Yume Suzuki

A study of the early stage of Dysphagia in amyotrophic lateral sclerosis.

In amyotrophic lateral sclerosis (ALS) patients, dysphagia eventually occurs independent of time of onset. We studied dysphagia conditions in the early stage of ALS, principally at the oral phase. Videofluoroscopic and manometric studies were conducted on 11 patients (5 males and 6 females, age range = 47–82 years) who were diagnosed at our Neurology Clinic as having ALS. All patients were able to ingest orally. Swallowing scores on the ALS severity scale were from 10 to 5. In the oral phase of swallowing, abnormal movements of the anterior and/or posterior tongue were recognized in 8 cases. Dysphagia severity tended to be particularly influenced by dysfunction of the posterior tongue. Manometric studies were almost normal in all cases except one. These results suggested that the early stage of dysphagia in ALS was mainly caused by oral dysfunction, and the oral phase disorders began in some cases with a decreased function of bolus transport at the anterior part of the tongue, and in other cases with a deteriorated function of holding the bolus at the posterior part of the tongue. In conclusion, the tongue function of holding the bolus in the oral cavity mainly affects the severity of the early stage of dysphagia in ALS.

The RNA-binding protein FUS/TLS is a common aggregate-interacting protein in polyglutamine diseases

Neuronal intranuclear inclusions (NIIs) are the pathological hallmark of polyglutamine (polyQ) diseases. We previously found that the RNA-binding protein FUS/TLS is the major component of nuclear polyQ aggregates of a cellular model of Huntington disease. In this study, we revealed that FUS/TLS binds to NIIs in the human brains from patients with spinocerebellar ataxia type 1, 2, 3, and dentatorubral-pallidoluysian atrophy. Recent reports have revealed that mutations in FUS/TLS gene are responsible for familial amyotrophic lateral sclerosis 6 (ALS6). Our results indicated that changing FUS/TLS to an insoluble form may be a common process in polyQ diseases and ALS6.

Distal myopathy with rimmed vacuoles

Distal myopathy with rimmed vacuoles is an autosomal recessively inherited disorder with preferential involvement of the anterior tibial muscle. Recently the gene was discovered to be mapped to chromosome 9, the same region as in familial inclusion body myopathy (rimmed vacuole myopathy sparing the quadriceps). The onset of the disease was in young adults 20-40 years of age, averaging 26 years. The disease was progressive and most of the patients became non-ambulant within 12 years after the onset. The striking and common pathologic finding was the presence of rimmed vacuoles in muscle fibers with little evidence of necrotic or regenerative processes. Nuclear change with tubulofilamentous inclusions probably induces focal myofibrillar degeneration which activates the lysosomal system, resulting in active autophagocytosis and myelin body formation, i.e. rimmed vacuole formation.

Visual event-related potentials in progressive supranuclear palsy, corticobasal degeneration, striatonigral degeneration, and Parkinson's disease

Abstract To determine whether there are characteristic changes in event-related potentials (ERPs) in parkinsonian syndromes we studied 8 patients with progressive supranuclear palsy (PSP), 10 patients with corticobasal degeneration (CBD), 9 patients with striatonigral degeneration (SND), and 16 patients with idiopathic Parkinsons disease (PD) with a mean duration of illness shorter than 5 years in each group. A visual oddball paradigm was employed to elicit P300. P300 to the rare target and rare nontarget stimuli and reaction time (RT) to rare target stimuli in each group were compared with those in the corresponding age-matched normal control group and to each other after age correction. The correlation of P300 and RT to motor disability score was also studied. In PSP P300 amplitude was markedly reduced while in CBD P300 latency was prolonged. P300 amplitude to rare nontargets in SND and PD was attenuated. The mean RT in the PSP and the CBD group was significantly longer than in the other two groups. The mean RT in PD and P300 amplitude to rare nontargets in both CBD and PD showed significant correlation with the severity of motor disability. Simultaneous measurement of P300 and RT may yield useful supplementary information in facilitating diagnosis of parkinsonian syndromes in addition to clinical criteria.

The correlation between P300 alterations and regional cerebral blood flow in non-demented Parkinson's disease.

P300 was evoked by a visual oddball and an S1-S2 task in 22 non-demented Parkinsons disease (PD) patients (13 in the early stage, nine in the late stage) and 18 normal controls. Reaction time was also measured. All patients undertook the (99)Tc-ECD SPECT examination. Quantitative regional cerebral blood flow (rCBF) was obtained by overlying SPECT image on the 3D-magnetic resonance image. In the PD patients in the late stage, P300 latency to S2-same and reaction time were significantly prolonged, while rCBF at bilateral frontal, temporal, and the right parietal lobes was decreased. P300 latency to S2-same was significantly correlated with the rCBF at bilateral temporal lobes. Reaction time was significantly correlated with the rCBF at the right frontal and parietal lobes, as well as the temporal and occipital lobes. The results suggest that P300 changes in non-demented PD in the late stage could be related to the temporal lobe dysfunction.

Apoptotic nuclear degeneration in Marinesco-Sjögren syndrome

Abstract In 12 patients with the clinical characteristics of Marinesco-Sjögren syndrome including an autosomal recessive inheritance, congenital cataracts, mental retardation, cerebellar ataxia and progressive muscle weakness, the most common pathological finding was rimmed vacuole formation comprising from 0.1% to 10% of fibers in their muscle biopsy samples. The nuclear changes varied from condensed chromatin granules to vacuolation with amorphous inclusions which were predominantly seen in younger patients with prominent rimmed vacuoles, suggesting a close relationship between nuclear change and rimmed vacuole formation. From the severe destructive changes in nuclei, we speculated that the nuclear changes in Marinesco-Sjögren syndrome play a primary role in muscle degeneration resulting in myofibrillar disorganization and rimmed vacuole formation. In 2 patients, the TUNEL method demonstrated scattered myonuclei with fragmented DNA, but “ladder formation” was not found, probably because of the small numbers of nuclei with fragmented DNA. Nuclear degeneration with focal myofibrillar degeneration seen in these muscle samples suggests that the apoptotic process may occur in muscle disorders, especially in diseases with rimmed vacuole formation.

