Utilizing Entropy of Cadence to Optimize Cycling Rehabilitation in Individuals With Parkinson's Disease.

BACKGROUND: Previous studies have established that increased Sample Entropy (SampEn) of cadence, a measure of non-linear variability, during dynamic cycling leads to greater improvements in motor function for individuals with Parkinson's disease (PD). However, there is significant variability in responses among individuals with PD due to symptoms and disease progression. OBJECTIVES: The aim of this study was to develop and test a paradigm for adapting a cycling exercise intervention using SampEn of cadence and rider effort to improve motor function. METHODS: Twenty-two participants were randomized into either patient-specific adaptive dynamic cycling (PSADC) or non-adaptive (NA) group. SampEn of cadence was calculated after each of the 12 sessions, and motor function was evaluated using the Kinesia test. Pearson's correlation coefficient was used to analyze the relationship between SampEn of cadence and motor function improvement. Multiple linear regression (MLR) was used to identify the strongest predictors of motor function improvement. RESULTS: Pearson's correlation coefficient revealed a significant correlation between SampEn of cadence and motor function improvements (R2 = -.545, P = .009), suggesting that higher SampEn of cadence led to greater motor function improvement. MLR demonstrated that SampEn of cadence was the strongest predictor of motor function improvement (ß = -8.923, t = -2.632, P = .018) over the BMI, Levodopa equivalent daily dose, and effort. CONCLUSIONS: The findings show that PSADC paradigm promoted a greater improvement in motor function than NA dynamic cycling. These data will be used to develop a predictive model to optimize motor function improvement after cycling in individuals with PD.

A positively charged residue at the Kv1.1 T1 interface is critical for voltage-dependent activation and gating kinetics.

Within the tetramerization domain (T1) of most voltage-gated potassium channels (Kv) are highly conserved charged residues that line the T1-T1 interface. We investigated the Kv1.1 residue R86 located at the narrowest region of the T1 interface. A Kv1.1 R86Q mutation was reported in a child diagnosed with lower limb dyskinesia [1]. The child did not present with episodic ataxia 1 (EA1) symptoms typically associated with Kv1.1 loss-of-function mutations. We characterized the electrophysiological outcome of the R86Q substitution by expressing Kv1.1 in Xenopus laevis oocytes. Mutated α-subunits were able to form functional channels that pass delayed rectifier currents. Oocytes that expressed only mutated α-subunits produced a significant reduction in Kv1.1 current and showed a positive shift in voltage-dependence of activation. In addition, there was substantially slower activation and faster deactivation implying a reduction in the time the channel is in its open state. Oocytes co-injected with both mutated and wild-type cRNA in equal amounts, to mimic the heterozygous condition of the disease, showed a decrease in current amplitude at -10mV and faster deactivation kinetics when compared to the wild-type channel. These findings indicate that T1 plays a role in Kv1.1's voltage-dependent activation and in its kinetics of activation and deactivation.

Functional Movement Disorder as a Prodromal Symptom of Parkinson's Disease-Clinical and Pathophysiological Insights.

Functional movement disorder (FMD) is a common manifestation of functional neurological disorder. FMD can occur alongside other neurological conditions, but especially in patients with established Parkinson's disease (PD). An interesting observation emerging across cohort studies and case series is that FMD can precede the diagnosis of PD, suggesting that FMD may itself be a prodromal symptom of neurodegeneration. Such a notion would have significant clinical implications for the assessment and management of people with FMD, particularly with respect to decisions around the use of auxiliary investigations, counselling, and follow-up. In this Viewpoint we review the evidence concerning the temporal relationship between FMD and PD. We discuss the potential explanations and mechanisms for FMD as a prodromal symptom of PD, and highlight clinical considerations and important outstanding questions in the field. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Severe Acute Motor Exacerbations (SAME) across Metabolic, Developmental and Genetic Disorders.

