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Biomedical subjects

G Cruccu

Publications and source records attributed to G Cruccu.

At least 19 recordsLinked to original sources

Measurement of skin temperature after infrared laser stimulation.

OBJECTIVES: Several types of lasers are available for eliciting laser evoked responses (LEPs). In order to understand advantages and drawbacks of each one, and to use it properly, it is important that the pattern of skin heating is known and duly considered. This study was aimed at assessing the skin temperature during and immediately after irradiation with pulses by Nd:YAP and CO(2) lasers. MATERIALS AND METHODS: The back of the non-dominant hand was irradiated in 8 subjects. Temperatures were measured by a fast analogical pyrometer (5 ms response time). Stimuli were tested on natural colour (white) and blackened skin. RESULTS: Nd:YAP pulses yielded temperatures that were correlated with pulse energy, but not with pulse duration; much higher temperatures were obtained irradiating blackened skin than white skin (ranges 100-194 degrees C vs 35-46 degrees C). Temperature decay was extremely slow in white skin, reaching its basal value in more than 30 s. CO(2) pulses delivered with power of 3W and 6W yielded temperatures of 69-87 degrees C on white skin, and 138-226 degrees C on blackened skin. Temperature decay was very fast (4-8 ms). CONCLUSIONS: Differences in peak temperatures and decay times between lasers and tested conditions depend on energy and volume of heated skin. The highest temperatures are reached with lesser degree of penetration, as in the case of CO(2) laser and blackened skin. Taking into account the temperature decay time of the skin, the minimum interstimulus interval to get reliable LEPs should be no less than 10 s for Nd:YAP and 100 ms for CO(2) laser. Another important practical consequence of the heating pattern is that the Nd:YAP pulses will activate warmth receptors more easily than CO(2).

Carbon Dioxide↗

Trigeminal sensory pathway function in patients with SUNCT.

OBJECTIVE: Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a rare primary headache whose origins are unclear. To seek information on its pathophysiology, we studied the trigeminal Abeta and Adelta pathways by recording trigeminal reflexes and laser evoked potentials (LEPs) in patients with SUNCT. METHODS: Trigeminal reflexes and LEPs were recorded in 11 consecutive patients. Ten patients had neuroimaging evidence documenting idiopathic SUNCT and one had a posterior fossa tumour that compressed the trigeminal nerve thus causing symptomatic SUNCT. RESULTS: Whereas the patients with idiopathic SUNCT had normal trigeminal reflex and LEP responses, the patient with symptomatic SUNCT had abnormal responses. CONCLUSIONS: Our neurophysiological findings show that idiopathic SUNCT spares the trigeminal sensory pathways whereas symptomatic SUNCT does not. SIGNIFICANCE: Neurophysiological testing can easily differentiate the idiopathic and symptomatic forms of SUNCT. It also suggests that the two forms are pathophysiologically distinct entities.

Adult↗

Experimental skin pain and muscle pain induce distinct changes in human trigeminal motoneuronal excitability.

Seeking information on the physiological properties of the trigeminal motoneuronal pool we investigated changes in the excitability of trigeminal motor system induced by two types of experimental pain (muscle and skin). In one session, we studied the effect of muscle pain induced by hypertonic saline infusion into the masseter muscle on the recovery cycle of the heteronymous H-reflex in the temporalis muscle and the homonymous silent period (SP) in the masseter muscle, both elicited by stimulation of the masseteric nerve in ten-healthy subjects. In another session, we studied the effect of laser stimuli applied to the perioral region, at conditioning intervals from 20 to 160 ms, on the temporalis H-reflex and masseter SP in nine healthy subjects. Whereas laser-induced skin pain significantly inhibited the temporalis H-reflex and facilitated the masseter SP (P < 0.01), muscle pain left the time course of the temporalis H-reflex and masseter SP unchanged (P > 0.05). The timing of temporalis H-reflex suppression and masseter-SP enhancement induced by laser stimuli indicates that facial skin nociceptors inhibit trigeminal motoneurones via multysynaptic reflex pathways. Hypertonic saline, a stimulus that predominantly activates group III and IV afferents, left both variables reflecting trigeminal motoneuron excitability unchanged. Due to the differences between the two experimental models, we cannot conclude that such inhibitory reflex pathway does not exist from muscle nociceptors to trigeminal motoneurones.

