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Safety and efficacy of preoperative embolization in the treatment of brain arteriovenous malformations with perinidal aneurysms and single draining vein: a multicenter study with propensity score-weighting
No full textBACKGROUND AND OBJECTIVES: Arteriovenous malformations (AVMs) with perinidal aneurysms and single draining vein are associated with an elevated risk of rupture and increased procedural complexity. The role of preoperative embolization in this high-risk anatomical subset remains unclear. This study aimed to evaluate the safety and efficacy of microsurgery with preoperative embolization, compared with microsurgery alone in patients with such AVMs. METHODS: We conducted a multicenter retrospective analysis of an AVM registry from the MISTA (Multicenter International Study for Treatment of Brain AVMs) consortium and included AVMs with perinidal aneurysms and a single draining vein. Baseline characteristics, angiographic outcomes, functional outcomes, and complication rates were compared. Propensity score weighting (PSW) using the covariate balancing method was applied to adjust for baseline differences. RESULTS: Out of a total of 1919 patients, 65 met the inclusion criteria; 45 patients underwent preoperative embolization followed by microsurgery, and 20 underwent microsurgery alone. After adjustment, complete obliteration rates were similar between groups (OR 0.87, 95% CI 0.04 to 16.33, P=0.92), as were rates of functional independence at discharge and follow-up. Overall complication, symptomatic complication, and mortality rates did not differ significantly between groups. However, permanent complications were significantly lower in patients with preoperative embolization (OR 0.06, 95% CI 0.004 to 0.84, P=0.03). DISCUSSION: In patients with AVMs featuring perinidal aneurysms and single draining vein, preoperative embolization followed by microsurgery was associated with fewer permanent complications and no increase in adverse outcomes compared with microsurgery alone. However, given the small number of events, this finding should be interpreted cautiously
The Neurosurgeon\u27s Role in the Brain Economy: How Strategic Investment in Neurosurgical Care and Innovation Will Improve Global Outcomes
No full textTrends in Thalamic Stereoelectroencephalography Utilization During Phase II Monitoring in North America: A Survey
No full textBACKGROUND AND OBJECTIVES: Thalamic neuromodulation is widely used in epilepsy surgery. However, thalamic sampling in invasive monitoring is not consistently used. We aimed to quantify current trends in thalamic stereoelectroencephalography (SEEG) utilization. METHODS: We performed a survey of epilepsy neurosurgeons and neurologists to gauge their attitudes and experience with thalamic SEEG. We contacted all members of the American Society for Stereotactic and Functional Neurosurgery and American Epilepsy Society organizations using a mailing list. RESULTS: We received 40 responses from centers using SEEG, including 31 neurosurgeons and 9 epileptologists. Among these respondents, 65% (26/40) included thalamic targets in their SEEG plans. The most common clinical rationales were to define the seizure network (22/26, 84.6%) or the high probability of targeted structure being a neuromodulation target (22/26, 84.6%). Over half of the respondents who used thalamic SEEG (15/26, 57.6%) endorsed that the findings informed target selection and feasibility of thalamic neuromodulation. The most commonly implanted thalamic targets included centromedian (23/26) and anterior nucleus of the thalamus (ANT) (22/26), followed by pulvinar (19/26). CONCLUSION: Thalamic SEEG is a diagnostic tool that is being increasingly used across epilepsy centers. This may be an important tool to support the paradigm shifts occurring in the surgical management of epilepsy
Brain and intracranial volumes are both enlarged and serve as potential risk factors in normal pressure hydrocephalus
No full textNormal pressure hydrocephalus (NPH) is a poorly understood neurodegenerative condition leading to gait impairment and ultimately dementia. Prior work has shown larger intracranial volume (ICV) among those with NPH which has been taken to establish a link to Benign external hydrocephalus of infancy (BEH) as a predisposing factor. These studies have not evaluated brain volume which we hypothesize will also be elevated in NPH and account for the increase in ICV. Automated analysis was performed on CT head examinations from 305 NPH patients and 294 controls. Brain volume was ~ 4.8% larger in females (p \u3c .001) and ~ 2.5% larger in males (p = .003) in NPH compared with controls and ICV was ~ 5.2% larger in females (p \u3c .001) and ~ 3.7% larger in males (p \u3c .001) with NPH compared with controls. The ratio of brain volume to intracranial volume in NPH versus controls was not significantly different for females (p = .4) or males, (p = .08). If BEH is a major cause of NPH this would then require that it also results in persistently enlarged brain volumes. Our data suggests large brain size itself is a risk factor for NPH and may help account for increased NPH risk among males
