Strength-Duration Time Constant in Peripheral Nerve: No Abnormality in Multiple Sclerosis

Objectives. To investigate the properties of the strength-duration time constant (SDTC) in multiple sclerosis (MS) patients. Methods. The SDTC and rheobase in 16 MS patients and 19 healthy controls were obtained following stimulation of the right median nerve at the wrist. Results. SDTC and rheobase values were 408.3 ± 60.0 μs and 4.0 ± 1.8 mA in MS patients, versus 408.0 ± 62.4 μs and 3.8 ± 2.1 mA in controls. The differences were not significant in SDTC or rheobase values between the patients and controls (P = 0.988 for SDTC and P = 0.722 for rheobase). Conclusion. Our study showed no abnormality in relapsing remitting MS patients in terms of SDTC, which gives some indirect information about peripheral Na+ channel function. This may indicate that alterations in the Na+ channel pattern in central nervous system (CNS) couldnot be shown in the peripheral nervous system (PNS) in the MS patients by SDTC. The opinion that MS can be a kind of channelopathy might be proven by performing other axonal excitability tests or SDTC in progressive forms of MS

Establishing an online resource to facilitate global collaboration and inclusion of underrepresented populations:Experience from the MJFF Global Genetic Parkinson's Disease Project

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, fostering collaborative research, and establishing a clinical trial-ready cohort is imperative. Based on a systematic review of the English literature on monogenic PD and a successful team science approach, we have built up a network of 59 sites worldwide and have collected information on the availability of data, biomaterials, and facilities. To enable access to this resource and to foster collaboration across centers, as well as between academia and industry, we have developed an interactive map and online tool allowing for a quick overview of available resources, along with an option to filter for specific items of interest. This initiative is currently being merged with the Global Parkinson's Genetics Program (GP2), which will attract additional centers with a focus on underrepresented sites. This growing resource and tool will facilitate collaborative research and impact the development and testing of new therapies for monogenic and potentially for idiopathic PD patients.</p

Embracing monogenic Parkinson's disease: the MJFF Global Genetic PD Cohort

© 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-1215-20014info:eu-repo/semantics/publishedVersio

Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

© 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.This project was funded by The Michael J. Fox Foundation (ID 15015.02)Peer reviewe

Sudden Unexpected Death in Epilepsy: Two Case Reports

Sudden Unexpected Death in Epilepsy (SUDEP) is generally defined as sudden, unexpected, witnessed or unwitnessed, non-traumatic, and non-drowning death in patients with epilepsy, excluding documented status epilepticus. Reported SUDEP cases in Turkey are limited. Two cases of patients who died with diagnosis of probable SUDEP are described in the present report. Case 1: A 33-year-old female patient with generalized tonic-clonic seizures for nearly 20 years was referred to the clinic because of lack of complete seizure control despite years of different antiepileptic drug combinations. While in treatment, patient had a healthy pregnancy and seizure control was achieved with lamotrigine. Upon recurrence of seizures after pregnancy, valproate 300 mg/day was added to lamotrigine 150 mg/day. Patient died with diagnosis of probable SUDEP 2 years after the birth of the child. Case 2: A 42-year-old female patient with intractable complex partial and secondary generalized tonic-clonic seizures for about 30 years was admitted to the clinic. She had a history of epilepsy surgery. Topiramate therapy was added to carbamazepine 1200 mg/day and levetiracetam 2000 mg/day treatment. Subsequently, posterior temporal resection was performed, vagal nerve stimulation (VNS) was applied and barbexaclone 25 mg/day was added. Five months after the application of VNS, the patient died with diagnosis of probable SUDEP. These 2 cases of probable SUDEP may contribute to increased awareness of SUDEP and its features among neurologists

Synthesis and tyrosinase inhibitory properties of novel isoquinoline urea/thiourea derivatives

PMID = 2359034

Congenital Cervical Dermal Sinuses

Congenital dermal sinuses are epithelium-lined tracts that extend from an opening in the skin through deeper tissues. These sinuses consist of incompletely separated cutaneous ectoderm from the neuroectoderm due to embryological maldevelopment. We present two cases of cervical dermal sinus that presented to our outpatient clinic with diminished hand muscle strength. These two cervical dermal sinus cases were followed-up with the diagnosis of polyneuropathy and motor neuron disease based on atrophy and weakness of the intrinsic hand muscles. The pathophysiology of the cases is discusse

Trends in Choosing Conventional Versus New Antiepileptic Drugs in Epilepsy Treatment

