Nerve Research Articles

NURSING CARE FOR PATIENTS WITH LEPROSY TREATED BY PRIMARY CARE: INTEGRATIVE REVIEW

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Its predilection for the skin and peripheral nerves gives this disease particular characteristics, making its diagnosis simple. Brazil continues to be the second country in the world in terms of the number of cases, after India. Approximately 94% of known cases in the Americas and 94% of newly diagnosed cases are reported in Brazil. The disease manifests itself in two stable and opposing poles (virchowian and tuberculoid) and two unstable groups (indeterminate and dimorphic). In another classification, the disease is divided into tuberculoid, borderline or dimorphic forms, which are divided into dimorphic-tuberculoid, dimorphic-dimorphic and dimorphic-lepromatous and lepromatous forms. Microscopic examination of smears is the most useful complementary test for diagnosis. Treatment of leprosy includes: specific chemotherapy, suppression of reactive eruptions, prevention of physical disability, physical and psychosocial rehabilitation. Polychemotherapy based on rifampicin, dapsone and clofazimine has proven to be very effective and the prospects for controlling the disease in Brazil are real in the short term.

Nerve ultrasound in amyotrophic lateral sclerosis: systematic review and meta-analysis

Background/ AimAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting upper and lower motor neurons, causing progressive atrophy of muscles, hypertonia, and paralysis. This study aimed to evaluate the current evidence and effectiveness of ultrasound in investigating nerve cross-sectional area (CSA) of peripheral nerves, vagus and cervical roots in those with ALS compared with healthy controls and to pool the CSA measurements.MethodsA systematic search was conducted on Cochrane, Clarivate Web of Science, PubMed, Scopus, and Embase for the mesh terms nerve, ultrasonography, and amyotrophic lateral sclerosis. A quality assessment was performed using the New-Ottawa scale. In addition, a double-arm meta-analysis using Review Manager 5 software version 5.4 was performed.ResultsFrom the seventeen studies included in this review, the overall mean difference showed that individuals with ALS had a significantly smaller CSA in comparison to healthy controls for median, ulnar, C6 root, and phrenic nerves. However, no significant difference in the CSA was found in radial, vagal, sural, and tibial nerves.DiscussionThis study confirmed results of some of the included studies regards the anatomic sites, where nerve atrophy in ALS could be detected to potentially support the diagnosis of ALS. However, we recommend further large, prospective studies to assess the diagnostic value of these anatomical sites for the diagnosis of ALS.ConclusionsOur findings confirmed specific anatomic sites to differentiate ALS patients from healthy controls through ultrasound. However, these findings cannot be used to confirm the ALS diagnosis, but rather assist in differentiating it from other diagnoses.Trial registrationRetrospectively registered on July 30th 2024 in PROSPERO (PROSPERO (york.ac.uk)) with ID574702.Graphical abstract

Nerve conduction studies of sensory nerves with proven vasculitic neuropathy often show an absent electrical response.

In vasculitic neuropathy (VN), it is not known whether nerve conduction studies (NCSs) showing low amplitude sensory nerve action potentials (SNAPs) or those with absent responses have a higher yield in detecting appropriate nerves for pathological confirmation. Our goal was to describe NCS findings of nerves prior to biopsy in patients with VN. We performed a retrospective study between January 2000 and April 2021 in patients with VN who either met pathological definite criteria for VN or criteria for clinically probable VN and had NCS of the sural or superficial radial sensory nerves prior to biopsy of the same nerve. We included 61 patients with VN. The pathological findings showed 37 (60.7%) definite, 14 (23%) probable, and 2 (3.3%) possible VN; eight (13%) samples did not meet Peripheral Nerve Society pathological criteria. Most patients who met definite (20 out of 37, 54%) and probable (9 out of 14, 64%) VN pathological criteria had absent SNAPs. Only three out of eight (37.5%) patients without VN pathological findings had absent SNAPs. There was no statistically significant correlation between pathological diagnosis and SNAP amplitude (χ2 = 1.98, p = .58). Additionally, no association was found between VN pathological criteria and use of immunomodulatory treatment (p = .67) or corticosteroids (p = .52). Most nerves with pathological VN findings showed no response on NCS. In patients with suspected VN, sural or superficial radial sensory nerves with absent responses on NCS are adequate biopsy targets as compared to nerves in which SNAPs can be recorded.

Harmonizing neuropathic pain research: outcomes of the London consensus meeting on peripheral tissue studies.

