Signs Of Reinnervation Research Articles

Restoration of elbow flexion after brachial plexus injury by free functional rectus femoris muscle transfer

A 22-year-old patient sustained a complex injury of the left brachial plexus. Primary brachial plexus reconstruction did not lead to any functional recovery. Twenty-six months later, the patient showed an upper brachial plexus palsy, which precluded the possibility for a latissimus dorsi muscle transfer. To re-establish elbow flexion, a free myocutaneous neurovascular rectus femoris flap, harvested from the left thigh, was neurotised to the accessory nerve using a sural nerve graft. Ten months after the free functional rectus femoris transfer, early electromyographic results were detected, and 7 months later, strong reinnervation signs occurred. Due to dissatisfaction with the aesthetic results including an impression in the left shoulder and pectoral region, two silicon implants were inserted 41 months after rectus femoris muscle transfer. A few hours after the operation, the patient experienced palsy of the transplanted muscle. The silicon implants were removed immediately. Initial recovery of muscle function was detected by electromyography 4 months later and complete reinnervation was observed 8 years postoperative. Elbow flexion was rated M4, and the patient had no functional donor-site morbidity. The authors conclude that free rectus femoris muscle transfer offers excellent results when effort is put into postoperative rehabilitation with extensive training programs.

Long-term Results After Microsurgical Repair of Traumatic Nerve Lesions of the Upper Extremities

Peripheral nerve injuries are still underestimated. This study examines the outcomes after surgical treatment of traumatic nerve lesions of the upper extremities. The different surgical techniques are analyzed with regard to the long-term outcome. This retrospective study presents the data of 93 patients (female: 24; male: 69) who were operated on for peripheral nerve injuries of the upper extremities in our department between 1991 and 2003. Mean age was 31 years (range, 5-67 years). Altogether 100 traumatic nerve lesions (ulnar nerve: 20; radial nerve: 22; median nerve: 25; axillary nerve: 6; accessory nerve: 7; musculocutaneous nerve: 2; long thoracic nerve: 1; digital nerve: 3; combined nerves: 7) were surgically treated. Surgical management included primary nerve suture in 16, neurolysis in 25, and nerve grafting in 59 patients. 74 patients (80%) were available for follow-up examination. The mean follow-up period was 35 months (range, 18-132 months). All patients up to the age of 20 years demonstrated good or excellent sensorimotor recovery. A good functional outcome was observed in 79% of the patients older than 20 years. Overall, good to excellent improvements of motor function were achieved for lesions of the musculocutaneous, radial, accessory and axillary nerves (100%, 89%, 100%, 100% functional useful muscle innervation, muscle recovery grade 3 and more). The length of grafts, in cases of secondary nerve reconstruction, did not influence functional outcome. Generally, early surgical repair of a nerve lesion predicted a better outcome. A good functional motor recovery was dependent on the age of the patient. Traumatic nerve lesions, without signs of reinnervation, should be treated surgically within a period of three months after injury.

Mechanisms behind the postprandial increase in cardiac output: a clue obtained from transplanted hearts

Consumption of a meal is followed by an increase in cardiac output (CO) which appears to be closely related to the concomitant increase in blood flow to the gastrointestinal organs. To gain information on the mechanism behind this increase in CO we have previously used Doppler ultrasound technique to record circulatory responses to a standardized meal in five patients with recently transplanted and thus denervated hearts. We obtained the surprising result that they reacted to the consumption of a meal with a greater increase in CO than did five matched normal controls. The patients also presented above-normal levels of heart rate (HR) and CO at rest. The same five patients have now been tested 18 months later to re-examine their remarkable cardiac response to ingestion of a meal. The hearts of two patients showed some signs of reinnervation, whereas the hearts of the other three were apparently still fully denervated. However, all five patients once again evolved a marked cardiac response to ingestion of a meal. Postprandial CO reached significantly higher levels in the patients than in the controls. The persistence of such a pronounced postprandial augmentation of CO in transplanted and largely denervated hearts strengthens the assumption that the heart is induced to increase its postprandial performance through the action of a humoral agent of some sort, possibly one of the hormones from the duodenal-pancreatic region.

