Development and internal validation of clinical prediction models for scrub typhus and doxycycline-treatable causes in paediatric acute encephalitis syndrome in Karnataka, India: a multicentre, prospective study.

Background: Scrub typhus and other doxycycline-treatable infections are significant contributors of acute encephalitis syndrome (AES) in India. Limited surveillance in South India has hindered their recognition and the inclusion of doxycycline in treatment protocols. We aimed to systematically investigate infectious aetiologies of AES in children from Karnataka, India, and develop clinical prediction models for diagnosing scrub typhus and guiding clinical decisions for doxycycline therapy.

Integrating patient and public involvement during the COVID-19 pandemic: lessons from COVID-clinical neuroscience study.

Background: The COVID-19 Clinical Neuroscience Study (COVID-CNS) was a large UK research initiative investigating the clinical features, outcomes and biological mechanisms behind neurological and psychiatric complications from COVID-19. Through partnerships and patient enrolment, the study aimed to inform patient care and treatment selection to improve outcomes.

Methods: Here, we evaluate the methodologies and results yielded from patient and public involvement (PPI) efforts within COVID-CNS, an important element of the research cycle which introduces patient perspectives and enhances research relevance.

Viral encephalitis - update on pathogenesis and treatment.

Purpose Of Review: Viral encephalitis is a potentially devastating condition of cerebral inflammation manifest as a combination of fever, altered mentation, and sometimes focal neurological signs and seizures. In this review we explore the new developments in understanding of the epidemiology, pathogenesis and treatment options.

Recent Findings: The WHO technical brief is a landmark document which sets the stage for the advancement of the surveillance, prevention and management of viral encephalitis.

Aetiologies, neuroradiological features, and risk factors for mortality and long-term neurosequelae of febrile coma in Malawian children: a prospective cohort study.

Background: Children in febrile coma in Africa are frequently hospitalised, with poorer outcomes than those in high-income settings. Cerebral malaria is historically the most common cause of febrile coma. Due to limited diagnostic and radiological resources and a decrease in malaria prevalence, there might be under-recognition of non-malarial coma.

The aetiologies, mortality, and disability of non-traumatic coma in African children: a systematic review and meta-analysis.

Background: Non-traumatic coma in African children is a common life-threatening presentation often leading to hospital attendance. We aimed to estimate the distribution of non-traumatic coma causes and outcomes, including disease-specific outcomes, for which evidence is scarce.

Methods: We systematically reviewed MEDLINE, Embase, and Scopus databases from inception to Feb 6, 2024.

A multifaceted intervention to improve diagnosis and early management of hospitalised patients with suspected acute brain infections in Brazil, India, and Malawi: an international multicentre intervention study.

Background: Brain infections pose substantial challenges in diagnosis and management and carry high mortality and morbidity, especially in low-income and middle-income countries. We aimed to improve the diagnosis and early management of patients admitted to hospital (adults aged 16 years and older and children aged >28 days) with suspected acute brain infections at 13 hospitals in Brazil, India, and Malawi.

Methods: With hospital stakeholders, policy makers, and patient and public representatives, we co-designed a multifaceted clinical and laboratory intervention, informed by an evaluation of routine practice.

Microbiological Investigations for Chikungunya Virus in Children With Acute Encephalitis Syndrome in a Non-Outbreak Setting in Southern India.

Chikungunya virus (CHIKV) is an emerging cause of acute encephalitis syndrome (AES) in India, with limited data on its role in childhood AES in southern India. We systematically evaluated children with AES in southern India during a non-epidemic period for CHIKV. Serum and cerebrospinal fluid (CSF) samples were tested for CHIKV using IgM ELISA and real-time reverse transcriptase PCR.

Patients with neurological or psychiatric complications of COVID-19 have worse long-term functional outcomes: COVID-CNS-A multicentre case-control study.

It is established that patients hospitalised with COVID-19 often have ongoing morbidity affecting activity of daily living (ADL), employment, and mental health. However, little is known about the relative outcomes in patients with COVID-19 neurological or psychiatric complications. We conducted a UK multicentre case-control study of patients hospitalised with COVID-19 (controls) and those who developed COVID-19 associated acute neurological or psychiatric complications (cases).

Crossing the blood-brain barrier: emerging therapeutic strategies for neurological disease.

The blood-brain barrier is a physiological barrier that can prevent both small and complex drugs from reaching the brain to exert a pharmacological effect. For treatment of neurological diseases, drug concentrations at the target site are a fundamental parameter for therapeutic effect; thus, the blood-brain barrier is a major obstacle to overcome. Novel strategies have been developed to circumvent the blood-brain barrier, including CSF delivery, intracranial delivery, ultrasound-based methods, membrane transporters, receptor-mediated transcytosis, and nanotherapeutics.

