Publications by authors named "Daniel O Claassen"

121 Publications

Cross-disorder comparison of sensory over-responsivity in chronic tic disorders and obsessive-compulsive disorder.

Compr Psychiatry 2021 Dec 17;113:152291. Epub 2021 Dec 17.

Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States. Electronic address:

Background: Sensory over-responsivity (SOR) refers to excessively intense and/or prolonged behavioral responses to environmental stimuli typically perceived as non-aversive. SOR is prevalent in several neurodevelopmental disorders, including chronic tic disorders (CTDs) and obsessive-compulsive disorder (OCD). Few studies have examined the extent and clinical correlates of SOR across disorders, limiting insights into the phenomenon's transdiagnostic clinical and biological relevance. Such cross-disorder comparisons are of particular interest for CTDs and OCD given their frequent co-occurrence.

Objective: We sought to compare the magnitude of SOR between adults with CTD and adults with OCD and to identify the clinical factors most strongly associated with SOR across these disorders.

Methods: We enrolled 207 age- and sex-matched participants across four diagnostic categories: CTD without OCD (designated "CTD/OCD-"; n = 37), CTD with OCD ("CTD/OCD+"; n = 32), OCD without tic disorder ("OCD"; n = 69), and healthy controls (n = 69). Participants completed a self-report battery of rating scales assessing SOR (Sensory Gating Inventory, SGI), obsessive-compulsive symptoms (Dimensional Obsessive-Compulsive Scale, DOCS), inattention and hyperactivity (Adult ADHD Self-Report Screening Scale for DSM-5, ASRS-5), anxiety (Generalized Anxiety Disorder-7), and depression (Patient Health Questionnaire-9). CTD participants were also administered the Yale Global Tic Severity Scale (YGTSS). To examine between-group differences in SOR, we compared SGI score across all groups and between pairs of groups. To examine the relationship of SOR with other clinical factors, we performed multivariable linear regression.

Results: CTD/OCD-, CTD/OCD+, and OCD participants were 86.7%, 87.6%, and 89.5%, respectively, more likely to have higher SGI total scores than healthy controls. SGI total score did not differ between CTD/OCD-, CTD/OCD+, and OCD groups. In the regression model of log-transformed SGI total score, OCD diagnosis, DOCS score, and ASRS-5 score each contributed significantly to model goodness-of-fit, whereas CTD diagnosis and YGTSS total tic score did not.

Conclusion: SOR is prevalent in adults with CTD and in adults with OCD but does not significantly differ in magnitude between these disorders. Across CTD, OCD, and healthy control adult populations, SOR is independently associated with both obsessive-compulsive and ADHD symptoms, suggesting a transdiagnostic relationship between these sensory and psychiatric manifestations. Future cross-disorder, longitudinal, and translational research is needed to clarify the role and prognostic import of SOR in CTDs, OCD, and other neurodevelopmental disorders.
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http://dx.doi.org/10.1016/j.comppsych.2021.152291DOI Listing
December 2021

Amphetamine-induced dopamine release and impulsivity in Parkinson disease.

Brain 2021 Dec 24. Epub 2021 Dec 24.

Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Impulsive-compulsive behaviors manifest in a substantial proportion of persons with Parkinson disease. Reduced ventral striatum dopamine receptor availability, and increased dopamine release is noted in patients with these symptoms. Prior studies of impulsivity suggest that midbrain D2 autoreceptors regulate striatal dopamine release in a feedback inhibitory manner, and in healthy populations, greater impulsivity is linked to poor proficiency of this inhibition. This has not been assessed in a Parkinson disease. Here, we applied [18F]fallypride PET studies to assess striatal and extrastriatal D2-like receptor uptake in a placebo-controlled oral dextroamphetamine sequence. We hypothesized that Parkinson disease patients with impulsive-compulsive behaviors would have greater ventral striatal dopaminergic response to dextroamphetamine, and that an inability to attenuate ventral striatal dopamine release via midbrain D2 autoreceptors would underlie this response. Twenty persons with Parkinson disease (mean age = 64.1 ± 5.8) both with (N = 10) and without (N = 10) impulsive-compulsive behaviors, participated in a single-blind dextroamphetamine challenge (oral; 0.43 mg/kg) in an off-dopamine state. All completed PET imaging with [18F]fallypride, a high-affinity D2-like receptor ligand, in the placebo and dextroamphetamine state. Both voxelwise, and region-of-interest analyses, revealed dextroamphetamine-induced endogenous dopamine release localized to the ventral striatum, and the caudal-medial orbitofrontal cortex. The endogenous dopamine release observed in the ventral striatum positively correlated with patient-reported participation in reward-based behaviors, as quantified by the self-reported Questionnaire for Impulsivity in Parkinson's disease Rating Scale. In participants without impulsive-compulsive behaviors, baseline midbrain D2 receptor availability negatively correlated with ventral striatal dopamine release; however, this relationship was absent in those with impulsive-compulsive behaviors. These findings emphasize that reward-based behaviors in PD are regulated by ventral striatal dopamine release, and suggest that loss of inhibitory feedback from midbrain autoreceptors may underlie the manifestation of impulsive-compulsive behaviors.
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http://dx.doi.org/10.1093/brain/awab487DOI Listing
December 2021

Real-World Adherence to Tetrabenazine or Deutetrabenazine Among Patients With Huntington's Disease: A Retrospective Database Analysis.

Neurol Ther 2021 Dec 14. Epub 2021 Dec 14.

Teva Pharmaceuticals, Parsippany, NJ, USA.

Introduction: Chorea, a common clinical manifestation of Huntington's disease (HD), involves sudden, involuntary movements that interfere with daily functioning and contribute to the morbidity of HD. Tetrabenazine and deutetrabenazine are FDA-approved to treat chorea associated with HD. Compared to tetrabenazine, deutetrabenazine has a unique pharmacokinetic profile leading to more consistent systemic exposure, less frequent dosing, and a potentially more favorable safety/tolerability profile. Real-world adherence data for these medications are limited. Here, we evaluate real-world adherence patterns with the vesicular monoamine transporter 2 inhibitors, tetrabenazine and deutetrabenazine, among patients diagnosed with HD.

Methods: Insurance claims data from the Symphony Health Solutions Integrated Dataverse (05/2017-05/2019) were retrospectively analyzed for patients diagnosed with HD (ICD-10-CM code G10). Patients were categorized into cohorts based on treatment. Outcomes included adherence, which was measured by proportion of days covered (PDC), adherence rate (PDC > 80%), and discontinuation rates during the 6-month follow-up period (after a 30-day dose stabilization period).