Diagnosis of Unilateral Recurrent Laryngeal Nerve Paralysis: Laryngeal Electromyography, Subjective Rating Scales, Acoustic and Aerodynamic Measures

To determine whether specific laryngeal electromyography (LEMG) patterns in patients with unilateral vocal fold paralysis/paresis (UVFP) are related to etiology of injury, time from onset of injury, patient perception of symptom severity, acoustic measures, and laryngeal aerodynamic measures. This is a retrospective review of 75 patients. Each patient received LEMG, acoustic and aerodynamic testing, and a subjective rating scale assessment (the Glottal Closure Index). Statistical analysis by groups were performed using both chi and single-factor analysis of variance testing. An iatrogenic etiology was associated with poor tone on LEMG (P = .05). Those individuals evaluated after 3 months after onset demonstrated more nascent units, a sign of reinnervation, compared with individuals evaluated before 3 months (P < .02). Individuals with fewer normal motor units on LEMG had significantly higher mean translaryngeal air flows (P = .044). Individuals with poor recruitment had significantly shorter maximum phonation times (P = .034) and higher mean flows (P = .044). Individuals with better laryngeal tone as noted on LEMG had significantly lower mean flows (P = .06). Specific LEMG patterns are related to the etiology of the UVFP and time course since recurrent laryngeal nerve injury. LEMG appears to reflect vocal fold muscle tone as seen on laryngeal function studies. In combination, these studies provide a cohesive assessment of laryngeal function in patients with UVFP.

Peripheral nerve palsy in a case of leptospirosis

We describe an unusual case of leptospirosis in a 54-year-old man presenting peripheral nerve palsy. The diagnosis of leptospirosis was confirmed by ELISA IgM and the microscopic agglutination test. Electrophysiological studies showed that no response could be obtained from the right fibular nerve. At 7 months after the initiation of treatment, additional electrophysiological studies and a neurological examination showed, respectively, a chronic axonal lesion of right fibular nerve with signs of re-innervation and a nearly complete clinical recovery. We feel that this case may serve to remind clinicians that peripheral nerve palsy is a potential clinical feature of leptospirosis.

Arterial Stiffening Influence of Sympathetic Nerve Activity

Studies in animals and humans suggest that sympathetic activity exerts a stiffening influence on large and middle-sized artery walls. We sought to obtain further evidence on this issue by measuring radial artery distensibility in an allotransplanted and thus denervated hand using the contralateral artery as control. In 2 men, blood pressure was measured by a semiautomatic device (Dinamap). Diastolic diameter, systo-diastolic diameter excursion (ultrasound Wall Track system), and distensibility (Reneman formula) of both radial arteries were measured at a level corresponding to 4 cm below the suture of the transplanted hand 40 days after surgery and every 4 weeks for the next 6 months. After surgery, systo-diastolic diameter excursion and distensibility were much greater in the transplanted radial artery than in the contralateral vessel, reaching values similar to the contralateral ones after 4 months, when signs of reinnervation of the transplanted hands had appeared. Radial deinnervation was accompanied by an increased arterial distensibility, which provides further evidence of the sympathetic stiffening effect on arterial wall in humans.

Different Evolutions in Heart Rate Variability after Heart Transplantation: 10-Year Follow-Up

After heart transplantation, the donor heart is extrinsically denervated. No input of sympathetic or vagal nerves can influence the heart rate, resulting in a flat power spectrum of the beat-to-beat variability. The occurrence and the significance of reinnervation remain controversial. We monitored the evolution of heart rate variability (HRV) after heart transplantation, starting from a few weeks postoperatively up to 10 years after surgery. Twenty-four-hour Holter recordings of 216 heart-transplant patients were analyzed using time and frequency domain analysis of HRV. Analysis of all data revealed an increase in 24-hour and night-time total power starting from 2 years after transplantation. Low-frequency oscillations calculated over the total 24 hours, day- and nighttime increased significantly starting from year 4 and onward (year 4-8: P < 0.005). No evolution was found in high-frequency power. Subgroup analysis revealed a group with a clear spectral component (n = 16), a group with a small component (n = 124), and a group with a flat spectrum (n = 76). Only the first group revealed an evolution in both high- and low-frequency power. These results indicate three different types of evolution in HRV, with reinnervating patterns present in only a minority of the patients. The vast majority of the patients show no signs of reinnervation.

