Tocilizumab use for optic nerve compression in thyroid eye disease: a prospective longitudinal cohort.

PURPOSE: To assess the effectiveness of tocilizumab in reverting the signs and symptoms of dysthyroid optic neuropathy (DON) in thyroid eye disease and the need for emergency orbital decompression. The secondary outcomes are to identify the optimal number of tocilizumab cycles to achieve the primary outcome, to analyze the association between thyroid stimulating immunoglobulin (TSI), clinical activity score (CAS) and proptosis in response to the treatment and the need for rehabilitative orbital decompression. METHODS: Prospective longitudinal cohort study that included 13 patients who had unilateral or bilateral dysthyroid optic neuropathy (DON) due to severe and progressive sight-threatening thyroid eye disease based on the CAS system. Patients were seen in this facility starting from July 2017, and all had received intravenous tocilizumab. RESULTS: Initial visual acuity mean was 0.52 ± 0.38 and the final were 0.93 ± 0.11 with a mean difference of 0.41 and P < 0.00245. The mean CAS prior to the initiation of the treatment was 7.92 ± 0.66 and the final was 2.85 ± 1.03 with mean difference of 5.07 and P < 0.00001. Initial mean proptosis was 24.85 ± 2.31 and the final was 21.78 ± 2.18 with a mean difference of 3.07 and P < 0.000497. No emergency orbital decompression was performed. TSI was high initially in all cases with a wide range of 2.4 to 40 IU/L and with a mean of 10.70 ± 13.40. The final TSI mean was 2.90 ± 3.90 with a mean difference of 7.81 and significant P value (P < 0.0272). CONCLUSION: Tocilizumab use in optic nerve compression showed promising results as it can be the primary or an alternative treatment option.

Lidocaine patch as noninvasive alternative treatment option in children with anterior cutaneous nerve entrapment syndrome: A retrospective case series.

BACKGROUND: Chronic abdominal pain in children is occasionally caused by anterior cutaneous nerve entrapment syndrome (ACNES). Diagnosing and treating this typical peripheral abdominal wall neuropathy is challenging. Management usually starts with minimally invasive tender point injections. Nevertheless, these injections can be burdensome and might even be refused by children or their parents. However, a surgical neurectomy is far more invasive. Treatment with a Lidocaine 5% medicated patch is successfully used in a variety of peripheral neuropathies. AIMS: This single center retrospective case series aimed to evaluate the effectiveness and tolerability of lidocaine patches in children with ACNES. METHODS: Children aged under 18 diagnosed with ACNES who were treated with a 10 day lidocaine patch treatment between December 2021 and December 2022 were studied. Patient record files were used to collect treatment outcomes including pain reduction based on NRS and complications. RESULTS: Twelve of sixteen children (mean age 13 years; F:M ratio 3:1) diagnosed with ACNES started the lidocaine patch treatment. Two patients achieved a pain free status and remained pain free during a 4 and 7 months follow-up. A third child reported a lasting pain reduction, but discontinued treatment due to a temporary local skin rash. Five additional patients reported pain reduction only during application of the patch. The remaining four children experienced no pain relief. No adverse effects were reported. CONCLUSION: Lidocaine patches provides pain relief in a substantial portion of children with ACNES.

Ultrasound-guided abdominal wall infiltration versus freehand technique in anterior cutaneous nerve entrapment syndrome (ACNES): randomized clinical trial.

BACKGROUND: The optimal technique of abdominal wall infiltration for chronic abdominal wall pain due to anterior cutaneous nerve entrapment syndrome (ACNES) is unknown. The aim of this study was to compare pain reduction after an abdominal wall anaesthetic injection by use of an ultrasound-guided technique (US) or given freehand (FH). METHODS: In this multicentre non-blinded randomized trial, adult patients with ACNES were randomized (1:1) to an US or a FH injection technique. Primary outcome was the proportion of injections achieving a minimum of 50 per cent pain reduction on the Numeric Rating Scale (range 0-10) 15-20 min after abdominal wall infiltration ('successful response'). Secondary outcomes were treatment efficacy after 6 weeks and 3 months, and the influence of the subcutaneous tissue thickness on treatment outcome. RESULTS: Between January 2018 and April 2020, 391 injections (US = 192, FH = 199) were administered in 117 randomized patients (US = 55, FH = 62; 76.0 per cent female, mean age 45 years). The proportion of successful responses did not significantly differ immediately after the injection regimen (US 27.1 per cent versus FH 33.2 per cent; P = 0.19) or after 3 months (US 29.4 per cent versus FH 30.5 per cent; P = 0.90). Success was not determined by subcutaneous tissue thickness. CONCLUSION: Pain relief following abdominal wall infiltration by a US or FH technique in ACNES is similar and not influenced by subcutaneous tissue thickness. REGISTRATION NUMBER: Dutch Clinical Trial Register NL8465.

