The immune system in Parkinson's disease: what we know so far.

Parkinson's disease (PD) is characterised neuropathologically by the degeneration of dopaminergic neurons in the ventral midbrain, the accumulation of α-synuclein (α-syn) aggregates in neurons, and chronic neuroinflammation. In the past two decades, in vitro, ex vivo and in vivo studies have consistently shown the involvement of inflammatory responses mediated by microglia and astrocytes, which may be elicited by pathological α-syn or signals from affected neurons and other cell types, and are directly linked to neurodegeneration and disease development. Besides the prominent immune alterations seen in the central nervous system (CNS), including the infiltration of T-cells into the brain, more recent studies have demonstrated important changes in the peripheral immune profile within both the innate and adaptive compartments, particularly involving monocytes, CD4+ and CD8+ T-cells. This review aims to integrate the consolidated understanding of immune-related processes underlying the pathogenesis of PD, focusing on both central and peripheral immune cells, neuron-glia crosstalk as well as the central-peripheral immune interaction during the development of PD. Our analysis seeks to provide a comprehensive view of the emerging knowledge of the mechanisms of immunity in PD and the implications of this for better understanding the overall pathogenesis of this disease.

FARS-ADL across Ataxias: Construct Validity, Sensitivity to Change, and Minimal Important Change.

BACKGROUND: Patient-focused outcomes present a central need for trial-readiness across all ataxias. The Activities of Daily Living part of the Friedreich Ataxia Rating Scale (FARS-ADL) captures functional impairment and longitudinal change but is only validated in Friedreich Ataxia. OBJECTIVE: Validation of FARS-ADL regarding disease severity and patient-meaningful impairment, and its sensitivity to change across genetic ataxias. METHODS: Real-world registry data of FARS-ADL in 298 ataxia patients across genotypes were analyzed, including (1) cross-correlation with FARS-stage, Scale for the Assessment and Rating of Ataxia (SARA), Patient-Reported Outcome Measure (PROM)-ataxia, and European Quality of Life 5 Dimensions visual analogue scale (EQ5D-VAS); (2) sensitivity to change within a trial-relevant 1-year median follow-up, anchored in Patient Global Impression of Change (PGI-C); and (3) general linear modeling of factors age, sex, and depression (nine-item Patient Health Questionnaire [PHQ-9]). RESULTS: FARS-ADL correlated with overall disability (rhoFARS-stage = 0.79), clinical disease severity (rhoSARA = 0.80), and patient-reported impairment (rhoPROM-ataxia = 0.69, rhoEQ5D-VAS = -0.37), indicating comprehensive construct validity. Also at item level, and validated within genotype (SCA3, RFC1), FARS-ADL correlated with the corresponding SARA effector domains; and all items correlated to EQ5D-VAS quality of life. FARS-ADL was sensitive to change at a 1-year interval, progressing only in patients with worsening PGI-C. Minimal important change was 1.1. points based on intraindividual variability in patients with stable PGI-C. Depression was captured using FARS-ADL (+0.3 points/PHQ-9 count) and EQ5D-VAS, but not FARS-stage or SARA. CONCLUSION: FARS-ADL reflects both disease severity and patient-meaningful impairment across genetic ataxias, with sensitivity to change in trial-relevant timescales in patients perceiving change. It thus presents a promising patient-focused outcome for upcoming ataxia trials. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Comparative Assessment of Gait and Balance in Patients with Parkinson's Disease and Normal Pressure Hydrocephalus.

