Parkinson Disease: Suzuki M

Emborg ME, Ebert AD, Moirano J, Peng S, Suzuki M, Capowski E, Joers V, Roitberg BZ, Aebischer P, Svendsen CN. · Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI, USA. · Cell Transplant. · Pubmed #18522241 No free full text.

Abstract: Human neural progenitor cells (hNPCs) have been proposed as a potential source of cells for ex vivo gene therapy. In this pilot study, three 5-year-old female cynomolgus monkeys received a single intracarotid infusion of MPTP, followed 1 week later by MRI-guided stereotaxic intrastriatal and intranigral injections of male hNPCs transgenic for GDNF. Immunosupression with oral cyclosporine (30-40 mg/kg) began 48 h before hNPC transplants and continued throughout the study. We monitored the animals using a clinical rating scale (CRS). Three months postsurgery, we euthanized the animals by transcardiac perfusion, then retrieved and processed their brains for morphological analysis. Our findings include the following. 1) hNPCs survived and produced GDNF in all animals 3 months postsurgery. 2) hNPCs remained in the areas of injection as observed by GDNF immunostaining and in situ hybridization for the human Y chromosome. 3) A "halo" of GDNF expression was observed diffusing from the center of the graft out into the surrounding area. 4) We observed increased TH- and VMAT2-positive fibers in areas of GDNF delivery in two of the three animals. The two animals with TH- and VMAT2-positive fibers also showed reductions in their CRS scores. 5) Some GFAP-positive perivascular cuffing was found in transplanted areas. 6) General blood chemistry and necropsies did not reveal any abnormalities. Therefore, we conclude that hNPCs releasing GDNF may be a possible alternative for intracerebral trophic factor delivery in Parkinson's disease.

Suzuki M, Urashima M, Oka H, Hashimoto M, Taira K. · Department of Neurology, The Jikei University School of Medicine, Tokyo, Japan. · Neuroreport. · Pubmed #18090328 No free full text.

Abstract: Cardiac iodine-123-labeled-metaiodobenzylguanidine uptake is reduced in early-stage Parkinson's disease, suggesting sympathetic nerve degeneration. The scintigraphic findings in patients with Parkinson's disease with different clinical features have, however, not been established. Iodine-123-labeled-metaiodobenzylguanidine myocardial scintigraphy was performed in 143 patients with Parkinson's 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.

Suzuki M, Hirai T, Ito Y, Sakamoto T, Oka H, Kurita A, Inoue K. · Department of Neurology, The Jikei University School of Medicine, 3 25 8, Nishi-Shinbashi, Minato-ku, Tokyo, 105 8461, Japan. · J Neurol Sci. · Pubmed #17826796 No free full text.

Abstract: We report a case of antecollis, or dropped head with Parkinson's 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.

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.

Suzuki M, Kurita A, Hashimoto M, Fukumitsu N, Abo M, Ito Y, Urashima M, Inoue K. · Department of Neurology, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan. · J Neurol Sci. · Pubmed #16199056 No free full text.

Abstract: BACKGROUND: Iodine-123-labeled metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy has been used to evaluate cardiac sympathetic denervation in Lewy body disease (LBD) including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Patients with LBD had marked reductions in cardiac MIBG accumulation, indicative of severe impairment of the cardiac sympathetic nervous systems. However, the differences in scintigraphy between DLB and PD have not been determined. OBJECTIVE: To compare cardiac sympathetic function in early disease stage measured with 123I-MIBG scintigraphy between DLB and PD. METHODS: 123I-MIBG myocardial scintigraphy was performed in 22 patients with early-stage DLB, 41 patients with early idiopathic PD and 15 normal control subjects who were matched for age and disease duration. The heart-to-mediastinum (H/M) ratio was calculated. RESULTS: 123I-MIBG uptake of the myocardium was significantly lower in patients with early DLB than in controls. The mean value of H/M ratio in patients with DLB was significantly lower than those in patients with PD, independent of the Hoehn and Yahr stage. CONCLUSIONS: Our findings suggest that cardiac sympathetic function in DLB is severely impaired even in the early disease stage.

Kurita A, Ochiai Y, Kono Y, Suzuki M, Inoue K. · Department of Neurology, Jikei University School of Medicine, Tokyo, Japan. · J Geriatr Psychiatry Neurol. · Pubmed #12967063 No free full text.

Abstract: Visual hallucinations (VHs) are common psychiatric symptoms in patients with long-standing Parkinson's disease (PD). Treatment with neuroleptics or withdrawal of anti-PD drugs may improve VHs but will worsen motor dysfunctions. The authors report on 3 patients with long-standing PD who were treated with the cholinesterase inhibitor donepezil for the treatment of VHs. Each received a daily dose of 5 mg of donepezil, after reducing or discontinuing anti-PD medications had failed to relieve the VHs. In 2 patients (patient 1, 2), donepezil decreased VHs without worsening motor dysfunctions. In addition, the cognitive status of patient 2 improved. In patient 3, donepezil also resolved VHs, but delusions developed during treatment. After discontinuing donepezil, delusions disappeared and VHs reappeared. Donepezil may ameliorate visual hallucinations in PD patients, but controlled, double-blind trials are necessary to further clarify the effect of this drug on VHs in PD.

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.