Quantitative Sensory Testing Thresholds Research Articles

Quantitative sensory testing in a large cohort of neuropathy patients

Background:
 Quantitative sensory testing (QST) is a subjective but reliable and quantifiable method to detect patient thresholds to different sensory stimuli. QST is used to measure small- and large-fiber nerve function and can be used in conjunction with other diagnostic modalities in the evaluation of peripheral neuropathy (PN). The utility of QST to distinguish among different types of PN, however, has not been explored. The objective of the study was to evaluate if different patterns of QST abnormalities could distinguish between PN types.
 Methods:
 This single-center retrospective cohort study evaluated the frequency of QST abnormalities to vibratory, cold and heat detection thresholds in a large population of PN cases evaluated at the University of Texas Southwestern Medical Center peripheral neuropathy clinic between 1995-2000. PN was categorized by etiology.
 Results:
 A total of 559 QST studies were performed in this study. The average age of patients (n=557) was 60 years with a male-to-female ratio of 1:1. The most common diagnosis was cryptogenic sensory polyneuropathy (CSPN, n=294), followed by Charcot–Marie–Tooth disease (n=84)). Meta-regression of vibration and cold indicate that the expected proportion of abnormal responses is less for the vibration test (p = 0.0002), relative to the cold test. However, no differences were observed between diagnoses.
 Conclusions:
 Though abnormal QST thresholds were seen in most patients with PN, patterns of QST abnormalities do not distinguish between different types of PN. The routine clinical utility of QST is likely limited.

Allodynia, Hyperalgesia, (Quantitative) Sensory Testing and Conditioned Pain Modulation in Patients With Complex Regional Pain Syndrome Before and After Spinal Cord Stimulation Therapy

ObjectivesComplex regional pain syndrome (CRPS) is a chronic debilitating disease characterized by sensory abnormalities. Spinal cord stimulation (SCS) is an effective therapy for CRPS, but few studies have investigated the effects of SCS therapy on sensory characteristics. Therefore, this study investigated the effect of SCS on allodynia, hyperalgesia, electrical quantitative sensory testing (QST) parameters, and conditioned pain modulation (CPM) effect. Materials and MethodsThis study is part of a multicenter randomized controlled trial (ISRCTN 36655259). Patients with CRPS in one extremity and eligible for SCS were included. The outcome parameters allodynia (symptom and sign), hyperalgesia (symptom), sensory thresholds with QST, CPM effect, and pain scores were tested before and after three months of SCS (40-Hz tonic SCS). Both the CRPS-affected extremity and the contralateral, clinically unaffected extremity were used to test three sensory thresholds with electrical QST: current perception threshold (CPT), pain perception threshold (PPT), and pain tolerance threshold (PTT). The PTT also was used as a test stimulus for the CPM paradigm both before and after the conditioning ice-water test. Nonparametric testing was used for all statistical analyses. ResultsIn total, 31 patients were included for analysis. Pain, allodynia (sign and symptom), and hyperalgesia (symptom) were all significantly reduced after SCS therapy. On the unaffected side, none of the QST thresholds (CPT, PPT, and PTT) was significantly altered after SCS therapy. However, the CPT on the CRPS-affected side was significantly increased after SCS therapy. A CPM effect was present both before and after SCS. ConclusionsStandard 40-Hz tonic SCS significantly reduces pain, hyperalgesia, and allodynia in patients with CRPS. These findings suggest that SCS therapy should not be withheld from patients who suffer from allodynia and hyperalgesia, which contradicts previous findings derived from retrospective analysis and animal research.ISRCTN Registry: The ISRCTN registration number for the study is ISRCTN 36655259.

