Movement Disorder Experts Research Articles

Dyskinesia estimation during activities of daily living using wearable motion sensors and deep recurrent networks

Levodopa-induced dyskinesias are abnormal involuntary movements experienced by the majority of persons with Parkinson’s disease (PwP) at some point over the course of the disease. Choreiform as the most common phenomenology of levodopa-induced dyskinesias can be managed by adjusting the dose/frequency of PD medication(s) based on a PwP’s motor fluctuations over a typical day. We developed a sensor-based assessment system to provide such information. We used movement data collected from the upper and lower extremities of 15 PwPs along with a deep recurrent model to estimate dyskinesia severity as they perform different activities of daily living (ADL). Subjects performed a variety of ADLs during a 4-h period while their dyskinesia severity was rated by the movement disorder experts. The estimated dyskinesia severity scores from our model correlated highly with the expert-rated scores (r = 0.87 (p < 0.001)), which was higher than the performance of linear regression that is commonly used for dyskinesia estimation (r = 0.81 (p < 0.001)). Our model provided consistent performance at different ADLs with minimum r = 0.70 (during walking) to maximum r = 0.84 (drinking) in comparison to linear regression with r = 0.00 (walking) to r = 0.76 (cutting food). These findings suggest that when our model is applied to at-home sensor data, it can provide an accurate picture of changes of dyskinesia severity facilitating effective medication adjustments.

Phenotypic Features of Isolated Essential Tremor, Essential Tremor Plus, and Essential Tremor-Parkinson’s Disease in a Movement Disorders Clinic

Background:Patients with essential tremor were initially considered to have isolated tremor, but additional motor and non-motor features have been increasingly recognized. The term “essential tremor plus” was adopted by the Task Force on Tremor of the International Parkinson and Movement Disorder Society to describe essential tremor patients with additional neurologic signs.Objectives:To characterize essential tremor patients and their phenotypes in a movement disorders clinic population in the context of the new tremor classification.Methods:Demographic, clinical, historical, treatment, and diagnostic data were retrospectively collected on 300 patients diagnosed by movement disorder experts with essential tremor. Patients were classified as having essential tremor, essential tremor plus, or essential tremor-Parkinson’s disease combination, and features between these groups were compared.Results:Of the 300 patients, 20.7% were classified as isolated essential tremor, 53.3% as essential tremor plus, and 26.0% as essential tremor-Parkinson’s disease. There was no significant difference in the duration of tremor symptoms. Essential tremor plus patients were more likely to have dystonia, tandem gait abnormalities, head tremor and greater tremor severity. Essential tremor-Parkinson’s disease patients were more likely to have RBD symptoms. There was no significant difference in cognitive impairment between essential tremor plus and essential tremor-Parkinson’s disease patients.Conclusions:Additional motor and non-motor features, including parkinsonism, are common in patients with essential tremor. Further studies are needed to clarify essential tremor phenotypes and to provide insights into possible subtypes.Highlights:300 patients with essential tremor from a movement disorders clinic were re-classified based on the Movement Disorder Society Consensus Statement on the Classification of Tremors. Additional motor and non-motor features, including parkinsonism, were common, and only 20.7% of patients remained classified as isolated essential tremor.

The TOPAZ study: a home-based trial of zoledronic acid to prevent fractures in neurodegenerative parkinsonism

The Trial of Parkinson’s And Zoledronic acid (TOPAZ, https://clinicaltrials.gov/ct2/show/NCT03924414) is a unique collaboration between experts in movement disorders and osteoporosis to test the efficacy of zoledronic acid, an FDA-approved parenteral treatment for osteoporosis, for fracture prevention in people with neurodegenerative parkinsonism. Aiming to enroll 3,500 participants age 65 years or older, TOPAZ is one of the largest randomized, placebo-controlled clinical trials ever attempted in parkinsonism. The feasibility of TOPAZ is enhanced by its design as a U.S.- wide home-based trial without geographical limits. Participants receive information from multiple sources, including specialty practices, support groups and websites. Conducting TOPAZ in participants’ homes takes advantage of online consent technology, the capacity to confirm diagnosis using telemedicine and the availability of research nursing to provide screening and parenteral therapy in homes. Home-based clinical research may provide an efficient, convenient, less expensive method that opens participation in clinical trials to almost anyone with parkinsonism.

