Glossopharyngeal Research Articles

Fascial layers encountered in the lateral skull base region: A cadaveric and radiological analysis.

In our experience, the anterior carotid sheath forms an important plane of dissection when excising temporal bone region cancers. However, its anatomical composition, relationships, and radiological appearance remains unclear. Eight sides of cadaveric heads were dissected. Anatomical findings were correlated with a high-resolution baseline T1 MRI. The anterior carotid sheath was formed by the tensor-vascular-styloid fascia, stylopharyngeal fascia, buccopharyngeal fascia (BPF), and longus capitis fascia (LCF), and appeared as a hypointense line on MRI. Not previously described, the glossopharyngeal nerve pierced the sheath 9.0 mm (SD 2.1 mm) below the skull base and traveled through its LCF and BPF layers to exit near the pharynx. Multiple fascial layers formed the anterior carotid sheath at the skull base, and this was radiologically identifiable. Further studies are required to validate findings and investigate the role this fascial plane has in forming an effective barrier to spread of malignancy.

Complete Second Branchial Cleft Fistulas: A Clinicosurgical Experience.

A complete second branchial fistula is very rare and has an internal opening at the tonsillar fossa and an external opening at the lower third of the sternocleidomastoid (SCM). Patients commonly present with persistent or intermittent mucoid or mucopurulent discharge from an external opening. The diagnosis is most often clinical and radiological investigations are rarely needed. Treatment of choice is complete surgical excision. The aim of this article is to aware young ENT surgeons of the various clinical and intraoperative surgical findings that can be encountered while dealing with these cases. This observational study was done for a period of 10years. A total of 20 cases of fistula were included which intraoperatively had a complete track from tonsillar fossa to neck. Excision of the tract was carried out via combined transcervical and transoral approach under general anaesthesia using two incisions in stepladder pattern. Each patient was seen after one year of surgery to assess for any recurrence. Different findings of patients including age/sex at surgery, initial presentation, family history, laterality of the fistula tract, Intraoperative surgical findings, complications, and recurrences. were noted. Of the 20 patients, 13 (65%) were females and 7 (35%) were Females. Most common complaint was fistulous opening with intermittent discharge(15patients; 75%).Branchial cleft fistulae more commonly affected the right neck (14 patients, 78%) among unilateral cases and 2 patients (10%) had bilateral fistulae. No patient had associated congenital anomaly/syndrome, family history or and visible opening in tonsillar area. Glossopharyngeal nerve was identified in 12 cases and track was seen passing lateral to it except in one case. The internal opening of track was seen over posterior tonsillar pillar in 15 cases (75%) while in 5 patient the track was seen entering tonsillar tissue or bed. Tonsillectomy was done in 5 cases while not done in 15 cases where track was seen entering posterior pillar. All patients were seen at one year follow up. No recurrence was seen at one year of follow up. Complete second branchial cleft fistulae are rare. They are usually right sided and unilateral. The track passes between carotid bifurcation and invariably passes lateral to both glossopharyngeal and hypoglossal nerves. Track usually ends at the posterior tonsillar pillar. Tonsillectomy is not routinely indicated. Recurrences are not typically seen.

Neurotization of the facial nerve as an effective way to treat paralysis of mimic muscles

Pathologies of the facial nerve are one of the most common types of pathology of the peripheral nervous system. In the structure of lesions of the cranial nerves, this pathology occupies the first place. The clinical picture of facial nerve damage of various genesis is rather monotonous and manifests itself as persistent paresis or paralysis of the facial muscles. The literature describes a large number of different highly effective techniques aimed at restoring the function of the facial nerve and mimic muscles, examples of which are numerous conservative and surgical methods for the treatment of facial nerve neuropathy. The review presents the most common method of mimic muscles paralysis surgical treatment facial nerve neurotization. The essence of this surgical intervention is in suturing to the affected facial nerve the trunk or a portion of individual fibers of the intact nerve-neurotic, which can be the hypoglossal, masticatory, phrenic, accessory, glossopharyngeal nerves, as well as the descending branch of the hypoglossal nerve and the anterior branches of the C2C3 cervical nerves. Currently, options for the combined use of various donor nerves and autoextensions are gaining popularity among neurosurgeons, due to more favorable results in restoring the function of the facial nerve, as well as with an individual approach to each patient. The main stages of neurotization of the facial nerve include the isolation and intersection of the facial nerve, the isolation and intersection of the trunk or individual fibers of the neurotizer, the execution of the suture of the nerve in the end to end or end to side method. Particular attention should be paid to the most innovative method of facial nerve neurotization facial nerve cross-plasty, during which an anastomosis between the damaged and intact facial nerves using autotransplants from the gastrocnemius nerve or a free muscle graft, including the tender muscle and the anterior branch of the obturator nerve is performed. The process of restoring facial nerve function and regressing characteristic symptoms takes a long period of time and requires specialized restorative treatment.

