Clinical associations of corneal neuromas with ocular surface diseases

Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.

Development and Validation of a Deep Learning Predictive Model Combining Clinical and Radiomic Features for Short-Term Postoperative Facial Nerve Function in Acoustic Neuroma Patients

Objective This study aims to construct and validate a predictable deep learning model associated with clinical data and multi-sequence magnetic resonance imaging(MRI)for short-term postoperative facial nerve function in patients with acoustic neuroma.Methods A total of 110 patients with acoustic neuroma who underwent surgery through the retrosigmoid sinus approach were included.Clinical data and raw features from four MRI sequences(T1-weighted,T2-weighted,T1-weighted contrast enhancement,and T2-weighted-Flair images)were analyzed.Spearman correlation analysis along with least absolute shrinkage and selection operator regression were used to screen combined clinical and radiomic features.Nomogram,machine learning,and convolutional neural network(CNN)models were constructed to predict the prognosis of facial nerve function on the seventh day after surgery.Receiver operating characteristic(ROC)curve and decision curve analysis(DCA)were used to evaluate model performance.A total of 1050 radiomic parameters were extracted,from which 13 radiomic and 3 clinical features were selected.Results The CNN model performed best among all prediction models in the test set with an area under the curve(AUC)of 0.89(95%CI,0.84–0.91).Conclusion CNN modeling that combines clinical and multi-sequence MRI radiomic features provides excellent performance for predicting short-term facial nerve function after surgery in patients with acoustic neuroma.As such,CNN modeling may serve as a potential decision-making tool for neurosurgery.

A decellularized nerve matrix scaffold inhibits neuroma formation in the stumps of transected peripheral nerve after peripheral nerve injury

Traumatic painful neuroma is an intractable clinical disease characterized by improper extracellular matrix(ECM)deposition around the injury site.Studies have shown that the microstructure of natural nerves provides a suitable microenvironment for the nerve end to avoid abnormal hyperplasia and neuroma formation.In this study,we used a decellularized nerve matrix scaffold(DNM-S)to prevent against the formation of painful neuroma after sciatic nerve transection in rats.Our results showed that the DNM-S effectively reduced abnormal deposition of ECM,guided the regeneration and orderly arrangement of axon,and decreased the density of regenerated axons.The epineurium-perilemma barrier prevented the invasion of vascular muscular scar tissue,greatly reduced the invasion ofα-smooth muscle actin-positive myofibroblasts into nerve stumps,effectively inhibited scar formation,which guided nerve stumps to gradually transform into a benign tissue and reduced pain and autotomy behaviors in animals.These findings suggest that DNM-S-optimized neuroma microenvironment by ECM remodeling may be a promising strategy to prevent painful traumatic neuromas.

Regenerative peripheral nerve interface prevents neuroma formation after peripheral nerve transection

Neuroma formation after peripheral nerve transection often leads to severe neuropathic pain.Regenerative peripheral nerve interface has been shown to reduce painful neuroma in the clinic.However,no reports have investigated the underlying mechanisms,and no comparative animal studies on regenerative peripheral nerve interface and other means of neuroma prevention have been conducted to date.In this study,we established a rat model of left sciatic nerve transfection,and subsequently interfered with the model using the regenerative peripheral nerve interface or proximal nerve stump implantation inside a fully innervated muscle.Results showed that,compared with rats subjected to nerve stump implantation inside the muscle,rats subjected to regenerative peripheral nerve interface intervention showed greater inhibition of the proliferation of collagenous fibers and irregular regenerated axons,lower expressions of the fibrosis markerα-smooth muscle actin and the inflammatory marker sigma-1 receptor in the proximal nerve stump,lower autophagy behaviors,lower expressions of c-fos and substance P,higher expression of glial cell line-derived neurotrophic factor in the ipsilateral dorsal root ganglia.These findings suggested that regenerative peripheral nerve interface inhibits peripheral nerve injury-induced neuroma formation and neuropathic pain possibly via the upregulation of the expression of glial cell line-derived neurotrophic factor in the dorsal root ganglia and reducing neuroinflammation in the nerve stump.