Effect of interstimulus interval on visual P300 in Parkinson’s disease

OBJECTIVE Visual event related potentials (ERPs) were studied during an oddball paradigm, to testify whether cognitive slowing in Parkinson’s disease exists and to investigate whether cognitive information processing can be influenced by different interstimulus intervals (ISIs) of an oddball task in patients with Parkinson’s disease and normal subjects. METHODS ERPs and reaction time were measured in 38 non-demented patients with Parkinson’s disease and 24 healthy elderly subjects. A visual oddball paradigm was employed to evoke ERPs, at three different interstimulus (ISI) intervals: ISI(S), 1600 ms; ISI(M), 3100 ms; and ISI(L), 5100 ms. The effect of ISIs on ERPs and reaction time was investigated. RESULTS Compared with the normal subjects, P300 latency at Cz and Pz was significantly delayed after rare target stimuli in patients with Parkinson’s disease only at ISI(L). Reaction time was prolonged in patients at all the three ISIs, compared with the normal controls. There was also significantly delayed N200 and reduced P300 amplitude at Cz and/or Pz to rare non-target stimuli in patients at the three ISIs, compared with the normal controls. During rare target visual stimulation, P300 latency and reaction time in the patients with Parkinson’s disease and reaction time in the normal subjects were gradually prolonged as the ISI increased. CONCLUSION Prolonged N200 latency to rare non-target stimuli might indicate that automatic cognitive processing was slowed in Parkinson’s disease. Cognitive processing reflected by P300 latency to rare target stimuli was influenced by longer ISI in patients with Parkinson’s disease.

Correlation between neurological dysfunction with vitamin E deficiency and gastrectomy

OBJECTIVE We previously reported on vitamin E malabsorption after gastrectomy. In this study, we focused on neurological dysfunction due to serum vitamin E decrease during the postgastrectomy period in lager number of patients. METHODS We examined the type of gastrectomy, type of reconstruction, serum vitamin E level, and neurological status for 96 gastrectomy patients. RESULTS Low serum vitamin E levels were observed in 20 patients, and 10 of those patients suffered some neurological symptoms, i.e., peripheral neuropathy, limb or truncal ataxia. Vitamin E levels tended to decrease with time after gastrectomy, and the number of patients with low serum vitamin E levels increased at about 50 months after gastrectomy. This relationship was stronger in total gastrectomy patients than in subtotal gastrectomy patients. Ten patients were given oral vitamin E, and serum vitamin E levels normalized in 9 of the patients and neurological abnormalities improved in 8 patients. An oral intake of 300 mg or more of vitamin E was necessary for normalization of vitamin E levels. CONCLUSIONS Gastrectomy should be considered a risk for vitamin E deficiency and neurological disturbance over the long-term clinical course. An oral vitamin E supply can improve serum vitamin E levels and neurological symptoms.

P1 and P2 components of human visual evoked potentials are modulated by depth perception of 3-dimensional images

OBJECTIVE To determine the cerebral activity correlated with depth perception of 3-dimensional (3D) images, by recording of human visual evoked potentials (VEPs). METHODS Two figures consisting of smaller and larger squares were presented alternately. VEPs were recorded in two conditions. In condition I, we used two figures which yielded flat 2-dimensional images. In condition II, we used two figures which yielded 3D images, which were concave and convex, respectively. RESULTS P1, P2, and N1/P2 amplitude were significantly greater in condition II than in condition I. The P1/N1 amplitude tended to be greater in condition II than in condition I. P1 and N1 were predominantly distributed over the right temporo-parieto-occipital regions. P2 and N2 were distributed over bilateral parieto-occipital regions. CONCLUSIONS The difference in P1 amplitude between two conditions can be explained by the difference between conditions, one of which yielded depth perception while the other did not, since previous studies showed that P1 and N1 are modulated by perception of images in depth. The role of P2 and the mechanism responsible for the increase in P2 amplitude during condition II remain unknown. SIGNIFICANCE We recorded VEPs and identified electrophysiological correlates of depth perception with 3D images produced by concave/convex figures.

Granulomatous myositis: pathologic re-evaluation by immunohistochemical analysis of infiltrating mononuclear cells

To characterize the non-caseating granuloma formation in granulomatous myositis, we analyzed infiltrating mononuclear cells in 7 patients including 2 sarcoid patients, using monoclonal antibodies with a modified immunoperoxidase method. All granulomas consisting of epithelioid, infiltrating mononuclear cells and multinucleated giant cells had markedly increased numbers of CD45Ro-positive cells. The infiltrating inflammatory cells were mostly T lymphocytes and macrophages. The majority of T lymphocytes behaved as T helper/inducer subtype, expressing CD4 positivity. Although the ratio of CD4- to CD8-positive cells in the granuloma in muscle biopsies was not significantly different from that in other organs seen in systemic sarcoidosis, T helper/inducer and T suppressor/cytotoxic cells showed some characteristic distributions: CD4-positive cells accumulated in the center of, and CD8-positive cells at the periphery of, the granuloma. The distribution of infiltrating cells did not differ between muscle biopsies from patients with and without systemic sarcoidosis, suggesting that both groups share the same pathogenetic mechanism in granuloma formation.