scholarly journals White Matter Integrity Changes and Neurocognitive Functioning in Adult-Late Onset DM1: A Follow-Up DTI Study

2021 ◽  
Author(s):  
Garazi Labayru ◽  
Borja Camino-Pontes ◽  
Antonio Jimenez-Marin ◽  
Joana Garmendia ◽  
Jorge Villanua ◽  
...  
Keyword(s):  
White Matter ◽  
Late Onset ◽  
Neurocognitive Functioning ◽  
Frontal Part ◽  
Multisystemic Disease ◽  
The Brain ◽  
Over Time ◽  
Anterior Posterior

Abstract Background: Myotonic Dystrophy Type 1 (DM1) is a multisystemic disease that affects gray and white matter (WM) tissues. WM changes in DM1 include increased hyperintensities and altered tract integrity distributed in a widespread manner. However, the precise spatiotemporal changes are yet undetermined. Methods: MRI data were acquired from 8 adult- and late-onset DM1 patients and 10 healthy controls (HC) at two different timepoints over 9.06 years. Fractional anisotropy (FA) variations were assessed with Tract-Based Spatial Statistics. Transversal and longitudinal intra- and intergroup analyses were conducted, along with correlation analyses with clinical and neuropsychological data.Results: At baseline, reduced FA values were found in patients in the uncinate, anterior-thalamic, fronto-occipital, and longitudinal tracts. At follow-up, the WM disconnection was shown to have spread from the frontal part to the rest of the tracts in the brain. Furthermore, WM lesion burden was negatively correlated with FA values, while visuo-construction and intellectual functioning were positively correlated with global and regional FA values at follow-up.Conclusion: DM1 patients showed a pronounced WM integrity loss over time compared to HC, with a neurodegeneration pattern that suggests a progressive anterior-posterior disconnection. The visuo-construction domain stands out as the most sensitive neuropsychological measure for WM microstructural impairment.

scholarly journals Differences in splicing defects between the grey and white matter in myotonic dystrophy type 1

2019 ◽  
Author(s):  
Masamitsu Nishi ◽  
Takashi Kimura ◽  
Mitsuru Furuta ◽  
Koichi Suenaga ◽  
Tsuyoshi Matsumura ◽  
...  
Keyword(s):  
White Matter ◽  
Myotonic Dystrophy ◽  
Cell Body ◽  
Neuronal Cell ◽  
Neuronal Cell Body ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
And Control ◽  
The Brain

AbstractMyotonic dystrophy type 1 (DM1) is a multi-system disorder caused by CTG repeats in the myotonic dystrophy protein kinase (DMPK) gene. This leads to sequestration of the splicing factor, muscleblind-like 2 (MBNL2), and aberrant splicing, mainly in the central nervous system. We investigated the splicing patterns of MBNL1/2 and genes controlled by MBNL2 in several regions of the brain and between the grey matter (GM) and white matter (WM) in DM1 patients using RT-PCR. Compared with the control, the percentage of spliced-in parameter (PSI) for most of the examined exons were significantly altered in most of the brain regions of DM1 patients, except for the cerebellum. The splicing of many genes was differently regulated between the GM and WM in both DM1 and control. The level of change in PSI between DM1 and control was higher in the GM than in the WM. The differences in alternative splicing between the GM and WM may be related to the effect of DM1 on the WM of the brain. We hypothesize that in DM1, aberrantly spliced isoforms in the neuronal cell body of the GM may not be transported to the axon. This might affect the WM as a consequence of Wallerian degeneration secondary to cell body damage. Our findings may have implications for analysis of the pathological mechanisms and exploring potential therapeutic targets.

scholarly journals Genome aging: somatic mutation in the brain links age-related decline with disease and nominates pathogenic mechanisms

