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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.
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Atrofia Óptica , Ataxias Espinocerebelosas , Degeneraciones Espinocerebelosas , Humanos , Espasticidad Muscular , Turquía/epidemiologíaRESUMEN
Background/aim: Epilepsy is a common chronic neurological problem that impairs daily activities, functionality, and quality of life. Childhood traumas (CTs) are known to be critical factors in the onset or development of many psychiatric and medical disorders. They also play a critical role in the development of temperament and personality. This study aimed to investigate the association between CTs and common temperament patterns and features seen in epilepsy patients. Materials and methods: The study included 38 patients who were diagnosed with juvenile myoclonic epilepsy (JME) and volunteered to participate in the study. In addition to the sociodemographic form and questions on disease features, Structured Clinical Interview for DSM-IV Axis I Disorders, Temperament Evaluation of Memphis, Pisa, Paris and San Diego Questionnaire (TEMPS-A), Childhood Trauma Questionnaire (CTQ), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were administered to all participants. In the present study, a cut-off value of 35 was used for the CTQ scale. The patients with CTQ scores lower than 35 (50%, n = 19, Group 1) and the patients with CTQ scores above 35 (50%, n = 19, Group 2) were compared. Results: The comparison of TEMPS-A and its subscale scores in the JME patients in the groups with CTQ scores above or below a cut-off value detected significant differences between the groups in depressive and irritable temperament scores. The mean BDI scores were also different between the two groups. Furthermore, a significant positive correlation was detected between the disease duration, anxiety, and depression scores in the JME patients. A significant relationship was detected between the emotional neglect subscale score of the JME patients and the BDI scores. A significant positive correlation was found between the total disease duration, BDI, and BAI. Significant moderate-level relationships were found between the BDI score and irritable, depressive, cyclothymic, and anxious temperaments and between the BAI score and irritable, depressive, cyclothymic, and anxious temperaments. Conclusion: Several temperamental features of JME patients are related to CTs. More depressive symptoms are seen in JME patients with higher disease durations.
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Experiencias Adversas de la Infancia , Epilepsia Mioclónica Juvenil , Temperamento/fisiología , Adolescente , Adulto , Experiencias Adversas de la Infancia/psicología , Experiencias Adversas de la Infancia/estadística & datos numéricos , Ansiedad/complicaciones , Ansiedad/epidemiología , Depresión/complicaciones , Depresión/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Epilepsia Mioclónica Juvenil/complicaciones , Epilepsia Mioclónica Juvenil/epidemiología , Epilepsia Mioclónica Juvenil/psicología , Trauma Psicológico , Psicometría , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Neurosyphilis (NS) has different clinical manifestations and can appear during any stage of syphilis. We aimed to identify the factors affecting poor outcome in NS patients. Patients with positive cerebrospinal fluid Venereal Disease Research Laboratory test, and positive serological serum treponemal or nontreponemal tests were classified as definite NS. The data of 141 patients with definite NS were submitted from 22 referral centers. Asymptomatic NS, syphilitic meningitis, meningovascular syphilis, tabes dorsalis, general paresis, and taboparesis were detected in 22 (15.6%), 67 (47.5%), 13 (9.2%), 10 (7%), 13 (9.2%), and 16 patients (11.3%), respectively. The number of HIV-positive patients was 43 (30.4%). The most common symptoms were headache (n = 55, 39%), fatigue (n = 52, 36.8%), and altered consciousness (50, 35.4%). Tabetic symptoms were detected in 28 (19.8%), paretic symptoms in 32 (22.6%), and vascular symptoms in 39 patients (27.6%). Eye involvement was detected in 19 of 80 patients (23.7%) who underwent eye examination and ear involvement was detected in eight of 25 patients (32%) who underwent ear examination. Crystallized penicillin was used in 109 (77.3%), procaine penicillin in seven (4.9%), ceftriaxone in 31 (21.9%), and doxycycline in five patients (3.5%). According to multivariate regression analysis, while headache was a protective factor in NS patients, double vision was significantly associated to poor outcome. We concluded that double vision indicated unfavorable outcome among NS patients. A high clinical suspicion is needed for the diagnosis NS. As determined in our study, the presence of headache in syphilitic patients can help in early diagnosis of central nervous system disease.
