Clinical spectrum of neuropathy after primary total knee arthroplasty: A series of 54 cases.

INTRODUCTION: Neuropathy after total knee arthroplasty (TKA) can cause significant morbidity but is inconsistently reported. METHODS: We reviewed the clinical, electrodiagnostic and perioperative features of all patients who underwent primary TKA at our institution and developed a new neuropathy within 8 weeks postoperatively. RESULTS: Fifty-four cases were identified (incidence 0.37% [95% confidence interval, 0.28-0.49]) affecting the following nerve(s): peroneal (37), sciatic (11), ulnar (2), tibial (2), sural (1), and lumbosacral plexus (1). In all cases with follow-up data, motor recovery typically occurred within 1 year and was complete or near-complete. CONCLUSIONS: Post-TKA neuropathy is uncommon, typically does not require intervention and usually resolves within 1 year. Post-TKA neuropathy most often affects the nerves surgically at risk. Anesthesia type does not correlate with post-TKA neuropathy. An inflammatory etiology for post-TKA neuropathy is rare but should be considered in specific cases. Muscle Nerve 59:679-682, 2019.

Saphenous nerve transfer: A new approach to restore sensation of the sole.

BACKGROUND: Loss of protective sensation of the sole may lead to repeated trauma, chronic nonhealing ulcers, and even amputation. Saphenous nerve (SN) to posterior tibial nerve (PTN) transfer can restore sensation of the sole. METHOD: This study was conducted in a tertiary referral center in Central India. Twenty-one patients (32 feet) diagnosed with loss of sensation of the sole were included in this study. Causes of loss of sensation were Hansen's disease (n = 18), complex sciatic nerve injury (n = 1), lumbosacral spinal tumor (n = 1), and lumbosacral meningomyelocele (n = 1). Seventeen feet (14 patients) had ulcers on the sole. Preoperative and postoperative sensory tests performed on the sole included tests for touch, pain, temperature, pressure, vibration, and two-point discrimination. Results were classified as per the British Medical Research Council (MRC) scoring system. RESULTS: Seventeen patients (26 feet) were available for follow-up at 6 months after surgery. All patients had improvement in sensory parameters. Ulcers completely healed in 13 feet and reduced in size in four feet. MRC score improved from S0 in 22 feet and S1 in 10 feet to S3 + in 20 feet, S3 in four feet, and S2 in two feet. CONCLUSIONS: Sensory neurotization with SN transfer to PTN can restore protective sensation to the sole and help in the healing of ulcers.

A Case of Posterior Tibial Nerve Injury After Arthroscopic Calcaneoplasty.

We report the first case of distal posterior tibial nerve injury after arthroscopic calcaneoplasty. A 59-year-old male had undergone right arthroscopic calcaneoplasty to treat retrocalcaneal bursitis secondary to a Haglund's deformity. The patient complained of numbness in his right foot immediately after the procedure. Two years later and after numerous assessments and investigations, a lateral plantar nerve and medial calcaneal nerve lesion was diagnosed. In the operating room, the presence of an iatrogenic lesion to the distal right lateral plantar nerve (neuroma incontinuity involving 20% of the nerve) and the medial calcaneal nerve (complete avulsion) was confirmed. The tarsal tunnel was decompressed, and both the medial and the lateral plantar nerve were neurolyzed under magnification. To the best of our knowledge, our case report is the first to describe iatrogenic posterior tibial nerve injury after arthroscopic calcaneoplasty. It is significant because this complication can hopefully be avoided in the future with careful planning and creation of arthroscopic ports and treated appropriately with early referral to a nerve specialist if the patient's symptoms do not improve within 3 months.

Metabolic brain activity suggestive of persistent pain in a rat model of neuropathic pain.

