Faculty Bibliography

OBJECTIVE:Primary angiitis of the central nervous system (PACNS) is a rare and devastating form of vasculitis that destroys the vessels of the brain and spinal cord, resulting in progressive and debilitating neurologic symptoms. The objective of the present study was to detail the diagnostic process of a case of a patient with PACNS who suffered from six intracerebral hemorrhages (ICHs). METHOD/METHODS:The patient was an African American woman with a history of recurrent ICHs of unclear etiology who received serial neuropsychological evaluations over the course of a 5-year period. Two comprehensive neuropsychological evaluations are included, as well as an overview of her clinical course, including differential diagnostic considerations and treatment planning. RESULTS:Neuropsychological assessment revealed marked deficits in visuospatial abilities and processing speed associated with her underlying neuropathology. Integrated review of her medical records indicated a probable diagnosis of PACNS as the likely etiology of her recurrent ICHs. CONCLUSIONS:This study demonstrates the importance of differential diagnosis of low base-rate conditions, functional neuroanatomy and neurobehavioral phenomenology, serial assessment, and cognitive reserve in clinical neuropsychological practice.

Light flashes, patterns, or color changes can provoke seizures in up to 1 in 4000 persons. Prevalence may be higher because of selection bias. The Epilepsy Foundation reviewed light-induced seizures in 2005. Since then, images on social media, virtual reality, three-dimensional (3D) movies, and the Internet have proliferated. Hundreds of studies have explored the mechanisms and presentations of photosensitive seizures, justifying an updated review. This literature summary derives from a nonsystematic literature review via PubMed using the terms "photosensitive" and "epilepsy." The photoparoxysmal response (PPR) is an electroencephalography (EEG) phenomenon, and photosensitive seizures (PS) are seizures provoked by visual stimulation. Photosensitivity is more common in the young and in specific forms of generalized epilepsy. PS can coexist with spontaneous seizures. PS are hereditable and linked to recently identified genes. Brain imaging usually is normal, but special studies imaging white matter tracts demonstrate abnormal connectivity. Occipital cortex and connected regions are hyperexcitable in subjects with light-provoked seizures. Mechanisms remain unclear. Video games, social media clips, occasional movies, and natural stimuli can provoke PS. Virtual reality and 3D images so far appear benign unless they contain specific provocative content, for example, flashes. Images with flashes brighter than 20 candelas/m² at 3-60 (particularly 15-20) Hz occupying at least 10 to 25% of the visual field are a risk, as are red color flashes or oscillating stripes. Equipment to assay for these characteristics is probably underutilized. Prevention of seizures includes avoiding provocative stimuli, covering one eye, wearing dark glasses, sitting at least two meters from screens, reducing contrast, and taking certain antiseizure drugs. Measurement of PPR suppression in a photosensitivity model can screen putative antiseizure drugs. Some countries regulate media to reduce risk. Visually-induced seizures remain significant public health hazards so they warrant ongoing scientific and regulatory efforts and public education.

This study cross-validated the Medical Symptom Validity Test (MSVT) in a mixed neuropsychiatric sample and examined its accuracy for identifying invalid neuropsychological performance using a known-groups design. Cross-sectional data from 129 clinical patients who completed the MSVT were examined. Validity groups were established using six, independent criterion performance validity tests, which yielded 98 patients in the valid group and 31 in the invalid group. All MSVT subtest scores were significantly lower in the invalid group (η

The interaction of the cerebellum with cerebral cortical dynamics is still poorly understood. In this paper, dynamical causal modeling is used to examine the interaction between cerebellum and cerebral cortex as indexed by MRI resting-state functional connectivity in three large-scale networks on healthy young adults (N = 200; Human Connectome Project dataset). These networks correspond roughly to default mode, task positive, and motor as determined by prior cerebellar functional gradient analyses. We find uniform interactions within all considered networks from cerebellum to cerebral cortex, providing support for the notion of a universal cerebellar transform. Our results provide a foundation for future analyses to quantify and further investigate whether this is a property that is unique to the interactions from cerebellum to cerebral cortex.

BACKGROUND:To analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome. METHODS:Multicentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications. RESULTS:A total of 230 COVID-19 patients with AIS were included. 67.0% (154/230) were older than 60 years, while 33.0% (76/230) were younger. Median (IQR) National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.0 (17.0) and 42.8% (89/208) presented with large vessel occlusion (LVO). Approximately 50.2% (102/203) of the patients had poor outcomes with an observed mortality rate of 38.8% (35/219). Age >60 years (aOR: 4.60, 95% CI 1.89 to 12.15, p=0.001), diabetes mellitus (aOR: 2.53, 95% CI 1.14 to 5.79, p=0.025), increased NIHSS at admission (aOR: 1.10, 95% CI 1.05 to 1.16, p<0.001), LVO (aOR: 3.02, 95% CI 1.27 to 7.44, p=0.014) and no IV tPA (aOR: 2.76, 95% CI 1.06 to 7.64, p=0.043) were significantly associated with poor functional outcome. CONCLUSION/CONCLUSIONS:There may be a relationship between COVID-19 associated AIS and severe disability or death. We identified several factors that predict worse outcomes, and these outcomes were more frequent compared with global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-dimer, predicted both morbidity and mortality.