Efficacy of 5% Dextrose Water Injection for Peripheral Entrapment Neuropathy: A Narrative Review.

Current non-surgical treatment for peripheral entrapment neuropathy is considered insignificant and unsustainable; thus, it is essential to find an alternative novel treatment. The technique of perineural injection therapy using 5% dextrose water has been progressively used to treat many peripheral entrapment neuropathies and has been proven to have outstanding effects in a few high-quality studies. Currently, the twentieth edition of Harrison's Principles of Internal Medicine textbook recommends this novel injection therapy as an alternative local treatment for carpal tunnel syndrome (CTS). Hence, this novel approach has become the mainstream method for treating CTS, and other studies have revealed its clinical benefit for other peripheral entrapment neuropathies. In this narrative review, we aimed to provide an insight into this treatment method and summarize the current studies on cases of peripheral entrapment neuropathy treated by this method.

Clemastine improves electrophysiologic and histomorphometric changes through promoting myelin repair in a murine model of compression neuropathy.

Compression neuropathies are common and debilitating conditions that result in variable functional recovery after surgical decompression. Recent drug repurposing studies have verified that clemastine promotes functional recovery through enhancement of myelin repair in demyelinating disease. We investigated the utility of clemastine as a treatment for compression neuropathy using a validated murine model of compression neuropathy encircling the compression tube around the sciatic nerve. Mice received PBS or clemastine solution for 6 weeks of compression phase. Mice taken surgical decompression received PBS or clemastine solution for 2 weeks of decompression phase. Electrodiagnostic, histomorphometric, and Western immunoblotting analyses were performed to verify the effects of clemastine. During the compression phase, mice treated with clemastine had significantly decreased latency and increased amplitude compared to untreated mice that received PBS. Histomorphometric analyses revealed that mice treated with clemastine had significantly higher proportions of myelinated axons, thicker myelin, and a lower G-ratio. The expression levels of myelin proteins, including myelin protein zero and myelin associated glycoprotein, were higher in mice treated with clemastine. However, the electrophysiologic and histomorphometric improvements were observed regardless of clemastine treatment in mice taken surgical decompression. Mice treated with clemastine during compression of the sciatic nerve demonstrated that clemastine treatment attenuated electrophysiologic and histomorphometric changes caused by compression through promoting myelin repair.

Role of TRPV4-P2X7 Pathway in Neuropathic Pain in Rats with Chronic Compression of the Dorsal Root Ganglion.

Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable non-selective cation channel that is involved in the development of neuropathic pain. P2X7 receptor (P2X7) belongs to a class of ATP-gated nonselective cation channels that plays an important role in neuropathic pain. Nevertheless, little is known about the interaction between them for neuropathic pain. In this paper, we investigated role of TRPV4-P2X7 pathway in neuropathic pain. We evaluated the effect of TRPV4-P2X7 pathway on neuropathic pain in a chronic compression of the dorsal root ganglion (DRG) (hereafter termed CCD) model. We analyzed the effect of P2X7 on mechanical and thermal hyperalgesia mediated by TRPV4 in CCD. Furthermore, we assessed the effect of TRPV4 on the expression of P2X7 and the release of IL-1ß and IL-6 in DRG after CCD. We found that intraperitoneal injection of TRPV4 agonist GSK-1016790A led to a significant increase of mechanical and thermal hyperalgesia in CCD, which was partially suppressed by P2X7 blockade with antagonist Brilliant Blue G (BBG). Then, we further noticed that GSK-1016790A injection increased the P2X7 expression of CCD, which was decreased by TRPV4 blockade with antagonist RN-1734 and HC-067047. Furthermore, we also discovered that the expressions of IL-1ß and IL-6 were upregulated by GSK-1016790A injection but reduced by RN-1734 and HC-067047. Our results provide evidence that P2X7 contributes to development of neuropathic pain mediated by TRPV4 in the CCD model, which may be the basis for treatment of neuropathic pain relief.

Immediate inhibition of spinal secretory phospholipase A2 prevents the pain and elevated spinal neuronal hyperexcitability and neuroimmune regulatory genes that develop with nerve root compression.

