Frequently Asked Questions

SUDOSCAN


Why test sudomotor function?

Testing sudomotor function can be a fast and accurate method for detecting early stages of neuropathies. Eccrine glands that are responsible for sweat response receive a rich supply of small blood vessels and are innervated by sympathetic C nerve fibers (autonomic nervous system). These fibers are thin and long and so can be impaired at the very early stage of different metabolic diseases. “Sweat response may be the most sensitive test in detecting distal small fiber neuropathy” (Pr Low and Pr Gibbons publications).

What is SUDOSCAN?

SUDOSCAN is a medical device that has been cleared by health authorities in many countries including EC (Europe), FDA (USA) and SFDA (China). The approval process in Japan is ongoing.

What does SUDOSCAN measure?

SUDOSCAN evaluates sudomotor function on the palm of the hands and sole of the feet where the density of sweat glands is greatest.

The underlying technology is based on established principles of the electrochemical reaction between chloride (found in sweat) and nickel (which is a component of the stainless-steel electrodes used in SUDOSCAN). A low DC voltage ≤ 4 volts is applied generating a current relative to chloride (ion) flow supplied by the sweat glands and ducts. An Electrochemical Skin Conductance (ESC) is calculated for each hand and each foot on the basis of the current generated and the voltage supplied.

Similar to cardiologic stress tests for which exercise is used as a stimulus to capture specific information that is not assessable in resting state, SUDOSCAN too relies on an electrical stimulus of sweat chloride to capture information about the sweat dysfunction that cannot be diagnosed in usual conditions. For a better understanding see the animation video on the web site.

Because the skin’s stratum corneum acts like an electrical capacitor when a low voltage stimulation is applied, the movement of chloride to the electrodes on the surface of the hands and feet can only occur via the sweat ducts, and, we can be certain that we’re targeting the underlying sweat gland and its sympathetic innervations.

This underlying theory has been confirmed in a comparative study performed on patients with Cystic Fibrosis (who have high sweat chloride concentration at the surface of the skin, basis of the sweat test) and controls (see publication by Hubert et al).

What information does SUDOSCAN provide

SUDOSCAN test results are provided as hands and feet conductances (mean of left and right side).  High conductances correlate with normal sweat function and healthy nerve innervation (small C-fibers).  Low conductances represent peripheral or autonomic neuropathy.

How can the physician use this information to help his/her patient?

Physicians get simple and immediate information on small autonomic fiber status and use it in various medical settings.

Proactive monitoring: Medicine is trending towards prevention of the onset of a disease or complication.  Since the long, unmyelinated, sympathetic c-fibers slowly degenerate yet quickly regenerate with changes in a patient’s lifestyle or therapy, physicians can use this information to determine whether or not a patient is “at risk” of developing a complication and take proactive measures with treatment options.

Assessing the level of intensive glycemic control for diabetics.  It is important to determine whether or not a patient has an autonomic neuropathy before prescribing intensive forms of glycemic treatment. Using this quick screening a physician can decide whether or not he/she must perform more specific but time-consuming tests to assess precisely autonomic function in these patients.

Patient drug or lifestyle compliance: SUDOSCAN allows a physician to quickly determine sudomotor functioning as a biomarker for peripheral nerve integrity.  Patient compliance can quickly be determined based on how good or how bad their results are.  This information is complimentary to traditional blood based testing, but is extremely fast and offers immediate results.  No subjectivity is introduced via patient verbal responses and quantitative results allow a precise follow-up.

Who should get tested on SUDOSCAN?

Anyone can get tested on SUDOSCAN to assess their sudomotor function unless they have a specific contra-indication that would prevent them from performing a scan. As previously described, the potential uses for SUDOSCAN include evaluation of peripheral neuropathy and follow-up for diabetic patients. It can be used in neurology when assessment of small fiber neuropathy especially autonomic is required (amyloidosis, Fabry disease, Parkinson’s Disease).

What are the reasons to get yourself tested on SUDOSCAN?

