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Creatine transporter deficiency (CTD), caused by pathogenic variants in SLC6A8, is the second most common cause of X-linked intellectual disability. Symptoms include intellectual disability, epilepsy, and behavioral disorders and are caused by reduced cerebral creatine levels. Targeted treatment with oral supplementation is available, however the treatment efficacy is still being investigated. There are clinical and theoretical indications that heterozygous females with CTD respond better to supplementation treatment than hemizygous males. Unfortunately, heterozygous females with CTD often have more subtle and uncharacteristic clinical and biochemical phenotypes, rendering diagnosis more difficult. We report a new female case who presented with learning disabilities and seizures. After determining the diagnosis with molecular genetic testing confirmed by proton magnetic resonance spectroscopy (1H-MRS), the patient was treated with supplementation treatment including creatine, arginine, and glycine. After 28 months of treatment, the patient showed prominent clinical improvement and increased creatine levels in the brain. Furthermore, we provide a review of the 32 female cases reported in the current literature including a description of phenotypes, genotypes, diagnostic approaches, and effects of supplementation treatment. Based on this, we find that supplementation treatment should be tested in heterozygous female patients with CTD, and a prospective treatment underlines the importance of diagnosing these patients. The diagnosis should be suspected in a broad clinical spectrum of female patients and can only be made by molecular genetic testing. 1H-MRS of cerebral creatine levels is essential for establishing the diagnosis in females, and especially valuable when assessing variants of unknown significance.
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Encefalopatías Metabólicas Innatas , Discapacidad Intelectual , Discapacidad Intelectual Ligada al Cromosoma X , Masculino , Humanos , Femenino , Discapacidad Intelectual/genética , Creatina , Encefalopatías Metabólicas Innatas/diagnóstico , Encefalopatías Metabólicas Innatas/genética , Encefalopatías Metabólicas Innatas/tratamiento farmacológico , Discapacidad Intelectual Ligada al Cromosoma X/diagnóstico , Discapacidad Intelectual Ligada al Cromosoma X/genética , Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática/genética , Proteínas del Tejido NerviosoRESUMEN
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), and particularly liver fibrosis, has been suggested as a risk factor of chronic kidney disease (CKD). Given that NAFLD affects every fourth person globally, better insight is needed. Our aim was to investigate the association between hepatic fibrosis and CKD in patients with type 2 diabetes and to compare different methods for diagnosing liver fibrosis in this study population. METHODS: Cross-sectional study including patients with type 2 diabetes with CKD stages 3-5 (N = 50) or without CKD (N = 50). CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 with or without proteinuria. Three methods were used to detect significant liver fibrosis defined as either ≥8 kilopascal measured by transient elastography (FibroScan®), fibrosis-4 (FIB-4) score ≥2.67, or NAFLD fibrosis score (NFS) >0.675. RESULTS: Significant liver fibrosis was found in 38% and 28% of the patients with and without CKD, respectively, using at least one of the three methods. Both FIB-4 score and NFS were significantly higher in patients with CKD (p < 0.0009 and p < 0.0001, respectively), although insignificant after adjustments for age, sex, body mass index, and duration of diabetes. In patients without CKD, a significant association between steatosis and fibrosis was observed (p = 0.0007). CONCLUSION: Our data do not support any strong independent association between liver fibrosis and established CKD as assessed by FibroScan, FIB-4 score, and NFS, respectively.
