Abnormal Quantitative Sensory Testing Research Articles

Cutaneous nerve biopsy in patients with symptoms of small fiber neuropathy: a retrospective study.

We aimed to investigate to what extent small fiber tests were abnormal in an unselected retrospective patient material with symptoms suggesting that small fiber neuropathy (SFN) could be present, and to evaluate possible gender differences. Nerve conduction studies (NCS), skin biopsy for determination of intraepidermal nerve fiber density (IENFD) and quantitative sensory testing (QST) were performed. Z-scores were calculated from reference materials to adjust for the effects of age and gender/height. Two hundred and three patients, 148 females and 55 males had normal NCS and were considered to have possible SFN. 45.3 % had reduced IENFD, 43.2 % of the females and 50.9 % of the males. Mean IENFD was 7.3±2.6 fibers/mm in females and 6.1±2.3 in males (p<0.001), but the difference was not significant when adopting Z-scores. Comparison of gender differences between those with normal and abnormal IENFD were not significant when Z-scores were applied. QST was abnormal in 50 % of the patients (48.9 % in females and 52.9 % in males). In the low IENFD group 45 cases out of 90 (50 %) were recorded with abnormal QST. In those with normal IENFD 51 of 102 (50 %) showed abnormal QST. Less than half of these patients had reduced IENFD, and 50 % had abnormal QST. There were no gender differences. A more strict selection of patients might have increased the sensitivity, but functional changes in unmyelinated nerve fibers are also known to occur with normal IENFD. Approval to collect data was given by the Norwegian data protection authority at University Hospital of North Norway (Project no. 02028).

Thermal threshold testing: call for a balance between the number of measurements and abnormalities in the diagnosis of sarcoidosis-associated small fiber neuropathy.

Several recent studies of diagnosing small fiber neuropathy (SFN) have shown a lack of uniformity in thermal threshold testing (TTT) or quantitative sensory testing (QST) which makes it a challenge to compare the data. It is known that the chance of finding an abnormality increases with increasing number of measurements. With this study, we first wanted to investigate whether TTT could benefit from a new approach focusing on the balance between the number of measurements, depending on the selection of parameters and measuring sites, and on number of abnormalities (NOAs). Second, we wanted to address the role of the method of levels (MLe) in possible desensitization during TTT measurements. One hundred seventeen participants were included (48 patients with sarcoidosis with probable SFN, 49 without SFN, and 20 healthy controls). Thermal threshold testing measurements and Small Fiber Neuropathy Screening List (SFNSL) questionnaire were used to assess SFN. A combination of measuring all thermal threshold parameters at both feet except for MLe showed the best diagnostic performance. Increasing TTT NOAs correlates with the severity of SFN. Adding the SFNSL questionnaire further improves diagnostic performance. Looking at TTT NOAs in all TTT parameters except for MLe at both feet should be considered as a new approach to improve the consistency and balance between the selection of TTT parameters, measuring sites, and definition of "abnormal QST." Moreover, the SFNSL questionnaire is a valuable tool to quantify SFN symptoms and could improve SFN diagnosis.

Pain associated with COVID-19 vaccination is unrelated to skin biopsy abnormalities.

Previous clinical observations raised the possibility that COVID-19 vaccination might trigger a small-fibre neuropathy. In this uncontrolled observational study, we aimed to identify small fibre damage in patients complaining of generalized sensory symptoms and pain after COVID-19 vaccination. We collected clinical data, including a questionnaire for assessing autonomic symptoms (Composite Autonomic Symptom Score-31), and investigated quantitative sensory testing (QST) and skin biopsy in 15 prospectively enrolled patients with generalized sensory symptoms and pain after COVID-19 vaccination. Nine patients complaining of orthostatic intolerance also underwent cardiovascular autonomic tests. We found that all patients experienced widespread pain, and most of them (11 of 15) had a fibromyalgia syndrome. All patients had normal skin biopsy findings, and in the 9 patients with orthostatic intolerance, cardiovascular autonomic tests showed normal findings. Nevertheless, 5 patients had cold and warm detection abnormalities at the QST investigation. In our study, most patients complaining of generalized sensory symptoms and pain after COVID-19 vaccination had clinical and diagnostic test findings compatible with a fibromyalgia syndrome. Although the abnormal QST findings we found in 5 patients might be compatible with a small-fibre neuropathy, they should be cautiously interpreted given the psychophysical characteristics of this diagnostic test. Further larger controlled studies are needed to define precisely the association between small fibre damage and COVID-19 vaccination.

