Presence Of Neurological Symptoms Research Articles

NCOG-28. SERUM PROTEIN BIOMARKERS LINKED TO NEURODEGENERATIVE PROCESSES ARE ELEVATED IN GLIOMA PATIENTS AND ASSOCIATED WITH SEVERITY OF NEUROLOGIC SYMPTOMS

Abstract BACKGROUND Glioma patients frequently report neurologic symptoms, adding to the complexity of cancer management and negatively impacting quality of life. However, mechanisms associated with the development of neurologic symptoms in glioma patients remain unclear. Pathological changes in the brain of glioma patients might result in elevated peripheral blood levels of proteins previously linked to central nervous system (CNS) damage and neurodegeneration, including neurofilament light chain (NfL), tau, and glial fibrillary acidic protein (GFAP). Here, we tested the hypothesis that the circulating levels of these proteins in blood are elevated in glioma patients and associated with the severity of neurologic symptoms. METHODS Patients (n=73) were enrolled in a natural history study (NCT02851706, PI T. Armstrong). Healthy subjects (n=39) were recruited by the National Institutes of Health Clinical Center Blood Bank. Neurologic symptom severity and walking interference were assessed using MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT). Serum proteins were analyzed using ultrasensitive assays (Meso Scale Discovery). RESULTS Participants were predominantly white (patients 74%, healthy subjects 67%) and male (patients 58%, healthy subjects 54%). The median age was 44 (range=24,74) for patients and 49 (range=19,78) for healthy volunteers. No significant differences in age, sex, or race were observed between patients and healthy subjects. Serum levels of NfL (p<0.0001), GFAP (p<0.0001), and tau (p<0.0001) were higher in glioma patients when compared to healthy subjects. Patients with walking interference had higher levels of GFAP (p=0.003), NfL (p=0.003), and tau (p=0.004), and those who reported numbness had higher levels of GFAP (p=0.012). CONCLUSIONS These findings suggest that serum levels of protein markers of neurodegeneration are elevated in glioma patients and associated with the presence of neurologic symptoms. Blood-based biomarkers have the potential to shed light on the mechanisms underlying symptoms and offer a non-invasive alternative for monitoring CNS damage that impact patient outcomes.

Spine injuries among severely injured trauma patients: A retrospective single-center cohort study.

We aimed to determine the incidence and severity of spine injuries among severely injured trauma patients (Injury Severity Score (ISS)/New Injury Severity Score (NISS) > 15) treated in a single tertiary trauma center over 15 years. We also wanted to compare the demographics between patients with and without spine injuries and to determine the mortality of spine-injury patients. Data from the years 2006-2020 from the Helsinki Trauma Registry (HTR), a local trauma registry of the trauma unit of the Helsinki University Hospital (HUH), were reviewed. We divided patients into two groups, namely those with traumatic spine injury (TSI) and those without traumatic spine injury (N-TSI). TSI patients were further subdivided into groups according to the level of injury (cervical, thoracolumbar, or multilevel) and the presence of neurological symptoms. We included 2529 patients: 1336 (53%) had a TSI and 1193 (47%) had N-TSI. TSI patients were injured more frequently by a high-fall mechanism (37% vs 21%, p < 0.001). Among TSI patients, 38% of high-fall injuries were self-inflicted. High falls, young age, and female gender were overrepresented in spine-injury patients with a self-inflicted injury mechanism. Cervical spine-injury patients were mostly elderly persons injured by a low-energy mechanism. Unlike other severely injured trauma patients, severely injured trauma patients with spine injuries are more frequently injured by a high-fall mechanism and self-injury.

Long-Term Outcome of Motor Functional Neurological Disorder After Rehabilitation.

Functional neurological disorder (FND) is defined as the presence of neurological symptoms that are inconsistent with a neurological disease. We performed a single-center retrospective study aimed at determining the long-term outcome of FND patients receiving inpatient rehabilitation and the predictors of a good outcome. A multidisciplinary graded exercise program was provided with one or two daily physiotherapy and occupational therapy sessions on 5 days each week, as well as weekly psychological support. Outcome was assessed using the motor part of the Functional Independence Measure scale (FIM; maximum score of 91) at admission, discharge, and follow-up, with the last assessment performed by phone interview. The 30 included patients were aged 43.6±14.7 years (mean±standard deviation), comprised 70% females, and received a mean of 4 weeks of rehabilitation. The admission FIM score (80.2±8.3) was significantly lower than the discharge FIM score (86.9±4.6; p<0.001, Wilcoxon signed-rank test). No notable difference was observed between discharge and follow-up FIM scores (85.5±8.5, p=0.54). The mean follow-up of the 36-month FIM scores at discharge and follow-up was dichotomized as a good outcome in cases where all items were scored ≥6 (functional independence). Binomial logistic regression showed that absence of a comorbid psychiatric disorder (p=0.039, odds ratio=10.7) was a predictive factor for a good outcome at follow-up. Other variables (e.g., sex and age) were not significant predictors of clinical outcome (all p≥0.058). These results suggest inpatient intensive rehabilitation for motor FND is effective and produces favorable long-term results. Further studies with larger groups are warranted so that the management protocols can be standardized.

