Contact Heat Evoked Potentials Research Articles

Failed Back Surgery Syndrome: is there a small fiber involvement? A contact heat evoked potentials (CHEPs) study (P6.133)

Failed Back Surgery Syndrome: is there a small fiber involvement? A contact heat evoked potentials (CHEPs) study (P6.133)

Improved Diagnosis of Cervical Spondylotic Myelopathy with Contact Heat Evoked Potentials

The aim of this study was to reveal the sensitivity and responsiveness of contact heat evoked potentials (CHEPs) to assess cervical spondylotic myelopathy (CSM). A total of 81 patients with clinically and radiologically confirmed spinal cord compression were reviewed. All patients underwent full clinical examinations with combined recordings of segmental CHEPs and somatosensory evoked potentials (dSSEPs) compared with healthy controls. Cross-sectional area, maximal canal compression, and maximal spinal cord compression were determined based on T2-weighted MRI. CHEPs exhibited the highest sensitivity (∼ 95%) to disclose at-level impairments in CSM patients. Normally appearing rostral segments above the level of lesion were impaired in 17% of patients. Comparatively, dSSEPs were less affected (24%) and predominantly impaired at and below the level of CSM. Longitudinal evaluation revealed that CHEPs became progressively impaired in parallel with clinical deterioration. CHEPs were sensitive to CSM, revealing evidence of impaired neurophysiology at and below the radiographic level of stenosis. The changes observed above the level of CSM suggest neurophysiological deficits beyond the focally damaged area. Deteriorating CHEPs were observed in a cohort of patients with worsening neurological symptoms, indicating their responsiveness to track CSM. The present study highlights the value of incorporating CHEPs into the diagnosis and prognosis of CSM.

Bi-phasic activation of the primary motor cortex by pain and its relation to pain-evoked potentials − an exploratory study

The primary motor cortex (M1) is a known target for brain stimulation aimed at pain alleviation in chronic pain patients, yet the mechanisms through which analgesia occurs, and the exact pain-motor interrelations are not fully understood. We used noxious contact heat evoked potentials (CHEPs) and cortical source analysis to further explore the relevance of M1 in pain processing. Twenty-four healthy young females received brief noxious heat stimuli to their left non-dominant volar forearm, simultaneously with CHEPs recordings. Thereafter, the pain-evoked activity of M1 and a control area in the occipital cortex (OC) was analyzed and estimated using sLORETA (standardized low-resolution brain electromagnetic tomography). This analysis revealed two phases of M1 pain-evoked activation (phase 1: the peak at 261.5±25.7ms; phase 2: the peak at 381.3±28.3ms). Canonical correlations revealed that M1, but not the OC, was the main factor contributing to the relation with the CHEPs components. In detail, the activity magnitude of M1 first and second phases was related to the N2 and P2 amplitude, respectively. The latency of the second phase was associated with both N2 and P2 latencies. In relation to pain, the latency of M1’s first activity phase was positively correlated with pain ratings, suggesting pain interference to synchronized activity in M1. Our results confirm the established relevance of the primary motor cortex to pain processing.

Biomarkers of neuropathic pain in skin nerve degeneration neuropathy: contact heat-evoked potentials as a physiological signature.

