IRF2BP2 mutation with autoimmune enteropathy, immune deficiency, and respiratory failure

Case history: We present the case of a 31-year-old Hispanic male with history of recurrent bronchiectasis, invasive aspergillosis, and severe persistent asthma, who is now status post lung transplant for end-stage lung disease. He initially presented at 7 years of age with diarrhea, failure to thrive, and nearly absent immunoglobulin levels (IgG < 33 mg/dL, IgA < 7 mg/dL, IgM = 11 mg/dL, IgE = 4 IU/dL) necessitating IVIG treatment. Small intestinal biopsy showed villous atrophy consistent with autoimmune enteropathy. Sweat chloride was reported as indeterminate (44 me/dL). Initial WBC, platelet, and T- and NK-cell counts were within normal range, and B-cell count and percentage were borderline low. Most recently, he was found to have increased immature B-cell count (CD21low), decreased memory B-cells, and poor pneumococcal vaccine antibody response. Patient has been hospitalized numerous times with increasingly severe bronchiectasis, pneumonitis, and COVID-19 infections twice despite vaccination, leading to respiratory failure and lung transplantation. Family history is negative for immune deficiency and lung diseases. Discussion(s): Of these 3 VUSs (see the table), the one in IRF2BP2 has the most pathogenic potential due to its autosomal dominant inheritance, its location in a conserved domain (Ring), and previous case reports of pathogenic variants at the same or adjacent alleles 1-3. Baxter et al reported a de novo truncating mutation in IRF2BP2 at codon 536 (c.1606CinsTTT), which is similar to our patient's mutation. This patient was noted to have an IPEX-like presentation, with chronic diarrhea, hypogammaglobulinemia, and recurrent infections. Variant Functional Prediction Score for our variant predicts a potentially high damage effect. There are 2 other case reports of heterozygous mutations in loci adjacent to this allele;one (c.1652G>A)2 with a similar clinical phenotype to our patient and the other (C.625-665 del)3 with primarily inflammatory features and few infections. Impact: This case highlights a variant in IRF2BP2 associated with severe hypogammaglobulinemia, recurrent pulmonary infections, and autoimmune enteropathy. [Table presented]Copyright © 2023 Elsevier Inc.

Different reversibility of skeletal muscle mass and strength in elderly Japanese women after the first wave of COVID-19

BackgroundRestrictions on outdoor movements due to the coronavirus disease (COVID-19) pandemic have led to a decreased physical activity;this can lead to sarcopenia and frailty in older adults. Our recent study has demonstrated a significant decrease in the trunk muscle mass immediately after the pandemic's first wave (April–May 2020) among Japanese community-dwelling older women. In the present study, we further examined whether muscle mass recovery or deterioration occurs after 1 year of the pandemic's first wave by comparing physical measurements among the following assessment periods: before the first wave, immediately after the first wave, and at 1-year follow-up thereafter.MethodsThis study included 77 women (78.0 ± 5.7 years) who underwent physical measurements for muscle mass, grip strength, one-leg stand-up ability (3 s), and oral motor skills and answered questionnaires on sociality (social network, participation, and support) in the three assessment periods.ResultsThe frequency of going out and the subjective vitality were significantly decreased immediately after the first wave;these recovered at the 1-year follow-up (P < 0.001). When comparing muscular measures, the trunk muscle mass index preferentially decreased immediately after the first wave but recovered significantly at the 1-year follow-up (P < 0.001). Conversely, the appendicular skeletal muscle mass index (ASMI) and grip strength continued to decrease until the 1-year follow-up (P < 0.001 and P = 0.03, respectively). The ability to perform a one-leg stand-up for 3 s and the oral motor skills did not change significantly across the assessment periods. The prevalence of pre-sarcopenia and sarcopenia tended to increase during these periods (P = 0.068). The reduction and subsequent recovery patterns for sociality were similar to those observed for the trunk muscle mass.ConclusionsOur findings demonstrated differences in the reversibility of skeletal muscle mass and strength at 1 year after the first wave of the COVID-19 pandemic: the trunk muscle mass declined acutely and recovered rapidly, whereas the ASMI and grip strength declined continuously. These differences in the skeletal muscle recovery and deterioration might help formulate short-term or long-term strategies for COVID-19-related sarcopenia prevention in community-dwelling older adults.