Objectives: We aim to compare balance and gait parameters in patients diagnosed with Parkinson's disease (PD) and normal pressure hydrocephalus (NPH). Methods: A total of 13 patients with NPH, 20 with PD, and 13 healthy controls (HC) recruited in the study. Three IMU sensors (Ambulatory PD Monitoring Inc., OR, USA) were placed on the lumbar area and the feet of the participants. The balance evaluations comprised eight successive standing tasks; the modified clinical test of sensory interaction on balance test. These tasks involved standing with feet apart and eyes open as well as eyes closed on a firm and foam surface, standing with feet together and eyes open as well as eyes closed, and tandem stance with the right foot front and the left foot front. Functional evaluations of gait were conducted using the 10-M Walk Test (10 MWT), the 2 min-Walk Test (2 MWT), and the timed-up and go (TUG). Parameters of the gait and balance were analyzed and then compared. Results: NPH patients displayed a notable decrease in both stride length and gait speed as compared with both PD patients and healthy participants. The balance tests revealed that the NPH group demonstrated significantly poorer performance, specifically in the feet-apart eyes-closed foam-surface test, and the tandem stance test. During the tasks while eyes were open on firm and foam surfaces, PD and NPH groups showed an increase in root mean square sway, range, and mean velocity (p<0.05) of sway in the anteroposterior plane. In addition, during the TUG test, the NPH group exhibited a significant prolongation in the time needed to complete the task and a decline in turning velocity as compared to PD, but no notable difference was seen in comparison to the HC group. Conclusion: Our study indicated that the patients with NPH exhibited notably worse gait and balance measurements in comparison to both the PD patients and HC groups. These findings emphasize the significance of monitoring and managing gait and balance impairments in NPH patients. Sensor-based technologies may offer objective parameters for a more precise and efficient follow-up of these patients in terms of gait and balance.

Perivascular PDGFRB+ cells accompany lesion formation and clinical evolution differentially in two different EAE models.

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that may lead to progressive disability. Here, we explored the behavioral pattern and the role of vasculature especially PDGFRB+ pericytes/ perivascular cells, in MS pathogenesis. METHODS: We have evaluated vascular changes in two different experimental allergic encephalomyelitis (EAE) mice models (MOG and PLP-induced). PDGFRB+ cells demonstrated distinct and different behavioral patterns. In both models, fibrosis formation was detected via collagen, fibronectin, and extracellular matrix accumulation. RESULTS: The PLP-induced animal model revealed that fibrosis predominantly occurs in perivascular locations and that PDGFRB+ cells are accumulated around vessels. Also, the expression of fibrotic genes and genes coding extracellular matrix (ECM) proteins are upregulated. Moreover, the perivascular thick wall structures in affected vessels of this model presented primarily increased PDGFRB+ cells but not NG2+ cells in the transgenic NG2-DsRed transgenic animal model. On the other hand, in MOG induced model, PDGFRB+ perivascular cells were accumulated at the lesion sites. PDGFRB+ cells colocalized with ECM proteins (collagen, fibronectin, and lysyl oxidase L3). Nevertheless, both MOG and PLP-immunized mice showed increasing EAE severity, and disability parallel with enhanced perivascular cell accumulation as the disease progressed from earlier (day 15) to later (day 40). CONCLUSION: As a result, we have concluded that PDGFRB+ perivascular cells may be participating in lesion progression and as well as demonstrating different responses in different EAE models.

Investigation of Factors Affecting the Side of the Disease Onset in Parkinson's Disease.

Introduction: Parkinson's disease (PD) is a progressive neurodegenerative disease that starts unilaterally in almost all cases and tends to emerge on the side of the dominant hand, but what we know about the cause of this lateralization is limited. Frequent use of the extremity and physical activity are argued to be protective from PD in preclinical and clinical studies. This study aimed to evaluate the effect of handedness and working in occupations that require continuous use of upper extremities on the disease onset-side. Methods: We retrospectively collected 84 PD patients who applied to Koç University Neurology outpatient clinic between July 2016-October 2018. We analyzed the parameters of the side and region of disease onset, age of onset, number of drugs used for PD, hand preference, and patients' occupations. Results: The median age of our study group was 61 (53-69). Thirty (36%) of the 84 patients were women. Seventy-nine patients (94%) were right-handed. Eighty-three (99%) had asymmetric onset. The disease started on the dominant hand side in 47 patients (57%) and on the non-dominant hand side in 36 (43%) patients. In our group with a median disease duration of four (2-7) years, the side with more severe complaints measured with the Unified Parkinson's Disease Evaluation Scale was consistent with the onset-side of the disease (p<0.001). In addition, the number of drugs used for PD and the scale score were higher in patients with longer disease duration (p=0.039, p=0.005). The number of drugs used for PD was also higher in patients with lower extremity-onset or both upper and lower extremities affected simultaneously than the upper extremity-onset (p=0.005). While the probability of starting on the dominant side was 43% in patients working in occupations requiring continuous use of upper extremities, it was 65% in others (p=0.027). Conclusion: According to this study, the onset of PD tends to be on the dominant hand side. Continuous upper extremity use may reduce the possibility of starting on the dominant side.

The clinical use of impulse oscillometry in neuromuscular diseases.

