Measurable Supratentorial White Matter Volume Changes in Patients with Diffuse Intrinsic Pontine Glioma Treated with an Anti-Vascular Endothelial Growth Factor Agent, Steroids, and Radiation

Purpose To evaluate the safety, maximum-tolerated dose, pharmacokinetics, and pharmacodynamics of vandetanib, an oral vascular endothelial growth factor receptor 2 (VEGFR2) and epidermal growth factor receptor inhibitor, administered once daily during and after radiotherapy in children with newly diagnosed diffuse intrinsic pontine glioma. Patients and Methods Radiotherapy was administered as 1.8-Gy fractions (total cumulative dose of 54 Gy). Vandetanib was administered concurrently with radiotherapy for a maximum of 2 years. Dose-limiting toxicities (DLTs) were evaluated during the first 6 weeks of therapy. Pharmacokinetic studies were obtained for all patients. Plasma angiogenic factors and VEGFR2 phosphorylation in mononuclear cells were analyzed before and during therapy. Results Twenty-one patients were administered 50 (n = 3), 65 (n = 3), 85 (n = 3), 110 (n = 6), and 145 mg/m2 (n = 6) of vandetanib. Only one patient developed DLT (grade 3 diarrhea) at dosage level 5. An expanded cohort of patients were treated at dosage levels 4 (n = 10) and 5 (n = 4); two patients developed grade 4 hypertension and posterior reversible encephalopathy syndrome while also receiving high-dose dexamethasone. Despite significant interpatient variability, exposure to vandetanib increased with higher dosage levels. The bivariable analysis of vascular endothelial growth factor (VEGF) before and during therapy showed that patients with higher levels of VEGF before therapy had a longer progression-free survival (PFS; P = .022), whereas patients with increases in VEGF during treatment had a shorter PFS (P = .0015). VEGFR2 phosphorylation was inhibited on day 8 or 29 of therapy compared with baseline (P = .039). Conclusion The recommended phase II dose of vandetanib in children is 145 mg/m2 per day. Close monitoring and management of hypertension is required, particularly for patients receiving corticosteroids.

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White matter volume changes in people who develop psychosis

The British Journal of Psychiatry ◽

10.1192/bjp.bp.107.043463 ◽

2008 ◽

Vol 193 (3) ◽

pp. 210-215 ◽

Cited By ~ 71

Author(s):

Mark Walterfang ◽

Philip K. McGuire ◽

Alison R. Yung ◽

Lisa J. Phillips ◽

Dennis Velakoulis ◽

...

Keyword(s):

White Matter ◽

Grey Matter ◽

White Matter Volume ◽

Volume Changes ◽

Matter Volume ◽

Original Group ◽

Magnetic Resonance Imaging Mri ◽

Longitudinal Comparison ◽

The Right

BackgroundGrey matter changes have been described in individuals who are pre- and peri-psychotic, but it is unclear if these changes are accompanied by changes in white matter structures.AimsTo determine whether changes in white matter occur prior to and with the transition to psychosis in individuals who are pre-psychotic who had previously demonstrated grey matter reductions in frontotemporal regions.MethodWe used magnetic resonance imaging (MRI) to examine regional white matter volume in 75 people with prodromal symptoms. A subset of the original group (n=21) were rescanned at 12–18 months to determine white matter volume changes. Participants were retrospectively categorised according to whether they had or had not developed psychosis at follow-up.ResultsComparison of the baseline MRI data from these two subgroups revealed that individuals who later developed psychosis had larger volumes of white matter in the frontal lobe, particularly in the left hemisphere. Longitudinal comparison of data in individuals who developed psychosis revealed a reduction in white matter volume in the region of the left fronto-occipital fasciculus. Participants who had not developed psychosis showed no reductions in white matter volume but increases in a region subjacent to the right inferior parietal lobule.DiscussionThe reduction in volume of white matter near the left fronto-occipital fasciculus may reflect a change in this tract in association with the onset of frank psychosis.

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Global and regional volume changes in the brains of patients with phenylketonuria

Neurology ◽

10.1212/01.wnl.0000204415.39853.4a ◽

2006 ◽

Vol 66 (7) ◽

pp. 1074-1078 ◽

Cited By ~ 22

Author(s):

B. Pérez-Dueñas ◽

J. Pujol ◽

C. Soriano-Mas ◽

H. Ortiz ◽

R. Artuch ◽

...

Keyword(s):

