Combining In Vivo Corneal Confocal Microscopy With Deep Learning-Based Analysis Reveals Sensory Nerve Fiber Loss in Acute Simian Immunodeficiency Virus Infection.

PURPOSE: To characterize corneal subbasal nerve plexus features of normal and simian immunodeficiency virus (SIV)-infected macaques by combining in vivo corneal confocal microscopy (IVCM) with automated assessments using deep learning-based methods customized for macaques. METHODS: IVCM images were collected from both male and female age-matched rhesus and pigtailed macaques housed at the Johns Hopkins University breeding colony using the Heidelberg HRTIII with Rostock Corneal Module. We also obtained repeat IVCM images of 12 SIV-infected animals including preinfection and 10-day post-SIV infection time points. All IVCM images were analyzed using a deep convolutional neural network architecture developed specifically for macaque studies. RESULTS: Deep learning-based segmentation of subbasal nerves in IVCM images from macaques demonstrated that corneal nerve fiber length and fractal dimension measurements did not differ between species, but pigtailed macaques had significantly higher baseline corneal nerve fiber tortuosity than rhesus macaques (P = 0.005). Neither sex nor age of macaques was associated with differences in any of the assessed corneal subbasal nerve parameters. In the SIV/macaque model of human immunodeficiency virus, acute SIV infection induced significant decreases in both corneal nerve fiber length and fractal dimension (P = 0.01 and P = 0.008, respectively). CONCLUSIONS: The combination of IVCM and robust objective deep learning analysis is a powerful tool to track sensory nerve damage, enabling early detection of neuropathy. Adapting deep learning analyses to clinical corneal nerve assessments will improve monitoring of small sensory nerve fiber damage in numerous clinical settings including human immunodeficiency virus.

[Ocular manifestations of viral diseases]. / Atteintes ophtalmologiques des infections virales.

Viral infections may involve all ocular tissues and may have short and long-term sight-threatening consequences. Among them, ocular infections caused by herpesviruses are the most frequent. HSV-1 keratitis and kerato-uveitis affect approximately are the leading cause of infectious blindness in the Western world, mainly because of corneal opacification caused by recurrences. For this reason, they may warrant long-term antiviral prophylaxis. Herpes zoster ophthalmicus, accounts for 10 to 20% of all shingles locations and can be associated with severe ocular involvement (keratitis, kerato-uveitis) of which a quarter becomes chronic/recurrent. Post herpetic neuralgias in the trigeminal territory can be particularly debilitating. Necrotizing retinitis caused by herpesviruses (HSV, VZV, CMV) are seldom, but must be considered as absolute visual emergencies, requiring urgent intravenous and intravitreal antiviral treatment. Clinical pictures depend on the immune status of the host. Adenovirus are the most frequent cause of infectious conjunctivitis. These most often benign infections are highly contagious and may be complicated by visually disabling corneal lesions that may last over months or years. Some arboviruses may be associated with inflammatory ocular manifestations. Among them, congenital Zika infections may cause macular or optic atrophy. Conjunctivitis is frequent during the acute phase of Ebola virus disease. Up to 15% of survivors present with severe chronic inflammatory ocular conditions caused by viral persistence in uveal tissues. Finally, COVID-19-associated conjunctivitis can precede systemic disease, or even be the unique manifestation of the disease. Utmost caution must be taken because of viral shedding in tears.

Colony Stimulating Factor-1 Receptor Expressing Cells Infiltrating the Cornea Control Corneal Nerve Degeneration in Response to HSV-1 Infection.