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Neurosífilis/epidemiología , Neurosífilis/fisiopatología , Adulto , Antibacterianos/uso terapéutico , Estudios de Cohortes , Diplopía , Femenino , Cefalea , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Neurosífilis/diagnóstico , Neurosífilis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Background/aim: Reflex seizures are defined as epilepsies with seizures induced by a specific afferent stimulus or patient activity alone or in combination with spontaneous seizures, and/or accompanied by photoparoxysmal response on electroencephalogram (EEG). The aim of this study is to review and analyze clinical, neuroradiological, and EEG findings in reflex epilepsies. Materials and methods: The records of 1598 follow-up patients out of 2237 patients who had been examined between July 1995 and August 2017 were analyzed retrospectively. Results: Eighty of 1598 patients had reflex epilepsy and 72 of those patients had seizures induced by visual stimuli. Considering the somatosensory stimuli, in one patient it was associated with eating while in 7 patients it was associated with hot water. The results of neurological examination were normal in 90% while cranial imaging was normal in 82.5% of the patients. Only 53 of 80 patients' EEGs revealed pathological EEG findings. Furthermore, in 43 patients, the most frequently prescribed drug was valproate. Conclusion: In this hospital-based study, reflex epilepsy frequency was 5% and cranial imaging was mostly found to be normal, as stated in the literature. However, patient histories revealed an unexpectedly high rate of head trauma before seizure onset and a family history of epilepsy.
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Electroencefalografía , Epilepsia Refleja/diagnóstico , Epilepsia Refleja/fisiopatología , Neuroimagen , Epilepsia Refleja/complicaciones , Humanos , Trastornos por Fotosensibilidad/complicaciones , Estudios RetrospectivosRESUMEN
AIMS: There is no report on the factors affecting the resolution of symptoms related to meningitis during treatment of tuberculous meningitis (TBM). Thus, we examined the factors associated with early therapeutic responses. MATERIALS AND METHODS: This multicenter study included 507 patients with microbiologically confirmed TBM. However, 94 patients eligible for the analysis were included in this study from 24 centers. Six out of 94 patients died and the statistical analysis was performed with 88 survivors. Early and late responder groups were compared in the statistical analysis. P < 0.05 were considered to show a significant difference. RESULTS: In the multivariate analysis, the presence of vasculitis (P = 0.029, OR = 10.491 [95% CI, 1.27-86.83]) was found to be significantly associated with a delayed fever response whereas hydrocephalus was associated with altered mental status for >9 days duration (P = 0.005, OR = 5.740 [95% CI, 1.68-19.57]). According to linear regression analysis, fever was significantly persisting (>7 days) in the presence of vasculitis (17.5 vs. 7, P< 0.001) and hydrocephalus (11 vs. 7, P = 0.029). Hydrocephalus was significantly associated with persisting headache (21 vs. 12, P = 0.025), delayed recovery of consciousness (19.5 vs. 7, P = 0.001), and a delay in complete recovery (21 vs. 14, P = 0.007) in the linear regression analysis. Following institution of treatment, the complaints seemed to disappear in up to 2 weeks among TBM survivors. CONCLUSIONS: In the absence of hydrocephalus or vasculitis, one week of anti-tuberculosis treatment seems to be adequate for the resolution of TBM symptoms. Hydrocephalus and vasculitis delay the resolution of TBM symptoms in response to antimycobacterial treatment.
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Antituberculosos/uso terapéutico , Hidrocefalia/complicaciones , Tuberculosis Meníngea/tratamiento farmacológico , Vasculitis/complicaciones , Humanos , Pronóstico , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Tuberculosis Meníngea/complicacionesRESUMEN
Data in the literature regarding the factors that predict unfavorable outcomes in adult herpetic meningoencephalitis (HME) cases are scarce. We conducted a multicenter study in order to provide insights into the predictors of HME outcomes, with special emphasis on the use and timing of antiviral treatment. Samples from 501 patients with molecular confirmation from cerebrospinal fluid were included from 35 referral centers in 10 countries. Four hundred thirty-eight patients were found to be eligible for the analysis. Overall, 232 (52.9%) patients experienced unfavorable outcomes, 44 died, and 188 survived, with sequelae. Age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.05), Glasgow Coma Scale score (OR, 0.84; 95% CI, 0.77 to 0.93), and symptomatic periods of 2 to 7 days (OR, 1.80; 95% CI, 1.16 to 2.79) and >7 days (OR, 3.75; 95% CI, 1.72 to 8.15) until the commencement of treatment predicted unfavorable outcomes. The outcome in HME patients is related to a combination of therapeutic and host factors. This study suggests that rapid diagnosis and early administration of antiviral treatment in HME patients are keys to a favorable outcome.
