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A mutant excision

A mutant excision+/integration- piggyBac transposase can be used to seamlessly excise a chromosomally integrated, piggyBac-compatible selection marker cassette from the Yarrowia lipolytica genome. This piggyBac transposase-based genome engineering process allows for both positive selection of targeted homologous recombination events and scarless or footprint-free genome modifications after precise marker recovery. Residual non-native sequences left in the genome after marker excision can be minimized (0-4 nucleotides) or customized (user-defined except for a TTAA tetranucleotide). Both of these options reduce the risk of unintended homologous recombination events in strains with multiple genomic edits. A suite of dual positive/negative selection marker pairs flanked by piggyBac inverted terminal repeats (ITRs) have been constructed and are available for precise genome engineering in Y. lipolytica using this method. This protocol specifically describes the split marker homologous recombination-based disruption of Y. lipolytica ADE2 with a piggyBac ITR-flanked URA3 cassette, followed by piggyBac transposase-mediated excision of the URA3 marker to leave a 50 nucleotide synthetic barcode at the ADE2 locus. The resulting ade2 strain is auxotrophic for adenine, which enables the use of ADE2 as a selectable marker for further strain engineering.

Efficient guide RNA expression often limits CRISPR-Cas9 implementation in new hosts. To address this limitation in fungal systems, we demonstrate the utility of a T7 polymerase system to effectively express sgRNAs. Initially, we developed a methodology in Saccharomyces cerevisiae using a modified version of the T7 P266L mutant polymerase with an SV40 nuclear localization signal to allow guide RNA expression immediately downstream of a T7 promoter. To improve targeting efficiency, guide RNA design was found to be tolerant to three mismatches or up to three additional bases appended to the 5' end. The addition of three guanines to a T7-based guide RNA improved guide RNA expression 80-fold and achieved transcriptional output similar to the strong Pol III snr52 promoter. Resulting gene editing and dCas9-guided gene regulation with a T7-based guide RNA was on par with the commonly used snr52 system in S. cerevisiae. Finally, 96% and 60% genome editing efficiencies were achieved in Kluyveromyces lactis and Yarrowia lipolytica respectively with minimal optimization of this system. Thus, T7-based expression of sgRNAs offers an orthogonal method for implementing CRISPR systems in fungal systems.

Functional imaging studies on responders and non-responders to therapeutic interventions in obese children are rare. We applied fMRI before and after a one-year sports therapy in 14 obese or overweight children aged 7–16 years. During scanning, participants observed a set of standardized pictures from food categories, sports, and pleasant and neutral images. We were interested in alterations of the cerebral activation to food images in association with changes in the BMI-standard deviation score (BMI-SDS) after therapy and therefore separated the observation group into two outcome subgroups. One with reduction of BMI-SDS >0.2 (responder group) and one without (non-responder group). Before therapy fMRI-activation between groups did not differ. After therapy we found the following results: in response to food images, obese children of the responder group showed increased activation in the left putamen when compared with the non-responder group. Pleasant images evoked increased insula activation in the responder group. Only the responder group showed enhanced activity within areas known to store trained motor patterns in response to sports images. Both the putamen and the insula are involved in the processing of emotional valence and were only active for the therapy responders during the observation of food or pleasant stimuli. Elevated activity in these regions might possibly be seen in the context of an increase of dopaminergic response to emotional positive stimuli during intervention. In addition, sport images activated motor representations only in those subjects who profited from the sports therapy. Overall, an altered response to rewarding and pleasant images and an increased recruitment of motor engrams during observations of sports pictures indicates a more normal cerebral processing in response to these stimuli after successful sports therapy in obese children.

Food cues yield different patterns of brain activation in obese compared with normal-weight adults in prefrontal and limbic/paralimbic areas. For children, no mapping studies comparing representation sites for food and other stimuli between obese and normal-weight subjects are available. We used a cross-sectional design of two age-matched subject groups to investigate differences in brain activation in response to visually presented food, pleasant, and neutral pictures between obese/overweight and normal children. 22 overweight/obese children were compared with 22 normal-weight children. Functional magnetic resonance imaging (of the whole head during perception of visually presented stimuli), psychological testing, and psychophysical measures of heart rate deceleration were assessed. Obese children showed higher activation of the dorsolateral prefrontal cortex (DLPFC) in response to food pictures. In addition, DLPFC activation was negatively correlated with self-esteem. In contrast, normal-weight children showed higher activation of the caudate and hippocampus specific to food pictures, and of the anterior cingulate cortex and thalamus to visual cues in general. In response to food stimuli, obese children showed a heart rate deceleration correlating positively with activation of the ventrolateral prefrontal cortex. Obese children react to food stimuli with increased prefrontal activation, which might be associated with increased inhibitory control.

Since 1981, the expansion in international markets is unprecedented in a history of world market evolution. Never have so many firms been involved in marketing to so many user s worldwide. Yet, the channel function tends to lag behind the other traditional areas, i.e. advertising, promotion, packaging pricing, and product differentiation. These areas have a good deal more “excitement” in their applications compared to the seemingly mundane task of moving goods and services through the channel. Furthermore, existing channel variation between countries poses a sizeable threat to the effectiveness of an integrated international distribution strategy.

