Does prophylactic decompression of distal nerves following nerve repair improve functional recovery? A systematic review.

BACKGROUND: Peripheral nerve injuries are burdensome on healthcare systems, individuals and society as a whole. The current standard of treatment for neurotmesis is primary neurorrhaphy or nerve grafting. However, several patients do not recover their full function. There has been a suggestion that primary distal neurolysis at common entrapment sites maximises surgical outcomes; however, no guidelines exist on this practice. This scoping review aims to ascertain the existing evidence on prophylactic distal decompression of peripheral nerves following repair. METHODS: A literature search was performed using Ovid Medline, PubMed, Embase and Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews for studies published in the past 50 years. Studies were screened using a selection criteria and study quality was assessed using standardised tools. Furthermore, thematic content analysis was performed. RESULTS: Six studies were eligible for inclusion after screening; all studies were retrospective and at most level 3 evidence. No studies were designed specifically to assess the efficacy of distal neurolysis following proximal repair, thus no comparative data with control cohorts are available. All studies that recommended distal decompression of proximally repaired nerves based their conclusions on cases observed by the authors in practice or from theories on nerve regeneration. CONCLUSIONS: This systematic review suggests that the evidence on the role of immediate distal neurolysis in primary neurorrhaphy is inadequate. Recommendations are limited by the lack of large-scale and generalisable data. Further research is needed with definitive objective outcomes and patient-related outcome measures.

An assessment of fatigability following nerve transfer to reinnervate elbow flexor muscles.

AIMS: Improvements in the evaluation of outcomes following peripheral nerve injury are needed. Recent studies have identified muscle fatigue as an inevitable consequence of muscle reinnervation. This study aimed to quantify and characterize muscle fatigue within a standardized surgical model of muscle reinnervation. PATIENTS AND METHODS: This retrospective cohort study included 12 patients who underwent Oberlin nerve transfer in an attempt to restore flexion of the elbow following brachial plexus injury. There were ten men and two women with a mean age of 45.5 years (27 to 69). The mean follow-up was 58 months (28 to 100). Repeated and sustained isometric contractions of the elbow flexors were used to assess fatigability of reinnervated muscle. The strength of elbow flexion was measured using a static dynamometer (KgF) and surface electromyography (sEMG). Recordings were used to quantify and characterize fatigability of the reinnervated elbow flexor muscles compared with the uninjured contralateral side. RESULTS: The mean peak force of elbow flexion was 7.88 KgF (sd 3.80) compared with 20.65 KgF (sd 6.88) on the contralateral side (p < 0.001). Reinnervated elbow flexor muscles (biceps brachialis) showed sEMG evidence of fatigue earlier than normal controls with sustained (60-second) isometric contraction. Reinnervated elbow flexor muscles also showed a trend towards a faster twitch muscle fibre type. CONCLUSION: The assessment of motor outcomes must involve more than peak force alone. Reinnervated muscle shows a shift towards fast twitch fibres following reinnervation with an earlier onset of fatigue. Our findings suggest that fatigue is a clinically relevant characteristic of reinnervated muscle. Adoption of these metrics into clinical practice and the assessment of outcome could allow a more meaningful comparison to be made between differing forms of treatment and encourage advances in the management of motor recovery following nerve transfer. Cite this article: Bone Joint J 2019;101-B:867-871.

A quantitative assessment of the functional recovery of flexion of the elbow after nerve transfer in patients with a brachial plexus injury.

