Phenotyping Down syndrome: discovery and predictive modelling with electronic medical records.

BACKGROUND: Individuals with Down syndrome (DS) have a heightened risk for various co-occurring health conditions, including congenital heart disease (CHD). In this two-part study, electronic medical records (EMRs) were leveraged to examine co-occurring health conditions among individuals with DS (Study 1) and to investigate health conditions linked to surgical intervention among DS cases with CHD (Study 2). METHODS: De-identified EMRs were acquired from Vanderbilt University Medical Center and facilitated creating a cohort of N = 2282 DS cases (55% females), along with comparison groups for each study. In Study 1, DS cases were one-by-two sex and age matched with samples of case-controls and of individuals with other intellectual and developmental difficulties (IDDs). The phenome-disease association study (PheDAS) strategy was employed to reveal co-occurring health conditions in DS versus comparison groups, which were then ranked for how often they are discussed in relation to DS using the PubMed database and Novelty Finding Index. In Study 2, a subset of DS individuals with CHD [N = 1098 (48%)] were identified to create longitudinal data for N = 204 cases with surgical intervention (19%) versus 204 case-controls. Data were included in predictive models and assessed which model-based health conditions, when more prevalent, would increase the likelihood of surgical intervention. RESULTS: In Study 1, relative to case-controls and those with other IDDs, co-occurring health conditions among individuals with DS were confirmed to include heart failure, pulmonary heart disease, atrioventricular block, heart transplant/surgery and primary pulmonary hypertension (circulatory); hypothyroidism (endocrine/metabolic); and speech and language disorder and Alzheimer's disease (neurological/mental). Findings also revealed more versus less prevalent co-occurring health conditions in individuals with DS when comparing with those with other IDDs. Findings with high Novelty Finding Index were abnormal electrocardiogram, non-rheumatic aortic valve disorders and heart failure (circulatory); acid-base balance disorder (endocrine/metabolism); and abnormal blood chemistry (symptoms). In Study 2, the predictive models revealed that among individuals with DS and CHD, presence of health conditions such as congestive heart failure (circulatory), valvular heart disease and cardiac shunt (congenital), and pleural effusion and pulmonary collapse (respiratory) were associated with increased likelihood of surgical intervention. CONCLUSIONS: Research efforts using EMRs and rigorous statistical methods could shed light on the complexity in health profile among individuals with DS and other IDDs and motivate precision-care development.

The action of curcumin against damage resulting from cerebral stroke: A systematic review.

Stroke is the second leading cause of morbidity and mortality globally. Treatments for stroke are limited, and preventive treatments are scarce. Curcumin (CUR) has several biological effects, as described in the literature, which highlight its antioxidant and neuroprotective effects. Therefore, this qualitative systematic review aimed to investigate the effects of CUR on damage caused by stroke in rodent models. A systematic search was performed on three databases PubMed, Scopus, and Web of Science. In addition, the risk-of-bias and quality of the studies were assessed using SYRCLE and Collaborative Approach for Meta-Analysis and Review of Animal Data from Experimental Studies, respectively. The selection, inclusion, and exclusion criteria were established by the authors. At the end of our systematic search of the three databases, we found a total of 728 articles. After excluding duplicates and triplicates and reading the abstracts, keywords, and full texts, 53 articles were finally included in this systematic review. CUR exerts several beneficial effects against the damage caused by both ischemic and hemorrhagic stroke, via different pathways. However, because of its low bioavailability, Free-form CUR only exerted significant effects when it was administered at high concentrations. In contrast, when CUR was administered using nanostructured systems, positive responses were observed even at low concentrations. The mechanisms of action of CUR, free or in nanostructure, are extremely important for the recovery of injured brain tissue after a stroke; CUR has neuroprotective, antioxidant, anti-inflammatory, and anti-apoptotic effects and helps to maintain the integrity of the blood-brain barrier. Finally, we concluded that CUR presents an extremely important and significant response profile against the damage caused by stroke, making it a possible therapeutic candidate for individuals affected by this disease.

Characterizing sleep disorders in an autism-specific collection of electronic health records.

