Diffuse intrinsic pontine glioma (DIPG): A review of current and emerging treatment strategies.

Diffuse intrinsic pontine glioma (DIPG) is a childhood malignancy of the brainstem with a dismal prognosis. Despite recent advances in its understanding at the molecular level, the prognosis of DIPG has remained unchanged. This article aims to review the current understanding of the genetic pathophysiology of DIPG and to highlight promising therapeutic targets. Various DIPG treatment strategies have been investigated in pre-clinical studies, several of which have shown promise and have been subsequently translated into ongoing clinical trials. Ultimately, a multifaceted therapeutic approach that targets cell-intrinsic alterations, the micro-environment, and augments the immune system will likely be necessary to eradicate DIPG.

Safety and Efficacy of Riluzole in Traumatic Spinal Cord Injury: A Systematic Review With Meta-Analyses.

Traumatic spinal cord injury (SCI) is a cause of significant morbidity, often resulting in long-term disability. We aimed to compare outcomes after riluzole versus patients who received placebo or standard of care with no specific intervention. MEDLINE, Embase, Scopus, and Cochrane Library database searches yielded 92 records, and five met the study inclusion criteria. Fixed-effect and random-effects models were used to establish odds ratios (ORs) and mean difference (MD) with 95% confidence intervals (CIs) for each outcome. The results of the pooled analysis showed that in patients with acute traumatic SCI, riluzole resulted in increased American Spinal Injury Association (ASIA) motor scores at 3 months (MD 0.26, 95% CI [-0.10,0.61], I2 = 0%; p = 0.157) and 6 months (MD 0.21, 95% CI [-0.17,0.60], I2 = 0%; p = 0.280) and change in ASIA Impairment Scale (AIS) at 3 months (OR 0.59, 95% CI [-0.12,1.30], I2 = 0%, p = 0.101) and 6 months (OR 0.28, 95% CI [-0.50,1.06], I2 = 0%, p = 0.479) in comparison to the control groups, though not to a level of statistical significance. Riluzole resulted in fewer adverse events than the control groups (OR -0.12, 95% CI [-1.59,1.35], I2 = 0%, p = 0.874) and lower mortality (OR -0.20, 95% CI [-1.03,0.63], I2 = 0%, p = 0.640), though also not to a level of statistical significance. These meta-analyses suggest that riluzole for the treatment of traumatic SCI is safe and results in improved neurological outcomes when compared to controls, though not to a level of statistical significance. More robust prospective, randomized studies are necessary to help inform the safety and efficacy of riluzole for traumatic SCI.

Neuroendoscopic Evacuation Improves Outcomes Compared with External Ventricular Drainage in Patients with Spontaneous Intraventricular Hemorrhage: A Systematic Review with Meta-Analyses.

BACKGROUND: Spontaneous intraventricular hemorrhage (IVH) is a cause of significant morbidity and mortality. Treatment for resulting obstructive hydrocephalus has traditionally been via an external ventricular drain (EVD). We aimed to compare patient outcomes after neuroendoscopic surgery (NES) evacuation of IVH versus EVD management. METHODS: MEDLINE, Embase, and Cochrane Library databases were searched on October 8, 2022. Of the 252 records remaining after removal of duplicates, 12 met study inclusion criteria. After extraction of outcomes data, fixed-effect and random-effects models were used to establish odds ratios (ORs) with 95% confidence intervals (CIs) for intensive care unit length of stay, rate of permanent cerebrospinal fluid diversion, Glasgow Outcome Scale score, and mortality rate. RESULTS: The results of the pooled analysis showed that intensive care unit length of stay was shorter (OR -2.61 [95% CI -5.02, -0.19]; I2 = 97.76%; P = 0.034), permanent cerebrospinal fluid diversion was less likely (OR -0.79, 95% CI [-1.17, -0.41], I2 = 46.96%, P < 0.001), higher Glasgow Outcome Scale score was more likely (OR 0.48, 95% CI [0.04, 0.93], I2 = 60.12%, P = 0.032), and all-cause mortality was less likely (OR -1.11, 95% CI [-1.79, -0.44], I2 = 0%, P = 0.001) in the NES evacuation group compared with the EVD group. CONCLUSIONS: NES for evacuation of spontaneous IVH results in reduced intensive care unit length of stay, reduced permanent cerebrospinal fluid diversion rates, improved Glasgow Outcome Scale score, and reduced mortality when compared with EVD. More robust prospective, randomized studies are necessary to help inform the safety and utility of NES for IVH.

