Keizo Yasui

Cervical spondylotic amyotrophy. Magnetic resonance imaging demonstration of intrinsic cord pathology.

Study Design. Three case reports. Objective. To elucidate the pathophysiology of cervical spondylotic amyotrophy. Summary of Background Data. Cervical spondylotic amyotrophy is the clinical syndrome in cervical spondylosis characterized by severe muscular atrophy in the upper extremities, with an absent or insignificant sensory deficit. Pathophysiology of this particular syndrome has not been well understood. Methods. Three cases of cervical spondylotic amyotrophy are presented in which magnetic resonance imaging confirmed the intrinsic cord disease as the cause of the syndrome. Results. The patients had segmental muscular atrophy of the proximal upper extremities, with an absent or insignificant sensory deficit. After initial disease progression, the symptoms stabilized for years. Sagittal T2‐weighted magnetic resonance images showed multisegmental linear high‐signal intensity within the compressed spinal cord. These high‐signal intensity lesions appeared to be located at the anterior horns on axial images. The spinal cord compression was less severe in the neck‐neutral position, but spinal canal stenosis increased when the neck was extended. Conclusions. The results suggest that one pathophysiology of this syndrome may be multisegmental damage to the anterior horns caused by dynamic cord compression, possibly through circulatory insufficiency.

Age-related morphologic changes of the central canal of the human spinal cord

Abstract To elucidate the role of the human central canal on the physiology and pathogenesis of acquired syringomyelia, we analyzed the age-related morphologic changes in the normal human central canal of the spinal cord. The subjects included 158 autopsy cases ranging in age from 1 week postnatally to 116 years of age. Each segment of the whole spinal cords was investigated from the C3 to S3 levels. The microscopic pictures of the central canal were classified as patent or occluded at each level for each age decade. The patency rate under 1 year of age was 100% in almost all the segments, which markedly decreased in the second decade, and the canals were occluded in all the segments with advancing age. According to the longitudinal pattern of the central canal occlusion, 19 of 20 cases where the canals were patent in all segment levels were less than 10 years of age. Cases in which the canals were occluded in all segment levels appeared in the second decade, and their number increased gradually with advancing age. The occlusion of the central canal started at the T6 and L5 to S2 levels. We suggest that the central canal does not function after infancy because of its occlusion, and that it is not involved in the development of syringomyelia in adult patients.

Differential response to corticosteroid therapy of MRI findings and clinical manifestations in spinal cord sarcoidosis

Abstract Spinal cord sarcoidosis is a rare disorder whose natural history and therapeutic outcome are not fully known. We examined four patients with spinal cord sarcoidosis both clinically and radiologically, particularly in relation to corticosteroid treatment. The initial manifestation was cervical myelopathy in three and uveitis in one. All four patients progressed slowly until corticosteroid therapy was initiated. The cervial spine was involved in all patients. Magnetic resonance imaging (MRI) showed spinal cord swelling with T2-weighted high intensity and linear leptomeningeal and patchy or diffuse intramedullary enhancement with gadolinium diethylene triaminepentaacetic acid. With corticosteroid therapy, dramatic improvement was seen on MRI, including disappearance or marked reduction of swelling and enhancement. Plasma levels of angiotensin-converting enzyme (ACE) were also markedly improved. In contrast, the clinical symptoms were little improved in one patient, unchanged in two, and rather worsened in one patient. Recurrence was seen on MRI at the maintenance dose in all four patients, without any dramatic change in clinical manifestation. MRI findings and plasma ACE are well correlated with active leasion of the spinal cord sarcoidosis, providing a useful marker for recurrence, but do not parallel the clinical manifestations.

