CSF neopterin, quinolinic acid and kynurenine/tryptophan ratio are biomarkers of active neuroinflammation.

Background: Defining the presence of acute and chronic brain inflammation remains a challenge to clinicians due to the heterogeneity of clinical presentations and aetiologies. However, defining the presence of neuroinflammation, and monitoring the effects of therapy is important given its reversible and potentially damaging nature. We investigated the utility of CSF metabolites in the diagnosis of primary neuroinflammatory disorders such as encephalitis and explored the potential pathogenic role of inflammation in epilepsy.

Treatment of severe acute necrotizing encephalopathy of childhood with interleukin-6 receptor blockade in the first 24 h as add-on immunotherapy shows favorable long-term outcome at 2 years.

Background: Acute necrotizing encephalopathy (ANE) of childhood is a rare and devastating infection-associated acute encephalopathy. While there are no consensus treatments for ANE, recent case reports suggest a beneficial role for the use of tocilizumab, a recombinant humanized monoclonal antibody against the interleukin-6 (IL-6) receptor. The correlation of the timing of add-on tocilizumab in relation to long-term outcome has not been reported.

Urgent computed tomography angiography in paediatric stroke.

Aim: To improve delivery of acute therapies for acute ischaemic stroke (AIS).

Method: We identified factors influencing the speed of diagnosis and delivery of acute therapies in a prospective cohort of 21 children with suspected AIS (eight with AIS, 13 stroke mimics) and explored them in a retrospective cohort with confirmed AIS.

Results: Approximately half of the prospective and total AIS cohorts presented with acute, sustained hemiparesis, and were diagnosed relatively quickly.

CSF neopterin, a useful biomarker in children presenting with influenza associated encephalopathy?

Purpose: Neurological complications of influenza cause significant disease in children. Central nervous system inflammation, the presumed mechanism of influenza-associated encephalopathy, is difficult to detect. Characteristics of children presenting with severe neurological complications of influenza, and potential biomarkers of influenza-associated encephalopathy are described.

High sensitivity and specificity in proposed clinical diagnostic criteria for anti-N-methyl-D-aspartate receptor encephalitis.

Aim: To determine the validity of the proposed clinical diagnostic criteria for anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis in paediatric patients.

Method: The diagnostic criteria for anti-NMDAR encephalitis proposed by Graus et al. (2016) use clinical features and conventional investigations to facilitate early immunotherapy before antibody status is available.

Utility of CSF Cytokine/Chemokines as Markers of Active Intrathecal Inflammation: Comparison of Demyelinating, Anti-NMDAR and Enteroviral Encephalitis.

Background: Despite the discovery of CSF and serum diagnostic autoantibodies in autoimmune encephalitis, there are still very limited CSF biomarkers for diagnostic and monitoring purposes in children with inflammatory or autoimmune brain disease. The cause of encephalitis is unknown in up to a third of encephalitis cohorts, and it is important to differentiate infective from autoimmune encephalitis given the therapeutic implications.

Aim: To study CSF cytokines and chemokines as diagnostic biomarkers of active neuroinflammation, and assess their role in differentiating demyelinating, autoimmune, and viral encephalitis.

Etiological associations and outcome predictors of acute electroencephalography in childhood encephalitis.

Objectives: To examine EEG features in a retrospective 13-year cohort of children with encephalitis.

Methods: 354 EEGs from 119 patients during their admission were rated blind using a proforma with demonstrated inter-rater reliability (mean k=0.78).

Postencephalitic epilepsy and drug-resistant epilepsy after infectious and antibody-associated encephalitis in childhood: Clinical and etiologic risk factors.

To define the risk factors for postencephalitic epilepsy (PE) and drug-resistant epilepsy (DRE) in childhood following infectious and autoimmune encephalitis, we included 147 acute encephalitis patients with a median follow-up of 7.3 years (range 2-15.8 years).

Symptomatic treatment of children with anti-NMDAR encephalitis.

Aim: We performed the first study on the perceived benefit and adverse effects of symptomatic management in children with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis.

Method: A retrospective chart review was undertaken at two tertiary paediatric hospitals in Australia and New Zealand. We included 27 children (12 males, 15 females; mean age at admission 7y 1mo) with anti-NMDAR antibodies in serum or cerebrospinal fluid with a typical clinical syndrome.

Infectious and autoantibody-associated encephalitis: clinical features and long-term outcome.

Background And Objectives: Pediatric encephalitis has a wide range of etiologies, clinical presentations, and outcomes. This study seeks to classify and characterize infectious, immune-mediated/autoantibody-associated and unknown forms of encephalitis, including relative frequencies, clinical and radiologic phenotypes, and long-term outcome.

