Cardiovascular dysautonomia in de novo Parkinson's disease

Oka, Hiroyuki; Mochio, Soichiro; Onouchi, Kenji; Morita, Masayo; Yoshioka, Masayuki; Inoue, Kiyoharu

doi:10.1016/j.jns.2005.10.014

“…3,4 Consistent with early involvement of peripheral autonomic or lower brainstem centers, several studies of de novo PD have reported evidence of cardiac noradrenergic denervation 5,8,14,22 or of decreased baroreflex-cardiovagal function. 1,2,6,14,18 Whether these abnormalities can actually precede symptomatic PD has been unknown.…”

Section: Author Manuscriptmentioning

confidence: 91%

“…Baroreflex-cardiovagal gain, calculated from the slope of the relationship between cardiac interbeat interval (with one beat delay) and systolic blood pressure during Phase II of the maneuver, was decreased at 3.2 msec/mm Hg; baroreflex-cardiovagal gain calculated from the data in Phase IV after release of the maneuver was also decreased at 3.1 msec/mm Hg). 11,14,15 Over several months in 2005 the patient noted progressive slowing of movement and inability to relax the arms, small handwriting, decreased facial expression, and decreased voice volume. The patient returned to the NIH in November 2005, to participate in a protocol on pseudopheochromocytoma, the evaluation again including 6-[ 18 F]fluorodopamine positron emission tomographic scanning and beat-to-beat blood pressure and heart rate associated with the Valsalva maneuver.…”

Section: Case Reportmentioning

confidence: 99%

“…3,4 Consistent with early involvement of peripheral autonomic or lower brainstem centers, several studies of de novo PD have reported evidence of cardiac noradrenergic denervation 5,8,14,22 or of decreased baroreflex-cardiovagal function. 1,2,6,14,18 Whether these abnormalities can actually precede symptomatic PD has been unknown. Here we report the case of a patient who had cardiac noradrenergic denervation, detected by 6-[ 18 F]fluorodopamine positron emission tomography, and decreased baroreflex-cardiovagal gain, detected by abnormal beat-to-beat blood pressure and heart rate responses to the Valsalva maneuver, 4 years before the clinical onset of PD.…”

mentioning

confidence: 91%

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Cardiac sympathetic denervation preceding motor signs in Parkinson disease

Goldstein

¹

,

Sharabi

²

,

Karp

³

et al. 2009

CCJM

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There is substantial interest in identifying biomarkers to detect early Parkinson disease (PD). Cardiac noradrenergic denervation and attenuated baroreflex-cardiovagal function occur in de novo PD, but whether these abnormalities can precede PD has been unknown. Here we report the case of a patient who had profoundly decreased left ventricular myocardial 6-[ 18 F]fluorodopamine-derived radioactivity and low baroreflex-cardiovagal gain, 4 years before the onset of symptoms and signs of PD. The results lead us to hypothesize that cardiac noradrenergic denervation and decreased baroreflex-cardiovagal function may occur early in the pathogenesis of PD.In Parkinson disease (PD), by the time the movement disorder develops, most of the nigrostriatal dopamine terminals have been lost. Identification of biomarkers of PD should improve early diagnosis and spur development of effective treatments.Correspondence: David S. Goldstein, MD, PhD, Clinical Neurocardiology Section, NINDS, NIH, 10 Center Drive MSC-1620, Building 10, Room 6N252, Bethesda, MD 20892-1620; goldsteind@ninds.nih.gov. No author conflicts of interest were reported in the original publication of this article. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptBraak has proposed a pathogenetic sequence beginning outside the brain, with invasion of peripheral, vulnerable autonomic neurons, followed by alpha-synucleinopathy in lower brainstem nuclei and then by alpha-synucleinopathy in the midbrain substantia nigra and then finally in the cerebral cortex. 3,4 Consistent with early involvement of peripheral autonomic or lower brainstem centers, several studies of de novo PD have reported evidence of cardiac noradrenergic denervation 5,8,14,22 or of decreased baroreflex-cardiovagal function. 1,2,6,14,18 Whether these abnormalities can actually precede symptomatic PD has been unknown. Here we report the case of a patient who had cardiac noradrenergic denervation, detected by 6-[ 18 F]fluorodopamine positron emission tomography, and decreased baroreflex-cardiovagal gain, detected by abnormal beat-to-beat blood pressure and heart rate responses to the Valsalva maneuver, 4 years before the clinical onset of PD. CASE REPORTA 56-year-old man was referred for possible pheochromocytoma, based on episodic hypertensive episodes and symptoms suggesting excessive catecholamine effects.He had no serious health problems until about 1998, when he began to experience malaise and exercise intolerance and episodes of hypertension or hypotension, palpitations, and chest tightness. He also had a long history of constipation and dyspepsia, a tendency to urinary retention, and complained of a sense of fullness in the left neck. The patient's career was in marketing and business development, until he quit work due to his symptoms. His mother had died of PD. Cardiac catheterization showed normal coronary arteries. Gastrointestinal endoscopy was unrevealing. Biochemical testing showed elevated plasma levels and urinary excretion of epin...

