Network Localization of Spontaneous Confabulation.

OBJECTIVE: Spontaneous confabulation is a symptom in which false memories are conveyed by the patient as true. The purpose of the study was to identify the neuroanatomical substrate of this complex symptom and evaluate the relationship to related symptoms, such as delusions and amnesia. METHODS: Twenty-five lesion locations associated with spontaneous confabulation were identified in a systematic literature search. The network of brain regions functionally connected to each lesion location was identified with a large connectome database (N=1,000) and compared with networks derived from lesions associated with nonspecific (i.e., variable) symptoms (N=135), delusions (N=32), or amnesia (N=53). RESULTS: Lesions associated with spontaneous confabulation occurred in multiple brain locations, but they were all part of a single functionally connected brain network. Specifically, 100% of lesions were connected to the mammillary bodies (familywise error rate [FWE]-corrected p<0.05). This connectivity was specific for lesions associated with confabulation compared with lesions associated with nonspecific symptoms or delusions (FWE-corrected p<0.05). Lesions associated with confabulation were more connected to the orbitofrontal cortex than those associated with amnesia (FWE-corrected p<0.05). CONCLUSIONS: Spontaneous confabulation maps to a common functionally connected brain network that partially overlaps, but is distinct from, networks associated with delusions or amnesia. These findings lend new insight into the neuroanatomical bases of spontaneous confabulation.

Cholinergic Nucleus 4 Degeneration and Cognitive Impairment in Isolated Rapid Eye Movement Sleep Behavior Disorder.

BACKGROUND: Cholinergic nucleus 4 (Ch4) degeneration is associated with cognitive impairment in Parkinson's disease and dementia with Lewy bodies, but it is unknown if Ch4 degeneration is also present in isolated rapid eye movement sleep behavior disorder (iRBD). OBJECTIVE: The aim was to determine if there is evidence of Ch4 degeneration in patients with iRBD and if it is associated with cognitive impairment. METHODS: We analyzed the clinical and neuropsychological data of 35 iRBD patients and 35 age- and sex-matched healthy controls. Regional gray matter density (GMD) was calculated for Ch4 using probabilistic maps applied to brain magnetic resonance imaging (MRI). RESULTS: Ch4 GMD was significantly lower in the iRBD group compared to controls (0.417 vs. 0.441, P = 0.02). Ch4 GMD was also found to be a significant predictor of letter number sequencing (ß-coefficient = 58.31, P = 0.026, 95% confidence interval [7.47, 109.15]), a measure of working memory. CONCLUSIONS: iRBD is associated with Ch4 degeneration, and Ch4 degeneration in iRBD is associated with impairment in working memory. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Interrater reliability of motor severity scales for hemifacial spasm.

To compare the inter-rater reliability (IRR) of five clinical rating scales for video-based assessment of hemifacial spasm (HFS) motor severity. We evaluated the video recordings of 45 HFS participants recruited through the Dystonia Coalition. In Round 1, six clinicians with expertise in HFS assessed the participants' motor severity with five scales used to measure motor severity of HFS: the Jankovic rating scale (JRS), Hemifacial Spasm Grading Scale (HSGS), Samsung Medical Center (SMC) grading system for severity of HFS spasms (Lee's scale), clinical grading of spasm intensity (Chen's scale), and a modified version of the Abnormal Involuntary Movement Scale (Tunc's scale). In Round 2, clinicians rated the same cohort with simplified scale wording after consensus training. For each round, we evaluated the IRR using the intraclass correlation coefficient [ICC (2,1) single-rater, absolute-agreement, 2-way random model]. The scales exhibited IRR that ranged from "poor" to "moderate"; the mean ICCs were 0.41, 0.43, 0.47, 0.43, and 0.65 for the JRS, HSGS, Lee's, Chen's, and Tunc's scales, respectively, for Round 1. In Round 2, the corresponding IRRs increased to 0.63, 0.60, 0.59, 0.53, and 0.71. In both rounds, Tunc's scale exhibited the highest IRR. For clinical assessments of HFS motor severity based on video observations, we recommend using Tunc's scale because of its comparative reliability and because clinicians interpret the scale easily without modifications or the need for consensus training.