Cervical nerve root injury induces a host of inflammatory mediators in the spinal cord that initiate and maintain neuronal hyperexcitability and pain. Secretory phospholipase A2 (sPLA2) is an enzyme that has been implicated as a mediator of pain onset and maintenance in inflammation and neural injury. Although sPLA2 modulates nociception and excitatory neuronal signaling in vitro, its effects on neuronal activity and central sensitization early after painful nerve root injury are unknown. This study investigated whether inhibiting spinal sPLA2 at the time of nerve root compression (NRC) modulates the pain, dorsal horn hyperexcitability, and spinal genes involved in glutamate signaling, nociception, and inflammation that are seen early after injury. Rats underwent a painful C7 NRC injury with immediate intrathecal administration of the sPLA2 inhibitor thioetheramide-phosphorlycholine. Additional groups underwent either injury alone or sham surgery. One day after injury, behavioral sensitivity, spinal neuronal excitability, and spinal cord gene expression for glutamate receptors (mGluR5 and NR1) and transporters (GLT1 and EAAC1), the neuropeptide substance P, and pro-inflammatory cytokines (TNFα, IL1α, and IL1ß) were assessed. Treatment with the sPLA2 inhibitor prevented mechanical allodynia, attenuated neuronal hyperexcitability in the spinal dorsal horn, restored the proportion of spinal neurons classified as wide dynamic range, and reduced genes for mGluR5, substance P, IL1α, and IL1ß to sham levels. These findings indicate spinal regulation of central sensitization after painful neuropathy and suggest that spinal sPLA2 is implicated in those early spinal mechanisms of neuronal excitability, perhaps via glutamate signaling, neurotransmitters, or inflammatory cascades.

The oculomotor neurovascular conflict: Literature review and proposal of management.

BACKGROUND: The Oculomotor nerve (OCN) lies in a close relationship with large arteries inside the basal cisterns. Therefore, it may be compressed by vascular malformations or aneurysms. Nevertheless, the compression is not always related to pathologic conditions. Indeed, some cases of neurovascular conflicts of the OCN have been described in the literature. METHODS: A case of neurovascular conflict of the OCN resolved after steroid treatment is reported. Additionally, a systematic literature review of those cases was performed. RESULTS: OCN palsy due to a neurovascular conflict has been described as acute or chronic persistent palsy, or with an intermittent presentation. Symptoms result from compression, although asymptomatic compression is not uncommon. Surgical treatment, pharmacological treatment, and observation have been reported as options in the literature. Microvascular decompression was employed effectively in some cases of OCN neurovascular conflict. Nevertheless, other cases were treated successfully with steroids (persistent presentation) and carbamazepine (intermittent presentation). A management algorithm based on the results of the literature review is proposed. CONCLUSIONS: Treatment options for OCN neurovascular conflicts and their results are heterogeneous. Based on the literature review, the pharmacological treatment seems to be the most appropriate first-line approach, reserving surgery for refractory cases. Collecting clinical information about new cases will allow defining treatment standards for this rare condition.

Notalgia parestésica, tratamiento con toxina botulínica tipo A / Notalgia paresthetica: treatment with botulinum toxin type A

La notalgia parestésica es una mononeuropatía sensitiva por atrapamiento localizada a nivel dorsal. Clínicamente se caracteriza por la presencia de prurito, parestesias y/o hiperalgesia asociados a placas hiperpigmentadas en el dermatoma correspondiente, que genera un gran impacto en la calidad de vida del paciente. Presentamos dos pacientes de entre 35 y 65 años con sintomatología crónica tratados en nuestro servicio mediante infiltraciones subcutáneas de toxina botulínica tipo A en las áreas afectadas. Observamos una disminución de la escala EVA de dolor y de la intensidad del prurito tras la infiltración, así como una disminución de la placa hiperpigmentada al mes, a los tres y a los seis meses y que se mantiene al año. Concluimos que el tratamiento con toxina botulínica tipo A podría ser una alternativa segura y útil en estos pacientes, ya que en nuestro estudio ha demostrado ser eficaz a más largo plazo que los tratamientos disponibles hasta la actualidad, aunque se necesitan más estudios con pacientes para confirmarlo

Notalgia paresthetica is a sensory mononeuropathy caused by compression localized in the dorsal region. The condition is clinically characterised by the presence of pruritus, paresthesias and hyperalgesia associated with a hyperpigmented patch in the correspondingt dermatoma, substantially impairing quality of life. We report the cases of two patients aged between 35 and 65 years with chronic symptoms and treated in our service with botulinum toxin type A in the affected areas. We observed a decrease in the EVA pain scale and the intensity of the pruritus after infiltrations, as well as a reduction in the hyperpigmented patch at the first, third and sixth months after the intradermal injections that has been maintained after a year. We conclude that botulinum toxin type A treatment could be a safe and useful alternative in these patients, as it has been shown to be effective over a longer term than available treatments to date, although further studies are required to confirm our findings

Ultrasound-Guided Perineural Injection for Pronator Syndrome Caused by Median Nerve Entrapment.

Patients and physicians have increasingly sought minimally invasive procedures such as ultrasound-guided injection for the treatment of peripheral nerve entrapment syndromes. In this series, we assessed subjective outcome data in 14 patients who underwent ultrasound-guided perineural hydrodissection and steroid injection for pronator syndrome secondary to median nerve entrapment in the pronator tunnel. Excellent symptomatic relief (≥75% improvement) was achieved in 70% of nerves with 3-month follow-up data, with no significant change in symptoms between 3 and 6 months. These outcomes suggest that this technique could play a role in the management of pronator syndrome due to median nerve entrapment.

