Hisayoshi Oka

Cardiovascular dysautonomia in de novo Parkinson's disease

BACKGROUND Clinical symptoms of Parkinsons disease (PD) include not only motor distress, but also autonomic dysfunction. OBJECTIVE To clarify the progression of autonomic nervous dysfunction in PD. METHODS The subjects were 44 patients with de novo PD. Autonomic nervous function, including cardiac sympathetic gain, was evaluated on the basis of cardiac radioiodinated metaiodobenzylguanidine (MIBG) uptake, the response to the Valsalva maneuver, and spectral analyses of the RR interval and blood pressure. RESULTS Decreased cardiac MIBG uptake was found even in patients with early stage PD. MIBG uptake gradually decreased with increased disease severity. Hemodynamic studies using the Valsalva maneuver revealed that patients with early stage PD had reduced baroreceptor reflex sensitivity (BRS) in phase II, but not phase IV. Blood pressures normally rose in phases II and IV, but the increments decreased with disease progression. In early stage PD, the low frequency power of the RR interval (RR-LF) and the ratio (LF/HF) of RR-LF to the high frequency component of the RR interval (RR-HF) were significantly lower than the respective control values, despite no significant difference in RR-HF; these variables decreased with disease progression. CONCLUSION Our results show that latent sympathetic nervous dysfunction without parasympathetic dysfunction, especially that involving the sinus node, is already present in early stage de novo PD. It is unclear whether the responsible lesion is central or peripheral.

Cardiovascular autonomic dysfunction in dementia with Lewy bodies and Parkinson's disease

OBJECTIVE We estimated the extent and pattern of cardiovascular autonomic dysfunction in dementia with Lewy bodies (DLB) as compared with that in Parkinsons disease (PD). METHODS We performed meta-iodobenzylguanidine ((123)I-MIBG) scintigraphy of the heart and hemodynamic autonomic function testing using the Valsalva maneuver in 27 patients with DLB, 46 with PD, and 20 controls. RESULTS (123)I-MIBG uptakes in DLB were reduced as compared with those in control and PD. Hemodynamic studies revealed that DLB had decreased baroreceptor reflex and reduced responses of SBP in phases II and IV as compared with PD and control. SBP responses on standing and the difference in plasma norepinephrine (NE) concentrations between supine and standing positions were reduced in PD as compared with those in control. Furthermore, SBP responses on standing, plasma NE concentrations in supine and standing positions, and the difference in plasma NE concentrations between these positions were significantly lower in DLB than in PD and control. Plasma NE concentrations in DLB with orthostatic hypotension (OH) were lower than that in DLB without OH, although some patients who had DLB with orthostatic hypotension had relatively normal plasma NE levels. CONCLUSION Cardiovascular autonomic dysfunction is more severe in DLB than in PD and is usually caused by the loss of postganglionic sympathetic nervous function, although dysautonomia in some patients with DLB may result from preganglionic dysfunction.

Cardiovascular dysautonomia in de novo Parkinson’s disease without orthostatic hypotension

Background:  Clinical symptoms of Parkinson’s disease (PD) include not only motor distress, but also autonomic dysfunction.

Reduced cardiac 123I-MIBG uptake reflects cardiac sympathetic dysfunction in Lewy body disease