One Minute of EEG Data Provides Sufficient and Reliable Data for Identifying Lewy Body Dementia.

OBJECTIVE: To determine the minimum duration of electroencephalography (EEG) data necessary to differentiate EEG features of Lewy body dementia (LBD), that is, dementia with Lewy bodies and Parkinson disease dementia, from non-LBD patients, that is, Alzheimer disease and Parkinson disease. METHODS: We performed quantitative EEG analysis for 16 LBD and 14 non-LBD patients. After artifact removal, a fast Fourier transform was performed on 90, 60, and thirty 2-second epochs to derive dominant frequency; dominant frequency variability; and dominant frequency prevalence. RESULTS: In LBD patients, there were no significant differences in EEG features derived from 90, 60, and thirty 2-second epochs (all P >0.05). There were no significant differences in EEG features derived from 3 different groups of thirty 2-second epochs (all P >0.05). When analyzing EEG features derived from ninety 2-second epochs, we found that LBD had significantly reduced dominant frequency, reduced dominant frequency variability, and reduced dominant frequency prevalence alpha compared with the non-LBD group (all P <0.05). These same differences were observed between the LBD and non-LBD groups when analyzing thirty 2-second epochs. CONCLUSIONS: There were no differences in EEG features derived from 1 minute versus 3 minutes of EEG data, and both durations of EEG data equally differentiated LBD from non-LBD.

Quality of life in isolated dystonia: non-motor manifestations matter.

OBJECTIVE: To evaluate the relationship between health-related quality of life (HR-QoL) and both physical and psychiatric factors in a large, international, multicentre cohort of patients with isolated dystonia, the Dystonia Coalition. METHODS: Natural history data from 603 patients with isolated dystonia (median age 57 years (IQR: 48 to 64 years), 67.0% women) were prospectively acquired and analysed. HR-QoL (RAND 36-Item Health Survey), severity of depressive symptoms, generalised anxiety (Hospital Anxiety and Depression Scale) and social anxiety (Liebowitz Social Anxiety Scale) were assessed. Dystonia severity (Burke-Fahn-Marsden Dystonia Rating Scale) and dystonic tremor were examined. Statistical predictors of HR-QoL were calculated using saturated path analysis. RESULTS: Reduced HR-QoL was strongly associated with the degree of depressive symptoms and generalised and social anxiety (8/8 RAND 36 subscales, p≤0.001). Increased dystonia severity was associated with worse physical functioning, physical and emotional role functioning and social functioning (all p≤0.001). The presence of tremor correlated with worse physical functioning and pain (all p≤0.006). Younger age was associated with reduced emotional well-being and vitality (all p≤0.006). There were no HR-QoL differences between sexes. CONCLUSION: HR-QoL in isolated dystonia is strongly associated with psychiatric and physical features. While current standard of care focus on motor aspects of dystonia, comprehensive care should address both physical and mental aspects of health.

A Multi-center Genome-wide Association Study of Cervical Dystonia.

