Effect of Thalamic versus Pallidal Deep Brain Stimulation on Head Tremor in Dystonic and Essential Tremor Patients-A Retrospective Video-Blinded Study.

BACKGROUND: Head tremor is common in dystonia syndromes and difficult to treat. Deep brain stimulation (DBS) is a therapeutic option in medically-refractory cases. In most DBS-centers, the globus pallidus internus (GPi) is targeted in patients with predominant dystonia and the ventrointermediate nucleus of the thalamus (Vim) in predominant tremor. The aim of the study was to evaluate the effect of GPi- versus Vim-DBS in dystonic or essential head tremor. METHODS: All patients with dystonia or essential tremor (ET) (n = 381) who underwent DBS surgery at our institution between 1999 and 2020 were screened for head tremor in our database according to predefined selection criteria. Of the 33 patients meeting inclusion criteria tremor and dystonia severity were assessed at baseline, short- (mean 10 months) and long-term follow-up (41 months) by two blinded video-raters. RESULTS: Twenty-two patients with dystonic head tremor received either GPi- (n = 12) or Vim-stimulation (n = 10), according to the prevailing clinical phenotype. These two groups were compared with 11 patients with ET, treated with Vim-stimulation. The reduction in head tremor from baseline to short- and long-term follow-up was 60-70% and did not differ significantly between the three groups. CONCLUSIONS: GPi-DBS effectively and sustainably reduced head tremor in idiopathic dystonia. The effect was comparable to the effect of Vim-DBS on head tremor in dystonia patients with predominant limb tremor and to the effect of Vim-DBS on head tremor in ET.

The interplay of sensory feedback, arousal, and action tremor amplitude in essential tremor.

Essential tremor (ET) amplitude is modulated by visual feedback during target driven movements and in a grip force task. It has not been examined yet whether visual feedback exclusively modulates target force tremor amplitude or if other afferent inputs like auditory sensation has a modulatory effect on tremor amplitude as well. Also, it is unknown whether the enhanced sensory feedback causes an increase of arousal in persons with ET (p-ET). We hypothesized that (1) amplitude of tremor is modulated by variation of auditory feedback in the absence of visual feedback in a force tremor paradigm; (2) increase of tremor amplitude coincides with pupillary size as a measure of arousal. 14 p-ET and 14 matched healthy controls (HC) conducted a computer-based experiment in which they were asked to match a target force on a force sensor using their thumb and index finger. The force-induced movement was fed back to the participant visually, auditory or by a combination of both. Results showed a comparable deviation from the target force (RMSE) during the experiment during all three sensory feedback modalities. The ANOVA revealed an effect of the high vs. low feedback condition on the tremor severity (Power 4-12 Hz) for the visual- and also for the auditory feedback condition in p-ET. Pupillometry showed a significantly increased pupil diameter during the auditory involved high feedback conditions compared to the low feedback conditions in p-ET. Our findings suggest that action tremor in ET is firstly modulated not only by visual feedback but also by auditory feedback in a comparable manner. Therefore, tremor modulation seems to be modality independent. Secondly, high feedback was associated with a significant pupil dilation, possibly mirroring an increased arousal/perceived effort.

Predictors and Pathophysiology of Axial Postural Abnormalities in Parkinsonism: A Scoping Review.

Background: Postural abnormalities involving the trunk are referred to as axial postural abnormalities and can be observed in over 20% of patients with Parkinson's disease (PD) and in atypical parkinsonism. These symptoms are highly disabling and frequently associated with back pain and a worse quality of life in PD. Despite their frequency, little is known about the pathophysiology of these symptoms and scant data are reported about their clinical predictors, making it difficult to prompt prevention strategies. Objectives: We conducted a scoping literature review of clinical predictors and pathophysiology of axial postural abnormalities in patients with parkinsonism to identify key concepts, theories and evidence on this topic. Methods: We applied a systematic approach to identify studies, appraise quality of evidence, summarize main findings, and highlight knowledge gaps. Results: Ninety-two articles were reviewed: 25% reported on clinical predictors and 75% on pathophysiology. Most studies identified advanced disease stage and greater motor symptoms severity as independent clinical predictors in both PD and multiple system atrophy. Discrepant pathophysiology data suggested different potential central and peripheral pathogenic mechanisms. Conclusions: The recognition of clinical predictors and pathophysiology of axial postural abnormalities in parkinsonism is far from being elucidated due to literature bias, encompassing different inclusion criteria and measurement tools and heterogeneity of patient samples. Most studies identified advanced disease stage and higher burden of motor symptoms as possible clinical predictors. Pathophysiology data point toward many different (possibly non-mutually exclusive) mechanisms, including dystonia, rigidity, proprioceptive and vestibular impairment, and higher cognitive deficits.

