Makiko Seto

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.

CAG repeat length and disease duration in Machado-Joseph disease: a new clinical classification

To evaluate the clinical characteristics of Machado-Joseph disease (MJD) with reference to CAG repeat length and disease duration, we analyzed neurologic findings in 108 patients from 84 families. The majority of MJD patients presented with an ataxic gait as the initial symptom. Dysarthria and nystagmus were observed from an early stage. Bulging eyes, muscle atrophy and bradykinesia developed later. Patients with a shorter CAG repeat length or later onset had more frequent involvement of proprioceptive sensory deficit. Incidence of abnormal reflexes, tones, and proprioceptive sensation was not associated with disease duration, but with CAG repeat length. Based on these results, we propose a new clinical classification: type A (juvenile type), with hyperreflexia and dystonia, but without a proprioceptive sensory deficit; type C (adult type), with hyporeflexia and a proprioceptive sensory deficit, but without dystonia; and type B (intermediate type), the remaining patients with a mixed presentation.

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.

Bunina bodies in motor and non-motor neurons revisited: A pathological study of an ALS patient after long-term survival on a respirator

Bunina bodies (BBs) are small eosinophilic neuronal cytoplasmic inclusions (NCIs) found in the remaining lower motor neurons (LMNs) of patients with sporadic amyotrophic lateral sclerosis (SALS), being a specific feature of the cellular pathology. We examined a case of SALS, unassociated with TDP‐43 or C9ORF72 mutation, of 12 years duration in a 75‐year‐old man, who had received artificial respiratory support for 9 years, and showed widespread multisystem degeneration with TDP‐43 pathology. Interestingly, in this patient, many NCIs reminiscent of BBs were observed in the oculomotor nucleus, medullary reticular formation and cerebellar dentate nucleus. As BBs in the cerebellar dentate nucleus have not been previously described, we performed ultrastructural and immunohistochemical studies of these NCIs to gain further insight into the nature of BBs. In each region, the ultrastructural features of these NCIs were shown to be identical to those of BBs previously described in LMNs. These three regions and the relatively well preserved sacral anterior horns (S1 and S2) and facial motor nucleus were immunostained with antibodies against cystatin C (CC) and TDP‐43. Importantly, it was revealed that BBs exhibiting immunoreactivity for CC were a feature of LMNs, but not of non‐motor neurons, and that in the cerebellar dentate nucleus, the ratio of neurons with BBs and TDP‐43 inclusions/neurons with BBs was significantly lower than in other regions. These findings suggest that the occurrence of BBs with CC immunoreactivity is intrinsically associated with the particular cellular properties of LMNs, and that the mechanism responsible for the formation of BBs is distinct from that for TDP‐43 inclusions.

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.

Experimental neonatal autoimmune myasthenia gravis: an immunohistochemical, ultrastructural and electrophysiological study of the motor end-plate

Neonatal rats born of and nursed by mothers immunized with Narke japonica acetylcholine receptor protein had elevated serum anti-acetylcholine receptor antibodies that reached the mothers level on day 10 after delivery and decreased rapidly after weaning. IgG was present at the motor end-plates up to day 170, and the motor end-plate fine structure remained abnormal up to day 80. Miniature end-plate potential amplitudes in the diaphragm were at the control levels within 10 days of birth, but were lower than those of the controls up to day 80 after birth. We could not obtain the direct evidence that transient synthesis of antibodies occurs in experimental autoimmune myasthenia gravis pups. This model can serve as an experimental model of transient neonatal myasthenia gravis in humans, exception for the route of antibody transfer and the time of the onset of illness.