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Background: There is scarce information in Middle-Eastern Europe regarding the prevalence of anxiety in patients with multiple sclerosis (pwMS) and its association with different clinical-demographic factors., Objective: We aimed to determine the prevalence of anxiety in Hungarian MS patients and to analyze associated factors., Materials and Methods: We evaluated 260 PwMS with the STAI-5 anxiety questionnaire. Fatigue (FIS), depression (BDI-II) and cognition (BICAMS) were also measured. Patients underwent standard neurological evaluations to evaluate Expanded Disability Status Scale (EDSS), and also measured the fine motor skills of the hand with the 9-hole peg test (9HPT), and the walking distance with the 25-foot walking test (T25FW)., Results: We identified 23.1% (N = 60) of the patients with anxiety (only state, trait or both forms concurrently). According to our two univariate, multivariable logistic regression analysis, fatigue and depression are strongly associated with both state and trait anxiety. In the absence of fatigue, the odds of trait anxiety are 82% lower (OR: 0.18; 95% CI: 0.06-0.53; p = 0.002), while in the case of pwMS without depression, the odds are reduced by 81% (OR: 0.19; CI95%= 0.07-0.51, p = 0.001). This association with fatigue (OR: 0.33; CI95%= 0.13-0.85, p = 0.021) and depression (OR: 0.14; CI95%=0.06-0.35; p < 0.001) can also be statistically verified on state anxiety. Importantly, a significant association with state anxiety was found in SPSM patients as well (OR: 34.94; CI95%=2.55-479.61; p = 0.008)., Conclusions: Anxiety was strongly associated with fatigue, depression, and secondary progressive disease form. These results emphasize the burden of psychiatric morbidity in pwMS., (© 2024. Fondazione Società Italiana di Neurologia.)

Background: Due to its heterogeneous manifestation an individualized approach to reach therapeutic goals in cervical dystonia (CD) is advantageous., Objectives: The aim of the current study was to adapt goal attainment scaling (GAS) to drive the management of CD., Methods: 38 patients with CD, regularly treated with botulinum neurotoxin (BoNT), were involved in the current exploratory observational pilot study. GAS, including domains of motor, pain, disability, and psychiatric features, was applied to set up individualized goals with the calculation of initial GAS T-scores. Following at least 4 BoNT injection cycles, patients were reassessed whether they reached the pre-set goals., Results: The initial GAS T-scores (median: 36.9, range: 22.8-40) significantly improved (P < 0.001) to the end of the study (the median of final GAS T-scores: 50, range: 25.5-63.6)., Conclusions: The applicability of GAS in CD patients was confirmed, but further large-scale studies are needed refining this innovative approach., (© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Cognitive impairment (CI) is a frequent symptom of multiple sclerosis (MS) and has a great impact on the patients' quality of life, so screening is essential. The brief international cognitive assessment for multiple sclerosis (BICAMS) was developed for this purpose. However, longitudinal data is lacking with the use of the battery., Objective: This study is to assess the performance of patients after 5 and 7 years of the original BICAMS validation study and to identify any influencing factors., Methods: BICAMS was used to measure cognitive function of 52 relapsing-remitting MS patients (RRMS) from the original validation study after 5 years (n = 43) and again, after 7 years (n = 42). Patients filled out the fatigue impact scale (FIS) and multiple sclerosis quality of life-54 (MSQoL-54) questionnaire, and we evaluated expanded disability status scale (EDSS)., Results: There was an improvement in the BVMT-R and the CVLT-II assessments at both the 5-year (p<0.001 and p=0.025) and the 7-year retest (p<0.001 and p=0.002). The prevalence of CI significantly decreased at the 5-year mark (p=0.021) but remained stable after that. There was no deterioration in MSQoL scores during the study. The basic cognitive performance is the most important influencing factor, but the duration of the disease, the EDSS score, and the escalation of the therapy also affect the cognitive scores., Conclusion: This is the longest longitudinal study utilizing the BICAMS battery, reinforcing its feasibility as a clinical screening tool. It seems that cognitive performance may improve in the long term and early initiation of effective therapy may influence this outcome., (© 2024. Fondazione Società Italiana di Neurologia.)

