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Benjamin Davidson, Lior M. Elkaim, Nir Lipsman, and George M. Ibrahim

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Jetan H. Badhiwala, Brij Karmur, Lior M. Elkaim, Naif M. Alotaibi, Benjamin R. Morgan, Nir Lipsman, Philippe De Vloo, Suneil K. Kalia, Andres M. Lozano, and George M. Ibrahim

OBJECTIVE

Although deep brain stimulation (DBS) is an accepted treatment for childhood dystonia, there is significant heterogeneity in treatment response and few data are available to identify ideal surgical candidates.

METHODS

Data were derived from a systematic review and individual patient data meta-analysis of DBS for dystonia in children that was previously published. Outcomes were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale for movement (BFMDRS-M) and for disability (BFMDRS-D). The authors used partial least squares, bootstrapping, and permutation statistics to extract patterns of contributions of specific preoperative characteristics to relationship with distinct outcomes, in all patients and in patients with primary and secondary dystonia separately.

RESULTS

Of 301 children undergoing DBS for dystonia, 167 had primary dystonia, 125 secondary dystonia, and 9 myoclonus dystonia. Three dissociable preoperative phenotypes (latent variables) were identified and associated with the following: 1) BFMDRS-M at last follow-up; 2) relative change in BFMDRS-M score; and 3) relative change in BFMDRS-D score. The phenotype of patients with secondary dystonia, with a high BFMDRS-M score and truncal involvement, undergoing DBS at a younger age, was associated with a worse postoperative BFMDRS-M score. Children with primary dystonia involving the trunk had greater improvement in BFMDRS-M and -D scores. Those with primary dystonia of shorter duration and proportion of life with disease, undergoing globus pallidus DBS, had greater improvements in BFMDRS-D scores at long-term follow-up.

CONCLUSIONS

In a comprehensive, data-driven, multivariate analysis of DBS for childhood dystonia, the authors identified novel and dissociable patient phenotypes associated with distinct outcomes. The findings of this report may inform surgical candidacy for DBS.

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Marie-Andrée Coulombe, Lior M. Elkaim, Naif M. Alotaibi, Daniel A. Gorman, Alexander G. Weil, Aria Fallah, Suneil K. Kalia, Nir Lipsman, Andres M. Lozano, and George M. Ibrahim

OBJECTIVE

Gilles de la Tourette syndrome (GTS) is a disorder characterized by motor and vocal tics. Although by definition the onset of GTS is before age 18 years, clinical trials of deep brain stimulation (DBS) have been conducted only in adults. Using individual participant data (IPD) meta-analysis methodology, the current study investigated the safety and efficacy of DBS as a treatment for GTS in children and youth.

METHODS

A systematic review with no date or language restrictions was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Three electronic databases were searched: PubMed, EMBASE, and Web of Science. From 843 articles screened, the IPD of 58 children and youth (ages 12–21 years) extracted from 21 articles were collected and analyzed. A mixed-effects univariable analysis followed by multivariable hierarchical regression was performed using change in the Yale Global Tic Severity Scale (YGTSS) score as the primary outcome and reported measures of comorbidities as secondary outcomes.

RESULTS

The authors’ results showed an average improvement of 57.5% ± 24.6% across studies on the YGTSS. They also found that comorbid depression and stimulation pulse width each correlated negatively with outcome (p < 0.05). In patients with less severe GTS, greater improvements were evident following thalamic stimulation. More than one-quarter (n = 16, 27.6%) of participants experienced side effects, the majority of which were minor.

CONCLUSIONS

DBS in the pediatric population may be an effective option with a moderate safety profile for treatment of GTS in carefully selected children and youth. Large, prospective studies with long-term follow-up are necessary to understand how DBS influences tic symptoms and may alter the natural course of GTS in children.

Restricted access

Nathan A. Shlobin, Andrew Wang, H. Westley Phillips, Han Yan, George M. Ibrahim, Lior M. Elkaim, Shuang Wang, Xiaoyan Liu, Lixin Cai, Dang K. Nguyen, Aria Fallah, and Alexander G. Weil

OBJECTIVE

The prevalence of long-term postoperative sensorimotor deficits in children undergoing perirolandic resective epilepsy surgery is unclear. The risk of developing these deficits must be weighed against the potential reduction in seizure frequency after surgery. In this study, the authors investigated the prevalence of sensorimotor deficits after resective surgery at ≥ 1 year postoperatively.

METHODS

A systematic review and individual patient data meta-analysis was conducted using PubMed, Embase, and Scopus databases. Subgroups of patients were identified and categorized according to their outcomes as follows: group A patients were denoted as seizure free with no postoperative sensorimotor deficits; group B patients experienced seizure recurrence with no deficit; group C patients were seizure free with deficits; and group D patients were not seizure free and with deficits. Rates of sensory deficits were examined in patients undergoing postcentral gyrus resection, and rates of motor deficits were aggregated in patients undergoing precentral gyrus resection.

