Temporal evolution of sporadic Creutzfeldt–Jakob disease monitored by 3-Tesla MR spectroscopy

Abstract

Creutzfeldt–Jakob disease (CJD) is a progressive neurodegenerative disease. How the lesions of CJD initiate and propagate in the brain remains largely unknown. Magnetic resonance (MR) techniques including proton MR spectroscopy (MRS) are useful for diagnosing CJD [1–3]. MRS allows for noninvasive and spatially resolved measurement of several brain compounds, including N-acetyl aspartate (NAA), a neuronal marker, and choline-containing compounds (Cho), a marker of membrane density and integrity [4]. However, the use of MRS to investigate the temporal evolution of CJD has been limited. We analyzed serial 3-Tesla MRS findings in patients with sporadic CJD (sCJD). Two patients with diagnoses of probable (case 1) and definite (case 2) sCJD [5] were enrolled. The profiles of patients are summarized in Table 1. MRS examinations were performed using a 3-Tesla MR unit (Signa 3T HDx; GE Medical Systems, Milwaukee, WI, USA). Each patient underwent the sessions twice at intervals of 4 (case 1) and 6 (case 2) weeks. MR spectra were obtained using the multivoxel method performed with chemical shift imaging (repetition time/echo time = 1,500/144 ms). The MRS values from voxels of interest in the left cerebrum were analyzed (Fig. 1a). The comparison was made between the two MRS studies in each patient. The values of NAA, Cho, lactate, and the Cho to NAA ratio (Cho/NAA) were compared using Student’s t tests. Statistical significance was accepted for p \ 0.05. This study was approved by the Ethics Committee and was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. In case 1, the MRS analysis showed a significant decrease in NAA (p \ 0.05, Fig. 1b), a trend toward increased Cho (mean values, 1,100 vs. 1,314, p = 0.07), and a significant increase in the Cho/NAA (p \ 0.005, Fig. 1c) over time. In case 2, although a decrease in NAA was found, it was not significant (mean values, 238 vs. 163, p = 0.29), there were no significant temporal changes in Cho (mean values, 428 vs. 470, p = 0.78), and the Cho/ NAA was significantly increased (p \ 0.005, Fig. 1d). Interestingly, lactate peaks were noted in all sessions of both cases. The lactate values were not significantly different in the serial studies of each case (mean values: case 1, 146 vs. 163, p = 0.52; case 2, 105 vs. 145, p = 0.25). In case 2, a necropsy of the left frontotemporal lobe confirmed the diagnosis of definite sCJD (Fig. 1e–f). Our study revealed that the Cho/NAA increased over time and lactate peaks were present in the 3-Tesla MRS studies of patients with sCJD. A reduced NAA to Cho ratio (or elevated Cho/NAA) has been reported in familial CJD [6]. Increases in Cho/NAA have also been reported in malignant tumors, cerebral infarctions, inflammation, and K. Fujita (&) Y. Izumi R. Kaji Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan e-mail: kof@clin.med.tokushima-u.ac.jp