A cross-sectional study of α-synuclein seed amplification assay in Alzheimer's disease neuroimaging initiative: Prevalence and associations with Alzheimer's disease biomarkers and cognitive function.

INTRODUCTION: Alzheimer's disease (AD) pathology is defined by ß-amyloid (Aß) plaques and neurofibrillary tau, but Lewy bodies (LBs; 𝛼-synuclein aggregates) are a common co-pathology for which effective biomarkers are needed. METHODS: A validated α-synuclein Seed Amplification Assay (SAA) was used on recent cerebrospinal fluid (CSF) samples from 1638 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, 78 with LB-pathology confirmation at autopsy. We compared SAA outcomes with neuropathology, Aß and tau biomarkers, risk-factors, genetics, and cognitive trajectories. RESULTS: SAA showed 79% sensitivity and 97% specificity for LB pathology, with superior performance in identifying neocortical (100%) compared to limbic (57%) and amygdala-predominant (60%) LB-pathology. SAA+ rate was 22%, increasing with disease stage and age. Higher Aß burden but lower CSF p-tau181 associated with higher SAA+ rates, especially in dementia. SAA+ affected cognitive impairment in MCI and Early-AD who were already AD biomarker positive. DISCUSSION: SAA is a sensitive, specific marker for LB-pathology. Its increase in prevalence with age and AD stages, and its association with AD biomarkers, highlights the clinical importance of α-synuclein co-pathology in understanding AD's nature and progression. HIGHLIGHTS: SAA shows 79% sensitivity, 97% specificity for LB-pathology detection in AD. SAA positivity prevalence increases with disease stage and age. Higher Aß burden, lower CSF p-tau181 linked with higher SAA+ rates in dementia. SAA+ impacts cognitive impairment in early disease stages. Study underpins need for wider LB-pathology screening in AD treatment.

Surgical outcomes of open and laser interstitial thermal therapy approaches for corpus callosotomy in pediatric epilepsy.

OBJECTIVE: Corpus callosotomy (CC) is a palliative surgical intervention for patients with medically refractory epilepsy that has evolved in recent years to include a less-invasive alternative with the use of laser interstitial thermal therapy (LITT). LITT works by heating a stereotactically placed laser fiber to ablative temperatures under real-time magnetic resonance imaging (MRI) thermometry. This study aims to (1) describe the surgical outcomes of CC in a large cohort of children with medically refractory epilepsy, (2) compare anterior and complete CC, and (3) review LITT as a surgical alternative to open craniotomy for CC. METHODS: This retrospective cohort study included 103 patients <21 years of age with at least 1 year follow-up at a single institution between 2003 and 2021. Surgical outcomes and the comparative effectiveness of anterior vs complete and open versus LITT surgical approaches were assessed. RESULTS: CC was the most common surgical disconnection (65%, n = 67) followed by anterior two-thirds (35%, n = 36), with a portion proceeding to posterior completion (28%, n = 10). The overall surgical complication rate was 6% (n = 6/103). Open craniotomy was the most common approach (87%, n = 90), with LITT used increasingly in recent years (13%, n = 13). Compared to open, LITT had shorter hospital stay (3 days [interquartile range (IQR) 2-5] vs 5 days [IQR 3-7]; p < .05). Modified Engel class I, II, III, and IV outcomes at last follow-up were 19.8% (n = 17/86), 19.8% (n = 17/86), 40.2% (n = 35/86), and 19.8% (n = 17/86). Of the 70 patients with preoperative drop seizures, 75% resolved postoperatively (n = 52/69). SIGNIFICANCE: No significant differences in seizure outcome between patients who underwent only anterior CC and complete CC were observed. LITT is a less-invasive surgical alternative to open craniotomy for CC, associated with similar seizure outcomes, lower blood loss, shorter hospital stays, and lower complication rates, but with longer operative times, when compared with the open craniotomy approach.

Neurosurgical management of non-spastic movement disorders.