OBJECTIVE/BACKGROUND: Sleep problems are common in people on the autism spectrum. This study reviews one detailed approach to querying the electronic health record (EHR) in a large tertiary care center. PATIENTS/METHODS: We developed methods for identifying people on the autism spectrum and defined their sleep problems using the key words, "sleep" or "melatonin", or International Classification of Diseases (ICD) codes. We examined treatment responses of these individuals to melatonin supplementation. RESULTS: Sleep problems were documented in 86% of patients with ages ranging from 6 to 30 years old. Our specific keyword search yielded more patients with sleep diagnoses than ICD codes alone. About two-thirds of patients who received melatonin supplementation reported benefit from its use. CONCLUSIONS: Our study provides a framework for using deidentified medical records to characterize sleep, a common co-occurring condition, in people on the autism spectrum. Using specific keywords could be helpful in future work that queries the EHR.

Long-term health sequelae and quality of life at least 6 months after infection with SARS-CoV-2: design and rationale of the COVIDOM-study as part of the NAPKON population-based cohort platform (POP).

PURPOSE: Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany. METHODS: The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, Würzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained. RESULTS: As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36% wished to participate and 1295 have already been examined at least once. CONCLUSION: NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00023742).

Antitumoral synergism between a copper(II) complex and cisplatin improves in vitro and in vivo anticancer activity against melanoma, lung and breast cancer cells.

BACKGROUND: Intrinsic resistance of cancer cells is a major concern for the success of chemotherapy, and this undesirable feature stimulates further research into the design of new compounds and/or alternative multiple drug chemotherapy protocols. METHODS: In this study, we investigated the antitumoral potential of the coordination compounds [Cu(HPClNOL)Cl]Cl (1), [Fe(HPClNOL)Cl2]NO3(2) and [Mn(HPClNOL)Cl2] (3). Using the human, MCF-7 and A549, and the murine melanoma, B16-F10, cell lines, we determined the cytotoxicity, DCFH oxidation, disruption of mitochondrial membrane potential (ΔΨm), Sub-G1 and TUNEL positive cells, and caspase 8 and 9 activities. Fractional inhibitory concentration (FIC) and xenograft models were also assessed to evaluate the efficacy of antitumoral potential. RESULTS: We observed that only complex 1 was cytotoxic. The treatment of cancer cells with complex 1 triggered ROS generation and promoted the disruption of ΔΨm. Complex 1 increased the number of Sub-G1 and TUNEL positive cells, and the measurement of caspase 8 and 9 activity confirmed that apoptosis was triggered by the intrinsic pathway. FIC demonstrated that the combination of complex 1 with cisplatin was additive for the A549 cells whilst it was synergic for MCF-7 and B16-F10. Treatment with complex 1, either alone or combined with cisplatin, reduced tumor growth on xenograft models. CONCLUSIONS: The present study brings new clues regarding the mechanism of action of [Cu(HPClNOL)Cl]Cl, either alone or in combination with cisplatin. GENERAL SIGNIFICANCE: These results indicate that complex 1, administered either singly or in combination with current drugs, has real potential for use in cancer therapy.

Randomized double-blind sham-controlled trial of thalamic versus GPi stimulation in patients with severe medically refractory Gilles de la Tourette syndrome.

BACKGROUND: There are still no sufficient data regarding the use of deep brain stimulation (DBS) in Gilles de la Tourette syndrome (GTS) and no agreement on optimal target. OBJECTIVE: To compare efficacy and safety of bilateral DBS of thalamus (centromedian-ventro-oral internus, CM-Voi) versus posteroventral lateral globus pallidus internus (pvl GPi)) versus sham stimulation, and baseline in severe medically refractory GTS. METHODS: In this randomized double-blind sham stimulation-controlled trial (RCT), 10 patients (3 women, mean age = 29.4 ± 10.2 SD, range 18-47) underwent three blinded periods each lasting three months including (i) sham, (ii) pvl GPi (on-GPi), and (iii) thalamic stimulation (on-thal) followed by an open uncontrolled long-term follow-up (up to 9 years) with individually determined target and stimulation settings. RESULTS: Nine patients completed the RCT. At group level, on-GPi - but not on-thal - resulted in a significant tic reduction compared to baseline, but had no effect on premonitory urges and psychiatric comorbidities. Direct comparisons of targets resulted in inconsistent or negative (compared to sham) findings. During follow-up, we found no improvement of tics, comorbidities, and quality of life at group level, however, single patients benefitted continuously from thalamic DBS. At last follow-up 89.9 months (mean) after surgery, 50% of patients had discontinued DBS. Hardware infections occurred in 3/10 patients. CONCLUSION: Our data suggest that the initial effect of pvl GPi DBS is superior to thalamic (CM-Voi) DBS. While half of the patients discontinued treatment, single patients benefitted from thalamic DBS even after years. It is likely that outcome is influenced by various factors beyond the mere change in tic severity.

