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Responsive neurostimulation as a treatment for super-refractory focal status epilepticus: a systematic review and case series

Lia D. Ernst, Ahmed M. Raslan, Angela Wabulya, Hae Won Shin, Sydney S. Cash, Jimmy C. Yang, Vishwanath Sagi, David King-Stephens, Eyiyemisi C. Damisah, Alexander Ramos, Batool Hussain, Sheela Toprani, David M. Brandman, Kiarash Shahlaie, Kiran Kanth, Amir Arain, Angela Peters, John D. Rolston, Meaghan Berns, Sima I. Patel, and Utku Uysal

OBJECTIVE

Super-refractory status epilepticus (SRSE) has high rates of morbidity and mortality. Few published studies have investigated neurostimulation treatment options in the setting of SRSE. This systematic literature review and series of 10 cases investigated the safety and efficacy of implanting and activating the responsive neurostimulation (RNS) system acutely during SRSE and discusses the rationale for lead placement and selection of stimulation parameters.

METHODS

Through a literature search (of databases and American Epilepsy Society abstracts that were last searched on March 1, 2023) and direct contact with the manufacturer of the RNS system, 10 total cases were identified that utilized RNS acutely during SE (9 SRSE cases and 1 case of refractory SE [RSE]). Nine centers obtained IRB approval for retrospective chart review and completed data collection forms. A tenth case had published data from a case report that were referenced in this study. Data from the collection forms and the published case report were compiled in Excel.

RESULTS

All 10 cases presented with focal SE: 9 with SRSE and 1 with RSE. Etiology varied from known lesion (focal cortical dysplasia in 7 cases and recurrent meningioma in 1) to unknown (2 cases, with 1 presenting with new-onset refractory focal SE [NORSE]). Seven of 10 cases exited SRSE after RNS placement and activation, with a time frame ranging from 1 to 27 days. Two patients died of complications due to ongoing SRSE. Another patient’s SE never resolved but was subclinical. One of 10 cases had a device-related significant adverse event (trace hemorrhage), which did not require intervention. There was 1 reported recurrence of SE after discharge among the cases in which SRSE resolved up to the defined endpoint.

CONCLUSIONS

This case series offers preliminary evidence that RNS is a safe and potentially effective treatment option for SRSE in patients with 1–2 well-defined seizure-onset zone(s) who meet the eligibility criteria for RNS. The unique features of RNS offer multiple benefits in the SRSE setting, including real-time electrocorticography to supplement scalp EEG for monitoring SRSE progress and response to treatment, as well as numerous stimulation options. Further research is indicated to investigate the optimal stimulation settings in this unique clinical scenario.

In Journal of Neurosurgery Publish Before Print

Open access

Safety and feasibility clinical trial of nucleus accumbens deep brain stimulation for treatment-refractory opioid use disorder

Ali R. Rezai, James J. Mahoney III, Manish Ranjan, Marc W. Haut, Wanhong Zheng, Laura R. Lander, James H. Berry, Daniel L. Farmer, Jennifer L. Marton, Padma Tirumalai, Ashley Mears, Daisy G. Y. Thompson-Lake, Victor S. Finomore, Pierre-François D’Haese, Will M. Aklin, David T. George, John D. Corrigan, and Sally L. Hodder

OBJECTIVE

There were more than 107,000 drug overdose deaths in the US in 2021, the most ever recorded. Despite advances in behavioral and pharmacological treatments, over 50% of those receiving treatment for opioid use disorder (OUD) experience drug use recurrence (relapse). Given the prevalence of OUD and other substance use disorders (SUDs), the high rate of drug use recurrence, and the number of drug overdose deaths, novel treatment strategies are desperately needed. The objective of this study was to evaluate the safety and feasibility of deep brain stimulation (DBS) targeting the nucleus accumbens (NAc)/ventral capsule (VC) and potential impact on outcomes in individuals with treatment-refractory OUD.

METHODS

A prospective, open-label, single-arm study was conducted among participants with longstanding treatment-refractory OUD (along with other co-occurring SUDs) who underwent DBS in the NAc/VC. The primary study endpoint was safety; secondary/exploratory outcomes included opioid and other substance use, substance craving, and emotional symptoms throughout follow-up and FDG-PET neuroimaging.

