Update on Viral Infections Involving the Central Nervous System in Pediatric Patients

Infections of the central nervous system (CNS) are mainly caused by viruses, and these infections can be life-threatening in pediatric patients. Although the prognosis of CNS infections is often favorable, mortality and long-term sequelae can occur. The aims of this narrative review were to describe the specific microbiological and clinical features of the most frequent pathogens and to provide an update on the diagnostic approaches and treatment strategies for viral CNS infections in children. A literature analysis showed that the most common pathogens worldwide are enteroviruses, arboviruses, parechoviruses, and herpesviruses, with variable prevalence rates in different countries. Lumbar puncture (LP) should be performed as soon as possible when CNS infection is suspected, and cerebrospinal fluid (CSF) samples should always be sent for polymerase chain reaction (PCR) analysis. Due to the lack of specific therapies, the management of viral CNS infections is mainly based on supportive care, and empiric treatment against herpes simplex virus (HSV) infection should be started as soon as possible. Some researchers have questioned the role of acyclovir as an empiric antiviral in older children due to the low incidence of HSV infection in this population and observed that HSV encephalitis may be clinically recognizable beyond neonatal age. However, the real benefit-risk ratio of selective approaches is unclear, and further studies are needed to define appropriate indications for empiric acyclovir. Research is needed to find specific therapies for emerging pathogens. Moreover, the appropriate timing of monitoring neurological development, performing neuroimaging evaluations and investigating the effectiveness of rehabilitation during follow-up should be evaluated with long-term studies.

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Neuroinvasion and Inflammation in Viral Central Nervous System Infections

Mediators of Inflammation ◽

10.1155/2016/8562805 ◽

2016 ◽

Vol 2016 ◽

pp. 1-16 ◽

Cited By ~ 51

Author(s):

Tobias Dahm ◽

Henriette Rudolph ◽

Christian Schwerk ◽

Horst Schroten ◽

Tobias Tenenbaum

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Treatment Strategies ◽

The Elderly ◽

Brain Barrier ◽

Cns Infection ◽

Proinflammatory Response ◽

Cns Inflammation ◽

Cns Infections ◽

Cytokines And Chemokines

Neurotropic viruses can cause devastating central nervous system (CNS) infections, especially in young children and the elderly. The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) have been described as relevant sites of entry for specific viruses as well as for leukocytes, which are recruited during the proinflammatory response in the course of CNS infection. In this review, we illustrate examples of established brain barrier models, in which the specific reaction patterns of different viral families can be analyzed. Furthermore, we highlight the pathogen specific array of cytokines and chemokines involved in immunological responses in viral CNS infections. We discuss in detail the link between specific cytokines and chemokines and leukocyte migration profiles. The thorough understanding of the complex and interrelated inflammatory mechanisms as well as identifying universal mediators promoting CNS inflammation is essential for the development of new diagnostic and treatment strategies.

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Infections of the central nervous system

Oxford Textbook of Neuropsychiatry ◽

10.1093/med/9780198757139.003.0020 ◽

2020 ◽

pp. 217-228

Author(s):

Guleed Adan ◽

Sam Nightingale ◽

Christine Burness ◽

Tom Solomon

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Psychiatric Symptoms ◽

Early Recognition ◽

Psychiatric Patients ◽

Cns Infection ◽

Cns Infections ◽

System P ◽

The Central Nervous System ◽

Psychiatric Manifestations

Central nervous system (CNS) infections, caused by various pathogens, can lead to a wide range of neuropsychiatric sequelae, including acute psychosis, mood disorders, and chronic dementias. Early recognition is critical as brain infections are often treatable and possible neuropsychiatric illness can be reversed if the diagnosis is timely. In addition to psychiatric symptoms, CNS infections may also present with other signs such as fever, meningism, cranial nerve deficit, and seizures. Although the presence of these additional features can often provide a clue to an underlying CNS infection, they are not always present; hence CNS infections should be considered in the differential diagnosis of psychiatric patients in certain situations. In this chapter, CNS infections that have psychiatric manifestations or have psychiatric sequelae are discussed, in particular HIV, neurosyphilis, meningitis, and encephalitis.

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Viral infections of the central nervous system in Qatar: epidemiology, pathogenesis and clinical outcomes

The Journal of Infection in Developing Countries ◽

10.3855/jidc.10156 ◽

2018 ◽

Vol 12 (02.1) ◽

pp. 29S

Author(s):

Fatma Ben Abed ◽

Muhamed Abukhattab ◽

Obada Khalil ◽

Ahmed Gohar ◽

Hafedh Gazwani ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Clinical Outcomes ◽

