Zoster Research Articles

Advancing Public Health Equity through Expanded Vaccination Services in prison: case studies from Italy and France

Abstract In Montpellier prison in France and San Vittore remand house in Italy, the provision of expanded, age-appropriate, coercion-free, and tailored vaccination services to PLP has emerged as a cornerstone in improving health outcomes within prison settings. The implementation of life course vaccination programs required the full integration of prison health into public health systems building on existing vaccination services covering HBV, flu and COVID-19. In San Vittore, a vaccination clinic aimed at people living in prison was set-up. Universal vaccination status assessment and vaccination catch-up was introduced targeting people admitted into prison. The vaccination clinic-related activities included information and awareness sessions on vaccination and health literacy offered regularly to PLP: increased vaccination knowledge is effective to enhance uptake. The vaccination clinic team consisted of infectious diseases physicians and a health assistant with an anthropological background, who ran the information and awareness sessions combining and adapting core content on vaccination with individual and community social and cultural contexts. Besides seasonal flu vaccination and anti-SARS-CoV-2 immunisation campaigns, vaccinations against pneumococcal pneumonia and herpes zoster were also offered to older and fragile individuals as per national immunization plan. One of the priority objectives of the vaccination clinic was the increase in vaccination coverage against HBV and HPV, not only as a tool for the prevention of infectious diseases, but as an innovative and effective tool of cancer prevention. As part of a more ambitious program to protect sexual health in prison and related to updated screening tools for the early diagnosis of lesions due to HPV infection, vaccination against HPV was also offered as part of a health empowerment project tailored to women in detention, with the aim of building self-awareness of their own health needs.

The role of sociodemographic factors on herpes zoster vaccine uptake among hard-to-reach populations

Abstract Background The anti-Herpes Zoster (HZ) vaccination program was expanded with the adjuvated recombinant vaccine (HZR) in the Lazio Region, Italy, in 2022, restricting its use only to certain categories at risk due to pathological conditions, such as dialysis patients or immunocompromised individuals. This study focuses on the role of clinical and socio-demographic factors on HZR vaccine uptake within the fragile resident population of the Local Health Authority Rome 2 (ASL RM2). Methods This population-based, retrospective cohort study leveraged data from various registries and databases. The study population comprised 835,779 individuals aged ≥18 years who were both RM2 residents and registered with an RM2 general practitioner (GP). Among these, 143,242 individuals with at least one chronic condition were assessed for vaccination uptake using a multivariate logistic model, exploring associations with gender, age, nationality, marital status, household size, and level of deprivation. Results At the conclusion of the study period, a small fraction (1.5%) of the fragile subjects had received at least one dose of the HZR vaccine, and a majority (78%) completed the vaccination course of two doses. The analysis indicated that vaccine adherence was significantly higher in males (OR = 1.15) and individuals aged 65 + (OR = 1.13) while lower among residents in areas of medium (OR = 0.61) and high deprivation (OR = 0.44) and with specific living arrangements - widowed people living alone (OR = 0.66) and families ≥ 6 people (OR = 0.63). Conclusions The ASL RM2 vaccination strategy for hard-to-reach individuals includes an integrated approach, with the engagement of local healthcare facilities and hospitals. Despite these efforts, lower adherence in socioeconomically disadvantaged fragile patients suggests a pressing need for targeted communication strategies and interventions to ensure equitable access to the HZ vaccine, as these groups are more vulnerable to developing chronic diseases. Key messages • Socio-demographic factors significantly influence Herpes Zoster vaccine uptake in hard-to-reach populations, with lower adherence in socially deprived groups. • Tailored, equity-driven approaches are essential for enhancing vaccine coverage among hard-to-reach fragile individuals, mitigating the higher disease risks in these communities.

