Evaluation of the finger wrinkling test: A pilot study

Abstract

Tilt table testing mainly evaluates the systemic cardiovascular part of the autonomic nervous system, while it is assumed that the finger wrinkling test assesses the peripheral part of the autonomic nervous system. In this study we explored whether the finger wrinkling test could be a useful test for autonomic dysfunction and whether the clinical evaluation of wrinkling can be improved by digital analysis of photographs.
As much as 20 healthy subjects and 15 patients underwent tilt table testing and finger wrinkling testing. During the finger wrinkling test the right hand was immersed in water at 40 degrees C. The degree of wrinkling was assessed with a 5-point clinical scale at baseline, 5, 15 and 30 min of immersion. Photographs were taken at the same intervals. Several features were evaluated using digital analysis: length and gradient of automatically detected wrinkle and mean, maximum, minimum, variance and derivative of grey value of pixels.
Clinical scoring of wrinkling allowed differentiation between healthy subjects and patients with a normal and an abnormal response to tilt table testing. Relevant features obtained with digital analysis were mean grey value and the gradient of automatically detected wrinkle. McNemar's test showed no difference in test results between the tilt table test and the finger wrinkling test with a kappa of 0.68.
The finger wrinkling test can be used as a screening test before tilt table testing. Visual evaluation of wrinkling is still superior to digital analysis of photographs.

Full text

RESEARCH ARTICLE
Evaluation of the finger wrinkling test: a pilot study
S. van Barneveld •J. van der Palen •
M. J. A. M. van Putten
Received: 10 January 2010 / Accepted: 20 April 2010 / Published online: 12 May 2010
ÓThe Author(s) 2010. This article is published with open access at Springerlink.com
Abstract
Purpose Tilt table testing mainly evaluates the systemic
cardiovascular part of the autonomic nervous system, while
it is assumed that the finger wrinkling test assesses the
peripheral part of the autonomic nervous system. In this
study we explored whether the finger wrinkling test could
be a useful test for autonomic dysfunction and whether the
clinical evaluation of wrinkling can be improved by digital
analysis of photographs.
Methods As much as 20 healthy subjects and 15 patients
underwent tilt table testing and finger wrinkling testing.
During the finger wrinkling test the right hand was
immersed in water at 40°C. The degree of wrinkling was
assessed with a 5-point clinical scale at baseline, 5, 15 and
30 min of immersion. Photographs were taken at the same
intervals. Several features were evaluated using digital
analysis: length and gradient of automatically detected
wrinkle and mean, maximum, minimum, variance and
derivative of grey value of pixels.
Results Clinical scoring of wrinkling allowed differenti-
ation between healthy subjects and patients with a normal
and an abnormal response to tilt table testing. Relevant
features obtained with digital analysis were mean grey
value and the gradient of automatically detected wrinkle.
McNemar’s test showed no difference in test results
between the tilt table test and the finger wrinkling test with
a kappa of 0.68.
Conclusion The finger wrinkling test can be used as a
screening test before tilt table testing. Visual evaluation of
wrinkling is still superior to digital analysis of photographs.
Keywords Autonomic dysfunction Tilt table test 
Finger wrinkling test Digital analysis
Introduction
In patients suffering from diabetes mellitus and hemipar-
kinsonism autonomic dysfunction is often present [1].
Diagnosis of autonomic dysfunction can be difficult to
establish. There are some tests available, like tilt table
testing, sympathetic skin response and sweat imprint test
[2,3]. Sympathetic skin response and sweat imprint test
evaluate the thermoregulatory part, while tilt table testing
mainly evaluates the cardiovascular part of the autonomic
nervous system [3]. Tilt table test is a simple, standardized
test with a sensitivity of 75% and specificity of 97%, when
performed by Westminister protocol. Unfortunately repro-
ducibility is poor [2]. Both sympathetic skin response and
sweat imprint test have a poor sensitivity compared to
S. van Barneveld (&)M. J. A. M. van Putten
Department of Clinical Neurophysiology,
Medisch Spectrum Twente, Haaksbergerstraat 55,
7513 ER Enschede, The Netherlands
e-mail: sylvia_van_barneveld@hotmail.com
J. van der Palen
Department of Epidemiology, Medisch Spectrum Twente,
Enschede, The Netherlands
S. van Barneveld
Department of Medicine, University of Groningen,
Groningen, The Netherlands
M. J. A. M. van Putten
MIRA Institute for Biomedical Technology and Technical
Medicine, University of Twente, Enschede, The Netherlands
J. van der Palen
Department of Research Methodology, Measurement and Data
Analysis, Faculty of Behavioral Sciences, University of Twente,
Enschede, The Netherlands
123
Clin Auton Res (2010) 20:249–253
DOI 10.1007/s10286-010-0071-9