Low-Pressure Hydrocephalus in Spontaneous Angiogram-Negative Subarachnoid Hemorrhage Following COVID-19 Infection.

A preliminary report warned that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could have neuro-invasive potential as it was observed that some patients showed neurologic symptoms such as headache, nausea, and vomiting. Following early speculation there have been reports of neurologic manifestations involving both the central nervous system and peripheral nervous system including reports that coronavirus disease 2019 (COVID-19) may increase the risk of acute ischemic stroke. Here we present a patient with recent COVID-19 infection who experienced low-pressure hydrocephalus requiring high-output cerebrospinal fluid (CSF) diversion following spontaneous angiogram-negative subarachnoid hemorrhage. We hypothesize that patients who are either currently or who have recently been infected with SARS-CoV-2 may have altered ventricular compliance and/or altered CSF hydrodynamics from mechanisms that are not yet understood but potentially related to previously described pathophysiologic mechanisms of the virus and associated inflammatory reaction.

Enlarging Ventriculus Terminalis in a Patient With Polyarteritis Nodosa.

Ventriculus terminalis (VT) is a cystic embryological remnant within the conus medullaris that normally regresses after birth. In rare cases, it may persist into adulthood and give rise to neurologic symptoms. The pathogenesis remains unclear but is thought to be related to failed embryonic regression with other proposed possible etiologies including vascular disturbances. We present an intriguing case of a slow-growing VT in a woman with progressive neurologic symptoms who experiences symptomatic relief following thoracic laminectomy and fenestration. Our case is the first to present a unique association with polyarteritis nodosa and only the third to report a case of documented enlargement of the VT over time successfully treated with surgical fenestration.

Compartmentalization: An Open Technique for Frontal Sinus Repair and Preservation-Description of Technique and Early Case Series.

Background Cranialization or obliteration is widely accepted intervention for traumatic or intentional breach of the frontal sinus. These techniques, however, result in the loss of frontal sinus function and have a persistent risk of cerebrospinal fluid (CSF) leak and mucocele. Compartmentalization is an open technique for repair of the frontal sinus using allograft onlay and a vascularized periosteal flap that allows for preservation of frontal sinus function. Objective The main objective of this article is to describe the technique for compartmentalization of the frontal sinus and demonstrate its efficacy and complication rate with an early patient series. Methods Our technique includes the following key components: harvesting of a pedicled periosteal flap, frontal sinus repair through a bifrontal craniotomy with minimal mucosa removal, ensuring the patency of the nasal frontal outflow tract, and separation of the brain from the frontal sinus with a dual layer of periosteum and allograft. All cases of frontal sinus repair using the compartmentalization technique at our institution were reviewed. Charts were reviewed for CSF leak, mucocele, and other complications. Results Twenty-three patients underwent the described frontal sinus repair technique 17 for tumor and 6 for trauma. There were no CSF leaks and no mucoceles. One patient experienced postoperative anemia and a "parameningeal reaction" that were managed with a short course of antibiotics. Conclusions Compartmentalization, due to its sinus preservation and low complication rate, represents a meaningful step forward in neurosurgical technique for open frontal sinus repair. However, long-term outcomes are necessary to fully evaluate risk of mucocele.

Orbital myxoma: A case report.