Adult↗

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%).

Adult↗

Pathophysiological mechanisms of neuropathic pain.

It is largely acknowledged that multiple and complex pathophysiological mechanisms may be at play in neuropathic pain. This short review summarises the current understanding of pathophysiology of neuropathic pain and focuses on how symptoms translate in mechanisms.

Humans↗

EFNS guidelines on pharmacological treatment of neuropathic pain.

Neuropathic pain treatment remains unsatisfactory despite a substantial increase in the number of trials. This EFNS Task Force aimed at evaluating the existing evidence about the pharmacological treatment of neuropathic pain. Studies were identified using first the Cochrane Database then Medline. Trials were classified according to the aetiological condition. All class I and II controlled trials (according to EFNS classification of evidence) were assessed, but lower-class studies were considered in conditions that had no top level studies. Only treatments feasible in an outpatient setting were evaluated. Effects on pain symptoms/signs, quality of life and comorbidities were particularly searched for. Most of the randomized controlled trials included patients with postherpetic neuralgia (PHN) and painful polyneuropathies (PPN) mainly caused by diabetes. These trials provide level A evidence for the efficacy of tricyclic antidepressants, gabapentin, pregabalin and opioids, with a large number of class I trials, followed by topical lidocaine (in PHN) and the newer antidepressants venlafaxine and duloxetine (in PPN). A small number of controlled trials were performed in central pain, trigeminal neuralgia, other peripheral neuropathic pain states and multiple-aetiology neuropathic pains. The main peripheral pain conditions respond similarly well to tricyclic antidepressants, gabapentin, and pregabalin, but some conditions, such as HIV-associated polyneuropathy, are more refractory. There are too few studies on central pain, combination therapy, and head-to-head comparison. For future trials, we recommend to assess quality of life and pain symptoms or signs with standardized tools.

AIDS-Associated Nephropathy↗

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.

Ataxia↗

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.

Adolescent↗

Laser evoked potentials and carbamazepine in epileptic patients.

AIMS OF THE STUDY: Nerve conduction studies have demonstrated that carbamazepine (CBZ), as well as other antiepileptic drugs (AEDs), can affect peripheral nerve conduction; reports on conventional somatosensory evoked potentials and CBZ are controversial. In a previous study, assessing laser-evoked potentials (LEPs) in CBZ-treated patients with idiopathic trigeminal neuralgia, we found that LEPs were dampened even after stimulation of the non-painful side, with a strong correlation between LEP latency and daily CBZ dose. No other study investigated the influence of AEDs on LEPs. In order to clarify the effect of CBZ on LEPs we sought possible LEP changes in epileptic patients taking CBZ. MATERIALS AND METHODS: We studied LEPs after trigeminal and hand CO(2)-laser stimulation in 20 patients with epilepsy taking CBZ and 20 age-matched controls. RESULTS: Although the trigeminal LEP mean latency was slightly longer in epileptic patients (P=0.11), we did not find significant differences between epileptic patients and controls for any LEP data. LEP data did not correlate with the daily CBZ dose, CBZ blood concentration, or duration of therapy (P>0.3). CONCLUSION: The lack of a CBZ-induced dampening of LEPs suggests that small-fibre pathways, compared to large-fibre, might be less susceptible to AED's toxic effect. Although the TN patients in our previous study were older than the epileptic patients in the present study, a possible combined effect induced by drug and age in patients with TN is unlikely because LEP latency is reportedly unaffected by age. The CBZ-induced effect in patients with trigeminal neuralgia is possibly related to pathophysiological changes specific to this disease.

