Search

Background: Working memory (WM) impairment is a common phenomenon after stroke; however, its management in rehabilitation is less researched. This systematic review and meta-analysis aimed to provide a quantitative synthesis of the impact of computerised cognitive training (CCT) and transcranial direct current stimulation (tDCS) on WM span in post-stroke individuals. Methods: The literature search in PubMed, Embase, Scopus, and Cochrane Library focused on randomized controlled trials testing the effect of CCT and tDCS on treated stroke patients as compared to untreated controls. Neuropsychological instruments such as Digit Span Forward/Backward and Visual Span Forward Tests defined the outcome of WM span. After extracting study characteristics and quality assessment using the Cochrane Risk of Bias Tool, we conducted a meta-analysis and meta-regression using standardised mean differences. Results: The search yielded 4142 articles, nine of which (N = 461) fulfilled the inclusion criteria. In the case of CCT, we found significant improvement in Digit Span Backward Test (Z = 2.65, P = 0.008; 95% CI [0.10, 0.67]) and Visual Span Forward Test performance (Z = 3.05, P = 0.002; 95% CI [0.15, 0.69]), while for tDCS, we could not find a sufficient number of studies for the analysis. Furthermore, no significant moderating factor was found in the meta-regression. Conclusions: In conclusion, CCT appears to be a suitable choice to enhance WM span performance after stroke. However, further research is needed to investigate the effect of tDCS due to the limited number of studies. Trial registration: The meta-analysis was conducted according to PRISMA (Preferred Reporting of Systematic Reviews and Meta-Analyses) standards with a PROSPERO registration protocol (ID: CRD42023387182). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. What is known: • CTNNB1 neurodevelopmental disorder is featured by two main symptoms: cognitive impairment and exudative vitreoretinopathy. Additional manifestations include truncal hypotonia, peripheral spasticity, dystonia, behavioral problems, microcephaly, refractive errors, strabismus, intrauterine growth restriction, feeding difficulties, and scoliosis. • CTNNB1 neurodevelopmental disorder develops as a consequence of de novo germline loss-of-function pathogenic variants of the catenin beta-1 (CTNNB1) gene. The CTNNB1 protein is a component of adherens junctions and contributes to the establishment and maintenance of epithelial layers and adhesion between cells. CTNNB1 is also involved in the WNT signaling pathway regulating several biological processes including cell proliferation or cell fate determination. What is new • The c.1902dupG, p.Ala636SerfsTer12 is a novel heterozygous frameshift variant in the 12th exon of the CTNNB1 gene. Based on the ACMG variant classification guideline, this variant could be classified as a likely pathogenic one, since null variants (frameshift) in gene CTNNB1 are predicted to cause loss-of-function, which is a known mechanism of the disease. • The c.1902dupG, p.Ala636SerfsTer12 variant affects the 10th amino acid of the last 40 amino acid–long ARM domain of the encoded protein, and after 12 amino acids it results in the formation of a premature termination codon, which may either cause a nonsense-mediated RNA decay or a severely mutated protein with a largely truncated ARM domain and a missing 3' end of the protein. ARM domains may mediate the interaction of CTNNB1 with its ligands; therefore, we hypothesized that the identified novel variant has a severe loss-of-function impact on protein functions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 Ca2+ currents, NMDA activation and lost L-type Ca2+ 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 Cav1.3 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Copyright of Clinical Neuroscience / Ideggyógyászati Szemle is the property of LifeTime Media Kft. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Clinical Neuroscience / Ideggyógyászati Szemle is the property of LifeTime Media Kft. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Clinical Neuroscience / Ideggyógyászati Szemle is the property of LifeTime Media Kft. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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 fromcontrol 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Wilson's disease is a hereditary disorder of copper metabolism resulting mainly in hepatic, neurological, and psychiatric symptoms. Multiple sclerosis (MS) is an immune-mediated demyelinating disease affecting the central nervous system (CNS). The co-occurrence of these two, although not unheard of in literature, is still considered to be very rare and can give rise to diagnostic difficulties. Also, comorbidity in MS highly influences quality of life and disease progression, which makes the timely diagnosis and treatment of these conditions essential.Case Presentation: The aim of this study is to present a patient exhibiting symptoms of both MS and Wilson's disease, as well as to conduct a detailed review of previously reported cases. The patient's neurological symptoms (sensory disorder) as well as MRI and CSF findings were characteristic for MS. The diagnosis of MS preceded that of Wilson's disease and was relatively mild in course. Currently, the patient receives cladribine as an immunomodulatory treatment after escalation from glatiramer acetate therapy. Apart from one episode of acute hepatic decompensation, during which transfusion, albumin supplementation and diuretic treatment was necessary, Wilson's disease manifested as chronic impairment of liver function. The diagnosis of Wilson's disease was established by the analysis of serum coeruloplasmin levels, histological examination and genetic findings. Continuous oral penicillamine therapy led to the slow normalization of hepatic function and significant amelioration of the patient's symptoms. Correlating with cases previously reported, the course of MS was relatively mild, and like in three out of four other known cases, the symptoms of Wilson's disease were mostly restricted to hepatic dysfunction.Conclusion: The case presented in our report is similar to those reported before. The co-occurrence of the two diseases seems to be more a coincidence than a sharing of common factors in their pathogenesis; however, they are considered to influence one another. Regarding rare co-occurrences such as this one, every new case is of high importance, as it enables a better evaluation and understanding of the clinical presentations that are more characteristic of these cases, thus aiding the estimation of disease course as well as possible therapeutic choices. [ABSTRACT FROM AUTHOR]