Hearing Preservation in Acoustic Neuroma Surgery

Objective To report the authors' experiences in hearing preservation during acoustic neuroma (AN) resection procedures. Methods Two cases of AN removal via retrosigmoid approach were reviewed. Hearing preservation was attempted in the aid of endoscopic technique along with continuous monitoring of the compound action potential (CAP) and auditory brainstem response(ABR) during the surgery. Results The tumor in Case 1 was 1.5 cm in diameter. The average pure-tone hearing threshold was 30 dB HL and ABR was normal. Waves I, III and V of ABR were present following tumor removal. At 7th month follow-up, audiometric thresholds and ABR inter-peak intervals had recovered to pre-operative levels, with normal facial nerve function. The patient in Case 2 had bilateral AN. The tumors measured 4.0 cm(left) and 5.0 cm (right) on MRI scans. The AN on the right side was removed first, followed by removal of the left AN four months later. Intraoperative CAP monitoring was employed during removal of the left AN. While efforts to preserve the cochlear nerve were not successful, CAPs were still present after tumor removal. Conclusions Intraoperatively recorded CAPs are not reliable in predicting postoperative hearing outcomes. In contrast, ABRs are an indicator of function of the peripheral auditory pathway. Presence of waves I, III and V following tumor removal may represent preservation of useful hearing.

Traumatic neuroma of remnant cystic duct mimicking duodenal subepithelial tumor:A case report

BACKGROUND Gastrointestinal subepithelial tumors(GSTs),incidentally detected during upper gastrointestinal(GI)endoscopy,may be lesions derived from the GI wall or may be caused by compression from external organs.In general,traumatic neuroma is a benign nerve tumor that results from postoperative nerve injury,occurring in the bile duct as one of the complications after cholecystectomy.This is the first case report demonstrating that neuroma of the cystic duct can be incorrectly perceived as a duodenal subepithelial tumor by compressing the duodenal wall.CASE SUMMARY We report the case of a 72-year-old man with traumatic neuroma of the cystic duct after cholecystectomy.This tumor was mistaken for a duodenal subepithelial tumor on preoperative upper GI endoscopy and endoscopic ultrasonography due to external compression of the GI wall.The patient had no symptoms,and his laboratory test results were normal.However,in a series of follow-up endoscopies,the tumor was found to have grown in size,so it was surgically resected.The lesion was completely removed by laparoscopic endoscopic cooperative surgery.The patient was discharged on postoperative day 7 without complications.CONCLUSION Traumatic neuroma of the cystic duct can be mistaken for GSTs in GI endoscopy.

Myelin-associated glycoprotein combined with chitin conduit inhibits painful neuroma formation after sciatic nerve transection

Studies have shown that myelin-associated glycoprotein(MAG)can inhibit axon regeneration after nerve injury.However,the effects of MAG on neuroma formation after peripheral nerve injury remain poorly understood.In this study,local injection of MAG combined with nerve cap made of chitin conduit was used to intervene with the formation of painful neuroma after sciatic nerve transfection in rats.After 8 weeks of combined treatment,the autotomy behaviors were reduced in rats subjected to sciatic nerve transfection,the mRNA expression of nerve growth factor,a pain marker,in the proximal nerve stump was decreased,the density of regenerated axons was decreased,the thickness of the myelin sheath was increased,and the ratio of unmyelinated to myelinated axons was reduced.Moereover,the percentage of collagen fiber area and the percentage of fibrosis marker alpha-smooth muscle actin positive staining area in the proximal nerve stump were decreased.The combined treatment exhibited superior effects in these measures to chitin conduit treatment alone.These findings suggest that MAG combined with chitin conduit synergistically inhibits the formation of painful neuroma after sciatic nerve transection and alleviates neuropathic pain.This study was approved by the Animal Ethics Committee of Peking University People’s Hospital(approval No.2019PHE027)on December 5,2019.

