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Parkinson's disease is a neurodegenerative disorder that causes motor and nonmotor symptoms due to the loss of dopaminergic nerves and is characterized by the presence of Lewy bodies, which are mainly composed of α-synuclein. Glucosylceramidase beta (GBA), which is a causative gene of autosomal recessive Gaucher disease, is also known to be a risk gene for Parkinson's disease. In this study, we tried to detect synergistic effects of α-synuclein accumulation and gba depletion on dopaminergic neurodegeneration in zebrafish.We generated a transgenic line of zebrafish overexpressing the A53T α-synuclein and gba mutant fish, and analyzed pathologies of α-synuclein aggregation and neurodegeneration.Zebrafish overexpressing the A53T α-synuclein did not exhibit α-synuclein aggregate formation. After the loss of gba function in this mutant α-synuclein transgenic line, we observed the marked presence of α-synuclein aggregates. Loss of gba function in zebrafish resulted in dopaminergic and noradrenergic neurodegeneration but this level of neurodegeneration was not exacerbated by overexpression of mutant α-synuclein.These results indicate that loss of gba function was sufficient to generate a neurodegenerative phenotype in zebrafish regardless of the expression of α-synuclein.

Mitochondrial dysfunction and lysosomal dysfunction have been implicated in Parkinson’s disease (PD), but the links between these dysfunctions in PD pathogenesis are still largely unknown. Here we report that cytosolic dsDNA of mitochondrial origin escaping from lysosomal degradation was shown to induce cytotoxicity in cultured cells and PD phenotypes in vivo. The depletion of PINK1, GBA and/or ATP13A2 causes increases in cytosolic dsDNA of mitochondrial origin and induces type I interferon (IFN) responses and cell death in cultured cell lines. These phenotypes are rescued by the overexpression of DNase II, a lysosomal DNase that degrades discarded mitochondrial DNA, or the depletion of IFI16, which acts as a sensor for cytosolic dsDNA of mitochondrial origin. Reducing the abundance of cytosolic dsDNA by overexpressing human DNase II ameliorates movement disorders and dopaminergic cell loss in gba mutant PD model zebrafish. Furthermore, IFI16 and cytosolic dsDNA puncta of mitochondrial origin accumulate in the brain of patients with PD. These results support a common causative role for the cytosolic leakage of mitochondrial DNA in PD pathogenesis., Mitochondrial and lysosomal dysfunction are central to Parkinson’s disease (PD) pathogenesis. Here, the authors show mitochondrial dsDNA in the cytosol in cellular and Zebrafish models of PD induces cytotoxicity and neurodegeneration; knock-down of IFI16, a cytosolic dsDNA sensor, rescues cytotoxicity, as does overexpression of lysosomal DNAse II.

Summary: Parkinson’s disease (PD) is a neurodegenerative disease characterized by α-synuclein-positive inclusion bodies and loss of neurons, including dopaminergic neurons. Difficulty in replicating PD phenotypes using animal models partly limits the understanding of PD and the therapy required. Although PD is strongly associated with aging, most experimental animals may not exhibit age-related symptoms. Herein, we demonstrate that Nothobranchius furzeri, a rapidly aging teleost with a short life span, exhibits age-dependent degeneration of dopaminergic and noradrenergic neurons and progression of α-synuclein pathologies. These pathological phenotypes are similar to those observed in human patients with PD. Amelioration of the cell loss by genetic depletion of α-synuclein suggests that α-synuclein is not a bystander but a causative protein of neurodegeneration. N. furzeri can reveal mechanisms underlying PD, especially of the idiopathic form that affects a majority of patients with PD, including α-synuclein-dependent neurodegeneration, age-dependent phenotypes, and progression of α-synuclein pathology. : Matsui et al. find that annual killifish, Nothobranchius furzeri, reveals age-dependent degeneration of dopamine neurons and accumulation of α-synuclein. Genetic depletion of α-synuclein rescues these phenotypes. Keywords: Nothobranchius furzeri, aging, Parkinson’s disease, α-synuclein

Parkinson's disease is a neurodegenerative disorder that involves movement discloses, degeneration of dopaminergic neurons, and presence of cytoplasmic inclusion bodies. Various animal models have been developed and small fish including zebrafish and medaka fish have recently been employed as a new model for Parkinson disease. In this review, we summarize fish models of Parkinson's disease mainly using our own findings and explain two major hypotheses of PD: lysosome dysfunction theory and mitochondrial dysfunction theory. Finally, we discuss the potential for future application of small fish model.

