Background. Neonatal hyperbilirubinemia (HB) may cause severe neurological damage, but serious consequences are effectively controlled by phototherapy and blood exchange transfusion. HB is still a serious health problem in economically compromised parts of the world. The long term outcome has been regarded favorable based on epidemiological data, but has not been confirmed in prospective follow-up studies extending to adulthood.Methods. We studied the long term consequences of HB in a prospective birth cohort of 128 HB cases and 82 controls. The cases are part of a neonatal at-risk cohort (n = 1196) that has been followed up to 30 years of age. HB cases were newborns ≥ 2500 g birth weight and ≥ 37 weeks of gestation who had bilirubin concentrations > 340 µmol/l or required blood exchange transfusion. Subjects with HB were divided into subgroups based on the presence (affected HB) or absence (unaffected HB) of diagnosed neurobehavioral disorders in childhood, and compared with healthy controls. Subjects were seen at discharge, 5, 9 and 16 years of life and parent’s and teacher’s assessments were recorded. At 30 years they filled a questionnaire about academic and occupational achievement, life satisfaction, somatic and psychiatric symptoms including a ADHD self-rating score. Cognitive functioning was tested using ITPA, WISC, and reading and writing tests at 9 years of life.Results. Compared to controls, the odds for a child with HB having neurobehavioral symptoms at 9 years was elevated (OR = 4.68). Forty-five per cent of the HB group were affected by cognitive abnormalities in childhood and continued to experience problems in adulthood. This was apparent in academic achievement (p < 0.0001) and the ability to complete secondary (p < 0.0001) and tertiary (p < 0.004) education. Also, the subgroup of affected HB reported persisting cognitive complaints e.g., problems with reading, writing and mathematics. Childhood symptoms of hyperactivity/impulsivity (p < 0.0001) and inattention (p < 0.02) were more common in HB groups, but in adulthood the symptoms were equal. The affected HB had lower scores in parameters reflecting life satisfaction, less controlled drinking, but not increased substance abuse.Discussion. Our results indicate that neonatal HB has negative consequences in adult age. A prospectively collected cohort with strict inclusion criteria enables to control most of the bias factors involved with retrospective data. The control and HB groups were remarkably similar at birth in terms of medical data, and the growth environment of the children, as well as the parents’ social groups, education, size of family, type of housing at birth and at 9 years of age. Our findings bear resemblance to disorders of the fronto-striatal network, and also symptoms of the ADHD spectrum were frequent in the HB group suggesting a link of HB to other neurodevelopmental disorders.
SUMMARY Thirteen patients with a dense appearance of the horizontal part of the middle cerebral artery (MCA) "dense middle cerebral artery sign" in CT scans taken within 24 hours after onset of ischaemic stroke had considerably poorer prognosis than controls with stroke, but without the sign. A hyperdense appearance of the MCA is known to be associated with thromboembolism, but dense middle cerebral artery sign is also an early warning of a large infarction, brain oedema and poor prognosis in infarction in the MCA area.In a period of 2 weeks, we saw three cases of MCA infarction with the dense middle cerebral artery sign in CT scans taken during the first 24 hours after onset of stroke. Each patient died within a week from the first symptoms. We investigated the possible predictive value of the dense middle cerebral artery sign, because hypodense lesions showing the area of infarction are likely not to be seen on CT during this time.The volume of infarction seen on CT scans is a prognostic sign.' Unfortunately, CT first becomes positive 8-24 hours after the onset of ischaemic stroke symptoms,2 thus not allowing immediate assessment of patients' prognosis. The dense appearance of the MCA on CT was first reported by Gacs et al3 in seven patients. They correlated the finding with thromboembolism, but not to clinical outcome. We now report that this early-phase CT finding indicates a poor clinical outcome in infarction in the MCA area. Patients and methodsWe searched for the presence of the dense middle cerebral artery sign in CT scans taken during the first 24 hours after onset of stroke in patients with acute ischaemic hemiparesis during a period of one year. All the scans were seen by a neuroradiologist (LK). Patients and controls were included in the study according
The hexanucleotide repeat expansion in intron 1 of the C9orf72 gene causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. In addition to the effects of the pathogenic expansion, a role of intermediate-length alleles has been suggested in ALS, corticobasal degeneration and Parkinson’s disease. Due to the rarity of intermediate-length alleles with over 20 repeats and the geographical variability in their frequency, large studies that account for population stratification are needed to elucidate their effects. To this aim, we used repeat-primed PCR and confirmatory PCR assays to determine the C9orf72 repeat allele lengths in 705 ALS patients and 3958 controls from Finland. After exclusion of expansion carriers (25.5% of the ALS patients and 0.2% of the controls), we compared the frequency of intermediate-length allele carriers of 525 ALS cases and 3950 controls using several intermediate-length allele thresholds (7–45, 17–45, 21–45, 24–45 and 24–30). The carriership of an intermediate-length allele did not associate with ALS (Fisher’s test, all p ≥ 0.15) nor was there any association with survival (p ≥ 0.33), when we divided our control group into three age groups (18–65, 66–84 and 85–105 years). Carriership of two intermediate-length alleles was associated with ALS, when the longer allele was ≥ 17 repeats (p = 0.002, OR 5.32 95% CI 2.02–14.05) or ≥ 21 repeats (p = 0.00016, OR 15.21 95% CI 3.79–61.0). Our results show that intermediate-length alleles are a risk factor of ALS when present in both alleles, whereas carrying just one intermediate-length allele was not associated with ALS or survival.
sICAM-5 is cleaved from CNS into CSF during acute encephalitis, and it may mediate leukocyte--neuron interactions. sICAM-5 release from cerebral neurons may actively regulate immune responses and leukocyte adhesion during microbial neuroinvasion in humans during encephalitis.
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