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Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Insuficiencia Renal Crónica , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Diabetes Mellitus Tipo 2/complicaciones , Estudios Transversales , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Fibrosis , Insuficiencia Renal Crónica/epidemiologíaRESUMEN
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is suggested as a risk factor for chronic kidney disease (CKD). The incidence of NAFLD is rising globally in parallel to the increasing incidences of obesity and type 2 diabetes. Diabetes remains the leading cause of CKD, but the co-existence of NAFLD, CKD, and type 2 diabetes is not well elucidated. Here, we evaluated the prevalence of NAFLD in patients with type 2 diabetes with and without CKD. METHODS: This was a cross-sectional study including 50 patients with type 2 diabetes and CKD stages 3-5 (no dialysis), and 50 patients with type 2 diabetes without CKD. Liver fat content was estimated by proton magnetic resonance spectroscopy and magnetic resonance imaging proton density fat fraction. NAFLD was defined as liver fat fraction ≥5.6% according to guidelines. RESULTS: Mean age was 72 ± 4.9 years in patients with CKD and 65.9 ± 7.8 years in patients without CKD (p < 0.0001). Three out of four participants were men. BMI was 28.6 ± 3.5 kg/m2 and 27 ± 4.0 kg/m2 in patients with and without CKD, respectively (p = 0.0087). NAFLD was identified in 22 (44%) patients with CKD and 19 (38%) patients without CKD (p = 0.6845). Median (IQR) liver fat fraction was 4.7% (3.0-8.5) and 4.1% (2.9-7.7) in patients with and without CKD, respectively (difference in geometric means 5.3%, 95% CI -23; 45, p = 0.7463). CONCLUSION: These findings do not support any association between NAFLD and CKD (stages 3-5) in patients with type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Insuficiencia Renal Crónica , Masculino , Humanos , Anciano , Femenino , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Estudios Transversales , Diálisis Renal/efectos adversos , Insuficiencia Renal Crónica/complicacionesRESUMEN
OBJECT: Improve shimming capabilities of ultra-high field systems, with addition of an accessible low-complexity B0 shim array for head MRI at 7 T. MATERIALS AND METHODS: An eight channel B0 shim coil array was designed as a tradeoff between shimming improvement and construction complexity, to provide an easy to use shim array that can be employed with the standard 7 T head coil. The array was interfaced using an open-source eight-channel shim amplifier rack. Improvements in field homogeneity for whole-brain and slice-based shimming were compared to standard second-order shimming, and to more complex higher order dynamic shimming and shim arrays with 32 and 48 channels. RESULTS: The eight-channel shim array provided 12% improvement in whole brain static shimming and provided 33% improvement when using slice-based shimming. With this, the eight-channel array performed similar to third-order dynamic shimming (without the need for higher order eddy current compensation). More complex shim arrays with 32 and 48 channels performed better, but require a dedicated RF coil. DISCUSSION: The designed eight-channel shim array provides a low-complexity and low-cost approach for improving B0 field shimming on an ultra-high field system. In both static and dynamic shimming, it provides improved B0 homogeneity over standard shimming.
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Encéfalo , Procesamiento de Imagen Asistido por Computador , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética , Ondas de Radio , Programas InformáticosRESUMEN
The major inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the dominant antioxidant glutathione (GSH) both play a crucial role in brain functioning and are involved in several neurodegenerative and psychiatric diseases. Magnetic resonance spectroscopy (MRS) is a unique way to measure these neurometabolites non-invasively, but the measurement is highly sensitive to head movements, and especially in specific patient groups, motion stabilization in MRS could be valuable. Conventional MRS is acquired at relatively short echo times (TE), however, for unambiguous detection of GABA and GSH, spectral editing techniques are typically used. These depend on longer TEs and use frequency selective spectral editing pulses to separate the low-intensity peaks of GABA and GSH from overlapping resonances, but results in further increased motion sensitivity. Low-intensity metabolite peaks are usually edited one-by-one, however, simultaneous editing of multiple metabolites can be achieved using a Hadamard scheme, resulting in a substantial reduction in scan time. To investigate and correct for motion sensitivity in both conventional short-TE MRS (PRESS) and edited MRS (HERMES), we implemented a navigator-based prospective motion correction strategy including reacquisition of corrupted data. PRESS and HERMES spectra were acquired without motion, with motion with correction (repeated twice), and with motion without correction. Results indicate that when sufficient retrospective outlier removal is used, no significant differences in concentration and spectral quality were observed between motion conditions, even without prospective correction. HERMES spectral editing data showed to be more sensitive to motion, as significant differences in metabolite estimates and variability of spectral quality measures were observed for tCr, GABA+ and GSH when only retrospective outlier removal was applied. When using both prospective and retrospective correction, spectral quality was improved to almost the level of the no-motion acquisition. No differences in metabolite ratios for GABA and GSH could be observed when using motion correction. In conclusion, edited MRS showed to be more prone to motion artifacts, and prospective motion correction can restore most of the spectral quality in both conventional and edited MRS.
