Satoru Morimoto

Volume of Interest Analysis of Spatially Normalized PRESTO Imaging to Differentiate between Parkinson Disease and Atypical Parkinsonian Syndrome

Purpose: Various magnetic resonance imaging (MRI) techniques including T2*-weighted imaging, susceptibility-weighted imaging, and MR relaxometry had been performed to evaluate different patterns of brain iron depositions in Parkinsonian syndrome. The aim of the present study was to evaluate the diagnostic value of a volume of interest (VOI) analysis on the principles of echo shifting with a train of observations (PRESTO) imaging using the statistical parametric mapping (SPM) 8 and the WFU PickAtlas program for the diagnosis of Parkinsonian syndrome. Methods: Fifty subjects, including 13 with the Parkinsonian variant of multiple system atrophy (MSA-P), 12 with progressive supranuclear palsy (PSP), 12 with Parkinson’s disease (PD) and 13 controls were evaluated in this study. After the spatial normalization of PRESTO images on SPM8, the WFU PickAtlas program was performed to create target VOIs in the putamen, red nucleus, substantia nigra, subthalamic nucleus, and dentate nucleus. The signal intensity ratio (SIR) was calculated by normalizing the signal of each VOI to that of the cerebrospinal fluid space. These SIRs were used as determinants in receiver operating characteristic (ROC) analyses. Results: SIR of the putamen was significantly lower in MSA-P than in PSP (P = 0.0051) and controls (P = 0.0004). In contrast, SIR of the red nucleus was significantly lower in PSP than in MSA-P (P = 0.0003), PD (P = 0.0029), and controls (P = 0.0011). In ROC analyses, SIR of the putamen exhibited the highest areas under the curves (AUCs) of 0.83 (vs. PSP) and 0.91 (vs. controls) in the diagnosis of MSA-P. On the other hand, SIR of the red nucleus exhibited the highest AUCs of 0.87 (vs. MSA-P), 0.90 (vs. PD), and 0.89 (vs. controls) in the diagnosis of PSP. Conclusions: The VOI analysis based on spatially normalized PRESTO images may be useful for depicting hypointensity, indicative of abnormal iron depositions, of the putamen and red nucleus in the diagnosis of MSA-P and PSP.

The feasibility of white matter volume reduction analysis using SPM8 plus DARTEL for the diagnosis of patients with clinically diagnosed corticobasal syndrome and Richardson’s syndrome

Purpose Diagnosing corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) is often difficult due to the wide variety of symptoms and overlaps in the similar clinical courses and neurological findings. The purpose of this study was to evaluate the utility of white matter (WM) atrophy for the diagnosis of patients with clinically diagnosed CBD (corticobasal syndrome, CBS) and PSP (Richardson’s syndrome, RS). Methods We randomly divided the 3D T1-weighted MR images of 18 CBS patients, 33 RS patients, and 32 age-matched controls into two groups. We obtained segmented WM images in the first group using Voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD) based on statistical parametric mapping (SPM) 8 plus diffeomorphic anatomical registration through exponentiated Lie algebra. A target volume of interest (VOI) for disease-specific atrophy was subsequently determined in this group using SPM8 group analyses of WM atrophy between patients groups and controls. We then evaluated the utility of these VOIs for diagnosing CBS and RS patients in the second group. Z score values in these VOIs were used as the determinant in receiver operating characteristic (ROC) analyses. Results Specific target VOIs were determined in the bilateral frontal subcortical WM for CBS and in the midbrain tegmentum for RS. In ROC analyses, the target VOIs of CBS and RS compared to those of controls exhibited an area under curve (AUC) of 0.99 and 0.84, respectively, which indicated an adequate diagnostic power. The VOI of CBS revealed a higher AUC than that of RS for differentiating between CBS and RS (AUC, 0.75 vs 0.53). Conclusions Bilateral frontal WM volume reduction demonstrated a higher power for differentiating CBS from RS. This VOI analysis is useful for clinically diagnosing CBS and RS.

Increased Oxidative Stress in Patients with Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex in the Kii Peninsula, Japan

Amyotrophic lateral sclerosis and Parkinsonism‐dementia complex of the Kii peninsula (Kii ALS/PDC) is an endemic and a tauopathy, which shows clinical symptoms of amyotrophy, parkinsonism, and dementia. The objective of this study was to report the role of oxidative stress on Kii ALS/PDC using biochemical analysis. Urinary 8‐hydroxydeoxyguanosine (8‐OHdG)/creatinine ratio was analyzed in 11 patients with Kii ALS/PDC and 8 normal controls. The mean level of urinary 8‐OHdG/creatinine ratio of the patients with Kii ALS/PDC was significantly higher than that of control subjects. Oxidative stress may be implicated in pathogenesis of Kii ALS/PDC.

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.