Purpose: Lesion number and burden can predict the long-term outcome of multiple sclerosis, while the localization of the lesions is also a good predictive marker of disease progression. These biomarkers are used in studies and in clinical practice, but the reproducibility of lesion count is not well-known. Methods: In total, five raters evaluated T2 hyperintense lesions in 140 patients with multiple sclerosis in six localizations: periventricular, juxtacortical, deep white matter, infratentorial, spinal cord, and optic nerve. Black holes on T1-weighted images and brain atrophy were subjectively measured on a binary scale. Reproducibility was measured using the intraclass correlation coefficient (ICC). ICCs were also calculated for the four most accurate raters to see how one outlier can influence the results. Results: Overall, moderate reproducibility (ICC 0.5–0.75) was shown, which did not improve considerably when the most divergent rater was excluded. The areas that produced the worst results were the optic nerve region (ICC: 0.118) and atrophy judgment (ICC: 0.364). Comparing high- and low-lesion burdens in each region revealed that the ICC is higher when the lesion count is in the mid-range. In the periventricular and deep white matter area, where lesions are common, higher ICC was found in patients who had a lower lesion count. On the other hand, juxtacortical lesions and black holes that are less common showed higher ICC when the subjects had more lesions. This difference was significant in the juxtacortical region when the most accurate raters compared patients with low (ICC: 0.406 CI: 0.273–0.546) and high (0.702 CI: 0.603–0.785) lesion loads. Conclusion: Lesion classification showed high variability by location and overall moderate reproducibility. The excellent range was not achieved, owing to the fact that some areas showed poor performance. Hence, putting effort toward the development of artificial intelligence for the evaluation of lesion burden should be considered. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is the inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS) that affects approximately 2.8 million people worldwide. In the last decade, a new era was heralded in by a new phenotypic classification, a new diagnostic protocol and the first ever therapeutic guideline, making personalized medicine the aim of MS management. However, despite this great evolution, there are still many aspects of the disease that are unknown and need to be further researched. A hallmark of these research are molecular biomarkers that could help in the diagnosis, differential diagnosis, therapy and prognosis of the disease. Proteomics, a rapidly evolving discipline of molecular biology may fulfill this dire need for the discovery of molecular biomarkers. In this review, we aimed to give a comprehensive summary on the utility of proteomics in the field of MS research. We reviewed the published results of the method in case of the pathogenesis of the disease and for biomarkers of diagnosis, differential diagnosis, conversion of disease courses, disease activity, progression and immunological therapy. We found proteomics to be a highly effective emerging tool that has been providing important findings in the research of MS. [ABSTRACT FROM AUTHOR]

Introduction: Multiple Sclerosis (MS) is the most common immune-mediated chronic neurodegenerative disease of the central nervous system (CNS) affecting young people. This is due to the permanent disability, cognitive impairment, and the enormous detrimental impact MS can exert on a patient's health-related quality of life. It is of great importance to recognise it in time and commence adequate treatment at an early stage. The currently used disease-modifying therapies (DMT) aim to reduce disease activity and thus halt disability development, which in current clinical practice are monitored by clinical and imaging parameters but not by biomarkers found in blood and/or the cerebrospinal fluid (CSF). Both clinical and radiological measures routinely used to monitor disease activity lack information on the fundamental pathophysiological features and mechanisms of MS. Furthermore, they lag behind the disease process itself. By the time a clinical relapse becomes evident or a new lesion appears on the MRI scan, potentially irreversible damage has already occurred in the CNS. In recent years, several biomarkers that previously have been linked to other neurological and immunological diseases have received increased attention in MS. Additionally, other novel, potential biomarkers with prognostic and diagnostic properties have been detected in the CSF and blood of MS patients. Areas covered: In this review, we summarise the most up-to-date knowledge and research conducted on the already known and most promising new biomarker candidates found in the CSF and blood of MS patients. Discussion: the current diagnostic criteria of MS relies on three pillars: MRI imaging, clinical events, and the presence of oligoclonal bands in the CSF (which was reinstated into the diagnostic criteria by the most recent revision). Even though the most recent McDonald criteria made the diagnosis of MS faster than the prior iteration, it is still not an infallible diagnostic toolset, especially at the very early stage of the clinically isolated syndrome. Together with the gold standard MRI and clinical measures, ancillary blood and CSF biomarkers may not just improve diagnostic accuracy and speed but very well may become agents to monitor therapeutic efficacy and make even more personalised treatment in MS a reality in the near future. The major disadvantage of these biomarkers in the past has been the need to obtain CSF to measure them. However, the recent advances in extremely sensitive immunoassays made their measurement possible from peripheral blood even when present only in minuscule concentrations. This should mark the beginning of a new biomarker research and utilisation era in MS. [ABSTRACT FROM AUTHOR]