Introduction: Parkinson's disease (PD) has a complex genetic background involving both rare and common genetic variants. Although a small percentage of cases show a clear Mendelian inheritance pattern, it is much more relevant to identify patients who present with a complex genetic profile of risk variants with different severity. The ß-glucocerebrosidase coding gene (GBA1) is recognized as the most frequent genetic risk factor for PD and Lewy body dementia, irrespective of reduction of the enzyme activity due to genetic variants., Methods: In a selected cohort of 190 Hungarian patients with clinical signs of PD and suspected genetic risk, we performed the genetic testing of the GBA1 gene. As other genetic hits can modify clinical features, we also screened for additional rare variants in other neurodegenerative genes and assessed the APOE-ε genotype of the patients., Results: In our cohort, we identified 29 GBA1 rare variant (RV) carriers. Out of the six different detected RVs, the highly debated E365K and T408M variants are composed of the majority of them (22 out of 32). Three patients carried two GBA1 variants, and an additional three patients carried rare variants in other neurodegenerative genes (SMPD1, SPG11, and SNCA). We did not observe differences in age at onset or other clinical features of the patients carrying two GBA1 variants or patients carrying heterozygous APOE-ε4 allele., Conclusion: We need further studies to better understand the drivers of clinical differences in these patients, as this could have important therapeutic implications., (© 2023. The Author(s).)

Objective: This study was undertaken to conduct external validation of previously published epilepsy surgery prediction tools using a large independent multicenter dataset and to assess whether these tools can stratify patients for being operated on and for becoming free of disabling seizures (International League Against Epilepsy stage 1 and 2)., Methods: We analyzed a dataset of 1562 patients, not used for tool development. We applied two scales: Epilepsy Surgery Grading Scale (ESGS) and Seizure Freedom Score (SFS); and two versions of Epilepsy Surgery Nomogram (ESN): the original version and the modified version, which included electroencephalographic data. For the ESNs, we used calibration curves and concordance indexes. We stratified the patients into three tiers for assessing the chances of attaining freedom from disabling seizures after surgery: high (ESGS = 1, SFS = 3-4, ESNs > 70%), moderate (ESGS = 2, SFS = 2, ESNs = 40%-70%), and low (ESGS = 2, SFS = 0-1, ESNs < 40%). We compared the three tiers as stratified by these tools, concerning the proportion of patients who were operated on, and for the proportion of patients who became free of disabling seizures., Results: The concordance indexes for the various versions of the nomograms were between .56 and .69. Both scales (ESGS, SFS) and nomograms accurately stratified the patients for becoming free of disabling seizures, with significant differences among the three tiers (p < .05). In addition, ESGS and the modified ESN accurately stratified the patients for having been offered surgery, with significant difference among the three tiers (p < .05)., Significance: ESGS and the modified ESN (at thresholds of 40% and 70%) stratify patients undergoing presurgical evaluation into three tiers, with high, moderate, and low chance for favorable outcome, with significant differences between the groups concerning having surgery and becoming free of disabling seizures. Stratifying patients for epilepsy surgery has the potential to help select the optimal candidates in underprivileged areas and better allocate resources in developed countries., (© 2023 International League Against Epilepsy.)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder which is characterized by the loss of both upper and lower motor neurons in the central nervous system. In a significant fraction of ALS cases - irrespective of family history- a genetic background may be identified. The genetic background of ALS shows a high variability from one ethnicity to another. The most frequent genetic cause of ALS is the repeat expansion of the C9orf72 gene. With the emergence of next-generation sequencing techniques and copy number alteration calling tools the focus in ALS genetics has shifted from disease causing genes and mutations towards genetic susceptibility and risk factors.In this review we aimed to summarize the most widely recognized and studied ALS linked repeat expansions and copy number variations other than the hexanucleotide repeat expansion in the C9orf72 gene. We compare and contrast their involvement and phenotype modifying roles in ALS among different populations., (© 2024. The Author(s).)

