Clinical application of laser evoked potentials using the Nd:YAG laser.

The clinical interest of a new type of laser evoked potentials (LEPs) using Nd:YAG laser was assessed in the diagnosis of peripheral neuropathies affecting the small-diameter nerve fibres, and of spinal cord lesions, affecting the spinothalamic tract. Twelve patients aged from 26 to 79 years with sensory neuropathies (n = 6) or spinal cord lesions (n = 6) underwent neurophysiological examination of the lower limbs comprising quantitative sensory testing, i.e., the determination of vibratory and thermal thresholds (VT and TT), somatosensory evoked potentials (SEPs) to electrical stimulation and Nd:YAG LEPs. VT and SEPs were used to assess large-diameter afferent nerve fibres and the lemniscal pathways while TT and LEPs were used to assess small-diameter afferent nerve fibres and the spinothalamic tract. In addition, patients with peripheral neuropathy underwent also standard nerve conduction studies to explore large fibres and the recording of sympathetic skin responses (SSRs) to explore small fibres, whereas motor evoked potentials were performed in patients with spinal cord lesion. LEPs were absent bilaterally in all patients with polyneuropathy, even when TT remained within the normal limits and SSRs were present. LEPs were absent after stimulation of the affected limb in all patients with a spinal cord lesion, and allowed to detect subclinical contralateral lesion in two cases. LEPs following Nd:YAG laser stimulation are sensitive in the diagnosis of peripheral and/or central nervous system disorders and they give complementary information as compared to routine electrophysiological tests.     

Usefulness of dorsal laser evoked potentials in patients with spinal cord damage: report of two cases

Stimulation of the dorsal skin with brief laser impulses easily evokes brain potentials (laser evoked potentials, LEPs). Dorsal LEPs were first used to study the conduction velocity in the human spinothalamic tract. In this study the diagnostic usefulness of this technique was assessed by recording dorsal LEPs in two patients with focal spinal cord lesions (one intrinsic and the other extrinsic) and spared lemniscal sensitivities. In both cases, the brain evoked potentials were normal after stimulation of the metamers above the lesion but absent after stimulation of those below. Dorsal LEP recordings may prove a useful tool in localising lesions and in the neurophysiological assessment of focal spinal cord lesions involving the anterolateral quadrants of the spinal cord.     

Physiological study of the spinothalamic tract conduction in multiple sclerosis.

This is the first paper to study the physiological function of the spinothalamic tract in multiple sclerosis (MS) using pain-related somatosensory evoked potentials (pain SEPs) following CO2 laser stimulation. Among 12 patients with MS, hand- and foot-stimulated pain SEPs were significantly delayed or absent in 3 and 7, respectively. These results were totally consistent with clinical impairment of pain-temperature sensation. In contrast, the results of conventional electrically-stimulated SEPs were compatible with impairment of vibration sensation. Therefore, the examination of both pain and electric SEPs is very useful to evaluate the physiological function of the ascending spinal tract in patients with MS.     

Somatosensory evoked potentials reflect the upper limb motor performance in multiple sclerosis

OBJECTIVE: The aim of this multicentric study was to multidimensionally evaluate the relationship among somatosensory evoked potentials (SEPs) parameters, patient's perspective and clinical measures of the upper limb impairment in patients with multiple sclerosis (MS). METHODS: We consecutively enrolled 39 MS patients. For median nerve SEPs we acquired the N9, P14, N20 responses and the N9-P14 and P14-N20 interpeak latencies on the dominant side. We also used a validated patient-oriented questionnaire (Disabilities of the Arm, Shoulder and Hand - DASH) and a test of dexterity quantification as the 9-Hole Peg Test (9-HPT). RESULTS: A significant longer time to complete the 9-HPT (p<0.00006) was observed in patients with abnormal SEPs. Patients with undetectable N20 or P14 responses performed the 9-HPT in a significant longer time than patients with detectable responses (p<0.0006 and p<0.001 respectively). Concerning the perspective of patient (evaluated with the DASH questionnaire) significant differences in patients with undetectable P14 response (p<0.01) were observed. CONCLUSIONS: Our data provide further information useful for interpretation of SEPs results, being the median nerve SEPs related to the upper limb performance in MS patients. SIGNIFICANCE: These data increase the significance of SEPs both in clinical practice and in experimental studies in MS.     