Severe Acute Respiratory Syndrome Coronavirus 2, Olfactory Mucosa, and the Entrance in the Central Nervous System: Expanding the Evidence?

Meinhardt, J, Radke, J, Dittmayer, C, et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat Neurosci 2021; 24( 2): 168– 175. https://doi.org/10.1038/s41593-020-00758-5. The world faces a unique and historic challenge as a result of the pandemic associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Beyond the respiratory compromise, SARS-CoV-2 infection produces a myriad of neurological manifestations that have been progressively characterized.1 These neurological manifestations can potentially be (1) a consequence of the pulmonary and systemic disease, (2) attributed to a postinfectious (immune-mediated) mechanism, or (3) related to the direct viral central nervous system (CNS) invasion (either via trans-synaptic spreading or through the disruption of the blood–brain barrier). The lack of detection of SARS-CoV-2 in the cerebrospinal fluid in most patients with coronavirus disease 2019 (COVID-19)–related encephalitis, despite evidence of brain inflammation, suggests an immune-mediated mechanism rather than a direct viral invasion.1, 2 The neurotropism of coronaviruses is known and the recent detection of viral RNA in the brains of a subset of patients with COVID-19 led to the hypothesis of SARS-CoV-2 to reach the CNS. Because of the high number of patients with COVID-19 experiencing hyposmia, the trans-synaptic olfactory pathway has been pointed to as the route for entry into the CNS.3 A ramification of this theory affecting us, movement disorders experts, is the hypothetical link between SARS-CoV-2 infection and Parkinson's disease development.4 The featured article by Meinhardt and colleagues5 represents the most extensive postmortem study published so far. The authors assessed the olfactory mucosa and several defined CNS regions to address the important question of whether the olfactory mucosa acts as an entrance for SARS-CoV-2 into the CNS.5 The rather comprehensive evaluation of the tissue samples from 33 patients who died in the context of severe COVID-19 infection included detailed histological and genetic assessments. As a first step, the authors mapped the regional presence of SARS-CoV-2 RNA by real-time quantitative polymerase chain reaction and subgenomic RNA. Interestingly, the olfactory mucosa revealed the highest viral load compared with other tissue samples such as the oral mucosa or trigeminal ganglion. Only active viral replication was identified in the olfactory and oral mucosa. In additional analyses, the SARS-CoV-2 RNA in situ hybridization technique showed intense signaling in the mucous layer and cells of the olfactory epithelium, whereas it was absent in the olfactory sensory neurons. In line with this result, the ultrastructural imaging using electron microscopy showed both extracellular and intracellular viral particles within different cellular compartments of the olfactory epithelium. To further characterize which cells within the olfactory mucosa were invaded by the virus, they performed immunofluorescence colocalization studies. Remarkably, in 3 of 33 patients, the authors found colocalization of the SARS-CoV-2 spike protein with Olig2, an oligodendrocyte marker. This finding provided evidence of the presence of the viral protein in the olfactory sensory neurons. Finally, SARS-CoV-2 was not found in the neuronal or glial cells of the CNS parenchyma of the studied patients. Overall, these data suggested that in the absence of angiotensin-converting enzyme 2 receptors, such as in the olfactory neuronal cells, SARS-CoV-2 infection could be mediated through a transcytosis mechanism: from the olfactory mucosa cells to the olfactory neuronal cells. However, it cannot be discarded that other receptors may facilitate cell entry and infectivity.6 Furthermore, the virus could have been transported through the blood vessels into the brain, as the virus was also found in blood vessel endothelium. The extent to which the virus might have spread into the CNS in those 3 cases remains speculative, as neither viral RNA within the brain parenchyma or neuron-to-neuron propagation were shown. In summary, these results provide evidence that SARS-CoV-2 neuroinvasion can occur at the olfactory neural–mucosal interface. This critical aspect may help to characterize further the extension and mechanisms underlying the entry and action of SARS-CoV-2 in the brain. Broader CNS sampling studies also elucidating the molecular details of SARS-CoV-2 infection and its repercussions in the human brain are needed. Ethical Compliance Statement: Informed patient consent was not necessary for this work. The approval of an institutional review board was not required. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflicts of Interest: No specific funding was received for this work. There are no conflicts of interest relevant to this work. Financial Disclosures for the Previous 12 Months: M.H.G.M. is an employee of the Department of Neurology, Northwestern University Feinberg School of Medicine and has received honoraria from the Autonomous University of Madrid and HM-Puerta del Sur University Hospital and speaker honoraria from Novartis Pharmaceutical.