BACKGROUND: Several monogenic causes for isolated dystonia have been identified, but they collectively account for only a small proportion of cases. Two genome-wide association studies have reported a few potential dystonia risk loci; but conclusions have been limited by small sample sizes, partial coverage of genetic variants, or poor reproducibility. OBJECTIVE: To identify robust genetic variants and loci in a large multicenter cervical dystonia cohort using a genome-wide approach. METHODS: We performed a genome-wide association study using cervical dystonia samples from the Dystonia Coalition. Logistic and linear regressions, including age, sex, and population structure as covariates, were employed to assess variant- and gene-based genetic associations with disease status and age at onset. We also performed a replication study for an identified genome-wide significant signal. RESULTS: After quality control, 919 cervical dystonia patients compared with 1491 controls of European ancestry were included in the analyses. We identified one genome-wide significant variant (rs2219975, chromosome 3, upstream of COL8A1, P-value 3.04 × 10-8 ). The association was not replicated in a newly genotyped sample of 473 cervical dystonia cases and 481 controls. Gene-based analysis identified DENND1A to be significantly associated with cervical dystonia (P-value 1.23 × 10-6 ). One low-frequency variant was associated with lower age-at-onset (16.4 ± 2.9 years, P-value = 3.07 × 10-8 , minor allele frequency = 0.01), located within the GABBR2 gene on chromosome 9 (rs147331823). CONCLUSION: The genetic underpinnings of cervical dystonia are complex and likely consist of multiple distinct variants of small effect sizes. Larger sample sizes may be needed to provide sufficient statistical power to address the presumably multi-genic etiology of cervical dystonia. © 2021 International Parkinson and Movement Disorder Society.

Predictive modeling of spread in adult-onset isolated dystonia: Key properties and effect of tremor inclusion.

BACKGROUND AND PURPOSE: Several clinical and demographic factors relate to anatomic spread of adult-onset isolated dystonia, but a predictive model is still lacking. The aims of this study were: (i) to develop and validate a predictive model of anatomic spread of adult-onset isolated dystonia; and (ii) to evaluate whether presence of tremor associated with dystonia influences model predictions of spread. METHODS: Adult-onset isolated dystonia participants with focal onset from the Dystonia Coalition Natural History Project database were included. We developed two prediction models, one with dystonia as sole disease manifestation ("dystonia-only") and one accepting dystonia OR tremor in any body part as disease manifestations ("dystonia OR tremor"). Demographic and clinical predictors were selected based on previous evidence, clinical plausibility of association with spread, or both. We used logistic regressions and evaluated model discrimination and calibration. Internal validation was carried out based on bootstrapping. RESULTS: Both predictive models showed an area under the curve of 0.65 (95% confidence intervals 0.62-0.70 and 0.62-0.69, respectively) and good calibration after internal validation. In both models, onset of dystonia in body regions other than the neck, older age, depression and history of neck trauma were predictors of spread. CONCLUSIONS: This predictive modeling of spread in adult-onset isolated dystonia based on accessible predictors (demographic and clinical) can be easily implemented to inform individuals' risk of spread. Because tremor did not influence prediction of spread, our results support the argument that tremor is a part of the dystonia syndrome, and not an independent or coincidental disorder.

Hemodynamic responses are abnormal in isolated cervical dystonia.

Neuroimaging studies using functional magnetic resonance imaging (fMRI), which measures brain activity by detecting the changes in blood oxygenation levels, are advancing our understanding of the pathophysiology of dystonia. Neurobiological disturbances in dystonia, however, may affect neurovascular coupling and impact the interpretability of fMRI studies. We evaluated here whether the hemodynamic response patterns during a behaviorally matched motor task are altered in isolated cervical dystonia (CD). Twenty-five CD patients and 25 healthy controls (HCs) underwent fMRI scanning during a paced finger tapping task (nondystonic task in patients). Imaging data were analyzed using a constrained principal component analysis-a statistical method that combines regression analysis and principal component analysis and enables the extraction of task-related functional networks and determination of the spatial and temporal hemodynamic response patterns associated with the task performance. Data from three patients and two controls were removed due to excessive movement. No significant differences in demographics or motor performance were observed. Three task-associated functional brain networks were identified. During task performance, reduced hemodynamic responses were seen in a sensorimotor network and in a network that included key nodes of the default mode, executive control and visual networks. During rest, reductions in hemodynamic responses were seen in the cognitive/visual network. Lower hemodynamic responses within the primary sensorimotor network in patients were correlated with the increased dystonia severity. Pathophysiological disturbances in isolated CD, such as alterations in inhibitory signaling and dopaminergic neurotransmission, may impact neurovascular coupling. Not accounting for hemodynamic response differences in fMRI studies of dystonia could lead to inaccurate results and interpretations.