RESULTS

Four male participants were enrolled and all tolerated DBS surgery well with no serious adverse events (AEs) and no device- or stimulation-related AEs. Two participants sustained complete substance abstinence for > 1150 and > 520 days, respectively, with significant post-DBS reductions in substance craving, anxiety, and depression. One participant experienced post-DBS drug use recurrences with reduced frequency and severity. The DBS system was explanted in one participant due to noncompliance with treatment requirements and the study protocol. FDG-PET neuroimaging revealed increased glucose metabolism in the frontal regions for the participants with sustained abstinence only.

CONCLUSIONS

DBS of the NAc/VC was safe, feasible, and can potentially reduce substance use, craving, and emotional symptoms in those with treatment-refractory OUD. A randomized, sham-controlled trial in a larger cohort of patients is being initiated.

In Journal of Neurosurgery Publish Before Print

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Subependymal giant-cell astrocytomas in the absence of tuberous sclerosis

Rebecca A. Reynolds, Diane J. Aum, Ignacio Gonzalez-Gomez, Michael Wong, Kaleigh Roberts, Sonika Dahiya, Luis F. Rodriguez, Jarod L. Roland, and Matthew D. Smyth

OBJECTIVE

Tuberous sclerosis is a rare genetic condition caused by TSC1 or TSC2 mutations that can be inherited, sporadic, or the result of somatic mosaicism. Subependymal giant-cell astrocytoma (SEGA) is a major diagnostic feature of tuberous sclerosis complex (TSC). This study aimed to present a series of cases in which a pathological diagnosis of SEGA was not diagnostic of tuberous sclerosis.

METHODS

The authors retrospectively reviewed a clinical case series of 5 children who presented with a SEGA tumor to Johns Hopkins All Children’s Hospital and St. Louis Children’s Hospital between 2010 and 2022 and whose initial genetic workup was negative for tuberous sclerosis. All patients were treated with craniotomy for SEGA resection. TSC genetic testing was performed on all SEGA specimens.

RESULTS

The children underwent open frontal craniotomy for SEGA resection from the ages of 10 months to 14 years. All cases demonstrated the classic imaging features of SEGA. Four were centered at the foramen of Monro and 1 in the occipital horn. One patient presented with hydrocephalus, 1 with headaches, 1 with hand weakness, 1 with seizures, and 1 with tumor hemorrhage. Somatic TSC1 mutation was present in the SEGA tumors of 2 patients and TSC2 mutation in 1 patient. Germline TSC mutation testing was negative for all 5 cases. No patient had other systemic findings of tuberous sclerosis on ophthalmological, dermatological, neurological, renal, or cardiopulmonary assessments and thus did not meet the clinical criteria for tuberous sclerosis. The average follow-up was 6.7 years. Recurrence was noted in 2 cases, in which 1 patient underwent radiosurgery and 1 was started on a mammalian target of rapamycin (mTOR) inhibitor (rapamycin).

CONCLUSIONS

There may be intracranial implications of somatic mosaicism associated with tuberous sclerosis. Children who are diagnosed with SEGA do not necessarily have a diagnosis of tuberous sclerosis. Tumors may carry a TSC1 or TSC2 mutation, but germline testing can be negative. These children should continue to be followed with serial cranial imaging for tumor progression, but they may not require the same long-term monitoring as patients who are diagnosed with germline TSC1 or TSC2 mutations.

In Journal of Neurosurgery: Pediatrics Publish Before Print

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Use of multiple rods and proximal junctional kyphosis in adult spinal deformity surgery

Jichao Ye, Sachin Gupta, Ali S. Farooqi, Tsung-Cheng Yin, Alex Soroceanu, Frank J. Schwab, Virginie Lafage, Michael P. Kelly, Khaled Kebaish, Richard Hostin, Jeffrey L. Gum, Justin S. Smith, Christopher I. Shaffrey, Justin K. Scheer, Themistocles S. Protopsaltis, Peter G. Passias, Eric O. Klineberg, Han Jo Kim, Robert A. Hart, D. Kojo Hamilton, Christopher P. Ames, and Munish C. Gupta

OBJECTIVE

Multiple rods are utilized in adult spinal deformity (ASD) surgery to increase construct stiffness. However, the impact of multiple rods on proximal junctional kyphosis (PJK) is not well established. This study aimed to investigate the impact of multiple rods on PJK incidence in ASD patients.

