Faculty Bibliography

BACKGROUND AND OBJECTIVE:This study characterizes the impact of race, ethnicity, insurance status, and geographic location on anti-vascular endothelial growth factor (VEGF) use for the treatment of diabetic macular edema (DME). PATIENTS AND METHODS:= 203,707). Multivariate regression analyses investigated associations between race, ethnicity, insurance status, and geographic location and anti-VEGF use and visual outcomes. RESULTS:< .01], respectively). CONCLUSION:.

BACKGROUND:Whether to approach distal occlusions endovascularly or not in medium-sized vessels secondary to proximal large vessel occlusion stroke remains unanswered. OBJECTIVE:To investigates the technical feasibility and safety of thrombectomy for secondary posterior circulation distal, medium vessel occlusions (DMVO). METHODS:TOPMOST (Treatment fOr Primary Medium vessel Occlusion STroke) is an international, retrospective, multicenter, observational registry of patients treated for distal cerebral artery occlusions. This study subanalysis endovascularly treated occlusions of the posterior cerebral artery in the P2 and P3 segment secondary preprocedural or periprocedural thrombus migration between January 2014 and June 2020. Technical feasibility was evaluated with the modified Thrombolysis in Cerebral Infarction (mTICI) scale. Procedural safety was assessed by the occurrence of symptomatic intracranial hemorrhage (sICH) and intervention-related serious adverse events. RESULTS:Among 71 patients with secondary posterior circulation DMVO who met the inclusion criteria, occlusions were present in 80.3% (57/71) located in the P2 segment and in 19.7% (14/71) in the P3 segment. Periprocedural migration occurred in 54.9% (39/71) and preprocedural migration in 45.1% (32/71) of cases. The first reperfusion attempt led in 38% (27/71) of all cases to mTICI 3. On multivariable logistic regression analysis, increased numbers of reperfusion attempts (adjusted odds ratio (aOR)=0.39, 95% CI 0.29 to 0.88, p=0.009) and preprocedural migration (aOR=4.70, 95% CI,1.35 to 16.35, p=0.015) were significantly associated with mTICI 3. sICH occurred in 2.8% (2/71). CONCLUSION/CONCLUSIONS:Thrombectomy for secondary posterior circulation DMVO seems to be safe and technically feasible. Even though thrombi that have migrated preprocedurally may be easier to retract, successful reperfusion can be achieved in the majority of patients with secondary DMVO of the P2 and P3 segment.

BACKGROUND AND PURPOSE/OBJECTIVE:In patients with dolichoectasia, it is uncertain how dilatation and/or elongation relate to each other. We aimed to examine the correlation between arterial diameter and length within arteries and across the circle of Willis (COW). METHODS:We included stroke-free participants in the Northern Manhattan Study who underwent magnetic resonance angiography. Intracranial artery diameters and lengths were obtained with semiautomated commercial software and were adjusted for head size. We first investigated the correlation between diameters and length using Pearson's correlation coefficient. We then built generalized linear models adjusted for demographics and risk factors. RESULTS:Among 1210 participants included in the analysis (mean age 71 ± 9 years, 59% women, 65% Hispanic), a larger basilar artery (BA) diameter correlated with greater BA length (r = .3), and left and right middle cerebral artery (MCA) diameters correlated with one another (r = .4). Across the COW, BA diameter correlated with MCA diameters (r = .3 for both). In adjusted analyses, MCA diameters were associated with larger posterior circulation diameters (β = 0.07), MCA and BA lengths (β = 0.003 and β = 0.002, respectively), presence of fetal posterior cerebral artery (PCA), (β = 0.11), and a complete COW (β = -0.02). Similarly, BA length was associated with a fetal PCA (β = 1.1), and BA diameter was associated with anterior circulation diameters (β = 0.15) and presence of fetal PCA (β = -0.4). CONCLUSIONS:COW configuration should be considered when using arterial diameter cutoffs to define dolichoectasia. Further studies are needed to discern whether arterial diameter or length best identify individuals at risk of vascular events attributable to dolichoectasia.

OBJECTIVE:Neuropsychological profiles are heterogeneous both across and within epilepsy syndromes, but especially in frontal lobe epilepsy (FLE), which has complex semiology and epileptogenicity. This study aimed to characterize the cognitive heterogeneity within FLE by identifying cognitive phenotypes and determining their demographic and clinical characteristics. METHOD/METHODS:One hundred and six patients (age 16-66; 44% female) with FLE completed comprehensive neuropsychological testing, including measures within five cognitive domains: language, attention, executive function, processing speed, and verbal/visual learning. Patients were categorized into one of four phenotypes based on the number of impaired domains. Patterns of domain impairment and clinical and demographic characteristics were examined across phenotypes. RESULTS:Twenty-five percent of patients met criteria for the Generalized Phenotype (impairment in at least four domains), 20% met criteria for the Tri-Domain Phenotype (impairment in three domains), 36% met criteria for the Domain-Specific Phenotype (impairment in one or two domains), and 19% met criteria for the Intact Phenotype (no impairment). Language was the most common domain-specific impairment, followed by attention, executive function, and processing speed. In contrast, learning was the least impacted cognitive domain. The Generalized Phenotype had fewer years of education compared to the Intact Phenotype, but otherwise, there was no differentiation between phenotypes in demographic and clinical variables. However, qualitative analysis suggested that the Generalized and Tri-Domain Phenotypes had a more widespread area of epileptogenicity, whereas the Intact Phenotype most frequently had seizures limited to the lateral frontal region. SIGNIFICANCE/CONCLUSIONS:This study identified four cognitive phenotypes in FLE that were largely indistinguishable in clinical and demographic features, aside from education and extent of epileptogenic zone. These findings enhance our appreciation of the cognitive heterogeneity within FLE and provide additional support for the development and use of cognitive taxonomies in epilepsy.

