Litigation involving sports-related spinal injuries: a comprehensive review of reported legal claims in the United States in the past 70 years.

BACKGROUND CONTEXT: Sports-related spinal injuries can be catastrophic in nature. Athletes competing in collision sports (eg, football) may be particularly prone to injury given the high-impact nature of these activities. Due to the oftentimes profound impact of sports-related spinal injuries on health and quality-of-life, they are also associated with a substantial risk of litigation. However, no study to date has assessed litigation risks associated with sports-related spinal injuries. A better understanding of the risk factors surrounding these legal claims may provide insights into injury prevention and other strategies to minimize litigation risks. In addition, it may allow the spine surgeon to better recognize the health, socioeconomic, and legal challenges faced by this patient population. PURPOSE: To provide a comprehensive assessment of reported legal claims involving sports-related spinal injuries, including a comparative analysis of legal outcomes between collision and non-collision sports. To discuss strategies to prevent sports-related spinal injuries and minimize litigation risks. STUDY DESIGN/SETTING: Retrospective review. PATIENT SAMPLE: Athletes experiencing spinal injuries during sports. OUTCOME MEASURES: Outcomes included verdict outcome (defendant vs. plaintiff), legal claims, injuries sustained, clinical symptoms, and award payouts. METHODS: The legal research database Westlaw Edge (Thomson Reuters) was queried for legal claims brought in the United States from 1950 to 2021 involving sports-related spinal injuries. Verdict or settlement outcomes were collected as well as award payouts, time to case closure, case year, and case location. Demographic data, including type of sport (ie collision vs. non-collision sport) and level of play were obtained. Legal claims, spinal injuries sustained, and clinical symptoms were also extracted. Furthermore, the nature of injury, injured spinal region, and treatment pursued were collected. Descriptive statistics were reported for all cases and independent-samples t-tests and chi-square tests were used to compare differences between collision and non-collision sports. RESULTS: Of the 840 cases identified on initial search, 78 met our criteria for in-depth analysis. This yielded 62% (n=48) defendant verdicts, 32% (n=25) plaintiff verdicts, and 6% (n=5) settlements, with a median inflation-adjusted award of $780,000 (range: $5,480-$21,585,000) for all cases. The most common legal claim was negligent supervision (n=38, 46%), followed by premises liability (n=23, 28%), and workers' compensation/no fault litigation (n=10, 12%). The most common injuries sustained were vertebral fractures (n=34, 44%) followed by disc herniation (n=14, 18%). Most cases resulted in catastrophic neurological injury (n=37, 49%), either paraplegia (n=6, 8%) or quadriplegia (n=31, 41%), followed by chronic/refractory pain (n=32, 43%). Non-collision sport cases had a higher percentage of premises liability claims (41% vs. 11%, p=.006) and alleged chronic/refractory pain (53% vs. 28%, p=.04). Conversely, collision sport cases had a higher proportion of workers' compensation/no fault litigation (23% vs. 4%, p=.03) and cases involving disc herniation (29% vs. 9%, respectively; p=.04). CONCLUSION: Sports-related spinal injuries are associated with multiple and complex health, socioeconomic, and legal consequences, with median inflation-adjusted award payouts nearing $800,000 per case. In our cohort, the most commonly cited legal claims were negligent supervision and premises liability, emphasizing the need for prevention guidelines for safe sports practice, especially in non-professional settings. Cases involving athletes participating in non-collision sports were significantly associated with claims citing chronic/refractory pain, highlighting the importance of long-term care in severely injured athletes.

MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations.