Purpose: Herpes simplex virus type-1 (HSV-1) is a leading cause of neurotrophic keratitis, characterized by decreased or absent corneal sensation due to damage to the sensory corneal innervation. We previously reported the elicited immune response to infection contributes to the mechanism of corneal nerve regression/damage during acute HSV-1 infection. Our aim is to further establish the involvement of infiltrated macrophages in the mechanism of nerve loss upon infection. Methods: Macrophage Fas-Induced Apoptosis (MAFIA) transgenic C57BL/6 mice were systemically treated with AP20187 dimerizer or vehicle (VEH), and their corneas, lymph nodes, and blood were assessed for CD45+CD11b+GFP+ cell depletion by flow cytometry (FC). Mice were ocularly infected with HSV-1 or left uninfected. At 2, 4, and/or 6 days post infection (PI), corneas were assessed for sensitivity and harvested for FC, nerve structure by immunohistochemistry, viral content by plaque assay, soluble factor content by suspension array, and activation of signaling pathways by Western blot analysis. C57BL6 mice were used to compare to the MAFIA mouse model. Results: MAFIA mice treated with AP20187 had efficient depletion of CD45+CD11b+GFP+ cells in the tissues analyzed. The reduction of CD45+CD11b+GFP+ cells recruited to the infected corneas of AP20187-treated mice correlated with preservation of corneal nerve structure and function, decreased protein concentration of inflammatory cytokines, and decreased STAT3 activation despite no changes in viral content in the cornea compared to VEH-treated animals. Conclusions: Our results suggest infiltrated macrophages are early effectors in the nerve regression following HSV-1 infection. We propose the neurodegeneration mechanism involves macrophages, local up-regulation of IL-6, and activation of STAT3.

Herpes Zoster Involving the Second Division of the Trigeminal Nerve: Case Report and Literature Review.

Herpes zoster along the maxillary division of the trigeminal nerve is a rare condition that is caused by reactivation of the varicella zoster virus that resides within the trigeminal ganglion after the primary infection of chickenpox. The disease may be manifested as a toothache during its prodromal stage. The active stage of the disease is characterized by the appearance of a vesicular rash. Postherpetic neuralgia is a common complication of herpes zoster after resolution of the facial and intraoral symptoms. There is increasing evidence for herpes zoster patients to develop stroke later in life. The present case reports the development of herpes zoster maxillaris in a 71-year-old man whose maxillary right canine was diagnosed as pulpal necrosis and symptomatic apical periodontitis and was subsequently treated endodontically by cleaning and shaping and filling the canal space with gutta-percha and an epoxy resin-based sealer. The patient presented 3 days later with midfacial ulceration, desquamation, and crusting as well as intraoral ulceration along the course of the V2 dermatome. After successful treatment with antiviral medication, postherpetic neuralgia developed within the next 2 months. Complete resolution of the neuralgia occurred at the 4-month recall with negligible facial scarring. Herpes zoster may mimic odontogenic pain during the prodromal stage of the disease. Reactivation of the virus has also been implicated in the pathogenesis of pulpal pathoses. These paradoxical facets are of interest to the endodontist and should be considered in the differential diagnosis of the disease.

Zóster com comprometimento do nervo trigêmeo: relato de caso / Zoster with Trigeminal Nerve Damage: Case Report

Zóster é uma doença viral pelo qual o mecanismo de reativação, ainda é pouco compreendido. Entretanto, parece estar relacionado com algum tipo de deficiência na imunidade, além do estresse também ser apontado como fator desencadeante. O diagnóstico, na maioria das vezes, é eminentemente clínico, usualmente determinado por lesões vesículobolhosas que envolvem a pele ao longo do trajeto do nervo branquial. O objetivo desse trabalho é relatar um caso clínico de uma paciente, 21 anos de idade, diagnosticada com zóster e comprometimento do nervo trigêmeo, nos ramos oftálmico, maxilar e mandibular. Verificouse aumento de volume em região de terços médio e inferior da face esquerda, edema palpebral, linfadenopatia em região submandibular, lesões cutâneas vesículo-bolhosas em região periorbital, massetérica, geniana e submandibular. As lesões não ultrapassavam a linha média da face. Após o tratamento a paciente não apresentou sequelas. Salientase a necessidade do conhecimento dessas lesões por parte do cirurgião dentista, a fim de estabelecer diagnóstico e tratamento imediato, para minimizar sintomatologia e acompanhamento da neuralgia pós-zóster... (AU)

Zoster is a viral disease in which the reactivation mechanism is poorly understood. However, it seems to be related to an immunity disability, in addition to stress, which is also be appointed as a triggering factor. The diagnosis, in most cases, is eminently clinical, usually determined by vesicle-bullous lesions involving the skin over the brachial nerve pathway. The aim of this study is to report a case of a 21-year-old patient, diagnosed with zoster, with commitment of the trigeminal nerve comprehending the ophthalmic, maxillary and mandibular branches. There was tissue growth in medium-third region and the lower left cheek, eyelid edema, lymphadenopathy in the submandibular region, vesicle-bullous skin lesions in the periorbital, masseteric, genian and submandibular regions. The injury did not exceed the midline of the face. After treatment the patient had no sequelae. It is emphasized the need of understanding these lesions by the dental surgeon, in order to establish diagnosis and the due immediate treatment in order to reduce the symptoms and the follow up of post-zoster neuralgia... (AU)

Atypical Presentation of Zoster Mimicking Headache and Temporomandibular Disorder: A Case Report.

