Spectrum Of Neurological Disorders Research Articles

ADCY5-related dyskinesia - case series with literature review.

ADCY5-related dyskinesia is a rare neurological disease caused by mutations in the gene encoding the adenylyl cyclase 5 (ADCY5) isoform, a protein that plays an important role in intracellular transmission. Variants in ADCY5 are associated with a spectrum of neurological disease encompassing dyskinesia, chorea, and dystonia. State of the-art. ADCY5 mutations result in clinically heterogeneous manifestations which comprise a range of core and less to highly variable symptoms. Due to the heterogeneous nature and difficulty in diagnosis of the disorder, available treatments are highly limited. ADCY5-related dyskinesia was reported in 52 individuals in the literature over a five-year period (January 2017 to January 2022). We have listed all the symptoms and their frequency. The most common symptom reported in these patients was dystonia. Over 50% of patients developed dyskinesia and chorea. We report two cases of familial occurrence of symptomatic ADCY5-related dyskinesia. A 45-year-old patient presented with involuntary movements which had been occurring since childhood. The proband's neurological examination revealed dysarthria, involuntary myoclonic twitches, and choreic movements. The patient's 9-year-old son had developed involuntary movements, mainly chorea and dystonia. This paper aims to summarise the recent literature on ADCY5-related neurological disorders and to present a new case of a Polish family with ADCY5 mutation. Genetic diagnostics are important in the context of possible future targeted treatments.

De novo GRIN variants in M3 helix associated with neurological disorders control channel gating of NMDA receptor

N-methyl-d-aspartate receptors (NMDARs) are members of the glutamate receptor family and participate in excitatory postsynaptic transmission throughout the central nervous system. Genetic variants in GRIN genes encoding NMDAR subunits are associated with a spectrum of neurological disorders. The M3 transmembrane helices of the NMDAR couple directly to the agonist-binding domains and form a helical bundle crossing in the closed receptors that occludes the pore. The M3 functions as a transduction element whose conformational change couples ligand binding to opening of an ion conducting pore. In this study, we report the functional consequences of 48 de novo missense variants in GRIN1, GRIN2A, and GRIN2B that alter residues in the M3 transmembrane helix. These de novo variants were identified in children with neurological and neuropsychiatric disorders including epilepsy, developmental delay, intellectual disability, hypotonia and attention deficit hyperactivity disorder. All 48 variants in M3 for which comprehensive testing was completed produce a gain-of-function (28/48) compared to loss-of-function (9/48); 11 variants had an indeterminant phenotype. This supports the idea that a key structural feature of the M3 gate exists to stabilize the closed state so that agonist binding can drive channel opening. Given that most M3 variants enhance channel gating, we assessed the potency of FDA-approved NMDAR channel blockers on these variant receptors. These data provide new insight into the structure–function relationship of the NMDAR gate, and suggest that variants within the M3 transmembrane helix produce a gain-of-function.

Utilising biosensor-based approaches for identifying neurotropic viruses.

Neurotropic viruses, with their ability to invade the central nervous system, present a significant public health challenge, causing a spectrum of neurological diseases. Clinical manifestations of neurotropic viral infections vary widely, from mild to life-threatening conditions, such as HSV-induced encephalitis or poliovirus-induced poliomyelitis. Traditional diagnostic methods, including polymerase chain reaction, serological assays, and imaging techniques, though valuable, have limitations. To address these challenges, biosensor-based methods have emerged as a promising approach. These methods offer advantages such as rapid results, high sensitivity, specificity, and potential for point-of-care applications. By targeting specific biomarkers or genetic material, biosensors utilise technologies like surface plasmon resonance and microarrays, providing a direct and efficient means of diagnosing neurotropic infections. This review explores the evolving landscape of biosensor-based methods, highlighting their potential to enhance the diagnostic toolkit for neurotropic viruses.

Are TrkB receptor agonists the right tool to fulfill the promises for a therapeutic value of the brain-derived neurotrophic factor?

