- What is R.I.S.C?
- What is IGHA?
- Cardiometabolic Risk
- Help in Results Reading
- R.I.S.C test: Guide for Physicians
Autonomic Nervous System (ANS) Baseline Analysis: Help in results reading
The autonomic nervous system controls important body functions such as blood pressure, heart rate, sweating, etc.
1. SDNN (standard deviation of all normal-to-normal R-R intervals) - it measures the heart’s ability to respond to hormonal fluctuations.
Normal Range: 40- 80 ms
Having low SDNN reading indicates:
- Weakened ANS’s ability to maintain internal body balance against internal/external environmental challenges.
- Lowered coping ability to various emotional/physical stress factors
- General weakness of health
2. RMSSD (Root Mean Square of Successive Differences) - it measures the variations in heart rate and the stability of the heart rhythm.
Normal Range: 35-65 ms
Decrease in RMSSD (below 10) accompanying lowered SDNN level (below 20) indicates high risk of heart disease.
3. T. Power (Total Power) - is used to measure the overall autonomic activity.
Normal Range: >= 1000 ms2
TP value below 1000 ms2 indicates a decrease in overall autonomic activity indicating underlying risk factors such as diabetes, heart disease, etc.
ANS (Autonomic Nervous System) Balance
1. LF (Low Frequency) – it is a strong indicator of sympathetic activity which enables the energy supply.
Normal Range:22- 46 %
Lowered Values of LF can indicate loss of energy and fatigue
2. HF (High Frequency) – This measure reflects parasympathetic (vagal) activity
Normal Range:22- 34 %
Reduced HF can indicate cardiac pathologies, stress, pain, anxiety or worry.
3. LF/HF - A higher value of LF/HF ratio indicates increased sympathetic activity or reduced parasympathetic activity.
Research suggests that increased sympathetic and decreased parasympathetic nervous system activity is associated with metabolic syndrome
Normal Range:0.5-02 %
Autonomic Nervous System (ANS) Baseline Analysis:Help in results reading
The R.I.S.C evaluates at rest (baseline)
1. ANS activity using Baseline HRV time domain analysis
2. ANS imbalance (sympathetic or parasympathetic predominance) using Baseline HRV time spectral analysis
The Scores are shared in 2 parts:ANS a Score (a stands for activity) and ANS b Score (bstands for Balance) The severity of the ANS activity and balance are quantitated using ANS scores algorithm for fast interpretation of results.
3 items are considered to determine the HRVa Score.
1. SDNN 2. RMSSD 3. TP
3 items are considered to determine the HRVb Score
1. HF 2. LF 3. LF/HF
Each item is scored 0 =normal, 1= borderline (yellow color) and 2= abnormal (orange or red color).
Results are referred to as normal (ANS score <2) or abnormal.
The abnormalities ranges are classified from mild ANS dysfunction (ANS score 2 -3), to moderate dysfunction (ANS score =4-5), or severe dysfunction
(ANS score =6).
The scores will be color coded as follow:
Green is considered as low risk, yellow as mild risk, orange as moderate risk and red as high risk.
ANS a Low Score reflects a decrease in vagal activity directed to the heart which leads to prevalence of sympathetic mechanisms and to cardiac electrical instability.
ANS Low score had been associated with:
? Early sign of cardiovascular events
? Bad prognostic for patient had MI
? Early detection of the clinical expression of autonomic neuropathy in diabetic patients
? Reduced VO2max and a sign of exercise intolerance
? Sign of fatigue or cardiovascular disorder
ANS b Low Score had been associated with:
? Sign of Anxiety
ANS a and b low score should be improved by lifestyle changes (quit smoking, regular exercises or healthy and balanced diet).
ANS Testing: Help in results reading
Sympathetic Nerve Damage Test
1.SPRV2 (Systolic pressure response to Valsalva maneuver in phase 2) Marker of sympathetic nerve damage.
Normal Range:-20 - - 40 mmHg
2.SPRV4 (Systolic pressure response to Valsalva maneuver in phase 4) Marker of sympathetic nerve damage.