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Antivirales/uso terapéutico , Encefalitis por Herpes Simple/diagnóstico , Encefalitis por Herpes Simple/tratamiento farmacológico , Adulto , Intervalos de Confianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: The aim of the present study was to evaluate the performance of 2 different multivariate statistical methods and artificial neural networks (ANNs) in predicting the mortality of hemorrhagic and ischemic patients within the first 10 days after stroke. METHODS: The multilayer perceptron (MLP) ANN model and multivariate statistical methods (multivariate discriminant analysis [MDA] and logistic regression analysis [LRA]) have been used to predict acute stroke mortality. The data of total 570 patients (230 hemorrhagic and 340 ischemic stroke), who were admitted to the hospital within the first 24 hours after stroke onset, have been used to develop prediction models. The factors affecting the prognosis were used as inputs for prediction models. Survival or death status of the patients was taken as output of the models. RESULTS: For the MLP method, the accuracies were 99.9% in a training data set and 80.9% in a testing data set for the hemorrhagic group, whereas 97.8% and 75.9% for the ischemic group, respectively. For the MDA method, the training and testing performances were 89.8%, 87.8% and 80.6%, 79.7% for hemorrhagic and ischemic groups, respectively. For the LRA method, the training and testing performances for the hemorrhagic group were 89.7% and 86.1%, and for the ischemic group were 81.7% and 80.9%, respectively. CONCLUSIONS: Training and test performances yielded different results for ischemic and hemorrhagic groups. MLP method was most successful for the training phase, whereas LRA and MDA methods were successful for the test phase. In the hemorrhagic group, higher prediction performances were achieved for both training and testing phases.
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Isquemia Encefálica/mortalidad , Hemorragias Intracraneales/mortalidad , Redes Neurales de la Computación , Accidente Cerebrovascular/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Pronóstico , Tasa de SupervivenciaRESUMEN
Brucellosis is a zoonotic disease with a wide range of ophthalmic manifestations, including optic neuritis. It is most commonly caused by the consumption of raw or unpasteurised dairy products. We report a case of a 43-year male patient with an altitudinal visual field defect and unilateral optic neuritis caused by Brucella. While his visual acuity improved within 6 months of receiving anti-Brucella therapy and corticosteroid therapy, the altitudinal visual field defect persisted. Brucellosis can affect the central nervous system and eyes, in addition to having systemic manifestations. The ocular involvement of Brucella remains poorly understood. Early diagnosis and appropriate treatment can prevent serious complications in endemic areas. Key Words: Optic neuritis, Neurobrucellosis, Ocular brucellosis.
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Brucella , Brucelosis , Neuritis Óptica , Humanos , Masculino , Campos Visuales , Brucelosis/complicaciones , Brucelosis/diagnóstico , Brucelosis/tratamiento farmacológico , Trastornos de la Visión/etiología , Neuritis Óptica/diagnóstico , Neuritis Óptica/tratamiento farmacológicoRESUMEN
OBJECTIVE: To investigate the F wave parameters (F duration, F minimum latency, F maximum latency, F mean latency, F chronodispersion, and F persistence) of the tibial nerve with unilateral S1 radiculopathy. We evaluated the differences of these parameters between the affected and unaffected sides and also with the control group. METHODS: The study was performed from September 2007 to January 2008 in the Electrophysiology Laboratory of Marmara University Medical Faculty, Istanbul, Turkey. Bilateral tibial F waves were obtained from 20 normal control subjects (control group) and 20 patients with unilateral S1 radiculopathy (patient group). Minimum, maximum, and mean F latency values were corrected by the subject`s height (F min/H, F max/H, F mean/H). Needle electromyography was performed in the patient group. The patients with a history of diabetes, alcoholism, or other abnormality known to affect peripheral nerves were excluded. RESULTS: In the control group, no significant differences were found in any of the F-wave parameters between the 2 sides. In the patient group, there were significant prolongations of F duration, F min/H, F max/H, F mean/H, and F chronodispersion on the lesion side. Patients` F durations of the affected and unaffected side were significantly longer than the control group. The F chronodispersion also showed significant prolongation on the affected side in the patient group compared with the control group. Among 20 patients, 15 had evidence of denervation or polyphasic potentials on needle electromyography. CONCLUSION: The F wave study can be clinically useful in the evaluation of S1 radiculopathies, especially in patients with mild and early stage of the disease. Both F duration and F chronodispersion have a higher diagnostic value as compared to F min in the diagnosis of lumbosacral radiculopathy, especially in cases with normal findings on needle electromyography.
