Trends in the Utilization of Teleneurology and Other Healthcare Resources Prior to and During the COVID-19 Pandemic in an Urban, Tertiary Health System.

BACKGROUND: Patient groups traditionally affected by health disparities were less likely to use video teleneurology (TN) care during the initial COVID-19 pandemic surge in the United States. Whether this asymmetry persisted later in the pandemic or was accompanied with a loss of access to care remains unknown. METHODS: We conducted a retrospective cohort study using patient data from a multicenter healthcare system in New York City. We identified all established pediatric or adult neurology patients with at least two prior outpatient visits between June 16th, 2019 and March 15th, 2020 using our electronic medical record. For this established pre-COVID cohort, we identified telephone, in-person, video TN or emergency department visits and hospital admissions for any cause between March 16th and December 15th, 2020 ("COVID period"). We determined clinical, sociodemographic, income, and visit characteristics. Our primary outcome was video TN utilization, and our main secondary outcome was loss to follow-up during the COVID period. We used multivariable logistic regression to model the relationship between patient-level characteristics and both outcomes. RESULTS: We identified 23,714 unique visits during the COVID period, which corresponded to 14,170 established patients from our institutional Neurology clinics during the pre-COVID period. In our cohort, 4,944 (34.9%) utilized TN and 4,997 (35.3%) were entirely lost to follow-up during the COVID period. In the adjusted regression analysis, Black or African-American race [adjusted odds ratio (aOR) 0.60, 97.5%CI 0.52-0.70], non-English preferred language (aOR 0.49, 97.5%CI 0.39-0.61), Medicaid insurance (aOR 0.50, 97.5%CI 0.44-0.57), and Medicare insurance (aOR 0.73, 97.5%CI 0.65-0.83) had decreased odds of TN utilization. Older age (aOR 0.98, 97.5%CI 0.98-0.99), female sex (aOR 0.90 97.5%CI 0.83-0.99), and Medicaid insurance (aOR 0.78, 0.68-0.90) were associated with decreased odds of loss to follow-up. CONCLUSION: In the first 9 months of the COVID-19 pandemic, we found sociodemographic patterns in TN utilization that were similar to those found very early in the pandemic. However, these sociodemographic characteristics were not associated with loss to follow-up, suggesting that lack of TN utilization may not have coincided with loss of access to care.

Cognitive Functioning of Glucocerebrosidase (GBA) Non-manifesting Carriers.

Mutations and variants in the glucocerebrosidase (GBA) gene are among the most common genetic risk factors for the development of Parkinson's disease (PD). Yet, penetrance is markedly reduced, and less is known about the burden of carrying a single mutation among those without diagnosed PD. Motor, cognitive, psychiatric, and olfactory functioning were assessed in 30 heterozygous GBA mutation carriers without PD (the majority of whom had mild GBA mutations) and 49 non-carriers without PD. Study focus was on domains affected in GBA mutation carriers with PD, as well as those previously shown to be abnormal in GBA mutation carriers without PD. GBA mutation carriers showed poorer performance on the Stroop interference measure of executive functioning when controlling for age. There were no group differences in verbal memory, Montreal Cognitive Assessment (MoCA), overall motor score, or presence of REM sleep behavior disorder or depression. Although total olfaction scores did not differ, GBA mutation carriers with hyposmia had lower global cognition scores than those without hyposmia. As anticipated by the low penetrance of GBA mutations, these findings suggest that pre-manifest non-motor or motor features of PD may not present in most GBA mutation carriers. However, there is support that there may be a subtle difference in executive functioning among some non-manifesting heterozygous GBA mutation carriers, and, combined with olfaction, this may warrant additional scrutiny as a potential biomarker for pre-manifest and pre-clinical GBA related PD.

Impulsivity and Compulsivity After Subthalamic Deep Brain Stimulation for Parkinson's Disease.

Impulsivity and compulsivity are prominent non-motor problems in Parkinson's disease (PD). Despite 20 years of research, there is still an ongoing debate as to whether subthalamic deep brain stimulation (STN DBS) for PD exacerbates or improves these symptoms. Here, we review how STN DBS affects clinical symptoms and neurocognitive aspects of impulsivity and compulsivity. When comparing patients post- to pre-surgery, in the majority of studies STN DBS for PD is associated with a decrease in clinically diagnosed impulse-control disorders and disorders of compulsivity. To avoid confounds, such as post-surgical decreases in dopaminergic medication doses, comparisons can also be made between DBS "On" versus "Off" conditions. These experimentally assayed effects of STN DBS with respect to neurocognitive aspects of impulsivity and compulsivity are more mixed. STN DBS improves behavioral flexibility without impairing negative feedback learning, delay discounting, or inhibitory control, as long as stimulation is restricted to the dorsal STN. However, STN DBS may drive impulsive actions when a subject is faced with competing choices. We discuss how motivated responses may be either enhanced or impaired by STN DBS depending on engagement of dorsal or ventral STN-mediated circuits. Future studies should combine structural and functional circuit measures with behavioral testing in PD patients on and off medication and stimulation. A more sophisticated understanding of how to modulate cortico-striatal-thalamo-cortical loops will increase the likelihood that these circuit manipulation techniques can successfully be applied to a wider range of neuropsychiatric disorders.

