Quantitative Sensation Testing Research Articles

The Use of Quantitative Sensation Testing to Identify the Physiological Differences Between the Median and Ulnar Nerves.

IntroductionSimilarities in morphology, physiological function, and neurophysiological findings between median and ulnar nerves are not unequivocal. Our previous study confirmed differences in motor fiber parameters between these nerves in healthy persons. We made an attempt to assess and compare the physiological parameters of different sensation modalities (temperature, pain, and vibration) in median and ulnar nerves.MethodsThe study was performed in 31 healthy, right-handed volunteers: 17 women, 14 men, mean age 44.8 ± 15.5 years. Standard sensory conduction tests in the median and ulnar nerves were performed together with the estimation of vibratory, temperature, and warm- and cold-induced pain thresholds in the C7 and C8 dermatomes on the palm, using quantitative sensory testing.ResultsThere were no statistically significant differences in the standard sensory conduction test in the median and ulnar nerves across the whole group: between right and left hands, and between women and men. We revealed differences in the temperature and pain thresholds between these nerves, mainly in low temperature perception. There were no differences in estimated thresholds between sides or in female and male groups. The vibratory limits did not differ significantly between nerves, and subgroups.ConclusionThe study confirmed the differences in the physiological sensory perception between the median and ulnar nerves. The median nerve is more sensitive to temperature stimulation than the ulnar nerve, but simultaneously less sensitive to pain-inducing temperature stimuli. These findings should be considered during the examination of hand nerve pathology.

The impact of chronic co-exposure to different heavy metals on small fibers of peripheral nerves. A study of metal industry workers

BackgroundChronic exposure to heavy metals affects various organs, among them the brain and peripheral nerves. Polyneuropathy is mainly length-dependent with predominantly sensory symptoms. There have been few studies on small fiber neuropathy due to heavy metal intoxication.MethodsWe investigated 41 metal industry workers, mean age 51.3 ± 10.5 years, with at least 5 years’ professional exposure to heavy metals, and 36 age- and sex-matched healthy controls. We performed neurological examinations, and assessed blood levels of cadmium, lead, and zinc protoporphyrin, urine levels of arsenic, standard, sensory and motor electrophysiological tests in the ulnar and peroneal nerves, sympathetic skin responses from the palm and foot, and quantitative sensation testing from dermatomes C8 and S1.DiscussionThe results of standard conduction tests of all nerves significantly differed between groups. The latency of sympathetic skin responses achieved from the foot was also statistically significantly prolonged in the study group. Significant differences were seen in both C8 and S1 regions for temperature and pain thresholds, and for vibratory threshold only in the S1 region, while the dispersions of low and high temperatures were important exclusively in the C8 region.ConclusionsWe can conclude that co-exposure to many heavy metals results in explicit impairment of peripheral nerves. The lesion is more pronounced within small fibers and is predominantly connected with greater impairment of temperature-dependent pain thresholds. The evaluation of small fiber function should be considered in the early diagnosis of toxic polyneuropathy or in low-dose exposure to heavy metals.

Kind and distribution of cutaneous sensation loss in hereditary transthyretin amyloidosis with polyneuropathy

ObjectiveReport on the kind and distribution of somatotopic sensation loss and its utility in assessing severity of sensation loss in study of a large international cohort of patients with hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN). MethodsSmart Somatotopic Quantitative Sensation Testing (S ST QSTing) using Computer Assisted Sensation Evaluator IVc (CASE IVc) was used to assess the somatotopic distribution of touch pressure (TP) and heat pain (HP) sensation loss twice of untreated hATTR-PN patients in the Ionis NEURO-TTR trial (www.clinicaltrials.gov, NCT01737398). ResultsOf the studied cohort of 169 patients, 163 (97%) had sensation loss, both TP and HP in 121/169 (75%), TP only in 39/169 (23%), and HP only in 3/169 (2%). Sensation loss typically affected both lower (152/169–90%) and upper limb (135/169–82%), and overall TP sensation loss was greater than HP loss, except for early-onset Val30Met patients in which HP exceeded TP loss. ConclusionUsing S ST QSTing, a highly quantitated, standardized, referenced, and automated QSTing approach of the body's surface distribution of sensation loss we have shown that: 1) reliable and useful measurement of the body surface distribution of sensation loss is possible; 2) this measure is abnormal in most patients with hATTR-PN and is an indication of polyneuropathy severity; and 3) cutaneous sensation loss involves both large and small sensory fibers in this disease but slightly more small fibers in early onset Val30Met patients.

