Jetan H. Badhiwala, Farshad Nassiri and Saleh A. Almenawer
JNSPG 75th Anniversary Invited Review Article
Jetan H. Badhiwala, Christopher S. Ahuja and Michael G. Fehlings
Acute traumatic spinal cord injury (SCI) is a devastating event with far-reaching physical, emotional, and economic consequences for patients, families, and society at large. Timely delivery of specialized care has reduced mortality; however, long-term neurological recovery continues to be limited. In recent years, a number of exciting neuroprotective and regenerative strategies have emerged and have come under active investigation in clinical trials, and several more are coming down the translational pipeline. Among ongoing trials are RISCIS (riluzole), INSPIRE (Neuro-Spinal Scaffold), MASC (minocycline), and SPRING (VX-210). Microstructural MRI techniques have improved our ability to image the injured spinal cord at high resolution. This innovation, combined with serum and cerebrospinal fluid (CSF) analysis, holds the promise of providing a quantitative biomarker readout of spinal cord neural tissue injury, which may improve prognostication and facilitate stratification of patients for enrollment into clinical trials. Given evidence of the effectiveness of early surgical decompression and growing recognition of the concept that “time is spine,” infrastructural changes at a systems level are being implemented in many regions around the world to provide a streamlined process for transfer of patients with acute SCI to a specialized unit. With the continued aging of the population, central cord syndrome is soon expected to become the most common form of acute traumatic SCI; characterization of the pathophysiology, natural history, and optimal treatment of these injuries is hence a key public health priority. Collaborative international efforts have led to the development of clinical practice guidelines for traumatic SCI based on robust evaluation of current evidence. The current article provides an in-depth review of progress in SCI, covering the above areas.
Jetan H. Badhiwala, Eric M. Thompson, Armando J. Lorenzo and Abhaya V. Kulkarni
Congenital spinal lipomas of the conus (SLCs) are among the most common closed neural tube defects. The treatment of SLC is an area of controversy because the true natural history of this condition is unknown. Here, the authors present two cases of SLC presenting in infancy with compromised lower urinary tract function, which was objectively confirmed by abnormal urodynamic studies. In both cases, there was spontaneous improvement in urodynamic parameters, with stable normal urinary function at the long-term follow-up. Although cases of spontaneous radiological regression of SLC have very infrequently been reported, they have not been associated with the reversal of already present neurological deficits. This report reinforces the need for further delineation of the true natural history of SLC and highlights the dynamic nature of associated neurological compromise over time.
Jetan H. Badhiwala, Chris J. Hong, Farshad Nassiri, Brian Y. Hong, Jay Riva-Cambrin and Abhaya V. Kulkarni
The optimal clinical management of intraventricular hemorrhage (IVH) and posthemorrhagic ventricular dilation (PHVD)/posthemorrhagic hydrocephalus (PHH) in premature infants remains unclear. A common approach involves temporary treatment of hydrocephalus in these patients with a ventriculosubgaleal shunt (VSGS), ventricular access device (VAD), or external ventricular drain (EVD) until it becomes evident that the patient needs and can tolerate permanent CSF diversion (i.e., ventriculoperitoneal shunt). The present systematic review and meta-analysis aimed to provide a robust and comprehensive summary of the published literature regarding the clinical outcomes and complications of these 3 techniques as temporizing measures in the management of prematurity-related PHVD/PHH.
The authors searched MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library for studies published through December 2013 on the use of VSGSs, VADs, and/or EVDs as temporizing devices for the treatment of hydrocephalus following IVH in the premature neonate. Data pertaining to patient demographic data, study methods, interventions, and outcomes were extracted from eligible articles. For each of the 3 types of temporizing device, the authors performed meta-analyses examining 6 outcomes of interest, which were rates of 1) obstruction; 2) infection; 3) arrest of hydrocephalus (i.e., permanent shunt independence); 4) mortality; 5) good neurodevelopmental outcome; and 6) revision.
Thirty-nine studies, representing 1502 patients, met eligibility criteria. All of the included articles were observational studies; 36 were retrospective and 3 were prospective designs. Nine studies (n = 295) examined VSGSs, 24 (n = 962) VADs, and 9 (n = 245) EVDs. Pooled rates of outcome for VSGS, VAD, and EVD, respectively, were 9.6%, 7.3%, and 6.8% for obstruction; 9.2%, 9.5%, and 6.7% for infection; 12.2%, 10.8%, and 47.3% for revision; 13.9%, 17.5%, and 31.8% for arrest of hydrocephalus; 12.1%, 15.3%, and 19.1% for death; and 58.7%, 50.1%, and 56.1% for good neurodevelopmental outcome.
This study provides robust estimates of outcomes for the most common temporizing treatments for IVH in premature infants. With few exceptions, the range of outcomes was similar for VSGS, VAD, and EVD.
