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© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., Michael J. Fox Foundation for Parkinson's Research. Grant Number: ID 15015.02. NIHR Cambridge Biomedical Research Centre. Grant Number: BRC-1215-20014

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., Koç Holding; Koç University

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., Science Academy's Young Scientists' Award Program (BAGEP)

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. / Amaç: farklı uzmanlık dallarından hekimlerin acil serviste fonksiyonel nörolojik (konversiyon) belirti bozukluğu ve bedensel belirti bozukluğunu yönetimini, pulmoner embolinin yönetimi ile karşılaştırarak incelemeyi ve hekimlerin mesleki ve kişisel özelliklerinin tanı tercihlerini nasıl etkilediğini araştırmayı amaçladık. Yöntem: vinyet yöntemi ve kesitsel tasarım kullanıldı. Olası fonksiyonel nörolojik belirti bozukluğu, bedensel belirti bozukluğu ve pulmoner emboli tanısı ile acil servise başvuran üç olgu, iç hastalıkları, acil tıp ve psikiyatri hekimlerine sunuldu. Bu olguların tanı ve tedavisine, ve hekimlerin mesleki ve kişisel özellikleri (çocukluk çağı travması, bağlanma biçimi) ne yönelik sorular içeren yapılandırılmış anket uygulandı. Bulgular: dahiliye ve acil tıp hekimleri, fonksiyonel nörolojik belirti bozukluğunu “temaruz” olarak görme eğilimindeyken, psikiyatristler pulmoner emboli vakasını psikiyatrik bir durum olarak görme eğilimindeydiler. Acil tıp hekimleri, fonksiyonel nörolojik belirti bozukluğunu kendileri yönetmeyi tercih ederken, diğer doktorlar psikiyatri konsültasyonu önerdi. Tek değişkenli modelde psikiyatri, acil tıp veya dahiliye hekimi olmak; uzman olmak, çocukluk çağı cinsel istismarı, kayıtsız ve korkulu bağlanma biçimleri, fonksiyonel nörolojik belirti bozukluğunu temaruz olarak tanımlamayı yordamaktaydı. Çok değişkenli modelde tek anlamlı yordayıcı psikiyatri uzmanlık dalıydı. Sonuç: nesnel olarak gözlenen anormal fonksiyonel nörolojik belirtiler ve öznel bedensel belirtiler hekimlerde farklı tepkilere yol açıyor olabilir. Acil serviste hekimlerin konversiyon bozukluğu tanı ve tedavi tercihleri, kişisel özelliklerinden ziyade konversiyon bozukluğu konusundaki eğitim eksikliğinden etkileniyor olabilir., NA

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., Koç Holding; Koç University

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., NA

Most of the primary brain tumours are located in the supratentorial region, and it is uncommon to see tumour growth on deep brain structures such as posterior corpus callosum (PCC). In addition, lesions in PCC are also difficult to recognise, because construction apraxia, visuospatial perception and attentional capacity impairment may be the only presenting symptoms. Here, we represent a rare case of gliobastoma multiforme located in PCC, which solely presents with depressive symptoms and visual memory deficits. Initial manifestations of primary brain tumours with psychiatric symptoms and memory disturbances, in addition to headaches and seizures, should be kept in mind., NA