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Epilepsy has been associated with a dysfunction of the blood-brain barrier. While there is ample evidence that a dysfunction of the blood-brain barrier contributes to epileptogenesis, blood-brain barrier dysfunction as a consequence of single epileptic seizures has not been systematically investigated. We hypothesized that blood-brain barrier dysfunction is temporally and anatomically associated with epileptic seizures in patients and used a newly-established quantitative MRI protocol to test our hypothesis. Twenty-three patients with epilepsy undergoing inpatient monitoring as part of their presurgical evaluation were included in this study (10 females, mean age ± standard deviation: 28.78 ± 8.45). For each patient, we acquired quantitative T1 relaxation time maps (qT1) after both ictal and interictal injection of gadolinium-based contrast agent. The postictal enhancement of contrast agent was quantified by subtracting postictal qT1 from interictal qT1 and the resulting ΔqT1 was used as a surrogate imaging marker of peri-ictal blood-brain barrier dysfunction. Additionally, the serum concentrations of MMP9 and S100, both considered biomarkers of blood-brain barrier dysfunction, were assessed in serum samples obtained prior to and after the index seizure. Fifteen patients exhibited secondarily generalized tonic-clonic seizures and eight patients exhibited focal seizures at ictal injection of contrast agent. By comparing ΔqT1 of the generalized tonic-clonic seizures and focal seizures groups, the anatomical association between ictal epileptic activity and postictal enhancement of contrast agent could be probed. The generalized tonic-clonic seizures group showed significantly higher ΔqT1 in the whole brain as compared to the focal seizures group. Specific analysis of scans acquired later than 3 h after the onset of the seizure revealed higher ΔqT1 in the generalized tonic-clonic seizures group as compared to the focal seizures group, which was strictly lateralized to the hemisphere of seizure onset. Both MMP9 and S100 showed a significantly increased postictal concentration. The current study provides evidence for the occurrence of a blood-brain barrier dysfunction, which is temporally and anatomically associated with epileptic seizures. qT1 after ictal contrast agent injection is rendered as valuable imaging marker of seizure-associated blood-brain barrier dysfunction and may be measured hours after the seizure. The observation of the strong anatomical association of peri-ictal blood-brain barrier dysfunction may spark the development of new functional imaging modalities for the post hoc visualization of brain areas affected by the seizure.

BackgroundThe measurement of maximal head circumference is a standard procedure in the examination of childrens’ cranial growth and brain development. The objective of the study was to evaluate the validity of maximal head circumference to cranial volume in the first year of life using a new method which includes ear-to-ear over the head distance and maximal cranial length measurement.Methods3D surface scans for cranial volume assessment were conducted in this method comparison study of 44 healthy Caucasian children (29 male, 15 female) at the ages of 4 and 12 months.ResultsCranial volume increased from measurements made at 4 months to 12 months of age by an average of 1174 ± 106 to 1579 ± 79 ml. Maximal cranial circumference increased from 43.4 ± 9 cm to 46.9 ± 7 cm and the ear-to ear measurement increased from 26.3 ± 21 cm to 31.6 ± 18 cm at the same time points. There was a monotone association between maximal head circumference (HC) and increase in volume, yet a backwards inference from maximal circumference to the volume had a predictive value of only 78% (adjusted R2). Including the additional measurement of distance from ear to ear strengthened the ability of the model to predict the true value attained to 90%. The addition of the parameter skull length appeared to be negligible.ConclusionThe results demonstrate that for a distinct improvement in the evaluation of a physiological cranial volume development, the additional measurement of the ear-to ear distance using a measuring tape is expedient, and, especially for cases with pathological skull changes, such as craniosynostosis, ought to be conducted.

Health authorities tend to favour an increase of the antigen dose in inactivated influenza vaccines from < or = 10 micrograms haemagglutinin (HA) per vaccine strain to 15 micrograms HA/strain. The increased dose is expected to yield a meaningful increase in the number of subjects to be protected after vaccination. To verify this expectation, we have reviewed 20 published reports (1978-1991) of serological studies in which anti-HA-IgG antibody after different doses was measured. In the review, stratification groups of previously primed subjects were formed and the antibody response was estimated for doses of 10 and 15 micrograms HA by linear k*2-chi 2 model. Despite a considerable heterogenicity of study populations, study designs, vaccine types and strains, and antibody assays, the results were consistent in revealing high protection rates (> or = 75%) for a 10 micrograms HA dose of influenza A vaccine components. For both response and protection rates, an increase of the antigenic load from 10 to 15 micrograms HA was not associated with a meaningful increase of seroresponse: in 38 out of 39 stratification groups, the increase of response and/or protection rate varied between -9% and +8%, with a median of 1.5%. These results do not justify the expectation that a vaccine dose of 15 micrograms HA per strain would be clinically superior to a dose of 10 micrograms HA. Only in a group of immune-compromised patients on chronic intermittent haemodialysis were results in favour of a higher dose found, which may justify further evaluation in this special population.