Visuospatial memory profile of patients with Parkinson's disease.

BACKGROUND: In Parkinson's Disease (PD) cognitive impairment may become evident at an early stage of the disease. Performance in the visuospatial domain has been pointed out as a possible predictor of cognitive decline for dementia. OBJECTIVES: The goal was to characterize the visuospatial memory profile, explore the predictive value of a set of visuospatial measures that better distinguish patients from controls, and investigate the relevance of the 10/36 SPART, providing cutoff scores. METHODS: A total of 43 PD patients and 45 healthy controls (HC) were recruited from the Centro Hospitalar Universitário de São João and the community, respectively. The protocol included a set of tests assessing global cognitive functioning, visuoperceptive abilities, and visuospatial memory. RESULTS: PD patients performed significantly worse than HC, showing difficulties in global cognition, visuospatial learning, and visuoconstructive and perceptive abilities. Through a discriminant analysis, the Clock Drawing Test and ACE-R's visuospatial domain were revealed as good tools to be included in the evaluation protocol. Regarding the 10/36 SPART's performance, four predictors were found (age, sex, education, and emotional distress) and cutoff scores were determined. CONCLUSIONS: The visuospatial memory profile found was congruent with that described in the literature. The results were discussed according to their relevance for clinical practice and future research.

Handicap as a Measure of Perceived-Health Status in Parkinson's Disease.

Background: Handicap is a patient-centered measure of health status that encompasses the impact of social and physical environment on daily living, having been assessed in advanced and late-stage Parkinson's Disease (PD). Objective: To characterize the handicap of a broader sample of patients. Methods: A cross-sectional study of 405 PD patients during the MDS-UPDRS Portuguese validation study, using the MDS-UPDRS, Unified Dyskinesias Rating Scale, Nonmotor symptoms questionnaire, PDQ-8 and EQ-5D-3L. Handicap was measured using the London Handicap Scale (LHS). Results: Mean age was 64.42 (±10.3) years, mean disease duration 11.30 (±6.5) years and median HY 2 (IQR, 2-3). Mean LHS was 0.652 (±0.204); "Mobility," "Occupation" and "Physical Independence" were the most affected domains. LHS was significantly worse in patients with longer disease duration, older age and increased disability. In contrast, PDQ-8 did not differentiate age groups. Handicap was significantly correlated with disease duration (r = -0.35), nonmotor experiences of daily living (EDL) (MDS-UPDRS-I) (r = -0.51), motor EDL (MDS-UPDRS-II) (r = -0.69), motor disability (MDS-UPDRS-III) (r = -0.49), axial signs of MDS-UPDRS-III (r = -0.55), HY (r = -0.44), presence of nonmotor symptoms (r = -0.51) and PDQ-8 index (r = -0.64) (all P < 0.05). Motor EDL, MDS-UPDRS-III and PDQ-8 independently predicted Handicap (adjusted R 2 = 0.582; P = 0.007). Conclusions: The LHS was easily completed by patients and caregivers. Patients were mild-moderately handicapped, which was strongly determined by motor disability and its impact on EDL, and poor QoL. Despite correlated, handicap and QoL seem to differ in what they measure, and handicap may have an added value to QoL. Handicap seems to be a good measure of perceived-health status in a broad sample of PD.

Bilateral deep brain stimulation of the subthalamic nucleus: Targeting differences between the first and second side / Estimulación cerebral profunda bilateral del núcleo subtalámico: diferencias de posicionamiento entre el primer y el segundo lado

Introduction and objectives Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a recognized treatment for drug-refractory Parkinson's disease (PD). However, the therapeutic success depends on the accuracy of targeting. This study aimed to evaluate potential accuracy differences in the placement of the first and second electrodes implanted, by comparing chosen electrode trajectories, STN activity detected during microelectrode recording (MER), and the mismatch between the initially planned and final electrode positions on each side. Materials and methods In this retrospective cohort study, we analyzed data from 30 patients who underwent one-stage bilateral DBS. For most patients, three arrays of microelectrodes were used to determine the physiological location of the STN. Final target location depended also on the results of intraoperative stimulation. The choice of central versus non-central channels was compared. The Euclidean vector deviation was calculated using the initially planned coordinates and the final position of the tip of the electrode according to a CT scan taken at least a month after the surgery. Results The central channel was chosen in 70% of cases on the first side and 40% of cases on the second side. The mean length of high-quality STN activity recorded in the central channel was longer on the first side than the second (3.07±1.85mm vs. 2.75±1.94mm), while in the anterior channel there were better MER recordings on the second side (1.59±2.07mm on the first side vs. 2.78±2.14mm on the second). Regarding the mismatch between planned versus final electrode position, electrodes on the first side were placed on average 0.178±0.917mm lateral, 0.126±1.10mm posterior and 1.48±1.64mm inferior to the planned target (AU)