The Role of Levodopa Challenge in Predicting the Outcome of Subthalamic Deep Brain Stimulation.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective and evidence-based treatment for idiopathic Parkinson's disease (iPD). A minority of patients does not sufficiently benefit from STN-DBS. Objective: The predictive validity of the levodopa challenge for individual patients is analyzed. Methods: Data from patients assessed with a preoperative Levodopa-test and a follow-up examination (mean ± standard deviation: 9.15 months ±3.39) from Kiel (n = 253), Berlin (n = 78) and Toronto (n = 98) were studied. Insufficient DBS outcome was defined as an overall UPDRS-III reduction <33% compared to UPDRS-III in med-off at baseline or alternatively if the minimal clinically important improvement of 5 points was not reached. Single UPDRS-items and sub-scores were dichotomized. Following exploratory analysis, we trained supervised regression- and classification models for outcome prediction. Results: Data analysis confirmed significant correlation between the absolute UPDRS-III reduction during Levodopa challenge and after stimulation. But individual improvement was inaccurately predicted with a large range of up to 30 UPDRS III points. Further analysis identified preoperative UPDRS-III/med-off-scores and preoperative Levodopa-improvement as most influential factors. The models for UPDRS-III and sub-scores improvement achieved comparably low accuracy. Conclusions: With large prediction intervals, the Levodopa challenge use for patient counseling is limited, though remains important for excluding non-responders to Levodopa. Despite these deficiencies, the current practice of patient selection is highly successful and builds not only on the Levodopa challenge. However, more specific motor tasks and further paraclinical tools for prediction need to be developed.

Characterizing Camptocormia in Parkinson's Disease Using Muscle Ultrasonography.

BACKGROUND: Camptocormia (CC) is the forward-bending of the spine of more than 30 degrees that can be found in Parkinson's disease (PD) as a disabling complication. Detection of changes in paraspinal lumbar musculature in CC is of value for choosing treatment strategies. OBJECTIVE: To investigate whether these changes can be detected using muscle ultrasonography (mUSG). METHODS: Age and sex-matched groups comprised 17 PD patients with CC (seven acute, PD-aCC; 10 chronic PD-cCC), 19 PD patients with no CC, and 18 healthy controls (HC). Lumbar paravertebral muscles (LPM) on both sides were assessed using mUSG by two different raters blinded to the group assignment. Groups were compared with regard to the linear measurements of the muscle thickness as well as semi-quantitative and quantitative (grayscale) analyses of muscle echogenicity using a univariate general linear model. RESULTS: All assessments showed substantial interrater reliability. The PD-cCC group had significantly thinner LPM compared to groups with no CC (PD and HC). Groups of PD-aCC and PD-cCC differed from the groups of no CC in quantitative and semi-quantitative analyses of LPM echogenicity, respectively. CONCLUSION: Assessment of LPM in PD patients with CC can be reliably performed using mUSG. Also, mUSG may be used as a screening tool to detect CC-related changes in thickness and echogenicity of the LPM in patients with PD.

Grey matter correlates of dystonic soft signs in essential tremor.

