Psychiatric Associations Of Adult-Onset Focal Dystonia Phenotypes

Background Depression and anxiety frequently accompany the motor manifestations of isolated adult-onset focal dystonias. Whether the body region affected when this type of dystonia first presents is associated with the severity of these neuropsychiatric symptoms is unknown. Objectives The aim of this study was to determine whether depression, anxiety and social anxiety vary by dystonia onset site and evaluate whether pain and dystonia severity account for any differences. Methods patients with isolated focal dystonia evaluated within 5 years from symptom onset, enrolled in the Natural history project of the Dystonia coalition, were included in the analysis. Individual onset sites were grouped into five body regions: cervical, laryngeal, limb, lower cranial and upper cranial. Neuropsychiatric symptoms were rated using the Beck Depression Inventory, hospital anxiety and Depression scale and Liebowitz social anxiety scale. pain was estimated using the 36-Item short Form survey. results Four hundred and seventy-eight subjects met our inclusion criteria. high levels of depression, anxiety and social anxiety occurred in all groups; however, the severity of anxiety and social anxiety symptoms varied by onset site group. The most pronounced differences were higher anxiety in cervical and laryngeal, lower anxiety in upper cranial and higher social anxiety in laryngeal. Increases in pain were associated with worse neuropsychiatric symptom scores within all groups. higher anxiety and social anxiety in laryngeal and lower anxiety in upper cranial persisted after correcting for pain and dystonia severity. Conclusion anxiety and social anxiety severity vary by onset site of focal dystonia, and this variation is not explained by differences in pain and dystonia severity

Gender as a Risk Factor for Functional Movement Disorders: The Role of Sexual Abuse.

BackgroundThe prevalence of functional movement disorders is 2 to 3 times higher in women than in men. Trauma and adverse life events are important risk factors for developing functional movement disorders. On a population level, rates of sexual abuse against women are higher when compared with the rates against men.ObjectivesTo determine gender differences in rates of sexual abuse in functional movement disorders compared with other neurologic disorders and evaluate if the gender prevalence is influenced by higher rates of sexual abuse against women.MethodsWe performed a case-control series including 199 patients with functional movement disorders (149 women) and 95 controls (60 women). We employed chi-squared test to assess gender and sexual abuse associations and Bayes formula to condition on sexual abuse.ResultsOur analysis showed an association between sexual abuse and functional movement disorders in women (odds ratio, 4.821; 95% confidence interval, 2.089-12.070; P < 0.0001), but not men. Bayesian analysis found the functional movement disorder prevalence ratio between women and men conditional on sexual abuse to be 4.87 times the unconditioned ratio.ConclusionsThere is a statistically significant association between sexual abuse and functional movement disorders in women and a greater likelihood that women who are sexually abused will develop functional movement disorders than men who are sexually abused. Our findings suggest that the increased prevalence of functional movement disorders in women is associated, at least in part, with sexual abuse and its sequelae; however, further research is needed to explore the role of other traumatic and nontraumatic factors

Isolated focal dystonia phenotypes are associated with distinct patterns of altered microstructure

Objective: Isolated adult-onset focal dystonia is considered a network disorder with disturbances to the motor basal ganglia and cerebellar circuits playing a pathophysiological role, but why specific body regions become affected remains unknown. We aimed to use diffusion tensor imaging to determine if the two most common phenotypes of focal dystonia are associated with distinguishing microstructural changes affecting the motor network. Methods: Fifteen blepharospasm patients, 20 cervical dystonia patients, and 30 age- and sex-matched healthy controls were recruited. Maps of fractional anisotropy and mean diffusivity were analyzed using a voxel-based approach and an automated region-of-interest technique to evaluate deep gray matter nuclei. Correlations between diffusion measures and dystonia severity were tested, and post hoc discriminant analyses were conducted. Results: Voxel-based analyses revealed significantly reduced fractional anisotropy in the right cerebellum and increased mean diffusivity in the left caudate of cervical dystonia patients compared to controls, as well as lower fractional anisotropy in the right cerebellum in cervical dystonia patients relative to blepharospasm patients. In addition to reduced fractional anisotropy in the bilateral caudate nucleus of cervical dystonia patients relative to controls and blepharospasm patients, region-of-interest analyses revealed significantly reduced fractional anisotropy in the right globus pallidus internus and left red nucleus of blepharospasm patients compared to both controls and cervical dystonia patients. Diffusivity measures in the red nucleus of blepharospasm patients correlated with disease severity. In a three-group discriminant analysis, participants were correctly classified with only modest reliability (67–75%), but in a two-group discriminant analysis, patients could be distinguished from each other with high reliability (83–100%). Conclusions: Different focal dystonia phenotypes are associated with distinct patterns of altered microstructure within constituent regions of basal ganglia and cerebellar circuits. Keywords: Blepharospasm, Cervical dystonia, Diffusion tensor imaging, Basal ganglia, Cerebellu

Gender as a Risk Factor for Functional Movement Disorders: The Role of Sexual Abuse.

