CA2709670A1 - A method for assessing abnormal sensations in humans - Google Patents

Abstract

This document describes a method for evaluating abnormal sensations in humans. Many conditions and injuries cause abnormal sensations in humans.
These include conditions affecting the nervous system directly and indirectly. In general, these abnormal sensations can be grouped into two categories - negative and positive phenomena. Negative phenomena include anesthesia, analgesia, proprioceptive loss and others. Positive phenomena include dysethesias, hyperpathia and others.
These subjective complaints are usually reported by the subject to a healthcare provider who diagnoses their root causes and severity. These sensory complaints are complex and are comprised of multiple different influences; including (a) the tissue injury itself usually peripheral nerve or nerve root; (b) central nervous system adaptations; (c) emotional components; [d] perceptual determinants and [e] depictive constituents.
The current method precisely combines several components: (a) new concept of external stimulation called the Aganaktic Recognition Level [ARL]; (b) the simultaneous measurement of an external sensory stimulatus with recording of verbal and non-verbal patient responses; (c) these non-verbal responses involve somatic and autonomic outputs that are ubiquitously evoked by an aganaktic stimulation; (d) recording these autonomic responses before, during, and after the ARL application to assess emotional components of the patient's experience; [e] comparing responses sequentially at matched control and test sites such that the person serves as his/her own control; and (f) routinely using multiple test sites and stimulation techniques to comprehensively evaluate the full extent of the subject's full sensory experience [including positive and negative phenomena].
One half of a sample trial run can be described as follows: (a) Electrodes are attached the subject to monitor autonomic responses (including skin conductance, heart rate, blood volume pulse, and others); (b) four surface EMG electrodes are applied to selected surface muscles; (c) once the electrodes are placed the patient is allowed to rest and enter a baseline state of relative relaxation; (d) at the specifically selected control site, a desired stimulation modality is gradually applied; (e) when the stimulus intensity reaches the Aganaktic Recognition Level, the patient depresses a button denoting that a level of sensory irritation has been reached; (f) this level of stimulus is maintained for several seconds and released; (g) the patient is allowed to rest;
autonomic and electromuscular responses are recorded before, during, and after ARL
application; (h) this process is repeated to insure reproducibility; (i) once the control site has been studied, the same process is (steps a though h) are reproduced exactly at the matched test site. This exact replication allows an intra-subject evaluation of physical tenderness and reactive responses between a neutral region and site of interest.
This sample trial is repeated using different paired sites and modalities in a sequential fashion until all sites and issues are addressed specific to that patient.
Usually, this requires two to four sets of trials for a given subject.
This specific combination of (a) simultaneous recording of verbal, autonomic and muscular reactions; (b) stimulation to an innovative, verbalized level of sensory experience; (c) systematic comparison of responses between precisely paired control and test sites; and (d) multiple trials of different sites and stimulus modes;
allows new conclusions and information concerning the physico-sensory, psychobiological, and sociodynamic bases for the test subject's pain experience.

Description

FIELD OF THE INVENTION. The invention broadly relates to the field of medicine, and more particularly relates to the field of the evaluation of sensory perception.

FIELD-BACKGROUND. Complaints of altered sensation are common in our society.
Sensory alterations occur in many medical conditions and injuries. These altered sensations can be grouped into two categories: negative and positive phenomena.
Negative phenomena include anesthesia, analgesia, proprioceptive loss, and others.
Positive phenomena include hyperpathia, dysesthesias and others. Currently, the evaluation of these phenomena relies primarily on the clinical examination.
For instance, a subject may complain of numbness and a healthcare professional will "examine" the patient at the bedside. The professional will stimulate the body region encompassed within the complaint. Dependent upon the stimulation intensity, the patient will verbally affirm or deny feeling the provoking stimulus. The intensity of the sensory aberration and its root substrates are then inferred by the professional. This non-specific process is extremely dependent on the accuracy of the claimant and the judgment of the observer.