Results: Patient demographic characteristics between the deutetrabenazine (N = 281) and tetrabenazine (N = 101) cohorts were comparable at baseline. Mean ± SD PDC was significantly higher in the deutetrabenazine versus tetrabenazine cohort (78.5% ± 26.7% vs. 69.3% ± 31.4%; P < 0.01). Similarly, a higher adherence rate was observed in the deutetrabenazine versus tetrabenazine cohort, though the difference was not statistically significant (64.1% vs. 55.4%; P = 0.1518). Discontinuation rates were significantly lower in the deutetrabenazine versus tetrabenazine cohort during the 6-month follow-up period (1 month, 3.5% vs. 9.2%; 3 months, 14.7% vs. 23.3%; 6 months, 25.4% vs. 37.2%; P < 0.05).

Conclusions: Results from this real-world analysis indicate that patients treated with deutetrabenazine are more adherent to treatment and have lower discontinuation rates compared with patients in the tetrabenazine cohort. However, a potential limitation is overestimated adherence, as claims for prescription fills may not capture actual use. Additional research is warranted to explore the differences in adherence patterns between treatments, which may inform treatment decision-making.
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http://dx.doi.org/10.1007/s40120-021-00309-5DOI Listing
December 2021

A MDS Evidence-Based Review on Treatments for Huntington's Disease.

Mov Disord 2021 Nov 29. Epub 2021 Nov 29.

Instituto de Medicina Molecular João Lobo Antunes, Lisbon, Portugal.

Background: Huntington's disease (HD) is a rare neurodegenerative disorder with protean clinical manifestations. Its management is challenging, consisting mainly of off-label treatments.

Objectives: The International Parkinson and Movement Disorder Society commissioned a task force to review and evaluate the evidence of available therapies for HD gene expansion carriers.

Methods: We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Eligible randomized controlled trials were identified via an electronic search of the CENTRAL, MEDLINE, and EMBASE databases. All eligible trials that evaluated one or more of 33 predetermined clinical questions were included. Risk of bias was evaluated using the Cochrane Risk of Bias tool. A framework was adapted to allow for efficacy and safety conclusions to be drawn from the balance between the GRADE level of evidence and the importance of the benefit/harm of the intervention.

Results: Twenty-two eligible studies involving 17 interventions were included, providing data to address 8 clinical questions. These data supported a likely effect of deutetrabenazine on motor impairment, chorea, and dystonia and of tetrabenazine on chorea. The data did not support a disease-modifying effect for premanifest and manifest HD. There was no eligible evidence to support the use of specific treatments for depression, psychosis, irritability, apathy, or suicidality. Similarly, no evidence was eligible to support the use of physiotherapy, occupational therapy, exercise, dietary, or surgical treatments.

Conclusions: Data for therapeutic interventions in HD are limited and support only the use of VMAT2 inhibitors for specific motor symptoms. © 2021 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28855DOI Listing
November 2021

D-Like Receptor Expression in the Hippocampus and Amygdala Informs Performance on the Stop-Signal Task in Parkinson's Disease.

J Neurosci 2021 12 8;41(48):10023-10030. Epub 2021 Nov 8.

Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee 37232

The stop-signal task is a well-established assessment of response inhibition, and in humans, proficiency is linked to dorsal striatum D receptor availability. Parkinson's disease (PD) is characterized by changes to efficiency of response inhibition. Here, we studied 17 PD patients (6 female and 11 male) using the stop-signal paradigm in a single-blinded d-amphetamine (dAMPH) study. Participants completed [F]fallypride positron emission topography (PET) imaging in both placebo and dAMPH conditions. A voxel-wise analysis of the relationship between binding potential (BP) and stop-signal reaction time (SSRT) revealed that faster SSRT is associated with greater D-like BP in the amygdala and hippocampus (right cluster = 0.026, left cluster = 0.002). A region of interest (ROI) examination confirmed this association in both the amygdala (coefficient = -48.26, = 0.005) and hippocampus (coefficient = -104.94, = 0.007). As healthy dopaminergic systems in the dorsal striatum appear to regulate response inhibition, we interpret our findings in PD to indicate either nigrostriatal damage unmasking a mesolimbic contribution to response inhibition, or a compensatory adaptation from the limbic and mesial temporal dopamine systems. These novel results expand the conceptualization of action-control networks, whereby limbic and motor loops may be functionally connected. While Parkinson's disease (PD) is characteristically recognized for its motor symptoms, some patients develop impulsive and compulsive behaviors (ICBs), manifested as repetitive and excessive participation in reward-driven activities, including sex, gambling, shopping, eating, and hobbyism. Such cognitive alterations compel a consideration of response inhibition in PD. To investigate inhibitory control and assess the brain regions that may participate, we assessed PD patients using a single-blinded d-amphetamine (dAMPH) study, with [F]fallypride positron emission topography (PET) imaging, and stop-signal task performance. We find a negative relationship between D-like binding in the mesial temporal region and top-signal reaction time (SSRT), with greater BP associated with a faster SSRT. These discoveries indicate a novel role for mesolimbic dopamine in response inhibition, and advocate for limbic regulation of action control in this clinical population.
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http://dx.doi.org/10.1523/JNEUROSCI.0968-21.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638685PMC
December 2021

Improving Patient Outreach by Defining Telehealth Suitability in a Tertiary Huntington's Disease Clinic.

J Huntingtons Dis 2021 ;10(4):479-484

Division of Behavioraland Cognitive Neurology, Department of Neurology, Vanderbilt University Medical Center (VUMC), Nashville, TN, USA.

Background: The COVID-19 pandemic has increased the need for remote healthcare options among patients with Huntington's disease (HD). However, since not every HD patient is suitable for telehealth, it is important to differentiate who can be seen virtually from who should remain as in-person. Unfortunately, there are no clinical guidelines on how to evaluate HD patients for telehealth eligibility.

Objective: To standardize the teleneurology selection process in HD by implementing a screening tool that accounts for patient-specific factors.

Methods: We organized various indications and contraindications to teleneurology into a flowchart. If any indications or contraindications were met, patients were assigned to telehealth or maintained as in-person, respectively. If no indications or contraindications were met, patients were given the option of telehealth or in-person for their upcoming appointments. In two implementation cycles, we tested this screening tool among all HD patients scheduled for clinic visits, aided by chart review and phone interview.

Results: In a cohort of 81 patients, telehealth acceptance among eligible patients increased from 45.0%to 83.3%. Frequency of telehealth visits increased from a pre-intervention baseline of 12.8%to 28.2%.

Conclusion: Teleneurology utilization among HD patients more than doubled across our study. Our intervention promotes consistency and patient-centeredness in HD clinical care and streamlines the overall telehealth selection process. Future studies can seek to reduce telehealth no-shows and also evaluate the utility of the motor and psychiatric criteria included in our screening tool.
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http://dx.doi.org/10.3233/JHD-210498DOI Listing
November 2021

Efficacy and Safety of Fixed-Dose Deutetrabenazine in Children and Adolescents for Tics Associated With Tourette Syndrome: A Randomized Clinical Trial.

JAMA Netw Open 2021 10 1;4(10):e2129397. Epub 2021 Oct 1.

