A rodent model of HIV protease inhibitor indinavir induced peripheral neuropathy.

HIV-associated sensory neuropathy (HIV-SN) is the most frequent manifestation of HIV disease. It often presents with significant neuropathic pain and is associated with previous exposure to neurotoxic nucleoside reverse transcriptase inhibitors. However, HIV-SN prevalence remains high even in resource-rich settings where these drugs are no longer used. Previous evidence suggests that exposure to indinavir, a protease inhibitor commonly used in antiretroviral therapy, may link to elevated HIV-SN risk. Here, we investigated whether indinavir treatment was associated with the development of a "dying back" axonal neuropathy and changes in pain-relevant limb withdrawal and thigmotactic behaviours. After 2 intravenous injections of indinavir (50 mg/kg, 4 days apart), adult rats developed hind paw mechanical hypersensitivity, which peaked around 2 weeks post first injection (44% reduction from baseline). At this time, animals also had (1) significantly changed thigmotactic behaviour (62% reduction in central zone entries) comparing with the controls and (2) a significant reduction (45%) in hind paw intraepidermal nerve fibre density. Treatment with gabapentin, but not amitriptyline, was associated with a complete attenuation of hind paw mechanical hypersensitivity observed with indinavir treatment. Furthermore, we found a small but significant increase in microglia with the effector morphology in the lumbar spinal dorsal horn in indinavir-treated animals, coupled with significantly increased expression of phospho-p38 in microglia. In summary, we have reported neuropathic pain-related sensory and behavioural changes accompanied by a significant loss of hind paw skin sensory innervation in a rat model of indinavir-induced peripheral neuropathy that is suitable for further pathophysiological investigation and preclinical evaluation of novel analgesics.

Spontaneous Age-related Changes of Peripheral Nerves in Cattle: Morphological and Biochemical Studies.

Peripheral nerve function is significantly affected by ageing. During ageing process, multiple changes occur on tissue cells and extracellular matrix. The aim of this work was to study the ageing-associated changes of peripheral nerves in adult and old regularly slaughtered cattle compared with young calves, and correlate them to the features reported in humans and laboratory animals. Samples of axial dorsal metacarpal nerves from 44 cows were collected immediately after slaughtering. Each nerve was dissected and divided into two fragments: one used for morphological evaluation (n = 43) and the other one for biochemical analysis (n = 31). Axonal degeneration, demyelination, thickness of perineurium and endoneurium and increase of mast cells were the most important features detected. The mean amount of glycosaminoglycan quantitative content recorded in the samples increased with the age. Axonal degeneration, demyelination and thickness of endoneurium were positively and significantly correlated with biochemistry. The presence of changes affecting the different elements of the peripheral nerves, similar to that reported in humans and in laboratory species, the easy availability of the nerve tissue in this species, the considerable size of the samples and the life conditions more similar to humans than to laboratory animals, allows the authors to consider cattle as a potential good model for the comparative study of spontaneous ageing nerve lesions.

Diagnostic yield of the palmomental reflex in patients with suspected frontal lesion.

BACKGROUND: The purpose of this study was to determine the diagnostic value of the palmomental reflex in order to identify frontal lesions in neurological outpatients. METHODS: Two hundred twenty-six neurological patients with suspected intracranial lesion with an indication for magnetic resonance imaging (MRI) were included. All patients underwent the same MRI protocol. The reflex was elicited by trained and standardized nurses, and was evaluated by two neurologists. The evaluation was blind and independent. The test's accuracy was calculated. The Kappa coefficient was used to calculate the interobserver and intra-observer reliability. RESULTS: The interobserver reliability between neurologists was 0.53 with 93% of agreement (p<0.001). The diagnostic accuracy measures were as follow: sensitivity of 19%, specificity of 93%, positive predictive value of 30%, negative predictive value of 88%, positive likelihood ratio of 2.7 and negative likelihood ratio of 0.87. The area under the curve was 0.56. CONCLUSION: The palmomental reflex is associated with frontal structural lesions but the sensitivity is low, indicating a high percentage of frontal lesions with a negative reflex. When the test is used on its own, it is insufficient to detect frontal damage.

Comparison of cortical activation patterns by somatosensory stimulation on the palm and dorsum of the hand.