AIMS: Improvements in the evaluation of outcome after nerve transfers are required. The assessment of force using the Medical Research Council (MRC) grades (0 to 5) is not suitable for this purpose. A ceiling effect is encountered within MRC grade 4/5 rendering this tool insensitive. Our aim was to show how the strength of flexion of the elbow could be assessed in patients who have undergone a re-innervation procedure using a continuous measurement scale. METHODS: A total of 26 patients, 23 men and three women, with a mean age of 37.3 years (16 to 66), at the time of presentation, attended for review from a cohort of 52 patients who had undergone surgery to restore flexion of the elbow after a brachial plexus injury and were included in this retrospective study. The mean follow-up after nerve transfer was 56 months (28 to 101, standard deviation (sd) 20.79). The strength of flexion of the elbow was measured in a standard outpatient environment with a static dynamometer. RESULTS: In total, 21 patients (81%) gained MRC grade 4 strength of flexion of the elbow. The mean force of flexion was 7.2 kgf (3 to 15.5, sd 3.3). CONCLUSION: This study establishes that the dynamometer may be used for assessing the strength of flexion of the elbow in the outpatient department after nerve reconstructive surgery. Cite this article: Bone Joint J 2016;98-B:1517-20.

Mycolactone-mediated neurite degeneration and functional effects in cultured human and rat DRG neurons: Mechanisms underlying hypoalgesia in Buruli ulcer.

BACKGROUND: Mycolactone is a polyketide toxin secreted by the mycobacterium Mycobacterium ulcerans, responsible for the extensive hypoalgesic skin lesions characteristic of patients with Buruli ulcer. A recent pre-clinical study proposed that mycolactone may produce analgesia via activation of the angiotensin II type 2 receptor (AT2R). In contrast, AT2R antagonist EMA401 has shown analgesic efficacy in animal models and clinical trials for neuropathic pain. We therefore investigated the morphological and functional effects of mycolactone in cultured human and rat dorsal root ganglia (DRG) neurons and the role of AT2R using EMA401. Primary sensory neurons were prepared from avulsed cervical human DRG and rat DRG; 24 h after plating, neurons were incubated for 24 to 96 h with synthetic mycolactone A/B, followed by immunostaining with antibodies to PGP9.5, Gap43, ß tubulin, or Mitotracker dye staining. Acute functional effects were examined by measuring capsaicin responses with calcium imaging in DRG neuronal cultures treated with mycolactone. RESULTS: Morphological effects: Mycolactone-treated cultures showed dramatically reduced numbers of surviving neurons and non-neuronal cells, reduced Gap43 and ß tubulin expression, degenerating neurites and reduced cell body diameter, compared with controls. Dose-related reduction of neurite length was observed in mycolactone-treated cultures. Mitochondria were distributed throughout the length of neurites and soma of control neurons, but clustered in the neurites and soma of mycolactone-treated neurons. Functional effects: Mycolactone-treated human and rat DRG neurons showed dose-related inhibition of capsaicin responses, which were reversed by calcineurin inhibitor cyclosporine and phosphodiesterase inhibitor 3-isobutyl-1-Methylxanthine, indicating involvement of cAMP/ATP reduction. The morphological and functional effects of mycolactone were not altered by Angiotensin II or AT2R antagonist EMA401. CONCLUSION: Mycolactone induces toxic effects in DRG neurons, leading to impaired nociceptor function, neurite degeneration, and cell death, resembling the cutaneous hypoalgesia and nerve damage in individuals with M. Ulcerans infection.

Nerve injuries associated with supracondylar fractures of the humerus in children: our experience in a specialist peripheral nerve injury unit.

AIMS: We aimed to identify the pattern of nerve injury associated with paediatric supracondylar fractures of the humerus. PATIENTS AND METHODS: Over a 17 year period, between 1996 and 2012, 166 children were referred to our specialist peripheral nerve injury unit. From examination of the medical records and radiographs were recorded the nature of the fracture, associated vascular and neurological injury, treatment provided and clinical course. RESULTS: Of the 166 patients (111 male, 55 female; mean age at time of injury was seven years (standard deviation 2.2)), 26 (15.7%) had neurological dysfunction in two or more nerves. The injury pattern in the 196 affected nerves showed that the most commonly affected nerve was the ulnar nerve (43.4%), followed by the median (36.7%) and radial (19.9%) nerves. A non-degenerative injury was seen in 27.5%, whilst 67.9% were degenerative in nature. Surgical exploration of the nerves was undertaken in 94 (56.6%) children. The mean follow-up time was 12.8 months and 156 (94%) patients had an excellent or good clinical outcome according to the grading of Birch, Bonney and Parry. CONCLUSION: Following paediatric supracondylar fractures we recommend prompt referral to a specialist unit in the presence of complete nerve palsy, a positive Tinel's sign, neuropathic pain or vascular compromise, for consideration of nerve exploration. TAKE HOME MESSAGE: When managed appropriately, nerve recovery and clinical outcomes for this paediatric population are extremely favourable. Cite this article: Bone Joint J 2016;98-B:851-6.

