Cutaneous anaesthesia of the lower leg can improve sensibility in the diabetic foot. A double-blind, randomized clinical trial.

AIMS: Impaired sensory function in the sole of the foot in diabetic patients is a substantial problem caused by unknown mechanisms. Hand or foot sensibility can be improved by cutaneous anaesthesia of the forearm or lower leg, respectively, in healthy subjects. Hypothetically, cutaneous anaesthesia induces a silent area in the primary somatosensory cortex, allowing adjacent cortical areas to expand; thus, resulting in enhanced sensory processing. Our aim was to improve sensory function in the foot in Type 1 and Type 2 diabetic patients by application of an anaesthetic cream to the lower leg. METHODS: In a double-blind study, 37 patients with Type 1 or Type 2 diabetes were randomly assigned to cutaneous application of either an anaesthetic cream (EMLA) or a placebo cream to the skin of the lower leg for 1.5 h. Sensibility at five points of the sole of the foot was assessed before and after 1.5 and 24 h. Vibrotactile sense was also assessed. Primary outcome was change of touch threshold at the first metatarsal head from pretreatment to 1.5 h assessment. RESULTS: Anaesthetic cream on the lower leg resulted in a significant improvement of touch threshold at the first metatarsal head after 1.5 and 24 h. In addition, improvement of touch thresholds was also observed at the other four assessment sites, together with a decreased vibration threshold at 125 Hz. CONCLUSIONS: The findings of improved touch thresholds open up new possibilities in treatment of sensibility disturbances in the diabetic foot, using a simple and non-invasive method.

Schwann cells, acutely dissociated from a predegenerated nerve trunk, can be applied into a matrix used to bridge nerve defects in rats.

BACKGROUND: The gold standard to reconstruct a nerve defect is a conventional autologous nerve graft. There may be a lack of such grafts in severe nerve injuries. Alternatives to autologous nerve grafts are needed. METHODS: We have developed a technique where mainly Schwann cells are acutely dissociated from the ends of the severed nerve trunk after nerve injury. The technique does not require long-term cell culture procedures. The obtained cells, which can be dissociated within a few hours, are applied to a silicone tube or a tendon autograft used to bridge a nerve defect. FINDINGS: Dissociated cells from the ends of the severed nerve ends consist of more than 85% of Schwann cells. The remaining cells are ED1 stained macrophages. The cells survive transfer to a silicone tube or a tendon autograft which bridge the nerve defect. Axons do grow through such a graft filled with dissociated cells. CONCLUSION: Our novel model to obtain mainly Schwann cells by dissociation of the cells from the severed nerve ends after injury and add them to a matrix, thereby creating an artificial nerve graft, may be a new technique with potential clinical application in nerve reconstruction.

Cortical reintegration of a replanted hand and an osseointegrated thumb prosthesis.

BACKGROUND: Following a peripheral nerve repair the injured nerve has to re-innervate its original cortical area, a process, which is poorly understood. Errors in this cortical re-innervation have been suggested as one key reason for the generally poor clinical outcome following nerve injuries in the hand. METHOD: Functional magnetic resonance imaging (fMRI) was used to assess cortical reintegration following amputation and reattachment of bodyparts in two different situations: a patient with a hand amputation followed by immediate surgical replantation and a patient with an osseointegrated thumb prosthesis. FINDINGS: The primary motor cortex rapidly returns to a normal activation pattern after amputation followed by replantation or application of an osseointegrated prosthesis. The primary somatosenory cortex changes from an initial ipsilateral to a bilateral activation pattern. Sensory stimulation of an osseointegrated prosthesis also shows a bilateral activation pattern in the primary somatosenory cortex. CONCLUSIONS: The primary motor cortex shows a more normal activation pattern possibly because most muscles controlling the hand are proximal to the injury and can be activated after an amputation. The primary somatosensory cortex reorganises more and the activation pattern is more bilateral compared to a healthy hand. This bilateral activation pattern could represent a compensatory mechanism for the inferior tactile function in the replanted hand and the osseointegrated prosthesis.

Enhanced sensory relearning after nerve repair by using repeated forearm anaesthesia: aspects on time dynamics of treatment.