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“…[41][42][43][44] The imaging findings were correlated with bradykinesia, age at onset, and disease duration, but not with sex, rigidity and postural stability. 45,46 These results are in line with clinical studies showing a correlation of autonomic symptoms with severity of limb and axial bradykinesia, but not with tremor or rigidity.…”

Section: Heartmentioning

confidence: 99%

Lesions outside the CNS in Parkinson's disease

Djaldetti

¹

,

Lev

²

,

Melamed

³

2009

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Parkinson's disease (PD) is not a simple movement disorder induced just by loss of dopaminergic neurons in the substantia nigra pars compacta. Apparently, the substantia nigra is not the only or the first brain region damaged in PD. Moreover, older and recent studies have shown that the degenerative process in PD is much more extensive and affects not only the central nervous system (CNS) but also the peripheral autonomic nervous system and the organs outside the brain that the latter innervates. These include mainly the gastrointestinal tract, the heart, kidneys, urogenital system, and skin. Additional extra-CNS organs that are involved in PD include the eye and the adrenal gland. This article reviews the anatomical, physiological, and clinical features of extracerebral manifestations of PD, and describes their relevance to the etiology and pathogenesis of the disease. It establishes this illness as a systemic CNS and peripheral disorder that warrants new hypotheses regarding its causation and progression.

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“…3,4 Consistent with early involvement of peripheral autonomic or lower brainstem centers, several studies of de novo PD have reported evidence of cardiac noradrenergic denervation 5,8,14,22 or of decreased baroreflex-cardiovagal function. 1,2,6,14,18 Whether these abnormalities can actually precede symptomatic PD has been unknown.…”

mentioning

confidence: 91%

Cardiac sympathetic denervation preceding motor signs in Parkinson disease

Goldstein

¹

,

Sharabi

²

,

Karp

³

et al. 2007

View full text Add to dashboard Cite

There is substantial interest in identifying biomarkers to detect early Parkinson disease (PD). Cardiac noradrenergic denervation and attenuated baroreflex-cardiovagal function occur in de novo PD, but whether these abnormalities can precede PD has been unknown. Here we report the case of a patient who had profoundly decreased left ventricular myocardial 6-[ 18 F]fluorodopamine-derived radioactivity and low baroreflex-cardiovagal gain, 4 years before the onset of symptoms and signs of PD. The results lead us to hypothesize that cardiac noradrenergic denervation and decreased baroreflex-cardiovagal function may occur early in the pathogenesis of PD.In Parkinson disease (PD), by the time the movement disorder develops, most of the nigrostriatal dopamine terminals have been lost. Identification of biomarkers of PD should improve early diagnosis and spur development of effective treatments.Correspondence: David S. Goldstein, MD, PhD, Clinical Neurocardiology Section, NINDS, NIH, 10 Center Drive MSC-1620, Building 10, Room 6N252, Bethesda, MD 20892-1620; goldsteind@ninds.nih.gov. No author conflicts of interest were reported in the original publication of this article. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptBraak has proposed a pathogenetic sequence beginning outside the brain, with invasion of peripheral, vulnerable autonomic neurons, followed by alpha-synucleinopathy in lower brainstem nuclei and then by alpha-synucleinopathy in the midbrain substantia nigra and then finally in the cerebral cortex. 3,4 Consistent with early involvement of peripheral autonomic or lower brainstem centers, several studies of de novo PD have reported evidence of cardiac noradrenergic denervation 5,8,14,22 or of decreased baroreflex-cardiovagal function. 1,2,6,14,18 Whether these abnormalities can actually precede symptomatic PD has been unknown. Here we report the case of a patient who had cardiac noradrenergic denervation, detected by 6-[ 18 F]fluorodopamine positron emission tomography, and decreased baroreflex-cardiovagal gain, detected by abnormal beat-to-beat blood pressure and heart rate responses to the Valsalva maneuver, 4 years before the clinical onset of PD. CASE REPORTA 56-year-old man was referred for possible pheochromocytoma, based on episodic hypertensive episodes and symptoms suggesting excessive catecholamine effects.He had no serious health problems until about 1998, when he began to experience malaise and exercise intolerance and episodes of hypertension or hypotension, palpitations, and chest tightness. He also had a long history of constipation and dyspepsia, a tendency to urinary retention, and complained of a sense of fullness in the left neck. The patient's career was in marketing and business development, until he quit work due to his symptoms. His mother had died of PD. Cardiac catheterization showed normal coronary arteries. Gastrointestinal endoscopy was unrevealing. Biochemical testing showed elevated plasma levels and urinary excretion of epin...

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Cardiovascular dysautonomia in de novo Parkinson's disease

Cited by 67 publications

References 34 publications

Cardiac sympathetic denervation preceding motor signs in Parkinson disease

Cardiac sympathetic denervation preceding motor signs in Parkinson disease

Lesions outside the CNS in Parkinson's disease

Cardiac sympathetic denervation preceding motor signs in Parkinson disease

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