Nerve Infiltration Research Articles

Critical evaluation of artificial intelligence as a digital twin of pathologists for prostate cancer pathology

Prostate cancer pathology plays a crucial role in clinical management but is time-consuming. Artificial intelligence (AI) shows promise in detecting prostate cancer and grading patterns. We tested an AI-based digital twin of a pathologist, vPatho, on 2603 histological images of prostate tissue stained with hematoxylin and eosin. We analyzed various factors influencing tumor grade discordance between the vPatho system and six human pathologists. Our results demonstrated that vPatho achieved comparable performance in prostate cancer detection and tumor volume estimation, as reported in the literature. The concordance levels between vPatho and human pathologists were examined. Notably, moderate to substantial agreement was observed in identifying complementary histological features such as ductal, cribriform, nerve, blood vessel, and lymphocyte infiltration. However, concordance in tumor grading decreased when applied to prostatectomy specimens (κ = 0.44) compared to biopsy cores (κ = 0.70). Adjusting the decision threshold for the secondary Gleason pattern from 5 to 10% improved the concordance level between pathologists and vPatho for tumor grading on prostatectomy specimens (κ from 0.44 to 0.64). Potential causes of grade discordance included the vertical extent of tumors toward the prostate boundary and the proportions of slides with prostate cancer. Gleason pattern 4 was particularly associated with this population. Notably, the grade according to vPatho was not specific to any of the six pathologists involved in routine clinical grading. In conclusion, our study highlights the potential utility of AI in developing a digital twin for a pathologist. This approach can help uncover limitations in AI adoption and the practical application of the current grading system for prostate cancer pathology.

Lingual Denervation Improves the Efficacy of Anti-PD-1 Immunotherapy in Oral Squamous Cell Carcinomas by Downregulating TGFβ Signaling.

Intratumoral nerve infiltration relates to tumor progression and poor survival in oral squamous cell carcinoma (OSCC). How neural involvement regulates antitumor immunity has not been well characterized. This study aims to investigate molecular mechanisms of regulating tumor aggressiveness and impairing antitumor immunity by nerve-derived factors. We performed the surgical lingual denervation in an immunocompetent mouse OSCC model to investigate its effect on tumor growth and the efficacy of anti-PD-1 immunotherapy. A trigeminal ganglion neuron and OSCC cell coculture system was established to investigate the proliferation, migration, and invasion of tumor cells and the PD-L1 expression. Both the neuron-tumor cell coculture in vitro model and the OSCC animal model were explored. Lingual denervation slowed down tumor growth and improved the efficacy of anti-PD-1 treatment in the OSCC model. Coculturing with neurons not only enhanced the proliferation, migration, and invasion but also upregulated TGFβ-SMAD2 signaling and PD-L1 expression of tumor cells. Treatment with the TGFβ signaling inhibitor galunisertib reversed nerve-derived tumor aggressiveness and downregulated PD-L1 on tumor cells. Similarly, lingual denervation in vivo decreased TGFβ and PD-L1 expression and increased CD8+ T-cell infiltration and the expression of IFNγ and TNFα within tumor. Neural involvement enhanced tumor aggressiveness through upregulating TGFβ signaling and PD-L1 expression in OSCC, while denervation of OSCC inhibited tumor growth, downregulated TGFβ signaling, enhanced activities of CD8+ T cells, and improved the efficacy of anti-PD-1 immunotherapy. This study will encourage further research focusing on denervation as a potential adjuvant therapeutic approach in OSCC. This study revealed the specific mechanisms for nerve-derived cancer progression and impaired antitumor immunity in OSCC, providing a novel insight into the cancer-neuron-immune network as well as pointing the way for new strategies targeting nerve-cancer cross-talk as a potential adjuvant therapeutic approach for OSCC.

Sema3A secreted by sensory nerve induces bone formation under mechanical loads

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A (Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement (OTM) model. Firstly, bone formation was activated after the 3rd day of OTM, coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor (NGF), highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells (hPDLCs) within 24 hours. Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.

Analysis of the influencing factors in the long-term survival of esophageal cancer.

