Theta frequency deep brain stimulation in the subthalamic nucleus improves working memory in Parkinson's disease.

Most research in Parkinson's disease focuses on improving motor symptoms. Yet, up to 80% of patients present with non-motor symptoms that often have a large impact on patients' quality of life. Impairment in working memory, a fundamental cognitive process, is common in Parkinson's disease. While deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms in Parkinson's disease, its impact on cognitive functions is less well studied. Here, we examine the effect of DBS in the theta, beta, low and high gamma frequency on working memory in 20 Parkinson's disease patients with bilateral STN-DBS. A linear mixed effects model demonstrates that STN-DBS in the theta frequency improves working memory performance. This effect is frequency-specific and was absent for beta and gamma frequency stimulation. Further, this effect is specific to cognitive performance, as theta frequency DBS did not affect motor function. A non-parametric cluster-based permutation analysis of whole-brain normative structural connectivity shows that working memory enhancement by theta frequency stimulation is associated with higher connectivity between the stimulated subthalamic area and the right middle frontal gyrus. Again, this association is frequency- and task-specific. These findings highlight the potential of theta frequency STN-DBS as a targeted intervention to improve working memory in patients with Parkinson's disease.

Dynamic properties in functional connectivity changes and striatal dopamine deficiency in Parkinson's disease.

Recent studies in Parkinson's disease (PD) patients reported disruptions in dynamic functional connectivity (dFC, i.e., a characterization of spontaneous fluctuations in functional connectivity over time). Here, we assessed whether the integrity of striatal dopamine terminals directly modulates dFC metrics in two separate PD cohorts, indexing dopamine-related changes in large-scale brain network dynamics and its implications in clinical features. We pooled data from two disease-control cohorts reflecting early PD. From the Parkinson's Progression Marker Initiative (PPMI) cohort, resting-state functional magnetic resonance imaging (rsfMRI) and dopamine transporter (DaT) single-photon emission computed tomography (SPECT) were available for 63 PD patients and 16 age- and sex-matched healthy controls. From the clinical research group 219 (KFO) cohort, rsfMRI imaging was available for 52 PD patients and 17 age- and sex-matched healthy controls. A subset of 41 PD patients and 13 healthy control subjects additionally underwent 18F-DOPA-positron emission tomography (PET) imaging. The striatal synthesis capacity of 18F-DOPA PET and dopamine terminal quantity of DaT SPECT images were extracted for the putamen and the caudate. After rsfMRI pre-processing, an independent component analysis was performed on both cohorts simultaneously. Based on the derived components, an individual sliding window approach (44 s window) and a subsequent k-means clustering were conducted separately for each cohort to derive dFC states (reemerging intra- and interindividual connectivity patterns). From these states, we derived temporal metrics, such as average dwell time per state, state attendance, and number of transitions and compared them between groups and cohorts. Further, we correlated these with the respective measures for local dopaminergic impairment and clinical severity. The cohorts did not differ regarding age and sex. Between cohorts, PD groups differed regarding disease duration, education, cognitive scores and L-dopa equivalent daily dose. In both cohorts, the dFC analysis resulted in three distinct states, varying in connectivity patterns and strength. In the PPMI cohort, PD patients showed a lower state attendance for the globally integrated (GI) state and a lower number of transitions than controls. Significantly, worse motor scores (Unified Parkinson's Disease Rating Scale Part III) and dopaminergic impairment in the putamen and the caudate were associated with low average dwell time in the GI state and a low total number of transitions. These results were not observed in the KFO cohort: No group differences in dFC measures or associations between dFC variables and dopamine synthesis capacity were observed. Notably, worse motor performance was associated with a low number of bidirectional transitions between the GI and the lesser connected (LC) state across the PD groups of both cohorts. Hence, in early PD, relative preservation of motor performance may be linked to a more dynamic engagement of an interconnected brain state. Specifically, those large-scale network dynamics seem to relate to striatal dopamine availability. Notably, most of these results were obtained only for one cohort, suggesting that dFC is impacted by certain cohort features like educational level, or disease severity. As we could not pinpoint these features with the data at hand, we suspect that other, in our case untracked, demographical features drive connectivity dynamics in PD. PRACTITIONER POINTS: Exploring dopamine's role in brain network dynamics in two Parkinson's disease (PD) cohorts, we unraveled PD-specific changes in dynamic functional connectivity. Results in the Parkinson's Progression Marker Initiative (PPMI) and the KFO cohort suggest motor performance may be linked to a more dynamic engagement and disengagement of an interconnected brain state. Results only in the PPMI cohort suggest striatal dopamine availability influences large-scale network dynamics that are relevant in motor control.