Acute presentation of severe motor disorders is a diagnostic and management challenge. We define severe acute motor exacerbations (SAME) as acute/subacute motor symptoms that persist for hours-to-days with a severity that compromise vital signs (temperature, breath, and heart rate) and bulbar function (swallowing/dysphagia). Phenomenology includes dystonia, choreoathetosis, combined movement disorders, weakness, and hemiplegic attacks. SAME can develop in diverse diseases and can be preceded by triggers or catabolic states. Recent descriptions of SAME in complex neurodevelopmental and epileptic encephalopathies have broadened appreciation of this presentation beyond inborn errors of metabolism. A high degree of clinical suspicion is required to identify appropriately targeted investigations and management. We conducted a comprehensive literature analysis of etiologies. Reported triggers are described and classified as per pathophysiological mechanism. A video of six cases displaying multiple SAME with diverse outcomes is provided. We identified 50 different conditions that manifest SAME, some associated with developmental regression. Etiologies include disorders of metabolism: energy substrate, amino acids, complex molecules, vitamins/cofactors, minerals, and neurotransmitters/synaptic vesicle cycling. Non-metabolic neurodegenerative and genetic disorders that present with movement disorders and epilepsy can additionally manifest SAME. A limited number of triggers are grouped here, together with an approach to investigations and general management strategies. Several neurogenetic and neurometabolic disorders manifest SAME. Identifying triggers can help in certain cases narrow the differential diagnosis and guide the expeditious application of targeted therapies to minimize adverse developmental and neurological consequences. This process may inform pathogenesis and eventually improve our understanding of the mechanisms that lead to the development of SAME. © 2024 International Parkinson and Movement Disorder Society.

Canine paroxysmal dyskinesia-a review.

Paroxysmal dyskinesias (PDs) are a group of involuntary, hyperkinetic movement disorders that recur episodically and may last seconds to hours. An important feature of PD is that there is no loss of consciousness during the episode. Using a clinical classification, three main types of PDs have been distinguished in canine PD: (1) paroxysmal kinesigenic dyskinesia (PKD) that commences after (sudden) movements, (2) paroxysmal non-kinesigenic dyskinesia (PNKD) not associated with exercise and can occur at rest, and (3) paroxysmal exertion-induced dyskinesia (PED) associated with fatigue. Canine PDs are diagnosed based on the clinical presentation, history, and phenomenology. For the latter, a video recording of the paroxysmal event is extremely useful. An etiological classification of canine PDs includes genetic (proven and suspected), reactive (drug-induced, toxic, metabolic, and dietary), structural (neoplasia, inflammatory, and other structural causes), and unknown causes. In this review, an overview of all reported canine PDs is provided with emphasis on phenotype, genotype, and, where possible, pathophysiology and treatment for each reported canine PD.

Performance of a Tic Screening Tool (MOVeIT) in Comparison to Expert Clinician Assessment in a Developmental-Behavioral Pediatrics Clinic Sample.

Youth with intellectual and developmental disabilities typically have higher rates of tics and stereotypies compared to children with otherwise typical development. Differentiating between these two pediatric movement disorders can be challenging due to overlapping clinical features, but is relevant due to distinct treatment modalities. The current study evaluated sensitivity and specificity of a tic screening measure, the Motor or Vocal Inventory of Tics (MOVeIT) in a pediatric sample enriched for stereotypy and tics. Children (n=199, age 2-15 years old) receiving care in a developmental-behavioral pediatrics clinic underwent a gold-standard diagnostic assessment by a tic expert; these evaluations were compared to the MOVeIT. The MOVeIT demonstrated good sensitivity (89.8%) and relatively lower specificity (57.1%) compared to tic expert for detecting tics in the overall sample. Specificity of the MOVeIT to identify tics improved to 75% when excluding children with co-occurring stereotypy. For children with tics and co-occurring stereotypy, sensitivity remained high (91.9%) but specificity was low (39.1%). The area under the curve (AUC) value to detect tics on the MOVeIT compared to the tic expert gold standard was significantly higher for children without stereotypy (AUC=85.7%) than those with stereotypy (AUC=64.3%, p <0.01). Overall, the ability to detect tics was better in those without co-occurring stereotypy symptoms. Further work is needed to establish the utility of the MOVeIT in populations where there is a high likelihood of co-occurring tics and stereotypy and in general population settings. Accurate distinction between tics and stereotypy will guide choices for intervention and anticipatory guidance for families.

