BACKGROUND

Traumatic peripheral nerve injury (TPNI) is a debilitating condition that may result in significant disability. There is variability in the epidemiology, clinical profile, and mechanism of injury worldwide, but data for low- and middle-income countries (LMICs) such as the Philippines are sparse.

We aimed to determine the demographic and clinical characteristics, management, and outcomes of patients who sustained TPNI in our center.

We performed a retrospective cohort study of all patients referred for TPNI at our institution from 2013 to 2019. Data on demographics, clinical features, etiology, surgical management, and status on last follow-up were collected.

Forty-four patients with injuries to 62 peripheral nerves were included in the cohort, which had a strong male predilection (98%). The mean age at diagnosis was 35.5 years, with 78% of patients aged between 16-45 years. The most common etiologies were laceration due to sharp objects (39%), stab wound (23%), hacking injury (14%), and vehicular crash (14%). In terms of mechanism of nerve injury, the most common was sharp laceration (80%), followed by stretch injury/nerve injury in continuity (14%). The most commonly injured nerves were the ulnar (36%) and median nerves (32%), more often on the right side (66%). Nerve repair surgery was performed in 80% of cases.

TPNIs in a tertiary center in the Philippines most commonly involved young males in the working age group and were caused by occupational and domestic accidents. Appropriate surgical management of TPNI is feasible in low resource settings.

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR. RESULTS: The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01). CONCLUSIONS EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Electroacupuncture ; Phosphatidylinositol 3-Kinase/metabolism* ; Facial Nerve Injuries/therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Beclin-1 ; Glial Cell Line-Derived Neurotrophic Factor ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Autophagy ; Mammals/metabolism*

Dengue hemorrhagic fever is a severe form of dengue presenting commonly with bleeding diathesis, but rarely with peripheral nervous system manifestations. Proximal median neuropathy comprises 1% of upper limb compression syndromes, and this case is the first to report injury to the proximal median nerve due to compression from hematoma formation. This case report presents the rehabilitation process of a 25-year-old Filipino female median nerve entrapment from venipuncture-associated hematoma presenting as burning sensation on the medial elbow, forearm and hand, weak flexion movement of her left thumb, index, and middle fingers. The patient was managed conservatively with pain medications, range of motion, gross and fine motor, and sensory re-education exercises. At 12 months, there was partial but functional recovery of median motor distribution and full recovery of median sensory distribution, as evidenced by improved sensory nerve action potential conduction velocity and amplitude, and compound motor action potential conduction velocity, with persistent decreased amplitude at 50%, and decrease in cross-sectional area of the left median nerve.

This paper highlights the functional outcomes of a conservatively managed median nerve entrapment from venipuncture hematoma from dengue hemorrhagic fever. This case report also emphasizes that in the presence of severe bleeding risk of surgery in the background of severe thrombocytopenia, timely rehabilitation medicine referral with monitoring through clinical evaluation, musculoskeletal ultrasound, and electrodiagnostic study presents a viable alternative in the management of compression neuropathy.

This is a case of a 63-year-old female with post-COVID-19 unilateral upper lip pain and numbness. Neurologic examination did not reveal any deficits other than deficits on pinprick in the maxillary division (V2) of the left trigeminal nerve. Brain neuroimaging showed signs of acute inflammation of the left maxillary sinus. Neuropraxia of the infraorbital nerve, a branch of the trigeminal nerve, was the diagnosis considered. Reports on trigeminal neurosensory changes following acute sinusitis are few, and isolated trigeminal neuropathy is rare except in cases of dental disorders. Up to this writing, there have been no reports on post-COVID-19 unilateral upper lip numbness and pain. This study will also serve as a concise review on the correlative neuroanatomy of the trigeminal nerve.
COVID-19 ; Trigeminal Nerve

Cranial nerve (CN) III palsy is rarely caused by intraorbital compression, let alone from a subgaleal abscess. We present a case of a hypertensive 55-year-old man with an acute isolated pupillary-sparing left CN III palsy from a left subgaleal abscess with associated pterional osteomyelitis and frontotemporal mass. This is the first reported such case and the third reported case of a chronic spontaneous subgaleal abscess. A seemingly routine case of an acute, pupillary-sparing, isolated CN III palsy from hypertension turned out to be a rare case in terms of etiology of the palsy and of the source of the abscess.
Cranial Nerve III ; palsy ; ptosis ; ophthalmoplegia