To analyze the prognosis and diagnostic value of relevant hematological indexes on the survival status of patients with esophageal squamous cell carcinoma after radical surgery. This study included 206 patients with esophageal cancer who underwent surgical R0 resection. The data, including the basic information, preoperative blood routine, albumin, fibrinogen, surgery-related information, postoperative pathology, and overall survival, of the patients were compared. The survival and death groups showed a significant difference in overall survival (OS), the degree of differentiation, depth of infiltration, pathological stage, vascular infiltration, nerve infiltration, fibrinogen, white blood cell, neutrophils, platelet, and platelet hematocrit (P<0.05). Tumor located in the middle thorax, larger lesion length, deeper invasion, later pathological stage, vascular infiltration, nerve infiltration, lymph node metastasis, cardiovascular disease, and higher smoking grade were risk factors for poor prognosis of esophageal squamous cell carcinoma (ESCC) (P<0.05). Cardiovascular disease, lower differentiation, tumor located in the middle thorax, and nerve infiltration were independent risk factors for the reduction of survival time of patients with ESCC (P<0.05). History of cardiovascular disease, tumor located in the middle chest, poorly differentiated esophageal squamous cell carcinoma, visible nerve cancer invasion, hematocrit (HCT), mean erythrocyte hemoglobin concentration (MCHC), and hemoglobin (HB) are independent risk factors for the long-term survival of patients with ESCC.

Recidiva orbital da leucemia linfoide aguda LLA em crianças: relato de caso

INTRODUCTION: The recurrence of childhood ALL involving the eyeball is a rare event, occurring in 2.2% of children. The presence of specific orbital and ocular lesions is associated with a higher frequency of bone marrow relapses and CNS involvement, leading to a lower survival rate. OBJECTIVES: Conduct a longitudinal observational analysis of cases of orbital recurrences of ALL in children undergoing treatment at a reference oncology hospital in Western Paraná. CASE REPORT 1: 1-year-old female patient, undergoing treatment for ALL, presented with a whitish lesion in her left eye. In consultation with an ophthalmologist, an alteration of the red reflex with vitritis was observed in the left eye, and in the right eye an elevated lesion suggestive of an intraocular mass was seen. After months of investigation, it was concluded that there was orbital recurrence of ALL, and treatment was initiated according to BFM-90 for recurrences. CASE REPORT 2: 2-year-old female patient, undergoing treatment for ALL, presented skin lesions, right periocular edema and divergent strabismus. MRI of the orbit showed diffuse thickening of the optic nerves in their intraconal and canicular segments and part of the cisternal path, suggestive of infiltration of the optic nerves by the underlying disease. After confirming the diagnosis of ALL orbital recurrence, treatment was carried out according to the BFM-90 protocol. CONCLUSION: Through this research, the importance of a thorough evaluation of ophthalmological signs and symptoms in patients diagnosed with ALL was evidenced, for an early diagnosis and treatment.

Comparison of Inferior Alveolar Nerve Block and Infiltration Anesthesia Techniques for Pain Control in Primary Mandibular Molar Extractions in pediatric patients

Comparison of Inferior Alveolar Nerve Block and Infiltration Anesthesia Techniques for Pain Control in Primary Mandibular Molar Extractions in pediatric patients

Review of craniofacial pain syndromes involving the greater occipital nerve: relevant anatomy, clinical findings, and interventional management.

Craniofacial pain syndromes exhibit a high prevalence in the general population, with a subset of patients developing chronic pain that significantly impacts their quality of life and results in substantial disabilities. Anatomical and functional assessments of the greater occipital nerve (GON) have unveiled its implication in numerous craniofacial pain syndromes, notably through the trigeminal-cervical convergence complex. The pathophysiological involvement of the greater occipital nerve in craniofacial pain syndromes, coupled with its accessibility, designates it as the primary target for various interventional procedures in managing craniofacial pain syndromes. This educational review aims to describe multiple craniofacial pain syndromes, elucidate the role of GON in their pathophysiology, detail the relevant anatomy of the greater occipital nerve (including specific intervention sites), highlight the role of imaging in diagnosing craniofacial pain syndromes, and discuss various interventional procedures such as nerve infiltration, ablation, neuromodulation techniques, and surgeries. Imaging is essential in managing these patients, whether for diagnostic or therapeutic purposes. The utilization of image guidance has demonstrated an enhancement in reproducibility, as well as technical and clinical outcomes of interventional procedures. Studies have shown that interventional management of craniofacial pain is effective in treating occipital neuralgia, cervicogenic headaches, cluster headaches, trigeminal neuralgia, and chronic migraines, with a reported efficacy of 60-90% over a duration of 1-9months. Repeated infiltrations, neuromodulation, or ablation may prove effective in selected cases. Therefore, reassessment of treatment response and efficacy during follow-up is imperative to guide further management and explore alternative treatment options. Optimal utilization of imaging, interventional techniques, and a multidisciplinary team, including radiologists, will ensure maximum benefit for these patients.