Brain-derived neurotrophic factor signaling via its receptor tropomyosin receptor kinase B regulates several crucial physiological processes. It has been shown to act in the brain, promoting neuronal survival, growth, and plasticity as well as in the rest of the body where it is involved in regulating for instance aspects of the metabolism. Due to its crucial and very pleiotropic activity, reduction of brain-derived neurotrophic factor levels and alterations in the brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling have been found to be associated with a wide spectrum of neurological diseases. However, because of its poor bioavailability and pharmacological properties, brain-derived neurotrophic factor itself has a very low therapeutic value. Moreover, the concomitant binding of exogenous brain-derived neurotrophic factor to the p75 neurotrophin receptor has the potential to elicit several unwanted and deleterious side effects. Therefore, developing tools and approaches to specifically promote tropomyosin receptor kinase B signaling has become an important goal of translational research. Among the newly developed tools are different categories of tropomyosin receptor kinase B receptor agonist molecules. In this review, we give a comprehensive description of the different tropomyosin receptor kinase B receptor agonist drugs developed so far and of the results of their application in animal models of several neurological diseases. Moreover, we discuss the main benefits of tropomyosin receptor kinase B receptor agonists, concentrating especially on the new tropomyosin receptor kinase B agonist antibodies. The benefits observed both in vitro and in vivo upon application of tropomyosin receptor kinase B receptor agonist drugs seem to predominantly depend on their general neuroprotective activity and their ability to promote neuronal plasticity. Moreover, tropomyosin receptor kinase B agonist antibodies have been shown to specifically bind the tropomyosin receptor kinase B receptor and not p75 neurotrophin receptor. Therefore, while, based on the current knowledge, the tropomyosin receptor kinase B receptor agonists do not seem to have the potential to reverse the disease pathology per se, promoting brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling still has a very high therapeutic relevance.

Emerging Promise of Phytochemicals in Ameliorating Neurological Disorders.

The field of medicine and synthetic drug development have advanced rapidly over the past few decades. However, research on alternative medicine such as phytochemicals cannot be ignored. The main reason for prominent curiosity about phytochemicals stems from the belief that usage of natural compounds is safer and has lesser detrimental side effects. The aim of the present review was to discuss in detail with several phytochemicals that have been studied or are being studied in the context of various neurological disorders including depression, Alzheimer's disease, Huntington's disease and even neuroinflammatory disorders such as encephalitis. The potential role of phytochemicals in the treatment or management of symptoms associated with neurological disorders have been included in this article. All data included in this paper has been pooled from various databases including Google Scholar, PubMed, Science Direct, Springer and Wiley Online Library. Phytochemicals have been widely studied for their therapeutic properties associated with neurological disorders. Using various experimental techniques for both in vivo and in vitro experiments, studies have shown that phytochemicals do have antioxidant, anti-inflammatory and neuroprotective activities which play major roles in the treatment of neurological diseases. Even though there has been compelling evidence of the therapeutic role of phytochemicals, further research is still required to evaluate the safety and efficacy of these medicines. Using previously published papers as foundation for additional research such as preclinical studies and clinical trials, phytochemicals can become a safer alternative to synthetic drugs for treating a spectrum of neurological diseases.

Spectrum of Diseases Affecting the Nervous System Associated with JC - Virus: A Review

The JC polyomavirus (JCPyV) belongs to the family Polyomaviridae, genus Betapolyomavirus. These are small, non-enveloped, double-stranded DNA viruses. Approximately 60-80% of the population is carriers of JC polyomavirus. Various ways of spread are being studied. These viruses are associated with a large spectrum of neurological diseases, including progressive multifocal leukoencephalopathy, JC-associated meningitis and encephalitis, JCV granule cell neuronopathy and numerous central nervous system malignancies. In the majority of individuals, the virus remains latent in the kidney tissue. However, in certain subgroups, it leads to the development of severe and frequently disabling or fatal diseases. These subgroups are usually immunosuppressed, which causes the virus to undergo lytic rearrangement. Understanding these diseases and the mechanisms by which they occur is paramount for making accurate diagnoses. Studying these diseases is necessary to develop effective treatments and limit their harmful effects.

Enterovirus characterized from cerebrospinal fluid in a cohort from the Eastern United States.

