Clinical outcomes following responsive neurostimulation implantation: a single center experience.

Background: Responsive neurostimulation (RNS) is an implantable device for persons with medically refractory focal-onset epilepsy. We report a single-center experience for RNS outcomes with special focus on stereoelectroencephalography (sEEG) for seizure onset localization. Methods: We performed retrospective review of patients with drug resistant focal epilepsy implanted with the RNS System for a minimum of six months between July 2014 and July 2019. Records were reviewed for demographic data, epilepsy duration, seizure frequency, number of prior antiepileptic drugs (AEDs), number of AEDs at RNS System implantation, prior epilepsy surgery or device use, previous seizure localization with sEEG, and RNS system information. Clinical response was defined as a 50% reduction in seizures. Differing response rates were calculated using Fisher Exact test. Results: 30 patients met inclusion criteria. Seventeen (57%) underwent previous sEEG. Average clinical follow up was 3.0 years. Overall response rate was 70%. Median seizure reduction was 74.5%. Response rate was 82.3% for patients with sEEG compared to 53.8% without (p = 0.08); 37.5% for prior epilepsy surgery compared to 81.8% without (p = 0.02); 70% for mesial temporal onset; 50% for previous vagal nerve stimulator compared to 77.3% without (p = 0.13). Conclusion: Our response rates match or surpass outcome metrics of previous studies. Although limited by small study size, subpopulation analyses show positive response rates in patients with previous sEEG versus no sEEG and in temporal versus extratemporal pathology. Additional research is needed to evaluate efficacy of RNS in patients with previous epilepsy surgery, and utility of sEEG in this population.

Magnetic resonance imaging-guided stereotactic laser ablation therapy for the treatment of pediatric epilepsy: a retrospective multiinstitutional study.

OBJECTIVE: The authors of this study evaluated the safety and efficacy of stereotactic laser ablation (SLA) for the treatment of drug-resistant epilepsy (DRE) in children. METHODS: Seventeen North American centers were enrolled in the study. Data for pediatric patients with DRE who had been treated with SLA between 2008 and 2018 were retrospectively reviewed. RESULTS: A total of 225 patients, mean age 12.8 ± 5.8 years, were identified. Target-of-interest (TOI) locations included extratemporal (44.4%), temporal neocortical (8.4%), mesiotemporal (23.1%), hypothalamic (14.2%), and callosal (9.8%). Visualase and NeuroBlate SLA systems were used in 199 and 26 cases, respectively. Procedure goals included ablation (149 cases), disconnection (63), or both (13). The mean follow-up was 27 ± 20.4 months. Improvement in targeted seizure type (TST) was seen in 179 (84.0%) patients. Engel classification was reported for 167 (74.2%) patients; excluding the palliative cases, 74 (49.7%), 35 (23.5%), 10 (6.7%), and 30 (20.1%) patients had Engel class I, II, III, and IV outcomes, respectively. For patients with a follow-up ≥ 12 months, 25 (51.0%), 18 (36.7%), 3 (6.1%), and 3 (6.1%) had Engel class I, II, III, and IV outcomes, respectively. Patients with a history of pre-SLA surgery related to the TOI, a pathology of malformation of cortical development, and 2+ trajectories per TOI were more likely to experience no improvement in seizure frequency and/or to have an unfavorable outcome. A greater number of smaller thermal lesions was associated with greater improvement in TST. Thirty (13.3%) patients experienced 51 short-term complications including malpositioned catheter (3 cases), intracranial hemorrhage (2), transient neurological deficit (19), permanent neurological deficit (3), symptomatic perilesional edema (6), hydrocephalus (1), CSF leakage (1), wound infection (2), unplanned ICU stay (5), and unplanned 30-day readmission (9). The relative incidence of complications was higher in the hypothalamic target location. Target volume, number of laser trajectories, number or size of thermal lesions, or use of perioperative steroids did not have a significant effect on short-term complications. CONCLUSIONS: SLA appears to be an effective and well-tolerated treatment option for children with DRE. Large-volume prospective studies are needed to better understand the indications for treatment and demonstrate the long-term efficacy of SLA in this population.

Case Report: PAFAH1B1 Mutation and Posterior Band Heterotopia With Focal Temporal Lobe Epilepsy Treated by Responsive Neurostimulation.