Preoperative Detection of Local Tumor Extent in Patients with Advanced Retinoblastoma: Predictive Value of MRI and Clinical Findings.

Before planned enucleation, local tumor extension in advanced retinoblastoma is routinely assessed preoperatively using high-resolution magnetic resonance imaging (MRI). The aim of our study was to analyse the predictive value of MRI and clinical characteristics for predicting tumor extent, as confirmed by histopathology postoperatively. All consecutive patients were included who underwent primary enucleation for advanced retinoblastoma after high-resolution MRI examination in our hospital between January 2011 and December 2021. The primary study endpoint was the evaluation of the predictability of histopathological risk factors on preoperative MRI examination. The sensitivity and specificity of the MRI examination with respect to clinically relevant optic nerve infiltration and choroidal infiltration were determined. The mean age of the 209 included patients was 1.6years (range 1 month to 4.7 years). MRI indicated optic nerve infiltration in 46 (22%) patients, extensive choroidal infiltration in 78 (40.2%) patients, and scleral infiltration in one patient (2.6%). Histopathological examination demonstrated postlaminar optic infiltration in 25 (12%) patients and extensive choroidal infiltration in 17 (8.1%) cases. Scleral infiltration was evident in 8 (3.8%) patients. In the final multivariate analysis, MRI findings of tumor infiltration and a preoperative intraocular pressure ≥ 20 mmHg were independently associated with histopathological evidence of clinically relevant optic nerve (p = 0.033/p = 0.011) and choroidal infiltration (p = 0.005/p = 0.029). The diagnostic accuracy of the prediction models based on the multivariate analysis for the identification of the clinically relevant optic nerve (AUC = 0.755) and choroidal infiltration (AUC = 0.798) was greater than that of purely MRI-based prediction (respectively 0.659 and 0.742). The sensitivity and specificity of MRI examination for determining histopathological risk factors in our cohort were 64% and 65% for clinically relevant optic infiltration and 87% and 64% for clinically relevant choroidal infiltration. The local tumor extent of retinoblastoma with infiltration of the optic nerve and choroid can be well estimated based on radiological and clinical characteristics before treatment initiation. The combination of clinical and radiological risk factors supports the possibility of early treatment stratification in retinoblastoma patients.

Infiltrative Optic Neuropathy in a Patient with Gastric Carcinoma: Case Report and State of the Art

Introduction: Metastatic tumors to the optic disc are a rare event. Infiltration of the optic nerve head is usually a unilateral process with characteristic funduscopic features. Loss of vision is its main symptom. Neuroimaging should be performed in every patient suspected of infiltrative optic neuropathy. The patient should be referred for appropriated chemotherapy for the systemic cancer plus external ocular irradiation. Case Presentation: The case of a 75-year-old man with progressive vision loss in his left eye is presented. Among his medical background a gastric adenocarcinoma (GAC) with multiple liver metastases is highlighted. The exploration showed an optic nerve head invaded by chalky whitish infiltrates, associated to flameshaped hemorrhages along the vascular arcades; the magnetic resonance imaging (MRI) demonstrated signal enhancement of the posterior region of the left ocular globe, affecting the optic nerve head. Orbital radiotherapy was ruled out due to patient’s systemic situation. Discussion: Metastases and optic nerve infiltration should be suspected in every oncologic patient who develops optic neuropathy. Though a rare condition with poor systemic prognosis, patients should be studied and offered orbital radiotherapy in order to stabilize the ocular progression.

Stiffened tumor microenvironment enhances perineural invasion in breast cancer via integrin signaling.