Purpose: We aimed to elucidate the underlying disease in a Hungarian family, with only one affected family member, a 16-year-old male Hungarian patient, who developed global developmental delay, cognitive impairment, behavioral problems, short stature, intermittent headaches, recurrent dizziness, strabismus, hypermetropia, complex movement disorder and partial pituitary dysfunction. After years of detailed clinical investigations and careful pediatric care, the exact diagnosis of the patient and the cause of the disease was still unknown., Methods: We aimed to perform whole exome sequencing (WES) in order to investigate whether the affected patient is suffering from a rare monogenic disease., Results: Using WES, we identified a novel, de novo frameshift variant (c.1902dupG, p.Ala636SerfsTer12) of the catenin beta-1 (CTNNB1) gene. Assessment of the novel CTNNB1 variant suggested that it is a likely pathogenic one and raised the diagnosis of CTNNB1 neurodevelopmental disorder (OMIM 615,075)., Conclusions: Our manuscript may contribute to the better understanding of the genetic background of the recently discovered CTNNB1 neurodevelopmental disorder and raise awareness among clinicians and geneticists. The affected Hungarian family demonstrates that based on the results of the clinical workup is difficult to establish the diagnosis and high-throughput genetic screening may help to solve these complex cases., (© 2024. The Author(s).)

Introduction: Current guidelines recommend transthoracic echocardiography (TTE) for routine screening of cardiac emboli; however, the visualization of the left atrial appendage (LAA) where the thrombi are commonly found is poor. Transesophageal echocardiography (TEE) would provide better detectability of LAA thrombus, but it is a time-consuming and semi-invasive method. Extending non-gated carotid computed tomography angiography (CTA) examination to the LAA could reliably detect thrombi and could also aid treatment and secondary prevention of stroke., Methods: We extended the CTA scan range of acute stroke patients 4 cm below the carina to include the left atrium and appendage. During the review, we evaluated LAA thrombi based on contrast relations. We then used gradient boosting to identify the most important predictors of LAA thrombi from a variety of different clinical parameters., Results: We examined 240 acute stroke patients' extended CTA scans. We detected LAA thrombi in eleven cases (4.58%), eight of them had atrial fibrillation. 23.75% of all patients (57 cases) had recently discovered or previously known atrial fibrillation. Windsack morphology was the most commonly associated morphology with filling defects on CTA. According to the gradient-boosting analysis, LAA morphology showed the most predictive value for thrombi., Conclusion: Our extended CTA scans reliably detected LAA thrombi even in cases where TTE did not and showed that 2 patients' LAA thrombus would have been untreated based on electrocardiogram monitoring and TTE. We also showed that the benefits of CTA outweigh the disadvantages arising from the slight amount of excess radiation., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objective: To evaluate direct user experience with wearable seizure detection devices in the home environment., Methods: A structured online questionnaire was completed by 242 users (175 caregivers and 67 persons with epilepsy), most of the patients (87.19%) having tonic-clonic seizures., Results: The vast majority of the users were overall satisfied with the wearable device, considered that using the device was easy, and agreed that the use of the device improved their quality of life (median = 6 on 7-point Likert scale). A high retention rate (84.58%) and a long median usage time (14 months) were reported. In the home environment, most users (75.85%) experienced seizure detection sensitivity similar (≥95%) to what was previously reported in validation studies in epilepsy monitoring units. The experienced false alarm rate was relatively low (0-0.43 per day). Due to the alarms, almost one third of persons with epilepsy (PWEs; 30.00%) experienced decrease in the number of seizure-related injuries, and almost two thirds of PWEs (65.41%) experienced improvement in the accuracy of seizure diaries. Nonvalidated devices had significantly lower retention rate, overall satisfaction, perceived sensitivity, and improvement in quality of life, as compared with validated devices., Significance: Our results demonstrate the feasibility and usefulness of automated seizure detection in the home environment., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Transcranial direct current stimulation (tDCS) has been tested to modulate cognitive control or response inhibition using various electrode montages. However, electrode montages and current polarities have not been systematically compared when examining tDCS effects on cognitive control and response inhibition. In this randomized, sham-controlled study, 38 healthy volunteers were randomly grouped into receiving one session of sham, anodal, and cathodal each in an electrode montage that targeted either the dorsolateral prefrontal cortex (DLPFC) or the fronto-medial (FM) region. Participants performed a combined flanker Go/No-Go task during stimulation. No effect of tDCS was found in the DLPFC and FM groups neither using anodal nor cathodal stimulation. No major adverse effects of tDCS were identified using either montage or stimulation type and the two groups did not differ in terms of the reported sensations. The present study suggests that single-session tDCS delivered in two two-electrode montages might not affect cognitive control or response inhibition, despite using widely popular stimulation parameters. This is in line with the heterogeneous findings in the field and calls for further systematic research to exclude less reliable methods from those with more pronounced effects, identify the determinants of responsiveness, and develop optimal ways to utilize this technique., (© 2023. The Author(s).)