Shortened Up-Dosing With 7 Injections of Subcutaneous Allergy Immunotherapy (Alutard SQ) Is Safe and Well Tolerated

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Neuroimaging Advances in Deep Brain Stimulation: Review of Indications, Anatomy, and Brain Connectomics.

Deep brain stimulation is an established therapy for multiple brain disorders, with rapidly expanding potential indications. Neuroimaging has advanced the field of deep brain stimulation through improvements in delineation of anatomy, and, more recently, application of brain connectomics. Older lesion-derived, localizationist theories of these conditions have evolved to newer, network-based "circuitopathies," aided by the ability to directly assess these brain circuits in vivo through the use of advanced neuroimaging techniques, such as diffusion tractography and fMRI. In this review, we use a combination of ultra-high-field MR imaging and diffusion tractography to highlight relevant anatomy for the currently approved indications for deep brain stimulation in the United States: essential tremor, Parkinson disease, drug-resistant epilepsy, dystonia, and obsessive-compulsive disorder. We also review the literature regarding the use of fMRI and diffusion tractography in understanding the role of deep brain stimulation in these disorders, as well as their potential use in both surgical targeting and device programming.

Curcumin-loaded nanoemulsion improves haemorrhagic stroke recovery in wistar rats.

Cerebrovascular diseases are currently a major global health problem. Considering the limitations of current therapy, the search for new alternatives for the treatment of these diseases is necessary and, in this context, curcumin, a molecule that has neuroprotective properties already described in the literature. A limiting factor when considering therapies for the nervous tissue is the presence of the blood-brain barrier which stimulates the search for new drug delivery strategies. In this context, nanoencapsulation seems to be a promising alternative. In this work, we compared the protective effects of free and nanoemulsified curcumin after intracerebral haemorrhage induced by collagenase (ICH) in Wistar rats. Injury area, motor activity, oxidative stress in the brain and serum biochemical parameters were investigated. Two hours after surgery, the first dose was injected intraperitoneally, followed by 24 and 48 h administration. Behavioural analysis was performed through 3 different tests: open field, beam walking and foot fault (24, 48 and 72 h respectively). At the end of the recovering time (3 days after injury), the animals were euthanized and the brain (for analysis of injury area and oxidative stress), blood (for biochemical parameters), kidney and liver (for histopathological examination) were investigated. Curcumin nanoemulsion 30 mg/kg was able to improve behavioural recovery, reduce the size of the haematoma and attenuate the weight loss caused by ICH. In terms of oxidative parameters, we observed that curcumin nanoemulsion modulated antioxidant responses with therapeutic potential against ICH. Only discrete results in few parameters were found with free-curcumin in the same dose.

Imaging of spindle cell lipoma.

AIM: To review the evaluation, diagnosis, and treatment of spindle cell lipoma (SCL) with emphasis on the location of these tumours and the spectrum of magnetic resonance imaging (MRI) and computed tomography (CT) appearances. MATERIALS AND METHODS: The MRI and CT findings of 27 histopathologically proven SCLs were evaluated retrospectively. Imaging features evaluated included margins, percentage visible fat, MRI signal characteristics, oedema, and contrast enhancement patterns. RESULTS: Patient ages ranged from 18 to 80 years with an average age of 56.5 years. Men were affected twice as frequently as women (M=18, F=9). SCLs ranged in size from 2 to 10 cm, with an average greatest dimension of 5.5 cm. Five lesions (19%) contained no visible fat on CT or MRI, and the leading differential diagnosis of high-grade soft-tissue sarcoma diagnosis was suggested by referring surgeons. Five lesions (19%) had <50% fatty areas, nine lesions (52%) demonstrated >50% but <90% fat at MRI or CT. Only three of 25 lesions (12%) had an appearance of a typical lipoma on unenhanced MRI sequences. All SCLs that were imaged with contrast medium (n = 18) demonstrated some degree of enhancement, with eight (44%) showing marked enhancement, four (22%) showing moderate, and six (33%) minimal enhancement. CONCLUSION: SCLs have considerably variable imaging appearances and may have minimal or no visible fat at MRI or CT. Imaging features may make it difficult to distinguish this benign tumour from a potentially higher-grade malignant tumour.

