Itsuro Tomita

Lewy body–type degeneration in cardiac plexus in Parkinson’s and incidental Lewy body diseases

Article abstract Heart tissues of patients with PD or incidental Lewy body (LB) disease (ILBD) were examined by light and electron microscopy. LBs and α-synuclein–positive neurites were identified in the hearts from 9 of 11 patients with PD and from 7 of 7 patients with ILBD. LBs were present in both tyrosine hydroxylase-positive and -negative nerve processes, which are nerves of extrinsic sympathetic and intrinsic origin, respectively. These findings provide histologic evidence that the postganglionic sympathetic and intrinsic neurons in the heart are involved in the PD disease process.

Plasmapheresis in treatment of human T-lymphotropic virus type-I associated myelopathy.

In 11 of 18 patients with human T-lymphotropic virus type-I (HTLV-I) associated myelopathy (HAM) gait, sensory, and/or sphincter disturbance improved with plasmapheresis (4 to 6 sessions in 2 weeks), and the effects were maintained for 2 to 4 weeks. Plasmapheresis lowered the titre of HTLV-I antibody in serum but not in cerebrospinal fluid, and change of HTLV-I antibody titres did not correlate with the effects of plasmapheresis. These results suggest that plasmapheresis is useful treatment, at least in producing a temporary improvement, in patients with HAM, and that some humoral factor(s), but not HTLV-I antibody, may be important in the pathogenesis of HAM.

Pathology and sensitivity of current clinical criteria in corticobasal syndrome.

The aim of this study was to investigate corticobasal syndrome with respect to underlying pathologies, the ability of current clinical criteria to detect early stages of disease, and symptoms and signs predicting background pathologies. We retrospectively analyzed the clinicopathological findings from patients with corticobasal syndrome. We also analyzed whether those findings fulfilled the diagnostic criteria for corticobasal degeneration (CBD). Finally, we investigated characteristic clinical features that are specific to each background pathology. Of 10 consecutive autopsied patients who had corticobasal syndrome (mean age ± standard deviation, 67.9 ± 9.3 years; male:female ratio, 6:4), three had corticobasal degeneration pathology, three had progressive supranuclear palsy, three had Alzheimers disease, and one had atypical four‐repeat tauopathy. Nine patients fulfilled Mayo criteria, and all 10 patients fulfilled modified Cambridge criteria at the later stage, but only two patients fulfilled either clinical criteria within 2 years of disease onset. Five patients fulfilled the clinical criteria for possible CBD (p‐CBD), and one patient fulfilled the clinical research criteria for probable sporadic CBD (cr‐CBD) at the later stage. Only two patients fulfilled the criteria for either p‐CBD or cr‐CBD within 2 years of disease onset. Although we could not find any predictive characteristic clinical features that were specific to CBD pathology, only patients with progressive supranuclear palsy developed apraxia of eyelid opening and cerebellar ataxia. Myoclonus and memory impairment, especially if they appear at an early stage of the disease, may predict Alzheimers disease pathology. Sensitivity of the available clinical criteria for corticobasal syndrome was poor within 2 years of disease onset.

Familial Creutzfeldt-Jakob Disease with a V180I Mutation: Comparative Analysis with Pathological Findings and Diffusion-Weighted Images

Background: Diffusion-weighted imaging (DWI) has been reported to be a useful technique for diagnosing Creutzfeldt-Jakob disease (CJD). The present study reported DWI results in cases of familial CJD with a V180I mutation (CJD180) in the prion protein gene as well as neurological findings. Methods: A retrospective analysis of 3 patients with V180I was performed. Cerebrospinal fluid (CSF) analysis, brain MRI, single-photon emission computed tomography (SPECT), and magnetic resonance spectroscopy (MRS) were included. CSF was analyzed for biochemical markers, and each patient underwent brain MRI, SPECT, and MRS analysis. A brain biopsy from the frontal cortex, which corresponded to the area of increased DWI signals, was utilized for neuropathological analysis. Results: CSF analysis results revealed elevated total tau protein and the absence of 14-3-3 protein, as well as decreased concentrations of neuron-specific enolase, S100 protein, and prostaglandin E2. All patients presented with unique MRI features. Brain biopsy showed severe spongiform morphology, but comparatively preserved neurons and mild astrocytic gliosis. Accumulations of PrPSc were not detected using the 3F4 antibody, and microglial activation was subtle. SPECT revealed hypoperfusion throughout both hemispheres. MRS revealed a reduced N-acetyl aspartate/creatine ratio. Conclusion: Results from this study suggested that increased DWI signals could reflect severe spongiform changes in CJD180 patients.

