Pathogenic Hydrogel? A Novel-Entrapment Neuropathy Model Induced by Ultrasound-Guided Perineural Injections.

Entrapment neuropathy (EN) is a prevalent and debilitative condition caused by a complex pathogenesis that involves a chronic compression-edema-ischemia cascade and perineural adhesion that results in excessive shear stress during motion. Despite decades of research, an easily accessible and surgery-free animal model mimicking the mixed etiology is currently lacking, thus limiting our understanding of the disease and the development of effective therapies. In this proof-of-concept study, we used ultrasound-guided perineural injection of a methoxy poly(ethylene glycol)-b-Poly(lactide-co-glycoilide) carboxylic acid (mPEG-PLGA-BOX) hydrogel near the rat's sciatic nerve to induce EN, as confirmed sonographically, electrophysiologically, and histologically. The nerve that was injected with hydrogel appeared unevenly contoured and swollen proximally with slowed nerve conduction velocities across the injected segments, thus showing the compressive features of EN. Histology showed perineural cellular infiltration, deposition of irregular collagen fibers, and a possible early demyelination process, thus indicating the existence of adhesions. The novel method provides a surgery-free and cost-effective way to establish a small-animal model of EN that has mixed compression and adhesion features, thus facilitating the additional elucidation of the pathophysiology of EN and the search for promising treatments.

Neuropatía óptica compresiva secundaria a reacción alérgica a hialuronidasa / Compressive optic neuropathy secondary to an allergic reaction to hyaluronidase

Una mujer de 58 años presentó quemosis intensa y oftalmoparesia en el ojo izquierdo 8 h después de cirugía de catarata no complicada bajo anestesia subtenoniana. Tras tratamiento corticoideo y antihistamínico, se observó recuperación de la motilidad extrínseca pero se apreciaron un edema de papila no hemorrágico y un defecto concéntrico de campo visual. El caso evolucionó a atrofia papilar con agudeza visual central preservada pero con una contracción significativa del campo visual. El estudio etiológico reveló una alergia a la hialuronidasa, usada como adyuvante a la anestesia. Esta complicación debe ser diagnosticada y tratada precozmente, puesto que el edema de los tejidos orbitarios puede dañar el nervio óptico

A 58 year-old woman presented with severe chemosis and ophthalmoparesis on her left eye 8 hours after uncomplicated cataract surgery under sub-tenon anaesthesia. Recovery of extrinsic motility was observed after corticosteroid and antihistamine treatment, but a non-haemorrhagic papillary oedema and a concentric defect of visual field were found. It progressed to papillary atrophy with preserved central vision, but with a significant visual field constriction. The aetiological study revealed an allergy to hyaluronidase that was used as adjuvant to the anaesthesia. This complication needs to be promptly diagnosed and treated, as the swelling of the orbital tissues can cause damage to the optic nerve

Compressive optic neuropathy secondary to an allergic reaction to hyaluronidase. / Neuropatía óptica compresiva secundaria a reacción alérgica a hialuronidasa.

A 58 year-old woman presented with severe chemosis and ophthalmoparesis on her left eye 8hours after uncomplicated cataract surgery under sub-tenon anaesthesia. Recovery of extrinsic motility was observed after corticosteroid and antihistamine treatment, but a non-haemorrhagic papillary oedema and a concentric defect of visual field were found. It progressed to papillary atrophy with preserved central vision, but with a significant visual field constriction. The aetiological study revealed an allergy to hyaluronidase that was used as adjuvant to the anaesthesia. This complication needs to be promptly diagnosed and treated, as the swelling of the orbital tissues can cause damage to the optic nerve.

Anterior Cutaneous Nerve Entrapment Syndrome Possibly Triggered by Oral Contraceptives.

We herein report a teenage girl who had been taking oral contraceptive pills for three months and complained of left lower abdominal pain that had continued for two months. A physical examination indicated anterior cutaneous nerve entrapment syndrome (ACNES), although no abnormality was found in various biochemical and imaging examinations. The pain was only transiently ameliorated by trigger-point injection, and neurectomy surgery was eventually effective. Sex steroids can be involved in the progress of local tissue edema causing ACNES. ACNES should be considered in cases of abdominal pain in patients taking oral contraceptives.

Meralgia Paresthetica as a Presentation of Acute Appendicitis in a Girl With Acute Lymphoblastic Leukemia.

