Spinal Meningiomas.

Spinal meningiomas are relatively rare, but account for a significant proportion of primary spinal tumors in adults. These meningiomas can be found anywhere along the spinal column and their diagnosis is often delayed due to their slow growth and the lack of significant neurological symptoms until they reach a critical size, at which point signs of spinal cord or nerve root compression generally manifest and progress. If left untreated, spinal meningiomas can cause severe neurological deficits including rendering patients paraplegic or tetraplegic. In this chapter we will review the clinical features of spinal meningiomas, their surgical management, and detail molecular features that differentiate them from intracranial meningiomas.

Unlocking the paradoxical endogenous stem cell response after spinal cord injury.

Nearly a century ago, the concept of the secondary injury in spinal cord trauma was first proposed to explain the complex cascade of molecular and cellular events leading to widespread neuronal and glial cell death after trauma. In recent years, it has been established that the ependymal region of the adult mammalian spinal cord contains a population of multipotent neural stem/progenitor cells (NSPCs) that are activated after spinal cord injury (SCI) and likely play a key role in endogenous repair and regeneration. How these cells respond to the various components of the secondary injury remains poorly understood. Emerging evidence suggests that many of the biochemical components of the secondary injury cascade which have classically been viewed as deleterious to host neuronal and glial cells may paradoxically trigger NSPC activation, proliferation, and differentiation thus challenging our current understanding of secondary injury mechanisms in SCI. Herein, we highlight new findings describing the response of endogenous NSPCs to spinal cord trauma, redefining the secondary mechanisms of SCI through the lens of the endogenous population of stem/progenitor cells. Moreover, we outline how these insights can fuel novel stem cell-based therapeutic strategies to repair the injured spinal cord.

The Cost-Effectiveness of 5-ALA in High-Grade Glioma Surgery: A Quality-Based Systematic Review.

BACKGROUND: High-grade gliomas (HGGs) are aggressive tumors that inevitably recur due to their diffusely infiltrative nature. Intraoperative adjuncts such as 5-aminolevulinic acid (5-ALA) have shown promise in increasing extent of resection. As the prospect of increased use of 5-ALA rises, a systematic overview of the health economics of this adjunct is critical. METHODS: Medline, EMBASE, Centre for Reviews and Dissemination, EconPapers, and Cochrane databases were searched for keywords relating to glioma, cost-effectiveness, and 5-ALA. Primary studies reporting on the health economics or cost-effectiveness of 5-ALA compared to white light surgery in HGG were included. Quality was assessed using the British Medical Journal guidelines. RESULTS: Three studies were identified. All were European and conducted from the perspective of national healthcare systems. Two studies demonstrated the cost-utility of 5-ALA compared to white light (C$12,817 and C$13,508/quality-adjusted life-years (QALYs)). One assessed the cost-utility per gross total resection (C$6,813). Both these values were below the national cost-effectiveness thresholds for each respective study. The third study demonstrated no significant difference in cost of 5-ALA in glioblastoma resection (C$14,732) compared to prior to its routine use (C$15,936). The quality of these studies ranged from moderate to average. None of these studies considered patient perspective or indirect costs in their analysis. CONCLUSIONS: Growing evidence exists examining the health economic benefit of 5-ALA as an intraoperative adjunct for HGG resection. Additional studies within the Canadian context using 5-ALA, specifically incorporating patient and societal perspectives into the cost-utility analyses, are necessary to solidify this line of evidence.

Ethical issues in geriatric cranial neurosurgery.

The global demographic shift to an older population has led to the emergence of the new field of geriatric neurosurgery. Beyond the complexities of disease states and multimorbidity, advanced age brings with it intricate ethical issues pertaining to both the practice and provision of medical and surgical care. In this paper, the authors describe the central ethical themes seen across the spectrum of common neurosurgical conditions in the elderly and highlight the use of foundational ethical principles to help guide treatment decision-making.

The vagus afferent network: emerging role in translational connectomics.

