Intramedullary Spinal Cord Tumors: Whole-Genome Sequencing to Assist Management and Prognosis.

Intramedullary spinal cord tumors (IMSCTs) harbor unique genetic mutations which may play a role in prognostication and management. To this end, we present the largest cohort of IMSCTs with genetic characterization in the literature from our multi-site institutional registry. A total of 93 IMSCT patient records were reviewed from the years 1999 to 2020. Out of these, 61 complied with all inclusion criteria, 14 of these patients had undergone genetic studies with 8 undergoing whole-genomic sequencing. Univariate analyses were used to assess any factors associated with progression-free survival (PFS) using the Cox proportional hazards model. Firth's penalized likelihood approach was used to account for the low event rates. Fisher's exact test was performed to compare whole-genome analyses and specific gene mutations with progression. PFS (months) was given as a hazard ratio. Only the absence of copy neutral loss of heterozygosity (LOH) was shown to be significant (0.05, p = 0.008). Additionally, higher risk of recurrence/progression was associated with LOH (p = 0.0179). Our results suggest LOH as a genetic predictor of shorter progression-free survival, particularly within ependymoma and glioblastoma tumor types. Further genomic research with larger multi-institutional datasets should focus on these mutations as possible prognostic factors.

Clinical features and neurological outcomes in pediatric immune-mediated thrombotic thrombocytopenic purpura: A report from a large pediatric hematology center.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a potentially life-threatening disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and severely reduced or absent ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) activity, with varying degrees of organ dysfunction. As TTP is rare in pediatrics, most of the medical and scientific literature has largely reported on adult patients. As a result, limited data exist regarding the clinical features, comorbidities, treatment response, and long-term outcomes in pediatric patients with immune-mediated TTP. METHODS: A single-center retrospective cohort study was conducted of all children and adolescents presenting to Children's Healthcare of Atlanta, Atlanta, Georgia, between the years 2001 and 2021 with immune-mediated TTP (iTTP). Clinical features, treatments, and outcomes, including long-term neurocognitive function, were analyzed. RESULTS: Eighteen individuals were identified, six of whom had a total of 10 relapses, amounting to 28 episodes overall. Thirty-eight percent of the patients experienced exacerbations but, ultimately, 85% achieved a clinical response and clinical remission. Only one in-hospital death occurred (mortality rate 5.5%). Seventy-three percent of analyzed patients demonstrated long-term neurocognitive abnormalities, including cognitive delay, learning difficulties, and severe depression. CONCLUSIONS: Children and adolescents recovering from iTTP are at high risk for neurocognitive deficits from initial and possibly ongoing microvascular disease. Due to risk for long-term neurological deficits, we recommend neuropsychological testing in addition to monitoring of other organ functions in all children with TTP, as well as long-term surveillance of ADAMTS13 activity during remission to detect and promptly treat early relapse.

Permanent Cerebrospinal Fluid Diversion in Adults With Posterior Fossa Tumors: Incidence and Predictors.

BACKGROUND: Posterior fossa tumors (PFTs) can cause hydrocephalus. Hydrocephalus can persist despite resection of PFTs in a subset of patients requiring permanent cerebrospinal fluid (CSF) diversion. Characteristics of this patient subset are not well defined. OBJECTIVE: To define preoperative and postoperative variables that predict the need for postoperative CSF diversion in adult patients with PFTs. METHODS: We surveyed the CNS (Central Nervous System) Tumor Outcomes Registry at Emory (CTORE) for patients who underwent PFT resection at 3 tertiary-care centers between 2006 and 2019. Demographic, radiographic, perioperative, and dispositional data were analyzed using univariate and multivariate models. RESULTS: We included 617 patients undergoing PFT resection for intra-axial (57%) or extra-axial (43%) lesions. Gross total resection was achieved in 62% of resections. Approximately 13% of patients required permanent CSF diversion/shunting. Only 31.5% of patients who required pre- or intraop external ventricular drain (EVD) placement needed permanent CSF diversion. On logistic regression, size, transependymal flow, use of perioperative EVD, postoperative intraventricular hemorrhage (IVH), and surgical complications were predictors of permanent CSF diversion. Preoperative tumor size was only independent predictor of postoperative shunting in patients with subtotal resection. In patients with intra-axial tumors, transependymal flow (P = .014), postoperative IVH (P = .001), surgical complications (P = .013), and extent of resection (P = .03) predicted need for shunting. In extra-axial tumors, surgical complications were the major predictor (P = .022). CONCLUSION: Our study demonstrates that presence of preoperative hydrocephalus in patients with PFT does not necessarily entail the need for permanent CSF diversion. We report the major predictive factors for needing permanent CSF diversion.