Connectivity based on glucose dynamics reveals exaggerated sensorimotor network coupling on subject-level in Parkinson's disease.

PURPOSE: While fMRI provides information on the temporal changes in blood oxygenation, 2- [18F]fluoro-2-deoxy-D-glucose ([18F]FDG)-PET has traditionally offered a static snapshot of brain glucose consumption. As a result, studies investigating metabolic brain networks as potential biomarkers for neurodegeneration have primarily been conducted at the group level. However, recent pioneering studies introduced time-resolved [18F]FDG-PET with constant infusion, which enables metabolic connectivity studies at the individual level. METHODS: In the current study, this technique was employed to explore Parkinson's disease (PD)-related alterations in individual metabolic connectivity, in comparison to inter-subject measures and hemodynamic connectivity. Fifteen PD patients and 14 healthy controls with comparable cognition underwent sequential resting-state dynamic PET with constant infusion and functional MRI. Intrinsic networks were identified by independent component analysis and interregional connectivity calculated for summed static PET images, PET time series and functional MRI. RESULTS: Our findings revealed an intrinsic sensorimotor network in PD patients that has not been previously observed to this extent. In PD, a significantly higher number of connections in cortical motor areas was observed compared to elderly control subjects, as indicated by both static PET and functional MRI (pBonferroni-Holm = 0.027), as well as constant infusion PET and functional MRI connectomes (pBonferroni-Holm = 0.012). This intensified coupling was associated with disease severity (ρ = 0.56, p = 0.036). CONCLUSION: Metabolic connectivity, as revealed by both static and dynamic PET, provides unique information on metabolic network activity. Subject-level metabolic connectivity based on constant infusion PET may serve as a potential marker for the metabolic network signature in neurodegeneration.

A Short Progressive Supranuclear Palsy Quality of Life Scale.

OBJECTIVE: The Progressive Supranuclear Palsy quality of life scale (PSP-QoL) has been shown to be a useful tool for capturing health-related quality of life of patients in "everyday life" and in progressive supranuclear palsy (PSP) research. However, at 45 items in length, the questionnaire can take a long time, exhausting PSP patients, in particular if cognitive impaired, which can have a negative impact on the assessment. The aim of this study was to establish a condensed version of the PSP-QoL for research and routine clinical care. METHODS: In this retrospective study, data originating from a German cohort of PSP patients was analyzed. Data from 245 PSP patients were included in this study. The short PSP-QoL questionnaire was created using a two-factor solution and item-total and inter-item correlations for mental and physical aspects of daily living of the PSP-QoL followed by confirmatory factor analysis. RESULTS: The final scale included 12 items representing mental (five items) and physical symptoms (seven items). The specified two-factor model displayed an excellent fit in the confirmatory factor analysis. The short Progressive Supranuclear Palsy Quality of Life scale (PSP-ShoQoL) correlated moderately with the PSP Rating Scale (r [243] = 0.514, P < 0.001) and Geriatric depression scale (r [231] = 0.548, P < 0.001). Sensitivity to change confirmed a significant decrease in QoL after 12 months. DISCUSSION: In this study, we created a 12-item PSP-ShoQoL designed to "facilitate" daily clinical work that correlated strongly with the PSP-QoL and was sensitive to change. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Tips and tricks in tremor treatment.

Tremor, whether arising from neurological diseases, other conditions, or medication side effects, significantly impacts patients' lives. Treatment complexities necessitate clear algorithms and strategies. Levodopa remains pivotal for Parkinson's tremor, though response variability exists. Some dopamine agonists offer notable tremor reduction targeting D2 receptors. Propranolol effectively manages essential tremor and essential tremor plus (ET/ET +), sometimes with primidone for added benefits, albeit dose-dependent side effects. As reserve medications anticholinergics and clozapine are used for treatment of parkinsonian tremor, 1-Octanol and certain anticonvulsant drugs for tremor of other orign, especially ET. Therapies such as invasive deep brain stimulation and lesional focused ultrasound serve for resistant cases. A medication review is crucial for all forms of tremor, but it is particularly important if medication may have triggered the tremor. Sensor-based detection and non-drug interventions like wristbands and physical therapy broaden diagnostic and therapeutic horizons, promising future tremor care enhancements. Understanding treatment nuances is a key for tailored tremor management respecting patient needs and tolerability. Successful strategies integrate pharmacological, non-invasive, and technological modalities, aiming for optimal symptom control and improved quality of life.