A Review of Syphilis Infection in Pediatric Patients

Nearly half of all sexually transmitted infections occur in adolescents and young adults. Among them, syphilis infections are on the rise in the United States. Sexually active adolescents, especially those who do not use condoms consistently or are men who have sex with men, are at particular risk for syphilis infection. With the rise in acquired syphilis infections, the incidence of congenital syphilis has also increased. Syphilis can have a variety of presentations based on infectious stage and central nervous system involvement. Careful physical examination and history can elicit the diagnosis. Screening with a nontreponemal test followed by treponemal testing can confirm the diagnosis, and staging is determined clinically. Testing for all sexually transmitted infections should be pursued because coinfections are common. Penicillin is the first-line treatment for syphilis, and duration of therapy depends on the presence of neurologic symptoms; all infants with possible congenital syphilis should receive treatment. Posttreatment monitoring is essential to confirm successful eradication of syphilis. All sexually active, at-risk patients, including pregnant persons, should be screened for syphilis, and those diagnosed as having syphilis should be counseled on disclosure to partners. Although not often found in a pediatric population, with the increasing incidence of syphilis infections in the United States, pediatric providers should have a low threshold for syphilis screening in adolescents and a high index of suspicion for congenital syphilis in infants.

Inflammation-Triggered Enlargement of Choroid Plexus in Subacute COVID-19 Patients with Neurological Symptoms.

To investigate whether choroid plexus volumes in subacute coronavirus disease 2019 (COVID-19) patients with neurological symptoms could indicate inflammatory activation or barrier dysfunction and assess their association with clinical data. Choroid plexus volumes were measured in 28 subacute COVID-19 patients via cerebral magnetic resonance imaging (MRI), compared with those in infection-triggered non-COVID-19 encephalopathy patients (n = 25), asymptomatic individuals after COVID-19 (n = 21), and healthy controls (n = 21). Associations with inflammatory serum markers (peak counts of leukocytes, C-reactive protein [CRP], interleukin 6), an MRI-based marker of barrier dysfunction (CSF volume fraction [V-CSF]), and clinical parameters like olfactory performance and cognitive scores (Montreal Cognitive Assessment) were investigated. COVID-19 patients showed significantly larger choroid plexus volumes than control groups (p < 0.001, η2 = 0.172). These volumes correlated significantly with peak leukocyte levels (p = 0.001, Pearson's r = 0.621) and V-CSF (p = 0.009, Spearman's rho = 0.534), but neither with CRP nor interleukin 6. No significant correlations were found with clinical parameters. In patients with subacute COVID-19, choroid plexus volume is a marker of central nervous system inflammation and barrier dysfunction in the presence of neurologic symptoms. The absence of plexus enlargement in infection-triggered non-COVID-19 encephalopathy suggests a specific severe acute respiratory syndrome coronavirus 2 effect. This study also documents an increase in choroid plexus volume for the first time as a parainfectious event. ANN NEUROL 2024.

OTHR-04. HEALTH SYSTEM DELAYS IN DIAGNOSIS AND TREATMENT OF CHILDREN WITH CENTRAL NERVOUS SYSTEM (CNS) TUMOURS IN SRI LANKA