Directional DBS leads show large deviations from their intended implantation orientation.

OBJECTIVE: Lead orientation is a new degree of freedom with directional deep brain stimulation (DBS) leads. We investigated how prevalent deviations from the intended implantation direction are in a large patient cohort. METHODS: The Directional Orientation Detection (DiODe) algorithm to determine lead orientation from postoperative CT scans was implemented into the open-source Lead-DBS toolbox. Lead orientation was analyzed in 100 consecutive patients (198 leads). Different anatomical targets and intraoperative setups were compared. RESULTS: Deviations of up to 90° from the intended implantation direction were observed. Deviations of more than 30° were seen in 42% of the leads and deviations of more than 60° in about 11% of the leads. Deviations were independent from the neuroanatomical target and the stereotactic frame but increased depending on which microdrive was used. DISCUSSION: Our results indicate that large deviations from the intended implantation direction are a common phenomenon in directional leads. Postoperative determination of lead orientation is thus mandatory for investigating directional DBS.

Adverse events associated with deep brain stimulation in patients with childhood-onset dystonia.

BACKGROUND: Data on pediatric DBS is still limited because of small numbers in single center series and lack of systematic multi-center trials. OBJECTIVES: We evaluate short- and long-term adverse events (AEs) of patients undergoing deep brain stimulation (DBS) during childhood and adolescence. METHODS: Data collected by the German registry on pediatric DBS (GEPESTIM) were analyzed according to reversible and irreversible AEs and time of occurrence with relation to DBS-surgery: Intraoperative, perioperative (<4 weeks), postoperative (4 weeks < 6 months) and long term AEs (>6 months). RESULTS: 72 patients with childhood-onset dystonia from 10 DBS-centers, who received 173 DBS electrodes and 141 implantable pulse generators (IPG), were included in the registry. Mean time of postoperative follow-up was 4.6 ±â€¯4 years. In total, 184 AEs were documented in 53 patients (73.6%). 52 DBS-related AEs in 26 patients (36.1%) required 45 subsequent surgical interventions 4.7 ±â€¯4.1 years (range 3 months-15 years) after initial implantation. The total risk of an AE requiring surgical intervention was 7.9% per electrode-year. Hardware-related AEs were the most common reason for surgery. There was a tendency of a higher rate of AEs in patients aged 7-9 years beyond 6 months after implantation. DISCUSSION: The intraoperative risk of AEs in pediatric patients with dystonia undergoing DBS is very low, whereas the rate of postoperative hardware-related AEs is a prominent feature with a higher occurrence compared to adults, especially on long-term follow-up. CONCLUSION: Factors leading to such AEs must be identified and patient management has to be focused on risk minimization strategies in order to improve DBS therapy and maximize outcome in pediatric patients.

Modulation of specific components of sleep disturbances by simultaneous subthalamic and nigral stimulation in Parkinson's disease.

OBJECTIVE: To compare the effect of simultaneous deep brain stimulation of the subthalamic nucleus and substantia nigra pars reticulata (STN+SNr-DBS) to conventional subthalamic stimulation (STN-DBS) on sleep quality in Parkinson's disease (PD) patients. METHODS: The study was a single-center, randomized, double-blind, cross-over clinical trial to compare the effect of STN-DBS vs. combined STN+SNr-DBS on subjective measures of sleep quality. Fifteen PD patients (2 female, age 62.5 ± 6.7 years) suffering from moderate idiopathic PD (disease duration: 12.0 ± 5.0 years, Hoehn & Yahr stage: 2.2 ± 0.4 in the MED-ON & STN-DBS-ON condition, Hoehn & Yahr stage: 2.6 ± 0.8 in the MED-OFF condition preoperatively) participated in the study. Sleep quality was evaluated in both stimulation conditions using the PDSS-2 score as a self-rating questionnaire covering several aspects of sleep disturbances. RESULTS: PD patients showed mild-moderate sleep disturbances (STN-DBS: PDSS-2 score 17.0 ± 11.0; STN+SNr-DBS: 14.7 ± 9.5) with slight but not significant differences between both stimulation conditions. Considering the different subitems of the PDSS-2, combined STN+SNr stimulation was superior to conventional STN stimulation in improving restless legs symptoms (RLS) at night (STN-DBS = 1.9 ± 2.7 STN+SNr-DBS = 1.0 ± 1.8; W = -2.06, p = 0.039) and immobility at night (STN-DBS = 1.5 ± 1.4 STN+SNr-DBS = 0.6 ± 0.8; W = -2.041, p = 0.041). CONCLUSION: This study demonstrates the safety of STN+SNr-DBS compared to conventional STN-DBS on sleep in general with potential beneficial input on RLS symptoms and akinesia at night.