Antidepressant use in patients with meningioma: is there an association with tumor recurrence?

OBJECTIVE With increasing general use of antidepressants (ADs), multiple studies have noted a small protective effect of ADs for patients with glioma, but their impact on meningioma has not been established. This study aims to evaluate the role of ADs in the context of additional clinical factors in relation to long-term risk of meningioma recurrence. METHODS One hundred five patients with an intracranial meningioma presenting from 2011-2014 with at least 3 years of follow-up (median 4.2 years) after resection were reviewed. AD use along with demographics, tumor characteristics, and outcomes were recorded. Multivariate logistic regression was used to analyze the association of AD use with tumor recurrence, including other clinical measures significantly associated with recurrence as covariates. RESULTS Twenty-nine patients (27.4%) were taking ADs (27 selective serotonin reuptake inhibitors, 2 norepinephrine-dopamine reuptake inhibitors) prior to tumor recurrence. Their tumors largely affected the frontal (31.0%) or parietal lobe (17.2%) and were located in convexity, parasagittal, or falcine (CPF) areas more frequently than skull base areas relative to the tumors of non-AD users (p = 0.035). AD use was found to be an independent predictor of recurrence, in addition to subtotal resection and WHO grade II/III classification (p values < 0.05). The median time from AD prescription to tumor recurrence was 36.6 months (interquartile range [IQR] = 20.9-62.9 months) and median length of AD use was 41.4 months (IQR = 24.7-62.8 months). CONCLUSIONS AD use was an independent predictor of meningioma recurrence. This association may be due to mood or affective changes caused by tumor location in CPF regions that may be a sign of early recurrence. The finding calls attention to AD use in the management of patients with meningioma, and warrants further exploration of an underlying relationship.

Epilepsy surgery in patients with autism.

OBJECTIVE The purpose of this study was to report outcomes of epilepsy surgery in 56 consecutive patients with autism spectrum disorder. METHODS Medical records of 56 consecutive patients with autism who underwent epilepsy surgery were reviewed with regard to clinical characteristics, surgical management, postoperative seizure control, and behavioral changes. RESULTS Of the 56 patients with autism, 39 were male, 45 were severely autistic, 27 had a history of clinically significant levels of aggression and other disruptive behaviors, and 30 were considered nonverbal at baseline. Etiology of the epilepsy was known in 32 cases, and included structural lesions, medical history, and developmental and genetic factors. Twenty-nine patients underwent resective treatments (in 8 cases combined with palliative procedures), 24 patients had only palliative treatments, and 3 patients had only subdural electroencephalography. Eighteen of the 56 patients had more than one operation. The mean age at surgery was 11 ± 6.5 years (range 1.5-35 years). At a mean follow-up of 47 ± 30 months (range 2-117 months), seizure outcomes included 20 Engel Class I, 12 Engel Class II, 18 Engel Class III, and 3 Engel Class IV cases. The age and follow-up times are stated as the mean ± SD. Three patients were able to discontinue all antiepileptic drugs (AEDs). Aggression and other aberrant behaviors observed in the clinical setting improved in 24 patients. According to caregivers, most patients also experienced some degree of improvement in daily social and cognitive function. Three patients had no functional or behavioral changes associated with seizure reduction, and 2 patients experienced worsening of seizures and behavioral symptoms. CONCLUSIONS Epilepsy surgery in patients with autism is feasible, with no indication that the comorbidity of autism should preclude a good outcome. Resective and palliative treatments brought seizure freedom or seizure reduction to the majority of patients, although one-third of the patients in this study required more than one procedure to achieve worthwhile improvement in the long term, and few patients were able to discontinue all AEDs. The number of palliative procedures performed, the need for multiple interventions, and continued use of AEDs highlight the complex etiology of epilepsy in patients with autism spectrum disorder. These considerations underscore the need for continued analysis, review, and reporting of surgical outcomes in patients with autism, which may aid in better identification and management of surgical candidates. The reduction in aberrant behaviors observed in this series suggests that some behaviors previously attributed to autism may be associated with intractable epilepsy, and further highlights the need for systematic evaluation of the relationship between the symptoms of autism and refractory seizures.

Psychiatric and Cognitive Effects of Deep Brain Stimulation for Parkinson's Disease.