Subcortical band heterotopia (SBH), also known as double cortex syndrome, is a malformation of cortical development caused by inherited or somatic gene variants. We present a case of a young adult with posterior SBH and electroclinical features of focal neocortical temporal lobe epilepsy. Genomic blood analysis identified a pathogenic somatic mosaicism duplication variant of the PAFAH1B1 gene. Despite bilateral cortical MRI abnormalities, the interictal and ictal EEG findings indicated a focal epileptogenic region in the left posterior temporal region. Chronic responsive cortical neurostimulation across two four-contact depth electrodes placed 5 mm on either side of the maximal interictal spiking identified during intraoperative electrocorticography resulted in a consistent 28% reduction in duration of electrographic seizures and as well as constricted propagation. Although electrographic seizures continued, the family reported no clinical seizures and a marked improvement in resistant behaviors. This observation supports that focal neocortical neuromodulation can control clinical seizures of consistently localized origin despite genetic etiology, bilateral structural brain abnormalities, and continuation of non-propagating electrographic seizures. We propose that a secondary somatic mutation may be the cause of the focal neocortical temporal lobe epilepsy.

Magnetic resonance-guided stereotactic laser ablation therapy for the treatment of pediatric brain tumors: a multiinstitutional retrospective study.

OBJECTIVE: This study aimed to assess the safety and efficacy of MR-guided stereotactic laser ablation (SLA) therapy in the treatment of pediatric brain tumors. METHODS: Data from 17 North American centers were retrospectively reviewed. Clinical, technical, and radiographic data for pediatric patients treated with SLA for a diagnosis of brain tumor from 2008 to 2016 were collected and analyzed. RESULTS: A total of 86 patients (mean age 12.2 ± 4.5 years) with 76 low-grade (I or II) and 10 high-grade (III or IV) tumors were included. Tumor location included lobar (38.4%), deep (45.3%), and cerebellar (16.3%) compartments. The mean follow-up time was 24 months (median 18 months, range 3-72 months). At the last follow-up, the volume of SLA-treated tumors had decreased in 80.6% of patients with follow-up data. Patients with high-grade tumors were more likely to have an unchanged or larger tumor size after SLA treatment than those with low-grade tumors (OR 7.49, p = 0.0364). Subsequent surgery and adjuvant treatment were not required after SLA treatment in 90.4% and 86.7% of patients, respectively. Patients with high-grade tumors were more likely to receive subsequent surgery (OR 2.25, p = 0.4957) and adjuvant treatment (OR 3.77, p = 0.1711) after SLA therapy, without reaching significance. A total of 29 acute complications in 23 patients were reported and included malpositioned catheters (n = 3), intracranial hemorrhages (n = 2), transient neurological deficits (n = 11), permanent neurological deficits (n = 5), symptomatic perilesional edema (n = 2), hydrocephalus (n = 4), and death (n = 2). On long-term follow-up, 3 patients were reported to have worsened neuropsychological test results. Pre-SLA tumor volume, tumor location, number of laser trajectories, and number of lesions created did not result in a significantly increased risk of complications; however, the odds of complications increased by 14% (OR 1.14, p = 0.0159) with every 1-cm3 increase in the volume of the lesion created. CONCLUSIONS: SLA is an effective, minimally invasive treatment option for pediatric brain tumors, although it is not without risks. Limiting the volume of the generated thermal lesion may help decrease the incidence of complications.

Utilizing neuronavigation for virtual electrode representation and safe resection following SEEG; a technical report.

Purpose: One of the most effective treatments for epilepsy is resection, but it remains underutilized. Efforts must be made to increase the ease, safety, and efficacy of epilepsy resection to improve utilization. Studies have shown an improved risk profile of stereoelectroencephalography (SEEG) over subdural grids (SDG) for invasive monitoring. One limitation to increased adoption of SEEG at epilepsy centers is the theoretical difficulty of planning a delayed resection once electrodes are removed. Our objective was to develop and present a technique using readily available neuronavigation technology to guide a cortical, non-lesional epilepsy resection with co-registration of imaging during invasive monitoring to imaging in an explanted patient, allowing for virtual visualization of electrodes. Methods: An example case taking advantage of the technique described above as an adjunct for an anatomically guided resection is presented with technical details and images. Results: Intraoperative neuronavigation was successfully used to virtually represent previously removed SEEG electrodes and accuracy could be easily verified by examining scars on the scalp, bone, dura and pia. Conclusions: The simple technique presented can be a useful adjunct to resection following SEEG. This may help increase the adoption of SEEG, even when resection is planned.