Anaesthetic method and short-term outcomes of preterm infants delivered by caesarean section at a tertiary hospital in South Africa

Background. There are inconsistent published data describing the influence of maternal anaesthetic type during caesarean section (CS) on outcomes of preterm neonates. Objectives. To describe indications and type of anaesthesia in preterm neonates, and their short-term outcomes, comparing spinal anaesthesia (SA) to general anaesthesia (GA). Methods. Data were collected retrospectively on preterm babies born at 28 - 35 weeks' gestation by CS between 1 January and 30 September 2014 at Groote Schuur Hospital, Cape Town, South Africa. Babies with missing data were excluded. The largest group of babies with similar indications for delivery were identified from the theatre register. Baseline characteristics and short-term outcomes for this group were extracted from an existing prospective data base, and compared between those delivered under SA and GA. Results. Data were available for 226 deliveries, having excluded 23 with incomplete data. Most babies (75%) were delivered under SA. The most common indication for CS was 'cardiotocograph abnormalities', in 139 deliveries. Within this group, SA was the more frequent (81.7% v. 12.9%), while GA was associated with lower Apgar scores (p<0.001) and more intubation at birth (p=0.004). There was no difference in mortality when comparing SA with GA. Conclusion. Our data suggest a sedative effect of maternal GA on preterm babies delivered by CS, and the need for staff with advanced resuscitation skills. This study provides novel baseline data in our setting, but these data need to be validated in a prospective study

The orthopaedic management of lower limb deformity in hypophosphataemic rickets.

BACKGROUND: Many patients with X-linked hypophosphataemic rickets (X-LHPR) demonstrate significant lower limb deformity despite optimal medical management. This study evaluates the use of guided growth by means of hemi-epiphysiodesis to address coronal plane deformity in the skeletally immature child. METHODS: Since 2005, 24 patients with X-LHPR have been referred to our orthopaedic unit for evaluation. All patients had standardised long leg radiographs that were analysed sequentially before and after surgery if any was performed. The rate of correction of deformity was calculated based on peri-articular angles and diaphyseal deformity angles measured at regular intervals using Traumacad software. Clinical records were reviewed to obtain relevant clinical and demographic details. Statistical analysis was performed using SPSS 23 (SPSS Inc., Chicago, IL, USA). RESULTS: The indication for surgical intervention was a mechanical axis progressing through Zone 2 or in Zone 3 despite one year of optimised medical treatment. The 15 patients underwent 16 episodes of guided growth (30 limbs, 38 segments) at a mean age of 10.3 years. In four limbs, surgery has only taken place recently; and in three limbs, correction is ongoing. Neutral mechanical axis was restored in 16/23 (70%) limbs: six improved and one limb (one segment) required osteotomy for residual deformity. The mean rate of angular correction per month was 0.3° for the proximal tibia and 0.7° for the distal femur. Patients with ≥ 3 years of growth remaining responded significantly better than older patients (p = 0.004). Guided growth was more successful in correcting valgus than varus deformity (p = 0.007). In younger patients, diaphyseal deformity corrected at a rate of 0.2° and 0.6° per month for the tibia and the femur, respectively. There has been one case of recurrent deformity. Patients with corrected coronal plane alignment did not complain of significant residual torsional malalignment. Serum phosphate and alkaline phosphatase levels did not affect response to surgery. CONCLUSIONS: Guided growth is a successful, minimally invasive method of addressing coronal plane deformity in X-LHPR. If coronal plane deformity is corrected early in patients with good metabolic control, osteotomy can be avoided.

Localization of beta and high-frequency oscillations within the subthalamic nucleus region.