Quantitative sensory testing in a large cohort of neuropathy patients

Background:&#x0D; 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.&#x0D; Methods:&#x0D; 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.&#x0D; Results:&#x0D; 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.&#x0D; Conclusions:&#x0D; 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.

Long-term alterations in somatosensory functioning in survivors of childhood cancer.

Cancer and its treatment can have lasting consequences on somatosensation, including pain, which is often underrecognized and undertreated. Research characterizing the impact of cancer on pain and sensory processing in survivors of childhood cancer is scarce. This study aimed to quantify generalized differences in pain and sensory processing in survivors of childhood cancer compared with reference data using a standardized thermal and mechanical quantitative sensory testing (QST) protocol. The association between demographic, clinical (eg, leukemia vs other cancers and treatment exposures), and psychosocial (eg, anxiety and pain catastrophizing) variables and sensitivity to pain and sensory stimuli were also evaluated. Participants were 56 survivors of various types of childhood cancer (52% male, Mage = 13.5 years, SD = 3.2, range = 8-17 years). On average, children were 7 years (SD = 4.1, range = 1.2-16.5) post treatment. Almost all participants (86%) had at least 1 abnormal QST parameter compared with age- and sex-matched reference data; however, few participants self-reported the presence of sensory abnormalities. Generally, participants exhibited reduced sensitivity across the QST parameters examined (Ps < 0.05, ds = 0.40-3.45). A significant minority (45%) also exhibited pain sensitization (P <0.001, d = 0.42). Several risk factors for changes in sensory processing were identified, including current age, history of leukemia, certain treatment exposures (eg, vincristine cumulative dose, major surgery, and bone marrow or stem cell transplant), time off treatment, and higher anxiety and pain catastrophizing scores. Overall, this study demonstrated that somatosensory changes are prevalent in survivors of childhood cancer years after the completion of treatment. Future research is needed to understand long-term implications of altered somatosensation in this complex population.

The analysis of epidermal nerve fibre spatial distribution improves the diagnostic yield of skin biopsy.

Small fibre neuropathy (SFN) diagnosis represents a challenge for neurologists. The diagnostic gold standard is intraepidermal nerve fibre (IENF) density, but in about 10-20% of patients with symptoms/signs and abnormalities on functional tests, it remains within normal range. We propose an adjunctive parameter to improve the efficiency of skin biopsy diagnosis. We recruited 31 patients with SFN symptoms/signs, normal nerve conduction study, abnormal quantitative sensory testing and normal IENF density. We also included 31 healthy controls and 31 SFN patients with reduced IENF density as control groups. We measured the distance between consecutive IENFs in the three groups. Mean inter-fibre distances did not differ between patients with normal counts and healthy controls (66.7±14.5μm vs. 76.7±13.4μm; P=0.052), while the relative standard deviation was significantly (P<0.001) higher in patients (79.3±29.9) compared to controls (51.6±12.2). Using ROC analysis, we identified an inter-fibre distance of 350µm as the measure that better differentiated patients from controls (AUC=0.85, sensitivity: 74%, specificity: 94%). At least one such segment was also observed in all patients with reduced IENF count. Irregular spatial distribution is an SFN intrinsic feature preceding actual nerve loss. The presence of a stretch of denervated epidermis longer than 350µm is a parameter able to increase the diagnostic efficiency of skin biopsy.

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.

Long-term small-fiber neuropathy and pain sensitization in survivors of pediatric acute lymphoblastic leukemia after stem cell transplantation

