Symptomatic subgemmal neurogenous plaque in patients with COVID-19: Is there an association?

BACKGROUND: Subgemmal neurogenous plaques (SNP) are composed of neural structures found in the posterolateral portion of the tongue, rarely biopsied as most of them are asymptomatic or eventually only clinically managed. We aimed to investigate a case series of possible correlation of symptomatic subgemmal neurogenous plaque (SNP) with coronavirus disease 2019 (COVID-19). METHODS: Eleven formalin-fixed paraffin-embedded cases from patients with previous confirmed COVID-19 (by RT-PCR) were retrieved from two pathology files. Histological sections were morphologically studied, and then submitted to immunohistochemical reactions against S-100 and neurofilament proteins, neuron-specific enolase, Glial fibrillary acidic protein (GFAP), synaptophysin, CD56, Ki67, cytokeratins (7, 8-18, 19, 20), nucleocapsid and spike proteins (SARS-CoV-1; and -2) and epithelial membrane antigen (EMA) antibodies. Clinical data were retrieved from the patients' medical files, including the symptoms and the complete history of the progression of the disease. RESULTS: The patients who had COVID-19 included in this study experienced painful lesions in the tongue that corresponded to prominent or altered SNP. Microscopically, neural structures were positive for S-100, GFAP and neurofilament protein. And the cellular proliferative index (by Ki-67) was very low. CONCLUSION: Thus, based on the current results, we hypothesize that symptomatic SNP may be a late manifestation of COVID-19 infection.

A pathological study of the tongues of rabid dogs in the Philippines.

During rabies virus infections, the minor salivary glands are one of the important organs for virus replication and excretion into the oral cavity. However, details of pathological findings and viral antigen distribution in the minor salivary glands remain poorly understood. In this study, we conducted pathological tests on the tongues of 71 rabid dogs in the Philippines; the minor salivary glands (von Ebner's glands, lingual glands), circumvallate papilla, autonomic ganglia, and skeletal muscles were evaluated. Inflammatory changes were observed in the von Ebner's glands of 20/71 dogs, in the circumvallate papilla of 10/71, and in the tongue muscle of 1/71. Conversely, no morphological changes were observed in the lingual glands and autonomic ganglia. Viral antigens were detected via immunohistochemistry-based methods in the cytoplasm of the acinar epithelium in the von Ebner's glands of all 71 dogs. Virus particles were confirmed in the intercellular canaliculi and acinar lumen via electron microscopy. In the autonomic ganglia, viral antigens were detected in 67/71 rabid dogs. Viral antigens were detected in the taste buds of all 71 dogs, and were distributed mainly in type II and III taste bud cells. In tongue muscle fibers, viral antigens were detected in 11/71 dogs. No virus antigens were detected in lingual glands. These findings suggest that rabies virus descends in the tongue along the glossopharyngeal nerve after proliferation in the brain, and von Ebner's glands and taste buds are one of the portals of virus excretion into the saliva in rabid dogs.

Unilateral nasal obstruction induces degeneration of fungiform and circumvallate papillae in rats.

BACKGROUND: In clinical orthodontic treatment, chronic respiratory disturbance or mouth breathing has been concerned symptoms and screening criteria. In this study, to analyze the relation between nasal obstruction and taste sensing, a unilateral nasal obstruction model was performed to investigate the taste papillae and taste buds in rats. METHODS: Fourteen 6-day-old male Wistar rats were randomly divided into control and experimental groups (n = 7 each). The experimental group underwent unilateral nasal obstruction at 8 days of age. The rats were euthanized at 9-week-old. The morphology of the circumvallate papillae and taste buds were identified by immunohistochemical methods. The fungiform papillae were visualized with 1% methylene blue and sectioned for taste bud observation. RESULTS: Some defects in the gustatory epithelium were observed after unilateral nasal obstruction. Rats in the experimental group had significantly fewer fungiform papillae and smaller volumes of taste bud. In circumvallate papillae, smaller total taste bud area was found in experiment group. CONCLUSION: Findings in the present study suggest that nasal obstruction might have significant influences on the gustatory function via morphologic change in the taste papillae and taste buds in tongue area.