Thoracic outlet syndromes in sport: a practical review in the face of limited evidence--unusual pain presentation in an athlete.

Despite thoracic outlet syndrome (TOS) being first described early in the 19th century, the subsequent literature seems limited, focusing on case reports and investigations providing little assistance in the management of equivocal presentations. Best practice clinical management, with little evidence base, poses great challenges for clinicians in deciding how to manage TOS, when to operate and which procedure should be undertaken. Furthermore, the implications of TOS and its surgical effects are poorly documented, with little evidence in the literature as to the impact of surgical intervention on athletes and their physiology or function. This paper describes a clinical example of TOS highlighting salient issues and examining the evidence to guide clinical management at each stage, in the case of a 26-year-old professional football player who suffered an acute onset of unilateral right shoulder to bicep pain associated with tingling in the hand. Clinicians managing similar cases in the future will have a reference point to assist their diagnosis, management and promote much needed research to further our understanding of this difficult syndrome.

Isolated latissimus dorsi transfer to restore shoulder external rotation in adults with brachial plexus injury.

In adults with brachial plexus injuries, lack of active external rotation at the shoulder is one of the most common residual deficits, significantly compromising upper limb function. There is a paucity of evidence to address this complex issue. We present our experience of isolated latissimus dorsi (LD) muscle transfer to achieve active external rotation. This is a retrospective review of 24 adult post-traumatic plexopathy patients who underwent isolated latissimus dorsi muscle transfer to restore external rotation of the shoulder between 1997 and 2010. All patients were male with a mean age of 34 years (21 to 57). All the patients underwent isolated LD muscle transfer using a standard technique to correct external rotational deficit. Outcome was assessed for improvement in active external rotation, arc of movement, muscle strength and return to work. The mean improvement in active external rotation from neutral was 24° (10° to 50°). The mean increase in arc of rotation was 52° (38° to 55°). Mean power of the external rotators was 3.5 Medical Research Council (MRC) grades (2 to 5). A total of 21 patients (88%) were back in work by the time of last follow up. Of these, 13 had returned to their pre-injury occupation. Isolated latissimus dorsi muscle transfer provides a simple and reliable method of restoring useful active external rotation in adults with brachial plexus injuries with internal rotational deformity.

Intra-operative neurophysiological prediction of upper trunk recovery in obstetric brachial plexus palsy with neuroma in continuity.

We investigated the predictive value of intra-operative neurophysiological investigations in obstetric brachial plexus injuries. Between January 2005 and June 2011 a total of 32 infants of 206 referred to our unit underwent exploration of the plexus, including neurolysis. The findings from intra-operative electromyography, sensory evoked potentials across the lesion and gross muscular response to stimulation were evaluated. A total of 22 infants underwent neurolysis alone and ten had microsurgical reconstruction. Of the former, one was lost to follow-up, one had glenoplasty and three had subsequent nerve reconstructions. Of the remaining 17 infants with neurolysis, 13 (76%) achieved a modified Mallet score > 13 at a mean age of 3.5 years (0.75 to 6.25). Subluxation or dislocation of the shoulder is a major confounding factor. The positive predictive value and sensitivity of the intra-operative EMG for C5 were 100% and 85.7%, respectively, in infants without concurrent shoulder pathology. The positive and negative predictive values, sensitivity and specificity of the three investigations combined were 77%, 100%, 100% and 57%, respectively. In all, 20 infants underwent neurolysis alone for C6 and three had reconstruction. All of the former and one of the latter achieved biceps function of Raimondi grade 5. The positive and negative predictive values, sensitivity and specificity of electromyography for C6 were 65%, 71%, 87% and 42%, respectively. Our method is effective in evaluating the prognosis of C5 lesion. Neurolysis is preferred for C6 lesions.