Neuropathic pain remains difficult to treat, with drug development hampered by an incomplete understanding of the pathogenesis of the condition, as well as a lack of biomarkers. The problem is compounded by the scarcity of relevant human peripheral tissues, including skin, nerves, and dorsal root ganglia. Efforts to obtain such samples are accelerating, increasing the need for standardisation across laboratories. In this white paper, we report on a consensus meeting attended by neuropathic pain experts, designed to accelerate protocol alignment and harmonization of studies involving relevant peripheral tissues. The meeting was held in London in March 2024 and attended by 28 networking partners, including industry and patient representatives. We achieved consensus on minimal recommended phenotyping, harmonised wet laboratory protocols, statistical design, reporting, and data sharing. Here, we also share a variety of relevant standard operating procedures as supplementary protocols. We envision that our recommendations will help unify human tissue research in the field and accelerate our understanding of how abnormal interactions between sensory neurons and their local peripheral environment contribute towards neuropathic pain.

Electrospun PCL/Alginate/Nanoclay Nerve Conduit with Olfactory Ectomesenchymal Stem Cells for Nerve Regeneration.

Biocompatible and biodegradable nerve growth conduits (NGCs) provide a promising alternative to conventional nerve grafting for peripheral nerve regeneration. Incorporating nanoclay (NC) has been shown to increase the hydrophilicity and flexibility of polymeric scaffolds. In the present study, poly caprolactone-alginate (PCL-ALG) conduits with varying percentages of NC (0.1%, 0.2%, and 0.5%) were fabricated using the electrospinning technique. The conduit containing 0.5% NC showed a greater increase in elongation (33%) and porosity, reaching 95% with the lowest contact angle (10°). For in vitro, human olfactory ectomesenchymal stem cells (OE-MSCs) were used as a favorable choice for neuronal differentiation owing to the origin from the neural crest. The viability and proliferation of OE-MSCs were maintained after 5 days on scaffolds with 0.5% NC, as confirmed by the MTT assay, cell adhesion analysis, and live/dead staining. Furthermore, the impact of 0.5% PCL-ALG-NC on the paracrine activity of OE-MSCs was studied for a period of 7 days. Our results indicated that human OE-MSCs, when cocultured with PC12 cells on NGC, have the capability to release nerve growth factor levels of up to 1392.83 pg/mL. In summary, the electrospun PCL-ALG conduit containing an optimal NC dosage (0.5%) and seeded with human OE-MSCs shows promising outcomes as NGC scaffold for peripheral nerve regeneration.

Association of polymorphic variants of the GSTP1 and GSTM1 genes with signs of tunnel syndromes in patients with vibration disease (pilot study)

Introduction. The data on the association between GSTs gene variants and the risk of developing carpal tunnel syndrome (CTS) determine the feasibility of studying the relationship with changes in the nerve structure of the upper limbs identified by ultrasound examination in patients with vibration disease (VD). The aim of the study was to investigate the association of polymorphic variants of the GSTP1 and GSTM1 genes with signs of tunnel syndromes in VD patients. Materials and methods. Polymorphic variants of the GSTP1 (rs1695 and rs1138272) and GSTM1 genes in one hundred forty male VD patients were studied using PCR-RT method. High-resolution ultrasonography parameters were used to evaluate the morphological structure of the peripheral nerves of the upper limbs in patients, including the cross-sectional area (CSA) of the peripheral nerves. Results. A significant gain in CSA maximum of the median nerve was found in carriers of the GSTM1–/– genotype relative to those in the GSTM1+ polymorphic variant of the GSTM1 gene (p=0.014). At the same time, AG-GSTP1 (Ile105Val) heterozygote carriers were less resistant to vibration exposure compared to the AA homozygote ones. The AG carriers had a shorter period of vibration exposure (p=0.017), which was observed against the background of a pronounced tendency to a decrease in the period of vibration exposure at the time of VD diagnosis (p=0.034). Limitations. Limitations include the small number of examined patients and the analysis of associations of polymorphic variants of GSTs genes only with CSA values without taking into account the clinical and functional status of patients. Conclusion. The results obtained indicate that GSTs genes involved in protection against oxidative stress, may be associated with the development of CTS in VD patients. Further investigations are needed involving a larger number of VD patients with simultaneous analysis of the morphological structure of peripheral nerves, as well as of electrophysiological and clinical studies.

A microfluidic model of the first sensory synapse for analgesic target discovery.