Incidence and Risk Factors of Cranial Nerve Palsy in Patients with Tuberculous Meningitis: A Retrospective Evaluation.

Tuberculous meningitis (TBM) is a common form of central nervous system (CNS) tuberculosis (TB). Cranial nerve palsy is a serious complication of TBM. Literature regarding this subject is still limited in China. This study evaluated the incidence of cranial nerve palsy in patients with TBM in South China, its association with the clinical forms of TB, and other patient characteristics. A retrospective chart review of patients with a diagnosis of TBM between January 2004 and December 2019 was conducted, and the demographic characteristics, clinical characteristics, and laboratory results of 114 patients were collected and followed up for 3 months. A multivariate logistic regression analysis model was used to explore the risk factors of cranial nerve palsy in patients with TBM. A total of 114 patients were enrolled in this study. Cranial nerve palsy was observed in approximately 38 (33.3%) of TBM patients. Among them, 13 (28.3%) had optic nerve palsy, 24 (52.2%) had oculomotor nerve palsy, 5 (10.9%) had abducens nerve palsy, 2 (4.3%) had auditory nerve palsy, 1 (2.2%) had glossopharyngeal nerve palsy, and 1 (2.2%) had vagus nerve palsy. Using logistic regression analysis, focal neurological deficit, extracranial TB and cerebrospinal fluid (CSF) total white cell count (WCC) were shown to be risk factors for cranial nerve palsy. The prevalence rate of cranial nerve palsy was 33.3% in patients with TBM. Focal neurological deficits, extracranial TB and CSF total WCC are important predictors of cranial nerve palsy in patients with TBM.

Combined four neurovascular compression syndromes: the first case report and literature review

BackgroundNeurovascular compression syndromes (NVCs) are cranial nerve syndromes caused by direct contact or compression of vascular structures on the cranial nerves at the root exit/entry zone. Cases of combined NVCs are extremely rare.CaseWe reported the first case of a 41-year-old woman with combined four NVCs presenting with left hemifacial spasm followed by simultaneous left glossopharyngeal neuralgia, left type-writer tinnitus and vestibular paroxysmia due to the left posterior inferior cerebellar artery compression at the root exit/entry of the left facial, vestibulocochlear and glossopharyngeal nerves. All the symptoms resolved immediately after microvascular decompression without recurrence in a period of follow-up for one year. In addition, we presented a literature review of combined three or more NVCs.ConclusionWe discussed the hypothesis of combined three or more NVCs development, especially the central hyperactivity of the cranial nerve nuclei mechanism.

Molecular taxonomy of nociceptors and pruriceptors.

Molecular taxonomy of nociceptors and pruriceptors.

Transcervical, retropharyngeal odontoidectomy - Anatomical considerations.