2019 ◽  
Vol 28 (R2) ◽  
pp. R197-R206 ◽  
Author(s):  
Michael A Lodato ◽  
Christopher A Walsh
Keyword(s):  
Human Brain ◽  
Somatic Mutation ◽  
Somatic Mutations ◽  
Late Onset ◽  
Whole Genome ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Age Related ◽  
The Brain ◽  
Over Time

AbstractAging is a mysterious process, not only controlled genetically but also subject to random damage that can accumulate over time. While DNA damage and subsequent mutation in somatic cells were first proposed as drivers of aging more than 60 years ago, whether and to what degree these processes shape the neuronal genome in the human brain could not be tested until recent technological breakthroughs related to single-cell whole-genome sequencing. Indeed, somatic single-nucleotide variants (SNVs) increase with age in the human brain, in a somewhat stochastic process that may nonetheless be controlled by underlying genetic programs. Evidence from the literature suggests that in addition to demonstrated increases in somatic SNVs during aging in normal brains, somatic mutation may also play a role in late-onset, sporadic neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. In this review, we will discuss somatic mutation in the human brain, mechanisms by which somatic mutations occur and can be controlled, and how this process can impact human health.

scholarly journals Brain imaging in myotonic dystrophy type 1

Neurology ◽  
2017 ◽  
Vol 89 (9) ◽  
pp. 960-969 ◽  
Author(s):  
Kees Okkersen ◽  
Darren G. Monckton ◽  
Nhu Le ◽  
Anil M. Tuladhar ◽  
Joost Raaphorst ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Imaging ◽  
Longitudinal Studies ◽  
Myotonic Dystrophy ◽  
Gray Matter ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Pooled Prevalence ◽  
The Brain

Objective:To systematically review brain imaging studies in myotonic dystrophy type 1 (DM1).Methods:We searched Embase (index period 1974–2016) and MEDLINE (index period 1946–2016) for studies in patients with DM1 using MRI, magnetic resonance spectroscopy (MRS), functional MRI (fMRI), CT, ultrasound, PET, or SPECT. From 81 studies, we extracted clinical characteristics, primary outcomes, clinical-genetic correlations, and information on potential risk of bias. Results were summarized and pooled prevalence of imaging abnormalities was calculated, where possible.Results:In DM1, various imaging changes are widely dispersed throughout the brain, with apparently little anatomical specificity. We found general atrophy and widespread gray matter volume reductions in all 4 cortical lobes, the basal ganglia, and cerebellum. The pooled prevalence of white matter hyperintensities is 70% (95% CI 64–77), compared with 6% (95% CI 3–12) in unaffected controls. DTI shows increased mean diffusivity in all 4 lobes and reduced fractional anisotropy in virtually all major association, projection, and commissural white matter tracts. Functional studies demonstrate reduced glucose uptake and cerebral perfusion in frontal, parietal, and temporal lobes, and abnormal fMRI connectivity patterns that correlate with personality traits. There is significant between-study heterogeneity in terms of imaging methods, which together with the established clinical variability of DM1 may explain divergent results. Longitudinal studies are remarkably scarce.Conclusions:DM1 brains show widespread white and gray matter involvement throughout the brain, which is supported by abnormal resting-state network, PET/SPECT, and MRS parameters. Longitudinal studies evaluating spatiotemporal imaging changes are essential.

scholarly journals Local connectome phenotypes predict social, health, and cognitive factors

2018 ◽  
Vol 2 (1) ◽  
pp. 86-105 ◽  
Author(s):  
Michael A. Powell ◽  
Javier O. Garcia ◽  
Fang-Cheng Yeh ◽  
Jean M. Vettel ◽  
Timothy Verstynen
Keyword(s):  
White Matter ◽  
Diffusion Mri ◽  
Social Health ◽  
Cognitive Factors ◽  
High Dimensional ◽  
Cognitive Measures ◽  
Human Connectome Project ◽  
Low Dimensional ◽  
The Brain ◽  
Over Time

