Near infrared spectroscopy (NIRS) has been used to measure concentration changes of cerebral hemoglobin and cytochrome in neonates, children, and adults, to study cerebral oxygenation and hemodynamics. To derive quantitative concentration changes from measurements of light attenuation, the optical path length must be known. This is obtained by multiplying the source/ detector separation by a laboratory measured differential path length factor (DPF) which accounts for the increased distance traveled by light due to scattering. DPF has been measured by time of flight techniques on small populations of adults and postmortem infants. The values for adults are greater than those for newborns, and it is not clear how to interpolate the present data for studies on children. Recent developments in instrumentation using phase resolved spectroscopy techniques have produced a bedside unit which can measure optical path length on any subject. We have developed an intensity modulated optical spectrometer which measures path length at four wavelengths. Two hundred and eighty three subjects from 1 d of age to 50 y were studied. Measurements were made at a fixed frequency of 200 MHz and a source detector separation of 4.5 cm. Results suggest a slowly varying age dependence of DPF, following the relation DPF690 = 5.38 + 0.049A0.877, DPF744 = 5.11 + 0.106A0.723, DPF807 = 4.99 + 0.067A0.814, and DPF832 = 4.67 + 0.062A0.819, where DPF690 is the DPF measured at 690 nm and A is age is expressed in years from full term. There was a wide scatter of values, however, implying that ideally DPF should be measured at the time of each study.

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ObjectiveTo report the clinical and investigative features of children with a clinical diagnosis of probable autoimmune encephalopathy, both with and without antibodies to central nervous system antigens.MethodPatients with encephalopathy plus one or more of neuropsychiatric symptoms, seizures, movement disorder or cognitive dysfunction, were identified from 111 paediatric serum samples referred from five tertiary paediatric neurology centres to Oxford for antibody testing in 2007–2010. A blinded clinical review panel identified 48 patients with a diagnosis of probable autoimmune encephalitis whose features are described. All samples were tested/retested for antibodies to N-methyl-D-aspartate receptor (NMDAR), VGKC-complex, LGI1, CASPR2 and contactin-2, GlyR, D1R, D2R, AMPAR, GABA(B)R and glutamic acid decarboxylase.ResultsSeizures (83%), behavioural change (63%), confusion (50%), movement disorder (38%) and hallucinations (25%) were common. 52% required intensive care support for seizure control or profound encephalopathy. An acute infective organism (15%) or abnormal cerebrospinal fluid (32%), EEG (70%) or MRI (37%) abnormalities were found. One 14-year-old girl had an ovarian teratoma. Serum antibodies were detected in 21/48 (44%) patients: NMDAR 13/48 (27%), VGKC-complex 7/48(15%) and GlyR 1/48(2%). Antibody negative patients shared similar clinical features to those who had specific antibodies detected. 18/34 patients (52%) who received immunotherapy made a complete recovery compared to 4/14 (28%) who were not treated; reductions in modified Rankin Scale for children scores were more common following immunotherapies. Antibody status did not appear to influence the treatment effect.ConclusionsOur study outlines the common clinical and paraclinical features of children and adolescents with probable autoimmune encephalopathies. These patients, irrespective of positivity for the known antibody targets, appeared to benefit from immunotherapies and further antibody targets may be defined in the future.

We investigated the genetic, phenotypic, and interferon status of 46 patients from 37 families with neurological disease due to mutations in ADAR1. The clinicoradiological phenotype encompassed a spectrum of Aicardi–Goutières syndrome, isolated bilateral striatal necrosis, spastic paraparesis with normal neuroimaging, a progressive spastic dystonic motor disorder, and adult-onset psychological difficulties with intracranial calcification. Homozygous missense mutations were recorded in five families. We observed a p.Pro193Ala variant in the heterozygous state in 22 of 23 families with compound heterozygous mutations. We also ascertained 11 cases from nine families with a p.Gly1007Arg dominant-negative mutation, which occurred de novo in four patients, and was inherited in three families in association with marked phenotypic variability. In 50 of 52 samples from 34 patients, we identified a marked upregulation of type I interferon-stimulated gene transcripts in peripheral blood, with a median interferon score of 16.99 (interquartile range [IQR]: 10.64–25.71) compared with controls (median: 0.93, IQR: 0.57–1.30). Thus, mutations in ADAR1 are associated with a variety of clinically distinct neurological phenotypes presenting from early infancy to adulthood, inherited either as an autosomal recessive or dominant trait. Testing for an interferon signature in blood represents a useful biomarker in this context.

The Castang Foundation, Bath Unit for Research in Paediatrics, National Institute of Health Research, the Royal United Hospitals Bath NHS Foundation Trust, BRONNER-BENDER Stiftung/Gernsbach, University Children's Hospital Zurich.