Persistent pain is a central characteristic of neuropathic pain conditions in humans. Knowing whether rodent models of neuropathic pain produce persistent pain is therefore crucial to their translational applicability. We investigated the spared nerve injury (SNI) model of neuropathic pain and the formalin pain model in rats using positron emission tomography (PET) with the metabolic tracer [18F]fluorodeoxyglucose (FDG) to determine if there is ongoing brain activity suggestive of persistent pain. For the formalin model, under brief anesthesia we injected one hindpaw with 5% formalin and the FDG tracer into a tail vein. We then allowed the animals to awaken and observed pain behavior for 30min during the FDG uptake period. The rat was then anesthetized and placed in the scanner for static image acquisition, which took place between minutes 45 and 75 post-tracer injection. A single reference rat brain magnetic resonance image (MRI) was used to align the PET images with the Paxinos and Watson rat brain atlas. Increased glucose metabolism was observed in the somatosensory region associated with the injection site (S1 hindlimb contralateral), S1 jaw/upper lip and cingulate cortex. Decreases were observed in the prelimbic cortex and hippocampus. Second, SNI rats were scanned 3weeks post-surgery using the same scanning paradigm, and region-of-interest analyses revealed increased metabolic activity in the contralateral S1 hindlimb. Finally, a second cohort of SNI rats was scanned while anesthetized during the tracer uptake period, and the S1 hindlimb increase was not observed. Increased brain activity in the somatosensory cortex of SNI rats resembled the activity produced with the injection of formalin, suggesting that the SNI model may produce persistent pain. The lack of increased activity in S1 hindlimb with general anesthetic demonstrates that this effect can be blocked, as well as highlights the importance of investigating brain activity in awake and behaving rodents.

Efficacy of short-term FK506 administration on accelerating nerve regeneration.

BACKGROUND: The slow rate of nerve regeneration following injury can cause extended muscle denervation, leading to irreversible muscle atrophy, fibrosis, and destruction of motor endplates. The immunosuppressant FK506 (tacrolimus) has been shown to accelerate the rate of nerve regeneration and functional recovery. However, the toxic and immunosuppressive properties of FK506 make it undesirable for long-term use. OBJECTIVE: To take advantage of the regeneration-enhancing effects of FK506 but avoid the potential adverse effects of long-term administration, the current study evaluates and quantifies the efficacy of short-term FK506 treatment in rat models. METHODS: Clinically relevant transection and graft models were evaluated, and walking track analysis (WTA) was used to evaluate functional recovery. FK506 was administered for 5 and 10 days post transection injury and 10 and 20 days post graft injury. Both groups involving a short course were compared with the continuous administration group. RESULTS: In the transection model, FK506 was administered for 5 and 10 days postoperatively. WTA demonstrated that 10 days of FK506 administration was sufficient to reduce functional recovery time by 29% compared with negative controls. In the graft model, FK506 was administered for 10 and 20 days postoperatively. Short treatment courses of 10 and 20 days reduced recovery time by 15% and 21%, respectively, compared with negative controls. Analysis of blood-nerve barrier (BNB) integrity demonstrated that FK506 facilitated early reconstitution of the BNB. CONCLUSIONS: The results of this study indicate that short-term FK506 delivery following nerve injury imparts a significant therapeutic effect.

Somatosensory evoked potential from S1 nerve root stimulation.

The objective of this study was to detect cerebral potentials elicited by proximal stimulation of the first sacral (S1) nerve root at the S1 dorsal foramen and to investigate latency and amplitude of the first cerebral potential. Tibial nerve SEP and S1 nerve root SEP were obtained from 20 healthy subjects and 5 patients with unilateral sciatic nerve or tibial nerve injury. Stimulation of the S1 nerve root was performed by a needle electrode via the S1 dorsal foramen. Cerebral potentials were recorded twice to document reproducibility. Latencies and amplitudes of the first cerebral potentials were recorded. Reproducible cerebral evoked potentials were recorded and P20s were identified in 36 of 40 limbs in the healthy subjects. The mean latency of P20 was 19.8 ± 1.6 ms. The mean amplitude of P20-N30 was 1.2 ± 0.9 µV. In the five patients, P40 of tibial nerve SEP was absent, while well-defined cerebral potentials of S1 nerve root SEP were recorded and P20 was identified from the involved side. This method may be useful in detecting S1 nerve root lesion and other disorders affecting the proximal portions of somatosensory pathway. Combined with tibial nerve SEP, it may provide useful information for diagnosis of lesions affecting the peripheral nerve versus the central portion of somatosensory pathway.

Tibial ischemic neuropathy as an unusual complication of interventional radiology.

Ischemia can be a rare cause of focal neuropathy. We report an 83-year-old man with right tibial ischemic neuropathy after a catheterization and embolization procedure to treat recurrent hemarthrosis of the right knee. The electrophysiological study confirmed a conduction block at the right tibial nerve (between the ankle and knee), without local compression.

Nerve repair by end-to-side nerve coaptation: histologic and morphometric evaluation of axonal origin in a rat sciatic nerve model.