Risk of spread in adult-onset isolated focal dystonia: a prospective international cohort study.

OBJECTIVE: Isolated focal dystonia can spread to muscles beyond the initially affected body region, but risk of spread has not been evaluated in a prospective manner. Furthermore, body regions at risk for spread and the clinical factors associated with spread risk are not well characterised. We sought here to prospectively characterise risk of spread in recently diagnosed adult-onset isolated focal dystonia patients. METHODS: Patients enrolled in the Dystonia Coalition with isolated dystonia affecting only the neck, upper face, hand or larynx at onset of symptoms were included. Timing of follow-up visits was based on a sliding scale depending on symptom onset and ranged from 1 to 4 years. Descriptive statistics, Kaplan-Meier survival curves and Cox proportional hazard regression models were used to assess clinical characteristics associated with dystonia spread. RESULTS: 487 enrolled participants (68.3% women; mean age: 55.6±12.2 years) met our inclusion/exclusion criteria. Spread was observed in 50% of blepharospasm, 8% of cervical dystonia, 17% of hand dystonia and 16% of laryngeal dystonia cases. Most common regions for first spread were the oromandibular region (42.2%) and neck (22.4%) for blepharospasm, hand (3.5%) for cervical dystonia and neck for hand (12.8%) and laryngeal (15.8%) dystonia. Increased spread risk was associated with a positive family history (HR=2.18, p=0.012) and self-reported alcohol responsiveness (HR=2.59, p=0.009). CONCLUSIONS: Initial body region affected in isolated focal dystonia has differential risk and patterns of spread. Genetic factors likely influence the risk of spread. These findings can aid clinical prognostication and inform future investigations into potential disease-modifying treatments.

Abnormal Neural Responses During Reflexive Blinking in Blepharospasm: An Event-Related Functional MRI Study.

BACKGROUND: The neurophysiological disruptions underlying blepharospasm, a disabling movement disorder characterized by increased blinking and involuntary muscle spasms of the eyelid, remain poorly understood. OBJECTIVE: To investigate the neural substrates underlying reflexive blinking in blepharospasm patients compared to healthy controls using simultaneous functional MRI and surface electromyography. METHODS: Fifteen blepharospasm patients and 15 healthy controls were recruited. Randomly timed air puffs to the left eye were used to induce reflexive eye blinks during two 8-minute functional MRI scans. Continuous surface electromyography and video recordings were used to monitor blink responses. Imaging data were analyzed using an event-related design. RESULTS: Fourteen blepharospasm patients (10 female; 61.6 ± 8.0 years) and 15 controls (11 female; 60.9 ± 5.5 years) were included in the final analysis. Reflexive eye blinks in controls were associated with activation of the right hippocampus and in patients with activation of the left caudate nucleus. Reflexive blinks in blepharospasm patients showed increased activation in the right postcentral gyrus and precuneus, left precentral gyrus, and left occipital cortex compared to controls. Dystonia severity negatively correlated with activity in the left occipital cortex, and disease duration negatively correlated with reflexive-blink activity in the cerebellum. CONCLUSIONS: Reflexive blinking in blepharospasm is associated with increased activation in the caudate nucleus and sensorimotor cortices, suggesting a loss of inhibition within the sensorimotor corticobasal ganglia network. The association between decreasing neural response during reflexive blinking in the cerebellum with disease duration suggests an adaptive role. © 2020 International Parkinson and Movement Disorder Society.

Clinical and Demographic Characteristics of Upper Limb Dystonia.