Small C fiber nerve damage can be observed in subjects with prediabetes or metabolic syndrome.  Because SUDOSCAN is non-invasive and takes only 3 minutes to run, you can benefit from knowing your hands and feet conductances – first to establish your baseline levels, then to repeat the test periodically to monitor your numbers.  SUDOSCAN allows you to have:

Immediate knowledge of sweat gland function as an indicator of peripheral nerve function;

Biofeedback: a way to quantify the “status” of your peripheral nerves upon lifestyle changes, e.g. Exercise and its benefits.

Does gender play a factor in the results?

Evaluation of sudomotor function using other tests such as Quantitative Sudomotor Axon Reflex Test (QSART) has shown generally lower measures (in sweat output) in women compared with those in men. This can be explained by lower sweat rates in women. Measurements performed by SUDOSCAN don’t depend on sweat rate. A study performed on more than 500 women and more than 200 men showed no significant differences in hands’ and feet’ ESC. This will be confirmed in future pending studies on larger group populations.

Does ethnicity play a role?

Studies have been performed in European countries, the USA, India and China in healthy volunteers and in patients with peripheral neuropathy diagnosed by referenced methods. Large databases are available allowing determination of threshold values according to ethnicity. For example healthy African-Americans have lower conductance values when compared to Caucasians. Reference threshold values for specific populations are available on request to allow correct interpretation of results. Larger studies are ongoing to increase our databases.

Can my age influence the SUDOSCAN reading?

A large database of healthy Caucasian volunteers demonstrated that SUDOSCAN measured conductance levels do not depend on age. It is in accordance with other methods that demonstrated that small fiber status does not depend on age in healthy volunteers.

Does room temperature affect the test results?

Clinical tests run at different temperatures (changes of more than 5°C) demonstrate that temperature variance does not impact test results. Hands and feet have a limited role in thermoregulation due to their small area and thus are less temperature dependent than other parts of the body for their sweat rate.

Theoretically, extreme cold temperature on the electrodes could result in vasoconstriction. Large studies will be performed to exactly quantify this effect. Therefore, avoid performing test measurements if the electrodes are too cold or on a patient immediately after coming in from an extremely cold environment. Quick warming by rubbing the hands is sufficient to avoid any disturbance in measurements.

Does exercising just before being evaluated impact test results?

Given sweat rate changes with exercise it was important to evaluate the effects of exercise on SUDOSCAN tests. Measurements were performed before and after high impact exercise on more than 100 subjects. Tests showed a coefficient of variation of 13 % for the hands and of 4% for the feet between these two measurements. These results confirm that SUDOSCAN measurements are not dependent on sweat rate.

Are SUDOSCAN measurements reproducible?

Reproducibility is critical for any screening test to be useful. SUDOSCAN has been tested for reproducibility in several clinical studies on large groups of patients with 5% coefficient of variation for feet ESC and 10% for hands ESC, which is excellent in an in-vivo environment. The reproducibility between measurements performed before and after an exercise is also excellent (see above).

Analyzing dynamic chloride-ionic flow of the sweat glands (as compared to sweat volume) provides better information since chloride levels do not change with sweat rate (see article by Quinton et al on web site)

Also noteworthy is that the reproducibility of SUDOSCAN is significantly better than HbA1c (especially finger stick methods) or the oral glucose tolerance test (both HbA1c and OGTT have an effective reproducibility rate of 20%).

Can children be tested?

There is no safety concern for testing children on SUDOSCAN. However due to hormonal changes in children, sweat function is not stabilized until 18 years of age. Due to lack of data in this population it is difficult to produce consistent and accurate ESC reference values. Studies in such populations is ongoing. Measures in children under the age of 18 must be interpreted with caution.

Can I use SUDOSCAN for type 1 diabetes?

Contrary to type 2 diabetes, diagnosis of type 1 can occur before the onset of complications including small C-fiber neuropathies. Thus at the early stages of the disease if the patient treatment is well-balanced sweat function should be normal and conductance values as measured by SUDOSCAN should not be decreased.  However with progression of the disease, especially if the patient treatment is not optimal, small C-fiber damage will occur and sweat dysfunction should be evidenced through a decrease in conductances as measured by SUDOSCAN. Due to the absence of a pre-diabetes stage small C-fiber damage in type 1 diabetes can be less and occur at later stages as compared to type 2 diabetes.

How does SUDOSCAN correlate with HbA1c?