Dystonia is a rare movement disorder which is characterized by sustained or intermittent muscle contractions causing abnormal and often repetitive movements, postures, or both. The two most common forms of adult-onset focal dystonia are cervical dystonia (CD) and benign essential blepharospasm (BSP). A total of 121 patients (CD, 74; BSP, 47) were included in the study. The average age of the patients was 64 years. For the next-generation sequencing (NGS) approach, 30 genes were selected on the basis of a thorough search of the scientific literature. Assessment of 30 CD- and BSP-associated genes from 121 patients revealed a total of 209 different heterozygous variants in 24 genes. Established clinical and genetic validity was determined for nine heterozygous variations (three likely pathogenic and six variants of uncertain significance). Detailed genetic examination is an important part of the work-up for focal dystonia forms. To our knowledge, our investigation is the first such study to be carried out in the Middle-European region.

Transorbital sonography (TOS) could be a swift and convenient method to detect the atrophy of the optic nerve, possibly providing a marker that might reflect other quantitative structural markers of multiple sclerosis (MS). Here we evaluate the utility of TOS as a complementary tool for assessing optic nerve atrophy, and investigate how TOS-derived measures correspond to volumetric brain markers in MS. We recruited 25 healthy controls (HC) and 45 patients with relapsing-remitting MS and performed B-mode ultrasonographic examination of the optic nerve. Patients additionally underwent MRI scans to obtain T1-weighted, FLAIR and STIR images. Optic nerve diameters (OND) were compared between HC, MS patients with and without history of optic neuritis (non-ON) using a mixed-effects ANOVA model. The relationship between within-subject-average OND and global and regional brain volumetric measures was investigated using FSL SIENAX, voxel-based morphometry and FSL FIRST. OND was significantly different between HC-MS (HC = 3.2 ± 0.4 mm, MS = 3 ± 0.4 mm; p < 0.019) and we found significant correlation between average OND and normalised whole brain (β = 0.42, p < 0.005), grey matter (β = 0.33, p < 0.035), white matter (β = 0.38, p < 0.012) and ventricular cerebrospinal fluid volume (β = - 0.36, p < 0.021) in the MS group. History of ON had no impact on the association between OND and volumetric data. In conclusion, OND is a promising surrogate marker in MS, that can be simply and reliably measured using TOS, and its derived measures correspond to brain volumetric measures. It should be further explored in larger and longitudinal studies., (© 2023. The Author(s).)