Pericallosal Lipoma and Cortical Dysplasia Masquerading as a Glioma.

Intracranial lipomas represent approximately 1% of intracranial lesions generally felt to represent the abnormal persistence of the meninx primitiva and are commonly accompanied by various developmental brain abnormalities. We report a case of midline intracranial lipoma and evolving frontal lobe fluid-attenuated inversion recovery (FLAIR) abnormality concerning for glial neoplasm in a patient with intractable epilepsy. Our case shows evolving magnetic resonance imaging (MRI) features over two decades raising suspicion for low-grade neoplasm which was ultimately found to represent cortical dysplasia.

Semaphorin4A and H-ferritin utilize Tim-1 on human oligodendrocytes: A novel neuro-immune axis.

Deficiency of trophic factors relating to the survival of oligodendrocytes, combined with direct interactions with the immune system, are favored paradigms that are increasingly implicated in demyelinating diseases of the central nervous system. We and others have previously shown that Sema4A and H-ferritin interact through the T-cell immunoglobulin and mucin domain (Tim-2) receptor in mice. H-ferritin has been identified as the iron delivery protein for oligodendrocytes, whereas Sema4A causes a direct cytotoxic effect. However, the expression of Tim-2 has not been detected in humans. Here, we demonstrate that, similar to rodents, human oligodendrocytes undergo apoptosis when exposed to Sema4A and take up H-ferritin for meeting iron requirements and that these functions are mediated via the Tim-1 receptor. Moreover, we also demonstrate the ability of H-ferritin to block Sema4A-mediated cytotoxicity. Furthermore, we show in a series of pilot studies that Sema4A is detectable in the CSF of multiple sclerosis patients and HIV-seropositive persons and can induce oligodendrocyte cell death. Together, these results identify a novel iron uptake mechanism for human oligodendrocytes and a connection between oligodendrocytes and the immune system.

The comparative accuracy of the ROSA stereotactic robot across a wide range of clinical applications and registration techniques.

Robot-assisted stereotactic neurosurgery is an emerging technology with a growing range of applications. The ROSA system is a robotic stereotactic system that has been shown to be accurate in laboratory studies and large case series. The goal of this study was to examine the accuracy of the ROSA across different registration methods as well as different clinical applications. Sixteen patients with one hundred and seventeen stereotactic trajectories were examined. Accuracy was compared by measuring the distance between the trajectory target and the actual termination of the device as determined by imaging. Entry error and angular deviation were also measured. Variables included bone fiducials vs. laser facial scanning, the clinical indication for stereotactic surgery, and the effect of lead deflection on accuracy. Bone fiducials did not offer an accuracy benefit over laser facial scanning (mean target error 4.5-3.9 mm, p = 0.34) in these clinical scenarios. Laser interstitial thermal therapy, responsive neurostimulation, and stereo electroencephalography were equally accurate when placed by the ROSA (mean target error 4.4-4.3-4.0 mm, respectively, p = 0.69). Deflection did not affect lead accuracy (mean target error 4.4-3.9 mm, p = 0.11). Similar results are seen for entry error and angular deviation. ROSA is a highly accurate stereotactic system. Laser facial scanning provides the same accuracy as bone fiducials in these stereotactic applications. The ROSA is equally accurate across a wide spectrum of applications. The ROSA is effective at limiting lead deflection, and when it does occur, it does not impact target accuracy in a significant way.

Robotic-Guided Bihippocampal and Biparahippocampal Depth Placement for Responsive Neurostimulation in Bitemporal Lobe Epilepsy.

BACKGROUND: Patients with bitemporal lobe epilepsy are generally not considered for surgical resection. Fortunately, responsive neurostimulation provides another avenue for the management of this challenging disease process. In conjunction with our epileptologist, we consider responsive neurostimulation for patients who have clinical features of temporal lobe epilepsy without clear localization on imaging and stereoelectroencephalography. METHODS: Here we describe our technique for implanting a responsive neurostimulator (NeuroPace, NeuroPace Inc., Mountain View, California) with depth electrodes monitoring the hippocampus and parahippocampus using stereotactic robotic guidance (ROSA, Medtech SA, Montpeillier, France). RESULTS: We have used this technique with 5 patients without morbidity. Four of 5 patients have received clinical benefit (Engel classification I-III). Promisingly, long-term seizure monitoring with use of the NeuroPace system has suggested lateralizing information on 3 of these patients that was not apparent on previous invasive monitoring. CONCLUSIONS: Robotically implanted responsive neurostimulation is a safe and effective treatment for bitemporal epilepsy and can possibly lead to valuable diagnostic information to guide future surgical management in patients who previously were not considered candidates for resective or ablative surgery.