Vagus nerve stimulation (VNS) is increasingly considered for the treatment of intractable epilepsy and holds potential for the management of a variety of neuropsychiatric conditions. The emergence of the field of connectomics and the introduction of large-scale modeling of neural networks has helped elucidate the underlying neurobiology of VNS, which may be variably expressed in patient populations and related to responsiveness to stimulation. In this report, the authors outline current data on the underlying neural circuitry believed to be implicated in VNS responsiveness in what the authors term the "vagus afferent network." The emerging role of biomarkers to predict treatment effect is further discussed and important avenues for future work are highlighted.

Postoperative surgical-site hemorrhage after kidney transplantation: incidence, risk factors, and outcomes.

Studies investigating the incidence, risk factors, and outcomes of surgical-site hemorrhage after kidney transplantation are limited. Patients who underwent a kidney transplant from 1 January 2000 to 30 September 2012 (followed until 31 December 2012) at Toronto General Hospital were included in this study. Postoperative surgical-site hemorrhage was defined as a drop in hemoglobin ≥20 g/l over a 24-hour period within 3 days of transplantation, followed by an ultrasound indicating a significant hematoma/collection. A total of 59 of 1203 (4.9%) kidney transplant recipients had postoperative surgical-site hemorrhage. Most cases (89.8%) occurred within 1 day after transplantation. Living donor transplants [OR 0.30 (95% CI: 0.16, 0.55)] and higher recipient BMI [OR 0.54 per 10 kg/m2 increase in BMI (95% CI: 0.30, 0.99)] were associated with a significantly lower risk of bleeding. Chronic preoperative anticoagulant usage led to an increased risk of bleeding but was not statistically significant [OR 1.75 (95% CI: 0.52, 5.88)]. Postoperative hemorrhage was associated with a higher risk of graft loss or death [HR 1.62 (95% CI: 1.01, 2.60)]. While the incidence of postoperative surgical-site hemorrhage in kidney transplantation is relatively low, it may be associated with an increased risk of graft loss or death.

The role of 5-aminolevulinic acid in enhancing surgery for high-grade glioma, its current boundaries, and future perspectives: A systematic review.

5-Aminolevulinic acid (5-ALA) has been approved as an intraoperative adjunct in glioma surgery in Europe, but not North America. A systematic review was conducted to assess the evidence regarding 5-ALA as a surgical adjunct. The MEDLINE, EMBASE, and CENTRAL databases were searched, using terms relevant to "5-ALA" and "high-grade gliomas." Included studies were based on adults aged ≥18 years who underwent surgical resection/biopsy. No language or date limitations were used. Forty-three studies (1830 patients) were identified. Thirty-six were coordinated by European countries, 2 were in the United States, and none were in Canada. One was randomized, 28 were prospective, and 14 were retrospective. Twenty-six studies assessed the utility of 5-ALA as a diagnostic tool, 24 assessed its influence on the extent of resection (EOR), 9 assessed survival, and 22 reported adverse events. 5-ALA had high sensitivity and positive predictive value, whereas its specificity increased with additional adjuncts. The EOR increased with 5-ALA, but only progression-free survival was significantly influenced. Reporting of adverse events was not systematic. The use of 5-ALA improved tumor visualization and thus enabled a greater EOR and perhaps increased survival. However, additional adjuncts may be necessary for maximizing the specificity of resection and patient safety. Additional parameters, such as patient quality of life and health economic analyses, would be informative. Thus, additional systematic collection of prospective evidence may be necessary for the global incorporation of this potentially valuable surgical adjunct into routine practice. Cancer 2016;122:2469-78. © 2016 American Cancer Society.

Experience with Canada's First Policy on Concussion Education and Management in Schools.