Abstract BACKGROUND Children with central nervous system(CNS) tumours have to navigate multiple layers of care to reach the only centre providing oncology care (chemotherapy and radiotherapy) in Sri Lanka. This can lead to significant delays and affect outcomes. METHODS This is a retrospective study of patients less than 19 years registered at the National Cancer Institute Sri Lanka(NCISL) from 1st January 2022 to 31st December 2023. Data was extracted from clinic records and interviewing caregivers. RESULTS From a total of 828 new children with cancer 135 had CNS tunours and data was available for 130 for analysis. Commonest cancers seen were low grade gliomas and medulloblastoma. Fifty-one percent were males and the median age was 6 years (Range 1-18). Most common presenting symptoms were headache and vomiting. Median time from onset of symptoms to first medical contact was 4 days (InterQuartile Range(IQR) 1-9.5) and to first imaging it was 44 days (IQR 3-151) for all symptoms. In the presence of neurological symptoms, the time to imaging was 26 days (IQR 2-141). Ninety-six(74%) had upfront surgery at a median time 14 days from first imaging (IQR 7-34.5) with a median time of additional 25 days to reach an oncology centre (Range 7-94). Patients who did not have upfront surgery took 13.5 days (IQR 2-36.5) for the same. After arriving at the oncology centre, radiotherapy (80/130, 62%) was initiated in 24 days. When calculated from date of surgery radiotherapy initiation time was 61 days. (Range 5-88) CONCLUSION Although there seem to be no significant delay in presentation of children with CNS tumours to the health system, there were significant delays in imaging and initiating adjuvant radiotherapy. Further studies are warranted to determine the attributing factors and corrective steps to be taken to expedite referral of affected children.

Non-bacterial thrombotic endocarditis and pancreatic cancer: A literature review.

e24002 Background: Non-bacterial thrombotic endocarditis (NBTE) is a condition in which sterile vegetations are deposited on the cardiac valves, disrupting their function, and posing a risk for embolic stroke. It is a rare condition with rates in autopsy studies ranging from 0.9-1.6%1, and with some of the highest rates observed in patients with pancreatic cancer (PC).2 A review of PC-associated NBTE was conducted to improve our understanding and recognition of this rare but serious clinical entity. Methods: We performed a literature search in PubMed from database inception to November 2023 pairing keywords “Non-Bacterial Thrombotic Endocarditis”, “NBTE”, “Marantic Endocarditis”, “Sterile Endocarditis”, and “Libman-Sacks Endocarditis” with “Pancreatic Cancer”, “Adenocarcinoma of the Pancreas”, and “Neuroendocrine Pancreatic Cancer”. We also used the search term “Marantic Endocarditis associated with Pancreatic Cancer: A case series”. The database was filtered only for full text, English language, and human species. Results: We reviewed 17 studies and included 19 patients in this review. Diagnostic presentation included cerebral vascular accident (CVA) (n = 8), endocarditis (n = 3), or a thrombotic pathology such as deep venous thrombosis (DVT) or pulmonary embolism (PE) (n =4). NBTE (n = 12) was predominantly diagnosed before pancreatic cancer (n = 5). Echocardiography was positive for vegetations in most specified cases (14/15), blood cultures were negative in all specified cases (12/12), and abdominal imaging was consistent with pancreatic cancer in all specified cases (15/15). Metastatic disease was found in 13 out of 19 cases, with spread to liver (n = 13), lung (n = 2), and the adrenal glands (n = 1). Valvular localization identified mitral valve (n = 13), aortic valve (n = 7), and the tricuspid valve (n = 2). Treatment primarily focused on anticoagulation (n = 17), with low molecular weight heparin (n = 8) being the most common agent followed by unfractionated heparin (n = 6). 14 patients had expired by study publication, with 7 deaths occurring due to complications from pancreatic cancer and 2 occurring due to complications from NBTE. Conclusions: NBTE is a rare condition with non-specific presentation, with some of the highest rates seen in PC. Diagnosis of NBTE should prompt immediate treatment as per guidelines and investigation for an underlying malignancy. In PC, especially with metastatic disease, clinicians should maintain a low threshold to initiate an endocarditis work-up in the presence of neurologic symptoms or evidence of cardiac dysfunction. However, it is also important to note that 31% of NBTE cases occurred in the absence of metastatic PC, suggesting that even patients without advanced disease are at risk. Although NBTE associated with PC remains rare, given the severity of both conditions, clinicians should consider work-up for one disease process in the presence of the other.

