CASE IV System: Theory of Operation for Quantitative Sensory Testing (QST)

Contents for this page:

	Just Noticeable Difference (JND steps Step) Scale
	Stimulus Characteristics
	Normative Data
	Description of Testing Methodologies
	Reproducibility of the CASE IV System Tests
	Scientific and Medical Applications of the CASE IV System
	Notes on Testing Procedures

All text and graphics copyright 1998-2002 by WR Medical Electronics Co. All rights reserved. .

Just Noticeable Difference (JND steps) Scale

The CASE IV System uses a discrete set of 25 standardized stimulation levels for patient testing and analysis. These 25 levels are termed “Just Noticeable Differences” or “JND steps,” and are similar to decibels. The concept of a JND steps is based on the fact that a sensitive person can detect fine differences between two levels of stimulation, whereas an insensitive person cannot. Because differences of less than one JND steps are difficult to distinguish, one JND steps is the smallest difference presented to patients.
     Stimuli based on the exponential JND steps scale can be used to test patients very efficiently and quickly, without compromising the significance of the clinical result. The JND steps stepss allow the minimum number of stimulus trials to be used, and eliminate unnecessary trials at unnecessary stimulus levels. The JND steps begin at a baseline level:
> For vibration stimuli, the baseline is 0 micrometers of displacement.
> For cooling stimuli, the baseline is usually set to 30 degrees C.; for heat-pain stimuli, the baseline is usually set to 34 degrees C.

Stimulus Characteristics

Vibration

The graph here indicates the onset, administration, and cessation of the vibration stimulus. The stimulus turns on with an exponential onset, and it turns off with an exponential decay. This method eliminates the touch-pressure artifact, which is caused by an instantaneous on/off.

Thermal

 
The thermal stimulator uses a 4-degree-per-second ramp up and down, and is typically operated in a range from 9 to 49 degrees C., with accuracy of ± 0.25 degrees C. (traceable to NIST standards). For high-magnitude thermal (warming) stimuli, a holding time is added to the waveform so that the absolute temperature is typically limited to 49 degrees C. for 10 seconds. The plateau lengthens the time that the stimulus is administered, providing more heat over time, ensuring the same physiologic sensation as a higher pyramidal waveform. For high-magnitude thermal (cooling) stimuli, the absolute temperature is limited to 9 degrees C.

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Normative Data

Accurate characterization of a patient’s responses to stimuli requires comparison to a statistically validated set of normative data. Therefore, with the CASE IV System software, a set of norms is provided (courtesy of Peter J. Dyck, MD). This 1999 set includes results from approximately 400 patients from Rochester, Minnesota.
     In addition, other normative data may be provided by our users at no charge to WR Medical, with the agreement that this data is to be redistributed to all other CASE IV users at no charge. Thus, the data is provided as a professional courtesy by our users for the purpose of aiding other users. WR Medical does not buy or sell normative data, nor can it make statements about the validity or inferences made by this other data.
     It is important to remember that the normative data will depend on the population studied, the algorithm used to determine the thresholds, technical characteristics of the measuring device, and other factors. We recommend highly that users build their own set of normative data using local or convenient populations.

Description of Testing Methodologies

The CASE IV System employs three testing algorithms. The approaches to testing and the algorithms for finding thresholds have been extensively tested using computer simulation and actual testing of healthy patients.

One-Time-Period with 4, 2, 1 Stepping

The one-time-period 4, 2, 1 Stepping Algorithm quickly assesses vibration, and cooling detection thresholds. For most routine testing, the 4, 2, 1 Stepping Algorithm is used. During the testing process, five null stimuli are placed randomly among a total of 20 stimulus trials to prevent false results and minimize pandering. Testing begins at a middle JND steps level (13). The system increases the next stimulation level if the patient cannot feel the stimulus, or decreases the next stimulation level if the patient feels the stimulus. As the test progresses, the number of steps that the stimulus level increases or decreases changes, beginning with a JND steps value of 4, decreasing to 2, and finally to a step value of 1, until the threshold is bounded. Because the 4, 2, 1 rule eliminates additional trials at unnecessary steps, the test is accurate, reliable, and time-efficient (a typical test on a normal male subject takes less than three minutes).

