Case Report: Microcephaly and abnormal neurological findings in newborns, together with intracranial calcification are indicative for intrauterine infection as well as for a subgroup of Aicardi-Goutières Syndrome. We report on a girl, born as the first child of nonconsanguineous Turkish parents. At birth, a microcephaly was noted and she developed nonresponsive seizures at the second day of life. A brain MRI showed hyperintense signals in the deep cortical gray matter and the thalami concordant with calcifications resulting from a congenital infection or intracerebral bleeding. Laboratory testing was normal despite for slightly elevated liver enzymes and a recurrent thrombocytopenia. A congenital infection was ruled out. Mutation analysis of genes associated with Aicardi-Goutières Syndrome was negative. A preliminary diagnose of an atypical Aicardi-Goutières Syndrome was made.

Pregnancy, birth and postnatal course were uneventful in all cases. One girl presented very early with a primary developmental delay, 2 children presented in the first year of life, 2 further children in the second year of life. Initial symptoms were in all cases a muscular hypotonia, ataxia, feeding difficulties, whereas metal and speech development were much better. 2 children present with a tachypnoea due to central lactatacidosis. Labatory tests showed lactic acidosis in plasma in some but not all samples however increased lactate in CSF was demonstrated in all cases. Muscle morphology showed no characteristic results. The analysis of the respiratory chain complexes showed severe COX-deficiency in all cases. Pathogenic mutations in the SURF1 gen could be found in all cases. Initial MRI-scans revealed in 4/5 cases typical symmetrical signal changes of variable intensity, in one case the initial MRT was normal and shows a Leigh-like picture in the course of the disease. None of the children had cardiac problems. Clinical all children show a progressive muscular hypotonia, ataxia and recurrent episodes of vomiting and regression. Frequency and intensity of these episodes were variable and partly very severe. Need for artificial ventilation was in 2 cases, 2 children show a benign course, one girl is able to walk with aid.

Photoparoxysmal response (PPR) is considered to be a risk factor for idiopathic generalised epilepsy (IGE) and it has a strong genetic basis. Two genome-wide linkage studies have been published before and they identified loci for PPR at 6p21, 7q32, 13q13, 13q31 and 16p13. Here we combine these studies, augmented with additional families, in a mega-analysis of 100 families. Non-parametric linkage analysis identified three suggestive peaks for photosensitivity, two of which are novel (5q35.3 and 8q21.13) and one has been found before (16p13.3). We found no evidence for linkage at four previously detected loci (6p21, 7q32, 13q13 and 13q31). Our results suggest that the different family data sets are not linked to a shared locus. Detailed analysis showed that the peak at 16p13 was mainly supported by a single subset of families, while the peaks at 5q35 and 8q21 had weak support from multiple subsets. Family studies clearly support the role of PPR as a risk factor for IGE. This mega-analysis shows that distinct loci seem to be linked to subsets of PPR-positive families that may differ in subtle clinical phenotypes or geographic origin. Further linkage studies of PPR should therefore include in-depth phenotyping to make appropriate subsets and increase genetic homogeneity.

Terahertz Time-Domain Spectroscopy (THz-TDS) is used to investigate water and soot contaminations in oils, exhibiting different dilution modes. For synthetic polyglycol oils, the water is dissolved due to the polar behavior of the oil, whereas in non polar mineral oils the water-oil compound forms an emulsion. This behavior is modeled with an effective medium approximation (EMA) formalism. Small soot agglomerates are remaining in suspension when mineral oils are polluted with soot particles. In this case, the absorption spectrum is dominated by scattering effects. Due to the small particle size of the soot agglomerates compared to the THz wavelength, coherent scattering is the dominant process.

Terahertz time-domain spectroscopy (THz-TDS) is used to investigate the water content in synthetic oils. For this purpose, water was added to polyglycol oils, which are able to dissolve a certain percentage of water. Applying THz-TDS, changes in the absorption coefficient and refractive index are observed and characterized. Comparison of the experimental data with predictions based on Beer–Lambert and Lorentz–Lorenz-theory, respectively, exhibits excellent agreement and clearly indicates that water is not dissolved in form of clusters but rather via hydrogen-bonded oil–water complexes.