Enteroviruses (EVs) are predominant causes of a spectrum of neurological diseases. To better understand the origins of the outbreaks of disease associated with EV, it is essential to develop an efficient surveillance system that identifies the circulating EVs and correlate their genomic evolution with the disease presentations. The clinical presentations of patients with positive EV from cerebrospinal fluid (CSF) between 2014 and 2022, diagnosed at the Johns Hopkins Medical Microbiology Laboratory, were compared from year to year. EV typing and whole genome sequencing were performed and correlated to the spectrum of disease. A total of 95 CSF specimens were positive for EV between 2014 and 2022. The percentage positivity ranged from the lowest of 1.1% in 2020 to the highest of 3.2% in 2015. The median ages declined from 22 years in 2014 to less than one year starting in 2016 to 34 in 2022. Typing using VP1 sequencing revealed that E30 and E6 were associated with meningitis in adults but coxsackieviruses (CVs-B3 and B5) were detected from pediatric patients with fever. Whole genome sequencing revealed multiple recombination events. In 2020, a recombinant CV-A9 was detected in a CSF sample associated with unusual presentation of sepsis, profound acute bilateral sensory neural hearing loss, and myofasciitis. EV genomic surveillance is needed for a better understanding of the genetic determinants of neurovirulence. Whole genome sequencing can reveal recombination events missed by traditional molecular surveillance methods.

PDZ interaction of the GABA transporter GAT1 with the syntenin-1 in Neuro-2a cells

The GABA transporter GAT1 regulates brain inhibitory neurotransmission and it is considered a potential therapeutic target for the treatment of wide spectrum of neurological diseases including epilepsy, stroke and autism. Syntenin-1 binds to syntaxin 1A, which is known to regulate the plasma membrane insertion of several neurotransmitter transporters. Previously, a direct interaction of syntenin-1 with the glycine transporter GlyT2 was reported. Here, we show that the GABA transporter GAT1 also directly interacts with syntenin-1, involving both unidentified protein interaction interface and the GAT1 C-terminal PDZ binding motif interacting mainly with syntenin-1 PDZ domain 1. The PDZ interaction was eliminated by the mutation of GAT1 isoleucine 599 and tyrosine 598 located in PDZ positions 0 and -1, respectively. This indicates an unconventional PDZ interaction and possible regulation of the transporter PDZ motif via tyrosine phosphorylation. Whole syntenin-1 protein fused to GST protein and immobilised on glutathione resin coprecipitated intact GAT1 transporter from an extract of GAT1 transfected neuroblastoma N2a cells. This coprecipitation was inhibited by tyrosine phosphatases inhibitor pervanadate. The fluorescence tagged GAT1 and syntenin-1 colocalized upon coexpression in N2a cells. The above results show that syntenin-1 might be, in addition to GlyT2, directly involved in the trafficking of GAT1 transporter.

Seasonal Variation in Neurologic Hospitalizations in the United States.

Certain neurologic diseases have been noted to vary by season, and this is important for understanding disease mechanisms and risk factors, but seasonality has not been systematically examined across the spectrum of neurologic disease, and methodologic guidance is also lacking. Using nationally representative data from the National Inpatient Sample, a stratified 20% sample of all non-federal acute care hospitalizations in the United States, we calculated the monthly rate of hospitalization for 14 neurologic diseases from 2016 to 2018. For each disease, we assessed seasonality of hospitalization using chi-squared, Edward, and Walter-Elwood tests and seasonal time series regression models. Statistical tests were adjusted for multiple hypothesis testing using Bonferroni correction. Meningitis, encephalitis, ischemic stroke, intracerebral hemorrhage, Guillain-Barre syndrome, and multiple sclerosis had statistically significant seasonality according to multiple methods of testing. Subarachnoid hemorrhage, status epilepticus, myasthenia gravis, and epilepsy had significant seasonality according to Edwards and Walter-Elwood tests but not chi-square tests. Seasonal time series regression illustrated seasonal variation in all 14 diseases of interest, but statistical testing for seasonality within these models using the Kruskal-Wallis test only achieved statistical significance for meningitis. Seasonal variation is present across the spectrum of acute neurologic disease, including some conditions for which seasonality has not previously been described, and can be examined using multiple different methods. ANN NEUROL 2023;93:743-751.