BACKGROUND: In response to the rising incidence of concussions among children and adolescents, the province of Ontario recently introduced the Ontario Policy/Program Memorandum on Concussions (PPM No. 158) requiring school boards to develop a concussion protocol. As this is the first policy of its kind in Canada, the impact of the PPM is not yet known. METHODS: An electronic survey was sent to all high school principals in the Toronto District School Board 1 year after announcement of the PPM. Questions covered extent of student, parent, and staff concussion education along with concussion management protocols. RESULTS: Of 109 high school principals contacted, 39 responded (36%). Almost all schools provided concussion education to students (92%), with most education delivered through physical education classes. Nearly all schools had return to play (92%) and return to learn (77%) protocols. Although 85% of schools educated staff on concussions, training was aimed at individuals involved in sports/physical education. Only 43.6% of schools delivered concussion education to parents, and many principals requested additional resources in this area. CONCLUSIONS: One year after announcement of the PPM, high schools in the Toronto District School Board implemented significant student concussion education programs and management protocols. Staff training and parent education required further development. A series of recommendations are provided to aid in future concussion policy development.

Timing of Decompressive Surgery in Patients With Acute Spinal Cord Injury: Systematic Review Update.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Surgical decompression is a cornerstone in the management of patients with traumatic spinal cord injury (SCI); however, the influence of the timing of surgery on neurological recovery after acute SCI remains controversial. This systematic review aims to summarize current evidence on the effectiveness, safety, and cost-effectiveness of early (≤24 hours) or late (>24 hours) surgery in patients with acute traumatic SCI for all levels of the spine. Furthermore, this systematic review aims to evaluate the evidence with respect to the impact of ultra-early surgery (earlier than 24 hours from injury) on these outcomes. METHODS: A systematic search of the literature was performed using the MEDLINE database (PubMed), Cochrane database, and EMBASE. Two reviewers independently screened the citations from the search to determine whether an article satisfied predefined inclusion and exclusion criteria. For all key questions, we focused on primary studies with the least potential for bias and those that controlled for baseline neurological status and specified time from injury to surgery. Risk of bias of each article was assessed using standardized tools based on study design. Finally, the overall strength of evidence for the primary outcomes was assessed using the GRADE approach. Data were synthesized both qualitatively and quantitively using meta-analyses. RESULTS: Twenty-one studies met inclusion and exclusion criteria and formed the evidence base for this review update. Seventeen studies compared outcomes between patients treated with early (≤24 hours from injury) compared to late (>24 hours) surgical decompression. An additional 4 studies evaluated even earlier time frames: <4, <5, <8 or <12 hours. Based on moderate evidence, patients were 2 times more likely to recover by ≥ 2 grades on the ASIA Impairment Score (AIS) at 6 months (RR: 2.76, 95% CI 1.60 to 4.98) and 12 months (RR: 1.95, 95% CI 1.26 to 3.18) if they were decompressed within 24 hours compared to after 24 hours. Furthermore, moderate evidence suggested that patients receiving early decompression had an additional 4.50 (95% CI 1.70 to 7.29) point improvement on the ASIA motor score. With respect to administrative outcomes, there was low evidence that early decompression may decrease acute hospital length of stay. In terms of safety, there was moderate evidence that suggested the rate of major complications does not differ between patients undergoing early compared to late surgery. Furthermore, there was no difference in rates of mortality, surgical device-related complications, sepsis/systemic infection or neurological deterioration based on timing of surgery. Firm conclusions were not possible with respect to the impact of ultra-early surgery on neurological, functional or safety outcomes given the poor-quality studies, imprecision and the overlap in the time frames examined. CONCLUSIONS: This review provides an evidence base to support the update on clinical practice guidelines related to the timing of surgical decompression in acute SCI. Overall, the strength of evidence was moderate that early surgery (≤24 hours from injury) compared to late (>24 hours) results in clinically meaningful improvements in neurological recovery. Further studies are required to delineate the role of ultra-early surgery in patients with acute SCI.

An Update of a Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Role and Timing of Decompressive Surgery.

