Mechanosensitive Ion Channel TMEM63A Gangs Up with Local Macrophages to Modulate Chronic Post-amputation Pain / 神经科学通报·英文版

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.

Mucosal Schwann cell hamartoma of the gallbladder

Mucosal Schwann cell hamartoma (MSCH) is a rare benign neurogenic tumor characterized by pure S100p positive spindle cell proliferation. Most cases occur in the distal colon. Involvement of the gall bladder is exceedingly rare. There have been no reports of recurrence or a syndromic association with MSCH. Herein, we describe a case of MSCH of the gallbladder in a 55-year-old female patient with prior history of gastrointestinal neurofibromas who presented with abdominal pain. MR imaging revealed choledocholithiasis, gallbladder thickening, and marked biliary and pancreatic ductal dilation. The patient subsequently underwent cholecystectomy with choledochoduodenostomy. Histologic evaluation of the gallbladder showed diffuse expansion of the mucosa with S100p positive cells with spindly nuclei and indistinct cytoplasmic borders and diagnosis of MSCH of the gallbladder was rendered.

Solitary circumscribed neuroma of the conjunctiva: Differential diagnosis from neurofibroma is a must? / Neuroma circunscrito solitário da conjuntiva: diagnóstico diferencial de neurofibroma obrigatório?

ABSTRACT A 42-year-old male presented with a 4-week history of a mass in the right inferior palpebral conjunctiva close to the punctum. An excisional biopsy of the lesion and histopathological examination revealed that the mass was composed of Schwann cells with thin conical nuclei, fine chromatin, and unnoticeable nucleoli. Immunohistochemically, the spindle cells were diffusely and strongly positive for S100 protein. Neurofilament immunostaining was also positive, which highlighted axons. In light of these findings, the tumor was diagnosed as solitary circumscribed neuroma. A comprehensive evaluation for multiple endocrine neoplasia type 2b was performed. However, no multiple endocrine neoplasia type 2b stigmata and no family history were detected. The diagnosis was therefore finalized as solitary circumscribed neuroma, which is considered as a rare condition. The differential diagnosis is based on the histopathological examination and immunohistochemical evaluation. As the tumor can be related with multiple endocrine neoplasia type 2b, it is essential to systematically investigate for multiple endocrine neoplasia type 2b in such cases.

RESUMO Um homem de 42 anos apresentou uma massa na conjuntiva palpebral inferior direita, próxima ao punctum, com evolução de 4 semanas. Uma biópsia excisional da lesão e o subsequente exame anatomopatológico revelaram que a massa era composta de células de Schwann com núcleos cônicos, croma­tina fina e nucléolos não visíveis. Ao exame imuno-histoquímico, as células fusiformes mostraram-se difusa e fortemente positivas para a proteína S100. A imunocoloração também foi positiva para neurofilamentos e evidenciou os axônios. Considerando esses achados, o tumor foi diagnosticado como um neuroma circunscrito solitário. Procedeu-se uma investigação completa para neoplasia endócrina múltipla tipo 2b, entretanto, estigmas característicos e história familiar não foram detectados. Assim, o diagnóstico foi firmado como neuroma circunscrito solitário, condição rara cujo diagnóstico diferencial baseia-se no exame anatomopatológico e na avaliação imuno-histoquímica. Já que esse tumor pode estar relacionado à neoplasia endócrina múltipla tipo 2b, torna-se essencial, nesses casos, a investigação da neoplasia de forma sistemática.