Neuroimaging in idiopathic adult-onset focal dystonia

We aimed to study the attitude of Italian neurologists in the use of conventional MRI in patients with idiopathic adult-onset focal dystonia. Patients were included in the Italian Dystonia Registry by experts working in different Italian centers. MRI was available for 1045 of the 1471 (71%) patients included in the analysis. Using logistic regression analysis, we found that MRI was more likely to be performed in patients with cervical dystonia, spasmodic dysphonia, or non-task-specific upper limb dystonia, whereas it was less likely to be performed in patients with blepharospasm or task-specific upper limb dystonia. We did not find differences in the number of MRIs performed between neurological centers in Northern, Central, and Southern Italy. We conclude that although the diagnosis of idiopathic adult-onset dystonia is mainly based on clinical grounds, many movement disorder experts rely on MRI to confirm a diagnosis of idiopathic dystonia. We suggest that neuroimaging should be used in patients with adult-onset focal dystonia to rule out secondary forms.

Video-based Parkinson’s disease assessments in a nationwide cohort of Fox Insight participants

IntroductionParkinson’s disease (PD) research is hampered by slow, inefficient recruitment and burdensome in-person assessments that may be challenging to conduct in a world affected by COVID-19. Fox Insight is an ongoing prospective clinical research study that enables individuals to participate in clinical research from their own homes by completing online questionnaires. To date, over 45,000 participants with and without PD have enrolled. We sought to validate self-reported PD diagnosis in the Fox Insight cohort, assess the validity of other self-reported health information, and evaluate the willingness of participants to participate in video-based research studies. MethodsIndividuals with and without self-reported PD enrolled in Fox Insight were invited to participate in this virtual research study. Participants completed online questionnaires and two virtual visits, during which we conducted standard cognitive and motor assessments. A movement disorder expert determined the most likely diagnosis, which was compared to self-reported diagnosis. ResultsA total of 203 participants from 40 U.S. states, 159 with remote clinician-determined PD and 44 without, completed the study (59% male, mean (SD) age 65.7 (9.8)). Level of agreement between self-reported PD diagnosis in Fox Insight and clinician-determined diagnosis was very good ((kappa = 0.85, 95% CI 0.76–0.94). Overall, 97.9% of participants were satisfied with the study, 98.5% were willing to participate in a future observational study with virtual visits, and 76.1% were willing to participate in an interventional trial with virtual visits. ConclusionAmong the Fox Insight cohort, self-reported diagnosis is accurate and interest in virtual research studies is high.

Technology-Enabled Care: Integrating Multidisciplinary Care in Parkinson's Disease Through Digital Technology.

Parkinson's disease (PD) management requires the involvement of movement disorders experts, other medical specialists, and allied health professionals. Traditionally, multispecialty care has been implemented in the form of a multidisciplinary center, with an inconsistent clinical benefit and health economic impact. With the current capabilities of digital technologies, multispecialty care can be reshaped to reach a broader community of people with PD in their home and community. Digital technologies have the potential to connect patients with the care team beyond the traditional sparse clinical visit, fostering care continuity and accessibility. For example, video conferencing systems can enable the remote delivery of multispecialty care. With big data analyses, wearable and non-wearable technologies using artificial intelligence can enable the remote assessment of patients' conditions in their natural home environment, promoting a more comprehensive clinical evaluation and empowering patients to monitor their disease. These advances have been defined as technology-enabled care (TEC). We present examples of TEC under development and describe the potential challenges to achieve a full integration of technology to address complex care needs in PD.