The synaptic connections between dorsal root ganglia (DRG) and dorsal horn (DH) neurons are a crucial relay point for the transmission of painful stimuli. To delineate how synaptic plasticity may modulate the excitability of DH neurons, we have devised a microfluidic co-culture model that recapitulates the first sensory synapse using postnatal mouse sensory neurons. We show that DRG-DH co-cultures characterize salient features of the in vivo physiology of sensory neurons. Immunocytcochemical experiments of the cultured DH neurons show a co-localization of MAP2 with VGLUT2 and of MAP2 with Synapsin 1, corroborating the glutamatergic identity of the DH neurons and further suggesting the formation of active synapses in this neuronal set. Fluorometric imaging experiments demonstrate the elicitation of calcium responses in DH neurons following the stimulation of DRG cell bodies or axons. Selective NMDA and AMPA receptor blockade appreciably silences DH neuron responses, suggesting that glutamatergic signaling is maintained in vitro. Last, a surrogate model of peripheral nerve injury is introduced in the form of an axotomy, which results in elevated and prolonged calcium responses of DH neurons. Overall, the microfluidic mouse co-cultures provide a method advancement in the study of periphery-to-center pain signaling, where the potential of utilizing the platform for drug target identification is underscored.

Malignant melanotic nerve sheath tumor

Malignant melanotic nerve sheath tumor, previously known as melanotic schwannoma, is a rare variant of peripheral nerve sheath tumor composed of melanin-producing Schwann cells and clinically misdiagnosed as melanoma. Malignant melanotic nerve sheath tumor is a rare tumor with uncertain biological behavior and variable treatment recommendations. Despite the histological features that seem benign, with a low proliferation index, the clinical course of this tumor often becomes malignant, with a high frequency of local relapses and the presence of tumor metastasis signs. Distinctive features of malignant melanotic tumor of the nerve sheath are a relatively young age of patients, the presence of the Carney complex signs and psammomatous bodies in the tumor. The article presents a case of malignant melanotic tumor of the nerve sheath localized in the neck with a recurrent course. In the described clinical observation, the patient underwent surgical treatment twice. Microscopic and immunohistochemical analysis of postoperative materials gave a positive result for melanoma markers and showed the absence of psammoma bodies and low mitotic activity. The clinical course of the disease was malignant, with the appearance of a relapse in the postoperative scar. Diagnosis of malignant melanotic tumor of the nerve sheath is a complex task, both from the radiological and pathological points of view. Communication between the surgeon, radiologist and pathologist, understanding the anatomical relationships of the lesion and careful attention to the histological findings are critical to making the correct diagnosis.

Small-molecule natural product sophoricoside reduces peripheral neuropathic pain via directly blocking of NaV1.6 in dorsal root ganglion nociceptive neurons.

Peripheral neuropathic pain poses a significant global health challenge. Current drugs for peripheral neuropathic pain often fall short in efficacy or come with severe side effects, emphasizing the critical need for the development of highly effective and well-tolerated alternatives. Sophoricoside (SOP) is a nature product-derived isoflavone that possesses various pharmacological effects on inflammatory and neuropathy diseases. Here, in this study, analgesic effect was investigated by intrathecally administration of SOP/vehicle to spared nerve injury (SNI) or paclitaxel-induced peripheral neuropathic pain (PINP) rodent models, and mechanical allodynia was measured in Von Frey tests. Ipsilateral L4-L6 dorsal root ganglia (DRG) were used for protein expression. In silico molecular docking analysis was applied for assessing compound-target binding affinity. Primary cultured DRG neurons were utilized to investigate SOP's effect on veratridine-triggered nociceptor activities and its selective inhibition of voltage-gated sodium channels subtype 1.6 (NaV1.6). The results showed SOP treatment alleviated mechanical allodynia in SNI and PINP rodent models (paw withdrawal threshold after 1 h of injection: SNI-vehicle: 1.385 ± 0.338 g; SNI-SOP: 9.963 ± 2.029 g, P < 0.001; PINP-vehicle: 5.040 ± 0.985 g; PINP-SOP: 8.287 ± 3.812 g, P = 0.004). SOP presented effects on both inhibiting veratridine-triggered nociceptor activities (oscillatory population: vehicle: 39.9 ± 7.3%; SOP: 30.7 ± 9.8%, P = 0.021) and selectively blocking NaV1.6 in DRG sensory neurons. Molecular docking analysis indicated direct binding between SOP and NaV1.6, leading to its endocytosis in DRG Sensory Neurons. In conclusion, SOP alleviated nociceptive allodynia induced by peripheral nerve injury via selectively blocking of NaV1.6 in DRG nociceptive neurons. we highlight its potential as an analgesic and elucidate its mechanism involving NaV1.6 endocytosis. This research opens avenues for exploring the analgesic effects of SOP and its potential impact on neuropathic pain therapy.

Targeting the Galectin-1/Ras Interaction for Treating Malignant Peripheral Nerve Sheath Tumors.