Normal Range:> 10 mmHg
3. BPRS (Blood pressure response to standing) - Marker of sympathetic nerve damage. Blood pressure response to standing is the simplest test for
the evaluation of sympathetic integrity. Normally, the blood pressure response that occurs when an individual moves to a standing position is a small
reduction in systolic blood pressure and a small increase in diastolic blood pressure.This imbalance lasts only for a few
seconds as it adjusts to the new posture.Orthostatic or postural hypotension occurs when there is a
sudden and significant decrease in the systolic and/or diastolic blood pressure when a person stands up. It occurs within three minutes of standing. It is caused by abnormal blood pressure regulation and becomes more common with aging.
Normal Range:< 10 mmHg
Parasympathetic Test - Parasympathetic nervous system controls activities such as salivation, urination, digestion
1. Vals.R (Valsalva Ratio):
It is a standard test of cardiovagal function i.e. (it measures the functioning of the vagal nerve- associated with heart rhythm) function.
Normal Range: >1.18 %
Reading that is greater than 1.18 indicates - normal heart rhythm
Reading that is lesser than 1.18 indicates – abnormal heart rhythm.
2. K30/15 - Indicator of Vaso-vagal syncope. (a temporary loss of consciousness associated with a drop in blood
pressure) This test helps in the diagnosis of orthostatic hypotension (a form of hypotension in which a person's
blood pressure suddenly falls when standing up or stretching) and vagal syndrome.
Normal Range:>1.10 %
A reading less than 1.10 % indicates that you are at risk of orthostatic hypotension or vagal syndrome.
3. E/I Ratio (Expiration/ Inspiration Ratio) - Testing of sinus arrhythmia (natural variation in heart rate)
reflecting parasympathetic damage.
Normal Range: >1.18 %
Reading that is greater than 1.18 indicates - normal heart rhythm and no autonomic nervous dysfunction. Reading that is lesser than 1.18 indicates – abnormal heart rhythm and autonomic nervous dysfunction.
Sudomotor Test - Indicator of sudomotor (sweat) dysfunction - one of the major clinical manifestations of diabetic autonomic neuropathy.
1. ESR NO -Electrical Skin Response voltage related to the skin blood flow
Normal Range: > = 900 mV
If the reading is less than 900 mV, it indicates decreased electrical skin response to voltage as a result of nerve damage.
2. ESR CL -Electrical Skin Response voltage related to the C-Fiber density
Normal Range: > = 1000 mV
If the reading is less than 1000 mV, it indicates decreased electrical skin response to voltage as a result of nerve damage.
3. Latency: Time of response of the right and left foot after electrical stimulation of the Skin C Fiber. It measures
the response of your nerves to electrical stimulation.
Normal Range: < 2 s
A reading of less than 2s indicates that your nerve response is quick and thus you have healthy nerves.
A reading that is greater than 2s may indicate nerve damage as the response is delayed- possibly a sign of diabetic neuropathy.
ANS Testing:Help in results reading
ANS Testing is used to detect the ANS nerve damage or response failure in 3 functions:1) cardiovagal, 2) adrenergic and 3) sudomotor.
ANS Testing Scoring System
Since the autonomic testing evaluates global autonomic nerve integrity, the results are interpreted in term of score. The dysautonomia is quantitated using Parasympathetic Testing Response Score (PTR score), Sympathetic testing Response Score (STR score) and Sudomotor response Score (SMR score) for fast interpretation of results.
PTR score comprises the analysis of 3 items:1) heart rate response to standing (K30/15) 2) heart rate response to deep breathing ( E/I ratio) and 3) heart rate response to Valsalva maneuver (Valsalva ratio) STR score comprises the analysis of 3 items: 1) Beat to beat of the systolic pressure response to Valsalva maneuver in phase 2 (SPRV2), 2) Beat to beat of the systolic pressure response to Valsalva maneuver in phase 4 (SPRV4), and 3) Systolic pressure response to standing.
SMR score comprises the analysis of 3 items: 1) Amplitude of Electro-Skin Response to Nitric Oxide (ESCNO) 2) Amplitude of Electro Skin Response to released Cl-(ESCCl) 3) Time of response from stimulation to the peak ESCCl (Latency). Each Test is scored 0 =normal, 1= borderline (yellow color) and 2= abnormal (orange or red color).And the scores will be related to the risk of damage and color coded as follows:
Green is considered as low risk, yellow as mild risk, orange as moderate risk and red as high risk.
The 3 parasympathetic tests are age adjusted.