From a scientific perspective, aberrant sensation is very complex. It has multiple substrates including (a] the triggering condition or injury itself; usually a nerve or nerve root condition; [b] central nervous system adaptive mechanisms that influence sensory encoding; [c] perceptual elements; [d] emotional determinates; and [e]
depictive constituents. These interactive phenomena render the bedside clinical evaluation inaccurate. This ambiguity has many confounding implications in circumstances where precision is important such as research (pharmaceutical and otherwise] and medicolegal situations. In these situations especially, it would be extremely desirable to be separate the pure neurological factors from the other confounding elements.

A common example of this conundrum is diabetic neuropathy. The patient may simply complain of discomfort and numbness [e.g., "I feel that I am always walking in sand"].
The examining professional may find a mixture of sensory loss, proprioceptive loss, and hyperpathic sensations involving the distal extremities. Variably the patient's verbalized complaints often do not correlate well with the clinical findings.
The explanation for this discordance lies in the complexity of the neurology itself plus the other determinants described above.

Currently, the above clinical evaluation is often supplemented by neurodiagnostic and imaging tests. MRI evaluations may look for abnormal nerve signals or edema (such as in carpal tunnel syndrome --another common entity]. Nerve conduction studies and somatosensory evoked potentials are used to assess electrophysiological correlates of the injuries. Neither of these strategies has good concordance with the severity or types of sensory experience. Again, the reasons for this discrepancy are complicated but have to do with the limitations of the current technology.

There is accumulating basic science information that many of these abnormal sensations are subserved biologically by differential adaptations of the peripheral nerves and their central sensory connections. Many stimulation modes of stimulation are used clinically to study and evaluate these diverse aberrant experiences, including dynamic mechanical, pressure, vibration, joint position, electric current, and thermal stimulus.
Most of these modal inputs can be quantitatively measured and are readily available.
The problem with the current assessment is how to unequivocally grade the patient's physiologic response. Current schemes rely purely on a verbal response. These usually involve either some assessment of perception thresholds or some patient grading system [such as an analog scale]. Two limitations of these methods are that the results fluctuate caused by: [a] patient-to-patient based on usual inter-subject variation, and [b] session-to-session deviations based on changes in mood, diurnal status, etc.
Furthermore, these methods attempt to focus on the neurological components and do nothing to assess the emotional, perceptual, and depictive constituent of the articulated experience, To overcome these deficiencies, the present invention describes a methodology that incorporates the available stimulation modes with non-verbal human somatic and autonomic reactions. It also describes a new concept in judging human responses.

As introduced above, asking subjects to grade a constant grade of sensory input is fraught with subject inconsistency. One person's grade of mild may be another person's moderate or severe. Thus, in sensory loss situations, one stoic individual may describe his carpal tunnel numbness as minimal while another histrionic person may describe the same loss as severe, The same variability occurs with the use of perception thresholds. The concept of perception threshold follows: a sensory mode's intensity is gradually increased [from zero upwards] until the person first perceives it.
The perception threshold has two limitations. It is quite variable from individual to individual due to biological diversity. Secondly, it cannot directly evaluate positive phenomena such as paresthesias, dysesthesias, etc.

SUMMARY OF THE INVENTION. Briefly, according to an embodiment of the present invention, a method for evaluating verbalized human abnormal sensory experiences is expressed. The invention uses commercially available stimulation devices [as described above] and commercially available autonomic and muscular recording equipment.
As summarized above, the methodology combines these two systems in novel ways to provide a new, comprehensive assessment of the abnormal sensory experience.

Conceptually, the method uses a new verbal stimulation response goal called the Aganaktic Recognition Levels for ARL]. ARL is very distinct from perception threshold.
The subject is asked to identify the intensity of stimulus mode that first becomes irritating; this stimulus is applied for a brief time frame. Based on the principles introduced above, the ARL is increased in situations were negative phenomena are tested whereas it is reduced in situations where positive phenomena are studied. ARL
therefore provides more information the perception threshold that cannot directly assess positive abnormal sensory phenomena such as paresthesias.

