When drug-resistant epilepsy is poorly localized or surgical resection is contraindicated, current neurostimulation strategies such as deep brain stimulation and vagal nerve stimulation can palliate the frequency or severity of seizures. However, despite medical and neuromodulatory therapy, a significant proportion of patients continue to experience disabling seizures that impair awareness, causing disability and risking injury or sudden unexplained death. We propose a novel strategy in which neuromodulation is used not only to reduce seizures but also to ameliorate impaired consciousness when the patient is in the ictal and postictal states. Improving or preventing alterations in level of consciousness may have an effect on morbidity (e.g., accidents, drownings, falls), risk for death, and quality of life. Recent studies may have elucidated underlying networks and mechanisms of impaired consciousness and yield potential novel targets for neuromodulation. The feasibility, benefits, and pitfalls of potential deep brain stimulation targets are illustrated in human and animal studies involving minimally conscious/vegetative states, movement disorders, depth of anesthesia, sleep-wake regulation, and epilepsy. We review evidence that viable therapeutic targets for impaired consciousness associated with seizures may be provided by key nodes of the consciousness system in the brainstem reticular activating system, hypothalamus, basal ganglia, thalamus, and basal forebrain.
Abhijeet Gummadavelli, Adam J. Kundishora, Jon T. Willie, John P. Andrews, Jason L. Gerrard, Dennis D. Spencer and Hal Blumenfeld
Aladine A. Elsamadicy, Andrew B. Koo, Adam J. Kundishora, Fouad Chouairi, Megan Lee, Astrid C. Hengartner, Joaquin Camara-Quintana, Kristopher T. Kahle and Michael L. DiLuna
Health policy changes have led to increased emphasis on value-based care to improve resource utilization and reduce inpatient hospital length of stay (LOS). Recently, LOS has become a major determinant of quality of care and resource utilization. For adolescent idiopathic scoliosis (AIS), the determinants of extended LOS after elective posterior spinal fusion (PSF) remain relatively unknown. In the present study, the authors investigated the impact of patient and hospital-level risk factors on extended LOS following elective PSF surgery (≥ 4 levels) for AIS.
The Kids’ Inpatient Database (KID) was queried for the year 2012. Adolescent patients (age range 10–17 years) with AIS undergoing elective PSF (≥ 4 levels) were selected using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Extended hospital LOS was defined as greater than the 75th percentile for the entire cohort (> 6 days), and patients were dichotomized as having normal LOS or extended LOS. Patient demographics, comorbidities, complications, LOS, discharge disposition, and total cost were recorded. A multivariate logistic regression model was used to determine the odds ratio for risk-adjusted LOS. The primary outcome was the degree to which patient comorbidities or postoperative complications correlated with extended LOS.
Comorbidities were overall significantly higher in the extended-LOS cohort than the normal-LOS cohort. Patients with extended LOS had a significantly greater proportion of blood transfusion (p < 0.001) and ≥ 9 vertebral levels fused (p < 0.001). The overall complication rates were greater in the extended-LOS cohort (20.3% [normal-LOS group] vs 43.5% [extended-LOS group]; p < 0.001). On average, the extended-LOS cohort incurred $18,916 more in total cost than the normal-LOS group ($54,697 ± $24,217 vs $73,613 ± $38,689, respectively; p < 0.001) and had more patients discharged to locations other than home (p < 0.001) than did patients in the normal-LOS cohort. On multivariate logistic regression, several risk factors were associated with extended LOS, including female sex, obesity, hypertension, fluid electrolyte disorder, paralysis, blood transfusion, ≥ 9 vertebrae fused, dural injury, and nerve cord injury. The odds ratio for extended LOS was 1.95 (95% CI 1.50–2.52) for patients with 1 complication and 5.43 (95% CI 3.35–8.71) for patients with > 1 complication.
The authors’ study using the KID demonstrates that patient comorbidities and intra- and postoperative complications all contribute to extended LOS after spinal fusion for AIS. Identifying multimodality interventions focused on reducing LOS, bettering patient outcomes, and lowering healthcare costs are necessary to improve the overall value of care for patients undergoing spinal fusion for AIS.