Teleost fish have recently been employed as a model for human neurodegenerative diseases. We used toxin exposure and genetic engineering to develop models of Parkinson's disease (PD) in the teleost fish, medaka. Among the toxins examined, 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), proteasome inhibitors, lysosome inhibitors, and tunicamycin all induced important features of PD in medaka. Specifically, these agents induced dopaminergic cell loss and reduced spontaneous movement, and the latter three toxins produced inclusion bodies that were ubiquitously distributed in the medaka brain. Despite the extensive distribution of these inclusion bodies, the middle diencephalic dopaminergic neurons were particularly susceptible to the effect of the toxins, suggesting that this cluster of dopaminergic neurons is analogous to the human substantia nigra. We have also created a variety of different genetic models using the Targeting Induced Local Lesions in Genomes (TILLING) method, and found that neither PTEN-induced putative kinase 1 (PINK1) mutants nor Parkin mutants disclosed significant dopaminergic cell loss. Surprisingly however, PINK1 and Parkin double mutants exhibited selective dopamine cell loss, as well as aggregation and deficit of mitochondrial activity. Another mutant, the ATP13A2 mutant, also expressed a PD phenotype, exhibiting marked cathepsin D reduction and fingerprint-like structures that are generally found in lysosome storage diseases. Taken together, these data indicate that medaka fish can serve as a new animal model for PD. In this review, we summarize our data and discuss the potential for future application of this animal model.

Objective : Auditory P300 has been reported to be abnormal in demented patients with Parkinson's disease. However, it is still controversial which factors in Parkinson's disease influence P300 parameters. Methods : Forty patients with Parkinson's disease were included. Patients were divided into two groups: patients with dementia (PDD) and without dementia (PDND). An ‘odd-ball’ paradigm was used for auditory event-related potentials. Results : P300 latency was markedly delayed in PDD patients. Age and DRS1 (attention) were the most important factors influencing P300 latency. Conclusions : Although there have been reports of P300 in the past, its abnormalities reflect the deficit of attention in Parkinson's disease.

Objective We compared brain perfusion image using 3D-SSP analysis of 123I-IMP SPECT between Parkinson's disease patients with auditory verbal hallucination and those without auditory hallucination. Methods Eighty-three cases with Parkinson's disease were studied. In 6 of these patients, auditory hallucination was noted. Among them, four cases had verbal hallucination and two other cases had elementary hallucination. Auditory hallucination was not found in the other 77 cases. Results Right thalamic perfusion was significantly increased in the verbal hallucination group compared to the group that lacked auditory hallucination. Conclusion In Parkinson's disease, the right thalamic hyperactive state may be related to verbal hallucination.

The pathophysiology of depression and anxiety in Parkinson’s disease remains obscure. We aimed to compare the fractional anisotropy (FA) values of Parkinson’s disease (PD) patients with and without depression to investigate the nature of depression in PD. Twenty-eight patients were divided into two groups: those with depression and those without. Diagnosis of depression was made using the DSM-IV criteria. Patients in the two groups were matched for Hoehn Yahr stage. There were significant reductions in FA values in the bilateral frontal ROIs possibly representing anterior cingulate bundles. The anterior cingulate bundles play an important role in depression in PD, and some aspects of depression in PD have pathological processes in common with de novo depression.