Natural History of SURF1 Deficiency: A Retrospective Chart Review

BackgroundThis retrospective chart review evaluated the clinical characteristics of SURF1-related neurological disease spectrum to better characterize the phenotypes. MethodsPatient demographics, magnetic resonance imaging abnormalities, neurological events, motor abnormalities, and gastrointestinal and respiratory assistance were evaluated in 27 patients with genetically diagnosed SURF1 deficiency. ResultsThe mean (S.D.) age of symptom onset collected from 13 patients was 19.7 (11.8) months. Mean (S.D.) age of diagnosis collected from 24 patients was 44.0 (45.1) months. The most common symptoms were gross motor delay (14 of 14), fine motor delay (10 of 11), verbal delay (9 of 10), and intellectual and learning disability (14 of 19). Neurological symptoms included ataxia (14 of 15), other abnormal movements (8 of 9), hypotonia (9 of 11), and dystonia (6 of 9). Three of nine reporting patients (33.3%) had a history of seizure, and 84.6% (11 of 13) had a history of regression/loss of acquired skills. Extraneurological clinical features included pulmonary complications (10 of 11) and feeding difficulties (13 of 13); cardiac complications were noted in three patients. Brainstem is frequently involved with the medulla and midbrain being the most common sites. As of July 2021, three patients were deceased. ConclusionsThe most common clinical symptoms were motor delay, verbal delay, intellectual and learning disability, dysphagia, feeding difficulties, and reflux. Neurological presentations include ataxia, hypotonia, visual/ocular abnormalities, dystonia, and imaging abnormalities include basal ganglia and brainstem lesions. Although heterogeneous, SURF1 deficiency should be considered with these clinical and imaging presentations and may support earlier identification.

A KCNC1-related neurological disorder due to gain of Kv3.1 function.

To further clarify genotype:phenotype correlations associated with variants in KCNC1 encoding the voltage-gated potassium (K+) channel subunit Kv3.1 and which are an emerging cause of a spectrum of neurological disease including intellectual disability, isolated myoclonus, progressive myoclonus epilepsy, and developmental and epileptic encephalopathy. We describe the clinical and genetic characteristics of a series of three patients with de novo heterozygous missense variants in KCNC1 associated with nonspecific developmental delay/intellectual disability and central hypotonia without epilepsy or ataxia. All three variants lead to amino acids alterations with mild predicted differences in physicochemical properties yet are localized to the S6 pore region of the Kv3.1 protein between the selectivity filter and PXP motif important for K+ channel gating. We performed whole-cell voltage clamp electrophysiological recording of wild-type versus variants in a heterologous mammalian expression system. We demonstrate a prominent leftward (hyperpolarized) shift in the voltage dependence of activation and slowed deactivation of all variants in the clinically defined series. Electrophysiological recordings are consistent with a gain of K+ channel function that is predicted to exert a loss of function on the excitability of Kv3-expressing high frequency- firing neurons based on the unique electrophysiological properties of Kv3 channels. These results define a clinical-genetic syndrome within the spectrum of KCNC1-related neurological disorders.

Spectrum of Common Pediatric Neurological Disorders: A Cross-Sectional Study From Three Tertiary Care Centres Across Pakistan

BackgroundThere is dearth of information on the spectrum of neurological disorders among children less than 18 years of age. The aim of this study is to identify the commonly presenting neurological disorders among children aged ≤ 18 years in Pakistan. MethodsWe conducted a cross-sectional study at three tertiary care hospitals in Pakistan. ResultsA total of 17,176 children were included in our study; 61.8% were boys and 38.2% females. The most commonly presenting neurological disorder was epilepsy (36%), followed by behavior disorders (16%) and cerebral palsy (10.5%). There was significant difference between children less than 5 years and greater than 5 years age groups, with less than 5 years age group showing higher prevalence for behavioral disorders (P < 0.001), cerebral palsy (P < 0.001), infections (P = 0.014), sequalae (P < 0.001), and developmental disorders (P < 0.001). Gender-wise distribution showed epilepsy to be the most common neurological disorder among both genders, with a significant difference being reported between gender and epilepsy (P = 0.009), headache disorders (P < 0.001), neuroinflammatory disorders (P = 0.025), neurocutaneous syndromes (P < 0.001), behavioral diseases (P < 0.001), cerebral palsy (P = 0.009), and movement disorders (P < 0.001). ConclusionsThe result of this analysis helps to assess the commonly presenting neurological disorders in children. This study will help health care workers in resource-poor settings within Pakistan to be mindful of the common neurological disorders while diagnosing a child with neurological symptoms in an outpatient setting. Health care providers need to be trained to identify and treat these common conditions; however, there is still a dire need for more trained neurologists across the country.