Assessing mNIS+7Ionis and international neurologists' proficiency in a familial amyloidotic polyneuropathy trial

Polyneuropathy signs (Neuropathy Impairment Score, NIS), neurophysiologic tests (m+7Ionis ), disability, and health scores were assessed in baseline evaluations of 100 patients entered into an oligonucleotide familial amyloidotic polyneuropathy (FAP) trial. We assessed: (1) Proficiency of grading neurologic signs and correlation with neurophysiologic tests, and (2) clinometric performance of modified NIS+7 neurophysiologic tests (mNIS+7Ionis ) and its subscores and correlation with disability and health scores. The mNIS+7Ionis sensitively detected, characterized, and broadly scaled diverse polyneuropathy impairments. Polyneuropathy signs (NIS and subscores) correlated with neurophysiology tests, disability, and health scores. Smart Somatotopic Quantitative Sensation Testing of heat as pain 5 provided a needed measure of small fiber involvement not adequately assessed by other tests. Specially trained neurologists accurately assessed neuropathy signs as compared to referenced neurophysiologic tests. The score, mNIS+7Ionis , broadly detected, characterized, and scaled polyneuropathy abnormality in FAP, which correlated with disability and health scores. Muscle Nerve 56: 901-911, 2017.

PL37: a new hope in the treatment of painful diabetic neuropathy?

Solomon Tesfaye speaks to Nick Ward, Commissioning Editor: Solomon Tesfaye, MB ChB, MD, FRCP, speaks about PL37; the first orally administered dual inhibitor of enkephalinases and its potential role in the treatment of painful diabetic neuropathy. Solomon Tesfaye is a Consultant Physician/Endocrinologist at Sheffield Teaching Hospitals and Honorary Professor of Diabetic Medicine at the University of Sheffield. His research projects include the epidemiology, risk factors, pathogenesis, CNS involvement and treatment of diabetic neuropathy and neuropathic pain. He was awarded the Prestigious Camillo Golgi Prize of the European Association for the Study of Diabetes (EASD) in 2014 for major scientific contributions in diabetic neuropathy. He has had international leadership roles including chairmanship of the International Expert Group on Diabetic Neuropathy, and of NEURODIAB (2006-2009). He is also a member of the Science and Research Committee of Diabetes UK; a review panel member for the MRC, a Board Member of the Global Quantitative Sensation Testing Society; a member of the Advisory Council of the Neuropathy Trust; and Secretary of International Insulin Foundation. He has served as a member of the MRC, JDRF, NIDDK and UK NIHR scientific review panels and as a member of a Diabetes and Neuropathic Pain Review Group for NICE.

Does prediabetes cause small fiber sensory polyneuropathy? Does it matter?