Despite extensive research, amyotrophic lateral sclerosis (ALS) remains a progressive and invariably fatal neurodegenerative disease. Limited knowledge of the underlying causes of ALS has made it difficult to target upstream biological mechanisms of disease, and therapeutic interventions are usually administered relatively late in the course of disease. Genetic forms of ALS offer a unique opportunity for therapeutic development, as genetic associations may reveal potential insights into disease etiology. Genetic ALS may also be amenable to investigating earlier intervention given the possibility of identifying clinically presymptomatic, at-risk individuals with causative genetic variants. There is increasing evidence for a presymptomatic phase of ALS, with biomarker data from the Pre-Symptomatic Familial ALS (Pre-fALS) study showing that an elevation in blood neurofilament light chain (NfL) precedes phenoconversion to clinically manifest disease. Tofersen is an investigational antisense oligonucleotide designed to reduce synthesis of superoxide dismutase 1 (SOD1) protein through degradation of SOD1 mRNA. Informed by Pre-fALS and the tofersen clinical development program, the ATLAS study (NCT04856982) is designed to evaluate the impact of initiating tofersen in presymptomatic carriers of SOD1 variants associated with high or complete penetrance and rapid disease progression who also have biomarker evidence of disease activity (elevated plasma NfL). The ATLAS study will investigate whether tofersen can delay the emergence of clinically manifest ALS. To our knowledge, ATLAS is the first interventional trial in presymptomatic ALS and has the potential to yield important insights into the design and conduct of presymptomatic trials, identification, and monitoring of at-risk individuals, and future treatment paradigms in ALS.

This study investigated the utility of four Stroop Color and Word Test (SCWT) indices, including the raw score and T score for the word reading (WR) and color naming (CN) trials, as embedded performance validity tests (PVTs) within a sample referred for evaluation of suspected or known attention-deficit/hyperactivity disorder (ADHD). Data were analyzed from a final sample of 317 patients consecutively referred for ADHD evaluation, which was divided into groups with invalid (n = 43; 14%) and valid neuropsychological test performance (n = 274; 86%). A subset of the valid group with confirmed ADHD diagnoses (n = 226; 71%) were also analyzed separately. Classification accuracy for the overall valid sample was in the acceptable range (AUCs = .757-.794), with optimal cut scores of WR raw ≤75 (54% sensitivity/90% specificity), WR T score ≤ 28 (54% sensitivity/88% specificity), CN raw ≤57 (42% sensitivity/90% specificity), and CN T score ≤ 30 (40% sensitivity/90% specificity). Classification accuracy was also in the acceptable range for the ADHD-confirmed subgroup (AUCs = .750-.790), with optimal cut scores of WR Raw ≤ 75 (54% sensitivity/89% specificity), WR T score ≤ 28 (54% sensitivity/87% specificity), CN Raw ≤ 57 (42% sensitivity/90% specificity), and CN T score ≤ 30 (40% sensitivity/90% specificity). These findings indicate that embedded PVTs derived from the SCWT, particularly those derived from the WR trial, are effective measures for determining validity status in samples with suspected or confirmed ADHD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

BACKGROUND:Viral induction of neurological syndromes has been a concern since parkinsonian-like features were observed in patients diagnosed with encephalitis lethargica subsequent to the 1918 influenza pandemic. Given the similarities in the systemic responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with those observed after pandemic influenza, there is a question whether a similar syndrome of postencephalic parkinsonism could follow coronavirus disease 2019 infection. OBJECTIVE:The goal of this study was to determine whether prior infection with SARS-CoV-2 increased sensitivity to a mitochondrial toxin known to induce parkinsonism. METHODS:K18-hACE2 mice were infected with SARS-CoV-2 to induce mild-to-moderate disease. After 38 days of recovery, mice were administered a non-lesion-inducing dose of the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and euthanized 7 days later. Subsequent neuroinflammation and substantia nigra pars compacta (SNpc) dopaminergic (DA) neuron loss were determined and compared with SARS-CoV-2 or MPTP alone. RESULTS:K18-hACE2 mice infected with SARS-CoV-2 or MPTP showed no SNpc DA neuron loss after MPTP. In mice infected and recovered from SARS-CoV-2 infection, MPTP induced a 23% or 19% greater loss of SNpc DA neurons than SARS-CoV-2 or MPTP, respectively (P < 0.05). Examination of microglial activation showed a significant increase in the number of activated microglia in both the SNpc and striatum of the SARS-CoV-2 + MPTP group compared with SARS-CoV-2 or MPTP alone. CONCLUSIONS:Our observations have important implications for long-term public health, given the number of people who have survived SARS-CoV-2 infection, as well as for future public policy regarding infection mitigation. However, it will be critical to determine whether other agents known to increase risk for PD also have synergistic effects with SARS-CoV-2 and are abrogated by vaccination. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.