Actigraphic correlates of neuropsychiatric symptoms in adults with focal epilepsy.

OBJECTIVES: Disability in patients with epilepsy (PWEs) is multifactorial: beyond seizure frequency/severity, PWEs are prone to a range of neuropsychiatric, cognitive, and somatic comorbidities that significantly affect quality of life. Here, we explored how variations in seizure severity and the burden of self-reported somatic/neuropsychiatric symptoms correlate with disruptions to 24 h activity patterns (rest-activity rhythms [RARs]), determined through wrist accelerometry/actigraphy. METHODS: Multiday wrist-actigraphy recordings were obtained from 59 adult patients with focal epilepsy (44% male, ages 18-72), who contemporaneously responded to validated psychometric instruments to measure anxiety, depression, sleepiness, and somatic symptoms. We conducted a similar in silico psychometric-actigraphic correlation in a publicly available data set of 1747 Hispanic subjects (35% male, ages 18-65) from the Study of Latinos (SOL) Sueño Ancillary Study. RARs were analyzed via a sigmoidally-transformed cosine model (quantifying amplitude, steepness, acrophase, and robustness) and nonparametric measures to estimate RAR stability, fragmentation, and sleep. RESULTS: Compared with matched SOL subjects, RARs from PWE subjects featured a significantly lower amplitude, a wider rest phase, and significantly more total daily sleep. Within PWEs, similar RAR distortions were associated with seizure intractability and/or anticonvulsant polytherapy, whereas high anxiety, depression, and somatic symptom scores were associated with lower RAR robustness and acrophase delay. We applied the SOL data set to train logistic regression models to dichotomously classify subjective anxiety, depression, and sleepiness symptoms using demographic and RAR parameters. When tested on PWEs, these models predicted prevalent anxiety and depression symptom burden (accuracy ~70%) but failed to predict subjective sleepiness. SIGNIFICANCE: Together these results demonstrate that RAR features may encode prevalent depression and anxiety symptoms in patients with focal epilepsy, potentially offering wearable-derived endpoints to adjunct clinical care and drug/device trials. With larger PWE-specific actigraphic-psychometric data sets, we may identify RAR signatures that may more precisely correlate with varying seizure frequency, the burden of anticonvulsant therapy, and prevalent mood/anxiety symptoms.

Genome Sequencing in the Parkinson Disease Clinic.

Background and Objectives: Genetic variants affect both Parkinson disease (PD) risk and manifestations. Although genetic information is of potential interest to patients and clinicians, genetic testing is rarely performed during routine PD clinical care. The goal of this study was to examine interest in comprehensive genetic testing among patients with PD and document reactions to possible findings from genome sequencing in 2 academic movement disorder clinics. Methods: In 203 subjects with PD (age = 63 years, 67% male), genome sequencing was performed and filtered using a custom panel, including 49 genes associated with PD, parkinsonism, or related disorders, as well as a 90-variant PD genetic risk score. Based on the results, 231 patients (age = 67 years, 63% male) were surveyed on interest in genetic testing and responses to vignettes covering (1) familial risk of PD (LRRK2); (2) risk of PD dementia (GBA); (3) PD genetic risk score; and (4) secondary, medically actionable variants (BRCA1). Results: Genome sequencing revealed a LRRK2 variant in 3% and a GBA risk variant in 10% of our clinical sample. The genetic risk score was normally distributed, identifying 41 subjects with a high risk of PD. Medically actionable findings were discovered in 2 subjects (1%). In our survey, the majority (82%) responded that they would share a LRRK2 variant with relatives. Most registered unchanged or increased interest in testing when confronted with a potential risk for dementia or medically actionable findings, and most (75%) expressed interest in learning their PD genetic risk score. Discussion: Our results highlight broad interest in comprehensive genetic testing among patients with PD and may facilitate integration of genome sequencing in clinical practice.

Quantitative mobility measures complement the MDS-UPDRS for characterization of Parkinson's disease heterogeneity.

INTRODUCTION: Emerging technologies show promise for enhanced characterization of Parkinson's Disease (PD) motor manifestations. We evaluated quantitative mobility measures from a wearable device compared to the conventional motor assessment, the Movement Disorders Society-Unified PD Rating Scale part III (motor MDS-UPDRS). METHODS: We evaluated 176 PD subjects (mean age 65, 65% male, 66% H&Y stage 2) during routine clinic visits using the motor MDS-UPDRS and a 10-min motor protocol with a body-fixed sensor (DynaPort MT, McRoberts BV), including the 32-ft walk, Timed Up and Go (TUG), and standing posture with eyes closed. Regression models examined 12 quantitative mobility measures for associations with (i) motor MDS-UPDRS, (ii) motor subtype (tremor dominant vs. postural instability/gait difficulty), (iii) Montreal Cognitive Assessment (MoCA), and (iv) physical functioning disability (PROMIS-29). All analyses included age, gender, and disease duration as covariates. Models iii-iv were secondarily adjusted for motor MDS-UPDRS. RESULTS: Quantitative mobility measures from gait, TUG transitions, turning, and posture were significantly associated with motor MDS-UPDRS (7 of 12 measures, p < 0.05) and motor subtype (6 of 12 measures, p < 0.05). Compared with motor MDS-UPDRS, several quantitative mobility measures accounted for a 1.5- or 1.9-fold increased variance in either cognition or physical functioning disability, respectively. Among minimally-impaired subjects in the bottom quartile of motor MDS-UPDRS, including subjects with normal gait exam, the measures captured substantial residual motor heterogeneity. CONCLUSION: Clinic-based quantitative mobility assessments using a wearable sensor captured features of motor performance beyond those obtained with the motor MDS-UPDRS and may offer enhanced characterization of disease heterogeneity.

A simple clinical score for prediction of nonepileptic seizures.

Psychogenic nonepileptic seizures (PNES), often mistaken for epilepsy in community practice, require inpatient video-EEG (VEEG) monitoring for diagnostic confirmation. We developed a simple score designed for use in an outpatient setting to predict the subsequent VEEG diagnosis of PNES. We retrospectively compared fifty-five consecutive patients with VEEG-proven PNES (N1=55) with a group of randomly selected patients with VEEG-proven epilepsy (N2=55). Patients were divided into two groups: I) a 'truly retrospective' group of 27 patients with PNES and 27 patients with epilepsy whose data served to develop the score, and II) a 'pseudoprospective' group of 28 patients each with PNES and epilepsy to whom the score was applied. Six features in the history of the Group I cohort appeared more prominent in patients with PNES than patients with epilepsy and were assigned escalating numerical values as follows: number of declared drug allergies (0, 0.5, 1), number of declared comorbidities (0, 0.5, 1), number of previous invasive medical interventions of any type (0, 0.5, 1), and a history of significant psychological or physical trauma (0 or 1). In addition, a score was assigned to verbal description of the seizures themselves as being consistent (=0), atypical (=1), or indeterminate (=0.5) for epilepsy. The values were added to yield an omnibus score ranging from 0 to 6. Scoring of Group II subjects in a blinded fashion revealed that in general patients with PNES had higher scores, and the majority obtained a score >2; most patients with epilepsy scored <1.5. Group difference in the mean between the PNES and epilepsy cohort was highly significant (p<0.0001, Wilcoxon rank-sum test). Our score is a simple clinical instrument based on the patient history that may find use in the triage of patients awaiting hospitalization for VEEG and in pre-VEEG counseling.