Contact heat-evoked potentials (CHEPs) have become an established method of assessing small-fiber sensory nerves; however, their potential as a physiological signature of neuropathic pain symptoms has not been fully explored. To investigate the diagnostic efficacy in examining small-fiber sensory nerve degeneration, the relationship with skin innervations, and clinical correlates with sensory symptoms, we recruited 188 patients (115 men) with length-dependent sensory symptoms and reduced intraepidermal nerve fiber (IENF) density at the distal leg to perform CHEP, quantitative sensory testing, and nerve conduction study. Fifty-seven age- and sex-matched controls were enrolled for comparison of CHEP and skin innervation. Among patients with neuropathy, 144 patients had neuropathic pain and 64 cases had evoked pain. Compared with quantitative sensory testing and nerve conduction study parameters, CHEP amplitudes showed the highest sensitivity for diagnosing small-fiber sensory nerve degeneration and exhibited the strongest correlation with IENF density in multiple linear regression. Contact heat-evoked potential amplitudes were strongly correlated with the degree of skin innervation in both patients with neuropathy and controls, and the slope of the regression line between CHEP amplitude and IENF density was higher in patients with neuropathy than in controls. Patients with evoked pain had higher CHEP amplitude than those without evoked pain, independent of IENF density. Receiver operating characteristic analysis showed that CHEP had better performance in diagnosing small-fiber sensory nerve degeneration than thermal thresholds. Furthermore, CHEPs showed superior classification accuracy with respect to evoked pain. In conclusion, CHEP is a sensitive tool to evaluate pathophysiology of small-fiber sensory nerve and serves as a physiological signature of neuropathic pain symptoms.

Attenuated contact heat-evoked potentials associated with sensory and social-emotional symptoms in individuals with autism spectrum disorder

Sensory disturbance is associated with socio-emotional problems in individuals with autism spectrum disorder (ASD). Most studies assess sensory symptoms by self-reports, which are largely limited by the language ability and self-awareness of the individuals. This study aims to investigate sensory disturbance by contact heat-evoked potentials (CHEP) in ASD individuals, and to examine the clinical correlates of CHEP parameters. We compared the CHEP parameters and reported pain between 31 ASD individuals (aged 20.5 ± 5.2 years) and and 22 typically-developing controls (TD, aged 21.4 ± 2.6), and correlated the CHEP parameters with self-reported sensory symptoms and attention/socio-emotional symptoms. We found that ASD individuals showed smaller P2-wave amplitudes than TD, even though they reported a similar level of pain. In TD individuals, a smaller P2-wave amplitude was related to higher scores on ‘low registration,’ ‘attention to detail,’ and ‘attention switching difficulties.’ In ASD individuals, longer N2-wave latency was related to higher scores on ‘sensory sensitivity’ and socio-emotional problems; while higher reported pain was associated with higher scores on ‘low registration,’ overall autistic severity, and longer N2-wave latency. Our findings of attenuated CHEP response in ASD, which was associated with sensory symptoms and socio-emotional problems, suggest a potential role for CHEP in studying sensory disturbances in ASD.

13. Which is the best evoked potential technique for assessing the nociceptive system? Preliminary results of a neurophysiological study in healthy humans

Laser evoked potentials (LEPs) and contact heat evoked potentials (CHEPs) are widely agreed method for investigating the nociceptive system. Concentric electrodes (CE) have also recently been introduced to measure pain-related evoked potentials (PREPs) and, thereby, to assess the nociceptive system in patients. Although some authors have reported that low intensity CE stimulation, evoking pinprick sensation, selectively activates nociceptive fibres, the CE reliability in the assessment of nociceptive system is still unclear. In this study we aimed to verify whether low and high intensity CE stimulations selectively activates nociceptive fibres. To do so we recorded LEPs, CHEPs and PREPs before and after capsaicin-induced skin denervation. To date, we have enrolled 6 healthy subjects. All subjects underwent a baseline recording of LEPs, CHEPs and PREPs after stimulation of the right forearm. For PREP recording we used both low intensity stimulation, evoking a distinct pinprick sensation and high intensity stimulation, evoking an electrical painless sensation. After the baseline evoked potential recordings, we applied an 8% capsaicin plaster on the right forearm. After one-two weeks, we recorded LEPs, CHEPs and PREPs after stimulation of the capsaicin-induced denervated forearm skin. In a small skin area spared by evoked potential stimulations we have also collected a skin biopsy for assessing the skin denervation. While LEPs and CHEPs were suppressed after topical application of capsaicin, low and high intensity PREPs did not differ before and after capsaicin-induced skin denervation. The skin biopsy documented the skin denervation induced by the capsaicin plaster. Our data indicate that both low and high intensity CE stimulation elicit PREPs after skin denervation, thus suggesting that the CE stimulation probably coactivates non-nociceptive fibres.