Jetan H. Badhiwala, Forough Farrokhyar, Waleed Alhazzani, Blake Yarascavitch, Mohammed Aref, Almunder Algird, Naresh Murty, Edward Kachur, Aleksa Cenic, Kesava Reddy and Saleh A. Almenawer
Information pertaining to the natural history of intramedullary spinal cord cavernous malformations (ISCCMs) and patient outcomes after surgery is scarce. To evaluate factors associated with favorable outcomes for patients with surgically and conservatively managed ISCCMs, the authors performed a systematic review and metaanalysis of the literature. In addition, they included their single-center series of ISCCMs.
The authors searched MEDLINE, EMBASE, CINAHL, Google Scholar, and The Cochrane Library for studies published through June 2013 that reported cases of ISCCMs. Data from all eligible studies were used to examine the epidemiology, clinical features, and neurological outcomes of patients with surgically managed and conservatively treated ISCCMs. To evaluate several variables as predictors of favorable neurological outcomes, the authors conducted a meta-analysis of individual patient data and performed univariate and multivariate logistic regression analyses. Variables included patient age, patient sex, lesion spinal level, lesion size, cerebral cavernomas, family history of cavernous malformations, clinical course, presenting symptoms, treatment strategy (operative or conservative), symptom duration, surgical approach, spinal location, and extent of resection. In addition, they performed a meta-analysis to determine a pooled estimate of the annual hemorrhage rate of ISCCMs.
Eligibility criteria were met by 40 studies, totaling 632 patients, including the authors' institutional series of 24 patients. Mean patient age was 39.1 years (range 2–80 years), and the male-to-female ratio was 1.1:1. Spinal levels of cavernomas were cervical (38%), cervicothoracic (2.4%), thoracic (55.2%), thoracolumbar (0.6%), lumbar (2.1%), and conus medullaris (1.7%). Average cavernoma size was 9.2 mm. Associated cerebral cavernomas occurred in 16.5% of patients, and a family history of cavernous malformation was found for 11.9% of evaluated patients. Clinical course was acute with stepwise progression for 45.4% of patients and slowly progressive for 54.6%. Symptoms were motor (60.5%), sensory (57.8%), pain (33.8%), bladder and/or bowel (23.6%), respiratory distress (0.5%), or absent (asymptomatic; 0.9%). The calculated pooled annual rate of hemorrhage was 2.1% (95% CI 1.3%–3.3%). Most (89.9%) patients underwent resection, and 10.1% underwent conservative management (observation). Outcomes were better for those who underwent resection than for those who underwent conservative management (OR 2.79, 95% CI 1.46–5.33, p = 0.002). A positive correlation with improved neurological outcomes was found for resection within 3 months of symptom onset (OR 2.11, 95% CI 1.31–3.41, p = 0.002), hemilaminectomy approach (OR 3.20, 95% CI 1.16–8.86, p = 0.03), and gross-total resection (OR 3.61, 95% CI 1.24–10.52, p = 0.02). Better outcomes were predicted by an acute clinical course (OR 1.72, 95% CI 1.10–2.68, p = 0.02) and motor symptoms (OR 1.76, 95% CI 1.08–2.86, p = 0.02); poor neurological recovery was predicted by sensory symptoms (OR 0.58, 95% CI 0.35–0.98, p = 0.04). Rates of neurological improvement after resection were no higher for patients with superficial ISCCMs than for those with deep-seated ISCCMs (OR 1.36, 95% CI 0.71–2.60, p = 0.36).
Intramedullary spinal cord cavernous malformations tend to be clinically progressive. The authors' findings support an operative management plan for patients with a symptomatic ISCCM. Surgical goals include gross-total resection through a more minimally invasive hemilaminectomy approach within 3 months of presentation.
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
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.
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.
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.
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.
Jetan H. Badhiwala, Farshad Nassiri, Christopher D. Witiw, Alireza Mansouri, Saleh A. Almenawer, Leodante da Costa, Michael G. Fehlings and Jefferson R. Wilson
Intraoperative neurophysiological monitoring (IONM) is a useful adjunct in spine surgery, with proven benefit in scoliosis-correction surgery. However, its utility for anterior cervical discectomy and fusion (ACDF) is unclear, as there are few head-to-head comparisons of ACDF outcomes with and without the use of IONM. The authors sought to evaluate the impact of IONM on the safety and cost of ACDF.
This was a retrospective analysis of data from the National (Nationwide) Inpatient Sample of the Healthcare Cost and Utilization Project from 2009 to 2013. Patients with a primary procedure code for ACDF were identified, and diagnosis codes were searched to identify cases with postoperative neurological complications. The authors performed univariate and multivariate logistic regression for postoperative neurological complications with use of IONM as the independent variable; additional covariates included age, sex, surgical indication, multilevel fusion, Charlson Comorbidity Index (CCI) score, and admission type. They also conducted propensity score matching in a 1:1 ratio (nearest neighbor) with the use of IONM as the treatment indicator and the aforementioned variables as covariates. In the propensity score–matched cohort, they compared neurological complications, length of stay (LOS), and hospital charges (in US dollars).