BACKGROUND: Non-spastic movement disorders in children are common, although true epidemiologic data is difficult to ascertain. Children are more likely than adults to have hyperkinetic movement disorders defined as tics, dystonia, chorea/athetosis, or tremor. These conditions manifest from acquired or heredodegenerative etiologies and often severely limit function despite medical and surgical management paradigms. Neurosurgical management for these conditions is highlighted. METHODS: We performed a focused review of the literature by searching PubMed on 16 May 2023 using key terms related to our review. No temporal filter was applied, but only English articles were considered. We searched for the terms (("Pallidotomy"[Mesh]) OR "Rhizotomy"[Mesh]) OR "Deep Brain Stimulation"[Mesh], dystonia, children, adolescent, pediatric, globus pallidus, in combination. All articles were reviewed for inclusion in the final reference list. RESULTS: Our search terms returned 37 articles from 2004 to 2023. Articles covering deep brain stimulation were the most common (n = 34) followed by pallidotomy (n = 3); there were no articles on rhizotomy. DISCUSSION: Non-spastic movement disorders are common in children and difficult to treat. Most of these patients are referred to neurosurgery for the management of dystonia, with modern neurosurgical management including pallidotomy, rhizotomy, and deep brain stimulation. Historically, pallidotomy has been effective and may still be preferred in subpopulations presenting either in status dystonicus or with high risk for hardware complications. Superiority of DBS over pallidotomy for secondary dystonia has not been determined. Rhizotomy is an underutilized surgical tool and more study characterizing efficacy and risk profile is indicated.

Family Experiences with Diagnosis of Craniosynostosis: Thematic Analysis of Online Discussion Boards.

OBJECTIVE: Apply thematic analysis of online discussion boards to characterize families' experiences and concerns regarding craniosynostosis diagnoses to aid physicians in tailoring care to families. DESIGN: Grounded theory-based qualitative analysis. SETTING: Discussion boards related to craniosynostosis identified via Google and Yahoo. PATIENTS/PARTICIPANTS: Posts about craniosynostosis between 2017-2022. INTERVENTIONS: Thematic analysis was performed using three rounds of coding. Post features including author type and use of technical language were examined. MAIN OUTCOME MEASURE: Overarching themes emerging from analysis of posts, with forums analyzed until sufficient thematic repetition was observed. RESULTS: 366 posts from 4 websites by 290 unique users were included. Parents of patients with craniosynostosis wrote 59% of posts while patients wrote 4%. Five selective codes were identified: 1) Building Community, 2) Diagnosis/Evaluation, 3) Treatment, 4) Outcomes, and 5) Emotional Concerns. Building Community was the most assigned code (85% of posts). 71% of parents' posts expressing emotional concerns expressed negative emotions, commonly regarding anxiety about diagnosis (71%), frustration about doctors' responses (21%), or negative reactions to online search results (17%). 88% of patients' posts expressed positive emotions, discussing positive long-term outcomes. Concerns that may guide physicians included anxiety about delayed diagnosis, difficulty distinguishing postpartum head shape changes from craniosynostosis, and difficulty finding a care team. CONCLUSIONS: Online discussion boards allow families of patients with craniosynostosis to share experiences and find community. Improving communication between surgeons, pediatricians, and families about timing of evaluation and revising online information about this condition may ameliorate some anxiety associated with this diagnosis.

Cognitive Development in Lambdoid Craniosynostosis: A Systematic Review and Meta-Analysis.

OBJECTIVE: Lambdoid craniosynostosis affects approximately 1 in 33 000 live births per year, and surgical correction is often sought in order to achieve normocephaly and allow for adequate brain growth. However, the effects of lambdoid synostosis and its treatment on cognitive development are unknown. DESIGN: Systematic review and meta-analysis. PATIENTS, PARTICIPANTS: A systematic review of Ovid Medline, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov was conducted in January 2022. Included studies assessed cognitive development of patients with nonsyndromic unilateral lambdoid craniosynostosis. MAIN OUTCOME MEASURES: Results of developmental tests were compared to normative data or controls to generate Hedges' g for meta-analysis. RESULTS: Nine studies met the inclusion criteria. Meta-analysis of 3 studies describing general cognition showed that cases scored significantly lower than their peers, but within 1 standard deviation (g = 0.37, 95% CI [-0.64, -0.10], P = .01). Meta-analysis of verbal and psychomotor development showed no significant differences in children with lambdoid synostosis. Studies were of fair quality and had moderate-to-high heterogeneity. CONCLUSIONS: Patients with lambdoid craniosynostosis may score slightly below average on tests of general cognition in comparison to normal controls, but results in other domains are variable. Analyses were limited by small sample sizes. Multidisciplinary care and involvement of a child psychologist may be helpful in identifying areas of concern and providing adequate scholastic support. Further research recruiting larger cohorts will be necessary to confirm these findings and extend them to other developmental domains such as attention and executive function.

Laser interstitial thermal therapy compared with open resection for treating subependymal giant cell astrocytoma.

