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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.

ObjectivesTo estimate the cancer risk of HIV-infected patients in the HAART era with respect to a general reference population and to determine risk factors for malignancy.MethodsLong term (1996-2009) cancer incidence of the Bonn single centre HIV cohort was compared to the incidence of the reference population of Saarland using standardized incidence ratios (SIR). Poisson regression analysis was used to identify predictors of cancer risk.Results1,476 patients entered the cohort, enabling 8,772 person years of observation. 121 tumours in 114 patients, 7 in-situ and 114 invasive cancers, were identified. Malignancies associated with infectious agents such as Kaposi sarcoma (SIRs: male: 5,683; female: 277), non-Hodgkin lymphoma (SIRs male: 35; female: 18), anal cancer (SIRs male: 88; female: 115) as well a cervical carcinoma (SIR female: 4) and Hodgkin's disease (SIR male: 39) and liver cancer (SIR male: 18) were substantially more frequent in HIV-infected patients than in the general population (p < 0.001, each), whereas all other types of cancer were not increased. Poisson regression identified HAART (incidence rate ratio IRR (95% CI): 0.28 (0.19-0.41), p < 0.001), CD4 count (IRR per 100 cells/μl increase: 0.66 (0.57-0.76), p < 0.001), hepatitis B (IRR: 2.15 (1.10-4.20), p = 0.046) and age (IRR per 10 year increase: 1.23 (1.03 - 1.46), p = 0.023) as independent predictors for the occurrence of any type of cancer.ConclusionsHAART and preserved CD4 cells preferentially reduce the risk of malignancies associated with oncogenic infections.

BACKGROUND AND PURPOSE: Limbic encephalitis is an autoimmune disease. A variety of autoantibodies have been associated with different subtypes of limbic encephalitis, whereas its MR imaging signature is uniformly characterized by mesiotemporal abnormalities across subtypes. Here, we hypothesized that patients with limbic encephalitis would show subtype-specific mesiotemporal structural correlates, which could be classified by supervised machine learning on an individual level. MATERIALS AND METHODS: T1WI MPRAGE scans from 46 patients with antibodies against glutamic acid decarboxylase and 34 patients with antibodies against the voltage-gated potassium channel complex (including 10 patients with leucine-rich glioma-inactivated 1 autoantibodies) and 48 healthy controls were retrospectively ascertained. Parcellation of the amygdala, hippocampus, and hippocampal subfields was performed using FreeSurfer. Volumes were extracted and compared between groups using unpaired, 2-tailed t tests. The volumes of hippocampal subfields were analyzed using a multivariate linear model and a binary decision tree classifier. RESULTS: Temporomesial volume alterations were most pronounced in an early stage and in the affected hemispheric side of patients. Statistical analysis revealed antibody-specific hippocampal fingerprints with a higher volume of CA1 in patients with glutamic acid decarboxylase-associated limbic encephalitis (P = .02), compared with controls, whereas CA1 did not differ from that in controls in patients with voltage-gated potassium channel complex autoantibodies. The classifier could successfully distinguish between patients with autoantibodies against leucine-rich glioma-inactivated 1 and glutamic acid decarboxylase with a specificity of 87% and a sensitivity of 80%. CONCLUSIONS: Our results suggest stage-, side-and antibody-specific structural correlates of limbic encephalitis; thus, they create a perspective toward an MR imaging-based diagnosis. ABBREVIATIONS: CASPR2 4 contactin-associated proteinlike 2; EEG 4 electroencephalogram; GAD 4 glutamic acid decarboxylase; GAD-LE 4 limbic encephalitis with glutamic acid decarboxylase-associated autoantibodies; LE 4 limbic encephalitis; LGI1 4 leucine-rich glioma-inactivated 1; VGKC 4 voltagegated potassium channel complex; VGKC-LE 4 limbic encephalitis with voltage-gated potassium channel complex-associated autoantibodies

Motor function after hemispheric lesions has been associated with the structural integrity of either the pyramidal tract (PT) or alternate motor fibers (aMF). In this study, we aimed to differentially characterize the roles of PT and aMF in motor compensation by relating diffusion-tensor-imagingderived parameters of white matter microstructure to measures of proximal and distal motor function in patients after hemispherotomy. Twenty-five patients (13 women; mean age: 21.1 years) after hemispherotomy (at mean age: 12.4 years) underwent Diffusion Tensor Imaging and evaluation of motor function using the Fugl-Meyer Assessment and the index finger tapping test. Regression analyses revealed that fractional anisotropy of the PT explained (p = 0.050) distal motor function including finger tapping rate (p = 0.027), whereas fractional anisotropy of aMF originating in the contralesional cortex and crossing to the ipsilesional hemisphere in the pons explained proximal motor function (p = 0.001). Age at surgery was found to be the only clinical variable to explain motor function (p < 0.001). Our results are indicative of complementary roles of the PT and of aMF in motor compensation of hemispherotomy mediating distal and proximal motor compensation of the upper limb, respectively. Neuroimaging has substantially advanced our understanding of the neuronal mechanisms of functional motor recovery after brain lesions, thereby, enhancing prediction of motor recovery 1. Diffusion Tensor Imaging (DTI) and tractography have proven useful for the in vivo delineation and assessment of white matter pathways 2. Different DTI-studies have associated motor function after hemispheric lesions with the microstructural integrity of the pyramidal tract (PT) or alternate motor fibers (aMF) 3-6. aMF are believed to constitute the imaging correlate of cortico-rubro-spinal or of cortico-reticulo-spinal pathways. They may be reconstructed by means of tractography as they descend from the precentral gyrus through the posterior limb of the internal capsule and the tegmentum pontis 7-10. Our understanding of aMF and their role as a compensatory corticospinal system was only recently investigated in patients and has been derived as a comparative neuroanatomical approach from numerous animal studies 11-13. Some studies have suggested that aMF could compensate for the damaged PT 6-8,14 , while other studies concluded that the portion of intact fibers of the affected PT determines the degree of motor recovery 3,4,15. A third possibility is that both systems contribute to motor recovery. Schulz and colleagues found no interaction between diffusivity parameters indexing the microstructural status of PT and aMF in patients after stroke, and thus concluded, that the manner in which they function is "synergistic, but independent" 7. Our hypothesis states that PT and aMF may operate synergistically by mediating distal and proximal motor functions