A total of 141,007 ACDF operations were identified. IONM was used in 9540 cases (6.8%). No significant association was found between neurological complications and use of IONM on univariate analysis (OR 0.80, p = 0.39) or multivariate regression (OR 0.82, p = 0.45). By contrast, age ≥ 65 years, multilevel fusion, CCI score > 0, and a nonelective admission were associated with greater incidence of neurological complication. The propensity score–matched cohort consisted of 18,760 patients who underwent ACDF with (n = 9380) or without (n = 9380) IONM. Rates of neurological complication were comparable between IONM and non-IONM (0.17% vs 0.22%, p = 0.41) groups. IONM and non-IONM groups had a comparable proportion of patients with LOS ≥ 2 days (19% vs 18%, p = 0.15). The use of IONM was associated with an additional $6843 (p < 0.01) in hospital charges.
The use of IONM was not associated with a reduced rate of neurological complications following ACDF. Limitations of the data source precluded a specific assessment of the effectiveness of IONM in preventing neurological complications in patients with more complex pathology (i.e., ossification of the posterior longitudinal ligament or cervical deformity).
Alireza Mansouri, Shervin Taslimi, Aram Abbasian, Jetan H. Badhiwala, Muhammad Ali Akbar, Naif M. Alotaibi, Saleh A. Almenawer, Alexander G. Weil, Aria Fallah, Lionel Carmant and George M. Ibrahim
The aim of this study was to describe the current state of epilepsy surgery and establish estimates of seizure outcomes following surgery for medically intractable epilepsy (MIE) in low- and middle-income countries (LMICs).
The MEDLINE and Embase databases were searched without publication date restriction. This search was supplemented by a manual screen of key epilepsy and neurosurgical journals (January 2005 to December 2016). Studies that reported outcomes for at least 10 patients of any age undergoing surgery for MIE in LMICs over a defined follow-up period were included. A meta-analysis with a random-effects model was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. Pooled estimates of seizure freedom and favorable seizure outcomes following anterior temporal lobectomy with or without amygdalohippocampectomy (ATL ± AH) were reported.
Twenty studies were selected, of which 16 were from Asian centers. The average age at surgery in all studies was less than 30 years, and the average preoperative duration of epilepsy ranged from 3 to 16.1 years. Mesial temporal sclerosis accounted for 437 of 951 described pathologies, and 1294 of the 1773 procedures were ATL ± AH. Based on 7 studies (646 patients) the pooled seizure freedom estimate following ATL ± AH was 68% (95% CI 55%–82%). Based on 8 studies (1096 patients), the pooled estimate for favorable seizure outcomes was 79% (95% CI 74%–85%).
Surgery for MIE in LMICs shows a high percentage of seizure freedom and favorable outcomes. These findings call for a concerted global effort to improve timely access to surgery for MIE patients in these regions, including investments aimed at refining existing and establishing additional centers.
Alireza Mansouri, Shervin Taslimi, Jetan H. Badhiwala, Christopher D. Witiw, Farshad Nassiri, Vincent J. J. Odekerken, Rob M. A. De Bie, Suneil K. Kalia, Mojgan Hodaie, Renato P. Munhoz, Alfonso Fasano and Andres M. Lozano
Deep brain stimulation (DBS) is effective in the management of patients with advanced Parkinson’s disease (PD). While both the globus pallidus pars interna (GPi) and the subthalamic nucleus (STN) are accepted targets, their relative efficacy in randomized controlled trials (RCTs) has not been established beyond 12 months. The objective of this study was to conduct a meta-analysis of RCTs to compare outcomes among adults with PD undergoing DBS of GPi or STN at various time points, including 36 months of follow-up.
The MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL databases were searched. Registries for clinical trials, selected conference proceedings, and the table of contents for selected journals were also searched. Screens were conducted independently and in duplicate. Among the 623 studies initially identified (615 through database search, 7 through manual review of bibliographies, and 1 through a repeat screen of literature prior to submission), 19 underwent full-text review; 13 of these were included in the quantitative meta-analysis. Data were extracted independently and in duplicate. The Cochrane Collaboration tool was used to assess the risk of bias. The GRADE evidence profile tool was used to assess the quality of the evidence. Motor scores, medication dosage reduction, activities of daily living, depression, dyskinesias, and adverse events were compared. The influence of disease duration (a priori) and the proportion of male patients within a study (post hoc) were explored as potential subgroups.
Thirteen studies (6 original cohorts) were identified. No difference in motor scores or activities of daily living was identified at 36 months. Medications were significantly reduced with STN stimulation (5 studies, weighted mean difference [WMD] −365.46, 95% CI −599.48 to −131.44, p = 0.002). Beck Depression Inventory scores were significantly better with GPi stimulation (3 studies; WMD 2.53, 95% CI 0.99–4.06 p = 0.001). The motor benefits of GPi and STN DBS for PD are similar.
The motor benefits achieved with GPi and STN DBS for PD are similar. DBS of STN allows for a greater reduction of medication, but not as significant an advantage as DBS of GPi with respect to mood. This difference is sustained at 36 months. Further long-term studies are necessary.