OBJECTIVE: Subependymal giant cell astrocytomas (SEGAs) are WHO grade 1 tumors associated with tuberous sclerosis that classically arise from the ventricular wall near the caudate groove and foramen of Monro. Laser interstitial thermal therapy (LITT) is a minimally invasive surgical technique, which works by heating a stereotactically placed laser fiber to ablative temperatures under MRI thermometry monitoring. In this paper, the authors present LITT as a surgical alternative to open resection of SEGAs. METHODS: Twelve patients with SEGAs who underwent 16 procedures between 2007 and 2022 at a single institution were retrospectively reviewed. These patients underwent either open resection or LITT. Clinical data, imaging, recurrence rate, further treatments, and related complications were analyzed. RESULTS: Among the 16 procedures, 9 were open resection and 7 were LITT. An external ventricular drain was placed in 66% (6/9) of open procedures and 57.1% (4/7) of LITT cases. A septostomy was performed in 56% (5/9) of open procedures and 29% (2/7) of LITT cases. Complication rates were higher in open cases than in LITT procedures (44% vs 0%, p < 0.05). Complications included hydrocephalus, transient venous ischemia, wound infection, and bone flap migration. The median length of hospital stay was 4 days (IQR 3.3-5.5 days) for open cases and 4 days (IQR 3.0-7.0 days) for LITT procedures. Recurrence or progression occurred after 3 open cases and 2 LITT cases (33% vs 33%, p = 0.803). For the recurrences, 2 open cases underwent stereotactic radiosurgery, 1 open case underwent LITT, and 1 LITT case underwent repeat LITT. Among the LITT cases, only the patients with no decrease in tumor size by 6 months experienced tumor progression afterward. The 2 LITT cases with progression were the only ones with calcification present on preoperative imaging. The median follow-up times for cases assessed for progression were 8.4 years (IQR 3.8-14.4 years) for open resection and 3.9 years (IQR 3.4-5.1 years) for LITT. CONCLUSIONS: The small size of this case series limits generalizability or adequate comparison of safety. However, this series adds to the literature supporting LITT as a less invasive surgical alternative to open resection of SEGAs and demonstrates that LITT has similar recurrence and/or progression rates to open resection. Additional studies with more data are necessary for comprehensive comparisons between open resection and LITT for treating SEGA.

Predictors and timing of hydrocephalus treatment in patients undergoing prenatal versus postnatal surgery for myelomeningocele.

OBJECTIVE: Although hydrocephalus rates have decreased with intrauterine surgery for myelomeningocele (MMC), 40%-85% of children with MMC still go on to develop hydrocephalus. Prenatal ventricle size is known to be associated with later development of hydrocephalus; however, it is not known how prediction measures or timing of hydrocephalus treatment differ between pre- and postnatal surgery for MMC. The goal of this study was to determine anatomical, clinical, and radiological characteristics that are associated with the need for and timing of hydrocephalus treatment in patients with MMC. METHODS: The authors retrospectively identified patients from Barnes Jewish Hospital or St. Louis Children's Hospital between 2016 and 2021 who were diagnosed with MMC prenatally and underwent either pre- or postnatal repair. Imaging, clinical, and demographic data were examined longitudinally between treatment groups and hydrocephalus outcomes. RESULTS: Fifty-eight patients were included (27 females, 46.6%), with a mean gestational age at birth of 36.8 weeks. Twenty-three patients (39.7%) underwent prenatal surgery. For the overall cohort, the ventricle size at prenatal ultrasound (HR 1.175, 95% CI 1.071-1.290), frontal-occipital horn ratio (FOHR) at birth > 0.50 (HR 3.603, 95% CI 1.488-8.720), and mean rate of change in head circumference (HC) in the first 90 days after birth (> 0.10 cm/day: HR 12.973, 95% CI 4.262-39.486) were identified as predictors of hydrocephalus treatment. The factors associated with hydrocephalus in the prenatal cohort were FOHR at birth > 0.50 (HR 27.828, 95% CI 2.980-259.846) and the rate of change in HC (> 0.10 cm/day: HR 39.414, 95% CI 2.035-763.262). The factors associated with hydrocephalus in the postnatal cohort were prenatal ventricle size (HR 1.126, 95% CI 1.017-1.246) and the mean rate of change in HC (> 0.10 cm/day: HR 24.202, 95% CI 5.119-114.431). FOHR (r = -0.499, p = 0.008) and birth HC (-0.409, p = 0.028) were correlated with time to hydrocephalus across both cohorts. For patients who underwent treatment for hydrocephalus, those in the prenatal surgery group were significantly more likely to develop hydrocephalus after 3 months than those treated with postnatal surgery, although the overall rate of hydrocephalus was significantly higher in the postnatal surgery group (p = 0.018). CONCLUSIONS: Clinical and imaging factors associated with hydrocephalus treatment differ between those receiving pre- versus postnatal MMC repair, and while the overall rate of hydrocephalus is lower, those undergoing prenatal repair are more likely to develop hydrocephalus after 3 months of age. This has implications for clinical follow-up timing for patients treated prenatally, who may live at a distance from the treatment site.