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Lateralidad Funcional , Conducción Nerviosa/fisiología , Radiculopatía/fisiopatología , Adulto , Anciano , Análisis de Varianza , Electromiografía/métodos , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Radiculopatía/patología , Tiempo de Reacción , Nervio Tibial/fisiopatología , Adulto JovenRESUMEN
INTRODUCTION: Paraneoplastic neurological syndromes (PNS) are rare neurological conditions and they are mostly triggered by autoimmune mechanisms. Cancer-related retinopathies (CAR) are even rarer and commonly related with breast tumor in woman. This limits our knowledge about pathophysiology of CAR. In this study, we question the association between histopathological findings and onconeural antibodies in breast cancer. METHOD: Thirty-two patients with newly diagnosed breast cancer admitted to the oncology outpatient clinic were included in the study. None of the participants have visual complaints. After the neurological examination of the patients, two tubes of 5 cc venous blood were obtained by screening onconeuronal antibodies. Samples were investigated in ASDETAE (Istanbul University Experimental Medicine Research Institute). RESULTS: Patients included in the study included one patinet (3.1%) with grade 1, 14 patients (43.8%) with grade 2 and 17 patients (53.1%) with grade 3 invasive breast cancer. Perineural invasion was detected in 5 (15.6%) patients. Progesterone receptor positivity was found in 26 (81.2%) patients and estrogen receptor positivity was found in 27 (84.4%) patients. In 7 (21.9%) patients, CERBB2 was positive and in 25 (78.1%) patients, Ki 67 was positive. A total of 12 (37.5%) patients had onconeuroneal antibody positivity. Antibody positivity was significantly higher in patients with high grade tumor (p=0.008). CONCLUSION: There may be a relationship between tumor grade and the presence of onconeuronal antibodies in breast cancer patients. By the detection of new biochemical markers, significant contribution can be made to the early diagnosis and treatment of underlying cancer.
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INTRODUCTION: To investigate retinal nerve fiber layer (RNFL), macular, foveal and parafoveal thickness in patient with early stage Parkinson's (PD) and Alzheimer's disease (AD) by optical coherence tomography (OCT) and to compare results with healthy control group and between both disease. METHODS: Participants with AD dementia (n: 15) and PD (n: 15), besides 15 age-sex matched controls were enrolled in the study and received OCT assessments. Clinical disability grade in PD was determined by the Unified Parkinson's Disease Rating Scale and Hoehn Yahr (H-Y) Scale was used to determine the stage of PD. Standardized Mini Mental Test (SMMT) and Montreal Cognitive Rating Scale (MOCA) were used for neurocognitive evaluation of patients with AD. The relationship between OCT and test results was analyzed. RESULTS: OCT measurements did show significant decrease in temporal, nasal, inferiorR (R means examination of retina in two sections as superior and inferior instead of four quadrants) RNFL thickness and foveal, parafoveal, macular thickness of AD group compared to control group. Temporal, inferior and inferiorR RNFL thickness were thinner in patients with PD than those of control group but these differences were not significant. However the superiorR and superior RNFL thickness decreased significantly in the PD group as the disease duration increased. There was no relationship between SMMT, MOCA, UPDRS, H-Y scores and OCT results. CONCLUSION: As several studies have reported different results so far, we thought that the use of OCT in early diagnosis and follow-up of the course of both diseases was not appropriate until many studies indicated the same result.