Somatosensory evoked potentials and sensory involvement in multiple sclerosis: comparison with clinical findings and quantitative sensory tests

Sensory disturbances are one of the most common findings in patients with multiple sclerosis (MS). However, they are usually assessed at the standard neurological examination only. Quantitative Sensory Tests (QSTs) for temperature and vibratory sense allow a more objective evaluation. In a group of 19 clinically definite MS patients, we compared vibratory and temperature thresholds with sensory symptoms or signs at clinical neurological examination and somatosensory evoked potentials (SEPs) at the four limbs. The frequency of abnormalities of clinical symptoms/signs, vibration threshold and median SEPs were 69%, 33% and 55%, respectively. Correlation between degree of abnormality of SEPs and clinically assessed vibration sense (V) was statistically significant (P<0.007; Spearmann rank coefficient), as well as between SEPs and vibration perception threshold (P<0.02). Clinical evaluation of thermal sense did not show false positive results compared to quantitative thermal threshold, but false negative findings (35%). This study suggests that the combined use of vibration threshold and SEPs allows a better objectivation of sensory function, allowing the detection of subclinical abnormalities and possibly reducing the number of false positive results introduced by clinical assessment. Moreover QSTs are to be preferred to clinical evaluation in the assessment of thermal sense, due to their superior sensitivity.     

Neurophysiological studies of pain pathways in peripheral and central nervous system disorders

Abstract. Standard clinical neurophysiological assessment of somatosensory pathways by sensory evoked potentials (SEPs) is limited to the tactile and proprioceptive systems consisting of large fibers in the peripheral nerve, the dorsal columns of the spinal cord and the medial lemniscus in the brainstem. This limitation means that about half of the lesions in the somatosensory system will not be detectable. In recent years, many clinical studies have confirmed that laser evoked potentials (LEPs) allow the assessment of the other half of the somatosensory system. Rapid heating of the skin by infrared laser pulses specifically activates the nociceptive and thermoreceptive pathways consisting of small fibers in the peripheral nerve and the anterolateral spinothalamic tract in the spinal cord and brainstem. Owing to the large degree of convergence of the somatosensory pathways on to common thalamic nuclei, the differential use of LEP vs. SEP is less evident for thalamocortical lesions. In contrast to standard SEPs, the LEP technique can be applied to non-glabrous skin in any dermatome. This review summarizes the principles of clinical neurophysiological studies of pain pathways and the findings obtained in patients with peripheral and central nervous system disorders. These data provide a rational basis for developing clinical indications for LEP testing.     

Dissociation of thalamic high frequency oscillations and slow component of sensory evoked potentials following damage to ascending pathways.

OBJECTIVE: Somatosensory evoked potentials (SEPs) recorded from the thalamus have a slow component and high frequency (approximately 1000 Hz) oscillations (HFOs). In this study, we examined how lesions in the sensory afferent pathway affect these components. METHODS: Thalamic SEPs to contralateral median nerve stimulation were recorded from deep brain stimulation electrodes in two patients. Patient 1 had spinal cord injury at the C4/5 level. Patient 2 had multiple sclerosis with mid brain lesions. Seven patients with no brain or cervical spinal cord lesions served as controls. RESULTS: In both patients, the low frequency component of the SEP (LF SEP) was delayed and/or prolonged and greatly decreased in amplitude compared with controls. HFOs were recorded in both patients. The latencies of onset and peak of the HFOs were approximately the same as those of the LF SEPs and their amplitudes were similarly reduced. However, their frequency was similar to that of the control group. Cortical SEPs were absent in both patients. CONCLUSIONS: Normal frequencies of thalamic HFOs in association with increased peak latencies, and decreased amplitudes provide further evidence that the HFOs are likely due to intrinsic oscillations in the thalamus rather than high frequency synchronous inputs. SIGNIFICANCE: Thalamic HFOs are closely associated with the LF SEP but are generated by a different mechanism.     