Dystonia and Tremor: A Cross-Sectional Study of the Dystonia Coalition Cohort.

To assess the clinical manifestations and predictors of different types of tremors in individuals with different types of isolated dystonia. Clinical manifestations of tremor were assessed in a multicenter, international cross-sectional, cohort study of 2,362 individuals with all types of isolated dystonia (focal, segmental, multifocal, and generalized) recruited through the Dystonia Coalition. Methodical and standardized assessments of all participants in this cohort revealed the overall prevalence of any type of tremor was 53.3%. The prevalence of dystonic tremor varied from 36.9% to 48.4%, depending on criteria used to define it. To identify the factors associated with tremors in dystonia, the data were analyzed by generalized linear modeling and cluster analyses. Generalized linear modeling indicated 2 of the strongest factors associated with tremor included body region affected by dystonia and recruitment center. Tremor was also associated with severity of dystonia and duration of dystonia, but not with sex or race. The cluster analysis distinguished 8 subgroups within the whole cohort; defined largely by body region with dystonia, and secondarily by other clinical characteristics. The large number of cases evaluated by an international team of movement disorder experts facilitated the dissection of several important factors that influence the apparent prevalence and phenomenology of tremor in dystonia. These results are valuable for understanding the many differences reported in prior studies, and for guiding future studies of the nosology of tremor and dystonia.

Spanish expert consensus on the use of safinamide in Parkinson's disease

Safinamide is a new add-on drug to levodopa for the treatment of Parkinson's disease (PD) with motor fluctuations. Due to the recent incorporation of safinamide into routine clinical practice, no post-authorisation phase IV studies on the safety of safinamide have been conducted to date. This study provides clinical management guidelines for safinamide based on the opinion of a group of experts in movement disorders. This project was developed in 2 phases: 16 local meetings in phase 1 and a national meeting in phase 2. The meetings followed a pre-established agenda. The present clinical practice guidelines are based on the main conclusions reached during the national meeting. The group concluded that safinamide is effective in reducing motor and non-motor fluctuations. PD patients with mild-to-moderate fluctuations benefit most from treatment, although the drug may also improve the clinical status of patients with advanced PD. The dose of other dopaminergic drugs may be reduced after introducing safinamide, which would contribute to reducing such adverse reactions as impulse control disorder. At doses higher than those usually prescribed, safinamide may also improve dyskinesia. The experts agreed that safinamide is well tolerated and causes few adverse reactions when compared with placebo.

High-Resolution Motor State Detection in Parkinson\u2019s Disease Using Convolutional Neural Networks

Patients with advanced Parkinson’s disease regularly experience unstable motor states. Objective and reliable monitoring of these fluctuations is an unmet need. We used deep learning to classify motion data from a single wrist-worn IMU sensor recording in unscripted environments. For validation purposes, patients were accompanied by a movement disorder expert, and their motor state was passively evaluated every minute. We acquired a dataset of 8,661 minutes of IMU data from 30 patients, with annotations about the motor state (OFF,ON, DYSKINETIC) based on MDS-UPDRS global bradykinesia item and the AIMS upper limb dyskinesia item. Using a 1-minute window size as an input for a convolutional neural network trained on data from a subset of patients, we achieved a three-class balanced accuracy of 0.654 on data from previously unseen subjects. This corresponds to detecting the OFF, ON, or DYSKINETIC motor state at a sensitivity/specificity of 0.64/0.89, 0.67/0.67 and 0.64/0.89, respectively. On average, the model outputs were highly correlated with the annotation on a per subject scale (r = 0.83/0.84; p < 0.0001), and sustained so for the highly resolved time windows of 1 minute (r = 0.64/0.70; p < 0.0001). Thus, we demonstrate the feasibility of long-term motor-state detection in a free-living setting with deep learning using motion data from a single IMU.