OBJECTIVES: Little is known about differences of cortical activation according to body location. We attempted to compare brain activation patterns by somatosensory stimulation on the palm and dorsum of the hand, using functional magnetic resonance imaging (fMRI). METHOD: We recruited 15 healthy right-handed volunteers for this study. fMRI was performed during touch stimulation using a rubber brush on an area of the same size on the palm or dorsum of the hand. Regions of interest (ROIs) were drawn at the primary sensory-motor cortex (SM1), posterior parietal cortex, and secondary somatosensory cortex. RESULTS: Group analysis of fMRI data indicated that touch stimulation on the palm resulted in production of more activated voxels in the contralateral SM1 and posterior parietal cortex than on the dorsum of the hand. The most activated ROI was found to be the contralateral SM1 by stimulation of the palm or dorsum, and the number of activated voxels (5875) of SM1 by palm stimulation was more than 2 times that (2282) of dorsum stimulation. The peak activated value in the SM1 by palm stimulation (16.43) was also higher than that of the dorsum (5.52). CONCLUSION: We found that stimulation of the palm resulted in more cortical activation in the contralateral SM1 than stimulation of the dorsum. Our results suggested that the palm of the hand might have larger somatotopy of somatosensory representation for touch in the cerebral cortex than the dorsum of the hand. Our results would be useful as a rehabilitation strategy when more or less somatosensory stimulation of the hand is necessary.

Different effects in tactile attention between the thumb and its metacarpus and the palm.

The aim of this study is to establish whether the thumb is represented independently of the palm. An exogenous spatial cueing paradigm was used, where participants had to detect a tactile stimulus that could appear on the proximal and distal phalanges or metacarpus of the thumb (thenar area; Experiment 1) and the metacarpus of the thumb or hypothenar area of the palm (Experiment 2) of the left hand. Our results suggest the thumb and its metacarpus share the same mental representation, which is distinct from the representation of the palm.

Modeling body state-dependent multisensory integration.

The brain often integrates multisensory sources of information in a way that is close to the optimal according to Bayesian principles. Since sensory modalities are grounded in different, body-relative frames of reference, multisensory integration requires accurate transformations of information. We have shown experimentally, for example, that a rotating tactile stimulus on the palm of the right hand can influence the judgment of ambiguously rotating visual displays. Most significantly, this influence depended on the palm orientation: when facing upwards, a clockwise rotation on the palm yielded a clockwise visual judgment bias; when facing downwards, the same clockwise rotation yielded a counterclockwise bias. Thus, tactile rotation cues biased visual rotation judgment in a head-centered reference frame. Recently, we have generated a modular, multimodal arm model that is able to mimic aspects of such experiments. The model co-represents the state of an arm in several modalities, including a proprioceptive, joint angle modality as well as head-centered orientation and location modalities. Each modality represents each limb or joint separately. Sensory information from the different modalities is exchanged via local forward and inverse kinematic mappings. Also, re-afferent sensory feedback is anticipated and integrated via Kalman filtering. Information across modalities is integrated probabilistically via Bayesian-based plausibility estimates, continuously maintaining a consistent global arm state estimation. This architecture is thus able to model the described effect of posture-dependent motion cue integration: tactile and proprioceptive sensory information may yield top-down biases on visual processing. Equally, such information may influence top-down visual attention, expecting particular arm-dependent motion patterns. Current research implements such effects on visual processing and attention.

Multislice computed tomography angiography of the fourth dorsal interosseous space in cadavers.

PURPOSE: To study computed tomography angiography (CTA) findings and compare anatomic correlation of the 4th dorsal metacarpal spaces and to determine the role of this technique for anatomic studies and flap design. METHODS: Hands from 17 cadavers were injected with a radiopaque mixture. The specimens were imaged using 16-detector-row computed tomography. Each image was analyzed by a radiologist, a plastic surgeon, and an anatomist. The following data were recorded: the presence of the 4th dorsal metacarpal artery, proximal and distal communicating branches and distal recurrent branch, and the number of cutaneous perforators. Afterwards, a meticulous dissection was carried out. A correlation between the radiologic findings and the gross anatomy was established. RESULTS: In all specimens, the 4th dorsal metacarpal artery and distal recurrent branch were identified. In 15 cases, at least 1 perforator was identified within the 4th space. In 2 cases, no perforator was identified. In all cases, the radiologic findings correlated with the anatomic findings in the dissection. CONCLUSIONS: Multislice CTA provides good-quality information about the vascular anatomy of the dorsal aspect of the hand, including perforator vessels less than 0.5 mm in diameter. Multislice CTA allows for observation of the axis, trajectory, and branching pattern of the blood vessels and, most importantly, demonstrates the anatomic relationships among blood vessels, bones, and soft tissue.

