Cerebral generators involved in the pathogenesis of the restless legs syndrome

Abstract

The pathophysiology of periodic limb movements and sensory leg discomfort in the restless legs syndrome is unknown. With high-resolution functional magnetic resonance imaging, we localized for the first time cerebral generators associated with sensory leg discomfort and periodic limb movements in 19 patients with restless legs syndrome. During sensory leg discomfort there was mainly bilateral activation of the cerebellum and contralateral activation of the thalamus. During the combined periodic limb movement and sensory leg discomfort conditions, patients also showed activity in the cerebellum and thalamus. In contrast to the sensory leg discomfort condition alone, the combined condition was associated with additional activation in the red nuclei and brainstem close to the reticular formation. Voluntary imitation of periodic limb movements by patients and control subjects was not associated with brainstem activity, but with additional activation in the globus pallidus and motor cortex. These findings indicate that cerebellar and thalamic activation may occur because of sensory leg discomfort and that the red nucleus and brainstem are involved in the generation of periodic limb movements in patients with restless legs syndrome.

Investigation of Unmedicated Early Onset Restless Legs Syndrome by Voxel-Based Morphometry, T2 Relaxometry, and Functional MR Imaging during the Night-Time Hours

“…33 In agreement with the present study, a previous fMRI study performed on patients with RLS during combined PLMs and SLD demonstrated activation of the thalamus. 10 The thalamus is an intermediate gateway for sensory input according to cognitive requirements. 45 SPECT evaluation of RLS demonstrated increased blood flow of the thalami with increasing pain.…”

“…6 fMRI during episodes of combined sensory and motor symptoms has revealed activity in the cerebellum, red nucleus, and thalamus. 10 Patients with late-onset RLS performing regular dorsiflexion and plantar flexion of the feet in hours of daylight demonstrated greater activation of the dorsolateral prefrontal cortex of the left middle gyrus and inferior frontal gyrus and, marginally, of the cingulate gyrus. 6 Although VBM, T2 relaxometry, and fMRI have all been used in the study of patients with RLS, the 3 techniques have never been applied simultaneously in the same patient population.…”

“…Small sample size, use of different techniques, inclusion of patients under medication, and lack of distinction between eRLS and late-onset RLS were probably responsible for the inconsistency in observations. [7][8][9] fMRI studies have been conducted in patients with RLS with undefined disease onset 10 and late onset. 6 fMRI during episodes of combined sensory and motor symptoms has revealed activity in the cerebellum, red nucleus, and thalamus.…”

Involuntary rhythmic leg movements time-locked with the respiratory cycle

“…The localization of the generators of such an involuntary activity remains unknown, despite suggestions of a locus in the brainstem [3]. We report a patient with features providing important clues to the location of one of these generators.…”

Restless Legs Syndrome

“…17 Localization of the RLS induced involuntary movements and their distribution patterns favor a brainstem or spinal cord origin of movements. The ®ndings by Bucher et al 72 indicated that the red nucleus and brainstem are involved in the generation of PLM in patients with RLS. The brainstem activation may re¯ect the disinhibition eects of the reticular formation on spinal pathways.…”