Robot Assisted Stereotactic Laser Ablation for a Radiosurgery Resistant Hypothalamic Hamartoma.

Hypothalamic hamartomas (HH) are benign tumors that can cause significant morbidity in adults as a cause of epilepsy, particularly gelastic seizures. Open and endoscopic resections of HH offer good seizure control but have high rates of morbidity and are technically challenging. Stereotactic radiosurgery has been an alternative treatment; however, it results in comparably poor seizure control. Recently, in children, stereotactic laser ablation has shown promise as a surgical technique that can combine the best features of both of these approaches for the treatment of HH. Here we present the first reported use of a frameless robot-assisted stereotactic system to treat an HH. The patient had failed two previous Gamma Knife radiosurgery treatments. Post-procedure he had a stable, but unintentional weight loss of 20 kg and a transient episode of hemiparesis the night of the operation. At six months postoperatively the patient remained seizure free. Stereotactic laser ablation may represent a new standard in the treatment of HH in adults, especially in those who have failed radiosurgery. Further study is warranted in this population to determine efficacy and safety profiles.

Intractable myoclonic seizures in an allogeneic stem cell transplant recipient: A rare case of myoclonic epilepsy.

INTRODUCTION: Myoclonus may be a rare complication of stem cell transplant but has limited discussion in the scientific literature. CASE: We present a case of an acute myeloid leukemia survivor who developed refractory myoclonic epilepsy four years after graft versus host disease (GVHD) developed six days following matched unrelated allogeneic hematopoietic stem cell transplant. DISCUSSION: Graft versus host disease occurs in 30-50% of allogenic hematopoietic stem cell transplant patients and may cause pharmacoresistant myoclonic epilepsy; however, the mechanisms by which GVHD leads to recurrent myoclonic seizures are not well understood (Lee, 2005) [1]. The paucity of clinical reports of such manifestation makes it difficult to diagnose and effectively manage these patients.

Spinal Cord Stimulation for the Treatment of Neuropathic Pain Associated With Leprosy: A Case Report.

BACKGROUND: Leprosy is a major source of nerve damage and may lead to neuropathic pain as well as complex regional pain syndrome (CRPS). Spinal cord stimulation is an effective treatment for CRPS, but there are no reports of this treatment in a patient with leprosy. CASE PRESENTATION: The patient is a 55-year-old man who presented with CRPS in the arms and legs secondary to leprosy that persisted despite multidrug therapy, steroid treatment, and intravenous immunoglobulin. His pain and opioid use were both decreased with insertion of cervical and thoracic spinal cord stimulators. CONCLUSION: Spinal cord stimulation may be a valuable intervention for patients with leprosy-induced CRPS.

Combined open decompressive laminectomy and vertebroplasty for treatment of thoracolumbar fractures retrospective review of 41 cases.

BACKGROUND: Vertebral compression fractures are common, and can occur concomitantly in patients with symptomatic degenerative stenosis. Less commonly, complicated vertebral body fractures may involve retropulsion of bone into the spinal canal, resulting in stenosis with myelopathy and/or radiculopathy. Decompression of the neural elements can lead to destabilization and progressive kyphotic deformity. Laminectomy combined with open vertebroplasty provides a way to decompress the neural elements and stabilize the anterior columns in patients who cannot tolerate extended surgical time or complications associated with instrumentation and fusion. The authors describe the combination of decompressive laminectomy and open transpedicular vertebroplasty as a means to decompress neural elements and simultaneously stabilize the anterior vertebral column. METHODS: Forty-one patients with a total of 51 thoracolumbar fractures were included in this retrospective case review. A decompressive laminectomy was performed first, followed by vertebroplasty using an open transpedicular approach. For subjective assessment of outcome, the patients were assessed using the Oswestry Low Back Disability Questionnaire and additional questions pertaining to the patient's condition. RESULTS: Out of 51 fractures, there were 15 burst fractures and 36 compression fractures. Fracture levels ranged from T12 to S1. The average follow-up period was 27 months (range, 0.5-60 months). The mean post-operative Oswestry score was 16 (range, 0-39), and all patients except for one were subjectively pleased with the results of the procedure and said they would recommend it to others. All patients were able to return to all routine activities of daily living. CONCLUSIONS: The authors' cases indicate combining open decompressive laminectomies with vertebroplasty can be an effective treatment for patients with complicated thoracic and lumbar fractures without involving bone fusion or spinal instrumentation and with good long-term outcomes.