Quantitative Sensory Testing in Children with Sickle Cell Disease

▪Background: Quantitative Sensory Testing (QST) is used in a variety of pain disorders such as arthritis and neuropathic pain syndromes, to characterize pain and predict prognosis and response to specific therapies. QST evaluates sensory function using a set of psychophysical procedures to measure subjective somatosensory responses to various physical stimuli. In Sickle Cell Disease (SCD) the painful vasoocclusive crisis is the most difficult management challenge and factors underlying the transition from acute to chronic pain and the wide interpatient variability in the pain experience are poorly understood. Optimal management for this complex pain syndrome remains unclear despite over three decades of basic and clinical research in the field.In this study, we aimed to duplicate results in the literature documenting altered QST thresholds in SCD and test the reproducibility of results over time to validate QST as a therapeutic endpoint for use in clinical trials evaluating novel preventative pain therapies.Objectives: Primary objectives were to test thermal thresholds in children with SCD versus African American controls and determine consistency over 6 months. Exploratory objectives were to correlate QST with clinical factors and select biomarkers and assess pressure pain thresholds (PPTs).Methods: Fifty-seven SCD and 60 control subjects aged 8-20 years underwent heat (wdt) and cold (cdt) detection and pain (hpt and cpt) threshold testing using a Medoc TSAII. A thermal composite score (TCS) was constructed by averaging the wdt, cdt, hpt, and cpt threshold responses from the testing instrument's starting temperature of 32°C. All participants were tested at baseline and 3 months; SCD subjects were additionally tested at 6 months and blood collected for future biomarker assessment. PPTs were performed using an SBMedic algometer. A single individual performed all QST. Descriptive statistics were computed and covariate-adjusted differences in thresholds within and between groups evaluated over time by mixed effects regression models with random intercepts and linear contrast tests. The intraclass correlation coefficient (ICC) from these models was used to assess within-subject consistency and Spearman's correlation was used to evaluate associations between thresholds and biomarkers. In addition, as a nested pseudo-intervention study, we analyzed a subset of “new” hydroxyurea (HU) users consisting of SCD subjects in whom HU was initiated within a few weeks prior to, or shortly after baseline testing. Significance was set at 0.05.Results: There were no significant differences in mean thermal or PPTs between SCD and control participants at baseline (Table 1) or month 3. QST measurements were consistent in SCD and control subjects for cpt, wdt, hpt and TCS (each ICC>0.55), but not necessarily for cdt (ICC = 0.37). Although generally internally consistent, there was some variability in mean thermal thresholds among SCD subjects over time, but the only significant difference between the 3 and 6 month means was for hpt (+0.67°C; 95% CI 1.15, 0.19). There was no association between mean thermal thresholds and chronic transfusion therapy. The group in whom HU was initiated shortly after baseline testing (n=6) demonstrated significant reductions in all thermal sensitivity and pain threshold measurements following HU initiation (Table 2).Conclusions: In contrast to Brandow's study (Brandow, American Journal Hematology, 2012), which documented thermal hypersensitivity in SCD, we have not demonstrated significant differences in thermal thresholds between SCD and control subjects. This could be due, in part, to differences in body sites used for testing. Results between second and third test sessions were highly consistent, indicating that reliability may improve once subjects have experience with QST. Subjects on whom HU was initiated shortly after baseline testing (new HU users) exhibited progressive and significant decreases in both cold and heat sensitivity from baseline to 6 months, suggesting that thermal testing is sensitive to effective therapy to prevent vasoocclusive pain. These findings are of critical importance to inform the planning of future SCD related clinical trials using QST as an endpoint in the evaluation of preventative pain therapies.Supported by National Institute of General Medical Sciences National Institutes of Health Award P20GM109021 and U54GM104941 [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Associations of Small Fiber Neuropathy with Geriatric Nutritional Risk Index and Arterial Stiffness in Hemodialysis.

Background Peripheral neuropathy is a common neurological complication in uremic patients, and quantitative sensory testing (QST) is effective for diagnosis of small fiber neuropathy. Malnutrition and arterial stiffness are prevalent in patients undergoing hemodialysis (HD). The associations of small fiber neuropathy with nutritional status and arterial stiffness remain uncertain in maintenance HD patients. Methods A total of 152 HD patients were included. Geriatric nutritional risk index (GNRI), an indicator of nutritional status, was calculated by serum albumin and actual and ideal body weight. Arterial stiffness was defined as brachial-ankle pulse wave velocity (baPWV) > 1400 cm/s. Small fiber neuropathy was assessed by an abnormal QST threshold of cold and warm sensation in patients' hands or feet. Multivariate forward logistic regression analysis was performed to examine the associations among abnormal QST threshold, GNRI, and arterial stiffness. Results baPWV and prevalence of abnormal QST threshold were significantly higher in diabetic patients. Multivariate logistic analyses revealed that older age (OR, 1.081; 95% CI, 1.026–1.139, p = 0.003) and male gender (OR, 4.450; 95% CI, 1.250–15.836, p = 0.021) were associated with abnormal warm threshold of hands. Furthermore, diabetes (OR, 3.966; 95% CI, 1.351–11.819, p = 0.012) and lower GNRI (per 1 unit increase, OR, 0.935, 95% CI, 0.887–0.985, p = 0.012) were associated with abnormal cold threshold of feet. Arterial stiffness (OR, 5.479, 95% CI, 1.132–22.870, p = 0.020) and higher calcium-phosphorus product (OR, 1.071, 95% CI, 1.013–1.132, p = 0.015) were associated with abnormal warm threshold of feet. Conclusions Lower GNRI and arterial stiffness were significantly associated with small fiber neuropathy in patients undergoing HD. Malnutrition risk and vascular factors might play important roles in small fiber neuropathy among patients undergoing HD.