tilt table testing and special equipment for testing is nec-
essary [3].
The finger wrinkling test could be a complementary test
to the above-mentioned tests, because one assumes that this
test evaluates the autonomic nervous system of the limbs
[4,5]. The main underlying mechanism of wrinkling dur-
ing water immersion is vasoconstriction by sympathetic
input [6]. During the finger wrinkling test a hand is
immersed in water at 40°C for 30 min [5] and the amount
of wrinkling is subsequently evaluated. The degree of
wrinkling is assessed by a 5-point clinical scale [7] (see
Table 1). However, this scale is a poor quantification
method, because there is a wide variety of interpretation
[4]. Previous studies have shown that the degree of wrin-
kling is less in patients with diabetes mellitus or hemi-
parkinsonism than in healthy subjects [7,8]. No correlation
in the results between tilt table testing and finger wrinkling
test has been evaluated [8] or found [7].
We explored whether the finger wrinkling test is a useful
test for autonomic dysfunction in particular if there is a
correlation between peripheral and systemic function of the
autonomic nervous system as evaluated by tilt table testing.
In addition, we investigated whether digital analysis of
photographs of the hand could improve the quantification
of wrinkling.
Methods
As much as 20 healthy subjects (10 men) were recruited
from hospital staff and students. Their average age was
26 years (range 21–52 years). Exclusion criteria were
cigarette smoking, skin disease, operation or trauma of the
hand and use of medication that might interfere with
autonomic function, such as beta blocking agents.
A total of 15 patients (8 men), who were referred for tilt
table testing were included. Their average age was 58 years
(range 21–78 years). Indications for referral were syncope
(n=8), dizziness (n=2), diabetes mellitus (n=2) and
Parkinsonism (n=3). All subjects gave informed consent
and underwent tilt table testing and finger wrinkling test-
ing. The study was conducted in accordance with the
Helsinki Declaration and was approved by the Ethics
Committee of Medisch Spectrum Twente, the Netherlands.
Participants were instructed not to use any cream or lotion
on their hands on the day of testing. Drinking coffee or tea
2 h prior to testing was not permitted.
During the tilt table test blood pressure, heart rate and
ECG were recorded for 10 min in a horizontal position,
10 min in tilted position of 60°and another 10 min in
horizontal position. The result was considered abnormal if
there were signs of orthostatic hypotension with a systolic
drop of more than 20 mmHg and diastolic drop of more
than 10 mmHg or/and if there was no compensatory heart
rate acceleration more than 10–20 bpm after tilting to 60°.
During the finger wrinkling test the right hand was
immersed in a tempex bucket filled with water at 40°C.
Temperature was measured before and after the finger
wrinkling test. Maximum decrease in temperature was 2°C
over the total measurement period of 30 min. The degree
of wrinkling was assessed with the 5-point clinical scale at
baseline, 5, 15 and 30 min of immersion. Only digiti 2–5
were judged, because it was difficult to make a good
photograph of the thumb. Scores of digiti 2–5 were
summed.
Photographs were taken at the same intervals. Before
taking a photograph the right hand was held in front of a
black background with the palm of the hand towards the
digital camera (CANON D200), which was positioned at a
distance of 94.5 cm of the black background. Diffuse
lighting with BOWENS BW 3610
TM
was used on the right
side of the right hand.
For digital analysis several features were calculated
using Matlab (2007, The Mathworks Inc.): length and
gradient of automatically detected wrinkles and mean,
maximum, minimum, variance and derivative of grey
values of the pixels. The result of digital analysis was
considered abnormal if the value was below the cutoff
point made by the ROC curve to determine optimal sen-
sitivity and specificity. For evaluation of the different
features of digital analysis the result of the finger wrinkling
test was considered abnormal if there was no increase in
score on the clinical scale or if the total score was less than
4 after finishing the finger wrinkling test.
Statistics
Mann–Whitney Utests were used for comparison of clin-
ical scale scores between healthy subjects and patients and
comparisons between patients with a normal and abnormal
tilt table result. To evaluate the features of digital analysis
Student’s Ttest was used to analyse if there was a signif-
icant difference in value of the feature between healthy
subjects and patients. Spearman’s correlation coefficients
were used to assess the degree of correlation between
clinical scale scores and the different digital features
Table 1 Explanation of the 5-point clinical scale [7]
Grade Description
0 No evidence of any skin wrinkling at the fingertip
1 The fingertip was not completely smooth
2 Two or less lines of wrinkling on the fingertip
3 Three or more lines of wrinkling on the fingertip
4 Wrinkling completely distorting the pulp of the fingertip
250 Clin Auton Res (2010) 20:249–253
123