Clinical, serological and genetic predictors of response to immunotherapy in anti-IgLON5 disease.

Anti-IgLON5 disease is a newly defined clinical entity characterized by a progressive course with high disability and mortality rate. While precise pathogenetic mechanisms remain unclear, features characteristic of both autoimmune and neurodegenerative diseases were reported. Data on immunotherapy are limited, and its efficacy remains controversial. In this study, we retrospectively investigated an anti-IgLON5 disease cohort with special focus on clinical, serological and genetic predictors of the immunotherapy response and long-term outcome. Patients were recruited from the GENERATE (German Network for Research on Autoimmune Encephalitis) registry. Along with clinical parameters, anti-IgLON5 immunoglobulin (Ig)G in serum and CSF, anti-IgLON5 IgG1-4, IgA and IgM in serum, neurofilament light chain and glial fibrillary acidic protein in serum as well as human leukocyte antigen-genotypes were determined. We identified 53 patients (symptom onset 63.8 ± 10.3 years, female:male 1:1.5). The most frequent initial clinical presentations were bulbar syndrome, hyperkinetic syndrome or isolated sleep disorder [at least one symptom present in 38% (20/53)]. At the time of diagnosis, the majority of patients had a generalized multi-systemic phenotype; nevertheless, 21% (11/53) still had an isolated brainstem syndrome and/or a characteristic sleep disorder only. About one third of patients [28% (15/53)] reported subacute disease onset and 51% (27/53) relapse-like exacerbations during the disease course. Inflammatory CSF changes were evident in 37% (19/51) and increased blood-CSF-barrier permeability in 46% (21/46). CSF cell count significantly decreased, while serum anti-IgLON5 IgG titre increased with disease duration. The presence of human leukocyte antigen-DRB1*10:01 [55% (24/44)] was associated with higher serum anti-IgLON5 IgG titres. Neurofilament light chain and glial fibrillary acidic protein in serum were substantially increased (71.1 ± 103.9 pg/ml and 126.7 ± 73.3 pg/ml, respectively). First-line immunotherapy of relapse-like acute-to-subacute exacerbation episodes resulted in improvement in 41% (11/27) of patients and early initiation within the first 6 weeks was a predictor for therapy response. Sixty-eight per cent (36/53) of patients were treated with long-term immunotherapy and 75% (27/36) of these experienced no further disease progression (observation period of 20.2 ± 15.4 months). Long-term immunotherapy initiation during the first year after onset and low pre-treatment neurofilament light chain were significant predictors for a better outcome. In conclusion, subacute disease onset and early inflammatory CSF changes support the primary role of autoimmune mechanisms at least at initial stages of anti-IgLON5 disease. Early immunotherapy, prior to advanced neurodegeneration, is associated with a better long-term clinical outcome. Low serum neurofilament light chain at treatment initiation may serve as a potential biomarker of the immunotherapy response.

A systematic practice review: Providing palliative care for people with Parkinson's disease and their caregivers.

BACKGROUND: People with Parkinson's disease has significant and increasing physical, psychosocial and spiritual needs, as well as problems with coordination and continuity of care. Despite the benefits that palliative care could offer, there is no consensus on how it should be delivered. AIM: The aim of this study is to provide a pragmatic overview of the evidence to make clinical recommendations to improve palliative care for people with Parkinson's disease and their caregivers. DESIGN: A systematic review method was adopted to determine the strength of evidence, supported by feedback from an expert panel, to generate the 'do', 'do not do' and 'do not know' recommendations for palliative care. DATA SOURCES: Searches were conducted via OVID to access CINAHL, MEDLINE, EMBASE and the Cochrane Library from 01/01/2006 to 31/05/2021. An additional search was conducted in December 2022. The search was limited to articles that included empirical studies of approaches to enabling palliative care. RESULTS: A total of 62 studies met inclusion criteria. There is evidence that education about palliative care and movement disorders is essential. palliative care should be multi-disciplinary, individualised and coordinated. Proactive involvement and support of caregivers throughout the illness is recommended. Limited data provide referral indicators for palliative care integration. Discussions about advance care planning should be held early. CONCLUSIONS: Consideration of palliative care integration based on symptom burden and personal preferences, coordination and continuity of care are needed to maintain the quality of life of people with Parkinson's disease and their caregivers.