Measuring peripheral nerve involvement in Friedreich's ataxia.

ObjectiveExperimental therapies under development for Friedreich’s Ataxia (FRDA) require validated biomarkers. In‐vivo reflectance confocal microscopy (RCM) of skin is a noninvasive way to quantify Meissner’s corpuscle (MC) density and has emerged as a sensitive measure of sensory polyneuropathies. We conducted a prospective, cross‐sectional study evaluating RCM of MCs and conventional peripheral nerve measures as candidate peripheral nerve markers in FRDA.MethodsSixteen individuals with FRDA and 16 age‐ and gender‐matched controls underwent RCM of MC density and morphology, skin biopsies for epidermal nerve fiber density (ENFD), nerve conduction studies (NCS), and quantitative sensory testing (QST) including touch, vibration, and cooling thresholds.ResultsMC densities were measurable in all participants with FRDA, and were lower at digit V (hand), thenar eminence, and arch (foot) compared to controls. By contrast, sensory NCS showed floor effects and were obtainable in only 13% of FRDA participants. QST thresholds for touch, vibration, and cooling were higher at the hand and foot in FRDA than controls. Reductions in ENFDs were present in more severely affected individuals with FRDA (Friedreich’s Ataxia Rating Scale (FARS) >60) compared to matched controls, although skin biopsies were not well tolerated in children. MC densities, ENFDs, and touch and vibration thresholds were associated with clinical disease severity (FARS and modified FARS) and duration since symptom onset.InterpretationMC density, ENFD, and QST thresholds provide structural and physiologic markers of sensory involvement in FRDA. Longitudinal evaluation is needed to determine whether these measures can identify changes associated with disease progression or treatment.

Effects of Stellate Ganglion Block on Analgesia Produced by Cervical Paravertebral Block as Established by Quantitative Sensory Testing: A Randomized Controlled Trial.

To use quantitative sensory testing (QST) to assess whether a stellate ganglion block (SGB) modulates the analgesia induced by cervical paravertebral block (CPVB). A prospective double-blind randomized controlled trial. Department of Anesthesia, Antwerp University Hospital, October 2011 to December 2015. Twenty-eight adults scheduled for arthroscopy of a nonfractured shoulder were enrolled. Participants were randomly assigned to receive either single CPVB (5 mL of levobupivacaine 0.5%) or combined CPVB + SGB (5 mL and 3 mL of levobubivacaine 0.5%, respectively). The detection thresholds for cold/warm sensations and cold/heat pain were established using thermal QST on the C4-C7 dermatomes before local anesthetic infiltration and at 0.5, 6, 10, and 24 hours thereafter. Our primary outcome was the time course of QST thresholds for the different neurosensitive/nociceptive modalities. As secondary and tertiary outcomes, we evaluated the degree of motor block and the time to first administration of rescue analgesics. We randomized 20 patients. There were no significant differences in the detection thresholds for the neurosensitive/nociceptive modalities, motor block, or timing for rescue analgesics between the groups (P = 0.15-0.94). All patients with CPVB + SGB exhibited Horner's signs, whereas patients in the CPVB group did not exhibit these signs; however, this does not exclude sympathetic block. We were unable to demonstrate any analgesic benefit of CPVB + SGB in arthroscopic shoulder surgery. It is therefore not unreasonable to suppose that pain from soft tissue injuries without bony lesions is transmitted mainly by somatic nerves with no or only minimal involvement of the sympathetic nervous system.