Exploration and neurolysis for the treatment of neuropathic pain in patients with a sciatic nerve palsy after total hip replacement.

The purpose of this study was to establish whether exploration and neurolysis is an effective method of treating neuropathic pain in patients with a sciatic nerve palsy after total hip replacement (THR). A total of 56 patients who had undergone this surgery at our hospital between September 1999 and September 2010 were retrospectively identified. There were 42 women and 14 men with a mean age at exploration of 61.2 years (28 to 80). The sciatic nerve palsy had been sustained by 46 of the patients during a primary THR, five during a revision THR and five patients during hip resurfacing. The mean pre-operative visual analogue scale (VAS) pain score was 7.59 (2 to 10), the mean post-operative VAS was 3.77 (0 to 10), with a resulting mean improvement of 3.82 (0 to 10). The pre- and post-neurolysis VAS scores were significantly different (p < 0.001). Based on the findings of our study, we recommend this form of surgery over conservative management in patients with neuropathic pain associated with a sciatic nerve palsy after THR.

Iatropathic brachial plexus injury: a complication of delayed fixation of clavicle fractures.

We present our experience of managing patients with iatropathic brachial plexus injury after delayed fixation of a fracture of the clavicle. It is a retrospective cohort study of patients treated at our peripheral nerve injury unit and a single illustrative case report. We identified 21 patients in whom a brachial plexus injury occurred as a direct consequence of fixation of a fracture of the clavicle between September 2000 and September 2011.The predominant injury involved the C5/C6 nerves, upper trunk, lateral cord and the suprascapular nerve. In all patients, the injured nerve was found to be tethered to the under surface of the clavicle by scar tissue at the site of the fracture and was usually associated with pathognomonic neuropathic pain and paralysis.Delayed fixation of a fracture of the clavicle, especially between two and four weeks after injury, can result in iatropathic brachial plexus injury. The risk can be reduced by thorough release of the tissues from the inferior surface of the clavicle before mobilisation of the fracture fragments. If features of nerve damage appear post-operatively urgent specialist referral is recommended.

Angiotensin II type 2 receptor (AT2 R) localization and antagonist-mediated inhibition of capsaicin responses and neurite outgrowth in human and rat sensory neurons.

BACKGROUND: The angiotensin II (AngII) receptor subtype 2 (AT2 R) is expressed in sensory neurons and may play a role in nociception and neuronal regeneration. METHODS: We used immunostaining with characterized antibodies to study the localization of AT2 R in cultured human and rat dorsal root ganglion (DRG) neurons and a range of human tissues. The effects of AngII and AT2 R antagonist EMA401 on capsaicin responses in cultured human and rat (DRG) neurons were measured with calcium imaging, on neurite length and density with Gap43 immunostaining, and on cyclic adenosine monophosphate (cAMP) expression using immunofluorescence. RESULTS: AT2 R expression was localized in small-/medium-sized cultured neurons of human and rat DRG. Treatment with the AT2 R antagonist EMA401 resulted in dose-related functional inhibition of capsaicin responses (IC50 = 10 nmol/L), which was reversed by 8-bromo-cAMP, and reduced neurite length and density; AngII treatment significantly enhanced capsaicin responses, cAMP levels and neurite outgrowth. The AT1 R antagonist losartan had no effect on capsaicin responses. AT2 R was localized in sensory neurons of human DRG, and nerve fibres in peripheral nerves, skin, urinary bladder and bowel. A majority sub-population (60%) of small-/medium-diameter neuronal cells were immunopositive in both control post-mortem and avulsion-injured human DRG; some very small neurons appeared to be intensely immunoreactive, with TRPV1 co-localization. While AT2 R levels were reduced in human limb peripheral nerve segments proximal to injury, they were preserved in painful neuromas. CONCLUSIONS: AT2 R antagonists could be particularly useful in the treatment of chronic pain and hypersensitivity associated with abnormal nerve sprouting.