Brain Volume Changes after COVID-19 Compared to Healthy Controls by Artificial Intelligence-Based MRI Volumetry.

Cohort studies that quantify volumetric brain data among individuals with different levels of COVID-19 severity are presently limited. It is still uncertain whether there exists a potential correlation between disease severity and the effects of COVID-19 on brain integrity. Our objective was to assess the potential impact of COVID-19 on measured brain volume in patients with asymptomatic/mild and severe disease after recovery from infection, compared with healthy controls, using artificial intelligence (AI)-based MRI volumetry. A total of 155 participants were prospectively enrolled in this IRB-approved analysis of three cohorts with a mild course of COVID-19 (n = 51, MILD), a severe hospitalised course (n = 48, SEV), and healthy controls (n = 56, CTL) all undergoing a standardised MRI protocol of the brain. Automated AI-based determination of various brain volumes in mL and calculation of normalised percentiles of brain volume was performed with mdbrain software, using a 3D T1-weighted magnetisation-prepared rapid gradient echo (MPRAGE) sequence. The automatically measured brain volumes and percentiles were analysed for differences between groups. The estimated influence of COVID-19 and demographic/clinical variables on brain volume was determined using multivariate analysis. There were statistically significant differences in measured brain volumes and percentiles of various brain regions among groups, even after the exclusion of patients undergoing intensive care, with significant volume reductions in COVID-19 patients, which increased with disease severity (SEV > MILD > CTL) and mainly affected the supratentorial grey matter, frontal and parietal lobes, and right thalamus. Severe COVID-19 infection, in addition to established demographic parameters such as age and sex, was a significant predictor of brain volume loss upon multivariate analysis. In conclusion, neocortical brain degeneration was detected in patients who had recovered from SARS-CoV-2 infection compared to healthy controls, worsening with greater initial COVID-19 severity and mainly affecting the fronto-parietal brain and right thalamus, regardless of ICU treatment. This suggests a direct link between COVID-19 infection and subsequent brain atrophy, which may have major implications for clinical management and future cognitive rehabilitation strategies.

The olfactory bulb - gateway for SARS-Cov-2?

Introduction. Anosmia and ageusia are one of the most common and characteristic symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection, with a frequency of almost 50% in patients in Western countries. Hypotheses proposing that the virus potentially affects the central nervous system (CNS) are on the rise. One hypothesis suggests that the virus enters via nasal mucosa and then enters the olfactory bulb via cribriform plate, with further dissemination to the CNS. Case report. A 34-year-old female patient experienced the loss of the sense of smell and taste about two months before testing positive for SARS-Cov-2. Coronavirus disease 2019 (COVID- 19) presented with minor pneumonia and worsening anosmia and ageusia. After treatment, the patient recovered well, but anosmia and ageusia appeared again, varying in intensity, and since February 2021, they have become persistent. The case was evaluated by an otorhinolaryngologist, pulmonologist, and finally, a neurologist. In the meantime, the patient tested negative for SARS-Cov-2 and received two doses of the Sputnik V vaccine. Brain magnetic resonance imaging (MRI) was performed, and it clearly showed severe bilateral olfactory bulb atrophy. The patient has had anosmia and ageusia up to this day, and future MRI follow- up is planned. Conclusion. Loss of sense of smell and taste may be a predictor of further CNS dissemination of the virus and possible neurological complications (which is still a subject of consideration). The olfactory bulb could be a gateway to COVID-19 intrusion into the CNS, and its atrophy could be an indicator of the process. Further investigation on this topic is required, including a wide application of MRI, in order to come to definite conclusions.