Sudomotor function Testing
LD Technology uses a new process to test the Sudomotor function or activity using a galvanic skin response (GSR) or sympathetic skin response (SSR) hardware and software.
Sudomotor is controlled by a division of sympathetic system and it is relating to, or being nerve fibers controlling the activity of sweat glands (post sympathetic cholinergic fiber or C-fibers).
Sudomotor dysfunction is using to definite a decreased sudomotor activity.
Traditional neurophysiologic measurements of sudomotor function include thermoregulatory sweat testing (TST), quantitative sudomotor axon reflex testing (QSART), silicone impressions and sympathetic skin response (SSR).
The SSR method uses 2 pairs of tactile large electrodes and it is performed by electrical stimulation of the skin and contralateral electrical stimulation of the C-fibers.
C –Fibers damage provokes pains, decreased peripheral blood flow and sensory disorder to temperature.
Mainly, Sudomotor function evaluation is performed to detect skin blood flow (microcirculation) and C-fiber density for early detection (first stages) of peripheral distal neuropathy in population at high risk such as diabetic patient. In addition, sudomotor dysfunction has been found in different diseases or medication side effect such as cancer treatment, antihypertensive treatment ( in particular Beta and alpha blockers and calcium antagonists), Metformin treatment, vitamin deficiency, Parkinson’s disease, AISD, amyotrophic lateral sclerosis, hypothyroidism, kidney and liver diseases, alcoholism, Alzheimer's disease and Guillain-Barre syndrome.
Peripheral distal neuropathy is a damage of the skin nerves Skin nerves comprise large fiber A-Alpha and Beta, A delta Fiber and C Fiber Thin, unmyelinated C-fibers:no protective coating – easily damaged Long:from spine to soles of feet: sensitive to length-dependent damage (dying back disorders)
Therefore sweat dysfunction will be the first detectable damage to the small fibers of the peripheral nervous system – BEFORE ANY CLINICAL SIGNS OR SYMPTOMS
Damage to small nerve fibers is reversible, unlike most damage to large myelinated fibers
Chart flow of evolutionary steps of peripheral distal neuropathy.
The evolutionary of peripheral foot neuropathy comprises 4 steps
Step 1: Microcirculation disorder and decreased skin blood flow
Step 2:Decreased of C-Fiber density
Step 3:Skin Nerve damage (including all the nerves as shown in figure 1 and not only the C-Fiber)
Step 4:Necrosis and amputation decision
Step 1 and 2 are reversible with effective treatment, unlike the steps 3 and 4 which have only palliative treatment.
LD Technology patented process of measurement can detect the asymptomatic phase 1 (Skin blood flow) and 2 (C-fiber density decreased) of the peripheral distal neuropathy when the treatment could be effective and could reverse the disease evolution to necrosis and amputation.
The electrical output signal is sending to the skin in contact with the active electrode. Because the voltage is lower than 10 V, it cannot penetrate the stratum corneum;the only way for the current to enter the body is through the eccrine sweat ducts.
The signal is carried by the interstitial fluid ions through the body via the interstitial fluid to reach the skin in contact with passive electrode. In the pathway, the signal provokes an electrical stimulation of the post sympathetic cholinergic fiber (C Fiber) which release acetylcholine.
Acetylcholine stimulates the nicotinic muscarinic receptors (M receptors).
The activation of M receptors will have 2 effects:
1. Effect on Skin blood flow: Activation of M3 on vascular endothelial cells causes increased synthesis of nitric oxide (NO), which diffuses to adjacent vascular smooth muscle cells and causes their relaxation and vasodilation.
2. Effect on the sweat glands function: Activation of Inositol polyphosphates (IPP's) causes intracellular calcium mobilization and calcium influx. The increased cytoplasmic calcium stimulates chloride channels in the apical (luminal) membrane, and potassium channels in the basolateral membrane of the secretory clear cell of the sweat glands, resulting in the efflux of both ions. Chloride enters the secretory cell via either a Na- 2Cl -K or Na - Cl cotransport system, and leaves the cells by diffusion into the lumen of the sweat duct.The movement of chloride across the apical membrane depolarizes the apical membrane and generates a negative luminal potential. This negative lumen charge then attracts sodium into the lumen across the intercellular junction (i.e. paracellular pathway). The 2 effects of the electrical stimulation process generate electrochemical reactions on the bulk of the passive electrode.
