Dopamine transporter imaging deficit predicts early transition to synucleinopathy in idiopathic rapid eye movement sleep behavior disorder

Iranzo, Álex; Santamaría, Joan; Valldeoriola, Francesc; Serradell, Mónica; Salamero, Manel; Gaig, Carles; Niñerola‐Baizán, Aida; Sánchez‐Valle, Raquel; Lladó, Albert; Marzi, Roberto De; Stefani, Ambra; Seppi, Klaus; Pavı́a, Javier; Högl, Birgit; Poewe, Werner; Tolosa, Eduard; Lomeña, Francisco

doi:10.1002/ana.25026

Cited by 169 publications

(134 citation statements)

References 37 publications

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“…However, up to 45% of patients showed, in concomitance, the presence of a symptom that has been linked to a higher PD risk, pointing out to the possibility that a subtle neuronal degeneration is taking place. Unfortunately, no risk factor able to predict prospectively the conversion from RBD to a neurodegenerative disease can be indicated ( 27 ), the only tool that has demonstrated reliable predictive value being 123 I-FP-DAT-SPECT ( 28 ). In this light, we believe that the consistent finding of VEMPs dysfunction in our cohort is potentially relevant in the context of the search of biomarkers for neurodegeneration in patients displaying prodromal conditions.…”

Section: Discussionmentioning

confidence: 99%

Vestibular Evoked Myogenic Potentials Are Abnormal in Idiopathic REM Sleep Behavior Disorder

et al. 2018

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Objectives: To investigate brainstem function in idiopathic REM sleep Behavior Disorder (iRBD), a condition occurring as a result of a derangement of connections within brainstem structures, with a battery of Vestibular Evoked Myogenic Potentials (VEMPs), neurophysiological tools suited for the functional investigation of the brainstem. Neurophysiological data were correlated with clinical characteristics of patients.Methods: Twenty patients with iRBD and 22 healthy controls underwent cervical (cVEMP), masseter (mVEMP) and ocular (oVEMP) VEMP recording. Patients were assessed clinically according to presence of motor as well as non-motor symptoms such as constipation, depression, and hyposmia. Also, they were screened for postural instability through the Berg Balance Scale (BBS). VEMPs were categorized as for increasing degrees of abnormalities, namely latency delay, amplitude reduction and absence; a VEMP score was built accordingly.Results: Compared with controls, iRBD had higher rates of abnormalities both in the VEMP battery (iRBD 75%, Controls 23%; p < 0.01) as well as in each single VEMP (cVEMP: 45 vs. 5%; mVEMP: 65 vs. 13.6%; oVEMP: 50 vs. 5%; p < 0.01), which exhibited significantly lower amplitudes (cVEMP and oVEMP: p < 0.0001; mVEMP: p = 0.001) in iRBD. Within altered reflexes, absence was predominant in oVEMP (81%), amplitude reduction in mVEMP (50%) and cVEMP (70%). Severity of VEMP alterations was significantly higher in iRBD compared with controls (p < 0.05 for all VEMPs), as indicated by the larger VEMP scores in the former. The oVEMP score correlated inversely with poor performances on the BBS.Conclusion: VEMPs unveil consistent and extensive brainstem abnormalities in iRBD patients. Further studies are warranted for testing the potential of VEMPs in the monitoring of the evolution of iRBD over time.

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Section: Discussionmentioning

confidence: 99%

Vestibular Evoked Myogenic Potentials Are Abnormal in Idiopathic REM Sleep Behavior Disorder

et al. 2018

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“…9 Another study in subjects with polysomnogram-confirmed RBD without a diagnosis of PD found that >50% of cases had evidence of a subclinical DAT deficit, and that these patients were more likely to develop PD or DLB over 4 years of follow-up. 11,13 A multicenter investigation of risk of neurodegeneration in RBD also found a high rate of conversion to either PD or DLB. 14 We did not observe a high rate of transition to a dementia phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…7,8 Some of these changes have been observed in cohorts with genetic risk factors for PD, 9,10 or in cohorts with rapid eye movement sleep behavior disorder (RBD). [11][12][13][14] However, the prodromal stage for sporadic PD has been less extensively studied.…”