Laterality patterns of resting state networks (RSN) change in various neuropsychiatric conditions. Multiple sclerosis (MS) causes neuro-cognitive symptoms involving dysfunctional large-scale brain networks. Yet, whether healthy laterality patterns of RSNs are maintained in MS and whether altered laterality patterns explain disease symptoms has not been explicitly investigated. We analysed functional MRI and diffusion tensor imaging data from 24 relapsing–remitting MS patients and 25 healthy participants. We performed group-level independent component analysis and used dual regression to estimate individual versions of well-established RSNs. Voxelwise laterality indices were calculated for each RSN. Group differences were assessed via a general linear model-based approach. The relationship between functional laterality and white matter microstructural asymmetry was assessed using Tract-Based Spatial Statistics. Spearman's correlation was calculated between laterality indices and Brief International Cognitive Assessment for Multiple Sclerosis scores. Functional laterality of the dorsal attention network showed a significant leftward shift in the MS group in the posterior intraparietal sulcus (p < 0.033). Default-mode network laterality showed a significant leftward shift in the MS group in the angular gyrus (p < 0.005). Diminished dorsal attention network laterality was associated with increased fractional anisotropy asymmetry in the superior longitudinal fasciculus (p < 0.02). In the default-mode network, leftward laterality of the angular gyrus was associated with higher BVMT-R scores (R = − 0.52, p < 0.023). Our results confirm previous descriptions of RSN dysfunction in relapsing–remitting MS and show that altered functional connectivity lateralisation patterns of RSNs might contibute to cognitive performance and structural remodellation even in patients with mild clinical symptoms. [ABSTRACT FROM AUTHOR]

Background: Balance impairment in Parkinson's disease is multifactorial and its changes due to subthalamic stimulation vary in different studies. Objective: We aimed to analyze the combination of predictive clinical factors of balance impairment in patients with Parkinson's disease treated with bilateral subthalamic stimulation for at least one year. Methods: We recruited 24 patients with Parkinson's disease treated with bilateral subthalamic stimulation and 24 healthy controls. They wore an Opal monitor (APDM Inc.) consisting of three-dimensional gyroscopes and accelerometers in the lumbar region. We investigated four stimulation conditions (bilateral stimulation OFF, bilateral stimulation ON, and unilateral right- and left-sided stimulation ON) with four tests: stance on a plain ground with eyes open and closed, stance on a foam platform with eyes open and closed. Age, disease duration, the time elapsed after implantation, levodopa, and stimulation responsiveness were analyzed. The distance of stimulation location from the subthalamic motor center was calculated individually in each plane of the three dimensions. We analyzed the sway values in the four stimulation conditions in the patient group and compared them with the control values. We explored factor combinations (with age as confounder) in the patient group predictive for imbalance with cluster analysis and a machine‐learning‐based multiple regression method. Results: Sway combined from the four tasks did not differ in the patients and controls on a group level. The combination of the disease duration, the preoperative levodopa responsiveness, and the stimulation responsiveness predicted individual stimulation-induced static imbalance. The more affected patients had more severe motor symptoms; primarily, the proprioceptive followed by visual sensory feedback loss provoked imbalance in them when switching on the stimulation. Conclusions: The duration of the disease, the severity of motor symptoms, the levodopa responsiveness, and additional sensory deficits should be carefully considered during preoperative evaluation to predict subthalamic stimulation-induced imbalance in Parkinson's disease. [ABSTRACT FROM AUTHOR]

Background and purpose: Antiseizure medications (ASMs) should be tailored to individual characteristics, including seizure type, age, sex, comorbidities, comedications, drug allergies, and childbearing potential. We previously developed a web‐based algorithm for patient‐tailored ASM selection to assist health care professionals in prescribing medication using a decision support application (https://epipick.org). In this validation study, we used an independent dataset to assess whether ASMs recommended by the algorithm are associated with better outcomes than ASMs considered less desirable by the algorithm. Methods: Four hundred twenty‐five consecutive patients with newly diagnosed epilepsy were followed for at least 1 year after starting an ASM chosen by their physician. Patient characteristics were fed into the algorithm, blinded to the physician's ASM choices and outcome. The algorithm recommended ASMs, ranked in hierarchical groups, with Group 1 ASMs labeled as the best option for that patient. We evaluated retention rates, seizure freedom rates, and adverse effects leading to treatment discontinuation. Survival analysis contrasted outcomes between patients who received favored drugs and those who received lower ranked drugs. Propensity score matching corrected for possible imbalances between the groups. Results: Antiseizure medications classified by the algorithm as best options had a higher retention rate (79.4% vs. 67.2%, p = 0.005), higher seizure freedom rate (76.0% vs. 61.6%, p = 0.002), and lower rate of discontinuation due to adverse effects (12.0% vs. 29.2%, p < 0.001) than ASMs ranked as less desirable by the algorithm. Conclusions: Use of the freely available decision support system is associated with improved outcomes. This drug selection application can provide valuable assistance to health care professionals prescribing medication for individuals with epilepsy. [ABSTRACT FROM AUTHOR]

