Corpus Callosum Atrophy in Patients with Hereditary Diffuse Leukoencephalopathy with Neuroaxonal Spheroids: An MRI-based Study

Abstract

Objective Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is an adult-onset white matter disease that presents clinically with cognitive, mental and motor dysfunction. Several autopsy reports have indicated that the corpus callosum (CC), the largest bundle of white matter, is severely affected in patients with HDLS. The aim of this study was to evaluate corpus callosum atrophy (CCA) quantitatively in HDLS patients. Methods We assessed CCA in six genetically-proven HDLS patients (HDLS group), in comparison with that observed in 20 patients with vascular dementia (VaD group) and 24 age-matched patients without organic central nervous system (CNS) disease (non-CNS group). Using midsagittal MR images, five measurements of the CC were obtained: the width of the rostrum (aa'), body (bb') and splenium (cc'), the anterior to posterior length (ab) and the maximum height (cd). Next, the corpus callosum index (CCI) was calculated as (aa' + bb' + cc')/ab. Results All HDLS patients had white matter lesions in the CC and frontoparietal lobes on the initial MRI scans. Compared with that observed in the VaD and age-matched non-CNS groups, the CCI was significantly decreased in the HDLS group (with VaD group, p<0.01; with non-CNS group, p<0.01). Conclusion This study showed significant atrophy of the CC in all HDLS patients on the initial MRI scans obtained 6-36 months after onset. We propose that the early appearance of CCA, frequently accompanied by high-intensity in the genu and/or splenium, on T2 images is an important diagnostic clue to HDLS.Key words: hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS), colony stimulating factor 1 receptor (CSF1R), white matter lesions (WMLs), corpus callosum atrophy (CCA), corpus callosum index (CCI)

Phenotypic characterization of a Csf1r haploinsufficient mouse model of adult-onset leukodystrophy with axonal spheroids and pigmented glia (ALSP)

“…Thinning of the corpus callosum (Kinoshita et al, 2014; Kondo et al, 2013; Konno et al, 2014) that may precede disease onset by up to 5 years (Konno et al, 2014), loss of myelin sheaths and axons and the presence of axonal spheroids, have been reported in ALSP patients (Axelsson et al, 1984; Freeman et al, 2009; Konno et al, 2014; Van Gerpen et al, 2008). We therefore examined the morphology of the corpus callosum by electron microscopy.…”

“…The median age of onset is 42 ± 13 years (range 8-78) with a disease duration of 5 ± 7 (range 1-34) years that is unrelated to the time of onset (Ahmed et al, 2013; Freeman et al, 2009; Guerreiro et al, 2013; Hoffmann et al, 2014; Karle et al, 2013; Kinoshita et al, 2014; Kleinfeld et al, 2013; Kondo et al, 2013; Konno et al, 2014; Mitsui et al, 2012; Rademakers et al, 2011; Sundal et al, 2012; Van Gerpen et al, 2008; Wider et al, 2009). Symptoms may vary according to gender (Hoffmann et al, 2014), and clinical presentation is variable.…”

“…CSF-1 or IL-34 activation of the CSF-1R on NPCs suppresses NPC self-renewal and stimulates neuronal survival and differentiation (Nandi et al, 2012). Furthermore, brains of Csf1r−/− nullizygous mice have gross anatomical and histological abnormalities (Erblich et al, 2011; Nandi et al, 2012) that affect areas (cortex, corpus callosum) disrupted in ALSP (Axelsson et al, 1984; Kinoshita et al, 2014; Konno et al, 2014; Rademakers et al, 2011; Schiffmann and van der Knaap, 2009; Wider et al, 2009). …”

Unexpected Occurrence of Fetal Hemophagocytic Syndrome in a Patient with Hereditary Diffuse Leukoencephalopathy with Spheroids

“…Although he was able to walk without any assistance, some of the daily life activities including bathing, clothing, and brushing of teeth were disturbed. Compared with magnetic resonance (MR) images at his second hospitalization 4 months ago, atrophy in the cerebral cortex and corpus callosum progressed (Evans index: from 0.328 to 0.349; corpus callosum index: from 0.215 to 0.183) [5]. Single photon emission computed tomography (SPECT) showed a decrease in the blood flow especially in the bilateral frontal and parietal lobes.…”

Brain magnetic resonance metabolic and microstructural changes in adult-onset autosomal dominant leukodystrophy

“…Moreover, conventional MR imaging in ADLD cases showed a significant thinning of CC. Macro-and microstructural changes in CC are typically related to different degrees of cognitive impairment as in Alzheimer's Disease (Di Paola et al, 2010), Fronto-Temporal Dementia (Tartaglia et al, 2012) and in white matter disorders such as Hereditary Diffuse Leukoencephalopathy with Neuroaxonal Spheroids (Kinoshita et al, 2014), Pelizaeus-Merzbacher disease (Laukka et al, 2013) and Metachromatic leukodystrophy (Groeschel et al, 2011). The genu of the CC regulates inter-hemispheric connections between pre-frontal associative areas that are involved in working memory, executive and attentive functions (Aung et al, 2013).…”