ADVANCES IN SURGICAL TREATMENT OF ACOUSTIC NEUROMA

Acoustic Neuroma (AN) arises from the eighth cranial nerve. It primarily involves the vestibular branch of the nerve and is therefore also called vestibular schwannoma(VS). To the date, diagnosis and surgical treatment of AN have advanced significantly. Along with advances in audiology and imaging technologies, cases of diagnosed AN have been increasing, making it a common

Surgical treatment outcome of painful traumatic neuroma of the infrapatellar branch of the saphenous nerve during total knee arthroplasty

BACKGROUND Development of infrapatellar saphenous neuroma(ISN)is a well-recognized reason for knee pain following total knee arthroplasty(TKA).So far,very few studies have addressed the development of painful ISN after TKA and its impact on functional outcome and patient satisfaction.AIM To present the results of surgical treatment for ISN after primary TKA,the level of pain relief,and the improvement of knee motion and function.METHODS Fifteen patients(13 women,2 men)with persistent medial pain for more than six months after primary TKA,due to osteoarthritis,underwent surgical excision of ISN.ISN diagnosis was confirmed with the presence of Tinel’s sign along the course of the infrapatellar branch of the saphenous nerve and with pain relief after selective nerve block using local anesthetic.Component loosening,malalignment,instability and infection were excluded systematically in all patients as a source of pain.Pain relief in terms of visual analog scale(VAS),active knee range of motion(ROM),and the Knee Society Score(KSS)for pain and function were evaluated preoperatively and at least six months postoperatively.RESULTS The mean patients’age was 71.3±5.4 years old.The mean interval between TKA and neuroma excision was 10 mo(range,6 to 14 mo),while the mean follow-up was 8 mo(range:6 to 11 mo).All 15 patients experienced almost complete immediate pain relief and resolution of allodynia and hyperesthesia after surgery.Pain on the VAS scale improved from 8.6±1.3 preoperatively to 0.8±0.9 at the final follow-up(P=0.001).KSS pain and function scores were improved from 49.3±5.9 and 62.7±12.8 before surgery to 91.8±4.2 and 75.3±11.3 after surgery,respectively(P=0.001 and P=0.015).Active knee ROM was also increased postoperatively from 96±4 to 105±6 degrees(P=0.001).There were no complications and no further operations required.CONCLUSION ISN should be considered a potential cause of persistent pain following TKA.Neuroma excision not only provides immediate pain relief and resolution of symptoms but may also improve the knee range of motion.

Role of imaging methods in diagnosis and treatment of Morton's neuroma

Among the many causes of forefoot pain, Morton's neuroma(MN) is often suspected, particularly in women, due to its high incidence.However, there remain controversies about its relationship with symptomatology and which diagnostic and treatment choices to choose.This article mainly focuses on the role of the various imaging methods and their abilities to support an accurate diagnosis of MN, ruling out other causes of forefoot pain, and as a way of providing targeted imaging-guided therapy for patients with MN.

Mechanism of the inhibition of neuroma formation by autogenous nerve replantation in situ after amputation in rabbits

Two experimental patterns of autogenous nerve replantation in situ and centrocentralnerve suture were performed on the rabbit median and ulnar nerves.The results of light andtransmission electron microscopy as well as immunohistochemistry showed that autogenous nervereplantation in situ could inhibit the formation of neuroma.The mechanism might be that twoproximal stump axons could touch within the interpolated graft segment.Simple end-to-endnerve suture failed to inhibit neuroma development because of a lack of proper environment forthe touching between two proximal stump axons.

Contrast-enhanced ultrasound of a traumatic neuroma of the extrahepatic bile duct:A case report and review of literature

BACKGROUND Traumatic neuromas result from nerve injury after trauma or surgery but rarely occur in the bile duct.However,it is challenging to diagnose traumatic neuromas correctly preoperatively.Although some previous reports have described the imaging features of traumatic neuroma in the bile duct,no features of traumatic neuromas in the bile duct have been identified by using contrast-enhanced ultrasound(CEUS)imaging before.CASE SUMMARY A 55-year-old male patient presented to our hospital with a 3-mo history of abdominal distension and anorexia and history of cholecystectomy 4 years ago.Grayscale ultrasound demonstrated mild to moderate intrahepatic bile duct dilatation.Meanwhile,a hyperechoic nodule was found in the upper extrahepatic bile duct.The lesion approximately 0.8 cm×0.6 cm with a regular shape and clear margins.The nodule of the bile duct showed slight hyperenhancement in the arterial phase and isoenhancement in the venous phase on CEUS.Laboratory tests showed that alanine aminotransferase and aspartate aminotransferase were increased significantly,while the tumor marker carbohydrate antigen 19-9 was increased slightly.Then,hilar bile duct resection and end-to-end bile ductal anastomosis were performed.The histological examination revealed traumatic neuroma of the extrahepatic bile duct.The patient had an uneventful recovery after surgery.CONCLUSION The current report will help enhance the current knowledge regarding identifying traumatic neuromas by CEUS imaging and review the related literature.