Background. Biomarkers for predicting treatment response to thrombolysis in acute ischemic stroke are currently lacking. Both, animal models and clinical studies have provided evidence that the kynurenine (KYN) pathway is activated in ischemic stroke. Objectives. In our pilot study, we aimed to investigate whether KYN pathway enzymes and metabolites could serve as potential biomarkers for treatment response in the hyperacute phase of ischemic stroke. Materials and methods. We included 48 acute ischemic stroke patients who received thrombolysis. Blood samples were taken both before and 12 h after treatment. Concentrations of 11 KYN metabolites were determined using ultra-high-performance liquid chromatography-mass spectrometry. To assess the treatment response, we used early neurological improvement (ENI), calculated as the difference between the admission and discharge National Institutes of Health Stroke Scale (NIHSS) scores. We performed receiver operating characteristic (ROC) analysis for KYN pathway metabolites and enzymes that showed a correlation with ENI. Results. In the samples taken before thrombolysis, significantly lower concentrations of kynurenic acid (KYNA) and kynurenine aminotransferase (KAT) activity were found in patients who had ENI (p = 0.01 and p = 0.002, respectively). According to the ROC analysis, the optimal cut-off value to predict ENI for KYNA was 37.80 nM (sensitivity (SN) 69.2%, specificity (SP) 68.4%) and 0.0127 for KAT activity (SN 92.3%, SP 73.7%). Conclusions. Our research is the first clinical pilot study to analyze changes in the KYN pathway in ischemic stroke patients who received thrombolytic treatment. Based on our results, baseline KYNA concentration and KAT activity could serve as potential biomarkers to predict early treatment response to thrombolysis. [ABSTRACT FROM AUTHOR]

Copyright of Clinical Neuroscience / Ideggyógyászati Szemle is the property of LifeTime Media Kft. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cerebral calcification may be caused by several potentially treatable conditions, however, in most cases it does not receive special attention in clinical practice. From the point of view of etiology, the diseases associated with cerebral calcification can be divided into two main groups: idiopathic (mostly incurable) and secondary (potentially treatable). The first group includes mainly the hereditary diseases identified before 2021 (primary familial brain calcification subtypes, previously known as Fahr's disease or Fahr's syndrome). In contrast, the second group includes diseases with cerebral calcification that develop generally as a consequence of metabolic/endocrine/autoimmune abnormalities. The aim of our research was to present hereditary and non-hereditary etiologies associated with extensive brain calcification. We compare the detailed clinical, radiological and laboratory results of 6 patients with prominent cerebral calcification identified in our clinic in the last 3 years (idiopathic and secondary etiologies as well). Our research draws attention to the complexity of the etiologies in the context of cerebral calcification. We recommend, beside NGS-based sequence analyses, the application of array comparative genomic hybridization as well, to identify potential genetic etiologies associated with brain calcification. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis may damage cognitive performance in several domains, including attention. Although attention network deficits were described during rest, studies that investigate their function during task performance are scarce. Objective: To investigate connectivity within and between task-related networks in multiple sclerosis during a visual attention task as a function of cognitive performance. Methods: A total of 23 relapsing-remitting multiple sclerosis (RRMS) patients and 29 healthy controls underwent task-functional magnetic resonance imaging (fMRI) scans using a visual attention paradigm on a 3T scanner. Scans were analysed using tensor-independent component analysis (TICA). Functional connectivity was calculated within and between components. We assessed cognitive function with the Brief International Cognitive Assessment for MS (BICAMS) battery. Results: TICA extracted components related to visual processing, attention, executive function and the default-mode network. Subject scores of visual/attention-related and executive components were greater in healthy controls (p < 0.032, p < 0.023). Connectivity between visual/attention-related and default-mode components was higher in patients (p < 0.043), correlating with Brief Visuospatial Memory Test–Revised (BVMT-R) scores (R = −0.48, p < 0.036). Patients showed reduced connectivity between the right intraparietal sulcus (rIPS) and frontal eye field (rFEF), and bilateral frontal eye fields (p < 0.012, p < 0.003). Reduced rIPS-rFEF connectivity came with lower Symbol Digit Modalities Test (SDMT)/BVMT-R scores in patients (R = 0.53, p < 0.02, R = 0.46, p < 0.049). Conclusion: Attention-related networks show altered connectivity during task performance in RRMS patients, scaling with cognitive disability. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disease caused by complex interaction between genetic and environmental factors. There is a growing body of evidence of the involvement of sirtuins (SIRTs) in disease pathomechanism. SIRTs are NAD+-dependent histone deacetylases which take part in various cellular functions. However, available data of the relationship between SIRT gene polymorphisms and PD is limited. Our aim was to investigate the possible association of 10 SNPs identified within non-mitochondrial SIRTs, SIRT1, -2 and -6 with the risk of PD in Hungarian population, and to compare the expression level of these SIRTs between healthy controls and PD patients. Our results showed that rs3740051 and rs3818292 of SIRT1 and rs350843, rs350844, rs107251, rs350845 and rs350846 of SIRT6 show weak association with PD risk. On the contrary rs12778366 and rs3758391 of SIRT1 and rs10410544 of SIRT2 did not show association with PD. Moreover, we detected that mRNA level of SIRT1 was down-regulated, and mRNA level of SIRT6 was up-regulated, while SIRT2 mRNA level was not altered in the peripheral blood of PD patients as compared to controls. The difference in both cases was more pronounced when comparing the early-onset PD group to the control cohort. Nevertheless, mRNA level changes did not show any association with the presence of any of the investigated SNPs either in the PD or in the control group. In conclusion, our findings suggest that non-mitochondrial sirtuins, SIRT1 and -6 but not SIRT2 might contribute to the pathogenesis of PD in the Hungarian population both via their altered mRNA levels and via gene alterations identified as specific SNPs. [ABSTRACT FROM AUTHOR]