Shoulder Weakness Following Intramuscular COVID- 19 Vaccine

History: Transient and generalized adverse effects are common following COVID-19 vaccination;among other adverse effects, shoulder injuries related to vaccine administration (SIRVA) have been known to occur. In this case, a previously healthy right-hand dominant 62-year-old male presented with left shoulder pain and weakness 3 months after receiving a COVID-19 intramuscular vaccine in the left deltoid. Approximately 2 weeks after the injection, he started experiencing pain and numbness around the injection site along with ipsilateral shoulder weakness. Despite conservative management with Motrin, Medrol Dosepak, gabapentin and physical therapy (PT), the pain and weakness persisted. Physical Exam: Left Shoulder-No calor or erythema;significant atrophy of the anterior and middle deltoid muscle relative to right side;abduction 4/5;external rotation with shoulder adducted 4/5;range of motion for active forward flexion was 150 degrees and passive was 170 degrees;passive range of motion for external rotation was 70 degrees;internal rotation to the level of L5;sensation to light touch was intact. Right Shoulder-Range of motion, strength, and sensation were intact. Cervical Spine-Full ROM;no cervical paraspinal tenderness noted. Negative Spurling's and Lhermitte's tests. Differential Diagnosis: 161. Axillary Nerve Palsy 2/2 Chemical Neurotoxicity 162. Brachial Neuritis 163. Mechanical Axillary Nerve Palsy 2/2 Vaccination 164. Partial-Tear of Left Supraspinatus Tendon 165. Acromioclavicular Osteoarthritis Test Results: Left Shoulder-XR:Mild pseudo-subluxation;MRI w/o contrast: 8x9mmpartial-thickness articular surface tear of the distal supraspinatus tendon (<50%fiber thickness). Minimal subacromial bursitis. Mild acromioclavicular joint osteoarthritis. EMG/NCV: Left and Right Axillary Motor Nerves: prolonged distal onset latency;Left Deltoid: increased insertion activity, moderately increased spontaneous activity, reduced recruitment;Remaining LUE muscles without evidence of electrical instability Final Diagnosis: Axillary Nerve Palsy Secondary To Chemical Neurotoxicity from Intramuscular COVID-19 Vaccine. Discussion(s): We postulate that the neurologic deficits presented in our case may be attributed to chemical neurotoxicity to the axillary nerve following vaccination as the delayed onset of pain and weakness are most consistent with this differential. There are several cases of brachial neuritis following vaccination for the prevention of COVID- 19, however, EMG/NCV results in our patient were not consistent with brachial plexopathy. Additionally, while there have been a handful of reported cases of bursitis following COVID-19 vaccines falling under the SIRVA classification of injuries, this is the first case of reported axillary nerve neurapraxia. Outcome(s): The patient's left shoulder numbness and pain improved with PT and medical management. While mild improvement in strength was noted, weakness and atrophy persisted even on the third follow up visit 6 months after the initial appointment. He was counseled on his injury and was recommended to undergo repeat EMG testing to document recovery after his 6-month follow-up appointment. Follow-Up: The patient did not follow-up for a repeatEMG after his 6-month follow-up appointment. At that time, the patient was clinically stable, tolerating PT, and expecting recovery of his deltoid function.

Mobile Information System for Determining the Level of Creatine in Food Products

The study of food products to determine the level of creatine in them is an actual task, taking into account the need for this substance for patients with Covid'19 and spinal muscular atrophy. The purpose of our research is to develop a mobile information system for determining the level of creatine in food products. The developed method for determining the level of creatine in food products by the user and the method for determining the level of creatine in food products using a mobile information system provide the user with the opportunity to quickly, conveniently, cheaply and effectively assess the presence and level of creatine in any food products, on the basis of which to build a rational diet from the point vision of body saturation with creatine. The proposed mobile information system for determining the level of creatine in food products provides convenience, low-cost, celerity, miniaturization and automation for measurement of concentration of creatine in any food products. The conclusion obtained from the system regarding the presence and level of creatine in this or that food product is useful and extremely important when preparing the diet of patients, especially patients with Covid'19 and/or spinal muscular atrophy. The proposed approach and mobile information system for determining the level of creatine in food products can be used not only for drawing up the diet of patients, especially patients with Covid'19 and/or spinal muscular atrophy, from the point vision of body saturation with creatine, but also for example, to check the quality of meat products. © 2023 Copyright for this paper by its authors.