Introducción y objetivos La estimulación cerebral profunda (ECP) del núcleo subtalámico (NST) es reconocida como un tratamiento para la enfermedad de Parkinson (EP) refractaria al tratamiento farmacológico. Sin embargo, el éxito de esta intervención depende de la precisión de la colocación de los electrodos. Este estudio tuvo como objetivo evaluar las posibles diferencias de precisión entre la colocación del primer y segundo electrodo, comparando las trayectorias elegidas para cada lado, la actividad del NST detectada durante el microrregistro (MER) y la discrepancia entre las posiciones inicialmente planeadas y las finales. Materiales y métodos En este estudio retrospectivo analizamos datos de 30 pacientes sometidos a ECP bilateral. En la mayoría de los casos se usaron tres conjuntos de microelectrodos para determinar la ubicación fisiológica del NST. El posicionamiento final del electrodo estuvo asimismo condicionado por los resultados de la estimulación intraoperatoria. Se comparó la elección de canales centrales vs. no centrales. El vector euclidiano del desvío se calculó a partir de las coordenadas planeadas inicialmente y la posición final de la punta del electrodo, según una tomografía computarizada realizada al menos un mes después de la cirugía. Resultados La trayectoria central se eligió en 70% de los casos en el primer lado y en el 40% de los casos en el segundo lado. La duración media de la actividad de alta calidad del NST registrada en el canal central fue mayor en el primer lado que en el segundo (3,07±1,85mm vs. 2,75±1,94mm), mientras que en el canal anterior hubo mejores registros de MER en el segundo lado (1,59±2,07mm en el primer lado vs. 2,78±2,14mm en el segundo) (AU)

Machine versus physician-based programming of deep brain stimulation in isolated dystonia: A feasibility study.

BACKGROUND: Deep brain stimulation of the internal globus pallidus effectively alleviates dystonia motor symptoms. However, delayed symptom control and a lack of therapeutic biomarkers and a single pallidal sweetspot region complicates optimal programming. Postoperative management is complex, typically requiring multiple, lengthy follow-ups with an experienced physician - an important barrier to widespread adoption in medication-refractory dystonia patients. OBJECTIVE: Here we prospectively tested the best machine-predicted programming settings in a dystonia cohort treated with GPi-DBS against the settings derived from clinical long-term care in a specialised DBS centre. METHODS: Previously, we reconstructed an anatomical map of motor improvement probability across the pallidal region using individual stimulation volumes and clinical outcomes in dystonia patients. We used this to develop an algorithm that tests in silico thousands of putative stimulation settings in de novo patients after reconstructing an individual, image-based anatomical model of electrode positions, and suggests stimulation parameters with the highest likelihood of optimal symptom control. To test real-life application, our prospective study compared results in 10 patients against programming settings derived from long-term care. RESULTS: In this cohort, dystonia symptom reduction was observed at 74.9 ± 15.3% with C-SURF programming as compared to 66.3 ± 16.3% with clinical programming (p < 0.012). The average total electrical energy delivered (TEED) was similar for both the clinical and C-SURF programming (262.0 µJ/s vs. 306.1 µJ/s respectively). CONCLUSION: Our findings highlight the clinical potential of machine-based programming in dystonia, which could markedly reduce the programming burden in postoperative management.

Bilateral deep brain stimulation of the subthalamic nucleus: Targeting differences between the first and second side.

