Cranial ultrasound findings in aspartoacylase deficiency (Canavan disease)

Abstract

Canavan disease (CD) is a rare leukodystrophy which is lethal in infancy or early childhood. The underlying biochemical abnormality in CD is a hereditary deficiency of N-aspartoacylase transmitted in an autosomal recessive fashion. We report on the ultrasound (US), CT, and MRI findings of three unrelated boys with biochemically confirmed CD. At 6 and 9 months of age, two CD patients with rapid neurological deterioration showed markedly enhanced acoustic attenuation of the white matter with the exception of the corpus callosum, giving the appearance of a reversed pattern of echogenicity of cortical gray and subcortical white matter. While gyri and sulci had an almost normal US appearance, the periventricular gray matter featured prominently with increased echogenicity. In contrast another CD patient with a more protracted course had ventricular enlargement when examined by US at 5 and 9 months but no alteration in white matter echogenicity. MRI showed impaired myelinization in all three patients with Canavan disease.

Ultrasound Findings in Follow-Up Investigations in a Case of Aspartoacylase Deficiency (Canavan Disease)

“…For the first time we present a well-documented long-term followup of ultrasound scans with the characteristic features of proven Canavan disease. The unusual ultrasound imaging that we found in our patient at the age of 6 months shows the same suspicious changes as in the presented case of Bührer et al [4]. Patel et al also described hyperechogenicity of the white matter; however, in addition multiple anechoic lesions were shown [11] which cannot be explained by neuropathological and neuroradiological findings [3,5,8,10,12].…”

“…There are very little data available about ultrasound imaging in leukodystrophies [2,6]. To our knowledge, only four cases on Canavan disease have been published, two of them with imaging [4,11]. For the first time we present a well-documented long-term followup of ultrasound scans with the characteristic features of proven Canavan disease.…”

Brain ultrasound in Canavan disease

“…In particular, in advance stages of the disease, we described a white matter hyperechogenicity characterized by a homogenous fine texture and an intense signal of pial demarcation. These findings, that can be assessed in previous reported images [7,8], seem to be highly characteristic of CD. By these two signs, together with a ''reversal'' of white and gray matter signal intensities, we suggest that brain US could be useful in discriminate CD.…”

“…Changes in white matter that are a consequence of a dystrophic process are very hyperechoic and can be irregularly shaped, linear or with undulating appearance [14]. To date, in literature, only five cases of brain US investigation in CD have been reported, of which only one with a US follow-up [6][7][8]. The findings here reported confirm brain US features of CD: remarkable increase, intensifying over time, of the echogenicity in white matter and nucleus caudatus and thalamus, and low echogenicity of gray matter giving an apparent reversed pattern of signal.…”

“…To date, there are few data of brain sonography in leukodystrophies in general and in CD in particular [6][7][8][9][10].…”