Adolescent↗

Operculoinsular cortex encodes pain intensity at the earliest stages of cortical processing as indicated by amplitude of laser-evoked potentials in humans.

Converging evidence from different functional imaging studies indicates that the intensity of activation of different nociceptive areas (including the operculoinsular cortex, the primary somatosensory cortex, and the anterior cingulate gyrus) correlates with perceived pain intensity in the human brain. Brief radiant laser pulses excite selectively Adelta and C nociceptors in the superficial skin layers, provide a purely nociceptive input, and evoke brain potentials (laser-evoked potentials, LEPs) that are commonly used to assess nociceptive pathways in physiological and clinical studies. Adelta-related LEPs are constituted of different components. The earliest is a lateralised, small negative component (N1) which could be generated by the operculoinsular cortex. The major negative component (N2) seems to be mainly the result of activation in the bilateral operculoinsular cortices and contralateral primary somatosensory cortex, and it is followed by a positive component (P2) probably generated by the cingulate gyrus. Currently, early and late LEP components are considered to be differentially sensitive to the subjective variability of pain perception: the late N2-P2 complex strongly correlates with perceived pain, whereas the early N1 component is thought to be a pre-perceptual sensory response. To obtain physiological information on the roles of the pain-related brain areas in healthy humans, we examined the relationship between perceived pain intensity and latency and amplitude of the early (N1) and late (N2, P2) LEP components. We found that the amplitude of the N1 component correlated significantly with the subjective pain ratings, both within and between subjects. Furthermore, we showed that the N2 and P2 late LEP components are differentially sensitive to the perceived sensation, and demonstrated that the N2 component mainly explains the previously described correlation between perceived pain and the amplitude of the N2-P2 vertex complex of LEPs. Our findings confirm the notion that pain intensity processing is distributed over several brain areas, and suggest that the intensity coding of a noxious stimulus occurs already at the earliest stage of perception processing, in the operculoinsular region and, possibly, the primary somatosensory area.

Adult↗

Brainstem reflex circuits revisited.

Our current understanding of brainstem reflex physiology comes chiefly from the classic anatomical-functional correlation studies that traced the central circuits underlying brainstem reflexes and establishing reflex abnormalities as markers for specific areas of lesion. These studies nevertheless had the disadvantage of deriving from post-mortem findings in only a few patients. We developed a voxel-based model of the human brainstem designed to import and normalize MRIs, select groups of patients with or without a given dysfunction, compare their MRIs statistically, and construct three-plane maps showing the statistical probability of lesion. Using this method, we studied 180 patients with focal brainstem infarction. All subjects underwent a dedicated MRI study of the brainstem and the whole series of brainstem tests currently used in clinical neurophysiology: early (R1) and late (R2) blink reflex, early (SP1) and late (SP2) masseter inhibitory reflex, and the jaw jerk to chin tapping. Significance levels were highest for R1, SP1 and R2 afferent abnormalities. Patients with abnormalities in all three reflexes had lesions involving the primary sensory neurons in the ventral pons, before the afferents directed to the respective reflex circuits diverge. Patients with an isolated abnormality of R1 and SP1 responses had lesions that involved the ipsilateral dorsal pons, near the fourth ventricle floor, and lay close to each other. The area with the highest probabilities of lesion for the R2-afferent abnormality was in the ipsilateral dorsal-lateral medulla at the inferior olive level. SP2 abnormalities reached a low level of significance, in the same region as R2. Only few patients had a crossed-type abnormality of SP1, SP2 or R2; that of SP1 reached significance in the median pontine tegmentum rostral to the main trigeminal nucleus. Although abnormal in 38 patients, the jaw jerk appeared to have no cluster location. Because our voxel-based model quantitatively compares lesions in patients with or without a given reflex abnormality, it minimizes the risk that the significant areas depict vascular territories rather than common spots within the territory housing the reflex circuit. By analysing statistical data for a large cohort of patients, it also identifies the most frequent lesion location for each response. The finding of multireflex abnormalities reflects damage of the primary afferent neurons; hence it provides no evidence of an intra-axial lesion. The jaw jerk, perhaps the brainstem reflex most widely used in clinical neurophysiology, had no apparent topodiagnostic value, probably because it depends strongly on peripheral variables, including dental occlusion.