Cutaneous silent periods in intramedullary spinal cord lesions

OBJECTIVE: The neurophysiological assessment of intramedullary spinal cord lesions has been unsatisfactory. Previous studies in patients with syringomyelia suggest that testing of cutaneous silent periods (CSPs) may be useful to assess centromedullary lesions. METHODS: The authors studied nine patients with intramedullary spinal cord lesions of different etiologies. Eight patients with cervical lesions presented with hypalgesia, hypothermesthesia, or pain in at least one upper extremity; five of them had also upper limb weakness or sensory impairment. One patient with a thoracic lesion had normal upper limb function. The authors recorded CSPs in abductor pollicis brevis muscle following digit II and digit V stimulation. Somatosensory evoked potentials (SEPs) were obtained following median and tibial nerve stimulation. Motor evoked potentials (MEPs) were obtained in biceps brachii, abductor digiti minimi and tibialis anterior muscles following transcranial magnetic or electrical stimulation. RESULTS: CSP abnormalities were found in all patients with cervical lesions, but not in the patient with a thoracic lesion. Cortical median nerve SEPs had normal latencies in all patients, while tibial nerve SEPs, upper limb MEPs, and lower limb MEPs were delayed in five patients each. In one patient, abnormal CSP were the only neurophysiological finding. CSP abnormalities were associated with hypalgesia and hypothermesthesia in 95% of the studies. CONCLUSION: Upper extremity CSP testing is a sensitive neurophysiological technique for the assessment of cervical intramedullary lesions. In particular, abnormal CSPs are highly associated with spinothalamic dysfunction.     

Somatosensory evoked potentials in amyotrophic lateral sclerosis.

Forty five patients with amyotrophic lateral sclerosis were investigated, by means of somatosensory evoked potentials, in order to detect the presence of subclinical sensory changes. Cervical SEPs from the median nerve and cortical SEPs from the median and tibial nerve were recorded, showing a delay of N13 and subsequent components; the latency of the first constant cortical potential was also increased in many patients. Only the SEPs from the tibial nerve showed a decrease of amplitude. These results suggest a pathological slowing of conduction along the central sensory pathways in amyotrophic lateral sclerosis.     

Small fiber sensory neuropathies: contribution of laser evoked potentials

Standard neurophysiological techniques evaluate exclusively large myelinated fibers, but are not useful to explore sensory small fibers. Quantitative sensory tests have been developed to explore the thermal nociceptive function but this exploration is only subjective. Laser evoked potentials (LEPs) represent a noninvasive and objective test to explore thermal and nociceptive pathways. The clinical interest of LEPs have been assessed recently in the diagnosis of small fibers sensory neuropathies. In routine, the determination of detection and nociceptive thresholds, the analysis of N2P2 latencies and amplitudes enable demonstration of a dysfunction of A delta nerve fibers, to quantify these lesions and to determine whether the neuropathies are length-dependent or not. The LEP amplitude is negatively correlated to deafferentation. The interest of LEPs remained to be studied compared to skin biopsy.     