Methods: By using consensus definitions and a retrospective single-center cohort of 164 Australian children, we performed clinical and radiologic phenotyping blinded to etiology and outcomes, and we tested archived acute sera for autoantibodies to N-methyl-D-aspartate receptor, voltage-gated potassium channel complex, and other neuronal antigens.

Confirmed enterovirus encephalitis with associated steroid-responsive acute disseminated encephalomyelitis: an overlapping infection and inflammation syndrome.

Background: Inflammatory disorders of the central nervous system have generally been separated into infectious or immune-mediated aetiologies. However, there are emerging examples of confirmed infectious viral infection of the brain followed by secondary inflammation or autoimmunity that is amenable to immune suppressive therapies.

Methods: We report four children with confirmed enterovirus encephalitis (CSF enterovirus PCR positivity), who had MRI evidence of inflammatory demyelination compatible with ADEM.

Movement disorders in children with anti-NMDAR encephalitis and other autoimmune encephalopathies.

Accurate recognition of movement disorder phenomenology may differentiate children with anti-N-methyl D-aspartate receptor (NMDAR) encephalitis, autoimmune basal ganglia encephalitis (BGE), and Sydenham's chorea (SC). Three neurologists blinded to the diagnoses recorded dominant and associated movement disorders seen on videos of 31 patients with anti-NMDAR encephalitis (n = 10), BGE (n = 12), and SC (n = 9). Stereotypy was only seen in anti-NMDAR encephalitis (8/10) and not in BGE and SC (P < 0.

Herpes simplex encephalitis relapse with chorea is associated with autoantibodies to N-Methyl-D-aspartate receptor or dopamine-2 receptor.

Background: Movement disorder relapses after herpes simplex virus 1 (HSV1) encephalitis have been hypothesized to be secondary to postviral autoimmunity. Recently, a proportion of patients with HSV1 encephalitis (HSE) were shown to produce autoantibodies against N-methyl-D-aspartate receptor (NMDAR).

Methods: We measured autoantibodies against NMDAR and dopamine-2 receptor (D2R) expressed at the cell surface in the stored acute serum of 9 children with HSE, 3 of whom had a relapsing course with chorea.

Cerebrospinal fluid CD19(+) B-cell expansion in N-methyl-D-aspartate receptor encephalitis.

There is increasing interest in the role of autoantibodies in acquired autoimmune central nervous system disorders. N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis defined by the presence of autoantibodies that bind to the NMDAR. Although there is evidence of NMDAR antibody pathogenicity, it is unclear which treatment results in the best outcome.

Antibodies to surface dopamine-2 receptor in autoimmune movement and psychiatric disorders.

Recent reports of autoantibodies that bind to neuronal surface receptors or synaptic proteins have defined treatable forms of autoimmune encephalitis. Despite these developments, many cases of encephalitis remain unexplained. We have previously described a basal ganglia encephalitis with dominant movement and psychiatric disease, and proposed an autoimmune aetiology.

Cortical hypometabolism demonstrated by PET in relapsing NMDA receptor encephalitis.

N-methyl-d-aspartate (NMDA) receptor encephalitis is a newly defined type of autoimmune encephalitis. Two girls (age 3 years, case 1, and 7 years, case 2) with relapsing NMDA receptor encephalitis each had the classic clinical features of encephalopathy, movement disorders, psychiatric symptoms, seizures, insomnia, and mild autonomic dysfunction. Both patients had persistent neuropsychiatric disability, despite immune therapies.

A prospective study of acute movement disorders in children.

Aim: The purpose of this study was to report a prospective cohort of children with acute-onset movement disorders.

Method: We report on 52 individuals (31 females, 21 males; mean age 6y 5mo, range 2mo-15y) with acute-onset movement disorders managed at a busy tertiary paediatric referral hospital over a 40-month period.

Results: In descending order of frequency, the movement disorders reported were chorea, dystonia, tremor, myoclonus, and parkinsonism.

N-methyl-D-aspartate receptor antibodies in pediatric dyskinetic encephalitis lethargica.

Encephalitis lethargica (EL) describes an encephalitis with psychiatric, sleep, and extrapyramidal movement disorders. Dyskinetic and parkinsonian forms have been described. EL shares clinical features with the anti-N-methyl-D-aspartate receptor (NMDAR-Ab) encephalitis.

Early relapse risk after a first CNS inflammatory demyelination episode: examining international consensus definitions.

The International Pediatric Multiple Sclerosis Study Group (IPMS) has recently proposed consensus definitions for paediatric multiple sclerosis (MS) and related disorders. The term 'acute disseminated encephalomyelitis' (ADEM) has been used previously to describe any monophasic episode of disseminated demyelination. The study group now propose that ADEM must be multifocal, polysymptomatic, and include encephalopathy (as an essential requirement).