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. .     

Inhibition of muscle sympathetic nerve activity during yawning

Yawning is a complex event that depends largely on the autonomic nervous system. Microneurographic techniques were used to study the mechanism involved in yawning. A series of spontaneous yawns displayed by a healthy 39-year-old male offered us the opportunity to study the muscle sympathetic nerve activity (MSNA) during this phenomenon. It was found that 2 s of yawning inhibited the MSNA recorded at the right peroneal nerve in the lateral knee area, while 3 s of slow expiration succeeding a yawn provoked an MSNA discharge. Blood pressure decreased with each slow expiration by 5–6 mmHg, and increased again with the renewed MSNA discharge. We conclude that yawning is associated with a sympathetic suppression that favours a parasympathetic dominance, as indicated by the MSNA and the decrease in blood pressure. The slow expiration following a yawn is associated with a sympathetic activation marked by an MSNA discharge and an increase in blood pressure.     

Lowered cardiac sympathetic nerve performance in response to exercise in Parkinson's disease

We examined whether cardiac sympathetic denervation influences the cardiovascular response to exercise in Parkinson's disease (PD). Sixteen patients with PD were divided into two groups, according to their cardiac uptake of ¹²³I‐metaiodobenzylguanidine (denervated group, 10 patients with heart to mediastinum (H/M) ratio < 1.7; innervated group, six patients with H/M ratio > 1.7) and compared changes in blood pressure (BP), heart rate (HR), and cardiac contractility with 13 control subjects during ergometric exercise stress. Velocity index (VI), an indicator of cardiac contractility, was measured using impedance cardiography and recorded every minute. Exercise began at a power output of 20 W for the first 2 min and increased 10 W every 2 min to a maximal intensity of 60 W. All control subjects accomplished the procedure while six patients with PD could not continue after the first minute of 50 W loading. There were no significant differences in BP or HR change between the three groups. However, a significant reduction in VI was observed from the first minute of the 30 W workload in the denervated group compared to the control group. This lowered response continued till 50 W loading and was significantly different to the innervated group at 50 W loading. No significant VI changes were observed between the control and innervated groups throughout the exercise test. Patients with PD with reduced MIBG uptake had a lowered cardiac contractility than innervated subjects during exercise, suggesting that this response represents theimpaired exercise capacity of patients with PD with cardiac sympathetic denervation. © 2010 Movement Disorder Society     

Relationship of muscle sympathetic nerve activity to insulin sensitivity

Purpose

An association between insulin resistance and activation of the sympathetic nervous system has been reported in previous studies. However, potential interactions between insulin sensitivity and sympathetic neural mechanisms in healthy people remain poorly understood. We conducted a study to determine the relationship between sympathetic activity and insulin resistance in young, healthy humans.

Methods

Thirty-seven healthy adults (18–35 years, BMI <28 kg m^?2) were studied. Resting muscle sympathetic nerve activity (MSNA) was measured with microneurography and insulin sensitivity of glucose and free fatty acid metabolism was measured during a hyperinsulinemic-euglycemic clamp with two levels of insulin.

Results

During lower doses of insulin, we found a small association between lower insulin sensitivity and higher MSNA (P < 0.05) but age was a cofactor in this relationship. Overall, we found no difference in insulin sensitivity between groups of low and high MSNA, but when women were analyzed separately, insulin sensitivity was lower in the high MSNA group compared with the low MSNA group of women.

Conclusions

These data suggest that MSNA and insulin sensitivity are only weakly associated with young healthy individuals and that age and sex may be important modifiers of this relationship.     

Skin nerve sympathetic activity reflex latency in Parkinson''s disease

Using a microneurographic method, skin nerve sympathetic activity (SSA) reflex latency was measured in 16 patients suffering from idiopathic Parkinson's disease (PD) and 11 age-matched normal subjects. The mean latency in patients with PD was significantly delayed (0.821 s, p less than 0.01), when compared with that in normal subjects (0.676 s). Reflex latency showed a significant positive linear correlation with arm length. By determining the SSA reflex latency, conduction velocities in post-ganglionic skin sympathetic nerve were measured indirectly. Averaged conduction velocities in PD and normal subjects, 1.76 m/s and 1.86 m/s, respectively, did not differ significantly (p greater than 0.1). This data suggests that the reflex pathway of SSA is disturbed in patients with PD and that the increased reflex latency is caused by a central/preganglionic delay.     