BACKGROUND: We describe a new principle for enhancing the effects of sensory re-education following nerve injury and repair. The outcome from nerve repair in adult patients is generally poor. One reason is the functional cortical reorganisation which always occurs because of axonal misdirection at the repair site. In healthy individuals selective anaesthesia of the forearm results in improved hand sensation. Here we hypothesised that this principle would be valid also after nerve injury and repair. METHOD: In a prospective, randomised, double blind study we studied the effects of cutaneous forearm anaesthesia combined with sensory reeducation on the outcome after median or ulnar nerve repair at wrist or distal forearm level. FINDINGS: EMLA-application four times over a two week period starting with beginning reinnervation of the fingers resulted in significantly improved sensory recovery (tactile gnosis) as compared to the placebo group and also at assessment four weeks after the last EMLA-session. However, at assessment 8-11 months after the first EMLA-treatment there was no difference between the groups. CONCLUSIONS: Our findings indicate that repeated cutaneous forearm anaesthesia over a two week period can enhance the effects of sensory re-education at least over the four following weeks. However, the optimal time protocol for EMLA-treatment, aiming at a long-lasting or permanent effect on sensory recovery still has to be defined.

Hand function after nerve repair.

Treatment of injuries to major nerve trunks in the hand and upper extremity remains a major and challenging reconstructive problem. Such injuries may cause long-lasting disabilities in terms of lost fine sensory and motor functions. Nowadays there is no surgical repair technique that can ensure recovery of tactile discrimination in the hand of an adult patient following nerve repair while very young individuals usually regain a complete recovery of functional sensibility. Post-traumatic nerve regeneration is a complex biological process where the outcome depends on multiple biological and environmental factors such as survival of nerve cells, axonal regeneration rate, extent of axonal misdirection, type of injury, type of nerve, level of the lesion, age of the patient and compliance to training. A major problem is the cortical functional reorganization of hand representation which occurs as a result of axonal misdirection. Although protective sensibility usually occurs following nerve repair, tactile discriminative functions seldom recover--a direct result of cortical remapping. Sensory re-education programmes are routinely applied to facilitate understanding of the new sensory patterns provided by the hand. New trends in hand rehabilitation focus on modulation of central nervous processes rather than peripheral factors. Principles are being evolved to maintain the cortical hand representation by using the brain capacity for visuo-tactile and audio-tactile interaction for the initial phase following nerve injury and repair (phase 1). After the start of the re-innervation of the hand (phase 2), selective de-afferentation, such as cutaneous anaesthesia of the forearm of the injured hand, allows expansion of the nerve-injured cortical hand representation, thereby enhancing the effects of sensory relearning. Recent data support the view that training protocols specifically addressing the relearning process substantially increase the possibilities for improved functional outcome after nerve repair.

Enhanced sensory recovery after median nerve repair using cortical audio-tactile interaction. A randomised multicentre study.

The "Sensor Glove System" offers an alternate afferent inflow from the hand early after nerve repair in the forearm, mediated through the hearing sense, implying that deprivation of one sense can be compensated by another sense. This sensory "by-pass" was used early after repair of the median nerve with the intention of improving recovery of functional sensibility by maintaining an active sensory map of the hand in the somatosensory cortex during the deafferentation period. In a prospective multicentre clinical study, one group (n=14) started early after surgery with sensory re-education using the Sensor Glove System and the control group (n=12) received conventional sensory re-education, starting 3 months postoperatively. The patients were checked regularly during a 1-year period, with focus on recovery of tactile gnosis. After 12, months, tactile gnosis was significantly better in the Sensor Glove System group. This highlights the timing for introduction of training after nerve repair, focusing on the importance of immediate sensory re-learning.

Improved sensory relearning after nerve repair induced by selective temporary anaesthesia - a new concept in hand rehabilitation.

