Objective: To detect changes in the modulation of the Startle Reflex induced by brainstem circuitry abnormalities both in isolated and PD related Rem Behaviour Disorder (RBD).

Background: Isolated form of RBD (IRBD), a parasomnia characterized by loss of normal muscle atony, vivid dreams and complex behaviors during REM sleep, is likely to convert ( 90%) to a neurodegenerative diseases of the alpha-synucleopathy group, mainly Parkinson’s disease (PD)1. RBD derives from excitatory and inhibitory input imbalance in different areas of the brainstem, including the laterodorsal-pedunculopontine complex (LTD-PPN)2. These structures are also involved in the execution and modulation of the startle reflex, a defensive response consisting of muscle contraction in reaction to sudden sensory stimuli3. Auditory startle responses (ASR) have been reported absent or reduced in parkinsonism disorders4.

Method: A total of 60 male and female subjects, aged 40-80 yrs. (namely 3 groups of 20 gender-and age-matched patients with IRBD, PD-RBD and healthy controls) were recruited (after signing the informed consent) from outpatients and their relatives at the Movement Disorder and Sleep Centers in Cagliari. RBD and PD diagnosis was made according to international criteria. The study included one night video-polysomnography recording, a neuropsychological assessment and a [123I]-FP-CIT dopamine transporter (DAT) scan where a semi-quantitative age-adjusted basal nuclei values BasGanV24 algorithm was used5. Startle Reflex was acquired by means of SR-HLABTM EMGÒ and latency and amplitude of Startle Response measured6. All indices will be compared between groups by two-way analyses of variance (ANOVAs).

Results: Twenty PDRBD patients (M=18; mean age:67.8±7.5 yrs, mean education 9.1±4.1 yrs), 20 iRBD patients (M=17; age:70.5±8.2; edu: 8.7±4.1 yrs.) and 20 sex- and age-matched control were enrolled. Among iRBD patients, n=15 had abnormal DAT-Scan and n= 6 had Mild Cognitive Impairment. An alteration of the startle reflex (latency prolongation) was observed in RBD with or without PD, compared to healthy controls (ANOVA one-way p <0.05), while no difference in amplitude was found.

Conclusion: Startle reflex is altered in both iRBD and PDRBD. Changes in iRBD may indicate an early expression of the neurodegenerative process underlying this disorder at the brainstem level, persisting in PDRBD. Startle Response might represent a tool to explore brainstem neurophysiology in RBD.

References: 1Iranzo, A., Santamaria, J. & Tolosa, E. Idiopathic rapid eye movement sleep behaviour disorder: diagnosis, management, and the need for neuroprotective interventions. Lancet Neurol. 15, 405–419 (2016). 2 Peever J, Luppi PH, Montplaisir J. Breakdown in REM sleep circuitry underlies REM sleep behavior disorder. Trends Neurosci. 2014 May;37(5):279-88 3 Calvini P, Rodriguez G, Inguglia F, Mignone A, Guerra UP, Nobili F. The basal ganglia matching tools package for striatal uptake semi-quantification: description and validation. Eur J Nucl Med Mol Imaging. 2007;34(8):1240-1253. 4 Blumenthal TD, Cuthbert BN, Filion DL, Hackley S, Lipp O V., Van Boxtel A. Committee report: Guidelines for human startle eyeblink electromyographic studies. Psychophysiology. 2005;42(1):1-15 5 Kofler M, Müller J, Wenning GK, Reggiani L, Hollosi P, Bösch S, Ransmayr G, Valls-Solé J, Poewe W. The auditory startle reaction in parkinsonian disorders. Mov Disord. 2001 Jan;16(1):62-71

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MDS Abstracts - https://www.mdsabstracts.org/abstract/modulation-of-the-startle-response-in-rem-sleep-behavior-disorder/