BACKGROUND: Knowledge of characteristics in upper limb dystonia remains limited, derived primarily from small, single-site studies. OBJECTIVE: The objective of this study was to characterize demographic and clinical characteristics of upper limb dystonia from the Dystonia Coalition data set, a large, international, multicenter resource. METHODS: We evaluated clinical and demographic characteristics of 367 participants with upper limb dystonia from onset, comparing across subcategories of focal (with and without dystonia spread) versus nonfocal onset. RESULTS: Focal onset occurred in 80%; 67% remained focal without spread. Task specificity was most frequent in this subgroup, most often writer's cramp and affecting the dominant limb (83%). Focal onset with spread was more frequent in young onset (<21 years). Focal onset occurred equally in women and men; nonfocal onset affected women disproportionately. CONCLUSIONS: Upper limb dystonia distribution, focality, and task specificity relate to onset age and likelihood of regional spread. Observations may inform clinical counseling and design, execution, and interpretation of future studies. © 2020 International Parkinson and Movement Disorder Society.

Transient Daily Episodes of Vision Loss Due to Parkinson's Disease.

Visual complaints are common in Parkinson's disease (PD), but transient visual loss has not previously been defined as a feature of parkinsonian-related disease. We report a patient with recurrent daily episodes of transient and disabling visual loss due to PD-related non-motor fluctuation. During his visit, he experienced one such episode, which allowed for close observation and examination during and after the visual loss. Implications for localization of the visual loss are reviewed in the context of visual pathway disturbances in PD.

Validation of a performance-based assessment of cognitive functional ability in Parkinson's disease.

BACKGROUND: Outcome measures that capture functional abilities related to cognition offer the potential to demonstrate real-world effectiveness of cognitive-enhancing treatments. However, distinguishing functional disability related to cognition from that attributed to motor symptoms can be difficult in PD. A performance-based functional assessment allows for direct observation of activity of daily living skills and separation of cognitive from motoric disabilities. OBJECTIVES: Validate the University of California San Diego Performance-Based Skills Assessment in PD. METHODS: One hundred PD participants, ranging from normal cognition to dementia, completed the University of California San Diego Performance-Based Skills Assessment, a performance-based measure of cognitively demanding activities of daily living, as well as a neuropsychological battery and motor examination. Cognitive classification was determined by consensus conference, blinded to University of California San Diego Performance-Based Skills Assessment scores. Psychometric properties of the University of California San Diego Performance-Based Skills Assessment, including internal consistency, test-retest and inter-rater reliability, and discriminant validity for dementia, were examined. RESULTS: The University of California San Diego Performance-Based Skills Assessment demonstrated strong internal consistency (Cronbach's α = 0.82) and test-retest reliability (r = 0.89) and correlated strongly with global cognition (Mattis Dementia Rating Scale: r = 0.80; P < 0.001). University of California San Diego Performance-Based Skills Assessment regression models indicated greater contribution from cognitive explanatory variables (marginal partial: R2 = 0.33) than motor variables (marginal partial: R2 = 0.05), controlling for age, education, disease duration, and l-dopa equivalent dose. Additionally, the University of California San Diego Performance-Based Skills Assessment exhibited strong discriminant validity for dementia (area under the curve = 0.91). CONCLUSIONS: The University of California San Diego Performance-Based Skills Assessment is a valid measure of functional abilities related to cognition rather than motor symptoms in PD. Furthermore, it reliably distinguishes demented from nondemented participants. The University of California San Diego Performance-Based Skills Assessment may be considered as an outcome measure that combines cognitive and functional abilities in treatment trials for cognitive impairment in PD. © 2018 International Parkinson and Movement Disorder Society.

Botulinum toxin for motor and phonic tics in Tourette's syndrome.