Electrophysiological and psychophysical correlates of spatial summation to noxious heat: the possible role of A-delta fibers

Although spatial summation of pain (SSP) is central to the processing of pain intensity and quality, its mechanism is not fully understood. We previously found greater heat SSP in hairy than in glabrous skin, suggesting that perhaps A-mechano-heat II (AMH-II) nociceptors are the dominant subserving system. In order to further explore the role of A-delta fibers in heat-induced SSP, we analyzed the electrophysiological correlates of SSP under conditions that minimize the influence of skin thicknesses. Among 17 subjects, fast rate of rise (70°C/sec) heat stimuli that induced a pre-fixed, similar, SSP magnitude for hairy and glabrous skin were repeatedly administered using large and small probes, during which time the contact heat-evoked potentials (CHEPs) and pain ratings were recorded. Both N2 and P2 amplitudes were larger in hairy than in glabrous skin, but a differential effect of SSP was found on the CHEPs. Despite similar psychophysical SSP in hairy and glabrous skin, the electrophysiological SSP reflected in N2 but not P2 amplitude was larger in hairy skin. Nevertheless, regardless of skin type, SSP was manifested by an increase in P2 amplitudes. Considering the uniform psychophysical SSP for the two skin types, the fast stimulation rate and lower activity of AMH-II in glabrous skin, a greater electrophysiological SSP in hairy than in glabrous skin may suggest that SSP is mainly subserved by AMH nociceptors. The overall SSP effect, manifested in greater P2 amplitude, may reflect specific brain responses aimed to prepare the individual to an increased potential tissue damage.

Normative data for the segmental acquisition of contact heat evoked potentials in cervical dermatomes.

Contact heat evoked potentials (CHEPs) represent a neurophysiological approach to assess conduction in the spinothalamic tract. The aim of this study was to establish normative values of CHEPs acquired from cervical dermatomes (C4, C6, C8) and examine the potential confounds of age, sex, and height. 101 (49 male) healthy subjects of three different age groups (18–40, 41–60, and 61–80 years) were recruited. Normal (NB, 35–52 °C) followed by increased (IB, 42–52 °C) baseline stimulation protocols were employed to record CHEPs. Multi-variate linear models were used to investigate the effect of age, sex, and height on the CHEPs parameters (i.e., N2 latency, N2P2 amplitude, rating of perceived intensity). Compared to NB, IB stimulation reduced latency jitter within subjects, yielding larger N2P2 amplitudes, and decreased inter-subject N2 latency variability. Age was associated with reduced N2P2 amplitude and prolonged N2 latency. After controlling for height, male subjects had significantly longer N2 latencies than females during IB stimulation. The study provides normative CHEPs data in a large cohort of healthy subjects from segmentally examined cervical dermatomes. Age and sex were identified as important factors contributing to N2 latency and N2P2 amplitude. The normative data will improve the diagnosis of spinal cord pathologies.

Sex dimorphism in a mediatory role of the posterior midcingulate cortex in the association between anxiety and pain sensitivity.