Aladine A. Elsamadicy, Andrew B. Koo, Megan Lee, Adam J. Kundishora, Christopher S. Hong, Astrid C. Hengartner, Joaquin Camara-Quintana, Kristopher T. Kahle and Michael L. DiLuna
In the past decade, a gradual transition of health policy to value-based healthcare has brought increased attention to measuring the quality of care delivered. In spine surgery, adolescents with scoliosis are a population particularly at risk for depression, anxious feelings, and impaired quality of life related to back pain and cosmetic appearance of the deformity. With the rising prevalence of mental health ailments, it is necessary to evaluate the impact of concurrent affective disorders on patient care after spinal surgery in adolescents. The aim of this study was to investigate the impact that affective disorders have on perioperative complication rates, length of stay (LOS), and total costs in adolescents undergoing elective posterior spinal fusion (PSF) (≥ 4 levels) for idiopathic scoliosis.
A retrospective study of the Kids’ Inpatient Database for the year 2012 was performed. Adolescent patients (age range 10–17 years old) with AIS undergoing elective PSF (≥ 4 levels) were selected using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Patients were categorized into 2 groups at discharge: affective disorder or no affective disorder. Patient demographics, comorbidities, complications, LOS, discharge disposition, and total cost were assessed. The primary outcomes were perioperative complication rates, LOS, total cost, and discharge dispositions.
There were 3759 adolescents included in this study, of whom 164 (4.4%) were identified with an affective disorder (no affective disorder: n = 3595). Adolescents with affective disorders were significantly older than adolescents with no affective disorders (affective disorder: 14.4 ± 1.9 years vs no affective disorder: 13.9 ± 1.8 years, p = 0.001), and had significantly different proportions of race (p = 0.005). Aside from hospital region (p = 0.016), no other patient- or hospital-level factors differed between the cohorts. Patient comorbidities did not differ significantly between cohorts. The number of vertebral levels involved was similar between the cohorts, with the majority of patients having 9 or more levels involved (affective disorder: 76.8% vs no affective disorder: 79.5%, p = 0.403). Postoperative complications were similar between the cohorts, with no significant difference in the proportion of patients experiencing a postoperative complication (p = 0.079) or number of complications (p = 0.124). The mean length of stay and mean total cost were similar between the cohorts. Moreover, the routine and nonroutine discharge dispositions were also similar between the cohorts, with the majority of patients having routine discharges (affective disorder: 93.9% vs no affective disorder: 94.9%, p = 0.591).
This study suggests that affective disorders may not have a significant impact on surgical outcomes in adolescent patients undergoing surgery for scoliosis in comparison with adults. Further studies are necessary to elucidate how affective disorders affect adolescent patients with idiopathic scoliosis, which may improve provider approach in managing these patients perioperatively and at follow-up in hopes to better the overall patient satisfaction and quality of care delivered.
Elena I. Fomchenko, E. Zeynep Erson-Omay, Adam J. Kundishora, Christopher S. Hong, Ava A. Daniel, August Allocco, Phan Q. Duy, Armine Darbinyan, Asher M. Marks, Michael L. DiLuna, Kristopher T. Kahle and Anita Huttner
Pediatric midline tumors are devastating high-grade lesions with a dismal prognosis and no curative surgical options. Here, the authors report the clinical presentation, surgical management, whole-exome sequencing (WES), and clonality analysis of a patient with a radically resected H3K27M-mutant pineal parenchymal tumor (PPT) and spine metastases consistent with PPT of intermediate differentiation (PPTID). They identified somatic mutations in H3F3A (H3K27M), FGFR1, and NF1 both in the original PPT and in the PPTID metastases. They also found 12q amplification containing CDK4/MDM2 and chromosome 17 loss of heterozygosity overlapping with NF1 that resulted in biallelic NF1 loss. They noted a hypermutated phenotype with increased C>T transitions within the PPTID metastases and 2p amplification overlapping with the MYCN locus. Clonality analysis detected three founder clones maintained during progression and metastasis. Tumor clones present within the PPTID metastases but not the pineal midline tumor harbored mutations in APC and TIMP2.
While the majority of H3K27M mutations are found in pediatric midline gliomas, it is increasingly recognized that this mutation is present in a wider range of lesions with a varied morphological appearance. The present case appears to be the first description of H3K27M mutation in PPTID. Somatic mutations in H3F3A, FGFR1, and NF1 have been suggested to be driver mutations in pediatric midline gliomas. Their clonality and presence in over 80% of tumor cells in our patient’s PPTID are consistent with similarly crucial roles in early tumorigenesis, with progression mediated by copy number variations and chromosomal aberrations involving known oncogenes and tumor suppressors. The roles of APC and TIMP2 mutations in progression and metastasis remain to be investigated.