Relationship between sweat gland nerve fiber density and neuropathy impairment score
SGNFD:Sweat Gland Nerve Fiber Density
NIS-LL: Neuropathy Impairment Score in the Lower Limbs
The device generates the reference voltage signal (1.28 V), in DC or frequency (20 Hz), that is fed to the active electrode which is connected to the skin of the patient. Then the signal passes through the interstitial liquid compartment of the patient and reaches the skin in contact with passive electrode.The noise is filtered by pass the low frequency filter and then through repeaters providing galvanic isolation and then the signal processing analysis is performed at the analog-digital converter in digital code.The digital code goes through a galvanic isolation to USB controller and then is released to the slot of the USB port of the computer for the further processing analysis by the software.
Software and new process of measurement
The software receives the digital code of the ADC and display the values in a graphic.
During the measurement, the software controls the sequence for each electrode activation and the polarity of the signal (electrical stimulation).
For each pair of electrode, the sequence and Polarity are as follow: Phase 1 the polarity is from cathode to anode during 30 seconds and then in phase 2 the polarity is switched from anode to cathode which generate a peak named peak phase 2
Phase 3 the polarity is from anode to cathode during 30 seconds and then in phase 4 the polarity is switched from cathode to anode which generate a peak named peak phase4
Time between the switch of polarity and peaks:
The peak cathode time is immediate, no delay.
The peak anode time is between 1 and 2 seconds:This time is named Latency.
Then, the software converts the ADC digital code in Voltage (mV) and Intensity (mA) according to the ACD manufacturer table.
Using the Ohm law formula the software converts also the data in Resistance (KOhm) and then in Conductance (micro Siemens) In fact, the patented LD technology process is based upon the switch of polarity during the measurement of each pathway between the pair of electrode and this method has the possibility to separate the 2 effects of the electrical stimulation of the C-Fiber.
The Chloride ions cannot discharge in the cathode due to the electronegativity and therefore we have in the cathode only the effect of the induced vasodilation (skin blood flow) and in anode the effect of the release of the chloride ions (C-fiber density). I.e.chart flow of the process
Chart flow of the new process of evaluation of the sudomotor activity.
Phase 1: the Current is sending from cathode E1 to anode E2.
Phase 2: the polarity is switched from anode E2 to cathode E1, the Chloride ions are blocked and the release of NO increases the skin blood flow and a Peak is detected in the graphic: The amplitude of the peak phase 2 reflects the skin blood flow in the skin in contact with the 2 electrodes.
Phase 3: the Current is sending from anode E2 to cathode E1
Phase 4: the polarity is switched from cathode E1 to anode E2, the Chloride ions are released and a second Peak is detected in the graphic: The amplitude of the peak phase 4 reflects the C-fiber density in the skin in contact with the 2 electrodes.
Normal Range of the measurement
Normal Range of the 2 peaks was evaluate in 200 supposed population without skin blood flow decreased nor reduced C-fiber density reduced
Peak 2 Normal range is greater than 900 mV
Peak 4 Normal range is greater than 1000 mV
Latency Normal ranger is less than 2 seconds
No differences were found according to gender and weight or height of the Tested population.However, elderly subjects have a lower voltage comparing to the young subjects (average of 15%).
Conditions of the measurement
The subject is measured in sitting or lying position and should relax during a period of 5 minutes to avoid the sympathetic activation induce by the standing position.
The temperature also should be comfortable from 23 to 25 degree Celsius to avoid the activation of the sweat glands from the adrenergic stimulation or vasoconstriction induced by cold plates or extremities.
The electrical stimulation of the nerve induces an action potential and this action potential will be reduced if the time of stimulation excess 1minute in continuous or if the stimulation is repeated several time.Therefore, successive exams could reduce the peak response and the time between 2 exams cannot be shorter than one hour.
Suggested interpretation of the results*
Peak readings less than 900mV for peak 2 suggests skin blood flow is decreased and peak readings less than 1000 mV for peak 4 suggests reduced C-fiber density. Both of these conditions suggest early peripheral distal neuropathy and causes should be considered and appropriate action taken to prevent further nerve damage and the need for more disruptive treatments in the future. Latency readings greater than 2 seconds suggest skin sensory disorders.
