Validation of MRI biomarker of white matter degeneration for ALS clinical trials

Neurology ◽  
2020 ◽  
Vol 95 (8) ◽  
pp. 327-328
Author(s):  
Hitoshi Shinotoh ◽  
Carmel Armon
Keyword(s):  
Clinical Trials ◽  
White Matter ◽  
White Matter Degeneration

scholarly journals Assessment of White Matter Injury and Outcome in Severe Brain Trauma

2012 ◽  
Vol 117 (6) ◽  
pp. 1300-1310 ◽  
Author(s):  
Damien Galanaud ◽  
Vincent Perlbarg ◽  
Rajiv Gupta ◽  
Robert D. Stevens ◽  
Paola Sanchez ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Clinical Trials ◽  
Brain Injury ◽  
White Matter ◽  
Receiver Operating Characteristic Curve ◽  
Receiver Operating Characteristic ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Unfavorable Outcome ◽  
Operating Characteristic Curve

Background Existing methods to predict recovery after severe traumatic brain injury lack accuracy. The aim of this study is to determine the prognostic value of quantitative diffusion tensor imaging (DTI). Methods In a multicenter study, the authors prospectively enrolled 105 patients who remained comatose at least 7 days after traumatic brain injury. Patients underwent brain magnetic resonance imaging, including DTI in 20 preselected white matter tracts. Patients were evaluated at 1 yr with a modified Glasgow Outcome Scale. A composite DTI score was constructed for outcome prognostication on this training database and then validated on an independent database (n=38). DTI score was compared with the International Mission for Prognosis and Analysis of Clinical Trials Score. Results Using the DTI score for prediction of unfavorable outcome on the training database, the area under the receiver operating characteristic curve was 0.84 (95% CI: 0.75-0.91). The DTI score had a sensitivity of 64% and a specificity of 95% for the prediction of unfavorable outcome. On the validation-independent database, the area under the receiver operating characteristic curve was 0.80 (95% CI: 0.54-0.94). On the training database, reclassification methods showed significant improvement of classification accuracy (P < 0.05) compared with the International Mission for Prognosis and Analysis of Clinical Trials score. Similar results were observed on the validation database. Conclusions White matter assessment with quantitative DTI increases the accuracy of long-term outcome prediction compared with the available clinical/radiographic prognostic score.

Are Gait Disturbances and White Matter Degeneration Early Indicators of Vascular Dementia?

1994 ◽  
Vol 5 (3-4) ◽  
pp. 197-202 ◽  
Author(s):  
Michael G. Hennerici ◽  
Manfred Oster ◽  
Simon Cohen ◽  
Andreas Schwartz ◽  
Lillian Motsch ◽  
...  
Keyword(s):  
White Matter ◽  
Vascular Dementia ◽  
White Matter Degeneration ◽  
Gait Disturbances ◽  
Early Indicators

scholarly journals A novel animal model for neuroinflammation and white matter degeneration

2017 ◽  
Author(s):  
Baohu Ji ◽  
Kerin Higa ◽  
Virawudh Soontornniyomkij ◽  
Atsushi Miyanohara ◽  
Xianjin Zhou
Keyword(s):  
Animal Model ◽  
Immune System ◽  
White Matter ◽  
Innate Immune System ◽  
D1 Receptor ◽  
Innate Immune ◽  
Small Interference Rna ◽  
Cell Defense ◽  
White Matter Degeneration ◽  
Short Hairpin Rnas

Small interference RNA has been widely used to suppress gene expression. Three different short-hairpin RNAs (shRNAs) against dopamine D1 receptor (Drd1), driven by mouse U6 promoter in self-complementary AAV8 vector (scAAV8), were used to silence mouse striatal Drd1 expression. Transduction of mouse striatum with all 3 scAAV8-D1shRNA virus, but not the control scAAV8 virus, causes extensive neuroinflammation, demyelination, and axon degeneration. RNA interference is known to be coupled to the innate immune system as a host cell defense against virus infection. Activation of the innate immune system may play a causal role in the development of neuroinflammation and white matter degeneration, providing a novel animal model for multiple sclerosis (MS) and other neuroinflammatory diseases.

scholarly journals Chronic White Matter Degeneration, but No Tau Pathology at One-Year Post-Repetitive Mild Traumatic Brain Injury in a Tau Transgenic Model

2019 ◽  
Vol 36 (4) ◽  
pp. 576-588 ◽  
Author(s):  
Benoit Mouzon ◽  
Corbin Bachmeier ◽  
Joseph Ojo ◽  
Christopher Acker ◽  
Scott Ferguson ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Mild Traumatic Brain Injury ◽  
Tau Pathology ◽  
Transgenic Model ◽  
White Matter Degeneration ◽  
One Year

Combining Low-Dose Radiation Therapy and Magnetic Resonance Guided Focused Ultrasound to Reduce Amyloid-β Deposition in Alzheimer’s Disease

2021 ◽  
pp. 1-4
Author(s):  
Paolo Farace ◽  
Stefano Tamburin
Keyword(s):  
Alzheimer’S Disease ◽  
Clinical Trials ◽  
Radiation Therapy ◽  
White Matter ◽  
Magnetic Resonance ◽  
Low Dose ◽  
Focused Ultrasound ◽  
Amyloid Β ◽  
Low Dose Radiation ◽  
Dose Radiation

Amyloid-β deposition is one of the neuropathological hallmarks of Alzheimer’s disease (AD), but pharmacological strategies toward its reduction are poorly effective. Preclinical studies indicate that low-dose radiation therapy (LD-RT) may reduce brain amyloid-β. Animal models and proof-of-concept preliminary data in humans have shown that magnetic resonance guided focused ultrasound (MRgFUS) can reversibly open the blood-brain-barrier and facilitate the delivery of targeted therapeutics to the hippocampus, to reduce amyloid-β and promote neurogenesis in AD. Ongoing clinical trials on AD are exploring whole-brain LD-RT, which may damage radio-sensitive structures, i.e., hippocampus and white matter, thus contributing to reduced neurogenesis and radiation-induced cognitive decline. However, selective irradiation of cortical amyloid-β plaques through advanced LD-RT techniques might spare the hippocampus and white matter. We propose combined use of advanced LD-RT and targeted drug delivery through MRgFUS for future clinical trials to reduce amyloid-β deposition in AD since its preclinical stages.

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