The role of occipital condyle and atlas anomalies on occipital cervical fusion outcomes in Chiari malformation type I with syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.

OBJECTIVE: Congenital anomalies of the atlanto-occipital articulation may be present in patients with Chiari malformation type I (CM-I). However, it is unclear how these anomalies affect the biomechanical stability of the craniovertebral junction (CVJ) and whether they are associated with an increased incidence of occipitocervical fusion (OCF) following posterior fossa decompression (PFD). The objective of this study was to determine the prevalence of condylar hypoplasia and atlas anomalies in children with CM-I and syringomyelia. The authors also investigated the predictive contribution of these anomalies to the occurrence of OCF following PFD (PFD+OCF). METHODS: The authors analyzed the prevalence of condylar hypoplasia and atlas arch anomalies for patients in the Park-Reeves Syringomyelia Research Consortium database who underwent PFD+OCF. Condylar hypoplasia was defined by an atlanto-occipital joint axis angle (AOJAA) ≥ 130°. Atlas assimilation and arch anomalies were identified on presurgical radiographic imaging. This PFD+OCF cohort was compared with a control cohort of patients who underwent PFD alone. The control group was matched to the PFD+OCF cohort according to age, sex, and duration of symptoms at a 2:1 ratio. RESULTS: Clinical features and radiographic atlanto-occipital joint parameters were compared between 19 patients in the PFD+OCF cohort and 38 patients in the PFD-only cohort. Demographic data were not significantly different between cohorts (p > 0.05). The mean AOJAA was significantly higher in the PFD+OCF group than in the PFD group (144° ± 12° vs 127° ± 6°, p < 0.0001). In the PFD+OCF group, atlas assimilation and atlas arch anomalies were identified in 10 (53%) and 5 (26%) patients, respectively. These anomalies were absent (n = 0) in the PFD group (p < 0.001). Multivariate regression analysis identified the following 3 CVJ radiographic variables that were predictive of OCF occurrence after PFD: AOJAA ≥ 130° (p = 0.01), clivoaxial angle < 125° (p = 0.02), and occipital condyle-C2 sagittal vertical alignment (C-C2SVA) ≥ 5 mm (p = 0.01). A predictive model based on these 3 factors accurately predicted OCF following PFD (C-statistic 0.95). CONCLUSIONS: The authors' results indicate that the occipital condyle-atlas joint complex might affect the biomechanical integrity of the CVJ in children with CM-I and syringomyelia. They describe the role of the AOJAA metric as an independent predictive factor for occurrence of OCF following PFD. Preoperative identification of these skeletal abnormalities may be used to guide surgical planning and treatment of patients with complex CM-I and coexistent osseous pathology.

Impact of neighborhood deprivation and social vulnerability on long-term outcomes and desire for revision in patients with craniosynostosis.

OBJECTIVE: The authors utilized the area deprivation index (ADI), a validated composite measure of socioeconomic disadvantage, and the social vulnerability index (SVI) to examine whether differences in neighborhood deprivation impact interventions and outcomes among patients with craniosynostosis. METHODS: Patients who underwent craniosynostosis repair between 2012 and 2017 were included. The authors collected data about demographic characteristics, comorbidities, follow-up visits, interventions, complications, desire for revision, and speech, developmental, and behavioral outcomes. National percentiles for ADI and SVI were determined using zip and Federal Information Processing Standard (FIPS) codes. ADI and SVI were analyzed by tertile. Firth logistic regressions and Spearman correlations were used to assess associations between ADI/SVI tertile and outcomes/interventions that differed on univariate analysis. Subgroup analysis was performed to examine these associations in patients with nonsyndromic craniosynostosis. Differences in length of follow-up among the nonsyndromic patients in the different deprivation groups were assessed with multivariate Cox regressions. RESULTS: In total, 195 patients were included, with 37% of patients in the most disadvantaged ADI tertile and 20% of patients in the most vulnerable SVI tertile. Patients in more disadvantaged ADI tertiles were less likely to have physician-reported desire (OR 0.17, 95% CI 0.04-0.61, p < 0.01) or parent-reported desire (OR 0.16, 95% CI 0.04-0.52, p < 0.01) for revision, independent of sex and insurance status. In the nonsyndromic subgroup, inclusion in a more disadvantaged ADI tertile was associated with increased odds of speech/language concerns (OR 4.42, 95% CI 1.41-22.62, p < 0.01). There were no differences in interventions received or outcomes among SVI tertiles (p ≥ 0.24). Neither ADI nor SVI tertile was associated with risk of loss to follow-up among nonsyndromic patients (p ≥ 0.38). CONCLUSIONS: Patients from the most disadvantaged neighborhoods may be at risk for poor speech outcomes and different standards of assessment for revision. Neighborhood measures of disadvantage represent a valuable tool to improve patient-centered care by allowing for modification of treatment protocols to meet the unique needs of patients and their families.