A 7-year-old girl with Philadelphia chromosome-positive acute lymphoblastic leukemia developed recurrent fever and meralgia paresthetica (MP) during chemotherapy, which resolved after administration of antibiotics. Five months after the onset of these symptoms, enhanced computed tomography showed a periappendiceal abscess extending into the psoas muscle. The cause of her fever and MP was thought to be appendicitis, which probably developed during induction chemotherapy but did not result in typical abdominal pain. Patients with recurrent fever and MP should be evaluated by imaging examinations including computed tomography to search for appendicitis.

Simvastatin-induced meralgia paresthetica.

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) cause mainly muscular adverse effects. During the last 20 years there has been solid evidence of peripheral neuropathy caused by statins, with a risk of one in 10,000 patients treated for 1 year. Meralgia paresthetica is an entrapment neuropathy occasionally encountered by primary care physicians. To date there has been no report of entrapment neuropathy that could have been caused or aggravated by statins. This case report presents meralgia paresthetica aggravated by simvastatin use that disappeared after simvastatin cessation.

Symptomatic ectopic bone formation after off-label use of recombinant human bone morphogenetic protein-2 in transforaminal lumbar interbody fusion.

OBJECT: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been approved for use in the lumbar spine in conjunction with the lumbar tapered cage. However, off-label use of this osteoinductive agent is observed with anterior fusion applications as well as with both posterior lumbar interbody fusion and transforaminal lumbar interbody fusion (TLIF). Complications using rhBMP-2 in the cervical spine have been reported. Although radiographic evidence of ectopic bone in the lumbar spine has been described following rhBMP-2 use, this finding was not previously believed to be of clinical relevance. METHODS: This study was a retrospective review of 4 patients who underwent minimally invasive spinal TLIF (MIS-TLIF) in which bone fusion was augmented with rhBMP-2 applied to an absorbable collagen sponge. Case presentations, operative findings, imaging data, and follow-up findings were reviewed. RESULTS: Four cases with delayed symptomatic neural compression following the off-label use of rhBMP-2 with MIS-TLIF were identified. CONCLUSIONS: Although previously believed to be only a radiographic finding, the development of ectopic bone following rhBMP-2 use in lumbar fusion can be clinically significant. This paper describes 4 cases of delayed neural compression following MIS-TLIF. The reader should be aware of this potential complication following the off-label use of rhBMP-2 in the lumbar spine.

Increased peripheral nerve excitability and local NaV1.8 mRNA up-regulation in painful neuropathy.

BACKGROUND: Neuropathic pain caused by peripheral nerve injury is a chronic disorder that represents a significant clinical challenge because the pathological mechanisms have not been fully elucidated. Several studies have suggested the involvement of various sodium channels, including tetrodotoxin-resistant NaV1.8, in affected dorsal root ganglion (DRG) neurons. We have hypothesized that altered local expression of NaV1.8 in the peripheral axons of DRG neurons could facilitate nociceptive signal generation and propagation after neuropathic injury. RESULTS: After unilateral sciatic nerve entrapment injury in rats, compound action potential amplitudes were increased in both myelinated and unmyelinated fibers of the ipsilateral sciatic nerve. Tetrodotoxin resistance of both fiber populations and sciatic nerve NaV1.8 immunoreactivity were also increased. Further analysis of NaV1.8 distribution revealed that immunoreactivity and mRNA levels were decreased and unaffected, respectively, in the ipsilateral L4 and L5 DRG; however sciatic nerve NaV1.8 mRNA showed nearly an 11-fold ipsilateral increase. Nav1.8 mRNA observed in the sciatic nerve was likely of axonal origin since it was not detected in non-neuronal cells cultured from nerve tissue. Absence of changes in NaV1.8 mRNA polyadenylation suggests that increased mRNA stability was not responsible for the selective peripheral mRNA increase. Furthermore, mRNA levels of NaV1.3, NaV1.5, NaV1.6, NaV1.7, and NaV1.9 were not significantly different between ipsilateral and contralateral nerves. We therefore propose that selective NaV1.8 mRNA axonal transport and local up-regulation could contribute to the hyperexcitability of peripheral nerves in some neuropathic pain states. CONCLUSION: Cuff entrapment injury resulted in significantly elevated axonal excitability and increased NaV1.8 immunoreactivity in rat sciatic nerves. The concomitant axonal accumulation of NaV1.8 mRNA may play a role in the pathogenesis of this model of neuropathic pain.

A rat model of radicular pain induced by chronic compression of lumbar dorsal root ganglion with SURGIFLO.