Clinical usefulness of laser-evoked potentials

In contrast to the function of the visual or auditory pathways which are electrophysiologically accessible by visual or auditory evoked potentials, the somatosensory pathway cannot be investigated as a whole by conventional somatosensory evoked potentials (SEP), because these only reflect function of large fibers, dorsal columns, medial lemniscus and their thalamo-cortical projections mediating sensations like touch and vibration. The other half of the somatosensory system, signaling temperature and pain perception, uses a different set of afferents and different central pathways, the function of which is accessible by laser-evoked potentials (LEPs). LEP can document lesions of the spinothalamic tract and (lateral) brainstem and of thalamo-cortical projections conveying thermo-nociceptive signals. In the peripheral nerve, LEP can help distinguish between large and small fiber neuropathies. The rapid heating of the skin by infrared laser pulses can easily be applied to non-glabrous skin in any dermatome. In recent years, many clinical studies have demonstrated that LEP can supply evidence for establishing clinical diagnoses when deficits of the nociceptive system are present. This review outlines principles and recording techniques for LEP in patients and compiles typical LEP findings in patients with lesions due to different diseases at various levels of the nociceptive pathways. Limitations for the use of LEP are pointed out, too, like the uncertainty of lesion location along these pathways and the fact that LEP can reliably show correlates of reduced nociceptive function but only rarely of enhanced transmission (like in hyperalgesia).     

接触性热痛诱发电位在多发性硬化患者中的应用

目的 建立接触性热痛诱发电位(CHEP)标准,并对多发性硬化(MS)患者进行痛温觉传导通路功能评价,评价CHEP在MS中的应用价值.方法 选取确诊的MS患者36例和健康人40名,应用接触性热痛诱发电位刺激器(Medoc,Israel),在2个强度水平(47、51℃)应用可调节脉冲,刺激部位选择右上肢前臂掌侧前1/3处、右下肢内踝上皮肤和腰部.受试者在每次刺激后,对刺激强度分级.以Keypoint.net仪器记录,记录点为Cz.测定刺激强度和疼痛分级的关系、诱发电位的主要成分的潜伏期和波幅.结果 健康对照组予以47℃和51℃分别刺激上下肢,CHEP的引出率为100%;MS组上肢4例,下肢5例未引出肯定CHEP波形.我们通过对下肢和腰部刺激计算得出A8纤维传导速度为(18.1±7.3)m/s.MS患者存在痛温觉减退症状的上肢21例,下肢29例,其反应性疼痛分级[视觉模拟评分(VAS),上肢6.1±0.9,下肢5.6±1.3]较对照组(上肢8.0±0.7,下肢7.9±0.7)低,差异有统计学意义(Z=-3.249、-5.272,P＜0.01).存在痛温觉障碍且能够诱发出CHEP波形(上肢17例,下肢24例)的上下肢N波潜伏期[上肢(387.3±34.2)ms,下肢(489.9±70.2)ms]较对照组[上肢(346.0±25.5)ms,下肢(400.8±24.4)ms]明显延长(t=4.790、4.798,P＜0.01)、N-P波幅[上肢(30.5±12.8)μV,下肢(28.2±16.2)μV]较对照组[上肢(49.3±16.0)μV,下肢(42.2±16.7)μV]明显减低(t=-4.612、-3.144,P＜0.01).MS患者下肢CHEP检测的异常率(26/36,72.2%)高于上肢(16/36,44.4%,P=0.031)和体感诱发电位(19/36,52.8%,χ~2=4.261,P=0.039).上肢未存在痛温觉障碍的15例MS患者中,有3例CHEP异常,下肢7例中有2例CHEP异常.结论 CHEP提供了一种临床实用的、非侵入性的客观检查方法,它与侧重于结构异常的MRI不同,重点检测伤害性通路的功能改变,所以结合MRI和其他诱发电位能够更有效的辅助诊断MS,评价伤害性通路的情况,揭示亚临床病灶的存在.     

Conduction velocity of the human spinothalamic tract as assessed by laser evoked potentials

To study the conduction velocity of the spinothalamic tract (STT) we delivered CO2 laser pulses, evoking pinprick sensations, to the skin overlying the vertebral spinous processes at different spinal levels from C5 to T10 and recorded evoked potentials (LEPs) in 15 healthy human subjects. These stimuli yielded large-amplitude vertex potentials consisting of a negative wave at a peak latency of about 200 ms followed by a positive wave at a peak latency of about 300 ms. The mean conduction velocity of the STT was 21 m/s, i.e. higher than the reported velocity of the corresponding primary sensory neurons (type II AMH). Because dorsal stimulation readily yields reproducible brain LEPs, we expect this technique to be useful as a diagnostic tool for assessing the level of spinal cord lesions.     