Background: Hypointense lesions on T1-weighted images have important clinical relevance in multiple sclerosis patients. Traditionally, spin-echo (SE) sequences are used to assess these lesions (termed black holes), but Fast Spoiled Gradient-Echo (FSPGR) sequences provide an excellent alternative. Objective: To determine whether the contrast difference between T1 hypointense lesions and the surrounding normal white matter is similar on the two sequences, whether different lesion types could be identified, and whether the clinical relevance of these lesions types are different. Methods: Seventy-nine multiple sclerosis patients' lesions were manually segmented, then registered to T1 sequences. Median intensity values of lesions were identified on all sequences, then K-means clustering was applied to assess whether distinct clusters of lesions can be defined based on intensity values on SE, FSPGR, and FLAIR sequences. The standardized intensity of the lesions in each cluster was compared to the intensity of the normal appearing white matter in order to see if lesions stand out from the white matter on a given sequence. Results: 100% of lesions on FSPGR images and 69% on SE sequence in cluster #1 exceeded a standardized lesion distance of Z = 2.3 (p < 0.05). In cluster #2, 78.7% of lesions on FSPGR and only 17.7% of lesions on SE sequence were above this cutoff value, meaning that these lesions were not easily seen on SE images. Lesion count in the second cluster (lesions less identifiable on SE) significantly correlated with the Expanded Disability Status Scale (EDSS) (R : 0.30, p ≤ 0.006) and with disease duration (R : 0.33, p ≤ 0.002). Conclusion: We showed that black holes can be separated into two distinct clusters based on their intensity values on various sequences, only one of which is related to clinical parameters. This emphasizes the joint role of FSPGR and SE sequences in the monitoring of MS patients and provides insight into the role of black holes in MS. [ABSTRACT FROM AUTHOR]

Background: Recent advances in therapeutic options may prevent deterioration related to Huntington's disease (HD), even at the pre-symptomatic stage. Be that as it may, a well-characterized patient population is essential for screening and monitoring outcome. Accordingly, the aim of this study was to describe the characteristics of a Hungarian subpopulation of HD patients and mutation carriers diagnosed at the University of Szeged.Methods: We conducted a search for International Classification of Diseases (ICD) code G10H0 in the local medical database for the period of 1 January 1998 to 31 December 2018.Results: We identified 90 HD cases (male: 45, female: 45) and 34 asymptomatic carriers (male: 15, female: 19). The median age of onset was 45 years (range: 16-79). There were 3 cases of juvenile onset (3.3%), and 7 of late disease onset (7.8%). The median repeat length was 43 (range: 36-70) for the pathological and 19 for the non-pathological alleles (range: 9-35). 17.5% of the pathological alleles were in the decreased penetrance range, while 7% of non-pathological alleles were intermediate.Conclusions: The genetic and clinical features of the population examined in the present study were in line with the previous Hungarian study, as well as with international literature. The exceptions were the higher ratio of reduced penetrance and intermediate alleles. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Considering the devastating symptoms, high prevalence, and lack of definitive diagnostic test, there is an urgent need to identify possible biomarkers and new therapeutic targets. Genes identified and/or proposed to be linked to PD encode proteins that fulfill diverse roles in cellular functions. There is a growing interest in identifying common traits which lead to the disease. Long non-coding RNAs have recently emerged as possible regulatory hubs of complex molecular changes affecting PD development. Among them, NEAT1 has attracted particular interest. It is a major component and the initiator of nuclear paraspeckles, thus regulating transcription and modifying protein functions. This review summarizes data available on the role of NEAT1 in PD. NEAT1 upregulation in PD has repeatedly been reported, however, whether this is part of a protective or a damaging mechanism is still a topic of debate. It has been proposed that NEAT1 propagates PD via its interaction with PINK1 and several micro RNAs and by modulating SNCA expression. On the other hand, findings of NEAT1 acting as a bona fide LRRK2 inhibitor argue for its protective role. These contradictory results could be due to the different disease models implemented. This calls attention to the difficulties posed by the complex patho-mechanisms of neurodegenerative disorders and the limitations of disease models. However, the potential of NEAT1 as a biomarker and as a therapeutic target for PD highly warrants further research to elucidate its exact role in this neurodegenerative disorder. [ABSTRACT FROM AUTHOR]

