Neurological Manifestations Research Articles

Outcome predictors of post-COVID conditions in the European Academy of Neurology COVID-19 registry.

Several neurological manifestations are part of the post-COVID condition. We aimed to: (1) evaluate the 6-month outcome in the cohort of patients with neurological manifestations during the COVID-19 acute phase and surviving the infection, and find outcome predictors; (2) define the prevalence and type of neurological symptoms persistent at six months after the infection. Data source was an international registry of patients with COVID-19 infection and neurological symptoms, signs or diagnoses established by the European Academy of Neurology. Functional status at six-month follow-up was measured with the modified Rankin scale (mRS), and defined as: "stable/improved" if the mRS at six months was equal as or lower than the baseline score; "worse" if it was higher than the baseline score. By October 30, 2022, 1,003 lab-confirmed COVID-19 patients were followed up for a median of 6.5months. Compared to their pre-morbid status, 522 patients (52%) were stable/improved, whereas 465 (46%) were worse (functional status missing for 16). Age, hospitalization, several pre-COVID-19 comorbidities, and COVID-19 general complications were predictors of a worse status. Amongst neurological manifestations, stroke carried the highest risk for worse outcome (OR 5.96), followed by hyperactive delirium (2.8), and peripheral neuropathies (2.37). On the other hand, hyposmia/hypogeusia (0.38), headache (0.40), myalgia (0.45), and COVID-19 vaccination (0.52) were predictors of a favourable prognosis. Persisting neurological symptoms or signs were reported by 316/1003 patients (31.5%), the commonest being fatigue (n = 133), and impaired memory or concentration (n = 103). Our study identified significant long-term prognostic predictors in patients with COVID-19 and neurological manifestations.

The neurological decline and psychological factors caused by coronavirus disease 2019 may be predictors of erectile dysfunction.

Since the outbreak of coronavirus disease 2019, it has had a serious impact on people's physical and mental health. However, in our clinical work, we have found that the erectile function of coronavirus disease 2019 patients with neurological decline was often seriously affected. To further explore the relationship between erectile dysfunction and neurological dysfunction caused by coronavirus disease 2019. We conducted a survey from August 2022 to February 2023 at the First Affiliated Hospital of Anhui Medical University and the Third People's Hospital of Linyi City. A total of 251 subjects with a history of coronavirus disease 2019 infection were included. Symptoms and changes in erectile function after the coronavirus disease 2019 infection were collected and assessed using the International Index of Erectile Function-5 scale and several targeted questions. In this study, we found that in patients infected with novel coronavirus, the proportion of erectile dysfunction was higher in those with neurological manifestations such as olfactory and taste impairment or psychological symptoms such as anxiety. We found that neurological decline and psychological factors were independent and significant risk factors for erectile dysfunction caused by coronavirus disease 2019. Patients with neurological damage or psychiatric symptoms are more likely to have erectile dysfunction, suggesting that the 2019 novel coronavirus may affect erectile function by damaging nerves. This provides a new insight into the mechanism of erectile dysfunction.

Cross Talks between CNS and CVS Diseases: An Alliance to Annihilate.

Cardiovascular and neurological diseases cause substantial morbidity and mortality globally. Moreover, cardiovascular diseases are the leading cause of death globally. About 17.9 million people are affected by cardiovascular diseases and 6.8 million people die every year due to neurological diseases. The common neurologic manifestations of cardiovascular illness include stroke syndrome which is responsible for unconsciousness and several other morbidities significantly diminished the quality of life of patients. Therefore, it is prudent need to explore the mechanistic and molecular connection between cardiovascular disorders and neurological disorders. The present review emphasizes the association between cardiovascular and neurological diseases specifically Parkinson's disease, Alzheimer's disease, and Huntington's disease.

Neurological manifestations and risk factors associated with poor prognosis in hospitalized children with Omicron variant infection.

