Development of a New Care Pathway for Depression and Anxiety in Adult-Onset Isolated Dystonia.

Background: Recently, we identified barriers and facilitators to the screening and treatment of depressive and anxiety symptoms in adult-onset isolated dystonia (AOID). These symptoms are common, functionally impairing, and often underdetected and undertreated. Objectives: To develop a care pathway for mood symptoms in AOID. Methods: We used a multistep modified Delphi approach to seek consensus among healthcare professionals with experience of AOID on the screening, diagnosis, and treatment of mood symptoms. A combination of face-to-face meetings and online surveys was performed from 2019 to 2020. We created the survey and then reviewed with stakeholders before 2 rounds of Delphi surveys, all of which was finally reviewed in a consensus meeting. A purposive sample of 41 expert stakeholders from 4 Canadian provinces, including neurologists, nurses, psychiatrists, psychologists, and family physicians, was identified by the research team. Results: The Delphi process led to consensus on 12 statements that operationalized a pathway of care to screen for and manage depression and anxiety in people with AOID. Key actions of the pathway included yearly screening with self-rated instruments, multidisciplinary involvement in management involving local networks of providers coordinated by movement disorders neurologists, and access to educational resources. The Delphi panel indicated the 2 core steps as the documentation of the most recent screening outcome and the documentation of a management plan for patients who were positive at the last screening. Conclusions: This new care pathway represents a potentially useful intervention that can be used to build an integrated model of care for AOID.

Dopaminergic Therapy for Motor Symptoms in Early Parkinson Disease Practice Guideline Summary: A Report of the AAN Guideline Subcommittee.

BACKGROUND AND OBJECTIVES: To review the current evidence on the options available for initiating dopaminergic treatment of motor symptoms in early-stage Parkinson disease and provide recommendations to clinicians. METHODS: A multidisciplinary panel developed practice recommendations, integrating findings from a systematic review and following an Institute of Medicine-compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence. RESULTS: Initial treatment with levodopa provides superior motor benefit compared to treatment with dopamine agonists, whereas levodopa is more likely than dopamine agonists to cause dyskinesia. The comparison of different formulations of dopamine agonists yielded little evidence that any one formulation or method of administration is superior. Long-acting forms of levodopa and levodopa with entacapone do not appear to differ in efficacy from immediate-release levodopa for motor symptoms in early disease. There is a higher risk of impulse control disorders associated with the use of dopamine agonists than levodopa. Recommendations on initial therapy for motor symptoms are provided to assist the clinician and patient in choosing between treatment options and to guide counseling, prescribing, and monitoring of efficacy and safety.

Inhibitory Control Deficits in Children with Tic Disorders Revealed by Object-Hit-and-Avoid Task.

Background: Tic disorders may reflect impaired inhibitory control. This has been evaluated using different behavioural tasks, yielding mixed results. Our objective was to test inhibitory control in children with tics through simultaneous presentation of multiple, mobile stimuli. Methods: Sixty-four children with tics (mean age 12.4 years; 7.5-18.5) were evaluated using a validated robotic bimanual exoskeleton protocol (Kinarm) in an object-hit-and-avoid task, in which target and distractor objects moved across a screen and participants aimed to hit only the targets while avoiding distractors. Performance was compared to 146 typically developing controls (mean age 13 years; 6.1-19.9). The primary outcome was the percentage of distractors struck. Results: ANCOVA (age as covariate) showed participants struck significantly more distractors (participants without comorbid ADHD, 22.71% [SE 1.47]; participants with comorbid ADHD, 23.56% [1.47]; and controls, 15.59% [0.68]). Participants with comorbid ADHD struck significantly fewer targets (119.74 [2.77]) than controls, but no difference was found between participants without comorbid ADHD (122.66 [2.77]) and controls (127.00 [1.28]). Participants and controls did not differ significantly in movement speed and movement area. Just over 20% of participants with tics fell below the age-predicted norm in striking distractors, whereas fewer than 10% fell outside age-predicted norms in other task parameters. Conclusions: In children with tics (without comorbid ADHD), acting upon both targets and distractors suggests reduced ability to suppress responses to potential triggers for action. This may be related to increased sensorimotor noise or abnormal sensory gating.

Current pharmacotherapy for tic disorders.