Background Few imaging studies investigated frontal dysfunctions in Parkinson's disease. Objectives We investigated relationships between Wisconsin Card Sorting Test (WCST) and brain perfusion in patients with non-demented Parkinson's disease. Methods Patients were divided into two groups according to WCST score: (1) CA (number of category achieved)≤2 or (2) CA≥3. We performed three-dimensional stereotactic surface projection and volume of interest analysis using 123I-IMP scintigraphy. Results Hypoperfusions of the bilateral posterior cingulate, rostrodorsal prefrontal, and left frontopolar cortices were shown in CA≤2 group, with the left cingulate and right rostrodorsal prefrontal cortices showing prominent hypoperfusion. CA and PE (perseverative errors) scores significantly correlated with perfusion of the left posterior cingulate cortex. PE score also correlated with perfusion of the right rostrodorsal prefrontal cortex. Conclusion Data indicated participations of various regions in task achievement. Careful interpretation of WCST scores is required.

Background Although excessive daytime sleepiness (EDS) in Parkinson's disease (PD) has received a great deal of attention, the underlying pathological mechanism of its development and the relative contributions of brain function to this process are poorly understood. Objective To compare the fractional anisotropy (FA) values of PD patients with EDS and those without EDS, and to investigate the mechanism of EDS in this disease. Methods Eleven patients with PD with EDS, 26 patients with PD without EDS and 10 controls participated in this study. Patients with an ESS (Epworth Sleepiness Scale) score ≥10 were defined as having EDS. The FA values of 5 regions of interest (ROI) including the fornix were compared between the three groups. Results There were significant reductions in FA values of the fornix fiber in patients with EDS. ESS scores had significant correlation with FA values of the fornix. Conclusions Our study is the first to find the fornix fiber degeneration in PD patients with EDS. These results indicate that fornix dysfunction may have some correlations with EDS in PD.

Pathophysiology of hallucinations in Parkinson’s disease is poorly understood. This study investigated relationships between visual hallucinations and visual acuity. Twenty-six consecutive patients with Parkinson’s disease participated in this study. Patients were divided into two groups: patients with visual hallucinations (VH group) and those without visual hallucinations (no-VH group). Unaided and corrected eyesight was evaluated in all patients, and if frequent use of prescription glasses or contact lenses was involved, eyesight using these lenses was also measured as the patient’s own best eyesight. If a patient did not use prescription glasses or contact lenses, the patient’s own best eyesight was defined as the unaided eyesight. Multivariate regression analysis demonstrated that agonist use and best eyesight were different after the backward elimination method. Visual hallucinations were closely related not to uncorrected eyesight or unaided eyesight but to the patient’s best eyesight. It is suggested that impaired visual acuity is a risk factor for visual hallucinations.

Objective – To compare brain perfusion image using three-dimensional stereotactic surface projection (3D-SSP) analysis of N-isopropyl-p-123I iodoamphetamine (123I-IMP) single photon emission computed tomography (SPECT) between patients with Parkinson's disease with orthostatic hypotension and those without orthostatic hypotension. Materials and methods – Fifteen patients with Parkinson's disease and orthostatic hypotension and 13 patients with Parkinson's disease without orthostatic hypotension were studied. We compared brain perfusion image between the two groups by 3D-SSP. Results – Bilateral anterior cingulate gyrus perfusion of the patients with orthostatic hypotension was significantly decreased compared to that of the patients without orthostatic hypotension. Conclusions – The disorder of anterior cingulate gyrus may participate in the autonomic failure in Parkinson's disease.