There are increasing reports of neurological manifestation in children with coronavirus disease 2019 (COVID-19). However, the frequency and clinical outcomes of in hospitalized children infected with the Omicron variant are unknown. The aim of this study was to describe the clinical characteristics, neurological manifestations, and risk factor associated with poor prognosis of hospitalized children suffering from COVID-19 due to the Omicron variant. Participants included children older than 28days and younger than 18years. Patients were recruited from December 10, 2022 through January 5, 2023. They were followed up for 30days. A total of 509 pediatric patients hospitalized with the Omicron variant infection were recruited into the study. Among them, 167 (32.81%) patients had neurological manifestations. The most common manifestations were febrile convulsions (n = 90, 53.89%), viral encephalitis (n = 34, 20.36%), epilepsy (n = 23, 13.77%), hypoxic-ischemic encephalopathy (n = 9, 5.39%), and acute necrotizing encephalopathy (n = 6, 3.59%). At discharge, 92.81% of patients had a good prognosis according to the Glasgow Outcome Scale (scores ≥ 4). However, 7.19% had a poor prognosis. Eight patients died during the follow-up period with a cumulative 30-day mortality rate of 4.8% (95% confidence interval (CI) 1.5-8.1). Multivariate analysis revealed that albumin (odds ratio 0.711, 95% CI 0.556-0.910) and creatine kinase MB (CK-MB) levels (odds ratio 1.033, 95% CI 1.004-1.063) were independent risk factors of poor prognosis due to neurological manifestations. The area under the curve for the prediction of poor prognosis with albumin and CK-MB was 0.915 (95%CI 0.799-1.000), indicating that these factors can accurately predict a poor prognosis. Conclusion: In this study, 32.8% of hospitalized children suffering from COVID-19 due to the Omicron variant infection experienced neurological manifestations. Baseline albumin and CK-MB levels could accurately predict poor prognosis in this patient population. What is Known: • Neurological injury has been reported in SARS-CoV-2 infection; compared with other strains, the Omicron strain is more likely to cause neurological manifestations in adults. • Neurologic injury in adults such as cerebral hemorrhage and epilepsy has been reported in patients with Omicron variant infection. What is New: • One-third hospitalized children with Omicron infection experience neurological manifestations, including central nervous system manifestations and peripheral nervous system manifestations. • Albumin and CK-MB combined can accurately predict poor prognosis (AUC 0.915), and the 30-day mortality rate of children with Omicron variant infection and neurological manifestations was 4.8%.

Clinical profile and prognosis of COVID-19 patients with neurological manifestations: A city-wide cross- sectional study in Iran

Background & Objective: In this study, we aimed to evaluate past medical and social history, initial symptoms, laboratory values, clinical course, and outcome of COVID-19 patients with neurological manifestations in Shahroud, Iran. Methods: In this cross-sectional study, data from all registered COVID-19 patients in Shahroud during March 2020 to July 2021 (n=30,228) were initially reviewed in terms of the prevalence of neurological symptoms. Additionally, the data of COVID-19 patients admitted to Shahroud’s hospital (n=8,412) was evaluated in details according to the clinical profile, socio-demographic characteristics, laboratory findings, and in-hospital outcomes. Data were compared between COVID-19 patients with and without neurological manifestations. Predictive factors of ICU admission and mortality in COVID-19 patients with neurological manifestations were also evaluated. Results: Fever, chills, anorexia, myalgia, arthralgia, nausea, vomiting, cough, dyspnea, diarrhea and abdominal pain were significantly more common among COVID-19 patients with neurological symptoms compared to COVID-19 patients without such symptoms. Furthermore, smoking, drug abuse and history of underlying diseases were significantly more prevalent among the former group. Patients with neurological symptoms were more likely to be admitted to the hospital and ICU and had higher mortality rates. In terms of laboratory findings, hemoglobin, hematocrit, platelet count, and albumin levels were significantly lower in the patients with neurological symptoms. Age ≥ 50 years and history of underlying diseases were associated with increased ICU admission in COVID-19 patients with neurological manifestations. Conclusions: The following strategies could prove beneficial for COVID-19 patients: (i.) reduction of smoking and substance abuse, (ii.) close monitoring of more symptomatic patients and patients with a history of underlying diseases for neurological manifestations, (iii.) providing appropriate intensive care for older patients and those with underlying diseases who have neurological manifestations and (iv.) early detection of anemia, thrombocytopenia, and hypoalbuminemia.