Intracranial complications of acute mastoiditis: Surgery not always necessary

IntroductionAcute mastoiditis (AM) can rapidly become life-threatening with various intracranial complications. The standard care includes antibiotics, mastoidectomy, and drainage. Reports show varying preferences for conservative and surgical treatments, with a more conservative approach gaining popularity. In this study we aim to evaluate the presenting symptoms, management and outcomes of patients presenting with intracranial complications secondary to acute mastoiditis. MethodsRetrospective review for all children admitted for acute mastoiditis for 12 years period (January 2010–December 2021). Children who had mastoiditis associated with intracranial complications were included in the study. STROBE guidelines were followed in this study. Results23 patients were diagnosed with acute mastoiditis with intracranial complications. The mean age was 2.1 years. The most common presenting sign was fever, followed by otalgia. The most common pathogens were Fusobacterium necrophorum and Streptococcus pneumoniae. The most common intracranial complication was sinus vein thrombosis (SVT) affecting 13 patients. Eventually, 10 patients underwent cortical mastoidectomy during 1–6 days upon admission, with an average of 3.2 days. During the follow-up period patients were monitored for clinical progression. Patients who did not show clinical improvement such as persistent fever, worsening symptoms, or the presence of neurological symptoms were treated surgically. The length of stay was an average of 15.5 days overall, with no significantly longer hospital stay in patients who were treated surgically compared to patients who were treated conservatively (17.1 days vs. 14.2 days, P = .26). ConclusionIntracranial complications of acute mastoiditis remain a significant challenge. Selected patients with intracranial complications can be treated conservatively with close monitoring, without increasing the risk of immediate or long-term complications. Initial antimicrobial treatment should cover anaerobic bacteria, as it correlates with severe complications.

Neurosyphilis is characterized by a compartmentalized and robust neuroimmune response but not by neuronal injury

Neurosyphilis is increasing in prevalence but its pathophysiology remains incompletely understood. This study assessed for CNS-specific immune responses during neurosyphilis compared to syphilis without neurosyphilis and compared these immune profiles to those observed in other neuroinflammatory diseases. Participants with syphilis were categorized as having neurosyphilis if their cerebrospinal fluid (CSF)-venereal disease research laboratory (VDRL) test was reactive and as having syphilis without neurosyphilis if they had a non-reactive CSF-VDRL test and a white blood cell count <5/μL. Neurosyphilis and syphilis without neurosyphilis participants were matched by rapid plasma reagin titer and HIV status. CSF and plasma were assayed for markers of neuronal injury and glial and immune cell activation. Bulk RNA sequencing was performed on CSF cells, with results stratified by the presence of neurological symptoms. CSF neopterin and five CSF chemokines had levels significantly higher in individuals with neurosyphilis compared to those with syphilis without neurosyphilis, but no markers of neuronal injury or astrocyte activation were significantly elevated. The CSF transcriptome in neurosyphilis was characterized by genes involved in microglial activation and lipid metabolism and did not differ in asymptomatic versus symptomatic neurosyphilis cases. The CNS immune response observed in neurosyphilis was comparable to other neuroinflammatory diseases and was present in individuals with neurosyphilis regardless of neurological symptoms, yet there was minimal evidence for neuronal or astrocyte injury. These findings support the need for larger studies of the CSF inflammatory response in asymptomatic neurosyphilis. This work was funded by the National Institutes of Health, grants K23MH118999 (S.F.F.) and R01NS082120 (C.M.M.).

Determinants of Symptomatic Intracranial Progression After an Initial Stereotactic Radiosurgery Course

Purpose: Clinical and imaging surveillance of patients with brain metastases (BMs) is important after stereotactic radiosurgery (SRS), as many will experience intracranial progression (ITCP) requiring multidisciplinary management. The prognostic significance of neurologic symptoms at the time of ITCP is poorly understood. Materials/MethodsThis was a multi-institutional, retrospective cohort study from 2015-2020, including all patients with BMs completing an initial course of SRS. The primary outcome was overall survival (OS) by presence of neurologic symptoms at ITCP. OS, freedom from ITCP (FF-ITCP), and freedom from symptomatic ITCP (FF-SITCP) were assessed via Kaplan-Meier method. Cox proportional hazard models tested parameters impacting FF-ITCP and FF-SITCP. Results: Among 1383 patients, median age was 63.4 years, 55% were female, and common primaries were non-small cell lung (49%), breast (15%), and melanoma (9%). At a median follow up of 8.72 months, asymptomatic and symptomatic ITCP were observed in 504 (36%) and 194 (14%) patients respectively. The majority of ITCP were distant ITCP (79.5%). OS was worse with SITCP (median 10.2 vs 17.9 months, p<0.001). SITCP was associated with clinical factors including total treatment volume (P = 0.012), melanoma histology (P = 0.001), prior WBRT (P = 0.003), number of brain metastases (P < 0.001), interval of 1-2 years from primary and brain metastasis diagnosis (P = 0.012), controlled extracranial disease (P = 0.042), and receipt of pre-SRS chemotherapy (P = 0.015). Patients who were younger and received post-SRS chemotherapy (P = 0.001), immunotherapy (P < 0.001), and targeted or small-molecule inhibitor therapy (P < 0.026) had better FF-SITCP. Conclusions: In this cohort study of BM patients completing SRS, neurologic symptoms at ITCP is prognostic for OS. This data informs post-SRS surveillance in clinical practice as well as future prospective studies needed in the modern management of BMs.