The outcome after nerve repair in adults is generally poor. We hypothesized that forearm deafferentation would enhance the sensory outcome by increasing the cortical hand representation. A prospective, randomized, double-blind study was designed to investigate the effects of cutaneous forearm anaesthesia combined with sensory re-education on the outcome after ulnar or median nerve repair. During a 2 week period, a local anaesthetic cream (EMLA (n = 7) or placebo (n=6) was applied repeatedly onto the flexor aspect of the forearm of the injured arm and combined with sensory re-education. Evaluation of sensory function was carried out at regular intervals and at 4 weeks after the last EMLA/placebo session. The EMLA group showed significant improvement compared to placebo in perception of touch/pressure, tactile gnosis and in the summarized outcome after 6 weeks. These results suggest that cutaneous forearm anaesthesia of the injured limb, in combination with sensory re-education, can enhance sensory recovery after nerve repair.

Classification of motor commands using a modified self-organising feature map.

In this paper, a control system for an advanced prosthesis is proposed and has been investigated in two different biological systems: (1) the spinal withdrawal reflex system of a rat and (2) voluntary movements in two human males: one normal subject and one subject with a traumatic hand amputation. The small-animal system was used as a model system to test different processing methods for the prosthetic control system. The best methods were then validated in the human set-up. The recorded EMGs were classified using different ANN algorithms, and it was found that a modified self-organising feature map (SOFM) composed of a combination of a Kohonen network and the conscience mechanism algorithm (KNC) was superior in performance to the reference networks (e.g. multi-layer perceptrons) as regards training time, low memory consumption, and simplicity in finding optimal training parameters and architecture. The KNC network classified both experimental set-ups with high accuracy, including five movements for the animal set-up and seven for the human set-up.

Herd-level risk factors for infectious diseases in Swedish dairy calves aged 0-90 days.

The effect of environmental factors and management routines on the risk of diarrhoea, respiratory disease and other infectious diseases was investigated in 3081 heifer calves 0-90 days old in 122 Swedish dairy herds. The farmers kept records on cases of diseases in their heifer calves and in addition, project veterinarians clinically examined all calves every 2-3 months. At each visit, the veterinarians also measured the ammonia concentration and relative air humidity in the housing facilities for the calves. The cleanliness of the animals and their environment was recorded as a measure of the hygienic status of the farm. The presence or absence of draught (i.e. wind velocity>0.5 m/s) was recorded twice during the study period. The effect of these factors, as well as the placing of the calf pens, the nature of the pen walls, air volume per animal, management factors (such as the status of the caretaker and feeding routines) and presence or absence of a bovine viral diarrhoea virus (BVDV) infection in the herd, was evaluated by means of a two-level variance component logistic model. The placing of calf pens along an outer wall was significantly associated with the risk of diarrhoea (odds ratio (OR): 1.92, P<0.01). The risk for respiratory disease was significantly associated with an ammonia concentration below 6 ppm (OR: 0.42, P<0.05) while the odds ratio for moderately to severely increased respiratory sounds was significantly associated with a BVDV infection in the herd (OR: 2.39, P<0.05) and draught (OR: 3.7, P<0.02). Absence of draught was significantly associated with the risk for infectious diseases other than diarrhoea and respiratory disease (OR: 0.42, P<0.01).

Injury to the human median and ulnar nerves in the forearm--analysis of costs for treatment and rehabilitation of 69 patients in southern Sweden.

This study analysed the costs of median and ulnar nerve injuries in the forearm in humans and factors affecting such costs. The costs within the health-care sector and costs of lost production were calculated in 69 patients with an injury to the median and/or ulnar nerve in the forearm, usually caused by glass, a knife, or a razorblade. Factors associated with the variation in costs and outcome were analysed. The total median costs for an employed person with a median and an ulnar nerve injury were EUR 51,238 and EUR 31,186, respectively, and 87% of the total costs were due to loss of production. All costs were higher for patients with concomitant tendon injuries (4 tendons). The costs within the health-care sector were also higher for patients who changed work after the injury and if both nerves were injured. Outcome was dependent on age and repair method.

The two-point discrimination test--time for a re-appraisal?

The two-point discrimination (2PD) test is the most frequently used test for the assessment of the sensory outcome after nerve repair. Here we focus on factors which explain the enormous and implausible variability in reported 2PD levels after nerve repair. We conclude that the 2PD testing technique is not at all standardized and that its use as the sole test for tactile gnosis recovery should be seriously questioned. Reports of 2PD results should always be accompanied by a detailed description of how the test was performed, especially with reference to the pressure applied and the testing protocol.

