Dieter Linden

Spontaneous blood pressure oscillations and cerebral autoregulation

The relationship between spontaneous oscillations in cerebral blood flow velocity (CBFV) and arterial blood pressure (ABP) was analysed in normal subjects in order to evaluate whether these relationships provide information about cerebral autoregulation. CBFV was measured using transcranial Doppler sonography and continuous ABP and heart rate using Finapres in 50 volunteers. Measurements were made over 5 min in a supine position and 6 min in a tilted position. Coefficients of variation were calculated using power- and cross-spectral analysis in order to quantify amplitudes within two frequency ranges: 3–9 cycles per min (cpm) (M-waves); and 9–20 cpm (R-waves). Correlations, coherence values, phase angle shifts and gains were also computed between corresponding waves in CBFV and in ABP. A clear correlation was seen for M-waves and R-waves between CBFV and ABP and coherence values were large enough to calculate phase angle shifts and gains. Phase angles for M-waves were larger and gains lower than was the case for R-waves, either tilted or supine. These data are consistent with a highpass filter model of cerebral autoregulation. Relatively high CBFV/ABP gain values (between 1.4 and 2.0) suggest that the principle of frequency-dependent vascular input impedances has to be considered in addition to autoregulatory feedback mechanisms. Spontaneous ABP oscillations in the M-wave and R-wave ranges may serve as a basis for continuous autoregulation monitoring.

The spectrum of differential diagnosis in neurological patients with livedo reticularis and livedo racemosa. A literature review.

AbstractLivedo is a cutaneous sign of striking violaceous netlike patterned erythema of the skin. This dermatological phenomenon is of special interest in the differential diagnosis in neurological patients. In 1907 Ehrmann distinguished two different patterns of livedo: the pathological livedo racemosa and the physiological livedo reticularis. Despite important clinical differences, in the English language literature the heading livedo reticularis is still used for all types of livedo. A literature review about the spectrum of differential diagnosis in patients with livedo reticularis (especially cutis marmorata and amantadine–induced livedo reticularis) and livedo racemosa (especially Sneddon’s syndrome, Divry–van Bogaert syndrome, systemic lupus erythematosus, antiphospholipid antibody syndrome, polyarteritis nodosa, cholesterol embolization syndrome, livedoid vasculopathy and haematological diseases) is provided.

The spectrum of differential diagnosis in neurological patients with livedo reticularis and livedo racemosa

AbstractLivedo is a cutaneous sign of striking violaceous netlike patterned erythema of the skin. This dermatological phenomenon is of special interest in the differential diagnosis in neurological patients. In 1907 Ehrmann distinguished two different patterns of livedo: the pathological livedo racemosa and the physiological livedo reticularis. Despite important clinical differences, in the English language literature the heading livedo reticularis is still used for all types of livedo. A literature review about the spectrum of differential diagnosis in patients with livedo reticularis (especially cutis marmorata and amantadine–induced livedo reticularis) and livedo racemosa (especially Sneddon’s syndrome, Divry–van Bogaert syndrome, systemic lupus erythematosus, antiphospholipid antibody syndrome, polyarteritis nodosa, cholesterol embolization syndrome, livedoid vasculopathy and haematological diseases) is provided.

Comparison of standard autonomic tests and power spectral analysis in normal adults

Standard autonomic measures [heart rate response to deep breathing (HRDB), systolic blood pressure response to orthostatic load, the 30 : 15 ratio, and the Valsalva ratio (VR)] and spectral measures of the heart rate (HR) and the arterial blood pressure (ABP) (MF: mid‐frequency band at 0.05–0.15 Hz; HF: high‐frequency band at 0.15–0.33 Hz) were performed in 50 healthy subjects. The supine HR‐HF and the tilt ABP‐MF were taken as indicators of parasympathetic and sympathetic outflow, respectively. The transfer function magnitude of HR related to the ABP in the mid‐frequency band estimated the baroreflex sensitivity. The HRDB and the 30 : 15 ratio were correlated with the parasympathetic spectral measure, and the VR was, surprisingly, only correlated with the sympathetic spectral measure. Significant baroreflex contribution was only evident for the 30 : 15 ratio. The spectral HR data were highly correlated with their corresponding spectral data of ABP. These results provide insights into autonomic regulation, but further studies on both basic physiological mechanisms of these methods and their clinical value have to be performed before a broad application can be recommended.