Non-lesional treatments for tremor in Parkinson's disease: A systematic review and meta-analysis.

INTRODUCTION: Tremor is often perceived as severely disabling by patients with idiopathic Parkinson's disease (iPD) and yet ranges among the most difficult symptoms to treat. To date, no comprehensive analysis of non-lesional therapies to manage tremor in iPD exists to base recommendations upon. We therefore present a systematic literature review and meta-analysis assessing the efficacy/effectiveness and safety of non-lesional treatments for tremor in iPD. METHODS: Three electronic databases were searched using a combination of title/abstract keywords complemented by hand-searching of reference lists. A random-effects meta-analysis of standardized mean change scores was conducted where appropriate. RESULTS: Some 114 studies met inclusion criteria involving 8045 patients. The meta-analysis revealed an overall reduction of standardized mean change scores by (-0.93 [CI: -1.42; -0.43], p < 0.001) by 14 different dopaminergic and non-dopaminergic classes of agents. No significant differences were identified between direct comparisons. Subgroup analysis comparing dopamine receptor agonists resulted in superior effects of pramipexole and rotigotine compared with ropinirole. There was little cumulative evidence to support the use of individual non-pharmacological interventions for tremor, except for electrical stimulation. CONCLUSIONS: The results of this meta-analysis suggest a large but nonspecific effect of established pharmacological therapies on tremor in iPD. Based on high-quality studies, there is sufficient evidence to support that levodopa, dopamine receptor agonists, and monoamine oxidase inhibitors provide tremor relief in most patients, while evidence supporting other treatments is less well established. Sufficient evidence to draw conclusions on effects of non-lesional treatments in cases with refractory tremor is lacking.

Prediction of Movement Ratings and Deep Brain Stimulation Parameters in Idiopathic Parkinson's Disease.

BACKGROUND: Deep brain stimulation (DBS) parameter fine-tuning after lead implantation is laborious work because of the almost uncountable possible combinations. Patients and practitioners often gain the perception that assistive devices could be beneficial for adjusting settings effectively. OBJECTIVE: We aimed at a proof-of-principle study to assess the benefits of noninvasive movement recordings as a means to predict best DBS settings. MATERIALS AND METHODS: For this study, 32 patients with idiopathic Parkinson's disease, under chronic subthalamic nucleus stimulation with directional leads, were recorded. During monopolar review, each available contact was activated with currents between 0.5 and 5 mA, and diadochokinesia, rigidity, and tapping ability were rated clinically. Moreover, participants' movements were measured during four simple hand movement tasks while wearing a commercially available armband carrying an inertial measurement unit (IMU). We trained random forest models to learn the relations between clinical ratings, electrode settings, and movement features obtained from the IMU. RESULTS: Firstly, we could show that clinical mobility ratings can be predicted from IMU features with correlations of up to r = 0.68 between true and predicted values. Secondly, these features also enabled a prediction of DBS parameters, which showed correlations of up to approximately r = 0.8 with clinically optimal DBS settings and were associated with congruent volumes of tissue activated. CONCLUSION: Movement recordings from customer-grade mobile IMU carrying devices are promising candidates, not only for remote symptom assessment but also for closed-loop DBS parameter adjustment, and could thus extend the list of available aids for effective programming beyond imaging techniques.

Blood-based biomarker in Parkinson's disease: potential for future applications in clinical research and practice.

The clinical presentation of Parkinson's disease (PD) is both complex and heterogeneous, and its precise classification often requires an intensive work-up. The differential diagnosis, assessment of disease progression, evaluation of therapeutic responses, or identification of PD subtypes frequently remains uncertain from a clinical point of view. Various tissue- and fluid-based biomarkers are currently being investigated to improve the description of PD. From a clinician's perspective, signatures from blood that are relatively easy to obtain would have great potential for use in clinical practice if they fulfill the necessary requirements as PD biomarker. In this review article, we summarize the knowledge on blood-based PD biomarkers and present both a researcher's and a clinician's perspective on recent developments and potential future applications.