Összefoglaló.Bevezetés: A COVID–19-járvány világszerte hónapokra átalakította a járóbeteg-ellátás működését is. Magyarországon a 2020. március 11-től 2020. június 17-ig fennálló egészségügyi veszélyhelyzeti rendelkezések szabták meg az új kereteket. Célkitűzés: Az első veszélyhelyzeti periódus második felében, 2020. április 22. és 2020. május 5. között mértük fel az epilepsziaellátásban részt vevő orvosok véleményét, hogy milyen mértékben változott a betegek ellátása, és hogyan élték meg a változásokat személyesen. Módszer: Internetes kérdőíves véleményfelmérés történt, a Magyar Epilepszia Liga 2020. április 16–17-re tervezett, de a COVID–19-járvány miatt elhalasztott XV. kongresszusára regisztrált neurológusok között. Kilenc egyszeres vagy többszörös feleletválasztós kérdés és 'szabad kommentár' mezők álltak rendelkezésre. Eredmények: A megkeresett 116 neurológus közül 33-an válaszoltak (28%), összesen 30 kommentár került rögzítésre. 73%-uk szerint a változások komoly nehézséget okoztak, 15%-uk gondolta, hogy ennek súlyos következményei lesznek. Új betegek fogadása 53%-ban leállt, 25%-ban nagy nehézségekbe ütközött. A gondozott betegek problémáit 49%-ban a távvizit lehetőségeivel élve meg tudták oldani, de 24%-ban ez nem sikerült. A beteg távollétében lebonyolított vizitek 68%-a dokumentált telefonbeszélgetések formájában zajlott. Az orvosok kétharmada veszélyeztetve érezte magát, hogy elkapja a vírust, ebből 40% úgy érezte, nem kap elegendő védelmet, 6% (2 fő) kapta el a fertőzést. Következtetés: A COVID–19-járvány a leginkább az új szakvélemények kiadását érintette, de a gondozási feladatokat sem mindig lehetett megfelelően megoldani. A károkat jelentősen enyhítette az ellátószemélyzet rugalmassága. A telefonvizitek, szükség esetén, az epileptológiában pótolhatják a személyes orvos-beteg találkozásokat. A járvány visszatérésének veszélye miatt a távvizit-alkalmazások technikai fejlesztése és ezek dokumentálási kérdéseinek megoldása fontos. A járványidőszakban a személyzet védelmére nagy figyelmet kell fordítani a fertőződés elkerülése és az orvosok biztonságérzetének fokozása érdekében. Orv Hetil. 2020; 161(46): 1939–1943. Summary.Introduction: COVID-19 pandemic has transformed the operation of outpatient care worldwide for months. The new framework was set in Hungary by the health emergency regulations that existed from 11. 03. 2020 to 17. 06. 2020. Objective: In the second half of the emergency period, between 22. 04. 2020 and 05. 05. 2020, we surveyed the opinion of physicians involved in epilepsy care about the extent to which patient care had changed and how they experienced the changes in person. Method: An internet questionnaire survey was conducted among neurologists registered for the annual congress of the Hungarian Chapter of the International League Against Epilepsy. Nine single- or multiple-choice questions and 'free comment' fields were available. Results: Of 116 neurologists contacted, 33 responded (28%), and a total of 30 comments were recorded. 73% said the changes caused a serious difficulty, 15% thought it would have serious consequences. Reception of new patients was stopped in 53%, and 25% encountered great difficulties. In 49%, the problems of the cared patients could be solved using remote visits, but 24% could not solve them properly. 68% of outpatient visits took the form of documented telephone conversations. Two-thirds of doctors feared catching the virus, 40% of whom felt they were not getting enough protection. 6% caught the infection. Conclusion: The COVID-19 pandemic has mostly affected the issuance of new expert opinions, but care tasks have not always been adequately addressed. The damage was significantly mitigated by the flexibility of the care staff. Telephone visits, if necessary, can replace personal doctor-patient encounters in epileptology. The technical development of remote visit applications and their documentation issues are important. During the pandemic period, great care must be taken to protect staff in order to avoid infection and increase the sense of safety of doctors. Orv Hetil. 2020; 161(46): 1939–1943. [ABSTRACT FROM AUTHOR]

Copyright of Clinical Neuroscience / Ideggyógyászati Szemle is the property of LifeTime Media Kft. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Clinical Neuroscience / Ideggyógyászati Szemle is the property of LifeTime Media Kft. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The potential role of Sirt1 and Sirt2 subtypes of Sirtuins (class III NAD+-dependent deacetylases) in the pathogenesis of Huntington's disease (HD) has been extensively studied yielding some controversial results. However, data regarding the involvement of Sirt3 and their variants in HD are considerably limited. The aim of this study was to assess the expression pattern of Sirt1 and three Sirt3 mRNA isoforms (Sirt3-M1/2/3) in the striatum, cortex and cerebellum in respect of the effect of gender, age and the presence of the transgene using the N171-82Q transgenic mouse model of HD. Striatal, cortical and cerebellar Sirt1-Fl and Sirt3-M1/2/3 mRNA levels were measured in 8, 12 and 16 weeks old N171-82Q transgenic mice and in their wild-type littermates. Regarding the striatum and cortex, the presence of the transgene resulted in a significant increase in Sirt3-M3 and Sirt1 mRNA levels, respectively, whereas in case of the cerebellum the transgene resulted in increased expression of all the assessed subtypes and isoforms. Aging exerted minor influence on Sirt mRNA expression levels, both in transgene carriers and in their wild-type littermates, and there was no interaction between the presence of the transgene and aging. Furthermore, there was no difference between genders. The unequivocal cerebellar Sirtuin activation with presumed compensatory role suggests that the cerebellum might be another key player in HD in addition to the most severely affected striatum. The mitochondrially acting Sirt3 may serve as an interesting novel therapeutic target in this deleterious condition. [ABSTRACT FROM AUTHOR]