STUDY DESIGN: Clinical practice guideline development. OBJECTIVES: Acute spinal cord injury (SCI) can result in devastating motor, sensory, and autonomic impairment; loss of independence; and reduced quality of life. Preclinical evidence suggests that early decompression of the spinal cord may help to limit secondary injury, reduce damage to the neural tissue, and improve functional outcomes. Emerging evidence indicates that "early" surgical decompression completed within 24 hours of injury also improves neurological recovery in patients with acute SCI. The objective of this clinical practice guideline (CPG) is to update the 2017 recommendations on the timing of surgical decompression and to evaluate the evidence with respect to ultra-early surgery (in particular, but not limited to, <12 hours after acute SCI). METHODS: A multidisciplinary, international, guideline development group (GDG) was formed that consisted of spine surgeons, neurologists, critical care specialists, emergency medicine doctors, physical medicine and rehabilitation professionals, as well as individuals living with SCI. A systematic review was conducted based on accepted methodological standards to evaluate the impact of early (within 24 hours of acute SCI) or ultra-early (in particular, but not limited to, within 12 hours of acute SCI) surgery on neurological recovery, functional outcomes, administrative outcomes, safety, and cost-effectiveness. The GRADE approach was used to rate the overall strength of evidence across studies for each primary outcome. Using the "evidence-to-recommendation" framework, recommendations were then developed that considered the balance of benefits and harms, financial impact, patient values, acceptability, and feasibility. The guideline was internally appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. RESULTS: The GDG recommended that early surgery (≤24 hours after injury) be offered as the preferred option for adult patients with acute SCI regardless of level. This recommendation was based on moderate evidence suggesting that patients were 2 times more likely to recover by ≥ 2 ASIA Impairment Score (AIS) grades at 6 months (RR: 2.76, 95% CI 1.60 to 4.98) and 12 months (RR: 1.95, 95% CI 1.26 to 3.18) if they were decompressed within 24 hours compared to after 24 hours. Furthermore, patients undergoing early surgery improved by an additional 4.50 (95% 1.70 to 7.29) points on the ASIA Motor Score compared to patients undergoing surgery after 24 hours post-injury. The GDG also agreed that a recommendation for ultra-early surgery could not be made on the basis of the current evidence because of the small sample sizes, variable definitions of what constituted ultra-early in the literature, and the inconsistency of the evidence. CONCLUSIONS: It is recommended that patients with an acute SCI, regardless of level, undergo surgery within 24 hours after injury when medically feasible. Future research is required to determine the differential effectiveness of early surgery in different subpopulations and the impact of ultra-early surgery on neurological recovery. Moreover, further work is required to define what constitutes effective spinal cord decompression and to individualize care. It is also recognized that a concerted international effort will be required to translate these recommendations into policy.

Neuroplasticity and regeneration after spinal cord injury.

Spinal cord injury (SCI) is a debilitating condition with significant personal, societal, and economic burden. The highest proportion of traumatic injuries occur at the cervical level, which results in severe sensorimotor and autonomic deficits. Following the initial physical damage associated with traumatic injuries, secondary pro-inflammatory, excitotoxic, and ischemic cascades are initiated further contributing to neuronal and glial cell death. Additionally, emerging evidence has begun to reveal that spinal interneurons undergo subtype specific neuroplastic circuit rearrangements in the weeks to months following SCI, contributing to or hindering functional recovery. The current therapeutic guidelines and standards of care for SCI patients include early surgery, hemodynamic regulation, and rehabilitation. Additionally, preclinical work and ongoing clinical trials have begun exploring neuroregenerative strategies utilizing endogenous neural stem/progenitor cells, stem cell transplantation, combinatorial approaches, and direct cell reprogramming. This review will focus on emerging cellular and noncellular regenerative therapies with an overview of the current available strategies, the role of interneurons in plasticity, and the exciting research avenues enhancing tissue repair following SCI.

Excitotoxic glutamate levels drive spinal cord ependymal stem cell proliferation and fate specification through CP-AMPAR signaling.

The adult spinal cord contains a population of ependymal-derived neural stem/progenitor cells (epNSPCs) that are normally quiescent, but are activated to proliferate, differentiate, and migrate after spinal cord injury. The mechanisms that regulate their response to injury cues, however, remain unknown. Here, we demonstrate that excitotoxic levels of glutamate promote the proliferation and astrocytic fate specification of adult spinal cord epNSPCs. We show that glutamate-mediated calcium influx through calcium-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (CP-AMPARs) in concert with Notch signaling increases the proliferation of epNSPCs via pCREB, and induces astrocytic differentiation through Hes1 upregulation. Furthermore, the in vivo targeting of this pathway via positive modulation of AMPARs after spinal cord injury enhances epNSPC proliferation, astrogliogenesis, neurotrophic factor production and increases neuronal survival. Our study uncovers an important mechanism by which CP-AMPARs regulate the growth and phenotype of epNSPCs, which can be targeted therapeutically to harness the regenerative potential of these cells after injury.