Rhombencephalitis associated with isolated Zic4-antibodies in Paraneoplastic cerebellar degeneration: a case report.

BACKGROUND: Cerebellar degeneration as a consequence of a malignancy is a rare condition most commonly related to the presence of anti-Yo, anti-Hu, and anti-Tr/DNER antibodies. In recent years, several reports have indicated Zinc-finger protein 4 (Zic4) antibodies being associated with paraneoplastic cerebellar degeneration (PCD) in patients with small cell lung carcinoma. However, the prevalence and the significance of Zic4-antibodies may be underestimated due to their co-occurrence with more frequent antibodies such as anti-Hu. A literature review of isolated Zic4 mediated paraneoplastic syndromes yielded 14 cases reporting mainly benign clinical courses when treated early. CASE PRESENTATION: We present the case of a 67-year-old woman with progressive Zic4 antibody mediated PCD and rhombencephalitis. Immunomodulatory treatment, including intravenous methylprednisolone, plasmaphereses, and intravenous immunoglobulin (IVIG) was administered. Small cell lung cancer (SCLC) was detected, lobectomy performed and cyclophosphamide started. Despite this considerable therapeutic effort, rhombencephalitis led to defiant dysautonomia. CONCLUSION: Paraneoplastic syndromes related to isolated Zic4 antibodies are rare and typically show a benign clinical course. Here, we present the first case of a rapidly progressive isolated Zic4 associated PCD and rhombencephalitis. Despite considerable therapeutic efforts, the patient passed away on autonomic dysfunction, highlighting the significance of Zic4 associated disease.

A functional micro-electrode mapping of ventral thalamus in essential tremor.

Deep brain stimulation enables the delivery of therapeutic interventions to otherwise inaccessible areas of the brain while, at the same time, offering the unique opportunity to record from these same regions in awake patients. The posterior ventrolateral thalamus has become a reliable deep brain stimulation target for medically-refractory patients suffering from essential tremor. However, the contribution of the thalamus in essential tremor, and even whether posterior ventrolateral thalamus is the optimal target, remains a matter of ongoing debate. There are several lines of evidence supporting clusters of activity within the posterior ventrolateral thalamus that are important for tremor emergence. In this study we sought to map the functional properties of these clusters through microelectrode recordings during deep brain stimulation surgery. Data were obtained from 10 severely affected patients with essential tremor (12 hemispheres) undergoing deep brain stimulation surgery. Our results demonstrate power and coherence maxima located in the inferior posterior ventrolateral thalamus and immediate ventral region. Moreover, we identified distinct yet overlapping clusters of predominantly efferent (driving) and afferent (feedback) activity, with a preference for more efferent contributors, consistent with a net role in the driving of tremor output. Finally, we demonstrate that resolvable thalamic spiking activity directly relates to background activity and that the strength of tremor may be dictated by phase relationships between efferent and afferent pockets in the posterior ventrolateral thalamus. Taken together, these results provide important evidence for the role of the inferior posterior ventrolateral thalamus and its border region in essential tremor pathophysiology. Such results progress our mechanistic understanding and promote the adoption of next-generation therapies such as high resolution segregated deep brain stimulation electrodes.

Tremor stability index: a new tool for differential diagnosis in tremor syndromes.

See Vidailhet et al. (doi:10.1093/brain/awx140) for a scientific commentary on this article. Misdiagnosis among tremor syndromes is common, and can impact on both clinical care and research. To date no validated neurophysiological technique is available that has proven to have good classification performance, and the diagnostic gold standard is the clinical evaluation made by a movement disorders expert. We present a robust new neurophysiological measure, the tremor stability index, which can discriminate Parkinson's disease tremor and essential tremor with high diagnostic accuracy. The tremor stability index is derived from kinematic measurements of tremulous activity. It was assessed in a test cohort comprising 16 rest tremor recordings in tremor-dominant Parkinson's disease and 20 postural tremor recordings in essential tremor, and validated on a second, independent cohort comprising a further 55 tremulous Parkinson's disease and essential tremor recordings. Clinical diagnosis was used as gold standard. One hundred seconds of tremor recording were selected for analysis in each patient. The classification accuracy of the new index was assessed by binary logistic regression and by receiver operating characteristic analysis. The diagnostic performance was examined by calculating the sensitivity, specificity, accuracy, likelihood ratio positive, likelihood ratio negative, area under the receiver operating characteristic curve, and by cross-validation. Tremor stability index with a cut-off of 1.05 gave good classification performance for Parkinson's disease tremor and essential tremor, in both test and validation datasets. Tremor stability index maximum sensitivity, specificity and accuracy were 95%, 95% and 92%, respectively. Receiver operating characteristic analysis showed an area under the curve of 0.916 (95% confidence interval 0.797­1.000) for the test dataset and a value of 0.855 (95% confidence interval 0.754­0.957) for the validation dataset. Classification accuracy proved independent of recording device and posture. The tremor stability index can aid in the differential diagnosis of the two most common tremor types. It has a high diagnostic accuracy, can be derived from short, cheap, widely available and non-invasive tremor recordings, and is independent of operator or postural context in its interpretation.

