Autonomic Dysfunction in Adult Migraineurs

SYNOPSIS
The autonomic nervous system (ANS) functions of 60 migraine patients, aged from 23 to 50 years, wereinvestigated during headache-free intervals by utilizing a number of cardiovascular reflexes as indices.Thirty-five healthy subjects of similar age served as a control group. The pulse rate (R-R-interval) variationwas recorded in normal and deep breathing, in the Valsalva manoeuvre, and in an orthostatic test (a tilttable was used); and the blood pressure reactions were recorded in an orthostatic test and in an isometricwork (hand grip) test.There were significant differences in the results between migraine patients and control subjects in theR-R-interval variation ratio, both in normal and deep breathing tests and in the Valsalva manoeuvre. Thedifferences between migraine patients and controls in pulse rate variation in orthostatic test and in bloodpressure reactions in isometric work test were highly significant (p < 0.001 ). There were no statisticallysignificant differences in cardiovascular reflex responses of various subgroups of migraine patients(common-classic, frequent-infrequent attacks, normal-abnormal EEGs). These results suggest mildparasympathetic hypo function, but more definite sympathetic hypofunction (Valsalva manoeuvre,orthostatic test and isometric work test) in adult migraine patients during headache-free intervals.     

Cardiovascular autonomic control is disturbed in nocturnal teethgrinders

Summary. To examine the hypothesis of disturbed autonomic function, non-invasive cardiovascular reflex tests were performed on 11 sleep bruxists in the waking state. The tests included the Valsalva manoeuvre, a deep-breathing test, and an orthostatic test (standing up). The R-R intervals were monitored continuously, and blood pressure was measured non-invasively and continuously using the Finapres method. In total, 64% of bruxists showed abnormalities in at least two variables reflecting the cardiovascular autonomic function. Abnormalities were found in blood pressure regulation during the Valsalva strain, and in the immediate biphasic heart rate response during standing up, but not in the vagally mediated deep-breathing difference. These findings suggest that bruxism is accompanied by abnormalities in autonomic function, particularly in sympathetic vasoconstrictor function.     

下蹲-站立试验测定糖尿病心脏植物神经病变

目的　寻找一种理想的心脏自主神经功能试验。方法　标准做法 :受试者静立 3分钟 ,然后下蹲 1分钟 ,最后在一个吸气期站立。下蹲 站立试验 (SST) :SST迷走 [SSTv] =下蹲前R R间期均值与下蹲后最长R R间期比值 ;SST交感[SSTs] =基础R R间期与站立后最短R R间期比值。结果　计算了 362例健康人和 2 19例糖尿病人 ,取得 2 0～ 64岁健康人的 95 %和 99%可信性区间 (CIs)的正常值。糖尿病人和健康人SSTv超出 99%CI分别是 91(42 % )和 5例 (1.4% )。SSTs分别是 88例 (40 % )和 3例 (0 .8% )。SST还与其它常用检查比较。结论　 (1)SST区别健康人和糖尿病人等于或优于其它试验。 (2 )SST可以同时给出交感和副交感神经功能的资料。     

Autonomic cardiovascular responses in old age

Summary. The effect of age on autonomically mediated cardiovascular responses to certain manoeuvres was studied in 15, healthy, old men and women (60–80 years). The results were compared with groups of healthy young (about 25 years) and middle-aged (about 45 years) subjects. There was no significant reduction in cardiovascular responses between the young and middle-aged groups. Respiratory sinus arrhythmia, and heart rate, blood-pressure and contralateral forearm blood flow increases to isometric hand grip, as well as the heart rate decrease during a dive reflex test, were significantly attenuated in the old age group. The Valsalva ratio, and the heart rate and blood-pressure changes during an 8 min orthostatic test did not differ between the old and the two younger age groups. There seems to be only a moderate attenuation of autonomic cardiovascular responses to about 60 years, after which there is a more rapid decline. The difference in reduction between different responses, even those mediated by the same type of autonomic nerve, suggests that the decreased responses are not due to an isolated impaired function of the peripheral autonomic nerve. The impairment may be due to the receptor organ or a combination of defects in function of several parts of the autonomic nervous system in old age.     