PurposeWe aimed at describing for the first time peripheral small-fiber neurotoxicity and pain sensitization in survivors of pediatric acute lymphoblastic leukemia after stem cell transplantation (SCT).MethodsIn a cross-sectional, retrospective, single-center study, we assessed 25 relapse-free long-term survivors (median age at SCT: 11 ± 4.9 years; median time between SCT and testing: 8.25 years, 19 males) using a reduced version of the pediatric-modified total neuropathy score for clinical assessment and Quantitative Sensory Testing (QST). Inclusion criteria: ge 6 years old at testing, le 18 years old at time of SCT, ge 1 year between SCT and testing.ResultsNine patients (36%) had peripheral neuropathy as defined by the clinical red-pmTNS (≥ 4). The QST parameters mechanical pain sensitivity, mechanical detection threshold, thermal sensory limen, vibration detection threshold and pressure pain threshold were significantly abnormal in the survivor cohort (p < 0.0038). Except for one, all survivors showed at least one abnormal QST parameter. When using QST, signs of small and large fiber dysfunction were present in 22 (88%) and 17 (68%) survivors, respectively. More than half of all survivors were found to experience pathologic sensitization to pain.Conclusions and implications for cancer survivorsSurvivors of pediatric acute lymphoblastic leukemia after SCT are at high risk for long-term peripheral neuropathy with a dominating small-fiber and pain sensitization pattern.

Do We Measure What Patients Feel?: An Analysis of Correspondence Between Somatosensory Modalities Upon Quantitative Sensory Testing and Self-reported Pain Experience.

Hyperalgesia and allodynia are typical signs of neuropathic pain. Quantitative sensory testing (QST) is a validated tool to clinically assess these phenomena. However, whether QST reveals findings that are reported by the patients is unclear. The aim of this study was therefore to investigate the association between self-reported symptoms assessed with the painDETECT questionnaire (PDQ) with results of validated QST. PDQ and QST data of 96 patients with chronic neuropathic pain were analyzed. Questions upon presence of painful light touch, painful cold or heat, light pressure triggering pain, and numbness upon PDQ were compared with findings of dynamic mechanical allodynia, increased sensitivity to heat, cold, or pressure pain as well as loss of detection upon QST, respectively. Self-reported pain symptoms upon PDQ showed only a small to moderate concordance with corresponding signs assessed upon QST, whereat the highest, but still only moderate association between self-reported symptoms and measured signs could be obtained for self-reported presence of painful light touch and dynamic mechanical allodynia upon QST. However, the positive and negative likelihood ratio to predict QST values with PDQ scores did not reach convincing values. Results demonstrate that self-reported PDQ symptoms cannot predict abnormal QST values. The poor predictive power of the PDQ may depend on several factors based on possibility of comparison between PDQ and QST and also on methodical issues. Both, symptoms (questionnaires) and signs address complementary aspects of the pain experience and should be considered for diagnosis and treatment of neuropathic pain.

A SOD2 Polymorphism is Associated with Abnormal Quantitative Sensory Testing in Type 2 Diabetic Patients.

Diabetes mellitus (DM) affects peripheral nerves inducing diabetic polyneuropathy (DPN). Mitochondrial dysfunction and oxidative stress are potential causes of DPN. Nerve conduction studies were performed in 20 type 2 DM patients (11 with DPN) and 15 healthy controls. Perception threshold values of cold, warm and vibration were measured by quantitative sensory testing. Variants of a superoxide dismutase 2 (SOD2) gene single nucleotide polymorphism (SNP) (rs5746136) were determined by polymerase chain reaction (PCR) and following NexteraXT DNA Library. DPN patients showed significantly increased threshold values. DM patients without DPN and healthy controls showed comparable values. TT variant of the SOD2 SNP was more prevalent in DM and DPN patients. DM patients with the TT variant displayed increased perception threshold values. Quantitative sensory testing is not superior to standard nerve conduction studies in DPN. Carriers of SOD2 SNP manifested increased sensory threshold levels which is important in further corroborating the link between oxidative stress and DPN.

Diagnostic Criteria for Small Fiber Neuropathy.

Despite its relative common occurrence, definitive diagnosis of small fiber neuropathy (SFN) remains problematic. In practice, patients with pain, numbness, and/or paresthesias in their lower limbs are diagnosed with SFN if found to have dissociated sensory loss in their feet, that is, impaired pinprick perception (PP) but relatively preserved vibration. We sought to assess the sensitivity and specificity of clinical examination and various diagnostic tools available for screening SFN. Medical records of 56 patients diagnosed with SFN were reviewed. Diagnosis was based on symptoms, detailed neurological examination that included PP, and abnormal results on at least one testing modality-quantitative sudomotor axon reflex (sweat) test (QSART), quantitative sensory testing (QST), and heart rate variability (HRV) testing. Sensitivity of PP was relatively consistent between modalities of about 63% in presence of appropriate sensory symptoms. Laboratory testing diagnosed 88% of patients when both QSART and QST are employed. QST was most sensitive for detection of SFN with the heat-pain testing having higher sensitivity than cooling. Heart rate variability testing revealed low correlation across all groups. The diagnostic yield for SFN increases by combining clinical features with various testing modalities. In symptomatic patients, we propose the following diagnostic criteria for diagnosis of SFN: Definite SFN-abnormal neurological examination and both QSART and QST; Probable SFN-abnormal neurological examination, and either QSART or QST; Possible SFN-abnormal neurological exam, QSART, or QST.