The second conceptual innovation involving the use of ARL stimulation is that it evokes non-verbal neurological reactions, specifically autonomic and somatic outputs, The autonomic outflows will include heart rate, skin conductive responses, blood volume pulse, and others. The somatic output will include surface EMG activity.2 Based on the ubiquitous biological facts, a threatening physical disturbance will cause a change in somatic and autonomic homeostasis. On the other hand, since ARL is an incipient irritative input, it will induce a temporally-linked, transient perturbation in autonomic levels. On the other hand, it is insufficient to cause anticipatory or prolonged responses that would be usually associated with potentially destructive or damaging inputs [with higher stimulus intensities]. Thus, the ARL corresponds to a well-defined intermediate sensory input that should helps distinguish the various elements of a subject's abnormal sensory experience.

An example should suffice to illustrate the principles. Consider a musician who develops unilateral carpal tunnel syndrome with biological components of paresthesias and numbness. Because the condition menaces professional goals, the musician's natural perception of the problem could be that it is severe although its biological elements are mild; therefore he grades both the paresthesias and numbness as 8/ 10 on The term "aganaktic" derives from the Greek for physical irritation.

2Clearly other autonomic phenomena could be considered in future variations on the invention. The listed variables are sufficient for most neuropathic conditions-an analog scale. When his ARL stimulus is applied, his autonomic-somatic responses will transiently and reactively change and recover coincident with stimulation onset and duration. This temporal concordance demonstrates a purely physical-sensory type of subject profile. The ARL stimulus for numbness will be tactile pressure; its value will be mildly increased consistent with mild tactile anesthesia. The ARL stimulus for paresthesias will be electrical stimulation [of a known type]; its value will be reduced compared to a control value consistent with mild hyperesthesia. The discrepancy between the ARL test values and the patient's verbalized severe sensory experience is explained by perceptual or descriptive factors of a psychosocial type. These insights are not readily available by current clinical and research tools.

Additional information is built into the invention's other features. The combination of a definitively measured input with quantifiable autonomic-somatic reactions provides additional information. Many medical conditions are tainted by comorbid emotional factors such as anxiety and depression that often go under-recognized by healthcare professionals. This is certainly true in neurological syndromes. The test protocol is designed to monitor and quantify subject's autonomic and somatic reactions before, during, and after the ictal provocation. If the subject's autonomic parameters modulate before or after the ictal event, that indicates an emotive substrate to the individual's clinical presentation. This information cannot be derived from clinical and research tools presently in use.

The final component of the invention protocol is the consistent use of control and test sites in pairs. It is well known that multiple biological factors influence perception thresholds including age and gender. There are other potentially confounding variables such as race, occupation, comorbid medical conditions, medications, and culture. To carefully account for this diversity, it is customary to have large normative populations and then attempt to compare the proband subject to the corresponding control group.
A more direct approach is to use a patient as his or her own control. This technique mitigates the biological diversity normally caused by the listed variables.

In summary, the current methodology describes multiple new features never before incorporated into the evaluation of the human abnormal sensations. These features include {a] the development of the Aganaktxc Recognition Level [ARL]; [b] the unique combination of different measurable sensory stimulation modes with defined quantifiable autonomic and somatic reactions; [c] the monitoring of autonomic-somatic reactions before and after the stimulation ictus; and [d] the use of pair control-test site results. These combined features provide insights into the multiple facets comprising a patient's experience of abnormal sensation. As illustrated above, the proper use of multiple stimulus modes at ARL intensity allows assessment of positive and negative sensory phenomena; the concomitant use of a verbalized analog scale permits appraisal of the sociodynamic-descriptive axis; the monitoring of autonomic-somatic reactions before and after the stimulation ictus evaluates the emotional components; and the combination of paired control-test sites mitigates confounding subject variables such as age, gender, comorbid medical conditions and medications, etc.