Cardiovascular Reflexes in Young Migraine Patients

SYNOPSIS
The autonomic nervous system functions of 49 young migraine patients, aged from 11 to 22 years, wereinvestigated during headache-free intervals by utilizing a number of cardiovascular reflexes as indices.Twenty-five healthy subjects of similar age served as a control group. The pulse rate (R-R-interval)variation was registered in normal and deep breathing, during the Valsalva manoeuvre, and in anorthostatic test (a tilt table was used); and the blood pressure measurements were performed in anorthostatic test and during an isometric work test. There were no significant differences between the groupof young migraine patients and the control group. Furthermore, all numeric mean values were in thenormal limits given in the literature; only incidental abnormal values were encountered, and even then inboth groups. Moreover, the cardiovascular reflex responses of various subgroups of migraine patients(common-classic, frequent -infrequent attacks, patients with or without autonomic nervous system dysfunction signs during attacks, normal-abnormal EEGs), did not significantly differ from each otherduring this interictal recording period. The results suggest intact autonomic nervous system functions inyoung migraine patients during headache free intervals.     

Cough test to assess cardiovascular autonomic reflexes in diabetes

Coughing induces cardioacceleratory responses under cholinergic control. The Cough Test (CT), a standardized test that uses a series of coughs with electrocardiographic monitoring, was used to assess the functional integrity of cardiovascular autonomic nerves. In 224 control subjects and 235 diabetic patients, heart-rate (HR) responses were compared with four established tests: lying to standing (LS), standing to lying (SL), deep breathing (DB), and Valsalva maneuver (VM). In control subjects, HR responses declined significantly with age in a curvilinear pattern. Log-transformed indices were used to estimate percentiles. The CT-HR responses were reproducible and significantly associated with other HR-response tests. Sixty-nine (29%) diabetic patients had an abnormal value less than or equal to 1st percentile, whereas only 2 control subjects had such an abnormality. Among diabetic patients, age and duration of diabetes exerted a significant negative influence. With the use of the criteria of two abnormal or one abnormal and two borderline tests (among CT, LS, SL, DB, or VM) as a minimal criteria for cardiovascular autonomic neuropathy, CT and LS had the least overlap between the control and diabetic populations and were significantly better than SL or VM (P less than 0.005 for CT, P less than 0.01 for LS). They were not different from DB. We found the CT to be simple to perform, reproducible, and useful for the assessment of cardiovascular autonomic reflexes.     

Prevalence of cardiovascular autonomic dysfunction assessed by spectral analysis and standard tests of heart-rate variation in newly diagnosed IDDM patients.

OBJECTIVE--To determine the prevalence of cardiovascular autonomic nerve dysfunction in patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) compared with healthy nondiabetic subjects. RESEARCH DESIGN AND METHODS--A battery of cardiovascular reflex tests was performed in 130 newly diagnosed IDDM patients aged 12-40 yr at mean blood glucose levels of 7.2 mM after insulin had been administered for 3-39 days. Age-dependent lower limits of normal of these tests were defined at the 2.3 percentile in 120 nondiabetic subjects. Tests of heart-rate variation (HRV) included the coefficient of variation (C.V.) and the low-frequency (LF), midfrequency (MF), and high-frequency (HF) bands of spectral analysis at rest, HRV during deep breathing (C.V., expiratory-inspiratory ratio, and mean circular resultant), Valsalva ratio, and maximum/minimum 30:15 ratio. In addition, spectral analysis on standing, the change in systolic blood pressure to standing, and diastolic blood pressure response to sustained handgrip were determined in 50 patients. RESULTS--A significantly higher percentage of abnormal test responses in the diabetic group compared with the control group was noted for power spectrum in the LF band (7.3 vs. 0.8%, P less than 0.05) and MF band (10.6 vs. 0%, P less than 0.001) at rest and HF band on standing (10.0 vs. 0.9%, P less than 0.05), maximum/minimum 30:15 ratio (25.4 vs. 5.0%, P less than 0.001), and Valsalva ratio (17.5 vs. 4.2%, P less than 0.001). There were no significant differences between both groups in regard to the remaining parameters. Ten (7.7%) diabetic patients but none of the nondiabetic subjects had cardiovascular autonomic neuropathy defined by the strict criterion of abnormal results in more than three of six tests (P less than 0.001). In addition, 12 (9.2%) patients but only 2 (1.7%) control subjects had abnormal results in two of six tests (P less than 0.01). CONCLUSIONS--Cardiovascular autonomic nerve dysfunction is relatively common in newly diagnosed IDDM patients after correction of the initial metabolic imbalance. A combination of tests based on spectral and conventional analysis of HRV appears suitable for detection of early abnormalities in autonomic function in diabetes.     