BACKGROUND: Radicular pain is a common and debilitating clinical pain condition. To date, the mechanisms of radicular pain remain unclear, partly because of the lack of suitable preclinical models. The authors report a modified rat model of radicular pain that could mimic a subset of clinical radicular pain conditions induced by the soft tissue compression on dorsal root ganglion. METHODS: A rat model of radicular pain was produced by infiltrating the L5 intervertebral foramen with 60 microl of a hemostatic matrix (SURGIFLO; Johnson & Johnson, Somerville, NJ) resulting in chronic compression of lumbar dorsal root ganglion. Thermal hyperalgesia and mechanical allodynia were measured with or without epidural treatment with triamcinolone. Western blot was used to assess the expression of the NR1 subunit of the N-methyl-D-aspartate receptor and inhibitory factor kappabeta-alpha, an inflammatory marker, within the affected L5 dorsal root ganglion and spinal cord dorsal horn. RESULTS: Chronic compression of lumbar dorsal root ganglion resulted in: (1) persistent mechanical allodynia and thermal hyperalgesia up to 4 or 5 postoperative weeks and (2) up-regulation of the N-methyl-D-aspartate receptor and inhibitory factor kappabeta-alpha within the ipsilateral L5 dorsal root ganglion and spinal cord dorsal horn. Epidural administration of triamcinolone (6.25-100 microg) on postoperative day 3 dose-dependently attenuated both thermal hyperalgesia and mechanical allodynia in rats with chronic compression of lumbar dorsal root ganglion. CONCLUSION: The data suggest that this modified rat model of chronic compression of lumbar dorsal root ganglion may be a useful tool to explore the mechanisms as well as new therapeutic options of radicular pain.

Chemotherapy-induced neuropathy.

Increasingly, surgeons are becoming aware of the successful treatment of symptomatic peripheral neuropathy by surgical decompression of peripheral nerves. Armed with the knowledge that patients can have underlying neuropathy with overlying anatomic compressions, surgeons have affected improvement in diabetes-induced neuropathy, neuropathy of unknown etiology, and chemotherapy-induced neuropathy. This article details the most well-known culprits in chemotherapy-induced neuropathy and discusses the putative mechanisms of action, medical management, and surgical data.

Compressive neuropathy of the brachial plexus and long thoracic nerve: a rare complication of heparin anticoagulation.

We present a case of a 69-year-old woman who developed brachial plexopathy and long thoracic nerve palsy secondary to compression from a hematoma while receiving heparin therapy for the treatment of a stroke. The patient was treated conservatively with discontinuation of heparin and had complete resolution of her compressive neuropathy. This is the first report of a patient with long thoracic nerve palsy with a brachial plexopathy complicating anticoagulation. We review the literature on hematoma-induced compressive neuropathies and treatment options. Our review concludes by emphasizing the importance of clinical judgment in determining the best therapeutic modality.

AANA Journal course: transient neurologic symptoms and spinal anesthesia.

A universal goal of anesthesia providers is to provide the safest, most effective anesthesia and analgesia for their patients. When reports emerge showing problems or complications with an agent or technique that previously was thought safe, recommendations often are adopted in anesthesia departments to avoid or abandon the agent or technique, or alternatives are sought. Hyperbaric 5% lidocaine has been an effective and safe spinal anesthetic agent for short procedures for years. During the past decade, controversy arose over its use because it was implicated as the cause of transient neurologic symptoms and cauda equina syndrome. Use of bupivacaine or tetracaine results in a much lower incidence, but these agents are not as well suited to brief or outpatient procedures as is the shorter acting lidocaine. Substantial research has been conducted detailing the search for reasons these complications occur and how to prevent them. A sample of the findings is summarized in an attempt to present current knowledge about the apparent causes and prevention of transient neurologic symptoms. There is promising research showing that safe and effective short-acting intrathecal anesthesia can be accomplished with procaine, prilocaine, meperidine, and sufentanil.

Cauda equina syndrome after spinal anaesthesia with hyperbaric 5% lignocaine: a review of six cases of cauda equina syndrome reported to the Swedish Pharmaceutical Insurance 1993-1997.