A deep learning model to classify neoplastic state and tissue origin from transcriptomic data.

Application of deep learning methods to transcriptomic data has the potential to enhance the accuracy and efficiency of tissue classification and cell state identification. Herein, we developed a multitask deep learning model for tissue classification combining publicly available whole transcriptomic (RNA-seq) datasets of non-neoplastic, neoplastic and peri-neoplastic tissue to classify disease state, tissue origin and neoplastic subclass. RNA-seq data from a total of 10,116 patient samples processed through a common pipeline were used for model training and validation. The model achieved 99% accuracy for disease state classification (ROC-AUC of 0.98) and 97% accuracy for tissue origin (ROC-AUC of 0.99). Moreover, the model achieved an accuracy of 92% (ROC-AUC 0.95) for neoplastic subclassification. This is the first multitask deep learning algorithm developed for tissue classification employing a uniform pipeline analysis of transcriptomic data with multiple tissue classifiers. This model serves as a framework for incorporating large transcriptomic datasets across conditions to facilitate clinical diagnosis and cell-based treatment strategies.

A Practical Classification System for Acute Cervical Spinal Cord Injury Based on a Three-Phased Modified Delphi Process From the AOSpine Spinal Cord Injury Knowledge Forum.

STUDY DESIGN: A modified Delphi study. OBJECTIVE: To assess current practice patterns in the management of cervical spinal cord injury (SCI) and develop a simplified, practical classification system which offers ease of use in the acute setting, incorporates modern diagnostic tools and provides utility in determining treatment strategies for cervical SCI. METHODS: A three-phase modified Delphi procedure was performed between April 2020 and December 2021. During the first phase, members of the AOSpine SCI Knowledge forum proposed variables of importance for classifying and treating cervical SCI. The second phase involved an international survey of spine surgeons gauging practices surrounding the role and timing of surgery for cervical SCI and opinions regarding factors which most influence these practices. For the third phase, information obtained from phases 1 and 2 were used to draft a new classification system. RESULTS: 396 surgeons responded to the survey. Neurological status, spinal stability and cord compression were the most important variables influencing decisions surrounding the role and timing of surgery. The majority (>50%) of respondents preferred to perform surgery within 24 hours post-SCI in clinical scenarios in which there was instability, severe cord compression or severe neurology. Situations in which <50% of respondents were inclined to operate early included: SCI with mild neurological impairments, with cord compression but without instability (with or without medical comorbidities), and SCI without cord compression or instability. CONCLUSIONS: Spinal stability, cord compression and neurological status are the most important variables influencing surgeons' practices surrounding the surgical management of cervical SCI. Based on these results, a simplified classification system for acute cervical SCI has been proposed.

Pathophysiology of Spinal Cord Injury.

Spinal cord injury (SCI) triggers a complex cascade of molecular and cellular events that leads to progressive cell loss and tissue damage. In this review, the authors outline the temporal profile of SCI pathogenesis, focusing on key mediators of the secondary injury, and highlight cutting edge insights on the alterations in neural circuits that largely define the chronic injury environment. They bridge these important basic science concepts with clinical implications for informing novel experimental therapies. Furthermore, emerging concepts in the study of SCI pathogenesis that are transforming fundamental research into innovative clinical treatment paradigms are outlined.

Management of Diffuse Low-Grade Glioma: The Renaissance of Robust Evidence.