White Matter ◽

Gray Matter ◽

Premotor Cortex ◽

Gray Matter Volume ◽

Relative Increase ◽

Volume Reduction ◽

Periventricular White Matter ◽

White Matter Volume ◽

Volume Changes ◽

Matter Volume

Background: Although phenylketonuria is a treatable disease, patients with late or nonoptimal phenylalanine-restricted diet may experience brain damage. The authors used tridimensional MRI and a voxelwise analysis method to investigate possible volume changes in the brain parenchyma of patients with phenylketonuria.Methods: The authors assessed 27 treated patients (mean age ± SD, 20 ± 7 years) and 27 matched control subjects. Global tissue volumes were compared, and statistical parametric maps of between-group regional volume differences were obtained for gray and white matter. Anatomic data were correlated with relevant clinical and biochemical variables.Results: Patients with phenylketonuria showed smaller gray matter volumes that were associated with lower IQ and older age at diagnosis. Voxel-based maps revealed that significant gray matter volume reduction occurred in motor and premotor cortex and thalamus. A relative increase in gray matter volume was observed in the ventral part of the striatum. The authors found no group differences for global white matter measurements. Higher recent phenylalanine levels, however, were associated with larger global white matter volume in early-treated patients. Voxel-based maps showed a relative volume reduction in periventricular white matter and a relative increase in the region of the internal capsule, extending to the adjacent thalamus and striatum.Conclusions: Treated patients may show significant gray and white matter volume changes related to the duration and strict observation of dietary treatment. Further studies are needed to investigate whether the presence of neurologic symptoms may be explained by specific anatomic alterations.

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Gray and white matter volume changes in early RRMS: A 2-year longitudinal study

Neurology ◽

10.1212/01.wnl.0000154526.22878.30 ◽

2005 ◽

Vol 64 (6) ◽

pp. 1001-1007 ◽

Cited By ~ 121

Author(s):

M. Tiberio ◽

D. T. Chard ◽

D. R. Altmann ◽

G. Davies ◽

C. M. Griffin ◽

...

Keyword(s):

Longitudinal Study ◽

White Matter ◽

White Matter Volume ◽

Volume Changes ◽

Matter Volume

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SIENA-XL for improving the assessment of gray and white matter volume changes on brain MRI

Human Brain Mapping ◽

10.1002/hbm.23828 ◽

2017 ◽

Vol 39 (3) ◽

pp. 1063-1077 ◽

Cited By ~ 8

Author(s):

Marco Battaglini ◽

Mark Jenkinson ◽

Nicola De Stefano ◽

Keyword(s):

White Matter ◽

Brain Mri ◽

White Matter Volume ◽

Volume Changes ◽

Matter Volume

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Voxel-based analysis derived from fractional anisotropy images of white matter volume changes with aging

NeuroImage ◽

10.1016/j.neuroimage.2008.03.021 ◽

2008 ◽

Vol 41 (3) ◽

pp. 657-667 ◽

Cited By ~ 73

Author(s):

Elisabetta Pagani ◽

Federica Agosta ◽

Maria A. Rocca ◽

Domenico Caputo ◽

Massimo Filippi

Keyword(s):

White Matter ◽

Fractional Anisotropy ◽

White Matter Volume ◽

Volume Changes ◽

Matter Volume

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Serum Brain–Derived Neurotrophic Factor and Vascular Endothelial Growth Factor Levels Are Associated With Risk of Stroke and Vascular Brain Injury

Stroke ◽

10.1161/strokeaha.113.001447 ◽

2013 ◽

Vol 44 (10) ◽

pp. 2768-2775 ◽

Cited By ~ 75

Author(s):

Aleksandra Pikula ◽

Alexa S. Beiser ◽

Tai C. Chen ◽

Sarah R. Preis ◽

Demetrios Vorgias ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Brain Injury ◽

White Matter ◽

Visual Memory ◽

Brain Mri ◽

White Matter Hyperintensity ◽

Vascular Endothelial ◽

Increased Risk ◽

Endothelial Growth Factor ◽

Serum Bdnf

Background and Purpose— Brain-derived neurotrophic factor (BDNF), a major neurotrophin and vascular endothelial growth factor (VEGF) have a documented role in neurogenesis, angiogenesis, and neuronal survival. In animal experiments, they impact infarct size and functional motor recovery after an ischemic brain lesion. We sought to examine the association of serum BDNF and VEGF with the risk of clinical stroke or subclinical vascular brain injury in a community-based sample. Methods— In 3440 Framingham Study participants (mean age, 65±11 years; 56% women) who were free of stroke/transient ischemic attack (TIA), we related baseline BDNF and logVEGF to risk of incident stroke/TIA. In a subsample with brain MRI and with neuropsychological tests available (n=1863 and 2104, respectively; mean age, 61±9 years, 55% women, in each), we related baseline BDNF and logVEGF to log-white matter hyperintensity volume on brain MRI, and to visuospatial memory and executive function tests. Results— During a median follow-up of 10 years, 193 participants experienced incident stroke/TIA. In multivariable analyses adjusted for age, sex, and traditional stroke risk factors, lower BDNF and higher logVEGF levels were associated with an increased risk of incident stroke/TIA (hazard ratio comparing BDNF Q1 versus Q2–Q4, 1.47; 95% confidence interval, 1.09–2.00; P =0.012 and hazard ratio/SD increase in logVEGF, 1.21; 95% confidence interval, 1.04–1.40; P =0.012). Persons with higher BDNF levels had less log-white matter hyperintensity volume (β±SE=−0.05±0.02; P =0.025), and better visual memory (β±SE=0.18±0.07; P =0.005). Conclusions— Lower serum BDNF and higher VEGF concentrations were associated with increased risk of incident stroke/TIA. Higher levels of BDNF were also associated with less white matter hyperintensity and better visual memory. Our findings suggest that circulating BDNF and VEGF levels modify risk of clinical and subclinical vascular brain injury.

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