Metaiodobenzylguanidine (MIBG) is an analog of norepinephrine that accumulates in sympathetic nerve endings soon after intravenous administration. The degree of accumulation reflects the uptake, storage and release of transmitters by noradrenergic neurons. Myocardial imaging with ¹²³I labeled MIBG ( ¹²³I-MIBG) can be used to estimate the extent of local myocardial sympathetic nerve damage, which has been widely used in the diagnosis and treatment of various heart diseases. In recent years, numerous studies have been carried out on the application of ¹²³I-MIBG in the diagnosis of degenerative diseases of the nervous system (such as Parkinson's disease and dementia of Lewy body), and have made some achievements. The purpose of this review is to summarize the current clinical application of ¹²³I-MIBG myocardial imaging in the diagnosis of dementia with Lewy bodies, the problems in imaging technology and the possible research directions in the future, so as to provide valuable reference information for clinicians to reasonably and accurately apply this technology in the early diagnosis and discrimination of dementia.
Humans ; Lewy Bodies ; 3-Iodobenzylguanidine ; Lewy Body Disease/diagnostic imaging* ; Iodine Radioisotopes

Alzheimer Disease ; China ; Consensus ; Humans ; Lewy Bodies ; Lewy Body Disease/drug therapy*

OBJECTIVES: Parkinson disease (PD) is frequently associated with olfactory disorder at early stage, which is caused by deposition of Lewy bodies emerging from the olfactory bulb to higher olfactory centers. Early detection of olfactory disorder in the patients with PD may lead to the early diagnosis and treatment for this refractory disease. METHODS: Visual analog scale (VAS), Jet Stream Olfactometry, and Japanese smell identification test, Open Essence (OE), were carried out on 39 patients with PD. Thirty-one patients with postviral olfactory disorder (PVOD), which was caused by the olfactory mucosal dysfunction, were also enrolled in this study as control. RESULTS: There were no significant differences in detection thresholds (2.2 vs. 1.4, P=0.13), recognition thresholds (3.9 vs. 3.5, P=0.39) and OE (4.8 vs. 4.2, P=0.47) between PVOD and PD, while VAS scores of PVOD and PD were significantly different (2.0 and 6.2, P<0.01). In OE, significant differences were observed in the accuracy rates of menthol (68% vs. 44%, P=0.04) and Indian ink (42% vs. 15%, P=0.01) between PVOD and PD. Of particular interest, patients with PVOD tended to select “no detectable,” while patients with PD tended to select wrong alternative other than “no smell detected.” CONCLUSION: Discrepancy between VAS and OE, and high selected rates of wrong alternative other than “undetectable” in OE might be significant signs of olfactory dysfunction associated with PD.
Asian Continental Ancestry Group ; Early Diagnosis ; Humans ; Ink ; Lewy Bodies ; Menthol ; Olfactometry ; Olfactory Bulb ; Parkinson Disease ; Rivers ; Smell ; Visual Analog Scale

Parkinson’s disease (PD) is one of the late-onset neurodegenerative movement disorder. Major pathological markers of PD include progressive loss of dopaminergic neurons, Lewy body formation, genetic mutations, and environmental factors. Epigenetic regulation of specific gene expression via impaired histone acetylation is associated with neuronal dysfunction in various neurodegenerative diseases. In this study, we hypothesized that histone deacetylase (HDAC) inhibitor, valproic acid (VPA), can improve motor function by enhancing cell survival in PD genetic model mice with LRRK2 R1441G mutation. To address this question, we administered VPA in LRRK2 R1441G transgenic mice to determine whether VPA affects 1) histone acetylation and HDAC expression, 2) dopaminergic neuron survival, 3) inflammatory responses, 4) motor or non-motor symptoms. As results, VPA administration increased histone acetylation level and the number of tyrosine hydroxylase (TH) positive neurons in substantia nigra of LRRK2 R1441G mice. VPA reduced iba-1 positive activated microglia and the mRNA levels of pro-inflammatory marker genes in LRRK2 R1441G mice. In addition, VPA induced the improvement of PD-like motor and non-motor behavior in LRRK2 R1441G mice. These data suggest that the inhibition of HDAC can be further studied as potential future therapeutics for PD.
Acetylation ; Animals ; Cell Survival ; Dopaminergic Neurons ; Epigenomics ; Gene Expression ; Histone Deacetylases ; Histones ; Lewy Bodies ; Mice ; Mice, Transgenic ; Microglia ; Models, Genetic ; Movement Disorders ; Neurodegenerative Diseases ; Neurons ; Neuroprotection ; RNA, Messenger ; Substantia Nigra ; Tyrosine 3-Monooxygenase ; Valproic Acid