A Study on Neurological Manifestations in Coronavirus Disease 2019 Patients Admitted to a Tertiary Care Hospital.

The coronavirus disease 2019 (COVID-19) is considered a pandemic by the World Health Organization (WHO). Although diffuse alveolar damage and acute respiratory failure are the main features of COVID-19, the involvement of other organs needs to be explored. Thus, this study is undertaken to analyze the neurological manifestations in patients with COVID-19 infection. To analyze the neurological manifestations in patients with COVID-19 infection. All COVID-19-positive patients who got neurology referrals from March 2020 to June 2021 were included in the study. Laboratory confirmation of COVID-19 infection was done by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) of throat swabs in patients who present with symptoms suggestive of COVID-19. Demographic characteristics, neurological complaints, comorbid conditions, neurological examination, and requisite investigations were analyzed. Among 160 patients, 107 (67%) were men, and the mean age was 61 years. Comorbidities included diabetes mellitus (51%) of subjects followed by hypertension (28%), chronic kidney disease (10%), and coronary artery disease (5%). Considering the COVID-19 severity, 28.75% had mild; 8.75% had moderate; and 62.5% had severe disease. The most common neurological symptoms included altered sensorium (62.5%), focal neurological symptoms (29.4%), anosmia (13.1%), headache (10.6%), and seizures (7.5%). The most prevalent neurological signs and/or syndromes were acute encephalopathy (62.5%), stroke (21.3%%), and mucormycosis (12.5%). The mortality rate in our study population was 16.3%, encephalopathy being the most common cause. In our study, encephalopathy was the major cause of morbidity and mortality among the COVID-19-related neurological manifestations. Encephalopathy was most seen in severe COVID-19 infection and was associated with increased neutrophil-to-lymphocyte (NL) ratio raised inflammatory markers. Stroke constituted 29.4% of the neurology referrals in COVID-19 patients confirming COVID-19 infection predisposes to thrombotic events. We found an increased incidence of Mucormycosis in COVID-19 patients, but early debridement and timely treatment with antifungal medications had reduced the mortality.

Overview of reemerging mpox infection with a focus on neurological manifestations.

Mpox, a reemerging zoonotic disease caused by the mpox virus, has garnered increasing attention due to its potential for severe clinical manifestations. While the cutaneous and systemic presentations of mpox have been well-documented, its neurological complications have recently emerged as an area of concern. This review provides a brief overview of the neurological aspects of mpox infection, highlighting the key findings and challenges in understanding and managing these complications. Neurological manifestations in mpox patients range from mild symptoms such as headaches and dizziness to more severe conditions, including encephalitis and seizures. The pathogenesis of neurological involvement is not yet fully elucidated but is thought to involve viral dissemination to the central nervous system. This dissemination may occur through haematogenous or neuronal routes, contributing to the diverse clinical spectrum observed. Early recognition and diagnosis of neurological complications in mpox are crucial for implementing appropriate therapeutic interventions and improving patient outcomes.

Neurologic Complications of the Central Nervous System after Allogeneic Stem Cell Transplantation: The Role of Transplantation-Associated Thrombotic Microangiopathy as a Potential Underreported Cause

neurological complications (NC), especially those of the central nervous system (CNS), represent a severe complication after allogeneic stem cell transplantation (allo-HSCT) and are associated with relevant morbidity and mortality. we aim to characterize the potential risk factors for the development of CNS-NC with a special focus on the role of calcineurin inhibitors (CNI) as a predisposing factor. For this purpose, we compared Cyclosporin A (CsA) versus Tacrolimus (TAC) with respect to their influence on the incidence and type of CNS-NC after allo-HSCT. we retrospectively analyzed incidence, risk factors and impact on outcome of CNS-NC diagnosed during the post-transplantation follow-up in patients with different high-risk hematological malignancies who underwent allo-HSCT at our institution over a time frame of 20 years. All patients included in the analysis received CNI (CsA or TAC) as graft versus host disease (GVHD) prophylaxis. we evaluated a total of 739 consecutive patients transplanted from 12/1999 to 04/2019. Within a median follow-up period of 6.8 years, we observed a CNS-NC incidence of 17%. The development of CNS-NC was associated with decreased overall survival (OS) and increased transplant-related mortality (TRM). The most frequent CNS-NC were infections (30%) and neurological adverse events related to the administration of CNI, TAC or CsA, as GVHD prophylaxis (42%). In the multivariable analysis, age, total body irradiation (TBI) and severe acute and chronic GVHD significantly impacted as risk factors on the development of CNS-NC. TAC as compared with CsA emerged as an independent predisposing factor for CNS-NC. The TAC-associated risk of CNS-NC was mostly due to the occurrence of transplant-associated thrombotic microangiopathy (TA-TMA) with neurological manifestations (Neuro-TA-TMA), even if the general TA-TMA incidence was comparable in the two CNI subgroups. CNS-NC are associated with poor prognosis after allo-HSCT with TAC emerging as a potential yet insufficiently characterized predisposing factor.

