Faculty Bibliography

BACKGROUND:Observe the relationship of anxiety and depression on quality of life outcomes after open and endovascular cerebrovascular procedures. METHODS:We retrospectively analyzed 349 patients who underwent a procedure for aneurysm, arteriovenous malformation, intraparenchymal hemorrhage, carotid stenosis, acute stroke, and conventional catheter angiogram over three years at a community hospital. We correlated pre-procedural anxiety and depression with Global Physical Health, Global Mental Health, and Modified Rankin Scale scores. We performed univariate and multivariate linear and logistic regression analyses adjusting for past medical history and sociodemographic factors. RESULTS:Anxiety or depression occurred in 18 % of patients. Patients with anxiety or depression were more likely to be female (81% vs 60.8%; p = 0.002) and younger (54 vs. 59 years old; p = 0.025). The groups did not differ in type or urgency of procedure, smoking or history of diabetes. Patients with anxiety or depression reported lower mental health scores at 30 days (45.1 vs 48.2; p = 0.002) post-procedure. In multivariate analyses, anxious or depressed patients had worse mental health scores at 30 days (t = - 2.893; p = 0.008) than those who did not have a history of anxiety or depression. There was no difference between groups in length of stay, mortality, physical health t-scores, functionality scores, or six month quality of life outcomes. CONCLUSIONS:Patients undergoing cerebrovascular procedures who self-reported anxiety or depression showed a significant difference in mental health outcomes at 30 days, but six month mental health and other medical and functional outcomes measures were similar to patients without these diagnoses.

PURPOSE/OBJECTIVE:Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblastoma. PATIENTS AND METHODS/METHODS:In this double-blind, randomized, phase II study (NCT01498328) conducted at 26 hospitals in the United States, bevacizumab-naïve patients with recurrent EGFRvIII-positive glioblastoma were randomized to receive rindopepimut or a control injection of keyhole limpet hemocyanin, each concurrent with bevacizumab. The primary endpoint was 6-month progression-free survival (PFS6) by central review with a one-sided significance of 0.2. RESULTS:< 0.0001). CONCLUSIONS:.

Williams syndrome (WS) is a rare neurodevelopmental disorder caused by the hemideletion of approximately 25-28 genes at 7q11.23. Its unusual social and cognitive phenotype is most strikingly characterized by the disinhibition of social behavior, in addition to reduced global IQ, with a relative sparing of language ability. Hypersociality and increased social approach behavior in WS may represent a unique inability to inhibit responses to specific social stimuli, which is likely associated with abnormalities of frontostriatal circuitry. The striatum is characterized by a diversity of interneuron subtypes, including inhibitory parvalbumin-positive interneurons (PV+) and excitatory cholinergic interneurons (Ch+). Animal model research has identified an important role for these specialized cells in regulating social approach behavior. Previous research in humans identified a depletion of interneuron subtypes associated with neuropsychiatric disorders. Here, we examined the density of PV+ and Ch+ interneurons in the striatum of 13 WS and neurotypical (NT) subjects. We found a significant reduction in the density of Ch+ interneurons in the medial caudate nucleus and nucleus accumbens, important regions receiving cortical afferents from the orbitofrontal and ventromedial prefrontal cortex, and circuitry involved in language and reward systems. No significant difference in the distribution of PV+ interneurons was found. The pattern of decreased Ch+ interneuron densities in WS differs from patterns of interneuron depletion found in other disorders.

OBJECTIVE:To investigate whether paresthesia of the lower extremities following exposure to the World Trade Center (WTC) disaster was associated with signs of neuropathy, metabolic abnormalities, or neurotoxin exposures. METHODS:Case-control study comparing WTC-exposed paresthesia cases with "clinic controls" (WTC-exposed subjects without paresthesias), and "community controls" (WTC-unexposed persons). RESULTS:Neurological histories and examination findings were significantly worse in cases than controls. Intraepidermal nerve fiber densities were below normal in 47% of cases and sural to radial sensory nerve amplitude ratios were less than 0.4 in 29.4%. Neurologic abnormalities were uncommon among WTC-unexposed community controls. Metabolic conditions and neurotoxin exposures did not differ among groups. CONCLUSIONS:Paresthesias among WTC-exposed individuals were associated with signs of neuropathy, small and large fiber disease. The data support WTC-related exposures as risk factors for neuropathy, and do not support non-WTC etiologies.

BACKGROUND:Following the results of randomized clinical trials supporting the use of mechanical thrombectomy (MT) with tissue plasminogen activator for emergent large vessel occlusion (ELVO), our state Stroke Task Force convened to: update legislation to recognize differences between Primary Stroke Centers (PSCs) and Comprehensive Stroke Centers (CSCs); and update Emergency Medical Services (EMS) protocols to triage direct transport of suspected ELVO patients to CSCs. PURPOSE/OBJECTIVE:We developed a single-session training curriculum for EMS personnel focused on the Los Angeles Motor Scale (LAMS) score, its use to correctly triage patients as CSC-appropriate in the field, and our state-wide EMS stroke protocol. We assessed the effect of our training on EMS knowledge. METHODS:We assembled a focus group to develop a training curriculum and assessment questions that would mimic real-life conditions under which EMS personnel operate. Ten questions were formulated to assess content knowledge before and after training, and scores were compared using generalized mixed models. RESULTS:Training was provided for 179 EMS providers throughout the state.Average pre-test score was 52.4% (95% CI 49% to 56%). Average post-test score was 85.6% (83%-88%, P<0.0001). Each of the 10 questions was individually assessed and all showed significant gains in EMS knowledge after training (P<0.0001). CONCLUSIONS:A brief educational intervention results in substantial improvements in EMS knowledge of prehospital stroke severity scales and severity-based field triage protocols. Further study is needed to establish whether these gains in knowledge result in improved real-world performance.

Mutations in GBA1, the gene mutated in Gaucher disease, are a common genetic risk factor for Parkinson disease, although the penetrance is low. We performed [¹⁸ F]-Fluorodopa PET studies of 57 homozygous and heterozygous GBA1 mutation carriers (15 with parkinsonism) and 98 controls looking for early indications of dopamine loss using voxel-wise analyses to identify group differences in striatal [¹⁸ F]-Fluorodopa uptake (K_i ). Forty-eight subjects were followed longitudinally. Cross-sectional and longitudinal comparisons of K_i and K_i -change found significant effects of Parkinson disease. However, at baseline and over time, striatal [¹⁸ F]-Fluorodopa uptake in mutation carriers without parkinsonism did not significantly differ from controls. This article is protected by copyright. All rights reserved.