Surgical management of craniospinal axis malignant peripheral nerve sheath tumors: a single-institution experience and literature review.

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is an exceedingly rare and aggressive tumor, with limited literature on its management. Herein, we present our series of surgically managed craniospinal MPNSTs, analyze their outcomes, and review the literature. METHODS: We retrospectively reviewed surgically managed primary craniospinal MPNSTs treated at our institution between January 2005 and May 2023. Patient demographics, tumor features, and treatment outcomes were assessed. Neurological function was quantified using the Frankel grade and Karnofsky performance scores. Descriptive statistics, rank-sum tests, and Kaplan-Meier survival analyses were performed. RESULTS: Eight patients satisfied the inclusion criteria (4 male, 4 female). The median age at presentation was 38 years (range 15-67). Most tumors were localized to the spine (75%), and 3 patients had neurofibromatosis type 1. The most common presenting symptoms were paresthesia (50%) and visual changes (13%). The median tumor size was 3 cm, and most tumors were oval-shaped (50%) with well-defined borders (75%). Six tumors were high grade (75%), and gross total resection was achieved in 5 patients, with subtotal resection in the remaining 3 patients. Postoperative radiotherapy and chemotherapy were performed in 6 (75%) and 4 (50%) cases, respectively. Local recurrence occurred in 5 (63%) cases, and distant metastases occurred in 2 (25%). The median overall survival was 26.7 months. Five (63%) patients died due to recurrence. CONCLUSIONS: Primary craniospinal MPNSTs are rare and have an aggressive clinical course. Early diagnosis and treatment are essential for managing these tumors. In this single-center study with a small cohort, maximal resection, low-grade pathology, young age (< 30), and adjuvant radiotherapy were associated with improved survival.

Clinical diagnostic and radiographic features of recurrent intracranial malignant triton tumor in an adult: illustrative case.

BACKGROUND: Malignant triton tumors (MTTs) are a rare and aggressive type of malignant peripheral nerve sheath tumor identified histologically by focal rhabdomyoblastic differentiation. OBSERVATIONS: A 37-year-old female with a prior history of Hodgkin lymphoma presented with acute-onset confusion, cognitive deficits, and weakness. Brain magnetic resonance imaging revealed a hemorrhagic intracranial mass later confirmed to be a malignant triton tumor. The patient underwent two resections and several courses of chemoradiation for multiple tumor recurrences and metastases. Unfortunately, despite extensive treatment, she died 2 years after initial presentation from complications of this tumor. Her overall survival (OS) of 26.7 months was double that reported in historical cohorts (OS ∼13 mos). LESSONS: The diagnosis and treatment of central nervous system MTTs are difficult and require a multidisciplinary team of neurosurgeons, radiologists, and oncologists. Histopathological analysis is required for confirmation of diagnosis. Gross-total resection of tumor and adjuvant radiation therapy have been shown to give patients the highest rates of survival and improved outcomes. Further studies and clinical trials are warranted to investigate the efficacy of chemotherapeutic agents like temozolomide, bevacizumab, and abemaciclib.

Longitudinal Clinical and Biological Characteristics in Juvenile-Onset Huntington's Disease.

BACKGROUND: Juvenile-onset Huntington's disease (JOHD) is a rare form of Huntington's disease (HD) characterized by symptom onset before the age of 21 years. Observational data in this cohort is lacking. OBJECTIVES: Quantify measures of disease progression for use in clinical trials of patients with JOHD. METHODS: Participants who received a motor diagnosis of HD before the age of 21 were included in the Kids-JOHD study. The comparator group consisted of children and young adults who were at-risk for inheriting the genetic mutation that causes HD, but who were found to have a CAG repeat in the non-expanded range (gene non-expanded [GNE]). RESULTS: Data were obtained between March 17, 2006, and February 13, 2020. There were 26 JOHD participants and 78 GNE participants who were comparable on age (16.03 vs. 14.43, respectively) and sex (53.8% female vs. 57.7% female, respectively). The mean annualized decrease in striatal volume in the JOHD group was -3.99% compared to -0.06% in the GNE (mean difference [MD], -3.93%; 95% confidence intervals [CI], [-4.98 to -2.80], FDR < 0.0001). The mean increase in the Unified Huntington's Disease Rating Scale Total Motor Score per year in the JOHD group was 7.29 points compared to a mean decrease of -0.21 point in the GNE (MD, 7.5; 95% CI, [5.71-9.28], FDR < 0·0001). CONCLUSIONS: These findings demonstrate that structural brain imaging and clinical measures in JOHD may be potential biomarkers of disease progression for use in clinical trials. Collaborative efforts are required to validate these results in a larger cohort of patients with JOHD. © 2022 International Parkinson and Movement Disorder Society.

Characterizing Early Changes in Quality of Life in Young Women With Breast Cancer.