Clinical profile of central nervous system space-occupying lesions and their association with CD4 counts in patients with HIV: A prospective observational study.

Neurological manifestations are one of the major concerns for patients with human immunodeficiency virus (HIV). The secondary spectrum includes space-occupying lesions (SOL), including tuberculoma, cryptococcosis, candidiasis, toxoplasmosis, primary central nervous system lymphoma (PCNSL), and progressive multifocal leukoencephalopathy (PML). To assess the neurological manifestations, disease outcome, and their associations with cluster of differentiation 4 (CD4) counts in patients with HIV. This single-center, prospective, observational study was performed in the Department of General Medicine of a tertiary care institute, over a period of 2 years (January 2017 to December 2018). The study included 150 known or newly diagnosed HIV patients with CNS SOL. The physical examination, laboratory investigations, and imaging were conducted on every patient, and the findings were noted. The patients mainly presented with hemiparesis (52%), had involvement of the frontal region (38.7%), and were diagnosed with tuberculoma (29.3%). Other diagnoses were toxoplasmosis (22.7%), PML (17.3%), PCNSL (15.3%), brain abscess (10%), and neurocysticercosis (5.3%). Of 150 patients, 136 (90.7%) were survivors, while 14 (9.3%) were non-survivors. The mean CD4 count was significantly less in patients with toxoplasmosis (P < 0.0001) and PCNSL (P = 0.02), and significantly higher in patients with tuberculoma (P < 0.0001) and brain abscess (P = 0.0009) relative to other causes of SOL. Moreover, the mean CD4 count was not significantly associated with survivors and non-survivors (P = 0.28). In patients with HIV, CD4 count was significantly low in toxoplasmosis and PCNSL, and high in tuberculoma and brain abscess.

Cerebellar degeneration in gluten ataxia is linked to microglial activation.

Gluten sensitivity has long been recognized exclusively for its gastrointestinal involvement; however, more recent research provides evidence for the existence of neurological manifestations that can appear in combination with or independent of the small bowel manifestations. Amongst all neurological manifestations of gluten sensitivity, gluten ataxia is the most commonly occurring one, accounting for up to 40% of cases of idiopathic sporadic ataxia. However, despite its prevalence, its neuropathological basis is still poorly defined. Here, we provide a neuropathological characterization of gluten ataxia and compare the presence of neuroinflammatory markers glial fibrillary acidic protein, ionized calcium-binding adaptor molecule 1, major histocompatibility complex II and cluster of differentiation 68 in the central nervous system of four gluten ataxia cases to five ataxia controls and seven neurologically healthy controls. Our results demonstrate that severe cerebellar atrophy, cluster of differentiation 20+ and cluster of differentiation 8+ lymphocytic infiltration in the cerebellar grey and white matter and a significant upregulation of microglial immune activation in the cerebellar granular layer, molecular layer and cerebellar white matter are features of gluten ataxia, providing evidence for the involvement of both cellular and humoral immune-mediated processes in gluten ataxia pathogenesis.