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OBJECTIVE: Myasthenia gravis (MG) is an autoimmune disease that may cause a disorder in transmission at the neuromuscular junction. Antibodies directed against acetylcholine receptors are responsible. The thymus is the place that that production of these antibodies mainly occurs. The thymus gland abnormalities and abnormal production of these antibodies are associated with MG. Consequently, thymectomy is a common treatment for MG. The nature of the disease makes it difficult to plan prospective, controlled trials; therefore, there is no current consensus among clinicians on a single algorithm of treatment, and the approach is frequently based on the observations and experiences of experts. The contributions to the literature largely consist of retrospective studies examining an approach to treatment and the effects of thymectomy on prognosis. In this retrospective study, evaluation of Turkish patients with myasthenia gravis was carried out for the importance of thymectomy and effects on prognosis. METHODS: In this study, 93 patients with myasthenia gravis whose followed up at Neuromuscular outpatient clinic between 1998-2018 were evaluated retrospectively. Type of disease, antibody status, treatment, thymectomy, thymus pathology and prognosis were assessed. RESULTS: Thymectomy had been a positive effect on the prognosis of the disease independent of the duration of disease and thymic pathology. The best results had been obtained with early thymectomy with short disease duration, younger age and patients with thymic hyperplasia. Success of therapy was limited with thymoma. With advanced age need for thymectomy was decreased. CONCLUSION: In the present study, evaluation of 93 patients with myasthenia gravis was done retrospectively and it was concluded that thymectomy had a positive effect on prognosis, especially in young patients when performed as early as possible. The most successful results were obtained in cases with thymic hyperplasia.
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OBJECTIVE: To evaluate the different localizing electrodiagnostic techniques of ulnar nerve entrapment at the elbow (UNE), particularly, comparison of the sensitivities of long segment stimulation across the elbow, versus short segment stimulation. METHODS: Patients who were referred to the Neurophysiology Laboratory of Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey between 2000-2004 with a preliminary diagnosis of UNE were retrospectively evaluated. We compared the sensitivity of studying long segments (8-12 cm) versus short segments (3 cm) for the diagnosis of UNE in 93 limbs. RESULTS: The study group consisted of 55 females and 31 males. Slowing of the conduction velocity (<50 m/sn) across the elbow was recorded in 48.4% of the limbs with long segment studies, and 73% of the limbs with short segment studies. In 82% of cases, an amplitude drop of the compound muscle action potential (CMAP) was also recorded. A CMAP amplitude drop of 10-30% between the wrist and elbow was recorded in 35 limbs (37.6%), while a drop of more than 50% was only recorded in 5 limbs (5.4%). CONCLUSION: Short segment studies are sensitive for the electrodiagnosis of UNE, and although a CMAP amplitude drop is recorded in most patients, an amplitude drop consistent with a conduction block (>50%) is rare.
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INTRODUCTION: To determine the lateralization of lesion by non-invasive methods through correlation of cranial magnetic resonance imaging (MRI) and electroencephalography (EEG) findings in patients with mesial temporal sclerosis (MTS). METHODS: This study included 40 patients (Age range, 19 to 55 years) among 1850 patients who were attending outpatient epilepsy clinic of Haydarpasa Numune Hospital between the years 2000 and 2013. Exclusion criteria were surgery due to MTS, metabolic and systemic disorders, indefinite diagnosis, and inadequate MRI and EEG evaluations. RESULTS: EEG findings were within normal limits in 10 (25%) patients who had MTS on MRI. Of these, 5 patients had right MTS, 4 had left MTS, and one patient had bilateral MTS. CONCLUSION: In this study, we used electrophysiological diagnostic methods together with MR imaging to determine epileptogenic localization in patients with MTS. We suggest that, when correlated with MRI, EEG is a non-invasive and easy method to identify lateralization findings.
