Renpei Sengoku

Incidence and Extent of Lewy Body-Related α-Synucleinopathy in Aging Human Olfactory Bulb

We investigated the incidence and extent of Lewy body (LB)-related &agr;-synucleinopathy (LBAS) in the olfactory bulb (OB) in 320 consecutive autopsy patients from a general geriatric hospital (mean age, 81.5 ± 8.5 years). Paraffin sections were immunostained with anti-phosphorylated &agr;-synuclein, tyrosine hydroxylase, phosphorylated tau, and amyloid &bgr; antibodies. LBAS was found in 102 patients (31.9%) in the central nervous system, including the spinal cord; the OB was involved in 85 (26.6%). Among these 85 patients, 2 had LBAS only in the anterior olfactory nucleus, 14 in the peripheral OB only, and 69 in both areas. In 5 patients, Lewy bodies were found only in the OB by hematoxylin and eosin stain; 3 of these patients had Alzheimer disease, and all had LBAS. Very few tyrosine hydroxylase-immunoreactive periglomerular cells exhibited LBAS. All 35 LBAS patients with pigmentation loss in the substantia nigra had LBAS in the OB. LBAS in the amygdala was more strongly correlated with LBAS in the anterior olfactory nucleus than with that in the OB periphery. LBAS did not correlate with systemic tauopathy or amyloid &bgr; amyloidosis. These results indicate a high incidence of LBAS in the aging human OB; they also suggest that LBAS extends from the periphery to the anterior olfactory nucleus and results in clinical manifestations of LB disease.

Analysis of the adrenal gland is useful for evaluating pathology of the peripheral autonomic nervous system in lewy body disease.

Abstract Lewy body disease is defined as Lewy body-related neuronal degeneration involving the nigrostriatal system, limbic-neocortical system, and peripheral autonomic nervous system (PANS). We investigated whether the adrenal gland, which is evolutionarily related to sympathetic ganglia and is routinely examined in general autopsy, could be used to assess pathology of the PANS in Lewy body disease. Brains, spinal cords, and adrenal glands from 783 consecutive autopsy cases from a general geriatric hospital were examined immunohistochemically with antiphosphorylated &agr;-synuclein antibodies and routine staining. Parkinson disease (PD) with dementia and dementia with Lewy bodies (DLB) were defined using 1996 Consensus Guidelines for DLB and the secondary Lewy body-related &agr;-synucleinopathy or amygdala variants using previously established criteria. Lewy body-related &agr;-synucleinopathy was found in 207 (26.4%) of 783 cases, with 1 case solely in the adrenal gland. In all 18 PD cases with or without dementia and in 33 of 38 DLB cases, the adrenal gland was involved, but it was spared in all cases of amygdala variants. Our results indicate that the adrenal gland can provide useful information for evaluation of the PANS in Lewy body disease.

Preserved myocardial [123I] metaiodobenzylguanidine uptake in autosomal recessive juvenile parkinsonism : first case report

A decrease in myocardial uptake of iodine‐123–labeled metaiodobenzylguanidine (123I‐MIBG) has been reported in idiopathic Parkinsons disease (PD) using 123I‐MIBG myocardial scintigraphy. However, the patient with autosomal recessive juvenile parkinsonism (AR‐JP), caused by the parkin gene, presented here showed normal 123I‐MIBG myocardial uptake, suggesting that AR‐JP is a distinct disease entity from PD. Although the clinical features of AR‐JP are sometimes quite similar to those of late‐onset idiopathic PD, 123I‐MIBG myocardial scintigraphy may be a powerful tool to differentiate PD from other parkinsonian syndromes, including AR‐JP.

Sudden death in Parkinson's disease: A retrospective autopsy study

The aim of this paper is to reveal the causes of death and to verify sudden death of Parkinsons disease (PD) in an autopsy study. We reviewed the clinical data and the causes of death in 16 PD patients who had postmortem examinations. Prior to autopsy, nine patients died of known causes: five patients died of aspiration pneumonia, two of myocardial infarction, one of asphyxia, and one of dilated cardiomyopathy. Autopsy confirmed that the putative causes of death were compatible with the pathological ones. The remaining seven patients died suddenly of unknown causes. Autopsy revealed that the causes of death were asphyxia in two patients and perforation of a duodenal ulcer in one patient. Autopsy did not determine the causes of unknown death in the remaining four patients. Consequently, autopsy revealed that eight patients died of swallowing problems such as aspiration pneumonia and asphyxia, four of sudden death, three of cardiac problems, and one of a gastrointestinal problem. Although there was a bias that all patients had a postmortem examination, our study revealed that several PD patients died of sudden death without any satisfactory causes of death determined even by autopsy. Therefore, we propose that a non-negligible number of PD patients die of sudden death.

