G. D. Iannetti

Reduced habituation to experimental pain in migraine patients: a CO2 laser evoked potential study

The habituation to sensory stimuli of different modalities is reduced in migraine patients. However, the habituation to pain has never been evaluated. Our aim was to assess the nociceptive pathway function and the habituation to experimental pain in patients with migraine. Scalp potentials were evoked by CO2 laser stimulation (laser evoked potentials, LEPs) of the hand and facial skin in 24 patients with migraine without aura (MO), 19 patients with chronic tension‐type headache (CTTH), and 28 control subjects (CS). The habituation was studied by measuring the changes of LEP amplitudes across three consecutive repetitions of 30 trials each (the repetitions lasted 5 min and were separated by 5‐min intervals). The slope of the regression line between LEP amplitude and number of repetitions was taken as an index of habituation. The LEPs consisted of middle‐latency, low‐amplitude responses (N1, contralateral temporal region, and P1, frontal region) followed by a late, high‐amplitude, negative–positive complex (N2/P2, vertex). The latency and amplitude of these responses were similar in both patients and controls. While CS and CTTH patients showed a significant habituation of the N2/P2 response, in MO patients this LEP component did not develop any habituation at all after face stimulation and showed a significantly lower habituation than in CS after hand stimulation. The habituation index of the vertex N2/P2 complex exceeded the normal limits in 13 out of the 24 MO patients and in none of the 19 CTTH patients (P<0.0001; Fishers exact test). Moreover, while the N1–P1 amplitude showed a significant habituation in CS after hand stimulation, it did not change across repetitions in MO patients. In conclusion, no functional impairment of the nociceptive pathways, including the trigeminal pathways, was found in either MO or CTTH patients. But patients with migraine had a reduced habituation, which probably reflects an abnormal excitability of the cortical areas involved in pain processing.

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.

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.

Topographical distribution of pinprick and warmth thresholds to CO2 laser stimulation on the human skin

We studied the topographical distribution of laser sensory thresholds on the human hairy skin, using a small laser beam for pinprick and a large beam for warmth sensations. The threshold for pinprick sensation correlated positively with the distance from the brain, suggesting that Adelta nociceptors, the fibers which convey pinprick sensation, are more dense at proximal than at distal body sites. This finding adds information to skin biopsy studies of epidermal free nerve endings which showed a similar gradient, but could not differentiate small myelinated from unmyelinated fiber afferents. Possibly because of a diffuse low density of warmth receptors, laser warmth thresholds showed no trend.

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.

A topodiagnostic investigation on body lateropulsion in medullary infarcts

Body lateropulsion may occur without signs of vestibular dysfunction and vestibular nucleus involvement. The authors examined 10 such patients with three-dimensional brainstem mapping. Body lateropulsion without limb ataxia reflected an impairment of vestibulospinal postural control caused by a lesion of the descending lateral vestibulospinal tract, whereas body lateropulsion with limb ataxia was probably the consequence of impaired or absent proprioceptive information caused by a lesion of the ascending dorsal spino-cerebellar tract.

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.

Is Ross syndrome a dysautonomic disorder only? An electrophysiologic and histologic study

OBJECTIVE To define the involvement of peripheral nerve fibers in Ross syndrome. METHODS Mechanical pain perception, tactile and thermal thresholds on hand, foot dorsum, thigh, median nerve orthodromic sensory conduction velocity (SCV) and motor conduction velocity (MCV), sural nerve antidromic SCV, peroneal nerve MCV, H-reflex, F-wave, median, tibial nerve somatosensory evoked potentials (SSEPs), perioral, hand CO(2) laser late (LEPs) and ultralate evoked potentials, sympathetic skin response (SSRs), cardiovascular, Minor sweat, silastic imprint, histamine, photopletysmographic and pupil pilocarpine tests, cutaneous innervation immunohistochemical techniques were studied in 3 patients with Ross syndrome. RESULTS Quantitative sensory testing showed altered results in patients 1 and 2, and patient 3 had a slight impairment of mechanical pain perception. Nerve conduction, except for a median nerve distal reduction of sensory conduction in patient 1, F-wave and SSEP findings were normal; H-reflex was absent at rest in all patients. Hand LEPs were absent in patient 2, ultralate potentials were absent in patients 1 and 2. Skin biopsy showed a disease duration related reduction of unmyelinated and myelinated sensory fibers and a lack of unmyelinated autonomic fibers in all patients. CONCLUSIONS Our data suggest that Ross syndrome is a degenerative disorder involving progressive sudomotor fibers, and then epidermal sensory unmyelinated and myelinated fibers.

Trigeminal small-fibre dysfunction in patients with diabetes mellitus: a study with laser evoked potentials and corneal reflex

OBJECTIVE To investigate trigeminal small-fibre function in patients with diabetes mellitus. METHODS In 52 diabetic patients we studied the trigeminal laser evoked potentials after stimulation of the skin bordering the lower lip. In the 21 patients with the severest peripheral nerve damage we also studied the electrically evoked corneal reflex. Both responses are mediated by small myelinated afferents. RESULTS Laser evoked potentials had a longer mean latency and lower amplitude in diabetic patients than in normal subjects (P<0.005). The abnormality frequency of the laser evoked potentials correlated with the severity of polyneuropathy (P<0.005). In contrast, the corneal reflex was normal. CONCLUSION Dysfunction of small afferents of the mandibular nerve is frequent in patients with diabetic polyneuropathy. We speculate that the primary cause could be segmental demyelination.

Somatotopic organization of the corticospinal tract in the human brainstem: a MRI-based mapping analysis.

To investigate the incompletely understood somatotopical organization of the corticospinal tract in the human brainstem, we performed a voxel‐based statistical analysis of standardized magnetic resonance scans of 41 prospectively recruited patients with pyramidal tract dysfunction caused by acute brainstem infarction. Motor hemiparesis was rated clinically and by the investigation of motor evoked potentials to arms and legs. Infarction affected the pons in 85% of cases. We found the greatest level of significance of affected brainstem areas between the pontomesencephalic junction and the mid pons. Lesion location was significantly more dorsal in patients with hemiparesis affecting more proximal muscles and was significantly more ventral in patients with predominantly distal limb paresis. Comparison of magnetic resonance lesion from patients with paresis predominantly affecting arm or leg did not show significant topographical differences. We conclude that a topographical arm/leg distribution of corticospinal fibers is abruptly broken down as the descending corticospinal tract traverses the pons. Corticospinal fibers, however, follow a somatotopical order in the pons with fibers controlling proximal muscles being located close to the reticular formation in the dorsal pontine base, and thus more dorsal than the fibers controlling further distal muscle groups. Ann Neurol 2005