Background: Neurofibromatosis type 1 (NF1) is a common inherited neurological disorder that can lead to the development of malignant peripheral nerve sheath tumors (MPNSTs), a highly aggressive form of sarcoma. Current treatment options for MPNSTs are limited, with poor prognosis and high recurrence rates. This study aims to explore the potential of targeting the Galectin-1 (Gal-1) and Ras interaction as a novel therapeutic strategy for MPNSTs. Methods: Molecular docking simulations were conducted to identify specific residues involved in the Gal-1 and H-Ras(G12V) interaction. LLS30, a compound designed to target the Ras binding pocket on Gal-1, was developed and tested. The efficacy of LLS30 was evaluated through in vitro assays, including cell viability, apoptosis, and co-immunoprecipitation studies, as well as in vivo assays using orthotopic MPNST xenograft and experimental lung metastasis models. Transcriptome sequencing was performed to analyze the impact of LLS30 on gene expression and signaling pathways. Results: Molecular docking revealed key residues involved in the Gal-1/Ras interaction, and LLS30 was shown to bind to these residues, disrupting the interaction. LLS30 treatment resulted in Ras delocalization from the plasma membrane and suppression of the Ras/Erk signaling pathway. In vitro, LLS30 significantly reduced MPNST cell proliferation and induced apoptosis. In vivo, LLS30 demonstrated potent anti-tumor activity, reducing tumor burden and metastasis while improving survival in animal models. Transcriptome analysis showed that LLS30 downregulates critical pathways, including KRAS signaling and epithelial-mesenchymal transition (EMT). Conclusions: Interference with the Gal-1/Ras interaction could lead to suppression of the Ras signaling pathway. LLS30 effectively disrupts the Gal-1/Ras interaction, resulting in significant anti-tumor and anti-metastatic effects in MPNST models. These findings indicated that targeting Gal-1 with LLS30 offers a promising therapeutic approach for treating MPNSTs and may also be applicable to other malignancies where Gal-1 and Ras are key oncogenic drivers.

Application of multimodal intraoperative neurophysiological monitoring technology in neurofibromatosis type 1 related peripheral nerve tumor surgery

To summarize application effect and clinical experience of multimodal intraoperative neurophysiological monitoring (IONM) technology in the surgery of neurofibromatosis type 1 (NF1) related peripheral nerve tumors. A retrospective study was conducted on NF1 patients, who admitted between January 2019 and December 2023 and treated with peripheral nerve tumor resection surgery assisted by multimodal IONM technology. There were 49 males and 45 females. The age ranged from 5 to 78 years, with an average of 33.7 years. Tumor morphological classification included 71 cases of nodular type, 13 cases of diffuse type, and 10 cases of mixed type. Target tumors were distributed in craniofacial region (47 cases), neck (11 cases), trunk (12 cases), and limbs (24 cases). Preoperatively, 44 cases had no obvious neurological symptoms, while the remaining patients had neurological symptoms, including 15 cases of visual impairment, 5 cases of hearing impairment, 16 cases of somatic movement disorders, and 31 cases of somatic sensory disorders, of which 7 cases had more than one symptom. IONM plans were selected based on the relevant nerves and adjacent important structures of the target tumor, including visual evoked potential (17 cases), somatosensory evoked potential (44 cases), motor evoked potential (88 cases), and electromyogram (94 cases). All surgeries were successfully completed. Ninety-three patients underwent total/near total resection and 1 patient underwent palliative resection. Pathological examination showed 80 cases of neurofibroma and 14 cases of malignant peripheral nerve sheath tumors. Complications included 2 cases of hematoma and 3 cases of incision infection. All patients were followed up 3-61 months (median, 15 months). During follow-up, no significant changes in neurological symptoms or tumor recurrence were found. Among the patients with preoperative visual impairment, there were 14 cases with no improvement in symptoms and 1 with improvement after surgery. Among the patients with somatic movement disorders, there were 11 cases with no improvement in symptoms, 3 cases with improvement, 2 cases with aggravation, 4 newly onset cases, and 1 case with significant impact on daily life after surgery. Among the patients with somatic sensory disorders, there were 17 cases with no improvement in symptoms, 14 cases with improvement, and 13 newly onset cases. The patients with hearing impairment showed improvement after surgery. The clinical manifestations of NF1 related peripheral nerve tumors are complex. Multimodal IONM technology can provide real-time detection of nerve provocation and damage. Surgical treatment with multimodal IONM technology is safe and can reduce complications.