Brainstem auditory-evoked potentials studied with paired stimuli in multiple sclerosis patients

In 19 patients with definite multiple sclerosis (MS) brainstem auditory-evoked potentials (BAEP) with paired stimuli were recorded. Only hearing pathways without abnormalities in usual BAEP were examined. The latencies of wave III and wave V were significantly increased with the paired-stimulus technique (using paired-click intervals of 1.5 and 4.0 ms duration) compared to single clicks. In 4 patients (21%) paired-click BAEP latencies exceeded the critical values of normal subjects. This technique might give new possibilities in detecting minor lesions in MS patients.     

Nociceptive inputs transmission in Huntington's disease: a study by laser evoked potentials

The aim of the present study was to evaluate pain perception and evoked responses by laser stimuli (LEPs) in mild not demented Huntington's Disease (HD) patients. Twenty-eight HD patients and 30 control subjects were selected. LEPs were obtained by four scalp electrodes, (Fz, Cz, referred to the nasion; T3, T4, referred to Fz), stimulating the dorsum of both hands. All patients were also evaluated by somatosensory evoked potentials (SEPs) by median nerve stimulation. Only 3 patients referred pain of arthralgic type. Laser pain perception was similar between HD patients and controls. An abnormal N2, P2 and N1 latency increase was evident in the majority of HD patients. LEPs features were similar between patients taking and not taking neuroleptics. The N2 and P2 latencies, showed a negative correlation with functional score and Mini Mental State Examination, and a positive correlation with the severity of hyperkinetic movements. A delay in nociceptive input processing emerged in HD, concurring with the main features of the disease, in absence of clinical evidence of abnormalities in pain perception. The dysfunction of pain signals transmission in HD may induce sub-clinical changes of sensory functions, which may probably interfere with sensory-motor integration and contribute to functional impairment.     

Median nerve somatosensory evoked potentials and their high-frequency oscillations in amyotrophic lateral sclerosis.

OBJECTIVE: To investigate sensory cortical changes in amyotrophic lateral sclerosis (ALS), we studied somatosensory evoked potentials (SEPs) and their high-frequency oscillation potentials. METHODS: Subjects were 15 healthy volunteers and 26 ALS patients. Median nerve SEPs were recorded and several peaks of oscillations were obtained by digitally filtering raw SEPs. The patients were sorted into three groups according to the level of weakness of abductor pollicis brevis muscle (APB): mild, moderate and severe. The latencies and amplitudes of main and oscillation components of SEP were compared among normal subjects and the three patient groups. RESULTS: The early cortical response was enlarged in the moderate weakness group, while it was attenuated in the severe weakness group. No differences were noted in the size ratios of oscillations to the main SEP component between the patients and normal subjects. The central sensory conduction time (CCT) and N20 duration were prolonged in spite of normal other latencies. CONCLUSIONS: The median nerve SEP amplitude changes are associated with motor disturbances in ALS. The cortical potential enhancement of SEPs with moderate weakness in ALS may reflect some compensatory function of the sensory cortex for motor disturbances. SIGNIFICANCE: The sensory cortical compensation for motor disturbances is shown in ALS, which must be important information for rehabilitation.     

Sensory deficits of a nerve root lesion can be objectively documented by somatosensory evoked potentials elicited by painful infrared laser stimulations: a case study.

Somatosensory evoked potentials (SEPs) in response to painful laser stimuli were measured in a patient with a unilateral sensory deficit due to radiculopathy at cervical levels C7 and C8. Laser evoked potentials (LEPs) were compared with SEPs using standard electrical stimulation of median and ulnar nerves at the wrist and mechanical stimulation of the fingertips by means of a mechanical stimulator. Early and late ulnar and median nerve SEPs were normal. Mechanical stimulation resulted in w shaped early SEPs from all five fingertips with some degree of abnormality at the fourth and fifth digits of the affected hand. Late LEPs were completely absent for stimulations at affected dermatomes and normal in the unaffected control dermatomes. The border between skin areas with normal or absent LEPs was very sharp and fitted the dermatomes of intact C6 and damaged C7 and C8 nerve roots. It is suggested that pain dermatomes are narrower than tactile dermatomes because thin fibres of the nociceptive system, activated by laser stimuli, probably do not overlap between adjacent spinal segments to the same extent as thick fibres of the mechanoreceptive system, activated by standard electrical or mechanical stimulation.     

