Diffusion Tensor-MRI Evidence for Extra-Axonal Neuronal Degeneration in Caudate and Thalamic Nuclei of Patients with Multiple Sclerosis

BACKGROUND AND PURPOSE: MS is an inflammatory demyelinating disease affecting both WM and GM. While WM lesions are easily visualized by conventional MR imaging, the detection of GM alterations remains challenging. This diffusion tensor MR imaging study aimed to detect and characterize diffuse microscopic alterations in 2 deep GM structures, the caudate nucleus and the thalamus, in patients with RR and SP MS. The relationship between diffusivity markers, and atrophy of the caudate and the thalamus, as well as brain lesion load and clinical status of the patients was also explored. MATERIALS AND METHODS: Twenty-three RR and 18 SP patients, along with 27 healthy controls, underwent MR imaging examination including anatomic and DTI acquisitions. Volumes, mean FA, and MD of the caudate and the thalamus, as well as WM lesion volumes, were assessed. RESULTS: FA was significantly (P < .001) increased in the caudate and the thalamus of patients with MS compared with controls, and was higher in SP compared with RR patients. Increased FA was associated with volume decreases of caudate (r = -0.712; P < .0011 and thalamus (r = 0.407; P < .011 in patients with MS. WM T2 lesion load was significantly associated with caudate (r = -0.611; P < .0011 and thalamic (r = 0.354; P < .051 FA. Caudate FA, and, to a lesser extent, thalamic FA, were associated with functional deficits, as measured by EDSS and MSFC. CONCLUSIONS: Increased FA in the caudate and the thalamus may constitute a sensitive marker of MS pathologic processes, such as loss of dendrites and/or swelling of neuronal cell bodies.