Stimulating at the right time: phase-specific deep brain stimulation.

SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects.

Optimum design and sequential treatment allocation in an experiment in deep brain stimulation with sets of treatment combinations.

In an experiment including patients who underwent surgery for deep brain stimulation electrode placement, each patient responds to a set of 9 treatment combinations. There are 16 such sets, and the design problem is to choose which sets should be administered and in what proportions. Extensions to the methods of nonsequential optimum experimental design lead to identification of an unequally weighted optimum design involving 4 sets of treatment combinations. In the actual experiment, patients arrive sequentially and present with sets of prognostic factors. The idea of loss due to Burman is extended and used to assess designs with varying randomization structures. It is found that a simple sequential design using only 2 sets of treatments has surprisingly good properties for trials with the proposed number of patients.

Time reproduction deficits in essential tremor patients.

BACKGROUND: Although motor symptoms predominate in essential tremor, increasing evidence indicates additional cognitive deficits. According to the pivotal role of cognitive functioning for temporal information processing and acknowledging the relevance of temporal information processing for movement coordination, we investigated whether essential tremor patients exhibit time reproduction deficits. METHODS: A total of 24 essential tremor patients and 24 healthy controls performed sub- and suprasecond visual duration reproduction tasks of 500 to 900 milliseconds and 1.6 to 2.4 seconds, respectively. To differentiate deficient time processing from motor or other cognitive dysfunctions, the average temporal reproduction errors were correlated with tremor severity, immediate and delayed word-list recall performance, and verbal fluency. RESULTS: Essential tremor patients significantly underreproduced sub- and suprasecond time intervals longer than 800 milliseconds. Moreover, time compression correlated significantly with semantic verbal fluency and word-list retrieval performance, but not with tremor severity. CONCLUSION: Data suggest impaired temporal processing in essential tremor, corroborating evidence for specific cognitive deficits. © 2016 International Parkinson and Movement Disorder Society.

Thalamomuscular coherence in essential tremor: hen or egg in the emergence of tremor?

Thalamomuscular coherence in essential tremor (ET) has consistently been detected in numerous neurophysiological studies. Thereby, spatial properties of coherence indicate a differentiated, somatotopic organization; so far, however, little attention has been paid to temporal aspects of this interdependency. Further insight into the relationship between tremor onset and the onset of coherence could pave the way to more efficient deep brain stimulation (DBS) algorithms for tremor. We studied 10 severely affected ET patients (six females, four males) during surgery for DBS-electrode implantation and simultaneously recorded local field potentials (LFPs) and surface electromyographic signals (EMGs) from the extensor and flexor muscles of the contralateral forearm during its elevation. The temporal relationship between the onset of significant wavelet cross spectrum (WCS) and tremor onset was determined. Moreover, we examined the influence of electrode location within one recording depth on this latency and the coincidence of coherence and tremor for depths with strong overall coherence ("tremor clusters") and those without. Data analysis revealed tremor onset occurring 220 ± 460 ms before the start of significant LFP-EMG coherence. Furthermore, we could detect an anterolateral gradient of WCS onset within one recording depth. Finally, the coincidence of tremor and coherence was significantly higher in tremor clusters. We conclude that tremor onset precedes the beginning of coherence. Besides, within one recording depth there is a spread of the tremor signal. This reflects the importance of somatosensory feedback for ET and questions the suitability of thalamomuscular coherence as a biomarker for "closed-loop" DBS systems to prevent tremor emergence.