Behavioral studies found greater pain sensitivity in females that vanishes fully or partially when controlling for the emotional state. Furthermore, pain-related brain activation hints at the role of limbic structures in sex differences in pain processing. We aimed to investigate the role of pain-related limbic structures in mediating the relation between subjects' affective state (i.e., anxiety) and pain. Contact heat-evoked potentials (CHEPs) were recorded in 26 healthy subjects (13 males) simultaneously with innocuous (42°C) baseline and target noxious (52°C) series of stimuli administered to the left non-dominant volar forearm. The N2 and P2 components were analyzed, and their generators' activity was estimated using standardized low-resolution brain electromagnetic tomography. Thereafter, structural equation modeling (SEM) was applied separately for females and males, examining the mediatory role of the CHEPs' limbic structures generators [posterior midcingulate cortex (pMCC), insula, amygdala, and hippocampus] in the anxiety-pain sensitivity association. Females exhibited greater P2 amplitudes that were highly associated with larger pMCC activity (r=0.910, p<0.001). This correlation was also evident in males, though with less strength (r=0.578, p=0.039). Moreover, the P2 amplitudes were associated both in females (r=0.645, p=0.017) and males (r=0.608, p=0.028) with the activity of the amygdala\hippocampus\insula. SEM revealed that the relationship between state anxiety and pain ratings was only in females fully mediated via the effect of the pMCC on the P2 amplitude. These findings suggest that sexual dimorphism in anxiety-related brain activity may explain the differences found in CHEPs and the sex-related association between anxiety and pain.

Pathophysiology of Small-Fiber Sensory System in Parkinson's Disease: Skin Innervation and Contact Heat Evoked Potential.

Sensory symptoms are frequent nonmotor complaints in patients with Parkinson's disease (PD). However, few investigations integrally explored the physiology and pathology of the thermonociceptive pathway in PD. We aim to investigate the involvement of the thermonociceptive pathway in PD.Twenty-eight PD patients (16 men, with a mean age and standard deviation of 65.6 ± 10.7 years) free of neuropathic symptoms and systemic disorders were recruited for the study and compared to 23 age- and gender-matched control subjects (12 men, with a mean age and standard deviation of 65.1 ± 9.9 years). We performed skin biopsy, contact heat-evoked potential (CHEP), and quantitative sensory tests (QST) to study the involvement of the thermonociceptive pathway in PD.The duration of PD was 7.1 ± 3.2 (range 2–17 years) years and the UPDRS part III score was 25.6 ± 9.7 (range 10–48) during the off period. Compared to control subjects, PD patients had reduced intra-epidermal nerve fiber (IENF) density (2.48 ± 1.65 vs 6.36 ± 3.19 fibers/mm, P < 0.001) and CHEP amplitude (18.02 ± 10.23 vs 33.28 ± 10.48 μV, P < 0.001). Twenty-three patients (82.1%) had abnormal IENF densities and 18 (64.3%) had abnormal CHEP. Nine patients (32.1%) had abnormal thermal thresholds in the feet. In total 27 patients (96.4%) had at least 1 abnormality in IENF, CHEP, or thermal thresholds of the foot, indicating dysfunctions in the small-fiber nerve system. In control subjects, CHEP amplitude linearly correlated with IENF density (P < 0.001). In contrast, this relationship disappeared in PD (P = 0.312) and CHEP amplitude was negatively correlated with motor severity of PD independent of age, gender, and anti-PD medication dose (P = 0.036), suggesting the influences of central components on thermonociceptive systems in addition to peripheral small-fiber nerves in PD.The present study suggested impairment of small-fiber sensory system at both peripheral and central levels is an intrinsic feature of PD, and skin biopsy, CHEP, and QST provided an integral approach for assessing such dysfunctions.

Neural correlates of heat-evoked pain memory in humans

The neural processes underlying pain memory are not well understood. To explore these processes, contact heat-evoked potentials (CHEPs) were recorded in humans with electroencephalography (EEG) technique during a delayed matching-to-sample task, a working memory task involving presentations of two successive painful heat stimuli (S-1 and S-2) with different intensities separated by a 2-s interval (the memorization period). At the end of the task, the subject was required to discriminate the stimuli by indicating which (S-1 or S-2) induced more pain. A control task was used, in which no active discrimination was required between stimuli. All event-related potential (ERP) analysis was aligned to the onset of S-1. EEG activity exhibited two successive CHEPs: an N2-P2 complex (∼400 ms after onset of S-1) and an ultralate component (ULC, ∼900 ms). The amplitude of the N2-P2 at vertex, but not the ULC, was significantly correlated with stimulus intensity in these two tasks, suggesting that the N2-P2 represents neural coding of pain intensity. A late negative component (LNC) in the frontal recording region was observed only in the memory task during a 500-ms period before onset of S-2. LNC amplitude differed between stimulus intensities and exhibited significant correlations with the N2-P2 complex. These indicate that the frontal LNC is involved in maintenance of intensity of pain in working memory. Furthermore, alpha-band oscillations observed in parietal recording regions during the late delay displayed significant power differences between tasks. This study provides in the temporal domain previously unidentified neural evidence showing the neural processes involved in working memory of painful stimuli.