The unique architecture of the human connectome is defined initially by genetics and subsequently sculpted over time with experience. Thus, similarities in predisposition and experience that lead to similarities in social, biological, and cognitive attributes should also be reflected in the local architecture of white matter fascicles. Here we employ a method known as local connectome fingerprinting that uses diffusion MRI to measure the fiber-wise characteristics of macroscopic white matter pathways throughout the brain. This fingerprinting approach was applied to a large sample ( N = 841) of subjects from the Human Connectome Project, revealing a reliable degree of between-subject correlation in the local connectome fingerprints, with a relatively complex, low-dimensional substructure. Using a cross-validated, high-dimensional regression analysis approach, we derived local connectome phenotype (LCP) maps that could reliably predict a subset of subject attributes measured, including demographic, health, and cognitive measures. These LCP maps were highly specific to the attribute being predicted but also sensitive to correlations between attributes. Collectively, these results indicate that the local architecture of white matter fascicles reflects a meaningful portion of the variability shared between subjects along several dimensions.

scholarly journals Residual Pituitary Function after Brain Injury-Induced Hypopituitarism: A Prospective 12-Month Study

2005 ◽  
Vol 90 (11) ◽  
pp. 6085-6092 ◽  
Author(s):  
Gianluca Aimaretti ◽  
Maria Rosaria Ambrosio ◽  
Carolina Di Somma ◽  
Maurizio Gasperi ◽  
Salvatore Cannavò ◽  
...  
Keyword(s):  
Brain Injury ◽  
High Risk ◽  
Gh Deficiency ◽  
Pituitary Function ◽  
Brain Injured ◽  
Injured Patients ◽  
The Brain ◽  
Over Time

Abstract Context: Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are conditions at high risk for the development of hypopituitarism. Objective: The objective of the study was to clarify whether pituitary deficiencies and normal pituitary function recorded at 3 months would improve or worsen at 12 months after the brain injury. Design and Patients: Pituitary function was tested at 3 and 12 months in patients who had TBI (n = 70) or SAH (n = 32). Results: In TBI, the 3-month evaluation had shown hypopituitarism (H) in 32.8%. Panhypopituitarism (PH), multiple (MH), and isolated (IH) hypopituitarism had been demonstrated in 5.7, 5.7, and 21.4%, respectively. The retesting demonstrated some degree of H in 22.7%. PH, MH, and IH were present in 5.7, 4.2, and 12.8%, respectively. PH was always confirmed at 12 months, whereas MH and IH were confirmed in 25% only. In 5.5% of TBI with no deficit at 3 months, IH was recorded at retesting. In 13.3% of TBI with IH at 3 months, MH was demonstrated at 12-month retesting. In SAH, the 3-month evaluation had shown H in 46.8%. MH and IH had been demonstrated in 6.2 and 40.6%, respectively. The retesting demonstrated H in 37.5%. MH and IH were present in 6.2 and 31.3%, respectively. Although no MH was confirmed at 12 months, two patients with IH at 3 months showed MH at retesting; 30.7% of SAH with IH at 3 months displayed normal pituitary function at retesting. In SAH, normal pituitary function was always confirmed. In TBI and SAH, the most common deficit was always severe GH deficiency. Conclusion: There is high risk for H in TBI and SAH patients. Early diagnosis of PH is always confirmed in the long term. Pituitary function in brain-injured patients may improve over time but, although rarely, may also worsen. Thus, brain-injured patients must undergo neuroendocrine follow-up over time.

scholarly journals Brain Metabolic Alterations in Patients with Type 1 Diabetes–Hyperglycemia-Induced Injury

2004 ◽  
Vol 24 (12) ◽  
pp. 1393-1399 ◽  
Author(s):  
Sari Mäkimattila ◽  
Kirsi Malmberg-Cèder ◽  
Anna-Maija Häkkinen ◽  
Kim Vuori ◽  
Oili Salonen ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
White Matter ◽  
Adhesion Molecules ◽  
Organ Injury ◽  
Resonance Spectroscopy ◽  
Vascular Cell Adhesion ◽  
Intercellular Adhesion Molecules ◽  
Water Intensity ◽  
The Brain