Reinnervation of motor units in intrinsic muscles of a transplanted hand

Functional recovery of transplanted hand can be evaluated clinically but until now there has been no direct assessment of muscle control. In October 2000 we transplanted the right hand of a brain-dead man aged 43 onto a man aged 35 who had lost his right dominant hand 22 years before. Starting from day 205 after the transplant, multi-channel surface electromyographic (EMG) signals were recorded from intrinsic muscles of the transplanted hand in order to assess their degree of reinnervation. Eleven months post-operatively, the first motor unit action potential train was detected from the abductor digiti minimi. One month later, also the abductor pollicis brevis and the opponens pollicis muscles showed motor unit activity, while, after 15 and 24 months, the first dorsal interosseous and the first lumbricalis muscles, respectively, showed activation of their first motor units. An increase in the number of active motor units was observed after the first signs of reinnervation, although the process was rather slow. In sustained maximal contractions, the motor unit discharge rate decreased from (mean ± S.D.) 34.0 ± 6.7 pps to 23.4 ± 5.1 pps in 60 s for the abductor digiti minimi, although the subject was verbally encouraged to maintain a maximal activation. Moreover, the subject was able to perform basic control tasks involving voluntary modulation of motor unit discharge rate. With a visual feedback, he could increase discharge rate of the abductor digiti minimi approximately linearly over time, from 13.4 ± 6.7 pps to 32.5 ± 11.2 pps in 60 s. In conclusion, we showed reinnervation of single motor units in a transplanted hand after 22 years of denervation. Moreover, voluntary modulation of discharge rates of these motor units could be performed since the first sign of reinnervation.

Recovery of Mechanoreception at the Initial Stage of Regeneration of Injured Sciatic Nerve in Rats in Conditions of Central Axotomy of Sensory Neurons

The ability of injured afferents of the rat sciatic nerve to regenerate in conditions of damage to their connections with the central nervous system (CNS) as a result of extensive rhizotomy was studied. Recording of spike activity from single nerve fibers demonstrated that rhizotomy, performed simultaneously with nerve injury, had virtually no effect on the initiation of regenerative processes in sensory nerve fibers. The first clear signs of reinnervation of the skin of the foot by decentralized nerve fibers was seen 30 days after nerve injury, which agrees with data obtained in standard conditions, i.e., without rhizotomy. Decentralization of sensory neurons was found to lead to increases in the threshold of perception of a mechanical stimulus in intact and regenerating receptors. However, regenerating receptors showed a significantly more marked decrease in stimulus sensitivity.

Sleep as a tool for evaluating autonomic drive to the heart in cardiac transplant patients.

The aim of this study was to investigate the autonomic drive to the heart in cardiac transplant patients (CTP) using heart rate (HR) and HR variability (HRV) analysis during non-rapid eye movement (NREM)-rapid eye movement (REM) sleep cycles, in particular during arousal associated with the emergence from slow wave sleep (SWS). In healthy subjects, this arousal is characterized by a pronounced HR surge, and HRV is lower during SWS than during the subsequent "active" sleep stage 2 and REM sleep. The participants were 24 adults, 14 CTP (men, n = 11; women, n = 3; mean age, 62.2 +/- 2.2 years; time after transplantation, 4-14 years) and 10 control subjects (men, n = 7; women, n = 3; mean age, 61.0 +/- 1.8 years). The subjects underwent polygraphic sleep, cardiac, and respiratory recordings during an experimental night. HR was measured during the arousal. HRV was estimated from the R-R intervals in 5-minute stationary segments preceding and following arousal, ie, during SWS and active sleep stage 2 from the first 2 complete NREM-REM sleep cycles. In controls, HR increased during arousal associated with the emergence from SWS during the 2 sleep cycles (P < .05). Sleep-stage-dependent increases of all HRV indexes were observed in the 2 sleep cycles. Concerning CTP, 5 of them displayed a smaller HR increase at arousal, whereas 9 other patients had no HR variation. This distinction between the 2 groups of CTP was confirmed by HRV analysis. The patients with HR reactivity to arousal presented significant sleep-stage-dependent increases in global HRV and sympathetic HRV indexes, whereas the nonreactive group was characterized by an inability of HRV to change with sleep-stage alternation. Sympathetic HRV indexes were significantly higher in the reactive patients than in nonreactive patients, but high frequency power reflecting parasympathetic activity did not differ. However, the absolute HRV indexes were greatly decreased in both groups of patients compared to controls. HR reactivity during arousal associated with the emergence from SWS, corroborated by HRV surrounding arousal, may suggest a partial improvement of the sympathetic drive to the heart in some CTP, with no indication of increased parasympathetic activity. Other signs of reinnervation have to be identified to validate this hypothesis.