Impaired Cardiovascular Reflexes in Cluster Headache and Migraine Patients: Evidence for an Autonomic Dysfunction

SYNOPSIS
To investigate autonomic nervous system involvement in cluster headache (CH) and migraine, we compared the cardiovascular reflex responses of common migraine and CH subjects to a group of controls. A battery of 5 well-codified autonomic tests was applied: (1) deep breathing test (DB); (2) lying to standing test (LS); (3) Valsalva manoeuvre (VAL); (4) postural hypotension test (PH); (5) blood pressure response to sustained handgrip (SHG). Our data confirm an autonomic dysfunction in CH, mainly affecting the parasympathetic system. Evidence for an impairment of sympathetic cardiovascular reflex regulation was obtained in the common migraine group.     

Attenuated Valsalva heart rate response in subjects with smoking history: possible role of autonomic dysfunction

Summary. The effects of smoking habits on aotnomic cardiovascular heart rate reflexes were studied in 143 healthy subjects by using the Valsalva manoeuvre and deep breathing tests. Smoking seemed to cause attenuation of the Valsalva heart rate response. This attenuation was present also after adjustment for possible confounding factors including alcohol consumption. Our findings show that in subjects with smoking history there may occur dysfunction in some part of the autonomic reflex arch mediating the Valsalva heart rate response.     

Noninvasive exploration of cardiac autonomic neuropathy. Four reliable methods for diabetes?

OBJECTIVE: The purpose of this work was to assess relevant information that could be provided by various mathematical analyses of spontaneous blood pressure (BP) and heart rate (HR) variabilities in diabetic cardiovascular neuropathy. RESEARCH DESIGN AND METHODS: There were 10 healthy volunteers and 11 diabetic subjects included in the study. Diabetic patients were selected for nonsymptomatic orthostatic hypotension in an assessment of their cardiovascular autonomic impairment. Cardiac autonomic function was scored according to Ewing's methodology adapted to the use of a Finapres device. The spontaneous beat-to-beat BP and HR variabilities were then analyzed on a 1-h recording in supine subjects. The global variabilities were assessed by standard deviation, fractal dimension, and spectral power. The cardiac baroreflex function was estimated by cross-spectral sequences and Z analyses. RESULTS: In diabetic patients, Ewing's scores ranged from 1 to 4.5, confirming cardiovascular autonomic dysfunction. In these diabetic patients, global indices of variabilities were consistently lower than in healthy subjects. Furthermore, some of them (standard deviation and fractal dimension of HR, spectral power of systolic blood pressure and HR) were significantly correlated with the Ewing's scores. The Z methods and the spectral analysis found that the cardiac baroreflex was less effective in diabetic subjects. However, the baroreflex sensitivity could not be reliably assessed in all the patients. The sequence method pointed out a decreased number of baroreflex sequences in diabetic subjects that was correlated to the Ewing's score. CONCLUSIONS: Indices of HR spontaneous beat-to-beat variability are consistently related to the degree of cardiac autonomic dysfunction, according to Ewing's methodology. The Z method and spectral analysis confirmed that the cardiac baroreflex was impaired in diabetic patients. These methods might be clinically relevant for use in detecting incipient neuropathy in diabetic patients.     