Clinically Effective Treatment of Fibromyalgia Pain With High-Definition Transcranial Direct Current Stimulation: Phase II Open-Label Dose Optimization

Despite promising preliminary results in treating fibromyalgia (FM) pain, no neuromodulation technique has been adopted in clinical practice because of limited efficacy, low response rate, or poor tolerability. This phase II open-label trial aims to define a methodology for a clinically effective treatment of pain in FM by establishing treatment protocols and screening procedures to maximize efficacy and response rate. High-definition transcranial direct current stimulation (HD-tDCS) provides targeted subthreshold brain stimulation, combining tolerability with specificity. We aimed to establish the number of HD-tDCS sessions required to achieve a 50% FM pain reduction, and to characterize the biometrics of the response, including brain network activation pain scores of contact heat-evoked potentials. We report a clinically significant benefit of a 50% pain reduction in half (n = 7) of the patients (N = 14), with responders and nonresponders alike benefiting from a cumulative effect of treatment, reflected in significant pain reduction (P = .035) as well as improved quality of life (P = .001) over time. We also report an aggregate 6-week response rate of 50% of patients and estimate 15 as the median number of HD-tDCS sessions to reach clinically meaningful outcomes. The methodology for a pivotal FM neuromodulation clinical trial with individualized treatment is thus supported. Online RegistrationRegistered in Clinicaltrials.gov under registry number NCT01842009. PerspectiveIn this article, an optimized protocol for the treatment of fibromyalgia pain with targeted subthreshold brain stimulation using high-definition transcranial direct current stimulation is outlined.

Contact heat evoked potentials (CHEPS) in patients with painful and non-painful polyneuropathies

Contact heat evoked potentials (CHEPS) in patients with painful and non-painful polyneuropathies

Contact heat evoked potentials (CHEPs) in painful autoimmune neuropathy (pain)

Contact heat evoked potentials (CHEPs) in painful autoimmune neuropathy (pain)

Single-sweep spectral analysis of contact heat evoked potentials: a novel approach to identify altered cortical processing after morphine treatment.

The cortical response to nociceptive thermal stimuli recorded as contact heat evoked potentials (CHEPs) may be altered by morphine. However, previous studies have averaged CHEPs over multiple stimuli, which are confounded by jitter between sweeps. Thus, the aim was to assess single-sweep characteristics to identify alterations induced by morphine. In a crossover study 15 single-sweep CHEPs were analyzed from 62 electroencephalography electrodes in 26 healthy volunteers before and after administration of morphine or placebo. Each sweep was decomposed by a continuous wavelet transform to obtain normalized spectral indices in the delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-32 Hz) and gamma (32-80 Hz) bands. The average distribution over all sweeps and channels was calculated for the four recordings for each volunteer, and the two recordings before treatments were assessed for reproducibility. Baseline corrected spectral indices after morphine and placebo treatments were compared to identify alterations induced by morphine. Reproducibility between baseline CHEPs was demonstrated. As compared with placebo, morphine decreased the spectral indices in the delta and theta bands by 13% (P = 0.04) and 9% (P = 0.007), while the beta and gamma bands were increased by 10% (P = 0.006) and 24% (P = 0.04). The decreases in the delta and theta band are suggested to represent a decrease in the pain specific morphology of the CHEPs, which indicates a diminished pain response after morphine administration. Hence, assessment of spectral indices in single-sweep CHEPs can be used to study cortical mechanisms induced by morphine treatment.

