F. Galeotti

Laser-evoked potentials: normative values.

OBJECTIVE Laser-evoked potentials (LEPs) currently represent the most reliable and widely agreed method of investigating the A delta-fibre pathways. Many studies dealt with the usefulness of LEPs in peripheral and central nervous system diseases. We aimed at gaining normative values for LEP data. METHODS Using a CO2 laser stimulator we recorded LEPs after face, hand, and foot stimulation in 100 normal subjects. We measured the perceptive threshold, latency and amplitude of the main vertex components, and their side-to-side differences. We also studied the correlations between LEP data and age and body height, as well as gender differences. RESULTS Laser perceptive threshold increased and LEP amplitude decreased from face to foot (P<0.0001). The latency of hand and foot-LEPs correlated significantly with body height (P<0.0001). The amplitude, though not the latency, correlated with age (P<0.0001). LEP data did not significantly differ between genders (P>0.1). CONCLUSIONS This study provides normative values for the main LEP data and their absolute and side-to-side limits, highlighting the physiological differences related to, body height, age, gender and stimulation site. SIGNIFICANCE Our data may help to improve the clinical reliability of LEPs as a diagnostic tool.

Trigeminal neuralgia and pain related to multiple sclerosis

ABSTRACT Although many patients with multiple sclerosis (MS) complain of trigeminal neuralgia (TN), its cause and mechanisms are still debatable. In a multicentre controlled study, we collected 130 patients with MS: 50 patients with TN, 30 patients with trigeminal sensory disturbances other than TN (ongoing pain, dysaesthesia, or hypoesthesia), and 50 control patients. All patients underwent pain assessment, trigeminal reflex testing, and dedicated MRI scans. The MRI scans were imported and normalised into a voxel‐based, 3D brainstem model that allows spatial statistical analysis. The onset ages of MS and trigeminal symptoms were significantly older in the TN group. The frequency histogram of onset age for the TN group showed that many patients fell in the age range of classic TN. Most patients in TN and non‐TN groups had abnormal trigeminal reflexes. In the TN group, 3D brainstem analysis showed an area of strong probability of lesion (P < 0.0001) centred on the intrapontine trigeminal primary afferents. In the non‐TN group, brainstem lesions were more scattered, with the highest probability for lesions (P < 0.001) in a region involving the subnucleus oralis of the spinal trigeminal complex. We conclude that the most likely cause of MS‐related TN is a pontine plaque damaging the primary afferents. Nevertheless, in some patients a neurovascular contact may act as a concurring mechanism. The other sensory disturbances, including ongoing pain and dysaesthesia, may arise from damage to the second‐order neurons in the spinal trigeminal complex.

Small-fiber dysfunction in trigeminal neuralgia: Carbamazepine effect on laser-evoked potentials

Background: In patients with trigeminal neuralgia, results of clinical examination of sensory function are normal. Reflex and evoked potential studies have already provided information on large-afferent (non-nociceptive) function. Using laser-evoked potentials (LEP), the authors sought information on small-afferent (nociceptive) function. Methods: The brain potentials evoked by CO2–laser pulses directed to the perioral and supraorbital regions were studied in 67 patients with idiopathic or symptomatic trigeminal neuralgia and 30 normal subjects. Of the 67 patients, 49 were receiving carbamazepine. Results: All patients with symptomatic and 51% of those with idiopathic trigeminal neuralgia had frankly abnormal LEP on the painful side. The mean latency was significantly higher and mean amplitude lower on the painful than the nonpainful side. However, even on the nonpainful side, the mean latency was significantly longer than that of the age-matched controls. The nonpainful-side latency correlated significantly with the carbamazepine dose. Conclusions: LEP detect severe impairment of the nociceptive afferent system on the painful side of patients with idiopathic as well as symptomatic trigeminal neuralgia. A dysfunction of small-myelinated afferents may play an important role in the pathophysiology of neuralgic pain. Carbamazepine markedly dampens these brain potentials. The authors propose that this effect may result from inhibition of nociceptive transmission in the cingulate gyrus.