Background and objectivesThe association between prediabetes and distal polyneuropathy (DPN) remains controversial. Here we test whether the prevalence of small fiber sensory distal polyneuropathy is increased in prediabetes. MethodsProspectively recruited cohorts of healthy subjects and those with prediabetes from Olmsted County, Minnesota, were assessed for positive neuropathic sensory symptoms, or pain symptoms characteristic of small fiber sensory DPN. Hyperalgesia and hypoalgesia were assessed by “smart” quantitative sensation testing (QST). The prevalence of symptoms and QST abnormalities were compared among the groups. ResultsThere was no significant increase in the prevalence of positive neuropathic sensory or pain symptoms, nor of hyper- or hypoalgesia in the prediabetes group. There was an increased prevalence of hypoalgesia of the foot only in newly diagnosed diabetes. ConclusionsBased on positive sensory and pain symptoms and QSTs, we did not find an increase in small fiber sensory DPN in prediabetes. Recognizing that obesity and diabetes mellitus are implicated in macro- and microvessel complications, physicians should encourage healthy living and weight loss in patients with prediabetes. In medical practice, alternate causes should be excluded before concluding that small fiber sensory distal neuropathy is secondary to prediabetes.

Retrospective study of a TTR FAP cohort to modify NIS + 7 for therapeutic trials

Protein stabilization and oligonucleotide therapies are being tested in transthyretin amyloid polyneuropathy (TTR FAP) trials. From retrospective analysis of 97 untreated TTR FAP patients, we test the adequacy of Neuropathy Impairment Score+7 tests (NIS+7) and modifications to comprehensively score impairments for use in such therapeutic trials.Our data confirms that TTR FAP usually is a sensorimotor polyneuropathy with autonomic features which usually is symmetric, length dependent, lower limb predominant and progressive. NIS+7 adequately assesses weakness and muscle stretch reflexes without ceiling effects but not sensation loss, autonomic dysfunction or nerve conduction abnormalities. Three modifications of NIS+7 are suggested: 1) use of Smart Somatotopic Quantitative Sensation Testing (S ST QSTing); 2) choice of new autonomic assessments, e.g., sudomotor testing of distributed anatomical sites; and 3) use of only compound muscle action potential amplitudes (of ulnar, peroneal and tibial nerves) and sensory nerve action potentials of ulnar and sural nerve — than the previously recommended attributes suggested for the sensitive detection of diabetic sensorimotor polyneuropathy. These modifications of NIS+7 if used in therapeutic trials should improve characterization and quantification of sensation and autonomic impairment in TTR FAP and provide better nerve conduction tests.

Results of computer-assisted sensory evaluation in 41 patients with erythromelalgia

Erythromelalgia is a rare disorder characterized by the clinical syndrome of burning pain, warmth and redness of the limbs. Neurological abnormalities (both large- and small-fibre neuropathy) are common. There have been few published reports on the sensory status of patients with erythromelalgia. To investigate the results of quantitative sensation testing in erythromelalgia using computer-assisted sensory evaluation, including vibratory detection threshold, cool detection threshold and heat-pain threshold (HPT). Patients who underwent dermatological or neurological evaluation of suspected erythromelalgia at our institution and received a final diagnosis of erythromelalgia were identified from a master diagnosis index covering the period January 1994 to June 2008. A retrospective chart review was performed. Main outcome measures were sensory abnormalities (e.g. pain, burning sensation, tingling) in response to heat, cooling and vibration during computer-assisted sensory testing. In total, 41 patients with erythromelalgia were enrolled in the study and underwent computer-assisted sensory evaluation. Of these, 34 patients (82.9%) had abnormal results. The commonest abnormality was isolated HPT: 11 patients (26.8%) had heat hypoalgesia and 18 (43.9%) had heat hyperalgesia, whereas only 2 (4.9%) of the healthy control patients had hyperalgesia on testing. Multiple sensory modalities were found to be abnormal in patients with erythromelalgia, with the commonest clinical abnormality being isolated heat-pain abnormality. These findings lend support to the notion that neuropathy underlies the clinical diagnosis of erythromelalgia. Future studies will explore the nature of the relationship between these sensory abnormalities and the clinical features of erythromelalgia.