RESULTS

Of 797 articles resulting from the database searches, 6 articles including 164 pediatric patients at a mean age of 7.7 ± 5.2 years with resection for drug-resistant perirolandic epilepsy were included in the study. Seizure freedom was observed in 118 (72.9%) patients at a mean follow-up of 3.4 ± 1.8 years. In total, 109 (66.5%) patients did not develop sensorimotor deficits at last follow-up, while 55 (33.5%) had permanent deficits. Ten (14.3%) of 70 patients with postcentral gyrus resection had permanent sensory deficits. Of the postcentral gyrus resection patients, 41 (58.6%) patients were included in group A, 19 (27.1%) in group B, 7 (10.0%) in group C, and 3 (4.3%) in group D. Forty (37.7%) of 106 patients with precentral resections had permanent motor deficits. Of the precentral gyrus resection patients, 50 (47.2%) patients were in group A, 16 (15.1%) in group B, 24 (22.6%) in group C, and 16 (15.1%) in group D. Patients without focal cortical dysplasia were more likely to have permanent motor deficits relative to those with focal cortical dysplasia in the precentral surgery cohort (p = 0.02).

CONCLUSIONS

In total, 58.6% of patients were seizure free without deficit, 27.1% were not seizure free and without deficit, 10.0% were seizure free but with deficit, and 4.3% were not seizure free and with deficit. Future studies with functional and quality-of-life data, particularly for patients who experience seizure recurrence with no deficits (as in group B in the present study) and those who are seizure free with deficits (as in group C) after treatment, are necessary to guide surgical decision-making.

Free access

Alexander G. Weil, Aria Fallah, Shelly Wang, George M. Ibrahim, Lior M. Elkaim, Prasanna Jayakar, Ian Miller, Sanjiv Bhatia, Toba N. Niazi, and John Ragheb

OBJECTIVE

Although hemispherectomy is an effective treatment for children with intractable hemispheric epilepsy syndromes, as many as 40% of patients eventually develop seizure recurrence. The causes of seizure recurrence in these patients are incompletely understood. The authors sought to evaluate the efficacy of hemispherectomy at their center and determine whether contralateral MRI abnormalities can predict seizure recurrence.

METHODS

A retrospective review of consecutive hemispherectomies performed at Miami Children’s Hospital between January 2000 and June 2014 was performed. Time-to-event analysis was performed. The “event” was defined as any seizures following resective epilepsy surgery (not including seizures in the first postoperative week and auras). Several preoperative variables were analyzed to determine their suitability to predict seizure recurrence following surgery.

RESULTS

Sixty-nine patients (44 boys) with a mean age of 8.2 ± 5.9 years (range 0.1–20.8 years) underwent 72 hemispherectomies; 67 of these were functional hemispherectomies, while another 5 were completion of a previous functional hemispherectomy (2 completions of functional hemispherectomies, 3 anatomical hemispherectomies). The duration of epilepsy was 5.8 ± 5.5 years with 66 cases (91.7%) having daily seizures. Etiology included stroke (n = 28), malformation of cortical development (n = 11), hemimegalencephaly (n = 11), encephalitis (n = 13), and other (n = 7). Engel class I outcome was achieved in 59 (86%) and 56 (81%) patients at 1 and 2 years of follow-up, respectively. The mean time to seizure recurrence was 33.5 ± 31.1 months. In univariate analyses, the absence of contralateral abnormalities on MRI (HR 4.09, 95% CI 1.41–11.89, p = 0.009) was associated with a longer duration of seizure freedom. The presence of contralateral MRI abnormalities was associated with contralateral ictal seizures on preoperative scalp EEG (p = 0.002). Fifteen patients experienced 20 complications (20/72, 27.8%), including the development of hydrocephalus necessitating CSF diversion in 9 cases (13%), hygroma in 1, hemispheric edema in 1, aseptic meningitis in 2, postoperative hemorrhage in 2, infection in 2, ischemic stroke in 2, and blood transfusion–contracted hepatitis C in 1 case.

CONCLUSIONS

Patients with bihemispheric abnormalities, as evidenced by contralateral MRI abnormalities, have a higher risk of earlier seizure recurrence following functional hemispherectomy.

Free access

Harrison J. Westwick, Lior M. Elkaim, Sami Obaid, Aria Fallah, Albert Tu, George M. Ibrahim, and Alexander G. Weil

OBJECTIVE

The lack of access to primary neurosurgical care presents a significant burden for patients in low- and middle-income countries (LMICs). Efforts to decrease the inequities in access to surgical care have become an increasing focus of initiatives and advocacy within the international neurosurgery community. Although residents may represent highly active members of international teams, the extent of their availability for and interest in global neurosurgery opportunities remains unclear. The objectives of this study were to assess the degree of participation, the level of interest, and the perceived barriers for residents of Canadian neurosurgery programs in engaging in neurosurgery initiatives in LMICs.

METHODS

A cross-sectional survey was administered to 144 residents from all accredited Canadian neurosurgery residency programs. The survey was used to determine the level of participation and interest in global neurosurgery initiatives.