Succinic semialdehyde dehydrogenase (SSADH) is involved in the degradation of the inhibitory neurotransmitter GABA and about 50% of patients with SSADH deficiency suffer from seizures. The gene encoding SSADH (gene symbol: ALDH5A1) maps in proximity to susceptibility loci for juvenile myoclonic epilepsy (JME) and photosensitivity on chromosome 6p22. The present study tested whether variation of the ALDH5A1 gene confers susceptibility to common syndromes of idiopathic generalized epilepsy (IGE) and an abnormal photoparoxysmal response (PPR). Mutation screening of the ALDH5A1 coding sequence of 35 IGE/PPR patients and four healthy control subjects identified 17 sequence variants, of which three resulted in an exchange of amino acids (H180Y, P182L, A237S). Association analysis was carried out for six single nucleotide polymorphisms (SNPs) and one trinucleotide repeat polymorphism (TNR, intron 1), covering the genomic ALDH5A1 sequence. The study sample comprised 566 unrelated German IGE patients, including 218 JME and 95 photosensitive IGE patients, 78 PPR probands without IGE, and 662 German population controls. None of the investigated ALDH5H1 polymorphisms showed evidence for an allelic or genotypic association with either IGE, JME, or PPR, when corrected for multiple tests. A tentative haplotypic association of the two-marker haplotype (rs1883415–TNR) covering the 5′-regulatory region in IGE patients (χ2 = 11.65, d.f. = 3, P = 0.009) warrants further replication studies. The present results do not provide evidence that any ALDH5A1 missense variant itself contributes a common and substantial susceptibility effect (RR > 2) to IGE syndromes or an increased liability to visually-induced cortical synchronization.

Terahertz time-domain spectroscopy (THz-TDS) is used to investigate water and soot contaminations in oils, exhibiting different dilution modes. For synthetic polyglycol oils, the water is dissolved due to the polar behavior of the oil, whereas in non polar mineral oils the water-oil compound forms an emulsion. This behavior is modeled with an effective medium approximation (EMA) formalism. Small soot agglomerates are remaining in suspension when mineral oils are polluted with soot particles. In this case, the absorption spectrum is dominated by scattering effects. Due to the small particle size of the soot agglomerates compared to the THz wavelength, coherent scattering is the dominant process.

The water content in polyglycol oils is investigated by Terahertz Time-Domain Spectroscopy (THz-TDS). These oils are able to dissolve a certain percentage of water. Changes in the absorption coefficient and refractive index are observed related to the amount of water added to the pure oils. Comparison of the experimental data with predictions based on Beer-Lambert and Lorentz-Lorenz-theory, respectively, exhibits an excellent agreement. Analyses with Fourier Transform Infrared (FTIR) Spectroscopy reveal sensitivity similar to the THz-TDS experiment. THz-TDS may offer powerful tools to quantitatively determine the water concentration in petroleum products.

Photosensitivity or photoparoxysmal response (PPR) is a common and highly heritable electroencephalographic trait characterized by an abnormal visual sensitivity of the brain in reaction to intermittent photic stimulation. PPR occurs frequently associated with idiopathic generalized epilepsies (IGEs). The present genomewide linkage scan was designed to map susceptibility loci for PPR and to explore their genetic relationship with IGE. The study included 60 families with at least two siblings displaying PPR. To dissect PPR-specific and IGE-related susceptibility loci, we defined two distinct family subgroups, comprising 19 families with predominantly pure PPR and photosensitive seizures (PPR-families) and 25 families, in which PPR was strongly associated with IGE (PPR/IGE-families). MOD score analyses provided significant evidence for linkage to the region 6p21.2 in the PPR-families (empirical p = 0.00004) and suggestive evidence for linkage to the region 13q31.3 in the PPR/IGE families (p = 0.00015), both with a best-fitting recessive mode of inheritance. In the PPR/IGE-families, linkage evidence was even stronger (p = 0.00003) when the trait definition was broadened by IGE traits. Our study shows two PPR-related susceptibility loci, depending on the familial background of IGE. The locus on 6p21.2 seems to predispose to PPR itself, whereas the locus on 13q31.3 also confers susceptibility to IGE.

Photosensitivity or photoparoxysmal response (PPR) is an epilepsy-related electroencephalographic trait evoked by standardised intermittent photic stimulation. It is characterised by a brain response with spike wave discharges, ranging from occipital spikes only to generalised spike waves (type I – IV). PPR is a common finding in the general population (up to 8%) and is frequently associated with idiopathic epilepsies. It has an especially high prevalence (up to 90%) in idiopathic generalised epilepsies (IGE). The molecular genetic dissection of the photoparoxysmal response as an endophenotype seems to be a suitable approach to elucidate the molecular genetic basis of IGE.