Palisaded encapsulated neuroma of the upper lip

Palisaded encapsulated neuroma (PEN;solitary circumscribed neuroma) is a benign and hyperplastic lesion consisting of Schwann cells. PEN of the lower lip was reported by Tomich and Moll [1] 35 years ago. However, the accumulation of the information about PEN which occurred in the oral mucosa was not enough. This article describes a case of a PEN on the upper lip of a 41-year-old woman. The lesion with 0.7 cm diameter was performed excisional biopsy. Histologically, the tumor was almost circumscribed by thin fibrous capsule, and consisted of diffusely and dense proliferation of the spindle shape cells arranged in interlacing fascicles. Focal suggestions of nuclear pal-isaded growth were indicated within the tumor. Immunohistochemicallly, the fascicles of tumor cells were positive for S-100 protein, and vimentin and negative for α-actin and GFAP. A few numbers of axons were demonstrated by anti-neurofilament antibody in this lesion. Therefore, the definitive diagnosis was PEN.

The Treatment of Morton’s Neuroma, a Significant Cause of Metatarsalgia for People Who Exercise

Morton’s Neuroma is a common metatarsalgia in athletes created due to the entrapment of the inter-digital nerve inside the transverse inter-metatarsal ligament. The purpose of the present study is to draw the necessary conclusions from the use of a particular surgical treatment to release the digital nerve, accompanied by neurolysis in adults who exercise. On the whole, twenty five patients with twenty-five suffering extremities were treated. Five of them simultaneously had a Hallux Valgus type deformity and that supports the belief of the mechanical induce of this condition. Both ultrasonography and Magnetic Resonance Imaging (MRI) were used for the clinical evaluation of this condition. The pain was estimated via the Visual Analogue Scale (VAS). The patients were re-examined after three (1st postoperative), twelve (2nd postoperative) and twenty-four (3rd postoperative) months. A significant improvement (p 0.0001) was noticed from the correlation between the pain before the surgery and the pain after the surgery via the Visual Analogue Scale (VAS). Most patients (15/25) did not display any discomfort or sensory disorder after surgery. The correct clinical evaluation as well as the correct and effective surgical intervention with the simultaneous repair of all the mechanical deformities of the foot provided better post-surgery progress in patients and increased the percentage of their rehabilitation of their previous activities.

Radiofrequency Thermo-Ablation of Morton’s Neuroma: A Valid Minimally Invasive Treatment Procedure in Patients Resistant to Conservative Treatment

Background: The authors present the personal results of the review of a group of cases treated for Morton’s neuroma with continuous radiofrequency (CRF) thermo-ablation of the plantar intermetatarsal nerve. Methods: This retrospective review consisted of 29 patients treated between January 2008 and December 2011, with a minimum 1 year follow-up. Three patients underwent bilateral treatment and 10 patients underwent concomitant treatment procedures for associated foot disorders: hallux valgus (7), tailor’s bunion (2) and hammertoe (5). The procedure was performed in a day hospital setting under direct fluoroscopic control. Results: The follow-up protocol used a visual analog scale (VAS) for pain (0 = no pain, 10 = worst pain) and a visual analog scale (VAS) for patient satisfaction (0 = no satisfaction, 10 = complete satisfaction). Success was defined by a decrease of 5 points in pain at 1 year after the treatment procedure. From these 29 cases, with a VAS pain score between severe and worst pain ever, treatment with CRF thermo-ablation at one year follow-up yielded these results: 14 cases with no pain (48%), 7 cases with mild pain (24%), 5 cases with moderate pain (17%), 3 cases still with severe pain (10%). The overall benefit was that 88% of the patients had significant pain improvements. From another point of view, 26 cases (89.6%) had a decrease of the VAS score between 5 and 10 points and in only 3 cases (10.3%) severe pain was reported, even though it was slightly diminished after the procedure. Conclusion: Continuous radiofrequency (CRF) thermo-ablation of Morton’s neuroma (Entrapment) was a safe and minimally invasive surgical procedure which gave these patients great satisfactions and a rapid return to normal activity.