INTRODUCTION AND OBJECTIVES: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a recognized treatment for drug-refractory Parkinson's disease (PD). However, the therapeutic success depends on the accuracy of targeting. This study aimed to evaluate potential accuracy differences in the placement of the first and second electrodes implanted, by comparing chosen electrode trajectories, STN activity detected during microelectrode recording (MER), and the mismatch between the initially planned and final electrode positions on each side. MATERIALS AND METHODS: In this retrospective cohort study, we analyzed data from 30 patients who underwent one-stage bilateral DBS. For most patients, three arrays of microelectrodes were used to determine the physiological location of the STN. Final target location depended also on the results of intraoperative stimulation. The choice of central versus non-central channels was compared. The Euclidean vector deviation was calculated using the initially planned coordinates and the final position of the tip of the electrode according to a CT scan taken at least a month after the surgery. RESULTS: The central channel was chosen in 70% of cases on the first side and 40% of cases on the second side. The mean length of high-quality STN activity recorded in the central channel was longer on the first side than the second (3.07±1.85mm vs. 2.75±1.94mm), while in the anterior channel there were better MER recordings on the second side (1.59±2.07mm on the first side vs. 2.78±2.14mm on the second). Regarding the mismatch between planned versus final electrode position, electrodes on the first side were placed on average 0.178±0.917mm lateral, 0.126±1.10mm posterior and 1.48±1.64mm inferior to the planned target, while the electrodes placed on the second side were 0.251±1.08mm medial, 0.355±1.29mm anterior and 2.26±1.47mm inferior to the planned target. CONCLUSION: There was a tendency for the anterior trajectory to be chosen more frequently than the central on the second side. There was also a statistically significant deviation of the second electrodes in the anterior and inferior directions, when compared to the electrodes on the first side, suggesting that another cause other than brain shift may be responsible. We should therefore factor this during planning for the second implanted side. It might be useful to plan the second side more anteriorly, possibly reducing the number of MER trajectories tested and the duration of surgery.

Predicting Outcome in a Cohort of Isolated and Combined Dystonia within Probabilistic Brain Mapping.

BACKGROUND: Probabilistic brain mapping is a promising tool to estimate the expected benefit of pallidal deep brain stimulation (GPi-DBS) in patients with isolated dystonia (IsoD). OBJECTIVES: To investigate the role of probabilistic mapping in combined dystonia (ComD). METHODS: We rendered the pallidal atlas and the volume of tissue activated (VTA) for a cohort of patients with IsoD (n = 20) and ComD (n = 10) that underwent GPi-DBS. The VTA was correlated with clinical improvement. Afterwards, each VTA was applied on the previously published probabilistic model (Reich et al., 2019). The correlation between predicted and observed clinical benefit was studied in a linear regression model. RESULTS: A good correlation between observed and predicted outcome was found for both patients with IsoD (n = 14) and ComD (n = 7) (r2 = 0.32; P < 0.05). In ComD, 42% of the variance in DBS response is explained by VTA-based outcome map. CONCLUSION: A probabilistic model would be helpful in clinical practice to circumvent unpredictable and less impressive motor results often found in ComD.

Inter and intra-generational phenotypic variability in a Portuguese family with DYT-GCH1.

DYT-GCH1 is the most common form of Dopa-responsive dystonia. We analysed a three-generation Portuguese family with the same variant of DYT-GCH1. Dystonia and parkinsonism were found, along with non-motor symptoms. There was a wide array of phenotypic manifestations. Further studies are needed to explain the wide clinical expression of this entity.

Long term mortality of patients with Parkinson's disease treated with deep brain stimulation in a reference center.

INTRODUCTION: Parkinson's disease (PD) is a common neurodegenerative disorder, with a higher risk of death than general population. Deep Brain Stimulation (DBS) has been used to treat PD for more than 2 decades, but few studies exist concerning mortality in this subset of patients. Our goal is to analyse mortality in PD patients treated with DBS in our centre. METHODS: retrospective evaluation of clinical files of patients with PD who underwent DBS surgery consecutively between October 2002 and May 2019. RESULTS: 346 patients were included in the analysis, 60 % male, with a mean age at disease onset of 48± 8 years (18-64), mean age at surgery of 60 ± 7 years (33-75), and mean disease duration until surgery of 14 ± 6 years (3-52). Mean follow-up after surgery was 7 ± 4 years (range 1-17). Overall mortality rate was 17.9 % and mean age at time of death was 71 ± 6 years. The main causes of death were pneumonia, dementia and acute myocardial infarction. In our series, male gender and disease duration until surgery were the only predictors of mortality in multivariate analysis. CONCLUSION: Our study showed a long-term survival higher than previously described, and suggests that the treatment of patients with shorter disease evolution might have a survival benefit. The leading causes of death in PD patients treated with DBS seems unrelated to surgery, as the main causes of death are comparable to non-DBS patients.