Objectives:An analysis of clinical practice trends in use of conventional drugs to treat epilepsy versus newer antiepileptic drugs (AEDs) was conducted.Methods:Medical records of patients who presented at the clinic with diagnosis of epilepsy 2007-2012 were investigated retrospectively.Results:Data of 1126 patients were evaluated. Among them, 624 (55%) patients were treated using monotherapy, 449 (40%) patients received polytherapy, and 53 (5%) patients had no therapy. While 916 (81%) of the patients were using conventional AEDs, 447 (40%) of the patients were using newer AEDs. A total of 887 (79%) of the patients were using either valproate or carbamazepine. Of the 624 patients using monotherapy, 523 (84%) were on conventional AEDs and 101 (16%) patients were taking newer AEDs.Conclusion:In a previous study, the authors found the percentage choosing newer AEDs to be 1% before 1994, 10% in the period 1995– 2000, and 14% in the period 2000–2007. Although the present study indicates that there was an increase (40%) in the use of newer AEDs in 2007–2012, it seems that conventional AEDs are still a first-line treatment choice, at least in Turkish clinical practice. Yet as both epileptologists and patients gain experience with newer AEDs, the trend is likely to change

Intravenous Thrombolytic Therapy in Acute Ischemic Stroke

OBJECTIVE: The aim of this study was to review the efficacy, adverse effects and contraindications of intravenous thrombolytic treatment in acute ischemic stroke and to determine the predictive value of stroke scales applied in the first 24 hours to the three months outcome. METHODS: We retrospectively evaluated the clinical data of 30 patients with ischemic stroke seen at our institution over the period October 2005 to October 2008; 12 of the patients received intravenous thrombolytic treatment while 18 patients were not treated despite being admitted within three hours. The neurological deficits were graded using NIHSS, RANKIN and BARTHEL scales. The relationship between time to treatment and clinical improvement and also the association between the scales at 24 hours and the three months clinical outcome were evaluated. The reasons for not treating the patients who were admitted within the therapeutic window were determined. RESULTS: Only 30 of 404 patients were admitted within three hours. Twelve patients were admitted within 134.58 ± 39.4 minutes of stroke onset. Clinical improvement, defined as an improvement of ≥ 25% NIHSS points, was observed in 6 of the 12 (50%) patients within 24 hours of therapy. An improvement of about 80% NIHSS points at three months was observed when compared with baseline scores. Two of the patients showed insufficient improvement, defined as an improvement of < 25% NIHSS points. Four patients died due to intracerebral hematoma, severe brain edema or cardiac causes. Of the 18 patients who did not receive treatment, this was due to contraindications in 17 and to failure to obtain consent for the treatment in 1. CONCLUSION: Our data suggest that an improvement of ≥ 25% NIHSS points at 24 hours predicts the prognosis at three months and supports the conclusion from previous studies that thrombolytic therapy is a reliable and feasible treatment in selected patients with acute ischemic strok

Synthesis, Biological Activity and Structure-Activity Relationship of Novel Diphenylurea Derivatives Containing Tetrahydroquinoline as Carbonic Anhydrase I and II Inhibitors

Gencer, Nahit/0000-0001-7092-8857;WOS: 000422674700030A series of novel tetrahydroquinoline derivatives containing urea moiety was synthesized and their invitro inhibitory effects on the human carbonic anhydrase isoenzymes (hCA-I and hCA-II) were evaluated by using the CO2 hydration method. All the synthesized compounds exhibited inhibitory activity against both hCA I and hCA II with 1-(4-fluorophenyl)-3-(4-(4-p-tolyl-5,6,7,8-tetrahydroquinolin-2-yl)phenyl)urea (7k, IC50 value of 5.28M and 5.51M, against hCA I and hCA II, respectively) as the strongest inhibitor in this study. Structure-activity relationships were also investigated. The results showed that most of synthesized compounds have a higher inhibitory activity against hCA I than hCA II. Also the substituents, containing two or more pairs of non-bonding electrons, generally increased the hCA I and II inhibitory activity. Furthermore, some electronic parameters such as the highest occupied molecular orbital and the lowest unoccupied molecular orbital (HOMO-LUMO) energy levels, electron affinity, total energy and dipole moments of the best inhibitors (7b, 7h and 7k) in this study were also calculated by using Gaussian software. The results revealed that HOMO-LUMO energy differences, total energy, chemical hardness and dipole moment of 7b, 7h and 7k showed a linear relationship with increasing inhibitory activity.Gaziosmanpasa University Scientific Research ProjectGaziosmanpasa University [2011/34]This work was supported by Gaziosmanpasa University Scientific Research Project (Project No: 2011/34)