Parkinson Disease: Yoshioka M

Oka H, Yoshioka M, Morita M, Mochio S, Inoue K. · Aoto Hospital, Department of Neurology, Jikei University School of Medicine. · Rinsho Shinkeigaku. · Pubmed #14658397 No free full text.

Abstract: We examined whether the results of 123I-MIBG scintigraphy reflect cardiac sympathetic nerve function in patients with Parkinson's disease (PD). The subjects were 62 patients with Parkinson's disease (age, 65.4 +/- 6.3 years) and 53 controls (65.2 +/- 7.1 years). All subjects underwent 123I-MIBG scintigraphy and QTc interval measurement on ECG. Hemodynamic autonomic function was estimated by the Valsalva maneuver in 37 subjects (63.9 +/- 5.2 years) randomly selected from the patients with PD. As control, the Valsalva maneuver was also done in 20 randomly selected controls (64.1 +/- 5.0 years), and 123I-MIBG scintigraphy was performed in 21 controls (67.7 +/- 5.3 years old). The subjects rested in a supine position for 20 min and were given an intravenous injection of 111 MBq 123I-MIBG. Relative organ uptake was determined by the region of interest (ROI) in the anterior view and the ratio of average pixel count in the heart (H) to that in the mediastinum (M) was calculated (H/M ratio) for early (after 15 min) and delayed (after 3 hrs) periods. The Valsalva maneuver was done by having the subjects exhale into a mouthpiece at an expiratory pressure of 40 mmHg for 15 seconds. Blood pressure and RR intervals were measured during the Valsalva maneuver by tonometry, using a noninvasive blood pressure monitoring system (ANS 508, Nihon Colin Co., Ltd.). Baroreceptor reflex sensitivities (BRS) of the second phase (BRS II) and fourth phase (BRS IV) of the Valsalva maneuver were calculated, and blood pressure elevations during the late second phase (IIp) and fourth phase (IVp) were measured. QTc was greater in the patients with PD (417 ms) than in the control subjects (409 ms). The H/M ratios of the early and delayed images in the patients with PD (1.76, 1.61) were significantly lower than those in the control subjects (2.56, 2.45). The early and delayed H/M ratios significantly correlated with the severity of disease according to Hoehn-Yahr stage. QTc interval and IVp significantly correlated with early and delayed H/M ratios. No other significant correlations were detected. The early H/M ratio in the patients with PD who had IVp within the normal range was lower than the early H/M ratio in control subjects. Our results show that early and delayed H/M ratio correlates with cardiac autonomic function, evaluated on the basis of QTc interval and the Valsalva maneuver, but not with baroreceptor reflex sensitivity or vasomotor autonomic function. Our findings suggest that silent cardiac autonomic dysfunction may be evaluated by 123I-MIBG scintigraphy, because early and delayed H/M ratios were lower in the patients with PD who had normal IVp than in the control subjects.

Kitta T, Matsumoto M, Tanaka H, Mitsui T, Yoshioka M, Nonomura K. · Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo 0608638, Japan. · Eur J Neurosci. · Pubmed #18554296 No free full text.

Abstract: The periaqueductal gray (PAG) is critically involved in the micturition reflex, but little is known about the neuronal mechanisms involved. The present study elucidated dynamic changes in dopamine (DA), glutamate and gamma-aminobutyric acid (GABA) in the rat PAG during the micturition reflex, with a focus on dopaminergic modulation using in vivo microdialysis combined with cystometrography. Extracellular levels of DA and glutamate increased, whereas levels of GABA decreased, in parallel with the micturition reflex. Application of a D(1) receptor antagonist into the PAG produced increases in maximal voiding pressure (MVP) and decreases in intercontraction interval (ICI), suggesting that the micturition reflex was facilitated by D(1) receptor blockade. The D(1) receptor antagonist prevented micturition-induced decreases in GABA efflux but had no effect on DA or glutamate. Neither a D(2) receptor antagonist nor a D(1)/D(2) receptor agonist affected these neurochemical and physiological parameters. Micturition-induced inhibition of GABA was not observed in 6-hydroxydopamine (6-OHDA)-lesioned rats, an animal model of Parkinson's disease. 6-OHDA-lesioned rats exhibited bladder hyperactivity evaluated by increases in MVP and decreases in ICI, mimicking facilitation of the micturition reflex induced by D(1) receptor blockade. These findings suggest that the micturition reflex is under tonic dopaminergic regulation through D(1) receptors, in which a GABAergic mechanism is involved. Bladder hyperactivity observed in 6-OHDA-lesioned rats may be caused by dysfunction of GABAergic regulation underlying the micturition reflex. The present findings contribute to our understanding not only of the neurophysiology of the micturition reflex but also of the pathophysiology of lower urinary tract dysfunction in patients with Parkinson's disease.