METHODS

ASD patients from a prospective multicenter database with a minimum follow-up of 1 year were retrospectively reviewed. Clinical and radiographic data were collected preoperatively, at 6 weeks postoperatively, at 6 months postoperatively, at 1 year postoperatively, and at every subsequent year postoperatively. PJK was defined as a kyphotic increase of > 10° in the Cobb angle from the upper instrumented vertebra (UIV) to UIV+2 as compared with preoperative values. Demographic data, radiographic parameters, and PJK incidence were compared between the multirod and dual-rod patient cohorts. PJK-free survival analysis was performed using Cox regression to control for demographic characteristics, comorbidities, level of fusion, and radiographic parameters.

RESULTS

Overall, 307/1300 (23.62%) cases utilized multiple rods. Cases with multiple rods were more likely to be revisions (68.4% vs 46.5%, p < 0.001), to be posterior only (80.7% vs 61.5%, p < 0.001), involve more levels of fusion (mean 11.73 vs 10.60, p < 0.001), and include 3-column osteotomy (42.9% vs 17.1%, p < 0.001). Patients with multiple rods also had greater preoperative pelvic retroversion (mean pelvic tilt 27.95° vs 23.58°, p < 0.001), greater thoracolumbar junction kyphosis (−15.9° vs −11.9°, p = 0.001), and more severe sagittal malalignment (C7–S1 sagittal vertical axis 99.76 mm vs 62.23 mm, p < 0.001), all of which corrected postoperatively. Patients with multiple rods had similar incidence rates of PJK (58.6% vs 58.1%) and revision surgery (13.0% vs 17.7%). The PJK-free survival analysis demonstrated equivalent PJK-free survival durations among the patients with multiple rods (HR 0.889, 95% CI 0.745–1.062, p = 0.195) after controlling for demographic and radiographic parameters. Further stratification based on implant metal type demonstrated noninferior PJK incidence rates with multiple rods in the titanium (57.1% vs 54.6%, p = 0.858), cobalt chrome (60.5% vs 58.7%, p = 0.646), and stainless steel (20% vs 63.7%, p = 0.008) cohorts.

CONCLUSIONS

Multirod constructs for ASD are most frequently utilized in revision, long-level reconstructions with 3-column osteotomy. The use of multiple rods in ASD surgery does not result in an increased incidence of PJK and is not affected by rod metal type.

In Journal of Neurosurgery: Spine Publish Before Print

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Vasospasm following brain tumor resection in children: institutional experience and systematic review

Rakan Bokhari, Lior M. Elkaim, Nathan A. Shlobin, Naif M. Alotaibi, Abdulrahman J. Sabbagh, Alexander G. Weil, Saleh Baeesa, Roy W. R. Dudley, Jeffrey Atkinson, and Jean-Pierre Farmer

OBJECTIVE

Delayed cerebral ischemia (DCI) associated with vasospasm is well described in the setting of aneurysmal subarachnoid hemorrhage (SAH). In addition, DCI is very infrequently encountered in patients who have undergone resection of a brain tumor with unclear pathophysiology. The occurrence of DCI in the pediatric population is exceedingly rare, and outcomes in this population have, to the authors’ knowledge, never been systematically reviewed. Therefore, the authors present what is to their knowledge the largest series of pediatric patients with this complication and systematically reviewed the literature for individual participant data.

METHODS

The authors conducted a retrospective review of 172 sellar and suprasellar tumors in pediatric patients who underwent surgery at the Montreal Children’s Hospital between 1999 and 2017 to identify cases of vasospasm occurring after tumor resection. Descriptive statistics, including patient characteristics, intraoperative and postoperative findings, and outcome status, were collected. A systematic review was also conducted using three databases (PubMed, Web of Science, Embase) to identify reported cases available in the literature of vasospasm after tumor resection in children and collect individual participant data on these patients for further analysis.