Delivering patient-centered care in Parkinson's disease: Challenges and consensus from an international panel

An international panel of movement disorders specialists explored the views and perceptions of people with Parkinson's disease (PD) about their condition and its treatment, including the potential mismatch between the clinician's view of the patient's condition and their own view of what aspects of the disease most affect their daily lives. The initiative was focused on Asian countries, so participants comprised experts in the management of PD from key centers in Asia, with additional insight provided by European and the North American movement disorders experts. Analysis of peer-reviewed publications on patient perceptions of PD and the factors that they consider important to their wellbeing identified several contributing factors to the mismatch of views, including gaps in knowledge of PD and its treatment, an understanding of the clinical heterogeneity of PD, and the importance of a multidisciplinary approach to patient care. The faculty proposed options to bridge these gaps to ensure that PD patients receive the personalized treatment they need to achieve the best possible outcomes. It was considered essential to improve patient knowledge about PD and its treatment, as well as increasing the awareness of clinicians of PD heterogeneity in presentation and treatment response. A multidisciplinary and shared-care approach to PD was needed alongside the use of patient-centered outcome measures in clinical trials and clinical practice to better capture the patient experience and improve the delivery of individualized therapy.

Hyperkinetic movement disorders in congenital disorders of glycosylation.

Congenital disorders of glycosylation (CDG) represent an increasing number of rare inherited metabolic diseases associated with abnormal glycan metabolism and disease onset in infancy or early childhood. Most CDG are multisystemic diseases mainly affecting the central nervous system. The aim of the current study was to investigate hyperkinetic movement disorders in patients affected by CDG and to characterize phenomenology based on CDG subtypes. Subjects were identified from a cohort of patients with CDG who were referred to the University Hospital of Catania, Italy. Patients were evaluated by neurologists with expertise in movement disorders and videotaped using a standardized protocol. A variety of hyperkinetic movement disorders was detected in eight unrelated CDG patients. Involuntary movements were generally observed early in childhood, maintaining a clinical stability over time. Distribution ranged from a generalized, especially in younger subjects, to a segmental/multifocal involvement. In patients with phosphomannomutase 2 CDG, the principal movement disorders included dystonia and choreo-athetosis. In patients affected by other CDG types, the movement disorders ranged from pure generalized chorea to mixed movement disorders including dystonia and complex stereotypies. Hyperkinetic movement disorder is a key clinical feature in patients with CDG. CDG should be considered in the differential diagnosis of childhood-onset dyskinesia, especially when associated with ataxia, developmental delay, intellectual disability, autism or seizure disorder.

Inter-rater variability in motor function assessment in Parkinson's disease between experts in movement disorders and nurses specialising in PD management

Introduction and objectiveIn clinical practice, assessing patients with Parkinson's disease (PD) is a complex, time-consuming task. Our purpose is to provide a rigorous and objective evaluation of how motor function in PD patients is assessed by neurologists specialising in movement disorders, on the one hand, and by nurses specialising in PD management, on the other. MethodsWe conducted an observational, cross-sectional, single-centre study of 50 patients with PD (52% men; mean age: 64.7±8.7 years) who were assessed between 5 January 2016 and 20 July 2016. A neurologist and a nurse evaluated motor function in the early morning hours using the Unified Parkinson's Disease Rating Scale (UPDRS) parts III and IV and Hoehn & Yahr (H&Y) scale. Tests were administered in the same PD periods (in 48 patients during the “off” time and in 2 patients during the “on” time). Inter-rater variability was estimated with the intraclass correlation coefficient (ICC). ResultsForty-nine patients (98%) were classified in the same H&Y stage by both raters. Assessment times were similar for both raters. ICC for UPDRS-IV and UPDRS-III total scores were 0.955 (P<.0001) and 0.954 (P<.0001), respectively. The greatest variability was found for UPDRS-III item 29 (gait; ICC=0.746; P<.0001) and the lowest, for item 30 (postural stability; ICC=0.918; P<.0001). ConclusionsMotor function assessment of PD patients by a trained nurse is equivalent to that made by an expert neurologist and takes the same time to complete.

