Explore the vast range of titles available.

Abstract BACKGROUND The low incidence of spinal chordoma precludes a prospective study of prognostic factors with a large patient cohort. OBJECTIVE To perform a comprehensive integrative analysis on the prognostic factors, treatment, and outcomes of patients with spinal chordoma using data from 2 institutions and the literature. METHODS Appropriate studies were identified per search criteria. The local database was retrospectively searched to include a similar patient cohort. RESULTS Overall, 108 studies from the literature and 30 patients from our local institution were identified, resulting in a total of 682 patients. The median age was 57 years old and 35.2% were female. The median follow-up was 46 months (range: 1-408). The median progression-free survival (PFS) and overall survival (OS) were 72 months and 115 months, respectively. Significant prognostic factors for PFS on multivariate analysis included age (pediatric vs adult, hazard ratio [HR]: 2.00-14.36), tumor location (mobile spine vs sacral spine, HR: 0.31-0.87), pathology (differentiated vs classic, HR: 2.48-10.90),and chemotherapy (HR:1.11-3.85). Significant prognostic factors for OS on multivariate analysis included age (geriatric vs adult, HR: 1.52-3.45 and pediatric vs adult, HR: 1.73-9.36), bladder or bowel dysfunction (HR: 1.27-5.43), pathology (dedifferentiated vs classic, HR: 2.38-11.09), recurrence or progression (HR: 1.72-4.48), and metastases (HR: 1.11-2.47). CONCLUSION In patients with spinal chordoma, young age, location in sacral spine, dedifferentiated pathology, and chemotherapy were negative predictors of PFS, while young and old age, bladder or bowel dysfunction at presentation, dedifferentiated pathology, recurrence or progression, and metastases portended a worse OS.

BACKGROUND:The role of brain biopsy in patients with cryptogenic neurological disease is uncertain. OBJECTIVE:To determine the risks and benefits of diagnostic brain biopsy for nonneoplastic indications in immunocompetent patients. METHODS:Appropriate studies were identified by searching electronic databases. RESULTS:We screened 3645 abstracts and included 20 studies with a total of 831 patients. Indications for biopsy were(1a) severe neurological disease of unknown etiology in adults (n = 7) and (1b) in children (n = 2); (2) suspected primary angiitis of the central nervous system (PACNS) (n = 3); (3) chronic meningitis of unknown cause (n = 3); (4) atypical dementia (n = 4); and (5) nonneoplastic disease (n = 1). Diagnostic success rates calculated for subgroups were 51.3% (34.5-68.1) for 1a, 53.8% (42.9-64.5) for 1b, 74.7% (64.0-84.1) for 2, 30.3% (17.2-45.4) for 3, and 60.8% (41.2-78.8) for 4. Clinical impact rates were 30.5% (13.6-50.6) for 1a (n = 6), 67.1% (42.8-87.3) for 1b (n = 2), 8.3% (2.3-20.0) for 3 (n = 1), and 14.2% (6.5-24.3) for 4 (n = 2). Lymphoma (n = 32) and Creutzfeldt-Jakob disease (n = 30) were the most common diagnoses on the final histopathology reports of positive brain biopsies in 1a. In 1b, encephalitis (n = 7), PACNS (n = 6), and demyelination (n = 6) were the most common. The odds ratio for achieving a diagnostic biopsy when there was a radiological target was 3.70 (P = .014, 95% confidence interval, 1.31-10.42). CONCLUSION:Brain biopsy in cryptogenic neurological disease was associated with the highest diagnostic yield in patients with suspected PACNS. The greatest clinical impact was seen in children with cryptogenic neurological disease. The presence of a radiological target was associated with a higher diagnostic yield. ABBREVIATIONS:CI, confidence intervalCJD, Creutzfeldt-Jakob diseaseCNS, central nervous systemPACNS, primary angiitis of the central nervous systemRCVS, reversible cerebral vasoconstriction syndrome

Early Alzheimer’s disease (AD) pathology can be found in cortical biopsies taken during shunt placement for Normal Pressure Hydrocephalus. This represents an opportunity to study early AD pathology in living patients. Here we report RNA-seq data on 106 cortical biopsies from this patient population. A restricted set of genes correlate with AD pathology in these biopsies, and co-expression network analysis demonstrates an evolution from microglial homeostasis to a disease-associated microglial phenotype in conjunction with increasing AD pathologic burden, along with a subset of additional astrocytic and neuronal genes that accompany these changes. Further analysis demonstrates that these correlations are driven by patients that report mild cognitive symptoms, despite similar levels of biopsy β-amyloid and tau pathology in comparison to patients who report no cognitive symptoms. Taken together, these findings highlight a restricted set of microglial and non-microglial genes that correlate with early AD pathology in the setting of subjective cognitive decline. Specific transcriptional changes in microglia associated with Alzheimer’s disease have been reported. Here, the authors show that transcriptional analysis of human hydrocephalus biopsies identifies changes in immune response genes associated with early AD pathology, including cognitive decline.