Teva Pharmaceuticals, Netanya, Israel.

Importance: Tourette syndrome is a neurodevelopmental disorder characterized by childhood onset of motor and phonic tics, often accompanied by behavioral and psychiatric comorbidities. Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor approved in the US for the treatment of chorea associated with Huntington disease and tardive dyskinesia.

Objective: To report results of the ARTISTS 2 (Alternatives for Reducing Tics in Tourette Syndrome 2) study examining deutetrabenazine for treatment of Tourette syndrome.

Design, Setting, And Participants: This phase 3, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study was conducted over 8 weeks with a 1-week follow-up (June 21, 2018, to December 9, 2019). Children and adolescents aged 6 to 16 years with a diagnosis of Tourette syndrome and active tics causing distress or impairment were enrolled in the study. Children were recruited from 52 sites in 10 countries. Data were analyzed from February 4 to April 22, 2020.

Interventions: Participants were randomized (1:1:1) to low-dose deutetrabenazine (up to 36 mg/d), high-dose deutetrabenazine (up to 48 mg/d), or a matching placebo, which were titrated over 4 weeks to the target dose followed by a 4-week maintenance period.

Main Outcomes And Measures: The primary efficacy end point was change from baseline to week 8 in the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) for high-dose deutetrabenazine. Key secondary end points included changes in YGTSS-TTS for low-dose deutetrabenazine, Tourette Syndrome Clinical Global Impression score, Tourette Syndrome Patient Global Impression of Impact score, and Child and Adolescent Gilles de la Tourette Syndrome-Quality of Life Activities of Daily Living subscale score. Safety assessments included incidence of treatment-emergent adverse events, laboratory parameters, vital signs, and questionnaires.

Results: The study included 158 children and adolescents (mean [SD] age, 11.7 [2.6] years). A total of 119 participants (75%) were boys; 7 (4%), Asian; 1 (1%), Black; 32 (20%), Hispanic; 4 (3%), Native American; 135 (85%), White; 2 (1%), multiracial; 9 (6%), other race; and 1 (0.6%), of unknown ethnic origin. Fifty-two participants were randomized to the high-dose deutetrabenazine group, 54 to the low-dose deutetrabenazine group, and 52 to the placebo group. Baseline characteristics for participants were similar between groups. Of the total 158 participants, 64 (41%) were aged 6 to 11 years, and 94 (59%) were aged 12 to 16 years at baseline. Mean time since Tourette syndrome diagnosis was 3.3 (2.8) years, and mean baseline YGTSS-TTS was 33.8 (6.6) points. At week 8, the difference in YGTSS-TTS was not significant between the high-dose deutetrabenazine and placebo groups (least-squares mean difference, -0.8 points; 95% CI, -3.9 to 2.3 points; P = .60; Cohen d, -0.11). There were no nominally significant differences between groups for key secondary end points. Treatment-emergent adverse events were reported for 34 participants (65%) treated with high-dose deutetrabenazine, 24 (44%) treated with low-dose deutetrabenazine, and 25 (49%) treated with placebo and were generally mild or moderate.

Conclusions And Relevance: In this fixed-dose randomized clinical trial of deutetrabenazine in children and adolescents with Tourette syndrome, the primary efficacy end point was not met. No new safety signals were identified.

Trial Registration: ClinicalTrials.gov Identifier: NCT03571256.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.29397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524312PMC
October 2021

Safety and Efficacy of Flexible-Dose Deutetrabenazine in Children and Adolescents With Tourette Syndrome: A Randomized Clinical Trial.

JAMA Netw Open 2021 10 1;4(10):e2128204. Epub 2021 Oct 1.

Teva Pharmaceuticals, Netanya, Israel.

Importance: Tourette syndrome is a neurodevelopmental disorder characterized by childhood onset of motor and phonic tics; treatments for tics are associated with safety concerns. Deutetrabenazine is a selective vesicular monoamine transporter 2 inhibitor approved for the treatment of chorea associated with Huntington disease and tardive dyskinesia in adults.

Objective: To examine whether deutetrabenazine is effective and safe for the treatment of Tourette syndrome in children and adolescents.

Design, Setting, And Participants: This phase 2/3, randomized, double-masked, placebo-controlled, parallel-group, dose-titration study included children and adolescents (aged 6-16 years) with Tourette syndrome with active tics causing distress or impairment (ie, Yale Global Tic Severity Scale-Total Tic Score [YGTSS-TTS] ≥20). The trial was conducted over 12 weeks, with 1 week of follow-up from February 2018 to November 2019 at 36 centers in the United States, Canada, Denmark, Russia, Serbia, and Spain. Data analysis was conducted from January 31 to April 22, 2020.

Intervention: Patients were randomized (1:1) to receive deutetrabenazine or placebo, titrated during 7 weeks to an optimal level, followed by a 5-week maintenance period. The maximum total daily deutetrabenazine dose was 48 mg/d.

Main Outcomes And Measures: The primary efficacy end point was change from baseline to week 12 in YGTSS-TTS. Key secondary end points included changes in Tourette Syndrome-Clinical Global Impression, Tourette Syndrome-Patient Global Impression of Impact, and Child and Adolescent Gilles de la Tourette Syndrome-Quality of Life Activities of Daily Living subscale score. Safety was assessed based on treatment-emergent adverse events, vital signs, questionnaires, and laboratory parameters.

Results: A total of 119 participants were randomized to deutetrabenazine (59 participants; mean [SD] age, 11.5 [2.5] years; 53 [90%] boys; 49 [83%] White; 3 [5%] Black) and placebo (60 participants; mean [SD] age, 11.5 [2.6] years; 51 [85%] boys; 53 [88%] White; 3 [5%] Black). At week 12, the difference in YGTSS-TTS score was not significant between deutetrabenazine and placebo (least squares mean difference, -0.7; 95% CI, -4.1 to 2.8; P = .69; Cohen d, -0.07). There were no nominally significant differences between groups for key secondary end points. Treatment-emergent adverse events were reported for 38 patients (66%) and 33 patients (56%) receiving deutetrabenazine and placebo, respectively, and were generally mild or moderate.

Conclusions And Relevance: In this study of deutetrabenazine in children and adolescents with Tourette syndrome, the primary efficacy end point was not met. No new safety signals were identified. These results may be informative for future studies of treatments for tics in Tourette syndrome.

Trial Registration: ClinicalTrials.gov Identifier: NCT03452943.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.28204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493441PMC
October 2021

Influences of dopaminergic system dysfunction on late-life depression.

Mol Psychiatry 2021 Aug 17. Epub 2021 Aug 17.

Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons and New York State Psychiatric Institute, New York, NY, USA.