Usefulness of laser-evoked potentials and quantitative sensory testing in the diagnosis of neuropathic spinal cord injury pain: a multiple case study.

A retrospective study. The aim of this study was to investigate the contribution of laser-evoked potentials (LEPs) and quantitative sensory testing (QST) to the diagnosis of neuropathic pain in patients with spinal cord injury (SCI) and inconclusive magnetic resonance imaging (MRI) findings. A multidisciplinary pain center. QST (DFNS protocol) and Tm-YAG-laser stimulation of the skin were applied within the pain site corresponding with dermatomes of altered sensation. Available MRI scans were reviewed. Thirteen individuals (50±16 years) with SCI were examined. In four cases with no detectable neural lesion on MRI, all QST but three LEP were abnormal. In four patients with poorly defined spinal lesion on MRI, all QST but three LEP only were abnormal. In four cases where pain was not matching adequately with MRI lesions, all patients had abnormal LEP and QST. In one patient showing a spinal cord atrophy, LEP was normal but QST was abnormal. Findings supported the diagnoses at-level (n=5) and below-level (n=8) SCI pain. Spinothalamic tract function assessed by LEP was normal in three cases, but QST was abnormal in all cases. As QST is a psychophysical examination depending on patient cooperation, we suggest that the combination of QST and LEP might be a valuable diagnostic tool to detect lesions of the somatosensory system in a subgroup of patients with neuropathic spinal cord injury pain and inconclusive MRI findings.

In Patients with an α-Galactosidase A Variant, Small Nerve Fibre Assessment Cannot Confirm a Diagnosis of Fabry Disease.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by an α-galactosidase A enzyme deficiency due to pathogenic variants in the α-galactosidase A gene (GLA). An increasing number of individuals with a GLA variant, but without characteristic FD features, are identified. A definite diagnosis of FD has important consequences for treatment and counselling. We assessed the diagnostic value of quantitative sensory testing (QST) and intraepidermal nerve fibre density (IENFD) for patients with an uncertain FD diagnosis. All patients with a GLA variant who initially presented at the Academic Medical Center with an uncertain FD diagnosis were included. A biopsy of an affected organ in a patient or family member showing FD characteristic storage is used as a reference standard for a diagnosis of FD. All patients underwent a comprehensive QST protocol and IENFD assessment which was compared to age and gender-matched healthy controls. Sensitivity and specificity were calculated for a combination of ≥1 abnormal QST modality and an abnormal IENFD. Twenty-six patients participated (nonclassical FD n = 18, 9 males; no FD n = 5, 3 males; uncertain n = 3, 1 male). Of the patients classified as nonclassical FD, 28% had ≥1 abnormal QST modalities, and 83% had an abnormal IENFD. From the patients without FD, 20% had ≥1 abnormal QST modality, and IENFD was abnormal in 25% (1 not available). Sensitivity was 28% and specificity 80%. In our study cohort, QST and IENFD could not reliably distinguish patients with FD from those without FD.

CORR Insights®: Abnormal quantitative sensory testing is associated with persistent pain one year after TKA.

CORR Insights®: Abnormal quantitative sensory testing is associated with persistent pain one year after TKA.

SAT0194 Evaluation of Systemic Sclerosis Patients by Quantitative Sensory Testing for the Presence of Neuropathy

BackgroundNeuropathy is a common feature of collagen tissue disorders. Although development of digital ulcerations may be associated with presence of neuropathy, percentage of systemic sclerosis (SSc) patients with documented neuropathy...