Objective: To examine the relation between the results of cardiac 123I-meta-iodobenzylguanidine (MIBG) scintigraphy and cardiovascular autonomic function in Lewy body disease (LBD). Methods: The subjects were 66 patients with LBD, 44 of whom had Parkinson disease (PD), 10 PD with dementia (PDD), and 12 dementia with Lewy bodies (DLB); 20 age-matched healthy subjects were studied as controls. Cardiovascular autonomic function was evaluated on the basis of cardiac 123I-MIBG uptake, cardiovascular autonomic response on the Valsalva maneuver (VM), and systolic blood pressure (SBP) response on head-up tilt table (HUT) testing. Results: Patients with LBD had reduced cardiac 123I-MIBG uptake, cardiovascular autonomic response on the VM, and SBP response on HUT testing as compared with controls. Cardiac 123I-MIBG uptake and cardiovascular autonomic function in PDD and DLB were severely impaired as compared with those in PD. Cardiac 123I-MIBG uptake in LDB was not significantly related to vasomotor sympathetic function, baroreceptor reflex gain, cardiac parasympathetic function, or the changes in SBP on HUT testing. Cardiac 123I-MIBG uptake was, however, significantly related to the blood pressure overshoot in phase IV of the VM. Conclusion: Cardiac 123I-meta-iodobenzylguanidine uptake clinically reflects cardiac sympathetic dysfunction in Lewy body disease. GLOSSARY: BRS = baroreceptor reflex sensitivity; DLB = dementia with Lewy bodies; H/M ratio = the ratio of the average pixel count in the heart to that in the mediastinum; HUT = head-up tilt table test; LBD = Lewy body disease; MIBG = 123I-meta-iodobenzylguanidine; MMSE = Mini-Mental State Examination; PD = Parkinson disease; PDD = Parkinson disease with dementia; phase II E = systolic blood pressure decreases in early phase II; phase II L = systolic blood pressure increases in late phase II; PRT = pressure recovery time; VM = Valsalva maneuver; ROI = region of interest; SBP = systolic blood pressure; TH = tyrosine hydroxylase.

Evaluation of Baroreflex Sensitivity by the Sequence Method Using Blood Pressure Oscillations and R–R Interval Changes during Deep Respiration

Background: Baroreflex sensitivity assessments have been considered to be important to evaluate cardiac autonomic neuropathy. The phenylephrine method, Valsalva maneuver or sequence method at rest caused several problems. We evaluated the usefulness of the sequence method during deep respiration. Method: Baroreflex sensitivity was evaluated in 20 normal volunteers and 50 patients with Parkinson’s disease. R–R intervals and systolic blood pressures were obtained by electrocardiogram and tonometry using a continuous blood pressure monitoring system. The sequence method is an evaluation of baroreflex sensitivity using sequences of 3 or more consecutive beats for 4 min. Baroreflex sensitivity was also assessed by the Valsalva maneuver at 5 beats before the peak systolic blood pressure of phase IV. The slope of the linear interrelationship between systolic blood pressure and the following R–R interval, i.e. baroreflex sensitivity (ms/mm Hg), was calculated with a correlation coefficient greater than 0.8. Result: The mean value of baroreflex sensitivity obtained by the Valsalva maneuver was 7.91 in normal volunteers and 5.35 in patients with Parkinson’s disease; the one obtained by the sequence method at rest was 9.10 in normal volunteers and 8.42 in patients with Parkinson’s disease, and the one obtained by the sequence method during deep respiration was 10.23 in normal volunteers and 6.73 in patients with Parkinson’s disease. In some cases with Parkinson’s disease, baroreflex sensitivities could not be found, whereas in all patients with Parkinson’s disease, the sequence method during deep respiration could be used for evaluations. Significant correlations were found among the baroreflex sensitivities obtained by the Valsalva maneuver, and the sequence method at rest or during deep respiration in normal volunteers and patients with Parkinson’s disease. Conclusions: The baroreflex sensitivity obtained by the sequence method during deep respiration could be investigated noninvasively in all cases with PD, being thus a useful method for clinical evaluation of baroreflex sensitivity.

Cardiac sympathetic denervation in bradykinesia-dominant Parkinson's disease.

Cardiac iodine-123-labeled-metaiodobenzylguanidine uptake is reduced in early-stage Parkinsons disease, suggesting sympathetic nerve degeneration. The scintigraphic findings in patients with Parkinsons disease with different clinical features have, however, not been established. Iodine-123-labeled-metaiodobenzylguanidine myocardial scintigraphy was performed in 143 patients with Parkinsons disease. The early and delayed heart to mediastinum ratios were analyzed according to the dominant motor deficit (tremor, bradykinesia, rigidity, and postural instability), age, sex, age at onset, disease duration, and Hoehn and Yahr stage. Both ratios correlated with bradykinesia, age at disease onset, and disease duration; but not with sex, Hoehn and Yahr stage, tremor, rigidity, and postural instability. Our results suggest a close link between myocardial sympathetic degeneration and bradykinesia, age at onset and disease duration.