Purpose: The recurrence of a lumbar disc herniation (LDH) is a common cause of poor outcome following lumbar discectomy. The aim of this study was to assess a potential relationship between the incidence of recurrent LDH and the surgical technique used. Furthermore, we tried to define the best surgical technique for the treatment of recurrent LDH to limit subsequent recurrences. Materials and Methods: A retrospective study was conducted on 979 consecutive patients treated for LDH. A multivariate analysis tried to identify a possible correlation between (1) the surgical technique used to treat the primary LDH and its recurrence; (2) technique used to treat the recurrence of LDH and the second recurrence; and (3) incidence of recurrence and clinical outcome. Data were analyzed with the Pearson's Chi-square test for its significance. Results: In 582 cases (59.4%), a discectomy was performed, while in 381 (40.6%), a herniectomy was undertaken. In 16 cases, a procedure marked as \"other\" was performed. Among all patients, 110 (11.2%) had a recurrence. Recurrent LDH was observed in 55 patients following discectomy (9.45%), in 45 following herniectomy (11.8%), and in 10 (62.5%) following other surgery. Our data showed that 90.5% of discectomies and 88.2% of the herniectomies had a good clinical outcome, whereas other surgeries presented a recurrence rate of 62.5% (Pearson's χ2 < 0.001). No statistical differences were observed between discectomy or herniectomy, for the treatment of the recurrence, and the incidence for the second recurrences (P > 0.05). A significant statistical correlation emerged between the use of other techniques and the incidence for the second recurrences (P < 0.05). Conclusions: The recurrence of an LDH is one of the most feared complications following surgery. Although the standard discectomy has been considered more protective toward the recurrence compared to herniectomy, our data suggest that there is no significant correlation between the surgical technique and the risk of LDH recurrence.

To the Editor： A 20-year-old female college student and soccer player presented to the Emergency Department with acute onset of abdominal pain, nausea, and vomiting. On the morning of presentation, she woke up with sudden onset of epigastric pain that was constant and 10/10 in severity. The patient denied any obstipation, constipation, diarrhea, any recent trauma to the abdomen, or any potential inciting event. Of note, the patient did endorse previous episodes of postprandial epigastric pain, but it was never this severe. Her past medical and surgical history was unremarkable.

ZCCHC17 is a master regulator of synaptic gene expression and has recently been shown to play a role in splicing of neuronal mRNA. We previously showed that ZCCHC17 protein declines in Alzheimer’s disease (AD) brain tissue before there is significant gliosis and neuronal loss, that ZCCHC17 loss partially replicates observed splicing abnormalities in AD brain tissue, and that maintenance of ZCCHC17 levels is predicted to support cognitive resilience in AD. Here, we assessed the functional consequences of reduced ZCCHC17 expression in primary cortical neuronal cultures using siRNA knockdown. Consistent with its previously identified role in synaptic gene expression, loss of ZCCHC17 led to loss of synaptic protein expression. Patch recording of neurons shows that ZCCHC17 loss significantly disrupted the excitation/inhibition balance of neurotransmission, and favored excitatory-dominant synaptic activity as measured by an increase in spontaneous excitatory post synaptic currents and action potential firing rate, and a decrease in spontaneous inhibitory post synaptic currents. These findings are consistent with the hyperexcitable phenotype seen in AD animal models and in patients. We are the first to assess the functional consequences of ZCCHC17 knockdown in neurons and conclude that ZCCHC17 loss partially phenocopies AD-related loss of synaptic proteins and hyperexcitability.

