A Case Report of Herpes Zoster of the Trigeminal Ganglion after Coronavirus 2019 Vaccination in a 22-year-Old Male

Introduction. Herpes zoster is an acute viral syndrome caused by the reactivation of latent varicella-zoster virus from a previous infection. It is characterized by a painful, unilateral vesicular rash which is distributed over the territory of a dermatome. It is a significant global burden with the incidence very common in the Asia Pacific region. The frequency is closely related with increasing age and is the most common risk factor for reactivation of varicella-zoster virus. Herpes zoster does not often appear after administration of vaccination. But in the advent of increasing vaccinations for COVID-19, there have been reports of herpes zoster following COVID-19 vaccination. Case: This is a case of a 22-year-old healthy male with a previous history of varicella-zoster virus infection during childhood who developed headache, unilateral vesicular rash over the territory of the left trigeminal nerve and left-sided facial pain and numbness. The patient had previously received the COVID-19 vaccine four days prior to the onset of symptoms. The diagnosis of herpes zoster was made on clinical grounds with no need for additional laboratory work-up to confirm the diagnosis. The patient was treated with herpes zoster antiviral therapy and analgesics where improvement of the patient's condition was noted with eventual crusting of the lesions and without development of complications. Conclusion(s): Herpes zoster is a common disease with a benign course in immunocompetent adults. There is a need for further studies to identify risk factors and explain the possible relationship between COVID-19 vaccination and the development of herpes zoster. Due to the increasing COVID-19 vaccination of the population worldwide, there is a possibility of an increase in the number of herpes zoster cases following COVID-19 vaccination.Copyright © 2022, Philippine College of Physicians. All rights reserved.

Clinical and Cytopathological Traits of Herpes Zoster: A Report of Two Cases

Introduction: Varicella zoster virus is a highly infectious alpha-herpesvirus, pathogenic only to humans. The primary infection of varicella zoster virus causes chickenpox, which is contagious and primarily infects children and adolescents in India. Following the primary infection, the virus remains dormant in sensory root ganglia. Activation of the dormant virus in later stages of life causes herpes zoster infection which may vary from subclinical infection to typical zoster, scattered vesicles, zoster sine herpete or disseminated zoster, which depends on the individual's immune status. Case report: In this case series, we present two patients with herpes zoster involving the mandibular branch of the trigeminal nerve. Cytology revealed characteristic features of the infection including nuclear moulding, multinucleated giant cells and ballooning degeneration. Conclusion(s): More recently, patients presenting with herpes zoster have been reported to have sub-clinical Covid-19 infection, suggesting a possibility that herpes zoster might be an indicator for latent Covid-19. Timely detection and treatment of this infection can reduce the risk of post herpetic neuralgia.Copyright © 2022 Sciendo. All rights reserved.

Transcutaneous Electrical Cranial-Auricular Stimulation (Tecas) for Treatment of Insomnia Disorder with Comorbid Major Depressive Disorder: A Case Series: E-Poster Viewing

Introduction: Insomnia disorder (ID) and major depressive disorder (MDD) are highly comorbid, above 80% of MDD patients have insomnia disorder. Acupuncture as a major complementary and alternative medicine (CAM) therapy, is utilized extensively in Asia to treat mental health disorders.Transcutaneous electrical cranial-auricular stimulation (TECAS) is a potential new type of acupuncture treatment for MDD and ID which combines the scalp points and auricular points most commonly used by acupuncturists. It has the advantages of portability, quantifiable stimulation parameters and comfort, especially for home treatment under the normal situation of COVID-19, which can avoid the risk of infection due to frequent hospital trips. Materials / Methods: 10 ID-MDD patients were treated by TECAS which was administered at the bilateral auricular acupoints, Bai Hui (GV-20) and Yin Tang (GV-29) (waveform:4/20 Hz, wave width: 0.2ms+/-30%) for twice a day last 8 weeks. Pittsburgh Sleep Quality Index (PSQI) and Hamilton Depression Rating Scale(HAMD) of ID-MDD patients were evaluated before and after treatment. Result(s): HAMD-17 scores of 10 patients were lower at 4 and 8 weeks than before TECAS treatment, and the reduction was greater at 4 weeks than at 8 weeks. PSQI scores of 8 patients decreased at 4 and 8 weeks compared with before treatment, and the decrease was greater in the fourth week than in the 8th week. Insomnia of 2 patients improved at 4 weeks of treatment, but became worse in the 8th week as before treatment.7 out of 10 patients showed full insomnia response (50% reduction in PSQI) and 8 patients showed full depression response (50% reduction in HAMD-17 scores). Discussion(s): We suggest TECAS is a good therapeutic strategy to modulate the vagus nerve and trigeminal nerve propagate through electrical stimulation projected by neurons from peripheral sites to the central nervous system. Furthermore, we speculate that TECAS can make the trigeminal nerve afferent fibers and vagus nerve auricular branch carry messages from head facial stimulation to NTS, locus coeruleus, raphe nucleus, medullary reticular activating system and structure of the thalamus, and then to feel, edge, cortical and subcortical structures, so the electrical stimulation subcortical can cause direct regulation, namely the change of cortical excitability. Conclusion(s): These preliminary results in this group of CID-MDD patients are encouraging and need to be replicated in prospective sham-controlled studies with larger sample sizes. In addition, for patients with insomnia and depression, it is important to consider combining TECAS with psychotherapy to avoid the interference of acute negative emergency events. Acknowledgements: The support of National Key R&D Program of China (No.2018YFC1705800) and Key Laboratory of Acupuncture and Chronobiology of Sichuan Province(No.2021004) for this project is gratefully acknowledged. Learning Objectives: 1. To provide a new non-drug method for acupuncture treatment of insomnia and depression;2. Provide preliminary experimental results for the large-sample experimental design of TECAS for the treatment of insomnia and depression;3. Compared with previous studies on insomnia and depression, the regularity and characteristics of TECAS in treating insomnia and depression were found. Keywords: Transcutaneous Electrical Cranial-Auricular Stimulation (TECAS), insomnia disorder, a case series, acupuncture, Major Depressive Disorder Copyright © 2022