Anomalies in early somatosensory evoked potentials in brain stem lesions (study of 64 cases)

Short latency somatosensory evoked potentials (SEPs) have been recorded in 64 patients with brainstem lesions documented by neuroimaging techniques. Patients were classified in four groups according to the lesion topography: cervico-medullary junction and medulla (16 cases), pons (19 cases), mesencephalon (8 cases), extensive (21 cases). SEPs were abnormal in 57.8% of cases either bilaterally (17.2%), or unilaterally (40.6%). The different components were affected as follows, P14: 34.4%; N20: 56.9%; P22 and N30: 54.7%, peripheral and spinal responses were always spared: N18 and P14 abnormalities were highly correlated. In cervico-medullary lesions P14 and N20 were constantly abnormal, P14 was normal in strictly mesencephalic lesions but could be abnormal in cases of subthalamic lesions with mesencephalic extension; in pontic lesions, P14 could be normal or not, and N20 was always very reduced. These results confirm that P14 has a supra-spinal origin and may have two generators. SEPs detected a subclinical dysfunction of the lemniscal pathways in 18% of patients with normal somatosensory performances and, as BAEPs (abnormal in 54% of the 54 recordings performed in this series) deserve to be recorded for the routine investigation of brainstem function.     

The diagnostic significance of long-latency reflexes in multiple sclerosis

Reflexes of thenar muscles after median or radial superficial nerve stimulation have been investigated in both hands of 47 patients with probable or definite multiple sclerosis (MS) and compared with somatosensory evoked potentials (SEPs) to median nerve stimulation. A delay or absence of long-latency reflexes (LLRs) was found as pathological patterns. The results after median or radial superficial nerve stimulation were usually both pathologic or both normal except in cases with latencies at the upper limit of normal values. Pathological results of reflex testing were obtained in 61% of the patients with probable MS and in 79% of those with definite MS. Abnormal SEPs were found in 44% of the patients with probable MS compared to 62% with definite MS. All cases which had pathologic SEPs also had pathologic LLR. Hence, LLR testing detected more abnormalities than the routine median nerve SEP testing that has been used.     

How response inhibition modulates nociceptive and non-nociceptive somatosensory brain-evoked potentials.

OBJECTIVE: To examine and compare the modulation of nociceptive somatosensory laser-evoked potentials (LEPs) and non-nociceptive somatosensory electrically-evoked potentials (SEPs) by brain processes related to response inhibition. METHODS: A warning auditory tone was followed by either an electrical or a laser stimulus. Subjects performed a Go/Nogo task in which they were instructed to respond to the laser stimulus and refrain from responding to the electrical stimulus in half of the runs. In the other half, they performed the opposite. The paradigm allowed a direct, within-subject comparison of the electrophysiological correlates of brain processes related to the Go/Nogo task in both somatosensory submodalities. RESULTS: In the Nogo-condition, SEPs displayed an enhanced N120 (early Nogo-response), a reduced vertex P240 and enhanced frontal P3 (late Nogo-responses). In contrast, LEPs only displayed late Nogo-related responses (reduced vertex P350 and enhanced frontal P3). CONCLUSIONS: The early Nogo-related enhancement of SEPs may reflect brain processes specific to the processing of non-nociceptive somatosensory stimuli. Later components of the Nogo-response may reflect cortical activity common to the processing of both nociceptive and non-nociceptive somatosensory stimuli. SIGNIFICANCE: Response inhibition significantly modulates both LEPs and SEPs. Part of these activities may be specific of the eliciting stimulus modality.