The outcome of extra-abdominal fibromatosis treated at a tertiary referral centre.

PURPOSE: To review the outcomes of patients with extra-abdominal fibromatosis treated at a tertiary referral centre. METHODS: A retrospective review of a series of 72 patients with fibromatosis treated at the Royal National Orthopaedic Hospital (RNOH) between 1980 and 2009, with a median follow up of 4 years (1-17 years). RESULTS: Forty patients were primary referrals, and 32 more had operations at the referring hospital. Five were treated non-operatively; 48 patients were treated by operation alone and 19 patients underwent surgery supplemented by adjuvant therapy. Recurrence was seen in 24 of the operation alone group and 10 in the operation and adjuvant therapy group. The rate of recurrence was lower with complete excision. However, complete excision was impossible in some cases because of extension into the chest or spinal canal, or involvement with the axial vessels and lumbosacral or brachial plexus. CONCLUSION: We suggest that operative excision should seek to preserve function and that supplementary adjuvant therapy may reduce the risk of recurrence, although excision margin appears to be the most important factor. The aggressive, infiltrative behaviour of deep fibromatoses and the associated genetic mutations identified, clearly distinguish them from the superficial fibromatoses and makes their treatment more difficult and dangerous, especially where vital structures are involved.

Severe brachial plexus injuries in rugby.

We describe the mechanisms, pattern of injuries, management and outcomes of severe injuries to the brachial plexus sustained during the play of rugby. Thirteen cases of severe injury to the brachial plexus caused by tackles in rugby had detailed clinical assessment, and operative exploration of the brachial plexus. Seventeen spinal nerves were avulsed, two were ruptured and there were traction lesions in continuity of 24 spinal nerves. The pattern of nerve lesion was related to the posture of the neck and the forequarter at the moment of impact. Early repair by nerve transfer enabled some functional recovery, and decompression of lesions in continuity was followed by recovery of nerve function and relief of pain.

Neuropathic pain following hip resurfacing due to a transneural suture.

A 60-year-old man developed severe neuropathic pain and foot-drop in his left leg following resurfacing arthroplasty of the left hip. The pain was refractory to all analgesics for 16 months. At exploration, a PDS suture was found passing through the sciatic nerve at several points over 6 cm and terminating in a large knot. After release of the suture and neurolysis there was dramatic and rapid improvement of the neuropathic pain and of motor function. This case represents the human equivalent of previously described nerve ligation in an animal model of neuropathic pain. It emphasises that when neuropathic pain is present after an operation, the nerve related to the symptoms must be inspected, and that removal of a suture or irritant may lead to relief of pain, even after many months.

Glenoplasty for complex shoulder subluxation and dislocation in children with obstetric brachial plexus palsy.

We describe the early results of glenoplasty as part of the technique of operative reduction of posterior dislocation of the shoulder in 29 children with obstetric brachial plexus palsy. The mean age at operation was five years (1 to 18) and they were followed up for a mean of 34 months (12 to 67). The mean Mallet score increased from 8 (5 to 13) to 12 (8 to 15) at final follow-up (p < 0.001). The mean passive forward flexion was increased by 18° (p = 0.017) and the mean passive abduction by 24° (p = 0.001). The mean passive lateral rotation also increased by 54° (p < 0.001), but passive medial rotation was reduced by a mean of only 7°. One patient required two further operations. Glenohumeral stability was achieved in all cases.

The supination deformity and associated deformities of the upper limb in severe birth lesions of the brachial plexus.