Immunogenicity and Safety of the Recombinant Adjuvanted Herpes Zoster Vaccine in Patients with Chronic Lymphocytic Leukemia and Multiple Myeloma

Background/objectives: Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are susceptible to viral infections, including varicella-zoster virus (VZV) reactivation due to both disease-related and treatment-induced immunosuppression. The recombinant adjuvanted herpes zoster vaccine (RZV) has shown high efficacy in immunocompetent adults, but immunogenicity data in CLL and MM patients are limited. This study evaluates the immunogenicity and safety of RZV in this population. Methods: Patients with CLL and MM vaccinated with RZV (administered in two doses at least one month apart) were included in the study. Pre- and post-vaccination anti-VZV IgM and IgG antibody levels were measured to assess immunogenicity, and adverse events (AEs) were captured for safety evaluation. Results: Seventy-eight patients received both vaccine doses, and 71 had post-vaccination samples. Most of the patients were IgM seronegative and IgG seropositive before vaccination. Pre-vaccination IgG levels were higher in CLL patients compared to MM patients (p = 0.001), while post-vaccination IgG levels significantly increased in both CLL (p < 0.0001) and MM (p < 0.0001) patients. In actively treated CLL patients, pre-vaccination IgG levels were significantly lower than in not actively treated patients (p = 0.002). Post-vaccination IgG levels were lower in MM patients receiving antiviral prophylaxis concurrently with the vaccination (p = 0.013). AEs were reported in 49.4% of patients after the first dose and 48.7% after the second dose, mostly mild (local or low-grade systemic). One case of immune thrombocytopenia was noted. Conclusions: RZV demonstrated strong immunogenicity and acceptable safety in CLL and MM patients, significantly boosting IgG levels, even in actively treated or heavily pretreated patients.

Earlobe Loss After Herpes Zoster Infection: An Uncommon Complication.

Earlobe Loss After Herpes Zoster Infection: An Uncommon Complication.

Immunogenicity to Herpes Zoster recombinant subunit vaccine in immune-mediated rheumatic patients under treatment with JAK inhibitors.

Patients with immune-mediated rheumatic diseases (IMRDs) face an elevated risk of varicella-zoster virus infection (VZV), and herpes zoster (HZ). Treatment with immunosuppressors further increases the risk. A new recently approved adjuvant recombinant inactive vaccine, offers safe protection against HZ. However, limited data exist on the efficacy of this new vaccine in patients with IMRDs treated with JAK inhibitors. We aimed to characterize B cell and T cell immune responses elicited by the HZ recombinant subunit vaccine in patients with IMRDs under treatment with JAK inhibitors, and to identify factors that might be associated with reduced immunogenicity, and therefore reduced protection. We investigated humoral, and cellular CD4 and CD8 immune responses following a two-dose regimen of the recombinant inactive vaccine in 43 patients with rheumatic diseases treated with different JAK inhibitors. The responses were compared with age, gender and disease-matched healthy controls. Patients with IMRDs treated with JAK inhibitors showed reduced seroconversion rate (63% vs 100% and lower VZV IgG titers (1222 ± 411 vs 3048 ± 556, p< 0.0001) as compared with healthy controls. Functional T CD4 (IL-2 plus IFN-γ secretion) and T CD8 (Granzyme A and/or Granzyme B secretion) immune responses were also significantly diminished in IMRDs patients. Negative correlation was found between VZV antibody titers and age, specific treatments (baricitinib, tofacitinib, upadacitinib), cumulative methotrexate and glucocorticoid doses, history of multiple DMARDs, and treatment duration with JAK inhibitors. Functional T-CD4 responses but not functional T-CD8 responses also showed similar negative correlations. Positive associations were observed between functional T-CD4 and T-CD8 responses. Our study provides valuable insights into the immune responses elicited by the recombinant inactive vaccine in patients with IMRDs treated with JAK inhibitors. In these patients we have observed a broad impact on the adaptive humoral and cellular immune responses, suggesting a potential reduction in protection against herpes zoster infection and VHZ reactivation.

Molecular Biology for Diagnosis of Congenital and Neonatal Infections in the Cerebrospinal Fluid of Newborns from a Brazilian Tertiary Hospital