Probable pathways of SARS-CoV-2 to central nervous system

Various reported cases related to the COVID-19 pandemic since 2019 has shown that SARS-CoV-2 directly or indirectly affects the nervous system besides the upper respiratory tract (Whittaker et al. 2020). SARS-CoV-2 is a zoonotic strain of coronavirus with various structural proteins. It is reported that spike protein, which is one of its structural proteins, can bind to or interact with Neuropilin-1, CD147 (Basigin), KREMEN1, ASGR1 (Asialoglycoprotein Receptor), Furin, LRP1 (Lipoprotein Receptor-Related Protein 1) and Ephrin receptors as well as ACE-2 (Angiotensin Converting Enzyme-2) and TMPRSS2 (Transmembrane Serine Protease 2) receptors. The related studies suggest that these possible receptors in the target of SARS-CoV- 2 cooperate with ACE-2, hence make the central nervous system an open target for the virus (Zalpoor et al. 2022). The first possible route of SARS-CoV-2 is seen as the route from the olfactory epithelium to its bulb via the trigeminal nerve (CN V) and olfactory nerve (CN I) pathway. Additionally, the virus entering the bloodstream can reach the Blood Brain Barier, cross the barrier and spread to neurons through the oligodendrocyte in a process called “Trojen horse”. Lastly, another route considered focuses on the vagal nerves of the enteric system associated with the central nervous system (Guadarrama-Ortiz et al. 2020). This literature review focuses on possible entry routes of SARS-CoV-2 into the nervous system. In this context, a route has been established based on the receptors in the nervous system cells, which are reported to be the target of SARS-CoV-2, based on the studies.

Unboxing herpes zoster ophthalmicus and the recombinant shingles vaccine

Reactivation of the varicella zoster virus as herpes zoster (shingles) typically affects the peripheral nerves, resulting in a painful rash, most often on the torso. However, it can also manifest ophthalmologically, affecting the ophthalmic division of the trigeminal nerve. This manifestation is associated with a particularly high level of morbidity and may result in blindness. A new recombinant shingles herpes zoster vaccine protects patients against this virus and post-infection sequelae, improving medical and psychosocial outcomes. © 2021 Medicine Today Pty Ltd. All rights reserved.

COVID-19 associated multiple cranial neuropathies

The polymorphism of the clinical manifestations of coronavirus infection often creates great diagnostic difficulties for the practitioners, especially in patients with a predominance of neurological symptoms. Of the latter, cranial neuropathies take a particular place, as they may be either one of the first symptoms or appear during the disease progression. Impairment of smell and taste is considered an early manifestation of SARS-CoV-2 infection. Similar to the involvement of the olfactory bulb, multiple cranial nerves involvement (for example, VII, VI, and III) has been described. Patients with COVID-19 associated multiple cranial neuropathies are more likely to experience partial recovery of impaired function. We present and discuss a rare case of COVID-19 associated multiple cranial neuropathies with a sequential involvement of the olfactory (I), right visual (II), frontal branch of the trigeminal (V), facial (VII), and hypoglossal (XII) nerves. Data on clinical manifestations and diagnostic criteria for this form of pathology are presented.