Accumulating studies have shown that tumors are regulated by nerves, and there is abundant nerve infiltration in the tumor microenvironment. Many solid tumors including breast cancer (BRCA) have different degrees of perineural invasion (PNI), which is closely related to the tumor occurrence and progression. However, the regulatory mechanism of PNI in BRCA remains largely unexplored. PNI-related molecular events are analyzed by the RNAseq data of BRCA samples deposited in The Cancer Genome Atlas (TCGA) database. Extracellular matrix (ECM) components within the tumor microenvironment are analyzed by immunohistochemical staining of α-SMA, Sirius red staining, and Masson trichrome staining. Soft and stiff matrix gels, living cell imaging, and dorsal root ganglion (DRG) coculture assay are used to monitor cancer cell invasiveness towards nerves. Western blotting, qRT-PCR, enzyme-linked immunosorbent assay combined with neutralizing antibody and small molecular inhibitors are employed to decode molecular mechanisms. Comparative analysis that the ECM was significantly associated with PNI status in the TCGA cohort. BRCA samples with higher α-SMA activity, fibrillar collagen, and collagen content had higher frequency of PNI. Compared with soft matrix, BRCA cells cultured in stiff matrix not only displayed higher cell invasiveness to DRG neurons but also had significant neurotrophic effects. Mechanistically, integrin β1 was identified as a functional receptor to the influence of stiff matrix on BRCA cells. Moreover, stiffened matrix-induced activation of integrin β1 transduces FAK-YAP signal cascade, which enhances cancer invasiveness and the neurotrophic effects. In clinical setting, PNI-positive BRCA samples had higher expression of ITGB1, phosphorylated FAK, YAP, and NGF compared with PNI-negative BRCA samples. Our findings suggest that stiff matrix induces expression of pro-metastatic and neurotrophic genes through integrin β1-FAK-YAP signals, which finally facilitates PNI in BRCA. Thus, our study provides a new mechanism for PNI in BRCA and highlights nerve-based tumor treatment strategies.

Optic Disc Swelling in Cancer Patients: Etiology and Implications.

To analyze the etiology and implications of optic disc swelling in cancer patients treated at a specialized tertiary cancer center in Jordan. This was a retrospective study of all cancer patients who had optic disc swelling between January 2019 and December 2020 at King Hussein Cancer Center (KHCC). Patients' data included age, sex, laterality, visual acuity, and the underlying cause and management for the optic disc swelling. Optic disc swelling was present in 58 cancer patients (96 eyes), with 38 (65%) having bilateral involvement. Among these, 33 (57%) were female, and 43 (74%) were ≤40 years old. At diagnosis, 58 (63%) eyes had a best-corrected visual acuity (BCVA) better than 0.5, improving to 73 (76%) eyes at the last follow-up. High intracranial pressure (ICP) was the most common primary cause (30 patients/52%), followed by tumor infiltration of the optic nerve (10 patients/17%), optic nerve compression (7 patients/12%), and optic nerve inflammation (5 patients/9%). Four patients had pseudopapilledema. Among the 30 patients with high ICP, CNS tumors were predominant (21 patients/70%), with only 3 having idiopathic intracranial hypertension. Medications, including ATRA (All-Trans Retinoic Acid) and systemic steroids, contributed to increased ICP in six patients (20%). BCVA was less than 0.5 in all eyes (100%) affected by tumor infiltration, optic nerve inflammation, and ischemic optic neuropathy, while only eight eyes (14%) with optic disc swelling due to elevated ICP had a BCVA less than 0.5 (p < 0.0001). Management included steroids (53 patients/91%), acetazolamide (30 patients/52%), chemotherapy (20 patients/34%), radiation therapy (13 patients/22%), frequent lumbar punctures (12 patients/21%), and surgery (28 patients/48%). Visual acuity improved in 40 eyes (42%), with only 4 eyes (4%) experiencing deterioration. At a 12-month median follow-up period, 11 (19%) patients were dead, 10 (10%) eyes had poor vision (BCVA less than 0.1), and 21 (22%) eyes had BCVA 0.5 or better. Various underlying pathologies can induce optic disc swelling in cancer patients, a grave condition capable of causing vision loss. Notably, tumor infiltration of the optic nerve tends to result in more profound visual impairment compared to papilledema due to elevated ICP. Timely detection is crucial, and immediate symptomatic treatment followed by addressing the underlying cause is essential to prevent irreversible optic nerve damage and vision loss in cancer patients.