Diagnostic And Post-Therapeutic Histopathology Of Hansen’s Disease in a Man With Rheumatoid Arthritis

Abstract Introduction/Objective Hansen’s Disease (leprosy), caused by Mycobacterium leprae, is a chronic infectious disease primarily affecting the skin and peripheral nerves. In the United States, leprosy remains rare, with less than 200 cases per year reported to the CDC. Diagnosis is often delayed, due to low clinical suspicion and lack of experience among healthcare providers, leading to potentially severe complications and increased transmission risk. Methods/Case Report A 71-year-old man presented to dermatology with a progressive, non-tender erythematous rash involving the arms and chest. He denied any travel history, or exposure to armadillos, and had no family history of a similar rash. His medical history was significant for rheumatoid arthritis, for which he was receiving methotrexate. The clinical differential included drug eruption, tinea infection, or sarcoidosis. Skin biopsy revealed extensive infiltration of the dermis by noncaseating granulomas surrounding cutaneous nerves, and AFB stain highlighted numerous bacilli consistent with Mycobacterium leprae, leading to the diagnosis of Hansen’s disease. The WHO classification was multibacillary leprosy, and the Ridley-Jopling classification was borderline tuberculoid (BT) to perhaps mid borderline (BB), based on clinical and histologic features. He was started on triple therapy, and biopsies performed during treatment, as well as at three years follow up showed marked improvement, with some remaining disease detected in unresolved rash. Results (if a Case Study enter NA) NA Conclusion This case presents a diagnostic challenge given the absence of typical risk factors for Mycobacterium leprae transmission. The patient’s immunocompromised status due to methotrexate therapy may have predisposed him to the disease. Documented cases of Hansen’s disease have more than doubled in the southeastern states since 2013, with concern for endemic regions emerging in Florida. Early recognition, classification, and prompt treatment are essential to prevent disease progression and reduce transmission. Increased education and awareness among healthcare providers are crucial to improving diagnostic accuracy and patient outcomes in cases of leprosy.

Malignant Peripheral Nerve Sheath Tumor of the Pancreas with Molecular Confirmation: A Case Report with Comprehensive Histopathologic and Molecular Characterization

Abstract Introduction/Objective Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue sarcomas arising from a peripheral nerve or exhibiting nerve sheath differentiation. They are often associated with neurofibromatosis type 1, and most often arise in the trunk, extremities, or head and neck region. In patients without neurofibromatosis type 1, sporadic de novo or radiotherapy-associated MPNSTs can pose a diagnostic challenge. MPNSTs arising from visceral organs are exceedingly rare. Here we report a case of MPNST arising in the pancreas. Methods/Case Report The patient is a 75-year-old female, MUTYH mutation carrier, with prior history of breast and bladder cancers, each treated with respective local excision and radiation therapy. Magnetic resonance imaging (MRI) performed for pancreatic cancer screening showed a 4.7 cm heterogeneous mass in the pancreatic tail suggestive of pancreatic neoplasm. Fine needle aspiration cytology was non-diagnostic. However, due to the radiologic concern for malignancy, the patient proceeded with surgical resection by distal pancreatectomy with splenectomy. Macroscopically, a 6.5 cm, tan-white, partially necrotic mass was identified in the pancreatic tail. Microscopic examination showed a spindle cell neoplasm arranged in a vague fascicular fashion with moderate nuclear pleomorphism, geographic necrosis, and frequent mitotic figures (15 per 10 high power fields). Fifteen lymph nodes were negative for metastasis. The tumor was confined to the pancreas grossly and microscopically. Immunohistochemical stains showed the neoplastic spindle cells to be positive for TLE1 (diffuse) and S100 (patchy), while negative for SOX10, CD117, DOG1, desmin, actin, MyoD1, ERG, STAT6, and ALK1. In addition, H3K27me3 showed loss of nuclear expression. Next generation sequencing (NGS) revealed gene mutations in NF1, TP53, PIK3CA, and PTEN, and copy number losses involving CDKN2A and CDKN2B. Genome-wide DNA methylation analysis was performed which revealed copy number losses of CDKN2A/B and gains of PTCH1 and MDM2. However, the Sarcoma DNA Methylation Classifier did not provide any diagnostic matches. Overall, the morphologic features, loss of H3K27me3 expression, presence of NF1 and TP53 mutations, and copy number losses in CDKN2A/B supported a diagnosis of high-grade MPNST. The patient has been followed clinically without adjuvant therapy. Results (if a Case Study enter NA) N/A Conclusion We report an extremely rare case of MPNST of the pancreas with molecular confirmation.

Radixin: Roles in the Nervous System and Beyond.