An alternative mechanism for skeletal muscle dysfunction in long-term post-viral lung disease.

Chronic lung disease is often accompanied by disabling extrapulmonary symptoms, notably skeletal muscle dysfunction and atrophy. Moreover, the severity of respiratory symptoms correlates with decreased muscle mass and in turn lowered physical activity and survival rates. Previous models of muscle atrophy in chronic lung disease often modeled chronic obstructive pulmonary disease (COPD) and relied on cigarette smoke exposure and LPS stimulation, but these conditions independently affect skeletal muscle even without accompanying lung disease. Moreover, there is an emerging and pressing need to understand the extrapulmonary manifestations of long-term post-viral lung disease (PVLD) as found in COVID-19. Here, we examine the development of skeletal muscle dysfunction in the setting of chronic pulmonary disease caused by infection due to the natural pathogen Sendai virus using a mouse model of PVLD. We identify a significant decrease in myofiber size when PVLD is maximal at 49 days after infection. We find no change in the relative types of myofibers, but the greatest decrease in fiber size is localized to fast-twitch-type IIB myofibers based on myosin heavy chain immunostaining. Remarkably, all biomarkers of myocyte protein synthesis and degradation (total RNA, ribosomal abundance, and ubiquitin-proteasome expression) were stable throughout the acute infectious illness and chronic post-viral disease process. Together, the results demonstrate a distinct pattern of skeletal muscle dysfunction in a mouse model of long-term PVLD. The findings thereby provide new insights into prolonged limitations in exercise capacity in patients with chronic lung disease after viral infections and perhaps other types of lung injury.NEW & NOTEWORTHY Our study used a mouse model of post-viral lung disease to study the impact of chronic lung disease on skeletal muscle. The model reveals a decrease in myofiber size that is selective for specific types of myofibers and an alternative mechanism for muscle atrophy that might be independent of the usual markers of protein synthesis and degradation. The findings provide a basis for new therapeutic strategies to correct skeletal muscle dysfunction in chronic respiratory disease.

Early immunological responses to the mRNA SARS-CoV-2 vaccine in patients with neuromuscular disorders.

Backgrounds: Intramuscular injection of the SARS-CoV-2 vaccine has raised concerns about its use in patients with neuromuscular disorders (NMDs). We evaluated the response of patients with NMDs to the BNT162b2 vaccine. Methods: Healthy subjects, patients with spinal muscular atrophy (SMA), and patients with Duchenne muscular dystrophy (DMD) were included. All participants received two BNT162b2 doses. SARS-CoV-2 antibody titers at baseline and 2 weeks after each vaccination were compared between groups. Residual muscle volume was evaluated in NMDs group. A questionnaire documented adverse reactions. Results: Eleven patients with NMDs (9 with SMA, 2 with DMD; 7 males; aged 32.7 ± 19.3 years) and 346 healthy subjects (60 males, aged 40.0 ± 12.4 years) were included. Antibody titers (U/mL) were similar between groups (baseline: <0.40 vs. <0.40, first vaccination, 145 ± 258 vs. 103 ± 1192, and second vaccination, 1528 ± 1265 vs. 1429 ± 944; p = 1.000, 0.909, and 0.736, respectively). A negative correlation was found between antibody titers and residual muscle volume but was not significant (Mercuri scale, r = -0.429, p = 0.249; fat infiltration rate, r = -0.194, p = 0.618). The adverse reactions were comparable between groups. Conclusion: The BNT162b2 vaccine is safe and effective in patients with NMDs.