Spectrum of Neurological Disorders in Neurology Outpatients Clinic in Tertiary Care Hospital: A Cross Sectional Study

Background: Neurological disorders are one of the most noticeable causes of morbidity and mortality that have a negative impact on patient’s lifestyle. A significant rate of these diseases exists in developing populations. However, there is lack and shortage of literature on neurological illnesses in Pakistan. This study was therefore carried out to determine the pattern of neurological diseases in this setting which can also provide a benchmark for planning and care for neurological illnesses at tertiary care level. Methodology: This is a Descriptive cross-sectional review conducted at the neurology outpatient clinic of the Lahore General Hospital, Lahore over the duration of 9 months between April, 2021 and December, 2021. Data was gathered through a predesigned questionnaire from the patients which included data regarding gender, age, marital status, occupation, residential status and affected disease. Results: Among all patients (140) who visited the neurology clinic over this duration, the most frequent neurological disorder was migraine (40%), followed by stroke (25%) and seizures (20%). The major age group that visited the neurology clinics was between 51 and 60 years (30%) and among them, most were males (60%). Conclusion: Stroke, migraine, and Parkinson's disease were the most common neurological disorders among participants of present study. Neurological diseases outnumber other diseases in Pakistan, affecting all age groups and genders. Headache, migraine, stroke, and seizure were found to be more common than AD and other dementias in Western countries and as significant reasons of morbidity. Keywords: Neurological disorders, neurology clinic, outpatients

Clinical profile of neurological disorders in children: a hospital-based experience of a tertiary care centre in Kashmir

Background: Neurological disorders in paediatric age group constitute a major cause of hospital visits both elective and emergent. Due to fast maturity of nervous system within the first few years of life they are more prone to neurological disorders, which mostly can be preventive and rehabilitative in nature. Purpose of this study was to know the pattern and spectrum of neurological disorders among children presenting to a tertiary health care facility in Kashmir.Methods: This was a retrospective analysis of the data of all the children in the age group 1 month to 18 years admitted with neurological disorders over a period of 12 month. Diagnosis was made on the basis of history, physical examination and relevant laboratory and radiological investigations.Results: Out of 21732 patients admitted during this study period, 562 patients had neurological disorders, an occurrence rate of 25 per 1000 hospitalized patients, with a male female ratio of 1.4:1. The most common neurological disorder was seizures followed by cerebral palsy and CNS infection.Conclusions: Neurological disorders constitute one of the common reasons for childhood hospitalization, implying a comprehensive must be set up in place to deal with these neurological problems as is existing elsewhere in our country, and in developed world for appropriate delivery of health care.

A differential of the left eye and right eye neurological pupil index is associated with discharge modified Rankin scores in neurologically injured patients

BackgroundAutomated infrared pupillometry (AIP) and the Neurological Pupil index (NPi) provide an objective means of assessing and trending the pupillary light reflex (PLR) across a broad spectrum of neurological diseases. NPi quantifies the PLR and ranges from 0 to 5; in healthy individuals, the NPi of both eyes is expected to be ≥ 3.0 and symmetric. AIP values demonstrate emerging value as a prognostic tool with predictive properties that could allow practitioners to anticipate neurological deterioration and recovery. The presence of an NPi differential (a difference ≥ 0.7 between the left and right eye) is a potential sign of neurological abnormality.MethodsWe explored NPi differential by considering the modified Rankin Score at discharge (DC mRS) among patients admitted to neuroscience intensive care units (NSICU) of 4 U.S. and 1 Japanese hospitals and for two cohorts of brain injuries: stroke (including subarachnoid hemorrhage, intracerebral hemorrhage, acute ischemic stroke, and aneurysm, 1,200 total patients) and 185 traumatic brain injury (TBI) patients for a total of more than 54,000 pupillary measurements.ResultsStroke patients with at least 1 occurrence of an NPi differential during their NSICU stay have higher DC mRS scores (3.9) compared to those without an NPi differential (2.7; P < .001). Patients with TBI and at least 1 occurrence of an NPi differential during their NSICU stay have higher discharge modified Rankin Scale scores (4.1) compared to those without an NPi differential (2.9; P < .001). When patients experience both abnormalities, abnormal (NPi < 3.0) and an NPi differential, the latter has an anticipatory relationship with respect to the former (P < .001 for z-score skewness analysis). Finally, our analysis confirmed ≥ 0.7 as the optimal cutoff value for the NPi differential (AUC = 0.71, P < .001).ConclusionThe NPi differential is an important factor that clinicians should consider when managing critically ill neurological injured patients admitted to the neurocritical care units.Trial registrationNCT02804438, Date of Registration: June 17, 2016.