Influence of ketamine and morphine on descending pain modulation in chronic pain patients: a randomized placebo-controlled cross-over proof-of-concept study

Descending inhibition of pain, part of the endogenous pain modulation system, is important for normal pain processing. Dysfunction is associated with various chronic pain states. Here, the effect of ketamine and morphine on descending inhibition is examined using the conditioned pain modulation (CPM) paradigm in chronic neuropathic pain patients. CPM responses were obtained in 10 adult neuropathic pain subjects (two men/eight women). All subjects had peripheral neuropathy as defined by abnormal quantitative sensory testing. The effects of S(+)-ketamine (0.57 mg kg(-1) h(-1) for 1 h) and morphine (0.065 mg kg(-1) h(-1) for 1 h) were tested in a randomized, placebo-controlled double-blind study. CPM was measured at baseline and 100 min after the start of treatment and was induced by immersion of the leg into a cold-water bath. The test stimulus was a 30 s static thermal stimulus to the skin of the forearm. Without treatment, no CPM was detectable. Treatment with ketamine, morphine, and placebo produced CPM responses of 40.2 (10.9)%, 28.5 (7.0)%, and 22.1 (12.0)%, respectively (for all treatments, CPM effect P<0.05), with no statistical difference in the magnitude of CPM among treatments. The magnitude of CPM correlated positively with the magnitude and duration of spontaneous pain relief. The observed treatment effects in chronic pain patients suggest a role for CPM engagement in analgesic efficacy of ketamine, morphine, and placebo treatment.

Gain of function NaV1.7 mutations in idiopathic small fiber neuropathy

Small nerve fiber neuropathy (SFN) often occurs without apparent cause, but no systematic genetic studies have been performed in patients with idiopathic SFN (I-SFN). We sought to identify a genetic basis for I-SFN by screening patients with biopsy-confirmed idiopathic SFN for mutations in the SCN9A gene, encoding voltage-gated sodium channel Na(V)1.7, which is preferentially expressed in small diameter peripheral axons. Patients referred with possible I-SFN, who met the criteria of ≥2 SFN-related symptoms, normal strength, tendon reflexes, vibration sense, and nerve conduction studies, and reduced intraepidermal nerve fiber density (IENFD) plus abnormal quantitative sensory testing (QST) and no underlying etiology for SFN, were assessed clinically and by screening of SCN9A for mutations and functional analyses. Twenty-eight patients who met stringent criteria for I-SFN including abnormal IENFD and QST underwent SCN9A gene analyses. Of these 28 patients with biopsy-confirmed I-SFN, 8 were found to carry novel mutations in SCN9A. Functional analysis revealed multiple gain of function changes in the mutant channels; each of the mutations rendered dorsal root ganglion neurons hyperexcitable. We show for the first time that gain of function mutations in sodium channel Na(V)1.7, which render dorsal root ganglion neurons hyperexcitable, are present in a substantial proportion (28.6%; 8 of 28) of patients meeting strict criteria for I-SFN. These results point to a broader role of Na(V)1.7 mutations in neurological disease than previously considered from studies on rare genetic syndromes, and suggest an etiological basis for I-SFN, whereby expression of gain of function mutant sodium channels in small diameter peripheral axons may cause these fibers to degenerate.

P7-20 Central and peripheral sensory pathway function in familial amyotrophic lateral sclerosis

Aim: To assess the clinical and neurophysiological features of the peripheral neuropathy associated with Fabry disease (FD) and to examine the function of the VIII cranial nerve. Methods: We prospectively examined 38 adults with FD (17 male, 21 female; mean age, 35.6 years. Each patient was assessed clinically. Nerve conduction studies (NCS) and quantitative sensory testing (QST) were performed: cold, warmth, vibratory, cold pain and heat pain detection thresholds were evaluated in one hand and one foot. Neurootologic signs and symptoms were evaluated in a subgroup of 20 consecutive patients with FD (6 male, mean age, 32 years; 14 female, mean age, 37 years) from within the cohort studies using: head thrust test and conventional caloric testing. The VIII cranial nerve was investigated using vestibular evoked myogenic potentials, pure tone audiometry and BAER. Results: All patients had signs or symptoms of FD. The most frequent manifestation was acroparaesthesia. In total, 92.1% of patients with FD presented with abnormal QST results: 73.7% showed increased cold detection thresholds and 65.8% had altered warmth detection thresholds. NCS were normal. Neuro-otologic manifestations: 80% of the patients were affected by auditory manifestations, 13/19 patients (68%) had both cochlear and vestibular symptoms Neuro-otologic involvement was peripheral in 15 cases and central in one case. Only 2/15 patients showed a congruent peripheral unilateral involvement of the superior and inferior vestibular tests with compromise of the ipsilateral cochlea. The main finding was that in 15 patients there was a lack of neural or vascular pattern in the involvement of the peripheral labyrinth. Conclusion: We identified signs and symptoms of peripheral neuropathy in both heterozygous and hemiyzygous patients with Fabry disease. Neuropathy predominantly affects small A-delta and C fibers. Neuro otologic involvement is frequent in Fabry disease, affecting the vestibular cochlear labyrinth in the majority of patients.