Time-related heart autonomic balance characteristics in healthy subjects

Changes of the heart autonomic balance between morning (8-9 h) and afternoon (14-15 h) measurements were studied in 22 healthy subjects. The selection of these two daytime periods was substantiated by the established higher risk of cardiovascular incidents in the morning and the relative balance of the vegetative nervous system in the afternoon hours. The changes were analysed by RR-variability indices from ECG recordings in the resting state and with vegetative nervous system stimulation by the handgrip test and Valsalva manoeuvre. It was shown that there were no significant differences between the morning and afternoon values of the respective indices, between morning and afternoon handgrip tests and between morning and afternoon Valsalva manoeuvres. However, there were significant differences in comparison of the index values between resting state and handgrip test and resting state and Valsalva manoeuvre, both from morning and afternoon measurements. Moreover, the significantly differing indices were clustered in different groupings, when comparing resting state recordings with morning and afternoon stimulation tests. For this reason, the authors introduced an indicator for time-related autonomic balance changes. The indicator evaluates the power of each RR-variability index to respond to changes in the autonomic control, in comparisons between resting state and stimulation data in the morning and afternoon measurements. These evaluations showed low power of the frequency-domain indices to respond to time-related autonomic balance changes in stimulation, with respect to the resting state. The time-domain indices have considerably higher power to react to relative morning and afternoon changes in the two vegetative nervous system components. Based on the estimations of the RR-variability indices obtained by the introduced indicator, a profile was constructed to represent time-related heart autonomic balance changes in healthy subjects. It was established that in spite of the relative stability of the vegetative nervous system in healthy subjects, hypersympatheticotonia and relatively lower parasympathetic tone were present in the risky morning hours.     

Afferent baroreflex dysfunction and age-related orthostatic hypotension.

1. To test the hypothesis that in apparently healthy elderly subjects with orthostatic hypotension there is afferent baroreflex dysfunction, cardiovascular and neurohumoral responses were measured after separate stimuli which activated baroreceptor (head-up tilt) and non-baroreceptor (cold stress, isometric exercise) afferent pathways. 2. In 15 healthy elderly control subjects blood pressure did not change with 60 degrees head-up tilting and there was a moderate increase in heart rate, whereas in 13 subjects with age-related orthostatic hypotension head-up tilting was associated with a marked fall in blood pressure but a similar heart rate response to that in the elderly control group. In contrast, both groups of subjects had similar blood pressure and heart rate responses to cold stress and sustained isometric exercise. 3. Nine subjects with autonomic neuropathy also showed a marked hypotensive response to head-up tilt, but produced no pressor response to cold stress or isometric exercise. 4. The plasma concentrations of noradrenaline, adrenaline and neuropeptide-Y-like immunoreactivity rose and that of atrial natriuretic peptide fell after head-up tilt in the study population as a whole. There were no significant differences between groups despite the much greater blood pressure drops in the subjects with autonomic neuropathy and in those with age-associated orthostatic hypotension. 5. The aorto-iliac pulse wave velocity index was significantly higher in subjects with age-associated orthostatic hypotension compared with that in control subjects. 6. The pattern of responses to the separate stresses observed in the group with age-associated orthostatic hypotension is characteristic and different from that in the elderly control subjects and the subjects with autonomic neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Patterns of QT/QS2 ratio in vasomotorically labile young men

The QT/QS2 ratio in seven 21-year-old men with a history of vasomotor lability was measured when they were resting supine and during orthostatic, Valsalva and diving reflex tests. The vasolability was characterized by an abnormal sympathicotonic heart rate (HR) response to the orthostatic test and vacillating inferoapical T waves in the ECG. The results of the vasolabile subjects were compared to those of seven fit control subjects of the same age. In spite of equal HR's in both groups the vasolabile subjects' QT/Q2 ratio constantly exceeded 1.00 during the whole test protocol and it was higher than of the controls (P = 0.04). The reversed QT/QS2 relationship in the test subjects seemed to be due both to a prolongation of the QT time and a shortening of the QS2 time. This difference prevailed throughout although the reaction pattern to autonomic stimulations was equal in both groups. We considered an inadequate neural control of the heart, possibly with metabolic and haemodynamic interactions, responsible for the prolongation of the electrical systole in relation to the electromechanical systole in the heart of the vasomotorically labile subjects.     