Functional Movement Disorder Is Associated with Abnormal Interoceptive Brain Activity: A Task-based Functional MRI Study.

Background: Aberrant interoceptive processing has been hypothesized to contribute to the pathophysiology of functional neurological disorder, although findings have been inconsistent. Here, we utilized functional magnetic resonance imaging (fMRI) to examine neural correlates of interoceptive attention - the conscious focus and awareness of bodily sensations - in functional movement disorder (FMD). Methods: We used voxelwise analyses to compare blood oxygenation level-dependent responses between 13 adults with hyperkinetic FMD and 13 healthy controls (HCs) during a task requiring attention to different bodily sensations and to an exteroceptive stimulus. Additionally, we examined between-group differences in self-reported measures of interoception and evaluated their relationship with neural activity. Results: Interoceptive conditions (heartbeat, stomach and 'body', indicating sensations from the body part or limb affected in FMD participants) activated a network involving the precuneus, the posterior cingulate cortex (PCC) and caudate nucleus (CN) bilaterally, and the right anterior insula (aINS) (p <0.05, corrected). Group differences in brain activity were mainly driven by processing of disease-related interoceptive signals, which in the FMD group was associated with a broader neural activation than monitoring gastric interoception, while no group differences were detected during cardiac interoception. Differences based on interoceptive focus (body vs heartbeat and stomach) between FMD subjects and HCs were found in PCC, CN, angular gyrus, thalamus, and in the mid-insula (p <0.05, corrected). Conclusions: This is, to our knowledge, the first study showing that FMD is associated with abnormal interoceptive processing in regions involved in monitoring body state, attentional focus, and homeostatic inference.

Trazodone-induced parkinsonism in a middle-aged male: A case report.

Introduction: Trazodone is an antidepressant agent approved for treating major depressive disorders and is also prescribed for insomnia due to its sedative effect. In a few cases, trazodone was associated with parkinsonism. Herein, we describe a case of parkinsonism after a brief exposure to a moderate dose of trazodone. Objective: To describe a case of a patient with trazodone-induced parkinsonism in which the diagnosis was suspected after the exclusion of other common and serious causes. Methods: A case report of trazodone-induced parkinsonism. Clinical Case: A 58-year-old male with sleeping problems was prescribed trazodone 50 mg daily at bedtime. The subject doubled the dosage without medical advice a week later. After 14 days of trazodone treatment, he started to experience difficulty in moving his upper limbs and recurrent falling. Neuroimaging, electrodiagnostic studies, and laboratory exams were unremarkable. Trazodone was discontinued, and the patient fully recovered. Noteworthy, the patient developed a recurrence of the motor symptoms with trazodone-rechallenge. Conclusion: Our case showed reversibly induced parkinsonism after a short intake of a moderate dose of trazodone which was prescribed for insomnia. The patient had a complete recovery after trazodone withdrawal. Noteworthy, the symptoms recurred upon trazodone-rechallenge.

Individualized Physiotherapy of Upper Body Functional Movement Disorder - Two Illustrative Cases.

Background: Information on specialist physiotherapeutic treatment for functional movement disorders is scarce. Previous studies focussed on functional gait disorders and availability of descriptions of the practical application especially for other body regions is very limited. Cases: We present two illustrative cases, demonstrating the key elements of physiotherapy for the treatment of functional movement disorders beyond gait difficulties. The individual applicability of the specific core elements of physiotherapy, adapted to the individual needs of each patient, are described. We also explain, how different sensory stimuli can be used to shift attention away from symptoms and thus reduce them. Moreover, we discuss how patients' agency can be encouraged and how this results in therapy key moments, contributing to a sustained improvement of symptoms. Conclusion: Thus, our case series are intended to guide clinicians and therapists alike, to promote disease-specific physiotherapy for this common and treatable neuropsychiatric disorder.