Previous studies support using two abbreviated tests of the Test of Memory Malingering (TOMM), including (a) Trial 1 (T1) and (b) the number of errors on the first 10 items of T1 (T1e10), as performance validity tests (PVTs). In this study, we examined the independent and aggregated predictive utility of TOMM T1 and T1e10 for identifying invalid neuropsychological test performance across two clinical samples. We employed cross-sectional research to examine two independent and demographically diverse mixed samples of military veterans and civilians (VA = 108; academic medical center = 234) of patients who underwent neuropsychological evaluations. We determined validity groups by patient performance on four independent criterion PVTs. We established concordances between passing/failing the TOMM T1e10 and T1, followed by logistic regression to determine individual and aggregated accuracy of T1e10 and T1 for predicting validity group membership. Concordance between passing T1e10 and T1 was high, as was overall validity (87-98%) across samples. By contrast, T1e10 failure was more highly concordant with T1 failure (69-77%) than with overall invalidity status (59-60%) per criterion PVTs, whereas T1 failure was more highly concordant with invalidity status (72-88%) per criterion PVTs. Logistic regression analyses demonstrated similar results, with T1 accounting for more variance than T1e10. However, combining T1e10 and T1 accounted for the most variance of any model, with T1e10 and T1 each emerging as significant predictors. TOMM T1 and, to a lesser extent, T1e10 were significant predictors of independent criterion-derived validity status across two distinct clinical samples, but they did not offer improved classification accuracy when aggregated.

OBJECTIVE:This study cross-validated the word choice test (WCT) in a diverse neuropsychiatric sample and examined the effect of increasing verbal memory impairment severity on WCT performance. METHOD/METHODS:Data from 147 clinically referred patients (113 valid/34 invalid) who completed the WCT, Rey Auditory Verbal Learning Test (RAVLT), and four independent criterion PVTs were analyzed. RAVLT memory impairment bands used were: ≥37T (normal memory); 30T-36T (below average scores/mild impairment); and ≤29T (extremely low scores/severe impairment). RESULTS:WCT and RAVLT were moderately correlated. The invalid group had significantly worse performance on the WCT and RAVLT. For the overall sample, the WCT yielded an area under the curve (AUC) = .79, with 62% sensitivity/93% specificity at a cut-score of ≤41. When the sample was subdivided by memory impairment severity, the severe impairment group had significantly lower WCT scores than the normal group. Moreover, the WCT retained moderate classification accuracy among the normal memory (AUC = .85) and mild memory impairment (AUC = .76) groups, with sensitivities of 65% and 62% (≥91% specificity) at their respective optimal cut-scores of ≤44 and ≤42. In contrast, the WCT had low classification accuracy among those with severe memory impairment (AUC = .66), with only 15% sensitivity/95% specificity at the optimal cut-score of ≤30. CONCLUSION/CONCLUSIONS:The WCT is generally useful for detecting invalid neuropsychological test performance, although, its classification accuracy was diminished among patients with severe memory impairment. Therefore, while the WCT remains a viable option for performance validity assessment, neuropsychologists should carefully consider its use when this level of severe memory impairment is known or suspected.

INTRODUCTION/BACKGROUND:Meningiomas that progress despite surgery and radiotherapy represent an unmet medical need. Expression of PD-1 and PDL-1 has been demonstrated in meningiomas and is proportional to tumor grade, suggesting a potential role for anti-PD-1/anti-PDL-1 inhibitor therapy. We explored the potential role of immunotherapy for recurrent meningiomas by describing progression-free survival (PFS) and overall survival (OS) in a single-center patient sample. METHODS:This is a retrospective chart review of patients with meningioma who were treated with PD-1 inhibitors at UPMC Hillman Cancer Center. Any patient over age 18 who received immunotherapy was included in this study. Patients received treatment until development of disease progression, intolerable toxicities or adverse events, death, or oncologist decision. Serial radiographic assessments were made every 3-6 months. RESULTS:Between January 2015 and November 2021, eight patients received anti-PD-1 therapy. All patients underwent tumor resection and radiosurgery, and four patients received prior systemic therapy. Six out of eight patients experienced symptomatic perilesional edema and three patients experienced exacerbation of seizures. Median PFS was 7 months (95% CI 1-24) and median OS was 1.75 years (95% CI 1.5-4.0). In patients with positive PD-1/PD-L1 expression, median PFS was 2 years and median OS was 3 years. CONCLUSION/CONCLUSIONS:Anti-PD-1 therapy was associated with a manageable safety profile in patients with recurrent meningiomas. Patients with WHO Grade III tumors and positive PD-1/PD-L1 expression were noted to have increased PFS and OS, suggesting a potential role for immunotherapy in these patients, but further studies are needed to investigate this in a larger patient population.

BACKGROUND:The relationship between cardiac function and mortality after thrombectomy for acute ischemic stroke is not well elucidated. METHODS:We analyzed the relationship between cardiac function and mortality prior to discharge in a cohort of patients who underwent thrombectomy for acute ischemic stroke at two large medical centers in New York City between December 2018 and November 2020. All analyses were performed using Welch's two sample t-test and logistic regression accounting for age, initial NIHSS and post-procedure ASPECTS score, where OR is for each unit increase in the respective variables. RESULTS:Of 248 patients, 41 (16.5%) died prior to discharge. Mortality was significantly associated with higher initial heart rate (HR; 89 ± 19 bpm vs 80 ± 18 bpm, p = 0.004) and higher maximum HR over entire admission (137 ± 26 bpm vs 114 ± 25 bpm, p < 0.001). Mortality was also associated with presence of NSTEMI/STEMI (63% vs 29%, p < 0.001). When age, initial NIHSS score, and post-procedure ASPECTS score were included in multivariate analysis, there was still a significant relationship between mortality and initial HR (OR 1.03, 95% CI 1.01- 1.05, p = 0.02), highest HR over the entire admission (OR 1.03, 95% CI 1.02-1.05, p < 0.001), and presence of NSTEMI/STEMI (OR 3.76, 95% CI 1.66-8.87, p = 0.002). CONCLUSIONS:Tachycardia is associated with mortality in patients who undergo thrombectomy. Further investigation is needed to determine whether this risk is modifiable.