Neurolymphomatosis in Non-Hodgkin's Lymphoma

non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of hematopoietic puffins, with diphun B-velicocyclotinous lymphoma accounting for 25% of all NHLs and having the greatest midline to axis growth (Leeuwenуе et al., 2014). Of all NHLs, the central and peripheral nervous systems are most often affected in diphytic B-lycocytic lymphoma (Padala, &amp; Kallam, 2022. Liu, &amp; Barta, 2019). In NHL, infiltration of cranial and peripheral nerves can be detected - neurolymphomatosis (NL) emerges. NL is a very rare condition and occurs in about 0.2% of patients with NHL (Baehring, Damek, Martin, Betensky &amp; Hochberg, 2003). These infiltrations can manifest with detection of mononeuropathy, multiple neuropathy, symmetric neuropathy or plexopathy (Grisold W., Grisold A., Marosi, Meng, &amp; Briani, 2015). The aim of the work was to study the features of the clinical course, diagnosis and treatment of neurolymphomatosis in the form of lesions of the trigeminal, facial cranial nerve and the left ulnar nerve in diffuse B-bollichelial non-Hodgkin lymphoma based on a clinical case. We present a review of a clinical case of peripheral nervous system involvement in a patient born in 1977 with diffuse B-cell non-Hodgkin's lymphoma. The diagnosis was established on the basis of clinical manifestations of lesions of the branches of the trigeminal and left facial nerves, the left ulnar nerve, magnetic resonance imaging of the head and brain, electroneuromyography, and immunohistochemical examination of the infiltrate biopsy from the affected buccal branch of the left facial nerve. In March 2022, the patient developed moderate peripheral paresis of the mimic muscles on the left side, burning pain with impaired tactile and pain sensitivity of the dorsum, wing of the nose, and left instep. A week later there was a decrease in the strength, tactile and pain sensitivity, and patience of the fourth and fifth fingers of the left hand. Within a month, the burning pain had spread to the left cheek, periorbital, and chin areas of the face. In 2021, the patient was diagnosed with B-bollichelial non-Hodgkin's lymphoma with involvement of the right axillary, supraclavicular lymph nodes, left breast, followed by chemotherapy and clinical remission. Magnetic resonance imaging of the head revealed a perineural lesion of the third branch of the right trigeminal nerve, the second branch of the left trigeminal nerve, and the cheek branch of the left facial nerve. Electroneuromyography revealed an axonal lesion of the left ulnar nerve. The results of examination of the infiltrate biopsy from the affected buccal branch of the facial nerve specimens confirmed non-Hodgkin's diffuse B-cell lymphoma, GCB-phenotype and nerve damage due to NHL. Treatment of multiple neuropathy with glucocorticosteroids, nonsteroidal anti-inflammatory drugs, acelicholinesterase inhibitors, and specific chemotherapy resulted in limited therapeutic effect. Prescribing pregabalin resulted in decreased reduction of neuropathic facial pain. Thus, neurolymphomatosis is a rather rare manifestation of non-Hodgkin's lymphomas, the use of magnetic resonance imaging of the head and brain as well as immunohistochemical examination of the affected nerve infiltrate biopsy is important to confirm the diagnosis.&#x0D; In the Ukrainian scientific medical literature, there are few descriptions of cases of neurolymphomatosis in NHL, although they occur in patients, and it is necessary to describe in more detail the peculiarities of the collicular course of the diagenesis and treatment in these cases.

