Diagnosing Autonomic Nervous System Disorders – Existing Guidelines and Future Perspectives


Techniques to quantify BRS include pharmacological methods using vasoactive drugs, the Valsalva manoeuvre, the neck chamber technique and analysis of spontaneous fluctuations of BP and HR.


Oxford Method


In this method, the alpha 1-adrenorecepor agonist, phenylephrine, is administered to induce a rapid increase in BP of between 15mmHg and 40mmHg and subsequent changes in HR are recorded. Administration of vasoconstrictor drugs primarily affects the cardiac vagal component of baroreceptor control. Modifications of the Oxford method calculate the baroreflex sensitivity after sequential injections of depressor and pressor drugs and can also help to investigate the responses of the efferent sympathetic branch. This is an invasive procedure, which is contraindicated in certain patients (e.g. those with arterial hypertension). In addition, there are controversies over the selectivity associated with using vasoactive drugs to test BRS. BP stimuli might induce other reflex arcs, mainly the cardiopulmonary receptors, which interfere with BRS.


This pharmacological approach was introduced by Smyth, Sleight and Pickering.17


Neck Chamber Technique


The need for elaborate equipment means that this technique is mainly used in research laboratories.12


Applying negative or positive


pressures to the neck allows for selective activation of carotid baroreceptors. A pressure increase within the neck chamber is sensed by the baroreceptors as a decrease in BP and vice versa. BP and HR responses are recorded.


The baroreflex is continuously active in order to keep BP at a stable level. Computer-based techniques allow assessment of BRS by correlation of spontaneous fluctuations of BP with consecutive HR changes. The methods may be devided into ‘time domain’ (i.e. sequence) or ‘frequency domain’ (i.e. spectral) techniques. Sequence and spectral techniques have proven reliability and have become a standard tool in many autonomic testing devices. Clinical and scientific interpretation of results should be based on a profound knowledge on the technique applied, however, and special care should be taken not to interpret measurements influenced by artifacts or ectopic activity.


Sequence Techniques


Therefore, the method should be selected carefully with regard to the pathophysiological background of the patient tested.


Spectral Techniques


Evaluation of BRS by spectral techniques is based on the concept that spontaneous oscillations in BP result in spontaneous oscillations in HR within the same frequency range. Two frequency bands are of interest: the low frequency band around 0.1Hz and the high frequency band around the respiratory frequency. Several algorithms have been developed to calculate spectral indices. Newer methods have demonstrated the capability of detecting impairment of BRS in


EUROPEAN NEUROLOGICAL REVIEW


A number of different sequence techniques have been published. Sequence techniques evaluate BRS by correlation of BP increase with subsequent HR decrease or vice versa. Significant agreement has been demonstrated between the sequence method and the ‘gold standard’ phenylephrine method. The methods are easy to apply and do not require the co-operation of the patient. Since there is no load on BP, only a small portion of the baroreceptor reflex is evaluated. Various sequence methods yield different results when applied to the same data sets, particularly in patients with impaired baroreflex function.18,19


structural cardiovascular disease. There is controversy over the comparability of these new techniques with the phenylephrine test. This might be explained by methodological differences: spectral algorithms focus on oscillatory changes around a set point, whereas the phenylephrine test relies on a strong unidirectional response.12 Interference from artifacts (noise, ectopic activity, etc) is a major limitation to any spectral technique. In patients with depressed BP variability, the signal-to-noise ratio tends to become high and influence BRS reliability. Further limitations have been described previously.


Sudomotor Function


particularly in early diabetes, and is used to provide a measure of cholinergic sympathetic function. A large number of different tests are available. They can assess central and peripheral sudomotor function, as the thermoregulatory sweat test (TST)21


Disorders of sweating (hypo- or hyperhidrosis) can be focal or generalised and appear quite frequently in ANS failure. Evaluation of sudomotor function can provide early diagnosis of small fibre neuropathy,20


, or postganglionic function alone, as the quantitative sudomotor axon reflex test (QSART),22


quantitative direct and indirect axon reflex test (QDIRT)23 dynamic sweat test (DST).24


the sympathetic skin response test (SSRT), the and the


Patterns of sweating can be visualised by


may be used to study sweat gland activity in more detail. Thermoregulatory Sweat Test


This test can assess central and peripheral sudomotor function21


topical application of indicators such as iodinate starch or sodium alizarin sulfonate after a sufficient thermal stimulus has been applied. Quantitative tests as QSART, QDIRT, DST, SSRT and the silastic imprint test (SIT)25


and is


performed in a temperature (45–50°C) and humidity controlled chamber. The whole body is covered with an indicator dye and the change in colour due to sweat production is documented. Asymmetric patterns due to focal anhidrosis or stocking- and glove-like distributions may be observed in length-dependent neuropathy. Limitations result from the visual analysis and the lack of differentiation between pre- and postganglionic lesions. The test is time-consuming and needs special equipment.


Quantitative Sudomotor Axon Reflex Test This test measures postganglionic axon reflex-mediated sweat production in a small restricted area of the skin over time.22


A


multicompartmental sweat capsule is used to stimulate sweat glands by iontophoresis of acetylcholine. A first, direct sweat response in the area of iontophoresis is discriminated from the indirect, axon reflex-mediated response in the surounding area (for details see the review by Illigens and Gibbons20


). Sweat can be sampled over a time


period and the results of the analysis correlated with other stimuli. Limitations are the expensive equipment, the very small detection area and the inability to detect preganglionic lesions.


Silastic Imprint Test


The test evaluates postganglionic sympathetic cholinergic sudomotor function by measuring the direct and axon-reflex mediated sweat response.25


Sweat glands are stimulated by iontophoresis of acetylcholine, pilocarpine or methacholine. This is followed by application of a thin layer of moldable silastic material to the skin. Sweat droplets displace the silicone material during polymerization, resulting in permanent impressions in the silastic material that can be quantified using various methods. Number of droplets, size and distribution are reported.


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