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BACKGROUND: An increased risk of ischemic stroke has been reported in patients with Parkinson's disease (PD). Atrial fibrillation (AF) is strongly associated with ischemic stroke. Prolonged atrial electromechanical delay (EMD) is an independent predictor for the development of AF. AIMS: The aim of the present study was to evaluate the atrial conduction parameters in patients with PD and to assess their relation with the severity of PD. STUDY DESIGN: We prospectively enrolled 51 consecutive patients with newly diagnosed PD and 31 age- and sex-matched non-PD subjects. METHODS: To assess atrial electromechanical coupling (PA), the time intervals from the onset of p wave on ECG to the late diastolic wave at the septal (PAs) and lateral (PAl) mitral annulus and lateral tricuspid annulus (PAt) were measured on Tissue Doppler Echocardiography (TDE). The difference between PAs-PAl, PAs-PAt, and PAl-PAt were defined as left intra-atrial, right intra-atrial, and interatrial EMD, respectively. P-wave dispersion (PWD) was calculated from the 12-lead ECG. RESULTS: PWD, PAs, PAl, and PAt durations were significantly prolonged in the PD group (all p < 0.001). Interatrial, right, and left intra-atrial EMD were also significantly longer in PD patients (p < 0.001, p < 0.001 and p=0.002, resp.). There were significant positive correlations between disease severity (UPDRS score) and PWD (r=0.34, p=0.041), left intra-atrial (r=0.39, p=0.005), and interatrial EMD (r=0.35, p=0.012). By multivariate analysis, PWD (OR: 1.13, 95% CI: 1.02-1.25; p=0.017), LA volume index (OR: 1.19, 95% CI: 1.02-1.37; p=0.021), left intra-atrial (OR: 1.12, 95% CI: 1.01-1.24; p=0.041), and interatrial EMD (OR: 1.08, 95% CI: 1.01-1.16; p=0.026) were found as independent predictors of PD. CONCLUSION: Atrial conduction times were longer and correlated with the severity of disease in PD patients. Prolonged inter- and intra-atrial-EMD intervals were also found as independent correlates of PD. These findings may suggest an increased predisposition to atrial fibrillation in PD.
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Parkinson's disease (PD) is a frequent neurodegenerative process in old age. Accumulation and aggregation of the lipid-binding SNARE complex component α-synuclein (SNCA) underlies this vulnerability and defines stages of disease progression. Determinants of SNCA levels and mechanisms of SNCA neurotoxicity have been intensely investigated. In view of the physiological roles of SNCA in blood to modulate vesicle release, we studied blood samples from a new large pedigree with SNCA gene duplication (PARK4 mutation) to identify effects of SNCA gain of function as potential disease biomarkers. Downregulation of complexin 1 (CPLX1) mRNA was correlated with genotype, but the expression of other Parkinson's disease genes was not. In global RNA-seq profiling of blood from presymptomatic PARK4 indviduals, bioinformatics detected significant upregulations for platelet activation, hemostasis, lipoproteins, endocytosis, lysosome, cytokine, Toll-like receptor signaling and extracellular pathways. In PARK4 platelets, stimulus-triggered degranulation was impaired. Strong SPP1, GZMH and PLTP mRNA upregulations were validated in PARK4. When analysing individuals with rapid eye movement sleep behavior disorder, the most specific known prodromal stage of general PD, only blood CPLX1 levels were altered. Validation experiments confirmed an inverse mutual regulation of SNCA and CPLX1 mRNA levels. In the 3'-UTR of the CPLX1 gene we identified a single nucleotide polymorphism that is significantly associated with PD risk. In summary, our data define CPLX1 as a PD risk factor and provide functional insights into the role and regulation of blood SNCA levels. The new blood biomarkers of PARK4 in this Turkish family might become useful for PD prediction.
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Proteínas Adaptadoras del Transporte Vesicular/genética , Biomarcadores/sangre , Predisposición Genética a la Enfermedad , Enfermedad por Cuerpos de Lewy/sangre , Proteínas del Tejido Nervioso/genética , Enfermedad de Parkinson/genética , Trastorno de la Conducta del Sueño REM/sangre , ARN/sangre , alfa-Sinucleína/deficiencia , Femenino , Heterocigoto , Humanos , Enfermedad por Cuerpos de Lewy/genética , Persona de Mediana Edad , Enfermedad de Parkinson/sangre , Trastorno de la Conducta del Sueño REM/fisiopatología , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , alfa-Sinucleína/sangre , alfa-Sinucleína/genéticaRESUMEN
BACKGROUND: Millions of people around the world regularly consume aspirin, but its value in determining stroke severity is still not clear. It has been stated that prior aspirin use might reduce the severity of ischemic stroke by reducing the size of fibrin-platelet emboli or by ameliorating platelet hyperaggregability that occurs in the microcirculation. However there are only few large studies focusing on the early outcome of stroke patients including both ischemic stroke and primary intracerebral hemorrhage patients with prior aspirin therapy. REVIEW SUMMARY: We retrospectively analyzed the medical records of 2509 consecutive stroke patients who were hospitalized in the 2nd Neurology Clinic of Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey, during the period of 1993-2003. We compared the early mortality rates in the patients with prior aspirin use versus the patients without. Of the patients without prior aspirin use, 20.1% died during the first 3 weeks of the stroke, while only 11.5% of the patients with prior aspirin use died during the same period. The difference in early mortality rate between 2 groups was extremely significant (P = 0.0008). Logistic regression analysis indicated that aspirin use was a significant (P < 0.01) and independent predictor of early stroke mortality. CONCLUSION: Daily low dose (100-300 mg) aspirin has a protective effect in reducing the risk of early death in stroke.