Alternatives to autologous nerve grafts.

The use of autologous nerve grafts for bridging defects in nerve continuity requires the sacrifice of healthy nerves. Development of alternatives to autologous nerve grafts is therefore well motivated. Such "bioartificial nerve grafts" can be tissue-engineered on the basis of the use of a stroma/matrix/scaffold acting in concert with cells and neurotrophic factors. Such a scaffold can be of synthetic or biological nature and can be resorbable or non-resorbable. It should act together with Schwann cells which can be pre-cultured or acutely dissociated. Neurotrophic factors, stimulating axonal growth, can be incorporated in the scaffold and can also be supplied by cells which are seeded into the stroma. So far, tissue-engineered nerve conduits have been used mainly for experimental purposes in experimental animals. However, an increasing amount of experience from the clinical use of alternatives to nerve grafts now exists, mainly tubes made of silicone or poly-glycolic acid (PGA), veins, collagen and muscle basal laminae.

Sensory re-education after nerve repair: aspects of timing.

The recovery of functional sensibility after nerve transection and repair is often disappointing. Here we address the timing of sensory re-education that aims at re-learning and modulating the changed sensory code from the hand after such an injury. Such training utilises the capacity for cortical functional re-modelling which characterises the young as well as the adult brain. Sensory re-education is traditionally not introduced until there is reinnervation in the hand, and such a late onset of training may be one explanatory factor for the poor functional results after nerve repair. Since functional reorganisation changes of the cortex occurring after changes in peripheral input are very fast processes, we suggest that this specific intervention should be introduced very early in the rehabilitation phase--already in the initial phase after nerve repair when no axons have yet arrived to the asensible hand. The goal is to avoid, minimise and modulate the central functional re-organisation which follows the de-afferentiation associated with nerve injury and repair. This early intervention can be done with the use of artificial sensibility the first post-operative day. According to this technique, based on sense substitution and utilising the multimodal capacity of the brain, miniature microphones on the fingertips of the asensible hand pick up the friction sound generated by active touch. The vibro-tactile signals are stereophonically transposed to vibro-acoustic signals, thereby providing an alternate feed-back which hypothetically helps to maintain or re-establish the cortical hand map.

Tubular repair of the median or ulnar nerve in the human forearm: a 5-year follow-up.

The long-term outcome from silicone tube nerve repair was compared with the outcome from routine microsurgical repair in a clinical randomized prospective study, comprising 30 patients with median or ulnar nerve injuries in the distal forearm. Postoperatively, the patients underwent neurophysiological and clinical assessments of sensory and motor function regularly over a 5-year period. After 5 years there was no significant difference in outcome between the two techniques except that cold intolerance was significantly less severe with the tubular technique. In the total group there was ongoing improvement of functional sensibility throughout the 5 years after repair. It is concluded that tubular repair of the median and ulnar nerves is at least as good as routine microsurgical repair, and results in less cold intolerance.

Dam-related effects on heart girth at birth, morbidity and growth rate from birth to 90 days of age in Swedish dairy calves.

We investigated the effects of dam-related factors (such as calving performance, milk leakage, diseases, milk production, and somatic-cell count (SCC)) on heart girth at birth and the incidence risk of diarrhoea and respiratory disease during the first 90 days in Swedish dairy calves. The effects of these dam-related factors and environmental and management-related (but not dietary) factors on the calves' growth rate during the first 90 days of life also were analysed. The study used nearly 3,000 heifer calves born in 1998 on 122 farms in the south-west of Sweden. Individual health records were kept by the farmers and visiting project veterinarians. The calf's heart girth was measured at birth and weaning. We used generalised linear mixed models for the size of the calf at birth and growth rate. Variables associated with the heart girth at birth were breed, calving performance, mastitis in the dam in the last 49 days before calving, milk production and parity. Variables associated with the growth rate were breed, calving performance, disease in the calf during its first 90 days of life, heart girth at birth, and housing of calves. The effect of the dam on the relative risk of diarrhoea and/or respiratory disease in the calf was evaluated by a generalised linear mixed model with a logit link. Morbidity in the dam during late pregnancy, retained placenta and SCC were associated with the relative risk of respiratory disease in the calf. None of the explanatory variables (other then breed) was associated with the relative risk of diarrhoea.

