UW Neurological Surgery Recent PubMed Publications

Vaccines targeting the complex pre-erythrocytic stage of Plasmodium parasites may benefit from inclusion of multiple antigens. However, discerning protective effects can be difficult because newer candidates may not be as protective as leading antigens like the circumsporozoite protein (CSP) in the conventional pre-clinical mouse model. We developed a modified mouse model challenge strategy that maximizes the contribution of T cells induced by novel candidate antigens at the sporozoite challenge...

We aimed to identify factors predicting additional surgical interventions in patients with drug-resistant epilepsy who continue experiencing seizures after mesial temporal laser interstitial thermal therapy (LITT). In a retrospective observational study, we analyzed consecutive patients with drug-resistant temporal epilepsy treated with mesial temporal LITT at the University of Washington between 2013-2022. The primary outcome was subsequent epilepsy surgery to improve seizure control after...

Hereditary spastic paraplegia (HSP) with thin corpus callosum can be due to a variety of genetic causes, the most common of which are biallelic variants in SPG11 (HSP11). Only six cases of neuropathologic examination of HSP11 have been reported. Here we present neuropathological findings in another case of HSP11 with novel mutation (homozygous c.6439_6442del) and clinical features of three additional cases of HSP11. These four cases of HSP11 had similar disease courses with prominent lower...

Cerebral vasospasm (CV) is a critical determinant of outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). Despite advances in neurocritical care, modifiable risk factors for CV remain poorly understood, and identifying them could significantly enhance patient management and treatment strategies. The present study explored the potential link between the reactivation of herpes simplex virus type 1 (HSV-1), a common resident virus in cranial nerves, and CV severity. It was...

CONCLUSIONS: Our results shed new insight into the biology of benign and aggressive NF2 mutant meningiomas and may have important implications for the efficacy of therapies targeting oncogenic YAP1 activity in NF2 mutant meningiomas.

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Pediatric-type high-grade gliomas frequently harbor gene fusions involving receptor tyrosine kinase genes, including neurotrophic tyrosine kinase receptor (NTRK) fusions. Clinically, these tumors show high initial response rates to tyrosine kinase inhibition but ultimately recur due to the accumulation of additional resistance-conferring mutations. Here, we develop a series of genetically engineered mouse models of treatment-naive and -experienced NTRK1/2/3 fusion-driven gliomas. All tested NTRK...

CONCLUSIONS: Overall, this study suggests that ISNCSCI motor scores and NME scores are strongly correlated and highly agreeable. When conducting SCI research, a thorough clinical motor examination may be a useful surrogate when ISNCSCI examinations are missing.

Gene-based burden tests are a popular and powerful approach for analysis of exome-wide association studies. These approaches combine sets of variants within a gene into a single burden score that is then tested for association. Typically, a range of burden scores are calculated and tested across a range of annotation classes and frequency bins. Correlation between these tests can complicate the multiple testing correction and hamper interpretation of the results. We introduce a method called the...

CONCLUSION: Our findings indicate that SRS has a significantly higher obliteration rate at last follow-up compared with endovascular embolization. Also, SRS has a higher tendency for fewer hemorrhagic complications and lower re-treatment rate. Further prospective studies are needed.

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Patients with brain tumours are motivated to participate in clinical trials involving repeat tissue sampling. Normalising the use of neoadjuvant and staged surgical trials necessitates collaboration among patients, regulatory agencies, and researchers. Initial and repetitive tissue sampling plays a crucial role in enhancing our understanding of resistance mechanisms and vulnerabilities in brain tumour therapy. Standardising biopsy techniques and ensuring technical uniformity across institutions...

Treatment of intracranial aneurysms is currently limited to invasive surgical and endovascular modalities, and some aneurysms are not treatable with these methods. Identification and targeting of specific molecular pathways involved in the pathogenesis of aneurysms may improve outcomes. Low frequency somatic variants found in cancer related genes have been linked to intracranial aneurysm development. In particular, mutations in the PDGFRB gene lead to constitutively activated ERK and nuclear...

CONCLUSION: Implementation of population-based SC concurrent with a substance use program resulted in a 25% reduction in the suicide attempt rate in the 90 days after primary care visits.

Importation of malaria infections is a suspected driver of sustained malaria prevalence on areas of Bioko Island, Equatorial Guinea. Quantifying the impact of imported infections is difficult because of the dynamic nature of the disease and complexity of designing a randomized trial. We leverage a six-month travel moratorium in and out of Bioko Island during the initial COVID-19 pandemic response to evaluate the contribution of imported infections to malaria prevalence on Bioko Island. Using a...

Mental health conditions and concussion history reported by a collegiate athlete may contribute to prolonged recovery and symptom severity after concussion. This work examined the potential associations among concussion history, preexisting conditions, and sex relative to initial symptom severity and recovery duration following sport-related concussion (SRC) in a cohort of Division 1 National Collegiate Athletic Association athletes. This prospective cohort study analyzed symptom severity,...

CONCLUSIONS: Practically negligible item-level bias was identified across education and ethnicity/language. Detected DIF can be described as benign, indicating that some items manifested differently between groups but had minimal impact on measurement properties. These results demonstrate that the SMCQ performs appropriately across demographic variables. Our findings also provide support for the associations of SMCQ scores with self-reported mood, cognitive status, and AD blood-based biomarkers.

Swallowing, both nutritive and non-nutritive, is highly dysfunctional in children with Leigh Syndrome (LS) and contributes to the need for both gastrostomy and tracheostomy tube placement. Without these interventions aspiration of food, liquid, and mucus occur resulting in repeated bouts of respiratory infection. No study has investigated whether mouse models of LS, a neurometabolic disorder, exhibit dysfunctions in neuromuscular activity of swallow and breathing integration. We used a genetic...

Chronic hepatitis B is a global health concern with a high risk of end-stage liver disease. Current standard-of-care agents have low cure rates, and new therapies are needed. Small interfering RNAs (siRNAs) that target viral RNAs fulfill a gap not addressed by standard-of-care agents and may contribute to a functional cure. Here, we describe the preclinical characterization of imdusiran (AB-729), a novel, pan-genotypic siRNA therapeutic that effectively reduces HBsAg, viral antigens, and viral...

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