Imaging Evidence of Nigrostriatal Degeneration in DYT-PRKRA.

https://onlinelibrary.wiley.com/page/journal/23301619/homepage/mdc312941-sup-v001.htm.

iHandU: A Novel Quantitative Wrist Rigidity Evaluation Device for Deep Brain Stimulation Surgery.

Deep brain stimulation (DBS) surgery is the gold standard therapeutic intervention in Parkinson's disease (PD) with motor complications, notwithstanding drug therapy. In the intraoperative evaluation of DBS's efficacy, neurologists impose a passive wrist flexion movement and qualitatively describe the perceived decrease in rigidity under different stimulation parameters and electrode positions. To tackle this subjectivity, we designed a wearable device to quantitatively evaluate the wrist rigidity changes during the neurosurgery procedure, supporting physicians in decision-making when setting the stimulation parameters and reducing surgery time. This system comprises a gyroscope sensor embedded in a textile band for patient's hand, communicating to a smartphone via Bluetooth and has been evaluated on three datasets, showing an average accuracy of 80%. In this work, we present a system that has seen four iterations since 2015, improving on accuracy, usability and reliability. We aim to review the work done so far, outlining the iHandU system evolution, as well as the main challenges, lessons learned, and future steps to improve it. We also introduce the last version (iHandU 4.0), currently used in DBS surgeries at São João Hospital in Portugal.

Automated and objective measures of gait dynamics in camptocormia Parkinson's Disease subthalamic deep brain stimulation.

OBJECTIVE: Axial motor features are common in Parkinson's disease (PD). These include gait impairment and postural abnormalities, such as camptocormia. The response of these symptoms to deep brain stimulation (DBS) is variable and difficult to assess objectively. For the first time, this study analyzes the treatment outcomes of two PD patients with camptocormia that underwent bilateral subthalamic nucleus (STN)-DBS evaluated with disruptive technologies. PATIENTS AND METHODS: Two patients with PD and camptocormia who underwent STN-DBS were included. Gait parameters were quantitatively assessed before and after surgery by using the NeuroKinect system and the camptocormia angle was measured using the camptoapp. RESULTS: After surgery, patient 1 improved 29 points in the UPDRS-III. His camptocormia angle was 68° before and 38° after surgery. Arm and knee angular amplitudes (117.32 ±â€¯7.47 vs 134.77 ±â€¯2.70°; 144.51 ±â€¯7.47 vs 169.08 ±â€¯3.27°) and arm swing (3.59 ±â€¯2.66 vs 5.40 ±â€¯1.76 cm) improved when compared with his preoperative measurements. Patient 2 improved 22 points in the UPDRS-III after surgery. Her camptocormia mostly resolved (47° before to 9° after surgery). Gait analysis revealed improvement of stride length (0.29 ±â€¯0.03 vs 0.35 ±â€¯0.03 m), stride width (18.25 ±â€¯1.16 vs 17.9 ±â€¯0.84 cm), step velocity (0.91 ±â€¯0.57 vs 1.33 ±â€¯0.48 m/s), arm swing (4.51 ±â€¯1.01 vs 7.38 ±â€¯2.71 cm) and arm and hip angular amplitudes (131.57 ±â€¯2.45° vs 137.75 ±â€¯3.18; 100.51 ±â€¯1.56 vs 102.18 ±â€¯1.77°) compared with her preoperative results. CONCLUSION: The gait parameters and camptocormia of both patients objectively improved after surgery, as assessed by the two quantitative measurement systems. STN-DBS might have a beneficial effect on controlling axial posturing and gait, being a potential surgical treatment for camptocormia in patients with PD. However, further studies are needed to derive adequate selection criteria for this patient population.

