As an early finding in PD

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In PD, OH can pose a major management problem. Studies have varied widely in reported frequencies of OH in PD. In 5 large studies involving more than 80 patients each, the frequency of OH ranged from 30 to 58% (Briebach et al., 1990; Magalhaes et al., 1995; Senard et al., 1997; Allcock et al., 2004; Korchounov et al., 2004). A substantial minority of PD patients therefore have OH.

More than a half century ago Nylin and Levander reported the case of a patient with OH who developed orthostatic intolerance at the age of 67. Eight years later he was diagnosed with OH from ''asympathicotonic orthostatism'' and over the course of the next year a resting unilateral tremor, masked face, and ''cogwheel'' rigidity, findings recognized by the authors as typical of PD (Nylin and Levander, 1948). The notion that OH can be an early finding in PD and even precede the movement disorder is therefore by no means new. Of 3 post-mortem case reports about PD + OH patients, where the timing of onset of OH with respect to the movement disorder was reported, in all 3 OH had developed first (Vanderhaeghen et al., 1970; Schober et al., 1975; Kaufmann et al., 2004).

Carrying out an analysis of the frequency of OH as an early finding in PD + OH would require evidence that the patients did not have multiple system atrophy (MSA), which is almost always associated with OH. Diagnosing MSA differentially from PD + OH can be very difficult clinically. Autopsy studies have revealed a disappointingly high frequency of erroneous diagnosis, even by well experienced academicians. To exclude patients with MSA, we took a novel tack based on results of cardiac sympathetic neuro-imaging. As discussed below, remarkably consistent and by now abundant literature shows that cardiac sympathetic neuroimaging distinguishes PD from MSA, with cardiac sympathetic denervation in the former but not the latter. We reviewed medical history data from patients with PD + OH evaluated at the NIH, to determine the frequency with which OH was an initial or early finding. Neuroimaging evidence of cardiac sympathetic denervation was used to exclude MSA.

We found that 21 (60%) of 35 PD + OH patients had an early onset of OH. In 4

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(13%), OH had developed before symptoms of a movement disorder. In 4 others the patients had no symptoms of a movement disorder at the time of evaluation but nevertheless had sufficient clinical signs to diagnose PD (Goldstein, 2005).

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