Cerebrovascular mechanisms in neurocardiogenic syncope with and without postural tachycardia syndrome

BACKGROUND AND PURPOSE Recent transcranial Doppler studies in patients with neurocardiogenic syncopes (NCS) have demonstrated that the cerebrovascular response to sudden systemic hypotension is vasoconstriction instead of compensatory vasodilation (autoregulation). We tried to characterize the conditions leading to this unexpected response in NCS patients further by continuously monitoring autoregulation and autonomic parameters during a standardized tilt-table test (TTT). METHODS Sixteen patients below the age of 50 years with a history of at least three syncopes of undetermined cause and tilt-table verified NCS and 20 normal controls were studied. Arterial blood pressure (ABP) and heart rate (HR) were monitored by Finapres and cerebral blood flow velocity (CBFV) of the left middle cerebral artery by transcranial Doppler. Baroreflex sensitivity and autoregulation parameters were measured continuously, using cross-spectral analysis of Mayer waves (3-9 cycles per minute oscillations) in ABP, HR and CBFV, respectively. Pulsatility indices (PI) of CBFV and ABP were determined continuously. Measurements were taken during 5 min in supine and during 5 min in tilted position. In patients, tilting was continued for a maximum of 45 min until the onset of syncope or presyncope. RESULTS According to the maximum increase in heart rate (deltaHR) during the first 5 min of standing, heart rate responses were classified as postural tachycardia syndrome (POTS) (deltaHR > 35/min) or as normal. Only one out of 20 control subjects showed a POTS (5%) in contrast to seven patients (44%). Patients with a POTS had significantly lower PI values in ABP and higher ratios between the PI of CBFV and the PI of ABP both in supine and in tilted positions. Baroreflex sensitivity during standing decreased significantly in POTS patients when compared to controls. Although autoregulation remained intact during standing, mean CBFV decreased significantly and continuously. The nine patients without a POTS showed almost the same cardiovascular and cerebrovascular responses as the control subjects. All 16 patients showed similar circulatory responses during syncope (sudden hypotension, relative or absolute bradycardia, reduced CBFV and increased PI in CBFV). CONCLUSIONS The development of a POTS during tilting indicates a high risk for fainting. The characteristic hemodynamic features in the initial phase of standing in these patients can be interpreted in terms of central hypovolemia (low PI of ABP) with sufficient ABP regulation and increased cerebrovascular resistance (defined as the ratio between PI of CBFV and ABP). Cerebral autoregulation seems not to be affected in patients suffering from NCS.

Subclinical autonomic disturbances in multiple sclerosis

We compared results from non-invasive autonomic testing [sympathetic skin responses (SSR), heart beat variation during deep breathing, and orthostatic manoeuvre with transcranial Doppler monitoring in 22 patients] with motor and somatosensory evoked potentials (MEP and SEP) in 30 unselected patients with multiple sclerosis. We found a similarly high yield of pathological results for SSR, MEP and SEP (66.7%, 65.5%, and 69%, respectively). When analysed for each limb (n = 120), SSR were highly correlated with MEP and SEP (for bothP < 0.001). Heart beat variation was reduced in only 3 patients. In 4 of 22 patients orthostatic manoeuvre induced a pathological decrease in cerebral blood flow velocity despite normal systemic blood pressure being maintained. We conclude that SSR may be a useful additional diagnostic tool in patients with multiple sclerosis. Cerebral dysautoregulation is a rather frequent finding, although its significance is not known.

Sympathetic cardiovascular dysfunction in long-standing idiopathic Parkinson's disease

Standard autonomic tests (heart rate response to deep breathing-HRdb, heart rate and systolic blood pressure response to tilt-ΔHR and ΔSBP) and spectral analysis of heart rate and arterial blood pressure and their transfer function (for the mid-frequency band a measure of baroreflex sensitivity) were performed in 20 patients with idiopathic Parkinsons disease (IPD) and 20 age-matched controls. Patients showed significantly diminished ΔSBP, and reduced sympathetic vasomotor and cardiomotor outflow (diminished Mayer waves), consistent with an alteration of the efferent arc of the baroreflex. These results were only significant in long-standing IPD (IPD-1, >5 years), whereas patients with short disease duration (IPD-s, <5 years) showed values comparable to controls. Respiratory-related heart rate variability was slightly reduced in IPD-1 but this was mainly due to diminished respiratory effort, indicated by low respiratoryrelated blood pressure variability. We conclude that autonomic abnormalities are only present in long-standing IPD and consist in reduced sympathetic vasomotor and cardiomotor outflow.