Herpes zoster in the prodromal stage may be mistaken for other diseases characterized by pain in the area of prodrome, such as dental pain. We report on a case of trigeminal herpes zoster, which presented as sudden onset headache and acute temporomandibular pain in the prodromal phase.

Trigeminal herpes zoster complicated by Ramsay Hunt syndrome.

We report the case of a 55-year-old woman with herpes zoster of the mandibular branch of the left trigeminal nerve, which was complicated within 4 days by ipsilateral Ramsay Hunt syndrome. Recently, a case of trigeminal herpes zoster and Ramsay Hunt syndrome was described, in which the MRI and CSF findings along with the clinical course urged the authors to suggest the possibility of transaxonal spread of the virus. In our case, the findings and particularly the temporal relation between the 2 conditions render more plausible other pathophysiological mechanisms, such as the spread of the virus through the CSF.

Rare involvement of herpes zoster in the mandibular branch of the trigeminal nerve: A case report and review of the literature.

Herpes zoster (HZ) infections rarely affect the mandibular branches of the trigeminal nerve. When the mandibular branches are involved, lesions may appear on the face, in the mouth, in the eye, or on the tongue. Additionally, this condition may be associated with devitalized teeth, internal resorption and spontaneous exfoliation of the teeth, and osteomyelitis of the alveolar bone. In this paper, the treatment of a case HZ of the mandibular branch of the trigeminal nerve is reported, and 22 articles on HZ cases with involvement of the mandibular branch are reviewed. This is the first literature review of HZ cases involving only the mandibular branch of the trigeminal nerve.

Nerve afflictions of maxillofacial region: a report of two cases.

Neurological disorders and conditions affecting the maxillofacial region result in disabilities that affect an individual's functioning. Sensory or motor disturbances of the nerves may be caused by trauma, infections, pressure effect or infiltration by tumours or other health conditions. Two rare cases of nerve afflictions are described here with their typical clinical features. The first case had an involvement of maxillary, mandibular and ophthalmic divisions of the trigeminal nerve (sensory) due to herpes zoster infection in a very young patient and the second case had a unilateral isolated hypoglossal nerve palsy (motor) secondary to infiltration of the nerve by carcinoma of pyriform fossa.

Maxillary osteonecrosis and spontaneous teeth exfoliation following herpes zoster.

BACKGROUND: Reports of osteonecrosis and spontaneous tooth loss following herpes zoster infection of the fifth cranial are extremely rare. Only 39 previously recorded cases of post-zoster osteonecrosis have been found in the literature. The unusual feature of the case of interest to the dental surgeon is a rare complication of tooth exfoliation and maxillary osteonecrosis. CASE REPORT: This article reports a case of 52-year-old man with herpes zoster infection of the trigeminal nerve and related alveolar bone necrosis and teeth loss. The etiology and management of herpes zoster infection associated with destructive sequelae are discussed. DISCUSSION: Very few cases of osteonecrosis and spontaneous teeth exfoliation secondary to herpes zoster are found in the literature. The exact mechanism by which herpes zoster induces these destructive changes in the alveolar bone and teeth cannot be proposed. As Varicella zoster virus is an aneurotropic virus, the possible provoking factors may be the infection of the nerves innervating the periosteum or the chronic inflammatory changes in the form of adverse periodontal disease and delayed healing of the extraction sockets associated with compromised host resistance.

Ramsay Hunt syndrome with unilateral polyneuropathy involving cranial nerves V, VII, VIII, and XII in a diabetic patient.

Ramsay Hunt syndrome is a rare complication of the varicella zoster virus, defined as a peripheral facial palsy that typically results from involvement of the facial and auditory nerves. Ramsay Hunt syndrome can be associated with cranial nerves V, VI, IX, and X but rarely with XII. We describe an atypical case of Ramsay Hunt syndrome with multiple cranial nerve involvement of nerves V, VII, VIII, and XII. Antiviral drugs, antibiotics, insulin, and traditional Chinese drugs were administered immediately after admission. After 3 months of combination therapy, the patient had recovered satisfactorily. Herpes zoster can cause severe infections in diabetic patients and should be treated as soon after detection as possible. Ramsay Hunt syndrome should be recognized as a polycranial neuritis characterized by damage to sensory and motor nerves. In addition to facial and vestibular nerve paralysis, Ramsay Hunt syndrome may also involve cranial nerves V and XII.