FIB4 score is increased in severe preeclampsia

Abstract Objectives This study aims to investigate how the fibrosis index based on four factors (FIB-4) is altered in preeclampsia and whether the FIB-4 score differs with respect to the severity of preeclampsia and the presence of fetal and maternal adverse outcomes. Methods One hundred and forty-two patients with mild preeclampsia (34.6 %), one hundred and ninety patients who have preeclampsia with severe features (46.2 %), and 79 healthy pregnant controls (19.2 %) were included in the study. Fetal adverse outcomes occurred in 40.1 %, and maternal adverse outcomes only appeared as neurological symptoms in 20.5 % of the preeclampsia patients. Results Healthy controls had significantly lower FIB-4 scores than women with mild preeclampsia, and women with mild preeclampsia had significantly lower FIB-4 scores than women who had preeclampsia with severe features (respectively 0.58±0.29 vs. 0.68±0.44 vs. 1.93±4.92, p=0.003). The FIB-4 scores of preeclampsia patients with neurologic symptoms and preeclampsia patients with fetal adverse events were found to be similar to preeclampsia patients who did not have these problems. In ROC curve analysis, FIB-4 scores ≥0.758 indicated the presence of neurologic symptoms in preeclampsia patients, with a sensitivity of 0.66 and a specificity of 0.66 (p=0.004). Conclusions To the best of our knowledge, this is the first study to establish the FIB-4 scores of preeclampsia patients and determine if FIB-4 scores change with respect to maternal and fetal adverse outcomes. Our findings suggest that FIB-4 might be used to predict pregnancies destined to be complicated with preeclampsia and preeclampsia patients who are more likely to experience maternal and fetal adverse outcomes.

Analysis of clinicopathological features and prognostic factors of breast cancer brain metastasis.

Breast cancer (BC) has become the most common malignancy in women. The incidence and detection rates of BC brain metastasis (BCBM) have increased with the progress of imaging, multidisciplinary treatment techniques and the extension of survival time of BC patients. BM seriously affects the quality of life and sur-vival prognosis of BC patients. Therefore, clinical research on the clinicopathological features and prognostic factors of BCBM is valuable. By analyzing the clinicopathological parameters of BCBM patients, and assessing the risk factors and prognostic indicators, we can perform hierarchical diagnosis and treatment on the high-risk population of BCBM, and achieve clinical benefits of early diagnosis and treatment. To explore the clinicopathological features and prognostic factors of BCBM, and provide references for diagnosis, treatment and management of BCBM. The clinicopathological data of 68 BCBM patients admitted to the Air Force Medical Center, Chinese People's Liberation Army (formerly Air Force General Hospital) from 2000 to 2022 were collected. Another 136 BC patients without BM were matched at a ratio of 1:2 based on the age and site of onset for retrospective analysis. Categorical data were subjected to χ2 test or Fisher's exact probability test, and the variables with P < 0.05 in the univariate Cox proportional hazards model were incorporated into the multivariate model to identify high-risk factors and independent prognostic factors of BCBM, with a hazard ratio (HR) > 1 suggesting poor prognostic factors. The survival time of patients was estimated by the Kaplan-Meier method, and overall survival was compared between groups by log-rank test. Multivariate Cox regression analysis showed that patients with stage III/IV tumor at initial diagnosis [HR: 5.58, 95% confidence interval (CI): 1.99-15.68], lung metastasis (HR: 24.18, 95%CI: 6.40-91.43), human epidermal growth factor receptor 2 (HER2)-overexpressing BC and triple-negative BC were more prone to BM. As can be seen from the prognostic data, 52 of the 68 BCBM patients had died by the end of follow-up, and the median time from diagnosis of BC to the occurrence of BM and from the occurrence of BM to death or last follow-up was 33.5 and 14 mo, respectively. It was confirmed by multivariate Cox regression analysis that patients with neurological symptoms (HR: 1.923, 95%CI: 1.005-3.680), with bone metastasis (HR: 2.011, 95%CI: 1.056-3.831), and BM of HER2-overexpressing and triple-negative BC had shorter survival time. HER2-overexpressing, triple-negative BC, late tumor stage and lung metastasis are risk factors of BM. The presence of neurological symptoms, bone metastasis, and molecular type are influencing prognosis factors of BCBM.