Findings of segmental zoster paresis on MRI

A 72-year-old man developed herpes zoster rash involving the left C3-5 dermatomes. The patient was receiving treatment for myasthenia gravis, which was very well controlled with oral prednisolone (25u2005mg). There was no muscle weakness or other complications on examination in the outpatient clinic. Ten days before the onset of rash, he noticed weakness of the left arm. On admission, the left arm weakness was limited to muscles controlled by the C5 myelomere. He had no clinical symptoms of myelitis, but the T2-weighted magnetic …

Olfactory function combined with morphology distinguishes Parkinson's disease

OBJECTIVEnThis study aimed to examine whether the volume of the olfactory bulbs and tracts (OB & T) on magnetic resonance imaging (MRI) is useful for differentiating Parkinsons disease (PD) from PD-related disorders.nnnMETHODSnThe study group comprised 13 patients with PD, 11 with multiple system atrophy (MSA), five with progressive supranuclear palsy, and five with corticobasal degeneration (PSP/CBD). All patients were evaluated using the odor stick identification test for Japanese (OSIT-J), (123)I-meta-iodobenzylguanidine (MIBG) scintigraphy, and brain MRI. OB & T areas on 1-mm-thick coronal images were measured and summed for volumes. We examined relationships between olfactory function and volume, and cardiovascular dysautonomia. We defined the cut-off values for OSIT-J score or MIBG uptake and OB & T volume to discriminate PD from PD-related disorders and calculated the proportional rate of PD in four categorized groups.nnnRESULTSnOB & T volume was smaller in PD than in MSA or PSP/CBD (p < 0.05 each). The cut-off for detecting PD patients was OSIT-J score <8, heart/mediastinum ratio <1.6, and OB & T volume <270 mm(3). In the group with OSIT-J score <8 and OB & T volume <270 mm(3), the proportion of PD patients among all patients with PD-related disorders was 91%. The rate of probable PD gradually increased as OSIT-J score and OB & T volume decreased (p < 0.001).nnnCONCLUSIONSnAlthough preliminary, these data obtained from a combined morphological and functional evaluation of OB or cardiovascular dysautonomia could be useful for further differential of PD and other PD-related disorders.

Stroke patients with cerebral microbleeds on MRI scans have arteriolosclerosis as well as systemic atherosclerosis.

Cerebral microbleeds (CMBs) are recognized as a manifestation of arteriolosclerosis in cerebral small vessels. However, little is known regarding whether stroke patients with CMBs often have systemic atherosclerosis. The aim of the present study was to elucidate this issue using the cardio–ankle vascular index (CAVI), a new index of systemic atherosclerosis, in acute ischemic stroke patients. We prospectively studied 105 patients (71 males, median age=70.0 years) with acute ischemic stroke. All of the patients were examined using T2*-weighted gradient echo magnetic resonance imaging (MRI) to look for and assess the CMBs and using fluid-attenuated inversion recovery to evaluate white matter hyperintensity (WMH). We assigned the patients into CMB and non-CMB groups and compared the clinical characteristics of these groups. The factors associated with CMBs were investigated using multivariate logistic regression analysis. T2*-weighted gradient echo MRI revealed CMBs in 47 patients (44.8%) and no CMBs in 58 patients (55.2%). The CAVI was significantly higher in the CMBs group (10.5 vs. 8.6, P<0.001). In the multivariate logistic regression analysis, CAVI per one point increase (odds ratio (OR), 1.50; 95% confidence interval (CI), 1.12–2.00; P=0.006), advanced WMH (OR, 4.78; 95% CI, 1.55–14.74; P=0.006) and impaired kidney function (OR, 3.31; 95% CI, 1.16–9.81; P=0.031) were independent factors associated with the presence of CMBs. A high CAVI was independently associated with CMBs in patients with acute ischemic stroke. Our results indicated that ischemic stroke patients with CMBs may have cerebral arteriolosclerosis as well as systemic atherosclerosis.