Deficits in cognition, reward processing, and motor function are clinical features relevant to both aging and depression. Individuals with late-life depression often show impairment across these domains, all of which are moderated by the functioning of dopaminergic circuits. As dopaminergic function declines with normal aging and increased inflammatory burden, the role of dopamine may be particularly salient for late-life depression. We review the literature examining the role of dopamine in the pathogenesis of depression, as well as how dopamine function changes with aging and is influenced by inflammation. Applying a Research Domain Criteria (RDoC) Initiative perspective, we then review work examining how dopaminergic signaling affects these domains, specifically focusing on Cognitive, Positive Valence, and Sensorimotor Systems. We propose a unified model incorporating the effects of aging and low-grade inflammation on dopaminergic functioning, with a resulting negative effect on cognition, reward processing, and motor function. Interplay between these systems may influence development of a depressive phenotype, with an initial deficit in one domain reinforcing decline in others. This model extends RDoC concepts into late-life depression while also providing opportunities for novel and personalized interventions.
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http://dx.doi.org/10.1038/s41380-021-01265-0DOI Listing
August 2021

Medicolegal Aspects of Huntington Disease.

J Am Acad Psychiatry Law 2021 12 2;49(4):565-571. Epub 2021 Aug 2.

Dr. McDonell, Dr. Darby, and Dr. Claassen are Assistant Professors of Neurology, Ms. Brown is Clinical Research Coordinator, and Ms. Hale is Licensed Medical Social Worker at the Department of Neurology, Vanderbilt University Medical Center. Dr. Stovall is Associate Professor of Psychiatry at the Department of Psychiatry, Vanderbilt University Medical Center. Dr. Compas is the Patricia and Rodes Hart Professor of Psychology and Human Development and Professor of Pediatrics at the Department of Psychology and Human Development, Vanderbilt University.

Unlawful behaviors have been reported in association with Huntington's disease (HD), although their overall prevalence and clinical significance remain unknown. Recognition of problematic behavior is limited by stigma and lack of routine clinical assessment, as well as the absence of validated screening measures. We performed a retrospective chart review of 289 patients treated for HD at Vanderbilt University Medical Center from 2006 to 2020 to assess the frequency of illegal activity in our HD population. We identified 31 patients with HD who have a documented history of unlawful behavior, comprising 11 percent of the charts reviewed. Physical violence was the most common behavior reported, followed by reckless driving, substance abuse, illegal financial activity, and inappropriate sexual behavior. Mean age at the time of the first offense was 37 years. Patients with criminal offenses were more likely to be male and in the early stages of disease with associated psychiatric symptoms. Our results emphasize that illegal activities are a significant clinical problem in individuals with HD, particularly young adult males with comorbid psychiatric symptoms. These findings highlight the need for improved screening measures to detect high-risk behaviors in individuals with HD, as well as evidence-based protocols to guide triage and management of patients engaging in potentially detrimental activities.
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http://dx.doi.org/10.29158/JAAPL.210008-21DOI Listing
December 2021

Clinical implications of photophobia in progressive supranuclear palsy.

Clin Park Relat Disord 2021 1;4:100097. Epub 2021 Jun 1.

Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States.

Objective: To determine the impact of photophobia on persons with Progressive Supranuclear Palsy (pwPSP) by determining the functional impact of light sensitivity using methods established in migraine research.

Methods: All 60 participants (pwPSP = 15, persons with Parkinson Disease (pwPD) = 15, Older adults = 30) completed a series of questionnaires designed to assess the impact of photophobia on activities of daily living. Group comparisons were controlled for multiple comparisons using a false discovery rate of 0.05.

Results: Most (14/15) pwPSP participants noted that bright light hurt their eyes, and this proportion was significantly greater than pwPD (6/15; p = 0.03, corrected). PSP participants reported statistically significantly more severe light sensitivity on a subjective 0-100 scale (p = 0.003, corrected), and noted reduced time spent in both indoor and outdoor activities. Some PSP participants (n = 3) noted that they needed to wear sunglasses indoors, but most noted a reluctance to leave their house during the day due to photophobia. PwPSP indicated that they require more help from others to complete daily tasks that require them to be outside during daylight hours.

Conclusions: Overall, we note a significant debility due to photophobia in PSP, and this impacts outdoor more than indoor activities. The functional disability in PSP caused by photophobia appears to cause a substantive reduction in quality of life. Future studies could consider incorporating specific metrics to evaluate measurable differences with photophobia onset and worsening severity.
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http://dx.doi.org/10.1016/j.prdoa.2021.100097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299976PMC
June 2021

Neurobiological and Psychosocial Correlates of Communication Between Huntington's Disease Patients and Their Offspring.

J Neuropsychiatry Clin Neurosci 2021 19;33(4):321-327. Epub 2021 Jul 19.

Department of Psychology and Human Development, Vanderbilt University, Nashville, Tenn. (Watson, Ciriegio, Jones, Grice, Compas); and Department of Neurology, Vanderbilt University Medical Center, Nashville, Tenn. (Pfalzer, Hale, Brown, Moroz, McDonell, Claassen).

Objective: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that presents significant challenges to family communication. The investigators examined observations of communication between parents with HD and their offspring talking about the challenges of HD and explored potential correlates of their communication.

Methods: The sample included parents with HD and their adolescent and young-adult offspring (N=64). Parent communication and chorea were independently coded from video recordings. Parents and offspring completed working memory assessments and self-reports of neuropsychiatric symptoms, stress, and coping.

Results: Evidence was found for the association of observed parent-offspring communication with disease markers, psychosocial characteristics, and neurocognitive function. For parents, disease markers and working memory were correlates of communication, whereas offspring's psychiatric symptoms, stress, and coping were associated with their communication.

Conclusions: These findings have potential implications for clinical interventions to enhance communication and quality of life for HD families.
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http://dx.doi.org/10.1176/appi.neuropsych.20120309DOI Listing
November 2021

Diffusion along perivascular spaces reveals evidence supportive of glymphatic function impairment in Parkinson disease.

Parkinsonism Relat Disord 2021 08 10;89:98-104. Epub 2021 Jun 10.

Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Reduced diffusion along perivascular spaces in adults with Alzheimer's-disease-related-dementias has been reported and attributed to reduced glymphatic function.

Objectives: To apply quantitative measures of diffusion along, and orthogonal to, perivascular spaces in a cohort of older adults with and without clinical symptoms of alpha-synuclein related neurodegeneration.

Methods: 181 adults with Parkinson disease (PD) or essential tremor (ET) additionally sub-classified by the presence of cognitive impairment underwent 3 T MRI. Diffusion-tensor-imaging (spatial resolution = 2x2x2 mm; b-value = 1000 s/mm; directions = 33) measures of diffusion (mm/s) parallel and orthogonal to perivascular spaces at the level of the medullary veins, and the ratio of these measures (ALPS-index), were calculated. Regions were identified by a board-certified neuroradiologist from T-weighted and T-weighted MRI. Evaluations of motor impairment and mild cognitive impairment (MCI) were interpreted by a board-certified neurologist and neuropsychologist, respectively. Multiple regression with false discovery rate correction was applied to understand how diffusion metrics related to (i) disease category (PD vs. ET), (ii) cognition (MCI status), and (iii) white matter disease severity from the Fazekas score.