Beyond the midbrain atrophy: wide spectrum of structural MRI finding in cases of pathologically proven progressive supranuclear palsy

PurposeRecently, it has been recognized that pathologically proven progressive supranuclear palsy (PSP) cases are classified into various clinical subtypes with non-uniform symptoms and imaging findings. This article reviews essential imaging findings, general information, and advanced magnetic resonance imaging (MRI) techniques for PSP and presents these MRI findings of pathologically proven typical and atypical PSP cases for educational purposes.MethodsWith the review of literatures, notably including atypical pathologically proven PSP cases, MRI and clinical information of 15 pathologically proven typical and atypical PSP cases were retrospectively evaluated.ResultsIn addition to typical symptoms, PSP patients can exhibit atypical symptoms including levodopa-responsive parkinsonism, pure akinesia, non-fluent aphasia, corticobasal syndrome, and predominant cerebellar ataxia. As well as clinical symptoms, the degree of midbrain atrophy, a well-known imaging hallmark, is not consistent in atypical PSP cases. This fact has important implications for the limitation of midbrain atrophy as a diagnostic imaging biomarker of PSP pathology. Additional evaluation of other imaging findings including various regional atrophies of the globus pallidus, frontal lobe, cerebral peduncle, and superior cerebellar peduncle is essential for the diagnosis of atypical PSP cases.ConclusionIt is necessary for radiologists to recognize the wide clinical and radiological spectra of typical and atypical PSP cases.

Unusual tau pathology of the cerebellum in patients with amyotrophic lateral sclerosis/parkinsonism–dementia complex from the kii peninsula, Japan

1 Department of Neuropathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan. 2 Department of Oncologic Pathology, Mie University School of Medicine, Mie, Japan. 3 Kii ALS/PDC Research Center, Mie University, Graduate School of Regional Innovation Studies, Mie, Japan. 4 Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. 5 Department of Medical Welfare, Suzuka University of Medical Science, Mie, Japan. 6 Pathology Division, Kuwana Medical Center, Mie, Japan.

Dinosaur Tail Sign: A Useful Spinal MRI Finding Indicative of Cerebrospinal Fluid Leakage

To evaluate the imaging characteristics and diagnostic utility of the “Dinosaur tail sign” in the diagnosis of cerebrospinal fluid (CSF) leakage.

Spinocerebellar ataxia type 2 presenting with rapidly progressing muscle weakness and muscular atrophy

changes and enteral nutrition support. Nutritional status improved continuously throughout follow up, with plasma albumin concentration up to 32 g/L. Exposure to pain led the patient to develop a contracture of the right knee (genu flexum). He was prescribed physiotherapy accompanied with a knee orthosis. Unfortunately, he never improved his limitation in knee extension, and had to use a wheelchair to get out of his room. After 4 months of management in the rehabilitation unit, the patient achieved complete wound healing (Fig. 1c), normalization of cognitive function and partial improvement in basic abilities of daily living. We met Mr S again 6 months after discharge, and he reported not experiencing any complications of this skin graft. He had finally become used to his wheelchair. Despite critical medical complications, Mr S managed to overcome NF and aggressive surgery. Given the poor prognosis, we assume that the patient might have been denied conservative surgery. Otherwise, his lower limb would have been amputated. Given the patient’s severe malnutrition and older age, non-surgical management might have been offered, affording little chance of him getting through. The key to success was a long-term vision backed up by attentive, well-coordinated, multidisciplinary management involving, anesthetists, plastic and orthopedic surgeons, and geriatricians. This case illustrates that advanced age, multiple comorbidities and severe malnutrition are not an insurmountable challenge.

β-N-methylamino-l-alanine analysis in the brains of patients with Kii ALS/PDC

The Kii Peninsula of Japan and the island of Guam are known as high-incidence areas of amyotrophic lateral sclerosis and parkinsonism–dementia complex (ALS/PDC). The disorder is clinically characterized by a variable presentation of parkinsonism, dementia, and motor neuron symptoms and pathologically by tau protein deposits in the CNS.1 Both genetic and environmental factors are implicated in ALS/PDC pathogenesis. Exposure to β-N-methylamino-l-alanine (BMAA), a neurotoxin produced by cyanobacteria, has been proposed as a risk factor for ALS/PDC in Guam.2 It is not known whether Kii ALS/PDC shares the same etiology as Guam ALS/PDC. To address these issues, we conducted BMAA analyses of brain samples from 5 patients with Kii ALS/PDC using high-performance liquid chromatography (HPLC) and liquid chromatography–tandem mass spectrometry (LC/MS/MS).

Dopaminergic Positron Emission Tomography Study on AmyotrophicLateral Sclerosis/ParkinsonismâÂÂDementia Complex in Kii, Japan

Background: Amyotrophic lateral sclerosis and parkinsonism-dementia complex in the Kii peninsula, Japan (Kii ALS/PDC) is an endemic and rare neurodegenerative disease. We conducted positron emission tomography (PET) study using C-11 CFT (2-b-carbomethoxy-3b-(4-fluorophenyl) tropane) and C-11 Raclopride for two patients with Kii ALS/PDC. Objective and methods: Patient #1 was 64 years old male having 12 years’ duration of the illness. Patient #2 was 68 years old female having 7 years’ duration of the illness. Results: In patient #1, CFT-PET showed marked decreased uptake in the bilateral corpus striatum, almost no signal in the posterior part of the putamen. RAC-PET showed mild decrease in the bilateral caudate nucleus and slight increase in the posterior part of the putamen. In patient #2, CFT-PET showed severe decrease in the bilateral corpus striatum, marked decrease in the posterior part of the putamen and in the caudate nucleus. RACPET showed the mild decrease in the bilateral corpus striatum. Conclusion: These results were compatible with L-dopa resistant Parkinsonism and similar to those of PSP.