Autonomic dysfunction in chronic inflammatory demyelinating polyradiculoneuropathy

Autonomic deficits in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have not been adequately quantitated. The Composite Autonomic Severity Score (CASS) is a validated instrument for laboratory quantitation of autonomic failure derived from standard autonomic reflex tests. We characterized dysautonomia in CIDP using CASS. Autonomic function was retrospectively analyzed in 47 patients meeting CIDP criteria. CASS ranges from 0 (normal) to 10 (pandysautonomia), reflecting summation of sudomotor (0-3), cardiovagal (0-3), and adrenergic (0-4) subscores. Severity of neurologic deficits was measured with Neuropathy Impairment Score (NIS). Degree of small fiber involvement was assessed with quantitative sensation testing. Thermoregulatory sweat test (TST) was available in 8 patients. Patients (25 men) were middle-aged (45.0 ± 14.9 years) with longstanding CIDP (3.5 ± 4.3 years) of moderate severity (NIS, 46.5 ± 32.7). Autonomic symptoms were uncommon, mainly gastrointestinal (9/47; 19%) and genitourinary (8/47; 17%). Autonomic deficits (CASS ≥1) were frequent (22/47; 47%) but very mild (CASS, 0.8 ± 0.9; CASS ≤3, all cases). Deficits were predominantly sudomotor (16/47; 34%) and cardiovagal (10/47; 21%) with relative adrenergic sparing (4/47; 9%). TST was abnormal in 5 of 8 patients (anhidrosis range, 2%-59%). Sudomotor impairment was predominantly distal and postganglionic. Somatic deficits (disease duration, severity, small fiber deficits) did not predict presence of autonomic deficits. Our data characterize the autonomic involvement in classic CIDP as mild, cholinergic, and predominantly sudomotor mainly as a result of lesions at the distal postganglionic axon. Extensive or severe autonomic involvement (CASS ≥4) in suspected CIDP should raise concern for an alternative diagnosis.

Dynametric assessment in CIDP

In this issue, Harbo and colleagues,3 use a number of common measures, including manual muscle testing, as done in the Neuropathy Impairment Score (NIS), attributes of nerve conduction (NCs), quantitative sensation testing (QST) using CASE IV, functional activity scales (9-hole peg and 40-meter walk), and short SF-36 quality of life scales for comparison with muscle force measurements of the Biodex System 3 PRO dynamometer (CIMP) in a trial of withholding and re-instituting IVIg treatment in patients with CIDP. They found that muscle force decreased by about 15 percent when treatment was withheld, and it improved by approximately 6 and 12 percent by days 5 and 10 after restarting IVIg treatment. These measured changes were significantly associated with “improved walking velocity and hand function.” With retreatment, the F-wave latency decreased, but manual muscle testing, NCs, QST and SF-36 did not show significant concomitant changes. They conclude that isokinetic dynamometry “…is a sensitive and clinically relevant method for monitoring the acute response to IVIG treatment in CIDP.”

Patterns Of Quantitative Sensation Testing Of Hypoesthesia And Hyperalgesia Are Predictive Of Diabetic Polyneuropathy—a Study Of Three Cohorts