Establishing a new model of cancer neuropathic pain in rats

To guide the treatment of malignant neuropathic pain (MNP) in clinical practice, by inoculating MADB-106 breast cancer cells into the right L4 nerve root in Sprague-Dawley rats, a rat model of MNP was established, providing basic conditions for the study of neuropathic pain and development and application of therapeutic drugs. As the tumor grew over time, it pressed the nerve roots, causing nerve damage. The spinal nerve ligation (SNL) model, which is a neuropathic pain model widely used in rats, was compared with the L4 nerve root SNL model, and histologic examination of the nerve tissue of both models was performed by electron microscopy. In addition to the infiltration and erosion of the L4 nerve by tumor cells, the tumor tissue gradually grew and compressed the L4 nerve roots, resulting in hyperalgesia of the rat's posterior foot on the operative side. Some spontaneous pain phenomena were also observed, such as constant lifting or licking of the posterior foot on the operative side under quiet conditions. Electron microscopy images showed that nerve injury was due to progressive compression by the tumor, cells of which were visualized, but the injury was lighter than that in SNL rats. Imaging showed a paravertebral tumor near the L4 nerve root in the carcinomatous neuropathic pain model rat. These results suggest that progressive compression of the nerve by a malignant tumor leads to nerve damage similar to the behavioral changes associated with chronic compression injury resulting from a loose ligature of the nerve. The cancer neuropathologic pain model at the L4 nerve root was successfully established in Sprague-Dawley rats.

Risk factors analysis and prediction model construction of submucosal deep infiltration of early colorectal tumor

Objective: To investigate the risk factors for the development of deep infiltration in early colorectal tumors (ECT) and to construct a prediction model to predict the development of deep infiltration in patients with ECT. Methods: The clinicopathological data of ECT patients who underwent endoscopic treatment or surgical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from August 2010 to December 2020 were retrospectively analyzed. The independent risk factors were analyzed by multifactorial regression analysis, and the prediction models were constructed and validated by nomogram. Results: Among the 717 ECT patients, 590 patients were divided in the within superficial infiltration 1 (SM1) group (infiltration depth within SM1) and 127 patients in the exceeding SM1 group (infiltration depth more than SM1). There were no statistically significant differences in gender, age, and lesion location between the two groups (P>0.05). The statistically significant differences were observed in tumor morphological staging, preoperative endoscopic assessment performance, vascular tumor emboli and nerve infiltration, and degree of tumor differentiation (P<0.05). Multivariate regression analysis showed that only erosion or rupture (OR=4.028, 95% CI: 1.468, 11.050, P=0.007), localized depression (OR=3.105, 95% CI: 1.584, 6.088, P=0.001), infiltrative JNET staging (OR=5.622, 95% CI: 3.029, 10.434, P<0.001), and infiltrative Pit pattern (OR=2.722, 95% CI: 1.347, 5.702, P=0.006) were independent risk factors for the development of deep submucosal infiltration in ECT. Nomogram was constructed with the included independent risk factors, and the nomogram was well distinguished and calibrated in predicting the occurrence of deep submucosal infiltration in ECT, with a C-index and area under the curve of 0.920 (95% CI: 0.811, 0.929). Conclusion: The nomogram prediction model constructed based on only erosion or rupture, local depression, infiltrative JNET typing, and infiltrative Pit pattern has a good predictive efficacy in the occurrence of deep submucosal infiltration in ECT.

Comparison of posterior superior alveolar and greater palatine nerve block with local infiltration for extraction of maxillary molars in oral surgery – A randomized controlled trial

Administration of local anesthetic drug that prevents pain during dental treatment is of absolute importance. Act of injecting local anesthetic should be nonpainful and atraumatic. The maxilla is very porous and highly vascular. Therefore, anesthesia of maxillary teeth can be accomplished more easily than with mandibular teeth. The aim of this study is to determine the anesthetic efficacy of the conventional technique of posterior superior alveolar (PSA) and greater palatine nerve(GP) block anesthesia as compared to the buccal and palatal technique in terms of pain during injection, after extraction, after 15mins of the procedure and quality of anesthesia during the extraction procedure. The study also intends to determine the incidence of positive aspiration in the infiltration technique. This randomized clinical study was carried out on 154 patients who reported to the Department of Oral and Maxillofacial Surgery, Sri Rajiv Gandhi College of Dental Sciences &amp; Hospital Bangalore, requiring extraction of maxillary second and third molar teeth. The patients received anesthesia using the conventional nerve block technique and infiltration technique randomly on each side of the mouth. Patients were assessed for pain during the injection, after extraction, and after 15mins of the procedure with each technique using Visual Analog Scale (VAS). The patients were also assessed for pain using the Verbal Response Scale (VRS). The positive aspiration was assessed for each technique. During tooth extraction, quality of anesthesia was assessed using an eight-point category rating scale. The results obtained were analyzed using Chi-square test. It was concluded that the buccal infiltration technique is less painful for the patient as compared to the posterior superior alveolar nerve block. This technique has a lower frequency of positive aspiration as compared with the PSA nerve block. However, the PSA nerve block technique provides better-quality of anesthesia. It can be concluded that the infiltration technique appears to be a successful alternative with additional advantages, as compared to the nerve block technique.

