Early abnormalities in 123I-ioflupane (DaTSCAN) imaging in the fragile X-associated tremor ataxia syndrome (FXTAS): a case report

Abstract

The fragile X-associated tremor/ataxia (FXTAS) is a late onset neurodegenerative disorder, occurring in male carriers of a premutation expansion (50–200 repeats CGG) in the fragile X mental retardation 1 (FMR1) gene [1], and clinically characterized by phenotypic predominance of either cerebellar ataxia or intention tremor, and variably associated with other features, such as parkinsonism, peripheral neuropathy, autonomic dysfunction and dementia [1]. MRI studies have shown T2-weighted periventricular, subcortical white matter changes, with a specific involvement of middle cerebellar peduncles [1]. The underlying mechanism of FXTAS-associated parkinsonism remains unclear. 123I-ioflupane (DaTSCAN) imaging studies have shown contrasting patterns. In some cases with clear tremor and parkinsonism, DAT scans have been normal [2, 3] although rarely they can be abnormal [4, 5]. In these cases, there has been suggestion of the involvement of the basal ganglia, specifically the dopaminergic system projecting to the putamen. Here, we describe a patient carrying a premutation of FMR1 (82 CGG repeat) and presenting only subtle clinical signs of tremor and typical MRI features and clearly abnormal DaTSCAN examination. A 65-year-old Italian man was admitted to our hospital for the recent appearance of a mild bilateral tremor at upper extremities, which did not impair daily function, and with a genetic confirmation of FMR1 (Xq27.3) premutation (82 CGG repeat expansions). The patient was tested for FMR1 mutations since his daughter was diagnosed with fragile X syndrome with mental retardation at onset. His medical history was not notable for hypertension, hyperlipidemia and thyroid dysfunction. Childhood and adolescent development were normal and his school performance was good. No family history of tremor or movement disorder was reported. General physical examination findings were notable for normal blood pressure without abnormal orthostatic changes. Neurological examination revealed mild action tremor of the upper extremities, with a prevalence of the right arm (7–11 Hz). A moderate rigidity was detected at upper extremities (right [ left). No bradykinesia was detected. Synergy, trajectory, and placement of upperand lower-extremity movements were normal. Cranial nerve findings, deep tendon reflexes, plantar responses, gait and stance were normal. MRI scans showed mild cerebral and cerebellar cortical atrophy. Patchy areas of subependymal and deep white matter of the cerebral hemispheres with increased T2 signal intensity were observed, in the absence of any obvious vascular risk factor. Of note, a slightly increased T2 signal intensity was observed in the middle cerebellar peduncles (Fig. 1). SPECT examination was obtained by injection i.v. with 111 MBq of [123I]FP-CIT for evaluation of striatal dopamine transporter (DAT) density. The uptake of [123I]FP-CIT was significantly reduced in both putamen G. Madeo F. Alemseged A. Pisani (&) Dipartimento di Medicina dei Sistemi, Clinica Neurologica, Universita degli Studi di Roma Tor Vergata, Roma, Italia e-mail: pisani@uniroma2.it