Pulmonary SARS-CoV-2 infection leads to para-infectious immune activation in the brain.

Neurological complications, including encephalopathy and stroke, occur in a significant proportion of COVID-19 cases but viral protein is seldom detected in the brain parenchyma. To model this situation, we developed a novel low-inoculum K18-hACE2 mouse model of SARS-CoV-2 infection during which active viral replication was consistently seen in mouse lungs but not in the brain. We found that several mediators previously associated with encephalopathy in clinical samples were upregulated in the lung, including CCL2, and IL-6.

Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction.

The spectrum, pathophysiology and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the 1-year cognitive, serum biomarker and neuroimaging findings from a prospective, national study of cognition in 351 COVID-19 patients who required hospitalization, compared with 2,927 normative matched controls. Cognitive deficits were global, associated with elevated brain injury markers and reduced anterior cingulate cortex volume 1 year after COVID-19.

Utilising accessible and reproducible neurological assessments in clinical studies: Insights from use of the Neurological Impairment Scale in the multi-centre COVID-CNS study.

Reproducible and standardised neurological assessment scales are important in quantifying research outcomes. These scales are often performed by non-neurologists and/or non-clinicians and must be robust, quantifiable, reproducible and comparable to a neurologist's assessment. COVID-CNS is a multi-centre study which utilised the Neurological Impairment Scale (NIS) as a core assessment tool in studying neurological outcomes following COVID-19 infection.

Using Multiphoton Intravital Microscopy to Study Neutrophil Transmigration and Blood-Brain Barrier Permeability in a Mouse Model of Herpes Simplex Virus Encephalitis.

Multiphoton intravital microscopy (MP-IVM) is an imaging technique used for the observation of living organisms at a microscopic resolution. The tissue of interest is exposed through a window allowing imaging of cells in real time. Using MP-IVM, the temporospatial kinetics of leukocyte transendothelial migration can be visualized and quantitated using reporter mice and cell-specific fluorophore-conjugated monoclonal antibodies to track the leukocytes within and outside of vascular beds.

Cognitive domains affected post-COVID-19; a systematic review and meta-analysis.

Background And Purpose: This review aims to characterize the pattern of post-COVID-19 cognitive impairment, allowing better prediction of impact on daily function to inform clinical management and rehabilitation.

Methods: A systematic review and meta-analysis of neurocognitive sequelae following COVID-19 was conducted, following PRISMA-S guidelines. Studies were included if they reported domain-specific cognitive assessment in patients with COVID-19 at >4 weeks post-infection.

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses.

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1-11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury.

A clinical approach to the investigation and management of long COVID associated neuropathic pain.

COVID-19 has been associated with a wide range of ongoing symptoms following recovery from the acute SARS-CoV-2 infection. Around one in three people with COVID-19 develop neurological symptoms with many reporting neuropathic pain and associated symptoms, including paraesthesia, numbness, and dysesthesia. Whilst the pathophysiology of long COVID-19-associated neuropathic pain remains unclear, it is likely to be multifactorial.

Pre-existing neurological conditions and COVID-19 co-infection: Data from systematic reviews, meta-analyses, and scoping reviews.

Background: Pre-existing neurological diseases have been identified as risk factors for severe COVID-19 infection and death. There is a lack of comprehensive literature review assessing the relationship between pre-existing neurological conditions and COVID-19 outcomes. Identification of high risk groups is critical for optimal treatment and care.

Mental health outcomes of encephalitis: An international web-based study.

Background And Purpose: Acute encephalitis is associated with psychiatric symptoms. Despite this, the extent of mental health problems following encephalitis has not been systematically reported.

Methods: We recruited adults who had been diagnosed with encephalitis of any aetiology to complete a web-based questionnaire.

Clinical predictors of encephalitis in UK adults-A multi-centre prospective observational cohort study.

Objectives: Encephalitis, brain inflammation and swelling, most often caused by an infection or the body's immune defences, can have devastating consequences, especially if diagnosed late. We looked for clinical predictors of different types of encephalitis to help clinicians consider earlier treatment.

Methods: We conducted a multicentre prospective observational cohort study (ENCEPH-UK) of adults (> 16 years) with suspected encephalitis at 31 UK hospitals.

Encephalitis: diagnosis, management and recent advances in the field of encephalitides.

Encephalitis describes inflammation of the brain parenchyma, typically caused by either an infectious agent or through an autoimmune process which may be postinfectious, paraneoplastic or idiopathic. Patients can present with a combination of fever, alterations in behaviour, personality, cognition and consciousness. They may also exhibit focal neurological deficits, seizures, movement disorders and/or autonomic instability.