Inhibition of stimulated dopamine release and hemodynamic response in the brain through electrical stimulation of rat forepaw.

The subcortical response to peripheral somatosensory stimulation is not well studied. Prior literature suggests that somatosensory stimulation can affect dopaminergic tone. We studied the effects of electrical stimulation near the median nerve on the response to an amphetamine-induced increase in synaptic dopamine. We applied the electrical stimulation close to the median nerve 20 min after administration of 3mg/kg amphetamine. We used fMRI and microdialysis to measure markers of dopamine (DA) release, together with the release of associated neurotransmitters of striatal glutamate (Glu) and gamma-aminobutyric acid (GABA). Changes in cerebral blood volume (CBV), a marker used in fMRI, indicate that electrical stimulation significantly attenuated increased DA release (due to AMPH) in the striatum, thalamus, medial prefrontal and cingulate cortices. Microdialysis showed that electrical stimulation increased Glu and GABA release and attenuated the AMPH-enhanced DA release. The striatal DA dynamics correlated with the CBV response. These results demonstrate that electrical stimulation near the median nerve activates Glu/GABA release, which subsequently attenuate excess striatal DA release. These data provide evidence for physiologic modulation caused by electroacupuncture at points near the median nerve.

In vitro evaluation of a single injection technique for diagnostic analgesia of the proximal suspensory ligament of the equine pelvic limb.

OBJECTIVE: To examine the anatomic relationship of the deep branch of the lateral plantar nerve (DBLPN) with structures of the proximal metatarsal region, and to define the anatomic location of a solution injected using a single injection technique for diagnostic analgesia of the proximal suspensory ligament (PSL). STUDY DESIGN: Descriptive study. ANIMALS: Cadaveric equine pelvic limbs (n=29). METHODS: The proximal metatarsal region of both pelvic limbs (n=5 horses, 10 limbs) was dissected and measurements were made of anatomic structures relative to the head of the 4th metatarsal bone (HMT4). A single injection technique was used to inject dye 15 mm distal to the HMT4, axial to the MT4 at a depth of 25 mm in each limb from 10 equine cadavers (19 limbs). Hindlimbs were dissected and the position of the dye was recorded. RESULTS: DBLPN branched from the lateral plantar nerve (LPN) at a mean distance of 30 mm proximal to the HMT4 and entered the PSL at a mean distance of 17 mm distal to the HMT4. A 2nd DBLPN was observed in 1 of 10 dissected limbs. Blue dye surrounded the DBLPN in 18 limbs (95%). CONCLUSIONS: A single injection technique was likely to have resulted in desensitization of the DBLPN in 18 of 19 limbs (95%). CLINICAL RELEVANCE: This technique provides a reliable method using a single needle puncture for perineural analgesia of the DBLPN for diagnosis of proximal suspensory desmitis of the pelvic limb with a minimal risk of inadvertently desensitizing structures within the tarsal sheath and the tarsometatarsal joint.

Treatment of palmar hyperhidrosis: T(4) level compared with T(3) and T(2).

OBJECTIVE: The aim of this study was to compare the outcomes of 3 different levels of sympathectomy. SUMMARY BACKGROUND DATA: Most surgeons still perform T(2) or T(2-3) sympathectomy for palmar hyperhidrosis, but both these treatments can cause severe side effects. Some recent articles have advocated T(4) sympathectomy and obtained satisfactory results. METHODS: Between January 2000 and August 2004, 234 records of patients treated for palmar hyperhidrosis were retrospectively reviewed. Of them, 86 patients were treated with endoscopic thoracic sympathectomy of T(2) (ETS(2)), 78 patients with ETS(3), and 70 patients with ETS(4). Follow-up data were collected using a telephone questionnaire with a scoring system. Multiple linear regressions were used to model markers for degree of satisfaction and severity of compensatory sweating (CS), including descriptive data, level of sympathectomy, clinical outcomes, and postoperative complications. RESULTS: Mean follow-up was 47.1 +/- 17.2 months. All 3 levels of sympathectomy could have achieved comparable improvement of palmar hyperhidrosis (P = 0.162). However, 88.5% of the patients noticed CS. Patients with ETS(4) presented the lowest incidence of CS (P = 0.030), had the least severity of CS (beta = -1.537, P = 0.002), and felt the least palmar overdryness (P < 0.001). None expressed regret for the procedure in the ETS(4) group (P = 0.022). Being obese did not increase the incidence of CS, but the severity of CS was directly related to body mass index (beta = 0.917, P < 0.001). The patients would be more satisfied if the severity of CS was minimal (beta = -0.185, P = 0.002). The degree of satisfaction may decrease with time (beta = -0.025, P = 0.003) and was lower when their palms were overdry (beta = -1.463, P < 0.001). CONCLUSIONS: Different from the current procedure of T(2) or T(3) sympathectomy for palmar hyperhidrosis, T(4) sympathectomy would be a better and more effective procedure with minimal long-term complications.

