Abstract Dystonia is a neurological movement disorder characterised by abnormal involuntary movements and postures, particularly affecting the head and neck. However, current clinical assessment ...methods for dystonia rely on simplified rating scales which lack the ability to capture the intricate spatiotemporal features of dystonic phenomena, hindering clinical management and limiting understanding of the underlying neurobiology. To address this, we developed a visual perceptive deep learning framework that utilizes standard clinical videos to comprehensively evaluate and quantify disease states and the impact of therapeutic interventions, specifically deep brain stimulation. This framework overcomes the limitations of traditional rating scales and offers an efficient and accurate method that is rater-independent for evaluating and monitoring dystonia patients. To evaluate the framework, we leveraged semi-standardized clinical video data collected in three retrospective, longitudinal cohort studies across seven academic centres. We extracted static head angle excursions for clinical validation and derived kinematic variables reflecting naturalistic head dynamics to predict dystonia severity, subtype, and neuromodulation effects. The framework was also applied to a fully independent cohort of generalised dystonia patients for comparison between dystonia sub-types. Computer vision-derived measurements of head angle excursions showed a strong correlation with clinically assigned scores. Across comparisons, we identified consistent kinematic features from full video assessments encoding information critical to disease severity, subtype, and effects of neural circuit interventions, independent of static head angle deviations used in scoring. Our visual perceptive machine learning framework reveals kinematic pathosignatures of dystonia, potentially augmenting clinical management, facilitating scientific translation, and informing personalized precision neurology approaches.
The differential diagnosis of Parkinson's disease has widened considerably in recent years. This chapter aims to summarize the current knowledge on the clinical differential diagnoses of sporadic ...Parkinson's disease. As the number of monogenic familial Parkinson's disease variants and risk factors is growing, so is the number of appreciated etiologies of atypical parkinsonian and other pallidopyramidal syndromes. This work aims at summarizing the current knowledge on both motor and nonmotor neurological signs and symptoms that aid the clinical diagnosis of Parkinson's disease and its differential diagnoses.
Although sleep-wake disturbances are prevalent and well described after traumatic brain injury, their pathophysiology remains unclear, most likely because human traumatic brain injury is a highly ...heterogeneous entity that makes the systematic study of sleep-wake disturbances in relation to trauma-induced histological changes a challenging task. Despite increasing interest, specific and effective treatment strategies for post-traumatic sleep-wake disturbances are still missing. With the present work, therefore, we aimed at studying acute and chronic sleep-wake disturbances by electrophysiological means, and at assessing their histological correlates after closed diffuse traumatic brain injury in rats with the ultimate goal of generating a model of post-traumatic sleep-wake disturbances and associated histopathological findings that accurately represents the human condition. We assessed sleep-wake behavior by means of standard electrophysiological recordings before and 1, 7, and 28 days after sham or traumatic brain injury procedures. Sleep-wake findings were then correlated to immunohistochemically labeled and stereologically quantified neuronal arousal systems. Compared with control animals, we found that closed diffuse traumatic brain injury caused increased sleep need one month after trauma, and sleep was more consolidated. As histological correlate, we found a reduced number of histamine immunoreactive cells in the tuberomammillary nucleus, potentially related to increased neuroinflammation. Monoaminergic and hypocretinergic neurotransmitter systems in the hypothalamus and rostral brainstem were not affected, however. These results suggest that our rat traumatic brain injury model reflects human post-traumatic sleep-wake disturbances and associated histopathological findings very accurately, thus providing a study platform for novel treatment strategies for affected patients.
Abstract
Digital assessments of motor severity could improve the sensitivity of clinical trials and personalise treatment in Parkinson’s disease (PD) but have yet to be widely adopted. Their ability ...to capture
individual
change across the heterogeneous motor presentations typical of PD remains inadequately tested against current clinical reference standards. We conducted a prospective, dual-site, crossover-randomised study to determine the ability of a 16-item smartphone-based assessment (the index test) to predict subitems from the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) as assessed by three blinded clinical raters (the reference-standard). We analysed data from 60 subjects (990 smartphone tests, 2628 blinded video MDS-UPDRS III subitem ratings). Subject-level predictive performance was quantified as the leave-one-subject-out cross-validation (LOSO-CV) accuracy. A pre-specified analysis classified 70.3% (SEM 5.9%) of subjects into a similar category to any of three blinded clinical raters and was better than random (36.7%; SEM 4.3%) classification. Post hoc optimisation of classifier and feature selection improved performance further (78.7%, SEM 5.1%), although individual subtests were variable (range 53.2–97.0%). Smartphone-based measures of motor severity have predictive value at the subject level. Future studies should similarly mitigate against subjective and feature selection biases and assess performance across a range of motor features as part of a broader strategy to avoid overly optimistic performance estimates.