Ictericia obstructiva por neuroma de amputación de vía biliar: Reporte de caso / Obstructive ictericia by neuroma of amputation of via biliar: Case report

Los neuromas del conducto biliar se desarrollan a partir de las fibras nerviosas simpáticas y parasimpáticas que envuelven la pared de la vía biliar. Mujer de 44 años de edad con antecedente de colecistectomía convencional seis meses previos al ingreso acude a emergencia por ictericia obstructiva de 15 días de evolución. En los estudios de imagen impresiona la presencia de una masa a nivel de las vías biliares considerándose el diagnostico de una neoplasia maligna. Por los antecedentes, ausencia de marcadores tumorales se decide realizar una biopsia percutánea sin resultados concluyente, realizándose posteriormente una intervención quirúrgica con estudio anatomo-patológico compatible con neuroma de amputación de vía biliar. El neuroma de amputación a nivel de la vía biliar es un tumor infrecuente. Puede manifestarse clínicamente como una ictericia obstructiva y suele simular a un tumor maligno de las vías biliares. El manejo quirúrgico es el tratamiento definitivo.

Neuromas of the bile duct develop from the sympathetic and parasympathetic nerve fibers that surround the wall of the bile duct. A 44-year-old woman with a history of conventional cholecystectomy six months prior to hospital admission attended emergency due to obstructive jaundice that lasted 15 days. In the imaging studies, the presence of a mass at the level of the bile ducts is considered, considering the diagnosis of a malignant neoplasm. Due to the antecedents, the absence of tumor markers, it was decided to perform a percutaneous biopsy without conclusive results, performing later a surgical intervention with anatomopathological study compatible with neuroma of biliary tract amputation. The amputation neuroma at the level of the bile duct is an infrequent tumor. It can manifest clinically as obstructive jaundice and usually simulates a malignant tumor of the bile ducts. Surgical management is the definitive treatment.

Ulcerated bleeding palisaded encapsulated neuroma of the tongue

@#Introduction: Palisaded encapsulated neuroma (PEN) is a benign lesion of Schwann cells and its occurrence in the oral mucosa especially the tongue is very rare. Case Report: This article describes a case of a 41-year-old male, a chronic smoker with an actively bleeding, ulcerated, solitary, firm lesion on the lateral border of the tongue which had bled thrice before. A differential diagnosis of pyogenic granuloma, haemangioma, fibroma, nerve sheath tumour, salivary gland tumour and malignancy was made and surgically excised. Histopathology of the excised specimen revealed a well-circumscribed lesion with spindle-shaped cells arranged in interlacing fascicles and with the help of immunohistochemical markers confirmed it to be a PEN. Discussion: To our knowledge, this is the first description of an ulcerated PEN presented with an active bleed.

Forefoot disorders and conservative treatment / 영남의대학술지

Forefoot disorders are often seen in clinical practice. Forefoot deformity and pain can deteriorate gait function and decrease quality of life. This review presents common forefoot disorders and conservative treatment using an insole or orthosis. Metatarsalgia is a painful foot condition affecting the metatarsal (MT) region of the foot. A MT pad, MT bar, or forefoot cushion can be used to alleviate MT pain. Hallux valgus is a deformity characterized by medial deviation of the first MT and lateral deviation of the hallux. A toe spreader, valgus splint, and bunion shield are commonly applied to patients with hallux valgus. Hallux limitus and hallux rigidus refer to painful limitations of dorsiflexion of the first metatarsophalangeal joint. A kinetic wedge foot orthosis or rocker sole can help relieve symptoms from hallux limitus or rigidus. Hammer, claw, and mallet toes are sagittal plane deformities of the lesser toes. Toe sleeve or padding can be applied over high-pressure areas in the proximal or distal interphalangeal joints or under the MT heads. An MT off-loading insole can also be used to alleviate symptoms following lesser toe deformities. Morton's neuroma is a benign neuroma of an intermetatarsal plantar nerve that leads to a painful condition affecting the MT area. The MT bar, the plantar pad, or a more cushioned insole would be useful. In addition, patients with any of the above various forefoot disorders should avoid tight-fitting or high-heeled shoes. Applying an insole or orthosis and wearing proper shoes can be beneficial for managing forefoot disorders.