We have previously identified a region containing 16 CpGs within the MGMT CpG islands which is critical for the transcriptional control of MGMT (Malley, Acta Neuropathol 2011). To investigate the patterns and incidence of MGMT methylation in astrocytic and oligodendroglial tumors, we quantitatively assessed methylation at these 16 CpGs using bisulfite modification followed by pyrosequencing of 362 gliomas not treated with temozolomide, and correlated the findings with previously identified patterns of genetic abnormalities, patients' age and survival. The MGMT gene was considered to be methylated when the mean methylation of the 16 CpGs was 10% or higher. This cut-off value distinguished diffuse astrocytomas with high and low MGMT expression. Within each tumor type, the patterns of methylation were highly variable and also highly heterogeneous across the 16 CpGs. A high incidence of MGMT methylation was observed in all subtypes of gliomas included in this study. Among a subset of 97 tumors where conventional methylation-specific PCR (MSP) was also applied, methylation was detected by both methods in 54 tumors, while the pyrosequencing results identified a further 17 tumors. No additional cases were found using MSP alone, indicating that pyrosequencing is a robust method for methylation analysis. All tumors with IDH1/IDH2 mutations except two had MGMT methylation, while there were many tumors with MGMT methylation, particularly primary glioblastomas, which had no mutations of IDH1/2. We suggest that MGMT methylation may be one of the earliest events in the development of astrocytic and oligodendroglial tumors.

A distinct region of the MGMT CpG island critical for transcriptional regulation is preferentially methylated in glioblastoma cells and xenografts.

O(6)-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that removes alkyl DNA adducts such as those induced by alkylating agents. Loss of MGMT expression through transcriptional silencing by hypermethylation of its CpG island (CGI) is found in diverse human cancers including glioblastomas. Glioblastomas that have MGMT methylation respond to temozolomide, an alkylating agent, resulting in improved survival. Consequently, assessment of MGMT methylation has become a therapy response and prognostic indicator. However, it is not clear whether the region of the MGMT CGI commonly analysed is the critical region involved in transcriptional control. We measured methylation levels at each CpG site for the entire MGMT CGI using bisulfite modification and pyrosequencing, and compared them with MGMT mRNA expression in glioblastoma cell lines, xenografts and normal brain tissues (41 samples). Two critical regions were identified (DMR1 and DMR2). DMR2 encompasses the commonly analysed region and was always methylated when DMR1 was methylated. A luciferase reporter assay showed that substitutions of several specific CpG sites within DMR2 significantly attenuated the promoter activity of the MGMT CGI. Our results indicate that several CpG sites within DMR2 play a critical role in the transcriptional control of MGMT, making DMR2 the optimal target for methylation testing. However, given the highly variable patterns of MGMT methylation associated with transcriptional silencing observed in this region among the tumours in this study, methylation levels need to be measured at a number of individual CpGs within DMR2 to confidently predict transcriptional silencing and thus sensitivity to alkylating agents.

Adult grade II diffuse astrocytomas are genetically distinct from and more aggressive than their paediatric counterparts.

Diffuse astrocytomas (WHO grade II) typically present as slow-growing tumours showing significant cellular differentiation, but possessing a tendency towards malignant progression. They account for ~10% of all astrocytic tumours, with a peak incidence between 30 and 40 years of age. Median survival is reported as around 6-8 years. Mutations of TP53 and IDH1 have been described as genetic hallmarks, while copy number alterations are also relatively common. However, there is some evidence to suggest that these characteristics may vary with age. Here, we present an integrated clinicopathologic, genomic and transcriptomic analysis suggesting that paediatric and adult tumours are associated with distinct genetic signatures. For example, no childhood tumour showed mutation of IDH1/2 or TP53, virtually no copy number changes were seen, and MGMT methylation was absent. In contrast, adult tumours showed IDH1/2 mutation in 94% and TP53 mutation in 69% of cases, with multiple copy number alterations per case and hypermethylation of MGMT in the majority of tumours. These differences were associated with a worse prognosis in the adult patients. The expression array data also revealed a significant difference in the expression of a number of genes putatively involved in neural stem cell maintenance and CNS development, including DLL3, HES5, BMP2, TIMP1 and BAMBI. Genes involved in DNA replication and the cell cycle were also enriched in the adult tumours, suggesting that their more aggressive behaviour may be due to derivation from a more rapidly dividing, less differentiated cell type.