The development of high-intensity magnetic resonance imaging (MRI)-guided focused ultrasound (MRIgFUS) ablation has widened the spectrum of interventional techniques for stereotactic functional ...neurosurgery of lesions. This has resulted in novel incisionless intervention approaches for the therapy of tremor disorders. The safety and efficacy is documented by recent study data.
This article encompasses a description of the technological basis and typical course of MRIgFUS interventions, a comparison to alternative open or incisionless surgical techniques as well as a review of the current evidence base for MRIgFUS ablation in the context of lesional interventions to treat tremor.
Narrative literature review and comparison.
Depending on the surgical target and tremor etiology published trials of MRIgFUS ablation report a reduction of tremor intensity of up to 80% after 6-12 months follow-up without the disadvantages of open brain surgery.
The MRIgFUS functional neurosurgery is conducted only at a limited number of treatment sites. First data on lesions of the thalamic ventral intermediary nucleus (V.im.) as well as subthalamic fiber tracts have been published. These results indicate an effective and safe treatment of tremor disorders by MRIgFUS ablation. Incisionless lesional surgery using MRIgFUS is a significant addition to the interventional armamentarium for functional stereotactic neurosurgery and a potentially valuable alternative to established interventional therapy options for tremor disorders.
IntroductionThe recent introduction of incision-less lesional neurosurgery using Gamma Knife and MRI-guided focused ultrasound has revived interest in lesional treatment options for tremor disorders. ...Preliminary literature researches reveal that the consistency of treatment effects after lesional neurosurgery for tremor has not formally been assessed yet. Similarly, the efficacy of different targets for lesional treatment and incidence of persistent side effects of lesional neurosurgical interventions has not been comprehensively assessed. This work therefore aims to describe a suitable process how to review the existing literature on efficacy and persistent side effects of lesional neurosurgical treatment for tremor due to Parkinson’s disease, essential tremor, multiple sclerosis and midbrain/rubral tremor.Methods and analysisWe will search electronic databases (Medline, Cochrane) and reference lists of included articles for studies reporting lesional interventions for tremor in cohorts homogeneous for tremor aetiology and intervention (technique and target). We will include cohorts with a minimum number of five subjects and follow-up of 2 months. One investigator will perform the initial literature search and two investigators then independently decide which references to include for final efficacy and safety analysis. After settling of disagreement, data will be extracted from articles using a standardised template. We will perform a random-effect meta-analysis calculating standardised mean differences (Hedge’s g) for comparison in Forest plots and subgroup analysis after assessment of heterogeneity using I2 statistics.Ethics and disseminationThis study will summarise the available evidence on the efficacy of lesional interventions for the most frequent tremor disorders, as well as for the incidence rate of persisting side effects after unilateral lesional treatment. This data will be useful to guide future work on incision-less lesional interventions for tremor.Systematic review registrationThis study has been registered with the PROSPERO database (no. CRD42016048049).
Abstract Background Diagnosis and treatment of tremor are largely based on clinical assessment. Whereas in some patients tremor may respond to dopaminergic treatment, in general l -Dopa response to ...tremor varies considerably. The aim of this study was to predict l -Dopa response by accelerometry. Methods We included 60 tremor patients and measured harmonic oscillations by accelerometry. In addition to neurological assessment, we performed l -Dopa challenge tests and the individual tremor response was compared to the amount of harmonic oscillations. Results We found a strong correlation between harmonic oscillations and clinical l -Dopa response. Similarly, harmonic oscillations were significantly greater in patients with subjective tremor reduction upon l -Dopa administration. Conclusions We conclude that harmonic oscillations are a measure for l -Dopa response to tremor irrespective of the underlying disease. Because of the observational character of the study, any causal relation remains speculative. Nevertheless, we propose a novel, non-invasive approach to predict l -Dopa response in tremor patients.