Results: The ALPS-index was reduced in PD compared to ET participants (p = 0.037). No association between the ALPS-index and MCI status, but an inverse association between the ALPS-index and Fazekas score (p = 0.002), was observed. The ALPS-index was inversely associated with age (p = 0.007).

Conclusion: Diffusion aberrations near perivascular spaces are evident in patients with alpha-synuclein related neurodegenerative disorders, and are related to age and white matter disease severity.
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http://dx.doi.org/10.1016/j.parkreldis.2021.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429254PMC
August 2021

Impact of Chorea on Self-care Activity, Employment, and Health-care Resource Use in Patients with Huntington's Disease.

J Health Econ Outcomes Res 2021 Jun 21;8(1):99-105. Epub 2021 Jun 21.

Teva Pharmaceuticals, West Chester, PA, USA.

Chorea is recognized as a prototypic motor feature of Huntington's disease (HD), but its effect on health-related quality of life (HRQoL) has not been fully explored. This study describes the impact of chorea on HRQoL in patients with HD. To determine the impact of HD-related chorea on employment, self-care activities, activities of daily living, and health-care resource utilization (HCRU). Data were drawn from the Adelphi HD Disease Specific Programme, a real-world point-in-time survey of 144 neurologists and 427 patients in the United States between July and October 2017. HD patients with and without chorea were identified and examined for differences in employment status, reasons for employment changes, self-care activities, and modifications to cope with involuntary movements. Bivariate tests and inverse probability weighted regression adjustment methods were used to determine differences in outcomes between patients with and without chorea. HD patients with (n=287) and without (n=140) chorea were identified. Patients with chorea were less likely to be employed full-time (16.7% vs 25.7%; <0.04) and more likely to be on long-term sick leave (17.4% vs 5.0%; <0.01). The onset of motor symptoms in HD-related chorea patients coincided with a change in employment status (42.7% vs 20.8%; <0.01). Among those still working (n=145), more than two-fifths of patients with chorea required changes to their workplace and required these changes more frequently (45% vs 17%; <0.001). HD patients with chorea required aid to help them get around significantly more frequently than those without chorea (55% vs 34%; <0.001). These results demonstrate that HD patients with chorea experienced greater negative impact to employment, self-care activities, and HCRU than patients without chorea experienced. These patients were more likely to stop working due to motor, cognitive, and behavioral symptoms; require modifications in the home and workplace; and need more assistance from caregivers than patients without chorea. Patients with HD-related chorea have greater detriments to emotional, interpersonal, and professional functioning that could be improved by reducing chorea.
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http://dx.doi.org/10.36469/001c.24620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216765PMC
June 2021

Empowering the Clinical Research Coordinator in Academic Medical Centers.

Mayo Clin Proc Innov Qual Outcomes 2021 Apr 25;5(2):265-273. Epub 2020 Dec 25.

Department of Neurology, Vanderbilt University Medical Center, Nashville, TN.

Objective: To identify factors associated with job satisfaction and retention, we surveyed a large cohort of clinical research coordinators (CRCs). In recent years, the clinical research coordinator has changed from a semi-permanent role to one that has a high turnover rate. The CRCs are integral to clinical research and instability in this role can cause patient stress and increase the burden on clinical teams through unnecessary delegation of resources toward hiring and retraining new talent. The cultural shift toward CRCs as a temporary position may be driven by the perspective that the role positions an individual for other health care careers, but understanding what influences low retention rates are necessary.

Methods: A survey containing 13 multiple choice or open-ended and 32 Likert scale questions was distributed to previous and current CRCs using REDCap. The questionnaires were self-administered and completed over a 12-month period between October 11, 2017, and September 16, 2018.

Results: A total of 85 CRCs completed the study. From the 32 potential predictors of retention, we investigated 9 significant predictors: salary, work setting, understanding the role, level of CRC, understanding protocol development, actively engaged principal investigator (PI), having a collaborative role with PI, feeling respected by PI, and having a close relationship with PI. Adequate salary, greater respect, collaboration, and engagement from the PI were significantly associated with higher retention. Surprisingly, greater workload and lack of opportunity for professional growth were not associated with retention.

Conclusion: The CRCs who feel respected and engaged by the PI and are adequately compensated are more likely to have higher job satisfaction and retention.
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http://dx.doi.org/10.1016/j.mayocpiqo.2020.09.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105545PMC
April 2021

Lifetime neuropsychiatric symptoms in Huntington's disease: Implications for psychiatric nursing.

Arch Psychiatr Nurs 2021 06 26;35(3):284-289. Epub 2021 Mar 26.

Department of Psychiatry, Vanderbilt University Medical Center, 1601 23rd Avenue South, Suite 3068, Nashville, TN 37212, USA.

Neuropsychiatric manifestations of Huntington's disease (HD) can present years before motor symptoms. Nurses with specialized training provide superior care for HD patients, but HD exposure in nursing education is limited. Here we aimed to describe the historical neuropsychiatric burden in 50 HD patients and discuss implications for psychiatric nurses. Fifty patients with HD were assessed by a board-certified psychiatrist and completed surveys about symptoms, social history, medication use, and quality of life outcomes. Descriptive statistics were used to summarize patient characteristics, and correlation analyses assessed the relationships between neuropsychiatric symptoms and quality of life outcomes. Most patients (72%) reported a history of neuropsychiatric symptoms prior to their HD diagnosis. Prodromal anger/irritability was most common (52%), though few patients received treatment for this. Anxiety was the most common current symptom (78%), yet 40% of patients had never been prescribed an SSRI. Anxiety was associated with poorer patient-reported quality of life outcomes (p < .01). HD patients in this sample experienced frequent, early-onset neuropsychiatric symptoms. In coming years, psychiatric nurses in community settings will be more likely to encounter gene-positive HD patients before they develop motor symptoms. Psychiatric nurses can address identified gaps through enhanced screening and encouraging early intervention in those at risk.
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http://dx.doi.org/10.1016/j.apnu.2021.03.006DOI Listing
June 2021

Symptoms of Medication Withdrawal in Parkinson's Disease: Considerations for Informed Consent in Patient-Oriented Research.

Pharmaceut Med 2021 05 29;35(3):163-167. Epub 2021 Apr 29.

Department of Neurology, Vanderbilt University Medical Center, 1161 21st Ave South A-0118, Nashville, TN, 37232, USA.

Introduction: Dopamine medication withdrawal in Parkinson's disease (PD) is commonly employed in clinical practice and can be required for participation in research studies. When asked to withdraw from medications, participants often enquire as to what symptoms they should expect.

Objectives: This study sought to improve the informed consent process by identifying patient-reported symptoms when dopamine treatment is withheld. We also sought to provide clinical guidance regarding the extent of these symptoms and consider participant willingness to undergo these assessments.