What determines the costs of repair and rehabilitation of flexor tendon injuries in zone II? A multiple regression analysis of data from southern Sweden.

The epidemiology and costs of repair and rehabilitation of zone II flexor tendon injuries in 135 patients from the southern part of Sweden were analysed. The little finger was most frequently injured (43%), usually with a knife (46%), and 30% of the injuries were work related. Total median costs within the health-care sector for the injuries were SEK 48,500 (1 EURO=9.23 SEK, 4/1/2002). Costs in other sectors were SEK 93,000. Active mobilization or mobilization with rubber band traction increased costs within the health-care sector (SEK 7400 or SEK 6000, respectively) but improved range of movement (5-7%). Immobilization had a higher complication rate (rupture or need for secondary procedures), which in itself increased total costs by 57%. Non-linear effects were found between age and costs within the health-care sector and the outcome.

Hand function tests and questions on hand symptoms as related to the Stockholm workshop scales for diagnosis of hand-arm vibration syndrome.

The severity of hand-arm vibration syndrome (HAVS) is usually graded according to the Stockholm workshop scales. Although the Stockholm workshop scales are regarded the gold standard for assessing the severity of HAVS, they are based primarily on subjective symptoms. The aim of the present study was to explore the agreement between Stockholm workshop scales and the outcome from ten well-defined clinical tests commonly used in hand rehabilitation for assessment of hand function. One hundred and eleven vibration-exposed workers participated in the study. Ten objective tests of hand function and four questions on subjective hand symptoms were included. The results indicated that, out of these tests, perception of vibration, perception of touch/pressure and dexterity showed a moderate agreement with Stockholm workshop scales. Among specific questions on hand symptoms, cold intolerance and pain showed a high agreement with Stockholm workshop scales. It is concluded that defined objective tests combined with directed questions on specific hand symptoms, together with the Stockholm workshop scales, may be helpful for diagnosing HAVS.

Hand-arm-vibration syndrome (HAVS): is there a central nervous component? An fMRI study.

Hand-held vibrating tools may result in neuromuscular dysfunction and vasospastic problems of the hand. Sensory and motor dysfunction can be explained by injury to peripheral structures, but could also be due to changes in cortical somatotopic mapping of the hand in the brain. The purpose of the present study was to use functional magnetic resonance imaging (fMRI) to assess the somatotopic cortical representation of the hands of workers subjected to occupational vibration. The study included six men with severe vibration exposures who were suffering from hand-arm-vibration syndrome (HAVS) and six controls. The analysis focused on the pattern and degree of activation of contra- and ipsilateral hemispheres of the brain with tactile stimulation and motor activation of the hand. These stimulations resulted in well-defined activation of the contralateral, and to a lesser extent the ipsilateral hemisphere. Statistical analysis of this limited patient material did not indicate any significant somatotopic cortical changes following long-term exposure to vibrating hand-held tools, although there was a tendency to a shift of activation towards the more cranial parts of the cortex in the patient group.

Hand muscle weakness in long-term vibration exposure.

Hand muscle strength was compared between workers regularly exposed to hand-held vibrating tools (n=81) and a non-exposed control group (n=45). Maximal voluntary strengths of hand grip, thumb pinch, thumb palmar abduction and index and little finger abduction were measured. The exposed workers had significantly weaker extrinsic (7%, P<0.01) and intrinsic (19%, P<0.0001) muscles than the controls. Reduced vibration perception was noted in nine vibration-exposed workers who presented with symptoms of hand muscle weakness (P<0.01). Cold intolerance following vibration exposure was found to precede sensorineural and vasospastic symptoms. We therefore postulate that cold intolerance may be a valuable marker for early detection of the adverse effects of vibration. This study emphasizes the need for tests of intrinsic muscle strength in order to evaluate the impairment of hand function observed in vibration-exposed workers.