Anterior craniocervical junction lesions have always been a challenge for neurosurgeons. Presenting with lower cranial nerve dysfunction and symptoms of brainstem compression, decompression is often required. While posterior approaches offer indirect ventral brainstem decompression, direct decompression via odontoidectomy is necessary when they fail. The transoral and endoscopic endonasal approaches have been explored but come with their own limitations and risks. A novel retropharyngeal approach to the cervical spine has shown promising results with reduced complications. This study aims to explore the feasibility and potential advantages of the anterior retropharyngeal approach for accessing the odontoid process. To investigate the anatomical aspects of the anterior retropharyngeal approach, a paramedian skin incision was performed below the submandibular gland on two cadaveric specimens. The subcutaneous tissue followed by the platysma is dissected, and the superficial fascial layer is opened. The plane between the vascular sheath laterally and the pharyngeal structures medially is entered below the branching point of the facial vein and internal jugular vein. After reaching the prevertebral plane, further dissection cranially is done in a blunt fashion below the superior pharyngeal nerve and artery. Various anatomical aspects were highlighted during this approach. The anterior, submandibular retropharyngeal approach to the cervical spine was performed successfully on two cadavers highlighting relevant anatomical structures, including the carotid artery and the glossopharyngeal, hypoglossal, and vagus nerves. This approach offered wide exposure, avoidance of oropharyngeal contamination, and potential benefit in repairing cerebrospinal fluid fistulas. For accessing the craniocervical junction, the anterior retropharyngeal approach is a viable technique that offers many advantages. However, when employing this approach, surgeons must have adequate anatomical knowledge and technical proficiency to ensure better outcomes. Further studies are needed to enhance our anatomical variations understanding and reduce intraoperative risks.

Comparative analysis of neurophysiological studies in the diagnosis of bulbar syndrome in patients with Chiari malformation Type 1

The incidence of bulbar syndrome in craniovertebral junction anomalies is between 12% and 35%. Although the use of evoked potentials intraoperatively and preoperatively has advanced in recent years, their use in predicting the development of neurological deficits remains a challenge. This research explores the predictive significance of evoked potentials in the diagnosis of bulbar syndrome in Chiari 1 anomaly. Data from 39 patients and 30 controls were reviewed. Standard multimodal neurophysiological investigations including Brainstem auditory evoked potentials (BAEPs), somatosensory evoked potentials (SSEPs), Nerve Conduction Studies (NCS), and Electromyogram (EMG) were performed. All studies were conducted on the 4-channel complex “Synapsis” (Neurotech, Russia) with computer data processing. The threshold Nerve conduction velocity (NCV) value was 21.5 m/s. The sensitivity and specificity were 75.5% and 71.2% respectively. The area under the ROC curve (AUC) was 0.96±0.36 (95% CI: 0.89-1.00) and p-value 0.004. The M-response amplitude threshold dividing the study group into high and low-risk groups was 1.01 microV. The sensitivity and specificity were 78.0 and 71.2%, respectively. The BAEPs interpeak intervals III-V and I-V were significantly prolonged (P˂ 0.05). SSEPs showed a decreased amplitude and reduced NCV (P ˂ 0.01). Glossopharyngeal nerve electroneuromyography is the most informative test. A decrease in M-response amplitude of bulbar muscles and NCV on efferent fibers is highly predictive of the development of bulbar disorders in patients with Chiari 1, even in subclinical cases.

Glossopharyngeal Neuralgia following Coronavirus Disease 2019 Infection

Abstract Glossopharyngeal neuralgia is a rare and painful syndrome that affects the sensory distribution of the glossopharyngeal nerve. Coronavirus disease 2019 (COVID-19) was first discovered in the Wuhan province of China in November 2019 and was declared a pandemic by the World Health Organization in early 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus strain that was responsible for COVID-19, may affect the central nervous system and cause neurological manifestations. We report a case of a 46-year-old female presenting with pain in her right ear and pharynx on swallowing, coughing, and sneezing. On physical examination, normocephaly, normal hearing, no oropharyngeal lesions, and bilaterally normal tonsils were observed. On neurologic examination, her speech was fluent without any abnormalities and testing revealed COVID-19 positivity. Cranial computed tomography scan, brain and spinal magnetic resonance imaging (MRI), cranial magnetic resonance angiogram, and soft-tissue neck MRI with and without contrast were unremarkable. Carbamazepine was initiated for neuropathic pain with success. Heightened awareness and early recognition of neurological complications related to SARS-CoV-2 infection may improve the prognosis. Monitoring the long-term nervous system complications of SARS-CoV-2 infection, including psychological and neurocognitive domains, is also necessary.