The risk of infection transmission from mother to fetus depends on the pathogen. TORCH agents cause some neuroinfections, including Toxoplasmosis, rubella, Cytomegalovirus, herpes simplex 1 and 2, and others (Varicella Zoster, Parvovirus B-19, Epstein–Barr virus, and Zika virus). The consequences can be stillbirth, prematurity, uterine growth restriction, and congenital malformations. The detection of DNA/RNA from CSF by molecular methods is a marker of the involvement of congenital infection in the central nervous system. This study aimed to identify the frequency of these pathogens in CSF samples from newborns (1 to 28 days old) at a tertiary hospital, using PCR, and determine the clinical consequences. Methods: This was a prospective descriptive study involving the molecular analysis of 151 CSF samples from neonates, collected for cytological and biochemical diagnosis from 2017 to 2021. After the results and consent from the participants’ caregivers were obtained, the leftover material was sent to the University’s Virology Laboratory and submitted for DNA/RNA extraction and Nested-PCR/RT-PCR. A review of the patients’ medical records and descriptive statistics was performed. This work was approved by the Ethics Committee (CAAE: 86760218.3.0000.5404). Results: A total of 151 CSF samples were obtained, 16 of which were positive (10.6% [95% CI%: 6.18–16.63%]). Two of these were PCR-positive for HSV-1 (1.3%), four for VZV (2.6%), one for CMV (0.67%), two for Toxoplasmosis (1.3%), four for Parvovirus B-19 (2.6%), and four for Zika (2.6%). The proportion of positive PCR results was higher in the group that presented with malformations (25.0% vs. 8.4%, p = 0.040). Conclusions: The pathogens identified by PCR were mostly Zika virus, VZV, and B-19, and these were mainly found in newborns with malformations.

Genotype of Varicella-zoster virus isolated in Jiangsu, China

ObjectiveTo analyze the genotypes of VZV in Jiangsu province to identify vaccine strains and wild strains, providing a molecular biological background for the effective prevention and control of varicella.MethodStratified sampling was used to collect herpes fluid or throat swab from patients diagnosed with varicella. ORF22 was carried out, and the restriction enzyme site of ORF38, ORF54 and ORF62 were detected.ResultsAll 207 virus strains were Clade 2 type by sequencing the PCR products of ORF22. The sequencing results showed that five SNP sites changed compared to the Dumas reference strain(Clade 1). From A to G at 37,902, from T to c at 38,055, from A to C at 38,081, and from G to A at 38,177, from G to A at 39,394. The prevalent VZV genotypes in Jiangsu is consistent with the P-Oka. The restriction enzyme site analysis of PCR amplification products from ORF38 (PstI), ORF54 (BglI), ORF62 (SmaI) showed that all 207 virus strains were wild-type. There were two different types of the wild strains, and 183 strains (88.4%) were PstI (+), BglI (+), SmaI (-). The wild strains between different regions showed no significant differences (χ2 = 0.05, P = 0.982).ConclusionsThe prevalent VZV genotypes are Clade 2 and the prevalent virus strains are wild strains in Jiangsu Province, the primary wild strain observed is mainly PstI (+), BglI (+), SmaI (-).

Causal effect of gut microbiota on occurrence of herpes zoster and postherpetic neuralgia, and role of Tyzzerella 3

BackgroundPrevious research has established connections between gut microbiota, immune modulation, and several virus-related diseases. However, no study has explored the relationships between gut microbiota and herpes zoster and postherpetic neuralgia (PHN).MethodsA total of 205 taxa of gut microbiota were regarded as exposures. The occurrences of herpes zoster and PHN were selected as outcomes. The causal effects of gut microbiota on herpes zoster and PHN were estimated with multiple methods for two-sample Mendelian randomization, such as inverse variance weighted (IVW), MR–Egger, and weighted median. All results were subjected to FDR correction to prevent from possibility of multiple comparison.ResultsAmong the significant findings, four taxa and one genus were identified as facilitators of herpes zoster and PHN, respectively. Conversely, six genera and eleven taxa were found to inhibit herpes zoster and PHN, respectively. The causal effect of the Tyzzerella 3 was confirmed through FDR correction, making it a key focus in this study. Specifically, it was found to causally facilitate herpes zoster primarily with IVW (OR 1.420, 95% CI 1.174–1.718, p < 0.001, q = 0.039), as there is no heterogeneity or horizontal pleiotropy found.ConclusionsWith investigation of the causal association between gut microbiota, and herpes zoster/PHN, significant findings were identified in 22 different taxa. Among them, Tyzzerella 3 keeps significant after multiple comparison correction, and displays potential to facilitate the occurrence of herpes zoster.Graphical