OBJECTIVE—To test quantitative sensation testing (QST) patterns of hypoesthesia and hyperalgesia as indicators of diabetic polyneuropathy (DPN) and its severity. RESEARCH DESIGN AND METHODS—We used Computer‐Assisted Sensory Examination IV characterized the QST results of the foot of each patient in three diabetic cohorts (similar to 1,500 patients) as hyperesthetic (less than or equal to 2.5th percentile), low‐normal (2.5th–50th percentiles), high‐normal (50th–97.5th percentiles), or hypoesthetic (greater than or equal to 97.5th percentile), and tested associations with symptoms, impairments, and test abnormalities. RESULTS—Overall neuropathic impairment was most severe in the pancreas‐renal transplant and nerve growth factor cohorts, but it was much less severe in the population‐based Rochester Diabetic Neuropathy Study (RDNS) cohort. The frequency distribution of sensory abnormalities mirrored this difference. When the QST spectra of diabetic cohorts were compared with those of the control subject cohort for vibration and cooling sensations, the only abnormality observed was hypoesthesia, which was expressed as an increased number of subjects with values at or above the 97.5th percentile or by an increased percentage of cases with high‐normal values. Symptoms and impairments of DPN were significantly more frequent in the subjects with Values at or above the 97.5th percentile than in the subjects whose values were between the 50th and 97.5th percentiles. For heat pain (HP) sensation thresholds (intermediate pain severity [HP:5], pain threshold [HP:0.5], and pain‐stimulus response slope [HP:5‐0.5]), an increased frequency of both hypoalgesia and hyperalgesia was observed (especially in the RDNS cohort). Steeper pain‐stimulus response slopes were significantly associated with sensory symptoms, including severity of pain. CONCLUSIONS—1) Decreased vibratory sensation (hypoesthesia) appears to be characteristic of mild DPN, whereas pan‐modality hypoesthesia is characteristic of severe DPN. 2) A shift of vibratory and cold detection thresholds and also of attributes of nerve conduction and a measure of autonomic dysfunction from low‐normal (2.5th–50th percentiles) to high‐normal (50th–37.5th percentiles) appears to precede overt expression of DPN and to thereby provide evidence of subclinical abnormality. 3) Heat stimulus‐induced hyperesthesia (low thresholds) occurs especially in mild DPN, and, because it correlates with DPN symptoms and impairments, it must be attributed to hyperalgesia rather than to supersensitivity. Therefore, hypoalgesia or hyperalgesia may be an indicator of early DPN.

Patterns of quantitative sensation testing of hypoesthesia and hyperalgesia are predictive of diabetic polyneuropathy: a study of three cohorts. Nerve growth factor study group.

To test quantitative sensation testing (QST) patterns of hypoesthesia and hyperalgesia as indicators of diabetic polyneuropathy (DPN) and its severity We used Computer-Assisted Sensory Examination IV; characterized the QST results of the foot of each patient in three diabetic cohorts (approximately 1,500 patients) as hyperesthetic (< or = 2.5th percentile), low-normal (2.5th-50th percentiles), high-normal (50th-97.5th percentiles), or hypoesthetic (> or = 97.5th percentile); and tested associations with symptoms, impairments, and test abnormalities. Overall neuropathic impairment was most severe in the pancreas-renal transplant and nerve growth factor cohorts, but it was much less severe in the population-based Rochester Diabetic Neuropathy Study (RDNS) cohort. The frequency distribution of sensory abnormalities mirrored this difference. When the QST spectra of diabetic cohorts were compared with those of the control subject cohort for vibration and cooling sensations, the only abnormality observed was hypoesthesia, which was expressed as an increased number of subjects with values at or above the 97.5th percentile or by an increased percentage of cases with high-normal values. Symptoms and impairments of DPN were significantly more frequent in the subjects with values at or above the 97.5th percentile than in the subjects whose values were between the 50th and 97.5th percentiles. For heat pain (HP) sensation thresholds (intermediate pain severity [HP:5], pain threshold [HP:0.5], and pain-stimulus response slope [HP:5-0.5]), an increased frequency of both hypoalgesia and hyperalgesia was observed (especially in the RDNS cohort). Steeper pain-stimulus response slopes were significantly associated with sensory symptoms, including severity of pain. 1) Decreased vibratory sensation (hypoesthesia) appears to be characteristic of mild DPN, whereas panmodality hypoesthesia is characteristic of severe DPN. 2) A shift of vibratory and cold detection thresholds (and also of attributes of nerve conduction and a measure of autonomic dysfunction) from low-normal (2.5th-50th percentiles) to high-normal (50th-97.5th percentiles) appears to precede overt expression of DPN and to thereby provide evidence of subclinical abnormality 3) Heat stimulus-induced hyperesthesia (low thresholds) occurs especially in mild DPN, and, because it correlates with DPN symptoms and impairments, it must be attributed to hyperalgesia rather than to supersensitivity Therefore, hypoalgesia or hyperalgesia may be an indicator of early DPN.