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. METHODS: A multi-center, retrospective case-series of children with influenza and neurological complications during 2017 was performed. Enrolled cases met criteria for influenza-associated encephalopathy or had status epilepticus. Functional outcome at discharge was compared between groups using the Modified Rankin Scale (mRS). RESULTS: There were 22 children with influenza studied of whom 11/22 had encephalopathy and 11/22 had status epilepticus. Only one child had a documented influenza immunization. The biomarker CSF neopterin was tested in 10/11 children with encephalopathy and was elevated in 8/10. MRI was performed in all children with encephalopathy and was abnormal in 8 (73%). Treatment of children with encephalopathy was with corticosteroids or intravenous immunoglobulin in 9/11 (82%). In all cases oseltamivir use was low (59%) while admission to the intensive care unit was frequent (14/22, 66%). Clinical outcome at discharge was moderate to severe disability (mRS score > 2) in the majority of children with encephalopathy (7/11, 64%), including one child who died. Children with status epilepticus recovered to near-baseline function in all cases. CONCLUSION: Raised CSF neopterin was present in most cases of encephalopathy, and along with diffusion restriction on MRI, is a useful diagnostic biomarker. Lack of seasonal influenza vaccination represents a missed opportunity to prevent illness in children, including severe neurological disease.

The Severity of Gliosis in Hippocampal Sclerosis Correlates with Pre-Operative Seizure Burden and Outcome After Temporal Lobectomy.

Astrogliosis and microgliosis in hippocampal sclerosis (HS) are widespread and are postulated to contribute to the pro-excitatory neuropathological environment. This study aimed to establish if seizure burden at the time of surgery or post-surgical outcome were correlated with the extent of gliosis in HS. As a secondary aim, we wanted to determine if the degree of gliosis could be predicted by pre-operative neuroimaging.Children and adults who underwent epilepsy surgery for HS between 2002 and 2011 were recruited (n = 43), and age-matched autopsy controls obtained (n = 15). Temporal lobe specimens were examined by DAB immunohistochemistry for astrocytes (glial fibrillary acidic protein (GFAP)) and microglia (CD68). Cell counting for GFAP and CD68 was performed and quantitative densitometry undertaken for GFAP. Seizure variables and outcome (Engel) were determined through medical record and patient review. Seizure frequency in the 6 months prior to surgery was measured to reflect the acute seizure burden. Duration of seizures, age at onset and age at operation were regarded to reflect chronic seizure burden. Focal, lobar and generalized atrophy on pre-operative MRI were independently correlated with the degree of cortical gliosis in the surgical specimen.In HS, both acute and chronic seizure burden were positively correlated with the degree of gliosis. An increase in reactive astrocyte number in CA3 was the strongest predictor of poor post-operative seizure outcome at 1 and 3 years post-operatively in this cohort. Changes in lower cortical astrocyte and upper cortical microglial number also correlated with post-operative outcome at 1 year. Post-surgical seizure outcome (1, 3 and 5 years) did not otherwise correlate with GFAP immunoreactivity (GFAP-IR) or CD68 immunoreactivity (CD68-IR). Increased microglial activation was detected in patients with pre-operative bilateral convulsive seizures, compared to those without convulsive seizures. Furthermore, focal, lobar and generalized atrophy on pre-operative neuroimaging were independently correlated with the degree of cortical gliosis in the surgical specimen.

Clinicopathological associations in temporal lobe epilepsy patients utilising the current ILAE focal cortical dysplasia classification.

OBJECTIVES: This study utilised the revised 2011 ILAE classification of focal cortical dysplasia (FCD) (Blümcke et al., 2011) to examine pathology in a cohort of children and adults who underwent temporal lobe epilepsy (TLE) surgery, and to describe the electroclinical and imaging features associated with these pathologies. METHODS: The sample population were children (n=26) and adults (n=47) who underwent TLE surgery between 2002 and 2011 at our institutions. Neuropathology and MRI studies were re-reviewed by experts blinded to the original diagnosis. EEG and clinical data including current seizure outcome were determined by patient file review and/or patient contact. Pre-operative data, post-operative outcome and pathological diagnoses were compared. RESULTS: The commonest pathology in the adult cohort was isolated hippocampal sclerosis (HS) (n=24, 51.1%) and in the paediatric cohort, isolated tumour (n=10, 38.5%). Overall, HS with associated FCD (FCD IIIA) was the third most common pathology (n=12, 16.4%). Temporal grey matter signal changes on MRI were associated with FCD IIIA (p=0.035). FCD IIIA had the poorest post-surgical seizure outcome compared to all other pathologies (p=0.026). A history of bilateral convulsive seizures was more common in adults (n=40, p<0.0005), and was associated with failure to achieve postoperative seizure freedom (p=0.045). Postoperatively, paediatric TLE had higher rates of seizure freedom (p=0.005) and more children had ceased medication (p<0.0005). SIGNIFICANCE: FCD IIIA is a comparatively common pathological subtype in TLE, with a poor post-surgical outcome. Pre-operative recognition of FCD IIIA may be feasible through grey matter signal change on MRI. Paediatric patients had a higher rate of seizure freedom than adults. Pre-operative bilateral convulsive seizures were associated with poor outcome after surgery.

Occult epiphyseal bone abscess: lessons for the unwary.

Two male children presented with increasing pain in the right knee and constitutional symptoms. Biochemical markers of inflammation were elevated. Plain radiography was reported as normal and bone scintigraphy was consistent with synovitis of the right knee in the first case. The second child underwent aspiration of the knee with drainage of turbid fluid 1 week after antibiotics. Slow response to therapy led to MRI and CT scanning in the second child, revealing an epiphyseal abscess. Review of the scintigraphic studies in the first child raised the possibility of osteomyelitis of the distal right femur. Further imaging was undertaken with MRI and CT scanning confirming an epiphyseal bone abscess. Failure of diagnosis of an epiphyseal bone abscess by combined plain radiography and scintigraphy has not previously been reported and provides a number of valuable lessons.