of robots is also gaining popularity for permanent stereotactic lead implantation applications such as in deep brain stimulation and responsive neurostimulation (RNS) procedures. Objective: We describe the evolution of our robotic stereotactic implantation technique for placement of occipital-approach hippocampal RNS depth leads. Methods: We performed a retrospective review of 10 consecutive patients who underwent robotic RNS hippocampal depth electrode implantation. Accuracy of depth lead implantation was measured by registering intraoperative post-implantation fluoroscopic CT images and post-operative CT scans with the stereotactic plan to measure implantation accuracy. Seizure data were also collected from the RNS devices and analyzed to obtain initial seizure control outcome estimates. Results: Ten patients underwent occipital-approach hippocampal RNS depth electrode placement for medically refractory epilepsy. A total of 18 depth electrodes were included in the analysis. Six patients (10 electrodes) were implanted in the supine position, with mean target radial error of 1.9 ± 0.9 mm (mean ± SD). Four patients (8 electrodes) were implanted in the prone position, with mean radial error of 0.8 ± 0.3 mm. The radial error was significantly smaller when electrodes were implanted in the prone position compared to the supine position (p = 0.002). Early results (median follow-up time 7.4 months) demonstrate mean seizure frequency reduction of 26% (n = 8), with 37.5% achieving ≥50% reduction in seizure frequency as measured by RNS long episode counts. Conclusion: Prone positioning for robotic implantation of occipital-approach hippocampal RNS depth electrodes led to lower radial target error compared to supine positioning. The robotic platform offers a number of workflow advantages over traditional frame-based approaches, including parallel rather than serial operation in a bilateral case, decreased concern regarding human error in setting frame coordinates, and surgeon comfort.

Clobazam monotherapy for focal or generalized seizures.

BACKGROUND: This is an updated version of the original Cochrane Review published in Issue 10, 2014. There is a need to expand monotherapy options available to a clinician for the treatment of new focal or generalized seizures. A Cochrane systematic review for clobazam monotherapy is expected to define its place in the treatment of new-onset or untreated seizures and highlight gaps in evidence. OBJECTIVES: To evaluate the efficacy, effectiveness, tolerability and safety of clobazam as monotherapy in people with new-onset focal or generalized seizures. SEARCH METHODS: For the latest update we searched the following databases on 19 March 2018: the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946- ), BIOSIS Previews (1969- ), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (ICTRP). There were no language restrictions. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials comparing clobazam monotherapy versus placebo or other anti-seizure medication in people with two or more unprovoked seizures or single acute symptomatic seizure requiring short-term continuous anti-seizure medication, were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Primary outcome measure was time on allocated treatment (retention time), reflecting both efficacy and tolerability. Secondary outcomes included short- and long-term effectiveness measures, tolerability, quality of life, and tolerance measures. Two authors independently extracted the data. MAIN RESULTS: We identified three trials fulfilling the review criteria, which included 206 participants. None of the identified studies reported the preselected primary outcome measure. A meta-analysis was not possible. Lack of detail regarding allocation concealment and a high risk of performance and detection bias in two studies prompted us to downgrade the quality of evidence (by using the GRADE approach) for some of our results due to risk of bias.Regarding retention at 12 months, we detected no evidence of a statistically significant difference between clobazam and carbamazepine (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.61 to 1.12; low-quality evidence). There was low-quality evidence that clobazam led to better retention compared with phenytoin (RR 1.43, 95% CI 1.08 to 1.90). We could not determine whether participants receiving clobazam were found to be less likely to discontinue it due to adverse effects as compared to phenytoin (RR 0.10, 95% CI 0.01 to 1.65, low-quality evidence). AUTHORS' CONCLUSIONS: We found no advantage for clobazam over carbamazepine for retention at 12 months in drug-naive children and a slight advantage of clobazam over phenytoin for retention at six months in adolescents and adults with neurocysticercosis in a single clinical trial each. At present, the available evidence is insufficient to inform clinical practice.