Changes in muscle sympathetic nerve activity during sleep in humans.

We microneurographically recorded muscle sympathetic nerve activity (MSA) during sleep in 12 healthy volunteers while simultaneously recording EEG, EOG, ECG, respiration, and blood pressure and determined the number of pulse-synchronous MSA bursts per minute (burst rate) for non-rapid eye movement (nonREM) sleep and rapid eye movement (REM) sleep. MSA decreased during nonREM sleep with progressively deeper sleep stages. During REM sleep, the burst rate of MSA increased and was associated with marked fluctuations in arterial blood pressure. During sleep stage 2, MSA bursts occurred approximately 1 second after spontaneous K-complexes. We conclude that (1) the decreases in MSA during nonREM sleep stages may indicate sleep-stage dependent central suppression of MSA activity; (2) increases in MSA during REM sleep suggest instability of the autonomic nervous system; and (3) a common pathway may exist for MSA bursts and K-complexes.     

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.Corresponding Author     

Parallel changes in resting muscle sympathetic nerve activity and blood pressure in a hypertensive OSAS patient demonstrate treatment efficacy

Studies comparing the efficacy of continuous positive airway pressure (CPAP) versus surgery in correcting cardiovascular abnormalities in OSAS are lacking. We describe an OSAS patient with hypertension who responded favorably to CPAP treatment, whereas subsequent uvulopalatopharyngoplasty (UPPP) was less successful. While CPAP markedly lowered daytime muscle sympathetic nerve activity (MSNA) and blood pressure (BP), findings after UPPP were comparable to pre-treatment baseline. Thus, parallel changes in MSNA and BP demonstrated treatment efficacy.     

Acute sex hormone suppression reduces skeletal muscle sympathetic nerve activity

Objectives  

Comparisons of sympathetic nervous system activity (SNA) between young and older women have produced equivocal results, in part due to inadequate control for potential differences in sex hormone concentrations, age, and body composition. The aim of the present study was to determine the effect of a short-term reduction in sex hormones on tonic skeletal muscle sympathetic nerve activity (MSNA), an indirect measure of whole body SNA, using an experimental model of sex hormone deficiency in young women. We also assessed the independent effects of estradiol and progesterone add-back therapy on MSNA.     

交感皮肤反应对帕金森病自主神经损害的诊断价值

目的探讨交感皮肤反应(SSR)对帕金森病(PD)患者自主神经损害的诊断价值。方法选择62例PD患者(PD组)和26例年龄、性别、身高相匹配的健康志愿者(健康对照组)进行上下肢SSR检测。将PD组根据有无自主神经症状分为有症状组和无症状组;根据Hoehn-Yahr分级将PD组分为早期PD组(1～2期)和中晚期PD组(3～5期)。结果①与健康对照组比较,PD无论有症状组还是无症状组SSR潜伏期延长和波幅下降(均P0.05);有症状组较无症状组潜伏期延长和波幅下降(均P0.05);②与健康对照组比较,不论中晚期PD组还是早期PD组SSR潜伏期延长和波幅下降(均P0.05),中晚期PD组较早期PD组潜伏期显著延长和波幅下降(均P0.05);③SSR上下肢潜伏期与Hoehn-YaHr分级呈显著性正相关(P0.01),SSR上下肢波幅与Hoehn-YaHr分级呈显著性负相关(P0.01)。结论①SSR是检测PD患者自主神经功能障碍的客观敏感手段,可发现亚临床自主神经损害,有助于早期诊断;②PD患者运动系统障碍越重,出现自主神经病变的程度越重。     

Enhanced muscle sympathetic nerve activity during sleep apnea in the elderly.

To examine how muscle sympathetic nerve activity (MSNA) becomes modified during sleep apnea in the elderly, we analyzed polysomnographic recording simultaneously with microneurographically recorded MSNA. Subjects were three healthy elderly males aged 72, 75, and 76. MSNA was suppressed with deeper non-REM sleep stages in these elderly subjects. In all three subjects, sleep apnea for 10 s or longer was observed during sleep of 00:00-06:00. During sleep apnea, MSNA was enhanced concomitantly with a blood pressure fall and a reduction in saturation rate of oxyhemoglobin. With the termination of sleep apnea, MSNA was maximally enhanced with a transient elevation of blood pressure. We conclude that sleep apnea induces an enhancement of MSNA, which may be responsible for hypertensive episodes during sleep.     