Refractory intercostal neuralgia due to intercostal schwannoma: A case report

Intercostal neuralgia is neuropathic pain that develops in the thorax and abdomen. It usually occurs as a result of injury or inflammation associated with the intercostal nerve triggered by trauma, surgery, or herpes zoster. Primary intercostal neuroma is a rare cause of intercostal neuralgia. A 69-year-old male patient without a history of thoracic trauma or surgery underwent repeated testing and intermittent treatment for refractory pain in the right chest and abdomen for several years. However, the treatment had limited effect. Abdominal computed tomography performed to diagnose recent pain aggravation revealed schwannoma of the 11th intercostal nerve. The patient's pain was relieved following surgical excision of the tumor.

Palisaded Encapsulated Neuroma Occuring at the Previous Excision Site of Epidermal Cyst on the Scalp / 대한피부과학회지

No abstract available.

Functional Improvement Following Revision Surgery in a Patient with the Dual Disability of a Complicated Residual Limb and Contralateral Hemiplegia: A Case Report

The number of reported cases with dual disability is increasing for the past few decades. Currently, dual disability of lower limb amputation and motor weakness after stroke became a strong issue in public concern. The functional levels of patients have shown in the wide range from independent community ambulation to non-ambulation. Thus, it indicates that favorable outcomes for dual disability may depend upon adopted rehabilitative strategies. We present the case of a man with left below-knee amputation and severe right-sided weakness following a huge putaminal hemorrhage. He had suffered from extreme pain and misfit of the prosthetic socket and the complicated residual limb for three years prior to the stroke. Forty days post-stroke, we performed a revision surgery to resolve the complications of bony overgrowth, verrucous hyperplasia, and neuroma and applied an ankle foot orthosis (AFO). Two years post-stroke, he was able to ambulate outside his home and negotiate stairs using a cane. This is the first case with the dual disability of lower limb amputation and contralateral hemiplegia to undergo revision surgery. The results suggest that an early revision surgery and use of an AFO are crucial for achieving a higher level of mobility in such cases.

Post-transplant Amputation Traumatic Neuroma of the Hilum and Extrahepatic Duct in a Liver Donor

No abstract available.

A Case of Rudimentary Polydactyly: Is It Truly Related to Polydactyly? / 대한피부과학회지

Rudimentary polydactyly is a congenital anomaly of the hand clinically ranging from a small wart-like tumor to a pedunculated structure near the thumb or little finger. The histology reveals a marked neural proliferation, dilated blood vessels, and some Meissner corpuscles in the dermis. The etiology is unknown and there are a few theories. First, Hare believed that it represented a vestigial form of supernumerary finger, and termed it rudimentary polydactyly. Since then, Shapiro et al. has argued that rudimentary polydactyly is an amputation neuroma after finding histological similarity between acquired traumatic neuroma and rudimentary polydactyly. Recently Brehmer- Andersson et al. asserted that rudimentary polydactyly is a neuroma that can arise in any area containing Meissner corpuscles after observing a penile lesion with similar histology as rudimentary polydactyly. We report a case of rudimentary polydactyly characteristically not showing any prominent Meissner corpuscles. With this case, we provide support for the theory of Shapiro et al.

Ultrasonographic features of traumatic neuromas in breast cancer patients after mastectomy

PURPOSE: The purpose of this study was to evaluate the ultrasonographic (US) features of traumatic neuromas in breast cancer patients after mastectomy. METHODS: This study was performed with approval from our Institutional Review Board, and the requirement for informed consent was waived. Six traumatic neuromas in five patients were included in this study. The US findings of traumatic neuromas were evaluated retrospectively by two radiologists according to the Breast Imaging-Reporting and Data System (BI-RADS) lexicon. The final assessment was also recorded. RESULTS: On US, all six lesions presented as a mass within the pectoralis muscle layer (mean size, 4.8 mm; range, 3.9 to 5.5 mm). Of the six masses, four had an oval shape with a circumscribed margin, and two had an irregular shape and an indistinct margin. They were all hypoechoic. Two lesions showed a non-parallel orientation. On color Doppler examinations, two lesions showed internal vascularity. Strain elastography was performed for four neuromas, resulting in scores of 1 (n=1), 4 (n=2), and 5 (n=1). The final assessment categories were BI-RADS 3 (n=2), 4A (n=2), and 4B (n=2). CONCLUSION: On US, an oval shape, circumscribed margin, parallel orientation, and hypoechogenicity were the most frequent features of traumatic neuromas in breast cancer patients after mastectomy. Neuromas may show increased vascularity on color Doppler imaging and present as a hard mass on elastography.

