[ 123 I]-FP-CIT-SPECT Demonstrates Dopaminergic Deficit in Orthostatic Tremor Regina Katzenschlager, MD, 1,2 Durval Costa, MD, PhD, FRCR, 3 Willibald Gerschlager, MD, 4,5 John O’Sullivan, MD, 6 Jan Zijlmans, MD, PhD, 1,2 Svetoslav Gacinovic, PhD, 3 Walter Pirker, MD, 5 Adrian Wills, MD, MRCP, 7 Kailash Bhatia, MD, FRCP, 1 Andrew J. Lees, MD, FRCP, 1,2 and Peter Brown, MD, FRCP 4 There is increasing evidence of a potential role of the dopaminergic system in orthostatic tremor (OT): Association with parkinsonism and treatment effects of L-dopa and dopamine agonists have been reported. Eleven patients with isolated OT had single-photon emission computed tomography (SPECT) using 123 I-FP-CIT ([ 123 I]-2-carbomethoxy-3-(-4- iodophenyl)-N-(3-fluoropropyl)-nortropane) as dopamine transporter tracer. Results were compared with 12 age-matched normal controls and 12 patients with Parkinson’s disease (PD). A marked reduction in striatal tracer binding was found in OT compared to normal controls ( p < 0.001). Tracer uptake was significantly higher and more symmetrical than in PD, and caudate and putamen were equally affected. L-dopa challenges, performed in seven patients, showed a small but non-significant improvement on EMG and a small but significant improvement in clinical parameters on blinded video rating. Two-month open-label L-dopa treatment (600 mg/day) led to a small improvement in two of five patients but no significant overall change. Olfactory function on University of Pennsylvania Smell Identification Test was normal. Our finding of a marked tracer uptake reduction on dopamine transporter SPECT supports a role of the dopaminergic system in OT. Lack of evidence of a clinically relevant therapeutic response to L-dopa suggests that other mechanisms must also be involved in the pathogenesis. Ann Neurol 2003;53:489 – 496 Orthostatic tremor (OT) originally was described in 1970 1 and first recognized as a distinct clinical entity in 1984. 2 It is a rare form of high frequency (13–18Hz) tremor predominantly involving legs and trunk. Owing to this high frequency, the tremor is not always easily visible to the naked eye and may be more evident on palpation or auscultation. 3 The main pre- senting symptom is subjective unsteadiness on stand- ing, which is relieved by walking, sitting, or lying down. Although falls are relatively rare, feelings of un- steadiness may be profoundly distressing 4 and can lead to considerable disability. Although the cause is unknown, there is substantial evidence of a centrally located generator. There is high intermuscular coherence among all affected muscles, and cranial muscles are involved electrophysiologi- cally. 5 Peripheral loading of the limbs with weights does not modulate tremor frequency, 6 and transcranial magnetic stimulation over the posterior fossa can reset the tremor phase. 7 Several recent reports have suggested a role for the dopaminergic system in OT. Wills and colleagues 8 re- ported a treatment trial with L-dopa in eight patients. Unsteadiness improved in those five patients who tol- erated L -dopa well enough to remain on it over the treatment period of 8 weeks. Overall, there was a sig- nificant mean improvement on the authors’ rating scale. Improvement on the dopamine agonist pramipexole also has been reported. 9 Moreover, there are observations suggesting a relatively frequent associ- ation of parkinsonism with OT. 9,10 We aimed to investigate the role of the dopaminer- gic system in OT by means of [ 123 I]-FP-CIT single- photon emission computed tomography (SPECT). The ligand [ 123 I]-FP-CIT ([ 123 I]-2-carbomethoxy-3-[-4- iodophenyl]-N-[3-fluoropropyl]-nortropane) binds spe- cifically and with high affinity to presynaptic dopamine transporters. Results obtained with [ 123 I]-FP-CIT have been shown to be reliable and reproducible 11–13 in showing a reduction of presynaptic tracer uptake that From the 1 National Hospital for Neurology and Neurosurgery; 2 Reta Lila Weston Institute of Neurological Studies, University Col- lege London; 3 Department of Nuclear Medicine, Middlesex Hospi- tal; 4 Sobell Department of Motor Neuroscience and Movement Disorders, Queen Square, London, United Kingdom; 5 Department of Neurology, University of Vienna, Austria; 6 Neurology Depart- ment, Royal Brisbane Hospital, Brisbane, Australia; and 7 Depart- ment of Neurology, Vrije Universiteit Medical Centre, Amsterdam, The Netherlands. Received Aug 13, 2002. Accepted for publication Nov 13, 2002. Address correspondence to Dr Lees, Reta Lila Weston Institute of Neurological Studies, Windeyer Building, 46 Cleveland Street, Lon- don W1 T 4JF, United Kingdom. E-mail: alees@ion.ucl.ac.uk © 2003 Wiley-Liss, Inc. 489