RESULTS

Six patients treated at Montreal Children’s Hospital were identified, with an average age of 9.5 years (range 6–15 years). The prevalence of vasospasm after tumor resection was 3.5% (6/172). Vasospasm in all 6 patients occurred after craniotomy was performed to treat a suprasellar tumor. The average interval from surgery to symptoms was 3.25 days (range 12 hours–10 days). The most common tumor etiology was craniopharyngioma, seen in 4 cases. Extensive tumor encasement of blood vessels requiring significant operative manipulation was described in all 6 patients. A rapid decrease in serum sodium (exceeding 12 mEq/L/24 hrs or below 135 mEq/L) was seen in 4 patients. On final follow-up, 3 patients were left with significant disability, and all patients had persistent deficits. A systematic review of the literature revealed a total of 10 other patients whose characteristics and treatment were compared with those of the 6 patients treated at Montreal Children’s Hospital.

CONCLUSIONS

Vasospasm after tumor resection in children and youth is likely a rare entity, with a prevalence of 3.5% in this case series. Suprasellar tumor location (particularly craniopharyngioma tumor etiology), significant encasement of blood vessels by the tumor, and postoperative hyponatremia may be predictive factors. Outcome is poor, with most patients having significant persistent neurological deficits.

In Journal of Neurosurgery: Pediatrics Publish Before Print

Open access

Neglected cervical meningocele in an adult: illustrative case

Abolfazl Rahimizadeh, Seyed Ali Ahmadi, Ali Mohammadi Moghadam, Shaghayegh Rahimizadeh, Walter Williamson, Mahan Amirzadeh, and Sam Hajaliloo Sami

BACKGROUND

Posterior cervical meningoceles are rare in adults because most are surgically excised early in life. Such meningoceles in adults are mostly presented as a cystic mass and their presentation as a solid mass is very rare.

OBSERVATIONS

An asymptomatic adult with cervical meningocele presented as a congenital midline skin covered solid mass in the posterior aspect of the neck is presented. Neuroradiological surveys showed attachment of the mass to intradural spinal cord. With diagnosis of a cervical meningocele, after excision of the solid sac, the stalk extending from the core of the mass to the dura was isolated. This was followed by intradural spinal cord detethering. The mass was compatible with rudimentary meningocele in pathology.

LESSONS

Neglected cervical meningocele is quite rare in adults. Surgical removal of the mass in adults is usually for cosmetic reasons rather than neurological impairment. However, surgical removal of the mass without intradural cord detethering is not sufficient. In such cases, late onset quadriparesis may be appear due to the spinal cord tethering scenario.

In Journal of Neurosurgery: Case Lessons Volume 5 (2023): Issue 23 (Jun 2023)

Open access

Radiation-induced cavernous malformations in the spine: patient series

Stefan W. Koester, Lea Scherschinski, Visish M. Srinivasan, Katherine Karahalios, Kavelin Rumalla, Dimitri Benner, Joshua S. Catapano, Robert F. Spetzler, and Michael T. Lawton

BACKGROUND

Radiation-induced spinal cord cavernous malformations (RISCCMs) are a rare subset of central nervous system lesions and are more clinically aggressive than congenital cavernous malformations (CMs). The authors assessed the characteristics and outcomes of patients with RISCCM at a single institution and systematically reviewed the pertinent literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

OBSERVATIONS

Among the 146 spinal CMs at the authors’ institution, 3 RISCCMs were found. Symptom duration ranged from 0.1 to 8.5 months (mean [standard deviation], 3.2 [4.6] months), and latency ranged from 16 to 29 years (22.4 [9.6] years). All 3 RISCCMs were surgically treated with complete resection; 2 patients had stable outcomes, and 1 improved postoperatively. A review of 1240 articles revealed 20 patients with RISCCMs. Six of these patients were treated with resection, 13 were treated conservatively, and in 1 case, the treatment type was not stated. Five of the 6 patients treated surgically reported improvement postoperatively or at follow-up; 1 was stable, and none reported worsened outcomes.