Intraoperative microelectrode recording in Parkinson's disease subthalamic deep brain stimulation: Analysis of clinical utility.

This retrospective study aims to explore the clinical utility of microelectrode recording (MER) during subthalamic deep brain stimulation (DBS) surgery in patients with Parkinson's disease (PD). We analyzed the data from 103 PD patients, who consecutively received bilateral subthalamic nucleus (STN) DBS at an experienced academic medical center. We collected demographic, clinical, and DBS related data, including intraoperative microelectrode recording data, electrode positioning, and clinical effects provided by intraoperative microstimulation. The 2 brain sides were independently analyzed and are described as first and second side (to be operated on); the first side is contralateral to motor symptoms onset. Patients were mostly men (64.1%). In both sides of the brain, percentage of agreement with the electrode final position was higher with clinical results than with intraoperative microelectrode recordings (98% vs 57% on the first implantation side, and 97% vs 58% on the second implantation side, respectively). Regarding electrode final implantation depth, 86% of electrodes were implanted between 0 mm and +2 mm in relation to anatomical target, and 95% of electrodes were implanted from -2 mm to +2 mm. Our study suggests that MER might not be necessary to achieve good clinical outcomes in PD patients undergoing STN DBS. These results support and inform the design of future prospective controlled research studies.

The impact of deep brain stimulation on health related quality of life and disease-specific disability in Meige Syndrome (MS).

Meige Syndrome (MS) is a disabling movement disorder which impairs daily routines such as eating and speaking and, when not responsive to best medical treatment, deep brain stimulation (DBS) of the globus pallidus interna (GPi) has been considered. Previous evidence has shown a significant improvement in motor dysfunction with DBS, however its benefit on disease-specific disability and quality of life has not been thoroughly studied. We describe two patients with severe MS submitted to GPi-DBS. Patient improvement was assessed preoperatively and 24 months after the surgery by applying the movement subscore of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMRS) and Jankovic Rating Scale (JRS) for motor function and the BFMRS disability subscore and Blepharospasm Disability Scale (BDS) for disability. At 24-month follow-up, dystonia improved 68% in Patient 1 and 96% in Patient 2, while disability improved 77%-92% respectively. No major adverse effects were observed. Improvement in motor function is in agreement with previous findings, but we emphasise the important improvement in disability and consequently in quality of life. Therefore, we suggest that DBS should be a therapeutic tool in refractory cases of MS.

Thalamic Deep Brain Stimulation for Neuropathic Pain: Efficacy at Three Years' Follow-Up.

OBJECT: Chronic neuropathic pain is estimated to affect 3-4.5% of the worldwide population, posing a serious burden to society. Deep Brain Stimulation (DBS) is already established for movement disorders and also used to treat some "off-label" conditions. However, DBS for the treatment of chronic, drug refractory, neuropathic pain, has shown variable outcomes with few studies performed in the last decade. Thus, this procedure has consensus approval in parts of Europe but not the USA. This study prospectively evaluated the efficacy at three years of DBS for neuropathic pain. METHODS: Sixteen consecutive patients received 36 months post-surgical follow-up in a single-center. Six had phantom limb pain after amputation and ten deafferentation pain after brachial plexus injury, all due to traumas. To evaluate the efficacy of DBS, patient-reported outcome measures were collated before and after surgery, using a visual analog scale (VAS) score, University of Washington Neuropathic Pain Score (UWNPS), Brief Pain Inventory (BPI), and 36-Item Short-Form Health Survey (SF-36). RESULTS: Contralateral, ventroposterolateral sensory thalamic DBS was performed in sixteen patients with chronic neuropathic pain over 29 months. A postoperative trial of externalized DBS failed in one patient with brachial plexus injury. Fifteen patients proceeded to implantation but one patient with phantom limb pain after amputation was lost for follow-up after 12 months. No surgical complications or stimulation side effects were noted. After 36 months, mean pain relief was sustained, and the median (and interquartile range) of the improvement of VAS score was 52.8% (45.4%) (p = 0.00021), UWNPS was 30.7% (49.2%) (p = 0.0590), BPI was 55.0% (32.0%) (p = 0.00737), and SF-36 was 16.3% (30.3%) (p = 0.4754). CONCLUSIONS: DBS demonstrated efficacy at three years for chronic neuropathic pain after traumatic amputation and brachial plexus injury, with benefits sustained across all pain outcomes measures and slightly greater improvement in phantom limb pain.

