Roberto Cilia1, Chiara Reale2, Anna Castagna2, Alessia Nasca2, Marco Muzi-Falconi2, Chiara Barzaghi2, Alberto Marzegan2, Magda Granata2, Giorgio Marotta2, Giorgio Sacilotto2, Davide Vallauri2, Gianni Pezzoli2, Stefano Goldwurm2, Barbara Garavaglia2. 1. From the Parkinson Institute (R.C., G.S., D.V., G.P., S.G.), Istituti Clinici di Perfezionamento, Milan; Unit of Molecular Neurogenetics (C.R., A.N., C.B., B.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; IRCCS Santa Maria Nascente Fondazione Don Gnocchi Milano (A.C., A.M.), Milan; Dipartimento di Bioscienze (M.M.-F., M.G.), Università degli Studi di Milano, Milan; Nuclear Medicine (G.M.), IRCCS-Ospedale Maggiore, Milan; and Department of Neurosciences (D.V.), S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy. roberto.cilia@gmail.com. 2. From the Parkinson Institute (R.C., G.S., D.V., G.P., S.G.), Istituti Clinici di Perfezionamento, Milan; Unit of Molecular Neurogenetics (C.R., A.N., C.B., B.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; IRCCS Santa Maria Nascente Fondazione Don Gnocchi Milano (A.C., A.M.), Milan; Dipartimento di Bioscienze (M.M.-F., M.G.), Università degli Studi di Milano, Milan; Nuclear Medicine (G.M.), IRCCS-Ospedale Maggiore, Milan; and Department of Neurosciences (D.V.), S. Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
Abstract
OBJECTIVE: To test the hypothesis that adult-onset primary dystonia may be the underlying etiology of tremulous patients with clinical diagnosis of Parkinson disease (PD) but without evidence of dopaminergic deficit at nigrostriatal SPECT imaging. METHODS: We retrospectively reviewed clinical and imaging data of patients with clinical diagnosis of PD assessed at our tertiary movement disorder clinic, who underwent dopamine transporter SPECT imaging consecutively between 2002 and 2011. Molecular screening for DYT1, DYT5, DYT6, DYT11, and DYT16 dystonia genes was performed in all cases who met the following criteria at the time of SPECT scan: (1) clinical diagnosis of PD; (2) normal dopamine transporter SPECT; (3) asymmetric rest tremor, with or without postural/kinetic component; (4) ≥ 12-month follow-up; and (5) normal brain MRI. We excluded subjects with (6) overt dystonic features, and (7) head or voice tremor. RESULTS: Twenty-three subjects were eligible for molecular analysis. Positive family history for tremor or PD was present in 45% of probands. We found one patient with a novel heterozygous frameshift mutation in the DYT11 gene (c.1058-1062 delCACCA/p.Gln352fsX376). Electrophysiologic study of tremor revealed that the main contributor was 5- to 6-Hz pseudo-rhythmic myoclonus, primarily involving extensor muscles. In 2 brothers, we found a missense variant in the DYT5 gene (c.334A>G; p.Thr112Ala) of uncertain pathogenicity in humans. CONCLUSION: Our findings provide further support to the hypothesis that adult-onset monogenic dystonia may underlie a "PD look-alike" clinical phenotype. In addition to dystonic tremor, pseudo-rhythmic myoclonus may be mischaracterized as "rest tremor."
OBJECTIVE: To test the hypothesis that adult-onset primary dystonia may be the underlying etiology of tremulous patients with clinical diagnosis of Parkinson disease (PD) but without evidence of dopaminergic deficit at nigrostriatal SPECT imaging. METHODS: We retrospectively reviewed clinical and imaging data of patients with clinical diagnosis of PD assessed at our tertiary movement disorder clinic, who underwent dopamine transporter SPECT imaging consecutively between 2002 and 2011. Molecular screening for DYT1, DYT5, DYT6, DYT11, and DYT16 dystonia genes was performed in all cases who met the following criteria at the time of SPECT scan: (1) clinical diagnosis of PD; (2) normal dopamine transporter SPECT; (3) asymmetric rest tremor, with or without postural/kinetic component; (4) ≥ 12-month follow-up; and (5) normal brain MRI. We excluded subjects with (6) overt dystonic features, and (7) head or voice tremor. RESULTS: Twenty-three subjects were eligible for molecular analysis. Positive family history for tremor or PD was present in 45% of probands. We found one patient with a novel heterozygous frameshift mutation in the DYT11 gene (c.1058-1062 delCACCA/p.Gln352fsX376). Electrophysiologic study of tremor revealed that the main contributor was 5- to 6-Hz pseudo-rhythmic myoclonus, primarily involving extensor muscles. In 2 brothers, we found a missense variant in the DYT5 gene (c.334A>G; p.Thr112Ala) of uncertain pathogenicity in humans. CONCLUSION: Our findings provide further support to the hypothesis that adult-onset monogenic dystonia may underlie a "PD look-alike" clinical phenotype. In addition to dystonic tremor, pseudo-rhythmic myoclonus may be mischaracterized as "rest tremor."
Authors: Aasef G Shaikh; Sinem Balta Beylergil; Laura Scorr; Gamze Kilic-Berkmen; Alan Freeman; Christine Klein; Johanna Junker; Sebastian Loens; Norbert Brüggemann; Alexander Münchau; Tobias Bäumer; Marie Vidailhet; Emmanuel Roze; Cecilia Bonnet; Joseph Jankovic; Joohi Jimenez-Shahed; Neepa Patel; Laura Marsh; Cynthia Comella; Richard L Barbano; Brian D Berman; Irene Malaty; Aparna Wagle Shukla; Stephen G Reich; Mark S Ledoux; Alfredo Berardelli; Gina Ferrazzano; Natividad Stover; William Ondo; Sarah Pirio Richardson; Rachel Saunders-Pullman; Zoltan Mari; Pinky Agarwal; Charles Adler; Sylvain Chouinard; Susan H Fox; Allison Brashear; Daniel Truong; Oksana Suchowersky; Samuel Frank; Stewart Factor; Joel Perlmutter; Hyder Azad Jinnah Journal: Neurology Date: 2020-10-12 Impact factor: 9.910