Takamura Nagasaka

NEUROFERRITINOPATHY IN A JAPANESE FAMILY WITH A DUPLICATION IN THE FERRITIN LIGHT CHAIN GENE

Neuroferritinopathy is a rare autosomal dominant movement disorder with the deposition of iron and ferritin within the basal ganglia. Four different pathogenic mutations in the ferritin light polypeptide (FTL) gene have been reported.1–4 The variety of its clinical features makes the diagnosis of neuroferritinopathy difficult. In this study we investigated a Japanese family with neuroferritinopathy to clarify the phenotypic and genetic spectrum of neuroferritinopathy. ### Proband. A 42-year-old Japanese man first developed hand tremors in his middle teens. He noticed his right foot dragging at age 35, and generalized hypotonia, hyperextensibility, aphonia, micrographia, hyperreflexia, and cognitive impairment (IQ = 66) at age 42. His unsteady gait with long steps, with his arms and legs dangling, seemed to be due mainly to hypotonus. Rigidity, spasticity, dystonia, or chorea were not observed. His serum ferritin concentration was 5 μg/L (normal = 33 to 330). A brain MRI revealed bilateral symmetric cystic changes of the pallidum and the striatum. Hyperintense lesions in the T2-weighted imaging involved the thalamus, dentate nucleus, and substantia nigra. The probands mother had developed hand tremors at age 10. She presented with difficulty walking at age 35 and developed …

Ipsilateral thalamic MRI abnormality in an epilepsy patient

In a 19-year-old patient with status epilepticus arising in the right parietal neocortex, unenhanced ictal MRI showed abnormalities mainly in the right cerebral cortex, contralateral cerebellum, and ipsilateral thalamus. The thalamus is considered a key site of functional abnormality in this patient.

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.

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.

Aging Effects of Sympathetic Reflex Activities on Skin Nerves

Background: Muscle sympathetic nerve activity (MSNA) at rest is widely known to increase with aging, but changes in skin sympathetic nerve activity (SSNA) with aging are less well defined. We examined the aging effects of reflex activities on SSNA, sympathetic skin response (SSR), and sympathetic flow response (SFR). Objective: We studied the aging effect of reflex activities on SSNA, SSR and SFR. Methods: SSNA, SSR and SFR were simultaneously recorded during randomly administered electrical stimuli. Results: The mean SSNA reflex latency was 763.1 ± 39.8 ms, mean SSNA amplitude was 12.6 ± 6.3 µV, mean SSR reflex latency was 1,809.0 ± 90.6 ms, mean SSR reflex amplitude was 0.519 ± 0.449 mV, mean SFR reflex latency was 4,398.9 ± 761.7 ms, and mean SFR reflex amplitude was 8.21 ± 5.14 ml/min/100 g. None of these parameters were significantly affected by aging. The reflex bursts on SSNA could be recorded in all subjects studied. While the frequencies of SSR and SFR were recorded in more than 80% of young subjects under age 40 years, the frequencies of SSR were recorded in less than 25% of subjects over age 80 years, and the frequencies of SFR were recorded in less than 5%. Conclusion: There were no differences in electrical stimuli-induced reflex SSNA between young and older subjects, but effector organ responses such as SSR and SFR were diminished in older subjects.

An aggressive familial amyloidotic polyneuropathy caused by a new variant transthyretin Lys 54

Article abstract Histologic examination of sural nerve of a 32-year-old man with an aggressive polyneuropathy associated with autonomic failure demonstrated amyloid deposition, and familial amyloidotic polyneuropathy (FAP) was diagnosed. Immunohistochemical staining showed transthyretin (TTR) staining of the amyloid deposits in nerve. Sequencing revealed G to A transition in the codon 54 causing TTR Lys 54. This is a new variant TTR associated with aggressive FAP.

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.

Intramedullary tuberculoma with syringomyelia

Intramedullary tuberculoma with syringomyelia is rare. We treated a woman with back pain and weakness of the left leg that had slowly progressed for more than 30 years. Radiologic evaluation demonstrated a crescent-shaped calcification at the level of the C6 vertebra, and syringomyelia from C7 to T9. Laminectomy and syringosubdural shunt placement were performed, and a tuberculoma was removed. Back pain resolved after the operation, and mobility was facilitated. We recommend surgery for intrathecal tuberculoma with syringomyelia even when the course has been prolonged with no active tuberculous lesion.