A novel electroencephalography-based tool for objective assessment of network dynamics activated by nociceptive stimuli.

Pain perception is typically assessed using subjective measures; an objective measure of the response to pain would be valuable. In this study, Brain Network Activation (BNA), a novel multivariate pattern analysis and scoring algorithm, was applied to event-related potentials (ERPs) elicited by cortical responses to brief heat stimuli. Objectives of this study were to evaluate the utility of BNA as a quantitative and qualitative measure of cortical response to pain. Contact Heat Evoked Potentials (CHEPs) data were collected from 17 healthy, right-handed volunteers (10 M, 7F) using 5 different temperatures (35, 41, 46, 49 and 52 °C). A set of spatio-temporal activity patterns common to all the subjects in the group (Reference Brain Network Model; RBNM) was generated using the BNA algorithm, based on evoked responses at 52 °C. Frame by frame 'unfolding' of the brain network across time showed qualitative differences between responses to painful and non-painful stimuli. Brain network activation scores were shown to be a better indicator of the individual's sensitivity to pain when compared to subjective pain ratings. Additionally, BNA scores correlated significantly with temperature, demonstrated good test-retest reliability, as well as a high degree of sensitivity, specificity and accuracy in correctly categorizing subjects who reported stimuli as painful. These results may provide evidence that the multivariate analysis performed with BNA may be useful as a quantitative, temporally sensitive tool for assessment of pain perception.

Contact heat evoked potentials: Normal values and use in small‐fiber neuropathy

Contact heat evoked potentials (CHEPs) may be an objective, non-invasive diagnostic tool in small-fiber neuropathy (SFN). This study establishes normal CHEP values and examines their applicability in SFN patients. Standardized CHEPs were administered at the wrist and ankle. The N2 and P2 latencies and N2 -P2 peak-peak amplitude were recorded by electroencephalography. We examined healthy subjects (n = 97), stratified by age and gender, and SFN patients with abnormal intraepidermal nerve fiber density (n = 42). CHEP reproducibility and interobserver values were also investigated. CHEP normative values were determined. There was a 9-16% increase in latency per centimeter of height with increasing age. Amplitudes were higher in women than men, and decreased (17-71%) with aging. Test-retest reproducibility and interobserver values were >0.61 and >0.96, respectively. CHEPs were abnormal in 73.8% of the patients. In this study we have established normal values, reliability, and clinical applicability of CHEPs in SFN.

Application of contact heat-evoked potentials in acute myelitis

Objective To study the characteristics of the central part of the nociceptive system in acute myelitis (AM) with contact heat evoked potentials (CHEPs) and to document the potentials in patients with AM. Methods Twenty patients with AM were recruited in this study as an experimental group, and twenty healthy subjects were chosen as a control group. A heat foil was used to elicit pain and CHEPs. Thermal stimuli were applied at 54.5 ℃ at five sites: the dorsum of the hand, the proximal volar surface of the forearm, the skin of the leg 5 cm proximal to the medial malleolus, and at the C7 and T12 acupuncture locations. The latency and waveform of the evoked potentials were recorded. The conduction velocity of the A8 fibers of the peripheral nerves and of the spinal part of the spinothalamic tract were analyzed. The somatosensory evoked potential (SEP) and sensory conduction velocity (SCV) of the limbs were also examined, and the results were compared with the CHEP results. The results were compared between the two groups. Results The N 550 latencies of the CHEP on the dorsum of the hand, the inside of the leg, and at C7 and T12 were prolonged significantly in the patients with AM compared to the healthy controls. There were no significant differences in the nerve conduction velocity of the Aδ fibers and the velocity or amplitude of sensory nerve conduction in the limbs between the groups. The conduction velocities of the spinothalamic tract were significantly reduced in the patients with AM compared to the control group, while the peak latencies of N13 and the interpeak latencies of N9-N13 and N13-N20 in the AM patients were significantly prolonged compared to the healthy persons. In the patients with AM, CHEP abnormality in the lower limbs (17/20, 85%) was significantly higher than in the upper limbs, total CHEP abnormality and CHEP abnormality in the lower limbs were significantly greater than SEP abnormality. Conclusion Persons with AM have abnormalities in the central part of the nociceptive system. When used with MRI and other electrophysiological examinations, CHEP may contribute to diagnosing AM. It could be helpful in the differential diagnosis of AM from motor neuron diseases and peripheral nerve lesions. It is of great potential value in clinical practice. Key words: Heat-evoked potentials; Acute myelitis; Somatosensory evoked potentials