Radixin is an ERM family protein that includes radixin, moesin, and ezrin. The importance of ERM family proteins has been attracting more attention, and studies on the roles of ERM in biological function and the pathogenesis of some diseases are accumulating. In particular, we have found that radixin is the most dramatically changed ERM protein in elevated glucose-treated Schwann cells. We systemically review the literature on ERM, radixin in focus, and update the roles of radixin in regulating cell morphology, interaction, and cell signaling pathways. The potential of radixin as a therapeutic target in neurodegenerative diseases and cancer was also discussed. Radixin research has focused on its cell functions, activation, and pathogenic roles in some diseases. Radixin and other ERM proteins maintain cell shape, growth, and motility. In the nervous system, radixin has been shown to prevent neurodegeneration and axonal growth. The activation of radixin is through phosphorylation of its conserved threonine residues. Radixin functions in cell signaling pathways by binding to membrane proteins and relaying the cell signals into the cells. Deficiency of radixin has been involved in the pathogenic process of diseases in the central nervous system and diabetic peripheral nerve injury. Moreover, radixin also plays a role in cell growth and drug resistance in multiple cancers. The trials of therapeutic potential through radixin modulation have been accumulating. However, the exact mechanisms underlying the roles of radixin are far from clarification. Radixin plays various roles in cells and is involved in developing neurodegenerative diseases and many types of cancers. Therefore, radixin may be considered a potential target for developing therapeutic strategies for its related diseases. Further elucidation of the function and the cell signaling pathways that are linked to radixin may open the avenue to finding novel therapeutic strategies for diseases in the nervous system and other body systems.

Primary Malignant Peripheral Nerve Sheath Tumor in the Liver with Glandular Differentiation

Abstract Introduction/Objective Malignant peripheral nerve sheath tumors (MPNST) most commonly affect the proximal extremities and paraspinal region. Primary hepatic MPNST is extremely rare. Here we report a primary hepatic MPNST with heterologous glandular differentiation in a patient with Neurofibromatosis type 1 (NF1). Methods/Case Report Review of the clinical features and histopathological findings of the resected specimen. A review of all the published cases of primary liver MPNST. Results (if a Case Study enter NA) A 69-year-old male patient with a history of NF1, Gastrointestinal Stromal Tumor and treated hepatitis C without pre-existed neurofibroma presented with jaundice. Imaging revealed an ill-defied hypodense mass in the left hepatic lobe. A segmentectomy of the liver revealed an infiltrating 10 cm heterogenous yellow-white-pink slightly firm tumor with 5% necrosis. The tumor showed biphasic histology composed of predominantly spindle cells and clusters of glandular components. The spindle cells showed fascicular growth pattern with vaguely marbled appearance. Focal osteoclast-like multinucleated cells were seen. The glands were well defined, mostly appeared to be low grade, and lined by cuboidal to columnar cells, with a bile-duct and intestinal-like appearance. However, focal malignant glands with hepatic differentiation were also noted. Immunohistochemistry showed patchy loss of H3K27me3 in the spindle cells. The glandular cells were positive for AE1/AE3, CK7 and CK20. The tumor cells showed rare reactivity to TLE1 and were negative for S-100, SOX10, CD34, CD117 and DOG1. These findings supported the diagnosis of MPNST with glandular differentiation. 13 cases of primary MPNST of liver have been reported, and only one case described epithelioid differentiation. Conclusion The differential diagnoses of a primary hepatic biphasic tumor include sarcomatoid carcinoma, carcinosarcoma, biphasic synovial sarcoma and MPNST. Our case illustrates a rare biphasic hepatic MPNST. The morphology and loss of H3K27me3 expression by immunohistochemistry in a patient with NF1 support this challenging diagnosis.

Electrophysiological Changes in Median Nerve among Young Male Cigarette Smokers

Background: Cigarette smoking has been associated with numerous cardiovascular and respiratory disorders. Chronic smoking may also disrupt neuronal function and damage neurons in the peripheral nervous system. Median nerve conduction study is an important electrodiagnostic test for the detection of peripheral nerve dysfunction. Objectives: To observe the impact of cigarette smoking on the electrophysiological status of median motor and sensory nerves in apparently healthy male cigarette smokers. Materials and Methods: This case-control study was carried out in the Department of Physiology, Sir Salimullah Medical College, Dhaka, from July 2017 to June 2018 on thirty male cigarette smokers aged 25 to 40 years. For comparison, thirty age and BMI matched non-smoker healthy male subjects were selected as controls. Motor and sensory nerve conduction parameters (latency, amplitude and nerve conduction velocity) of right median nerve were evaluated by standard methods, using standard nerve conduction study and electromyography machines in the Department of Neurology, Dhaka Medical College Hospital. For statistical analysis, unpaired t test was performed. Results: In this study, median sensory nerve latency was significantly prolonged (p ˂ 0.001) and sensory nerve conduction velocity was significantly slower (p ˂ 0.001) in cigarette smokers. The mean amplitude was also slightly reduced in smokers, but statistically, it was insignificant. However, the distal latency of median motor nerve was slightly prolonged whereas, the amplitude and motor nerve conduction velocity were slightly reduced in cigarette smokers in comparison to those of non-smokers. But the differences were not statistically significant. In addition, 10% of cigarette smokers had subclinical impairment in median sensory nerve function. Conclusion: Chronic cigarette smoking induces significant electrophysiological changes in median sensory nerve fibers and causes sensory nerve dysfunction, while it does not markedly affect median motor nerve fibers in young individuals. KYAMC Journal Volume: 15, No: 01, April 2024: 03-07.

