Kazumasa Shindo

Increased sympathetic outflow to muscles in patients with amyotrophic lateral sclerosis: a comparison with other neuromuscular patients

We investigated the effects of muscle loss and limitation of daily activities on sympathetic outflow to muscles by measuring muscle sympathetic nerve activity (MSNA) in 12 patients with amyotrophic lateral sclerosis (ALS) as compared with other 15 neuromuscular patients (controls). The burst incidence of MSNA at rest was significantly higher in patients with ALS, even in elderly patients, compared with controls (p < 0.01). There were no differences in the level of disability, heart rate or blood pressure at rest between two groups. Blood pressure and MSNA were less changed by head-up tilting in patients with ALS compared with controls. MSNA of ALS was not correlated with the disability score, PaO2, PaCO2, forced vital capacity, the disease duration or prognosis. MSNA at rest was increased in ALS patients, regardless of the severity of muscle loss or disability. It might be suggested that autonomic motor neurons seem to become affected by the same pathologic process that kills motor neurons.

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 …

Microneurographic analysis of muscle sympathetic nerve activity in amyotrophic lateral sclerosis

Muscle sympathetic nerve activity by (microneurograph) blood pressure and heart rate has been studied in patients with amyotrophic lateral sclerosis and in age-matched normal subjects (controls) at rest and during head-up tilt. Muscle sympathetic nerve activity in amyotrophic lateral sclerosis patients was significantly increased at rest unlike controls. There was no correlation between muscle sympathetic nerve activity and age in the patients with amyotrophic lateral sclerosis. Elevated muscle sympathetic nerve activity was present mainly in younger patients. There were no differences between blood pressure or heart rate in either group at rest or during head-up tilt in amyotrophic lateral sclerosis. The increase in muscle sympathetic nerve activity following tilt in the amyotrophic lateral sclerosis patients was less than in the controls, but they had no postural hypotension. The possible reasons for this observation of increased muscle sympathetic nerve activity at rest in amyotrophic lateral sclerosis are discussed.

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.

Unilateral tongue atrophy due to an enlarged emissary vein in the hypoglossal canal

A 16-year-old girl presented to our clinic with right-sided tongue atrophy and fasciculations of 1-year duration. Enlargement of the outer opening of the hypoglossal canal was reveal by conventional and computed tomography of the skull. Magnetic resonance imaging disclosed an enlarged venous system extending from the jugular vein to the internal jugular vein on the right, with low signal density suggestive of a flow void. A right-sided occipital craniotomy was performed. When the hypoglossal canal was opened, an enlarged emissary vein compressing the hypoglossal nerve was identified. This is the first reported case of unilateral tongue atrophy and an enlarged hypoglossal canal due to an enlarged emissary vein.

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.