Objectives: Lamotrigin (LTG) was reported to have a positive cognitive profile. Do physicians and parents of children with long-term LTG treatment confirm this?

Objectives: Feedback of slow cortical potentials (SCP) in adult patients with epilepsy showed positive therapeutic effects. Could SCP-Feedback be a useful therapeutic method for children?

PURPOSE:Benign familial infantile convulsions (BFIC) is a form of idiopathic epilepsy. It is characterized by clusters of afebrile seizures occurring around the sixth month of life. The disease has a benign course with a normal development and rare seizures in adulthood. Previous linkage analyses defined three susceptibility loci on chromosomes 19q12-q13.11, 16p12-q12, and 2q23-31. However, a responsible gene has not been identified. We studied linkage in 16 further BFIC families. METHODS:We collected 16 BFIC families, without an additional paroxysmal movement disorder, of German, Turkish, or Japanese origin with two to eight affected individuals. Standard two-point linkage analysis was performed. RESULTS:The clinical picture included a large variety of seizure semiologies ranging from paleness and cyanosis with altered consciousness to generalized tonic-clonic seizures. Interictal EEGs showed focal epileptiform discharges in six patients, and three ictal EEGs in three distinct patients revealed a focal seizure onset in different brain regions. In all analyzed families, we found no evidence for linkage to the BFIC loci on chromosomes 19q and 2q, as well as to the known loci for benign familial neonatal convulsions on chromosomes 8q and 20q. In 14 of the families, the chromosome 16 locus could be confirmed with a cumulative maximum two-point lod score of 6.1 at marker D16S411, and the known region for BFIC could be narrowed to 22.5 Mbp between markers D16S690 and D16S3136. CONCLUSIONS:Our data confirm the importance of the chromosome 16 locus for BFIC and may narrow the relevant interval.

We present a review of phenotype-genotype correlation and the genetics of photosensitivity. The photoparoxysmal response in EEG (PPR) is still one of the best paradigms for exogenously triggered brain responses based on a genetic predisposition. The definition of the PPR phenotype requires multiple, precise methodologic guidelines. Individual factors such as age and gender but also other, unknown factors influence the expression of the PPR. For example, PPRs occur during adolescence and can disappear at a later age. As a consequence, it is difficult to assign nonaffected disease status correctly. Autosomal dominant inheritance has been found in clinical studies of relatives of PPR-positive epilepsy and nonepilepsy subjects. Genetic heterogeneity of the PPR is obvious because the PPR also can be evoked in a number of autosomal recessive diseases. PPR is most commonly associated with idiopathic generalized epilepsies (IGEs) such as juvenile myoclonic epilepsy (JME). This comorbidity suggests that a genetic factor involved in photosensitivity also may influence the susceptibility for JME. Finding the gene for PPR also might represent a step forward in unraveling the genetic background of JME. The search for the genetic factors causing PPRs should focus on the genes affected in such epilepsies, such as genes (coding) for ion channels and neurotransmitters and their receptors. The expression of defined proteins with as-yet-undetermined functions, is changed in a few types of epilepsies with a mendelian mode of inheritance. These additional genes and the human equivalents of the genes found to be mutated in animal models also are candidates for molecular genetic studies of the PPR.

Multiphoton microscopy is based on the simultaneous absorption of two photons emitted by a pulsed infrared laser source. In this technique, the excitation is restricted to a very small focus and thus results in optical sectioning a priori without the need of a confocal aperture. Multiphoton microscopy was introduced in live cell imaging as an alternative to confocal microscopy due to its superior qualities, such as the deep penetration depth, the reduced photodamage and the lack of out‐of‐focus bleaching. However, during the past years, examinations revealed severe limitations to the initial expectations. In the focal plane, photodamage and photobleaching can be worse than in single photon microscopy. However, studies showed that with low excitation intensity and by special technical adaptations photodamage could be avoided successfully. For functional biological imaging, multiphoton excitation provides an excellent tool such as the release of caged compounds in a diffraction‐limited volume combined with multiphoton or confocal imaging.