Progressive multiple sclerosis (MS) is a chronic disease with a unique pattern, which is histologically classified into the subpial type 3 lesions in the autopsy. The lesion is also homologous to that of cuprizone (CPZ) toxin-induced animal models of demyelination. Aberration of the tryptophan (TRP)-kynurenine (KYN) metabolic system has been observed in patients with MS; nevertheless, the KYN metabolite profile of progressive MS remains inconclusive. In this study, C57Bl/6J male mice were treated with 0.2% CPZ toxin for 5 weeks and then underwent 4 weeks of recovery. We measured the levels of serotonin, TRP, and KYN metabolites in the plasma and the brain samples of mice at weeks 1, 3, and 5 of demyelination, and at weeks 7 and 9 of remyelination periods by ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) after body weight measurement and immunohistochemical analysis to confirm the development of demyelination. The UHPLC-MS/MS measurements demonstrated a significant reduction of kynurenic acid, 3-hydoxykynurenine (3-HK), and xanthurenic acid in the plasma and a significant reduction of 3-HK, and anthranilic acid in the brain samples at week 5. Here, we show the profile of KYN metabolites in the CPZ-induced mouse model of demyelination. Thus, the KYN metabolite profile potentially serves as a biomarker of progressive MS and thus opens a new path toward planning personalized treatment, which is frequently obscured with immunologic components in MS deterioration.

Amyotrophic lateral sclerosis (ALS) is a lethal multisystem neurodegenerative disease associated with progressive loss of motor neurons, leading to death. Not only is the clinical picture of ALS heterogenous, but also the pain sensation due to different types of pain involvement. ALS used to be considered a painless disease, but research has been emerging and depicting a more complex pain representation in ALS. Pain has been detected even a couple years before the symptomatic stage of ALS, referring to primary pain associated with muscle denervation, although secondary pain due to nociceptive causes is also a part of the clinical picture. A new non-contact dying-back injury mechanism theory of ALS recently postulated that the irreversible intrafusal proprioceptive Piezo2 microinjury could be the primary damage, with underlying genetic and environmental risk factors. Moreover, this Piezo2 primary damage is also proposed to dysregulate the primary pain pathways in the spinal dorsal horn in ALS due to the lost imbalanced subthreshold Ca 2+ currents, NMDA activation and lost L-type Ca 2+ currents, leading to the lost activation of wide dynamic range neurons. Our investigation is the first to show that the likely pathogenic variants of the Ca v 1.3 encoding CACNA1D gene may play a role in ALS pathology and the associated dysregulation or loss of the pain sensation. Furthermore, our reanalysis also shows that the SCN1A gene might also contribute to the dysregulated pain sensation in ALS. Finally, the absence of pathogenic variants of Piezo2 points toward the new non-contact dying-back injury mechanism theory of ALS. However, molecular and genetic investigations are needed to identify the functionally diverse features of this proposed novel critical pathway.

Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited., Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD., Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed., Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published., Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background and Purpose:

Cervical dys&shy;tonia (CD) is the most common form of focal dystonias, where the identification of the involved muscles, the determination of optimal botulinum neurotoxin A (BoNT-A) dose per muscle injection, and precise tar&shy;ge&shy;ting may be challenging. The aim of the current study is to compare local centre data with international data, enabling the iden&shy;tification of population and me&shy;tho&shy;do&shy;&shy;lo&shy;gical factors behind the differences, there&shy;by further improvement of the care of Hun&shy;ga&shy;rian patients with CD.

The data of all consecutive CD patients, who were injected with BoNT-A at the botulinum neurotoxin outpatient clinic at the Department of Neurology, University of Szeged between 11 August and 21 Sep&shy;tember 2021, were retrospectively col&shy;lected and analysed in a cross-sectional manner. The frequency of the involved muscles, determined by the application of the collum-caput (COL-CAP) concept, and the parameters for the BoNT-A formulations, injected via ultrasound (US)-guidance, were calculated and compared with available international data.

