T2 relaxometry and fMRI of the brain in late-onset restless legs syndrome

Objective: To assess in patients with late-onset idiopathic restless legs syndrome (RLS) the brain iron content with magnetic resonance relaxometry, and brain activation during dorsiflexion and plantar flexion of both feet, using fMRI. Methods: The study was approved by the institutional review board, and informed consent was obtained. Twenty-five RLS patients (14 women, 11 men; age range 55–82 years; mean 66.5 ± 8.9 years; disease duration 6.5 ± 4.5 years) and 12 sex- and age-matched controls were studied. A T1-weighted high-resolution three-dimensional spoiled gradient echo sequence was used for structural imaging, a multislice spin echo Τ2-weighted sequence was used for T2 relaxometry, and a single-shot multislice gradient echo planar sequence was used for fMRI. The motor paradigm consisted of alternating periods of rest and movement, each 40 seconds in duration. Region of interest analysis was used on the T2 relaxometry maps. Statistical parametric mapping software was used for analysis of the functional data. Results: T2 relaxation time was significantly higher in patients than in controls in the substantia nigra pars compacta. Within-group analysis showed that both patients and controls activated the primary motor cortex, the primary somatosensory cortex, the somatosensory association cortex, and the middle cerebellar peduncles. Patients also activated the thalamus, putamen, middle frontal gyrus, and cingulate gyrus. Between-group analysis showed that patients had higher activation of the dorsolateral prefrontal cortex. Conclusion: Late-onset restless legs syndrome is associated with low iron content of the basal ganglia and increased activity of the dorsolateral prefrontal cortex. GLOSSARY: C = constant offset parameter added to compensate for background noise bias; CN = caudate nucleus; DMT1 = divalent metal transporter 1; DN = dentate nucleus; EPI = echo planar imaging; GP = globus pallidus; IRLS = International RLS Study Group Rating Scale; JHRLSS = Johns Hopkins RLS Severity Scale; MIP = maximum intensity projection; MR = magnetic resonance; PLMS = periodic limb movements in sleep; Pu = putamen; RLS = restless leg syndrome; RN = red nucleus; ROI = region of interest; SN = substantia nigra; SNc = substantia nigra pars compacta; SNr = substantia nigra pars reticulata; So = signal amplitude at echo time = 0; SPM = statistical parametric mapping; S(TE) = signal intensity at echo time; TE = echo time; Th = thalamus; TR = repetition time.