Reduced taste function and taste papillae density in children with chronic kidney disease.

BACKGROUND: Taste loss may contribute to the loss of appetite in children with chronic kidney disease (CKD) and other serious medical conditions that result in malnutrition. Traditional methods for measurement of taste loss commonly use aqueous tastant solutions that can induce nausea, vomiting, or even pain in the mouth. An alternative is to measure fungiform papillae density on the anterior tongue since this correlates with taste sensitivity. Here we aimed to develop a non-invasive method for assessing papillae density on the anterior tongue and to use the method to determine if CKD patients [estimated glomerular filtrate (eGFR < 60 ml/min/1.73 m(2))] have a lower density than clinical controls (CC)(eGFR > 89 ml/min/1.73 m(2)). METHODS: Thirty-five healthy adults participated in the development of a method, which was assessed by 24 children, 12 of whom were CKD patients and 12 were clinical controls. RESULTS: Similar papillae densities were found using invasive and non-invasive methods (F(1,34) = 0.647, p = 0.427). The CKD group had a significantly lower papillae density (X(2) = 7.17, p = 0.007) and poorer taste sensitivity than the CC group (p = 0.0272), and the density correlated significantly with eGFR (r = 0.56, p < 0.01). CONCLUSIONS: Loss of taste in children with CKD is due to the reduced number of papillae and their taste-sensing receptor cells.

Degeneration of fungiform and circumvallate papillae following molar extraction in rats.

OBJECTIVE: Proper occlusion facilitates food intake and gustatory function is indispensable for the enjoyment of food. Although an interaction between dentoalveolar and gustatory afferent neurons has been suggested by previous studies, the relationship between occlusion and gustation remains unclear. This study investigated the effect of upper molar extraction which diminished occlusal support on peripheral gustatory receptors in rats. MATERIALS AND METHODS: Thirty-six 7-week-old male Wistar rats were randomly assigned to either the experimental or the control group. All maxillary molars were extracted from rats in the experimental group under anesthesia, while a sham operation was conducted in the control group. The rats were euthanized 7, 14 or 28 days after the procedure. The morphology of the circumvallate papillae and taste buds using immunohistochemical methods and the fungiform papillae were visualized with 1% methylene blue. RESULTS: Defects in the gustatory epithelium were observed after maxillary molar extraction. Rats in the experimental group had significantly fewer fungiform papillae, narrower circumvallate papillae, shallower trench depth, smaller trench area, smaller taste bud area, lower ratios of taste bud area to trench area and fewer taste buds than those in the control group. CONCLUSIONS: The findings indicate that molar extraction would affect peripheral gustatory receptors. This is the first study to characterize changes in rat fungiform and circumvallate papillae after maxillary molar extraction. This study suggests a possible synergic relationship between dentoalveolar perception and gustatory function, which has clinical implications that occlusion is closely correlated with gustatory perception.

Standing gustatory papillae biopsy procedure for antemortem diagnosis of equine grass sickness.