Synucleinopathies are neurodegenerative disorders characterized by the progressive accumulation of α-synuclein (α-syn) in neurons and glia and include Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In this review, we consolidate our key findings and recent studies concerning the role of Toll-like receptor 2 (TLR2), a pattern recognition innate immune receptor, in the pathogenesis of synucleinopathies. First, we address the pathological interaction of α-syn with microglial TLR2 and its neurotoxic inflammatory effects. Then, we show that neuronal TLR2 activation not only induces abnormal α-syn accumulation by impairing autophagy, but also modulates α-syn transmission. Finally, we demonstrate that administration of a TLR2 functional inhibitor improves the neuropathology and behavioral deficits of a synucleinopathy mouse model. Altogether, we present TLR2 modulation as a promising immunotherapy for synucleinopathies.
Animals ; Autophagy ; Dementia ; Immunotherapy ; Lewy Bodies ; Mice ; Neurodegenerative Diseases ; Neuroglia ; Neurons ; Neuropathology ; Parkinson Disease ; Toll-Like Receptor 2 ; Toll-Like Receptors

OBJECTIVE: To clarify the specificity of the ‘hot cross bun’ sign (HCBS) for multiple system atrophy (MSA) in adult cerebellar ataxia or parkinsonism. METHODS: The radiologic information systems at an academic center and affiliated veterans' hospital were queried using the keywords ‘hot cross bun,’ ‘pontocerebellar,’ ‘cruciate,’ ‘cruciform,’ ‘MSA,’ ‘multiple system atrophy,’ and ‘multisystem atrophy.’ Scans were reviewed by a neurologist and neuroradiologist to identify the HCBS. Subjects with the HCBS were reviewed by 2 neurologists to identify the most likely etiology of the patient's neurologic symptoms. RESULTS: Eleven cases were identified. Etiologies included MSA (4 probable, 2 possible), hereditary cerebellar ataxia (3/11), probable dementia with Lewy bodies (1/11), and uncertain despite autopsy (1/11). CONCLUSION: MSA was the most common etiology. However, 5 of the 11 patients did not have MSA. The most common alternate etiology was an undefined hereditary cerebellar ataxia (3/11).
Adult ; Autopsy ; Cerebellar Ataxia ; Dementia ; Hexachlorobenzene ; Humans ; Lewy Bodies ; Magnetic Resonance Imaging ; Multiple System Atrophy ; Neurologic Manifestations ; Olivopontocerebellar Atrophies ; Parkinsonian Disorders ; Radiology Information Systems ; Sensitivity and Specificity

The aggregation of α-synuclein (α-syn) has been implicated in the pathogenesis of many neurodegenerative disorders, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Postmortem analyses of α-syn pathology, especially that of PD, have suggested that aggregates progressively spread from a few discrete locations to wider brain regions. The neuron-to-neuron propagation of α-syn has been suggested to be the underlying mechanism by which aggregates spread throughout the brain. Many cellular and animal models has been created to study cell-to-cell propagation. Recently, it has been shown that a single injection of preformed fibrils (PFFs) made of recombinant α-syn proteins into various tissues and organs of many different animal species results in widespread α-syn pathology in the central nervous system (CNS). These PFF models have been extensively used to study the mechanism by which aggregates spread throughout the brain. Here, we review what we have learned from PFF models, describe the nature of PFFs and the neuropathological features, neurophysiological characteristics, and behavioral outcomes of the models.
alpha-Synuclein ; Animals ; Brain ; Central Nervous System ; Dementia ; Lewy Bodies ; Models, Animal ; Multiple System Atrophy ; Neurodegenerative Diseases ; Parkinson Disease ; Pathology