BACKGROUND: The patients with neuromuscular diseases (NMD) are very fragile and it is hard to evaluate respiratory involvement of the primary disease in this group. Therefore, our study aimed to reveal the relationship between pulmonary function tests (PFT) and impulse oscillometry (IOS) and their correlation with respiratory clinical findings in NMD. MATERIAL AND METHODS: A total of 86 consecutive patients with NMD were included. The clinical findings of respiratory involvement, PFT, and IOS results of the patients were analyzed. RESULTS: Forty patients out of 86 were female. There were 29 patients with amyotrophic lateral sclerosis, four patients with myasthenia gravis, and 53 patients with muscular dystrophies/myopathies. According to the PFT results, 47 patients had restrictive PFT. However, there was no difference in IOS parameters when we compared the patients according to restrictions in PFT. A positive correlation was found with FVC %pred and X5. PEF %pred values were positively correlated with X10, X15, and X20, and negatively correlated with AX and R5-20. The patients with worse swallowing capability had increased Rrs levels, and more negative Xrs levels. The shortness of breath led to lower FEV1 %pred., higher R5, AX and R5-20, and also more negative X10, X15, and X35. CONCLUSION: Clinically reported dysphagia, a decreased capability of coughing, and shortness of breath in patients with NMD make Rrs increase in general, but Xrs parameters, which mainly express rib cage elasticity, turn more negative. In patients with NMD, IOS monitoring may help in evaluating the regression in respiratory functions, however, future studies are needed to understand more.

Hand Pronation-Supination Movement as a Proxy for Remotely Monitoring Gait and Posture Stability in Parkinson's Disease.

The Unified Parkinson's Disease Rating Scale (UPDRS) is a subjective Parkinson's Disease (PD) physician scoring/monitoring system. To date, there is no single upper limb wearable/non-contact system that can be used objectively to assess all UPDRS-III motor system subgroups (i.e., tremor (T), rigidity (R), bradykinesia (B), gait and posture (GP), and bulbar anomalies (BA)). We evaluated the use of a non-contact hand motion tracking system for potential extraction of GP information using forearm pronation-supination (P/S) motion parameters (speed, acceleration, and frequency). Twenty-four patients with idiopathic PD participated, and their UPDRS data were recorded bilaterally by physicians. Pearson's correlation, regression analyses, and Monte Carlo validation was conducted for all combinations of UPDRS subgroups versus motion parameters. In the 262,125 regression models that were trained and tested, the models within 1% of the lowest error showed that the frequency of P/S contributes to approximately one third of all models; while speed and acceleration also contribute significantly to the prediction of GP from the left-hand motion of right handed patients. In short, the P/S better indicated GP when performed with the non-dominant hand. There was also a significant negative correlation (with medium to large effect size, range: 0.3-0.58) between the P/S speed and the single BA score for both forearms and combined UPDRS score for the dominant hand. This study highlights the potential use of wearable or non-contact systems for forearm P/S to remotely monitor and predict the GP information in PD.

Genetic variants of vitamin D metabolism-related DHCR7/NADSYN1 locus and CYP2R1 gene are associated with clinical features of Parkinson's disease.

PURPOSE/AIM OF THE STUDY: Parkinson's disease (PD) is the second most common neurodegenerative disorder. Vitamin D deficiency is suggested to be related to PD. A genome-wide association study indicated that genes involved in vitamin D metabolism affect vitamin D levels. Among these genes, single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) and vitamin D binding protein (VDBP/GC) genes have also been demonstrated to be associated with PD risk. Our aim was to investigate the relevance of SNPs within the 7-dehydrocholesterol reductase/nicotinamide adenine dinucleotide synthetase 1 (DHCR7/NADSYN1) locus and vitamin D 25-hydroxylase (CYP2R1) gene, which encode important enzymes that play a role in the vitamin D synthesis pathway, with PD and its clinical features. MATERIALS AND METHODS: Genotypes of 382 PD patients and 240 cognitively healthy individuals were evaluated by a LightSNiP assay for a total of 10 SNPs within the DHCR7/NADSYN1 locus and CYP2R1 gene. RESULTS: There were no significant differences in the allele and genotype distributions of any of the SNPs between any patient groups and healthy subjects. However, our results indicated that all of the SNPs within the DHCR7/NADSYN1 locus and CYP2R1 gene, except rs1993116, were associated with clinical motor features of PD including initial predominant symptom, freezing of gait (FoG) and falls as well as disease stage and duration of the disease. CONCLUSIONS: In conclusion, genetic variants of the DHCR7/NADSYN1 locus and the CYP2R1 gene might be related to the inefficient utilization of vitamin D independent from vitamin D levels, and it might result in differences in the clinical features of PD patients.