Introduction: Younger age at diagnosis is a risk factor for poor health-related quality of life (HRQOL) in long-term breast cancer survivors. However, few studies have specifically addressed HRQOL in young adults with breast cancer (i.e., diagnosed prior to age 40), nor have early changes in HRQOL been fully characterized. Methods: Eligible female patients with breast cancer were identified through our local cancer center. To establish HRQOL, patients completed the Functional Assessment of Cancer Therapy-Breast (FACT-B) around diagnosis and 12 months later. Sociodemographic factors, genetic susceptibility to cancer, tumor- and treatment-related factors, and comorbidities (e.g., depression/anxiety) were abstracted from medical records and the local oncology registry. Mixed-effects models were used to identify changes in FACT-B scores during the first year of treatment and to determine whether any demographic/treatment-related factors modulated changes in scores. Results: Health-related quality of life in young patients with breast cancer was within normal limits at baseline, with a FACT-B overall well-being score of 108.5 (95% confidence limits [CI] = 103.7, 113.3). Participants reported slight improvements over a 12-month period: FACT-B overall well-being scores increased 6.6 points (95% CI = 2.1, 11.1, p < 0.01), functional well-being improved 3.0 points (95% CI = 2.0, 4.1, p < 0.01), emotional well-being improved 1.9 points (95% CI = 0.9, 2.8, p < 0.01), and physical well-being improved 1.5 points (95% CI = 0.2, 2.8, p = 0.03), on average. Participants with anxiety/depression at baseline reported greater improvements in FACT-B overall well-being (change: 12.9, 95% CI = 6.4, 9.5) and functional well-being (change: 5.2, 95% CI = 3.5, 6.9) than participants who did not have anxiety/depression at baseline (change in FACT-B overall well-being: 4.9, 95% CI = 0.2, 9.7; change in functional well-being: 2.3, 95% CI = 1.1, 3.4). Marital status, reconstructive surgery, and baseline clinical staging were also significantly associated with changes in aspects of HRQOL, although their impact on change was relatively minimal. Conclusion: Young women with breast cancer do not report HRQOL concerns during the first year of treatment. Improvements in HRQOL during the first year of treatment may be attributable to a sense of relief that the cancer is being treated, which, in the short run, may outweigh the negative late effects of treatment.

Behavioral features in child and adolescent huntingtin gene-mutation carriers.

INTRODUCTION: We compared neuropsychiatric symptoms between child and adolescent huntingtin gene-mutation carriers and noncarriers. Given previous evidence of atypical striatal development in carriers, we also assessed the relationship between neuropsychiatric traits and striatal development. METHODS: Participants between 6 and 18 years old were recruited from families affected by Huntington's disease and tested for the huntingtin gene expansion. Neuropsychiatric traits were assessed using the Pediatric Behavior Scale and the Behavior Rating Inventory of Executive Function. Striatal volumes were extracted from 3T neuro-anatomical images. Multivariable linear regression models were conducted to evaluate the impact of group (i.e., gene nonexpanded [GNE] or gene expanded [GE]), age, and trajectory of striatal growth on neuropsychiatric symptoms. RESULTS: There were no group differences in any behavioral measure with the exception of depression/anxiety score, which was higher in the GNE group compared to the GE group (estimate = 4.58, t(129) = 2.52, FDR = 0.051). The growth trajectory of striatal volume predicted depression scores (estimate = 0.429, 95% CI 0.15:0.71, p = .0029), where a negative slope of striatal volume over time was associated with lower depression/anxiety. CONCLUSIONS: The current findings show that GE children may have lower depression/anxiety compared to their peers. Previously, we observed a unique pattern of early striatal hypertrophy and continued decrement in volume over time among GE children and adolescents. In contrast, GNE individuals largely show striatal volume growth. These findings suggest that the lower scores of depression and anxiety seen in GE children and adolescents may be associated with differential growth of the striatum.

Characterizing academic performance in pediatric acute lymphoblastic leukemia with population-based achievement tests.

BACKGROUND: Recent shifts from radiation to chemotherapy-based treatment for acute lymphoblastic leukemia (ALL) have contributed to reduced long-term morbidity. Despite this, ALL survivors remain at increased risk for long-term cognitive impairments. AIM: To identify demographic and treatment factors associated with school performance in pediatric survivors of ALL. METHODS: We collected standardized test scores for reading, math, and science obtained in a school setting from grades 3-11 in 63 ALL survivors (46.0% boys). Most participants were assessed across multiple grades (median number of grades n = 5, range 1-7), and 269 observations were considered in the analyses. Treatment exposures were extracted from medical records. Socio-economic status was estimated using participation in free/reduced lunch programs at school. Mixed effects linear regression models were conducted to determine factors associated with school performance. RESULTS: ALL survivors' scores were comparable to state norms on reading, math, and science performances. On multivariable analysis, participation in free/reduced lunch programs was significantly associated with lower reading scores (ß = -12.52; 95% CI -22.26:-2.77, p = .01). Exposure to radiation during treatment was also associated with lower reading test scores (ß = -30.81, 95% CI -52.00:-9.62, p = .01). No significant associations between demographics and treatment parameters were observed for math and science test scores. CONCLUSIONS: We utilized population-based achievement tests conducted from grades 3-11 to characterize school performance in ALL survivors. Our results imply that survivors with low socio-economic status and those exposed to radiation during treatment could benefit from early monitoring and intervention to maximize academic success.