RESULTS

The survey response rate from residents at Canadian neurosurgery programs was 45/144 (31%), although not all respondents answered every question; thus, the denominator for each question is not always 45. Most neurosurgery residents (n = 30, 68%) were unaware of any global neurosurgery opportunities available during residency. Despite 64% of residents having an interest in participation (strongly agree/agree; n = 28), with most residents planning on participating as attending staff (strongly agree/agree; n = 28, 64%), only 3 residents (7%) had taken part in LMIC neurosurgery initiatives. The most cited perceived limitations for participation were lack of time (n = 37, 84%) and finances (n = 26, 59%).

CONCLUSIONS

Among surveyed residents from Canadian neurosurgery programs, there was a low participation rate in global neurosurgery initiatives and limited knowledge of available opportunities, despite relatively high interest. Many respondents identified time and financial constraints as barriers to participation. Many residents felt that interest could increase were there a structured program dedicated to global neurosurgery available in their residency program.

Restricted access

Han Yan, Lior M. Elkaim, Flavia Venetucci Gouveia, Joelene F. Huber, Jurgen Germann, Aaron Loh, Juan Carlos Benedetti-Isaac, Paresh K. Doshi, Cristina V. Torres, David J. Segar, Gavin J. B. Elias, Alexandre Boutet, G. Rees Cosgrove, Alfonso Fasano, Andres M. Lozano, Abhaya V. Kulkarni, and George M. Ibrahim

OBJECTIVE

Individuals with autism spectrum disorder (ASD) may display extreme behaviors such as self-injury or aggression that often become refractory to psychopharmacology or behavioral intervention. Deep brain stimulation (DBS) is a surgical alternative that modulates brain circuits that have yet to be clearly elucidated. In the current study the authors performed a connectomic analysis to identify brain circuitry engaged by DBS for extreme behaviors associated with ASD.

METHODS

A systematic review was performed to identify prior reports of DBS as a treatment for extreme behaviors in patients with ASD. Individual patients’ perioperative imaging was collected from corresponding authors. DBS electrode localization and volume of tissue activated modeling were performed. Volumes of tissue activated were used as seed points in high-resolution normative functional and structural imaging templates. The resulting individual functional and structural connectivity maps were pooled to identify networks and pathways that are commonly engaged by all targets.

RESULTS

Nine patients with ASD who were receiving DBS for symptoms of aggression or self-injurious behavior were identified. All patients had some clinical improvement with DBS. Connectomic analysis of 8 patients (from the systematic review and unpublished clinical data) demonstrated a common anatomical area of shared circuitry within the anterior limb of the internal capsule. Functional analysis of 4 patients identified a common network of distant brain areas including the amygdala, insula, and anterior cingulate engaged by DBS.

CONCLUSIONS

This study presents a comprehensive synopsis of the evidence for DBS in the treatment of extreme behaviors associated with ASD. Using network mapping, the authors identified key circuitry common to DBS targets.

Restricted access

Lior M. Elkaim, Greg McIntosh, Nicolas Dea, Rodrigo Navarro-Ramirez, W. Bradley Jacobs, David W. Cadotte, Supriya Singh, Sean D. Christie, Aaron Robichaud, Philippe Phan, Jérôme Paquet, Andrew Nataraj, Hamilton Hall, Christopher S. Bailey, Y. Raja Rampersaud, Kenneth Thomas, Neil Manson, Charles Fisher, and Michael H. Weber

OBJECTIVE

Degenerative cervical myelopathy (DCM) is an important public health issue. Surgery is the mainstay of treatment for moderate and severe DCM. Delayed discharge of patients after DCM surgery is associated with increased healthcare costs. There is a paucity of data regarding predictive factors for discharge destination after scheduled surgery for patients with DCM. The purpose of this study was to identify factors predictive of home versus nonhome discharge after DCM surgery.

METHODS

Patients undergoing scheduled DCM surgery who had been enrolled in a prospective DCM substudy of the Canadian Spine Outcomes and Research Network registry between January 2015 and October 2020 were included in this retrospective analysis. Patient data were evaluated to identify potential factors predictive of home discharge after surgery. Logistic regression was used to identify independent factors predictive of home discharge. A multivariable model was then used as a final model.

RESULTS

Overall, 639 patients were included in the initial analysis, 543 (85%) of whom were discharged home. The mean age of the entire cohort was 60 years (SD 11.8 years), with a BMI of 28.9 (SD 5.7). Overall, 61.7% of the patients were female. The mean length of stay was 2.72 days (SD 1.7 days). The final internally validated bootstrapped multivariable model revealed that younger age, higher 9-Item Patient Health Questionnaire score, lower Neck Disability Index scores, fewer operated levels, mJOA scores indicating mild disease, anterior cervical discectomy and fusion procedure, and no perioperative adverse effects were predictive of home discharge.

CONCLUSIONS

Younger age, less neck-related disability, fewer operated levels, more significant depression, less severe myelopathy, anterior cervical discectomy and fusion procedure, and no perioperative adverse effects are predictive of home discharge after surgery for DCM. These factors can help to guide clinical decision-making and optimize postoperative care pathways.