*When the patient present symptom(s), further supplementary exams should be including for diagnosis (i.e.Toronto Score)
ANS Testing with Challenges
1. Cardiovagal evaluation with Valsalva ratio: this is the ratio of heart rate phase IV/heart rate phase II, and is essentially a measure of vagal function. The normal response is an increase in heart rate during phase II (SPVR2) in response to the fall in blood pressure, and the baroreflex response to the blood pressure overshoot in phase IV (SPRV4) is transient bradycardia. In dysautonomia patients, there is typically a loss of both the blood pressure overshoot and the reflex bradycardia.Age-adjusted normal Valsalva ratios are used as controls for the Valsalva ratio.
2. Adrenergic evaluation with Beat-to-beat blood pressure response to the Valsalva maneuver: phase II may be divided into early and late phases. In early phase II, reduced preload and stroke volume lead to a fall in cardiac output despite the tachycardia caused by decreased vagal activity. Total peripheral resistance increases due to increased sympathetic discharge (nucleus tractus solitarius) and an increase in plasma epinephrine concentration. The fall in blood pressure is thus arrested, and is termed “late phase II”; in normal patients there is actually a rise in blood pressure just before release. Interestingly, this phase can be blocked with alphaantagonists (e.g., phentolamine) while phase IV can be blocked with
beta-blockers.Patients with peripheral adrenergic failure due to involvement of autonomic fibers will have absent late phase II and in fact can have such dramatic drops in blood pressure during forced expiration that syncope may occur.
Deep breathing tests cardiac parasympathetic functions. Because the heart responses to deep breathing are mediated by the vagal nerve, the test is also referred to as cardiovagal testing. During inspiration, intra thoracic pressure is reduced, which will decrease venous return from the pulmonary circulation to the left atrium of the heart and decrease preload; heart rate will therefore increase slightly to compensate and maintain the same cardiac output.The opposite happens during expiration; intra thoracic pressure rises, increasing pulmonary venous return (and therefore preload), so heart rate will decrease to maintain constant cardiac output. The results is expressed as E/I Ratio (expiration/Inspiration Ratio)
1. Cardiovagal evaluation with K30/15:At the standing position, the heart rate increased during the first 15 seconds and then decreased and stabilized at 30 seconds.
2. Adrenergic evaluation with systolic pressure response to standing (BPRS). At the standing position, the blood pressure should increase and should be at least no less than 10 mmHg comparing to the blood pressure lying or sitting position.
Help in result reading autonomic testing
Scoring system:Each Test is scored 0 =normal, 1= borderline (yellow color) and 2= abnormal (orange or red color). Sympathetic additional comments
If SPRV2 > -20 => Increased Norepinephrine response (áreceptors) blood volume increased
If SPRV2 < -40 => decreased Norepinephrine response (á receptors), blood volume decreased
SPRV4 < +10 or BPRS >10 => decreased epinephrine response (â receptors),
SPRV4 > 20 OR BPRS < -20 => increased epinephrine response (â receptors),
Symptoms associated with autonomic neuropathy
Some people with nerve damage have no symptoms.Others may have symptoms of nerve damage.
The symptoms may include
? Numbness, tingling, or pain in the toes, feet, legs, hands, arms, and fingers
? People with foot neuropathy typically describe the pain of peripheral neuropathy as tingling or burning, while they may compare the loss of sensation to the feeling of wearing a thin stocking or glove.
? Indigestion, nausea, or vomiting
? Exercise intolerance
? Diarrhea or constipation
? Dizziness or faintness due to a drop in blood pressure after standing or sitting up
? Problems with urination
? Erectile dysfunction in men or vaginal dryness in women
? Symptoms that are not due to neuropathy, but often accompany it, include weight loss and depression.
What causes autonomic neuropathies?
Nerve damage is likely due to a combination of factors:
? Metabolic factors, such as high blood glucose, long duration of diabetes, abnormal blood fat levels, and possibly low levels of insulin
? Neurovascular factors, leading to damage to the blood vessels that carry oxygen and nutrients to nerves
? Autoimmune factors that cause inflammation in nerves
? Mechanical injury to nerves, such as carpal tunnel syndrome or inherited traits that increase susceptibility to nerve disease
? Lifestyle factors, such as smoking or alcohol use
? Vitamin deficiencies, particularly B vitamins
? Biemer’s Anemia
? Infections, such as Lyme disease, shingles (varicella-zoster), Epstein-Barr, hepatitis C and HIV/AIDS
? Kidney, liver or thyroid disorders
? Exposure to toxins
? Repetitive physical stress, possibly from occupational activities
Suggested Autonomic neuropathy Treatment
The first treatment step is to bring blood glucose levels within the normal range to help prevent further nerve damage.