OBJECTIVE: Diagnosing equine grass sickness (EGS) requires histopathological evidence of chromatolysis and/or neuronal loss in peripheral autonomic ganglia. Previous investigators performed postmortem biopsies of gustatory papillae located on the tongue and found chromatolytic subgemmal neurons in all 13 EGS horses. The present study aimed to design a standardized lingual biopsy sampling method through a transbuccal approach in healthy standing horses and assess the quality of the obtained samples, to allow antemortem diagnosis of EGS in clinical cases. ANIMALS: 6 healthy horses. METHODS: A transbuccal approach was performed bilaterally in 6 healthy standing horses. After having reached a deep level of sedation, horses were placed in stocks and a Günther mouth gag was inserted. Local anesthesia followed by a vertical full thickness incision was performed on both cheeks. Foliate papillae biopsies were carried out using an arthroscopic rongeur inserted through each incision site under oral endoscopic control. Tongue movements were restricted with diazepam. Histological assessment of taste buds and subgemmal plexi neurons was performed using H&E-stained longitudinal sections. RESULTS: The procedure was well tolerated in all horses. Minor complications observed were a transient facial paralysis, some incisional fluid collection, and abscesses. Ten samples (10/12) were suitable for assessment of neuronal perikarya. CLINICAL RELEVANCE: This procedure was safe for subgemmal plexus biopsy in healthy standing horses. The obtained samples were adequate as long as they were neatly cut lengthwise for inclusion. The technique was also used for 2 clinical cases and revealed the complete absence of neuronal perikarya, confirming chronic EGS.

New method for determining surface roughness of tongue.

OBJECTIVE: The degree of atrophy of the lingual papillae in elderly individuals was evaluated using a quantitative method. SUBJECTS AND METHODS: One hundred and eighty-two subjects living in nursing homes and 20 healthy adults as controls were studied. To express the degree of atrophy of the lingual papillae quantitatively, lingual surface roughness was determined by taking an impression with silicone dental material. Based on the impressions obtained from the elderly subjects, they were classified by three expert dentists into three groups: Normal, Smooth and Rough. The same determinations were also performed in the 20 healthy controls and compared with 38 of the elderly subjects who had agreement from all of the experts and without the presence of fissures (Normal, n = 6; Smooth, n = 12; Rough, n = 20). RESULTS: The roughness average value for the controls was 65.0 µm, while that for the elderly subjects in the Normal, Smooth and Rough groups was 73.9 µm, 42.2 µm and 94.1 µm, respectively, which were significantly different. CONCLUSION: The present results indicate that the present technique of obtaining an impression of the tongue surface is simple and reliable for routine evaluation and quantification of the degree of atrophy as well as morphology of the lingual papillae.

Orofacial and systemic manifestations in 212 paediatric HIV patients from Chennai, South India.

BACKGROUND: Lesions in the mouth and in other tissues and organs (oral and systemic lesions) in paediatric HIV infection are diverse and show differences in clinical presentation and severity from that of adults. Very little data exist for oral lesions in paediatric population in India. AIM: To document and study oral and more widespread lesions in paediatric HIV seropositive patients. DESIGN: A cross-sectional study. SETTING: Paediatric HIV seropositive patients at tertiary centers: Ragas Dental College and Hospital and YRG CARE, Chennai, India. PATIENTS AND METHODS: Two hundred and twelve paediatric HIV patients aged 0-14 years seen over a period of 1 year were included in the study. Clinical history, oral and systemic examinations were recorded by qualified dental surgeons and physicians. RESULTS: One hundred and thirty-two patients had oral lesions ranging in number from one to three. Oral lesions included oral candidiasis (OC) (56.1%), gingivitis (10.8%), oral pigmentation (6.1%), depapillation of the tongue (5.7%), ulcers (4.2%), and oral hairy leukoplakia (1.4%). The most common systemic lesion observed was nonspecific lymphadenopathy (74.1%) followed by pruritic eruptions (53.8%), measles (51.4%), and tuberculosis (TB) (49.1%). Thirty-three (26%) patients were not immunosuppressed, 74 (58%) were moderately immunosuppressed, and 20 (15%) were severely immunosuppressed. Oral lesions exhibited positive correlation with lesions in other parts of the body. CONCLUSION: Oral lesions are a common feature in paediatric HIV infection. Their management is vital to improve the quality of life of the infected children.

Simplifying the assessment of the recovery from surgical injury to the lingual nerve.