Neurodevelopment in unilateral coronal craniosynostosis: a systematic review and meta-analysis.

OBJECTIVE: The current literature on unilateral coronal craniosynostosis is replete with repair techniques and surgical outcomes; however, information regarding neurodevelopment remains unclear. Therefore, the aim of this systematic review and meta-analysis was to comprehensively assess the neurodevelopmental outcomes of patients with unicoronal craniosynostosis compared with their healthy peers or normative data. METHODS: A systematic review of the Ovid MEDLINE, Embase, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov databases from database inception to January 19, 2022, was performed. Included studies assessed neurodevelopment of patients with unicoronal craniosynostosis. Two independent reviewers selected studies and extracted data based on a priori inclusion and exclusion criteria. Results of developmental tests were compared with normative data or controls to generate Hedges' g statistics for meta-analysis. The quality of included studies was evaluated using the National Institutes of Health Assessment Tool. RESULTS: A total of 19 studies were included and analyzed, with an overall fair reporting quality. A meta-analysis of 325 postoperative patients demonstrated that scores of general neurodevelopment were below average but within one standard deviation of the norm (Hedges' g = -0.68 [95% CI -0.90 to -0.45], p < 0.001). Similarly, postoperative patients exhibited lower scores in verbal, psychomotor, and mathematic outcome assessments. CONCLUSIONS: This systematic review and meta-analysis found that patients with unicoronal craniosynostosis had poorer neurodevelopment, although scores generally remained within the normal range. These data may guide implementation of regular neurocognitive assessments and early learning support of patients with unicoronal craniosynostosis.

Impact of age at endoscopic metopic synostosis repair on anthropometric outcomes.

OBJECTIVE: Endoscopic strip craniectomy for metopic craniosynostosis relies on rapid growth and postoperative helmeting for correction. Endoscopic repair is generally performed before patients reach 4 months of age, and outcomes in older patients have yet to be quantified. Here, the authors examined a cohort of patients treated with endoscopic repair before or after 4 months of age to determine aesthetic outcomes of delayed repairs. METHODS: Data from eligible patients were retrospectively assessed and aggregated in a dedicated metopic synostosis database. Inclusion criteria were radiographically confirmed metopic synostosis and endoscopic treatment. Patients were dichotomized into two groups: those younger than 4 months and those 4 months or older at the time of repair. The frontal width and interfrontal divergence angle (IFDA) were measured on reconstructed CT images. These measurements, alongside operative time, estimated blood loss, and transfusion rates, were compared between groups using the Student t-test or chi-square test. RESULTS: The study population comprised 28 patients treated before 4 months of age and 8 patients treated at 4-6 months of age. Patient sex and perioperative complications did not differ by age group. Older age at repair was not significantly associated with 1-year postoperative IFDA (140° ± 4.2° vs 142° ± 5.0°, p = 0.28) or frontal width (84 ± 5.2 vs 83 ± 4.4 mm, p = 0.47). CONCLUSIONS: One-year postoperative IFDA and frontal width do not differ significantly between patients treated before and after 4 months of age. Further study with longer follow-up is necessary to confirm the longevity of these results at skeletal maturity.

Genetic and histopathological associations with outcome in pediatric pilocytic astrocytoma.