Six cases of cauda equina syndrome with varying severity were reported to the Swedish Pharmaceutical Insurance during the period 1993-1997. All were associated with spinal anaesthesia using hyperbaric 5% lignocaine. Five cases had single-shot spinal anaesthesia and one had a repeat spinal anaesthetic due to inadequate block. The dose of hyperbaric 5% lignocaine administered ranged from 60 to 120 mg. Three of the cases were most likely caused by direct neurotoxicity of hyperbaric 5% lignocaine. In the other 3 cases, direct neurotoxicity was also probable, but unfortunately radiological investigations were not done to definitely exclude a compressive aetiology. All cases sustained permanent neurological deficits. We recommend that hyperbaric lignocaine should be administered in concentrations not greater than 2% and at a total dose preferably not exceeding 60 mg.

[Hypothesis concerning the anatomical basis of cauda equina syndrome and transient nerve root irritation after spinal anesthesia]. / Hipótesis sobre las bases anatómicas del síndrome de cauda equina e irritación radicular transitoria postanestesia espinal.

OBJECTIVE: Cauda equine syndrome is a rare neurological complication associated with subarachnoid anesthesia, and particularly with the use of 5% hyperbaric lidocaine and small gauge catheters. Our aim was to study a possible anatomical factor that might impede adequate dilution of local anesthetic and explain the development of cauda equine syndrome and transitory radicular irritation. MATERIAL AND METHOD: The spinal dura matters and their contents from two male human cadavers were examined after organs had been extracted for transplantation. Both men had recently died at ages 56 and 65 years of age. Samples were fixed in a glutaraldehyde phosphate buffer and dehydrated in acetone, which was then removed by critical point elimination. The samples were then metallized with gold and observed under a scanning electron microscope. RESULTS: We found that one portion of the arachnoids was more compact and another was lax. The compact portion had a laminar structure formed by the fusion of fibers and cell components lining the inner surface of the dural mater. The lax portion was comprised of a weblike network of filaments and few cells bodies. This portion extended from the compact inner arachnoid lamina to the cell plane of the pia mater, where it dispersed, sending out compact arachnoid projections that wrapped around structures in the subarachnoid space. We termed these wrappings "arachnoid sheaths".

Abdominal wall pain caused by cutaneous nerve entrapment in an adolescent girl taking oral contraceptive pills.

The etiology of chronic abdominal pain can be elusive. The diagnostic workup, therefore, often includes superfluous and expensive tests, as well as invasive procedures which do not contribute to the final diagnosis. Studies have shown that some patients suffer from prolonged pain in the abdominal wall and often are misdiagnosed and treated as having a visceral source for their complaints. The abdominal wall might be considered to be an unlikely source of prolonged abdominal pain, but one study reported that in 15% of patients with prolonged, nonspecific abdominal pain, the abdominal wall was the source of the complaint. Abdominal pain resulting from cutaneous nerve entrapment has not been reported previously in children and adolescents, nor has nerve entrapment been reported as a complication of oral contraceptives. The case of a 15-year-old girl who came to the hospital emergency room with abdominal pain of 3 months duration is reported. A comprehensive workup had not established a specific cause for the pain. On the basis of the clinical findings, the possibility of a cutaneous nerve entrapment was suggested. After the involved cutaneous nerve was selectively blocked by subcutaneous infiltration, the pain disappeared immediately and completely. Recognition of this apparently unusual condition can lead to gratifying results. It is proposed that oral contraceptive therapy may have caused changes in the abdominal wall which led to nerve entrapment and the ensuing severe, prolonged pain.

PIP: Women with prolonged pain in the abdominal wall are often subjected to expensive tests and invasive procedures that do little to clarify the pain's etiology. Cutaneous nerve entrapment syndrome is an easily curable yet frequently overlooked cause of such pain. This article reports the first case of abdominal wall pain caused by cutaneous nerve entrapment in an adolescent and as a complication of oral contraceptive (OC) use. The 15-year-old girl presented to an Israeli medical center with right lower abdominal pain of 3 months' duration. She had commenced use of a combined OC a few days before the onset of pain. Prior to this hospital visit, the adolescent had made three visits to the emergency room for intense abdominal pain, had been examined by 12 specialists, and underwent a battery of tests--all of which produced normal results. When cutaneous nerve entrapment was finally considered as a possible diagnosis, the patient was treated by local infiltration and block of the cutaneous nerves in the abdominal wall--a regimen that produced immediate, complete pain relief. It is speculated that the estrogen or progesterone in the OC caused a redistribution or retention of fluids in the abdominal wall, eventually causing pressure on a cutaneous abdominal nerve in the area of a scar from a previous appendectomy. The teen was able to continue OC use.