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Jean Claude Willer

Publications and source records attributed to Jean Claude Willer.

11 recordsLinked to original sources
PubMed2006

Related timing for peripheral and central plasticity in hypoglossal-facial nerve anastomosis.

The aim of this work was to determine the role of peripheral facial muscle reinnervation in the central reorganization of the blink reflex (BR) after hypoglossal-facial anastomosis (HFA). An electrophysiological study was performed on seven patients who underwent HFA after facial nerve transection during surgery for acoustic neuroma. HFA was performed within 15 days after surgery in five patients (group 1) and later for the two others (group 2). We studied the motor responses (MR) and the BR evoked on the affected side, before and over 3 years after the HFA. The MR appeared by the third month for the first group, and by the sixth and twelfth for the second group. After 36 months, the amplitude of MR was significantly higher than its control value, showing hyperinnervation of the facial muscles. Study of the BR evoked only an R1-type blink response that was observed 4 and 6 months after the MR for groups 1 and 2, respectively. This central reorganization appeared closely correlated with muscle reinnervation and its related timing. The occurrence of peripheral nerve-muscle contacts seems to be a necessary condition for reorganization of the trigemino-hypoglossal-facial reflex.

Adult↗
PubMed2005

The lower limb flexion reflex in humans.

The flexion or flexor reflex (FR) recorded in the lower limbs in humans (LLFR) is a widely investigated neurophysiological tool. It is a polysynaptic and multisegmental spinal response that produces a withdrawal of the stimulated limb and resembles (having several features in common) the hind-paw FR in animals. The FR, in both animals and humans, is mediated by a complex circuitry modulated at spinal and supraspinal level. At rest, the LLFR (usually obtained by stimulating the sural/tibial nerve and by recording from the biceps femoris/tibial anterior muscle) appears as a double burst composed of an early, inconstantly present component, called the RII reflex, and a late, larger and stable component, called the RIII reflex. Numerous studies have shown that the afferents mediating the RII reflex are conveyed by large-diameter, low-threshold, non-nociceptive A-beta fibers, and those mediating the RIII reflex by small-diameter, high-threshold nociceptive A-delta fibers. However, several afferents, including nociceptive and non-nociceptive fibers from skin and muscles, have been found to contribute to LLFR activation. Since the threshold of the RIII reflex has been shown to correspond to the pain threshold and the size of the reflex to be related to the level of pain perception, it has been suggested that the RIII reflex might constitute a useful tool to investigate pain processing at spinal and supraspinal level, pharmacological modulation and pathological pain conditions. As stated in EFNS guidelines, the RIII reflex is the most widely used of all the nociceptive reflexes, and appears to be the most reliable in the assessment of treatment efficacy. However, the RIII reflex use in the clinical evaluation of neuropathic pain is still limited. In addition to its nocifensive function, the LLFR seems to be linked to posture and locomotion. This may be explained by the fact that its neuronal circuitry, made up of a complex pool of interneurons, is interposed in motor control and, during movements, receives both peripheral afferents (flexion reflex afferents, FRAs) and descending commands, forming a multisensorial feedback mechanism and projecting the output to motoneurons. LLFR excitability, mediated by this complex circuitry, is finely modulated in a state- and phase-dependent manner, rather as we observe in the FR in animal models. Several studies have demonstrated that LLFR excitability may be influenced by numerous physiological conditions (menstrual cycle, stress, attention, sleep and so on) and pathological states (spinal lesions, spasticity, Wallenberg's syndrome, fibromyalgia, headaches and so on). Finally, the LLFR is modulated by several drugs and neurotransmitters. In summary, study of the LLFR in humans has proved to be an interesting functional window onto the spinal and supraspinal mechanisms of pain processing and onto the spinal neural control mechanisms operating during posture and locomotion.

Electric Stimulation↗
PubMed2005

A1152D mutation of the Na+ channel causes paramyotonia congenita and emphasizes the role of DIII/S4-S5 linker in fast inactivation.

Missense mutations in the human skeletal muscle Na+ channel alpha subunit (hSkM1) are responsible for a number of muscle excitability disorders. Among them, paramyotonia congenita (PC) is characterized by episodes of muscle stiffness induced by cold and aggravated by exercise. We have identified a new PC-associated mutation, which substitutes aspartic acid for a conserved alanine in the S4-S5 linker of domain III (A1152D). This residue is of particular interest since its homologue in the rat brain type II Na+ channel has been suggested as an essential receptor site for the fast inactivation particle. To identify the biophysical changes induced by the A1152D mutation, we stably expressed hSkM1 mutant or wild-type (WT) channels in HEK293 (human embryonic kidney) cells, and recorded whole-cell Na+ currents with the patch-clamp technique. Experiments were performed both at 21 and 11 degrees C to better understand the sensitivity to cold of paramyotonia. The A1152D mutation disrupted channel fast inactivation. In comparison to the WT, mutant channels inactivated with slower kinetics and displayed a 5 mV depolarizing shift in the voltage dependence of the steady-state. The other noticeable defect of A1152D mutant channels was an accelerated rate of deactivation from the inactivated state. Decreasing temperature by 10 degrees C amplified the differences in channel gating kinetics between mutant and WT, and unveiled differences in both the sustained current and channel deactivation from the open state. Overall, cold-exacerbated mutant defects may result in a sufficient excess of Na+ influx to produce repetitive firing and myotonia. In the light of previous reports, our data point to functional as well as phenotypic differences between mutations of conserved S4-S5 residues in domains II and III of the human skeletal muscle Na+ channel.

