Left-hemispheric predominance of nigrostriatal deficit in isolated REM sleep behavior disorder

Abstract

ObjectiveUnilateral onset of parkinsonism due to nigrostriatal damage of the contralateral hemisphere is frequent in Parkinson disease (PD). There is evidence for a left-hemispheric bias of motor asymmetry in right-handed patients with PD indicating a hemispheric dominance. Isolated REM sleep behavior disorder (IRBD) constitutes the prodromal stage of PD and other synucleinopathies. To test the hypothesis that right-handed patients with IRBD exhibit left-hemispheric predominance of subclinical nigrostriatal dysfunction, we evaluated this aspect using neuroimaging instruments.MethodsIn 167 right-handed patients with IRBD without parkinsonism, we evaluated in each hemisphere the integrity of the striatal dopaminergic terminals by dopamine transporter (DAT)-SPECT and the substantia nigra echogenicity by transcranial sonography.ResultsDAT-SPECT showed lower specific binding ratio (SBR) in the left striatum and left caudate nucleus than in the right striatum and right caudate nucleus. The percentage of patients with lower SBR was greater in the left striatum and left caudate nucleus than in the right striatum and right caudate nucleus. In those who developed a synucleinopathy in <5 years from DAT-SPECT, there was a lower SBR in the left putamen and left caudate nucleus than in the right putamen and right caudate nucleus. Substantia nigra echogenic size was greater in the left than in the right side in patients with hyperechogenicity and among individuals who phenoconverted in <5 years from transcranial sonography.ConclusionRight-handed patients with IRBD exhibit left-hemispheric predominance of subclinical nigrostriatal dysfunction. In premotor PD, the neurodegenerative process begins asymmetrically, initially impairing the nigrostriatal system of the dominant hemisphere.

Dopamine transporter imaging predicts clinically‐defined α‐synucleinopathy in REM sleep behavior disorder

“…Regarding other CSF biomarkers, the lack of substantial differences in CSF total α ‐synuclein between the iRBD group and the HC group highlights the ongoing need for more accurate CSF biomarkers in PD including assays specific to pathologic forms of α ‐synuclein. As for the pattern of striatal denervation indicated by the DAT binding measures, it was similar to that seen in PD 36,37 : DAT binding in putamen < caudate, with bilateral involvement but mild asymmetry, though less severe as compared to the PD group. Similarly, clinical abnormalities at baseline were less severe than in the PD group as well.…”

A Study of the Relationship Between Uric Acid and Substantia Nigra Brain Connectivity in Patients With REM Sleep Behavior Disorder and Parkinson's Disease

“…While previous nigrocortical and cortico-cortical connectivity studies using resting state fMRI have reported left lateralized connectivity changes ( 38 , 50 , 70 ) consistent with left hemispheric predominance of nigrostriatal dysfunction ( 71 ), the laterality of connectivity results in the present study require further investigation. Laterality of disease onset is determined by neurologic exam and it is only possible to make these clinical determinations for the PD patients who show motor impairment.…”

Enlarged Area of Mesencephalic Iron Deposits in Adults Who Stutter

“…Theoretically, one could have expected ME to be unilateral in stuttering, but this was not the case. Indeed, an asymmetry of ME was found only recently in a large sample of more than hundred individuals at risk of developing PD, with a stronger ME contralateral to the dominant hand (Iranzo et al, 2020). We assume that our sample size is much too limited to detect subtle side differences.…”