HbA1C is used to monitor glycemic levels for the past 3 months period. SUDOSCAN is not a blood-based test but focuses on assessment of the small C nerve fiber damage.  As such, SUDOSCAN is a test that can be performed in complement to HbA1c. In addition small fiber neuropathy in type 2 diabetes especially depends not only on hyperglycemia also on other metabolic disturbances such as hyperlipidemia. There is no strict correlation evidenced between HbA1C and Sudocan results.  In research studies performed, we’ve observed cases where there were significant decreases in ESC results while no difference measured by HbA1c testing was evidenced.

How do nerve conduction studies or EMG correlate with SUDOSCAN?

Nerve conduction studies (NCS, also known as EMG) measure the function of large, myelinated nerves. They can be used for evaluating motor nerves and sensory nerves, but not the sensory nerves that are thin, umyelinated – such as heat, cold, and pain perception.

SUDOSCAN specifically measures the function of sympathetic C-fibers on the sweat glands. The function of these nerves correlates closely with small sensory nerves of the C-fiber variety. However SUDOSCAN and nerve conduction studies are not likely to correlate since they measure 2 different categories of nerves. Studies are ongoing in neurology to measure if Sudocan findings could precede EMG abnormalities, especially in chemotherapy induced neurotoxicity.

What is a ‘length-dependent’ neuropathy? Why is a SUDOSCAN test showing only abnormal hand ESC not length-dependent?

A length-dependent neuropathy is a pathological disorder in which nerve damage starts at the distal-most part of the nerve and progresses backwards along the nerve (retrograde). This is the most commonly accepted theory on the development and progression of diabetic peripheral neuropathy (DPN). Other neuropathies may attack the myelin sheath, or the neuron body, or cause compression at a distinct spot on the nerve axon.

Since SUDOSCAN measures nerve function on the palms and soles, the most distant parts of the body from the spine, it is very accurate at assessing length-dependent neuropathies of the small fibers.

A SUDOSCAN test revealing low hand scores may or may not be length-dependent. Some small fiber neuropathies (e.g. some infectious or autoimmune neuropathies) may be more severe in the hands, but also start at the nerve tips and so are length-dependent.

Also, in the early development of DPN, there may be a phase of compensatory ‘over-sweating’ in which the feet ESC scores are abnormally elevated while the hand scores may be lower. So a SUDOSCAN with low hand scores and normal feet scores may or may not be a ‘length-dependent’ neuropathy.

How often can you or should you retest?

Testing intervals should be based on Sudocan results and physician recommendations.  If your conductances are within normal limits, testing every 9 to 12 months is typical. Patients with peripheral neuropathies can be tested every 3 to 6 months to follow-up treatment protocols.

Can SUDOSCAN be used to follow the course of neuropathy over time?

Yes. The ability of SUDOSCAN to follow the course of peripheral small fiber and autonomic neuropathy over time is one of its greatest advantages over many other nerve function tests.

SUDOSCAN is able to do this for 2 major reasons:

–          Small nerve fibers, and in particular autonomic fibers, will degenerate and regenerate faster than most other nerves. Therefore a positive or negative response of the neuropathy to a change in therapy or to patient compliance or non-compliance may be demonstrated in as little as 3 months.

–          SUDOSCAN has a very high reproducibility rate. When a patient has 2 SUDOSCAN tests on the same day, the feet ESC scores will not vary by more than about 5%. So any ESC score change of more than 8 or 10 μS signals a pathological change, not device margin of error.

Is SUDOSCAN part of the protocol regimen for physicians today?

At the moment physicians have no tool to quickly and easily screen for peripheral small fiber neuropathy, other than the use of skin biopsies that are clearly invasive in nature.  Skin biopsies are not performed routinely, especially on diabetic patients with feet lesions.  This leaves SUDOSCAN, which has a huge potential to be used by physicians to follow-up patients with Type 2 diabetes as part of the ADA or European guidelines.

Can I get tested if I have a pacemaker?

Since only direct current is applied during a SUDOSCAN test, it does not
interfere with pacemaker electronics; therefore SUDOSCAN should be safe to use
in a subject with a pacemaker.