Modeling MOG Antibody-Associated Disorder and Neuromyelitis Optica Spectrum Disorder in Animal Models: Visual System Manifestations.

Mechanisms of visual impairment in aquaporin 4 antibody (AQP4-IgG) seropositive neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disorder (MOGAD) are incompletely understood. The respective impact of optic nerve demyelination and primary and secondary retinal neurodegeneration are yet to be investigated in animal models. Active MOG35-55 experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6Jrj mice, and monoclonal MOG-IgG (8-18C5, murine), recombinant AQP4-IgG (rAb-53, human), or isotype-matched control IgG (Iso-IgG, human) was administered 10 days postimmunization. Mobility impairment was scored daily. Visual acuity by optomotor reflex and ganglion cell complex thickness (GCC, 3 innermost retinal layers) by optical coherence tomography (OCT) were longitudinally assessed. Histopathology of optic nerve and retina was investigated during presymptomatic, acute, and chronic disease phases for immune cells, demyelination, complement deposition, natural killer (NK) cell, AQP4, and astrocyte involvement, retinal ganglion cells (RGCs), and Müller cell activation. Groups were compared by nonparametric tests with a p value <0.05 indicating statistical significance. Visual acuity decreased from baseline to chronic phase in MOG-IgG (mean ± standard error of the mean: 0.54 ± 0.01 to 0.46 ± 0.02 cycles/degree, p < 0.05) and AQP4-IgG EAE (0.54 ± 0.01 to 0.43 ± 0.02, cycles/degree, p < 0.05). Immune cell infiltration of optic nerves started in presymptomatic AQP4-IgG, but not in MOG-IgG EAE (5.85 ± 2.26 vs 0.13 ± 0.10 macrophages/region of interest [ROI] and 1.88 ± 0.63 vs 0.15 ± 0.06 T cells/ROI, both p < 0.05). Few NK cells, no complement deposition, and stable glial fibrillary acid protein and AQP4 fluorescence intensity characterized all EAE optic nerves. Lower GCC thickness (Spearman correlation coefficient r = -0.44, p < 0.05) and RGC counts (r = -0.47, p < 0.05) correlated with higher mobility impairment. RGCs decreased from presymptomatic to chronic disease phase in MOG-IgG (1,705 ± 51 vs 1,412 ± 45, p < 0.05) and AQP4-IgG EAE (1,758 ± 14 vs 1,526 ± 48, p < 0.01). Müller cell activation was not observed in either model. In a multimodal longitudinal characterization of visual outcome in animal models of MOGAD and NMOSD, differential retinal injury and optic nerve involvement were not conclusively clarified. Yet optic nerve inflammation was earlier in AQP4-IgG-associated pathophysiology. Retinal atrophy determined by GCC thickness (OCT) and RGC counts correlating with mobility impairment in the chronic phase of MOG-IgG and AQP4-IgG EAE may serve as a generalizable marker of neurodegeneration.

Anti-MOG antibody optic neuritis in AML – A case report

We report a unique presentation of anti-myelin oligodendrocyte (MOG) optic neuritis in a patient with AML in remission. An elderly man presented with diminished vision in the right eye associated with headache and jaw pain. Systemic investigations revealed no leukemic recurrence. The presence of anti-MOG antibodies and optic nerve enhancement suggested of unilateral optic neuritis. Steroid therapy resulted in the resolution of disc edema. We faced a diagnostic dilemma in a patient with unilateral disc edema in the background of multiple systemic diseases. A methodical approach to investigations helped us in accurate diagnosis, institution of prompt therapy, and minimizing visual morbidity. We present this case to highlight the importance of differentiating leukemic optic nerve infiltration from other causes of unilateral disc edema, as their therapeutic approaches are different.