Early detection of Foot Neuropathy:
Treatments that are applied to the skin— typically to the feet—include capsaicin cream and lidocaine patches (Lidoderm, Lidopain). Studies suggest that nitrate sprays or patches for the feet may relieve pain. Studies of alpha-lipoic acid, an antioxidant, and/or B12 vitamin and evening primrose oil suggest they may help relieve symptoms and improve nerve function in some patients.
Pains: Duloxetine and Pregabalin are approved by the U.S. Food and Drug Administration specifically for treating painful autonomic neuropathy.
? When symptoms are severe, doctors may prescribe erythromycin
to speed digestion, metoclopramide to speed digestion and help
relieve nausea, or other medications to help regulate digestion or
reduce stomach acid secretion.
? To relieve diarrhea or other bowel problems, doctors may prescribe an antibiotic such as tetracycline, or other medications appropriate.
? Increase the amount of fluid you drink, and choose foods that are low in fat and high in fiber, which typically improves digestion.
Dizziness and Weakness:
? Raising the head of the bed or wearing elastic stockings may help.
? Some people benefit from increased salt in the diet and treatment with salt-retaining hormones. Physical therapy can help when muscle weakness or loss of coordination is a problem.
Urinary and Sexual Problems:
? To clear up a urinary tract infection, the doctor will probably prescribe an antibiotic. Drinking plenty of fluids will help prevent another infection.
? To treat erectile dysfunction in men, the doctor will first do tests to rule out a hormonal cause. Several methods are available to treat erectile dysfunction caused by neuropathy. Medicines are available to help men have and maintain erections by increasing blood flow to the penis.
Some are oral medications and others are injected into the penis or inserted into the urethra at the tip of the penis. Mechanical vacuum devices can also increase blood flow to the penis. Another option is to surgically implant an inflatable or semirigid device in the penis.
? Vaginal lubricants may be useful for women when neuropathy causes vaginal dryness. To treat problems with arousal and orgasm, the doctor may refer women to a gynecologist.
Blood Pressure Analysis: Help in results reading
1. Sys (Systolic Blood Pressure) - measures the pressure the blood puts on the walls of the arteries when the heart contracts.
Normal Range:110-140 mmHg
If the reading is greater than 140 mmHg, it indicates High Systolic Blood Pressure/ Hypertension. If the reading is less than 90 mmHg, it could indicate Low Systolic Blood Pressure/ Hypotension.
2. Dias (Diastolic Blood Pressure) - measures the pressure the blood puts on the walls of the arteries when the heart relaxes.
Normal Range:75-90 mmHg
If the reading is greater than 90 mmHg, it indicates High Diastolic Blood Pressure/ Hypertension. If the reading is less than 75 mmHg, it could indicate Low Diastolic Blood Pressure/ Hypotension.
3. SVR (Systemic Vascular Resistance) - measures the resistance to blood flow offered by the walls of the artery.
The body tends to adjust its blood pressure by varying the diameter of the arteries.
Normal Range:< 1500 dyn-s-cm2
A reading less than 1500 indicates that the arteries are responding well to the blood pressure.A reading greater than 1500 could indicate arteriosclerosis (hardening of the arteries).
Syst. Time I.
1.LVETi (Left Ventricular Ejection Time):
It is the time interval from the opening to the closing of the aortic valve (mechanical systole). It checks for ventricular performance i.e.the performance of the ventricles of the heart.
Normal Range:370- 420 ms
2. PEP (Pre-Ejection Period):
it is the time interval from the beginning of electrical stimulation of the ventricles to the opening of the aortic valve (electrical systole). It checks for left ventricular (LV) inotropy i.e.weakening of the contraction of the ventricles.
Normal Range:90- 110ms
3. PEPi/LVETi (Marker of Cardiac Performance)
Ratio of PEPi/LVETi measures cardiac output.