Palisaded encapsulated [solitary circumscribed] neuroma of the buccal mucosa: a rare case

The rarity of oral soft tissue spindle cell tumors combined with overlapping microscopic patterns can make challenges in their diagnosis and treatment. Oral cavity palisaded encapsulated neuroma is an uncommon lesion which occurs often on the hard palate. It is essential for oral pathologists to be familiar with its histopathology of this lesion is essential since many lesions are probably diagnosed microscopically as neurofibroma or schwannoma. Here, we report a case of oral palisaded encapsu-lated [solitary circumscribed] neuroma in an unusual site

Unusual Presentation of Traumatic Neuroma of the Medial Plantar Nerve after Deep Laceration Mimicking a Foreign Body Granuloma: A Case Report / 대한족부족관절학회지

Traumatic neuromas are rare benign tumors that are common after trauma or surgery and are usually accompanied by obvious symptoms of pain. Most reports show neuromas in the face, neck, and limbs, and the traumatic neuroma of the medial plantar nerve has rarely been reported. We encountered a traumatic neuroma of the medial plantar nerve after a deep laceration mimicking a foreign body granuloma. A small mass lesion was found around plantar aponeurosis with heterogeneous high signal intensity in the T2 fat suppression view and slightly enhanced intensity in the magnetic resonance imaging that suggested a foreign body granuloma. The lesion was diagnosed pathologically as a traumatic neuroma. A satisfactory clinical result was obtained after excision of the traumatic neuroma and burial of the proximal and distal stumps to the adjacent muscle at the secondary operation.

Extracorporeal Shock Wave Therapy For Treatment of Intractable Stump Pain

Amputation stump pains can be developed in amputation sites after high voltage electrical burn injuries. We experienced one case of these severe stump pains in an upper extremity amputation patient. A 35-year-old man had a 38% total body surface area high voltage electrical burn. The patient underwent skin grafting and left shoulder disarticulation. During the rehabilitation period, he complained about severe stump area pains and phantom pains. We injected 0.5% Bupivacaine and Triamcinolone on the stump neuroma site but the pain sustained. After extracorporeal shock wave therapy (ESWT,) the pain subsided and did not recur. The patient was satisfied with functional and pain outcomes, so we report this case.

Nerve Repair and Nerve Grafting in Brachial Plexus Injuries

Brachial plexus injuries (BPI) can have devastating effects on upper extremity function, however, treatment in this injuries remains a difficult problem. Several kinds of surgical methods have been used to treat BPI, and nerve repair and nerve grafting have been traditionally used in postganglionic injury of brachial plexus. Because the several studies reported that nerve transfer to restore shoulder and elbow function has yielded superior results to historical reports for nerve grafting in partial BPI, the indication of nerve repair and nerve grafting has been decreased. Nonetheless, nerve repair and nerve grafting is still useful in focal damage in brachial plexus, such as laceration or gunshot wound and postganglionic neuroma in continuity without conduction of nerve action potential. In this paper, we described the basic concept, detailed indication and outcomes of nerve repair or nerve grafting in BPI.