Introduction: Though many unanswered questions about the pathophysiology of Tourette Syndrome remain, several pharmacotherapies for tics have been studied, with varying results in terms of efficacy and the strength of evidence.Areas covered: This literature review encompasses pharmacotherapies for tics. The pharmacotherapies discussed in this review include: alpha agonists, antipsychotics, topiramate, botulinum toxin, and dopamine depleters.Expert opinion: Once the presence of tics is confirmed and psychoeducation and support are provided to patients and caregivers, one must examine the degree of tic-related impairment and the presence of psychiatric comorbidities. These factors influence treatment decisions as the presence of comorbidity and related impairment may shift the treatment target. When selecting a medication for tics, the presence of ADHD (the most frequent comorbidity) strengthens the case for choosing an alpha agonist. The case for antipsychotic medications is strongest when tic-related impairment is severe and/or the tics are refractory to more conservative measures. All medications require drug safety monitoring procedures and reevaluation over time.

Prescriptions for Alpha Agonists and Antipsychotics in Children and Youth with Tic Disorders: A Pharmacoepidemiologic Study.

Background: Trends in the use of antipsychotics and alpha agonists for the treatment of tic disorders in Canadian children, and how closely these trends align with evidence-based guidelines on the pharmacotherapy of tic disorders, have not been explored. Methods: IQVIA's Canadian Disease and Therapeutic Index, a survey-based data set, was used to identify prescription patterns by physicians. Respondents recorded all patient visits during a 48-hour period in each quarter of the year, including patient age, gender, drug recommendation and therapeutic indication. Recommendations for alpha agonists and antipsychotics from 2012 to 2016 were analysed for children and adolescents with tic disorders. Results: Risperidone and clonidine were the most commonly recommended medications for tic disorders over the study period, with 36,868 and 35,500 recommendations in 2016, respectively. Recommendations for clonidine increased over the study period, whereas those for risperidone decreased. Guanfacine (approved in Canada in 2013) was used less frequently than clonidine. Clonidine was more frequently recommended than antipsychotics in children younger than 6, in whom antipsychotic recommendations were uncommon. Aripiprazole was the second most commonly recommended antipsychotic for tic disorders, with 22,892 recommendations in 2016. Of the first-generation antipsychotics, pimozide was most commonly recommended (11,334 recommendations in 2016); haloperidol was infrequently recommended. Discussion: The trends observed are in line with guideline recommendations reflected in the decreasing use of risperidone, and the growing use of clonidine and guanfacine. The growing use of aripiprazole is likely due to emerging evidence from clinical trials supporting its efficacy for tics. Recommendations for pimozide and haloperidol were limited, likely due to the greater adverse effects associated with these medications.

Knowledge and Attitudes About Epilepsy Surgery Among Family Doctors in Ontario.

BACKGROUND: Approximately 30% of patients with epilepsy have medically intractable seizures, and a proportion of them are candidates for surgical treatment. The efficacy and safety of epilepsy surgery have been supported by a large number of studies, yet only a small minority of such patients in Ontario receive surgery. METHODS: Family physicians in Ontario were surveyed regarding demographics, referral practices and general knowledge about epilepsy surgery. Four hundred surveys were mailed to randomly selected family physicians using contact information from the College of Physicians and Surgeons of Ontario website. RESULTS: The response rate was 50%. The majority of family physicians (81%) always refer patients with epilepsy, most often to neurologists. General knowledge of epilepsy was mixed, with 53.7% feeling that surgery should be considered in selected cases for the treatment of epilepsy, though 53.2% did not know what type of epilepsy could be surgically treated. CONCLUSIONS: The results suggest a relatively low level of knowledge among family physicians in terms of when surgery ought to be considered, the types of epilepsy that are amenable to surgical treatment and the risks and benefits of epilepsy surgery. A lack of knowledge in these areas may partly underlie the low referral rates of epilepsy patients, though the results show that the majority of family physicians refer their patients with epilepsy to neurologists. Other factors must be considered, such as access to neurologists, epileptologists and surgical resources. Education campaigns directed at family physicians may improve knowledge and change referral practices. Future studies need to examine these possibilities.

Visual cues signaling object grasp reduce interference in motor learning.