Healthcare System ◽

Case Definition ◽

Cns Infection ◽

Viral Etiology ◽

Gulf Region ◽

Cns Infections ◽

The Central Nervous System

Introduction: Virus-induced diseases of the central nervous system (CNS) represent a significant burden to human health worldwide. They are common causes of morbidities and mortality. There are no previous epidiomologic studies about viral CNS infections done in Qatar or in the Gulf region. We conducted this study to determine the etiology, clinical and epidimiological characteristics, and outcome of viral central nerveous system infection in patients across a larger national healthcare system. Methodology: We retrospectively evaluated all cerebrospinal fluid findings from January 2011 – March 2015 at any of the 7 hospitals in the Hamad Medical Corporation healthcare system. We included those with an abnormal CSF finding in our study. We excluded those with missing medical records, those with no clinical evidence of CNS infection or proven bacterial CNS infection. Based on pre-defined clinical and CSF (lab, culture, PCR) criteria, persons with abnormal CSF and CNS clinical findings were classified as having meningitis, meningoencephalitis, encephalitis or myelitis. We reviewed the laboratory results to determine the proportion of persons with confirmed viral etiology. Results: Among 7690 patients with available CSF results, 550 cases met the case definition criteria for viral CNS infection (meningitis 75%; meningoencephalitis 16%; encephalitis 9%; myelitis 0.4%). Two-thirds (65%) were male and 50% were between 16-60 years old. Persons from Southeast Asia (India, Pakistan, Bangladesh, Nepal, and Sri Lanka) accounted for 39.6 of all infections. A definitive virologic etiologic agent was found in 38%, among whom enterovirus was the most common (44.3%) followed by Epstein-Barr virus (31%) and varicella zoster virus (12.4%). The clinical outcome was overall good, only 2 cases died and the rest discharged to home. Ninety-eight per cent were admitted to medical ward (mean stay 7.8±6.4 days) and 2 % to an intensive care unit. (mean stay 2.7±5.4 days). Among those with confirmed viral etiology, 83.8% received ceftriaxone, 38% received vancomycin and 38% received at least one other antibiotic. Conclusion: Viral etiology is not uncommon among those evaluated for CNS infection in Qatar, and is most commonly seen in Southeast Asian immigrants. Clinical outcomes are generally excellent in this group of patients. Antibiotics are overly used even when a viral etiology is confirmed. There is a need for clinician education regarding etiology and treatment of CNS infections.

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Vertebral Body Sparing Craniospinal Irradiation for Pediatric Patients With Cancer of the Central Nervous System

Case Medical Research ◽

10.31525/ct1-nct04276194 ◽

2020 ◽

Author(s):

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Vertebral Body ◽

Pediatric Patients ◽

Craniospinal Irradiation ◽

Patients With Cancer ◽

The Central Nervous System

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Self-buffering capacity of a human sulfatase for central nervous system delivery

Scientific Reports ◽

10.1038/s41598-021-86178-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yi Wen ◽

Nazila Salamat-Miller ◽

Keethkumar Jain ◽

Katherine Taylor

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Buffering Capacity ◽

The Self ◽

High Concentration ◽

Formulation Design ◽

The Central Nervous System ◽

Therapeutic Enzymes ◽

Intrathecal Space

AbstractDirect delivery of therapeutic enzymes to the Central Nervous System requires stringent formulation design. Not only should the formulation design consider the delicate balance of existing ions, proteins, and osmolality in the cerebrospinal fluid, it must also provide long term efficacy and stability for the enzyme. One fundamental approach to this predicament is designing formulations with no buffering species. In this study, we report a high concentration, saline-based formulation for a human sulfatase for its delivery into the intrathecal space. A high concentration formulation (≤ 40 mg/mL) was developed through a series of systematic studies that demonstrated the feasibility of a self-buffered formulation for this molecule. The self-buffering capacity phenomenon was found to be a product of both the protein itself and potentially the residual phosphates associated with the protein. To date, the self-buffered formulation for this molecule has been stable for up to 4 years when stored at 5 ± 3 °C, with no changes either in the pH values or other quality attributes of the molecule. The high concentration self-buffered protein formulation was also observed to be stable when exposed to multiple freeze–thaw cycles and was robust during in-use and agitation studies.

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Metagenomic Next-Generation Sequencing for Pathogen Detection and Transcriptomic Analysis in Pediatric Central Nervous System Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab104 ◽

2021 ◽

Author(s):

Nanda Ramchandar ◽

Nicole G Coufal ◽

Anna S Warden ◽

Benjamin Briggs ◽

Toni Schwarz ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Next Generation Sequencing ◽

Usual Care ◽

Transcriptomic Analysis ◽

Cns Infection ◽

Metagenomic Sequencing ◽

Next Generation ◽

Cns Infections ◽

Generation Sequencing

Abstract Background Pediatric central nervous system (CNS) infections are potentially life-threatening and may incur significant morbidity. Identifying a pathogen is important, both in terms of guiding therapeutic management, but also in characterizing prognosis. Usual care testing by culture and PCR is often unable to identify a pathogen. We examined the systematic application of metagenomic next-generation sequencing (mNGS) for detecting organisms and transcriptomic analysis of cerebrospinal fluid (CSF) in children with CNS infections. Methods We conducted a prospective multi-site study that aimed to enroll all children with a CSF pleocytosis and suspected CNS infection admitted to one of three tertiary pediatric hospitals during the study timeframe. After usual care testing had been performed, the remaining CSF was sent for mNGS and transcriptomic analysis. Results We screened 221 and enrolled 70 subjects over a 12-month recruitment period. A putative organism was isolated from CSF in 25 (35.7%) subjects by any diagnostic modality. mNGS of the CSF samples identified a pathogen in 20 (28.6%) subjects, which were also all identified by usual care testing. The median time to result was 38 hours. Conclusion Metagenomic sequencing of CSF has the potential to rapidly identify pathogens in children with CNS infections.

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CHRONIC LEAD ENCEPHALOPATHY

PEDIATRICS ◽

10.1542/peds.25.2.309 ◽

1960 ◽

Vol 25 (2) ◽

pp. 309-315

Author(s):

Harry H. White ◽

Fred D. Fowler

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Pediatric Patients ◽

Early Recognition ◽

Central Nervous System Involvement ◽

Fast Screening ◽

The Central Nervous System ◽

Lead Encephalopathy ◽

Urinary Coproporphyrin

Chronic lead encephalopathy must be considered in the differential diagnosis of pediatric patients who present with manifestations of schizophrenia, behavior disorders or degenerative diseases of the central nervous system. Determination of urinary coproporphyrin is a simple, fast screening procedure applicable to office practice. The prognosis for normal mental development following encephalopathy is poor. It is hoped that early recognition of the more subtle signs of central nervous system involvement will allow treatment to be instituted soon enough to prevent the crippling mental deterioration which is so often a sequela of lead poisoning.

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