Two-Time-Period “Forced Choice” with 4, 2, 1 Stepping

The alternative “Forced Choice Algorithm” also can be used for vibration and cooling detection thresholds. Within each trial are two time periods. The system always presents a stimulus in one of the periods. For each trial, the patient has to determine the period in which stimulus occurred. Testing begins at JND steps level 13, and a patient is tested up to eight times at a given stimulus level before the next stimulus levels are raised or lowered. Subsequent stepping to larger or smaller levels occurs in JND steps increments of 4, then 2, and finally 1, until the threshold is bounded. The algorithm is very accurate and repeatable, and a great quantity of research and data on this algorithm is available in the public domain.

Heat-Pain Non-Repeating Ascending with Null Stimuli

The Heat-Pain Non-Repeating Ascending with Null Stimuli Algorithm, or simply the “Heat-Pain” test, ascertains a patient’s ability to determine when a stimulus begins to feel painful, not merely hot, in order to develop a “pain perception profile.” The patient answers orally to the test operator, who inputs the responses into the computer via the keyboard. This test uses a visual scale to help the patient decide on an answer. The zero corresponds to any stimulus that the patient cannot feel, is warm, or is hot but not painful. On the other hand, if any discomfort or pain is associated with the stimulus, the patient should rate that feeling from one to ten (one being the least painful). Two pain threshold values are calculated. The first, the onset point of pain, is called the HP:0.5 threshold value. The second, a standardized intermediate level of pain, is the HP:5.0 value. The difference between the HP:5.0 and the HP:0.5, an indicator of how tolerant the patient is to increasingly painful stimuli, is also calculated. The test is quite repeatable, especially with a given individual from test to test.

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Reproducibility of the CASE IV System Tests

Because the CASE IV components are carefully calibrated and the software routines that deliver precisely defined waveforms are tightly controlled, at any one level the stimulus waveforms are highly reproducible and are thought to be efficient and validated. (The CASE IV System has been shown to be repeatable to within two JND stepss on a normal population.) For a controlled clinical trial at multiple centers, one can therefore state that differences found among centers should not be due to difference in stimuli or algorithm of testing, but might be due to differences in patients.
     Of course, other factors may influence results, such as incomplete patient preparation and instruction, inconsistency in environment, or the deliberate falsifying of responses. If, for example, the subject or patient is poorly instructed and a practice session is not given, spurious results could be obtained because the patient did not understand the test properly. Another reason for variability of results is the patient him/herself. There is no way one can prevent a patient from falsifying results if they choose to do so. Dyck and colleagues have observed that highly neurotic patients or psychotic patients, drowsy patients, or patients on tranquilizing drugs may give spurious results (see Selected References).
     With research patients entering controlled clinical trials using the CASE IV System, reproducibility of results has been surprisingly good. Dyck and associates looked at the reproducibility of neuropathic tests in the “Rochester Diabetic Neuropathy Study” (see Selected References). The correlation coefficients for the vibration and cooling detection thresholds were greater than 0.9. This was found to be very similar to the reproducibility of the best nerve conduction attributes and better than quite a number of them. The reproducibility of the heat-pain 0.5 and heat-pain 5.0 algorithms has also been evaluated. In a 1996 article in the Journal of the Neurological Sciences, highly reproducible results were obtained (see Selected References). The paper states that “based on a study of 25 healthy subjects, the reproducibility of the test falls within ±1.0 stimulus steps 88 percent of the time for HP:5.0 and 76 percent of the time for HP:0.5.”

Scientific and Medical Applications of the CASE IV System

The system is ideally suited for the assessment of Cooling Detection Threshold (CDT), Vibration Detection Threshold (VDT), and Heat-Pain Detection Threshold (HPDT) in:

1. Physiologic studies assessing differences in health and the influence of anatomical site, handedness, age, and sex.
2. Anatomic-physiologic studies assessing the influence of density, depth, and type of receptors on various thresholds.
3. Identification of sensory abnormality due to diseases of the cutaneous sensory receptors, sensory nerve fibers, central nervous system pathways, or integrative centers, and further:
   > following the course of the disease;
   > monitoring the treatment effect;
   > recognizing a pattern of sensory loss indicative of a disease process (for example, dissociated sensory loss).
4. Epidemiologic surveys:
   > a screening method to detect sensory loss (for example, in populations of persons with a disease such as diabetes, or in examinations of persons possibly exposed to toxins such as those found in industrial plants);
   > an end-point of a disease (for example, a criterion for the diagnosis of neuropathy);
   > a marker of disease severity;
   > controlled clinical trials;
   > specific research studies (for example, the study of the interaction of physical stimuli and electro-physiologic events).