To confirm that there is no safety concern tests have be performed to check
Electromagnetic Compatibility according to ANSI/AAMI PC69:2007 : Active implantable medical devices— Electromagnetic compatibility— EMC test protocols for implantable cardiac pacemakers and implantable cardioverter guidelines.
The conclusion of the tests performed by Laboratoire Centrale des Industries
Electriques (LCIE, Fontenay aux Roses, France) is that “SUDOSCAN is compliant
according to ANSI/AAMI PC69: 2007 (Annexe M) standard”. (Report October, 2012).

However we recommend that patients with pacemakers perform SUDOSCAN testing
in the presence of a medical doctor.

What if I’m on Beta blockers?

Cardioselective beta-blockers should not interfere with SUDOSCAN measurements. However additional testing is needed to confirm this and the potential effect of other cardiovascular drugs.

What drugs can interfere with SUDOSCAN results?

As SUDOSCAN is based on measurements of sweat glands innervated by cholinergic small C fibers, drugs with high anti-cholinergic effects can influence SUDOSCAN results.

Thus tricyclic antidepressant agents (in particular amitriptyline), can significantly decrease ESC measured by SUDOSCAN. It is recommended that patients on such medications omit the drug for a period of 2 ½ half-lives (e.g. 48h) prior to SUDOSCAN testing.

If this is not possible results must be interpreted with caution. The effect of medications on ESC measurements is a key point and is under continuous investigation in ongoing studies.

What if I’m on anti diabetic drugs?

At the moment an observational study performed in an outpatient consult
clinic in Germany on two groups of patients with type 2 diabetes, the first one
receiving insulin, the second one other anti-diabetic drugs, evidenced that after
one year of follow-up patients receiving insulin had an improvement in their
conductances while the others had a small decrease. These preliminary results
have to be confirmed in a clinical study performed on a larger population.

Are you sure it is diabetes?

Small fiber neuropathy has been associated with many medical conditions including glucose dysmetabolism (diabetes or prediabetes). Several recent studies have found a high prevalence of impaired glucose tolerance in patients with peripheral neuropathies with a rate up to 42% in cases initially thought to be idiopathic compared with 14% in the general population (see article on small fiber neuropathy). Furthermore, peripheral neuropathies are not always diagnosed. Depending on the population studied and the diagnostic methods, up to 90% of patients with diabetes have confirmed peripheral neuropathies.

Another study showed that patients with metabolic syndrome were twice as likely to present with neuropathy as those without.

However there are other causes for polyneuropathies: metabolic syndrome, alcoholism, chemotherapy drug induced neurotoxicity. In all these cases neuropathies are symmetrical as opposed to mononeuropathies which are asymmetrical.

If sweat dysfunction is detected by SUDOSCAN, the possibility is high that a lesion of the peripheral autonomic nervous system exists. The cause must be investigated with further clinical assessment and the precise diagnosis confirmed by a more specific (but less sensitive) test, typically glucose based measurements (fasting or post glucose load test i.e. oral glucose tolerance test, OGTT) or HbA1C and lipid profile.

Can skin conditions affect SUDOSCAN scores?

Atopic dermatitis has been shown to increase intraepidermal nerve fiber density (IENFD). This makes sense since many such ailments lead to excessive itching from overly sensitive small nerve fibers.

SUDOSCAN measures sympathetic C-fbers, and these nerves tend to be affected in a similar fashion to the small sensory fibers. However, we have not completed studies using SUDOSCAN on patients with atopic dermatitis or any other skin condition and therefore cannot make a statement on how skin conditions affect SUDOSCAN results.

Note however, that the skin of the palms and soles MUST be intact – without open sores, ulcers, or lacerations – for SUDOSCAN results to be valid.

How should patients’ hands and feet be cleaned prior to SUDOSCAN testing?

Palms and soles must be free of dirt, ointments, or lotions prior to testing. Washing with soap and water is always the best option. However, antibacterial hand wipes such as Wet Ones® have been used extensively and do not appear to interfere with SUDOSCAN results.

Keep in mind: the palms and soles must be DRY prior to placement on the electrodes; and Surfa Safe – an industrial chemical – is NOT deemed appropriate or safe to clean skin prior to testing.

If there is more surface area of the palms and soles on the sensors, will this result in higher conductances and therefore higher microSiemens measurements?