Digital nerve blocks: More gain with less pain.

Digital nerve blocks are commonly used and effective techniques for achieving anaesthesia of the digit for the purposes of enabling a variety of surgical procedures to be performed. Several techniques have been described including the traditional method, the metacarpal block and the transthecal approach. We favour the traditional technique, and describe a variation of the technique.

[Repair of finger deep burn with the island skin flap nourished by the cutaneous nerve nutrient vessel of the dorsum of hand].

OBJECTIVE: To investigate the reverse island skin flap nourished by the cutaneous nerve nutrient vessel of the dorsum of hand in the repair of the finger deep burn. METHODS: Fifteen reverse island skin flaps nourished by the cutaneous nerve nutrient vessel of the dorsum of hand were used to repair finger deep burn in 15 patients. The size of the reverse island skin flap ranged from 5 cm x 3 cm to 3 x 2 cm. RESULTS: All the flaps survived. Postoperative follow-up showed satisfactory results in appearance, function and aesthesia. CONCLUSIONS: The reverse island skin flap nourished by the cutaneous nerve nutrient vessel of the dorsum of hand has reliable blood supply, without damage of a known vessel, can meet the demands of fingertip reconstruction. The flap also has the advantages of minor injury of the donor site, easy manipulation and popularization.

[Anatomical study of the nerve supply of the trapeziometacarpal joint. Fifteen dissections]. / Etude anatomique de l'innervation de l'articulation trapézo-métacarpienne. A propos de 15 dissections.

PURPOSE OF THE STUDY: When the radiological signs are minimal in patients with a painful carpal syndrome involving the trapeziometacarpal joint (TMCJ), selective articular denervation can be proposed as an alternative after failure of conservative treatment. Results have been variable, sometimes disappointing, suggesting the anatomic basis of denervation should be revisited. The purpose of this work was to study the nerve supply to the TMCJ in order to acquire the indispensable elements necessary for performing effective selective articular denervation. MATERIAL AND METHODS: This anatomical study was performed by dissection under magnification (4.5-x350) of 15 upper limb cadaver specimens. The median nerve, its thenar and volar cutaneous branches and the terminal sensorial branches of the radial nerve were dissected. Articular branches to the TMCJ were carefully identified. Histological samples were taken to verify the neurological nature of the elements dissected. RESULTS: All TMCJs dissected exhibited radial and median nerve supply. Branches of the median nerve predominated in number and caliber. The volar cutaneous branch gave rise to articular branches in eleven dissections and the thenar branch gave rise to articular branches via a retrograde arciform trajectory between the short abductor and the opponens digiti pollicis in thirteen. For five dissections, the TMCJ branches arose directly from the median nerve within the carpal tunnel. At histological analysis the dissected elements were identified as nerves. DISCUSSION: There have been few anatomic studies concerning the nerve supply of the TMCJ. Unlike the findings reported by Cozzi in 1960, we did not find the dorsal sensorial branch of the radial nerve to play an exclusive or preponderant role in the innervation of the TMCJ. The median nerve supply to the TMCJ appeared to be more significant, particularly for the volar cutaneous and especially thenar branches. CONCLUSION: Total and definitive selective denervation of the TMCJ appears to be a most difficult procedure which would require a very wide access and extensive dissection, including the thenar branch which would raise the risk of significant complications.

[Trapeziometacarpal denervation. Description of surgical technique and preliminary results from a prospective series of 14 cases]. / Dénervation trapézométacarpienne. Description de la technique chirurgicale et résultats préliminaires dans une série prospective de 14 cas.