LESSONS

RISCCMs are rare sequelae following radiation that inadvertently affect the spinal cord. Altogether, the frequency of stable and improved outcomes on follow-up suggests that resection could prevent further patient decline caused by symptoms of RISCCM. Therefore, surgical management should be considered primary therapy in patients presenting with RISCCMs.

In Journal of Neurosurgery: Case Lessons Volume 5 (2023): Issue 23 (Jun 2023)

Open access

Vessel wall imaging and carotid artery stenting for recurrent cervical internal carotid artery vasospasm syndrome: illustrative case

Shinya Tokunaga, Yukihiro Yamao, Takakuni Maki, Akira Ishii, Tomoaki Miyake, Ken Yasuda, Yu Abekura, Masakazu Okawa, Takayuki Kikuchi, Yasutaka Fushimi, Kazumichi Yoshida, and Susumu Miyamoto

BACKGROUND

Recurrent cervical internal carotid artery vasospasm syndrome (RCICVS) causes cerebral infarction, ocular symptoms, and occasionally chest pain accompanied by coronary artery vasospasm. The etiology and optimal treatment remain unclear.

OBSERVATIONS

The authors report a patient with drug-resistant RCICVS who underwent carotid artery stenting (CAS). Magnetic resonance angiography revealed recurrent vasospasm in the cervical segment of the internal carotid artery (ICA). Vessel wall imaging during an ischemic attack revealed vascular wall thickening of the ICA, similar to that in reversible cerebral vasoconstriction syndrome. The superior cervical ganglion was identified at the anteromedial side of the stenosis site. Coronary artery stenosis was also detected. After CAS, the symptoms of cerebral ischemia were prevented for 2 years, but bilateral ocular and chest symptoms did occur.

LESSONS

Vessel wall imaging findings suggest that RCICVS is a sympathetic nervous system-related disease. CAS could be an effective treatment for drug-resistant RCICVS to prevent cerebral ischemic events.

In Journal of Neurosurgery: Case Lessons Volume 5 (2023): Issue 23 (Jun 2023)

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Calibration of a comprehensive predictive model for the development of proximal junctional kyphosis and failure in adult spinal deformity patients with consideration of contemporary goals and techniques

Peter S. Tretiakov, Renaud Lafage, Justin S. Smith, Breton G. Line, Bassel G. Diebo, Alan H. Daniels, Jeffrey Gum, Themistocles Protopsaltis, D. Kojo Hamilton, Alex Soroceanu, Justin K. Scheer, Robert K. Eastlack, Gregory Mundis Jr., Pierce D. Nunley, Eric O. Klineberg, Khaled Kebaish, Stephen Lewis, Lawrence Lenke, Richard Hostin, Munish C. Gupta, Christopher P. Ames, Robert A. Hart, Douglas Burton, Christopher I. Shaffrey, Frank Schwab, Shay Bess, Han Jo Kim, Virginie Lafage, and Peter G. Passias

OBJECTIVE

The objective of this study was to calibrate an updated predictive model incorporating novel clinical, radiographic, and prophylactic measures to assess the risk of proximal junctional kyphosis (PJK) and failure (PJF).

METHODS

Operative patients with adult spinal deformity (ASD) and baseline and 2-year postoperative data were included. PJK was defined as ≥ 10° in sagittal Cobb angle between the inferior uppermost instrumented vertebra (UIV) endplate and superior endplate of the UIV + 2 vertebrae. PJF was radiographically defined as a proximal junctional sagittal Cobb angle ≥ 15° with the presence of structural failure and/or mechanical instability, or PJK with reoperation. Backstep conditional binary supervised learning models assessed baseline demographic, clinical, and surgical information to predict the occurrence of PJK and PJF. Internal cross validation of the model was performed via a 70%/30% cohort split. Conditional inference tree analysis determined thresholds at an alpha level of 0.05.

