Progressive Olfactory Impairment and Cardiac Sympathetic Denervation in REM Sleep Behavior Disorder

Annette Janzen; David Vadasz; Jan Booij; Markus Luster; Damiano Librizzi; Martin T Henrich; Lars Timmermann; Mahboubeh Habibi; Elisabeth Sittig; Geert Mayer; Fanni Geibl; Wolfgang Oertel

doi:10.3233/JPD-223201

Progressive Olfactory Impairment and Cardiac Sympathetic Denervation in REM Sleep Behavior Disorder

J Parkinsons Dis. 2022;12(6):1921-1935. doi: 10.3233/JPD-223201.

Authors

Annette Janzen¹, David Vadasz¹, Jan Booij², Markus Luster³, Damiano Librizzi³, Martin T Henrich^{1

4}, Lars Timmermann¹, Mahboubeh Habibi¹, Elisabeth Sittig¹, Geert Mayer^{1

5}, Fanni Geibl^{1

4}, Wolfgang Oertel¹

Affiliations

¹ Department of Neurology, Philipps-University Marburg, Marburg, Germany.
² Department of Radiology and Nuclear Medicine, Amsterdam UMC, location Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
³ Department of Nuclear Medicine, Philipps-University Marburg, Marburg, Germany.
⁴ Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
⁵ Department of Neurology, Hephata Clinic, Treysa, Germany.

Abstract

Background: Isolated rapid eye movement sleep behavior disorder (iRBD) is prodromal for Parkinson's disease (PD) and dementia with Lewy bodies (DLB).

Objective: We investigated the use of cardiac [123I]meta-iodo-benzyl-guanidine scintigraphy ([123I]MIBG) and olfactory testing- in comparison to [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single photon emission computed tomography ([123I]FP-CIT-SPECT)- for identifying iRBD patients as prodromal phenotype of PD/DLB.

Methods: 37 RBD subjects underwent cardiac [123I]MIBG and brain [123I]FP-CIT-SPECT at baseline. Olfactory (Sniffin' Sticks), cognitive and motor functions were tested annually for ∼4 years.

Results: 29/37 (78.4%) subjects had a pathological [123I]MIBG, of whom 86.2% (25/29) presented at least a moderate hyposmia at baseline (threshold/discrimination/identification-(TDI-)score ≤25). 20/37 (54.1%) subjects had a pathological [123I]FP-CIT-SPECT, always combined with a pathological [123I]MIBG. In subjects with pathological [123I]MIBG, olfactory function worsened (mainly due to threshold and discrimination subscores) from baseline to follow-up (p = 0.005). Olfaction was more impaired in subjects with pathological [123I]MIBG compared to those with normal [123I]MIBG at baseline (p = 0.001) and follow-up (p < 0.001). UPDRS-III scores increased in subjects with both pathological [123I]MIBG and [123I]FP-CIT-SPECT. In this group, seven subjects phenoconverted to PD, all- except for one- presented with at least moderate hyposmia at baseline.

Conclusion: A combination of the biomarkers "pathological [123I]MIBG" and "hyposmia" likely identifies iRBD patients in an early prodromal stage of PD/DLB, i.e., before nigrostriatal degeneration is visualized. One-third of the subjects with pathological [123I]MIBG had a normal [123I]FP-CIT-SPECT. Noteworthy, in iRBD subjects with pathological [123I]MIBG, olfactory impairment is progressive independent of the [123I]FP-CIT-SPECT status.

Keywords: Biomarker; [123I]FP-CIT-SPECT; cardiac [123I]MIBG scintigraphy; hyposmia; isolated rapid eye movement sleep behavior disorder; prodromal progression marker.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3-Iodobenzylguanidine
Humans
Lewy Body Disease* / diagnostic imaging
Olfaction Disorders* / diagnostic imaging
Olfaction Disorders* / etiology
Parkinson Disease* / complications
Parkinson Disease* / diagnostic imaging
REM Sleep Behavior Disorder* / diagnostic imaging
Sympathectomy
Tomography, Emission-Computed, Single-Photon
Tropanes

Substances

Tropanes
3-Iodobenzylguanidine