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Aspirina/administración & dosificación , Fibrinolíticos/administración & dosificación , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/complicaciones , Hemorragia Cerebral/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/etiologíaRESUMEN
Predicting unfavorable outcome is of paramount importance in clinical decision making. Accordingly, we designed this multinational study, which provided the largest case series of tuberculous meningitis (TBM). 43 centers from 14 countries (Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria, Turkey) submitted data of microbiologically confirmed TBM patients hospitalized between 2000 and 2012. Unfavorable outcome was defined as survival with significant sequela or death. In developing our index, binary logistic regression models were constructed via 200 replicates of database by bootstrap resampling methodology. The final model was built according to the selection frequencies of variables. The severity scale included variables with arbitrary scores proportional to predictive powers of terms in the final model. The final model was internally validated by bootstrap resampling. A total of 507 patients' data were submitted among which 165 had unfavorable outcome. Eighty-six patients died while 119 had different neurological sequelae in 79 (16%) patients. The full model included 13 variables. Age, nausea, vomiting, altered consciousness, hydrocephalus, vasculitis, immunosuppression, diabetes mellitus and neurological deficit remained in the final model. Scores 1-3 were assigned to the variables in the severity scale, which included scores of 1-6. The distribution of mortality for the scores 1-6 was 3.4, 8.2, 20.6, 31, 30 and 40.1%, respectively. Altered consciousness, diabetes mellitus, immunosuppression, neurological deficits, hydrocephalus, and vasculitis predicted the unfavorable outcome in the scoring and the cumulative score provided a linear estimation of prognosis.
Asunto(s)
Evaluación de Resultado en la Atención de Salud , Resultado del Tratamiento , Tuberculosis Meníngea/diagnóstico , Tuberculosis Meníngea/terapia , Adulto , Ensayos Clínicos como Asunto , Estudios de Cohortes , Femenino , Humanos , Cooperación Internacional , Modelos Logísticos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Tuberculosis Meníngea/mortalidadRESUMEN
AIMS: There is a growing interest in the understanding of a possible role of DNA repair systems in ageing and neurodegenerative diseases after DNA damage is observed in the brain of individuals affected by neurodegenerative diseases. In the light of these findings, we investigated whether DNA repair gene polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met XPD Lys751Gln, XPG Asp1104His, APE1 Asp148Glu, and HOGG1 Ser326Cys) account for an increased risk of Parkinson's disease (PD). METHODS: The present analyses are based on 60 case subjects with PD and 108 unrelated healthy controls. Genotyping of DNA repair gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We, for the first time, demonstrated the positive association of APE1, XRCC1, and XRCC3 DNA repair gene variants with PD risk. In our study, the frequencies of Glu/Glu genotype in APE1, Gln+ genotype of XRCC1, and Thr+ genotype of XRCC3 are higher in patients than in controls (p=0.028, p=0.002 and p=0.046, respectively). CONCLUSIONS: In conclusion, our findings have suggested that APE1, XRCC1, and XRCC3 genetic variants may be a risk factor by increasing oxidative stress that might cause the loss of dopaminergic cells in the substantiata nigra and locus caeruleus, leading to abnormal signal transmittion, and ultimately, the development of PD. In addition, generation of reactive oxygen species from dopamine might affect the other DNA repair pathway proteins that we did not examine in the current study. Further studies with larger sample groups are necessary to clarify the role of DNA repair genes and the development of PD.