Epithelial plasticity enhances regeneration of committed taste receptor cells following nerve injury

Taste receptor cells are taste bud epithelial cells that are dependent upon the innervating nerve for continuous renewal and are maintained by resident tissue stem/progenitor cells. Transection of the innervating nerve causes degeneration of taste buds and taste receptor cells. However, a subset of the taste receptor cells is maintained without nerve contact after glossopharyngeal nerve transection in the circumvallate papilla in adult mice. Here, we revealed that injury caused by glossopharyngeal nerve transection triggers the remaining differentiated K8-positive taste receptor cells to dedifferentiate and acquire transient progenitor cell-like states during regeneration. Dedifferentiated taste receptor cells proliferate, express progenitor cell markers (K14, Sox2, PCNA) and form organoids in vitro. These data indicate that differentiated taste receptor cells can enter the cell cycle, acquire stemness, and participate in taste bud regeneration. We propose that dedifferentiated taste receptor cells in combination with stem/progenitor cells enhance the regeneration of taste buds following nerve injury.

Comparison between landmark and ultrasound-guided percutaneous peristyloid glossopharyngeal nerve block for post-tonsillectomy pain relief in children: a randomized controlled clinical trial

ABSTRACT Background Glossopharyngeal nerve (GPN) block is a useful treatment option for acute post-tonsillectomy pain. This study aimed to assess safety and efficacy of the landmark (LM) technique versus the ultrasound (US)-guided technique for GPN block in children undergoing tonsillectomy. Methods This double-blinded, parallel-group, randomized trial enrolled 54 children of both genders who were American Society of Anesthesiologists physical status grade I–II and were scheduled for tonsillectomy under general anesthesia. All patients underwent percutaneous peristyloid GPN block. In the LM group, 27 patients were managed by insertion of the needle at midpoint of the line between the mastoid process and angle of the mandible. In the US group, 27 patients were managed with the US-guided technique to locate the styloid process. The outcomes were time to first analgesic requirement, pain in rest and during swallowing, easiness of the technique, time required for the technique performance, recovery time from anesthesia, and anesthetist, surgeon, parent, and staff satisfaction. Results The post-tonsillectomy pain score during rest and swallowing, rescue analgesic request, recovery time from general anesthesia, anesthetist’, surgeon’, staff nurses’, and parents’ satisfactions were comparable between the LM technique and US-guided percutaneous peristyloid GPN block (all p ˃ 0.05). However, the LM technique was significantly easier and required shorter duration than the US-guided technique (p ˂ 0.05). Conclusion In tonsillectomy surgery, both the LM technique and the percutaneous peristyloid US-guided GPN block were safe and effective in reducing postoperative pain. Furthermore, the LM technique was easier and had shorter duration to perform than the US-guided technique.

Glossopharyngeal neuralgia as a postoperative complication of tonsillectomy: a case report

Tonsillectomy is one of the most common procedures performed by otolaryngologists. Post-operative complications commonly include temporary pain, infection, and bleeding. Glossopharyngeal neuralgia is a rare complication that has been previously documented in the literature. Glossopharyngeal neuralgia is a rare type of facial pain syndrome that is characterised by radiating pain in the sensory distribution of the glossopharyngeal nerve. It can cause sharp shooting pain in the face, ears and/or back of the throat. Pain is exacerbated with repetitive movements such as chewing, speaking, and swallowing. The majority of glossopharyngeal neuralgia is idiopathic in origin; however, we report a case of a 37-year-old lady that developed glossopharyngeal neuralgia immediately after tonsillectomy. Her condition was managed with intraoral injection of alcohol and saline preparation in the tonsillar fossa with good effect.