Rare red cell enzymopathies in the indian population: A comprehensive review

Red blood cell enzyme deficiencies are a rare category of hemolytic anaemia presented in children with varying degrees of hemolysis, indirect hyperbilirubinemia and splenomegaly. Glucose 6-phosphate dehydrogenase deficiency is the most common enzyme deficiency, followed by pyruvate kinase deficiency. This article aims to understand the pathophysiology of the rare enzymopathies due to deficiencies in the Embden-Meyerhoff pathway, glutathione metabolism, hexose monophosphate shunt and Nucleotide metabolism pathway, and to study clinical symptoms, diagnostic strategy, management and incidence of enzyme deficiencies in Indian patients. Most RBC enzyme deficiencies are inherited in an autosomal recessive fashion except for glucose 6- phosphate dehydrogenase, and phosphoglycerate kinase deficiency which has X-linked inheritance. Presentation depends on the representation of the enzyme on different tissues of the body, hence some enzyme deficiencies may present with neurological or muscular manifestations. In patients with suspected hemolytic anaemia, complete blood count and peripheral smear help in differentiating from hemoglobinopathies etc. To clinch the diagnosis enzyme levels and genetic testing may be required. These tests are important to guide antenatal diagnosis in subsequent pregnancies. Management of RBC enzymopathies will depend on the predominant symptoms and severity of hemolysis. Patients with marked hemolysis require regular blood transfusions and hence appropriate chelation therapy. Hematopoeitic stem cell transplant is attempted in patients with severe spectrum with variable results. Newer drugs like Mitapivat have proven to be beneficial in adults with PK deficiency and ongoing trials in children are showing promising results.

Evaluation of cognitive functions and dementia two years after COVID-19 infection

Background: The Coronavirus disease 2019 (COVID-19) causes high morbidity and mortality in the acute period. Some patients with COVID-19 continue to have symptoms for a long time. However, data on the long-term effects of COVID-19, particularly on cognitive disorders is scarce. We aimed to evaluate cognitive functions and dementia in patients who survived two years after discharge from hospital due to acute covid-19 infection. Methods: Two hundred and five patients who had neurological symptoms during index hospitalization for COVID-19 infection were evaluated two years after discharge, and 64 patients were included in the study. According to cognitive assessments, patients were grouped as having normal cognitive levels (48 patients) or impaired cognitive levels (16 patients). Results: The impaired cognitive level was found in 16 (25.0%) of patients who underwent cognitive tests. Age, the pre-existence of neurological comorbidity, mean intensive care unit day, and Beck’s Anxiety Inventory and Beck’s Depression Inventory scores in the impaired cognitive level group were significantly higher than the normal cognitive level group (p:0.001, p:0.013, p:0.015, p:0.004 and p:0.008). The frequency of cognitive impairment in patients who developed altered mental state during hospitalization was 36.0%, while it was 17.9% in patients with normal mental state. Age, the pre-existence of neurological comorbidity, and anxiety were determined as independent risk factors for impaired cognitive level. In addition, we detected new-onset dementia in 8 patients (12.5%). Conclusion: We found a high frequency of cognitive impairment and new-onset dementia among COVID-19 survivors who developed neurological manifestations during the acute infection phase.

Preclinical Evidence-based Neuroprotective Potential of Silibinin.

Neurodegeneration is an elucidating feature of many neuronal disorders including Alz- heimer's, disease, Parkinson's disease, and cerebral ischemia. These neurodegenerative disorders are a major public health concern with high mortality and morbidity rates around the world. Pres- ently, researchers have concentrated their efforts on determining the neuroprotective activity of natural products for the management of neurological manifestation associated with neurodegener- ation or aging. Silibinin, an active component of the plant Silybum marianum (family: Asteraceae) was used for the treatment of liver diseases from ancient times. Recently several preclinical stud- ies provide supportive evidence for the neuroprotective activity of silibinin in experimental ani- mals. Besides its antioxidant effect, silibinin exhibits neuroprotective activities by altering several cellular and molecular signaling pathways like BDNF, ER/PI3/Akt, NfκB, JNK, IR & IGF-IR, mTOR, and many more against brain-related neurotoxicity. This review provided a comprehen- sive summary of the chemistry, pharmacokinetics, side effects, and pharmacological effects of silibinin against various neurodegenerative disorders with a prominent cellular and molecular mechanism. The literature reviews and preclinical studies demonstrated that silibinin could be an alternate candidate for the management of neurodegenerative disorders. Thus, there is a scope for further preclinical and clinical research to introduce this phytoconstituent as a therapeutic alterna- tive candidate.