Commencing Novel Therapies for Adult Sma Patients: Experience from a Hybrid Clinic

Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder that affect both adults and children. Two novel therapies were approved for patients in England by NICE (Nusinersen via Management Access Agreement (MAA) and Risdiplam via Early Access to Medicine scheme (EAMS)). Setting up baseline assessments, designing new pathways, acquiring personnel and resources have been challenging. We present a pathway analysis of the new clinic set-up, process of patient choice, risk minimisation in intro- ducing the two novel therapies, and the impact therapies have had on adult cohort of SMA patients. Total of 58 patients included (31 had type 2 SMA and 27 had type 3[only 11/27 were ambulant]. The average age of patients with type 2 and 3 SMA was 25 and 33 respectively. 19 patients chose risdiplam (oral) and 22 are on nusinersen (intra thecal). We analysed factors that govern patients' treatment decisions. We report factors that helped early success in our hybrid clinic set-up. Set criteria on each scheme;but potential side effects, information availability, route of administration (mainly previous spinal surgery), speed at treatment initiation but not COVID directed many patients' treatment decisions. A battery of outcome measures were analysed to establish treatment impact at 12 months.

Bilateral optic neuritis and myocarditis after the first dose of COVID-19 vaccine

Since the introduction of COVID-19 vaccine, various adverse events have been reported including injection site pain, fatigue, headaches, and myocarditis. Cranial neuropathies and optic neuritis, have been also rarely reported, however, the significance of these autoimmune manifestations after the administration of COVID-19 vaccine remain controversial. In this report we present a case of myocarditis and bilateral optic neuritis that occurred in a young healthy male patient after the administration of first dose of mRNA-1273 vaccine (Moderna).Copyright © 2022 The Author(s)

Hyponatremia in Empty Sella Syndrome: Is it a Covid Sequelae?

The symptoms associated with empty sella syndrome (ESS) include headache, giddiness, vomiting, visual field deficits, and endocrine problems, as well as the radiological appearance of an enlarged sella turcica. This case report highlights a 45-year-old female who had a COVID-19 infection 2 months back and presented with chronic headache, giddiness, and lethargy having persistent hyponatremia later diagnosed as empty sella syndrome on brain magnetic resonance imaging. In this case, we tried to correlate all of these clinical and radiological features as COVID-19 sequelae due to post-Covid hypothalamic-pituitary axis dysfunction.Copyright © 2023 Authors. All rights reserved.

Morphological, Cellular, and Molecular Basis of Brain Infection in COVID-19 Patients and Its Association to Psychiatric Symptoms

Background: Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. Method(s): We performed a broad translational investigation, employing brain imaging and cognitive tests in 81 living COVID-19 patients (mildly infected individuals) as well as flow cytometry, respirometry, microscopy, proteomics, and metabolomics in postmortem brain samples, and in preclinical in vitro and ex vivo models. Result(s): We observed orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms in living individuals. Postmortem brain tissue from 26 individuals who died of COVID-19 revealed histopathological signs of brain damage. Five individuals out of the 26 exhibited foci of SARS- CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell-derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a non-canonical mechanism that involves spike-NRP1 interaction. SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that significantly reduces neuronal viability. Conclusion(s): Our data support the model in which COVID-19 alter cortical thickness, promoting psychiatric symptoms. In addition, SARS-CoV-2 is able to reach the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients. Funding Source: Sao Paulo Research Foundation (FAPESP) Keywords: COVID-19, Anxiety, Astrocytes, Multi-omics, Brain Magnetic Resonance Imaging (MRI)Copyright © 2023

Po251 / #854 Noninvasive Closed Loop Diaphragm Stimulation for Ventilated Icu Patients: E-Poster Viewing