Background: Decreased cardiac metaiodobenzylguanidine (MIBG) uptake was reported in Parkinson’s disease and this contributes to the differential diagnosis between Parkinson’s disease and other forms of parkinsonism such as multiple system atrophy. However, decreased MIBG uptake of the thyroid has not been demonstrated. Objective: To compare MIBG uptake of the thyroid among Parkinson’s disease, multiple system atrophy and controls. Methods: Twenty-six patients with Parkinson’s disease, 11 patients with multiple system atrophy and 14 controls were examined in this study. Planar images were taken 15 minutes (early images) and 3 hours (late images) after intravenous injection of 111 MBq 123 I-MIBG. Results: MIBG uptake of the thyroid on early images decreased significantly in Parkinson’s disease compared to controls (p < 0.0001) and multiple system atrophy (p = 0.018). MIBG uptake of the thyroid on early images decreased significantly also in multiple system atrophy compared to controls (p = 0.027). On late images, thyroid uptake differed significantly only between Parkinson’s disease and controls (p = 0.010). Conclusions: Our study is the first to demonstrate decreased MIBG uptake of the thyroid in Parkinson’s disease. Sympathetic nervous denervation of Parkinson’s disease occurred not only in the heart but also in the thyroid.

Objective: The pathophysiology of hallucinations in Parkinson disease is poorly understood. This study investigated the relation between visual hallucination and visual evoked potentials (VEPs) in Parkinson disease. Methods: Nineteen patients with Parkinson disease were studied. The authors divided patients into 2 groups: patients with visual hallucinations (VH group) and those without visual hallucinations (no-VH group). VEPs using a checkerboard stimulus were recorded under a drug-free state. Results: On multivariate regression analysis, only the average P100 latency was selected and remained significant after the backward elimination method. Conclusion: The authors demonstrated a close association between visual hallucinations and elongated VEP latency in Parkinson disease. VEPs may become one of the predictors for visual hallucination.

Background Intellectual deterioration occurs in 10-40% of patients with Parkinson’s disease. However, there are many conflicting studies on its relation with brain perfusion and the nature of this dementing process remains controversial.Objective To compare cortical perfusion by SPECT using 123I-IMP between Parkinson’s disease patients with dementia and those without dementia and to investigate the correlation between dementia in Parkinson’s disease and brain perfusion in various areas.Methods Fifty-two cases of Parkinson’s disease and 10 control cases were studied. The Parkinson’s disease with dementia group included 30 cases and the Parkinson’s disease without dementia group included 22 cases.,Results By multiple logistic regression method, we demonstrated significant hypoperfusion in the occipital cortex in Parkinson’s disease with dementia.Conclusions The cause of dementia in Parkinson’s disease may vary. We demonstrated that occipital hypoperfusion was closely correlated to dementia in Parkinson’s disease compared to frontal, parietal and temporal perfusion.

In recent years, considerable effort has been devoted to the development of a fish model for Parkinson’s disease (PD) to examine the pathological mechanisms of neurodegeneration. To effectively evaluate PD pathology, the ability to accurately and reliably count dopaminergic neurons is important. However, there is currently no such standardized method. Due to the relatively small number of dopaminergic neurons in fish, stereological estimation would not be suitable. In addition, serial sectioning requires proficiency to not lose any sections, and it permits double counting due to the large size of some of the dopaminergic neurons. In this study, we report an optimized protocol for staining dopaminergic neurons in zebrafish and provide a reliable counting method. Finally, using our optimized protocol, we confirmed that administration of 6-hydroxydopamine (a neurotoxin) or the deletion of the PINK1 gene (one of the causative genes of familiar PD) in zebrafish caused significant reduction in the number of dopaminergic and noradrenergic neurons. In summary, this method will serve as an important tool for the appropriate evaluation and establishment of fish PD models.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by selective dopaminergic cell loss in the substantia nigra, but its pathogenesis remains unclear. The recessively inherited familial PD genes PARK2 and PARK6 have been attributed to mutations in the Parkin and PTEN-induced kinase 1 (PINK1) genes, respectively. Recent reports suggest that PINK1 works upstream of Parkin in the same pathway to regulate mitochondrial dynamics and/or conduct autophagic clearance of damaged mitochondria. This phenomenon is preserved from Drosophila to human cell lines but has not been demonstrated in a vertebrate animal model in vivo. Here, we developed a medaka fish (Oryzias latipes) model that is deficient in Pink1 and Parkin. We found that despite the lack of a conspicuous phenotype in single mutants for Pink1 or Parkin, medaka that are deficient in both genes developed phenotypes similar to that of human PD: late-onset locomotor dysfunction, a decrease in dopamine levels and a selective degeneration of dopaminergic neurons. Further analysis also revealed defects in mitochondrial enzymatic activity as well as cell death. Consistently, PINK1 and Parkin double-deficient MEF showed a further decrease in mitochondrial membrane potential and mitochondrial complex I activity as well as apoptosis compared with single-deficient MEF. Interestingly, these mitochondrial abnormalities in Parkin-deficient MEF were compensated by exogenous PINK1, but not by disease-related mutants. These results suggest that PINK1 and Parkin work in a complementary way to protect dopaminergic neurons by maintaining mitochondrial function in vertebrates.