Oka H, Yoshioka M, Onouchi K, Morita M, Mochio S, Suzuki M, Hirai T, Urashima M, Inoue K. · Department of Neurology, Jikei University School of Medicine, Tokyo, Japan. · Mov Disord. · Pubmed #17516497 No free full text.

Abstract: We assessed the relations of visual hallucinations (VH) to cardiovascular autonomic dysfunction in patients with Parkinson's 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.

Oka H, Morita M, Onouchi K, Yoshioka M, Mochio S, Inoue K. · Department of Neurology, Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Tokyo, 105-8461, Japan. · J Neurol Sci. · Pubmed #17306830 No free full text.

Abstract: OBJECTIVE: We estimated the extent and pattern of cardiovascular autonomic dysfunction in dementia with Lewy bodies (DLB) as compared with that in Parkinson's 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.

Oka H, Mochio S, Onouchi K, Morita M, Yoshioka M, Inoue K. · Department of Neurology, Aoto Hospital, Jikei University School of Medicine, Tokyo, Japan. · J Neurol Sci. · Pubmed #16325862 No free full text.

Abstract: BACKGROUND: Clinical symptoms of Parkinson's 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.

Oka H, Mochio S, Yoshioka M, Morita M, Inoue K. · Department of Neurology, Aoto Hospital, Jikei University School of Medicine, Tokyo, Japan. · Eur Neurol. · Pubmed #14634268 No free full text.

Abstract: 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.

Yoshioka M, Oka H, Morita M, Inoue K. · Department of Neurology, Aoto Hospital, Jikei University School of Medicine. · Rinsho Shinkeigaku. · Pubmed #14582362 No free full text.

Abstract: Autonomic dysfunction is often associated with the progression of Parkinson's disease (PD). The most frequent manifestations of autonomic dysfunction are cardiovascular symptoms, bladder and bowel dysfunction, and sudomotor dysfunction. However, sudomotor dysfunction in PD remains poorly understood. To evaluate sudomotor function in PD, we quantitatively measured sweating during untreated conditions in 20 patients with PD (age, 62 +/- 5 years) and in 10 age-matched control subjects (60 +/- 6 years). An evaporimeter can measure small amounts of water (g/m2h) evaporated from the body. This device was used to quantify sweating at different sites of the skin (forehead, arm, dorsal part of hand, chest wall, femur, and dorsal part of foot). Sweating demonstrated as amount of evaporated water (mean +/- SD g/m2h) was less in the patients with PD than in the control participants on the dorsal parts of the hand (13.7 +/- 5.2 vs. 23.9 +/- 5.5, p < 0.001) and foot (16.0 +/- 6.0 vs. 22.1 +/- 8.3, p < 0.05). On the dorsal part of the hand, sweating in the patients with PD at Yahr stages I and II was less than that in the control-Participants (15.2 +/- 6.3 vs. 23.9 +/- 5.5, p < 0.05). Sweating in the patients with PD at Yahr stages III and IV was less than that in the control participants on the dorsal parts of the hand (10.8 +/- vs. 2.7 vs. 23.9 +/- 5.5, p < 0.001), and foot (10.9 +/- 2.3 vs. 22.1 +/- 8.3, p < 0.005). Sweating on the dorsal part of the foot was less in the patients with PD at Yahr stages III and IV than that in those at Yahr stages I and II (10.9 +/- 2.3 vs. 18.4 +/- 6.1, p < 0.05). Sweating on the forehead in the patients with PD at Yahr stages I and II stage was slightly but not significantly less than that in the control participants (21.8 +/- 3.8 vs. 32.7 +/- 11.9, p < 0.2). Sweating on the forehead in the patients with PD at Yahr stages III and IV was sightly but not significantly greater than that in those at Yahr stages I and II (25.4 +/- 5.6 vs. 21.8 +/- 3.8, p < 0.2). Increased sweating on the forehead skin might compensate for decreased sweating on the extremital skin. Our results suggest that sudomotor dysfunction in PD primarily affects the distal parts of the upper and lower extremities. Sudomotor dysfunction affecting distal parts of the extremities worsens with increased severity of PD.