Introduction: Many COVID-19 patients need prolonged artificial ventilation. Skeletal muscle wastes rapidly when deprived of neural activation, and in ventilated patients the diaphragm muscle begins to atrophy within 24 hours (ventilator induced diaphragmatic dysfunction, VIDD). This profoundly weakens the diaphragm, complicating the weaning of the patient off the ventilator, and increasing the risk of complications such as bacterial pneumonia. 40% of the total duration of mechanical ventilation in ITU patients is accounted for by the weaning period, after the initial illness has resolved. Prevention of VIDD would therefore both improve individual outcomes, and also release ITU capacity. We aim to prevent VIDD by exercising the diaphragm with electrical stimulation of the nerves that control it. Evidence suggests that muscle wasting can be prevented by quite low levels of exercise (e.g. 200 contractions per day). Materials / Methods: The diaphragm is activated by the phrenic nerves, formed from branches of the C3-C5 nerve roots in the neck. These nerves may be electrically stimulated in the lower neck. An electrode array is positioned on each side of the neck using surface landmarks. The system automatically determines the best electrode to use in each array. Sensors built into the ventilatory circuit are monitored both to match stimulation to the respiratory cycle and to determine the effects of stimulation. Result(s): We have designed and built a prototype system for unsupervised noninvasive phrenic nerve stimulation. The system delivers one contraction every 7 minutes, synchronised to early inspiration so as not to disrupt ventilation. Electrode impedances are measured before each stimulus, and the closed loop system continuously monitors the effects of stimulation on airflow and adjusts stimulation parameters to compensate for changes in coupling, for example due to head movement. Discussion(s): This stimulator system overcomes several limitations of existing solutions, namely the resource implications and risk profile of invasive electrodes, and the requirement for supervised operation. While invasive systems are applied selectively for these reasons, routine use of our system can be envisaged. This system was inspired by COVID-19 patients but is not limited to them, and has broad applicability to ventilated intensive care patients in general, for example patients with traumatic brain injury. Conclusion(s): Non-invasive stimulation of the phrenic nerves using pressure-free skin surface electrodes is feasible and safe. It offers the potential for prevention of VIDD and thereby faster ventilator weaning and shorter stay on ITU. Clinical trials are planned in 2022. Learning Objectives: After this presentation delegates should be aware of: 1. Ventilation induced diaphragm dysfunction (VIDD) and its importance in patients having lengthy periods of ventilation, as in many cases of COVID-19. 2. The fact that low levels of activity can maintain the condition of skeletal muscles including the diaphragm muscle 3. The potential for noninvasive stimulation of the phrenic nerves to provide 'diaphragm exercise' and prevent VIDD. Keywords: phrenic nerve stimulation, diaphragm, ventilation, COVID-19Copyright © 2022

Coordination and Cognition in Pure Nutritional Wernicke's Encephalopathy with Cerebellar Degeneration after COVID-19 Infection: A Unique Case Report.

BACKGROUND: Alcoholic cerebellar degeneration is a restricted form of cerebellar degeneration, clinically leading to an ataxia of stance and gait and occurring in the context of alcohol misuse in combination with malnutrition and thiamine depletion. However, a similar degeneration may also develop after non-alcoholic malnutrition, but evidence for a lasting ataxia of stance and gait and lasting abnormalities in the cerebellum is lacking in the few patients described with purely nutritional cerebellar degeneration (NCD). METHODS: We present a case of a 46-year-old woman who developed NCD and Wernicke's encephalopathy (WE) due to COVID-19 and protracted vomiting, resulting in thiamine depletion. We present her clinical course over the first 6 months after the diagnosis of NCD and WE, with thorough neuropsychological and neurological examinations, standardized clinical observations, laboratory investigations, and repeated MRIs. RESULTS: We found a persistent ataxia of stance and gait and evidence for an irreversible restricted cerebellar degeneration. However, the initial cognitive impairments resolved. CONCLUSIONS: Our study shows that NCD without involvement of alcohol neurotoxicity and with a characteristic ataxia of stance and gait exists and may be irreversible. We did not find any evidence for lasting cognitive abnormalities or a cerebellar cognitive-affective syndrome (CCAS) in this patient.

Regression of treatment-resistant gyrate atrophy-associated intraretinal cystic spaces using long-term diet restriction: A case report.