Aged↗
PubMed2004

Influence of sensory and proprioceptive impairment on the development of phantom limb syndrome during regional anesthesia.

BACKGROUND: The relation between impairment of sensorimotor function and occurrence of phantom limb syndrome (PLS) during regional anesthesia has not been described. This study assessed the temporal relation between PLS and the progression of sensorimotor impairment during placement of a brachial plexus nerve block. METHODS: Fifty-two patients had their arm randomly placed either alongside their body (group A) or in 90 degrees abduction (group B) immediately after brachial plexus nerve block placement. Responses to pin prick, cold, heat, touch, proprioception, and voluntary movement were assessed every 5 min for 60 min. Meanwhile, patients described their perceptions of the size, shape, and position of their anesthetized limb. RESULTS: Phantom limb syndrome occurred 19 +/- 9 min after nerve block placement. Proprioception was impaired and abolished after 22 +/- 9 and 43 +/- 17 min, respectively (P < 0.05 vs. PLS onset). When PLS occurred, responses to pin prick, cold, heat, and proprioception were abolished in 96, 94, 87, and 4% of patients, respectively. Patients were more likely to feel their anesthetized limb in adduction and in abduction in groups A and B (P < 0.05 vs. group A), respectively. After PLS had become motionless, two stereotyped positions were identified: arm adduction, elbow flexion, hand over the abdomen (68% of group A patients) and arm abduction, elbow flexion, hand held close to the homolateral ear (48% of group B patients). CONCLUSIONS: This study provides a better understanding of the determinants of PLS by showing that the final position of PLS is related both to the abolition of proprioception and the initial position of the anesthetized limb.

Adult↗
PubMed2004

Time sequence of sensory changes after upper extremity block: swelling sensation is an early and accurate predictor of success.

BACKGROUND: Sensory assessment to estimate spread and effectiveness of a peripheral nerve block is difficult because no clinical test is specific for small sensory fibers. Occurrence of a swelling illusion (SI) during a peripheral nerve block corresponds to the impairment of small sensory fibers. The authors investigated the usefulness of SI in predicting successful peripheral nerve block by assessing the temporospatial correlation between progression of sensory impairment in cutaneous distributions anesthetized and localization of SI during peripheral nerve block installation. METHODS: Interscalene, infracoracoid, or sciatic nerve blocks were performed using a nerve stimulator and 1.5% mepivacaine in 53 patients, with a total of 201 nerves to be anesthetized. Pinprick, cold, warm, touch, and proprioception were assessed every 3 min, while patients were asked to describe their perception of size and shape of their anesthetized limb and localization of these illusions. Data are presented as mean +/- SD and percentage (95% confidence interval). RESULTS: Failure occurred in 12 cutaneous distributions out of a total of 201 theoretically blocked nerves. SI appeared earlier than warmth impairment (4.3 +/- 2.7 vs. 6.2 +/- 2.0 min; P < 0.05), always corresponding to successfully anesthetized cutaneous distributions, with the exception of 1 patient, who developed SI in 2 cutaneous distributions while sensory testing indicated failure in 1 distribution. SI successfully predicted the blockade of a cutaneous distribution with a sensitivity of 1.00 (0.98-1.00), a specificity of 0.92 (0.65-0.99), and an accuracy of 0.99 (0.97-1.00). CONCLUSIONS: Swelling illusion may provide an early assessment of the success of a peripheral nerve block in unsedated patients.

Adult↗
PubMed2003

Functional characterization and cold sensitivity of T1313A, a new mutation of the skeletal muscle sodium channel causing paramyotonia congenita in humans.