A Brazilian Rare-Disease Center's Experience with Glucosylsphingosine (lyso-Gb1) in Patients with Gaucher Disease: Exploring a Novel Correlation with IgG Levels in Plasma and a Biomarker Measurement in CSF.

Gaucher disease (GD, OMIM 230800) is one of the most common lysosomal disorders, being caused by the deficient activity of the enzyme acid β-glucocerebrosidase (Gcase). Three clinical forms of Gaucher's disease (GD) are classified based on neurological involvement. Type 1 (GD1) is non-neuronopathic, while types 2 (GD2) and 3 (GD3) are neuronopathic forms. Gcase catalyzes the conversion of glucosylceramide (GlcCer) into ceramide and glucose. As GlcCer accumulates in lysosomal macrophages, it undergoes deacylation to become glycosylsphingosine (lyso-Gb1), which has shown to be a useful and reliable biomarker for the diagnosis and monitoring of treated and untreated patients with GD. Multiple myeloma (MM) is one of the leading causes of cancer-related death among patients with GD and monoclonal gammopathy of undetermined significance (MGUS) is a non-neoplastic condition that can be a telltale sign of a B clonal proliferation caused by the chronic activation of B cells. This study aimed to quantify Lyso-Gb1 levels in dried blood spots (DBS) and cerebrospinal fluid (CSF) as biomarkers for Gaucher disease (GD) and discuss the association of this biomarker with other clinical parameters. This is a mixed-methods study incorporating both cross-sectional and longitudinal elements within a cohort design with a convenience-sampling strategy. Data collection took place from January 2012 to March 2023. Lyso-Gb1 extraction from DBS involved the use of a methanol-acetonitrile-water mixture, followed by incubation and centrifugation. Analysis was performed using UPLC-MS/MS with MassLynx software version 4.2 and the control group for the DBS measurements included general newborns. CSF Lyso-Gb1 was extracted using ethyl acetate, analyzed by UPLC-MS/MS with a calibration curve, and expressed in pmol/L. Lysosomal activity in CSF was assessed by measuring chitotriosidase (Cht), and other lysosomal enzyme activities were assessed as previously described in the literature. Patients with metachromatic leukodystrophy (MLD) were used as controls. Thirty-two treated patients (twenty-nine GD1 and three GD3, all on ERT except for one GD type on SRT with eliglustat) and three untreated patients (one GD1, one GD2, and one GD3) were included. When analyzing only the treated GD1 group, a significant correlation was found between lyso-Gb1 and age (rho = -0.447, p = 0.001), ChT, and IgG levels (rho = 0.73, p < 0.001; and rho = 0.36, p = 0.03, respectively). Five GD1 patients (three females, mean age 40 years) also had their CSF collected and analyzed. The average measurement of lyso-Gb1 in CSF was 94 pmol/L (range: 57.1-157.9 pmol/L) versus <6.2 pmol/L in the control group (MLD). This is the first time, to the best of our knowledge, that lyso-Gb1 has been associated with IgG levels. While this finding reflects a risk for MGUS or MM and not only chronic plasma B-cell activation, it still requires further studies. Moreover, the analysis of CSF lyso-Gb1 levels in GD1 patients was demonstrated to be significantly higher than the control group. This raises the hypothesis that CSF lyso-Gb1 may serve as a valuable indicator for neurological involvement in GD, providing insights into the potential implications for neurological manifestations in GD, including GD1. The correlation between lyso-Gb1 and ChT levels in treated GD1 patients further underscores the interconnectedness of lysosomal markers and their relevance in monitoring.

Modern ideas about concentric sclerosis Balo: a clinical case

Balo's concentric sclerosis (BCS) is a rare demyelinating disease of the central nervous system, characterized by concentric areas of demyelination alternating with areas of preserved myelin in the form of a pathognomonic pathomorphological substrate of varying degrees of severity in the form of «annual rings on a tree cut». The pathogenesis of BCS is diverse and complex, today there are several theories of its occurrence, among which hypoxic, vascular and closely related genetic, as well as a number of other theories are distinguished. The BCS clinic is variable, represented by both focal neurological manifestations and general cerebral symptoms. The diagnosis is based on the data of magnetic resonance imaging of the brain. The drugs of choice for BCS therapy are glucocorticosteroids (prednisolone or methylprednisolone).