Flow characteristics of cerebrospinal fluid shunt tubing.

OBJECT: Cerebrospinal fluid shunt systems malfunction for a multitude of reasons, including malpostitioning, obstruction of the ventricular or distal catheter, obstruction of the shunt valve, and catheter disruptions or disconnections. The goal of this study was to examine the hydrodynamic resistance and flow in new and explanted catheters and also in catheters with 1 or 2 straight connectors. METHODS: Explanted catheters of multiple lengths, 2-piece catheters, 3-piece catheters, and new catheters were attached to a proximal and distal manometer. A flask with artificial CSF attached to the proximal end provided flow. The flow was allowed to stabilize over 1 hour; then the change in pressure between the proximal and distal end of the catheter was measured. RESULTS: The resistance to flow was calculated for new, never-implanted catheters and compared with the resistance of explanted distal shunt catheters. The resistance of the new catheters was examined after the addition of 1 and 2 straight connectors. Explanted catheters exhibited a slight increase in the resistance to flow of artificial CSF compared with new catheters. Two-piece and 3-piece catheters had a significant increase in resistance to flow compared with new catheters. For all catheters, resistance to flow increased as length increased (new, p = 0.01; explanted, p = 0.009; 1 connector, p = 0.01; 2 connectors, p = 0.03). In this paper, effective diameter is defined as the available cross-sectional area of catheter contacted by the artificial CSF. For new and explanted catheters, a decrease in the effective diameter of the catheter was associated with an increase in the resistance to flow of artificial CSF (new, p = 0.1083; explanted, p = 0.0091). However, after the addition of 1 or 2 connectors, an inverse trend was observed: resistance to flow increased with effective diameter. CONCLUSIONS: There appears to be some increase in resistance of CSF shunt catheters as they age, altering flow dynamics. In addition, the use of straight connectors within a CSF shunt system increases the resistance to flow of artificial CSF within the shunt system. The increase in resistance appears to be related to the duration of implantation and the length of the catheter and inversely related to the diameter of the catheter. This increase in resistance may be related to sterile shunt malfunction. The addition of straight connectors is associated with a significant increase in resistance in comparison with catheters without connectors (p = 0.005).

Intracranial leptomeningeal metastasis from thymic carcinoma: case report and review.

BACKGROUND: Thymic carcinoma is an uncommon malignant tumor of the anterior mediastinum. Meningeal metastasis from this type of neoplasm is extraordinarily rare and the prognosis is abysmal. CASE DESCRIPTION: This article presents the case of a 45-year-old man with known metastatic thymic carcinoma who presented with intractable headaches. An MRI scan was highly suggestive of a meningioma, and it was initially suspected that this patient had 2 primary tumors. Surgical resection of the mass both demonstrated a metastatic thymic lesion and ameliorated the patient's quality of life. CONCLUSION: The authors report a case of intracranial meningeal metastasis from a lymphoepithelioma-like poorly differentiated metastatic thymic carcinoma, which was treated by resection and WBRT. A review of the current literature revealed no other cases of this uncommon alhistologic subtype of thymic carcinoma metastatic to the cranium. The incidence, histologic classification of subtypes, and treatment are discussed. This case also illustrates the importance of maintaining a high degree of suspicion for a metastasis in patients with known primary malignancy who present with an MRI highly suspicious for meningioma.

Direct anatomical localization of the subthalamic nucleus on CT with comparison to Schaltenbrand-Wahren atlas.

Stimulation of the subthalamic nucleus (STN) has become an accepted treatment for motor symptoms of Parkinson's disease. Generally, localization of the target is based on stereotactic atlas coordinates and magnetic resonance (MR) images. In this paper a method of direct anatomical localization of the STN on computed tomography (CT) images is described and compared with the Schaltenbrand-Wahren atlas. Serial CT scans were obtained at 1.5-mm interval and scan thickness of 3 mm, with the CT gantry and glabella-inion plane of the patient's head vertical. The STN was identified as a dense structure medial to the inner semicircular border of the internal capsule in the subthalamic region. Its visibility was increased by changing the window and level settings on the CT workstation computer. The center of the STN in relationship to the intercommissural line, determined by this technique, was similar to those found on standard atlases.