The Quality in Quality of Life in Parkinson's Disease: A Qualitative Meta-Synthesis.

BACKGROUND: Quality of life (QoL) is known to be impaired in people with Parkinson's disease (PwPD). Not surprisingly, a considerable effort of health interventions is aimed at maintaining or improving QoL. Yet, little is known about its determinants from a PwPD perspective to inform person-centered health care interventions. OBJECTIVES: This systematic review aims to overcome this information gap by synthesizing existing evidence on factors associated with PwPD' self-perceived QoL. METHODS: We searched six electronic databases (MEDLINE, EMBASE, PsycINFO, CINAHL, Web of Science, Cochrane Library) from inception to January 2022 for eligible qualitative studies of QoL in PwPD, supplemented by citation tracking and hand searching. Study quality was assessed using the QualSyst tool. In order to characterize the determinants of QoL in PwPD, we conducted a qualitative meta-synthesis. RESULTS: Our analysis revealed a wide range of facilitators and barriers to QoL relating to seven overarching themes: Illness experience, health care, everyday life, social life, identity, spirituality/religion, and environment. CONCLUSIONS: Our systematic review reinforces the impact of symptom experience on PwPD's QoL. However, it also highlights the need to consider the non-physical dimensions of PD when assessing patients' QoL. It is therefore essential that health care professionals acknowledge the psychological, social and spiritual repercussions of PD and endeavor to respond to these concerns through a comprehensive and patient-centered strategy. Further research is needed to gain a deeper understanding of these facets of PD and to formulate successful interventions aimed at improving the QoL of PwPD.

Paradoxical Kinesia Induced by Nightmare: Unique Case Report and Insights regarding the Neural Mechanism Based on Human and Rat Studies.

Introduction: Bradykinesia, characterized by slowed movement, stands out as a primary symptom observed in individuals with Parkinson's disease (PD). Nonetheless, there are instances where PD patients exhibit sudden and effective movements despite the presence of bradykinesia. This phenomenon, referred to as paradoxical kinesia, has remained a subject of interest for neuroscientists, who have struggled to unravel its underlying neural mechanisms for decades. Case Presentation: We describe a patient who is suffering from advanced PD. The patient has severe motor limitations, including difficulty rising from bed and walking, as well as cognitive decline and visual impairment. However, an interesting occurrence took place during a nightmare episode. Surprisingly, the patient was able to get out of bed and quickly run away from the perceived threat within the nightmare, without any assistance. Conclusion: This report presents the first documented case of paradoxical kinesia induced by nightmares in a patient with PD. This phenomenon raises questions about the neurological mechanisms involved, which are still not fully understood. Based on existing research conducted on both animal and human subjects, we propose that after processing the emotion of fear, the brain aversive system activates motor outputs to generate appropriate behavior. Thus, the brain aversive system converts the emotion of fear into action through projections from the inferior colliculus to motor-related areas such as the mesencephalic locomotor region, pontine nuclei, and substantia nigra.

Utilization of MANAGE-PD Tool in a Real-World Setting in Germany: A Cross-Sectional Study.

MANAGE-PD is a validated, web-based tool to assist physicians in identifying patients with Parkinson's disease (PD) whose symptoms are inadequately controlled by oral medication. Also, a modified patient version of MANAGE-PD (Parkinson Check) is available in Germany. However, prospective research into the clinical utility of MANAGE-PD is lacking. This non-interventional study aimed to assess the real-world clinical utility of the MANAGE-PD and Parkinson Check in PD patients attending a single visit at specialist clinics and neurologist practices in Germany in 2022. Participants' disease control was rated by the physicians using their own judgment, and by completing the MANAGE-PD, and by the patients completing the Parkinson Check. Concordance was calculated between the unassisted physician's assessment and the outcome of MANAGE-PD, as well as the Parkinson Check. A total of 278 patients from 19 sites were included in the analyses, of whom 160 patients (57.6%) were assigned to the same category of disease control by physicians' judgment and the MANAGE-PD. Concordance was higher in patients treated in specialist clinics (63.9%) than in neurologist practices (43.7%). Concordance between physicians' and patients' responses was high (>80%) for each question in the Parkinson Check. MANAGE-PD proved to be especially valuable for general neurologists in identifying patients who should be referred to specialist clinics. The Parkinson Check self-assessment generated promising outcomes that merit its more widespread use.