Cerebellar peduncle damage in Langerhans cell histiocytosis-associated neurodegenerative disease revealed by diffusion tensor imaging.

To confirm the hypothesis that brain white matter damage is involved in the pathogenesis and disease progression of Langerhans cell histiocytosis (LCH)-associated neurodegenerative disease (ND), we aimed to analyze pediatric patients with LCH using diffusion tensor imaging (DTI). We enrolled 33 patients with LCH and obtained 33 DTI datasets. Using DTI-based tractography, fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD) were measured in the cerebral and cerebellar white matter tracts. The participants were divided into three groups-non-ND, ND without clinical symptoms (r-ND), and ND with clinical symptoms (c-ND)-according to their clinical status during the examination with DTI. We compared the DTI parameters in white matter tracts were compared among the three groups. In the order of non-ND, r-ND, and c-ND groups, the FA in superior cerebellar peduncle (SCP) and middle cerebellar peduncle (MCP) significantly decreased, the ADC, AD, and RD of MCP, and the RD of SCP were significantly elevated (FA-SCP; p < 0.001, FA-MCP; p = 0.026, ADC-MCP; p < 0.001, AD-MCP; p = 0.002, RD-MCP; p = 0.003, and RD-SCP; p = 0.018). Furthermore, in the simple linear regression analysis, the FA, ADC, AD, and RD values in the MCP and the FA value in the SCP were significantly influenced by the presence of neurological symptoms and ND findings on MRI (all p < 0.001). In LCH-ND, we identified microstructural damage in the SCP and MCP. DTI parameters in these tracts may help monitor LCH-ND; therefore, future studies are required to validate these results in a large cohort.

The Prevalence, Seroprevalence, and Risk Factors of Tick-Borne Encephalitis Virus in Dogs in Lithuania, a Highly Endemic State.

The rising awareness and increasing number of case reports of tick-borne encephalitis (TBE) in dogs indicate that the virus might be an important tick-borne pathogen in dogs, especially in endemic areas. Therefore, the aim of the present study was to investigate the prevalence rate of TBEV RNA and TBEV-specific antibodies in clinical samples of dogs living in a highly endemic region of Lithuania and to evaluate the main risk factors for severe disease course and death. The blood samples (n = 473) of dogs were collected in two veterinary clinics in central Lithuania. Tick-borne encephalitis virus (TBEV) RNA was detected in 18.6% (88/473; CI 95% 15.2-22.4) and TBEV-specific antibodies were found in 21.6% (102/473; CI 95% 17.9-25.6) of dog blood serum samples after confirmation with a virus neutralization test. The death/euthanasia rate was 18.2% (16/88; CI 95% 10.8-27.8) in PCR-positive dogs. Male dogs were more likely to develop neurological symptoms (p = 0.008). Older dogs (p = 0.003), dogs with the presence of neurological symptoms (p = 0.003), and dogs with the presence of TBEV-specific antibodies (p = 0.024) were more likely to experience worse outcomes of the disease. The results of the present study demonstrate that TBEV is a common and clinically important pathogen in dogs in such endemic countries as Lithuania.

Knowledge, attitude and practice among mothers on the relationship between honey and botulism in Saudi Arabian infants: a cross-section study

Background Botulism is a rare disease, and infant botulism (IB) even rarer, especially when steering the condition to honey consumption. IB is considered a life-threatening disease as it leads to severe neurological symptoms. Exploring the knowledge, attitude, and practice (KAP) among mothers on the relationship between honey and IB will help public health professionals implement appropriate maternal health education materials targeting infant health and increase the awareness of the paediatric primary care providers, physicians, and nurse practitioners about the risk of IB among their patients. Objectives To determine the knowledge of mothers from Hail city in Saudi Arabia (SA) regarding IB and assess their attitude and practice towards feeding honey to their infants before 12 months of age. Methods Using a comparative cross-sectional study, in February 2022, we broadcasted an online questionnaire through social networking and evaluated the KAP of 385 mothers. Results Less than half (48%) of the mothers have heard about IB, 40% of them knew the relation between honey ingestion and IB and only 6.5% acknowledged that they knew the causative agent for IB. The prevalence of feeding honey to infants before 12 months was 52%. Mothers from Hail city were less likely to provide honey to their infants (p = 0.002). Conclusion The study revealed that mothers from Hail city have relatively low knowledge of IB and that they hold favourable perceptions of using honey as a food supplement and feeding honey to their infants before 12 months. Considering the high prevalence of honey feeding with the known low incidence of IB in SA, Medical professionals should consider IB in their differential diagnosis particularly in the presence of neurological symptoms.