Adult↗

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.

Evoked Potentials, Somatosensory↗

Excitability of the Adelta nociceptive pathways as assessed by the recovery cycle of laser evoked potentials in humans.

To investigate the excitability of Adelta nociceptive pathways and the nature of the vertex laser evoked potentials (LEPs), we studied the recovery cycle of the P2-LEP component and compared it with that of the P200 of the somatosensory evoked potential (SEP). Using two identical CO(2)-laser stimulators, we delivered paired stimuli to two adjacent skin spots on the hand at interstimulus intervals ranging from 250 ms to 2 s. The test P2-LEP was strongly inhibited at the 250-ms interstimulus interval ( P<0.01) and progressively recovered by the 2-s interval. The P200-SEP, after paired stimuli to the median nerve, showed a time course even slower than the P2-LEP ( P<0.01). Besides providing the LEP recovery curve in normal subjects, our findings indicate that the P2-LEP relays through a number of synapses similar to (or even lower than) that for the P200-SEP, thus lending further support to the view that the nociceptive P2-LEP is not an endogenous potential equivalent to the P300.

Adult↗

Cutaneous silent period in hand muscle is evoked by laser stimulation of the palm, but not the hand dorsum.

Painful electrical stimulation of the fingers evokes an inhibitory response in hand muscles (cutaneous silent period, CSP). The aim of this study was to determine whether purely nociceptive thermal stimuli applied to the hand evoke a CSP. High-intensity laser pulses (205 +/- 44 mJ) were delivered to the dorsum and palm of the hand in five volunteers. Electromyographic signals were recorded from the ipsilateral first dorsal interosseous muscle. We then compared the laser-evoked CSP with the CSP induced by electrical stimulation. A clear laser CSP (latency 90 +/- 7 ms) was evoked in all subjects when laser pulses were applied to the palm of the hand, whereas no response was recorded after stimulation of the dorsum. Electrical stimulation of both the dorsum and the palm evoked a CSP (latency 65 +/- 5 ms), although the reflex threshold was significantly lower after stimulation of the palm. This study confirms that the CSP is a nociceptive response specific to limbs that grasp. In humans, palm nociceptors are probably more functionally effective than dorsal nociceptors in inducing the hand-muscle inhibition that interrupts hand prehension (so that a potentially noxious source is dropped) before proximal muscles withdraw the limb.

Adult↗

Adelta nociceptor response to laser stimuli: selective effect of stimulus duration on skin temperature, brain potentials and pain perception.

OBJECTIVE: To disclose a possible effect of duration of pulsed laser heat stimuli on Adelta nociceptor responses, skin temperature profiles, brain evoked potentials and pain perception. METHODS: We used a laser stimulator which works in the millisecond range and allows us to change the duration of the pulse while keeping the total energy of the stimulus constant. In 10 healthy volunteers, we measured the intensity of perceived pain with a 0-10 scale and the latency and amplitude of the early N1 and late N2 components of the scalp potentials evoked by laser pulses of equal energy and three different stimulus durations (2, 10, and 20 ms). Using a specifically developed pyrometer with a temporal resolution lower than 1 ms we also measured stimulus-induced changes of skin temperature. RESULTS: Stimulus duration significantly influenced temperature rise times, pain perception, and brain potentials. Shorter stimulus durations yielded steeper slopes in the skin temperature profiles and higher pain ratings, shortened the latency of the N1 and N2 components, and increased the amplitude of N1. CONCLUSIONS AND SIGNIFICANCE: The shorter stimulus duration shortens receptor activation times and yields a more synchronous afferent volley, thus providing a stronger spatial-temporal summation at central synapses that enhances intensity of first pain and brain potentials. This may prove useful in clinical applications.

Adult↗