The surgical management of diffuse low-grade gliomas (DLGGs) has undergone a paradigm shift toward striving for maximal safe resection when feasible. While extensive observational data supports this transition, unbiased evidence in the form of high quality randomized-controlled trials (RCTs) is lacking. Furthermore, despite a high volume of molecular, genetic, and imaging data, the field of neuro-oncology lacks personalized care algorithms for individuals with DLGGs based on a robust foundation of evidence. In this manuscript, we (1) discuss the logistical and philosophical challenges hindering the development of surgical RCTs for DLGGs, (2) highlight the potential impact of well-designed international prospective observational registries, (3) discuss ways in which cutting-edge computational techniques can be harnessed to generate maximal insight from high volumes of multi-faceted data, and (4) outline a comprehensive plan of action that will enable a multi-disciplinary approach to future DLGG management, integrating advances in clinical medicine, basic molecular research and large-scale data mining.

Klippel Feil Syndrome: Clinical Phenotypes Associated With Surgical Treatment.

STUDY DESIGN: Retrospective study. OBJECTIVE: To define distinct Klippel-Feil syndrome (KFS) patient phenotypes that are associated with the need for surgical intervention. SUMMARY OF BACKGROUND DATA: KFS is characterized by the congenital fusion of cervical vertebrae; however, patients often present with a variety of other spinal and extraspinal anomalies suggesting this syndrome encompasses a heterogeneous patient population. Moreover, it remains unclear how the abnormalities seen in KFS correlate to neurological outcomes and the need for surgical intervention. METHODS: Principal component (PC) analysis was performed on 132 KFS patients treated at a large pediatric hospital between 1981 and 2018. Thirty-five variables pertaining to patient/disease-related factors were examined. Significant PCs were included as independent variables in multivariable logistic regression models designed to test associations with three primary outcomes: cervical spine surgery, thoracolumbar/sacral spine surgery, and cranial surgery. RESULTS: Fourteen significant PCs accounting for 70% of the variance were identified. Five components, representing four distinct phenotypes, were significantly associated with surgical intervention. The first group consisted of predominantly subaxial cervical spine fusions, thoracic spine abnormalities and was associated with thoracolumbar/sacral spine surgery. The second group was largely represented by axial cervical spine anomalies and had high association with cervical subluxation and cervical spine surgery. A third group, heavily represented by Chiari malformation, was associated with cranial surgery. Lastly, a fourth group was defined by thoracic vertebral anomalies and associations with sacral agenesis and scoliosis. This phenotype was associated with thoracolumbar/sacral spine surgery. CONCLUSION: This is the first data-driven analysis designed to relate KFS patient phenotypes to surgical intervention and provides important insight that may inform targeted follow-up regimens and surgical decision-making. LEVEL OF EVIDENCE: 3.

Reinitiation of Anticoagulation After Surgical Evacuation of Subdural Hematomas.

BACKGROUND: Chronic subdural hematoma (cSDH) is an increasingly common condition due to the growing use of anticoagulation. Currently, there remains a lack of evidence to guide the optimal timing of anticoagulant reinitiation for stroke prevention in atrial fibrillation after cSDH evacuation. We aimed to better understand the perceived risks of hemorrhagic and embolic complications along with current practice patterns on restarting anticoagulation after surgical evacuation of cSDH. METHODS: We conducted a survey of Canadian neurosurgeons and stroke neurologists using a novel self-administered questionnaire using clinical cases that included questions on clinical experience, practice setting, practice patterns, and perceptions on stroke/bleeding risk with anticoagulation reinitiation after cSDH evacuation. The instrument was evaluated for clinical sensibility by 5 neurosurgeons, neurologists, and intensivists. RESULTS: The response rate after 4 mailings was 40% for neurosurgeons (55/136) and 21% for stroke neurologists (26/122). Almost all participants would restart anticoagulation for stroke prevention in atrial fibrillation after cSDH evacuation (91.8% in low-risk patients, 98.6% in high-risk patients). Time to reinitiation of anticoagulation varied considerably, particularly for high-risk patients where 36% of participants would restart anticoagulation within 1 week of surgery, 44% between 1 and 4 weeks after surgery, and 19% after 4 weeks postoperatively. The perceived risk of stroke and SDH reaccumulation varied considerably among participants and was dependent on timing of anticoagulation reinitiation. CONCLUSIONS: There is considerable variation in current practice patterns and perceived risks of embolic and hemorrhagic complications with anticoagulation reinitiation after cSDH evacuation. These results demonstrate clinical equipoise that warrant further targeted investigation in large-scale randomized controlled trials.