Morton’s Neuroma;Surgical Exploration Is an Option in Symptomatic Patients with Normal Investigation

Morton neuroma is well described problem to metatarsophalangeal Joint (MTPJ) Etiology of Morton’s Neuroma which has wide range of problems from trauma, and nerve hypertrophy etc. Clinical evaluation is very important for diagnosis and sometimes investigations like ultrasound or MRI scan are helpful for conformation of diagnosis. Management varies from orthotics, shoe modification, injections or surgical excision. We are reporting a case which showed importance of surgical exploration when investigation is normal and difficulty in making diagnosis clinically.

Does Greek Foot Predispose to Morton’s Neuroma?

Background: Morton’s neuroma is the enlargement of an interdigital nerve most commonly located between the third and fourth metatarsals. Greek foot is a normal variant where the first metatarsal is shorter than the second metatarsal. To our knowledge, there is currently no reported association between Greek foot and Morton’s neuroma in the literature. Methods: Retrospective study of 184 patients. Two separate cohorts were recruited. Cohort A comprised of 100 randomly selected asymptomatic patients. Cohort B comprised of 84 patients with a history of foot pain and histologically confirmed Morton’s neuroma. Foot shape was determined by using a self-assessment tool and plain radiographs. Statistical analyses were performed using the Chi-square test on the association between Greek foot and Morton’s neuroma. A p-value of ﹣9). Conclusions: This study has shown a possible association between the presence of a Greek foot and the presence of Morton’s neuroma. Although our study design has limitations and does not allow full statistical analysis, we do believe that the shown association between Greek foot and Morton’s neuroma can help clinicians and other health care providers in establishing the diagnosis of Morton’s neuroma in patients with a painful foot.

Evaluation of the best follow-up period and curative effect for acoustic neuroma treated with a gamma knife

Objective: To determine the best follow-up period with regard to curative effect for acoustic neuroma treated with a gamma knife. Methods: Sixty cases of acoustic neuroma were treated with a gamma knife. The follow-up period was from 3 to 102 months. Changes in the lesions and peripheral tissues and clinical symptoms were compared and the curative effectiveness of gamma knife treatment was evaluated. Results: The highest total effective rate (92.3%) was in the third period. There was a significant difference in the tumor size postoperatively. There was no edema in the peripheral tissues surrounding the tumor. It was not obvious that clinical symptoms changed. Conclusion: In this report, the best follow-up period was 24-36 months. Gamma knife treatment was still effective after 60 months post-operation.

Traumatic Neuromas in Breast Cancer Patients after Mastectomy

OBJECTIVE Traumatic neuromas are rare benign lesions occurring post-mastectomy,which are usually suspected as tumour recurrences before excision biopsy.We report six cases presenting with palpable nodules post-mastectomy,to emphasize the differential diagnosis of traumatic neuroma from recurrent cancer.METHODS Six cases were reviewed.The age of patients ranged from 33 to 61 years.Nodular masses were found close to the mastectomy scar during follow-up over a period of 2.8 to 8 years.RESULTS In one patient three nodular masses were detected.Five patients had received chemotherapy,three of which had also received ra-diotherapy.Ultrasound examinations showed a well-circumscribed,homoge-neous,hypo-echoic subcutaneous nodular lesion in four cases,and a poorly defined hypo-echoic nodule with good conduction in two cases.No obvious distant metastases had been identified.Each patient underwent surgical excisional biopsy.All of nodules had a diameter less than 1 cm.Histopatho-logical examination showed proliferation of nerve fibre bundles,which were disordered,oriented and well circumscribed in fibro-adipose tissue.CONCLUSION It was concluded that all of the lesions were traumatic neuromas,independent from the initial tumor.Traumatic neuromas occur-ring in mastectomy scars are difficult to distinguish from a tumor recurrence.Although radiological evaluation of the mass with ultrasound is of value,the diagnosis can only be confirmed following a histopathological evaluation.

Facial nerve preservation following microsurgical removal of large and huge acoustic neuroma

Objective To evaluate the long-term facial nerve funtion of patients following microsurgical removal of large and huge acoustic neuroma,and to indentify the factors that influence these outcomes. Methods A retrospective review was performed,which included 176 consecutive patients with a