OBJECTIVE: To determine the sensitivity of conventional sensory assessment in monitoring lingual nerve recovery subsequent to third molar surgery and to evaluate if the assessment methods can be predictive of injury outcome. METHOD: A prospective case series of 94 patients presenting with lingual nerve injuries evaluated using objective mechanosensory and subjective methods during the recovery period of up to 12 months. RESULTS: The conventional tests were often unable to diagnose the presence of injury due to variability and they were not predictive of outcome. As a result of this study, we are able to identify patients more likely to have permanent rather than temporary lingual nerve injury at four to eight weeks post injury, using patient reported subjective function. The subjective function test also minimises the requirements for specialist training or equipment providing an ideal method for general dental practice. CONCLUSIONS: The development of these simple subjective tests may enable us to identify which patients are at risk of permanent lingual nerve injuries in the early post injury phase, thus allowing expeditious therapy when indicated.

Trigeminal small-fiber sensory neuropathy causes burning mouth syndrome.

Burning mouth syndrome is a common disorder that frequently affects women in the 5th-7th decade. It is characterized by persisting painful symptoms mainly involving the anterior two-thirds of the tongue. For several years it has been attributed to psychological causes. We investigated the innervation of the epithelium of the tongue to assess whether damage of peripheral nerve fibers underlies the pathogenesis of the disease. We examined 12 patients with clinically definite burning mouth syndrome for at least 6 months. We obtained superficial biopsies of the lateral aspect of the anterior two-thirds of the tongue from all patients and nine healthy controls. Immunohistochemical and confocal microscope co-localization studies were performed with cytoplasmatic, cytoskeletric, Schwann cell, and myelin markers for pathological changes. The density of epithelial nerve fibers was quantified. Patients showed a significantly lower density of epithelial nerve fibers than controls, with a trend toward correlation with the duration of symptoms. Epithelial and sub-papillary nerve fibers showed diffuse morphological changes reflecting axonal degeneration. Our study demonstrates that burning mouth syndrome is caused by a trigeminal small-fiber sensory neuropathy and that superficial biopsy of the tongue can be helpful in assessing the diagnosis. These findings shed light into the pathogenesis of this common disorder and could contribute to evaluate targeted therapies in patients.

The role of sensory input of the chorda tympani nerve and the number of fungiform papillae in burning mouth syndrome.

OBJECTIVE: The aim of this study was to evaluate patients suffering from burning mouth syndrome (BMS) and control subjects by means of sensory testing and fungiform papillae count. STUDY DESIGN: The left and right anterior two-thirds of the tongue of of 25 BMS subjects and 20 healthy control subjects were evaluated for electric taste and electric detection threshold. The number of fungiform papillae/cm(2) was evaluated by using close-up digital photography. RESULTS: The electric taste/tingling detection threshold ratio was significantly higher in BMS compared with control subjects (P = .041). No difference was found between the number of fungiform papillae/cm(2) in the BMS compared with the control subjects (P = .277). Patients suffering from BMS for a prolonged period of time presented with a significantly elevated electric taste/tingling detection threshold ratio (P = .031). CONCLUSIONS: BMS may be a neurodegenerative process with chorda tympani nerve hypofunction potentially playing a role in the pathophysiology of this disorder.

Atrophic change of tongue papilla in 44 patients with Sjögren syndrome.

OBJECTIVE: The purpose of this study was to investigate the atrophic change of tongue papilla in Sjögren syndrome (SjS) patients and the correlation with characteristic features of the disease. STUDY DESIGN: Atrophic change of tongue papilla, investigated by a digital microscope, was classified from score 0 (normal) to score 6 (severe) and compared among 44 SjS patients, 20 xerostomia patients, and 20 healthy subjects. In SjS patients, correlation of the atrophic score of tongue papilla with characteristic changes in sialometry, sialography, lip biopsy, and serologic tests was also investigated. RESULTS: The atrophic score of tongue papilla was significantly higher in SjS patients and correlated with the decrease of salivary secretion, the stage on sialography, and the histologic grade of the minor salivary gland. CONCLUSION: Atrophic change of tongue papilla is significant in SjS patients and is correlated with the characteristic features of the disease.