Disease progression in blepharospasm: a 5-year longitudinal study.

The clinical manifestation of dystonic spasms in blepharospasm (BSP) patients may be heterogeneous. Whether the varying phenomenology of eyelid spasms becomes manifest sequentially during the course of the disease or aggregates in separate clusters according to different disease courses is still unclear. For this purpose, the clinical features in BSP patients were evaluated longitudinally over a 5-year period and also the blink reflex recovery cycle was tested in a subgroup of BSP patients. Sixty BSP patients were videotaped at time 0 and after approximately 5years of follow-up. Two experts in movement disorders, who were blinded to the video order, reviewed the videotapes and scored the severity of BSP using the Blepharospasm Severity Rating Scale. Changes in the R2 recovery index were also evaluated in 18 patients twice, i.e. upon enrolment and at the follow-up. The severity of BSP worsened significantly over the 5-year follow-up period owing to the appearance or the increased duration and frequency of prolonged spasms. It was also found that the blink reflex recovery cycle worsened at follow-up in comparison with the baseline. This study shows that the disease progression of BSP is characterized by the appearance or worsening of prolonged spasms. Prolonged spasms are accompanied by changes in the excitability of brainstem interneurons. Aging-related effects may exacerbate the pathophysiological mechanisms underlying spasms.

Tackling the care crisis in PD in East-Saxony, Germany – #Improve diagnosis and therapy in Parkinson's disease #Telemedicine-based care management #Intersectoral and interdisciplinary collaboration #Cost containment and quality improvement

Introduction: Four major problems in Parkinson's disease PD frame the current care crisis in Saxony and beyond in Germany: 1. Prevalence of PD in Germany is reported with 220:100.000. Data from AOK Plus in Saxony shows that the PD population with ICD code G20. idiopathic PD is at 20,000 which is far higher than what would be expected from prevalence alone. In Saxony alone, the population in need is already 2.5 times higher than expected with growing trends due to life expectancy. 2. Specialist care of PD nowadays takes place predominantly in larger cities, while in many rural regions there is an under-supply. Due to limited capacities of office-based neurologists time and specialised knowledge, motor fluctuations in advanced PD are often recognized at a late stage, leading to suboptimal treatment, unnecessary handicaps in daily life, frequent shifts to neurological clinics where patients are usually hospitalized for often unnecessary multi-modal complex treatment. This blocks capacities at expert centres, leading to long waitinglists and patients with advanced PD do not receive timely access to advancded threrapies Deep-Brain-Stimulation, Apomorphin infusion, Duodopa pumps. 3. Lack of objective measurements prevents effective and timely management of PD in clinical practice, especially in the outpatient setting. Current methods patient histories, diaries show validity and reliability problems and test and retest scores in current methods e.g. UPDRS have low intra and inter-rated reliability. 4. Uncontrolled PD e.g. dyskinesia, fluctuations is associated with significantly higher overall costs than controlled PD. Cost drivers of PD include onset of motor fluctuations & dyskinesias and increasing costs with worse motor off/on & UPDRS state. Bad mobility is a predictor of hospitalization and a high re-hospitalization rate. Method: Care Concept - Introduction of telemedicine-based care management for improved diagnosis and treatment of PD will sustainably change intersectoral and interdisciplinary collaboration, especially in East-Saxony with low supply. Through health economic evaluation based on profitability calculation, a prospective analysis of saving potentials and quality of care improvements was conducted. Results: By incorporating specialized expertise of movement disorder experts via telemedical approach, diagnostic accuracy can be improved. In particular, if improving guideline-based treatment across all care sectors inter-sectoral and interdisciplinary through a consistently structured and controlled care process. Objective measurement by means of the Parkinson-Kineto-Graph PKG, can accurate depict motor symptoms which drives the decision to start or change treatment dose; type, timing. For patients, this can improve the quality of life and increases safety, by preventing events e.g. fractures caused by fall. Cost savings based on population in East-Saxony achievable: ∼€18.9mio overall – savings that could provide economical provision of care for PD for 3 years. Savings can be achieved through case shifts from inpatient to outpatient care, non-medical and reduced drug costs. Conclusions: The new care approach is tackling the crisis at its roots. It changes the current treatment setting to address the need for specialised care. Specialists’ knowledge on the treatment of PD can be made available locally, releaving the distress of office-based neurologists by enabling them to treat their patients most accurately.