Ramsay hunt syndrome: a case report

Ramsay hunt syndrome (RHS) is a neurological condition comprising of complications with varicella zoster virus (VZV) which results in inflammation of geniculate ganglion. In the days to weeks following zoster, various cranial nerve palsies can develop because the varicella-zoster virus is latent in the cranial nerve ganglia. The trigeminal and facial nerves were the most commonly affected by zoster, based on the cranial nerve involvement. Another common impacted nerve was the vestibulocochlear nerve. As VZV is exclusively human pathogen, research on VZV latency is limited to only human ganglia examination. This case report describes about Ramsay Hunt Syndrome induced or also called as Herpes Zoster Oticus caused by Varicella zoster virus. Diagnosis mainly involved laboratory investigations, patient history, treatment data and other relevant information co-related from various literature. A 46-year-old female patient was diagnosed Ramsay hunt syndrome on the basis of clinical findings as right facial palsy, blisters over right pinna, otalgia and right ear erythematous lesions. Patient also exhibited deviation of angle of mouth to left side and unable to close right eye. This was accompanied by elevated erythrocyte sedimentation rate (ESR) exhibiting acute inflammation. Hemoglobin was low and total leukocyte count was high. Following that, corticosteroids and antivirals were prescribed to assist her medical condition. Remission is slow for RHS, hence patient was also advised for rehabilitation therapy to improvise her lower motor neuron facial palsy. Recurrence is possible in long term so it is imperative to initiate early treatment within 72 hours as soon as the symptoms are observed for better patient care.

Clinical Spectrum and Perspective in Bilateral Acute Retinal Necrosis: Systematic Review

Bilateral acute retinal necrosis (BARN) represents a broad ophthalmological field of severe retinal pathologies associated with poor visual prognosis and blindness. The purpose of this review is to examine the clinical spectrum in detail over the past few years, exploring laboratory and instrumental diagnosis, and providing useful and up-to-date guidance in this field. A systematic review of this field has been performed through the PRISMA guidelines, searching in the PUBMED database. Serological laboratory tests on blood or polymerase chain reaction (PCR) on aqueous humor or vitreous samples are crucial to identifying the underlying cause and choosing the timeliest strategic treatments. Often, the main cause remains herpesviruses, with Varicella zoster (VZV) predominating over the others. There are also other causes that one needs to be carefully aware of. Anatomical and functional recovery is unfavorable if they are not individuated in a quick time. Early diagnosis and timely treatment offer a better chance of visual improvement and the avoidance of complications. Complications worsen the visual prognosis over months and may require a surgical approach.

Vaccinations in pulmonary diseases - part 2: herpes zoste, RSV, pneumococcal infection and pertussis

RSV is a common cause of respiratory tract infections, posing a risk of severe disease, particularly for newborns and infants, as well as in older individuals with pre-existing conditions. Two safe and effective RSV vaccines were approved in 2023. These vaccines elicit protective antibodies and offer robust protection with no additional benefit from annual boosters. Both vaccines have been approved for individuals aged 60 years and older, while one of the vaccines has also been approved in pregnant women to elicit maternal immunity for passive protection of the unborn child. In Germany, RSV vaccination is currently recommended for all individuals aged 75 years and older, as well as people aged 60-74 years of age with severe underlying conditions. PNEUMOCOCCAL INFECTION: Streptococcus pneumoniae is a primary cause of community-acquired pneumonia (CAP). Since early 2022, a 20-valent conjugate vaccine (PCV20) is approved and recommended for people over 60 years of age and individuals over 18 years of age with risk factors. PCV20 replaces the 23-valent polysaccharide vaccine (PPV23) previously recommended for those over 60 years of age. Although viewed primarily as a childhood disease, the majority of infections affect adults. Patients with chronic respiratory diseases are at a higher risk for severe clinical course of pertussis infection. It has therefore been recommended that all adults should get a pertussis booster with their next scheduled tetanus vaccination, given as a combination vaccine (Tdap). For risk groups (healthcare personnel, community facilities) a booster vaccination every 10 years is recommended. Herpes Zoster (shingles) is caused by the varicella-zoster virus, and reactivations can lead to painful skin lesions and potential complications such as herpes zoster oticus, meningitis, or postherpetic neuralgia. People with chronic lung diseases such as COPD or asthma are at increased risk of herpes zoster-related complications. A recombinant adjuvanted inactivated vaccine was approved in 2018 and offers robust protection against herpes zoster and its complications. The vaccine is recommended for all people over 60 years of age and for certain risk groups over 50 years of age.