Not necessarily. Patients with large feet/hands or small feet/hands have been tested, and the patients with larger extremities do not test higher than those with smaller extremities. If, however, the surface area of a hand or foot is severely reduced (e.g. from a previous second or third degree burn or an amputation) with obliteration of the sweat glands, the results will definitely be reduced.



EZSCAN


What does EZSCAN measure exactly?

EZSCAN evaluates sudomotor function on the palm of the hands and sole of the feet where the density of sweat glands is maximal.

The method is based on an electrochemical reaction between the sweat chloride and the electrodes. A low DC voltage ≤ 4 volts is applied generating a current relative to chloride (ion) flow supplied by the sweat glands and ducts. An Electro Skin Conductance (ESC) is calculated for the hands and feet on this basis of the current and the voltage that is generated.

Similarly to the cardiologic stress test for which the exercise is used as a stimulus to capture specific information that is not assessable in resting state, EZSCAN too relies on an electrical stimulus of sweat chloride to capture information about the sweat dysfunction that cannot be diagnosed in usual conditions. For a better understanding see animation on the web site.

Because the skin’s stratum corneum acts like an electrical capacitor allowing only the conduction of chloride to pass to the surface hands and feet electrodes via the sweat duct when a low voltage stimulation is applied, we can be certain that we’re targeting the underlying sweat gland and its sympathetic innervations.

This underlying theory has been confirmed in a comparative study performed on patients with Cystic Fibrosis (who have high sweat chloride concentration) and controls (see publication by Hubert et al).

Are you sure it is diabetes?

Small fiber neuropathy has been associated with many medical conditions including glucose dysmetabolism (diabetes or prediabetes). Several recent studies have found a high prevalence of impaired glucose tolerance in patients with peripheral neuropathies with a rate up to 42% in cases initially thought to be idiopathic compared with 14% in the general population (see article on small fiber neuropathy). Further, peripheral neuropathies are not always diagnosed. Depending on certain population and diagnostic methods, up to 90% of patients with diabetes have confirmed peripheral neuropathies.

Another study showed that patients with metabolic syndrome were twice as likely to present with neuropathy as those without.

However there are other causes for polyneuropathies: alcoholism, chemotherapy drug induced neurotoxicity. In all these cases neuropathies are symmetrical as opposed to mononeuropathies which are asymmetrical.

If sweat dysfunction is detected by EZSCAN, the possibility is high that a lesion of peripheral autonomic nervous system exists. The cause must be investigated with further clinical assessment and the precise diagnosis confirmed by a more specific (but less sensitive) test typical with glucose based measurements (fasting or post charge test i.e. oral glucose tolerance test, OGTT) or HbA1C and lipid metabolism.

Are EZSCAN measurements reproducible?

Reproducibility is critical for any screening test to be useful. EZSCAN has been tested for reproducibility in several clinical studies on large groups of patients with 5% coefficient of variation for feet ESC and 10% for hands ESC, which is excellent in an en-vivo environment. The reproducibility between measurements performed before and after an exercise is also excellent (see below).

Analyzing dynamic chloride-ionic flow of the sweat glands when stimulated by current that are high comparatively to physiologic current (between 1 and 4 V vs mV) provides better information as compared to methods based on sweat volume since chloride concentrations do not change with sweat rate (see article by Quinton et al on web site)

Also noteworthy is that the reproducibility of EZSCAN is significantly better than HbA1c (especially finger methods) or the oral glucose tolerance test (both HbA1c and OGTT have an effective reproducibility rate of about 20%).

For more information about the reproducibility and robustness of these tests, refer to the article of P Schwarz and et al (accepted for publication in British Journal of Diabetes and Vascular Diseases).

What are the effects of treatments?

The effect of treatments is a key point and is under investigation.

A preliminary study comparing a small group of patients comparable for age and BMI with or without pioglitazone has shown that patients receiving pioglitazone had higher feet ESC although a longer diabetes duration. This preliminary study will be extended on a larger group of patients with measures performed before pioglitazone administration and after 3 or 6 months with pioglitazone. The effect of other diabetes treatments will be tested.