Eagle’s syndrome in tertiary health institution, southern region of Nigeria

Eagle’s syndrome is a condition caused by elongation of the styloid process or ossification of the styloid ligament resulting in non-specific symptoms related to pressure on vital blood vessels of the neck, the internal carotid artery, internal jugular vein, and nerves; the glossopharyngeal and vagus nerves. Eagle’s syndrome may have varied presentations with numerous symptoms: Pain in the throat/neck radiating to the ear and pharynx, foreign body sensation in the throat, dysphagia, otalgia, trismus, and intense facial pain. A high index of suspicion with a prompt resort to a three-dimensional CT skull could be helpful to give a quick diagnosis of Eagle’s syndrome amid numerous differential diagnoses. We present a 59-year-old male with an 18-month history of left-sided neck pain, cheek pain, and the feeling of a foreign body in the throat. He had pain relievers and other drugs to no avail. A three-dimensional CT scan of his skull revealed features of Eagle’s syndrome. The excision of the styloid process through the extraoral route relieves his symptoms. The second patient is a 42-year-old female with symptoms of peptic ulcer disease, dysphagia, pain in the throat, and sometimes fainting attacks when she moves her neck swiftly to the left side. A three-dimensional CT skull scan confirmed features of an elongated styloid process bilaterally suggestive of Eagle’s syndrome. Treatment offered to her was conservative, with a diclofenac suppository only because she refused surgery. Restricted and limited neck movement relieved her of syncope attacks.

Difficult intubation and postoperative aspiration pneumonia associated with Moebius syndrome: a case report

BackgroundMoebius syndrome is a rare congenital disorder characterized by non-progressive palsy of the abducens (VI) and facial (VII) cranial nerves. Its common features include dysfunctions associated with other cranial nerves, orofacial abnormalities, skeletal muscle hypotonia, and other systemic disorders of differing severities. There are several concerns in the perioperative management of patients with Moebius syndrome.Case presentationWe present a report on the management of general anesthesia of a 14-year-old male patient with Moebius syndrome who was scheduled for mandibular cystectomy. The patient was diagnosed with Moebius syndrome at the age of 7 years based on his clinical manifestations of nerve palsy since birth and cranial nerve palsy of the trigeminal (V), facial (VII), glossopharyngeal (IX), vagus (X), and sublingual nerves (XII). The patient’s oral morphological abnormalities made intubation difficult. He also experienced dysphagia and aspiration pneumonia on a daily basis. Oral secretions were frequently suctioned postoperatively. However, after discharge, the patient developed aspiration pneumonia and was readmitted to the hospital.ConclusionsThe main problem arising when administering general anesthesia to patients with this syndrome is difficult airway management. The oral abnormalities in these patients, such as small jaw and extreme dental stenosis, make mask ventilation and intubation difficult. Furthermore, this syndrome often involves respiratory impairment and dysphagia due to cerebral nerve palsy, so there is a high risk of postoperative respiratory complications. Since multiple organs are affected in patients with Moebius syndrome, appropriate perioperative management strategies must be prepared for these patients.

PO230 / #511 NON-INVASIVE VAGAL NERVE STIMULATION FOR PAIN RELIEF OF OROPHARYNGEAL CANCER: E-POSTER VIEWING

Glossopharyngeal nerve block has been described for patients with cancer of the throat or other painful conditions arising in the innervation of the glossopharyngeal nerve. The technique of Ultrasound guided glossopharyngeal nerve block for cancer pain was first described by the author in 19893 and was reported most recently in 2019 by Liu eta al 4 who used it for glossopharyngeal neuralgia in 12 patients with excellent results. The standard described technique for delivering the stimulation over the carotid artery will also stimulate the glossopharyngeal nerve as it moves anteriorly just below the Styloid process ( Figure 1)( Figure 2).Our thesis was that we would be providing peripheral nerve stimulation to the glossopharyngeal nerve as well as the vagus nerve.

Terminal field volume of the glossopharyngeal nerve in adult rats reverts to prepruning size following microglia depletion with PLX5622.