BackgroundThe prevalence of functional movement disorders is 2 to 3 times higher in women than in men. Trauma and adverse life events are important risk factors for developing functional movement disorders. On a population level, rates of sexual abuse against women are higher when compared with the rates against men.ObjectivesTo determine gender differences in rates of sexual abuse in functional movement disorders compared with other neurologic disorders and evaluate if the gender prevalence is influenced by higher rates of sexual abuse against women.MethodsWe performed a case-control series including 199 patients with functional movement disorders (149 women) and 95 controls (60 women). We employed chi-squared test to assess gender and sexual abuse associations and Bayes formula to condition on sexual abuse.ResultsOur analysis showed an association between sexual abuse and functional movement disorders in women (odds ratio, 4.821; 95% confidence interval, 2.089-12.070; P < 0.0001), but not men. Bayesian analysis found the functional movement disorder prevalence ratio between women and men conditional on sexual abuse to be 4.87 times the unconditioned ratio.ConclusionsThere is a statistically significant association between sexual abuse and functional movement disorders in women and a greater likelihood that women who are sexually abused will develop functional movement disorders than men who are sexually abused. Our findings suggest that the increased prevalence of functional movement disorders in women is associated, at least in part, with sexual abuse and its sequelae; however, further research is needed to explore the role of other traumatic and nontraumatic factors

Microstructural changes within the basal ganglia differ between Parkinson disease subtypes

Diffusion tensor imaging (DTI) of the substantia nigra has shown promise in detecting and quantifying neurodegeneration in Parkinson disease (PD). It remains unknown, however, whether differences in microstructural changes within the basal ganglia underlie PD motor subtypes. We investigated microstructural changes within the basal ganglia of mild to moderately affected PD patients using DTI and sought to determine if microstructural changes differ between the tremor dominant (TD) and postural instability/gait difficulty (PIGD) subtypes. Fractional anisotropy, mean diffusivity, radial and axial diffusivity were obtained from bilateral caudate, putamen, globus pallidus and substantia nigra of twenty-one PD patients (12 TD and 9 PIGD) and 20 age-matched healthy controls. T-tests and ANOVA methods were used to compare PD patients, subtypes, and controls, and Spearman correlations tested for relationships between DTI and clinical measures. We found our cohort of PD patients had reduced fractional anisotropy within the substantia nigra and increased mean and radial diffusivity within the substantia nigra and globus pallidus compared to controls, and that changes within those structures were largely driven by the PIGD subtype. Across all PD patients fractional anisotropy within the substantia nigra correlated with disease stage, while in PIGD patients increased diffusivity within the globus pallidus correlated with disease stage and motor severity. We conclude that PIGD patients have more severely affected microstructural changes within the substantia nigra compared to TD, and that microstructural changes within the globus pallidus may be particularly relevant for the manifestation of the PIGD subtype

The Rise and Fall of Slow Wave Tides: Vacillations in Coupled Slow Wave/Spindle Pairing Shift the Composition of Slow Wave Activity in Accordance With Depth of Sleep

Slow wave activity (SWA) during sleep is associated with synaptic regulation and memory processing functions. Each cycle of non-rapid-eye-movement (NREM) sleep demonstrates a waxing and waning amount of SWA during the transitions between stages N2 and N3 sleep, and the deeper N3 sleep is associated with an increased density of SWA. Further, SWA is an amalgam of different types of slow waves, each identifiable by their temporal coupling to spindle subtypes with distinct physiological features. The objectives of this study were to better understand the neurobiological properties that distinguish different slow wave and spindle subtypes, and to examine the composition of SWA across cycles of NREM sleep. We further sought to explore changes in the composition of NREM cycles that occur among aging adults. To address these goals, we analyzed subsets of data from two well-characterized cohorts of healthy adults: (1) The DREAMS Subjects Database ( n = 20), and (2) The Cleveland Family Study ( n = 60). Our analyses indicate that slow wave/spindle coupled events can be characterized as frontal vs. central in their relative distribution between electroencephalography (EEG) channels. The frontal predominant slow waves are identifiable by their coupling to late-fast spindles and occur more frequently during stage N3 sleep. Conversely, the central-associated slow waves are identified by coupling to early-fast spindles and favor occurrence during stage N2 sleep. Together, both types of slow wave/spindle coupled events form the composite of SWA, and their relative contribution to the SWA rises and falls across cycles of NREM sleep in accordance with depth of sleep. Exploratory analyses indicated that older adults produce a different composition of SWA, with a shift toward the N3, frontal subtype, which becomes increasingly predominant during cycles of NREM sleep. Overall, these data demonstrate that subtypes of slow wave/spindle events have distinct cortical propagation patterns and differ in their distribution across lighter vs. deeper NREM sleep. Future efforts to understand how slow wave sleep and slow wave/spindle coupling impact memory performance and neurological disease may benefit from examining the composition of SWA to avoid potential confounds that may occur when comparing dissimilar neurophysiological events

A Review of the Current Evidence Connecting Seborrheic Dermatitis and Parkinson\u27s Disease and the Potential Role of Oral Cannabinoids.

