Brain structural and functional abnormalities in Fahr’s disease : a report of two cases

Abstract

Dear Sirs, Fahr’s disease is a sporadic or familial rare syndrome characterized by calcification of the basal ganglia, dentate nucleus of the cerebellum, thalamus and centrum semiovale. The most common clinical presentations include movement disorders, cognitive impairment, ataxia, speech abnormalities and psychiatric symptoms. Diagnosis is established by brain computed tomography (CT) or magnetic resonance imaging (MRI). Even if calcium deposits can result in heterogeneous signal intensities, most frequently appear as hyperdense on CT, hypointense on T2weighted MR images and hyperintense on T1-weighted images. Laboratory tests allow exclusion of parathyroid dysfunction, thus confirming the diagnosis and ruling out other major differential diagnoses [3, 4, 7]. In this report, we used voxel based morphometry (VBM) and resting state (RS) functional MRI (fMRI) to define the structural and functional brain abnormalities in two patients with sporadic Fahr’s disease and migraine with aura (MWA). The two patients (patient 1: male, age = 43 years, Fahr’s disease duration from diagnosis = 5 years, MWA disease duration = 10 years; patient 2: female, age = 42 years, Fahr’s disease duration from diagnosis = 10 years, MWA disease duration = 1 year) had a diagnosis of Fahr’s disease based on a typical clinical and neuroimaging pattern (Fig. 1). In addition to MWA, they also suffered from neuropsychiatric symptoms (both of them had panic attacks and patient 1 also had major depression). Neurological examination and biochemical tests (serum calcium, phosphorus, parathyroid hormone and calcitonin) were normal. A neuropsychological assessment disclosed marked deficits in short-term visuospatial memory in both patients. Patient 1 had also mild deficits of attention and inhibitory control and poor verbal fluency; patient 2 showed mild deficits in short-term verbal memory and visuoconstructive ability. Structural (T2and 3D T1-weighted scans) and RS fMRI scans were obtained using a 3.0 Tesla scanner. Regional abnormalities of gray matter (GM) volumes were assessed using VBM, and RS functional connectivity (FC) modifications were estimated using an independent component analysis, as described elsewhere [1, 11]. Patients findings were compared to those of two control groups with a normal neurological examination, consisting of 15 patients with MWA (seven males; mean age = 39 years; mean disease duration = 8 years) and 15 healthy controls (nine males; mean age = 37 years). Compared to MWA patients and controls, Fahr’s disease patients showed atrophy of the left orbitofrontal gyrus (OFG). Compared to controls, they had also atrophy of the left hippocampus. At fMRI analysis, compared to MWA patients and controls, Fahr’s disease patients had decreased RS FC of the executive control and working memory networks. Increased RS FC in the salience, sensorimotor and visual networks was also found. Compared to controls, Fahr’s disease and MWA patients showed decreased RS FC of the left fusiform gyrus (Table 1; Fig. 1). R. Messina M. A. Rocca M. Filippi (&) Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina, 60, 20132 Milan, Italy e-mail: m.filippi@hsr.it