Methods: Participants were recruited from community-based PD programs and support groups in Nashville, Tennessee, USA. A patient-based questionnaire determined the frequency and severity of motor and nonmotor symptoms. The questionnaire also assessed whether patients would be willing to abstain from medication at a future date and under what circumstances.

Results: A total of 31/90 participants reported willingness to withdraw from dopaminergic medications for clinical or research purposes. Tremor, walking, and balance were the most common motor symptoms that worsened during this time. Sleep dysfunction, constipation, and tremor were noted as the most severe symptoms. Of note, 10% of participants indicated that they would not be willing to go off medications again, suggesting that a minority of patients find this to be most discomforting. When prompted for a reason why participants would be willing to come off of their medications again, "for clinical purposes" was selected the most.

Conclusions: Study teams should list these symptoms in the applications to their institutional review board and in the informed consent to provide guidance for participants.
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http://dx.doi.org/10.1007/s40290-021-00387-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721843PMC
May 2021

Choroid plexus perfusion in sickle cell disease and moyamoya vasculopathy: Implications for glymphatic flow.

J Cereb Blood Flow Metab 2021 10 28;41(10):2699-2711. Epub 2021 Apr 28.

Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.

Cerebrospinal fluid (CSF) and interstitial fluid exchange have been shown to increase following pharmacologically-manipulated increases in cerebral arterial pulsatility, consistent with arterial pulsatility improving CSF circulation along perivascular glymphatic pathways. The choroid plexus (CP) complexes produce CSF, and CP activity may provide a centralized indicator of perivascular flow. We tested the primary hypothesis that elevated cortical cerebral blood volume and flow, present in sickle cell disease (SCD), is associated with fractionally-reduced CP perfusion relative to healthy adults, and the supplementary hypothesis that reduced arterial patency, present in moyamoya vasculopathy, is associated with elevated fractional CP perfusion relative to healthy adults. Participants (n = 75) provided informed consent and were scanned using a 3-Tesla arterial-spin-labeling MRI sequence for CP and cerebral gray matter (GM) perfusion quantification. ANOVA was used to calculate differences in CP-to-GM perfusion ratios between groups, and regression analyses applied to evaluate the dependence of the CP-to-GM perfusion ratio on group after co-varying for age and sex. ANOVA yielded significant (p < 0.001) group differences, with CP-to-GM perfusion ratios increasing between SCD (ratio = 0.93 ± 0.28), healthy (ratio = 1.04 ± 0.32), and moyamoya (ratio = 1.29 ± 0.32) participants, which was also consistent with regression analyses. Findings are consistent with CP perfusion being inversely associated with cortical perfusion.
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http://dx.doi.org/10.1177/0271678X211010731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504961PMC
October 2021

Healthcare Delivery and Huntington's Disease During the Time of COVID-19.

J Huntingtons Dis 2021 ;10(2):313-322

Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Safer-at-home orders during the COVID-19 pandemic altered the structure of clinical care for Huntington's disease (HD) patients. This shift provided an opportunity to identify limitations in the current healthcare infrastructure and how these may impact the health and well-being of persons with HD.

Objective: The study objectives were to assess the feasibility of remote healthcare delivery in HD patients, to identify socioeconomic factors which may explain differences in feasibility and to evaluate the impact of safer-at-home orders on HD patient stress levels.

Methods: This observational study of a clinical HD population during the 'safer-at-home' orders asked patients or caregivers about their current access to healthcare resources and patient stress levels. A chart review allowed for an assessment of socioeconomic status and characterization of HD severity.

Results: Two-hundred and twelve HD patients were contacted with 156 completing the survey. During safer-at-home orders, the majority of HD patients were able to obtain medications and see a physician; however, 25% of patients would not commit to regular telehealth visits, and less than 50% utilized an online healthcare platform. We found that 37% of participants were divorced/single, 39% had less than a high school diploma, and nearly 20% were uninsured or on low-income health insurance. Patient stress levels correlated with disease burden.

Conclusion: A significant portion of HD participants were not willing to participate in telehealth services. Potential explanations for these limitations may include socioeconomic barriers and caregiving structure. These observations illustrate areas for clinical care improvement to address healthcare disparities in the HD community.
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http://dx.doi.org/10.3233/JHD-200460DOI Listing
July 2021

Clinical Correlates of Health-Related Quality of Life in Adults With Chronic Tic Disorder.

Front Psychiatry 2021 10;12:619854. Epub 2021 Mar 10.

Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States.

Tics are the hallmark feature of Tourette syndrome (TS), but psychiatric and sensory symptoms are widely prevalent and increasingly recognized as core manifestations of the disorder. Accumulating evidence suggests that these psychiatric and sensory symptoms exert greater influence on quality of life (QOL) than tics themselves. However, much remains uncertain about determinants of QOL in TS due to the complexity of the clinical presentation. Here, we sought to clarify the association between health-related QOL (HRQOL) and common psychiatric and sensory symptoms in adults with TS and other chronic tic disorders. To do so, we prospectively recruited 52 patients from a tertiary care clinic to complete self-report measures assessing HRQOL (Gilles de la Tourette-Quality of Life Scale, GTS-QOL), depression (Patient Health Questionnaire-9, PHQ-9), anxiety (Generalized Anxiety Disorder Scale-7, GAD-7), obsessive-compulsive symptoms (Dimensional Obsessive-Compulsive Scale, DOCS), attention deficit hyperactivity disorder symptoms (Adult ADHD Self-Report Screening Scale for DSM-5, ASRS-V), and premonitory urge (Premonitory Urge to Tic Scale, PUTS). All participants were also administered the Yale Global Tic Severity Scale (YGTSS) to quantify tic severity. Using correlational analysis and multivariable linear regression modeling, we found that GTS-QOL score was significantly associated with scores from all other rating scales, with the exception of the PUTS. GTS-QOL was most strongly associated with PHQ-9, followed by ASRS-V, GAD-7, DOCS, and YGTSS total tic score. The regression model including these five independent variables, as well as sex, explained 79% of GTS-QOL score variance [ = 29.6, < 0.001]. Specific psychiatric symptoms differentially impacted physical, psychological, and cognitive HRQOL. Systematic assessment of psychiatric comorbidities is imperative for clinical care and clinical research efforts directed at improving QOL in adults with chronic tic disorders.
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http://dx.doi.org/10.3389/fpsyt.2021.619854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987653PMC
March 2021

Anatomical texture patterns identify cerebellar distinctions between essential tremor and Parkinson's disease.

Hum Brain Mapp 2021 Jun 23;42(8):2322-2331. Epub 2021 Mar 23.

Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, Tennessee, USA.