Small C fibers innervating sweat glands are sympathetic fibers, and rely on acetylcholine to support neurotransmitter function. The effect of treatment that could act on sympathetic nervous system (i.e. beta-blockers that are not specific for the heart) has not been yet tested. In the same way the effect of atropinic agents has not yet be tested. These agents are known to decrease sweat rate and have been shown to negatively influence other sudomotor function tests such as QSART (Quantitative Sudomotor Axon Reflex Testing) that are based on sweat rate, as opposed to EZSCAN which do not depend on sweat rate.

Does room temperature affect test results?

Clinical tests run at different temperatures (changes of more than 5°C) demonstrate that temperature variance do not have impact on test results. Hands and feet that are poorly involved in thermoregulation due to their small area and thus are less temperature dependant than other parts of the body for their sweat rate. The role of sweat on hands and feet is to increase friction between skin and substrate, to increase the toughness of the skin, and to increase tactile sensitivity.

Theoretically, extreme cold temperature on the electrodes could result in vasoconstriction, whose effect has not been yet studied.

Therefore, avoid performing test measurements if the electrodes are too cold.

What’s the impact of exercise?

Given sweat rate changes with exercise it was important to evaluate the effects of exercise on EZSCAN tests. Measurements were performed before and after high level exercise on more than 100 subjects. They evidenced a coefficient of variation of 13 % for the hands and of 4% for the feet between these two measurements. These results confirm that EZSCAN measurements performed by don’t depend on sweat rate.

Does gender play a factor in the results?

Evaluation of sudomotor function using other tests such as QSART has shown generally lower measures (in sweat output) in women compared with those on men. This can be explained by lower sweat rates in women. Measurements performed by EZSCAN don’t depend on sweat rate. A study performed on more than 500 women and more than 200 men show no significant differences in hands’ and feet’ ESC. This will be confirmed in future pending studies on larger group populations.

Why and how does the blood pressure affect EZSCAN measurements?

Blood pressureinfluences local vascularisation. Chronic high blood pressure levels induce micro vascular lesions potentially affecting the renal function. Sweat glands representing small nephrons and comparable lesions could be observed in both apparatus. In addition high chronic levels of blood pressure are a risk factor and impact sudomotor function as evidenced by several methods (QSART, skin biopsies….) (see article by Low et al).

With high chronic levels of blood pressure, a decrease in ESC is expected given the relationship with sweat dysfunction.

High acute blood pressure levels should not affect EZSCAN measurements as EZSCAN does not depend on sweat rate.

What additional benefits and applications exist with EZSCAN (for the screening, or follow-up)?

EZSCAN is an objective measurement unlike the use of questionnaires which depend on a patient’s understanding of the questions and subjectivity. Questionnaires need to be adapted to target the screened population. The EZSCAN risk score (classified into at-risk/moderate risk/no-risk color coded quadrants) can greatly help the patient and physician visualize the results.

EZSCAN is quantitative so it can be used for the follow-up of the subject to evaluate their improvement when involved in a prevention program. EZSCAN provide a simple and easy user interface (e.g., using color classification) that can make for a useful tool – for example in displaying an improve change in risk score/health status could be highly motivating for a patient undergoing intervention/treatment.

For patients involved in a training program, usual tools or the follow-up, weight, waist the only parameters that will change in a questionnaire need time to go down that can decrease motivation of the subject.

What are the parameters used to calculate the EZSCAN score?

The EZSCAN score, calculated from hands and feet ESC values relies on the following parameters:

  • comparison between hands and feet patterns
  • demographic data (age and BMI)

The algorithm was developed and refined through numerous clinical studies and is continuously improved with new data.

What is the shelf life of the electrodes?

Electrodes are made of stainless steel with high Nickel grade, so they are more resistant to corrosive influences. Their shelf-life depends on how often they are used and how good their cleaning is done. Cleaning must be performed after each patient using the proper ANIOS cleaner product. This cleaning is necessary

  1. to respect hygiene and safety standards
  2. to stop the corrosion process being initiated by electrochemical reaction

In one French hospital in which the EZSCAN system has experienced moderately heavy use, the electrodes are still functional and performing satisfactorily even after 5 years.

A large study is ongoing in Netherlands with more than 15000 people tested with 4 devices (electrodes are still in service).


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