1. Diagnosing polyneuropathy – Achievements and perspectives

The lecture aims at summarizing latest possibilities and trends in the diagnostics of polyneuropathy with stress laid on neurophysiological methods. Diagnostics of polyneuropathy is traditionally based on clinical findings and electromyography (EMG). EMG confirms diffuse involvement of peripheral nervous system (PNS) usually detected clinically; in addition, it more closely characterizes PNS involvement (distribution, degree, duration of involvement, its dynamics, type of involvement including differentiation between axonal and demyelinating neuropathy), and it may detect subclinical involvement. Standardization, reproducibility and availability are among advantages of the EMG. On the other hand, EMG reflects the involvement of large myelinated fibres (with a diameter >7 μm), that form about 15% of nerve fibres only and they usually did not serve as the initial target in most of polyneuropathies. Diagnosing demyelinating polyneuropathy is reliable in motor fibres only and is based on the detection of conduction slowing, temporal dispersion and conduction block. Criteria of conduction block have been changing last decades and with respect to experimental findings they have finally been agreed on >50% area of a proximal compound muscle action potential reduction relative to a distal one. Differential diagnosis of demyelinating conduction block in addition to inadequate stimulation especially from Erb’s point from technical reasons comprises blocks of other than demyelinating origin (such as in multifocal motor neuropathy). In axonal neuropathies, s.c. pseudoblock (“length dependent conduction block”) due to ongoing Wallerian degeneration, or axonal block (“reversible acute conduction failure”) due to dysfunction of sodium channels in nodal region caused by autoantibodies (for instance in acute motor axonal neuropathy – AMAN) could be encountered. The presence of axonal block could lead to underestimation of AMAN in Guillain–Barre syndrome (GBS) that is falsely marked as acute inflammatory demyelinating polyneuropathy (AIDP) during one-time examination. This fact indicates the necessity of repeated neurophysiological evaluation of GBS. There are, however, no generally accepted neurophysiological criteria for both GBS and chronic inflammatory demyelinating neuropathy (CIDP). Involvement of small sensory and autonomic fibres – s.c. small fibre neuropathy (SFN) is a prevalent and usually initial type of involvement in diabetic polyneuropathy and most polyneuropathies of other origin. Valid diagnostic methods detecting SFN, however, have been lacking until recently. Involvement of sensory small fibres manifests itself by positive sensory symptoms including neuropathic pain. Validated screening methods, such as DN4, PainDETECT or recently validated Czech version of the Neuropathic Pain Symptom Inventory are used for differentiation between neuropathic and nociceptive pain. Verification of thermal and pain perception is a necessary part of clinical evaluation. Semi-quantitative bedside sensory tests are easily available, but offers rough estimate only. Quantitative sensory testing, especially psychophysical method of evaluation of thermal sensory perception, is much more valid. Recently proposed diagnostic criteria for diabetic polyneuropathy, in addition to the evidence of large fibre involvement proved by EMG, also comprises proof of SFN with a validated class A marker, represented currently by the decrease of intra-epidermal nerve fibre density obtained with skin biopsy. Corneal confocal microscopy quantifying sensory small fibres in the Bowman layer of corneal becomes a promising non-invasive alternative of skin biopsy in the detection of SFN. The only neurophysiological method that showed ability to detect SFN are contact heat-evoked potentials.