In the current study, 58 patients (19 males and 39 females) were involved with mean age of 58.4 (&plusmn; SD 13.6, range 24-81) years. The most common subtype was torticaput (29.3%). Tremor affected 24.1% of patients. The most injected muscles were trapezius (56.9% of all cases), followed by the levator scapulae (51.7%), splenius capitis (48.3%), sternocleidomastoid (32.8%), and semispinalis capitis (22.4%). The injected mean doses per patient were 117 &plusmn; SD 38.5 (range: 50-180) units for onaBoNT-A, 118 &plusmn; SD 29.8 (range: 80-180) units for incoBoNT-A, and 405 &plusmn; SD 162 (range: 100-750 units) for aboBoNT-A.

Although there were several similarities between the results of the current and the multicentre studies, all were carried out using the COL-CAP concept and US-guided BoNT-A injections, authors should pay attention to better distinction of torti-forms and the more frequent injection of especially the obliquus capitis inferior, mainly in cases with no-no tremor.

Spinocerebellar ataxia (SCA) 40 is an extremely rare subtype of the phenotypically and genetically diverse autosomal dominant ataxias caused by mutations of the CCDC88C gene. Most reported cases of SCA40 are characterized by late-onset cerebellar ataxia and variable extrapyramidal features; however, there is a report of a patient with early-onset spastic paraparesis as well. Here, we describe a novel missense CCDC88C mutation (p.R203W) in the hook domain of the DAPLE protein encoded by the CCDC88C gene that was identified in a female patient who developed late-onset ataxia, dysmetria and intention tremor. To explore the molecular consequences of the newly identified and previously described CCDC88C mutations, we carried out in vitro functional tests. The CCDC88C alleles were expressed in HEK293 cells, and the impact of the mutant DAPLE protein variants on JNK pathway activation and apoptosis was assessed. Our results revealed only a small-scale activation of the JNK pathway by mutant DAPLE proteins; however, increased JNK1 phosphorylation could not be detected. Additionally, none of the examined mutations triggered proapoptotic effect. In conclusion, we identified a novel mutation of the CCDC88C gene from a patient with spinocerebellar ataxia. Our results are not in accord with previous observations and do not support the primary role of the CCDC88C mutations in induction of JNK pathway activation in ataxia. Therefore, we propose that CCDC88C mutations may exert their effects through different and possibly in much broader, yet unexplored, biological processes.

Introduction: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. The median age of disease onset is around 60 years. From a genetic point of view, PD is basically considered a sporadic, idiopathic disease, however, hereditary components can be detected in 5-10% of patients. Expanding data are available regarding the targeted molecular therapy of the disease., Areas Covered: The aim of this current review article is to provide brief clinical and molecular insight into three important genetic forms (LRRK2, SNCA, GBA) of hereditary PD subtypes and to present the human clinical trials in relation to these forms of the disease., Expert Opinion: These small hereditary subgroups are crucially important in drug development, because the general trend is that clinical trials that treat PD patients as a large group, without any separation, do not meet expectations. As a result, no long term conclusions can currently be drawn regarding the effectiveness of the molecules tested in these phase 1 and 2 studies. Further precise studies are needed in the near future.

Background: Earlier studies reported alterations of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism in Parkinson's disease (PD). The first rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan dioxygenase were observed upregulated, resulting elevated KYN/TRP ratios in the serum and cerebrospinal fluid samples of patients with PD. More and more single nucleotide polymorphisms (SNPs) have been identified in a population of PD. However, little is known about the impact of genetic variations of the IDO on the pathogenesis of PD., Methods: SNP analysis of IDO1 was performed by allelic discrimination assay with fluorescently labelled TaqMan probes and a subgroup analysis was conducted according to the age of PD onset. The frame shifts variant rs34155785, intronic variant rs7820268, and promotor region variant rs9657182 SNPs of 105 PD patients without comorbidity were analyzed and compared to 129 healthy controls., Results: No significant correlation was found in three SNPs between PD patients and healthy controls. However, the subgroup analysis revealed that A alleles of rs7820268 SNP or rs9657182 SNP carriers contribute to later onset of PD than non-carriers., Conclusions: The study suggested that SNPs of IDO1 influenced the age onset of PD and genotyping of SNPs in certain alleles potentially serves as a risk biomarker of PD., Competing Interests: Given his role as Guest Editor, Masaru Tanaka had no involvement in the peer-review of this article and has no access to information regarding its peer-review. Full responsibility for the editorial process for this article was delegated to Graham Pawelec. The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