Autosomal recessively inherited, loss of function mutations in PTEN‐induced kinase 1 (PINK1) typically lead to early onset Parkinson disease (EOPD).1 The PINK1 protein is expressed ubiquitously throughout the human brain.2 Impaired mitochondrial function and morphology have been described in both human PINK1 mutant patient tissue and different PINK1‐deficient in vitro or in vivo model systems.3 PINK1 has also been implicated in oxidative stress defense, mitophagy, and the regulation of mitochondrial calcium homeostasis.3 However, the precise mechanisms leading to neuronal cell death remain unclear. Pink1 knockout mice do not develop loss of dopamine (DA) neurons in the substantia nigra and can therefore only be of limited use in investigating the mechanisms leading to neuronal cell death in human Parkinson disease (PD).6 Zebrafish are increasingly being used to model neurodegenerative diseases.7 As vertebrates, they are closer to humans than other genetically tractable model organisms such as Drosophila or Caenorhabditis elegans. Zebrafish embryos develop externally, are transparent, and have a well‐characterized DA nervous system.8 To date, investigations of the functional consequences of PD gene dysfunction in zebrafish have relied on the injection of morpholino antisense oligonucleotides (MOs).7 A major limitation of this approach is that MOs injected into the fertilized egg lose their effect within 3 to 5 days postfertilization, thus precluding investigation of the morphological, biochemical, or behavioral effects of gene dysfunction at larval and adult stages. In addition, morpholinos are frequently associated with nonspecific, off‐target effects.9 Previous studies using the MO strategy to investigate the effects of PINK1 deficiency in zebrafish have led to conflicting results.10 Using the targeting induced local lesions in genomes (TILLING) approach, we have now established a stable line carrying a premature stop mutation in the kinase‐encoding domain of pink1 (Y431*), the zebrafish orthologue of human PINK1. We provide confirmation that this mutation leads to inactivation of PINK1 catalytic activity and decreased mRNA stability. We further demonstrate that PINK1 deficiency in Danio rerio results in highly specific abnormalities in early development, which closely match the biochemical and morphological manifestations of the human disease, with persisting loss of dopaminergic neurons in adulthood and also persisting mitochondrial impairment. Genome‐wide gene expression studies identified upregulation of TigarB, the zebrafish homologue of the TP53‐induced glycolysis and apoptosis regulator (TIGAR).13 Remarkably, TigarB knockdown resulted in normalization of mitochondrial function and complete rescue of ascending dopaminergic neurons. Modulation of TIGAR‐related mechanisms may therefore be a promising novel strategy to develop disease‐modifying therapy for PINK1‐related PD.

Parkinson's disease (PD) is the second most common neurodegenerative disease. It is associated with the degeneration of dopaminergic neurons in the substantia nigra pars compacta and other areas of the brain. The pathology of PD is characterized by the accumulation of a cytoplasmic fibrillar structure, wherein alpha-synuclein is the major component. Most occurrences of PD were believed to be sporadic and associated with aging and environmental stress. However, there is now strong evidence for genetic inheritance in a small number of families. Although the pathological mechanisms of PD are still largely unknown, we present the major hypotheses and discuss the future directions of studies in this area.