The validity of a hyperventilation test for an investigation of autonomic failure: assessment in patients with multiple system atrophy and Parkinson's disease

Although heart rate (HR) responses to hyperventilation (HV) have been used as a cardiovascular autonomic function test, autonomic involvement during HV remains uncertain. To clarify the relationship between autonomic activity and cardiovascular changes during HV, we compared cardiovascular responses during HV among subjects with different autonomic function, namely 16 patients with probable multiple system atrophy (MSA), 16 with possible MSA, 28 with Parkinson's disease (PD) and 28 healthy controls. Abnormalities of cardiovascular responses to head-up postural change and the Valsalva maneuver were definitely present in the order of probable MSA, possible MSA and PD, and abnormal HR and blood pressure (BP) responses during HV were observed in probable MSA and possible MSA, but not in PD. Unlike the significant difference in standard cardiovascular autonomic function tests, the HR and BP responses during HV were equivalent between probable and possible MSA. These findings suggest that cardiovascular control during HV may be affected not only by autonomic activity but also by other factors.     

Is pancreatic polypeptide response to food ingestion a reliable index of vagal function in type 1 diabetes?

OBJECTIVE: The diagnosis of autonomic neuropathy in diabetic patients is based on cardiovascular reflex tests. Since cardiac function may be affected by arteriosclerosis and cardiomyopathy in type 1 diabetes mellitus, alternative tests reflecting vagal nerve function, in other organ systems, are needed. In this study the pancreatic polypeptide (PP) response to a mixed meal was evaluated in healthy subjects and in recently diagnosed type 1 diabetic patients. MATERIAL AND METHODS: The PP response was studied at different levels of the vagally mediated reflex arch by application of different stimuli: meal ingestion, i.v. edrophonium (a cholinesterase inhibitor) injection and arginine infusion. RESULTS: Meal ingestion (stimulation of cerebral/vagal level) resulted in a significant and similar PP response in the two groups; i.v. edrophonium injection (stimulating at the second neuron level) resulted in a smaller increase in PP concentrations in the type 1 diabetic patients as compared with the healthy subjects, whereas direct PP-cell stimulation by arginine infusion resulted in similar increments in PP concentrations in the two groups. Thus, in recently diagnosed type 1 diabetic patients with no known manifestations of diabetic neuropathy, the cholinergic second neuron function of the vagal arch to the pancreas is impaired, whereas intrinsic PP-cell function is unaffected. CONCLUSIONS: This abnormality in cholinergic second neuron function of the vagal reflex arch and the fact that three of the healthy subjects had no increase in PP concentrations at all during the meal test indicates that PP response to a mixed meal is unsuitable for the diagnosis of autonomic neuropathy in type 1 diabetes. The nature of the defect in the second neuron of the vagal innervation of the pancreas in type 1 diabetes remains to be elucidated.     

Autonomic Dysfunction in Migraine: A Survey of 188 Patients

SYNOPSIS
Autonomic nervous system functions were studied in 188 patients with migraine during headache free intervals by measuring cardiovascular reflex responses. Eighty-five healthy subjects served as a control group.
Pulse rate (R-R- interval) variation in normal and deep breathing, during Valsalva manoeuvre and orthostatic test was diminished in migraine patients. Diastolic blood pressure rises in orthostatic test and isometric work test were lower than in the controls. The results of patients with classic and common migraine did not deviate from each other. The same was true for the results of the female and male patients.
The results of the patients with frequent migraine attacks (>4/month) showed more severe disturbance than those with infrequent attacks. Disturbances gradually developed with age, being minimal or totally lacking in young migraine patients. The results confirm the development of sympathetic and parasympathetic hypofunction in migraine patients during the course of the disorder.     

An automated computerized method using Finapres for measuring cardiovascular reflexes.