Parkinson\u27s disease (PD) is a neurodegenerative disorder associated with multiple comorbidities, including seborrheic dermatitis (SD), which develops in more than half of PD patients. SD in patients with PD can be severe and frequently intractable by traditional topical therapy. Cannabinoids possess anti-inflammatory and neuromodulatory properties working within the intrinsic endocannabinoid system, the activation of which may alleviate the motor symptoms of PD. The effect of cannabinoids on SD is unknown. Here we explore the pathophysiological mechanisms and possible therapeutic role of oral cannabinoids in PD patients with SD, and review speculative mechanisms underlying the association of PD and SD. Current data supporting the use of cannabinoids in both PD and SD, as well as oral cannabinoid safety and tolerability, are presented. Cannabinoids may provide the possibility of simultaneous treatment of both SD and PD. Specific SD studies and additional safety data on oral cannabinoids are needed

The Aging Slow Wave: A Shifting Amalgam of Distinct Slow Wave and Spindle Coupling Subtypes Define Slow Wave Sleep Across the Human Lifespan

Slow wave and spindle coupling supports memory consolidation, and loss of coupling is linked with cognitive decline and neurodegeneration. Coupling is proposed to be a possible biomarker of neurological disease, yet little is known about the different subtypes of coupling that normally occur throughout human development and aging. Here we identify distinct subtypes of spindles within slow wave upstates and describe their relationships with sleep stage across the human lifespan. Coupling within a cross-sectional cohort of 582 subjects was quantified from stages N2 and N3 sleep across ages 6-88 years old. Results were analyzed across the study population via mixed model regression. Within a subset of subjects, we further utilized coupling to identify discrete subtypes of slow waves by their coupled spindles. Two different subtypes of spindles were identified during the upstates of (distinct) slow waves: an "early-fast" spindle, more common in stage N2 sleep, and a "late-fast" spindle, more common in stage N3. We further found stages N2 and N3 sleep contain a mixture of discrete subtypes of slow waves, each identified by their unique coupled-spindle timing and frequency. The relative contribution of coupling subtypes shifts across the human lifespan, and a deeper sleep phenotype prevails with increasing age. Distinct subtypes of slow waves and coupled spindles form the composite of slow wave sleep. Our findings support a model of sleep-dependent synaptic regulation via discrete slow wave/spindle coupling subtypes and advance a conceptual framework for the development of coupling-based biomarkers in age-associated neurological disease

Mapping sleep's oscillatory events as a biomarker of Alzheimer's disease

Abstract INTRODUCTION Memory‐associated neural circuits produce oscillatory events including theta bursts (TBs), sleep spindles (SPs), and slow waves (SWs) in sleep electroencephalography (EEG). Changes in the “coupling” of these events may indicate early Alzheimer's disease (AD) pathogenesis. METHODS We analyzed 205 aging adults using single‐channel sleep EEG, cerebrospinal fluid (CSF) AD biomarkers, and Clinical Dementia Rating® (CDR®) scale. We mapped SW‐TB and SW‐SP neural circuit coupling precision to amyloid positivity, cognitive impairment, and CSF AD biomarkers. RESULTS Cognitive impairment correlated with lower TB spectral power in SW‐TB coupling. Cognitively unimpaired, amyloid positive individuals demonstrated lower precision in SW‐TB and SW‐SP coupling compared to amyloid negative individuals. Significant biomarker correlations were found in oscillatory event coupling with CSF Aβ 42 /Aβ 40 , phosphorylated‐ tau 181 , and total‐tau. DISCUSSION Sleep‐dependent memory processing integrity in neural circuits can be measured for both SW‐TB and SW‐SP coupling. This breakdown associates with amyloid positivity, increased AD pathology, and cognitive impairment. Highlights At‐home sleep EEG is a potential biomarker of neural circuits linked to memory. Circuit precision is associated with amyloid positivity in asymptomatic aging adults. Levels of CSF amyloid and tau also correlate with circuit precision in sleep EEG. Theta burst EEG power is decreased in very early mild cognitive impairment. This technique may enable inexpensive wearable EEGs for monitoring brain health