Evaluation of suprascapular nerve neurotization after nerve grafting or transfer in the treatment of brachial plexus traction lesions

Object The aim of this retrospective study was to evaluate the restoration of shoulder function by means of supra-scapular nerve neurotization in adult patients with proximal C-5 and C-6 lesions due to a severe brachial plexus traction injury (BPTI). The primary goal of brachial plexus reconstructive surgery was to restore the biceps muscle function and, secondarily, to reanimate shoulder function. Methods Suprascapular nerve neurotization was performed by grafting the C-5 nerve in 24 patients and by accessory or hypoglossal nerve transfer in 29 patients. Additional neurotization involving the axillary nerve could be performed in 18 patients. Postoperative needle electromyography studies of the supraspinatus, infraspinatus, and deltoid muscles showed signs of reinnervation in most patients; however, active glenohumeral shoulder function recovery was poor. In nine (17%) of 53 patients supraspinatus muscle strength was Medical Research Council (MRC) Grade 3 or 4 and in four (8%) infraspinatus muscle power was Grade 3 or 4. In 18 patients in whom deltoid muscle reinnervation was attempted, MRC Grade 3 or 4 function was demonstrated in two (11%). In the overall group, eight patients (15%) exhibited glenohumeral abduction with a mean of 44 ± 17° (standard deviation [SD]) (median 45°) and four patients (8%) exhibited glenohumeral exorotation with a mean of 48 ± 24° (SD) (median 53°). In only three patients (6%) were both functions regained. Conclusions The reanimation of shoulder function in patients with proximal C-5 and C-6 BPTIs following supra-scapular nerve neurotization is disappointingly low.

Severe Peripheral Neuropathy With Areflexic and Flaccid Quadriplegia Complicating Legionnaires' Disease in an Adult Patient

Severe Peripheral Neuropathy With Areflexic and Flaccid Quadriplegia Complicating Legionnaires' Disease in an Adult Patient

Sensory Reinnervation of Myocutaneous Flaps Revealed by Infrared Laser Evoked Sensations and Brain Potentials

The aim of this study was to examine the recovery of sensory function in myocutaneous flaps comparing 2 test methods. Eight flaps in 7 patients were examined by using clinical neurological test procedures (CNT) in comparison with psychophysics and evoked brain potentials (LEP) following infrared laser stimuli. The authors found that only 3 out of 8 flaps in 7 patients exhibited signs of reinnervation when tested with CNT. Three grades of reinnervation appeared in 7 flaps when tested with the laser. Grade 1 indicated the recovery of unmyelinated C-fiber function in 7 flaps accounting for the ability to discriminate laser intensities by different degrees of warmth. Grade 2 appeared in 3 of these flaps and was characterized by the additional ability to sense pinprick pain and the elicitation of late components of LEP mediated by thinly myelinated Aγ-nociceptors. Grade 3 involved the additional sensibility for superficial touch indicating the recovery of thickly myelinated Aβ-fibers noted in 2 of these flaps. The authors conclude that the LEP method is more sensitive than standard neurological test procedures to objectively document early signs of reinnervation after reconstructive flap surgery. This result is promising to investigate greater patient populations comparing different surgical techniques in future studies.

93rd ENMC international workshop: non-5q-spinal muscular atrophies (SMA) – clinical picture (6–8 April 2001, Naarden, The Netherlands)

This 93rd SMA workshop followed the European Neuromuscular Centre (ENMC) tradition to combine clinical and molecular topics with the aim of not only exchanging current knowledge but also initiating collaborative studies. Despite important milestones in research on autosomal recessive SMA with localisation on chromosome 5q (SMA 5q) in the past 10 years, we are just beginning to understand the molecular basis and phenotypic spectrum of non-5q-SMA entities. The possibility of analysing the SMN gene allowed the delineation of the diagnostic criteria of ‘classical’ proximal SMA and its clinical variability. On the other hand, different entities of SMA could be defined that show atypical features and proved to be unlinked to chromosome 5q. The field of interest has therefore been focussed on further genes responsible for anterior horn cell loss. This will contribute to further understand the underlying pathogenetic pathways, the complex protein interactions and genotype–phenotype correlations in various types of motor neuron disorders. The workshop was structured in a first part, briefly reviewing the current status of SMA 5q including animal models which have been generated. The second part included different sessions on non-5q-SMA forms; clinical and diagnostic criteria were discussed and adapted to current knowledge. These were summarized by invited chairpersons (named in brackets) and followed by contributions of the participants. The following short summaries cover the essentials of the reviews, the discussion and the consensus achieved. 1. Update on SMA 5q