Acute-Onset Hemiparkinsonism Secondary to Subacute-Chronic Subdural Hematoma.

Subdural hematomas constitute rare causes of secondary Parkinsonism in elderly. Subacute or chronic subdural hematomas occur in the elderly following minor head trauma or even without a remarkable history of trauma. A 69-year-old woman admitted with a rapidly progressive acute-onset hemiparkinsonism on the left side of her body. She denied any precipitating event before the onset of her symptoms, and her medical history was unremarkable. The anti-Parkinsonian therapy showed no benefit, but gradually worsening of the symptoms was observed. Her brain magnetic resonance imaging revealed a large subacute-chronic subdural hematoma on the right side with a mass effect on the basal ganglia structures, contralateral to her symptomatology. On thorough questioning, she confessed to having fallen out of the bed at night almost four weeks ago, three-weeks before the onset of her symptomatology. She had no complications associated with this fall and merely remembered this event. She denied any history of rapid eye movements (REM) sleep behavior disorder. The anti-Parkinsonian treatment was discontinued; the subdural hematoma was evacuated via burr hole drainage surgery. Her symptoms disappeared instantly after the surgery, with a normal neurologic examination one week after the surgery.

How do Physicians Manage Functional Neurological Symptom Disorder and Somatic Symptom Disorder in the Emergency Department? A Vignette Study.

INTRODUCTION: We aimed to explore how physicians from different specialties approach the management of functional neurological symptom (conversion) and somatic symptom disorders in the emergency department compared with pulmonary embolism and how physicians' professional and personal characteristics influence their diagnostic preferences. METHODS: Using a vignette methodology, and cross-sectional design, three emergency department case vignettes of possible functional neurological symptom, somatic symptom disorder, and pulmonary embolism were presented to physicians from internal medicine, emergency medicine, and psychiatry. A structured survey including questions on diagnosis and management of these cases, and physicians' professional and personal characteristics (childhood trauma, attachment style) was conducted. RESULTS: Physicians from internal medicine and emergency medicine tended to consider functional neurological symptom disorder as 'malingering' while psychiatrists tended to diagnose the pulmonary embolism case as a psychiatric condition. Emergency medicine physicians preferred to manage functional neurological symptom disorder themselves, while other doctors endorsed recommending a psychiatric consultation. In the univariable model, being a physician from psychiatry, emergency medicine, or internal medicine; being a specialist, history of childhood sexual abuse, dismissive, and fearful attachment styles of doctors were significant predictors of diagnosing functional neurological symptom disorder as malingering. Being a psychiatrist stayed as the only significant predictor in the multivariable model. CONCLUSION: Objectively-aberrant functional neurological symptoms and subjective somatic symptoms may be creating different reactions in physicians. In the emergency department, physicians' diagnostic and treatment preferences of conversion disorder may be influenced by lack of training in conversion disorder, rather than their personal characteristics.

Production and comprehension of co-speech gestures in Parkinson's disease.

This study examined how impairments in sensorimotor abilities of individuals with Parkinson's Disease (PD) can be related to the use and understanding of co-speech hand gestures involving literal and figurative actions. We tested individuals with PD (n = 18, 12 males, Mage = 56.5, SDage = 8.16, PD duration since onset: M = 5.36 years, SD = 3.51, Hoehn and Yahr Scale:MH&Y = 2.09, SDH&Y = 0.50) and age- and education-matched neurotypical controls (n = 18, 14 males, Mage = 56.61, SDage = 8.88) with two experimental tasks. In the gesture production task, participants retold the narratives presented to them in a written format. In the gesture comprehension task, participants were asked to match a gesture with a novel verb in literal and figurative sentence contexts. Results showed that patients with PD gestured significantly less than the neurotypical controls. No group differences were found for the type of gesture use. Individuals with PD performed worse than controls on matching gestures with novel verbs, particularly for figurative meanings. Individuals' severity in the disease negatively correlated with their performance for these figurative novel verb-gesture matches. The performances in the two tasks did not correlate. These findings suggest that problems in sensorimotor abilities resulting from PD can influence overall gesture production and gesture comprehension, providing further evidence on the relations between PD and the impaired use of multimodal language.