Prolongation of QTc Interval in Patients with Parkinson’s Disease

QTc intervals were measured in 30 patients with Parkinsons disease and 30 healthy control subjects. The mean value of QTc intervals in patients with Parkinsons disease significantly exceeded that of healthy controls (418 +/- 14 ms vs. 403 +/- 18 ms). Prolongation of the QTc interval was unrelated to the administration of levodopa. The mean QTc interval in patients whose Hoehn and Yahr score was III or more was significantly greater than that of patients whose score was II or less (424 +/- 12 ms vs. 410 +/- 12 ms). A significant correlation between the QTc interval and the Valsalva ratio, as well as the overshoot, was identified. The QTc interval is closely related to autonomic nervous system dysfunction, including abnormal baroreceptor reflex function, in patients with Parkinsons disease.

Pramipexole-induced antecollis in Parkinson's disease.

We report a case of antecollis, or dropped head with Parkinsons disease (PD) induced by pramipexole, a nonergot dopamine agonist. An 80-year-old woman presented with progressively severe neck flexion, which developed within a few weeks of taking pramipexole at 3 mg/day. She had a disturbed gait and complained of difficulty in daily activity because of restricted visual field and severe stooped posture. Surface EMG showed disproportionate tonus of the neck muscles but needle EMG of the neck muscles was normal. Withdrawal of pramipexole resulted in immediate improvement; the patient could keep the head in natural position and walk normally. Pramipexole-induced antecollis may be serious, but is a reversible dystonia in patients with PD. Clinicians should be aware of such complication.

Spectral analyses of R-R interval and systolic blood pressure in diabetic autonomic neuropathy

We studied autonomic nervous system function using the principle of maximum entropy (ME) to perform spectral analyses of the R-R interval and systolic blood pressure in 32 diabetic patients and 40 healthy controls. The R-R interval and systolic blood pressure were measured using a continuous, noninvasive monitoring system. The power spectra of both the R-R interval (RR) and systolic blood pressure (SYS) were obtained using ME and the areas of two frequency components were measured: a low- (LFC) and a high-frequency component (HFC). The RR-LFC, RR-HFC and SYS-LFC of diabetic patients were significantly smaller than those of healthy controls. The results of the spectral analyses in diabetic patients correlated with neither disease duration nor nephropathy, while the SYS-LFC showed significant correlations with both retinopathy and the delay in median motor nerve conduction velocity. In the mild autonomic neuropathy group, the RR-LFC and SYS-LFC were not differ from those of healthy controls or patients without autonomic neuropathy. However, the RR-HFC was significantly smaller than that of healthy controls or patients without atonomic neuropathy. In the setting of mild diabetic autonomic neuropathy, it was suggested that cardiac parasympathetic dysfunction preceded both alpha and beta sympathetic dysfunction.

Impaired cardiovascular autonomic function in Parkinson's disease with visual hallucinations.

We assessed the relations of visual hallucinations (VH) to cardiovascular autonomic dysfunction in patients with Parkinsons disease (PD). The subjects were 37 patients without VH (VH(−)) and 31 with VH (VH(+)). Autonomic function was evaluated on the basis of cardiac 123‐radioiodinated metaiodobenzylguanidine (123I‐MIBG) uptake and hemodynamic testing with Valsalva maneuver. Systolic blood pressure (SBP) and plasma norepinephrine concentrations (NE) were measured by tilt‐table testing. 123I‐MIBG uptake was lower in VH(+) than VH(−). Hemodynamic studies showed that VH(−) had only cardiac sympathetic and parasympathetic dysfunction, while VH(+) additionally had reduced vasomotor sympathetic functions. The fall in SBP during tilt‐table testing was greater in VH(+) than VH(−). NE and its difference in the supine and upright positions were decreased in VH(+). We conclude that cardiac and vasomotor sympathetic dysfunction is more severe in VH(+) than in VH(−). Severe dysfunction in PD with VH is probably attributed to Lewy‐body lesions or neuronal loss in sympathetic ganglia, the central autonomic system, or both.