A needs assessment of pediatric epilepsy surgery in Haiti.

OBJECTIVE: Epilepsy disproportionately affects low- and/or middle-income countries (LMICs). Surgical treatments for epilepsy are potentially curative and cost-effective and may improve quality of life and reduce social stigmas. In the current study, the authors estimate the potential need for a surgical epilepsy program in Haiti by applying contemporary epilepsy surgery referral guidelines to a population of children assessed at the Clinique d'Épilepsie de Port-au-Prince (CLIDEP). METHODS: The authors reviewed 812 pediatric patient records from the CLIDEP, the only pediatric epilepsy referral center in Haiti. Clinical covariates and seizure outcomes were extracted from digitized charts. Electroencephalography (EEG) and neuroimaging reports were further analyzed to determine the prevalence of focal epilepsy or surgically amenable syndromes and to assess the lesional causes of epilepsy in Haiti. Lastly, the toolsforepilepsy instrument was applied to determine the proportion of patients who met the criteria for epilepsy surgery referral. RESULTS: Two-thirds of the patients at CLIDEP (543/812) were determined to have epilepsy based on clinical and diagnostic evaluations. Most of them (82%, 444/543) had been evaluated with interictal EEG, 88% of whom (391/444) had abnormal findings. The most common finding was a unilateral focal abnormality (32%, 125/391). Neuroimaging, a prerequisite for applying the epilepsy surgery referral criteria, had been performed in only 58 patients in the entire CLIDEP cohort, 39 of whom were eventually diagnosed with epilepsy. Two-thirds (26/39) of those patients had abnormal findings on neuroimaging. Most patients (55%, 18/33) assessed with the toolsforepilepsy application met the criteria for epilepsy surgery referral. CONCLUSIONS: The authors' findings suggest that many children with epilepsy in Haiti could benefit from being evaluated at a center with the capacity to perform basic brain imaging and neurosurgical treatments.

Assessment and treatment of childhood epilepsy in Haiti.

OBJECTIVE: The global burden of pediatric epilepsy is disproportionately concentrated in low- and middle-income countries (LMICs). However, little is known about the effectiveness of current treatment programs in this setting. We present the outcomes of children who were assessed and treated at the Clinique D'Épilepsie de Port-au-Prince (CLIDEP), the only pediatric epilepsy referral center in Haiti. METHODS: A 10-year retrospective review of children consecutively assessed and treated at CLIDEP was performed. The primary outcome was seizure control following treatment for epilepsy. The secondary outcome was an accurate determination of the diagnosis of epilepsy. A data-driven principle component regression (PCR) analysis was used to identify variables associated with outcomes of interest. RESULTS: Of the 812 children referred for evaluation, most children (82%) underwent electroencephalography to investigate a possible epilepsy diagnosis. Very few children (7%) underwent cranial imaging. Although many patients were lost to follow-up (24%), most children who returned to clinic had less frequent seizures (51%) and compliance with medication was relatively high (79%). Using PCR, we identified a patient phenotype that was strongly associated with poor seizure control which had strong contributions from abnormal neurological examination, higher number of antiepileptic drugs, comorbid diagnoses, epileptic encephalopathy or epilepsy syndrome, and developmental delay. Head circumference also contributed to epilepsy outcomes in Haiti with smaller head sizes being associated with a poor seizure outcome. A dissociable phenotype of febrile seizures, suspected structural abnormality, epileptic encephalopathy or epilepsy syndrome, and higher seizure frequency was associated with a diagnosis of epilepsy. SIGNIFICANCE: We describe the current landscape of childhood epilepsy in Haiti with an emphasis on diagnosis, treatment and outcomes. The findings provide evidence for the effectiveness of programs aimed at the diagnosis and management of epilepsy in LMICs and may inform the allocation of resources and create more effective referral structures.