We investigated the effect of deep brain stimulation on dynamic balance during gait in Parkinson's disease with motion sensor measurements and predicted their values from disease-related factors. We recruited twenty patients with Parkinson's disease treated with bilateral subthalamic stimulation for at least 12 months and 24 healthy controls. Six monitors with three-dimensional gyroscopes and accelerometers were placed on the chest, the lumbar region, the two wrists, and the shins. Patients performed the instrumented Timed Up and Go test in stimulation OFF, stimulation ON, and right- and left-sided stimulation ON conditions. Gait parameters and dynamic balance parameters such as double support, peak turn velocity, and the trunk's range of motion and velocity in three dimensions were analyzed. Age, disease duration, the time elapsed after implantation, the Hoehn-Yahr stage before and after the operation, the levodopa, and stimulation responsiveness were reported. We individually calculated the distance values of stimulation locations from the subthalamic motor center in three dimensions. Sway values of static balance were collected. We compared the gait parameters in the OFF and stimulation ON states and controls. With cluster analysis and a machine-learning-based multiple regression method, we explored the predictive clinical factors for each dynamic balance parameter (with age as a confounder). The arm movements improved the most among gait parameters due to stimulation and the horizontal and sagittal trunk movements. Double support did not change after switching on the stimulation on the group level and did not differ from control values. Individual changes in double support and horizontal range of trunk motion due to stimulation could be predicted from the most disease-related factors and the severity of the disease; the latter also from the stimulation-related changes in the static balance parameters. Physiotherapy should focus on double support and horizontal trunk movements when treating patients with subthalamic deep brain stimulation., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kelemen, Halász, Muthuraman, Erőss, Barsi, Zádori, Laczó, Kis, Klivényi, Fekete, Bognár, Bereczki and Tamás.)

Visual dysfunction is a recognized early symptom of Parkinson's disease (PD) that partly scales motor symptoms, yet its background is heterogeneous. With additional deficits in visuospatial attention, the two systems are hard to disentangle and it is not known whether impaired functional connectivity in the visual cortex is translative in nature or disrupted attentional modulation also contributes. In this study, we investigate functional connectivity modulation during a visuospatial attention task in patients with PD. In total, 15 PD and 16 age-matched healthy controls performed a visuospatial attention task while undergoing fMRI, in addition to a resting-state fMRI scan. Tensorial independent component analysis was used to investigate task-related network activity patterns. Independently, an atlas-based connectivity modulation analysis was performed using the task potency method. Spearman's rank correlation was calculated between task-related network expression, connectivity modulation, and clinical characteristics. Task-related networks including mostly visual, parietal, and prefrontal cortices were expressed to a significantly lesser degree in patients with PD ( p < 0.027). Resting-state functional connectivity did not differ between the healthy and diseased cohorts. Connectivity between the precuneus and ventromedial prefrontal cortex was modulated to a higher degree in patients with PD ( p < 0.004), while connections between the posterior parietal cortex and primary visual cortex, and also the superior frontal gyrus and opercular cortex were modulated to a lesser degree ( p < 0.001 and p < 0.011). Task-related network expression and superior frontal gyrus-opercular cortex connectivity modulation were significantly associated with UPDRSIII motor scores and the Hoehn-Yahr stages ( R = -0.72, p < 0.006 and R = -0.90, p < 0.001; R = -0.68, p < 0.01 and R = -0.71, p < 0.007). Task-related networks function differently in patients with PD in association with motor symptoms, whereas impaired modulation of visual and default-mode network connectivity was not correlated with motor function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Veréb, Kovács, Antal, Kocsis, Szabó, Kincses, Bozsik, Faragó, Tóth, Király, Klivényi, Zádori and Kincses.)