Brain Mechanisms in Combined RBDExtrapyramidal Disorders

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What brain mechanisms may be involved in subclinical and clinical RBD associated with various extrapyramidal disorders? The pedunculopontine nucleus (PPN) is likely to be prominently involved in the disruption of the REM-atonia circuitry, for at least three reasons. First, there is a strong reciprocal connectivity between the PPN and the substantia nigra (Garcia-Rill, 1991), the main site of pathology accounting for the cardinal signs of PD (Koller, 1992). Second, the neuropathology of PD includes prominent neuronal loss within the PPN (Jellinger,

1991). Third, the PPN has strong links with both the REM-atonia and REM-phasic generator circuitry (Lai and Siegel, 1990; Garcia-Rill, 1991; Shouse and Siegel,

1992). The retrorubral nucleus is located near the substantia nigra, and appears to be implicated in the linked PD-RBD pathology (Lai and Siegel, 1990). The retrorubral nucleus projects to the caudate and putamen (extrapyramidal motor system); experimental lesions to the retrorubral nucleus in cats releases abnormal motor activity during both sleep and wakefulness, ranging from myoclonic twitches to rhythmic leg movements and locomotion (Lai and Siegel, 1997). In addition, the substantia nigra also is closely connected to the REM-phasic generator circuitry and may play a major role in the genesis of PGO waves, a characteristic REM sleep phasic event (Datta et al, 1991). In regard to MSA, pontine involvement has been revealed by both gross neuropathological examination and histo-chemical studies, as cited by Plazzi et al. (1997). Functional magnetic resonance brain imaging studies and postmortem brain analyses are required to definitively elucidate the underlying neuropathology responsible for combined RBD-extra-pyramidal disorders. In this regard, it is important to consider that extrapyramidal dysfunction has just been found in idiopathic RBD, with reduced striatal dopamine transporters being identified by single-photon emission computed tomography (SPECT) in 5 patients compared to 7 controls (Eisensehr et al, 2000).

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