Zenji Shiozawa

Cu/Zn superoxide dismutase-like immunoreactivity in Lewy body-like inclusions of sporadic amyotrophic lateral sclerosis

Cu/Zn superoxide dismutase (SOD)-like immunoreactivity (LI) was found within Lewy body-like inclusions (LBIs) in the spinal cords of patients with sporadic amyotrophic lateral sclerosis (ALS) by using an antibody to human Cu/ZnSOD. LBIs were detected in the anterior horn cells in 10 of 20 patients with sporadic ALS. In each of these patients, 7 to 60% of LBIs showed Cu/ZnSOD-LI. No Cu/ZnSOD-LI was detected in intact neurons and glia in the 20 ALS patients, as well as in these cells in 10 normal control individuals. The skein-like inclusions and Bunina bodies, which were found in all of the 20 ALS cases, showed no Cu/ZnSOD-LI. Thus, Cu/ZnSOD appears to play roles in the production and/or degradation process of LBIs.

Clinical and histopathological features of progressive-type familial amyloidotic polyneuropathy with TTR Lys54

The purpose of this study was to evaluate the clinical and pathological features in patients with progressive-type familial amyloidotic polyneuropathy (FAP) using autopsy and biopsy specimens. A proband is a 33-year-old man with FAP type I who developed motor, sensory and autonomic impairments with neuropathy, heart failure, and anorexia. Genetic findings of transthyretin (TTR) revealed G to A transition in codon 54 causing a rare mutation of TTR Lys54. He died of pneumonia and severe cardiac failure 4 years after onset. Autopsy showed heavy amyloid deposition in the heart, peripheral nerves, thyroid, skin, fat tissue, prostate and testis, moderate in the sympathetic nerve trunk, vagal nerve, celiac plexus, pelvic plexus, bladder, gastrointestinal tract, tongue, pancreas, lung, pituitary, blood vessel, gall bladder, adrenals and muscles, and free in the central nervous system, liver, kidney and spleen. Sural nerve biopsy in a sibling confirmed TTR amyloidosis immunohistochemically. Electronmicroscopic findings of amyloid fibrils were similar to that of FAP Met30. Immunoelectronmicroscopic findings indicated the relationship between amyloid fibrils or non-fibrillar structure and collagen fibers. The distribution of amyloid deposition, heavy in the heart and lacking in the kidney, is a characteristic feature and reflected severity of FAP with TTR Lys54.

Chronological changes of sympathetic outflow to muscles in amyotrophic lateral sclerosis

To confirm correlations between muscle sympathetic nerve activity (MSNA) and patients chronological data, we selected 40 consecutive patients with sporadic amyotrophic lateral sclerosis (ALS) recorded by similar methods. MSNA at rest was quantified as the number of sympathetic bursts per 100 heartbeats and as the value expressed as a percentage of the predicted value based on control data. Twelve patients who underwent recordings of MSNA twice at intervals of 6 months or more showed marked decreases in MSNA amplitudes and frequencies between examinations. There was a slightly positive correlation between the frequency of MSNA and age, though younger patients exhibited higher values of MSNA than older patients. The standardized value of MSNA correlated negatively with disease duration and disability levels (p<0.01, 0.05, respectively), but several patients with duration shorter than 12 months showed low values of MSNA. Twelve patients who underwent repeated recordings of MSNA showed a significant decrease in the mean standardized value of MSNA (102.6+/-24.9%) at the second examination, compared to the value (114.3+/-18.9%) at the first one. In ALS, sympathetic outflow to muscles tends to increase initially and then decrease with increasing age and duration. This pattern may be similar to chronological changes at motor neurons.

Sympathetic sudomotor and vasoconstrictive neural function in patients with Parkinson's disease

To evaluate sympathetic sudomotor and vasoconstrictive neural function in Parkinsons disease (PD), we simultaneously recorded sympathetic skin response (SSR) and skin blood flow (SVR; skin vasomotor reflex), as well as skin sympathetic nerve activity (SSNA) measured in peroneal nerves by microneurography, comparing 12 patients with idiopathic PD with 16 healthy controls. Resting SSNA frequency (8.8+/-4.3 bursts/min) was significantly lower in PD patients than in controls (p<0.01). Frequency increases in response to performing mental arithmetic were slightly smaller in PD patients than in controls. PD patients exhibited normal SSNA reflex latencies compared with controls. Although no significant relationship was found between resting SSNA frequency and disease duration or degree of disability, a significantly negative correlation between increases in SSNA with mental arithmetic and PD duration was observed. Occurrence of SSR and SVR following SSNA bursts induced by electrical stimuli was reduced in PD (p<0.05). In patients with PD, sympathetic sudomotor and vasoconstrictive neural function was decreased at rest, but SSNA reflex latencies in the legs were nearly normal. Since responses of peripheral target organs may be impaired, both central and peripheral factors may contribute to autonomic symptoms in PD.

Sympathetic sudomotor neural function in amyotrophic lateral sclerosis

Abstract In patients with amyotrophic lateral sclerosis (ALS), sudomotor and vasomotor function have been considered to be impaired based on sympathetic skin response (SSR) or cutaneous blood flow measurements. We evaluated sympathetic sudomotor and vasoconstrictive neural function in ALS. We simultaneously recorded SSR, skin blood flow, and skin sympathetic nerve activity (SSNA) by microneurography in 20 patients with sporadic ALS and 20 healthy controls. Resting frequency of SSNA was significantly higher in ALS patients than in controls (p <0.05), but the increase of SSNA associated with mental arithmetic was smaller in ALS patients than controls (p <0.05). ALS patients also exhibited slight prolongation of SSNA reflex latencies compared with controls (p <0.05). In conclusion, sympathetic hyperactivity was observed in relation to sudomotor and vasoconstrictive skin responses. Since SSNA reflex latencies reflect central sympathetic function, the central autonomic pathways may be slightly impaired in patients with ALS.