Tanaka K, Yoshioka M, Miyazaki I, Fujita N, Ogawa N. · Department of Brain Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikatacho, Okayama 700-8558, Japan. · Neurosci Lett. · Pubmed #11872253 No free full text.

Abstract: We investigated both the antioxidant activities of GPI1046, a non-immunosuppressive derivative of FK506, and the in vivo neuroprotective properties against toxicity of intracerebroventricular 6-hydroxydopamine (6-OHDA) in mice. The 6-OHDA-induced reduction in dopamine and its metabolites in the striatum was significantly normalized by daily administration of GPI1046. Moreover, GPI1046 significantly reduced lipid peroxidation in vivo. Further, GPI1046 significantly increased striatal glutathione (GSH) levels by activating GSH synthesis, although the striatal catalase and superoxide dismutase activities did not change. We conclude that GPI1046 may have neuroprotective effects both in cell cultures and in vivo.

Minami M, Hamaue N, Endo T, Hirafuji M, Terado M, Ide H, Yamazaki N, Yoshioka M, Ogata A, Tashiro K. · Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan. · Nippon Yakurigaku Zasshi. · Pubmed #10629878 No free full text.

Abstract: Isatin (indole-2,3-dione), an endogenous inhibitor of monoamine oxidase (MAO), has several physiological properties for stress and anxiety. We previously identified isatin in the brain of stroke-prone spontaneously hypertensive rats (SHRSP) using gas-chromatography mass spectrometry. This study elucidated the effects of isatin on the ACh and DA levels of brain tissues in rats. Furthermore, we evaluated the effect of isatin on DA levels in a rat model of Parkinson's disease induced by Japanese encephalitis virus. Striatal ACh and DA levels significantly increased at 2 hours after isatin (50-200 mg/kg, i.p.) administration. Perfused through a microdialysis probe, isatin (10(-6)-10(-4) M) also produced a significant and concentration-dependent increase in the ACh and DA concentrations in the perfusate from the rat striatum. Furthermore, urinary isatin concentrations in patients with Parkinson's disease tend to increase according to the severity of disease. Isatin (100 mg/kg, i.p.) significantly increased striatal DA levels in a rat model of Parkinson's disease. These results suggest that urinary isatin may become a diagnostic marker for the clinical severity of Parkinson's disease and that endogenous isatin, a new biological modulator, may play a role in the regulation of the brain levels of ACh by increasing the level of DA under stress.

Oka H, Yoshioka M, Morita M, Onouchi K, Suzuki M, Ito Y, Hirai T, Mochio S, Inoue K. · Department of Neurology, Jikei University School of Medicine, Tokyo, 105-8461, Japan. · Neurology. · Pubmed #17909159 No free full text.

Abstract: OBJECTIVE: To examine the relation between the results of cardiac (123)I-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 (123)I-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 (123)I-MIBG uptake, cardiovascular autonomic response on the VM, and SBP response on HUT testing as compared with controls. Cardiac (123)I-MIBG uptake and cardiovascular autonomic function in PDD and DLB were severely impaired as compared with those in PD. Cardiac (123)I-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 (123)I-MIBG uptake was, however, significantly related to the blood pressure overshoot in phase IV of the VM. CONCLUSION: Cardiac (123)I-meta-iodobenzylguanidine uptake clinically reflects cardiac sympathetic dysfunction in Lewy body disease.