OBJECTIVE: We compared the origin and quality of regenerating myelinated axons after end-to-side neurorrhaphy or end-to-end neurorrhaphy. METHODS: Transected adult rat tibial nerves were either end-to-end coapted or the distal stump was sutured to a perineurial window of the fibular nerve. Electromyographic recordings from the gastrocnemius muscle 8 weeks later revealed reinnervation by tibial nerve axons. Retrograde tracing of neurons projecting across the coaptation sites was performed with Dil for the tibial nerve and FluoroGold for the fibular nerve to reveal the origin of regenerating axons. Orientation of regenerating axons was demonstrated by immunohistochemical staining of the coaptation sites. Nerve cross-sections proximal and distal to the coaptation sites were evaluated regarding quality and quantity of myelinated axons inside the donor and acceptor nerves in comparison to nonoperated nerve samples. RESULTS: Compound muscle action potential responses were not different 8 weeks after end-to-side as compared with end-to-end coaptation. Double fluorescence of spinal motoneurons (L4-L6) and dorsal root ganglion neurons (L4-L6) elucidated events of collateral sprouting of sensory and motor donor axons. Morphometric analysis demonstrated significantly higher numbers of regenerated myelinated axons distal to end-to-end as distal to end-to-side repair. Furthermore, events of axonal sprouting in the donor nerve proximal to the end-to-side coaptation site were discovered. However, with quantitative parameters such as fiber density and g-ratio, no impairment of the donor nerve was evident. CONCLUSION: The current study supports the hypothesis that end-to-side neurorrhaphy represents an opportunity for peripheral nerve repair when a proximal nerve stump is not available.

Noradrenergic neurons in the locus coeruleus contribute to neuropathic pain.

Current theories of neuropathic hypersensitivity include an imbalance of supraspinal inhibition and facilitation. Our overall hypothesis is that the locus coeruleus (LC), classically interpreted as a source of pain inhibition, may paradoxically result in facilitation after tibial and common peroneal nerve transection (spared sural nerve injury--SNI). We first tested the hypothesis that non-noxious tactile hind paw stimulation of the spared sural innervation territory increases neuronal activity in the LC in male rats. We observed a bilateral increase in the stimulus-evoked expression of transcription factors Fos and phosphorylated CREB (pCREB) in LC after SNI but not sham surgery; these markers of neuronal activity correlated with the intensity of tactile allodynia. We next tested the hypothesis that noradrenergic neurons contribute to the development of neuropathic pain. To selectively destroy these neurons, we delivered antidopamine-beta-hydroxylase saporin (anti-DbetaH-saporin) into the i.c.v. space 2 weeks before SNI. We found that anti-DbetaH-saporin, but not an IgG-saporin control, reduced behavioral signs of tactile allodynia, mechanical hyperalgesia, and cold allodynia from 3 to 28 days. after SNI. Our final experiment tested the hypothesis that the LC contributes to the maintenance of neuropathic pain. We performed SNI, waited 2 weeks for maximal allodynia and hyperalgesia to develop, and then administered the local anesthetic lidocaine (4%) directly into the LC parenchyma. Lidocaine reduced all behavioral signs of neuropathic pain in a reversible manner, suggesting that the LC contributes to pain facilitation. We conclude that, in addition to its well-known inhibition of acute and inflammatory pain, the LC facilitates the development and maintenance of neuropathic pain in the SNI model. Further studies are needed to determine the facilitatory pathways emanating from the LC.

Sciatic cross-over in patients with peroneal and tibial intraneural ganglia confirmed by knee MR arthrography.

BACKGROUND: A predictable mechanism and stereotypic patterns of peroneal intraneural ganglia are being defined based on careful analysis of MRIs. Peroneal and tibial intraneural ganglia extending from the superior tibiofibular joint which extend to the level of the sciatic nerve have been observed leading to the hypothesis that sciatic cross-over could exist. Such a cross-over phenomenon would allow intraneural cyst from the peroneal nerve by means of its shared epineurial sheath within the sciatic nerve to cross over to involve the tibial nerve, or vice versa from a tibial intraneural cyst to the peroneal nerve. METHOD AND FINDINGS: One patient with a peroneal intraneural ganglion and another with a tibial intraneural ganglion each underwent a knee MR arthrogram. These studies were not only definitive in demonstrating the communication of the cyst to the superior tibiofibular joint connection but also in confirming sciatic cross-over. Contrast injected into the knee could be demonstrated tracking to the superior tibiofibular joint and then proximally into the common peroneal or tibial nerve respectively, crossing over at the sciatic nerve, and then descending down the tibial and peroneal nerves. The arthrographic findings mirrored MR images upon their retrospective review. CONCLUSIONS: This study provides direct in vivo proof of the nature of sciatic cross-over theorized by critical review of MRIs and/or experimental dye injections done in cadavers. This study is important in clarifying the potential paths of propagation of intraneural cysts at points of major bifurcation.