17. Pain modulation in patients with Multiple Sclerosis, pain and spasticity after oromucosal cannabinoid spray (THC/CBD): A study with quantitative sensory testing and laser evoked potentials

Oromucosal cannabinoid (THC/CBD) spray administration for the treatment of pain in patients affected by Multiple Sclerosis (MS) has been well documented and MS patients generally complain of different kind of pain, including spasticity-related and neuropathic pain. Our purpose was to examine pain modulation and thermal/pain threshold of MS patients before and after THC/CBD. 16 MS patients underwent clinical examination (including NRS scale), Quantitative Sensory Testing (QST) and Laser Evoked Potentials (LEPs) before and after one month of oromucosal spray. Psychophysiological and neurophysiological testing were compared to sex- and age-matched controls. Patients reported a significant reduction in pain (NRS 7,2 /4,7 before/after THC/CBD); QST thresholds were altered in patients and did not change after THC/CBD; there was a significant reduction of LEPs amplitude and increase of LEPs latency in MS patients compared to controls and no significant threshold or LEPs parameters change was noted after drug administration. Our results suggest that THC/CBD is effective on pain but LEPs and QST are not sensitive enough to detect pain modulation; the fact may be dependent on different factors, including the high disease burden as well as different kind of pains (nociceptive and neuropathic) affecting MS patients.

Somatosensory impairments are common after stroke but have only a small impact on post-stroke shoulder pain

To investigate whether somatosensory impairments are more common in individuals with post-stroke shoulder pain than in those without post-stroke shoulder pain and healthy controls. Descriptive analysis of a convenience sample. Forty-nine individuals with stroke, 24 with and 25 without post-stroke shoulder pain (median age 65 years), and 11 age- and sex-matched healthy controls. Perception and pain thresholds for cold, warm and heat (thermal thresholds), and pain thresholds for pressure and pin prick (mechanical thresholds) were assessed using quantitative sensory testing (QST). Passive range of motion, motor function, resistance to passive movements, light touch and proprioception were assessed in the upper extremities. Shoulder pain characteristics were recorded in the post-stroke shoulder pain group. There were no significant differences between the group with post-stroke shoulder pain and the group without post-stroke shoulder pain in any of the QST assessments, but more participants in the post-stroke shoulder pain group reported abnormal cold sensation in the affected side. Both stroke groups had generally higher thermal thresholds and more extreme low or high mechanical thresholds than the healthy controls. Somatosensory impairments are common among individuals with stroke compared with healthy controls. The non-significant differences in QST thresholds between the group with post-stroke shoulder pain and the group without post-stroke shoulder pain indicate that somatosensory impairments have only a small impact on post-stroke shoulder pain.

The association between pre-operative pain sensitisation and chronic pain after knee replacement: an exploratory study

Chronic pain after total knee replacement (TKR) is a prevalent condition, affecting about 20% of patients. The aim of this study was to explore the relationship between pre-operative pain thresholds and chronic pain after TKR. Patients listed for a TKR because of osteoarthritis participated in a Quantitative Sensory Testing (QST) session prior to surgery. Pressure pain thresholds (PPTs) and hot pain thresholds were assessed at the osteoarthritic knee and the forearm. Patients were followed-up at 1-year after TKR, and the severity of pain in the replaced knee was assessed using the WOMAC Pain score. Pre-operative median QST thresholds were compared to thresholds from a normative database collected from 50 people with no knee pain. The relationship between pre-operative pain thresholds and pain severity post TKR were tested using correlations. Fifty-one patients participated in a pre-operative QST session and completed a 1-year WOMAC Pain score. Pre-operatively, patients demonstrated evidence of localised (knee) and widespread (forearm) pain sensitisation in response to pressure stimuli compared to healthy participants. Pre-operative PPTs at the forearm were found to be significantly correlated with 1-year WOMAC Pain scores (r=0.37, P=0.008). This study provides preliminary evidence that pre-operative widespread pain sensitisation, measured using pressure algometry, may be associated with chronic pain after TKR. Further research is needed to explore the predictive value of an assessment of pre-operative widespread pain sensitisation in identifying who is likely to develop chronic pain after TKR.

Can widespread hypersensitivity in carpal tunnel syndrome be substantiated if neck and arm pain are absent?