Expression and its clinical significance of cell-cycle dependent kinase 1 in malignant peripheral nerve sheath tumors

To explore the role and clinical significance of cell-cycle dependent kinase 1 (CDK1) and its upstream and downstream molecules in the development of malignant peripheral nerve sheath tumor (MPNST) through the analysis of clinical tissue samples. A total of 56 tumor samples from MPNST patients ("Tianjin" dataset) who underwent surgical resection, confirmed by histology and pathology between September 2011 and March 2020, along with 17 normal tissue samples, were selected as the research subjects. MPNST-related hub genes were identified through transcriptome sequencing, bioinformatics analysis, immunohistochemistry staining, and survival analysis, and their expression levels and prognostic associations were analyzed. Transcriptome sequencing and bioinformatics analysis revealed that upregulated genes in MPNST were predominantly enriched in cell cycle-related pathways, with CDK1 occupying a central position among all differentially expressed genes. Further differential analysis demonstrated that CDK1 mRNA expression in sarcoma tissues was significantly higher than in normal tissues [based on searching the cancer genome atlas (TCGA) dataset, P<0.05]. In MPNST tissues, CDK1 mRNA expression was not only significantly higher than in normal tissues (based on Tianjin, GSE141438 datasets, P<0.05), but also significantly higher than in neurofibromatosis (NF) and plexiform neurofibromas (PNF) (based on GSE66743 and GSE145064 datasets, P<0.05). Immunohistochemical staining results indicated that the expression rate of CDK1 protein in MPNST tissues was 40.31%. Survival analysis results demonstrated that CDK1 expression was associated with poor prognosis. The survival time of MPNST patients with high CDK1 mRNA expression was significantly lower than that of the low expression group ( P<0.05), and the overall survival trend of patients with positive CDK1 protein expression was worse than that of patients with negative CDK1 expression. Additionally, differential analysis of CDK family genes (CDK1-8) revealed that only CDK1 was significantly upregulated in MPNST, NF, and PNF. Increased expression of CDK1 is associated with poor prognosis in MPNST patients. Compared to other CDK family members, CDK1 exhibits a unique expression pattern, suggesting its potential as a therapeutic target for MPNST.

Correlation between Delayed Relief after Microvascular Decompression and Morphology of the Lateral Spread Response in Patients with Hemifacial Spasm-Further Examination with Compound Motor Action Potentials.

Although microvascular decompression (MVD) is a reliable treatment for hemifacial spasm (HFS), postoperative delayed relief is one of its main issues. We previously evaluated the morphology of the lateral spread response (LSR) and reported correlation between delayed relief after MVD and polyphasic morphology of the LSR. This study aimed to investigate the morphology of LSR and the course of recovery of the compound motor action potential (CMAP), to better understand the pathophysiology of delayed healing of HFS. Based on the pattern of the initial LSR morphology on temporal and marginal mandibular branches stimulation, patients were divided into two groups: the monophasic and polyphasic groups. The results of MVD surgery and sequential changes in the CMAP were evaluated 1 week, 1 month, 1 year, and final follow-up after the surgery. Significantly higher rates of persistent postoperative HFS were observed in patients with the polyphasic type of initial LSR at 1 week and 1 month after the surgery (P < 0.05, respectively). In the polyphasic group, the amplitude of the CMAP tended to gradually improve with time, while in the monophasic group, the amplitude of the CMAP decreased on the seventh postoperative day, followed by its gradual improvement. There is a significant correlation between delayed relief after MVD and polyphasic morphology of the initial LSR in patients with HFS. In the polyphasic group, CMAP recovered earlier and showed less reduction in amplitude, suggesting segmental demyelination, with less damage to peripheral nerves.