extracted. Sensitivity and specificity were determined with
ROC curves. Mc Nemar’s test was used to determine the
correlation between the result of the finger wrinkling test
and the tilt table test. With kappa the strength of the above-
mentioned relationship was analysed. Sensitivity and
specificity for three cutoff values (4, 8 and 12) of the finger
wrinkling test were determined with tilt table testing as
gold standard.
Results
Figure 1shows an example of photographs taken during
the finger wrinkling test with a normal and an abnormal
result. Clinical wrinkling scores are significantly higher for
healthy subjects than for patients (P\0.001). Also clinical
scale scores are significantly higher for patients with a
normal result of the tilt table test than patients with an
abnormal result (P=0.02) (Table 2).
The features calculated for digital analysis have to meet
the following criteria. First the features must show a dif-
ferent value for patients and for healthy subjects. Second
the feature must correlate with the clinical scale (r[0.30)
with sufficient sensitivity and specificity. Two features met
the above-mentioned criteria, namely mean of grey value
and gradient of automatically detected wrinkle. The char-
acteristics of these two features are shown in Table 3.
Sensitivity is 100% for mean of grey value, specificity is
97% for gradient of automatically detected wrinkle (t=15
to t=0) and there is a correlation of 0.77 with clinical
scale score for gradient of automatically detected wrinkle
(t=30 to t=0).
As much as 28 persons had normal results on both tests,
while 4 persons had abnormal results on both tests
(Table 4). McNemar’ s test showed that there is no dif-
ference in test results between both tests (P=1.00).
Kappa of this relationship is 0.68, which is considered
good. When the finger wrinkling test is assessed by digital
analysis the results are not so clear with kappa values
between 0.19 and 0.30 for the two features with the best
qualities.
Table 5shows that a cutoff value of 4 has a sensitivity
of 80% and specificity of 93%. As cutoff values increase,
sensitivity increases and specificity decreases.
Discussion
Our primary aim of this pilot study was to evaluate the
finger wrinkling test for the evaluation of autonomic dys-
function. In addition, we explored if we could improve the
clinical quantification of wrinkling by analysis of digital
photographs.
We found a significant correlation between the results of
the finger wrinkling test and tilt table testing, which indi-
cates that patients with an abnormal result on the finger
wrinkling test have a higher probability of having an
abnormal result on the tilt table test than patients with a
normal result on the finger wrinkling test.
This contrasts findings of Clark et al. [7], who found no
correlation between the result of autonomic function tests
and the degree of wrinkling in diabetics. Detailed com-
parison with this study is difficult, however, because the
Fig. 1 The photographs are taken from left to right at t=0, 5, 15
and 30 min. aPatient with an abnormal result on finger wrinkling test.
Score at clinical scale at t=30 min is 1. bResult of a healthy
subject. Score at clinical scale at t=30 min is 4
Table 2 Values of the clinical wrinkling scale for healthy controls
and patients
Time Healthy subjects Patients
Median Interquartile range Median Interquartile range
0 0 0–0 0 0–8
5 4 4–6.25 4 4–8
15 10 8–12 8 4–12
30 15 11.25–16 12 8–14
Median and interquartile range are used because of non-normal dis-
tribution. Scores of digiti 2–5 were summed
Table 3 Overview of differentiating characteristics of two features
Feature Sensitivity Specificity Correlation with clinical scale
Mean of grey values t=30 to t=0 100 72 0.34
Gradient of detected wrinkle t=15 to t=0 67 97 0.50
Gradient of detected wrinkle t=30 to t=0 83 76 0.77
Clinical scores on the finger wrinkling test were used as a gold standard
Clin Auton Res (2010) 20:249–253 251
123