Cranial Nerve Palsies as Initial Presentation of Acute Lymphoblastic Leukemia – A Case Report

The clinical manifestations of acute leukemia are diverse and can range from asymptomatic to life-threatening Complications.1 Cranial nerve palsies as a presenting feature of this disease is relatively rare. It can be attributed to leukemic infiltration of cranial nerves, or the development of cranial nerve palsies secondary to intracranial complications such as subdural hematoma. Our patient presented with 4-month history of progressively worsening eye and visual disturbances. On examination, there was bilateral ptosis and proptosis. The right pupil was dilated and non-responsive to light with complete blindness. Left pupil had a sluggish response to light and had decreased visual acuity. There was 6th nerve palsy on left side and bilateral sensorineural hearing loss. Bone marrow biopsy showed Acute Lymphoblastic Leukemia. He was diagnosed with Acute Lymphoblastic Leukemia with brain (CNS) infiltration causing 2nd, 3rd, 6th and 8th cranial nerve palsies.

Adipose-derived stem cells modulate neuroinflammation and improve functional recovery in chronic constriction injury of the rat sciatic nerve.

Compressive neuropathy, a common chronic traumatic injury of peripheral nerves, leads to variable impairment in sensory and motor function. Clinical symptoms persist in a significant portion of patients despite decompression, with muscle atrophy and persistent neuropathic pain affecting 10%-25% of cases. Excessive inflammation and immune cell infiltration in the injured nerve hinder axon regeneration and functional recovery. Although adipose-derived stem cells (ASCs) have demonstrated neural regeneration and immunomodulatory potential, their specific effects on compressive neuropathy are still unclear. We conducted modified CCI models on adult male Sprague-Dawley rats to induce irreversible neuropathic pain and muscle atrophy in the sciatic nerve. Intraneural ASC injection and nerve decompression were performed. Behavioral analysis, muscle examination, electrophysiological evaluation, and immunofluorescent examination of the injured nerve and associated DRG were conducted to explore axon regeneration, neuroinflammation, and the modulation of inflammatory gene expression. Transplanted ASCs were tracked to investigate potential beneficial mechanisms on the local nerve and DRG. Persistent neuropathic pain was induced by chronic constriction of the rat sciatic nerve. Local ASC treatment has demonstrated robust beneficial outcomes, including the alleviation of mechanical allodynia, improvement of gait, regeneration of muscle fibers, and electrophysiological recovery. In addition, locally transplanted ASCs facilitated axon remyelination, alleviated neuroinflammation, and reduced inflammatory cell infiltration of the injured nerve and associated dorsal root ganglion (DRG). Trafficking of the transplanted ASC preserved viability and phenotype less than 7 days but contributed to robust immunomodulatory regulation of inflammatory gene expression in both the injured nerve and DRG. Locally transplanted ASC on compressed nerve improve sensory and motor recoveries from irreversible chronic constriction injury of rat sciatic nerve via alleviation of both local and remote neuroinflammation, suggesting the promising role of adjuvant ASC therapies for clinical compressive neuropathy.

Perineural Invasion (PNI) Definition, Histopathological Parameters of PNI in Oral Squamous Cell Carcinoma With Molecular Insight and Prognostic Significance.

Oral squamous cell carcinoma is associated with severe morbidity, recurrence of tumor, and reduced survival rate despite advances in treatment. Perineural invasion (PNI) is associated with neurotropic malignancy. PNI is due to the tropism of cancer cells toward nerve bundles in tissue. The aim of this literature review is to study the definition, patterns of PNI, Prognostic and therapeutic significance, and mechanism of PNI along with a molecular insight into oral cavity squamous cell carcinoma. Liebig type A pattern defines PNI as the presence of tumor cells within the peripheral nerve sheath & infiltration into the epineurium, perineurium, or endoneurium. Liebig type B pattern defines PNI as a tumor encircling at least 33% of a nerve. Few studies demonstrated an association between PNI and cervical metastasis which indicate poor prognosis. A higher level of expression of nerve growth factor and tyrosine kinase is associated with PNI in OSCC which can be considered as a biomarker of PNI. PNI needs to be studied in detail as it is associated with the aggressiveness of the tumor and decreased survival.