Morton's Neuroma / 대한정형외과학회잡지

Morton's neuroma, also known as interdigital neuroma, is a common cause of forefoot pain. It is a compressive neuropathy of the interdigital nerve, which is compressed by the overlying transverse metatarsal ligament. It is not a true tumor. The symptoms are forefoot pain that radiates into the toes, according to the involved nerve branches. Its histological findings are fibrosis around the nerve, demyelination. The clinical diagnosis can be obtained from a detailed history and physical examination, such as the compressive test. Moreover, ultrasonography and magnetic resonance imaging can also be used. Conservative treatment is the common initial treatment modality for interdigital neuroma. Surgical excision or decompression is indicated after a failure of conservative treatments.

Comparison of palmar digital neurectomy by the guillotine technique and palmar digital neurotomy associated with end-to-side neurorrhaphy in mares / Comparação entre neurectomia por técnica de guilhotina e neurotomia associada à neurorrafia em alça de balde em nervo digital palmar de éguas

Five mares were submitted to palmar digital neurectomy by the guillotine technique and palmar digital neurotomy followed by end-to-side neurorrhaphy (right and left thoracic limbs, respectively). Mares were checked for local pain sensation using hoof tester and submitted to lameness workup at 15-day intervals. No evidence of painful neuroma formation was detected. Palmar digital nerve (PDN) stump segments were collected within 60 days of surgery. Mean left and right limb PDN stump thickness corresponded to 5.96 mm and 7.16 mm, respectively. Schwann cells prevailed over connective healing tissue in all PDN stumps studied. Well-formed nerve-like structures with better organized nervous tissue and predominance of parallel nerve fiber orientation were documented in left limb PDN stumps. End-to-side neurorrhaphy tended to promote tissue organization, potentially reducing the chances of neuroma formation...

O nervo digital palmar (NDP) lateral do membro torácico direito (MTD) de cinco equinos fêmeas foi submetido à neurectomia pela técnica da guilhotina, e o do membro torácico esquerdo (MTE) à neurotomia e neurorrafia término-lateral. Os animais foram avaliados a cada 15 dias quanto ao teste de sensibilidade cutânea com pressão local com pinça de casco e de claudicação, não sendo notados sinais clínicos de neuroma doloroso. Aos 60 dias pós-cirurgia coletou-se segmentos dos cotos proximais dos NDPs. Os dos MTDs apresentavam em média, a espessura de 7,16 mm e aos dos MTEs de 5,96 mm. Nos cotos proximais dos nervos dos membros direito e esquerdo notou-se predominância de células de Schwann à grande quantidade de tecido conjuntivo cicatricial. Os do MTEs apresentavam estruturas de nervo típico, bem constituídas, com maior organização do tecido nervoso e predomínio de fibras nervosas orientadas paralelamente. A neurorrafia termino-lateral apresentou tendência a ocasionar maior organização entre as estruturas analisadas, o que lhe conferiu menor potencial em desenvolver neuromas dolorosos...

Accidental injury of the inferior alveolar nerve due to the extrusion of calcium hydroxide in endodontic treatment: a case report

During clinical endodontic treatment, we often find radiopaque filling material beyond the root apex. Accidental extrusion of calcium hydroxide could cause the injury of inferior alveolar nerve, such as paresthesia or continuous inflammatory response. This case report presents the extrusion of calcium hydroxide and treatment procedures including surgical intervention. A 48 yr old female patient experienced Calcipex II extrusion in to the inferior alveolar canal on left mandibular area during endodontic treatment. After completion of endodontic treatment on left mandibular first molar, surgical intervention was planned under general anesthesia. After cortical bone osteotomy and debridement, neuroma resection and neurorrhaphy was performed, and prognosis was observed. But no improvement in sensory nerve was seen following surgical intervention after 20 mon. A clinician should be aware of extrusion of intracanal medicaments and the possibility of damage on inferior alveolar canal. Injectable type of calcium hydroxide should be applied with care for preventing nerve injury. The alternative delivery method such as lentulo spiral was suggested on the posterior mandibular molar.