Dementia with Lewy bodies(DLB) is the second most common neurodegenerative disease. However, DLB might not be adequately diagnosed due to its variety of clinical symptoms. The authors present 65-year-old Mrs. A. who showed Parkinson's movement, cognitive decline, psychological symptoms, and autonomic dysfunction. According to the clinical features and biological markers in the recently revised DLB criteria, Mrs. A. was diagnosed with probable DLB. Differential diagnoses of delirium, Parkinson's dementia, and Alzheimer's dementia were discussed. Psychopharmacological treatments of antidepressants or anxiolytics caused intolerable side effects and showed little efficacy to Mrs. A. She experienced two episodes of hyponatremia during her one-year treatment. Recovery from neurological symptoms due to the first hyponatremia was time-consuming, and in the second, it was associated with changes in the level of consciousness despite relatively mild hyponatremia. A fall that occurred in the latter part of treatment triggered remarkable deterioration of DLB symptoms and daily life function. Prevention of falls is important for maintaining the quality of life of patients with DLB.
Accidental Falls ; Aged ; alpha-Synuclein ; Anti-Anxiety Agents ; Antidepressive Agents ; Biomarkers ; Consciousness ; Delirium ; Dementia ; Diagnosis ; Diagnosis, Differential ; Humans ; Hyponatremia ; Lewy Bodies ; Neurodegenerative Diseases ; Quality of Life

In recent years, several radiotracers that selectively bind to pathological tau proteins have been developed. Evidence is emerging that binding patterns of in vivo tau positron emission tomography (PET) studies in Alzheimer's disease (AD) patients closely resemble the distribution patterns of known neurofibrillary tangle pathology, with the extent of tracer binding reflecting the clinical and pathological progression of AD. In Lewy body diseases (LBD), tau PET imaging has clearly revealed cortical tau burden with a distribution pattern distinct from AD and increased cortical binding within the LBD spectrum. In progressive supranuclear palsy, the globus pallidus and midbrain have shown increased binding most prominently. Tau PET patterns in patients with corticobasal syndrome are characterized by asymmetrical uptake in the motor cortex and underlying white matter, as well as in the basal ganglia. Even in the patients with multiple system atrophy, which is basically a synucleinopathy, ¹⁸F-flortaucipir, a widely used tau PET tracer, also binds to the atrophic posterior putamen, possibly due to off-target binding. These distinct patterns of tau-selective radiotracer binding in the various degenerative parkinsonisms suggest its utility as a potential imaging biomarker for the differential diagnosis of parkinsonisms.
Alzheimer Disease ; Basal Ganglia ; Diagnosis, Differential ; Electrons ; Globus Pallidus ; Humans ; Lewy Bodies ; Mesencephalon ; Motor Cortex ; Multiple System Atrophy ; Neurofibrillary Tangles ; Parkinsonian Disorders ; Pathology ; Positron-Emission Tomography ; Putamen ; Supranuclear Palsy, Progressive ; tau Proteins ; White Matter

OBJECTIVE: Donepezil is used to improve cognitive impairment of dementia with Lewy bodies (DLB). Visuo-spatial dysfunction is a well-known symptom of DLB. Non-verbal Raven’s Colored Progressive Matrices (RCPM) were used to assess both visual perception and reasoning ability in DLB subjects treated with donepezil. METHODS: Twenty-one DLB patients (mean age, 78.7±4.5 years) were enrolled. RCPM assessment was performed at the time of starting donepezil and within one year after starting donepezil. RESULTS: There were significant improvements of RCPM in the total scores between one year donepezil treatment (p=0.013), in both Set A score (p=0.002) and Set AB score (p=0.015), but trend in the Set B score (p=0.083). CONCLUSION: Donepezil is useful for improving visuo-spatial impairment in DLB, but not for problem-solving impairment.
Cholinesterase Inhibitors ; Cognition Disorders ; Dementia* ; Humans ; Lewy Bodies* ; Lewy Body Disease ; Spatial Processing ; Visual Perception