RESULTS

Seven hundred seventy-nine patients with ASD (mean 59.87 ± 14.24 years, 78% female, mean BMI 27.78 ± 6.02 kg/m2, mean Charlson Comorbidity Index 1.74 ± 1.71) were included. PJK developed in 50.2% of patients, and 10.5% developed PJF by their last recorded visit. The six most significant demographic, radiographic, surgical, and postoperative predictors of PJK/PJF were baseline age ≥ 74 years, baseline sagittal age-adjusted score (SAAS) T1 pelvic angle modifier > 1, baseline SAAS pelvic tilt modifier > 0, levels fused > 10, nonuse of prophylaxis measures, and 6-week SAAS pelvic incidence minus lumbar lordosis modifier > 1 (all p < 0.015). Overall, the model was deemed significant (p < 0.001), and internally validated receiver operating characteristic analysis returned an area under the curve of 0.923, indicating robust model fit.

CONCLUSIONS

PJK and PJF remain critical concerns in ASD surgery, and efforts to reduce the occurrence of PJK and PJF have resulted in the development of novel prophylactic techniques and enhanced clinical and radiographic selection criteria. This study demonstrates a validated model incorporating such techniques that may allow for the prediction of clinically significant PJK and PJF, and thus assist in optimizing patient selection, enhancing intraoperative decision making, and reducing postoperative complications in ASD surgery.

In Journal of Neurosurgery: Spine Publish Before Print

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Clinical outcomes of pediatric hemispherectomy following unsuccessful subhemispheric resection for refractory epilepsy: a case review study

Lisa F. Akiyama, Emma A. Roberts, Hillary A. Shurtleff, Dwight Barry, Russell P. Saneto, Edward J. Novotny, Christopher C. Young, Molly H. Warner, Jason S. Hauptman, Jeffrey G. Ojemann, and Ahmad Marashly

OBJECTIVE

Epilepsy surgery remains one of the most underutilized procedures in epilepsy despite its proven superiority to other available therapies. This underutilization is greater in patients in whom initial surgery fails. This case series examined the clinical characteristics, reasons for initial surgery failure, and outcomes in a cohort of patients who underwent hemispherectomy following unsuccessful smaller resections for intractable epilepsy (subhemispheric group [SHG]) and compared them to those of a cohort of patients who underwent hemispherectomy as the first surgery (hemispheric group [HG]). The objective of this paper was to determine the clinical characteristics of patients in whom a small, subhemispheric resection failed, who went on to become seizure free after undergoing a hemispherectomy.

METHODS

Patients who underwent hemispherectomy at Seattle Children’s Hospital between 1996 and 2020 were identified. Inclusion criteria for SHG were as follows: 1) patients ≤ 18 years of age at the time of hemispheric surgery; 2) initial subhemispheric epilepsy surgery that did not produce seizure freedom; 3) hemispherectomy or hemispherotomy after the subhemispheric surgery; and 4) follow-up for at least 12 months after hemispheric surgery. Data collected included the following: patient demographics; seizure etiology; comorbidities; prior neurosurgeries; neurophysiological studies; imaging studies; and surgical details—plus surgical, seizure, and functional outcomes. Seizure etiology was classified as follows: 1) developmental, 2) acquired, or 3) progressive. The authors compared SHG to HG in terms of demographics, seizure etiology, and seizure and neuropsychological outcomes.

RESULTS

There were 14 patients in the SHG and 51 patients in the HG. All patients in the SHG had Engel class IV scores after their initial resective surgery. Overall, 86% (n = 12) of the patients in the SHG had good posthemispherectomy seizure outcomes (Engel class I or II). All patients in the SHG who had progressive etiology (n = 3) had favorable seizure outcomes, with eventual hemispherectomy (1 each with Engel classes I, II, and III). Engel classifications posthemispherectomy between the groups were similar. There were no statistical differences in postsurgical Vineland Adaptive Behavior Scales Adaptive Behavior Composite scores or postsurgical full-scale IQ scores between groups when accounting for presurgical scores.

CONCLUSIONS

Hemispherectomy as a repeat surgery after unsuccessful subhemispheric epilepsy surgery has a favorable seizure outcome, with stable or improved intelligence and adaptive functioning. Findings in these patients are similar to those in patients who had hemispherectomy as their first surgery. This can be explained by the relatively small number of patients in the SHG and the higher likelihood of hemispheric surgeries to resect or disconnect the entire epileptogenic lesion compared to smaller resections.

In Journal of Neurosurgery: Pediatrics Publish Before Print