BACKGROUND: Questionable signs of dystonia are a common finding in patients with essential tremor (ET). Brain structural alterations in ET patients plus dystonic soft signs (ET + ds) in comparison to ET patients without dystonic soft signs (ET-ds) or patients with tremor associated with manifest dystonia (TAWD) have not been examined yet. Therefore, our study aims to explore alterations of brain grey matter in patients with ET + ds. METHODS: A total of 68 elderly patients with ET-ds (n = 32), ET + ds (n = 20) or idiopathic cervical dystonia with dystonia associated action tremor of the upper limbs (TAWD, n = 16) and 42 age-matched healthy controls underwent a clinical and electrophysiological assessment and 3T MRI. For grey matter alterations T1 MRI images were analysed by voxel-based morphometry. Additionally, regression analyses with clinical parameters (tremor frequency, severity and disease duration) were performed. RESULTS: VBM showed a significant increase of grey matter in the right lentiform nucleus in ET + ds and TAWD compared to HC and ET-ds. Further, an increase of cortical grey matter in the middle frontal gyrus in ET + ds was shown. The hypertrophy of the lentiform nucleus in ET + ds was correlated with disease severity and duration. CONCLUSION: Patients with ET + ds showed grey matter brain structural alterations similar to TAWD. Our findings suggest an involvement of the basal ganglia-cortical loop in ET + ds which may indicate a pathophysiological similarity with TAWD rather than ET.

Three-Dimensional Mesh Recovery from Common 2-Dimensional Pictures for Automated Assessment of Body Posture in Camptocormia.

Background: Three-dimensional (3D) human body estimation from common photographs is an evolving method in the field of computer vision. It has not yet been evaluated on postural disorders. We generated 3D models from 2-dimensional pictures of camptocormia patients to measure the bending angle of the trunk according to recommendations in the literature. Methods: We used the Part Attention Regressor algorithm to generate 3D models from photographs of camptocormia patients' posture and validated the resulting angles against the gold standard. A total of 2 virtual human models with camptocormia were generated to evaluate the performance depending on the camera angle. Results: The bending angle assessment using the 3D mesh correlated highly with the gold standard (R = 0.97, P < 0.05) and is robust to deviations of the camera angle. Conclusions: The generation of 3D models offers a new method for assessing postural disorders. It is automated and robust to nonperfect pictures, and the result offers a comprehensive analysis beyond the bending angle.

Proceedings of the Ninth Annual Deep Brain Stimulation Think Tank: Advances in Cutting Edge Technologies, Artificial Intelligence, Neuromodulation, Neuroethics, Pain, Interventional Psychiatry, Epilepsy, and Traumatic Brain Injury.

DBS Think Tank IX was held on August 25-27, 2021 in Orlando FL with US based participants largely in person and overseas participants joining by video conferencing technology. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging deep brain stimulation (DBS) technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank IX speakers was that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. After collectively sharing our experiences, it was estimated that globally more than 230,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. As such, this year's meeting was focused on advances in the following areas: neuromodulation in Europe, Asia and Australia; cutting-edge technologies, neuroethics, interventional psychiatry, adaptive DBS, neuromodulation for pain, network neuromodulation for epilepsy and neuromodulation for traumatic brain injury.

Quantitative assessment of posture in healthy controls and patients with Parkinson's disease.

INTRODUCTION: A stooped posture is a main clinical feature of Parkinson's disease (PD). The assessment of posture is important to measure treatment effects. The aim of this study was to investigate the reliability of a standardized postural rating tool, to calculate minimal detectable change scores and to assess the role of gender and age. METHODS: Two independent raters assessed total camptocormia (TCC), upper camptocormia (UCC) and Pisa angles of 192 PD patients and 78 healthy controls (HC) with the free NeuroPostureApp©(http://www.neuroimaging.uni-kiel.de/NeuroPostureApp). Reliabilities and linear models were calculated for different effects. Three subgroups were defined based on two thresholds (mean+2SD of HC and PD): A) normal, B) presumed stooped/lateral bended posture and C) postural disorder. RESULTS: Intraclass correlation coefficients ranged between 0.71 and 0.95 for the interrater and test-retest reliability of the three angles. The minimal detectable change values in the PD patients were 3.7°, 6.7° and 2.1° for the TCC, UCC and Pisa angles, respectively. Men had a more stooped posture than women (p < 0.05). Patients with PD had a worse posture than HC (p < 0.001) in all three angles. For the TCC angle, 39.1% of the patients had a normal posture (<17.4°), 47.9% a presumed stooped posture (>17.4°, <30.2°) and 6.3° had camptocormia (>30.2°). CONCLUSIONS: The NeuroPostureApp© is reliable. Our results confirmed gender differences and the progression of postural deviation in PD patients with age and empirically support the ≥30° TCC angle as a defining criterium for camptocormia. Diagnostic criteria for UCC and Pisa syndrome should be further explored in future studies.