INTRODUCTION Multi‐omics studies in Alzheimer's disease (AD) revealed many potential disease pathways and therapeutic targets. Despite their promise of precision medicine, these studies lacked Black Americans (BA) and Latin Americans (LA), who are disproportionately affected by AD. METHODS To bridge this gap, Accelerating Medicines Partnership in Alzheimer's Disease (AMP‐AD) expanded brain multi‐omics profiling to multi‐ethnic donors. RESULTS We generated multi‐omics data and curated and harmonized phenotypic data from BA (n = 306), LA (n = 326), or BA and LA (n = 4) brain donors plus non‐Hispanic White (n = 252) and other (n = 20) ethnic groups, to establish a foundational dataset enriched for BA and LA participants. This study describes the data available to the research community, including transcriptome from three brain regions, whole genome sequence, and proteome measures. DISCUSSION The inclusion of traditionally underrepresented groups in multi‐omics studies is essential to discovering the full spectrum of precision medicine targets that will be pertinent to all populations affected with AD. Highlights Accelerating Medicines Partnership in Alzheimer's Disease Diversity Initiative led brain tissue profiling in multi‐ethnic populations. Brain multi‐omics data is generated from Black American, Latin American, and non‐Hispanic White donors. RNA, whole genome sequencing and tandem mass tag proteomicsis completed and shared. Multiple brain regions including caudate, temporal and dorsolateral prefrontal cortex were profiled.

INTRODUCTION Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early Alzheimer's disease (AD) pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify cerebrospinal fluid  (CSF) biomarkers for AD‐related central nervous system (CNS) pathophysiologic changes using tissue and fluids with early pathology, free of post mortem artifact. METHODS We analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes. RESULTS AD pathology on biopsy correlates with CSF β‐amyloid‐42/40, neurofilament light chain (NfL), and phospho‐tau‐181(p‐tau181)/β‐amyloid‐42, while several gene expression modules correlate with NfL. Proteomic analysis highlights seven core proteins that correlate with pathology and gene expression changes on biopsy, and metabolomic analysis of CSF identifies disease‐relevant groups that correlate with biopsy data. DISCUSSION As additional biomarkers are added to AD diagnostic panels, our work provides insight into the CNS pathophysiology these markers are tracking. Highlights AD CSF biomarkers correlate with CNS pathology and transcriptomic changes. Seven proteins correlate with CNS pathology and gene expression changes. Inflammatory and neuronal gene expression changes correlate with YKL‐40 and NPTXR, respectively. CSF metabolomic analysis identifies pathways that correlate with biopsy data. Fatty acid metabolic pathways correlate with β‐amyloid pathology.

Abstract BACKGROUND: The role of brain biopsy in patients with cryptogenic neurological disease is uncertain. OBJECTIVE: To determine the risks and benefits of diagnostic brain biopsy for nonneoplastic indications in immunocompetent patients. METHODS: Appropriate studies were identified by searching electronic databases. RESULTS: We screened 3645 abstracts and included 20 studies with a total of 831 patients. Indications for biopsy were: (1a) severe neurological disease of unknown etiology in adults (n = 7) and (1b) in children (n = 2); (2) suspected primary angiitis of the central nervous system (PACNS) (n = 3); (3) chronic meningitis of unknown cause (n = 3); (4) atypical dementia (n = 4); and (5) nonneoplastic disease (n = 1). Diagnostic success rates calculated for subgroups were 51.3% (34.5-68.1) for 1a, 53.8% (42.9-64.5) for 1b, 74.7% (64.0-84.1) for 2, 30.3% (17.2-45.4) for 3, and 60.8% (41.2-78.8) for 4. Clinical impact rates were 30.5% (13.6-50.6) for 1a (n = 6), 67.1% (42.8-87.3) for 1b (n = 2), 8.3% (2.3-20.0) for 3 (n = 1), and 14.2% (6.5-24.3) for 4 (n = 2). Lymphoma (n = 32) and Creutzfeldt-Jakob disease (n = 30) were the most common diagnoses on the final histopathology reports of positive brain biopsies in 1a. In 1b, encephalitis (n = 7), PACNS (n = 6), and demyelination (n = 6) were the most common. The odds ratio for achieving a diagnostic biopsy when there was a radiological target was 3.70 (P = .014, 95% confidence interval, 1.31-10.42). CONCLUSION: Brain biopsy in cryptogenic neurological disease was associated with the highest diagnostic yield in patients with suspected PACNS. The greatest clinical impact was seen in children with cryptogenic neurological disease. The presence of a radiological target was associated with a higher diagnostic yield.