OBJECTIVE: To explore the brain effect mechanism and the correlation between brain functional imaging and cognitive function in treatment of depressive disorder (DD) with transcutaneous auricular vagus nerve stimulation (taVNS) based on the resting-state functional magenetic reasonance imaging (rs-fMRI). METHODS: Thirty-two DD patients were included in a depression group and 32 subjects of healthy condition were enrolled in a normal group. In the depression group, the taVNS was applied to bilateral Xin (CO₁₅) and Shen (CO₁₀), at disperse-dense wave, 4 Hz/20 Hz in frequency and current intensity ≤20 mA depending on patient's tolerance, 30 min each time, twice daily. The duration of treatment consisted of 8 weeks. The patients of two groups were undertaken rs-fMRI scanning. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Wisconsin card sorting test (WCST) were observed in the normal group at baseline and the depression group before and after treatment separately. The differential brain regions were observed before and after treatment in the two groups and the value of degree centrality (DC) of fMRI was obtained. Their correlation was analyzed in terms of HAMD, HAMA and WCST scores. RESULTS: The scores of HAMD and HAMA in the depression group were all higher than those in the normal group (P<0.05). After treatment, the scores of HAMD and HAMA were lower than those before treatment in the depression group; the scores of total responses, response errors and perseverative errors of WCST were all lower than those before treatment (P<0.05). The brain regions with significant differences included the left inferior temporal gyrus, the left cerebellar peduncles region 1, the left insula, the right putamen, the bilateral supplementary motor area and the right middle frontal gyrus. After treatment, the value of DC in left supplementary motor area was negatively correlated to HAMD and HAMA scores respectively (r=-0.324, P=0.012; r=-0.310, P=0.015); the value of DC in left cerebellar peduncles region 1 was negatively correlated to the total responses of WCST (r=-0.322, P=0.013), and the left insula was positively correlated to the total responses of WCST (r=0.271, P=0.036). CONCLUSION The taVNS can modulate the intensity of the functional activities of some brain regions so as to relieve depressive symptoms and improve cognitive function.
Humans ; Depression/therapy* ; Magnetic Resonance Imaging/methods* ; Vagus Nerve Stimulation/methods* ; Brain/diagnostic imaging* ; Transcutaneous Electric Nerve Stimulation/methods* ; Vagus Nerve

BACKGROUND: Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Here, we tried to identify the effects of the axon guidance factor semaphorin-3F (SEMA3F) on rituximab resistance as well as its therapeutic value in DLBCL. METHODS: The effects of SEMA3F on the treatment response to rituximab were investigated by gain- or loss-of-function experiments. The role of the Hippo pathway in SEMA3F-mediated activity was explored. A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects. The prognostic value of SEMA3F and TAZ (WW domain-containing transcription regulator protein 1) was examined in the Gene Expression Omnibus (GEO) database and human DLBCL specimens. RESULTS: We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen. Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity (CDC) activity induced by rituximab. We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20. Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter. Moreover, in patients with DLBCL, SEMA3F expression was negatively correlated with TAZ, and patients with SEMA3F low TAZ high had a limited benefit from a rituximab-based strategy. Specifically, treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo . CONCLUSION Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.
Humans ; Animals ; Mice ; Rituximab/therapeutic use* ; Hippo Signaling Pathway ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Prognosis ; Semaphorins/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Membrane Proteins/genetics* ; Nerve Tissue Proteins/genetics*

Malignant peripheral nerve sheath tumor (MPNST) is a rare neurogenic malignant tumor. MPNST has aty-pical clinical symptoms and imaging presentations, difficult diagnosis, a high degree of malignancy, and poor prognosis. It usually occurs in the trunk, approximately 20% in the head and neck, and rarely in the mouth. This paper reports a case of MPNST of the tongue. A summary of the clinical features, diagnosis, and treatment of MPNST is presented in combination with a literature review to provide a reference for the diagnosis and treatment of this disease.
Humans ; Nerve Sheath Neoplasms/pathology* ; Neurofibrosarcoma ; Tongue/pathology*