Parkinsonian bradykinesia and rigidity are typically associated with excessive beta band oscillations in the subthalamic nucleus. Recently another spectral peak has been identified that might be implicated in the pathophysiology of the disease: high-frequency oscillations (HFO) within the 150-400 Hz range. Beta-HFO phase-amplitude coupling (PAC) has been found to correlate with severity of motor impairment. However, the neuronal origin of HFO and its usefulness as a potential target for deep brain stimulation remain to be established. For example, it is unclear whether HFO arise from the same neural populations as beta oscillations. We intraoperatively recorded local field potentials from the subthalamic nucleus while advancing DBS electrodes in 2 mm steps from 4 mm above the surgical target point until 2 mm below, resulting in 4 recording sites. Data from 26 nuclei from 14 patients were analysed. For each trajectory, we identified the recording site with the largest spectral peak in the beta range (13-30 Hz), and the largest peak in the HFO range separately. In addition, we identified the recording site with the largest beta-HFO PAC. Recording sites with largest beta power and largest HFO power coincided in 50% of cases. In the other 50%, HFO was more likely to be detected at a more superior recording site in the target area. PAC followed more closely the site with largest HFO (45%) than beta power (27%). HFO are likely to arise from spatially close, but slightly more superior neural populations than beta oscillations. Further work is necessary to determine whether the different activities can help fine-tune deep brain stimulation targeting.

In vitro treatment of Toxoplasma gondii with copper(II) complexes induces apoptosis-like and cellular division alterations.

Toxoplasma gondii is the causative agent of toxoplasmosis, which is one of the most common parasitic diseases in the world. This pathogen causes severe damage to immunocompromised hosts, and the most frequently used therapy is the combination of pyrimethamine and sulfadiazine, which has side effects. Thus, there is a need for new therapies that target T. gondii. Herein, we present the anti-Toxoplasma effect of two new copper(II) complexes: [(H2L1) Cu (µ-Cl)2 Cu(H2L1)] Cl2·5H2O (1) and [(H2L2) Cu (µ-Cl)2 Cu(H2L2)] Cl2·6H2O (2). Complexes (1) and (2) irreversibly controlled parasite growth in vitro, with IC50 values of 0.78µM and 3.57µM, respectively, after 48h. These complexes induced part of the tachyzoite population to convert to bradyzoites, which eventually die. The cell death mechanism was unknown, but signs of apoptosis, such as membrane blebs and nuclear fragmentation, and necrosis, such as plasma membrane disruption, intense cytoplasm vesiculation and the release of cellular contents, were seen. In addition, complex (2) interfered with the correct disposition of the inner membrane complex of the parasite, affecting cell division. These results indicate that these copper complexes have potential effects against T. gondii and may be used as drugs in the future or serve as prototypes for the development of new drugs to treat toxoplasmosis.

Impact of Combined Subthalamic Nucleus and Substantia Nigra Stimulation on Neuropsychiatric Symptoms in Parkinson's Disease Patients.

The goal of the study was to compare the tolerability and the effects of conventional subthalamic nucleus (STN) and combined subthalamic nucleus and substantia nigra (STN+SNr) high-frequency stimulation in regard to neuropsychiatric symptoms in Parkinson's disease patients. In this single center, randomized, double-blind, cross-over clinical trial, twelve patients with advanced Parkinson's disease (1 female; age: 61.3 ± 7.3 years; disease duration: 12.3 ± 5.4 years; Hoehn and Yahr stage: 2.2 ± 0.39) were included. Apathy, fatigue, depression, and impulse control disorder were assessed using a comprehensive set of standardized rating scales and questionnaires such as the Lille Apathy Rating Scale (LARS), Modified Fatigue Impact Scale (MFIS), Becks Depression Inventory (BDI-I), Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (QUIP-RS), and Parkinson's Disease Questionnaire (PDQ-39). Three patients that were initially assigned to the STN+SNr stimulation mode withdrew from the study within the first week due to discomfort. Statistical comparison of data retrieved from patients who completed the study revealed no significant differences between both stimulation conditions in terms of mean scores of scales measuring apathy, fatigue, depression, impulse control disorder, and quality of life. Individual cases showed an improvement of apathy under combined STN+SNr stimulation. In general, combined STN+SNr stimulation seems to be safe in terms of neuropsychiatric side effects, although careful patient selection and monitoring in the short-term period after changing stimulation settings are recommended.