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Encéfalo/metabolismo , Glutatión/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Movimiento (Física) , Ácido gamma-Aminobutírico/metabolismo , Adulto , Artefactos , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Espectroscopía de Resonancia Magnética/normas , Masculino , Estudios Prospectivos , Estudios Retrospectivos , Adulto JovenRESUMEN
After publication of the original article [1], the authors have notified us that an updated version of Figures 1, 2 and 3 should have been published. The incorrect and revised figures can be found below.
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INTRODUCTION: Subject movements lead to severe artifacts in magnetic resonance (MR) brain imaging. In this study we evaluate the diagnostic image quality in T1-weighted, T2-weighted, and time-of-flight angiographic MR sequences when using a flexible, navigator-based prospective motion correction system (iMOCO). METHODS: Five healthy volunteers were scanned during different movement scenarios with and without (+/-) iMOCO activated. An experienced neuroradiologist graded images for image quality criteria (grey-white-matter discrimination, basal ganglia, and small structure and vessel delineation), and general image quality on a four-grade scale. RESULTS: In scans with deliberate motion, there was a significant improvement in the image quality with iMOCO compared to the scans without iMOCO in both general image impression (T1 p<0.01, T2 p<0.01, TOF p = 0.03) and in anatomical grading (T1 p<0.01, T2 p<0.01, TOF p = 0.01). Subjective image quality was considered non-diagnostic in 91% of the scans with motion -iMOCO, but only in 4% of the scans with motion +iMOCO. iMOCO performed best in the T1-weighted sequence and least well in the angiography sequence. iMOCO was not shown to have any negative effect on diagnostic image quality, as no significant difference in diagnostic quality was seen between scans -iMOCO and +iMOCO with no deliberate movement. CONCLUSION: The evaluation showed that iMOCO enables substantial improvements in image quality in scans affected by subject movement, recovering important diagnostic information in an otherwise unusable scan.
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Algoritmos , Encéfalo/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Angiografía por Resonancia Magnética/métodos , Movimiento , Neuroimagen/métodos , Adulto , Femenino , Humanos , Aumento de la Imagen , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Curva ROCRESUMEN
BACKGROUND: Sildenafil and calcitonin gene-related peptide both dilate the intradural segments of the middle meningeal artery measured with 3.0 tesla (T) MR angiography. Here we hypothesized that an increase in field strength to 7.0 T and concomitant enhanced voxel resolution would lower variance in measurements of dilation in the intradural middle meningeal artery. METHODS: Five subjects completed two sessions at respectively 3.0 T and 7.0 T. Each session comprised MR angiography scans once before and twice after administration of sildenafil, calcitonin gene-related peptide or placebo in a three-way, crossover, double-blind, placebo-controlled design. RESULTS: Standard deviations of arterial circumference revealed no difference between 3.0 T and 7.0 T measurements (p = 0.379). We found a decrease in standard deviation from our original angiography analysis software (QMra) to a newer (LAVA) software package (p < 0.001). Furthermore, we found that the dilation after sildenafil and calcitonin gene-related peptide were comparable between 3.0 T and 7.0 T. CONCLUSIONS: Our findings suggest no gain from the increase in voxel resolution but cemented dilatory findings from earlier. The implemented software update improved variance in circumference measurements in the intradural middle meningeal artery, which should be exploited in future studies. TRIAL REGISTRATION: The study is part of a parent study, which is registered at ClinicalTrials.gov ( NCT03143465 ).