Rinsho Shinkeigaku (Clinical Neurology)

Special article by the winner of Narabayashi Prize

Clinical and pathological study on early diagnosis of Parkinson's disease and dementia with Lewy bodies

Satoshi Orimo, M.D., Ph.D.

Department of Neurology, Kanto Central Hospital

[123I] Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy has been used to evaluate postganglionic cardiac sympathetic innervation in heart diseases and some neurological disorders. To see clinical usefulness of MIBG myocardial scintigraphy to differentiate Parkinson's disease (PD) and dementia with Lewy bodies (DLB) from related movement disorders and Alzheimer disease (AD), we performed MIBG myocardial scintigraphy in patients with these disorders. Cardiac uptake of MIBG is specifically reduced in PD and DLB, and this imaging approach is a sensitive diagnostic tool that possibly differentiates PD and DLB from related movement disorders and AD.
To see pathological basis of the reduced cardiac uptake of MIBG in Lewy body disease, we immunohistichemically examined cardiac tissues from patients with PD, DLB, related movement disorders and AD using antibodies against tyrosine hydroxylase (TH) and phosphorylated neurofilament (NF). Not only TH- but also NF-immunoreactive (ir) axons in the epicardial nerve fascicles were markedly decreased in Lewy body disease, namely cardiac sympathetic denervation, which accounts for the reduced cardiac uptake of MIBG in Lewy body disease. Patients with PD and DLB have Lewy bodies (LBs) in the nervous system, whereas patients with multiple system atrophy (MSA), progressive supranuclear palsy, corticobasal degeneration, parkin-associated PD and AD have no LBs in the nervous system. Even in patients with MSA, cardiac sympathetic denervation was associated with the presence of LBs. Therefore, cardiac sympathetic denervation is closely related to the presence of LBs in a wide range of neurodegenerative processes. Taken together, we conclude that the reduced cardiac uptake of MIBG is a potential biomarker for the presence of LBs.
Because α-synuclein is one of the key molecules in the pathogenesis of PD, we further investigate how α-synuclein aggregates are involved in degeneration of the cardiac sympathetic nerve in PD. We immunohistochemically examined cardiac tissues from patients with incidental Lewy body disease (ILBD) and PD using antibodies against TH and phosphorylated α-synuclein. We found that (1) α-synuclein aggregates in the epicardial nerve fascicles, namely the distal axons of the cardiac sympathetic nerve, were much more abundant in ILBD with preserved TH-ir axons than in ILBD with decreased TH-ir axons and PD; (2) α-synuclein aggregates in the epicardial nerve fascicles were closely related to the disappearance of TH-ir axons; (3) in ILBD with preserved TH-ir axons, α-synuclein aggregates were consistently more abundant in the epicardial nerve fascicles than in the paravertebral sympathetic ganglia (pSG); and (4) this distal-dominant accumulation of α-synuclein aggregates was reversed in ILBD with decreased TH-ir axons and PD, which both showed decreased or depleted TH-ir axons but more abundant α-synuclein aggregates in the pSG. These findings indicate that accumulation of α-synuclein aggregates in the distal axons of the cardiac sympathetic nervous system precedes that of neuronal somata or neurites in the pSG and that heralds centripetal degeneration of the cardiac sympathetic nerve in PD. This chronological and dynamic relationship between α-synuclein aggregates and distal-dominant degeneration of the cardiac sympathetic nervous system may represent the pathological mechanism underlying a common degenerative process in PD.
Full Text of this Article in Japanese PDF (1258K)

(CLINICA NEUROL, 48: 11－24, 2008)
key words: Parkinson's disease, dementia with Lewy bodies, meta-iodobenzylguanidine (MIBG), cardiac sympathetic denervation, α-synuclein

(Received: 26-Jan-07)