Voxel-based morphometry is an established technique to study focal structural brain differences in neurologic disease. More recently, texture-based analysis methods have enabled a pattern-based assessment of group differences, at the patch level rather than at the voxel level, allowing a more sensitive localization of structural differences between patient populations. In this study, we propose a texture-based approach to identify structural differences between the cerebellum of patients with Parkinson's disease (n = 280) and essential tremor (n = 109). We analyzed anatomical differences of the cerebellum among patients using two features: T1-weighted MRI intensity, and a texture-based similarity feature. Our results show anatomical differences between groups that are localized to the inferior part of the cerebellar cortex. Both the T1-weighted intensity and texture showed differences in lobules VIII and IX, vermis VIII and IX, and middle peduncle, but the texture analysis revealed additional differences in the dentate nucleus, lobules VI and VII, vermis VI and VII. This comparison emphasizes how T1-weighted intensity and texture-based methods can provide a complementary anatomical structure analysis. While texture-based similarity shows high sensitivity for gray matter differences, T1-weighted intensity shows sensitivity for the detection of white matter differences.
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http://dx.doi.org/10.1002/hbm.25331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090778PMC
June 2021

Elevated cerebral blood flow in patients with pure autonomic failure.

Clin Auton Res 2021 06 7;31(3):405-414. Epub 2021 Mar 7.

Department of Neurology, Vanderbilt University Medical Center, 1161 21st Ave South A-0118, Nashville, TN, 37232, USA.

Purpose: Pure autonomic failure (PAF) results from an impaired peripheral autonomic nervous system, and clinical symptoms present with orthostatic hypotension. While the impact on cardiovascular indices of orthostatic intolerance are well-characterized, more limited information is available regarding cerebral hemodynamic dysfunction in PAF. The objective of this study was to test the hypothesis that cerebral blood flow (CBF) is reduced in PAF, and to quantify the relationship between CBF and clinical indicators of disease severity, including peripheral supine arterial blood pressure.

Methods: Participants with PAF (n = 17) and age- and sex-matched normotensive healthy controls (n = 17) were examined using established clinical rating scales, cardiovascular autonomic function tests, and 3T MRI measurements of CBF. CBF-weighted images were also used to determine the prevalence of venous hyperintensities from the major dural sinuses as evidence of abnormal capillary flow. Nonparametric tests and general linear models were used to evaluate differences and correlations between study variables.

Results: Gray matter CBF was higher in PAF (51.1 ± 13.4 mL/100 g/min) compared to controls (42.9 ± 6.5 mL/100 g/min, p = 0.007). Venous hyperintensities were more prevalent in PAF relative to controls, and the presence and degree of venous hyperintensities was associated with higher mean CBF (p = 0.027). In PAF participants, CBF and supine systolic blood pressure were inversely related (Spearman's rho = -0.545, p = 0.024).

Conclusions: Findings suggest that PAF patients may exhibit elevated CBF and provide evidence that this condition exerts a hemodynamic impact in the central nervous system.
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http://dx.doi.org/10.1007/s10286-021-00792-8DOI Listing
June 2021

State-of-the-art pharmacological approaches to reduce chorea in Huntington's disease.

Expert Opin Pharmacother 2021 Jun 8;22(8):1015-1024. Epub 2021 Feb 8.

Department of Neurology, Division of Behavioral and Cognitive Neurology, Vanderbilt University Medical Center, Nashville, United States.

Chorea is a common motor manifestation of Huntington's disease (HD). Two vesicular monoamine transporter type 2 (VMAT-2) inhibitors have been approved by the FDA for treatment of HD chorea, and a third is currently being assessed in a phase 3 trial. Antipsychotic therapies are used off-label for treatment of chorea and can treat comorbid psychiatric symptoms. There is considerable clinical equipoise regarding the safe and effective treatment of chorea and comorbid symptoms in HD.: The authors review existing medications used to treat HD chorea in the United States of America (USA). Implications for common comorbid symptoms (e.g. psychiatric, metabolic) are also discussed. Available therapies vary widely in cost, dosing frequency, and off -target effects, both beneficial or negative.: Treatment considerations for chorea should account for patient comorbidities. The authors recommend prospective, observational clinical effectiveness studies which can evaluate the long-term comparative effectiveness and safety of VMAT-2 inhibitors and antipsychotics in HD. Data regarding safety of dual therapy is another critical need. This is especially timely given the changing landscape of HD therapies which may increase cost burden and possibly extend both asymptomatic and symptomatic years for HD patients.
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http://dx.doi.org/10.1080/14656566.2021.1876666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222076PMC
June 2021

Perceived Effects of Neuropsychiatric Symptoms on Functional Status in Early-stage Huntington Disease.

West J Nurs Res 2021 Feb 5:193945921992545. Epub 2021 Feb 5.

Department of Neurology, Division of Behavioral and Cognitive Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.

Neuropsychiatric symptoms in Huntington disease (HD) are commonly encountered, but their effects on functional status are poorly understood. In this qualitative study guided by the Theory of Unpleasant Symptoms, 15 HD patients and caregivers completed semi-structured interviews regarding perceived effects of neuropsychiatric symptoms on functional status. Physical, cognitive, and social functional effects were reported, with negative effects on daily activities and social withdrawal being reported by the greatest number of subjects. Participants also reported improved function with intervention for neuropsychiatric symptoms. This study provides a novel description of the lived experiences of HD patients with neuropsychiatric symptoms.
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http://dx.doi.org/10.1177/0193945921992545DOI Listing
February 2021

Mapping the orbitofrontal cortex using temporal fluctuations in cerebral blood flow.

Brain Behav 2021 03 13;11(3):e02034. Epub 2021 Jan 13.

Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.

Introduction: The orbitofrontal cortex (OFC) is involved in diverse cognitive and behavioral processes including incentive valuation, decision-making, and reinforcement learning. Anatomic and cytoarchitectonic studies divide the OFC along both medial-lateral and rostral-caudal axes. OFC regions diverge in structure and function, assessed in vivo using white matter tractography and blood oxygenation level-dependent (BOLD) MRI, respectively. However, interpretation of T *-weighted BOLD is limited by susceptibility artifacts in the inferior frontal lobes, with the spatial pattern of these artifacts frequently assuming the geometry of OFC organization. Here, we utilize a novel perfusion-weighted arterial spin labeling (ASL) functional connectivity approach, which is minimally susceptibility-weighted, to test the hypothesis that OFC topology reflects correlated temporal hemodynamic activity.

Methods: In healthy participants (n = 20; age = 29.5 ± 7.3), 3D ASL scans were acquired (TR/TE = 3,900/13 ms; spatial resolution = 3.8 mm isotropic). To evaluate reproducibility, follow-up scanning on a separate day was performed on a participant subset (n = 8). ASL-based connectivity was modeled for gray matter OFC voxels, and k-means clustering (k = 2-8) applied to correlation statistics.

Results: These approaches revealed both medial-lateral and rostral-caudal OFC divisions, confirming our hypothesis. Longitudinal reproducibility testing revealed 84% voxel clustering agreement between sessions for the k = 2 solution.