Effect of the free radical scavenger edaravone on peripheral nerve ischemia–reperfusion injury

We investigated the effects of edaravone, a free radical scavenger, on peripheral nerve ischemia–reperfusion injury caused by ligation of vessels supplying the sciatic and tibial nerves in rats. The control group was administered a placebo, the standard‐dose group was given 3 mg/kg of edaravone intraperitoneally every 24 hours, and the low‐dose group was given 1 mg/kg of edaravone. At 7 days after reperfusion, neurological and electrophysiological parameters were improved in the standard‐dose group as compared with the control group. After 14 days, however, these differences were no longer observed. After 21 days, persistent edema and nerve fiber degeneration were noted in the standard‐dose group, but not in the control or low‐dose groups. Edaravone was effective during the early reperfusion period, but chronic inhibition of reactive oxygen species may be detrimental for nerve regeneration after ischemia–reperfusion injury. Further studies are necessary to confirm the long‐term influence of edaravone. Muscle Nerve, 2009

Analysis of the relationship between muscle sympathetic nerve activity and cardiac 123I-metaiodobenzylguanidine uptake in patients with Parkinson's disease.

To analyze the correlation between muscle sympathetic nerve activity (MSNA) and cardiac 123I‐metaiodobenzylguanidine (MIBG) uptake in patients with Parkinsons disease (PD), we measured both parameters in 14 PD patients who were 51 to 82 years of age (mean, 63.1 ± 8.7 years). The duration of PD was 2 to 26 years, and the disability level (modified Hoehn and Yahr stage) ranged from 2.0 to 4.0 (mean, 3.2 ± 0.5). MSNA was recorded from the peroneal nerve fascicles using microneurographic methods, and then cardiac MIBG scintigraphy was performed within 1 month. We analyzed the correlation between the standardized MSNA, expressed as a percentage of the predicted value based on control subject data, and the heart‐to‐mediastinum ratio (H/M) or washout ratio (WR) from early and delayed MIBG images. The relationships between disease duration or disability and MSNA, the H/M ratio, or the WR were also analyzed. No significant correlations were found between MSNA and H/M ratio or WR. Although MSNA was inversely correlated with disease duration and with disability level, neither the H/M ratio nor the WR showed a significant correlation with disease duration or disability level. Because MSNA and MIBG abnormalities were not related, functional changes in addition to organic changes in cardiac sympathetic nerve endings may result in abnormal uptake of MIBG in Parkinsons disease.

Localization of lipocaline-type prostaglandin D synthase in rat brain: immunoelectron microscopic study

The distribution of lipocaline-type prostaglandinxa0D synthase (L-PGDS) in rat brain was investigated by immunoelectron microscopy using a proteinxa0A-gold technique. In perivascular cells adjacent to the basement membrane of arterioles in the pia-arachnoid and of blood vessels in the subpial cortex, gold labeling was confined to the lumen of the dilated rough endoplasmic reticulum, and not found in the few lysosomes present in the cytoplasm. The results suggest that the perivascular cells secrete L-PGDS and seem not to degrade lipophilic molecules carried by L-PGDS. Moreover, gold particles representing the antigenic sites of L-PGDS were found in the Golgi apparatus, rough endoplasmic reticulum, vesicles, and nuclear envelope of arachnoid trabecular cells, arachnoid barrier cells, and arachnoid pia mater cells. The labeling was less detectable in the same organelles of choroid plexus epithelial cells, compared with leptomeningeal cells. In meningeal macrophages and parenchymal microglia, L-PGDS was detected in lysosomes, multivesicular bodies, and endocytic vesicles. The production of L-PGDS in perivascular cells is important to the various functions of this enzyme in brain parenchyma.

Rhythmic pupillary oscillation in Creutzfeldt‐Jakob disease associated with the Glu/Lys mutation of prion protein codon 200

We report two Creutzfeldt‐Jakob disease (CJD) patients with rhythmic pupillary and palpebral oscillation who had a mutation of prion protein codon 200 that resulted in the substitution of lysine for glutamate (Glu/Lys). Alternating dilation and constriction of the pupils combined with elevation and descent of the eyelids occurred in correspondence with periodic sharp wave complexes (PSWCs) on the electroencephalogram and with myoclonus of the head, face, and extremities. The onset of pupillary dilation and palpebral elevation coincided with the PSWCs. Initiation of these rhythmic pupillary and palpebral movements may depend on sympathetic activity, but the site of the generator is unclear. Such rhythmic pupillary and palpebral oscillation may be a feature of rapidly progressive CJD with predominant right hemispheric involvement.

A case of recurrent polymyalgia rheumatica-like complications with pregnancy

We encountered a 26-year-old Japanese woman with recurrent episodes of polymyalgia rheumatica-like symptoms associated with pregnancy. At a 13-week pregnancy, she was admitted to our outpatient clinic, complaining of myalgia on both thighs, shoulders and upper limbs. Laboratory examinations of blood yielded normal creatine kinase and mild elevation of erythrocyte sedimentation rate. After administration of oral prednisolone (10xa0mg/day) was begun, her symptoms were gradually resolved by 1xa0week. Further epidemiologic studies should be needed.