INTRODUCTION: The main goal of first carpometacarpal arthritis surgical treatment is to relieve pain. The main disadvantages of the usual techniques (trapeziectomy, implant arthroplasty) are loss of strength or presence of a prosthetic device. It is difficult to propose such extensive surgery at an early stage of the disease. Selective denervation of the first carpometacarpal joint seems to be an interesting choice. We propose a new technique of denervation based on our previous anatomical investigations. TECHNIQUE: Two incisions are needed to cut all the articular branches derive from the superficial branch of the radial nerve, the palmar cutaneous branch of the median nerve, the thenar branch of the median nerve and the lateral ante brachial cutaneous nerve. MATERIAL: Fourteen patients were prospectively included in our study with a mean follow-up of 5 months. RESULTS: Pain relief was very satisfying in 12 cases (mean decrease 84%). An increase in grip and key pinch strength was noted. Complications were uncommon, excepted temporary paresthésia in the radial nerve area. DISCUSSION: This technique seems to be promising and a good indication for patients with no disabling deformity, but only long-term results will confirm the place of denervation in the treatment of first carpometacarpal arthritis.

Denervation of the radiocarpal joint. A follow-up study in 22 patients.

Denervation surgery has been a mainstay of our management of chronic pain in the wrist. If there is useful movement at the wrist we prefer denervation to arthrodesis. We have reviewed 22 patients at a mean of 50 months after such denervation surgery at the wrist. This was the only treatment in 16 patients; the other six also had other treatments. Pain was reduced in 16 patients, and 17 were satisfied or improved. None of the patients wished to have a supplementary arthrodesis. We stress the importance of preoperative blockade tests and of a very detailed knowledge of the local anatomy.

Histology and ultrastructure of arteries, veins, and peripheral nerves during limb lengthening.

The effects of lengthening of the metacarpal bone on peripheral nerves and blood vessels were studied in 8 calves. Specimens for light and electron microscopy were obtained from the palmar neurovascular bundle at 1 cm (8% of the initial length), 2.5 cm (20% of the initial length), and 4 cm (33% of the initial length) of metacarpal lengthening. In 2 calves, specimens were studied 2 months after the end of the lengthening procedure. At 8% of lengthening, myelinated fibers of the palmar nerve showed moderate degenerative changes in the myelin sheath. This became severe at 20% and 33% of lengthening, and affected the axoplasm as well. At 20% of lengthening, the palmar vein started to show fibrous metaplasia of the smooth muscle tissue of the tunica media. This became much thinner than normal. The palmar artery showed moderate alterations of the inner part of the tunica media and the intima. The palmar nerve and blood vessels recovered their normal structure almost completely 2 months after the end of the lengthening procedure. The morphologic alterations of peripheral nerves and vessels may constitute the pathophysiologic basis of the nervous and circulatory disturbance observed in clinical practice.

Comparison of digital versus metacarpal blocks for repair of finger injuries.

STUDY OBJECTIVE: This study compared efficacy, degree of discomfort, and time to anesthesia of digital blocks and metacarpal blocks for digital anesthesia. DESIGN: Randomized, prospective, nonblinded, clinical study conducted from April 1992 to January 1993. Patients served as their own controls. SETTING: Inner-city and community hospital emergency departments. TYPE OF PARTICIPANTS: Convenience sample of 30 adult patients, with third or fourth finger injuries including and distal to the proximal interphalangeal joint that required digital anesthesia. INTERVENTIONS: Digital blocks and a metacarpal blocks were performed (one per side) on all 30 patients (total of 60 blocks). The order of the blocks was randomized. MEASUREMENTS: A digital block and a metacarpal block were performed on each patient. Patients immediately rated the pain associated with each technique on a nonsegmented visual analog scale. Efficacy was assessed by requirement for additional anesthesia and anesthesia to pinprick. Time to anesthesia was assessed after each block in 23 patients. RESULTS: Mean visual analog scale pain scores were 2.53 for digital block and 3.38 for metacarpal block (P = .1751, Student's t-test). Metacarpal block failed anesthesia to pinprick in 23% of patients compared to 3% for digital block (P = .0227, chi 2). Time to anesthesia was significantly shorter for digital block compared to metacarpal block, with a mean of 2.82 minutes versus 6.35 minutes (P < .0001, Student's t-test). CONCLUSION: Digital block and metacarpal block, as described in this study, are equally painful procedures. Digital block, however, is more efficacious and requires significantly less time to anesthesia for the injured finger.