We reviewed 42 consecutive children with a supination deformity of the forearm complicating severe birth lesions of the brachial plexus. The overall incidence over the study period was 6.9% (48 of 696). It was absent in those in Narakas group I (27.6) and occurred in 5.7% of group II (13 of 229), 9.6% of group III (11 of 114) and 23.4% of group IV (18 of 77). Concurrent deformities at the shoulder, elbow, wrist and hand were always present because of muscular imbalance from poor recovery of C5 and C7, inconsistent recovery of C8 and T1 and good recovery of C6. Early surgical correction improved the function of the upper limb and hand, but there was a tendency to recurrence. Pronation osteotomy placed the hand in a functional position, and increased the arc of rotation of the forearm. The supination deformity recurred in 40% (17 of 42) of those treated by pronation osteotomy alone, probably because of remodelling of the growing bone. Children should be followed up until skeletal maturity, and the parents counselled on the likelihood of multiple operations.

Brachial plexus-avulsion causing Brown-Sequard syndrome: a report of three cases.

We describe three patients with pre-ganglionic (avulsion) injuries of the brachial plexus which caused a partial Brown-Séquard syndrome.

TRPA1 receptor localisation in the human peripheral nervous system and functional studies in cultured human and rat sensory neurons.

TRPA1 is a receptor expressed by sensory neurons, that is activated by low temperature (<17 degrees C) and plant derivatives such as cinnamaldehyde and isoeugenol, to elicit sensations including pain. Using immunohistochemistry, we have, for the first time, localised TRPA1 in human DRG neurons, spinal cord motoneurones and nerve roots, peripheral nerves, intestinal myenteric plexus neurones, and skin basal keratinocytes. TRPA1 co-localised with a subset of hDRG neurons positive for TRPV1, the heat and capsaicin receptor. The number of small/medium TRPA1 positive neurons (< or =50 microm) was increased after hDRG avulsion injury [percentage of cells, median (range): controls 16.5 (7-23); injured 46 (34-55); P<0.005], but the number of large TRPA1 neurons was unchanged [control 19.5 (13-31); injured 21 (11-35)]. Similar TRPA1 changes were observed in cultured hDRG neurons, after exposure to a combination of key neurotrophic factors NGF, GDNF and NT-3 (NTFs) in vitro. We used calcium imaging to examine responses of HEK cells transfected with hTRPA1 cDNA, and of human and rat DRG neurons cultured with or without added NTFs, to cinnamaldehyde (CA) and isoeugenol (IE). Exposure to NTFs in vitro sensitized cultured human sensory neuronal responses to CA; repeated CA exposure produced desensitisation. In rDRG neurons, low (225 microM) CA preincubation enhanced capsaicin responses, while high (450 microM and 2mM) CA caused inhibition which was partially reversed in the presence of 8 bromo cAMP, indicating receptor dephosphorylation. While TRPA1 localisation is more widespread than TRPV1, it represents a promising novel drug target for the treatment of chronic pain and hypersensitivity.

Intractable neurostenalgia of the ulnar nerve abolished by neurolysis 18 years after injury.

A 39 year-old farmer sustained a closed rupture of the left brachial artery, which was successfully managed by emergency vein graft repair of the artery. Adjacent nerve trunks were seen to be intact, but stretched. Burning pain in the distribution of the ulnar nerve started at day seven postoperatively, and worsened over the ensuing years. There was no response to membrane stabilising drugs, amitryptiline, nor to regional sympatholytic or local anaesthetic blocks. Neurolysis of the ulnar nerve, which was densely adherent to the dilated vein graft, abolished his pain.

Cyclical sciatica: endometriosis of the sciatic nerve.

We describe a case of sciatic endometriosis in a 25-year-old woman diagnosed by MRI and histology with no evidence of intrapelvic disease. The presentation, diagnosis and management of this rare condition are described. Early diagnosis and treatment are important to prevent irreversible damage to the sciatic nerve.