Programmed reduction of synapses is a hallmark of the developing brain, with sensory systems emerging as useful models with which to study this pruning. The central projections (terminal field) of the gustatory glossopharyngeal nerve (GL) of the rat are a prime example of developmental pruning, undergoing an approximate 66% reduction in volume from postnatal day 15 (P15) to P25. Later in adulthood, developmental GL pruning can be experimentally reversed, expanding to preweaning volumes, suggesting mature volumes may be actively maintained throughout the life span. Microglia are central nervous system glia cells that perform pruning and maintenance functions in other sensory systems, including other gustatory nerves. To determine their role in GL pruning, we depleted microglia from Sprague-Dawley rat brains from P1 to P40 using daily intraperitoneal injections of the colony-stimulating factor 1 receptor inhibitor PLX5622. This prevented GL developmental pruning, resulting in preweaning terminal field volumes and innervation patterns persisting through P40, 2weeks after pruning is normally completed. These findings show microglia are necessary for developmental GL pruning. Ceasing PLX5622 treatments at P40 allowed microglia repopulation, and within 4weeks the GL terminal field had reduced to control volumes, indicating that pruning can occur outside of the typical developmental period. Conversely, when microglia were depleted in adult rats, GL terminal fields expanded, reverting to sizes comparable to the neonatal rat. These data indicate that microglia are required for GL pruning and may continue to maintain the GL terminal field at a reduced size into adulthood.

Immunohistochemical localization of vesicular nucleotide transporter in small intensely fluorescent (SIF) cells of the rat superior cervical ganglion

Our previous study reported that a part of small intensely fluorescent (SIF) cells in the rat superior cervical ganglion were innervated by P2X3 purinoceptor-expressing glossopharyngeal sensory nerve endings, suggesting the occurrence of adenosine 5′-triphosphate (ATP)-mediated transmission between them. The present study investigated the immunolocalization of vesicular nucleotide transporter (VNUT) in SIF cells of the superior cervical ganglion in male Wistar rats. VNUT was immunohistochemically localized in tyrosine hydroxylase-immunoreactive SIF cells and sympathetic postganglionic neurons, but not in a few SIF cells with immunoreactivity for dopamine beta-hydroxylase. P2X3-immunoreactive ramified nerve endings formed flat leaf-like or spherical terminal parts to surround some VNUT-immunoreactive SIF cells, but not other VNUT-immunoreactive SIF cells attached to ganglionic neurons. VNUT-immunoreactive SIF cells contained bassoon-immunoreactive products at the contacting surface of P2X3-immunoreactive nerve endings. Immunoreactivity for ectonucleoside triphosphate diphosphohydrolase 2, which hydrolyzes extracellular ATP, was observed in S100B-immunoreactive satellite glial cells surrounding VNUT-immunoreactive SIF cells, but not in the attachment surfaces between SIF cells and nerve endings with P2X3 immunoreactivity. The present results suggest that SIF cells release ATP by exocytosis to modulate the excitability of sensory nerve endings and postganglionic neurons in the superior cervical ganglion.

Prognostic factors for long-term outcomes of microvascular decompression in the treatment of glossopharyngeal neuralgia: a retrospective analysis of 97 patients.

The authors aimed to investigate predictors of postoperative outcomes of microvascular decompression (MVD) for the treatment of glossopharyngeal neuralgia (GPN). A cohort of 97 patients with medically refractory GPN who underwent MVD at the authors' institution between January 2010 and July 2019 was retrospectively reviewed. Univariate and multivariate regression models were used to identify predictors of long-term outcome in patients after MVD. Eighty-nine patients (91.8%) reported immediate and complete relief of pain after the procedure. Of the remaining 8 patients (8.2%), 6 achieved partial pain relief and pain gradually diminished within 2 weeks after surgery, and 2 did not experience postoperative pain relief. In univariate Cox regression analysis, venous compression of the glossopharyngeal nerve root entry zone (HR 3.591, 95% CI 1.660-7.767, p = 0.001) and lower degree of neurovascular conflict (HR 2.449, 95% CI 1.177-5.096, p = 0.017) were significantly associated with worse pain-free survival. In multivariate Cox regression analysis, venous compression (HR 8.192, 95% CI 2.960-22.669, p < 0.001) and lower degree of neurovascular conflict (HR 5.450, 95% CI 2.069-14.356, p = 0.001) remained independently associated with worse pain-free survival. Venous compression of the glossopharyngeal nerve root entry zone and lower degree of neurovascular conflict were significantly correlated with shorter pain-free survival in patients who underwent MVD for GPN. Microvascular decompression is a safe, feasible, and durable approach with a low complication rate for the treatment of GPN.