Objective – Dementia occurs frequently in patients with Parkinson’s disease (PD). However, the nature of the dementing process remains controversial. We evaluated various cognitive functions in patients with PD, compared fractional anisotropy (FA) values between PD patients with and without dementia. Methods – Thirty-seven consecutive patients with Hoehn-Yahr stage III or IV PD participated in this study. Patients were divided into two groups: (i) PD with dementia group (PDD) and (ii) PD without dementia group (PDND). There were 11 PDD and 26 PDND cases. Ten controls were also studied. Results – The PDD group showed significant FA reduction in the bilateral posterior cingulate bundles compared with PDND. FA values in the left posterior cingulate bundle showed significant correlations with many cognitive parameters. Interpretation – Our results showed that the posterior cingulate areas play some important roles in the dementing process in PDD. However, as the pathological processes responsible for dementia in PD patients may be multifaceted, further studies are necessary.

Introduction – It is generally assumed that executive dysfunctions in Parkinson's disease (PD) are caused by degeneration of the basal ganglia or frontal cortex or both. However, there have been few studies investigating the relationship between executive dysfunctions and cerebral pathological change. The objective of this study was to evaluate various cognitive functions in non-demented patients with PD, and to compare the fractional anisotropy (FA) values of PD patients with and without executive dysfunction. Materials and Methods – Twenty-one consecutive non-demented patients with PD were enrolled in this study. Patients were divided into two groups on the basis of their Wisconsin Card Sorting Test score. Results – There was significant FA reduction in the left parietal white matter in the group in which the number of categories achieved was ≤2 relative to the group that achieved >2. Conclusion – Accumulating evidence suggests that conventional ‘frontal’ tasks correlate with both frontal lobe and parietal lobe function, and we suggest that pathological changes in the left parietal lobe may cause, in part, disturbances in executive tasks in PD.

We examined patients with and without auditory hallucinations, using n-isopropyl-p-[123I]iodoamphetamine single photon emission computed tomographic imaging. We assessed verbal hallucinations in the present study: patients with nonverbal auditory hallucinations were excluded. A total of 11 patients with verbal and visual hallucinations and 17 patients with visual hallucinations only were enrolled. Patients with both verbal and visual hallucinations revealed significant hypoperfusion in the bilateral prefrontal cortex and right superior temporal gyrus compared to patients with visual hallucinations only. There were no significant hyperperfusion in patients with verbal plus visual hallucinations. These results may support the release hallucination theory in verbal hallucinations of Parkinson's disease, although another explanations may be more appropriate and further studies are required.

STUDY OBJECTIVES The underlying pathologic mechanism of excessive daytime sleepiness (EDS) in Parkinson disease and the relative contributions of brain function to this process are poorly understood. We compared brain perfusion images between patients with Parkinson disease and EDS and those without EDS using n-isopropyl-p-1231 iodoamphetamine single photon emission computed tomography. DESIGN Clinical study. SETTING Sumitomo Hospital. PATIENTS Thirteen patients with Parkinson disease with EDS (EDS group) and 27 patients with Parkinson disease without EDS (no-EDS group) were studied. Whether or not each case had EDS was determined according to the response to the Epworth Sleepiness Scale: patients with an Epworth Sleepiness Scale score > or = 10 were included in the EDS group, and patients with an Epworth Sleepiness Scale score < or = 9 were included in the no-EDS group. MEASUREMENTS AND RESULTS There were significant hypoperfusions in the left parietal and temporal association cortex in the EDS group. In the multivariable logistic regression model, attention and decreased regional cerebral blood flow of the left parietal association cortex and right caudate and increased regional cerebral blood flow of the right thalamus were the independent and significant factors. CONCLUSIONS The cortical hypofunction relative to hyperfunction of the brain stem may relate to EDS in Parkinson disease. This is the first imaging study about EDS in Parkinson disease, and further studies are required.