Objective To investigate the clinical value of high-frequency ultrasound in the diagnosis of pronator teres syndrome (PTS). Methods The high-frequency ultrasound was employed to examine and measure the median nerve of the pronator teres muscle in 30 patients with PTS and 30 healthy volunteers (control group).The long-axis diameter (LA),short-axis diameter (SA) and cross-sectional area (CSA) of the median nerve were measured.The receiver operating characteristic curve of the median nerve ultrasonic measurement results was established,and the area under the curve (AUC) was calculated.The diagnostic efficiency of each index for PTS was compared with the surgical results as a reference. Results The PTS group showed larger LA[(5.02±0.50) mm vs.(3.89±0.41) mm;t=4.38,P=0.013],SA[(2.55±0.46) mm vs.(1.70±0.41) mm;t=5.19,P=0.009],and CSA[(11.13±3.72) mm² vs.(6.88±2.68) mm²;t=8.42,P=0.008] of the median nerve than the control group.The AUC of CSA,SA,and LA was 94.3% (95%CI=0.912-0.972,Z=3.586,P=0.001),77.7% (95%CI=0.734-0.815,Z=2.855, P=0.006),and 78.8% (95%CI=0.752-0.821,Z=3.091,P=0.004),respectively.With 8.63 mm² as the cutoff value,the sensitivity and specificity of CSA in diagnosing PTS were 93.3% and 90.0%,respectively. Conclusion High-frequency ultrasound is a practical method for diagnosing PTS,and the CSA of median nerve has a high diagnostic value.
Humans ; Forearm/innervation* ; Muscle, Skeletal/innervation* ; Median Nerve/diagnostic imaging* ; Ultrasonography/methods* ; Sensitivity and Specificity

To investigate the antidepressant mechanism of Shenling Kaixin Granules(SLKX) in treating chronic unpredictable mild stress(CUMS) model rats. Ninety male SD rats were randomly divided into control group, model group, Shugan Jieyu Capsules(110 mg·kg~(-1)) group and SLKX low-(90 mg·kg~(-1)), medium-(180 mg·kg~(-1)), and high-dose(360 mg·kg~(-1)) groups. Depression rat model was replicated by CUMS method. After treatment, the behavioral changes of rats were evaluated by sugar preference, open field, elevated cross maze and forced swimming experiments. The contents of interleukin 1 beta(IL-1β), tumor necrosis factor α(TNF-α), brain-derived neurotrophic factor(BDNF) and 5-hydroxytryptamine(5-HT) in serum were determined by enzyme linked immunosorbent assay(ELISA), and the activities of superoxide dismutase(SOD) and catalase(CAT) in hippocampal CA1 region were also detected. Pathological changes in hippocampal CA1 region were detected by hematoxylin-eosin(HE) staining, and Western blot was used to determine the expression of nerve growth factor(NGF), BDNF, phospho-tyrosine kinase receptor(p-TrkB)/TrkB, phospho-cAMP-response element binding protein(p-CREB)/CREB, nuclear factor E2 related factor 2(Nrf2), heme oxygenase 1(HO-1), B-cell lymphoma-2(Bcl-2)/Bcl-2 associated X protein(Bax) and caspase-3 in hippocampal CA1 region. RESULTS:: showed that compared with the control group, the model group had decreased sugar preference, reduced number of entries and time spent in the center of open field and shortened total distance of movement, reduced number of entries and proportion of time spent in open arm, and increased number and time of immobility in forced swimming experiment. Additionally, the serum contents of IL-1β and TNF-α and the expression of caspase-3 were higher, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1 and Bcl-2/Bax, and the Nrf2 nuclear translocation were lower in model group than in control group. Compared with the conditions in model group, the sugar preference, the number of entries and time spent in the center of open, total distance of movement, and the number of entries and proportion of time spent in open arm in treatment groups were increased while the number and time of immobility in forced swimming experiment were decreased; the serum contents of IL-1β and TNF-α and the expression of caspase-3 were down regulated, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1, Bcl-2/Bax, and Nrf2 nuclear translocation were enhanced. In conclusion, SLKX might regulate the Nrf2 nucleus translocation by activating BDNF/TrkB/CREB pathway, lower oxidative stress damage in hippocampus, inhibit caspase-3 activity, and reduce apoptosis of hippocampal nerve cells, thereby playing an antidepressant role.
Rats ; Male ; Animals ; bcl-2-Associated X Protein/metabolism* ; Caspase 3/metabolism* ; Nerve Growth Factor/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Signal Transduction ; Tumor Necrosis Factor-alpha/metabolism* ; Serotonin/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Rats, Sprague-Dawley ; Antidepressive Agents/pharmacology* ; Hippocampus/metabolism* ; Superoxide Dismutase/metabolism* ; Sugars/pharmacology* ; Depression/genetics* ; Stress, Psychological/metabolism*