Long-Term Changes in Axon Calibers after Injury: Observations on the Mouse Corticospinal Tract.

White matter pathology is common across a wide spectrum of neurological diseases. Characterizing this pathology is important for both a mechanistic understanding of neurological diseases as well as for the development of neuroimaging biomarkers. Although axonal calibers can vary by orders of magnitude, they are tightly regulated and related to neuronal function, and changes in axon calibers have been reported in several diseases and their models. In this study, we utilize the impact acceleration model of traumatic brain injury (IA-TBI) to assess early and late changes in the axon diameter distribution (ADD) of the mouse corticospinal tract using Airyscan and electron microscopy. We find that axon calibers follow a lognormal distribution whose parameters significantly change after injury. While IA-TBI leads to 30% loss of corticospinal axons by day 7 with a bias for larger axons, at 21 days after injury we find a significant redistribution of axon frequencies that is driven by a reduction in large-caliber axons in the absence of detectable degeneration. We postulate that changes in ADD features may reflect a functional adaptation of injured neural systems. Moreover, we find that ADD features offer an accurate way to discriminate between injured and non-injured mice. Exploring injury-related ADD signatures by histology or new emerging neuroimaging modalities may offer a more nuanced and comprehensive way to characterize white matter pathology and may also have the potential to generate novel biomarkers of injury.

Predicting the functional effects of voltage-gated potassium channel missense variants with multi-task learning.

SummaryBackgroundVariants in genes encoding voltage-gated potassium channels are associated with a broad spectrum of neurological diseases including epilepsy, ataxia, and intellectual disability. Knowledge of the resulting functional changes, characterized as overall ion channel gain- or loss-of-function, is essential to guide clinical management including precision medicine therapies. However, for an increasing number of variants, little to no experimental data is available. New tools are needed to evaluate variant functional effects.MethodsWe catalogued a comprehensive dataset of 959 functional experiments across 19 voltage-gated potassium channels, leveraging data from 782 unique disease-associated and synthetic variants. We used these data to train a taxonomy-based multi-task learning support vector machine (MTL-SVM), and compared performance to several baseline methods.FindingsMTL-SVM maintains channel family structure during model training, improving overall predictive performance (mean balanced accuracy 0·718 ± 0·041, AU-ROC 0·761 ± 0·063) over baseline (mean balanced accuracy 0·620 ± 0·045, AU-ROC 0·711 ± 0·022). We can obtain meaningful predictions even for channels with few known variants (KCNC1, KCNQ5).InterpretationOur model enables functional variant prediction for voltage-gated potassium channels. It may assist in tailoring current and future precision therapies for the increasing number of patients with ion channel disorders.FundingThis work was supported by intramural funding of the Medical Faculty, University of Tuebingen (PATE F.1315137.1), the Federal Ministry for Education and Research (Treat-ION, 01GM1907A/B/G/H) and the German Research Foundation (FOR-2715, Le1030/16-2, He8155/1-2).

ERK1/2 Signalling Pathway Regulates Tubulin-Binding Cofactor B Expression and Affects Astrocyte Process Formation after Acute Foetal Alcohol Exposure.