OBJECTIVE: Pilocytic astrocytomas (PAs) have a generally favorable prognosis; however, progression or recurrence after resection is possible. The prognostic value of histopathological qualifiers (defined below) or BRAF alterations is not well understood. The aim of this study was to identify the prognostic value of genetic and histopathological features of pediatric PAs. METHODS: Patients treated for a WHO grade I PA at a single institution were analyzed for histopathological and genetic features and outcomes. "Histopathological qualifier" refers to designations such as "WHO grade I PA with increased proliferative index." BRAF alterations include gene fusions and point mutations. Patients with neurofibromatosis type 1 were excluded. RESULTS: A total of 222 patients were analyzed (51% female, mean age 9.6 years). Tumors were located in the cerebellum/fourth ventricle (51%), optic pathway/hypothalamus (15%), brainstem (12%), and cerebral cortex (11%). BRAF alterations were screened for in 77 patients and identified in 56 (73%). Histopathological qualifiers were present in 27 patients (14%). Resection was performed in 197 patients (89%), 41 (21%) of whom displayed tumor progression or recurrence after resection. Tumor progression or recurrence was not associated with histopathologic qualifiers (p = 0.36) or BRAF alterations (p = 0.77). Ki-67 proliferative indices were not predictive of progression or recurrence (p = 0.94). BRAF alterations, specifically KIAA1549 fusions, were associated with cerebellar/fourth ventricular tumor location (p < 0.0001) and younger patient age (p = 0.03). Patients in whom gross-total resection was achieved had lower rates of progression and recurrence (p < 0.0001). CONCLUSIONS: Histopathological features/qualifiers and BRAF alterations were not associated with tumor recurrence/progression in pediatric PAs. The extent of resection was the only factor analyzed that predicted outcome.

Complications and outcomes of posterior fossa decompression with duraplasty versus without duraplasty for pediatric patients with Chiari malformation type I and syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.

OBJECTIVE: The aim of this study was to determine differences in complications and outcomes between posterior fossa decompression with duraplasty (PFDD) and without duraplasty (PFD) for the treatment of pediatric Chiari malformation type I (CM1) and syringomyelia (SM). METHODS: The authors used retrospective and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM1-SM who received PFD or PFDD and had at least 1 year of follow-up data. Preoperative, treatment, and postoperative characteristics were recorded and compared between groups. RESULTS: A total of 692 patients met the inclusion criteria for this database study. PFD was performed in 117 (16.9%) and PFDD in 575 (83.1%) patients. The mean age at surgery was 9.86 years, and the mean follow-up time was 2.73 years. There were no significant differences in presenting signs or symptoms between groups, although the preoperative syrinx size was smaller in the PFD group. The PFD group had a shorter mean operating room time (p < 0.0001), fewer patients with > 50 mL of blood loss (p = 0.04), and shorter hospital stays (p = 0.0001). There were 4 intraoperative complications, all within the PFDD group (0.7%, p > 0.99). Patients undergoing PFDD had a 6-month complication rate of 24.3%, compared with 13.7% in the PFD group (p = 0.01). There were no differences between groups for postoperative complications beyond 6 months (p = 0.33). PFD patients were more likely to require revision surgery (17.9% vs 8.3%, p = 0.002). PFDD was associated with greater improvements in headaches (89.6% vs 80.8%, p = 0.04) and back pain (86.5% vs 59.1%, p = 0.01). There were no differences between groups for improvement in neurological examination findings. PFDD was associated with greater reduction in anteroposterior syrinx size (43.7% vs 26.9%, p = 0.0001) and syrinx length (18.9% vs 5.6%, p = 0.04) compared with PFD. CONCLUSIONS: PFD was associated with reduced operative time and blood loss, shorter hospital stays, and fewer postoperative complications within 6 months. However, PFDD was associated with better symptom improvement and reduction in syrinx size and lower rates of revision decompression. The two surgeries have low intraoperative complication rates and comparable complication rates beyond 6 months.

Early Effects of COVID-19 Pandemic on Neurosurgical Training in the United States: A Case Volume Analysis of 8 Programs.

OBJECTIVE: To determine the impact of the 2019 novel coronavirus disease (COVID-19) pandemic on operative case volume in 8 U.S. neurosurgical residency training programs in early 2020 and to survey these programs regarding training activities during this period. METHODS: A retrospective review was conducted of monthly operative case volumes and types for 8 residency programs for 2019 and January through April 2020. Cases were grouped as elective cranial, elective spine, and nonelective emergent cases. Programs were surveyed regarding residents' perceptions of the impact of COVID-19 on surgical training, didactics, and research participation. Data were analyzed for individual programs and pooled across programs. RESULTS: Across programs, the 2019 monthly mean ± SD case volume was 211 ± 82; 2020 mean ± SD case volumes for January, February, March, and April were 228 ± 93, 214 ± 84, 180 ± 73, and 107 ± 45. Compared with 2019, March and April 2020 mean cases declined 15% (P = 0.003) and 49% (P = 0.002), respectively. COVID-19 affected surgical case volume for all programs; 75% reported didactics negatively affected, and 90% reported COVID-19 resulted in increased research time. Several neurosurgery residents required COVID-19 testing; however, to our knowledge, only 1 resident from the participating programs tested positive. CONCLUSIONS: This study documents a significant reduction in operative volume in 8 neurosurgery residency training programs in early 2020. During this time, neurosurgery residents engaged in online didactics and research-related activities, reporting increased research productivity. Residency programs should collect data to determine the educational impact of the COVID-19 pandemic on residents' operative case volumes, identify deficiencies, and develop plans to mitigate any effects.