Movement disorders phenomenology in focal motor seizures

IntroductionAlthough focal motor seizures may resemble one or more movement disorders their phenomenology and prevalence remain uncertain. MethodsTo examine the extent to which focal motor seizures can present with a phenomenology fulfilling diagnostic criteria for movement disorders, 100 consecutive patients with focal motor seizures were rated by movement disorders experts, epileptologists, and general neurologists. ResultsA focal motor seizure phenomenologically manifested as a defined movement disorder in 29% of the patients from a consecutive video-EEG documented cohort as per consensus among experts: myoclonus and dystonia (10 and 9 cases, respectively) were the most common movement disorders, followed by chorea (4), stereotypies (3) myoclonus-dystonia (2), and tremor (1). ConclusionsMovement disorders and focal motor epilepsy share overlapping movement phenomenology.

Expert recommendations for diagnosing cervical, oromandibular, and limb dystonia.

Diagnosis of focal dystonia is based on clinical grounds and is therefore open to bias. To date, diagnostic guidelines have been only proposed for blepharospasm and laryngeal dystonia. To provide practical guidance for clinicians with less expertise in dystonia, a group of Italian Movement Disorder experts formulated clinical diagnostic recommendations for cervical, oromandibular, and limb dystonia. A panel of four neurologists generated a list of clinical items related to the motor phenomenology of the examined focal dystonias and a list of clinical features characterizing neurological/non-neurological conditions mimicking dystonia. Thereafter, ten additional expert neurologists assessed the diagnostic relevance of the selected features and the content validity ratio was calculated. The clinical features reaching a content validity ratio > 0.5 contributed to the final recommendations. The recommendations retained patterned and repetitive movements/postures as the core feature of dystonia in different body parts. If present, a sensory trick confirmed diagnosis of dystonia. In the patients who did not manifest sensory trick, active exclusion of clinical features related to conditions mimicking dystonia (features that would be expected to be absent in dystonia) would be necessary for dystonia to be diagnosed. Although reliability, sensitivity, and specificity of the recommendations are yet to be demonstrated, information from the present study would hopefully facilitate diagnostic approach to focal dystonias in the clinical practice and would be the basis for future validated diagnostic guidelines.

Consenso de expertos españoles sobre el uso de la safinamida en la enfermedad de Parkinson

Safinamide is a new add-on drug to levodopa for the treatment of Parkinson's disease (PD) with motor fluctuations. Due to the recent incorporation of safinamide into routine clinical practice, no post-authorisation phase IV studies on the safety of safinamide have been conducted to date. This study provides clinical management guidelines for safinamide based on the opinion of a group of experts in movement disorders. This project was developed in 2 phases: 16 local meetings in phase 1 and a national meeting in phase 2. The meetings followed a pre-established agenda. The present clinical practice guidelines are based on the main conclusions reached during the national meeting. The group concluded that safinamide is effective in reducing motor and non-motor fluctuations. PD patients with mild-to-moderate fluctuations benefit most from treatment, although the drug may also improve the clinical status of patients with advanced PD. The dose of other dopaminergic drugs may be reduced after introducing safinamide, which would contribute to reducing such adverse reactions as impulse control disorder. At doses higher than those usually prescribed, safinamide may also improve dyskinesia. The experts agreed that safinamide is well tolerated and causes few adverse reactions when compared with placebo.