Deep brain stimulation (DBS) is effective for Parkinson's disease (PD), dystonia, and essential tremor (ET). While motor benefits are well documented, cognitive and psychiatric side effects from the subthalamic nucleus (STN) and globus pallidus interna (GPi) DBS for PD are increasingly recognized. Underlying disease, medications, microlesions, and post-surgical stimulation likely all contribute to non-motor symptoms (NMS).

A randomized, double-blind, placebo-controlled trial of donepezil to improve memory in epilepsy.

PURPOSE: To determine whether an acetylcholinesterase inhibitor, such as donepezil, would improve memory or other cognitive/psychological functions in epilepsy patients with subjective memory complaints. METHODS: Twenty-three epilepsy patients with subjective memory difficulty were randomized to either 3 months of donepezil (10 mg/day) or 3 months of placebo treatment, and then crossed over to the other treatment arm. Patients and physicians were blinded to treatment phase throughout data acquisition. Assessment of memory and other cognitive functions, subjective memory, mood, and self-rated quality of life (QOL) and social functioning was performed at baseline and following completion of both treatment phases. Seizure frequency and severity as well as treatment emergent adverse effects were also monitored. RESULTS: Donepezil treatment was not associated with improvement in memory or other cognitive functions, mood, social functioning or QOL. Comparable increases in self-rated memory functioning relative to baseline were evident during donepezil and placebo phases. Donepezil treatment was not associated with increased seizure frequency or severity. Similar to group results, analysis of change within individual patients as a function of treatment phase also showed neither significant benefit nor detriment associated with donepezil. CONCLUSION: This study found no benefit on memory or other cognitive/psychological functions in a heterogeneous group of epilepsy patients with subjective memory difficulty. Further investigation would be required to determine whether individual patients, or those with particular epilepsy syndromes, might benefit from donepezil or other acetylcholinesterase inhibitors, or if a higher dosage might be effective.

Mapping of a quantitative trait locus for morphine withdrawal severity.

Chronic morphine exposure results in physical dependence, manifested by physical symptoms during naloxone-precipitated withdrawal. Jumping frequency is widely considered the most sensitive and reliable index of withdrawal intensity in mice. Inbred mouse strains surveyed for naloxone-precipitated withdrawal display large and significant strain differences in jumping frequency, including an approximately tenfold difference between C57BL/6 and 129P3 mice. In the present study, (B6 x 129)F2 hybrid mice were given daily morphine injections for four days using an escalating dosing schedule, and naloxone-precipitated withdrawal on day 5 was measured. A full-genome scan for linkage to phenotypic data was performed using polymorphic microsatellite markers. Significant linkage was observed between withdrawal jumping frequencies and a 28 cM-wide region of Chromosome 1 (32-60 cM; peak at 51 cM), accounting for 20% of the overall phenotypic variance. Two other suggestive QTLs were found, on Chromosomes 5 and 10, and an additive model fitting all three loci accounted for 43% of the total variance. F2 mice were also assessed for changes in morphine analgesic potency using the tail-withdrawal test in dose-response studies on days 1 and 4. No linkage was observed between Chromosomes 1, 5, and 10 and morphine analgesic tolerance, suggestive of genetic dissociation of naloxone-precipitated withdrawal from morphine and chronic morphine intake per se. The significant quantitative trait locus for naloxone-precipitated withdrawal severity in morphine-dependent mice, which we name Depmq1, may prove to be of considerable heuristic value once the underlying gene or genes are identified.

Genetic variation in morphine analgesic tolerance: a survey of 11 inbred mouse strains.

The present study assessed the analgesic potency of morphine in 11 inbred mouse strains before and after chronic morphine treatment. Using the 49 degrees C tail-withdrawal test, significant strain differences in morphine AD(50) estimates derived from cumulative dose-response curves were noted prior to tolerance induction on Day 1. AD(50) estimates were reassessed on Day 4, after three daily systemic morphine injections for 3 days using an escalating dose schedule (10, 20, and 40 mg/kg sc). In 9 of 11 strains, morphine potency was significantly reduced from 2-fold to as much as 11-fold. Two strains (129P3 and LP) displayed no evidence whatsoever of tolerance development. Neither initial baseline withdrawal latency nor morphine analgesic sensitivity was significantly correlated with tolerance magnitude. Also observed were strain-dependent alterations (mostly hyperalgesia) in baseline tail-withdrawal latencies as a result of chronic morphine treatment. The magnitude of hyperalgesia and analgesic tolerance was significantly correlated among strains, implicating common genetic substrates and supporting their proposed association. The present work demonstrates that the presence and magnitude of morphine analgesic tolerance is genotype-dependent and identifies strains with widely divergent liabilities that should facilitate identification of trait-relevant genes.