Unraveling belly dancer's dyskinesia and other puzzling diagnostic contortions: A narrative literature review.

Belly dancer's dyskinesia (BDD) is characterized by involuntary abdominal wall movements that are rhythmic, repetitive, and dyskinetic. The present study aims to review BDD's etiology, pathophysiology, and management. We searched six databases to locate existing reports on BDD published from 1990 to October 2023 in electronic form. A total of 47 articles containing 59 cases were found. The majority of the patients affected by BDD were female, accounting for 61.01% (36/59) of the cases. The mean and median ages were 49.8 (standard deviation: 21.85) and 52 years (range: 7-85), respectively. The BDD was unilateral in only 3.38% (2/59). The most commonly reported causes associated with BDD were 17 idiopathic, 11 drug-induced, 11 postsurgical procedures, 5 pregnancies, and 4 Vitamin B12 deficiencies. BDD is a diagnosis of exclusion, and other more common pathologies with similar presentation should be ruled out initially. Differential diagnostic reasoning should include diaphragmatic myoclonus, cardiac conditions, truncal dystonia, abdominal motor seizures, propriospinal myoclonus, and functional or psychiatric disorders.

Level of knowledge and perceived challenges associated with learning movement disorders topics: a critical review of final-year medical students at a Nigerian private university.

Background: To determine the level of knowledge and challenges associated with learning movement disorders among final-year medical students. Methodology: A cross-sectional survey of 79 final-year medical students at the Madonna University, Elele, Rivers State. Consenting students filled out the study questionnaire, which consisted of socio-demographic variables and questions on the knowledge and challenges of learning movement disorders. Data were collected and analysed using the Statistical Package for Social Sciences Version 20. Results: The mean age of the study participants was 27.41±2.78 years, with a male-to-female ratio of 1.3:1. Almost (91.1%) all the study participants had heard about parkinsonism from their lectures, followed by chorea (88.6%). More than half of the participants knew about one type of movement disorder or the other. Forty-three (54.4%) students expressed difficulty understanding movement disorder lectures. Inadequate exposure to patients with movement disorders and lack of audiovisual aids to enhance learning experience were the greatest challenges in learning movement disorders. Conclusion: Parkinsonism was the most recognized movement disorder among the study participants. More than half of the participants admitted to having challenges with movement disorder lectures. Paucity of movement disorders cases during clinical rotation and lack of teaching aids were cited as major challenges affecting learning and appreciation of movement disorder lectures. Medical educators are encouraged to deploy appropriate methods that optimize learning experience among medical students during movement disorder lectures.

Movement disorder rounds: A 32-year old lady who developed a complex generalized movement disorder in all four limbs after plasma exchange for myelitis.

A 32-year old lady with AQP4-Antibody positive neuromyelitis optica developed a new-onset complex movement disorder after therapeutic plasma exchange, which was initially suspected to be hypocalcemic carpo-pedal spasm. However, when her bilateral, distal predominant, paroxysmal, stereotypic, wrist and finger flexor tonic contractions did not respond to serum calcium correction, other diagnoses were considered. The patient had a dramatic response to oral carbamazepine suggesting that the tonic spasms were likely a spinal movement disorder due to the primary demyelinating pathology.

Dynamic gait stability in people with mild to moderate Parkinson's disease.

BACKGROUND: Falls are a serious health threat for people with Parkinson's disease. Dynamic gait stability has been associated with fall risk. Developing effective fall prevention interventions requires a sound understanding of how Parkinson's disease affects dynamic gait stability. This study compared dynamic gait stability within the Feasible Stability Region framework between people with and without Parkinson's disease during level walking at a self-selected speed. METHODS: Twenty adults with Parkinson's disease and twenty age- and gender-matched healthy individuals were recruited. Dynamic gait stability at two gait instants: touchdown and liftoff, was assessed as the primary outcome measurement. Spatiotemporal gait parameters, including stance phase duration, step length, gait speed, and cadence were determined as explanatory variables. FINDINGS: People with Parkinson's disease walked more slowly (p < 0.001) with a shorter step (p = 0.05), and prolonged stance phase (p = 0.04) than their healthy peers with moderate to large effect sizes. Dynamic gait stability did not show any group-associated differences (p > 0.36). INTERPRETATION: Despite the different gait parameters between groups, people with Parkinson's disease exhibited similar dynamic gait stability to their healthy counterparts. To compensate for the potential dynamic gait stability deficit resulting from slow gait speed, individuals with Parkinson's disease adopted a short step length to shift the center of mass motion state closer to the Feasible Stability Region. Our findings could provide insight into the impact of Parkinson's disease on the control of dynamic gait stability.