Homovanillic acid and 5-hydroxyindole acetic acid as biomarkers for dementia with Lewy bodies and coincident Alzheimer’s disease: An autopsy-confirmed study

Dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) are the two most common causes of dementia. Both pathologies often coexist, and AD patients with concomitant neocortical LB pathology (referred to as the Lewy body variant of AD) generally show faster cognitive decline and accelerated mortality relative to patients with pure AD. Thus, discriminating among patients with DLB, AD, and coincident DLB and AD is important in clinical practice. We examined levels of homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), tau, phosphorylated tau (p-tau), and beta-amyloid (Aβ) 1–42 in cerebrospinal fluid (CSF) to evaluate their viability as biomarkers to discriminate among different forms of dementia. We obtained a total of 3498 CSF samples from patients admitted to our hospital during the period from 1996 to 2015. Of these patients, we were able to carry out a brain autopsy in 94 cases. Finally, 78 neuropathologically diagnosed cases (10 AD, six DLB, five DLB with AD, five controls without neurological diseases, and 52 cases with other neurological diseases) were studied. CSF levels of HVA and 5-HIAA were consistently decreased in pathologically advanced Lewy body disorder (LBD; Braak LB stages >3) compared with pathologically incipient LBD (Braak LB stages <2). These results suggest that if an individual has LB pathology in the central nervous system, CSF levels of HVA and 5-HIAA may decrease after the onset of clinical symptoms. In addition, CSF levels of HVA and 5-HIAA decreased with LB pathology, and were especially low in cases of DLB and DLB with AD. Furthermore, the combination of HVA, 5-HIAA, and brain specific proteins t-tau, p-tau, and Aβ 1–42 in CSF were useful for discriminating among DLB, DLB with AD, and AD with high diagnostic accuracy.

Anhedonia and its correlation with clinical aspects in Parkinson's disease

Anhedonia is one of the non-motor symptoms observed in the Parkinsons disease (PD). However, there is no clear relationship between anhedonia and its correlation with other symptoms of PD. The aim of this study is to evaluate the characteristics of anhedonia and its correlation with clinical aspects of PD in a relatively large cohort. We enrolled 318 patients with PD and 62 control subjects for this study. Patients and subjects were tested using the Snaith-Hamilton Pleasure Scale Japanese version and the Beck Depression Inventory 2nd edition for the assessment of anhedonia and depression. We also investigated the correlation among clinical aspects of PD, anhedonia, and depression in patients with PD. The Snaith-Hamilton Pleasure Scale Japanese version and the Beck Depression Inventory 2nd edition scores were significantly higher in patients with PD than in control subjects (p=0.03 and p=0.0006, respectively). All PD patients with anhedonia had a significantly higher score on the unified Parkinsons disease rating scale (UPDRS) parts I and II compared to PD patients without anhedonia. Additionally, all PD patients with depression scored significantly higher on UPDRS part I-IV than PD patients without depression. The patients with anhedonia and without depression had mild motor severity and their treatment was relatively low dosage. These results suggest that anhedonia and depression are slightly linked, but not the same. PD patients with only anhedonia may be closely linked apathy found in untreated early stages of PD.

Rhinorrhea in Parkinson's disease: A consecutive multicenter study in Japan

Recent reports suggest that rhinorrhea, defined as the presence of a runny nose unrelated to respiratory infections, allergies, or sinus problems, occurs more frequently among patients with Parkinsons disease (PD) than among healthy controls. We conducted a questionnaire survey in a multicenter study throughout Japan and compared the frequency of rhinorrhea between 231 PD and 187 normal control (NC) subjects. After excluding patients with rhinitis or paranasal sinusitis, a total of 159 PD and 59 NC subjects were included in our analysis. Rhinorrhea occurred more frequently in PD patients than NC subjects (33.3% vs. 11.9%; P=0.01). Among PD patients, rhinorrhea was more common in men than women (P=0.005). Rhinorrhea was not correlated with disease duration, modified Hoehn and Yahr score, disease type (akinesia rigidity vs. tremor dominant), or cardiac sympathetic function (evaluated by (123)I-metaiodobenzylguanidine uptake). To our knowledge, this is the first multicenter study on the frequency of PD-related rhinorrhea in Asian countries.