Pathophysiology of pain in postherpetic neuralgia: A clinical and neurophysiological study

Abstract Postherpetic neuralgia is an exceptionally drug‐resistant neuropathic pain. To investigate the pathophysiological mechanisms underlying postherpetic neuralgia we clinically investigated sensory disturbances, pains and itching, with an 11‐point numerical rating scale in 41 patients with ophthalmic postherpetic neuralgia. In all the patients we recorded the blink reflex, mediated by non‐nociceptive myelinated Aβ‐fibers, and trigeminal laser evoked potentials (LEPs) related to nociceptive myelinated Aδ‐ and unmyelinated C‐fiber activation. We also sought possible correlations between clinical sensory disturbances and neurophysiological data. Neurophysiological testing yielded significantly abnormal responses on the affected side compared with the normal side (P < 0.001). The blink reflex delay correlated with the intensity of paroxysmal pain, whereas the Aδ‐ and C‐LEP amplitude reduction correlated with the intensity of constant pain (P < 0.01). Allodynia correlated with none of the neurophysiological data. Our study shows that postherpetic neuralgia impairs all sensory fiber groups. The neurophysiological‐clinical correlations suggest that constant pain arises from a marked loss of nociceptive afferents, whereas paroxysmal pain is related to Aβ‐fiber demyelination. These findings might be useful for a better understanding of pain mechanisms in postherpetic neuralgia.

Representation of different trigeminal divisions within the primary and secondary human somatosensory cortex

Clinical, neurophysiological, and neuroimaging studies have yielded controversial results about the representation of the face in the somatosensory cortex. To clarify this issue we mechanically stimulated the left forehead (ophthalmic trigeminal division, V1) and left lower lip (mandibular trigeminal division, V3) in 14 healthy volunteers during acquisition of whole-brain fMRI images. During V1 and V3 stimulation the fMRI signal in the primary (SI) and secondary (SII) somatosensory cortices in the contralateral hemisphere increased. Within both SI and SII, the foci activated by stimulation of the two trigeminal divisions largely overlapped. In contrast, the ipsilateral representation differed. Whereas V3 stimulation activated the contralateral somatosensory cortex alone, V1 stimulation activated SI and SII bilaterally. These results to some extent contrast with electrophysiological data in monkeys and disclose distinct cortical representations within facial territories in humans.

Laser evoked potentials for assessing sensory neuropathy in human patients

Sensory neuropathy usually impairs tactile sensations related to large myelinated afferents (Abeta) as well as thermal-pain sense related to small myelinated (Adelta) and unmyelinated (C) afferents. By selectively affecting large or small fibres, some sensory neuropathies may also provoke a dissociated sensory loss. Standard nerve conduction studies and somatosensory evoked potentials assess Abeta-fibre function only. Laser pulses selectively excite free nerve endings in the superficial skin layers and evoke Adelta-related brain potentials (LEPs). From earlier studies and new cases we collected data on 270 patients with sensory neuropathy. LEPs often disclosed subclinical dysfunction of Adelta fibres and proved a sensitive and reliable diagnostic tool for assessing small-fibre function in sensory neuropathy.

Inhibition of cortical responses to Aδ inputs by a preceding C-related response : Testing the first come, first served hypothesis of cortical laser evoked potentials

Abstract Although laser pulses activate concomitantly Aδ and C fibres, the corresponding brain evoked responses remain strictly limited to the Aδ component, without any potential consistent with C‐fibre activation. To investigate whether this phenomenon depends on the order of arrival to the cortex (“first come first served” hypothesis) or is simply explained by A‐to‐C inhibition and/or lower energy associated with the desynchronised C‐fibre input, we devised an experiment where the physiological order of arrival to the cortex was artificially inverted. Following a conditioning C‐pulse, the cortical response to a second laser stimulus was significantly attenuated, whether it was Aδ or C. Thus, a C‐volley was able to depress the response to a subsequent Aδ stimulus, in support of the “first come first served” hypothesis. However, the conditioning C‐fibre stimulus attenuated significantly more a subsequent C‐volley than a subsequent Aδ‐volley, indicating that the suppression effect does not depend solely on the order of arrival to the cortex, but also on the ratio of energy per unit time conveyed by the successive inputs. This supports the notion that cortical evoked potentials to laser pulses (and probably to other sensory stimuli) reflect networks detecting rapid energy changes relative to a preceding baseline. The output of such networks should depend both on the time elapsed between successive inputs and on the relative energy per unit time conveyed by successive volleys. Such dedicated networks aimed at detecting energy changes may be related to orienting reactions, and can be dissociated from subjective perception.