Associations of Mid- and Late-Life Physical Activities With New-Onset Depression and Anxiety Among Older Adults
No full textOBJECTIVE: The authors of this prospective cohort study sought to examine associations between mid- and late-life physical activities and incident clinical depression and anxiety among community-dwelling older adults. METHODS: The sample included 2,630 adults to examine the outcome of clinical depression (median follow-up length=5.4 years) and 2,444 to examine clinical anxiety (median follow-up length=5.6 years). Participants were ages ≥70 years, were enrolled in the Mayo Clinic Study of Aging, and did not have dementia or the respective neuropsychiatric symptoms at baseline. Mid- and late-life physical activities were assessed as predictors with a validated questionnaire, and physical activity composite scores were calculated. Outcomes of interest were new onset of clinical depression and anxiety, measured with the Beck Depression Inventory (score \u3e13) and Beck Anxiety Inventory (score \u3e7), respectively. The authors used Cox proportional hazard models, adjusted for age (timescale), sex, education, apolipoprotein E ε4 genotype status, and comorbid medical conditions. RESULTS: Higher overall physical activity in late life was associated with a decreased risk for incident clinical depression (hazard ratio [HR]=0.85, 95% CI=0.74-0.98, p=0.025). Higher late-life overall physical activity (HR=0.79, 95% CI=0.71-0.89, p\u3c0.001) and moderate-to-vigorous physical activity (MVPA; HR=0.86, 95% CI=0.77-0.95, p=0.003) were associated with a decreased risk for incident clinical anxiety. Higher midlife overall physical activity (HR=1.16, 95% CI=1.05-1.28, p=0.003) and MVPA (HR=1.12, 95% CI=1.02-1.23, p=0.019) were associated with an increased risk for new-onset clinical anxiety but not depression. CONCLUSIONS: Engagement in late-life physical activity was associated with reduced risk for new-onset depression and anxiety among community-dwelling older adults without dementia
Characterizing the Journey of Early Alzheimer\u27s Disease in Patients Initiating Lecanemab Treatment in the United States: A Real-World Evidence Study
No full textINTRODUCTION: With the advent of disease-modifying therapies for early Alzheimer\u27s disease (AD), a comprehensive characterization of patients initiating lecanemab in the USA is needed to understand its use in real-world settings. METHODS: This retrospective observational study used administrative claims from the Komodo Research Database (1/1/2023-6/30/2024). Eligible patients had ≥ 1 lecanemab administration (first claim defined the index date) and ≥ 12 months of clinical activity/insurance eligibility before the index date. Patient characteristics, diagnostic process, and AD-related medications were evaluated within 12 months before the index date (baseline), whereas lecanemab treatment patterns and concomitant medications were evaluated on or after the index date (follow-up). Outcomes were reported using descriptive statistics and persistence to lecanemab was evaluated using Kaplan-Meier analysis. RESULTS: Of 3155 patients included in the study, mean age was 75.0 years, 55.8% were female, 44.2% were male, and most (93.3%) received their index lecanemab administration in an urban setting. Diagnoses of AD (83.8%) and mild cognitive impairment (60.8%) were common at baseline, and 67.6% of patients used AD symptomatic medications. Average time from earliest diagnosis to first lecanemab administration was 4.9 months among patients with a diagnosis in January 2023 (accelerated approval date) or onwards. Over a mean follow-up of 138.8 days, the monthly mean number of administrations of lecanemab was 1.9, with an average of 16.5 days between consecutive administrations and 47.4 days to the first follow-up head magnetic resonance imaging. Persistence to lecanemab was 87.6% at 4 months after treatment initiation. CONCLUSION: Lecanemab was utilized in appropriate patient populations according to the prescribing information approved by the US Food and Drug Administration. Findings from our study provide first insights into the real-world use of lecanemab in the USA and shed light on the need for increased and timely lecanemab initiation for the long-term management of early AD
Developmental deletion of amyloid precursor protein precludes transcriptional and proteomic responses to brain injury