Neuropsychiatric Symptoms of COVID-19 Explained by SARS-CoV-2 Proteins' Mimicry of Human Protein Interactions.

The first clinical symptoms focused on the presentation of coronavirus disease 2019 (COVID-19) have been respiratory failure, however, accumulating evidence also points to its presentation with neuropsychiatric symptoms, the exact mechanisms of which are not well known. By using a computational methodology, we aimed to explain the molecular paths of COVID-19 associated neuropsychiatric symptoms, based on the mimicry of the human protein interactions with SARS-CoV-2 proteins. Methods: Available 11 of the 29 SARS-CoV-2 proteins' structures have been extracted from Protein Data Bank. HMI-PRED (Host-Microbe Interaction PREDiction), a recently developed web server for structural PREDiction of protein-protein interactions (PPIs) between host and any microbial species, was used to find the "interface mimicry" through which the microbial proteins hijack host binding surfaces. Classification of the found interactions was conducted using the PANTHER Classification System. Results: Predicted Human-SARS-CoV-2 protein interactions have been extensively compared with the literature. Based on the analysis of the molecular functions, cellular localizations and pathways related to human proteins, SARS-CoV-2 proteins are found to possibly interact with human proteins linked to synaptic vesicle trafficking, endocytosis, axonal transport, neurotransmission, growth factors, mitochondrial and blood-brain barrier elements, in addition to its peripheral interactions with proteins linked to thrombosis, inflammation and metabolic control. Conclusion: SARS-CoV-2-human protein interactions may lead to the development of delirium, psychosis, seizures, encephalitis, stroke, sensory impairments, peripheral nerve diseases, and autoimmune disorders. Our findings are also supported by the previous in vivo and in vitro studies from other viruses. Further in vivo and in vitro studies using the proteins that are pointed here, could pave new targets both for avoiding and reversing neuropsychiatric presentations.

The Complex Genetic Landscape of Hereditary Ataxias in Turkey and Implications in Clinical Practice.

BACKGROUND: The genetic and epidemiological features of hereditary ataxias have been reported in several populations; however, Turkey is still unexplored. Due to high consanguinity, recessive ataxias are more common in Turkey than in Western European populations. OBJECTIVE: To identify the prevalence and genetic structure of hereditary ataxias in the Turkish population. METHODS: Our cohort consisted of 1296 index cases and 324 affected family members. Polymerase chain reaction followed by Sanger sequencing or fragment analysis were performed to screen for the trinucleotide repeat expansions in families with a dominant inheritance pattern, as well as in sporadic cases. The expansion in the frataxin (FXN) gene was tested in all autosomal recessive cases and in sporadic cases with a compatible phenotype. Whole-exome sequencing was applied to 251 probands, selected based on the family history, age of onset, and phenotype. RESULTS: Mutations in known ataxia genes were identified in 30% of 1296 probands. Friedreich's ataxia was found to be the most common recessive ataxia in Turkey, followed by autosomal recessive spastic ataxia of Charlevoix-Saguenay. Spinocerebellar ataxia types 2 and 1 were the most common dominant ataxias. Whole-exome sequencing was performed in 251 probands with an approximate diagnostic yield of 50%. Forty-eight novel variants were found in a plethora of genes, suggesting a high heterogeneity. Variants of unknown significance were discussed in light of clinical data. CONCLUSION: With the large sample size recruited across the country, we consider that our results provide an accurate picture of the frequency of hereditary ataxias in Turkey. © 2021 International Parkinson and Movement Disorder Society.

Intrinsic Auricular Muscle Zone Stimulation Improves Walking Parameters of Parkinson's Patients Faster Than Levodopa in the Motion Capture Analysis: A Pilot Study.