Ayurvedic Management along with Hypnotherapy in Functional Neurological Symptom Disorder (Conversion Disorder)

Functional neurological symptom disorder (FND)/Conversion disorder may be broadly defined as the presence of neurologic symptoms in the absence of a neurologic diagnosis, or when a neurologic diagnosis exists, it does not fully account for all of the patient’s symptoms. The cardinal symptom is limited solely to neurological symptoms. The diagnosis is made on the basis of the positive findings of the examination demonstrating preserved neurological function. Yoshapasmara, described in Madhava nidana, is comparable to FND where gathi / samvedhana (motor or sensory functions) are lost in the absence of underlying neurological conditions.&#x0D; A 29-year female was admitted with C/o Weakness and numbness in the left lower limb for 6 months. She had severe stress factors due to family conflicts. One day after a conflict with her mother-in-law, she felt difficulty walking on her left leg. They consulted a neurologist and done imaging, which was normal. On detailed clinical examination, the diagnosis was FND. She was managed with Internal medications and Udwartana, Abyanga, and Vyathyasa chikitsa (Dry and unctuous therapies alternatively). Hypnotherapy was administered in addition to Ayurvedic management to address stress factors. There were noticeable changes in the Perceived Stress Scale (PSS), muscle strength, and could walk without assistance with some difficulty after treatment. The neuropsychiatric perspective incorporating biopsychosocial aspects at the individual level, including consideration of Psychological and Spiritual aspects wherever relevant, is crucial for better outcomes in such cases.

Diagnostic Challenges of Rosai-Dorfman Disease Presenting as Pachymeningitis and Meningiomatosis: A Report of Two Unusual Cases Involving the Spinal Cord

Rosai-Dorfman disease (RDD) is an exceptionally rare medical condition, with spinal cord involvement even more infrequent. It is frequently misidentified as another malignancy or infectious disease. In this report, we present two cases of RDD with spinal cord involvement. Each patient presented with spinal intradural extramedullary masses within the thoracic and cervical levels, respectively. The differential diagnoses remained uncertain, with the potential for pachymeningitis and meningiomatosis due to the shared nature of nonspecific imaging findings and clinical symptoms in both conditions. Given the presence of neurologic symptoms and spinal cord compression, the individual lesions were surgically excised. Subsequent pathological analysis definitively confirmed the diagnosis of RDD. As an adjunctive therapeutic measure, both patients were orally administered prednisolone. Both patients exhibited favorable neurologic improvement. These cases highlight the diagnostic challenges of RDD when solely relying on imaging studies. Surgical intervention, in conjunction with a meticulous pathologic examination, is imperative for a precise diagnosis and guides appropriate treatment strategies. The multifaceted spatial manifestation of this disease further underscores the potential for multifocal occurrences within the central nervous system, providing an avenue for improved comprehension of the underlying mechanisms contributing to its dissemination.

Clinical Management and Therapy of Precocious Puberty in the Sapienza University Pediatrics Hospital of Rome, Italy.

Puberty identifies the transition from childhood to adulthood. Precocious puberty is the onset of signs of pubertal development before age eight in girls and before age nine in boys, it has an incidence of 1/5000-1/10,000 with an F:M ratio ranging from 3:1 to 20:1. Precocious puberty can be divided into central, also known as gonadotropin-dependent precocious puberty or true precocious puberty, and peripheral, also recognized as gonadotropin-independent precocious puberty or precocious pseudopuberty. Thus, the main aim of this narrative report is to describe the standard clinical management and therapy of precocious puberty according to the experience and expertise of pediatricians and pediatric endocrinologists at Policlinico Umberto I, Sapienza University of Rome, Italy. In the suspicion of early sexual maturation, it is important to collect information regarding the age of onset, the speed of maturation of secondary sexual features, exposure to exogenous sex steroids and the presence of neurological symptoms. The objective examination, in addition to the evaluation of secondary sexual characteristics, must also include the evaluation of auxological parameters. Initial laboratory investigations should include serum gonadotropin levels (LH and FSH) and serum levels of the sex steroids. Brain MRI should be performed as indicated by the 2009 Consensus Statement in all boys regardless of chronological age and in all girls with onset of pubertal signs before 6 years of age. The gold standard in the treatment of central precocious puberty is represented by GnRH analogs, whereas, as far as peripheral forms are concerned, the triggering cause must be identified and treated. At the moment there are no reliable data establishing the criteria for discontinuation of GnRH analog therapy. However, numerous pieces of evidence suggest that the therapy should be suspended at the physiological age at which puberty occurs.

