Nasu-Hakola disease also known as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, is a very rare autosomal recessive disease characterized by a combination of progressive young-onset dementia and multifocal bone cysts. Recently, cases with mutations in TREM2 have been described to present phenotypes resembling behavioral variant frontotemporal dementia (bvFTD). A differential diagnosis is important because Nasu-Hakola disease is a pure genetic disorder and may also affect other systems such as skeletal system. We present 7 Nasu-Hakola patients (all had TREM2 mutations) 2 of whom are women. All patients underwent a cranial magnetic resonance imaging (MRI). Cranial computed tomography of the brain is available for 5 of the patients. All patients have dementia resembling behavioral variant frontotemporal dementia (bvFTD). The mean age of the patients was 41.7± 5.52 years and the mean duration of the disease was 6.85±1.95 years. In MRI findings, all patients had significant thinning of the corpus callosum and marked ventricular enlargement not attributable to atrophy. Symmetrical global atrophy of the brain mainly affecting frontoparieatal and lateral temporal areas were found in all patients but atrophy of the medial temporal lobe structures including hippocampus were evidentonly 3 of 7 patients. 6 of 7 patients had diffuse periventricular white matter abnormalities where the one patient had abnormalitiesonly in posterior periventricular white-matter. CT of the brain was available only 5 patients and 3 of these 5 patients had bilateral calcification in the basal ganglia. Specific neuroimaging findings, especially thinning of corpus callosum with ventricular enlargement may be helpful in the differential diagnosis of FTD. Molecular genetic analysis could be recommended in suspicious cases and if a mutation is found appropriate genetic counseling should be provided to individuals and family members.
The cover image is based on the Data Article Revisiting the complex architecture of ALS in Turkey: Expanding genotypes, shared phenotypes, molecular networks, and a public variant database by Ceren Tunca et al., https://doi.org/10.1002/humu.24055.
Wernicke's encephalopathy (WE) is an underdiagnosed neuropsychiatric disorder especially in non-alcoholic groups that causes morbidity-mortality if diagnosis is delayed. Korsakoff syndrome is a chronic consequence of this condition characterized by persistent memory impairment. In this study we present a series of non-alcoholic patients with WE. The purpose of this study was to analyze the predisposing factors in non-alcoholic patients with WE and emphasize the importance of early diagnosis and treatment with thiamine supplementation.The clinical records of 6 cases with WE followed by gastrointestinal tract disease and/or surgery who were admitted to our Medical Faculty between 2012 and 2014 were retrospectively reviewed.The study included 3 men and 3 women in the age range of 24 to 55. All patients had gastrointestinal tract diseases and/or had undergone gastrointestinal surgeries, and were non-alcoholic. Vomiting, weight loss, and parenteral nutrition were the frequent precipitating factors. The classic triad of mental impairment, oculomotor alterations and gait ataxia was present in 4 of the 6 patients. Magnetic Resonance Imaging showed typical signal alterations in the medial thalami, mammillary bodies and the periaqueductal region of patients in various degrees. Clinical improvement was seen in each patient after thiamine supplementation.Physicians should be aware of the predisposing factors and symptoms to prevent or optimize the management of this potentially devastating disease. Thiamine supplementation should be considered in patients with gastrointestinal tract diseases or those who have undergone surgery.