Microangiopathic end-organ injury is common in type 1 diabetes. However, the pathophysiology of diabetic encephalopathy is poorly understood. The authors studied 10 normotensive patients with type 1 diabetes with retinopathy, autonomic neuropathy, but without nephropathy, and 10 healthy subjects. Proton magnetic resonance spectroscopy was performed at 1.5 T in the frontal cortex, thalamus, and posterior frontal white matter. There was no change in N-acetyl–containing compounds (NA), but choline-containing compounds (Cho) were increased in the white matter and in the thalamus; myo-inositol was increased in the white matter, glucose excess was found in all brain, and water intensity was increased in the cortical voxel in the patients. Calculated lifetime glycemic exposure correlated inversely with Cho and NA in white matter and with Cho in thalamus. Concentrations of soluble intercellular adhesion molecules and vascular cell adhesion molecules were increased in the patients. In conclusion, in patients with type 1 diabetes, the increase in adhesion molecules and an association between altered brain metabolites and glycemic exposure suggest the presence of a vascularly mediated, progressive metabolic disturbance in the brain.

scholarly journals Development of white matter fibre density and morphology over childhood: a longitudinal fixel-based analysis

2018 ◽  
Author(s):  
Sila Genc ◽  
Robert E Smith ◽  
Charles B Malpas ◽  
Vicki Anderson ◽  
Jan M Nicholson ◽  
...  
Keyword(s):  
White Matter ◽  
Cross Section ◽  
Repeated Measures ◽  
Pubertal Stage ◽  
Full Spectrum ◽  
Fibre Density ◽  
Fibre Development ◽  
Over Time ◽  
Time Point

AbstractPurposeWhite matter fibre development in childhood involves dynamic changes to microstructural organisation driven by increasing axon diameter, density, and myelination. However, there is a lack of longitudinal studies that have quantified advanced diffusion metrics to identify regions of accelerated fibre maturation, particularly across the early pubertal period. We applied a novel longitudinal fixel-based analysis (FBA) framework, in order to estimate microscopic and macroscopic white matter changes over time.MethodsDiffusion-weighted imaging (DWI) data were acquired for 59 typically developing children (27 female) aged 9 – 13 years at two time-points approximately 16 months apart (time-point 1: 10.4 ± 0.4 years, time-point 2: 11.7 ± 0.5 years). Whole brain FBA was performed using the connectivity-based fixel enhancement method, to assess longitudinal changes in fibre microscopic density and macroscopic morphological measures, and how these changes are affected by sex, pubertal stage, and pubertal progression. Follow-up analyses were performed in sub-regions of the corpus callosum to confirm the main findings using a Bayesian repeated measures approach.ResultsThere was a statistically significant increase in fibre density over time localised to medial and posterior commissural and association fibres, including the forceps major and bilateral superior longitudinal fasciculus. Increases in fibre cross-section were substantially more widespread. The rate of fibre development was not associated with age or sex. In addition, there was no significant relationship between pubertal stage or progression and longitudinal fibre development over time. Follow-up Bayesian analyses were performed to confirm the findings, which supported the null effect of the longitudinal pubertal comparison.ConclusionUsing a novel longitudinal fixel-based analysis framework, we demonstrate that white matter fibre density and fibre cross-section increased within a 16-month scan rescan period in specific regions. The observed increases might reflect increasing axonal diameter or axon count. Pubertal stage or progression did not influence the rate of fibre development in the early stages of puberty. Future work should focus on quantifying these measures across a wider age range to capture the full spectrum of fibre development across the pubertal period.

scholarly journals Follow Up of Value of the Intrarenal Resistivity Indices and Different Renal Biomarkers for Early Identification of Diabetic Nephropathy in Type 1 Diabetic Patients