4. Neurophysiological methods in evaluation of pain in multiple sclerosis

Pain of various origin is a common symptom in patients with multiple sclerosis (MS) with the estimated prevalence between 50% and 85%. Central neuropathic pain (which is defined as a pain arising as a direct consequence of a lesion or disease affecting the somatosensory nervous system) affects about 30% of this group of patients. According to current EFNS (European Federation of Neuropathic Societies) guidelines on neuropathic pain assessment, neurophysiological and psychophysiological methods play an important role in the diagnostic process of neuropathic pain, together with clinical examination and validated screening tools and questionnaires, and functional neuroimaging. Psychophysiological measures are mainly based on quantitative sensory testing (QST) and its dynamic applications. Common QST methods may be defined as a measurement of perception in response to external stimuli of controlled intensity, which allows the evaluation of detection and pain thresholds for various modalities. A detailed QST protocol has recently been developed and validated by German Research Network on Neuropathic Pain. This protocol consists of the assessment of 13 parameters reflecting the sensitivity and pain perception for thermal, touch, pressure, vibration and pinprick stimuli, and allows the detailed clinical description of particular patient with the evaluation of complex sensory profile. In neuropathic pain patients, it may help to characterize particular painful neuropathic syndromes, and predict or monitor treatment effects including effect of treatments upon different pain components. So called “dynamic QST” (dQST) is a group of methods, where the pain-perceiving system is stimulated in a way that exposes a certain mechanism of pain processing, particularly its central modulation These methods include the tests of central integration, such as temporal summation (TS, also called wind-up) and spatial summation, and tests of descending control, e.g., the conditioned pain modulation (CPM). These methods can’t be used for diagnosis or confirmation of the presence of pain. However, their setting is probably one of the factors, predetermining the development of chronic pain. They thus may reflect the ,,pro-nociceptive“ disposition of the particular patient. Among neurophysiological methods, pain-related evoked potentials and some of the pain-related reflexes are the most relevant tests for the assessment of pain in MS patients. Pain-related evoked potentials are the easiest and most reliable neurophysiological methods for assessing the function of nociceptive sensory pathways. Various types of stimuli can be used to evoke the response of pain-related neuronal structures: laser-evoked potentials (LEPs), contact-heat evoked potentials (CHEPs) and potentials elicited by a surface concentric electrode that provides a preferential activation of superficial terminals (i.e. small-diameter afferents) (PREPs). These methods show a clear correlation with pain and are highly specific in its confirmation, while their sensitivity depends on the definition of abnormality (being quite low if only the absence of the response is considered to be abnormal, with a rapid increase if also a reduction of amplitude is taken into consideration). Pain-related reflexes appear to be diagnostically useful particularly for facial pain (e.g. trigeminal neuralgia, which represents one of the most frequent types of pain in MS patients). Two brainstem reflexes (early (R1) blink reflex and early (SP1) masseter inhibitory reflex) are efficient tools to reveal symptomatic forms of trigeminal neuralgia with a very satisfactory sensitivity and specificity. The cutaneous silent period (CSP) is a spinal inhibitory reflex with cortical modulation. The response is recorded from the small hand muscles after noxious stimulation of the fingers, which reflects the suppression of activity in spinal motor nuclei. The method has been tested in various pain conditions and is clearly related to clinical symptoms of thermal and pain perception disturbance. CSP was not systematically studied multiple sclerosis, but has repeatedly been shown to display clear abnormalities in spinal cord lesions (e.g. cervical myelopathy). However, its correlation with presence of pain seems to be limited. Supported by MH CZ-DRO (FNBr, 65269705) and IGA CR NT13523-4.