BRIEF DESCRIPTION OF THE FIGURES.
A. Figure One - Block Diagram of the Trial Methodology. This diagram details the steps followed during the current embodiment of this methodology. These steps are summarized briefly here and are described in detail during the next section.
Step 1 occurs after a directed history and physical exam by the technician [a physical therapist or similarly trained individual]. The patient is placed in a relaxed recumbent position with relevant body areas exposed for the trial. During this activity, data will be gathered concerning the present intensity of the subject's abnormal sensory experience.
Step 2 is the placement and calibration of the Autonomic recording electrodes to monitor changes in skin conductance, heart rate, blood volume pulse, temperature and other autonomic variables]. Step 3 is the placement and calibration of several surface electromyography electrodes; these electrodes will collect data before, during, and after the ARL administration period. During Step 4, the test trial is explained to the subject who is placed in a relaxed state. During Step 5, the actual control-site trial is run, Step 5 A is the first ARL administration period; as mentioned reaction data is recorded before, during, and after the ARL administration which can be variable in time length.
Step 5B is a rest period wherein the subject is allowed to return to a resting state. Step 5C repeats Steps SA and 5B to make sure that the ARL administration data is reproducible and reliable. Step 6 allows the subject to relax; electrodes can be repositioned as warranted. Step 7 repeats Step 4 through SC specifically at the paired test site [using the same stimulation mode and comparable electrode placements]. Step 8 repeats Steps 3 through 7 at a different pair of control-test site trials and/or different stimulation modes as clinically warranted by the differential diagnosis.

B. Figure Two. Block Diagram representing the physical set-up of one embodiment of this invention. The NeuroEvaluation recording system presently monitors skin conductance, heart rate, and blood volume pulse although other autonomic parameters are possible. The NeuroEvaluation recording system also currently uses surface EMG
recordings although needle electrodes may be used for certain applications.
The stimulation modalities include: palpatory pressure; various electrical current applications; joint proprioceptive by motion [e.g., goniometry or inclinornetry]; and others. As mentioned these are often combined in a single subject's session to specifically evaluate the different aspects of the subject's abnormal sensory experience[s]. The computer interface requires proprietary written soft-ware to specifically maximize data capture and analysis. Standard computer outputs are applicable.

DETAILED DESCRIPTION.

According to the current embodiment of the present invention, a method for evaluating the human subject's abnormal sensory experience is disclosed. Unlike other e.-dsting methods, the current invention is designed to comprehensively assess biological, perceptual, and emotional aspects of that experience. This is accomplished by combining several elements: [a] the invention of a new stimulation technique termed ART,; this allows the evaluation of both positive and negative abnormal sensory phenomena, while simultaneously avoiding the emotional and psychological sequelae of stronger stimulation intensities; [b] the innovative combination of verbal, graded verbal, and non-verbal data; the later non-verbal data includes somatic and automatic reactions to ARL application; this allows the distinction between purely physical-sensory and perceptual-descriptive components of someone's complaint; [d] the gathering of the autonomic-electromuscular data before, during and after the ARL
application; this allows the differentiation between physical-sensory and emotional aspects of the patient's presentation; [e] the use of paired control-test sites in a scientific paradigm to mitigate inter-subject variability issues; and [f] the use of precisely defined time periods for accurate data collection and analysis [described more fully below].

This section will describe the actual steps of the methodology, Step 1. Based on the referral information, a directed history and physical exam, the appropriate total protocol is selected. For illustrative purposes, assume the referred subject is sent with diagnosis of right upper extremity paresthetic numbness after a multiple sclerosis exacerbation; the patient is a musician by trade. The intake sensory information reveals that she is anxious, depressed, and grades her changes [both paresthesias and numbness] as severe. The intake physical examination finds mildly decreased light touch and mild hyperesthesia to pinwheel stimulation; joint position sense is severely affected even at the wrist. The subject's left arm is asymptomatic and normal by examination; it will serve for the control site. The stimulation modes will include electrical current stimulation to evaluate the paresthesias; pressure to evaluate the light touch loss; and range of motion to evaluate the proprioceptive complaints-Step 2. Autonomic recording electrodes are placed on the digits of the left hand to record general autonomic parameters including skin conduction response, heart rate, and blood volume pulse. Connections and recording stability are confirmed, Step 3. Non-specific surface EMG electrodes are placed over the left deltoid and trapezius to monitor general muscle tensions. Because the first trial will begin with the left leg, site-specific sEMG electrodes are placed over appropriate forearm muscles to assess local muscle guarding and movement.