Background Nature of the dementing process in Parkinson's disease, and particularly its relationship with Alzheimer's disease, diffuse Lewy body disease or frontal dementia remains controversial. Objective We hypothesize that origins of dementia in Parkinson's disease are heterogeneous, so we compared cortical regional cerebral blood flow (rCBF) between Parkinson's disease patients with and without dementia. Patients Forty consecutive patients with Hoehn-Yahr stage III or IV Parkinson's disease were used (13 patients had dementia (PDD group), and 27 patients had no dementia (PDND group)). Results There were significant rCBF reductions in the left parietal association cortex and left frontal association cortex in PDD. Multiple logistic regression analysis demonstrated that only rCBF of the left frontal association cortex was significant. PDD patients were divided into three groups according to rCBF patterns: frontal hypoperfusion group, Alzheimer's disease-like group, and diffuse Lewy body disease-like group. Conclusions Controversial study results involving PDD patients may be mainly due to heterogeneity in dementing processes in Parkinson's disease.

Depression is common in individuals with Parkinson's disease. However, the pathophysiology of depression in Parkinson's disease remains obscure. Here we compared brain perfusion images of Parkinson's disease patients with and without depression to investigate correlations between depression and brain perfusion images in Parkinson's disease. We divided 40 consecutive patients with Parkinson's disease into two groups: patients with minor depression (n = 22) and patients without depression (n = 18). We then compared brain perfusion images between the two groups. As a result, hypoperfusion of the left superior and inferior frontal gyrus was demonstrated in depressed patients. These results were partially in agreement with previous studies on de novo and parkinsonian major depression. We could not conclude on whether pathophysiological mechanisms differed between de novo depression and depression with Parkinson's disease, and between major and minor depressions.

The objective was to compare brain perfusion image using 3-dimensional stereotactic surface projection analysis of N-isopropyl-p-123I iodoamphetamine single photon emission computed tomography between Parkinson’s disease patients with a high frontal assessment battery score and those with a low frontal assessment battery score. Thirty nondemented patients with Parkinson’s disease were studied. Patients were divided into 2 groups: a high-scoring group whose frontal assessment battery score was 12 or more and a low-scoring group whose frontal assessment battery score was 11 or less. The high-scoring group included 21 patients, and the low-scoring group included 9 patients. They underwent N-isopropyl-p-123I iodoamphetamine single photon emission computed tomography, and we analyzed the data by the 3-dimensional stereotactic surface projection method. Results showed that left inferior parietal lobule and left supramarginal gyrus perfusion of the low-scoring group were significantly decreased compared with the high-scoring group. It is concluded that_patients with Parkinson’s disease may have frontal lobe dysfunction, but the decreased frontal assessment battery score may be caused not by progressed frontal lobe dysfunction but by parietal lobe dysfunction added to their preexisting frontal lobe impairment.

Objectives To compare MIBG (metaiodobenzylguanidine) uptake between Parkinson's disease patients with and without autonomic symptoms to investigate meanings of MIBG scintigraphy and correlations between autonomic symptoms and MIBG uptake. Methods Forty consecutive patients with Hoehn–Yahr III or IV Parkinson's disease and 12 controls were enrolled. We compared cardiac MIBG uptake between patients with and without orthostatic hypotension. Similar comparisons were performed for constipation and bladder dysfunction. Results MIBG uptake did not significantly correlate with age, disease duration, Hoehn–Yahr stage, Unified Parkinson's Disease Rating Scale (UPDRS) motor score or levodopa equivalent daily doses. There were no significant correlations between orthostatic hypotension/constipation and cardiac MIBG uptake. Only bladder symptoms significantly correlated with MIBG uptake. Conclusion Meanings of MIBG uptake abnormalities in Parkinson's disease and relationship between MIBG uptake and clinical parameters remain to be resolved in future studies.