The continuous increase in the number of newly medically attended cases of herpes zoster did not accelerate during the coronavirus disease 2019 pandemic in Kanagawa, Japan.

Possible changes in the epidemiology of herpes zoster (HZ) since the emergence of the coronavirus disease 2019 (COVID-19) pandemic is an unfolding topic. The number of newly medically attended cases (NMAC) of HZ during the pandemic in Kanagawa Prefecture, Japan, was quantitatively investigated using a claims database. The study period was from April 2017 to March 2022. The number of NMAC of HZ showed a continuously increasing trend throughout the study period, which could be attributed to population aging. Autoregressive integrated moving average modeling and forecasting revealed that the increase in the actual number of NMAC of HZ since the start of the pandemic was generally similar to that predicted based on a model fitted using data from the pre-pandemic period, but at a slightly reduced pace. This slowdown suggests that refraining from medical visits during the pandemic affected HZ surveillance.

Concurrent Zoster Sine Herpete and Hepatosplenic Fungal Infection in a Cancer Patient: A Case Report

Concurrent Zoster Sine Herpete and Hepatosplenic Fungal Infection in a Cancer Patient: A Case Report

Paederus dermatitis after travelling: a case of misdiagnosis and clinical resolution.

A case of paederus dermatitis misdiagnosed as herpes zoster highlights the importance of clinical suspicion in returning travellers.

Atypical disseminated herpes zoster infections in patients with demyelinating disease treated with dimethyl fumarate.

We report two patients who developed atypical, disseminated herpes zoster infections while on dimethyl fumarate (DMF) treatment, one with varicella zoster virus (VZV) encephalitis and another with herpes zoster oticus resulting in lasting motor and sensory deficits. We recommend vaccination against VZV prior to DMF initiation be incorporated as standard of care, as ensuring patients are protected against VZV before starting DMF can prevent such severe outcomes.

Exploring the association between chronic prostatitis and the risk of herpes zoster in a cohort study in Taiwan.

The aim of the cohort research was to study the association between chronic prostatitis and the probability of herpes zoster in Taiwan. Using the National Health Insurance Research Database (NHIRD) of Taiwan, we selected male persons newly diagnosed with chronic prostatitis aged 20-84 years between 2013 and 2020. These male persons were then matched with a non-prostatitis group who did not have a diagnosis of prostatitis by using 1:1 propensity score matching on age and relevant comorbidities. All participants were observed either until a new diagnosis of herpes zoster was noted or until the completion of the study period in 2020. Cox proportional hazards regression analysis was employed to study the hazard ratio (HR) and 95% confidence interval (CI) for the risk of herpes zoster associated with chronic prostatitis. A total of 69 239 participants with chronic prostatitis and 69 239 participants with non-prostatitis were included in the analysis. The incidence rate of herpes zoster was higher in participants with chronic prostatitis compared to the non-prostatitis group (8.03 per 1000 person-years for chronic prostatitis group versus 4.74 per 1000 person-years for non-prostatitis group, incidence rate ratio = 1.69, and 95%CI = 1.59-1.81). After adjusting for co-variables, participants with chronic prostatitis were found to have a higher risk of developing herpes zoster compared to the non-prostatitis group (adjusted HR = 1.69, 95%CI = 1.59-1.81, and p < 0.001). This cohort research suggests that people with chronic prostatitis may have a greater risk of developing herpes zoster compared to the non-prostatitis group in Taiwan. Preventive strategies, such as the administration of the herpes zoster vaccine, might be beneficial in people with chronic prostatitis.

A Survey on Knowledge and Attitudes Towards Vaccination Against Herpes Zoster Virus Among Medical Oncologists for Patients with Solid Tumors.