A case of Creutzfeldt-Jakob disease with a point mutation at codon 232: Correlation of MRI and neurologic findings

Creutzfeldt-Jakob disease (CJD) is a subacute spongiform encephalopathy characterized clinically by progressive dementia with myoclonus and extrapyramidal symptoms. If no characteristic EEG findings are found, clinical diagnosis is difficult. CT is of little use. MRI has been reported both to be of little value1 and to be helpful in the diagnosis of CJD.2-4 A few CJD patients with a point mutation at codon 232 of prion protein gene have been reported.5-7 We describe MRI changes in the cerebral cortex of a patient with a mutation at codon 232. Case report. A 64-year-old woman who had about a years history of difficulty in dressing was admitted to our hospital. At that time, she had developed abnormalities in her cortical functions (dressing apraxia, constructional apraxia, limb-kinetic apraxia, idiomotor apraxia, ideational apraxia, and apraxic agraphia). She showed no disturbance of recent or remote memory. Her past medical and family histories were unremarkable, and she …

Role of the macrophage in the pathogenesis of experimental autoimmune myasthenia gravis

To clarify the role of Ia antigen positive macrophages which invade motor end-plates in the induction of the chronic phase, experimental autoimmune myasthenia gravis (EAMG) rats were injected intraperitoneally with silica dust on day 6 after immunization. Silica injection partially inhibited the invasion of motor end-plates with macrophages as compared with a saline injection. The titer of antibodies to the Narke acetylcholine receptor (AChR) in the chronic phase did not differ in either the saline or the silica groups, while the titer of antibodies to rat-AChR (non-crossreactive antibodies) was lower in the silica group than in the saline group. The silica group survived longer than the saline group. These results suggest that Ia antigen positive macrophages in the acute phase act as antigen-presenting cells and play an important role in the production of antibodies to self-AChR in the chronic phase.

Central motor conduction time in patients with HTLV-1 associated myelopathy

ABSTRACT— Transcranial electrical stimulation of the motor cortex was performed in 7 patients with human T‐lymphotropic virus type‐I associated myelopathy (HAM) and 15 normal subjects. The mean value of central motor conduction time (CCT) for the thenar and hypothenar muscles in patients with HAM was not different from that in normal subjects. In contrast, mean CCT value for the tibialis anterior and gastrocnemius muscles in patients with HAM was 8.54‐10.34 ms longer than the value in normal subjects. These findings indicate that the lesion of pyramidal tract involvement in patients with HAM is mainly localized in the descending corticomotoneuron pathways at the thoracic spinal cord level. This technique could be used in a clinical study without untoward side effects, and may be valuable in detecting clinically silent lesions involving the pyramidal tract.

OBSERVED SIMILAR FINDINGS OF 123I-MIBG MYOCARDIAL SCINTIGRAPHY IN DLB/PD AND REM SLEEP BEHAVIOR DISORDER (RBD), BUT NOT IN OTHER NEURODEGENERATIVE DISORDERS

temporal dementia (FTDbv), traumatic encephalopathy, depression with anxiety and non-AD mild cognitive impairment (MCI). PETCT scan had clinical impact in all cases by altering therapeutic management in 6 (46%) and confirming proposed management plan in the remaining 7 patients (53%). It was a conclusive investigation in 12 out of 13 cases. Only one person required further diagnostic tests after amyloid PET-CT (FDG-PET). The time from referral to diagnosis varied between 6 and 39 months, with the shorter intervals observed in more recently referred patients who had access to amyloid imaging. The number of the investigations, including structural imaging (MRI), FDG-PET, CSF analysis and neuropsychological assessment varied between 1 (usually MRI) to 5 (including sequential neuropsychological assessments). Conclusions: This data indicates FFlorbetapir-PET-CT has a significant impact on the confidence of referring clinicians in all cases by altering therapeutic management in 46%, and confirming clinical impression in the others. Amyloid imaging can be a useful technique in diagnostically challenging cases where differential diagnosis includes AD in community memory clinic setting. The considerable cost of the scans may be offset by reducing the time from referral to diagnosis and the number of tests needed to confirm it.

PREDICTING PROGRESSION FROM MILD COGNITIVE IMPAIRMENT (MCI) TO ALZHEIMER’S DISEASE USING PERFUSION BRAIN SPECT IMAGING ANALYSIS OF THE INITIAL HOSPITAL VISIT

[.58,.61,.06] outperforms the other three models: LR [.53,.51,.07], SVM: [.54,.55,.08], and RF:[.52,.54,.10]. Significant improvement is seen with HC modality with NN model compared to baseline models. All four model classes show boost in performance when HC and CT modalities are combined. Conclusions:The correlation scores validate the utility of NN as prediction model. The proposed modular architecture of the NN provides a framework for multimodal analysis, and can be extended to incorporate other data modalities and/or predicting other clinical scales.