Paramyotonia congenita (PC) is a dominantly inherited skeletal muscle disorder caused by missense mutations in the SCN4A gene encoding the pore-forming alpha subunit (hSkM1) of the skeletal muscle Na+ channel. Muscle stiffness is the predominant clinical symptom. It is usually induced by exposure to cold and is aggravated by exercise. The most prevalent PC mutations occur at T1313 on DIII-DIV linker, and at R1448 on DIV-S4 of the alpha subunit. Only one substitution has been described at T1313 (T1313M), whereas four distinct amino-acid substitutions were found at R1448 (R1448C/H/P/S). We report herein a novel mutation at position 1313 (T1313A) associated with a typical phenotype of PC. We stably expressed T1313A or wild-type (hSkM1) channels in HEK293 cells, and performed a detailed study on mutant channel gating defects using the whole-cell configuration of the patch-clamp technique. T1313A mutation impaired Na+ channel fast inactivation: it slowed and reduced the voltage sensitivity of the kinetics, accelerated the recovery, and decreased the voltage-dependence of the steady state. Slow inactivation was slightly enhanced by the T1313A mutation: the voltage dependence was shifted toward hyperpolarization and its steepness was reduced compared to wild-type. Deactivation from the open state assessed by the tail current decay was only slowed at positive potentials. This may be an indirect consequence of disrupted fast inactivation. Deactivation from the inactivation state was hastened. The T1313A mutation did not modify the temperature sensitivity of the Na+ channel per se. However, gating kinetics of the mutant channels were further slowed with cooling, and reached levels that may represent the threshold for myotonia. In conclusion, our results confirm the role of T1313 residue in Na+ channel fast inactivation, and unveil subtle changes in other gating processes that may influence the clinical phenotype.

Adult↗
PubMed1998

Different strategies of modulation can be operative during hypnotic analgesia: a neurophysiological study.

Nociceptive electrical stimuli were applied to the sural nerve during hypnotically-suggested analgesia in the left lower limb of 18 highly susceptible subjects. During this procedure, the verbally reported pain threshold, the nociceptive flexion (RIII) reflex and late somatosensory evoked potentials were investigated in parallel with autonomic responses and the spontaneous electroencephalogram (EEG). The hypnotic suggestion of analgesia induced a significant increase in pain threshold in all the selected subjects. All the subjects showed large changes (i.e., by 20% or more) in the amplitudes of their RIII reflexes during hypnotic analgesia by comparison with control conditions. Although the extent of the increase in pain threshold was similar in all the subjects, two distinct patterns of modulation of the RIII reflex were observed during the hypnotic analgesia: in 11 subjects (subgroup 1), a strong inhibition of the reflex was observed whereas in the other seven subjects (subgroup 2) there was a strong facilitation of the reflex. All the subjects in both subgroups displayed similar decreases in the amplitude of late somatosensory evoked cerebral potentials during the hypnotic analgesia. No modification in the autonomic parameters or the EEG was observed. These data suggest that different strategies of modulation can be operative during effective hypnotic analgesia and that these are subject-dependent. Although all subjects may shift their attention away from the painful stimulus (which could explain the decrease of the late somatosensory evoked potentials), some of them inhibit their motor reaction to the stimulus at the spinal level, while in others, in contrast, this reaction is facilitated.

Adult↗
PubMed1992

Morphine blocks descending pain inhibitory controls in humans.

In man, heterotopic painful thermal conditioning stimuli induce parallel decreases in the spinal nociceptive flexion (RIII) reflex and the concurrent sensation of pain elicited by electrical stimulation of the sural nerve at the ankle. Such phenomena may be related to the diffuse noxious inhibitory controls (DNIC) which were initially described in the rat and subsequently documented in humans. In 9 subjects in the present study, a 2 min application of a moderately noxious temperature (46 degrees C) to the contralateral hand strongly depressed the RIII reflex elicited in the biceps femoris muscle by electrical stimulation of the sural nerve at 1.2 times the reflex threshold. These depressive effects were maximal during the second min of the conditioning period, showing a 80% inhibition of the RIII reflex which gradually recovered to its baseline value 7 min after the end of the conditioning period. Such inhibitory effects were completely blocked 15-26 min after administration of a low dose of morphine hydrochloride (0.05 mg/kg, i.v.). The lifting of the inhibitions was compatible with an action at the opioid receptors since the inhibitions were re-observed 5-16 min after naloxone injection (0.006 mg/kg, i.v.). During all the experimental sessions, heart and respiratory rates remained stable at their control levels. Since it has been shown previously that such a dose of morphine could not have a direct effect within the spinal cord (Willer 1985), it is concluded that this opiate blocks, in a naloxone-reversible fashion, those bulbo-spinal controls which are triggered by heterotopic nociceptive events. Possible implications for hypoalgesia based on the principles of counter-irritation are discussed.

Adult↗
PubMed1988

Low dose epidural morphine does not affect non-nociceptive spinal reflexes in patients with postoperative pain.

In order to determine the selectivity of the antinociceptive effect of epidural morphine, the electrophysiological features of a monosynaptic reflex were investigated before and after epidural morphine (2-3 mg) required for pain relief, in 4 patients suffering from postoperative pain. The reflex tested was the H reflex from the soleus muscle. Not only the classical Hmax/Mmax ratio, but also the threshold and the slope of the rising phase of the recruitment curve of H and M responses were analyzed. It was found that epidural morphine did not change significantly any of these parameters, at least during the 60 min post-injection period. By contrast, as usually observed clinically, epidural morphine produced an onset of pain relief by the 25th-30th min following injection. These data support the hypothesis that epidural morphine produced a 'selective spinal analgesia in man.'

Anesthesia, Epidural↗