Faculty Bibliography

BACKGROUND:The development of mobile health (mHealth) technologies is progressing at a faster pace than that of the science to evaluate their validity and efficacy. Under the International Committee of Journal Medical Editors (ICMJE) guidelines, clinical trials that prospectively assign people to interventions should be registered with a database before the initiation of the study. OBJECTIVE:The aim of this study was to better understand the smartphone mHealth trials for high-burden neuropsychiatric conditions registered on ClinicalTrials.gov through November 2018, including the number, types, and characteristics of the studies being conducted; the frequency and timing of any outcome changes; and the reporting of results. METHODS:We conducted a systematic search of ClinicalTrials.gov for the top 10 most disabling neuropsychiatric conditions and prespecified terms related to mHealth. According to the 2016 World Health Organization Global Burden of Disease Study, the top 10 most disabling neuropsychiatric conditions are (1) stroke, (2) migraine, (3) major depressive disorder, (4) Alzheimer disease and other dementias, (5) anxiety disorders, (6) alcohol use disorders, (7) opioid use disorders, (8) epilepsy, (9) schizophrenia, and (10) other mental and substance use disorders. There were no date, location, or status restrictions. RESULTS:Our search identified 135 studies. A total of 28.9% (39/135) of studies evaluated interventions for major depressive disorder, 14.1% (19/135) of studies evaluated interventions for alcohol use disorders, 12.6% (17/135) of studies evaluated interventions for stroke, 11.1% (15/135) of studies evaluated interventions for schizophrenia, 8.1% (11/135) of studies evaluated interventions for anxiety disorders, 8.1% (11/135) of studies evaluated interventions for other mental and substance use disorders, 7.4% (10/135) of studies evaluated interventions for opioid use disorders, 3.7% (5/135) of studies evaluated interventions for Alzheimer disease or other dementias, 3.0% (4/135) of studies evaluated interventions for epilepsy, and 3.0% (4/135) of studies evaluated interventions for migraine. The studies were first registered in 2008; more than half of the studies were registered from 2016 to 2018. A total of 18.5% (25/135) of trials had results reported in some publicly accessible location. Across all the studies, the mean estimated enrollment (reported by the study) was 1078, although the median was only 100. In addition, across all the studies, the actual reported enrollment was lower, with a mean of 249 and a median of 80. Only about a quarter of the studies (35/135, 25.9%) were funded by the National Institutes of Health. CONCLUSIONS:Despite the increasing use of health-based technologies, this analysis of ClinicalTrials.gov suggests that only a few apps for high-burden neuropsychiatric conditions are being clinically evaluated in trials.

OBJECTIVE:We postulated that cerebral amyloid angiopathy (CAA) is associated with white matter atrophy (WMA) and that WMA can be related to cognitive changes in CAA. METHODS:White matter volume expressed as percent of intracranial volume (pWMV) of prospectively enrolled patients without dementia diagnosed with probable CAA was compared to age-matched healthy controls (HC) and patients with Alzheimer disease (AD). Cognitive scores were also sought to understand the potential effects of WMA on cognitive function. RESULTS:= 0.003, respectively). All associations remained independent in multivariable analyses. Within the CAA cohort, higher pWMV independently correlated with better scores of executive function. CONCLUSIONS:Patients with CAA show WMA when compared to age-matched HC and patients with AD. WMA independently correlates with the number of lobar microbleeds, a marker of CAA severity. Consistent spatial patterns of WMA especially in posterior regions might be related to CAA. The association between WMA and measures of executive function suggests that WMA might represent an important mediator of CAA-related neurologic dysfunction.

Neurological complications of COVID-19 are not well described. We report two patients who were diagnosed with COVID-19 after presenting with diplopia and ophthalmoparesis.

There have been significant advances in the understanding of the vasculitides in the past several years, leading to more precise classification and nosology. Ophthalmologic manifestations may be the presenting feature of and a clue to the diagnosis of vasculitis, or develop in the course of the illness owing to a common disease mechanism. Precise diagnosis and prompt treatment prevents short- and long-term ophthalmologic sequela.