The effects of sialoadenectomy and exogenous EGF on taste bud morphology and maintenance.

Taste buds on the dorsal tongue surface are continually bathed in saliva rich in epidermal growth factor (EGF). In the following experiment, taste bud number and morphology were monitored following submandibular and sublingual salivary gland removal (sialoadenectomy), to determine if EGF plays a role in the maintenance and formation of taste buds. Adult male rats were divided into four groups: sialoadenectomized (SX, n = 4); sialoadenectomized with EGF replacement (SX + EGF, n = 5); sham-operated (SH, n = 4); and sham-operated with exogenous EGF (SH + EGF, n = 5). After a 3 week recovery, SX + EGF and SH + EGF animals were given 50 microg/day EGF in their drinking water for 14 days. At day 14, saliva was collected, the animals were killed and the presence of EGF determined by radioligand-binding assay. Tongues were removed and histologically examined for the presence and morphology of taste buds on fungiform and circumvallate papillae, or immunostained for the presence of EGF, TGFalpha (transforming growth factor alpha) and EGFR (EGF receptor). The removal of submandibular and sublingual salivary glands resulted in the loss of fungiform taste buds and normal fungiform papillae morphology. These effects were reversed by EGF supplementation, indicating a role for EGF in fungiform taste bud maintenance. In addition, supplementation of EGF to sham-operated animals increased the size of fungiform taste buds. In contrast, removal of salivary glands had no effect on the size, numbers, or morphology of circumvallate taste buds, suggesting that the formation and maintenance of taste buds in fungiform and circumvallate papillae may involve different and distinct processes. EGF, TGFalpha and EGFR were localized to distinct layers of the dorsal epithelium and to within both fungiform and circumvallate taste buds. Their expression within the epithelium or taste buds was not altered with sialoadenectomy, indicating that the actions of endogenous EGF and TGFalpha are distinct and not regulated by exogenous EGF and TGFalpha supplied in saliva.

[Contact endoscopic quantification of fungiform papillae--correlation to taste ability?]. / Kontaktendoskopische Quantifizierung der fungiformen Papillen--Korrelation zum Schmeckvermögen?

BACKGROUND: Besides anamnestic data and taste test, the clarification of epithelial taste disorders makes macroscopic evaluation of the surface of the tongue necessary. METHODS: In this article the contact endoscopy is evaluated for examination of the tongue epithelium and for quantification of the fungiforme papillae. These results are related to the results of the spatial taste test (1. chemical taste test with sodium chloride in 2 different suprathreshold concentrations and sucrose in also 2 different suprathreshold concentrations; 2. electrogustometry with a bipolar electrode). PATIENTS: In a prospective study we performed contact endoscopy in 16 healthy volunteers from ages 7 to 68 years. The subjects were divided into 2 age groups (< or = 45 years and > 45 years) and 2 papillae density groups. In 34 patients with either taste disorders of unknown cause or in patients with macroscopic changes at the tongue surface, the spatial and whole mouth taste tests and contact endoscopy were used to clarify the cause of the complaints. RESULTS: Density and shape of the fungiform papillae as well as the shape of the subepithelial vessels of the papillae vary among the investigated human subjects in the different age groups. No correlation between intensity ratings, papillae density und age was found after stimulation with 40 % sucrose at the tongue tip in the younger age group. Stimulation of the tongue edge with 15 % sodium chloride, however, showed a relationship between the two different density groups and the different age groups. CONCLUSIONS: The contact endoscopy allows the evaluation of the epithelium in the oral cavity. It is a nondestructive method and is additionally easy to handle, but the evaluation of the observed epithelia needs interdisciplinary co-operation with pathologists. No relevant informations are supplied in diagnostics of taste disorders.