Section: ---------------------------------------------------------mentioning

confidence: 99%

Clinical and Imaging Progression in the PARS Cohort: Long‐Term Follow‐up

et al. 2020

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Background and Objectives The PARS (Parkinson Associated Risk Syndrome) study was designed to test whether screening for hyposmia followed by dopamine transporter imaging can identify risk for conversion to clinical PD, and to evaluate progression markers during the prodromal period. Methods Subjects with hyposmia completed annual clinical evaluations and biennial [123I]ß‐CIT single‐photon emission computed tomography scans. Subjects were categorized as normal (>80% age‐expected tracer uptake; n = 134), indeterminate (>65–80%; n = 30), and dopamine transporter deficit (≤65%; n = 21) by their baseline scan, and survival analysis was used to compare risk of conversion to motor PD. Progressing to a scan with a dopamine transporter deficit was assessed for those subjects with either normal or indeterminate baseline imaging. Results Over a mean of 6.3 [standard deviation: 2.2] years of follow‐up, 67% (n = 14) of dopamine transporter deficit subjects, 20% (n = 6) of dopamine transporter indeterminate subjects, and 4% (n = 6) of dopamine transporter normal subjects converted to a PD diagnosis (P < 0.0001). Among subjects without dopamine transporter deficit at baseline, a reduction to ≤65% age‐expected uptake occurred in 12 of 30 (40%) with indeterminate dopamine transporter and 7 of 134 (5%) with no dopamine transporter DAT deficit (P < 0.0001). Imaging conversion during follow‐up was associated with subsequent clinical conversion (hazard ratio: 9.6; P = 0.0157). Discussion and Conclusions Long‐term follow‐up of the PARS cohort demonstrated a high rate of conversion to clinical PD in subjects who either had abnormal dopamine transporter imaging at baseline or developed abnormal imaging during follow‐up. These data extend the earlier PARS findings and present new results showing the sequence of incident imaging deficit, imaging progression, and clinical changes that occur in prodromal PD. © 2020 International Parkinson and Movement Disorder Society

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“…Whereas the conversion rate to synucleinopathy in clonazepam-treated RBD patients is high [2, 3, 6], no comparable data are available yet for melatonin-treated RBD patients. Our observation warrants further documentation of positive melatonin effects on conversion rate in RBD patients.…”

Section: Discussionmentioning

confidence: 99%

“…In patients suspected to suffer from a beginning synucleinopathy, DA transporter density scintigraphy (DaTSCAN) is the diagnostic tool of choice to prove pathology [5]. Moreover, a DA transporter imaging deficit predicts early transition to synucleinopathy in RBD patients [6]. …”

Section: Introductionmentioning

confidence: 99%

Twenty Years After: Another Case Report of Melatonin Effects on REM Sleep Behavior Disorder, Using Serial Dopamine Transporter Imaging

Kunz

Bes

2017

Neuropsychobiology

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Introduction: REM sleep behavior disorder (RBD) is considered a prodromal phase of α-synucleinopathy like Parkinson disease (PD). PD is characterized by a progressive decline of dopamine (DA) in the striatum. Here we report the surprising increase in DA transporter density over successive years in an RBD patient treated with melatonin. Case Presentation: A then 72-year-old man was clinically suspected to suffer from PD in 2011. DA transporter scintigraphy (DaTSCAN) revealed reduced DA transporter density, and the patient was diagnosed with developing PD. Because of outacting dreams every night (speaking, yelling, kicking, pushing) he was referred to our clinic. Video-assisted polysomnography (PSG) confirmed the diagnosis of RBD in 2012. Management and Outcome: Melatonin treatment (2 mg slow release/day; 30 min prior to habitual bedtime; always at the same clock time) was initiated after PSG and continued. After 6 months of gradual improvement, clinical signs of RBD were absent. Control PSG in 2014 confirmed normalized REM sleep with atonia. Furthermore, no clinical sign of neurodegeneration occurred ever since. Additional DaTSCANs were performed in 2013 and 2015. Whereas the 2011 scan prior to melatonin treatment bore clear signs of PD, the 2013 scan was considered borderline and the 2015 scan without any sign of PD. Discussion: To the best of our knowledge, DA transporter density increase over time has never been reported in a single subject, neither healthy aged individuals nor patients suffering from RBD or PD. We interpret these results as a possible neuroprotective role for melatonin in synucleinopathy.

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Dopamine transporter imaging deficit predicts early transition to synucleinopathy in idiopathic rapid eye movement sleep behavior disorder

Cited by 169 publications

References 37 publications

Vestibular Evoked Myogenic Potentials Are Abnormal in Idiopathic REM Sleep Behavior Disorder

Vestibular Evoked Myogenic Potentials Are Abnormal in Idiopathic REM Sleep Behavior Disorder

Clinical and Imaging Progression in the PARS Cohort: Long‐Term Follow‐up

Twenty Years After: Another Case Report of Melatonin Effects on REM Sleep Behavior Disorder, Using Serial Dopamine Transporter Imaging

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