PURPOSE: Gyrate atrophy of the choroid and retina (GA) is a rare genetic ophthalmologic condition which primarily manifests in childhood. It is characterized by hyperornithinemia and progressive chorioretinal atrophy. Patients may develop macular intraretinal cystic spaces (ICS) for which various treatment modalities have been reported. We report a patient who failed to demonstrate visual or anatomic improvement following multiple treatments for GA-associated ICS but showed improvement following prolonged dietary modification and vitamin supplementation. CASE DESCRIPTION: A 6-year-old male patient presented with previously undiagnosed GA associated with ICS. He received 6 consecutive monthly intravitreal bevacizumab injections as well as topical nepafenac and dorzolamide for treatment of ICS without significant change detected by optical coherence tomography (OCT) following treatment. He was also maintained on an arginine restricted diet with vitamin B6 supplementation. Over the course of the ensuing year, the patient was lost to follow-up due to the coronavirus disease 2019 pandemic. When he returned, his vision was stable, and OCT showed regression of the ICS. His mother reported that he had continued only on dietary restriction and vitamin B6 supplementation with no other medications or interventions. Plasma ornithine level measurement confirmed dietary compliance. Further follow-up showed continued stabilization of the condition. CONCLUSION: In addition to retarding progressive chorioretinal atrophy, prolonged dietary modifications may result in improvement of treatment-resistant GA-associated ICS. Parents' education on the value of dietary modifications for patients with GA is highly recommended.

A Review: Zinc as an Antivirus Alternative Treatment for Herpes Simplex Virus Infection

This study aimed to review zinc's effectiveness as an antivirus in treating herpes simplex virus infection. The authors use international journals published from 2000-2022, and use search engines such as Google Scholar, PubMed, and Science Direct with the keywords "zinc and herpes simplex virus". The herpes simplex virus that often causes symptoms in humans are HSV type 1 and type 2. The lesions appear as vesicles which then rupture into ulcers. Zinc is one of the most abundant nutrients or metals in the human body besides iron. Studies about the effects of zinc on HSV have shown that it has the function of inhibiting the viral life cycle. HSV attaches to the host cells to replicate and synthesize new viral proteins. Zinc can inhibit this process by depositing on the surface of the virion and inactivating the enzymatic function which is required for the attachment to the host cell, disrupting the surface glycoprotein of the viral membrane so it could not adhere and carry out the next life cycle, it can also inhibit the function of DNA polymerase that works for viral replication in the host cell. This article showed that zinc has effectiveness as an antivirus against the herpes simplex virus, therefore, patients infected with HSV can be treated with zinc as an alternative to an antivirus drug.Copyright © 2022 The Authors. Published by Innovare Academic Sciences Pvt Ltd.

NEUROCUTANEOUS MELANOCYTOSIS WITH MANIFESTATION IN ADULTHOOD.

A 20-year-old patient was presented with subacute onset of headache, nausea and vomiting. Testing of nasal/oropharyngeal swabs indicated the presence of SARS-CoV-2 RNA, and later the antibodies to this virus were found. The treatment in the hospital for Coronavirus 19 Disease (COVID-19) provided only temporary relief, and the patient then was referred to the Regional Stroke Center (RSC) to exclude a subarachnoid hemorrhage. RSC neurologists drew attention to multiple skin nevi in the patient. Brain MRI demonstrated abnormal T1 hyperintensity in the brain leptomeninges, with leptomeningeal contrast enhancement as well as hyperintensity in amygdala regions on T1 weighted images, bilaterally. The anomaly of the Dandy-Walker malformation complex was also revealed. Cerebrospinal fluid (CSF) analysis showed elevated protein (0.52 g/L), low lymphocytosis (lymphocytes, 6 in mm3), and decreased glucose (1.8 mmol/L). Neurocutaneous melanocytosis (NCM) was diagnosed, which neurological manifestation was probably triggered by COVID-19. The patient's vision gradually progressively worsened. In 2.5 months after the clinical manifestation of NCM, fundoscopy revealed optic discs atrophy (despite the absence of previous edema), and repeated CSF analysis showed atypical cells with characteristics corresponding to melanoma. Malignant transformation of cerebral melanocytosis was suspected, and the patient was referred to an oncological dispensary for further therapy. In the presented literature review, special attention is paid to the issues of neuroimaging, cytological and immunocytochemical diagnostics of NCM.Copyright © Russian Neurological Journal. All rights reserved.