Extradural decompression versus duraplasty in Chiari malformation type I with syrinx: outcomes on scoliosis from the Park-Reeves Syringomyelia Research Consortium.

OBJECTIVE: Scoliosis is common in patients with Chiari malformation type I (CM-I)-associated syringomyelia. While it is known that treatment with posterior fossa decompression (PFD) may reduce the progression of scoliosis, it is unknown if decompression with duraplasty is superior to extradural decompression. METHODS: A large multicenter retrospective and prospective registry of 1257 pediatric patients with CM-I (tonsils ≥ 5 mm below the foramen magnum) and syrinx (≥ 3 mm in axial width) was reviewed for patients with scoliosis who underwent PFD with or without duraplasty. RESULTS: In total, 422 patients who underwent PFD had a clinical diagnosis of scoliosis. Of these patients, 346 underwent duraplasty, 51 received extradural decompression alone, and 25 were excluded because no data were available on the type of PFD. The mean clinical follow-up was 2.6 years. Overall, there was no difference in subsequent occurrence of fusion or proportion of patients with curve progression between those with and those without a duraplasty. However, after controlling for age, sex, preoperative curve magnitude, syrinx length, syrinx width, and holocord syrinx, extradural decompression was associated with curve progression > 10°, but not increased occurrence of fusion. Older age at PFD and larger preoperative curve magnitude were independently associated with subsequent occurrence of fusion. Greater syrinx reduction after PFD of either type was associated with decreased occurrence of fusion. CONCLUSIONS: In patients with CM-I, syrinx, and scoliosis undergoing PFD, there was no difference in subsequent occurrence of surgical correction of scoliosis between those receiving a duraplasty and those with an extradural decompression. However, after controlling for preoperative factors including age, syrinx characteristics, and curve magnitude, patients treated with duraplasty were less likely to have curve progression than patients treated with extradural decompression. Further study is needed to evaluate the role of duraplasty in curve stabilization after PFD.

Dural augmentation approaches and complication rates after posterior fossa decompression for Chiari I malformation and syringomyelia: a Park-Reeves Syringomyelia Research Consortium study.

OBJECTIVE: Posterior fossa decompression with duraplasty (PFDD) is commonly performed for Chiari I malformation (CM-I) with syringomyelia (SM). However, complication rates associated with various dural graft types are not well established. The objective of this study was to elucidate complication rates within 6 months of surgery among autograft and commonly used nonautologous grafts for pediatric patients who underwent PFDD for CM-I/SM. METHODS: The Park-Reeves Syringomyelia Research Consortium database was queried for pediatric patients who had undergone PFDD for CM-I with SM. All patients had tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and ≥ 6 months of postoperative follow-up after PFDD. Complications (e.g., pseudomeningocele, CSF leak, meningitis, and hydrocephalus) and postoperative changes in syrinx size, headaches, and neck pain were compared for autograft versus nonautologous graft. RESULTS: A total of 781 PFDD cases were analyzed (359 autograft, 422 nonautologous graft). Nonautologous grafts included bovine pericardium (n = 63), bovine collagen (n = 225), synthetic (n = 99), and human cadaveric allograft (n = 35). Autograft (103/359, 28.7%) had a similar overall complication rate compared to nonautologous graft (143/422, 33.9%) (p = 0.12). However, nonautologous graft was associated with significantly higher rates of pseudomeningocele (p = 0.04) and meningitis (p < 0.001). The higher rate of meningitis was influenced particularly by the higher rate of chemical meningitis (p = 0.002) versus infectious meningitis (p = 0.132). Among 4 types of nonautologous grafts, there were differences in complication rates (p = 0.02), including chemical meningitis (p = 0.01) and postoperative nausea/vomiting (p = 0.03). Allograft demonstrated the lowest complication rates overall (14.3%) and yielded significantly fewer complications compared to bovine collagen (p = 0.02) and synthetic (p = 0.003) grafts. Synthetic graft yielded higher complication rates than autograft (p = 0.01). Autograft and nonautologous graft resulted in equal improvements in syrinx size (p < 0.0001). No differences were found for postoperative changes in headaches or neck pain. CONCLUSIONS: In the largest multicenter cohort to date, complication rates for dural autograft and nonautologous graft are similar after PFDD for CM-I/SM, although nonautologous graft results in higher rates of pseudomeningocele and meningitis. Rates of meningitis differ among nonautologous graft types. Autograft and nonautologous graft are equivalent for reducing syrinx size, headaches, and neck pain.