Agrypnia Excitata: A microneurographic study of muscle sympathetic nerve activity

ObjectiveAgrypnia Excitata (AE) is characterized by autonomic over-activity and cardiovascular fluctuations but direct evidence of sympathoexcitation is lacking. AE is a common feature of acquired (i.e. Morvan’s syndrome – MS) and genetic (i.e. fatal familial insomnia – FFI) conditions where a dysfunction of the thalamo-limbic system has been suggested. The aim of this study is to report the first microneurographic recordings of sympathetic activity in acquired and genetic AE to investigate the pattern of sympathetic activation.MethodsWe describe two patients presenting acquired AE (MS) as demonstrated by elevated serum antibody levels to voltage-gated potassium channels and one patient with genetically confirmed FFI. Patients and fifteen sex and age-matched healthy controls underwent microneurography from peroneal nerve to assess muscle sympathetic nerve activity (MSNA) and heart rate (HR).ResultsMean level of resting awake MSNA and HR was significantly increased in patients compared to controls. Patients presented a similar pattern of MSNA with a normal cardiac rhythmicity and a very high burst incidence expressed in approximately each cardiac beat.ConclusionsAcquired and genetic AE presented a resting awake sympathetic over-activity.SignificanceAE patients may develop high blood pressure and/or cardiovascular instability potentially increasing the morbility/mortality of the underlying disorders.     

Subthalamic neuron activity related to tremor and movement in Parkinson's disease

Single cell activity recorded in the subthalamic nucleus (STN) of Parkinson's patients and the effect of tremor, passive and voluntary movement upon the same cells are described. Three types of cells were distinguished by the pattern of discharge: tonic, phasic and rhythmic. They all demonstrated high mean firing rates (65, 59 and 69 Hz, respectively). Simultaneous recordings of muscle activity and tremor helped in defining cell activity. The implantation of the definitive stimulating electrode in the patients was based on the number of STN cells related to tremor, active and passive movements (mean = 68%) along the track chosen. Cells were related to tremor (n = 21; 11%), modified the discharge with differences in the amplitude of tremor (n = 4), and changed the rate and pattern when tremor stopped spontaneously or artificially (n = 6). Movement-related cells (n = 97; 51%) showed a cyclic activity correlated with phases of the movement, or modified the firing rate along the performance of the movement. Tremor and movement-related cells (n = 11; 6%) revealed an interesting sensory-motor integrative function.     

Cardiac sympathetic denervation in bradykinesia-dominant Parkinson's disease

Cardiac iodine-123-labeled-metaiodobenzylguanidine uptake is reduced in early-stage Parkinson's disease, suggesting sympathetic nerve degeneration. The scintigraphic findings in patients with Parkinson's disease with different clinical features have, however, not been established. Iodine-123-labeled-metaiodobenzylguanidine myocardial scintigraphy was performed in 143 patients with Parkinson's disease. The early and delayed heart to mediastinum ratios were analyzed according to the dominant motor deficit (tremor, bradykinesia, rigidity, and postural instability), age, sex, age at onset, disease duration, and Hoehn and Yahr stage. Both ratios correlated with bradykinesia, age at disease onset, and disease duration; but not with sex, Hoehn and Yahr stage, tremor, rigidity, and postural instability. Our results suggest a close link between myocardial sympathetic degeneration and bradykinesia, age at onset and disease duration.     

Increased muscle sympathetic nerve activity and impaired baroreflex control in isolated REM-sleep behavior disorder

ObjectiveChanges in baroreflex sensitivity have been reported in patients with idiopathic Parkinson’s disease (PD). We sought to investigate the hypothesis that patients with isolated rapid eye movement (REM)-sleep behavior disorder (iRBD), known to be a prodromal stage for PD, will show abnormalities in baroreflex control.MethodsTen iRBD patients were compared to 10 sex- and age-matched healthy controls. Their cardiovascular parameters and muscle sympathetic nerve activity (MSNA) were evaluated at rest and during baroreflex stimulation.ResultsMSNA at rest was higher in iRBD patients (burst frequency [BF]: 44 ± 3 bursts/min; burst incidence [BI]: 60 ± 8 bursts/100 heartbeats) as compared to the controls (BF: 29 ± 3 bursts/min, p < 0.001; BI: 43 ± 9 bursts/100 heartbeats, p < 0.001). During baroreflex stimulation, iRBD patients showed increased absolute values of MSNA (BF: F = 62.728; p < 0.001; BI: F = 16.277; p < 0.001) as compared to the controls. The iRBD patients had decreased diastolic blood pressure at baseline and during lower body negative pressure, but the level of significance was not met.ConclusionOur study shows increased MSNA and impaired baroreflex control in iRBD patients. We propose that the inhibitory effect of locus coeruleus on baroreflex function might be impaired, leading to the disinhibition of sympathetic outflow.SignificanceThese findings might reflect the destruction of brain areas due to the ascending P-α-synuclein deposits in iRBD patients.     