2017 ◽  
Vol 5 (2) ◽  
pp. 188-192 ◽  
Author(s):  
Soha M. Abd El Dayem ◽  
Abo El Magd El Bohy ◽  
Mona Hamed ◽  
Solaf Ahmed
Keyword(s):  
Diabetic Nephropathy ◽  
Lipid Profile ◽  
Diabetic Patients ◽  
Creatinine Ratio ◽  
Albumin Creatinine Ratio ◽  
Resistivity Index ◽  
Type 1 Diabetic Patients ◽  
Over Time

AIM: To evaluate intrarenal resistivity index (RI) and different biomarkers of diabetic nephropathy (DN) with clinical signs of DN and its progression over time as early detection of DN.PATIENTS AND METHODS: This longitudinal study included 48 type 1 diabetic patients who were studied at baseline and after three years. A blood sample was taken for assessment of glycosylated haemoglobin (HbA1), lipid profile and a urine sample was taken for assessment of albumin/creatinine ratio, Neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid binding protein (L-FABP) and kidney injury molecule-1 (Kim-1) at baseline and after three years. Forty diabetic patients did renal Doppler at baseline & after three years.RESULTS: HbA1, waist/hip ratio, albumin/creatinine ratio, lipid profile, NGAL, KIM-1, L-FABP and resistivity index (RI) were significantly increased in follow-up. Twenty patients (41.7%) showed progression to albuminuria. RI showed a significant increase in follow-up study. ROC curve showed that RI and NGAL had the highest sensitivity (100%), followed by L-FABP (90%) and lastly KIM-1 (63.6%) in the prediction of DN.CONCLUSION: High RI, NGAL, KIM-1 & L-FABP can be considered as early markers of diabetic nephropathy in type 1 diabetics and are associated with its progression over time, independent of albuminuria.

scholarly journals Longitudinal changes of ADHD symptoms in association with white matter microstructure: a tract-specific fixel-based analysis

2021 ◽  
Author(s):  
Christienne G Damatac ◽  
Sourena Soheili-Nezhad ◽  
Guilherme Blazquez Freches ◽  
Marcel P Zwiers ◽  
Sanne de Bruijn ◽  
...  
Keyword(s):  
White Matter ◽  
Fiber Density ◽  
Cross Sectional ◽  
White Matter Microstructure ◽  
Brain Structure And Function ◽  
White Matter Development ◽  
And Function ◽  
Symptom Trajectory ◽  
Over Time

Background: Variation in the longitudinal course of childhood attention deficit/hyperactivity disorder (ADHD) coincides with neurodevelopmental maturation of brain structure and function. Prior work has attempted to determine how alterations in white matter (WM) relate to changes in symptom severity, but much of that work has been done in smaller cross-sectional samples using voxel-based analyses. Using standard diffusion-weighted imaging (DWI) methods, we previously showed WM alterations were associated with ADHD symptom remission over time in a longitudinal sample of probands, siblings, and unaffected individuals. Here, we extend this work by further assessing the nature of these changes in WM microstructure by including an additional follow-up measurement (aged 18-34 years), and using the more physiologically informative fixel-based analysis (FBA). Methods: Data were obtained from 139 participants over 3 clinical and 2 follow-up DWI waves, and analyzed using FBA in regions-of-interest based on prior findings. We replicated previously reported significant models and extended them by adding another time-point, testing whether changes in combined and hyperactivity-impulsivity (HI) continuous symptom scores are associated with fixel metrics at follow-up. Results: Clinical improvement in HI symptoms over time was associated with more fiber density at follow-up in the left corticospinal tract (lCST) (tmax=1.092, standardized effect[SE]=0.044, pFWE=0.016), and improvement in combined symptoms over time was associated with more fiber cross-section at follow-up in the lCST (tmax=3.775, SE=0.051, pFWE=0.019). Conclusions: Aberrant white matter development involves both lCST micro- and macrostructural alterations and its path may be moderated by preceding symptom trajectory.

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