1. The major drawback of the cardiovascular reflex tests used to study autonomic failure is the time involved in calculating the results. To overcome this disadvantage, we have developed an automated computerized program using a FINger Arterial PRESsure instrument for the measurement of beat-to-beat heart rate and blood pressure on a finger. 2. This program calculates heart rate variability during three standardized tests, forced breathing, standing up and the Valsalva manoeuvre, and records blood pressure values in response to standing up and sustained handgrip. The time taken to perform the test and to calculate the results is usually 25 min. 3. The reproducibility of the tests in 21 normal subjects was comparable with the reproducibility obtained with conventional test methods using an ECG and a sphygmomanometer. 4. In addition, we determined the age-dependent normal values of the seven test parameters in 124 subjects aged 20-90 years. 5. Using this program in 10 patients with longstanding (14-50 years) complicated diabetes, in each of them four or more abnormal test results were found.     

Cardiovascular Sympathetic Hypofunction in Muscle Contraction Headache and Migraine

There have been some recent reports proposing that muscle contraction headache (MCH) and migraine are similar and may have a common etiology. It has been hypothesized that derangement of the autonomic nervous system (ANS) plays an important role in the pathogenesis of migraine. However, reports on the ANS function in MCH have rarely been submitted. Therefore, in this report, MCH patients were investigated as well as migraine patients. The cardiovascular reflex responses by orthostatic test, isometric work test and the pulse rate (R-R interval) variation in fifteen MCH patients and fifteen migraine patients were recorded during headache-free intervals. The plasma norepinephrine (NE) levels were also measured throughout the orthostatic tests. Fifteen healthy subjects served as the age-matched control group. In the MCH group and the migraine group, blood pressure immediately after going from the supine to the erect position decreased more significantly than in the control group. The basal NE level was significantly low in both the MCH group and the migraine group, in comparison with the control group. MCH patients as well as migraine patients showed cardiovascular sympathetic hypofunction.     

Physiological and clinical correlates of cardiorespiratory reflexes in diabetes mellitus

Cardiorespiratory reflexes (CRRs) were studied by measuring heart-rate (HR) variation during 6 breaths/min respiration (delta R6) and Valsalva maneuver (VR) in 145 healthy and 417 type I (insulin-dependent) diabetic subjects. HR variation with breathing at 12 breaths/min and ventilatory response to hypercapnia/hypoxia were measured in fewer subjects. CRR results were compared with symptoms of autonomic dysfunction, the neurological examination, nerve conduction studies, and quantitative sweat testing. The objective was to compare the sensitivity of various methods of characterizing diabetic patients and to use this information when staging patients for clinical therapeutic trials. CRR responses were age dependent in both populations. Either delta R6 or VR was abnormal in 74% of diabetic patients, delta R6 being more sensitive. CRRs correlated well with the presence of symptoms of autonomic dysfunction, abnormalities on the neurological examination, results of nerve conduction studies, and sweating activity in the feet of the same patients. However, both CRRs and sweating were abnormal in a high proportion of patients without any clinical manifestations of neuropathy. The ventilatory reflex response to moderate hypercapnia/hypoxia was also measured. It was normal in most of the diabetic patients tested, including many with severe reduction of CRRs. We conclude from the combined results of CRR, ventilatory response, and other studies that the causative factors for abnormal CRR may not be confined to the vagus nerves, and that in most instances, the depressed CRR may be due to a decrease in the efficacy of sensorimotor nerve conduction around the reflex arc.     

The value of cardiovascular autonomic function tests: 10 years experience in diabetes

Five simple, noninvasive cardiovascular reflex tests have been used to assess autonomic function in one center over the past 10 yr. Seven hundred seventy-four diabetic subjects were tested for diagnostic and research purposes. In 543 subjects completing all five tests, abnormalities of heart rate tests occurred in 40%, while abnormal blood pressure tests occurred in less than 20%. Their results were grouped as normal (39%), early (15%), definite (18%), and severe (22%) involvement. Six percent had an atypical pattern of results. Two hundred thirty-seven diabetic subjects had the tests repeated greater than or equal to 3 mo apart: 26% worsened, 71% were unchanged, and only 3% improved. The worsening followed a sequential pattern with first heart rate and later additional blood pressure abnormalities. Comparison between a single test (heart rate response to deep breathing) and the full battery in 360 subjects showed that one test alone does not distinguish the degree or severity of autonomic damage. These tests provide a useful framework to assess autonomic neuropathy simply, quickly, and noninvasively.