Determinants of heart rate variability during deep breathing: Basic findings and clinical applications

The measurement of heart rate variation during forced breathing (HRDB) is a well-known clinical test of parasympathetic function. It is known that normal values of HRDB are strongly dependent on age. However, little is known about other physiological factors that may lead to reduced HRDB values that may mimic parasympathetic failure. Thirty-two normal subjects (age 56.7±12.4 years) and 32 neurological patients with pathological autonomic test findings (age 57.9±10.2) were studied. Oscillations in heart rate and in mean arterial blood pressure were recorded in the supine position during forced breathing (6 cycles/min) using the Finapres monitor. Amplitudes of heart rate and blood pressure waves at 6 cycles/min (HR6 and ABP6) as well as gain values (Gain6=HR6/ABP6) and phase differences ({ie131-1}) between HR and ABP waves were calculated by means of spectral analysis. The mean (±SD) HR6 in normal subjects was 6.34±3.36 cycles/min with a mean ABP6 of 5.11±2.49 mmHg. HR6 correlated significantly with age (r=−0.426) and with ABP6 (r=0.602). No significant correlation was found between HR6 and mean blood pressure, mean heart rate or sex. From 24 patients with pathological findings in the classical HRDB value, only nine could be classified as pathological when the effect of ABP6 was considered. In conclusion, ABP variations significantly influence the amplitude of heart rate variations during forced breathing. We interpret these findings in terms of a baroreflex mechanism of HRDB including both vagal and sympathetic efferents. Normal reference value tables for clinical HRDB studies should not only consider age but also the amplitude of blood pressure variations.

Reduced baroreflex sensitivity and cardiorespiratory transfer in amyotrophic lateral sclerosis

INTRODUCTION Clinically relevant autonomic disturbances have been reported for respirator-dependent ALS patients while subclinical involvement may be present in the early course. METHODS Eighteen patients with early-stage ALS and 18 age-matched controls were studied by means of standard autonomic tests (heart off + response to deep breathing and tilt-table testing), and spectral analysis of heart rate (HR) and arterial blood pressure (ABP), using the associated transfer function as a measure of baroreflex sensitivity for the mid-frequency band (MF band, 0.05-0.15 Hz) and as a measure of cardiorespiratory transfer for the high-frequency band (HF band, 0.15-0.33 Hz). RESULTS Mean HR and ABP were increased in ALS, while results of standard autonomic tests were similar for ALS and controls. Transfer function analysis revealed reduced baroreflex sensitivity and diminished cardiorespiratory transfer during normal breathing. CONCLUSIONS Cardiovascular autonomic functions are intact in patients with ALS. There is evidence of sympathetic enhancement and vagal withdrawal, accompanied by reduced baroreflex sensitivity. These findings are similar to those reported for essential hypertension and may point to a common central autonomic derangement in both disorders.

Autonomic evaluation by means of standard tests and power spectral analysis in multiple sclerosis

Standard autonomic tests [heart rate response to deep breathing (HRDB), change in systolic blood pressure due to tilt], and spectral analysis of heart rate (HR), arterial blood pressure (ABP), and the associated transfer function analysis (gains and phases) were performed in 20 patients with multiple sclerosis to determine their diagnostic value. Transfer function analysis suggested impairment of baroreflex function in 7 patients and an alteration of cardiorespiratory coupling on a brain stem level in 4 patients. In addition, sympathetic vasomotor outflow was reduced in 2 patients (spectral ABP measures in the mid frequency band) and a decrease of vagal outflow was suggested by abnormal respiratory HR parameters in another 2 patients. An abnormal HRDB was present in 5 patients and was probably due to a central alteration (cardiorespiratory coupling) in 2 patients and due to diminished respiratory effort in 1 patient. Spectral analysis of both HR and ABP oscillations and their transfer function may considerably improve the pathophysiological interpretation of cardiovascular autonomic dysfunction in patients with central nervous system disease.