Mechanisms of pain in distal symmetric polyneuropathy: A combined clinical and neurophysiological study

&NA; In patients with distal symmetric polyneuropathy we assessed non‐nociceptive A&bgr;‐ and nociceptive A&dgr;‐afferents to investigate their role in the development of neuropathic pain. We screened 2240 consecutive patients with sensory disturbances and collected 150 patients with distal symmetric polyneuropathy (68 with pain and 82 without). All patients underwent the Neuropathic Pain Symptom Inventory to rate ongoing, paroxysmal and provoked pains, a standard nerve conduction study (NCS) to assess A&bgr;‐fibre function, and laser‐evoked potentials (LEPs) to assess A&dgr;‐fibre function. Patients with pain had the same age (P > 0.50), but a longer delay since symptom onset than those without (P < 0.01). Whereas the LEP amplitude was significantly lower in patients with pain than in those without (P < 0.0001), NCS data did not differ between groups (P > 0.50). LEPs were more severely affected in patients with ongoing pain than in those with provoked pain (P < 0.0001). Our findings indicate that the impairment of A&bgr;‐fibres has no role in the development of ongoing or provoked pain. In patients with ongoing pain the severe LEP suppression and the correlation between pain intensity and LEP attenuation may indicate that this type of pain reflects damage to nociceptive axons. The partially preserved LEPs in patients with provoked pain suggest that this type of pain is related to the abnormal activity arising from partially spared and sensitised nociceptive terminals. Because clinical and neurophysiological abnormalities followed similar patterns regardless of aetiology, pain should be classified and treated on mechanism‐based grounds.

Trigeminal small-fibre function assessed with contact heat evoked potentials in humans

Abstract Contact heat stimuli have been reported to excite mechano‐thermal nociceptors and to evoke brain potentials (CHEPs) from the limbs. We investigated whether contact heat evokes reproducible CHEPs from the trigeminal territory and may prove a reliable diagnostic tool in facial neuropathic pain. We applied contact heat stimuli to the perioral and supraorbital regions; CHEPs were recorded from the vertex in 20 controls and 2 patients with facial neuropathic pains, and reflex responses from the orbicularis oculi and masticatory muscles in 5 controls. We studied the correlation between CHEP data and perceptive ratings, site of stimulation, and age. Finally, we compared CHEPs with laser evoked potentials (LEPs). Contact heat stimuli at 51 °C evoked vertex potentials consisting of an NP complex similar to that elicited by laser pulses, though with a latency some 100‐ms longer. Perioral stimulation yielded higher pain intensity ratings, shorter latency and larger amplitude CHEPs than supraorbital stimulation. CHEP data correlated significantly with age. Contact heat stimuli at 53 °C evoked a blink‐like response in the relaxed orbicularis oculi muscle and a silent period in the contracted masseter muscle. In patients with facial neuropathic pain the CHEP abnormalities paralleled those seen with LEPs. We were unable to achieve reproducible signals related to C‐receptor stimulation by contact heat stimuli at 41 °C in the ten subjects in whom they were tested. Contact heat stimulation, as well as laser stimulation, easily yields large‐amplitude brain potentials and nociceptive reflexes, both related to the Aδ input. However CHEPs are not suitable for C‐fibres potentials recording.

Diagnostic accuracy of trigeminal reflex testing in trigeminal neuralgia

The authors prospectively studied 120 consecutive patients with trigeminal neuralgia (TN) to identify the clinical and laboratory features that most accurately distinguished symptomatic from classic TN. After a standardized evaluation, they identified 24 patients with symptomatic TN. Age, sensory examination, and affected division were not useful in the differential diagnosis. In contrast, electrophysiologic testing of trigeminal reflexes accurately distinguished symptomatic from classic TN (sensitivity 96%, specificity 93%).