Adult Primary Extramedullary Spindle Cell Neoplasms of the Spinal Cord: Algorithmic Approach to a Frozen Section Dilemma

Abstract Introduction/Objective Spinal cord lesions can be designated as either (1) intramedullary, located within the spinal cord, or (2) extramedullary, located outside of the spinal cord, with further craterization as intradural and extradural. Neoplasms with a spindle cell phenotype can be challenging to optimally classify at the time of frozen section with immunohistochemistry necessary for optimal classification. This study looks at a spectrum of spinal cord tumors with a significant spindle cell component and offers an algorithmic approach for intraoperative consultation. Methods/Case Report A series of extramedullary spindle cell cases was compiled for comparison and contrast. A PubMed and Google literature search was undertaken. Results (if a Case Study enter NA) A total of 10 cases, age range 33-67, were compiled including meningioma with predominantly spindle cell features (WHO grade 1 and grade 2), solitary fibrous tumor, schwannoma lacking nuclear palisades and Verocay bodies, neurofibroma; malignant peripheral nerve sheath tumor, perineurioma, and spindle cell (tanycytic) ependymoma. During intraoperative consultation, touch preparations and frozen section features often overlapped. Radiologic localization of the neoplasm was essential to effective frozen section diagnosis as some lesions had a distinctly astrocytic phenotype. A general diagnosis was often employed, specifically spindle cell neoplasm with or without high-grade features. A differential diagnosis was provided when characteristic features were identified, including whorls, psammoma bodies, and intranuclear cytoplasmic inclusions favoring meningioma; abundant collagen between cells; nuclear palisades and Verocay bodies suggestive of Schwannoma; abundant extracellular matrix suggestive of neurofibroma; and perivascular pseudorosettes suggestive of extramedullary ependymoma variant. Conclusion This study provides a summary of extramedullary spinal region lesions that overlap with respect to imaging and frozen section characteristics. It emphasizes the need for clinical-radiologic-pathologic correlation on such lesions, the challenges in generating the differential diagnosis prior to histologic evaluation, and the pragmatism to rendering a diagnosis of spindle cell neoplasm with a differential diagnosis at frozen section.

Clinical features and surgical treatments of neurofibromas associated with neurofibromatosis type 1

To explore the clinical features, surgical treatment, and effectiveness of neurofibromas associated with neurofibromatosis type 1 (NF1). A clinical data of 41 patients with NF1 admitted between December 2018 and April 2024 was retrospectively analyzed. There were 15 males and 26 females, with an average age of 27.5 years (range, 5-61 years). Only one type of neurofibroma existed in 3 patients and the rest of the patients had more than two types of neurofibromas. Fourteen patients had total resection of multiple cutaneous neurofibromas (CNF). Eighteen patients of diffuse neurofibromas underwent total, near-total, or subtotal resection. Among the 13 patients of localized nodular neurofibromas, 9 of benign tumors underwent total sub-capsular resection and 4 of malignant peripheral nerve sheath tumor (MPNST) underwent maginal resection, and only 1 underwent postoperative radiotherapy and chemotherapy. Among the 15 patients of plexiform neurofibromas (PNF), 5 patients underwent both superficial and deep PNF resection, 2 underwent the superficial PNF resection, and 8 underwent the large nodular lesions in the deep PNF resection. There were 8 MPNST, of which 7 cases underwent total sub-capsular resection and large tumor capsule resection under neurophysiological monitoring, and 1 case with the tumor located on the top of the head underwent wide resection and skin grafting. One patient underwent proton knife therapy after surgery, 2 patients did not receive radiotherapy, and the remaining patients received conventional radiotherapy. All patients were followed up after surgery, and the follow-up time was 3-66 months, with an average of 25.0 months. Patients with CNF recovered satisfactorily after surgery, and there was no recurrence during follow-up. Patients with diffuse neurofibromas relieved preoperative symptoms after surgery. Three patients with diffuse neurofibromas located in the head and face recurred during follow-up. The patients with benign localized nodular neurofibromas recovered well after surgery, and only 1 patient had transient regional neuralgia after surgery. Among the patients with MPNST, 2 patients died of recurrence and lung metastasis, while the remaining 2 patients had no recurrence and metastasis during follow-up. All preoperative symptoms disappeared in patients with benign PNF, and no tumor recurrence was observed during follow-up. Two patients with PNF located in the brachial plexus had difficulty in shoulder abduction after surgery, 1 patient with PNF located in vagus developed hoarseness after surgery. Among the 8 patients with MPNST in PNF, 1 died of lung metastases and 1 died of systemic failure. The remaining 6 patients were in stable condition during follow-up, and no tumor recurrence or metastasis was observed. According to the clinical features of neurofibromas in patients with NF1, choosing appropriate surgical approaches can obtain good effectiveness. Because of the difficulty of completely resection, diffuse neurofibromas, especially those located in the head and face, are prone to recurrence after surgery. MPNST has the worst prognosis, high incidence of recurrence/metastasis, and short survival period. Total resection combined with radiotherapy can decrease local recurrence.