Integrative Korean Medicine Treatment for Idiopathic Glossopharyngeal Neuralgia: A Case Report

Glossopharyngeal neuralgia is a skin-sensitive condition/disease that causes severe pain in the facial area predominantly innervated by the glossopharyngeal nerve. A 51-year-old man diagnosed with glossopharyngeal neuralgia who was hospitalized with severe pain that limited his daily life activities. From November 18, 2021, to March 4, 2022, he received inpatient (10 days) and outpatient treatment (35 times) using acupuncture, pharmacopuncture, and herbal medicine. His symptoms were assessed using the Numerical Rating Scale, Neuropathic Pain Scale, and the Self-report Leeds Assessment of Neuropathic Symptom and Signs. The pain reduced after 4 days of initiating Korean medicine treatment and was completely resolved within 4 months of treatment (Numerical Rating Scale score 4 to 0; Neuropathic Pain Scale score 49 to 8; Self-report Leeds Assessment of Neuropathic Symptoms and Signs score 18 to 0). Korean medicine treatment could be an option for treating patients with neuropathy who rely on analgesics.

Neuroprotective Drug Discovery From Phytochemicals and Metabolites for CNS Viral Infection: A Systems Biology Approach With Clinical and Imaging Validation.

BackgroundRecent studies have reported that pulmo-neurotropic viruses can cause systemic invasion leading to acute respiratory failure and neuroinfection. The tetracycline class of secondary metabolites of microorganisms is effective against several migrating neurotropic viral disorders, as Japanese-Encephalitis (JE), Severe-Acute-Respiratory-Syndrome Coronavirus-2 (SARS-COV2), Human-Immunodeficiency-Virus (HIV), and Simian-Immunodeficiency-Virus (SIV). Another microbial secondary metabolite, cephalosporin, can be used for anti-viral combination therapy. However, a substantial public health debacle is viral resistance to such antibiotics, and, thus, one needs to explore the antiviral efficiency of other secondary metabolites, as phytochemicals. Hence, here, we investigate phytochemicals like podophyllotoxin, chlorogenic acid, naringenin, and quercetin for therapeutic efficiency in neurotropic viral infections.MethodsTo investigate the possibility of the afferent neural pathway of migrating virus in man, MRI scanning was performed on human subjects, whereby the connections between cranial nerves and the brain-stem/limbic-region were assessed by fiber-tractography. Moreover, human clinical-trial assessment (n = 140, p = 0.028) was done for formulating a quantitative model of antiviral pharmacological intervention. Furthermore, docking studies were performed to identify the binding affinity of phytochemicals toward antiviral targets as (i) host receptor [Angiotensin-converting Enzyme-2], (ii) main protease of SARS-COV2 virus (iii) NS3-Helicase/Nucleoside triphosphatase of Japanese-encephalitis-virus, and the affinities were compared to standard tetracycline and cephalosporin antibiotics. Then, network pharmacology analysis was utilized to identify the possible mechanism of action of those phytochemicals.ResultsHuman MRI-tractography analysis showed fiber connectivity, as: (a) Path-1: From the olfactory nerve to the limbic region (2) Path-2: From the peripheral glossopharyngeal nerve and vagus nerves to the midbrain-respiratory-center. Docking studies revealed comparable binding affinity of phytochemicals, tetracycline, and cephalosporin antibiotics toward both (a) virus receptors, (b) host cell receptors where virus-receptor binds. The phytochemicals effectively countered the cytokine storm-induced neuroinflammation, a critical pathogenic pathway. We also found that a systems-biology-based double-hit mathematical bi-exponential model accounts for patient survival-curve under antiviral treatment, thus furnishing a quantitative-clinical framework of secondary metabolite action on virus and host cells.ConclusionDue to the current viral resistance to antibiotics, we identified novel phytochemicals that can have clinical therapeutic application to neurotropic virus infection. Based on human MRI scanning and clinical-trial analysis, we demarcated the anatomical pathway and systems-biology-based quantitative formulation of the mechanism of antiviral action.