Polyneuropathy in type 1 and type 2 diabetes: comparison of nerve conduction studies, thermal perception thresholds and intraepidermal nerve fibre densities

To evaluate possible differences in distal polyneuropathy (PN) characteristics and degree of abnormalities for various small and large fibre parameters in diabetes type 1 (DM1) and type 2 (DM2). Sixty-six DM1 and 57 DM2 patients with or without PN symptoms were included. Nerve conduction studies (NCS), quantitative sensory testing (QST) and quantification of intraepidermal nerve fibres (IENFs) were performed. Z-scores were calculated from reference materials. In both groups, 42% had abnormal NCS classification, 42% (DM1) and 39% (DM2) abnormal QST, as well as 40% (DM1) and 32% (DM2) abnormal IENF density. Seventy percent (DM1) and 65% (DM2) had one of the three tests abnormal (differences not significant). Correlations were found between most Z-score parameters and disease duration and HbA1c in DM1, but fewer in DM2. In multivariate analysis, some NCS and QST Z-scores were more abnormal in DM2. Symptom scoring correlated better with NCS and QST parameters in DM1. The differences could be referred to disease duration, glycaemic control and possibly patient age. The various parameters from NCS, QST and IENF analysis contribute differently in the assessment of polyneuropathy.

The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology

Small fibre neuropathy (SFN), a condition dominated by neuropathic pain, is frequently encountered in clinical practise either as prevalent manifestation of more diffuse neuropathy or distinct nosologic entity. Aetiology of SFN includes pre-diabetes status and immune-mediated diseases, though it remains frequently unknown. Due to their physiologic characteristics, small nerve fibres cannot be investigated by routine electrophysiological tests, making the diagnosis particularly difficult. Quantitative sensory testing (QST) to assess the psychophysical thresholds for cold and warm sensations and skin biopsy with quantification of somatic intraepidermal nerve fibres (IENF) have been used to determine the damage to small nerve fibres. Nevertheless, the diagnostic criteria for SFN have not been defined yet and a ‘gold standard’ for clinical practise and research is not available. We screened 486 patients referred to our institutions and collected 124 patients with sensory neuropathy. Among them, we identified 67 patients with pure SFN using a new diagnostic ‘gold standard’, based on the presence of at least two abnormal results at clinical, QST and skin biopsy examination. The diagnosis of SFN was achieved by abnormal clinical and skin biopsy findings in 43.3% of patients, abnormal skin biopsy and QST findings in 37.3% of patients, abnormal clinical and QST findings in 11.9% of patients, whereas 7.5% patients had abnormal results at all the examinations. Skin biopsy showed a diagnostic efficiency of 88.4%, clinical examination of 54.6% and QST of 46.9%. Receiver operating characteristic curve analysis confirmed the significantly higher performance of skin biopsy comparing with QST. However, we found a significant inverse correlation between IENF density and both cold and warm thresholds at the leg. Clinical examination revealed pinprick and thermal hypoesthesia in about 50% patients, and signs of peripheral vascular autonomic dysfunction in about 70% of patients. Spontaneous pain dominated the clinical picture in most SFN patients. Neuropathic pain intensity was more severe in patients with SFN than in patients with large or mixed fibre neuropathy, but there was no significant correlation with IENF density. The aetiology of SFN was initially unknown in 41.8% of patients and at 2-year follow-up a potential cause could be determined in 25% of them. Over the same period, 13% of SFN patients showed the involvement of large nerve fibres, whereas in 45.6% of them the clinical picture did not change. Spontaneous remission of neuropathic pain occurred in 10.9% of SFN patients, while it worsened in 30.4% of them.