Recent motor learning studies show that human subjects and nonhuman primates form neural representations of novel mechanical environments and associated forces. Whereas proficient adaptation is seen for a single force field, when faced with multiple novel force environments, movement performance and in particular the ability to switch between different force environments declines. It is difficult to reconcile these findings with the notion that primates can proficiently switch between multiple motor skills. Conceivably, particular kinds of sensory, cognitive, or perceptual contextual cues are required. This study examined the effect of visual feedback on motor learning, in particular, cues that simulated interaction with a virtual object. A robot arm was used to deliver novel patterns of forces (force fields) to the limb during reaching movements. We tested the possibility that subjects transition more easily between novel forces and their sudden absence when they are accompanied by visual cues that relate to object grasp. We used a virtual display system to present subjects with different kinds of visual feedback during reaching, including illusory feedback, indicating grasp of a virtual object during reaching in the force field, and object release in the absence of forces. Throughout the experiment, subjects in fact maintained grasp of the robot. We found that, indeed, the most effective visual cues were those associating the force field with grasp of the virtual object and the absence of the force field with release of the object. Our findings show more broadly that specific visual cues can protect motor skills from interference.

Distinct haptic cues do not reduce interference when learning to reach in multiple force fields.

BACKGROUND: Previous studies of learning to adapt reaching movements in the presence of novel forces show that learning multiple force fields is prone to interference. Recently it has been suggested that force field learning may reflect learning to manipulate a novel object. Within this theoretical framework, interference in force field learning may be the result of static tactile or haptic cues associated with grasp, which fail to indicate changing dynamic conditions. The idea that different haptic cues (e.g. those associated with different grasped objects) signal motor requirements and promote the learning and retention of multiple motor skills has previously been unexplored in the context of force field learning. METHODOLOGY/PRINCIPLE FINDINGS: The present study tested the possibility that interference can be reduced when two different force fields are associated with differently shaped objects grasped in the hand. Human subjects were instructed to guide a cursor to targets while grasping a robotic manipulandum, which applied two opposing velocity-dependent curl fields to the hand. For one group of subjects the manipulandum was fitted with two different handles, one for each force field. No attenuation in interference was observed in these subjects relative to controls who used the same handle for both force fields. CONCLUSIONS/SIGNIFICANCE: These results suggest that in the context of the present learning paradigm, haptic cues on their own are not sufficient to reduce interference and promote learning multiple force fields.

Proactive interference as a result of persisting neural representations of previously learned motor skills in primary motor cortex.

Learning to control movements in different dynamic environments is marked by proactive interference; learning a first skill interferes with the subsequent learning of a second one. The neural basis of this effect is poorly understood. We tested the idea that proactive interference results from persisting neural representations of previously learned skills in the primary motor cortex (M1). We used repetitive transcranial magnetic stimulation (rTMS) of M1 to disrupt retention of a recently learned motor skill. If interference results from the retention of this skill then its disruption should be associated with reduced interference. Subjects reached to targets while interacting with a robotic arm that applied force fields to the limb. Fifteen minutes of 1-Hz rTMS to M1 impaired the retention of a first force field, and more importantly, reduced proactive interference when subjects learned a second one. Our findings suggest that retention and interference are linked at the level of M1.

Role of cocontraction in arm movement accuracy.

Cocontraction (the simultaneous activation of antagonist muscles around a joint) provides the nervous system with a way to adapt the mechanical properties of the limb to changing task requirements-both in statics and during movement. However, relatively little is known about the conditions under which the motor system modulates limb impedance through cocontraction. The goal of this study was to test for a possible relationship between cocontraction and movement accuracy in multi-joint limb movements. The electromyographic activity of seven single- and double-joint shoulder and elbow muscles was recorded using surface electrodes while subjects performed a pointing task in a horizontal plane to targets that varied randomly in size. Movement speed was controlled by providing subjects with feedback on a trial-to-trial basis. Measures of cocontraction were estimated both during movement and during a 200-ms window immediately following movement end. We observed an inverse relationship between target size and cocontraction: as target size was reduced, cocontraction activity increased. In addition, trajectory variability decreased and endpoint accuracy improved. This suggests that, although energetically expensive, cocontraction may be a strategy used by the motor system to facilitate multi-joint arm movement accuracy. We also observed a general trend for cocontraction levels to decrease over time, supporting the idea that cocontraction and associated limb stiffness are reduced over the course of practice.