DOORS [deafness, onychodystrophy, osteodystrophy, intellectual disability (mental retardation), and seizures] syndrome can be caused by mutations in the TBC1D24 and ATP6V1B2 genes, both of which are involved in endolysosomal function. Because of its extreme rarity, to date, no detailed neuropathological assessment has been performed to establish clinicopathological relationships and, thereby, understand better the neurobiology of this disease in aged cases. Accordingly, the aim of the current study was to highlight the clinicopathological characteristics of a novel case with a presumable de novo mutation in the ATP6V1B2 gene from a neuropathological point of view. This Caucasian male patient, who died at the age of 72 years, presented all the typical cardinal signs of DOORS syndrome. In addition, behavioral alterations, pyramidal signs, and Parkinsonism were observed. The p.R506X pathogenic mutation identified in the ATP6V1B2 gene was responsible for the clinical phenotype. The detailed neuropathological assessment revealed a limbic-predominant tauopathy in the forms of argyrophilic grain disease, primary age-related tauopathy, and age-related tau-astrogliopathy. In summary, we present the first detailed clinicopathological report of a patient with DOORS syndrome harboring a pathogenic mutation in the ATP6V1B2 gene. The demonstrated tauopathy may be considered as a consequence of lysosomal and/or mitochondrial dysfunction, similar to that found in Niemann–Pick type C disease, which is another lysosomal disorder characterized by premature neurodegenerative disorder. [ABSTRACT FROM AUTHOR]

Copyright of Clinical Neuroscience / Ideggyógyászati Szemle is the property of LifeTime Media Kft. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have been proposed as a new therapeutic way to enhance the cognition of patients with dementia. However, serious methodological limitations appear to affect the estimates of their efficacy. We reviewed the stimulation parameters and methods of studies that used TMS or tDCS to alleviate the cognitive symptoms of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Moreover, we evaluated the risk of bias in these studies. Our aim was to highlight the current vulnerabilities of the field and to formulate recommendations on how to manage these issues when designing studies. Methods: Electronic databases and citation searching were used to identify studies administering TMS or tDCS on patients with AD or MCI to enhance cognitive function. Data were extracted by one review author into summary tables with the supervision of the authors. The risk of bias analysis of randomized-controlled trials was conducted by two independent assessors with version 2 of the Cochrane risk-of-bias tool for randomized trials. Results: Overall, 36 trials were identified of which 23 randomized-controlled trials underwent a risk of bias assessment. More than 75% of randomized-controlled trials involved some levels of bias in at least one domain. Stimulation parameters were highly variable with some ranges of effectiveness emerging. Studies with low risk of bias indicated TMS to be potentially effective for patients with AD or MCI while questioned the efficacy of tDCS. Conclusions: The presence and extent of methodical issues affecting TMS and tDCS research involving patients with AD and MCI were examined for the first time. The risk of bias frequently affected the domains of the randomization process and selection of the reported data while missing outcome was rare. Unclear reporting was present involving randomization, allocation concealment, and blinding. Methodological awareness can potentially reduce the high variability of the estimates regarding the effectiveness of TMS and tDCS. Studies with low risk of bias delineate a range within TMS parameters seem to be effective but question the efficacy of tDCS. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Behind the symptoms there is a complex pathological mechanism which leads to a dopaminergic cell loss in the substantia nigra pars compacta. Despite the strong efforts, curative treatment has not been found yet. To prevent a further cell death, numerous molecules were tested in terms of neuroprotection in preclinical (in vitro, in vivo) and in clinical studies as well. The aim of this review article is to summarize our knowledge about the extensively tested neuroprotective agents (Search period: 1991–2019). We detail the underlying pathological mechanism and summarize the most important results of the completed animal and clinical trials. Although many positive results have been reported in the literature, there is still no evidence that any of them should be used in clinical practice (Cochrane analysis was performed). Therefore, further studies are needed to better understand the pathomechanism of PD and to find the optimal neuroprotective agent(s). [ABSTRACT FROM AUTHOR]

Background: The neurochemical background of the evolution of headache disorders, still remains partially undiscovered. Accordingly, our aim was to further explore the neurochemical profile of Complete Freund's adjuvant (CFA)-induced orofacial pain, involving finding the shift point regarding small molecule neurotransmitter concentrations changes vs. that of the previously characterized headache-related neuropeptides. The investigated neurotransmitters consisted of glutamate, γ-aminobutyric acid, noradrenalin and serotonin. Furthermore, in light of its influence on glutamatergic neurotransmission, we measured the level of kynurenic acid (KYNA) and its precursors in the kynurenine (KYN) pathway (KP) of tryptophan metabolism. Methods: The effect of CFA was evaluated in male Sprague Dawley rats. Animals were injected with CFA (1 mg/ml, 50 μl/animal) into the right whisker pad. We applied high-performance liquid chromatography to determine the concentrations of the above-mentioned compounds from the trigeminal nucleus caudalis (TNC) and somatosensory cortex (ssCX) of rats. Furthermore, we measured some of these metabolites from the cerebrospinal fluid and plasma as well. Afterwards, we carried out permutation t-tests as post hoc analysis for pairwise comparison. Results: Our results demonstrated that 24 h after CFA treatment, the level of glutamate, KYNA and that of its precursor, KYN was still elevated in the TNC, all diminishing by 48 h. In the ssCX, significant concentration increases of KYNA and serotonin were found. Conclusion: This is the first study assessing neurotransmitter changes in the TNC and ssCX following CFA treatment, confirming the dominant role of glutamate in early pain processing and a compensatory elevation of KYNA with anti-glutamatergic properties. Furthermore, the current findings draw attention to the limited time interval where medications can target the glutamatergic pathways. [ABSTRACT FROM AUTHOR]