Conclusion: To our knowledge, this constitutes the first in vivo cortical parcellation based on perfusion fluctuations. Our approach confirms functional OFC subdivisions predicted from anatomy using a less susceptibility-sensitive method than the conventional approach.
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http://dx.doi.org/10.1002/brb3.2034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994685PMC
March 2021

Sensory Hypersensitivity Severity and Association with Obsessive-Compulsive Symptoms in Adults with Tic Disorder.

Neuropsychiatr Dis Treat 2020 2;16:2591-2601. Epub 2020 Nov 2.

Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Sensory hypersensitivity, defined as heightened awareness of and reactivity to external stimuli, is a bothersome symptom that affects up to 80% of adults with Tourette syndrome (TS). Such widespread prevalence suggests sensory hypersensitivity is a core feature of the disorder, but its severity and association with other clinical features of TS remain largely unexplored. Complicating matters, sensory hypersensitivity has been observed in two neurodevelopmental disorders commonly comorbid with TS: obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD).

Objective: We sought to measure sensory hypersensitivity in TS patients relative to healthy controls and to investigate the relationship of sensory hypersensitivity with OCD and ADHD symptoms in the context of TS.

Methods: We recruited 34 adults with TS or chronic tic disorder to undergo evaluation with the Yale Global Tic Severity Scale (YGTSS) and a battery of validated self-report instruments assessing sensory hypersensitivity (Sensory Gating Inventory, SGI; Sensory Perception Quotient, SPQ), premonitory urge (Premonitory Urge to Tic Scale, PUTS), OCD (Dimensional Obsessive-Compulsive Scale, DOCS), and ADHD (Adult ADHD Self-Report Screening Scale for DSM-5, ASRS-V). Age- and sex-matched healthy controls were recruited to complete SGI and psychiatric measures.

Results: SGI and SPQ scores strongly correlated ( = -0.73, < 0.0001) within patients. SGI total score was significantly higher in patients versus controls (119.0 vs 67.6, =-5.3, < 0.0001), indicating greater sensory hypersensitivity in the tic disorder group. SGI score correlated modestly with PUTS, DOCS, and ASRS-V scores but not with YGTSS total tic score. Hierarchical linear regression analysis revealed that, of the tested variables, only DOCS score contributed significantly to mean SGI score, with β ranging from 1.03 ( = 0.044) to 1.41 ( = 0.001). A simple linear regression model with DOCS as the independent variable accounted for 31.9% of SGI score variance.

Conclusion: Sensory hypersensitivity is prominent in adults with tic disorder and is independently associated with obsessive-compulsive symptom severity.
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http://dx.doi.org/10.2147/NDT.S274165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646442PMC
November 2020

Risk-Taking Behaviors in Huntington's Disease.

J Huntingtons Dis 2020 ;9(4):359-369

Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Risky behaviors are common in Huntington's disease (HD) and can lead to significant adverse consequences. However, the prevalence and scope of these symptoms have not been studied systematically, and no empirically validated measures are available to screen for them.

Objective: To test a novel screening tool designed to assess risk-taking behaviors in HD.

Methods: We administered the Risk Behavior Questionnaire (RBQ-HD) to HD patients and caregivers at Vanderbilt University Medical Center between 2018-2019. Patients completed the questionnaire based on self-report; caregivers provided collateral reports. Clinical and demographic information were obtained from the electronic medical record.

Results: 60 patients and 60 caregivers completed the RBQ-HD. 80% of patients (n = 48) and 91.7% of caregivers (n = 60) reported at least one risky behavior. Adverse social behaviors, impulsive/compulsive behaviors, and reckless driving were the most common behavioral domains reported. Male patients were more likely to report risky behaviors than females (92.3% vs. 70.6%, p = 0.04). The number of risky behaviors reported by patients and caregivers was negatively correlated with patient age (r = -0.32, p = 0.01; r = -0.47, p = 0.0001, respectively). Patient and caregiver reports were highly correlated in matched pairs (n = 30; r = 0.63, p = 0.0002).

Conclusion: These findings emphasize that risky behaviors are highly prevalent in HD and can be effectively identified through the use of a novel screening measure. We hypothesize that early pathological involvement of frontostriatal and mesolimbic networks may be important factors in the development of these behaviors.
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http://dx.doi.org/10.3233/JHD-200431DOI Listing
November 2021

Measuring Functional Status in Huntington's Disease.

Mov Disord 2021 03 27;36(3):757-761. Epub 2020 Oct 27.

Department of Neurology, Division of Behavioral and Cognitive Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Background: Neuropsychiatric and cognitive symptoms account for substantial morbidity in Huntington's disease (HD), but their impact on functional status may not be captured using the Total Functional Capacity (TFC) scale. The objective of this study was to assess the impact of motor, cognitive, and neuropsychiatric symptoms on functional status in persons with HD, comparing two instruments.

Methods: Multiple regression analyses assessed the relationship between neuropsychiatric, cognitive, and motor symptoms and functional status as measured using TFC and Adult Functional Adaptive Behavior (AFAB) scales.

Results: Greater burden of neuropsychiatric (P = 0.017), cognitive (P = 0.001), and motor (P = 0.001) symptoms was associated with greater impairments to functional status as measured by the AFAB scale. Only motor symptoms were associated with TFC scores (P = 0.002). The 3 symptom domains explained more of the variance in AFAB than TFC scores (P = 0.016).

Conclusions: TFC may have limited applicability, particularly in early-stage HD patients, as a measure of functional status. The AFAB scale can be used in HD studies as a more holistic measure of functional status. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28363DOI Listing
March 2021

The Regulation of Cerebral Spinal Fluid Flow and Its Relevance to the Glymphatic System.

Curr Neurol Neurosci Rep 2020 10 19;20(12):58. Epub 2020 Oct 19.

Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.

Purpose Of Review: The glymphatic system is a relatively new concept that has been associated with regulation of cerebrospinal fluid (CSF), as well as brain waste clearance. Novel techniques to study glymphatic dysfunction have in turn prompted a reassessment of brain physiology and underlying elements of neurological disease. This review incorporates a contemporary imaging perspective focused on understanding the regulation of CSF flow, thus expanding the putative clinical relevance of this system and the relationships between CSF flow and glymphatic function.

Recent Findings: MR imaging studies, especially those that employ intrathecal gadolinium contrast, have identified potentially new pathways regulating CSF production, absorption, and clearance. These studies, when viewed in the context of more historical anatomic descriptors of CSF production and absorption, provide a more robust description of CSF physiology and waste clearance. CSF production and resorption are under-investigated and could be related to various pathophysiologic processes in neurodegeneration. Anatomically based clinical exemplars of CSF clearance are discussed. Future studies should focus on linking glymphatic functionality with neurological disease.
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http://dx.doi.org/10.1007/s11910-020-01077-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864223PMC
October 2020
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