Impairment of VGLUT2 but not VGLUT1 signaling reduces neuropathy-induced hypersensitivity.

Glutamate is the major excitatory neurotransmitter in the central nervous system with an important role in nociceptive processing. Storage of glutamate into vesicles is controlled by vesicular glutamate transporters (VGLUT). Null mutants for VGLUT1 and VGLUT2 were poorly viable, thus, pain-related behavior was presently compared between heterozygote VGLUT1 and VGLUT2 mice and their respective wild-type littermates using a test battery that included a variety of assays for thermal and mechanical acute nociception, and inflammatory and neuropathic pain syndromes. Behavioral analysis of VGLUT1 mutant mice did not show important behavioral changes in the pain conditions tested. Reduction of VGLUT2 also resulted in unaltered acute nociceptive and inflammatory-induced pain behavior. Interestingly, VGLUT2 heterozygote mice showed an attenuation or absence of some typical neuropathic pain features (e.g., absence of mechanical and cold allodynia after spared nerve injury). Chronic constriction injury in VGLUT2 heterozygote mice showed also reduced levels of cold allodynia, but had no impact on mechanical thresholds. Together, these data suggest that VGLUT2, but not VGLUT1, plays a role in neuropathy-induced allodynia and hypersensitivity, and might be a therapeutic target to prevent and/or treat neuropathic pain.

Sensitivity of plantar cutaneous sensation and postural stability.

BACKGROUND: Impaired plantar cutaneous sensation is often seen clinically and can lead to postural instability. It is not clear if the severity of such sensory loss would be associated with postural stability, and if such an association would be affected by sensory redundancy and task difficulty. The purpose of this study was to investigate the association of the degree of somatosensory loss and postural stability by experimentally induced somatosensory loss in healthy young adults. METHODS: Twenty-one healthy young adults performed four quiet standing tasks (normal or narrow base, and eyes open or closed) on a force platform under three somatosensory conditions induced by ischemic blocking of afferent conduction below the ankle, normal, partial loss and complete loss. Differences in the standing center of pressure motion between the three sensory loss conditions were compared. FINDINGS: There was a significant trend of greater center of pressure motion with increasing severity of sensory loss in all task conditions. The differences in the center of pressure motion between partial and total loss conditions were significant only in conditions where vision was removed and the support surface was narrow. INTERPRETATION: Increased severity of experimentally induced loss of plantar cutaneous sensitivity was associated with greater postural sway. Such an association was affected by the availability of visual input and the size of the support surface. Clinically for patients with somatosensory impairments of the foot, postural stability should be given special attention.

Chondrotinase ABC enhances axonal regeneration across nerve gaps.

We evaluated the effects of chondroitinase ABC on axonal regeneration across peripheral nerve gaps. We compared axonal regeneration after 15-mm tibial nerve resection and repair with a silicone tube filled with type I collagen gel (negative control group), with a silicone tube filled with type I collagen gel containing chondroitinase ABC at three different concentrations (2.5 units/mL, 5 units/mL, 10 units/mL) (chondroitinase ABC groups), and with an autologous nerve segment (nerve autograft group). Electrophysiological and histological assessments were carried out 12 weeks after surgery. In the electrophysiological study, compound muscle action potentials (CMAPs) and nerve conduction velocities (NCVs) were recorded in all groups except the negative control group. Although both CMAPs and NCVs were highest in the nerve autograft group, there were no significant differences among the three chondroitinase ABC groups in either parameter. Histological findings were consistent with electrophysiological results. Based on these findings, we conclude that topical injection of chondroitinase ABC can significantly increase the critical length of nerve gap repair by tubulization or artificial nerve placement.

Dynamic phases of peroneal and tibial intraneural ganglia formation: a new dimension added to the unifying articular theory.