Assessment of war and accidental nerve injuries in children

Eleven children with war-related peripheral nerve injury and 16 children with accident-related nerve injury between the ages of 3 and 15 years were assessed clinically and electromyoneurographically for 1-15 months. Lesions of 32 peripheral nerves were registered in children with war injuries. Children with accidentally acquired injuries had lesions of 27 peripheral nerves. A complete loss of voluntary motor unit potentials and signs of total axonal damage were recorded in the upper arms of seven of 11 children with war injuries and in five of 16 children with accidental injuries. There was a diminished number of motor unit potentials and a reduction in compound muscle action potential amplitudes, indicating partial nerve lesions, in 11 of 16 children with accidental injuries (mostly after humeral fracture) and in three of 11 children with brachial plexus war injuries. Reinnervation signs first occurred after 5-9 months (mean = 6.2 months) in war-injured children receiving conservative treatment and after 2-7 months (mean = 3.4 months) in children with accidentally acquired injuries. War-related peripheral nerve injuries in children are more frequently associated with complete denervation followed by slower or delayed nerve regeneration. In children with accidentally acquired nerve injuries the course is significantly better.

Sección del nervio mediano en la muñeca

The usefulness of neurophysiological studies of peripheral nerves depends basically on an understanding of the physiopathology, especially of the evolutionary aspects of the phenomena of reinnervation. We present the case of a girl with complete section and immediate anastomosis of the two cut ends of the median nerve, at the wrist. Sixty two days later she had unmistakable signs of reinnervation (response in the thenar eminence to an electrical stimulus of 300 uV in amplitude and 42 ms in latency, with denervation and reinnervation on the EMG of the abductor pollicis brevis muscle). The findings in our patient show a rather faster rate of nerve regeneration than is usually accepted in the literature. This may have been due to suitable selection of some of the parameters of the neurophysiological study, such as time of analysis and sensitivity, which when not satisfactory may lead to an impression of failure or delay in reinnervation.

Evidence for differential sympathetic and parasympathetic reinnervation after heart transplantation in humans

During heart transplantation (HTX) all neural connections are severed. In humans, signs of autonomic reinnervation have been found. In this study non-invasive tests were used to compare signs of sympathetic and parasympathetic reinnervation. Non-invasive autonomic function tests and heart rate variability parameters (HRV; 24 h electrocardiographic registration) were used to investigate signs of reinnervation. 16 HTX patients (14 males) were compared with age- and sex-matched controls. Parasympathetic heart rate changes in HTX compared to controls were attenuated during the diving test, deep breathing, the Valsalva maneuver and standing up but not during carotid sinus massage. Sympathetic heart rate increases were lower during the cold presser test and mental stress. The blood pressure responses were comparable to the control group, but not during active standing and tilting. This finding suggests an obligatory `blood pressure' role for the innervated heart in these two tests. All HRV parameters were lower in HTX. One or more normal parasympathetic responses were found in 13 out of 16 patients versus 4 out of 16 with normal sympathetic responses ( p<0.05). Heart rate variations were less in case of a higher donor age, and higher in case of a longer time after HTX. Parasympathetic signs of reinnervation are more common than sympathetic signs of reinnervation. A higher donor age reduces signs of reinnervation. If the sympatho-vagal balance is a prognostic factor in HTX patients as it is in other cardiac diseases these findings are clinically relevant.

Inclusion body myositis: no evidence for a neurogenic component.

Because electrophysiologic, clinical, and histopathologic observations have suggested that inclusion body myositis (IBM) may have a coexistent neurogenic component, we used macro-electromyography (macro-EMG) to search for changes in the motor unit territory and signs of reinnervation. We studied 11 patients, aged 53 to 77 years (mean, 65.2 years), with typical, nonfamilial IBM lasting a mean of 8.5 years, and eight healthy volunteers aged 54 to 70 years (mean, 64.6 years), as control subjects. Nerve conduction studies showed focal abnormalities in 5 of the patients, but no evidence of a polyneuropathy. Concentric needle EMG in various proximal and distal muscles of the upper and lower limbs revealed short- or long-duration complex motor unit potentials (MUPs) or a mixture of both types of MUPs. Macro-EMG studies in the tibialis anterior muscle showed smaller macro-MUP amplitudes and areas in patients than in normal subjects. Four patients had abnormal macro-EMG studies with an increased number of small macro-MUPs, 1 patient had an equivocal study with large-amplitude but normal-area macro-MUPs, and the remaining 6 patients had normal studies. These findings are consistent with a primary muscle disorder similar to those seen in other myopathies. We conclude that macro-EMG does not support a coexistent neurogenic component in patients with IBM compared with normal subjects of similar age.