Oka H, Yoshioka M, Onouchi K, Morita M, Mochio S, Suzuki M, Hirai T, Ito Y, Inoue K. · Department of Neurology, Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo, Japan. · Brain. · Pubmed #17673498 links to  free full text

Abstract: Clinical symptoms of Parkinson's disease (PD) include not only motor distress but also autonomic dysfunction. Orthostatic hypotension (OH) occurs in one-fifth to one-half of all patients with PD. We examined the relation of this type of hypotension to clinical features and cardiovascular parameters such as cardiac 123I-meta-iodobenzylguanidine (MIBG) uptake, changes on the Valsalva maneuver, and plasma norepinephrine concentrations on head-up tilt-table testing (HUT). We performed HUT in 55 patients with PD and divided them into two groups according to the presence or absence of OH, defined as a drop in systolic blood pressure (SBP mmHg) by 20 mmHg or more on standing. We evaluated cardiac sympathetic function by 123I-MIBG scintigraphy and assessed cardiovascular autonomic function by using the Valsalva maneuver in all subjects. We also performed HUT, 123I-MIBG scintigraphy and assessed cardiovascular autonomic function by using the Valsalva maneuver in 20 controls. The results of HUT showed that 20 patients had OH and 35 did not. The hypotension was associated with gender, older age, longer disease duration, posture and gait instability phenotype, low mini-mental state examination scores and visual hallucinations. Cardiac 123I-MIBG uptakes were lower in patients with OH. SBP fell further during early second phase in patients with OH than in patients without the condition and their increase in SBP during the late second phase and the overshoot of SBP during the fourth phase were lower. The blood pressure recovery time during the fourth phase on the Valsalva maneuver was longer in patients with OH than in those without OH. There was, however, no association between the fall in SBP on HUT and baroreflex sensitivity or the plasma norepinephrine concentrations, adjusted by age, disease duration, disease severity and dopaminergic medication using multiple regression analyses. Patients without OH already had impaired cardiac sympathetic and baroreceptor reflex functions as early abnormalities of cardiovascular autonomic control. Our results suggest that pronounced vasomotor and cardiac sympathetic dysfunction is the primary cause of OH in PD, although baroreceptor reflex failure may also make a minor contribution. It was unclear whether vasomotor and cardiac sympathetic dysfunction in patients with PD was caused primarily by the impairment of preganglionic or postganglionic lesions.

Oka H, Mochio S, Yoshioka M, Morita M, Onouchi K, Inoue K. · Department of Neurology, Aoto Hospital, Tokyo, Japan. · Acta Neurol Scand. · Pubmed #16542160 No free full text.

Abstract: OBJECTIVES: To determine whether Parkinson's disease (PD) can be distinguished from multiple system atrophy (MSA) on the basis of the assessment of iodine-123 meta-iodobenzylguanidine (123I-MIBG) radioactivity in heart and cardiovascular autonomic function. PATIENTS AND METHODS: Seventeen patients with MSA, 39 with PD, and 25 healthy volunteers underwent 123I-MIBG scintigraphy and hemodynamic autonomic function tests using Valsalva maneuver (VM). Baroreceptor reflex sensitivity (BRS) was measured using the slope of the relation between RR interval and blood pressure during the fourth phase. RESULTS: 123I-MIBG radioactivity in heart of patients with PD was lower than that of control subjects and patients with MSA, but there was some overlap between PD and MSA. BRS in patients with PD who had a 123I-MIBG radioactivity similar to that in MSA was larger than that in patients with MSA, with no overlap in any patient. CONCLUSION: Assessment of BRS may be useful for differentiating between MSA and PD that had a 123I-MIBG radioactivity similar to MSA.