A Rare Presentation of Functional Movement Disorder Mimicking Normal Pressure Hydrocephalus.

Herein, we describe a 55-year-old female patient with a functional movement disorder (FMD) who presented with normal pressure hydrocephalus (NPH)-like clinic. The neuroimaging data and positive response to the tap test initially suggested NPH. However, a detailed investigation of the clinic features yielded a final diagnosis of FMD. Via the presentation of this patient, we expand the phenomenology of FMD. To our knowledge, this is the first presentation of a patient with FMD mimicking NPH. Therefore, we think this rare illustration is interesting and may provide valuable perspectives for clinical practice.

Integrated model of care for functional movement disorder: targeting brain, mind and body.

PURPOSE: To describe the therapy approaches and clinical outcomes of an integrated care model for patients with functional movement disorder (FMD). MATERIALS AND METHODS: A retrospective chart review was conducted for all treated individuals with a primary diagnosis of FMD between January 2020 and July 2022. Patients received time-limited integrated therapy (n = 21) (i.e., simultaneous therapy delivered by psychiatry, neurology and physiotherapy), physiotherapy (n = 18) or virtual physiotherapy alone (n = 9). Primary outcomes included the Simplified-Functional Movement Disorders Rating Scale (S-FMDRS) and Clinical Global Impression-Improvement scale (CGI-I) collected at baseline and post-intervention. RESULTS: Forty-eight patients completed treatment (42% male; mean age, 48.5 ± 16.6 years, median symptom duration 30 months). The most common presentations were gait disorder, tremor and mixed hyperkinetic FMD. Common comorbidities included pain and fatigue. Three-quarters of patients had a comorbid psychiatric diagnosis. There was a significant reduction in S-FMDRS score following therapy (71%, p < 0.0001) and 69% had "much" or "very much" improved on the CGI-I. There was no difference between therapy groups. Attendance rates were high for both in-person (94%) and virtual (97%) visits. CONCLUSIONS: These findings support that a time-limited integrated model of care is feasible and effective in treating patients with FMD.

An integrated approach that draws from both mental health and physiotherapy-oriented strategies reframes functional movement disorder treatment targets and clinical outcomes, influences triage criteria, and produces new and innovative therapies.Successful outcomes depend on triaging suitable participants and individualized treatment plans that focus on functional goals.Virtual telerehabilitation in functional movement disorder is effective and offers the opportunity to work with patients in real-time in the environment where they most often experience functional neurological symptoms.

Functional Movement Disorders: Updates and Clinical Overview.

Functional movement disorder (FMD) is a type of functional neurological disorder that is common but often difficult to diagnose or manage. FMD can present as various phenotypes, including tremor, dystonia, myoclonus, gait disorders, and parkinsonism. Conducting a clinical examination appropriate for assessing a patient with suspected FMD is important, and various diagnostic testing maneuvers may also be helpful. Treatment involving a multidisciplinary team, either outpatient or inpatient, has been found to be most effective. Examples of such treatment protocols are also discussed in this review. While recognition and understanding of the disorder has improved over the past few decades, as well as the development of treatments, it is not uncommon for patients and physicians to continue to experience various difficulties when dealing with this disorder. In this review, I provide a practical overview of FMD and discuss how the clinical encounter itself can play a role in patients' acceptance of the diagnosis. Recent neuroimaging studies that aid in understanding the pathophysiology are also discussed.