Herpes zoster (HZ) virus reactivation is a significant medical problem among immunocompromised patients, especially considering its potential complications. Although the recombinant HZ vaccine has demonstrated > 90% efficacy against HZ in adults, its use is not as frequent as needed in daily oncology practice due to several barriers, including oncologists' knowledge, patients' willingness, and organizational issues. A web-based survey was sent to 139 oncologists treating solid tumors concerning their knowledge and attitudes toward the adjuvanted gE-based recombinant HZ vaccination. The survey included questions regarding the characteristics of medical oncologists participating, such as the type of hospital, main field of expertise, percent of work with patients, awareness of the HZ risk in cancer patients, knowledge of scientific data and scientific societies guidelines on HZ vaccination, familiarity with vaccinations, frequency of HZ detection in clinical practice, barriers, and challenges toward vaccine administration. Fifty-four physicians (46%; 95% CI 0.2918 to 0.5069) responded to all the questions. The main reason for non-response was the lack of time due to the overwhelming burden of assistance. When the survey was launched, 31 participants reported good knowledge of scientific and clinical data of HZ vaccines, 10% none, and 36 were aware of guidelines. Reported barriers included knowledge of the problem, patients' willingness, and organizational issues. Surveying medical oncologists on the adjuvanted gE-based recombinant HZ vaccination provides essential insights into their knowledge, attitudes, and practices regarding vaccination for cancer patients. These data suggest that continuing medical education is necessary to implement HZ vaccination prescription among oncologists.

The risk of postherpetic neuralgia in COVID-19 vaccination-associated herpes zoster: A retrospective cohort study using TriNetX

BackgroundThe administration of the COVID-19 vaccine has been linked to the development of herpes zoster (HZ). However, studies examining the clinical outcomes in COVID-19 vaccination-associated and non-COVID-19 vaccination-associated HZ are lacking. ObjectiveTo investigate the risk of postherpetic neuralgia (PHN) in COVID-19 vaccination associated HZ. MethodsA total of 7200 patients with COVID-19 vaccination-associated HZ and 7200 matched controls were enrolled from the US Collaborative Network in the TriNetX database. The main outcome of this study was the development of PHN.Patients were followed-up from 3 months after HZ until PHN diagnoses, withdrawal from the database, or October 8, 2024. ResultsWe observed that patients with COVID-19 vaccination-associated HZ had a significantly higher risk of developing PHN as compared to the control group, with hazard ratio of 1.69 (> 3 months), 1.80 (> 6 months), 1.86 (> 1 year), and 1.93 (>2 years), respectively. Additionally, the association remained significant in the stratified analysis, which included sex, age, malignancy status, and initial use of antiviral agents. ConclusionThis study showed that COVID-19 vaccination-associated HZ demonstrated a significantly higher risk of developing PHN.

Efficacy of Second-Line Biological Therapies in Moderate to Severe Ulcerative Colitis Patients with Prior Failure of Anti-Tumor Necrosis Factor Therapy: A Multi-Center Study.

Few studies have compared the efficacy and safety of second-line biological therapies in ulcerative colitis (UC) patients with prior exposure to anti-tumor necrosis factor (TNF) therapy. We aim to compare the efficacy and safety between ustekinumab, vedolizumab, and tofacitinib, a current option as second-line biological therapy with different mechanisms in those patients. This retrospective multi-center study was conducted across five institutions from 2011 to 2022. We enrolled patients with moderate to severe UC who failed anti-TNF therapy and subsequently received ustekinumab, vedolizumab, or tofacitinib as second-line biological therapy. The outcomes were analyzed for clinical response/remission and endoscopic improvement/remission rates after induction therapy, drug persistency, and adverse events. A total of 70 UC patients were included and grouped into ustekinumab (11 patients), vedolizumab (40 patients), and tofacitinib (19 patients) treatments. The clinical response/remission rates after induction therapy were similar between ustekinumab (90.9/81.8%), vedolizumab (92.5/65.0%), and tofacitinib (94.7/73.7%). There were no significant differences in the endoscopic improvement/remission rates between the three groups: 90.9/18.2% for ustekinumab, 72.5/12.5% for vedolizumab, and 84.2/26.3% for tofacitinib. Drug persistence was similar across the three agents (p = 0.130). Three patients of the tofacitinib group experienced adverse events (herpes zoster and hypertriglyceridemia). Based on real-world data, second-line biological therapy with ustekinumab, vedolizumab, and tofacitinib showed comparable efficacy in patients with moderate to severe UC with prior exposure to anti-TNF therapy.

Unveiling the Masked Culprit: Central Nervous System Infection With Varicella-Zoster Virus Diagnosed by Multiplex PCR in an Elderly Patient With Atypical Neurological Symptoms

Unveiling the Masked Culprit: Central Nervous System Infection With Varicella-Zoster Virus Diagnosed by Multiplex PCR in an Elderly Patient With Atypical Neurological Symptoms