Early deep brain stimulation in patients with myoclonus-dystonia syndrome.

Myoclonus-dystonia (MD) is a rare movement disorder which is disabling and frequently refractory to medical treatment. Deep brain stimulation (DBS) of the globus pallidus interna (GPi) has been used to treat some patients. Although there is significant motor improvement with DBS, the impact on disability and on quality of life has been infrequently reported. Also, the benefit of the procedure is not established in patients without ε-sarcoglycan gene (SGCE) mutations. We present two patients with severe MD treated with GPi-DBS, one of the patients without a SGCE mutation. Motor improvements (rest/action/total subscores of the Unified Myoclonus Rating Scale and movement subscore of the Burke-Fahn-Marsden Dystonia Rating Scale [BFMRS]) and disability (BFMRS disability subscore) were carefully evaluated preoperatively and at 6 and 12months after surgery. Quality of life (addressed using the Portuguese version of the Medical Outcomes Study 36-item Short-Form General Health Survey, version 2.0 [SF-36v2]) was tested preoperatively and 12months after DBS. At 12-month follow-up, myoclonus improved 78.6% in Patient 1 and 80.7% in Patient 2, while dystonia improved 37% and 86.7%, respectively. Improvements in disability ranged from 71.4% to 75%. With regard to quality of life, all parameters addressed by the SF-36v2 improved or stabilized in both patients. No major adverse effects were noticed. Improvements in motor symptoms are consistent with reports in the literature and were obtained regardless of the identification of a SGCE gene mutation. There were also significant benefits on disability and quality of life. DBS should be considered for MD.

A novel portable, low-cost kinect-based system for motion analysis in neurological diseases.

Many neurological diseases, such as Parkinson's disease and epilepsy, can significantly impair the motor function of the patients, often leading to a dramatic loss of their quality of life. Human motion analysis is regarded as fundamental towards an early diagnosis and enhanced follow-up in this type of diseases. In this contribution, we present NeuroKinect, a novel system designed for motion analysis in neurological diseases. This system includes an RGB-D camera (Microsoft Kinect) and two integrated software applications, KiT (KinecTracker) and KiMA (Kinect Motion Analyzer). The applications enable the preview, acquisition, review and management of data provided by the sensor, which are then used for motion analysis of relevant events. NeuroKinect is a portable, low-cost and markerless solution that is suitable for use in the clinical environment. Furthermore, it is able to provide quantitative support to the clinical assessment of different neurological diseases with movement impairments, as demonstrated by its usage in two different clinical routine scenarios: gait analysis in Parkinson's disease and seizure semiology analysis in epilepsy.

An adaptive model approach for quantitative wrist rigidity evaluation during deep brain stimulation surgery.

Intraoperative evaluation of the efficacy of Deep Brain Stimulation includes evaluation of the effect on rigidity. A subjective semi-quantitative scale is used, dependent on the examiner perception and experience. A system was proposed previously, aiming to tackle this subjectivity, using quantitative data and providing real-time feedback of the computed rigidity reduction, hence supporting the physician decision. This system comprised of a gyroscope-based motion sensor in a textile band, placed in the patients hand, which communicated its measurements to a laptop. The latter computed a signal descriptor from the angular velocity of the hand during wrist flexion in DBS surgery. The first approach relied on using a general rigidity reduction model, regardless of the initial severity of the symptom. Thus, to enhance the performance of the previously presented system, we aimed to develop models for high and low baseline rigidity, according to the examiner assessment before any stimulation. This would allow a more patient-oriented approach. Additionally, usability was improved by having in situ processing in a smartphone, instead of a computer. Such system has shown to be reliable, presenting an accuracy of 82.0% and a mean error of 3.4%. Relatively to previous results, the performance was similar, further supporting the importance of considering the cogwheel rigidity to better infer about the reduction in rigidity. Overall, we present a simple, wearable, mobile system, suitable for intra-operatory conditions during DBS, supporting a physician in decision-making when setting stimulation parameters.