Normal Range: <0.38%
Blood Pressure Analysis:Help in results reading
Three blood pressure measurements are performed during the R.I.S.C exam:
The first one is taken after the patient relaxes for at least 5 minutes in sitting position and the measurement is synchronized with the beat t beat stoke volume to asses the cardiac output* and arterial stiffness and HRV variability analysis to assess the predominance of the 2 components of ANS .
The second one is taken during the Valsalva maneuver and beat to beat blood pressure is performed.
The last one is taken in standing position.
These 3 measurements will be used to assess the sympathetic system damage (e.g.Refer to Autonomic Testing help in reading).
The blood pressure control is quantitated using BPC Score algorithm for fast interpretation of results.
6 items are considered to determine the BPC Score.
1. Systolic Pressure
2. Diastolic Pressure
3. PEPi/LVETi :marker of heart contractility
4. SPVR2:Marker of Norepinephrine
5. SPVR4:Marker of epinephrine
6. SVR* :Systemic Vascular resistance
Each item is scored 0 =normal, 1= borderline (yellow color) and 2= abnormal (orange or red color).
Results are referred to as normal (BPC Score < 4) or abnormal.
The abnormalities ranges are classified from mild uncontrolled (BPC score from 4-6), to moderate uncontrolled (BPC score from 6-8 ), or severe uncontrolled (BPC score >8).
BPC Score should be used to indicate the need for further evaluation of repeated BP measurements - not as a basis for diagnosis.
JNC Guidelines are the reference to treat and maintain normal BP However , In adjunct to the JNC 7 guidelines , the measured items will be usefull for choosing or avoiding the anti hypertensive agents as regard to the mode of action of the medications**.
*Off label use
**This application is only an adjunct to the JNC7 , the practitionner has the responsibility of the treatment
Blood Pressure treatment and systolic time interval (STI)
Calcium antagonist increased STI
Blood Pressure treatment and PTGTPi and Systemic vascular resistance (SVR)
PTGTPi is the main marker of Insulin Resistance and it has been compared to the gold standard. PTGTPi Increased should be an indication of ACE for protecting the kidney function. In addition, ACE are recommended if SVR is increased
Blood Pressure treatment and Valsalva maneuver markers
The fall of the Systolic pressure during the phase 2 (SPRV2) should be <-20 mmHg and >-40 mmHg
The value SPRV2 reflects the Norepinephrine response and plasma volume.
The Alpha-Blockers and diuretics decreased SPRV2 value.
The Overshot of the systolic pressure in phase 4 (SPRV4) should be > -10 mmHg
The value SPRV4 reflects the epinephrine response.
The Beta-Blockers decreased SPRV4 value.
IR-IGT( Insulin Resistance- Impaired Glucose Tolerance) Markers
1. PTGTPi (Plethysmography Total Power Index ): Indicates risk of Insulin Resistance
Normal Range: <377 c.u.
2. Stress Index: Measures cardiac muscle oxygen demand related to heart work.
3. PTGVLFi (Plethysmography very low frequency Index): Indicator of
Beta cell activity – Beta cells are insulin producing cells located in Pancreas.
Normal Range: <25 c.u.
1. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology.Heart rate variability. Standards of measurement, physiologic interpretation, and clinical use.Circulation 1996 93:1043-1065.
2. Tsuji H, Martin G, Larson ScD, Ferdinand J, Veditti Jr, Manders ES, Evans JC, Larson MG, Feldman CL, Levy D. Impact of Reduced heart rate variability on risk for Cardiac Events .The Framingham Heart Study.Circulation, Vol.94,No 11, December, 1, 1996
3. Circulation.1994;90:878-883Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ, and the Multicenter Post-Infarction Research Group. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction.Am J Cardiol. 1987;59:256262.
4. Kitney RI, Byrne S, Edmonds ME, Watkins PJ, Roberts VC.Heart rate variability in the assessment of autonomic diabetic neuropathy. Automedica 1982;4:155–67.
5. Schroeder E.B , Chambless L.E , Liao D, Prineas R.J, Evans G.W, Rosamond W.D , Heiss G.Diabetes, Glucose, Insulin, and Heart R a t e V a r i a b i l i t y . T h e Atherosclerosis Risk in Communities (ARIC) study.Diabetes Care March 2005 vol.28 no.3 668-674
6. Chizmadzhev YA, Indenbom AV, Kuzmin PI, Galichenko SV, Weaver JC, Potts RO. Electrical properties of skin at moderate voltages: contribution of appendageal macropores. Biophys J.1998;74(2) 843–856.