Diversities in Leigh Syndrome Associated with MT-ATP6 Gene Variants.

Leigh syndrome (LS) is clinically and genetically heterogeneous and presents defective mitochondrial bioenergetics. Patients present neurological symptoms and imagiological features that may result in early death [1]. The LS has been associated with mitochondrial DNA (mtDNA) variants, e.g., m.8993T>G (L156R) and m.8993T>C (L156P), in the MT-ATP6 gene. They lead to the substitution of a highly conserved amino acid in subunit 6 of ATP synthase, affecting the F0 domain and ATP synthesis [1-3]. We present five cases with m.8993T>G and a family harbouring m.8993T>C+m.1555A>G (proband and four relatives). Our laboratory received 48 samples from LS-suspected patients. The samples (various tissues) were assessed for bioenergetics (activity of mitochondrial respiratory chain (MRC) complexes, ubiquinone content) and genetic analyses (mtDNA copy number, Sequencing and PCR-RFLP) by established protocols. Bioenergetics were assessed in 5 patients (various tissues) with varying levels of MRC/ATP synthase impairment. Six cases had a mtDNA pathogenic variant in the 8993 nucleotide associated with LS. Five cases presented the m.8993T>G variant, one of which (P5) possibly de novo. This variant was homoplasmy (P1-3) or very high heteroplasmy (P4/5, 90-95%). Of the four patients with bioenergetics assessment, three (P1/3/4) had deficiencies of MRC complexes, and P5 had small deficits. The other case (familial, proband and 4 relatives) presented a combination of m.1555A>G (homoplasmy) and m.8993T>C (heteroplasmy) variants. The proband presents m.8993T>C in 95% heteroplasmy and 85-35% in three relatives. All have m.1555A>G in homoplasmy, including the fourth relative without m.8993T>C. A deficiency (31%) was found in complex V activity in muscle for proband. We present a case series of patients harbouring pathogenic variants in the 8993 nucleotide of mtDNA, which have been associated with LS and impairment of MRC's complex V. These cases highlight the variability in clinical symptoms and their severity, as well as genetic heterogeneity within LS. Many patients will not present a classic pathogenic variant and there are many cases of asymptomatic relatives (carriers). It is important to get a broader view of the cases - classical methods and multiple tissue analysis are still valuable tools for the comprehensive characterization of patients.

Long-term treatment outcomes of temozolomide-based chemoradiation in patients with adult-type diffuse IDH-mutant grade 2 astrocytoma

PurposeTo report the long-term outcomes in adult patients with grade 2 IDH-mutant astrocytoma treated with temozolomide (TMZ)-based chemoradiation. Methods: One hundred and three patients with histologically proven grade 2 astrocytoma received radiation therapy (RT), 50.4–54 Gy in 1.8 Gy fractions, and adjuvant TMZ up to 12 cycles. Fifty-two patients received RT at the time of tumor progression and 51 in the early postoperative period for the presence of at least one high-risk feature (age > 40 years, preoperative tumor size > 5 cm, large postoperative residual tumor, tumor crossing the midline, or presence of neurological symptoms). Overall survival (OS) and progression-free survival (PFS) were calculated from the time of diagnosis.ResultsWith a median follow-up time of 9.0 years (range, 1.3–15 years), median PFS and OS times were 9 years (95%CI, 6.6–10.3) and 11.8 years (95%CI, 9.3–13.4), respectively. Median PFS was 10.6 years in the early treatment group and 6 years in delayed treatment group (hazard ratio (HR) 0.30; 95%CI 0.16–0.59; p = 0.0005); however, OS was not significantly different between groups (12.8 vs. 10.4 years; HR 0.64; 95%CI 0.33–1.25; p = 0.23). Extent of resection, KPS, and small residual disease were associated with OS, with postoperative tumor ≤ 1 cc that emerged as the strongest independent predictor (HR: 0.27; 95%CI 0.08–0.87; p = 0.01).ConclusionsTMZ-based chemoradiation is associated with survival benefit in patients with grade 2 IDH-mutant astrocytoma. For this group of patients, chemoradiation can be deferred until time of progression in younger patients receiving extensive resection, while early treatment should be recommended in high-risk patients.