No full textINTRODUCTION: Amyloid precursor protein (APP) undergoes striking changes following traumatic brain injury (TBI). Considering its role in the control of gene expression, we investigated whether APP regulates transcription and translation following TBI. METHODS: We assessed brain morphology (n = 4-9 mice/group), transcriptome (n = 3 mice/group), proteome (n = 3 mice/group), and behavior (n = 17-27 mice/group) of wild-type (WT) and APP knock-out (KO) mice either untreated or 10-weeks following TBI. RESULTS: After TBI, WT mice displayed transcriptional programs consistent with late stages of brain repair, hub genes were predicted to impact translation and brain proteome showed subtle changes. APP KO mice largely replicated this transcriptional repertoire, but showed no transcriptional nor translational response to TBI. DISCUSSION: The similarities between WT mice following TBI and APP KO mice suggest that developmental APP deficiency induces a condition reminiscent of late stages of brain repair, hampering the control of gene expression in response to injury. HIGHLIGHTS: 10-weeks after TBI, brains exhibit transcriptional profiles consistent with late stage of brain repair. Developmental APP deficiency maintains brains perpetually in an immature state akin to late stages of brain repair. APP responds to TBI by changes in gene expression at a transcriptional and translational level. APP deficiency precludes molecular brain changes in response to TBI
Fosgonimeton in mild-to-moderate Alzheimer\u27s disease
No full textBACKGROUND: Fosgonimeton, a small-molecule positive modulator of the neurotrophic hepatocyte growth factor (HGF) system, was studied in participants with Alzheimer\u27s disease (AD). OBJECTIVE: To assess the efficacy and safety of fosgonimeton in AD. METHODS: LIFT-AD was a randomized, placebo-controlled, Phase 2/3 trial (NCT04488419; 23Jun2020), the primary analysis (N = 287) included participants with mild-to-moderate AD not receiving concomitant acetylcholinesterase inhibitors (AChEIs) randomized 1:1 to daily subcutaneous fosgonimeton 40 mg or placebo. The primary endpoint, the Global Statistical Test (GST) score, combined ADAS-Cog11 and ADCS-ADL23. Secondary endpoints included ADAS-Cog11, ADCS-ADL23, and NfL. Exploratory endpoints included plasma biomarkers of AD. Safety included all dosed participants, including those receiving and not receiving AChEIs or randomized to fosgonimeton 70 mg (N = 549). RESULTS: The trial did not achieve its primary or secondary endpoints; between-group difference in the least-square mean change (SE) from baseline to Week 26 in the GST score was -0.08 (0.10) (p = 0.70), -0.70 (0.77) (p = 0.35) in ADAS-Cog11, and +0.67 (0.92) (p = 0.61) in ADCS-ADL23. This showed small differences favoring fosgonimeton versus placebo. Nominally significant changes in plasma biomarkers were observed in p-τ217 only. Fosgonimeton had an acceptable safety profile. Serious AEs were balanced between groups (4.2% fosgonimeton, 6.9% placebo). More participants in the fosgonimeton group (14.2%) discontinued due to AEs versus placebo (4.6%), mostly from injection site reactions. CONCLUSIONS: Fosgonimeton did not significantly improve ADAS-Cog11 or ADCS-ADL23 versus placebo. However, the consistently observed non-significant improvements favoring fosgonimeton suggests potentially relevant biological activity with fosgonimeton and that positive modulation of HGF signaling may impact components of the pathophysiologic processes of neurodegenerative diseases
Frailty in prodromal Parkinson\u27s disease in Medicare beneficiaries
No full textINTRODUCTION: Frailty, a common syndrome of aging associated with a decline in physiological reserve, places individuals with Parkinson\u27s disease (PD) at a greater risk of poor health outcomes. We hypothesized that frailty would also be greater in prodromal PD patients compared to the general population and, thus, could be part of the prodromal phase of PD. METHODS: We conducted a population-based case-control study of incident PD cases (N = 82,560) and controls (N = 96,482) ages 70-90 identified in 2009. Using 2004-2009 Medicare data, we examined frailty in five individual 12-month time windows during the prodromal period using the claims-based frailty index (CFI), categorized as nonfrail, mildly frail, and moderately-to-severely frail. For each time window, we calculated the odds ratios (ORs) and 95 % confidence intervals (CIs) for the association between frailty and PD, while adjusting for age, sex, race/ethnicity, and use of care. We examined variables in CFI that were associated with PD in the 12 months prior to diagnosis. RESULTS: Mildly frail (OR = 1.70, 95 % CI 1.62-1.78) and moderately-to-severely frail (OR = 1.29, 95 % CI 1.16-1.43) were associated with PD five years prior to diagnosis. This association strengthened in the final year prior to diagnosis: mildly frail (OR = 7.75, 95 % CI 7.51-7.99); moderately-to-severely frail (OR = 10.22, 95 % CI 9.63-10.86). In the 12 months prior to PD diagnosis, the CFI variable encompassing psychiatric/cognitive disorders had the most marked association with PD (OR = 4.63, 95 % CI 4.50-4.77). CONCLUSIONS: Medicare beneficiaries with PD are frailer than controls in the prodromal period. Frailty was highest in the 12 months prior to PD diagnosis