Step 4. The examination is explained to the subject. The first trial will involve the control left leg to reduce examination-related anxiety. Pressure is the first selected stimulation mode. The concept of ARL is carefully explained and demonstrated to minimize stimulation-related anxiety. Specifically, the subject is instructed to press a button and verbally state now when she first feels pressure-evoked physical irritation.
As mentioned previously, using ARL application mitigates stimulation-induced psychobiological reactions.3 It also eliminates the ambiguities associated with higher stimulation stimuli required to acquire verbal responses for moderate or intolerable experiences.4 Step 5. Step 5 constitutes the ARL application period. In the illustrative subject [the female with multiple sclerosis); the first control site will be the left anterior forearm using a pressure mode stimulus [to evaluate light touch examination findings).
Step five can be subdivided into three parts.

Step 5A[i]. The Immediate Pre- and Post-ARL periods. The Immediate Pre- and Post-ARL data collection constitute an innovation not seen previously in prior stimulation techniques for the study of human experience/ It is critical for the proper identification of significant psychobiological factors [such as generalized or event-related amdety].5 3 Many people are naturally fearful of intense physical experiences and have anticipatory and reactive anxiety responses. This fear increases with rising stimulus intensity. Thus, high stimulating intensities can cause natural psychobiological responses that confound the separation between domains. In relaxed healthy individuals, ARL application does not evoke such rest period perturbations.

Subjects vary greatly in the perceptions of what they personally deem as a "moderate" or "unacceptably severe" intensity, Take for example, most people will agree that an temperature of approximately 82 degrees is warm, but there will be a great deal of variation as to what ambient temperature is deemed hot or intolerable. These perceptions are affected by multiple non-physical-sensory factors such as personality style, gender, cultural background, and other issues. There are also influenced by descriptive style such as stoic, histrionic, or emotive. Thus, the higher the stimulation intensity becomes, individual subjective factors become more and more influential.

Prior techniques do not access this data because they have usually relied on purely verbal responses to stimulation. The process described here requires the acquisition of non-verbal reactions by a reliable and reproducible data collection system.

Such patients will commonly show autonomic perturbations during the Pre- and Post-ARL periods not seen in healthy [e.g., non-anxious] volunteers; these autonomic perturbations may be accompanied by sEMG changes reflecting heightened muscle tension. Similar findings may occur in subjects with strong sociodynamic influences.6 Step SA(ii). The ARL test period. The ARL period is subdivided into five discrete subdivisions. These include: [1] a short pre-stimulus period lasting five seconds to collect baseline autonomic data for mathematical analysis; [2] an ARL ramping phase where the stimulation begins at zero intensity and gradually increases. This will be of variable length dependent on stimulation mode but lasts seconds; [3] an ARL
maintenance phase that begins when the subject presses a hand-held device that signals that ARL intensity is reached; this maintenance period is brief lasting 4 seconds; [4] an Initial recovery period lasting 10 seconds; and [5] a Final recovery period lasting approximately 15-20 seconds. These recovery periods allow the equipment to record the ARL-related autonomic and somatic changes and their return to baseline homeostasis. There is no parallel to this design in any prior assessment technique, This uniqueness is attributable to the combination of the verbal and non-verbal information gathering process which significant surpasses the analysis gathered by utilizing an isolated verbal response.?

Step 5B is an mtra-run rest period that allows the subject to completely return to baseline. During the rest period, autonomic and somatic data will be captured as well.
This rest period data is extremely helpful in capturing biomarker information concerning post-stimulation psychobiological and sociodynamic non-verbal reactions.
It also guarantees ample time to allow the patient to return to homeostatic autonomic and muscular stability prior to the second ARL run.

Step SC repeats steps 5A[i], 5A[ii[, and 5B to ensure reproducibility of the process, By utilizing these repetitions, the data can be group using standard statistical methods such as means and standard deviations for more accurate mathematical analysis later.
The successful completion of the repetition ends the analysis of the first control site.
Step 6 is constitutes a break between sites. The patient is allowed to move, reposition, and talk. Electrodes are reset or moved as needed clinically.