A case of zoster sine herpete of the trigeminal nerve.

Varicella-zoster virus reactivation causes zoster (shingles), a syndrome characterized by severe pain and a vesicular rash. The present report details a case of varicella-zoster virus reactivation of the maxillary and mandibular division of the right trigeminal nerve without evidence of vesicular rash (zoster sine herpete). It is difficult to identify owing to no typical clinical signs such as vesicular eruption. Zoster sine herpete of the trigeminal nerve, in particular, is rarely reported. In this case, the diagnosis was based on clinical findings and was supported by the demonstration of an immunoglobulin G antibody. Zoster sine herpete of the trigeminal nerve, in particular, should be considered in patients with severe facial pain over specific dermatomes, if they do not demonstrate appreciable findings of traumatic neuropathy, tumor or herpes zoster.

Gustatory dysfunction after mandibular zoster.

Varicella zoster, limited to the mandibular nerve, is rare. Classical symptoms are pain, hypesthesia and vesicular eruption restricted to the third trigeminal segment (V3). Little is known on taste affection after mandibular nerve zoster. We report two cases of patients suffering from mandibular zoster associated with subjective taste disorder. In both cases, gustatory measures confirmed ipsilateral hemiageusia of the anterior two-thirds of the tongue. After 2 months, the symptoms regressed and psychophysical measures came back to normal values, whereas post-zoster neuralgia lasted for more than 1 year. Gustatory dysfunction is a possible symptom after mandibular nerve zoster. In contrast to post-zoster neuralgia, taste function seems to recover quickly.

Herpes zoster with progression to acute varicella zoster virus-meningoencephalitis.

BACKGROUND: Acute meningoencephalitis (ME) from varicella zoster virus (VZV) reactivation is a rare and serious complication of herpes zoster (HZ). OBJECTIVES AND METHODS: As early diagnostic detection is mandatory to prevent long-term sequelae, any clinical indication is helpful to identify patients that are at higher risk of the development of VZV-ME. In order to find such risk factors, the clinical data of 38 patients consecutively hospitalized for the treatment of HZ over a 1-year period were analyzed. RESULTS: Four of the 38 patients with HZ developed ME. Of these, three had involvement of the trigeminal nerve branch, one including an ophthalmic affection, and one presented with disseminated HZ. All were women with an average age of 83.5 years, in comparison with patients with HZ but without ME who had an average age of 69.3 years and a female preponderance of 60%. The first clinical signs of ME were rapidly progressing somnolence and meningism. Patients with HZ-ME were treated with intravenous acyclovir, oral glucocorticosteroids, and antiseizure therapy, and recovered almost completely without major residual symptoms. CONCLUSION: Progression of HZ to ME seems to occur more often than normally believed. Female patients above 80 years of age with either ophthalmic involvement or disseminated HZ are at a potentially high risk of the development of ME. The general recommendation of starting oral glucocorticosteroids from day 1 of antiviral treatment in older patients must be questioned, as it may stimulate VZV replication and dissemination.

Pseudozoster clinical presentation of Demodex infestation after prolonged topical steroid use.

A 60-year-old man presented with a plaque lesion on the upper right half of the face, which had developed after ophthalmic varicella zoster infection about 2 years previously. The lesion, which was burning and itchy, included a few tiny erythematous pustules, and was slightly squamous and infiltrated. The lesion covered the upper two-thirds of the right trigeminal nerve dermatome, involving half of the face with the forehead, the periorbital area, upper part of the cheek and the nose. The lesion became more marked after continuous topical anaesthetic and corticosteroid use. A standardized skin-surface biopsy was taken, and revealed a large number of Demodex folliculorum (38/cm(2)) in the lesion area. The lesions completely abated after topical 5% permethrin treatment, and no recurrence was observed during follow-up. Demodicosis may have atypical clinical presentations, other than the well-known classic forms. To our knowledge, this is the first unilateral trigeminal, pseudozoster presentation in the literature.