BACKGROUND: Gilles de la Tourette syndrome, or Tourette's syndrome, is defined as the presence of both motor and vocal (phonic) tics for more than 12 months, that manifest before the age of 18 years, in the absence of secondary causes. Treatment of motor and phonic tics is difficult and challenging. OBJECTIVES: To determine the safety and effectiveness of botulinum toxin in treating motor and phonic tics in people with Tourette's syndrome, and to analyse the effect of botulinum toxin on premonitory urge and sensory tics. SEARCH METHODS: We searched the Cochrane Movement Disorders Group Trials Register, CENTRAL, MEDLINE, and two trials registers to 25 October 2017. We reviewed reference lists of relevant articles for additional trials. SELECTION CRITERIA: We considered all randomised, controlled, double-blind studies comparing botulinum toxin to placebo or other medications for the treatment of motor and phonic tics in Tourette's syndrome for this review. We sought both parallel group and cross-over studies of children or adults, at any dose, and for any duration. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods to select studies, assess risk of bias, extract and analyse data. All authors independently abstracted data onto standardized forms; disagreements were resolved by mutual discussion. MAIN RESULTS: Only one randomised placebo-controlled, double-blind cross-over study met our selection criteria. In this study, 20 participants with motor tics were enrolled over a three-year recruitment period; 18 (14 of whom had a diagnosis of Tourette's syndrome) completed the study; in total, 21 focal motor tics were treated. Although we considered most bias domains to be at low risk of bias, the study recruited a small number of participants with relatively mild tics and provided limited data for our key outcomes. The effects of botulinum toxin injections on tic frequency, measured by videotape or rated subjectively, and on premonitory urge, are uncertain (very low-quality evidence). The quality of evidence for adverse events following botulinum toxin was very low. Nine people had muscle weakness following the injection, which could have led to unblinding of treatment group assignment. No data were available to evaluate whether botulinum injections led to immunoresistance to botulinum. AUTHORS' CONCLUSIONS: We are uncertain about botulinum toxin effects in the treatment of focal motor and phonic tics in select cases, as we assessed the quality of the evidence as very low. Additional randomised controlled studies are needed to demonstrate the benefits and harms of botulinum toxin therapy for the treatment of motor and phonic tics in patients with Tourette's syndrome.

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.

Meta-analysis of real-time fMRI neurofeedback studies using individual participant data: How is brain regulation mediated?

An increasing number of studies using real-time fMRI neurofeedback have demonstrated that successful regulation of neural activity is possible in various brain regions. Since these studies focused on the regulated region(s), little is known about the target-independent mechanisms associated with neurofeedback-guided control of brain activation, i.e. the regulating network. While the specificity of the activation during self-regulation is an important factor, no study has effectively determined the network involved in self-regulation in general. In an effort to detect regions that are responsible for the act of brain regulation, we performed a post-hoc analysis of data involving different target regions based on studies from different research groups. We included twelve suitable studies that examined nine different target regions amounting to a total of 175 subjects and 899 neurofeedback runs. Data analysis included a standard first- (single subject, extracting main paradigm) and second-level (single subject, all runs) general linear model (GLM) analysis of all participants taking into account the individual timing. Subsequently, at the third level, a random effects model GLM included all subjects of all studies, resulting in an overall mixed effects model. Since four of the twelve studies had a reduced field of view (FoV), we repeated the same analysis in a subsample of eight studies that had a well-overlapping FoV to obtain a more global picture of self-regulation. The GLM analysis revealed that the anterior insula as well as the basal ganglia, notably the striatum, were consistently active during the regulation of brain activation across the studies. The anterior insula has been implicated in interoceptive awareness of the body and cognitive control. Basal ganglia are involved in procedural learning, visuomotor integration and other higher cognitive processes including motivation. The larger FoV analysis yielded additional activations in the anterior cingulate cortex, the dorsolateral and ventrolateral prefrontal cortex, the temporo-parietal area and the visual association areas including the temporo-occipital junction. In conclusion, we demonstrate that several key regions, such as the anterior insula and the basal ganglia, are consistently activated during self-regulation in real-time fMRI neurofeedback independent of the targeted region-of-interest. Our results imply that if the real-time fMRI neurofeedback studies target regions of this regulation network, such as the anterior insula, care should be given whether activation changes are related to successful regulation, or related to the regulation process per se. Furthermore, future research is needed to determine how activation within this regulation network is related to neurofeedback success.