Kinetics and Competing Mechanisms of Antibody Aggregation via Bulk- and Surface-Mediated Pathways.

Non-native protein aggregation is a long-standing obstacle in the biopharmaceutical industry. Proteins can aggregate through different mechanisms, depending on the solution and stress conditions. Aggregation in bulk solution has been extensively studied in a mechanistic context and is known to be temperature dependent. Conversely, aggregation at interfaces has been commonly observed for liquid formulations but is less understood mechanistically. This work evaluates the combined effects of temperature and compression/dilation of air-water interfaces on aggregation rates and particle formation for anti-streptavidin immunoglobulin gamma-1. Aggregation rates are quantified via size-exclusion chromatography, dynamic light scattering, and microflow imaging as a function of temperature and extent of air-liquid interface compressions. Competition exists between bulk- and surface-mediated aggregation mechanisms. Each has a largely different temperature dependence that leads to a crossover between the dominant aggregation mechanisms as the sample temperature changes. Surface-mediated aggregation rates are pH dependent and correlate with electrostatic protein-protein interactions but do not mirror the pH dependence of bulk aggregation rates that instead follow trends for conformational stability. Mechanistic insights were informed by quiescent incubation of solutions before and after interface compressions. Detailed mechanistic conclusions require direct dynamic observation at the interface. Microbubble tensiometry is introduced as a promising tool for such measurements.

Defects in breathing and thermoregulation in mice with near-complete absence of central serotonin neurons.

Serotonergic neurons project widely throughout the CNS and modulate many different brain functions. Particularly important, but controversial, are the contributions of serotonin (5-HT) neurons to respiratory and thermoregulatory control. To better define the roles of 5-HT neurons in breathing and thermoregulation, we took advantage of a unique conditional knock-out mouse in which Lmx1b is genetically deleted in Pet1-expressing cells (Lmx1b(f/f/p)), resulting in near-complete absence of central 5-HT neurons. Here, we show that the hypercapnic ventilatory response in adult Lmx1b(f/f/p) mice was decreased by 50% compared with wild-type mice, whereas baseline ventilation and the hypoxic ventilatory response were normal. In addition, Lmx1b(f/f/p) mice rapidly became hypothermic when exposed to an ambient temperature of 4 degrees C, decreasing core temperature to 30 degrees C within 120 min. This failure of thermoregulation was caused by impaired shivering and nonshivering thermogenesis, whereas thermosensory perception and heat conservation were normal. Finally, intracerebroventricular infusion of 5-HT stimulated baseline ventilation, and rescued the blunted hypercapnic ventilatory response. These data identify a previously unrecognized role of 5-HT neurons in the CO(2) chemoreflex, whereby they enhance the response of the rest of the respiratory network to CO(2). We conclude that the proper function of the 5-HT system is particularly important under conditions of environmental stress and contributes significantly to the hypercapnic ventilatory response and thermoregulatory cold defense.

Aging and perception of visual form from temporal structure.

In this study, the authors examined age-related changes in participants' ability to perceive global spatial structure defined by temporal fine structure among elements undergoing rapid, irregular change. Participants were also tested on a task involving form recognition from luminance contrast and on a task dependent on perception of 3-dimensional shape from motion. Compared with young adults, older individuals were less sensitive to spatial form defined by temporal structure. In contrast, older observers performed as well as young adults on the other two tasks that were not dependent on temporal sensitivity, ruling out nonsensory factors as the cause of the deficits on the temporal structure task. This selective deficit may reveal reduced sensitivity within the temporal impulse response of the aging visual system, a deficit that could be related to reduced effectiveness of neural inhibition.

Drug-induced autoimmune hepatitis associated with turmeric dietary supplement use.

Turmeric dietary supplement sales, which accounted for US$69 million in spending in 2016, have been increasing exponentially in the USA, making this one of the most popular botanical supplements sold in the USA. Herbal supplement use, which is generally regarded as safe by consumers, is not usually reported to healthcare providers. We reported here on a case of autoimmune hepatitis, occurring in a 71-year-old woman taking turmeric dietary supplements for the maintenance of cardiovascular health, which resolved rapidly following discontinuation of the turmeric supplements. Of particular note, turmeric use was not documented in the patient's medical records and the potential causative role of the turmeric supplementation was ultimately identified by the patient rather than the healthcare providers. To our knowledge, this is the first documented report of turmeric supplement-induced autoimmune hepatitis.