FUS immunoreactivity of neuronal and glial intranuclear inclusions in intranuclear inclusion body disease

F. Mori, K. Tanji, T. Kon, S. Odagiri, M. Hattori, Y. Hoshikawa, C. Kono, K. Yasui, S. Yokoi, Y. Hasegawa, M. Yoshida and K. Wakabayashi (2012) Neuropathology and Applied Neurobiology38, 322–328

Chronological changes of 123I-MIBG myocardial scintigraphy and clinical features of Parkinson's disease

Objectives The aim of this study was to investigate chronological changes of 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy and its relation to clinical features in patients with Parkinsons disease (PD), and to characterise patients with PD with normal or mildly low MIBG uptakes at their early stages. Methods The participants were 70 patients with PD who underwent 123I-MIBG myocardial scintigraphy twice or more. A cluster analysis was performed using parameters calculated from heart to mediastinum (H/M) ratio and washout ratio (WR). Results At baseline, the mean early H/M ratio (H/M(E)), delayed H/M ratio (H/M(D)) and WR were 1.83, 1.69 and 41.7%, respectively. After a mean interval of 3.0 years, follow-up studies showed significantly declined H/M(E) (1.69, p<0.001), declined H/M(D) (1.47, p<0.001) and enhanced WR (43.8%, p=0.007). Our longitudinal observations revealed that there existed heterogeneous changes in MIBG uptakes among patients. The cluster analysis classified the patients into two subgroups: 42 patients with markedly low MIBG uptakes at baseline (group A) and 28 patients with normal or mildly low MIBG uptakes at baseline (group B). Group B showed a significantly higher ratio of females, younger age at onset, lower Hoehn and Yahr stage and less demented, compared with group A. Conclusions Follow-up studies of MIBG divided the patients with PD into two major subgroups. A subgroup of patients with PD with normal or mildly low MIBG uptakes at the early stages of illness was characterised by female-dominant, young onset, slow progression in motor dysfunctions and preserved cognitive function. Trial registration number 1033.

Ubiquitin-related proteins in neuronal and glial intranuclear inclusions in intranuclear inclusion body disease

Recent studies have shown that eosinophilic intranuclear inclusions (INI) in the brain of patients with intranuclear inclusion body disease (INIBD) are immunopositive for ubiquitin and ubiquitin‐related proteins (URP). However, the extent and frequency of URP‐immunoreactive inclusions in INIBD are uncertain. We immunohistochemically examined the brain, spinal cord and dorsal root ganglia from five patients with INIBD, using a virtual slide system with sequential staining of the same sections with hematoxylin and eosin and by immunolabeling with antibodies against ubiquitin and URP (NEDD8, NUB1, SUMO‐1 and SUMO‐2). Intranuclear inclusions were widely distributed in neurons and glial cells in all the cases. Sequential staining revealed that 100% of INI in neurons and glial cells were positive for ubiquitin. Moreover, the majority or a significant proportion of INI were positive for NEDD8, NUB1, SUMO‐1 and SUMO‐2. However, the proportions of NEDD8‐, NUB1‐ and SUMO‐1‐positive inclusions were significantly higher in neurons than in glial cells (P < 0.05). These findings suggest that proteins related to ubiquitination and proteasomal degradation are involved in the formation of INI in INIBD.

Distinctive distribution of brain volume reductions in MELAS and mitochondrial DNA A3243G mutation carriers: A voxel-based morphometric study.

OBJECTIVE The aim of this study was to investigate the clinically latent brain atrophy of patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) harboring a mitochondrial DNA A3243G mutation (A3243G) and A3243G carriers without stroke-like episodes (SEs). METHODS We used voxel-based morphometry (VBM) with magnetic resonance imaging to investigate gray matter (GM) and white matter (WM) volume reductions in four MELAS patients and in five A3243G carriers compared to 16 healthy controls. In addition, we investigated the regions of previous SEs using conventional MRI. RESULTS All four MELAS patients showed significant GM volume reductions in the left superior parietal lobule (SPL), right precuneus, right middle temporal gyrus (MTG), and bilateral posterior lobes of the cerebellum. These areas of GM volume reduction were beyond the regions of previous SEs. As for A3243G carriers, GM volume reductions in the left SPL, right precuneus, right MTG, and bilateral posterior lobes of the cerebellum were detected in three, one, two, and five subjects, respectively. All four MELAS patients showed significant WM volume reductions in the bilateral or unilateral temporal sub-gyral regions, which were included in the regions of previous SEs. No A3243G carriers showed WM volume reductions. CONCLUSION The distribution patterns of GM volume reductions in VBM may reflect a common vulnerability of the brains among MELAS patients and A3243G carriers.