Abstract Background The Rapid Cognitive Screen (RCS) is a brief, easy to administer score screening tool for cognitive dysfunction which can be very useful for cognitive screening in busy clinical settings. We aimed to cross‐culturally adapt and validate RCS in Turkish. Methods A total of 172 community‐dwelling older participants from geriatric and neurology clinics, aged 60 and older were included. The translation and cultural adaptation process was carried out in five stages: (i) two initial translations from English to Turkish; (ii) combination of these two translations; (iii) backward translations; (iv) an expert committee that consisted of three geriatricians and two neurologists, one Turkish lecturer reviewed to compare backward translations with the English test; and (v) pretest. The inter‐rater reliability and test–retest reliability were performed. To diagnose each type of dementia, gold standard diagnostic criteria specifically defined for each dementia were used. Performances of RCS test for dementia and mild cognitive impairment (MCI) were analyzed by using sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The receiver operating characteristic analysis was performed to determine the area under the curve (AUC) with 95% confidence intervals (CI). Results Among participants, 37.2% were considered as cognitively normal, 25.6% with MCI and 37.2% with dementia. The sensitivity, specificity, PPV, and NPV of RCS (cut‐off point of 4) for dementia were 89.06%, 92.56%, 87.7%, and 93.5%, respectively whereas the values were 77.27%, 51.56%, 52.3%, and 76.7% for MCI with a cut‐off point of 8. The RCS predicted dementia (AUC = 0.972, 95% CI: 0.935–0.991) and MCI (AUC = 0.720%, 95% CI: 0.626–0.802). Conclusion The cross‐cultural adaptation was successfully achieved. The Turkish‐RCS was found to be a reliable and valid test for screening of cognitive dysfunction.
Abstract Background Copy number variations (CNVs) arise from copied or deleted regions of the genome. These regions vary in size and may span genes known to play a role in human disease. For example, duplications and triplications of SNCA have been shown to cause forms of Parkinson’s disease, while extra copies of APP are associated with early onset Alzheimer’s disease (AD). We have previously studied a Turkish dementia cohort for variants in known disease‐causing genes for both AD and frontotemporal dementia (FTD) and have also reported variants in the new AD‐associated genes TREM2 and NOTCH3 . The goal of the current study was to perform a systematic analysis of CNVs in order to further characterize the genetic causes of dementia in this Turkish dementia cohort. Method Ninety‐nine Turkish individuals, either at risk of dementia due to family history, diagnosed with mild cognitive impairment, AD or FTD, were whole‐genome genotyped using Illumina HumanOmniExpress chips. We used GenomeStudio cnvPartition v3.2.1 plug‐in (Illumina, Inc) to analyze the data. Result We did not identify any CNVs segregating with disease in any of the four dementia families present in the studied cohort. We also did not observe any CNVs across our entire data set overlapping genes which have been previously associated with neurodegenerative diseases. We identified 9 distinct CNVs overlapping regions previously reported to have potential disease‐associated gene dosage alterations in patients with dementia phenotypes using PennCNV‐1.0.5; these were confirmed by manually checking CNVs on GenomeStudio. We observed potential disease‐associated CNVs in single individuals overlapping LOC286367 , ABCA1 , NIPSNAP3A , NIPSNAP3B , OR13C2 , OR13C5 , OR13C8 , OR13C9 , OR13D1 , CNTN6 , NIPA1 , CYFIP1 , GALNTL6 , NLGN1 , XPO1 , SNORA70B , USP34 , and HLA‐G . Additionally, two identical heterozygous duplications spanning MICA were identified in two AD patients; CNVs spanning this gene have been previously reported in four AD patients and no controls. Conclusion In this study, we integrated whole‐genome genotyping results from a Turkish cohort with previously reported findings and data publicly available to add further evidence to the role of specific CNVs in the pathogenesis of dementia.
A cross-sectional, population-based, 2-stage prevalence study was conducted in a sample of 1019 community-dwelling persons over the age of 70 years living in Istanbul. In the first phase, participants were screened with the Mini-Mental State Examination for evidence of cognitive impairment. In the second phase, 79% of those who screened positive (n = 322) and 9% of screen-negatives (n = 63) underwent a standardized diagnostic workup. Diagnosis of dementia and Alzheimer's disease (AD) was made according to established criteria. Ninety-three cases of dementia were identified, 58 of whom were diagnosed with probable AD. Based on these numbers, the prevalence rates of probable AD and dementia were calculated to be 11.0% (95% CI, 7.0% to 15.0%) and 20.0% (95% CI, 14.0% to 26.0%), respectively, in this population. Prevalence rates of dementia and AD in Istanbul, Turkey, are comparable with those seen in the Western world.
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