OBJECT: The pathogenesis of intraneural ganglia has been a controversial issue for longer than a century. Recently the authors identified a stereotypical pattern of occurrence of peroneal and tibial intraneural ganglia, and based on an understanding of their pathogenesis provided a unifying articular explanation. Atypical features, which occasionally are observed, have offered an opportunity to verify further and expand on the authors' proposed theory. METHODS: Three unusual cases are presented to exemplify the dynamic features of peroneal and tibial intraneural ganglia formation. RESULTS: Two patients with a predominant deep peroneal nerve deficit shared essential anatomical findings common to peroneal intraneural ganglia: namely, 1) joint connections to the anterior portion of the superior tibiofibular joint, and 2) dissection of the cyst along the articular branch of the peroneal nerve and proximally. Magnetic resonance (MR) images obtained in these patients demonstrated some unusual findings, including the presence of a cyst within the tibial and sural nerves in the popliteal fossa region, and spontaneous regression of the cysts, which was observed on serial images obtained weeks apart. The authors identified a clinical outlier, a case that could not be understood within the context of their previously reported theory of intraneural ganglion cyst formation. Described 32 years ago, this patient had a tibial neuropathy and was found at surgery to have tibial, peroneal, and sciatic intraneural cysts without a joint connection. The authors' hypothesis about this case, based on their unified theory, was twofold: 1) the lesion was a primary tibial intraneural ganglion with proximal extension followed by sciatic cross-over and distal descent; and 2) a joint connection to the posterior aspect of the superior tibiofibular joint with a remnant cyst within the articular branch would be present, a finding that would help explain the formation of different cysts by a single mechanism. The authors proved their hypothesis by careful inspection of a recently obtained postoperative MR image. CONCLUSIONS: These three cases together with data obtained from a retrospective review of the authors' clinical material and findings reported in the literature provide firm evidence for mechanisms underlying intraneural ganglia formation. Thus, expansion of the authors' unified articular theory permits understanding and elucidation of unusual presentations of intraneural cysts. Whereas an articular connection and fluid following the path of least resistance was pivotal, the authors now incorporate dynamic aspects of cyst formation due to pressure fluxes. These basic principles explain patterns of ascent, cross-over, and descent down terminal nerve branches based on articular connections, paths of diminished resistance to fluid flow within recognized anatomical compartments, and the effects of fluctuating pressure gradients.

Ultrasonography of the tibial nerve in vasculitic neuropathy.

Ultrasonography is a new imaging method for visualizing peripheral nerves. In vasculitic neuropathy, pain or axonopathy often can prevent the lesion from being localized during electrophysiological examinations, but the ability of ultrasonography to evaluate it morphologically is unknown. Our aim was to determine whether ultrasonography could be used to detect abnormalities in tibial vasculitic neuropathy at the medial ankle. We evaluated 11 tibial nerves in 8 patients with tibial vasculitic neuropathy, and 35 tibial nerves in 35 control subjects. In the controls, the tibial nerve was successfully visualized as a hyperechoic nodule with multiple round hypoechoic areas transversely; in the patients, the tibial nerve appeared enlarged and hypoechoic. The affected nerve area was significantly larger (13.5 +/- 3.7 mm(2)) than in controls (7.2 +/- 1.5 mm(2)). Our results suggest that ultrasonography is a useful neuroimaging method for evaluation of tibial vasculitic neuropathy, especially when nerve conduction study findings are inconclusive.

Hereditary neuropathy with liability to pressure palsy combined with schwannomas of the median and medial plantar nerves.

A 42-year-old woman was surgically treated for carpal tunnel syndrome, revealing schwannoma of the median nerve. A year later, she developed a tarsal tunnel syndrome. At time of this diagnosis, hereditary neuropathy with liability to pressure palsies (HNPP) was diagnosed genetically and a schwannoma of the medial plantar nerve was treated surgically. The occurrence of HNPP and schwannomas in the same patient might be purely coincidental, but it is tempting to speculate that they share a common genetic basis.

Does the tibial and sural nerve transection model represent sympathetically independent pain?

Neuropathic pain can be divided into sympathetically maintained pain (SMP) and sympathetically independent pain (SIP). Rats with tibial and sural nerve transection (TST) produce neuropathic pain behaviors, including spontaneous pain, tactile allodynia, and cold allodynia. The present study was undertaken to examine whether rats with TST would represent SMP- or SIP-dominant neuropathic pain by lumbar surgical sympathectomy. The TST model was generated by transecting the tibial and sural nerves, leaving the common peroneal nerve intact. Animals were divided into the sympathectomy group and the sham group. For the sympathectomy group, the sympathetic chain was removed bilaterally from L2 to L6 one week after nerve transection. The success of the sympathectomy was verified by measuring skin temperature on the hind paw and by infra red thermography. Tactile allodynia was assessed using von Frey filaments, and cold allodynia was assessed using acetone drops. A majority of the rats exhibited withdrawal behaviors in response to tactile and cold stimulations after nerve stimulation. Neither tactile allodynia nor cold allodynia improved after successful sympathectomy, and there were no differences in the threshold of tactile and cold allodynia between the sympathectomy and sham groups. Tactile allodynia and cold allodynia in the neuropathic pain model of TST are not dependent on the sympathetic nervous system, and this model can be used to investigate SIP syndromes.