Recent studies demonstrated that patients with carpal tunnel syndrome (CTS) have signs of thermal and mechanical hyperalgesia in extra-median territories suggesting an involvement of central pain mechanisms. As previous studies included patients with shoulder/arm symptoms or neck pain, a potential influence of these coexisting disorders cannot be excluded. This study therefore evaluated whether widespread sensory changes (hypoesthesia or hyperalgesia) are present in patients with unilateral CTS in the absence of coexisting disorders. Twenty-six patients with unilateral CTS with symptoms localised to their hand and 26 healthy controls participated in the study. A comprehensive quantitative sensory testing (QST) protocol including thermal and mechanical detection and pain thresholds was performed over the hands (median, ulnar and radial innervation area), lateral elbows, neck and tibialis anterior muscle. Patients with CTS demonstrated thermal and mechanical hypoesthesia in the hand but not at distant sites. Thermal or mechanical hyperalgesia was not identified at any location with traditional QST threshold testing. However, patients with CTS rated the pain during thermal pain testing significantly higher than healthy participants. This was especially apparent for heat pain ratings which were elevated not only in the affected hand but also in the neck and tibialis anterior muscle. In conclusion, CTS alone in the absence of coexisting neck and arm pain does not account for sensory changes outside the affected hand as determined by traditional QST threshold testing. Elevated pain ratings may however be an early indication of central pain mechanisms.

Somatosensory Symptoms and Signs and Conditioned Pain Modulation in Chronic Post-Stroke Shoulder Pain

Persistent shoulder pain is a common complication after stroke. Its etiology and underlying mechanisms are not well understood and treatment is generally unsatisfactory. The objective of this study was to assess the role of central sensitization and disinhibition in chronic stroke patients with chronic PSSP (n = 19), pain-free stroke patients (n = 29), and healthy controls (n = 23). Positive and negative somatosensory symptoms and signs were assessed using clinical examination and electrical and mechanical quantitative sensory testing (QST). Conditioned pain modulation (CPM) was assessed by comparing QST thresholds before and after applying a cold pressor test. Sensory abnormalities were more frequently observed and more severe in patients with PSSP, including positive signs such as allodynia at the affected side and generalized hyperalgesia at the unaffected side. CPM was similar in stroke patients and healthy controls. This study showed that chronic PSSP was associated with several positive and negative somatosensory signs, implicating a role for central sensitization and possibly for disinhibition. Since the causal relationship remains unclear, and may be related to either neuroplasticity induced by ongoing nociception as well as to the neuropathic brain lesion, prospective studies are warranted. The assessment of somatosensory symptoms and signs and endogenous pain modulation demonstrated a role for central sensitization and possibly for disinhibition in chronic PSSP. Prevention and treatment of PSSP could benefit from a more detailed analysis of both peripheral and central pain mechanisms.

The report of the study to somatofom disorders by quantitative sensory testing

Objective This study was to find the change of the patiens with somatoform disorders.Methods The quantitative sensory testing(QST)threshold values of CS,WS,HP,CP,WT were got by method of Limit and Level,and compare those values of the somatoform disorders group with those of control group.Results The Limit method showed that the threshold values was significantly different in two groups,except tlle CP,WT of left upper limb,the CP of fight upper limb,the CS,CP of right lower timb(LA-HP:39.79±1.29,43.17±1.10,t=9.2835,P＜0.01,LF-HP:16.46±3.41 14.72±1.10,t=2.1410,P＜0.05),and 11 QST threshold values of the somatoform disorders group were lower than those of control group,and the rate of steping down was higher than that of steping up(55%to 20%,x2=5.2267,P＜0.05).The Level method showed that the threshold values was significantly different in two groups,except the CS of right lower limb(RF-WT:1.07 ±0.13 1.33±0.03,t=8.5327,P＜0.01,LF-CS:28.73±0.69 28.08±0.63 t=3.2587,P＜0.01),and 8 QST threshold values of the somatoform disorders group were lower than those of control group,and the rate of steping down was higher than that of steping up(67%to 20%,x2=4.1958,P＜0.05).The rates of cutting down and stepping up were There were no significant deviation on the rates of cutting down or stepping up in both methods(P＞0.05).Conclusion Both Limit and Level show that the QST threshold values of the somatoform disorders step down,and it was more sensitivity in the somatoform disorders.The sensory disturbance generating from the somatoform disorders was related to the higher sensitivity in periphery nerve and central nerve. Key words: Somatoform disorders; Quantitative sensory testing