Clinicobiochemical Profile and Outcome of Children with Small Molecule Neurometabolic Disorders: A Tertiary Care Hospital Experience from India

AbstractInborn Errors of Metabolism (IEM), though heterogenous, are not uncommon. Neurologic manifestations predominate. Without universal newborn screening, early diagnosis and treatment may lessen neuromorbidity. Hence, this study was done to understand small molecule neurometabolic disorders' presentation, diagnostic clues, and outcome.Small molecule neurometabolic disorder was diagnosed in 45 children (postneonatal onset) over 14 years (2008–2022) in a tertiary care hospital. Clinical and laboratory data were retrospectively analyzed.There were 26 boys and 19 girls. The median age at diagnosis was 19 months (interquartile range [IQR] 8–38 months). The median diagnostic delay was 12 months in chronic encephalopathy (IQR 1–24 months) and 1 month (IQR 0.2–5.5 months) in the acute encephalopathy group (p ≤ 0.01). The presentation mode was chronic encephalopathy/myopathy in 29 (64.4%) and acute encephalopathy in 11 (24.4%). Diagnostic clues included unexplained developmental delay (n = 27, 60%), tone abnormalities (n = 26, 57.7%), movement disorder and ataxia (n = 16, 35.5%), acute encephalopathy (n = 11, 24.4%), neuroregression (n = 10, 22.2%), macrocephaly (n = 10, 22.2%), and alopecia (n = 4, 8.9%). Diagnostic/suggestive blood-spot tandem mass spectrometry (TMS) was seen in 34/38 (89.5%) children. Neuroimaging helped clinch the diagnosis in 17 (47%) children. Diagnostic categories were organic acidemias (n = 25, 55.6%), urea cycle disorders (n = 11, 24.4%), aminoacidopathies (n = 5, 11.1%), and fatty acid oxidation disorders (n = 4, 8.9%). The neurodevelopmental outcome was normal in 13 (28.8%), mild delay in 12 (26.6%), severe delay in 11 (24.4%), 3 deaths (6.6%), and 6 (13.3%) children being lost to follow-up. Overall, the outcome was favorable in 55% of cases.Unexplained developmental delay with tone abnormalities with or without movement disorders is a joint presentation of late-onset neurometabolic diseases. Neuroimaging studies and laboratory tests like blood-spot TMS help identify many small molecule disorders.

Comparison between SARS-CoV-2-Associated Acute Disseminated Encephalomyelitis and Acute Stroke: A Case Report

The neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are underrecognized. Ischemic stroke and thrombotic complications have been documented in patients with SARS-CoV-2 infection. Acute disseminated encephalomyelitis (ADEM) associated with coronavirus disease 2019 (COVID-19) is rare but can occur; the incidence of COVID-19-associated ADEM is still not clear due to the lack of reporting of cases. ADEM may have atypical stroke-like manifestations, such as hemiparesis, hemiparesthesia and dysarthria. The treatment strategies for ADEM and acute stroke are different. Early identification and prompt management may prevent further potentially life-threatening complications. We report a patient with SARS-CoV-2 infection presenting with stroke-like manifestations. We also make a comparison between demyelinating diseases, COVID-19-associated ADEM and acute stroke. This case can prompt physicians to learn about the clinical manifestations of SARS-CoV-2-associated ADEM.