Epochs Of Sternutation Induced By Coronavirus 19

Objective: To understand that COVID-19 can cause epochs of sneezing. Background: While Coronavirus 19 has been reported to inhibit sternutation (Mattu, 2021), Coronavirus-induced epochs of sternutation has not henceforth been described. Case Study: 38-year-old right-handed nasute woman, seven months prior to presentation, experienced an acute onset of loss of smell and taste, with a positive nasopharyngeal swab for SARS COV-2. Since then there has been no improvement in her chemosensory complaints and has developed periods of sternutation, whereby she sneezes 18 times in a row every morning. Results: Abnormalities of physical examination: Neurological Examination: Motor Examination: Drift testing: Left pronator drift with left abductor digiti minimi sign. Cerebellar examination: dysmetria in both upper extremities, left more than right. High frequency low amplitude tremor on extension of both upper extremities. Reflexes: 3+ biceps and brachioradialis and absent ankle jerks bilaterally. Bilateral Hoffman reflexes. Chemosensory testing: Alcohol Sniff Test: 0 (anosmia). Olfactory Retronasal Smell Test Index: 0 (anosmia). Gustatory testing: Propylthioruacil Disk Taste Test: 0 (ageusia). Conclusions: The neuroanatomy of the sneeze reflex suggests that it occurs through the afferent pathway from the trigeminal nerve to the rostral dorsolateral medullary sneezing center where the efferent discharge of the autonomic nervous system occurs through the nervous intermedius to the greater superficial petrosal nerve and to the sphenopalatine ganglion. In any of these afferent or efferent pathways or in the central nervous system itself, COVID may have acted to cause intermittent irritation and thus epochs of sneezing (Songu, 2009;Herman, 1983). The common experience of sneezing occurring in threes may be centrally mediated and this occurred with eighteen sneezes may just be a prolonged variant of such a chronobiological reflex. In those who present with COVID-19, query as to epochs of sternutation may be revealing.

COVID-19 can cause blink reflex abnormalities.

Background and purpose: Neurological symptoms and complications associated with coronavirus 2019 (COVID-19) are well known. It was aimed to evaluate the brainstem and trigeminal/facial nerves and the pathways between these structures in COVID-19 using the blink reflex test. Methods: Thirty patients with post COVID-19 (16 males, 14 females) and 30 healthy individuals (17 males, 13 females) were included in this prospective study. Individuals who previously had a positive nose swap polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 and whose previously clinical features were compatible with COVID-19 were included in the post COVID-19 patient group. Neurological examination of the participants should be normal. Blink reflex test was performed on all participants. R1, ipsilateral R2 (IR2), and contralateral R2 (CR2) waves obtained from the test were analyzed. Results: The mean ages of healthy individuals and post COVID-19 patients were 34.0±6.4 and 38.4±10.6 years, respectively. Both age and gender were matched between the groups. R1, IR2, and CR2 latencies/amplitudes were not different between the two groups. The side-to-side R1 latency difference was 0.5±0.3 and 1.0±0.8 ms in healthy individuals and post COVID-19 patients, respectively (p=0.011). One healthy individual and 12 patients with post COVID-19 had at least one abnormal blink reflex parameter (p=0.001). Conclusion: This study showed that COVID-19 may cause subclinical abnormalities in the blink reflex, which includes the trigeminal nerve, the seventh nerve, the brainstem, and pathways between these structures.

Assessment of Smell and Taste Disturbances among COVID-19 Convalescent Patients: A Cross-Sectional Study in Armenia.

BACKGROUND AND OBJECTIVES: Neurological manifestations of Coronavirus Disease 2019 (COVID-19) such as olfactory and gustatory disturbance have been reported among convalescent COVID-19 patients. However, scientific data on the prevalence of smell and taste disturbance are lacking. Therefore, we present findings on the degree of smell and taste disturbances among the Armenian population. METHODS: Study participants were randomly recruited and then categorized into two groups based on their course of the disease. A cross-sectional study was performed to assess participants' sensitivity to smell triggered by the olfactory and the trigeminal nerves; their ability to differentiate between various odors; and to evaluate their gustatory perception. RESULTS: The smell test revealed that the degree of olfactory nerve disturbance was different by 30.7% in those participants of the early group as compared to those of the late group, and the degree of trigeminal nerve disturbance was different by 71.3% in the early group as compared to the late group. A variation of the differentiating ability among the participants of the early and late groups was detected. Gustatory disturbances for all flavors were also found to be different in both the groups. A moderate positive correlation (0.51) was found between the overall sensitivity of smell and the ability to differentiate between various odors as cumulatively stimulated by both the olfactory and trigeminal nerves. Also, a moderate positive correlation (0.33) was found between headache and smell sensitivity through the olfactory nerve and a high negative correlation (-0.71) was found between headache and smell sensitivity through the trigeminal nerve. CONCLUSION: Pathological changes in the olfactory and trigeminal perceptive abilities caused disturbances in smell sensation, with the trigeminal nerve being more affected. The capacity to differentiate fragrances did not improve with time and the disturbance severity of bitter taste perception was higher among the study participants.