BACKGROUND: Myxomas are rare, locally infiltrative, benign neoplasms of mesenchymal origin. Although benign, these tumors are locally aggressive with a high rate of recurrence following conservative resection. Their relative infrequency, variable location, and insidious growth present a diagnostic challenge to clinicians. Cases of myxomas have been described throughout the body, but intraosseous myxomas of the orbit are exceedingly rare. CASE DESCRIPTION: We report a case of a 53-year-old male with a history of chronic sinusitis and symptoms of hyposmia and bifrontal headaches refractory medical management who presented for neurosurgical evaluation after radiographic findings of an orbital lesion. Physical examination was unremarkable with intact extraocular movements. Prior radiographic workup demonstrated a 2.4 × 2.7 × 2.2 cm expansile lesion involving the bony left superior and lateral orbit. A prior open biopsy was performed which demonstrated a low-grade spindle cell neoplasm consistent with intraosseous myxoma. Definitive resection was recommended through the left orbitozygomatic craniotomy. The patient tolerated the procedure well without complications. Gross total resection was achieved. Reconstruction of the orbital roof and lateral orbital wall was performed with a frontal bone autograft and titanium plating. Postoperative course was uneventful, and the patient was discharged home postoperative day 2. At 1-month follow-up visit, the patient remained neurologically intact. Surveillance imaging at 6 months and 1 year remained stable without signs of recurrence. CONCLUSION: Intraosseous orbital myxomas are exceedingly rare entities. Although they are considered benign neoplasms, myxomas demonstrate high recurrence rates. The authors report a unique case of an orbital myxoma that was successfully treated through an orbitozygomatic approach achieving gross total resection.

Radiographic and CT Evaluation of Recombinant Human Bone Morphogenetic Protein-2-assisted Cervical Spinal Interbody Fusion.

STUDY DESIGN: This was a retrospective study. OBJECTIVE: To radiographically demonstrate the distinct fusion pattern of recombinant human bone morphogenetic protein-2 (rhBMP-2) in the setting of anterior cervical discectomy and fusion. SUMMARY OF BACKGROUND DATA: Studies investigating spinal fusion assisted with rhBMP-2 have yielded promising results, suggesting rhBMP-2 is an efficacious alternative to iliac crest autografts. rhBMP-2-assisted spinal fusion both hastens healing and eliminates patient morbidity from iliac crest autograft. Unique to rhBMP-assisted spinal fusion is its distinct radiographic fusion pattern as fusion is achieved. Despite promising results and increased clinical use of rhBMP-2, there remains a paucity of literature documenting this radiographic process. MATERIALS AND METHODS: This study included 26 patients who underwent single-level anterior cervical discectomy and fusion using rhBMP-2. All data used for this study was collected from a prior FDA Investigational Device Exemption study. RESULTS: A polyetheretherketone cage was used as an interbody disk spacer in all 26 patients. Patients were evaluated between 2 and 6 weeks after surgery and subsequently at 3, 6, 12, and 24 months postoperative. All patients underwent plain radiography at every follow-up visit, and computed tomograhy evaluation was performed at 3, 6, 12, and 24 months as part of the study protocol. Earliest fusion was observed at 3 months in 38% of patients. Likely fusion was observed in all patients by 12 months postoperative. CONCLUSIONS: rhBMP-2 leads to both successful interbody fusion and an enhanced fusion rate with unique imaging characteristics. Additional characteristics of BMP observed in 100% of patients included prevertebral soft-tissue swelling and early endplate resorption. Other common features included polyetheretherketone cage migration, heterotopic bone formation and cage subsidence.

Using automated electronic medical record data extraction to model ALS survival and progression.

BACKGROUND: To assess the feasibility of using automated capture of Electronic Medical Record (EMR) data to build predictive models for amyotrophic lateral sclerosis (ALS) outcomes. METHODS: We used an Informatics for Integrating Biology and the Bedside search discovery tool to identify and extract data from 354 ALS patients from the University of Kansas Medical Center EMR. The completeness and integrity of the data extraction were verified by manual chart review. A linear mixed model was used to model disease progression. Cox proportional hazards models were used to investigate the effects of BMI, gender, and age on survival. RESULTS: Data extracted from the EMR was sufficient to create simple models of disease progression and survival. Several key variables of interest were unavailable without including a manual chart review. The average ALS Functional Rating Scale - Revised (ALSFRS-R) baseline score at first clinical visit was 34.08, and average decline was - 0.64 per month. Median survival was 27 months after first visit. Higher baseline ALSFRS-R score and BMI were associated with improved survival, higher baseline age was associated with decreased survival. CONCLUSIONS: This study serves to show that EMR-captured data can be extracted and used to track outcomes in an ALS clinic setting, potentially important for post-marketing research of new drugs, or as historical controls for future studies. However, as automated EMR-based data extraction becomes more widely used there will be a need to standardize ALS data elements and clinical forms for data capture so data can be pooled across academic centers.