7. Girach A, Manner D, Porta M.Diabetic microvascular complications:Can patients at risk be identified? A review.Int J Clin Pract.
8. Shahani BT, Halperin J.J, Boulu P, Cohen J. Sympathetic skin response-a method of assessing unmyelinated axon dysfunction in peripheral neuropathies. Journal of Neurology, Neurosurgery, and Psychiatry 1984;47:536-542
9. Schlereth T, Brosda N, Birklein F.Somatotopic arrangement of sudomotor axon reflex sweating in humans.AutonomNeurosci.2005;123:76-81.
10. Gibbons, C.H., Illigens, B.M., Wang, N., Freeman, R., 2009.Quantification of sweat gland innervation:a clinical-pathologic correlation.Neurology 72, 1479–1486.
11. Sommer P, Kluschina O, Schley M, Namer B, Schmelz M, Rukwied R. Electrically induced quantitative sudomotor axon reflex test in human volunteers. Autonomic Neuroscience: Basic and Clinical 159 (2011) 111–116.
12. Hashimoto K.Demonstration of the intercellular spaces of the human eccrine sweat gland by lanthanum.I.The secretory coil.J Ultrastruct Res.1971;36:249–262.
13. Stanley EF.Single calcium channels and acetylcholine release at a presynaptic nerve terminal.Neuron.1993 Dec;11(6):1007-11.
14. Mishra A, Greaves R, and Massie J.The Relevance of Sweat Testing for the Diagnosis of Cystic Fibrosis in the Genomic Era.Clin Biochem Rev.2005 November; 26(4): 135–153.
15. Grimmes S, Martinsen ØG.Electrolytics. In:Bioimpedance and Bioelectricity Basics.Maryland Heights, MO:Academic Press;2008.
16. Statistical analysis of EIS-GS measurements in healthy subjects.Unpublished
17. Shahani BT, Halperin J.J, Boulu P, Cohen J. Sympathetic skin response-a method of assessing unmyelinated axon dysfunction in peripheral neuropathies. Journal of Neurology, Neurosurgery, and Psychiatry 1984;47:536-542
18. Levy DM, Reid G, Rowley DA, and Abraham RR. Quantitative measures of sympathetic skin response in diabetes: relation to sudomotor and neurological function.J Neurol Neurosurg Psychiatry.1992 October; 55(10):902–908
19. Gin H, Baudoin R, Raffaitin CH, Rigalleau V, Gonzalez C. Non-invasive and quantitative assessment of sudomotor function for peripheral diabetic neuropathy evaluation.Diabetes Metab.2011 Dec;37(6):527-32.
24. National Diabetes Information Clearinghouse.Diabetic Neuropathies:The Nerve Damage of Diabetes
25. Vinik AI, Erbas T:Recognizing and treating diabetic autonomic neuropathy.Cleve Clin J Med 68:928–944, 2001
26. Freeman R:The peripheral nervous system and diabetes.In Joslin’s Diabetes Mellitus.Weir G, Kahn R, King GL, Eds.Philadelphia, Lippincott, 2002
27. American Diabetes Association and American Academy of Neurology: Report and recommendations of the San Antonio Conference on diabetic neuropathy (Consensus Statement).Diabetes 37:1000–1004, 1988
28. Ziegler D:Cardiovascular autonomic neuropathy: clinical manifestations and measurement.Diabetes Reviews 7:300– 315, 1999
29. Pfeifer MA, Weinberg CR, Cook DL, Reenan A, Halter JB, Ensinck JW, Porte DJr: Autonomic neural dysfunction in recently diagnosed diabetic subjects. Diabetes Care 7:447–453, 1984
30. Ewing DJ:Cardiovascular reflexes and autonomic neuropathy.Clin Sci Mol Med 55:321–327, 1978
31. Clarke BF, Ewing DJ, Campbell IW:Diabetic autonomic neuropathy.Diabetologia 17:195–212, 1979
32. Vinik AI:Diagnosis and management of diabetic neuropathy.Clin Geriatr Med 15:293–320, 1999