Sympathetic sudomotor neural function in amyotrophic lateral sclerosis.

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.

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 Parkinson's 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.

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 (123)I-metaiodobenzylguanidine (MIBG) uptake in patients with Parkinson's 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 Parkinson's disease. .

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.

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 microV, 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.

A comparison of sympathetic outflow to muscles between cervical spondylotic amyotrophy and ALS.

To confirm the diagnostic usefulness of muscle sympathetic nerve activity (MSNA) in differentiation between cervical spondylotic amyotrophy (CSA) and amyotrophic lateral sclerosis (ALS) with cervical spondylosis (CS), MSNA, heart rate (HR) and blood pressure (BP) were recorded in 10 patients with CSA and ALS with CS, and age-matched healthy volunteers at rest and during head-up tilting. There were no differences in age, disability scores, pulmonary function, and HR or BP at rest between ALS and CSA groups. Resting MSNA was significantly greater in patients with ALS with CS than in comparison groups (P<0.001) with virtually no overlap between ALS and the CSA groups. During head-up tilting, changes in BP and MSNA were significantly less in patients with ALS than in patients with other subjects. MSNA at rest clearly differentiated CSA from ALS with CS, suggesting diagnostic utility.