Photoinactivation of an identified motoneurone in the locust Locusta migratoria.

1. The common inhibitory motoneurone 1 (CI1) in the mesothoracic ganglion of the locust was photoinactivated using a helium-cadmium laser or a mercury lamp as light source. Treated animals showed no signs of abnormal locomotory behaviour over periods of up to 40 days. 2. Photoinactivation of part of the neurone in the ganglion, i.e. the soma and the primary neurite, is sufficient to cause irreversible degeneration of all the peripheral extensions of the neurone. Three weeks after photoinactivation, all GABA immunoreactivity had disappeared from the axon branches of the photoinactivated neurone and from their terminals on one of the target muscles investigated, the anterior coxa rotator M92, and inhibitory postsynaptic potentials could no longer be elicited through stimulation. This was taken as proof of functional denervation of the muscle with regard to its inhibitory input. By this time, the axon of CI1 in nerve N3C1, which supplies M92, had also disappeared. 3. Animals treated during the fourth or fifth instars showed a permanent loss of the photoinactivated mesothoracic CI1 neurone after moulting into adulthood. 4. Denervation of M92 in the middle legs of instars and adults by axotomy of N3 always led to rapid functional reinnervation of the muscle. The first sign of reinnervation (excitatory neuromuscular activity upon mechanical stimulation of the tarsi) was detected electrophysiologically as early as 8 days after severing the motor nerve. 5. The elimination of CI1 by photoinactivation for a period of up to 40 days did not influence parameters of the target muscle, such as size, number of fibres and phenotypes of fibres defined histochemically according to their myofibrillar ATPase isoforms, irrespective of whether the operation was performed in instars or adults. Similarly, the short period of denervation following axotomy before reinnervation took place did not affect the fibre type composition of the muscle.

Reflex sympathetic dystrophy: Skin blood flow, sympathetic vasoconstrictor reflexes and pain before and after surgical sympathectomy

To examine the pathophysiological mechanisms of vascular disturbances and to assess the role of the sympathetic nervous system, 12 patients with reflex sympathetic dystrophy (RSD) of the hand were studied using laser Doppler flowmetry. Cutaneous blood flow, skin resistance and skin temperature were measured at the affected and contralateral hands. Sympathetic vasoconstrictor reflexes were induced bilaterally by deep inspiration. Four patients were treated with unilateral surgical sympathectomy and pain and vascular changes were documented in follow-up investigations. (1) After acclimatization in cold environment (≤18 °C) blood flow and skin temperature were considerably lower on the affected side in 10 patients. No additional vasoconstrictor reflexes could be elicited. (2) After acclimatization in warm environment (22–24°C) blood flow and skin temperature demonstrated no side differences in all cases. Vasoconstrictor responses were the same on both sides. (3) After sympathectomy vasoconstrictor reflexes were absent. Skin resistance was considerably higher on the affected side. In the first 4 weeks the affected hand was warmer and blood flow was higher compared with the healthy side. Thereafter, skin temperature and perfusion slowly decreased and the affected hand turned from warm to cold. Very regular high amplitude vasomotion waves occurred unilaterally. There were no signs of reinnervation. Two patients had long-term pain relief. We conclude as follows. (1) Side differences in skin temperature and blood flow are no static descriptors in RSD. They are dynamic values depending critically on environmental temperature. Therefore, they have to be interpreted with care when defining reliable diagnostic criteria. (2) Vascular disturbances in RSD are not due to constant overactivity of sympathetic vasoconstrictor neurons. Changes in vascular sensitivity to cold temperature and circulating catecholamines may be responsible for vascular abnormalities. Alternatively, RSD may be associated with an abnormal (side different) reflex pattern of sympathetic vasoconstrictor neurons due to thermoregulatory and emotional stimuli generated in the central nervous system. (3) After sympathectomy, denervation supersensitivity of blood vessels and intense vasomotion may be associated with recurrence of pain in some patients.