Relative burst amplitude in human muscle sympathetic nerve activity: a sensitive indicator of altered sympathetic traffic

Microneurographically recorded sympathetic outflow to the human muscle vascular bed is traditionally quantified by identifying pulse-synchronous bursts of impulses in a mean voltage neurogram and expressing them in terms of bursts per minute (burst frequency) or bursts per 100 heart beats (burst incidence). As both these measures show large inter-individual differences in resting healthy subjects, a problem arises when comparing sympathetic traffic in cross-sectional studies, making moderate differences in muscle sympathetic nerve activity (MSA) between groups difficult to identify. Absolute measures of the strength of the sympathetic discharges (burst amplitude or area) can also be evaluated. However, as they critically depend on the proximity of the microelectrode to the recorded fibres, such measures cannot be used for inter-individual comparisons.The aim of the present study was to evaluate the use of relative burst amplitude spectra for quantification of MSA, describing the proportion of small vs large bursts in a neurogram. We recorded MSA in 18 patients with mild to moderate congestive heart failure (CHF) (New York Heat Association functional classes I–IIIA) and 18 matched healthy controls. Sympathetic activity was expressed as burst frequency, burst incidence and burst amplitude spectra. When comparing the traditional burst counts between the groups (presented as the median and 25th–75th percentiles) there was a tendency towards higher MSA in CHF patients, but the difference was not significant (42 (34–52) vs 53 (41–63) bursts/min, 62 (51–78) vs 69 (52–84) bursts/100 heart beats, both ns). Relative burst amplitude spectra, on the other hand, were clearly shifted to the right in the CHF group compared to the control group (median burst amplitudes 42 (34–45) vs 30 (28–35),P=0.0002).Relative burst amplitude spectra thus appear to provide a more sensitive indicator of altered MSA than traditional burst counts. The right-ward shift of these spectra may suggest that sympatho-excitation occurs early in the development of CHF.     

Effect of L-threo-3,4-dihydroxyphenylserine on muscle sympathetic nerve activity in humans.

To clarify the effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), a precursor of norepinephrine (NE), the effect of this drug on microneurographically recorded muscle sympathetic nerve activity (MSA) from the tibial nerve was analyzed in ten healthy male volunteers. A single dose of 600 mg of L-threo-DOPS was orally administered and the effect of this norepinephrine precursor on MSA at resting and at upright standing positions, as well as the MSA responsiveness to head-up tilting was examined by comparing the data obtained after administration of the drug with those obtained under control conditions. The plasma NE levels were determined in two subjects. The results were as follows: (1) resting MSA increased significantly 80 min after administration of L-threo-DOPS and was accompanied by an increase in plasma NE levels; (2) standing MSA when treated with the drug was not significantly different from values obtained under control conditions; and (3) MSA responsiveness to orthostasis was reduced after L-threo-DOPS. We conclude from the activation of MSA by L-threo-DOPS that this drug raised blood pressure not only through an increase in metabolized plasma NE levels, but also through the enhancement of MSA by activation of descending noradrenergic or adrenergic pathways proximal to the recording site of the sympathetic discharge.     

Reduced arterial baroreflex control of muscle sympathetic nerve activity in young borderline hypertensives

Mean arterial pressure (MAP), heart interval (HI) and muscle sympathetic nerve activity (MSNA) were measured before and after a bolus injection of phenylephrine in 11 normotensives (NT) and 12 borderline hypertensives (BHT). (1) Basal MSNA was elevated in BHT compared to NT. (2) Both baroreflex slope for HI and that for MSNA were significantly less in BHT. (3) There was an inverse correlation between the slope for MSNA and the basal MSNA (r = -0.63). Thus, arterial baroreflex control of sympathetic activity may be reduced in BHT and the reduction may be involved in the elevated sympathetic nerve activity in these subjects.