Gait disturbance is a cardinal symptom in patients with Parkinson's disease. Among the gait disturbances, freezing of gait is a unique and troublesome symptom, but its mechanism is unclear. We compared brain perfusion images using three-dimensional stereotactic surface projection analysis of N-isopropyl-p-123I iodoamphetamine single photon emission computed tomography between Parkinson's disease patients with freezing of gait and those without. Twenty-four cases (freezing of gait group) with Parkinson's disease with freezing of gait, and 31 Hoehn and Yahr stage-matched cases (no freezing of gait group) with Parkinson's disease without freezing of gait were studied. Bilateral Brodmann area 11 perfusion of the freezing of gait group decreased significantly compared to that of the no freezing of gait group. The Brodmann area 11 may play important roles in gait, and impairment in this region may have a close relationship with freezing of gait in Parkinson's disease. © 2005 Movement Disorder Society

We compared MIBG uptake at various parts of the body in controls and patients with Parkinson's disease and multiple system atrophy. In the heart, MIBG uptake in Parkinson's disease (early H/M: 1.668+/-0.325, late H/M: 1.500+/-0.402) was less than that in multiple system atrophy (early H/M: 2.395+/-0.186, late H/M: 2.530+/-0.391) and controls (early H/M: 2.635+/-0.508, late H/M: 2.575+/-0.635) (early: P0.0001, late: P0.0001). There were no significant differences in uptake by the lung, thyroid, or liver in the three groups. Only on early images, uptake in the shoulder in multiple system atrophy (early S/M: 0.473+/-0.78) and Parkinson's disease (early S/M: 0.470+/-0.710) was decreased compared to that in controls (early S/M: 0.560+/-0.118) (P=0.0252). MIBG is reported to be taken up in the terminal part of sympathetic nerves and demonstrates sympathetic nerve activity, especially on late images. The cause of differences between the heart and other parts of the body remains unknown. We consider the following possibilities: (a) differences in the sympathetic nervous system between Parkinson's disease and multiple system atrophy are more subtle in organs other than the heart; (b) the cause of MIBG uptake reduction by the heart in Parkinson's disease involves factors in addition to sympathetic nervous system damage; and (c) MIBG uptake by organs other than the heart involves not only the sympathetic nervous system but also non-neuronal components. In conclusion, MIBG uptake by organs other than the heart cannot differentiate Parkinson's disease from multiple system atrophy at present.

Background The patterns of regional cerebral blood flow in Parkinson's disease and multiple system atrophy remain inconsistent. Objectives To compare brain perfusion images of 123 I-IMP SPECT between Parkinson's disease, multiple system atrophy with predominant parkinsonian features (MSA-P) and controls. Methods Eighty-two patients with Parkinson's disease, 10 patients with MSA-P and 14 controls were studied. We performed 3D-SSP and volume of interest analysis using 123 I-IMP scintigraphy. Results Occipital perfusion of MSA-P increased compared to that of Parkinson's disease and perfusion in the cerebellum and primary sensorimotor cortex of Parkinson's disease increased compared to that of MSA-P. Perfusion in the putamen of MSA-P decreased compared to that of Parkinson's disease. Conclusion Our study demonstrated perfusion differences in 123 I-IMP SPECT between the two diseases.

We report two cases of Parkinson's disease in which visual hallucinations disappeared after cataract surgery. Patient 1 was a 72-year-old woman with Parkinson's disease, visual hallucinations and musical hallucinations. Patient 2 was a 77-year-old woman with Parkinson's disease and visual hallucinations. Both patients had severe bilateral cataracts. Though it was difficult to control their visual hallucinations with medication only, cataract surgery made them disappeared quickly. The visual hallucinations of Parkinson's disease are similar to those of Charles Bonnet syndrome. For example, both hallucinations often happen in dim light, at night and when patients are awake with eyes open. Though there have been many reports describing visual hallucinations in Parkinson's disease, there have been few reports discussing the relation between these hallucinations and impaired visual acuity. Similar to the hallucinations of Charles Bonnet syndrome, impaired visual acuity should be related to the visual hallucinations of Parkinson's disease. When Parkinson's disease, visual hallucinations and severe cataract coexist, visual hallucinations may disappear after cataract surgery.