Cranial nerve involvement in mucormycosis in post-COVID patients: a case series

Background: One of the largest outbreaks of rhinosinocerebral mucormycosis (RSCM) occurred in India close to the second wave of the SARS-CoV-2 infection. RSCM is a rare infection caused by several fungal species occurring in immunocompromised subjects. Mucor shows a high propensity to invade the central nervous system. There have been limited studies, mostly isolated case reports, on the neurological manifestations of RSCM. The outbreak of mucormycosis infection was thus the most opportune to study the neurological manifestations and cranial nerve involvement in mucormycosis in greater depths. Aim of the study: The purpose of the study was to investigate and review the involvement of cranial nerves in a series of cases of rhinosinocerebral mucormycosis associated with the novel coronavirus disease caused by SARS-CoV-2. Results: It was a retrospective cross-sectional study of seven patients who were undergoing treatment of RSCM with a recent history of coronavirus disease caused by SARS-CoV-2 infection within the last 3 months. Patients with cranial nerve involvement were identified by magnetic resonance imaging (MRI) at a single institution. Demographic details of the patients, clinical presentation, imaging, microbiological and pathological findings were recorded. All subjects had two or more cranial nerves affected by fungal infection. The most commonly involved cranial nerve was found to be the optic nerve followed by the trigeminal nerve and its branches. We document three cases with extensive involvement of the inferior alveolar branch of the mandibular division of the trigeminal nerve (V3), a previously unreported finding. In one case, in addition to the second and fifth cranial nerves, the third, fourth, sixth, seventh, eighth, and twelfth cranial nerves were involved without any sensory or motor long tract involvement, suggestive of Garcin syndrome secondary to intracranial abscesses and skull base osteomyelitis due to invasive fungal infection. This case is of rare occurrence in the literature, and our study provides one such example. Conclusion: Cranial nerve involvement in patients of mucormycosis tends to have a poor prognosis, both cosmetic and functional. Radical surgeries and aggressive medical management is needed in such cases to improve the outcome.

Electrical stimulation of the trigeminal nerve as a novel intervention to improve smell function

COVID-19 presented a renewed awareness of the importance of smell, including the striking impact of smell loss on daily functioning, as well as the lack of available evidencebased interventions to improve smell. While medical and surgical treatments exist for inflammatory-related smell loss, interventions to treat loss due to other etiologies are limited. Given the role of the intranasal trigeminal system in smell function, we conducted a proof-of-concept study to determine the effects of electrical stimulation of the trigeminal nerve (TNS) on sensitivity to phenyl ethyl alcohol (PEA) and guaiacol (GUA), 2 odorants with low and high trigeminal properties, respectively. TNS is an emerging form of “bottom-up” brain stimulation in which low-level electrical current is delivered to superficial trigeminal nerve branches innervating the face and forehead. Twenty healthy adults (8M/12F, 27±8.1 years old) were recruited from MUSC and the surrounding community to participate in this double-blind, placebo-controlled, pilot. PEA and GUA thresholds were determined at baseline, immediately postintervention, and again 30-min post-intervention. In a randomized cross-over design, participants received active and sham TNS on separate visits. Results indicated a significant stimulation x odor x time interaction (F[2,76]=3.56, p=.024, η 2=.093). Detection of GUA, but not PEA, was significantly enhanced by active, but not sham, TNS (16% and 9% increase from baseline at the 1st and 2nd follow-up time points respectively). TNS is safe, noninvasive, inexpensive, and easy to administer, rendering it highly scalable. Future study should determine the full effects and durability of TNS on smell function across different stimulation parameters, odorants, and patient populations.

Patients with COVID-19-associated olfactory impairment also show impaired trigeminal function.

OBJECTIVE: Next to olfactory function, the nose can also perceive chemestetic sensations mediated by the trigeminal nerve. While olfactory dysfunction as a symptom of COVID-19 is well described, there has been little research on the limitation of other nasal sensory inputs due to SARS-CoV-2 infection. The aim of this study was to determine possible limitations of nasal chemesthesis after COVID-19 infection by a psychophysiological diagnostic tool. METHODS: In 65 patients with a PCR-confirmed, former COVID-19 disease, olfaction was tested by means of a sniffin' sticks test, tasting by taste sprays and chemesthesis with a menthol dilution series. The subjective self-assessment of the patients was recorded via a questionnaire. RESULTS: We found a restriction of nasal chemesthesis and the extent correlated with the loss of smell, as well as with the values of the taste score, but not with subjective self-assessment. CONCLUSION: Not only the ability to smell and taste, but also nasal chemesthesis is affected by COVID-19.