It has been demonstrated that intrinsic auricular muscles zone stimulation (IAMZS) can improve the motor symptoms of Parkinson's disease (PD) patients who are examined with the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores. In the present pilot study, using motion capture technology, we aimed to investigate the efficacy of IAMZS compared to medication alone or in combination with medication. Ten PD patients (mean age: 54.8 ± 10.1 years) were enrolled. Each participant participated in three different sessions: sole medication, sole stimulation-20 min of IAMZS, and combined IAMZS (20 min) and medication. Each session was performed on different days but at the same time to be aligned with patients' drug intake. Motion capture recording sessions took place at baseline, 20, 40, and 60 min. Statistical analysis was conducted using one-way repeated measures ANOVA. Bonferroni correction was implemented for pairwise comparisons. The sole medication was ineffective to improve gait-related parameters of stride length, stride velocity, stance, swing, and turning speed. In the sole-stimulation group, pace-related gait parameters were significantly increased at 20 and 40 min. These improvements were observed in stride length at 20 (p = 0.0498) and 40 (p = 0.03) min, and also in the normalized stride velocity at 40 min (p-value = 0.02). Stride velocity also tended to be significant at 20 min (p = 0.06) in the sole-stimulation group. Combined IAMZS and medication demonstrated significant improvements in all the time segments for pace-related gait parameters [stride length: 20 min (p = 0.04), 40 min (p = 0.01), and 60 min (p < 0.01); stride velocity: 20 min (p < 0.01), 40 min (p = 0.01), and 60 min (p < 0.01)]. These findings demonstrated the fast action of the IAMZS on PD motor symptoms. Moreover, following the termination of IAMZS, a prolonged improvement in symptoms was observed at 40 min. The combined use of IAMZS with medication showed the most profound improvements. The IAMZS may be particularly useful during medication off periods and may also postpone the long-term side effects of high-dose levodopa. A large scale multicentric trial is required to validate the results obtained from this pilot study. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03907007.

Comparison of suture material for vesico-urethral anastomosis in robotic radical prostatectomy.

INTRODUCTION: The aim of this study was to compare outcomes after vesicourethral anastomosis (VUA) with barbed suture (BS) and non-barbed monofilament suture (NBS) in robot-assisted laparoscopic radical prostatectomy (RALRP) in a match - pairs design. MATERIAL AND METHODS: Medical recordings of 385 consecutive patients with prostate carcinoma have been evaluated, and 70 patients who have undergone RALRP-BS were compared with 70 patients with RALRP-NBS in a matched - pairs design. Preoperative clinical parameters (age, prostate-specific antigen, clinical stage, Gleason score of the prostate biopsy, and prostate volume) and operative data (operation, docking, console, posterior reconstruction (PR), anastomosis times, duration of catheter, length of hospital stay, estimated blood loss, time to perform the anastomosis and its quality) were evaluated, as well as postoperative parameters (pathological stage, Gleason score, specimen weight, follow-up duration, biochemical recurrence, complication rates, and duration of postoperative analgesic treatment). RESULTS: No statistically significant difference was found for pre-operative parameters between the two groups. Although, anastomosis time, quality of anastomosis, duration of urethral catheter and total anesthesia time were significantly less in the RALRP-BS group than in the RALRP-NBS group (P <0.01). Other peri- and postoperative parameters were not statistically significant between the two groups. Pathological data and the follow-up period and complication rates were similar between the two groups. CONCLUSIONS: This study showed that, RALRP-BS is a safe, efficient and cost-effective PR and VUA during RALRP than compared with RALRP-NBS. Shorter anastomosis time, operative time and posterior reconstruction time, while it may be equivalent with regard to estimated blood loss (EBL), catheterization time and early continence rates at 4-6 weeks.

A novel shoulder disability staging system for scapulothoracic arthrodesis in patients with facioscapulohumeral dystrophy.

BACKGROUND: Scapulothoracic arthrodesis (STA) is a well-established surgical technique to provide scapular stabilisation in patients with facioscapulohumeral dystrophy (FSHD). There is no staging or scoring systems available to guide surgical decision. The aim of this study was to develop a staging system to evaluate the shoulder disability in patients with FSHD to guide surgical decision-making and assess its reliability among surgeons. METHODS: Fifty-seven shoulders of 29 patients (15 male, 14 female) with an average age of 34.5 years (13-73) were included. Six stages of the disease were defined to create a system consisting of shoulder elevation, deltoid function and scapular winging. Patients were assessed by two independent orthopaedic surgeons who were blind to each other. Statistical analyses included mean and standard deviation for descriptive variables, Pearson's correlation and Cohen's Kappa for inter- and intraobserver agreement. RESULTS: Measurement of elevation showed excellent correlation in both inter- and intraobserver assessment. There was substantial agreement on deltoid function and moderate agreement on scapular winging. Decisions on stage showed excellent agreement on interobserver and substantial agreement on intraobserver assessment. Surgical decision using the stage showed excellent agreement on both inter- and intraobserver assessment. CONCLUSION: This novel staging system has an excellent inter observer agreement on FSHD patients' shoulder disability. This would provide surgeons a beneficial tool to define patient groups that would have negatively or positively affected from STA.