Suprasellar Cysticercosis Cyst with Optic Nerve Compression Masquerading as an Arachnoid Cyst.

Cysticercosis is a parasitic infection caused by the larvae of the cestode Taenia solium. Ocular parasitosis in humans is well recognized; however, cysticercosis of the optic nerve is rare. Here, we report a case of an adult male who presented with right-sided headache and a gradual loss of vision in the right eye. Optical coherence tomography indicated severe loss of ganglion cells in the right eye. Magnetic resonance imaging showed a predominantly suprasellar cystic lesion thought to represent an arachnoid cyst. We performed a craniotomy to excise the cyst. Histopathological examination of the excised cyst revealed internal living larvae of T. soilum. After co-administration of praziquantel and albendazole, vision was restored, and the headaches ceased. Vision has since been restored in both eyes. A higher degree of neurocysticercosis suspicion should be maintained for patients living in endemic areas who present with ophthalmic symptoms where the brain scans show cystic lesions.

Abdominal Cutaneous Nerve Entrapment Syndrome, Case Report and Diagnostic Evaluation

Abdominal cutaneous nerve entrapment is a rarely diagnosed condition that leads to intense neuropathic pain in the anterolateral wall of the abdomen. Generally, it is triggered by some factor implied in the increase of the pressure on the nerve in its passage by the abdominal wall. Its most important differential diagnosis is pain of visceral origin. We present a case in which the clinical findings confirmed on ultrasound and other imaging tests established the diagnosis and in which the noninvasive treatment was effective.

Relief of Neuropathic Pain Through Epidermal Growth Factor Receptor Inhibition: A Randomized Proof-of-Concept Trial.

OBJECTIVE: Case reports and a case series have described relief of neuropathic pain (NP) after treatment with epidermal growth factor receptor inhibitors (EGFR-Is). These observations are supported by preclinical findings. The aim of this trial was to explore a potential clinical signal supporting the therapeutic efficacy of EGFR-Is in NP. METHODS: In a proof-of-concept trial using a randomized, double-blind, placebo-controlled design, 14 patients with severe, chronic, therapy-resistant NP due to compressed peripheral nerves or complex regional pain syndrome were randomized to receive a single infusion of the EGFR-I cetuximab and placebo in crossover design, followed by a single open-label cetuximab infusion. RESULTS: The mean reduction in daily average pain scores three to seven days after single-blinded cetuximab infusion was 1.73 points (90% confidence interval [CI] = 0.80 to 2.66), conferring a 1.22-point greater reduction than placebo (90% CI = -0.10 to 2.54). Exploratory analyses suggested that pain reduction might be greater in the 14 days after treatment with blinded cetuximab than after placebo. The proportion of patients who reported ≥50% reduction in average pain three to seven days after cetuximab was 36% (14% after placebo), and comparison of overall pain reduction suggests a trend in favor of cetuximab. Skin rash (grade 1-2) was the most frequent side effect (12/14, 86%). CONCLUSIONS: This small proof-of-concept evaluation of an EGFR-I against NP did not provide statistical evidence of efficacy. However, substantial reductions in pain were reported, and confidence intervals do not rule out a clinically meaningful treatment effect. Evaluation of EGFR-I against NP therefore warrants further investigation.

Neurosurgical treatment of leprosy neuropathy in a low-incidence, European country.

INTRODUCTION: Leprosy is nowaday increasingly encountered in non-endemic countries. Nerve involvement is common. Swelling of the nerves may lead to entrapment neuropathy causing pain and neurological deficits. Delay in diagnosis and treatment may lead to loss of chance of improvement. Surgical decompression in conjunction with medical therapy allows relief of symptoms. METHODS: We present a retrospective series of 21 patients surgically treated in our center for leprosy entrapment neuropathy. We report presentation, treatment, and outcome at follow-up including a brief literature review. RESULTS: Twenty-one patients were treated for nerve entrapments in four different anatomical districts. We reported good clinical outcomes mainly in motor deficits but also in improvement of sensitive deficits and pain symptoms. We did not experience surgical complications. DISCUSSION: Although there is a lack of high-quality prospective studies comparing medical and surgical treatment of leprosy neuropathy, benefits of surgery are widely reported in series and case reports from endemic countries. There is scant literature from low-incidence countries even if leprosy incidence is nowaday increasing in these countries and will likelihood further increase in the future. Our results are in line with the literature presenting good outcomes after surgery. CONCLUSION: We believe that a precise knowledge of the pathology and its management is crucial also for physicians who work in low-incidence countries to maximize healing chances with timely diagnosis and treatment.