Parkinson\u2019s Disease Diagnostic Observations (PADDO): study rationale and design of a prospective cohort study for early differentiation of parkinsonism

BackgroundDifferentiation of Parkinson’s disease (PD) from the various types of atypical parkinsonism (AP) such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), corticobasal syndrome (CBS) and vascular parkinsonism (VP), can be challenging, especially early in the disease course when symptoms overlap. A major unmet need in the diagnostic workup of these disorders is a diagnostic tool that differentiates the various disorders, preferably in the earliest disease stages when the clinical presentation is similar. Many diagnostic tests have been evaluated, but their added value was studied mostly in retrospective case-control studies that included patients with a straightforward clinical diagnosis. Here, we describe the design of a prospective cohort study in patients with parkinsonism in an early disease stage who have an uncertain clinical diagnosis. Our aim is to evaluate the diagnostic accuracy of (1) detailed clinical examination by a movement disorder specialist, (2) magnetic resonance imaging (MRI) techniques and (3) cerebrospinal fluid (CSF) biomarkers.Methods/designPatients with parkinsonism with an uncertain clinical diagnosis and a disease course less than three years will be recruited. Patients will undergo extensive neurological examination, brain MRI including conventional and advanced sequences, and a lumbar puncture. The diagnosis (including level of certainty) will be defined by a movement disorders expert, neuroradiologist and neurochemist based on clinical data, MRI results and CSF results, respectively. The clinical diagnosis after three years’ follow-up will serve as the “gold standard” reference diagnosis, based on consensus criteria and as established by two movement disorder specialists (blinded to the test results). Diagnostic accuracy of individual instruments and added value of brain MRI and CSF analysis after evaluation by a movement disorder expert will be calculated, expressed as the change in percentage of individuals that are correctly diagnosed with PD or AP.DiscussionThis study will yield new insights into the diagnostic value of clinical evaluation by a movement disorder specialist, brain MRI and CSF analysis in discriminating PD from AP in early disease stages. The outcome has the potential to help clinicians in choosing the optimal diagnostic strategy for patients with an uncertain clinical diagnosis.Trial registrationNCT01249768, registered November 26 2010.

Diagnostic Criteria for Parkinson's Disease: From James Parkinson to the Concept of Prodromal Disease.

The diagnosis of Parkinson’s disease (PD) is based on clinical features and differently to the common opinion that detecting this condition is easy, seminal clinicopathological studies have shown that up one-fourth of patients diagnosed as PD during life has an alternative diagnosis at postmortem. The misdiagnosis is even higher when only the initial diagnosis is considered, since the diagnostic accuracy improves by time, during follow-up visits. Given that the confirmation of the diagnosis of PD can be only obtained through neuropathology, to improve and facilitate the diagnostic–therapeutic workup in PD, a number of criteria and guidelines have been introduced in the last three decades. In the present paper, we will critically re-appraise the main diagnostic criteria proposed for PD, with particular attention to the recently published criteria by the International Parkinson and Movement Disorder Society (MDS) task force, underlying their novelty and focusing on the diagnostic issues still open. We also emphasize that the MDS-PD criteria encompass the two main previous sets of diagnostic criteria (United Kingdom PD Society Brain Bank and Gelb’s criteria), introducing at the same time new aspects as the use of non-motor symptoms as additional diagnostic features, and the adoption of the concept of prodromal PD, crucial to enroll in clinical trials PD patients in the very early phase of the disease. To better understand the real diffusion of the new MDS-PD diagnostic criteria among neurologists, we have also collected selective opinions of sixteen movement disorder experts from various world regions on their practical approach for the clinical diagnosis of PD. Results from this brief survey showed that, although innovative and complete, the revised diagnostic criteria produced by MDS task force are still scarcely employed among clinicians. We believe that both national and international scientific societies should operate in the future for a broader diffusion of these criteria with specific initiatives, including dedicated events and teaching courses.