Neurology of Fabry disease

Fabry disease has diverse neurological manifestations, many of which influence morbidity and quality of life. The aim of the study was to document the clinical and subclinical neurological manifestations in a cohort of Australian patients with Fabry disease, using multiple clinical tools and a multidisciplinary approach. Participants completed focused questionnaires and underwent clinical neurological examination, Neurocognitive testing using Mini Mental State Examination and Neuropsychiatry Unit Cognitive Screen, Quantitative Sensory Testing (QST), autonomic assessment using RR interval variation, intracranial magnetic resonance imaging (MRI) and audiology. In subsets of patients who had previously undergone QST and/or prospective serial quality-of-life assessments over the previous 5 years, results before and after enzyme replacement therapy were compared. Twenty hemizygotes and two heterozygotes were recruited. The age (mean +/- standard deviation (SD)) of male participants was 40.4 +/- 11.9 years (range 20-62 years); the women were aged between 20 and 56 years. Increasing age was strongly associated with increasing neurological disability. Clinical peripheral neuropathy predominantly affected thermal sensation in all patients, with variable involvement of pinprick and light touch. QST confirmed these findings. Clinical cerebellar tests were commonly abnormal: this has not been previously reported in the absence of symptomatic cerebrovascular disease. There was hearing loss was in 90% of patients and no patient older than 44 years had normal hearing. MRI lesion prevalence increased with age. Despite neurological complications being common, formal cognitive testing was basically normal. QST thresholds for pain showed a significant change after enzyme replacement therapy. Neurological complications in Fabry disease are common, complex and may be devastating. All patients studied had neurological involvement, with protean and diverse manifestations.

Pain ratings at the thresholds are necessary for interpretation of quantitative sensory testing

Published databases of quantitative sensory testing (QST) for sensory thresholds provide a means for detecting deficits of the thermonociceptive sensory nervous system. These databases, however, do not assist in the assessment of neuropathic pain, which is characterized by pain or hyperalgesia, or both. We utilized the method of levels for innocuous thermal stimuli, warm and cool, and the method of limits for noxious thermal stimuli, hot pain and cold pain, to determine QST thresholds. Stimuli were applied to distal and proximal sites in the upper and lower limbs of 50 healthy volunteers, ranging in age from 19 to 59 years. Thresholds for innocuous and noxious stimuli in this study were similar to previously published results. The mean pain rating across all sites at thresholds for noxious heat and cold stimuli was 4.10, as rated on a 0-10 numeric scale. Suggestions are provided for combining threshold information for innocuous and noxious stimuli and related pain ratings for the evaluation of sensory nervous system function and, specifically, neuropathic pain.

Thermal innocuous and noxious thresholds and pain ratings at thresholds in distal and proximal limbs of normal subjects

Psychophysical studies have shown that quantitative sensory testing (QST) of sensory thresholds provides valuable information about the functional status of the somatosensory nervous system. However, normative data for QST thresholds at distal and proximal sites of upper and lower limbs or pain at thresholds have not well studied. This QST study, utilizing the innocuous and noxious thermal stimuli was conducted with 50 healthy volunteers, ranging in age from 19 to 59 years. Thresholds in this study for innocuous and noxious stimuli at distal and proximal sites were similar to studies published over past 40years, though this dataset is most comprehensive for the tested sites.

2',3'-dideoxycytidine (ddC) toxic neuropathy: a study of 52 patients.

We administered the antiviral agent 2',3'-dideoxycytidine (ddC) to HIV-infected patients with either ARC or AIDS as part of the AIDS Clinical Treatment Group protocol 012 and serially evaluated them with neuropathic symptom questionnaires, neurologic examinations, nerve conduction studies, and quantitative sensory testing (QST). All patients treated with high-dose ddC (0.06 and 0.03 mg/kg every 4 hours) developed a painful, predominantly sensory peripheral neuropathy, with a mean onset of 7.7 weeks, which reached severe intensity over several days. Abnormalities of vibration QST threshold preceded clinical symptoms. Treatment with 0.01 mg/kg every 4 hours produced a similar neuropathy, although of milder severity, later onset (mean, 9.3 weeks), and slower progression. In these patients, the onset of clinical symptoms and QST abnormalities were coincident. Only two of six patients treated with 0.005 mg/kg every 4 hours developed clinical or laboratory evidence of neuropathy; in both cases it was very mild and delayed in onset (26 weeks). All patients treated with high-dose ddC reported progression of symptoms (coasting) for 2 to 3 weeks following discontinuation of therapy. This study documents a painful sensory neuropathy resulting from treatment with ddC. With high-dose treatment, only the rapidity of onset and progression differentiated it from the distal, predominantly sensory neuropathy of AIDS.