study populations and methods are quite different [7].
Clark et al. only explored a correlation between autonomic
function tests and wrinkling among the included diabetics.
Also the result of the finger wrinkling was not defined in
normal and abnormal.
Recent studies suggest that the finger wrinkling test
evaluates the more distal portion of the autonomic nervous
system [9,10]. Teoh et al. [9] showed that the finger
wrinkling test is a useful supportive test for diagnosing
small fibre neuropathy. Wilder-Smith et al. [10] established
that the finger wrinkling test can be used for predicting
intraepidermal nerve fibre density. The correlation between
the results of tilt table testing and finger wrinkling testing
found in our pilot study suggests that in a significant
fraction of patients both parts of the autonomic system are
affected.
A striking result of this pilot study is the differentiation
between healthy subjects and patients by clinical scores at
baseline. There are some explanations for this finding.
There were three patients with wrinkled hands at baseline.
All these patients had abnormal results on tilt table test.
Maybe wrinkled hands predict the outcome of the tilt table
test. Also the average age was significantly higher for
patients with abnormal results on tilt table test than other
patients and healthy subjects.
The results of digital analysis of the photographs taken
during the finger wrinkling test were disappointing. Only 2
out of the 11 evaluated features had differentiating char-
acteristics. Most likely, the quality of the photographs was
not sufficient to develop an accurate quantification method.
The major problem was the illumination, which caused a
strong shadow on the lower side of the fingers. We were
not able to remove this shadow sufficiently, which inter-
fered with the digital analysis of the amount of wrinkling.
As a first step in developing several features for analysis
of digital photographs, our aim was to define features that
differentiate between the presence and the absence of
wrinkles. This motivated the use of a cutoff value of 4
since any wrinkle in a finger evaluated was considered
abnormal. This contrast the cutoff value used by Teoh et al.
[9], where a cutoff value of 8 was used. A second criterion
for successful use of the digital analysis is that features
must differentiate between various degrees of wrinkling.
However, due to disappointing results obtained in the first
step, as outlined above, we did not further pursue this
approach.
Another problem of evaluating whether analysis of
digital photographs is a better quantification method than
the clinical evaluation is the lack of a gold standard.
Although initially the sympathetic skin response (SSR)
was proposed as potential gold standard [3], various
studies have shown now that SSR is a poor autonomic
function test. Vasudevan et al. [11] showed that this
response did not have more advantages than the finger
wrinkling test with equal sensitivity and specificity. Also
Teoh et al. [9] reported that the sympathetic skin response
was less useful in diagnosing small fibre neuropathy than
the finger wrinkling test or intraepidermal nerve fibre
density.
Given the limited specificity that we found in our
comparison (*70%), abnormal results in finger wrinkling
are not always due to dysfunction of the autonomic nervous
system. For instance abnormal results could also be caused
by smoking, trauma of the hand or medication interfering
with the autonomic nervous system. These causes were not
used as an exclusion criterion in patients, because we
wished to investigate the practical relevance of the finger
wrinkling test in a typical patient cohort referred for tilt
table testing.
In summary, our pilot study suggests that the finger
wrinkling test can be used as a screening test before tilt
table testing. The assessment of wrinkling with the 5-point
clinical scale is still superior to digital analysis.
Acknowledgments We would like to thank Mr. R. Elsjan, Mr. S.
van der Meer and Ms. M. Lenselink of our hospital for their advices
and their photograph material. Also Prof. C.H. Slump, Mr. D.J.
Kroon, Mrs. M. Heijblom, Mrs. M.C. Cloostermans, Mrs. L. Mel-
ching and Mrs. S. Sharifi are acknowledged for their contribution to
the technical aspects of this pilot study. The assistance of the tech-
nicians of the department of clinical neurophysiology is also highly
appreciated.
Conflict of interest statement The authors declare that they have
no conflict of interest.
Open Access This article is distributed under the terms of the
Creative Commons Attribution Noncommercial License which per-
mits any noncommercial use, distribution, and reproduction in any
medium, provided the original author(s) and source are credited.
Table 4 Correlation between the results of the tilt table test and the
finger wrinkling test
Tilt table test Finger wrinkling test
Normal Abnormal
Normal 28 2
Abnormal 1 4
Table 5 Three different cutoff values with their corresponding sen-
sitivity and specificity
Cutoff value Sensitivity (%) Specificity (%)
48093
8 100 83
12 100 60
Gold standard is tilt table testing
252 Clin Auton Res (2010) 20:249–253
123

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