Step 7 continues the first trial with the acquisition of ARL data at the first test site. In our illustration, this would be at the right anterior forearm [in a region congruent with the immediately previous control site]. The stimulus mode would again be pressure.
Steps 5A through 5C are repeated exactly as described above. When this has been finished, the first pair control-test trial is done- In the final data analysis, this specific pairing will allow accurate control-to-test site comparisons yielding a thorough 6 These inferences arise deductively- When a subject is resting, the autonomic and electromuscular activity should remain constant. Any perturbations cannot be due to external forces since these are not present. By cause-and-effect deduction, any such perturbations must arise from the subject's internal matters [psychobiological or sociodynamic in origin].

7 Without such monitoring, there is no system to record peri-stimulus response data because no such data exists. There are no independent methods to verify or refute that a physico-sensory response has resulted from the OIT stimulation.

assessment of the abnormal sensory experiences Steps 5 through 7 can therefore be viewed as a continuum to complete Trial One of the designed clinical study Step 8 repeats steps 5 through 7 using different body sites and stimulation modes as warranted for a thorough clinical analysis of the patient's symptoms. In our illustrative case, there would be a second control-test trial [number two] using the medial forearms [left-control; right-test] but switching the stimulation mode to electrical stimulation for an analysis of the hyperesthesia to pin prick]. The third and last trial repeats steps 5 through 7 using range of motion [indinometryj at the wrists. At the end of trial three, the entire study would be finished. The raw data will be graphically recorded and summarized; the information will be presented in a tabular format. The interpreting physician will therefore have access to the original raw data from the recorded reaction information and stimulation values; the data will be tabulated and a clinical report generated.

Table One depicts the tabular data from our hypothetical MS patient.

As previously mentioned, the power of this comparison lies in the fact that each trial serves as its own internal control. Thus, the results are not as affected by subject-to-subject variables such as gender, age, personality, cultural background, etc.

TABLE ONE TABULATED STUDY RESULTS
Trw Stimulus Stimulus VAS Mean ARL value ARL Rest mode site score responses Responses 1 Pressure Con- L arm 4 kg/cm2 ++ +++
Test - R arm 8110 5 kg/cm2 ++ ++

2 Electrical Con - L am 3 mamps ++ ++
current Test - R arm 8/10 2 mumps ++ ++

3 Inelino- Con - L arm 70 deg Eat + +++
Metry Test- R arm 8/10 80 deg Lit + +++
These results are consistent with mild analgesia to light touch, moderate hypersensitivity [dysesthesias] to current, and mild-to-moderate proprioceptive loss [at the wrist]. There is a substantial amount of superimposed anxiety. These outcomes clarify the complex interactions between the patient's complaints of severe deficits. The actual findings are that the sensory loss and proprioceptive loss are mild; the discomfort is moderate, and a majority of the experience is due to a reactive anxiety/depression. Counseling for the anxiety and treatment of the dysesthesias with neuropathic medications will offer the patient a substantial improvement in her symptoms with her best outcome [rather than intensive rehabilitation].

This type of information would not be plausible with older test methods [such as the King technique]. They do not capture the PRC information nor do they assiduously compare control-test site responses in the above systematic fashion. As explained previously, these former tests were designed other purposes. They do not make the distinctions betweens the four domains of human pain experience; they do not attempt to evaluate different tissue odynic generators-In summary, the current embodiment of the invention contains multiple novel developments not previously seen. As this new technology is developed, the precise timing and structure of the actual trial protocols will modify but the underlying principles will remain the same; specifically, ARL level stimulation will be used for most applications; autonomic and electromuscular NeuroEvaluation tracings and data will be obtained; control-test condition comparisons will continue. On the other hand, new stimulation modes will be developed to address presently non-accessible issues such as gastrointestinal, urologic, and other interior body pain syndromes. As dictated by physiological reaction times and pragmatic considerations, modifications of the actual trial epochs are anticipated.

Claims