Foetal alcohol spectrum disorders (FASDs) are a spectrum of neurological disorders whose neurological symptoms, besides the neuronal damage caused by alcohol, may also be associated with neuroglial damage. Tubulin-binding cofactor B (TBCB) may be involved in the pathogenesis of FASD. To understand the mechanism and provide new insights into the pathogenesis of FASD, acute foetal alcohol exposure model on astrocytes was established and the interference experiments were carried out. First, after alcohol exposure, the nascent astrocyte processes were reduced or lost, accompanied by the absence of TBCB expression and the disruption of microtubules (MTs) in processes. Subsequently, TBCB was silenced with siRNA. It was severely reduced or lost in nascent astrocyte processes, with a dramatic reduction in astrocyte processes, indicating that TBCB plays a vital role in astrocyte process formation. Finally, the regulating mechanism was studied and it was found that the extracellular signal-regulated protease 1/2 (ERK1/2) signalling pathway was one of the main pathways regulating TBCB expression in astrocytes after alcohol injury. In summary, after acute foetal alcohol exposure, the decreased TBCB in nascent astrocyte processes, regulated by the ERK1/2 signalling pathway, was the main factor leading to the disorder of astrocyte process formation, which could contribute to the neurological symptoms of FASD.

Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis.

BackgroundNeurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome.MethodsWe conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models.ResultsWe included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67–82]), than encephalopathy (54% [42–65]). Intensive care use was high (38% [35–41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27–32]. The hazard of death was comparatively lower for patients in the WHO European region.InterpretationNeurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission.

MO161: Comparison of Therapeutic Plasma Exchange with Centrifugation and Filter Technique with a Focus on Efficacy, Safety, Platelet Loss and Patients' Comfort

Abstract BACKGROUND AND AIMS Therapeutic plasma exchange (TPE) is an established therapy in the treatment of various immunologic kidney and neurological diseases. Humoral factors as antibodies, complement factors, cytokines and immune complexes, which all are assumed to play a role in demyelinating or inflammatory disorders as multiple sclerosis, can be eliminated. TPE has been implemented into therapeutic guidelines of a broad spectrum of neurological diseases [1–3]. Centrifugal (cTPE) and membrane-based (mTPE) are the methods of choice for TPE. Head to head studies comparing both methods are scarce and patients’ comfort has not yet been investigated [4–7]. Our aim was to compare cTPE (Spectra Optia™, TerumoBCT) with mTPE (multiFiltrate™, Fresenius Medical Care) with a focus not only on safety and efficacy parameters but also on patients’ comfort with the present monocentric, prospective and randomized crossover study. This is, to the best of our knowledge, the first study addressing patients’ comfort comparing both systems. METHODS The study was conducted as an open-label prospective trial with a cross-over design comparing cTPE using the Spectra Optia™ (Terumo BCT, Lakewood, CO, USA), and mTPE using the multiFiltrate™ with the plasmafilter plasmaFluxP2dry™ (Fresenius Medical Care, Bad Homburg, Germany). The first two treatments were performed within the study for each patient: one with the Spectra Optia and one with the multiFiltrate. Duration of set-up and priming of the devices, total procedure time, blood flow, total plasma volume exchanged, volume of the removal bag, volume of the anticoagulant and the type of vascular access were documented. Laboratory parameters such as IgG, IgA, IgM, fibrinogen, white blood cell, red blood count and thrombocytes were documented before and after treatment. Data from the first two treatments were documented. The differences of the parameters were compared using the Wilcoxon matched-pairs signed-rank or Mann-Whitney (U) test. RESULTS A total of 26 patients (17 women /9 mem) were included in the study and 52 treatments were documented. A median of 3000 mL of plasma was treated; the median duration of the procedure was 117 min (cTPE) versus 154 min (mTPE) (P = .03). Despite removal of fibrinogen (P = .04), no significant differences were found for the removal IgG (P = .09), IgM (P = .18) and IgA (P = .57). Both methods were equally effective. Erythrocyte loss was higher with mTPE (P = .003), platelet loss tended to be higher with mTPE, but without reaching a level of significance (P = .22; Table 1). The results of the patient questionnaire are shown in Figure 1. CONCLUSION Both procedures can be performed safely with comparable results regarding parameters of quality as fibrinogen, IgG, IgM and IgA with a trend to better elimination with cTPE. Comparing the duration of the procedure, cTPE was significantly superior to mTPE. An advantage regarding cell loss (RBC) was seen for cTPE, platelet loss tended to be higher with mTPA, but without statistical significance. Finally, as a result of shorter duration, patients’ comfort was significantly higher with cTPE.