The Effect of Medication and Deep Brain Stimulation on Posture in Parkinson's Disease.

Introduction: Postural abnormalities are common in Parkinson's disease (PD) and increasing with disease progression. While many studies focus on balance and gait, postural alignment is only infrequently studied. Purpose: The aim of the present study was to examine the immediate and long-term effects of medication and deep brain stimulation (DBS) in the subthalamic nucleus on postural alignment in PD. Materials and Methods: PD patients (n = 192) in an advanced stage of disease were videotaped during a standardized l-dopa trial before and after DBS. The patients were tested with and without medication pre-surgical and retested post-surgical (6-24 months) in all treatment combinations of medication and DBS regarding the on and off conditions. The forward bending as total camptocormia (TCC) and upper camptocormia (UCC) angles and lateral bending as Pisa angle were assessed with the free downloadable NeuroPostureApp (http://www.neuroimaging.uni-kiel.de/NeuroPostureApp/). Three subgroups were defined according to normative values of healthy controls and according to clinical criteria: patients with normal posture, with stooped posture, and with postural disorders. Results: A stooped posture was found in 82% of the patients with regard to the TCC angle and in 54% for the UCC angle. Sixty-two percent had an abnormal Pisa angle. Camptocormia was diagnosed in ~7% and a Pisa syndrome in 1% of the patients. Medication and DBS both significantly improved postural alignment in the entire cohort. Female and male patients benefit similarly by medication and stimulation. Subgroup analyses revealed that the effects were also significant for patients with stooped posture, and the effects were strongest for patients with camptocormia: they led to angles below the diagnostical criterion for camptocormia for 13 of 14 patients with TCC and 11 of 26 patients with UCC. DBS had an additional effect to medication over time for the Pisa angle. Conclusion: Medication and DBS both improved postural alignment in PD patients, but effects were small for the entire cohort. Patients with camptocormia according to the TCC angle benefit strongest. The large differences of the treatment effects may indicate distinct pathological mechanisms for stooped posture and postural disorders. The TCC angle was shown to be sensitive to change. The UCC angle was less sensitive but may be a useful assessment tool for a subgroup.

Measurement of camptocormia trunk flexion using a dual-sensor measurement setup.

Assessing the flexion of the trunk of patients with camptocormia is a key factor in developing therapies for camptocormia and monitoring their success. Currently used methods to measure this camptocormia angle are based on photographs or short videos. Both methods are not able to take the ability of patients into account to compensate their symptoms for short amounts of time. We propose a simple two sensor measurement setup based on two accelerometers to measure the angle in accordance with the established perpendicular measurement method [1]. We show that our method yields an average deviation of -1.74° with a maximum deviation of +2° and -6° compared to visual assessment with a motion capturing system.

Consensus for the measurement of the camptocormia angle in the standing patient.

INTRODUCTION: Camptocormia is characterized by a pathological forward flexion of the trunk, which is reversible when lying and worsened by standing and walking. So far there is no consensus on how to measure the angle of flexion, and studies therefore give differing results. Harmonization is needed for both research and clinical practice. Orthopedic measures are not useful for this purpose. METHODS: Two expert raters independently analyzed the photographs of 39 Parkinson patients with camptocormia while standing. They used four different methods to determine the camptocormia angle. The results were compared statistically. An international Consensus Group reviewed the results and drafted recommendations. RESULTS: The four methods yielded camptocormia angles that differed by up to 50% in the same patient. Inter-rater reliability and test-retest reliability also differed, but were satisfactory to excellent. CONCLUSION: This Consensus Group concluded that two of the methods qualified as reliable measures of the trunk angles in standing patients based on their clinimetric properties. They propose that the 'total camptocomia angle' be the angle between the line from the lateral malleolus to the L5 spinous process and the line between the L5 spinous process and the spinous process of C7. They also propose that the 'upper camptocormia angle' be the angle of the lines between the vertebral fulcrum to the spinous processes of L5 and C7, respectively. An app is provided on the web for these measurements (http://www.neurologie.uni-kiel.de/de/axial-posturale-stoerungen/camptoapp).