Phenytoin-Induced Ataxia and Diplopia in a Patient with Recent Subarachnoid Hemorrhage: A Case Report

This case report presents a 25-year-old male with a complex medical history, including a recent subarachnoid hemorrhage (SAH) and a prescription for phenytoin. The patient exhibited neurological symptoms, such as ataxia, blurring of vision, and diplopia, prompting an intricate diagnostic evaluation. The medical history encompassed a prior road traffic accident resulting in a jaw injury, adding to the complexity of potential aetiologies, including cerebellar dysfunction, sequelae from the accidents, medication-related side effects (particularly phenytoin), or infectious/inflammatory causes. Given the reported symptoms, there arose a suspicion of phenytoin-induced ataxia and diplopia, common neurological side effects associated with this anticonvulsant. These symptoms, suggestive of cerebellar dysfunction, required a comprehensive examination, including neurological assessments and imaging studies, to elucidate the precise etiology. This case underscores the importance of meticulous medication review, particularly for drugs like phenytoin, and emphasizes the necessity of a multidisciplinary approach involving neurologists to navigate the complexities associated with neurological manifestations in the context of SAH and medication use. The findings contribute to understanding potential complications arising from anticonvulsant therapy in SAH patients and highlight the need for tailored diagnostic and management strategies in such intricate clinical scenarios.

Trypanosoma cruzi interaction with host tissues modulate the composition of large extracellular vesicles

Trypanosoma cruzi is the protozoan that causes Chagas disease (CD), an endemic parasitosis in Latin America distributed around the globe. If CD is not treated in acute phase, the parasite remains silent for years in the host's tissues in a chronic form, which may progress to cardiac, digestive or neurological manifestations. Recently, studies indicated that the gastrointestinal tract represents an important reservoir for T. cruzi in the chronic phase. During interaction T. cruzi and host cells release extracellular vesicles (EVs) that modulates the immune system and infection, but the dynamics of secretion of host and parasite molecules through these EVs is not understood. Now, we used two cell lines: mouse myoblast cell line C2C12, and human intestinal epithelial cell line Caco-2to simulate the environments found by the parasite in the host. We isolated large EVs (LEVs) from the interaction of T. cruzi CL Brener and Dm28c/C2C12 and Caco-2 cells upon 2 and 24 h of infection. Our data showed that at two hours there is a strong cellular response mediated by EVs, both in the number, variety and enrichment/targeting of proteins found in LEVs for diverse functions. Qualitative and quantitative analysis showed that proteins exported in LEVs of C2C12 and Caco-2 have different patterns. We found a predominance of host proteins at early infection. The parasite-host cell interaction induces a switch in the functionality of proteins carried by LEVs and a heterogeneous response depending on the tissues analyzed. Protein–protein interaction analysis showed that cytoplasmic and mitochondrial homologues of the same parasite protein, tryparedoxin peroxidase, were differentially packaged in LEVs, also impacting the interacting molecule of this protein in the host. These data provide new evidence that the interaction with T. cruzi leads to a rapid tissue response through the release of LEVs, reflecting the enrichment of some proteins that could modulate the infection environment.

Small vessel disease in primary familial brain calcification with novel truncating PDGFB variants.

Primary familial brain calcification (PFBC) is a neurodegenerative disease characterised by bilateral calcification in the brain, especially in the basal ganglia, leading to neurological and neuropsychiatric manifestations. White matter hyperintensities (WMH) have been described in patients with PFBC and pathogenic variants in the gene for platelet-derived growth factor beta polypeptide (PDGFB), suggesting a manifest cerebrovascular process. We present below the cases of two PFBC families with PDGFB variants and stroke or transient ischaemic attack (TIA) episodes. We examine the possible correlation between PFBC and vascular events as stroke/TIA, and evaluate whether signs for vascular disease in this condition are systemic or limited to the cerebral vessels. Two Swedish families with novel truncating PDGFB variants, p.Gln140* and p.Arg191*, are described clinically and radiologically. Subcutaneous capillary vessels in affected and unaffected family members were examined by light and electron microscopy. All mutation carriers showed WMH and bilateral brain calcifications. The clinical presentations differed, with movement disorder symptoms dominating in family A, and psychiatric symptoms in family B. However, affected members of both families had stroke, TIA, and/or asymptomatic intracerebral ischaemic lesions. Only one of the patients had classical vascular risk factors. Skin microvasculature was normal. Patients with these PDGFB variants develop microvascular changes in the brain, but not the skin. PDGFB-related small vessel disease can manifest radiologically as cerebral haemorrhage or ischaemia, and may explain TIA or stroke in patients without other vascular risk factors.