A questionnaire survey of general practitioners in Japan in relation to management of transient ischemic attack

A transient ischemic attack (TIA) is a medical emergency associated with a high risk of early ischemic stroke (1,2). General practitioners (GPs) play an important role in clinical management of TIA. The purpose of this study was to clarify the management of TIA among GPs in Japan. We conducted a choice questionnaire survey concerning TIA among 329 GPs in the Osaka area and 158 GPs in the Nagoya area. Figure 1 shows responses to the question related to “the strategy for patients who developed hemiparesis one hour ago. In cases where symptoms persisted at the time of visit, 85% of respondents in the Osaka area and 87% of respondents in the Nagoya area indicated that they would refer patients to a stroke specialty hospital immediately, and 5% in the Osaka area and 6% in the Nagoya area indicated that they would refer patients to a stroke specialty hospital, but not immediately. In contrast, among patients in whom symptoms disappeared at the time of the visit, 42% and 42%, and 36% and 35%, gave these respective responses (P < 0·001, P < 0·001). Most respondents (70% in the Osaka area and 63% in the Nagoya area) indicated that they had some difficulties with clinical management of patients with TIA, including lack of confidence regarding the diagnosis, lack of familiarity with referral criteria, and lack of knowledge about which hospitals to use for referral. This survey suggests that GPs in Japan seem to regard TIA as less of a medical emergency than stroke, and that most GPs had some troubles managing patients with TIA. Results were similar in two areas. It is necessary to enlighten GPs about the importance of immediate assessment and treatment after TIA, and to establish a close relationship between GPs and stroke specialty hospitals.

Active brain changes after initiating fingolimod therapy in multiple sclerosis patients using individual voxel-based analyses for diffusion tensor imaging

ABSTRACT Voxel-based analysis (VBA) of diffusion tensor images (DTI) and voxel-based morphometry (VBM) in patients with multiple sclerosis (MS) can sensitively detect occult tissue damage that underlies pathological changes in the brain. In the present study, both at the start of fingolimod and post-four months clinical remission, we assessed four patients with MS who were evaluated with VBA of DTI, VBM, and fluid-attenuated inversion recovery (FLAIR). DTI images for all four patients showed widespread areas of increased mean diffusivity (MD) and decreased fractional anisotropy (FA) that were beyond the high-intensity signal areas across images. After four months of continuous fingolimod therapy, DTI abnormalities progressed; in particular, MD was significantly increased, while brain volume and high-intensity signals were unchanged. These findings suggest that VBA of DTI (e.g., MD) may help assess MS demyelination as neuroinflammatory conditions, even though clinical manifestations of MS appear to be in complete remission during fingolimod.

Pathological background of subcortical hyperintensities on diffusion-weighted images in a case of neuronal intranuclear inclusion disease.

AIMS Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder with eosinophilic intranuclear inclusion bodies. The variable symptoms of NIID increase the difficulty in an antemortem diagnosis. NIID shows leukoencephalopathy on brain magnetic resonance imaging MRI, but the significance of the radiological findings have not been clarified. METHODS We examined an autopsied case of NIID with subcortical linear hyperintensities on diffusion weighted imaging (DWI) and leukoencephalopathy on fluid attenuation inversion recovery (FLAIR) imaging. Semiquantitative analysis was performed by merging coronal sections of DWI and identical hematoxylin-eosin (H & E) stained brain specimens. The severity of spongiotic changes, the common pathological findings of NIID, were quantified and compared with MRI lesions classified by DWI signals. RESULTS The white matter showed diffuse myelin pallor, and multiple focal spongiotic changes were present in the subcortical white matter proximal to the U-fibers. Spongiotic changes were restricted in the lesions with subcortical linear DWI high signals. CONCLUSION Subcortical DWI high signals in NIID strongly correlate with pathological spongiotic changes of NIID. Subcortical spongiotic changes may be a characteristic finding of NIID.
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