Volume 25, Issue 9, 2010, pp. 1143-1149
Authors: Mutsumi Iijima, MD, PhD,* Mikio Osawa, MD, PhD, Mitsuru Momose, MD, PhD, Tatsu Kobayakawa, PhD, Sachiko Saito, PhD, Makoto Iwata, MD, PhD, and Shinichiro Uchiyama, MD, PhD
1 Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan
2 Department of Radiology, Tokyo Women's Medical University, Tokyo, Japan
3 National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan
4 Saito Sachiko Taste and Smell Institute, Tsukuba, Japan
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Autonomic and olfactory dysfunctions are considered markers for preclinical diagnosis in Parkinson's disease (PD), because pathological changes in these systems can start before motor symptoms develop. We investigated whether cardiac sympathetic function and olfactory function are associated in PD. Participants comprised 40 nondemented patients with idiopathic PD, and age-matched controls. Cardiac sympathetic function was evaluated by 123 I-metaiodobenzylguanidine (MIBG) uptake, in terms of the heart to mediastinum (H/M) ratio in both early and delayed images, and the washout rate (WR). Olfactory function was evaluated using the Odor Stick Identification Test for Japanese, which evaluates the detection of 12 odorants familiar to Japanese participants. Smell identification scores were significantly lower (P < 0.001) in patients with PD than in controls. Smell identification scores correlated positively with early (P < 0.05) and delayed H/M ratios (P < 0.01), and inversely with the WR (P < 0.005) especially in patients with early PD (below 5 years of the start of motor ymptoms), whereas smell identification scores did not correlate with any parameters of MIBG in the advanced PD (above 5 years of the start of motor symptoms). There was no correlation between motor symptom scores and smell identification scores, H/M ratios, or WR. The results suggest that the cardiac sympathetic nervous system might degenerate in parallel with the olfactory system in patients with early PD, and that these two systems might degenerate at a different rate of speed in advanced PD.
© 2010 Movement Disorder Society
Summary and review by Marcelo Merello, MD, PhD, Director, Neuroscience Department, Head Movement, Disorders Section, Institute for Neurological Research Raul Carrea (FLENI), Buenos Aires
Epidemiological studies of non-motor manifestations of Parkinson's disease, such as constipation, anxiety disorders, rapid eye movement, sleep behavior disorder and anemia suggest that the preclinical period extends at least 20 years before motor manifestations occur. Olfactory impairment and depression may also precede the onset of motor manifestations; however, lag time may be shorter. The sensitivity of olfactory disturbance as a marker of PD is 80-90%, and the proportion of patients with olfactory disturbance who develop PD is 7-10%.
On the other hand, autonomic dysfunction is common in Lewy body disorders such as Parkinson's disease, Dementia with Lewy Bodies, Pure Autonomic Failure, and REM sleep disorder. The loss of post-ganglionic myocardial sympathetic nerve fibers is a prominent feature of autonomic dysfunction in such disorders. (123) I-metaiodobenzylguanidine (MIBG) scintigraphy allows in vivo visualization of catecholaminergic terminals and is used as a biomarker to detect cardiac sympathetic degeneration. Abnormal MIBG scintigraphy uptake has been consistently reported in Lewy body disorders and correlates with disease severity. Conversely, atypical parkinsonian syndromes, including Multiple System Atrophy and Progressive Supranuclear Palsy among others, only show modest reductions of cardiac MIBG scintigraphy uptake, not in correlation with disease severity. It has been published that MIBG scintigraphy is moderately sensitive and specific in differentiating Parkinson's disease from such syndromes.
In this prospective trial, Iijima and coworkers investigated whether cardiac sympathetic function and olfactory function were associated in PD. They studied 40 non-demented patients with idiopathic PD, and age-matched controls. Cardiac sympathetic function was evaluated by MIBG scintigraphy uptake, in terms of the heart to mediastinum (H/M) ratio in both early and delayed images, and the washout rate (WR) . Olfactory function was evaluated using the Japanese version of the Odor Stick Identification Test.
Authors found significant positive correlation between smell identification scores and H/M ratios in both early and delayed images, and a significant inverse correlation between smell identification scores and WR in patients with early PD. The sensitivity of early H/M ratio, delayed H/M ratio and WR on MIBG scintigraphy in PD was 40.0, 62.5, and 80.0%, respectively. Smell identification score in patients with PD was significantly lower than that in controls, and sensitivity in PD was 50.0%.
Authors concluded that MIBG scintigraphy H/M ratios and WR correlated significantly with odor identification function in patients with early PD, whereas there was no correlation between odor identification function and MIBG scintigraphy in patients with advanced PD.
The results suggest that the cardiac sympathetic nervous system might degenerate in parallel with the olfactory system in patients with early PD, and that these two systems might degenerate at a different rate in advanced PD. Since immunoreactive nerve fibers for tyrosine hydroxylase and density of positive neurites for alpha synuclein correlate with the Braak I PD stage, and Lewy bodies first develop in the olfactory bulb and the anterior olfactory nucleus, the authors findings are very important. They provide clinical correlation of the degeneration process at least in early patients. Perhaps this correlation will prove useful for detecting PD at pre motor stages. Why this correlation is lost in more advanced cases will have to be elucidated in future studies.
About Dr. Marcelo Merello, MD, PhD
Dr. Marcelo Merello, MD, PhD, is the Director of Neuroscience Department, Head Movement Disorders Section, Institute for Neurological Research Raul Carrea (FLENI) in Buenos Aires.