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The Neurobiology and Physiology of Cutaneous Sensation

The anatomy and physiology of cutaneous sensation is outside the scope of this descriptive sheet, but an excellent introduction can be found in various chapters of Peripheral Neuropathy, Dyck, P. J., Thomas, P. K., et al., published by WB Saunders in 1993 (see Selected References). Sensory receptors, some simple, and others quite complex, are topographically distributed over the surface of the body. Some are located superficially in the skin and provide exact topographical information, whereas others are more deeply located and provide information about generalized disturbances of the environment (for example, pacinian corpuscles and tremors of the earth).

Sensory Detection Thresholds

Primary afferent neurons whose somas lie in spinal ganglia connect cutaneous receptors to second- and third-order neurons in the central nervous system. The ability to detect vibratory stimuli is conveyed by a class of neurons (fibers) which are called “A Alpha.” A raised vibration threshold, assuming it is not due to drowsiness, inattention, volition, or physiologic disturbance, usually implies a loss of function or loss of sensory units of myelinated fibers having a large diameter. Theoretically, this may result from disease of receptors, or large-diameter afferent fibers in peripheral nerve or central tracts of the spinal cord and brain. A raised threshold of cool, warm, or heat-pain implies dysfunction or loss of receptors or nerve fibers either in the A Delta (small-diameter sensory myelinated fibers) or in the C (unmyelinated dorsal root fibers) fiber group in peripheral nerves. The assessment of this sensory loss (raised threshold) and whether it affects large or small fibers, or both, therefore provides useful characterizing information for the physician.

Heat-Pain Detection Threshold

In certain disorders of sensory fibers of peripheral nerve or central tracts, hypersensitivity phenomena may be elicited even when levels are below, at, or above threshold. Thus, a heat stimulus whose magnitude generally elicits only the perception of warmth may be experienced as painful. Using a visual analog scale from one through ten, it is also possible to determine the onset and rate of increase of the subjective experience of pain to externally applied stimuli. Such studies may be used to study the responses of heat-pain nociceptors in health and disease.

Role in Research and Drug Trials

Because the CASE IV System has demonstrated sensitive, specific, reproducible, and time-efficient test results, it has become the instrument of choice for quantitative sensory testing (QST). Such precision is accomplished by:
> carefully calibrated hardware that provides repeatable stimuli;
> statistically robust algorithms for altering the level of stimuli for each trial based on the patient’s responses;
> and carefully controlling patient instruction and environmental factors.

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Notes on Testing Procedures

Patient Preparation and Instruction

The tests should be administered in a quiet, distraction-free room that has sufficient light and air circulation, a comfortable temperature, and is free from drafts, vibration, or noise -- anything that might distract the patient. The CASE IV System should be placed on a rolling cart for easy maneuvering. Please contact WR for additional furniture and room considerations.

Positioning the Stimulators

For evaluation of neuropathy and central nervous system tracts, favorable sites are the following (a variety of other sites may be chosen depending, on the study’s purpose):
> Vibration Testing: foot (midline of the great toe between the base of the nail and the first knuckle); hand (base of the nail of the index finger).
> Thermal Testing: foot (dorsal surface); hand (dorsal surface); lateral shoulder (apex of the deltoid muscle -- lateral aspect of the shoulder); volar forearm (midpoint of the distance between the medial epicondyle to the end of the radius); anterior thigh (midpoint of a line from the inguinal crease to the midpoint of the patella); lateral leg (midpoint of a line from the tip of the head of the fibula to the tip of the lateral malleolus).

Time Required for Testing

Several factors affect the length of testing: the time required to explain the test, the speed in which the patient makes decisions, the alertness of the patient, and the number of stimuli needed to find the threshold. For thermal testing, the time also depends on the level of sensitivity because larger stimulus magnitudes for longer times are needed for insensitive patients. Test completion times for a normal male aged 37 are:
> Vibration: one-time-period 4,2,1 Stepping Algorithm, approximately 2.5 minutes; two-time-period Forced Choice, approximately 9 minutes.
> Thermal: one-time-period 4,2,1 Stepping Algorithm, approximately 2.5 minutes; two-time-period Forced Choice, approximately 11 minutes.

Test Output

After a test is completed, the results are simultaneously printed out and written to data files on the Host Computer’s hard drive. Test results are always appended to these files, so that the existing file is never overwritten. The threshold of a patient is given as a level of stimulus intensity, which are based on the JND steps scale. These levels are directly convertible into micrometers of displacement (for vibratory testing), or degrees Celsius (for thermal testing).