Evaluation of chromosomal abnormalities and Y-chromosome microdeletions in 1696 Turkish cases with primary male infertility: A single-center study.

OBJECTIVE: The aim of this study was to determine the frequencies of chromosomal abnormalities and Y-chromosome microdeletions in Turkish cases with primary male infertility in a single center. MATERIAL AND METHODS: Chromosomal abnormalities and Y-chromosome microdeletions were investigated in 1696 cases with primary male infertility between 2012 and 2017. Karyotype analyzes and Y-chromosome microdeletions analyzes [azoospermia factor (AZF) regions] were performed in all cases by using standard cytogenetic methods and the multiplex polymerase chain reaction method, respectively. RESULTS: Chromosomal abnormalities were found in 142 cases (8.4%; 142/1696). Y-chromosome microdeletions were detected in 46 cases (2.7%; 46/1696). Y-chromosome microdeletions in the AZFc region were found in 20 of 46 cases (43%). CONCLUSION: This study is one of the few were a large number of cases was studied in Turkey. It indicates that cytogenetic and Y-chromosome microdeletion studies should be conducted in cases with primary male infertility prior to selecting assisted reproductive techniques.

Spinal fusion in facioscapulohumeral dystrophy for hyperlordosis: A case report.

RATIONALE: Facioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular dystrophy, which is associated with facial, shoulder girdle, and paraspinal muscle atrophy. Most of the patients develop hypokyphosis and hyperlordosis in the course of the disease, to preserve standing posture. Corrective fusion is contraindicated in these patients as the surgery results with loss of compensatory hyperlordosis and leads to loss of trunk balance while standing. Although spinal fusion in neuromuscular scoliosis is a known treatment option, there are no studies in the literature on the spinal fusion of this specific patient group. PATIENT CONCERNS: In this case report we have presented a 66-year-old woman, who was admitted with back and abdominal pain, inability to sit straight, abdominal discomfort, and numbness in the lower extremities after prolonged sitting. DIAGNOSES: The patient developed severe hyperlordosis causing intra-abdominal disorders, radicular symptoms, and sitting discomfort due to FSHD. INTERVENTIONS: The patient underwent T2-S1 fusion and successful fusion was achieved. OUTCOMES: Individualized Neuromuscular Quality of Life Questionnaire (INQoL) was used to assess preoperative and 3 years postoperative functional outcomes. All domains and total score improved at the end of the follow-up period and successful fusion was verified radiologically. LESSONS: This case suggests that spinal fusion may provide functional improvement in carefully selected patient groups. Patient stratification considering spinal disability is required for further studies in this specific indication.

Visual clarity of irrigants used during flexible ureterorenoscopy: an in vitro comparison.

INTRODUCTION: Saline solution is the standard irrigant used during ureteroscopy. However, there is an opinion that water has better visual clarity. We aimed to compare the visual clarities of saline, water, and 5% mannitol as an irrigant during ureteroscopy. MATERIAL AND METHODS: An in vitro model consisting of an irrigant-filled container and a fiberoptic flexible ureteroscope was designed. A 1951 USAF Resolution Test Target and color checker within irrigants were used to evaluate the clarity of vision. The visual clarity was compared for 0.9% saline, distilled water and 5% mannitol solution with screen resolution and color contrast. The tests were repeated after adding human blood (2/400 ml) and contrast (20/400 ml) to the irrigants. RESULTS: There was no significant difference in resolution values of three plain irrigants at a distance of 10 mm. However, when blood was added to the irrigants, a better resolution of 29.3% for water and 20.6% for mannitol was achieved compared to saline. At 20 mm of distance, it was observed that the difference was more pronounced in irrigants with blood. Water and mannitol had 55.6% and 37.1% better resolution than saline, respectively. In the color reproduction test, there was no significant difference in the three plain irrigants, however, water had better color contrast compared to the others. CONCLUSIONS: Water and 5% mannitol did not provide a significant image clarity advantage compared to saline. However, when blood was added to the irrigants, water provided significantly better visual clarity compared to saline. The use of water during various clinical scenarios in flexible ureteroscopy should be further investigated.