Levodopa modulates small-world architecture of functional brain networks in Parkinson's disease.

BACKGROUND: PD is associated with disrupted connectivity to a large number of distributed brain regions. How the disease alters the functional topological organization of the brain, however, remains poorly understood. Furthermore, how levodopa modulates network topology in PD is largely unknown. The objective of this study was to use resting-state functional MRI and graph theory to determine how small-world architecture is altered in PD and affected by levodopa administration. METHODS: Twenty-one PD patients and 20 controls underwent functional MRI scanning. PD patients were scanned off medication and 1 hour after 200 mg levodopa. Imaging data were analyzed using 226 nodes comprising 10 intrinsic brain networks. Correlation matrices were generated for each subject and converted into cost-thresholded, binarized adjacency matrices. Cost-integrated whole-brain global and local efficiencies were compared across groups and tested for relationships with disease duration and severity. RESULTS: Data from 2 patients and 4 controls were excluded because of excess motion. Patients off medication showed no significant changes in global efficiency and overall local efficiency, but in a subnetwork analysis did show increased local efficiency in executive (P = 0.006) and salience (P = 0.018) networks. Levodopa significantly decreased local efficiency (P = 0.039) in patients except within the subcortical network, in which it significantly increased local efficiency (P = 0.007). CONCLUSIONS: Levodopa modulates global and local efficiency measures of small-world topology in PD, suggesting that degeneration of nigrostriatal neurons in PD may be associated with a large-scale network reorganization and that levodopa tends to normalize the disrupted network topology in PD. © 2016 International Parkinson and Movement Disorder Society.

Clinical and demographic characteristics related to onset site and spread of cervical dystonia.

BACKGROUND: Clinical characteristics of isolated idiopathic cervical dystonia such as onset site and spread to and from additional body regions have been addressed in single-site studies with limited data and incomplete or variable dissociation of focal and segmental subtypes. The objectives of this study were to characterize the clinical characteristics and demographics of isolated idiopathic cervical dystonia in the largest standardized multicenter cohort. METHODS: The Dystonia Coalition, through a consortium of 37 recruiting sites in North America, Europe, and Australia, recruited 1477 participants with focal (60.7%) or segmental (39.3%) cervical dystonia on examination. Clinical and demographic characteristics were evaluated in terms of the body region of dystonia onset and spread. RESULTS: Site of dystonia onset was: (1) focal neck only (78.5%), (2) focal onset elsewhere with later segmental spread to neck (13.3%), and (3) segmental onset with initial neck involvement (8.2%). Frequency of spread from focal cervical to segmental dystonia (22.8%) was consistent with prior reports, but frequency of segmental onset with initial neck involvement was substantially higher than the 3% previously reported. Cervical dystonia with focal neck onset, more than other subtypes, was associated with spread and tremor of any type. Sensory tricks were less frequent in cervical dystonia with segmental components, and segmental cervical onset occurred at an older age. CONCLUSIONS: Subgroups had modest but significant differences in the clinical characteristics that may represent different clinical entities or pathophysiologic subtypes. These findings are critical for design and implementation of studies to describe, treat, or modify disease progression in idiopathic isolated cervical dystonia. © 2016 International Parkinson and Movement Disorder Society.

Non convulsive status epilepticus masquerading as stroke.

This case describes a patient with multiple stroke risk factors­including prior stroke­who presented to the emergency department with symptoms suggestive of stroke and who received a rapid stroke work up but was later found to be in non convulsive status epilepticus (NCSE). This case report highlights the challenge and importance of making an accurate diagnosis in NCSE, and we have included teaching points to help clinicians understand the clinical manifestations and diagnosis of NCSE as well as how it may impact a patient's prognosis. Given the growing attention to rapid stroke protocols in emergency departments across the country, it is important to remember that not all that appears as stroke is stroke, even in people who are at high risk for stroke or in whom stroke is the most likely cause of their neurologic deficits.