Copyright of Clinical Neuroscience / Ideggyógyászati Szemle is the property of LifeTime Media Kft. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: The prevalence of xeroderma pigmentosum (XP) is quite low in Europe, which may result in a delay in determining the appropriate diagnosis. Furthermore, some subtypes of XP, including XPA, may manifest themselves with quite severe neurological symptoms in addition to the characteristic dermatological lesions. Accordingly, the aim of the current study is to highlight the predominant neurological aspects of XPA, as well as mild-to-moderate dermatological signs in a Hungarian family with 5 affected siblings.Case Reports: The symptoms of the Caucasian male proband started to develop at 13-14 years of age with predominantly cerebellar, hippocampal, and brainstem alterations. His elder sister and three younger brothers all presented similar, but less expressed neurological signs. The diagnostic work-up, including clinical exome sequencing, revealed 2 novel compound heterozygous mutations (p.Gln146_Tyr148delinsHis, p.Arg258TyrfsTer5) in the XPA gene. Surprisingly, only mild-to-moderate dermatological alterations were observed, and less severe characteristic ophthalmological and auditory signs were detected.Conclusions: In summary, we present the first family with genetically confirmed XPA in the Central-Eastern region of Europe, clearly supporting the notion that disturbed function of the C-terminal region of the XPA protein contributes to the development of age-dependent neurologically predominant signs. This case series may help clinicians recognize this rare disorder. [ABSTRACT FROM AUTHOR]

The genetic analysis of early-onset Parkinsonian disorder (EOPD) is part of the clinical diagnostics. Several genes have been implicated in the genetic background of Parkinsonism, which is clinically indistinguishable from idiopathic Parkinson's disease. The identification of patient's genotype could support clinical decision-making process and also track and analyse outcomes in a comprehensive fashion. The aim of our study was to analyse the genetic background of EOPD in a Hungarian cohort and to evaluate the clinical usefulness of different genetic investigations. The age of onset was between 25 and 50 years. To identify genetic alterations, multiplex ligation-dependent probe amplification (n = 142), Sanger sequencing of the most common PD-associated genes (n = 142), and next-generation sequencing (n = 54) of 127 genes which were previously associated to neurodegenerative disorders were carried out. The genetic analysis identified several heterozygous damaging substitutions in PD-associated genes (C19orf12 , DNAJC6 , DNAJC13 , EIF4G1 , LRRK2 , PRKN , PINK1 , PLA2G6 , SYNJ1). CNVs in PRKN and SNCA genes were found in five patients. In our cohort, nine previously published genetic risk factors were detected in three genes (GBA , LRRK2 , and PINK1). In nine cases, two or three coexisting pathogenic mutations and risk variants were identified. Advances of sequencing technologies make it possible to aid diagnostics of PD by widening the scope of analysis to genes which were previously linked to other neurodegenerative disorders. Our data suggested that rare damaging variants are enriched versus neutral variants, among PD patients in the Hungarian population, which raise the possibility of an oligogenic effect. Heterozygous mutations of multiple recessive genes involved in the same pathway may perturb the molecular process linked to PD pathogenesis. Comprehensive genetic assessment of individual patients can rarely reveal monogenic cause in EOPD, although it may identify the involvement of multiple PD-associated genes in the background of the disease and may facilitate the better understanding of clinically distinct phenocopies. Due to the genetic complexity of the disease, genetic counselling and management is getting more challenging. Clinical geneticist should be prepared for counselling of patients with coexisting disease-causing mutations and susceptibility factors. At the same time, genomic-based stratification has increasing importance in future clinical trials. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Evaluation of transorbital sonography measures of optic nerve diameter in the context of global and regional brain volume in multiple sclerosis." The original article contained an incomplete Acknowledgements section, which has now been corrected. The authors of the article have been supported by various grants and funding sources. The correction has been made by Szabolcs István Antal, Bálint Kincses, Dániel Veréb, András Király, Eszter Tóth, Bence Bozsik, Péter Faragó, Nikoletta Szabó, Krisztián Kocsis, Krisztina Bencsik, Péter Klivényi, and Zsigmond Tamás Kincses. [Extracted from the article]

Correction to: I Scientific Repots i https://doi.org/10.1038/s41598-023-31706-5, published online 05 April 2023 The Acknowledgements section in the original version of this Article was incomplete. The author (ZTK) was supported by an OTKA Grant (K 139415)." now reads: "The author (SIA) was supported by the ÚNKP-22-3-SZTE-232 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund. [Extracted from the article]