NEUROCUTANEOUS MELANOCYTOSIS WITH MANIFESTATION IN ADULTHOOD.

A 20-year-old patient was presented with subacute onset of headache, nausea and vomiting. Testing of nasal/oropharyngeal swabs indicated the presence of SARS-CoV-2 RNA, and later the antibodies to this virus were found. The treatment in the hospital for Coronavirus 19 Disease (COVID-19) provided only temporary relief, and the patient then was referred to the Regional Stroke Center (RSC) to exclude a subarachnoid hemorrhage. RSC neurologists drew attention to multiple skin nevi in the patient. Brain MRI demonstrated abnormal T1 hyperintensity in the brain leptomeninges, with leptomeningeal contrast enhancement as well as hyperintensity in amygdala regions on T1 weighted images, bilaterally. The anomaly of the Dandy-Walker malformation complex was also revealed. Cerebrospinal fluid (CSF) analysis showed elevated protein (0.52 g/L), low lymphocytosis (lymphocytes, 6 in mm3), and decreased glucose (1.8 mmol/L). Neurocutaneous melanocytosis (NCM) was diagnosed, which neurological manifestation was probably triggered by COVID-19. The patient's vision gradually progressively worsened. In 2.5 months after the clinical manifestation of NCM, fundoscopy revealed optic discs atrophy (despite the absence of previous edema), and repeated CSF analysis showed atypical cells with characteristics corresponding to melanoma. Malignant transformation of cerebral melanocytosis was suspected, and the patient was referred to an oncological dispensary for further therapy. In the presented literature review, special attention is paid to the issues of neuroimaging, cytological and immunocytochemical diagnostics of NCM.Copyright © Russian Neurological Journal. All rights reserved.

NEUROCUTANEOUS MELANOCYTOSIS WITH MANIFESTATION IN ADULTHOOD.

A 20-year-old patient was presented with subacute onset of headache, nausea and vomiting. Testing of nasal/oropharyngeal swabs indicated the presence of SARS-CoV-2 RNA, and later the antibodies to this virus were found. The treatment in the hospital for Coronavirus 19 Disease (COVID-19) provided only temporary relief, and the patient then was referred to the Regional Stroke Center (RSC) to exclude a subarachnoid hemorrhage. RSC neurologists drew attention to multiple skin nevi in the patient. Brain MRI demonstrated abnormal T1 hyperintensity in the brain leptomeninges, with leptomeningeal contrast enhancement as well as hyperintensity in amygdala regions on T1 weighted images, bilaterally. The anomaly of the Dandy-Walker malformation complex was also revealed. Cerebrospinal fluid (CSF) analysis showed elevated protein (0.52 g/L), low lymphocytosis (lymphocytes, 6 in mm3), and decreased glucose (1.8 mmol/L). Neurocutaneous melanocytosis (NCM) was diagnosed, which neurological manifestation was probably triggered by COVID-19. The patient's vision gradually progressively worsened. In 2.5 months after the clinical manifestation of NCM, fundoscopy revealed optic discs atrophy (despite the absence of previous edema), and repeated CSF analysis showed atypical cells with characteristics corresponding to melanoma. Malignant transformation of cerebral melanocytosis was suspected, and the patient was referred to an oncological dispensary for further therapy. In the presented literature review, special attention is paid to the issues of neuroimaging, cytological and immunocytochemical diagnostics of NCM.Copyright © Russian Neurological Journal. All rights reserved.