Understanding the complex pathophysiology of idiopathic intracranial hypertension and the evolving role of venous sinus stenting: a comprehensive review of the literature.

Idiopathic intracranial hypertension (IIH) is a disease defined by elevated intracranial pressure without established etiology. Although there is now consensus on the definition of the disorder, its complex pathophysiology remains elusive. The most common clinical symptoms of IIH include headache and visual complaints. Many current theories regarding the etiology of IIH focus on increased secretion or decreased absorption of cerebrospinal fluid (CSF) and on cerebral venous outflow obstruction due to venous sinus stenosis. In addition, it has been postulated that obesity plays a role, given its prevalence in this population of patients. Several treatments, including optic nerve sheath fenestration, CSF diversion with ventriculoperitoneal or lumboperitoneal shunts, and more recently venous sinus stenting, have been described for medically refractory IIH. Despite the availability of these treatments, no guidelines or standard management algorithms exist for the treatment of this disorder. In this paper, the authors provide a review of the literature on IIH, its clinical presentation, pathophysiology, and evidence supporting treatment strategies, with a specific focus on the role of venous sinus stenting.

Acute postoperative seizures as predictors of seizure outcomes after epilepsy surgery.

OBJECTIVES: This meta-analysis was performed to determine if acute postoperative seizures (APOS) predict epilepsy surgery outcomes. Additionally, we estimated pooled prevalence for APOS and explored if certain APOS characteristics predict surgical outcomes. METHODS: A systematic literature search was performed for studies reporting seizure outcomes after epilepsy surgery in patients with and without APOS. APOS were defined as seizure(s) occurring within 30days of surgery. After data extraction, pooled Mantel-Haenszel odds ratio (OR) with 95% confidence intervals (CI) was calculated for 1-year seizure-free outcome in patients with and without APOS using random-effects meta-analysis. Sub-group meta-analysis for pediatric studies, time of occurrence, and APOS semiology were also performed. A meta-regression was performed to explore source(s) of heterogeneity. RESULTS: Seventeen studies were included in the final synthesis. Pooled prevalence of APOS was found to be 22.58%. A significantly higher proportion of patients without APOS within 30days of surgery (73.49%) were seizure-free at ≥1-year (OR 4.20, 95% CI 2.97-5.93, p<0.0001) compared to those with APOS (38.96%). Among the pediatric studies (n=6) 77.14% of patients without APOS were seizure-free at ≥1-year, compared to 35.94% of those with APOS (OR 5.71, 95% CI 3.32-9.80, p<0.0001). Patients having APOS within 24h of surgery and APOS semiology different from habitual pre-surgical seizures were more likely to achieve seizure-free outcomes, but these results failed to achieve statistical significance. CONCLUSIONS: APOS reliably predict 1-year seizure outcomes after epilepsy surgery. This information should help counsel patients and families.

Mechanisms of toxin inhibition and transcriptional repression by Escherichia coli DinJ-YafQ.

Bacteria encounter environmental stresses that regulate a gene expression program required for adaptation and survival. Here, we report the 1.8-Å crystal structure of the Escherichia coli toxin-antitoxin complex YafQ-(DinJ)2-YafQ, a key component of the stress response. The antitoxin DinJ dimer adopts a ribbon-helix-helix motif required for transcriptional autorepression, and toxin YafQ contains a microbial RNase fold whose proposed active site is concealed by DinJ binding. Contrary to previous reports, our studies indicate that equivalent levels of transcriptional repression occur by direct interaction of either YafQ-(DinJ)2-YafQ or a DinJ dimer at a single inverted repeat of its recognition sequence that overlaps with the -10 promoter region. Surprisingly, multiple YafQ-(DinJ)2-YafQ complexes binding to the operator region do not appear to amplify the extent of repression. Our results suggest an alternative model for transcriptional autorepression that may be novel to DinJ-YafQ.