Pleomorphic xanthoastrocytoma (PXA) is a rare type of brain tumor that affects children and young adults. Molecular prognostic markers of PXAs remain poorly established. Similar to gangliogliomas, PXAs show prominent immune cell infiltrate, but its composition also remains unknown. In this study, we correlated DNA methylation and BRAF status with clinical outcome and explored the tumor microenvironment. We performed DNA methylation in 21 tumor samples from 18 subjects with a histological diagnosis of PXA. MethylCIBERSORT was used to deconvolute the PXA microenvironment by analyzing the associated immune cell-types. Median age at diagnosis was 16 years (range 7-32). At median follow-up of 30 months, 3-year and 5-year overall survival was 73% and 71%, respectively. Overall survival ranged from 1 to 139 months. Eleven out of 18 subjects (61%) showed disease progression. Progression-free survival ranged from 1 to 89 months. Trisomy 7 and CDKN2A/B (p16) homozygous deletion did not show any association with overall survival (p = 0.67 and p = 0.74, respectively). Decreased overall survival was observed for subjects with tumors lacking the BRAF V600E mutation (p = 0.02). PXAs had significantly increased CD8 T-cell epigenetic signatures compared with previously profiled gangliogliomas (p = 0.0019). The characterization of immune cell-types in PXAs may have implications for future development of immunotherapy.

BACKGROUND:Transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy is a novel and effective treatment for controlling tremor in essential tremor patients. OBJECTIVE:To provide a comprehensive characterization of the radiological, topographical, and volumetric aspects of the tcMRgFUS thalamic lesion, and to quantify how they relate to the clinical outcomes. METHODS:In this study, clinical and radiological data from forty patients with medically-refractory essential tremor treated with unilateral tcMRgFUS thalamotomy were retrospectively analyzed. Treatment efficacy was assessed with Clinical Rating Scale for Tremor (CRST). Lesions were manually segmented on T1, T2, and susceptibility-weighted images, and 3-dimensional topographical analysis was then carried out. Statistical comparisons were performed using nonparametric statistics. RESULTS:The greatest clinical improvement was correlated with a more inferior and posterior lesion, a bigger lesion volume, and percentage of the ventral intermediate nucleus covered by the lesion; whereas, the largest lesions accounted for the occurrence of gait imbalance. Furthermore, the volume of the lesion was significantly predicted by the number of sonications surpassing 52°C. CONCLUSION:Here we provide a comprehensive characterization of the thalamic tcMRgFUS lesion including radiological and topographical analysis. Our results indicate that the location and volume of the lesion were significantly associated with the clinical outcome and that mid-temperatures may be responsible for the lesion size. This could serve ultimately to improve targeting and judgment and to optimize clinical outcome of tcMRgFUS thalamotomy.

We present a patient who was diagnosed 20 yr prior to current presentation with a spinal arteriovenous malformation. This patient had a 10-yr history of worsening back pain (and underwent lumbar fusion), urinary dysfunction leading to 3-yr dependence on intermittent catheterization, lower extremity paresthesias and pain, and progressive weakness with multiple falls, leading to walker then wheelchair dependence for mobility. Magnetic resonance studies showed extensive thoracic cord expansion and edema with enlarged spinal cord surface veins and flow voids extending from spinal levels T6 to the conus medullaris. Partial embolization at an outside institution elicited transient symptom improvement. Repeated spinal angiogram demonstrated persistent T10 pial arteriovenous fistula (AVF) supplied by the posterior spinal artery arising from the right T11 segmental artery as well as by the anterior spinal artery from the left T10 segmental artery. Because additional embolization carried significant risk, we planned open surgery with fistula resection. Informed consent for the surgery and video recording was obtained. The patient was placed in the prone position, and a radial artery access was obtained for intraoperative angiogram. Following a posterior T9-T11 laminectomy and dural opening, a pial dissection was performed to expose the AVF. Intraoperative indocyanine green angiography was used to assist in identifying the feeders and major drainage of the AVF. Post-AVF resection, a formal intraoperative radial access spinal angiogram demonstrated complete resection of the lesion with no residual shunt or early venous drainage. The patient improved significantly and, on last follow-up, is ambulating without any assistive devices.

This study examines cultural differences in genetic and environmental influences on Five-Factor Model (FFM) across Croatian, German and Serbian cultures. Participants were 1021 monozygotic and 722 dizygotic twin pairs and NEO Five-Factor Inventory"“ NEO-FFI is used to assess FFM personality traits. Results show a similar pattern of genetic and environmental contribution to the variance of all FFM dimensions, indicating that culture has no significant effect on the genetic and environmental variance of personality traits. The best fitted common factor - common AE pathway models show that FFM dimensions are accounted for by the common latent factor. Although FFM dimensions clearly share some common sources of variance, the effects of specific genetic and environmental factors are more pronounced than common ones. Different patterns of genetic and environmental correlations across three samples may reflect the way that the synergy of personality traits responds to the specificities of a particular culture, as well as possible subtle differences in item translation, testing conditions, and measurement error.