In a retrospective study brainstem acoustic evoked potentials (BAEP) were evaluated in 222 children with psychomotor retardation or dysmorphic signs. Registrations were done, when no clear response to acoustic stimuli of medium intensity (60-80 dBA) could be obtained during clinical examination. Only 118 children (53%) had normal BAEP. 50 patients (22%) suffered from hearing impairment. 39 children (17%) showed disturbances of neuronal conduction. In 15 cases (7%) a combination of both conditions occurred. The mean age of our children with hearing impairment was 33.1 months, no case having been diagnosed before. In 57% the impairment was of the conductive type with an amount of less than 40 dB nHL This type was predominant in children with skeletal dysplasias (43%), chromosomal aberrations (43%) and malformation syndromes (40%). Severe hearing deficits of the sensorineural type with more than 69 dB nHL were found in children with malformation syndromes (28%), perinatal injuries (23%) and cns malformations (16%). As far as reference data were available, the hearing impairment in the BAEP was confirmed in 92% by our pedaudiologists. As a consequence hearing aids were first prescribed in 10 children, their medium age being 33.6 months. In 18 cases grommets were inserted. 9 children required paracentesis and 4 adenotomy. Disturbances of neuronal conduction with increased interpeak latencies and deformed potentials were predominantly found in the group of children with neurometabolic diseases (67%) and cns malformations (32%). Early diagnosis of hearing impairment in children with psychomotor retardation remains a problem as it is in the general population. More attention in clinical examination and appropriate screening is necessary. BAEP provide a powerful tool for hearing screening and additional information for differential diagnosis especially in children with neurometabolic diseases.

Wir berichten uber den Fall eines 14 Jahre alten Madchens mit bekannter Migrane ohne Aura, die wenige Stunden nach einer Commotio cerebri plotzlich heftigste pulsierende rechtstemporale Kopfschmerzen mit Ubelkeit und Erbrechen entwickelte und eine vollstandige Parese des N. oculomotorius rechts zeigte. Die morphologische Evaluation des ZNS mittels Dopplersonographie, Rontgen, CT, NMR und Angio-NMR sowie erganzende neurophysiologische und laborchemische Untersuchungen waren unauffallig. Die Ophthalmoplegie zeigte sich ab dem 6. postkommotionellen Tag rucklaufig, ab dem 10. Tag konnte eine vollstandige Restitutio ad integrum dokumentiert werden. In den folgenden 2 Monaten zeigte die Patientin, neben ihren typischen Migraneattacken, insgesamt 3 weitere ophthalmoplegische Kopfschmerzattacken mit zunehmend prolongiertem Verlauf, die durch die sonst gut wirksame Selbstmedikation mit Domperidon und Azetylsalizylsaure kaum beeinflust und erst durch die parenterale Gabe von Lysinazetylsalizylat, Prednisolon und Sumatriptan zufriedenstellend behandelt werden konnten. Diskussion: Die ophthalmoplegische Migrane ist eine seltene Migranevariante, bei der wiederholte Kopfschmerzattacken in Verbindung mit einer Parese des III., IV. und/oder VI. Hirnnervs beobachtet werden. Die Erstmanifestation eines opthalmoplegischen Verlaufs erfordert durch umfangreiche Untersuchungen den Ausschlus sekundarer Ursachen. Bei unauffalligen Befunden, typischer Klinik und entsprechender Anamnese kann im Verlauf die Diagnose einer ophthalmoplegischen Migrane gestellt und bei Bedarf eine spezifische Behandlung durchgefuhrt werden.

Benign epilepsy of childhood with rolandic spikes (BECRS) is an electroclinical syndrome characterized by partial sensorimotor seizures with centrotemporal spikes. We report a detailed localization analysis of spontaneous magnetic brain activities in seven BECRS patients using magnetoencephalography (MEG). All patients had BECRS diagnosis with typical seizures and electroencephalographic findings and five patients had minor psychomotor deficits. MEG was recorded over both parieto-temporal regions using a 2x37-channel biomagnetic system. The collected data were digitally bandpass-filtered (2-6, 14-30, or 1-70 Hz) to analyze slow- and fast-wave magnetic activities and rolandic spikes. Slow-wave activity was increased in four hemispheres of three patients. Increased fast-wave activity was found in all five patients with minor neuropsychological deficits. The presence of increased fast-wave magnetic brain activity appeared to cause functional anomalies in the higher brain function processes. In the spike analysis, the dipoles of rolandic spikes which constantly manifested anterior positivity in direction were concentrated in the superior rolandic region in four cases and the inferior rolandic region in three cases. The localizations of increased slow- and fast-wave activities were identical with those of the spikes. The seizure profiles were frequently characterized by the spike locations. Source localizations of the focal brain activities and rolandic spikes by MEG will contribute to the different diagnosis and pathophysiological elucidation of BECRS.

The Chiari-syndrome Type I being a malformation of the posterior cranial fossa often leads to syringomyelia. The disease becomes apparent in adolescence with kyphoscoliosis, headache, vertigo, ataxy, hearing loss, partial paralysis and other neurological disorders. The onset is typically characterized by dissociated anesthesia, due to the frequent localization of the syrinx in the neighborhood of the posterior column of the spinal cord. It is reported a case of an 15-years-old-girl suffering from intensive headache, recurrent left-sided paresthesias and progredient scoliosis. Somatosensory evoked potentials of left ulnar and tibial nerves revealed a complete loss of cortical response. Diagnostic imaging showed an Chiari-malformation I with herniation of cerebellar tonsils and secondary syringomyelia of the cervical spinal cord. After surgical treatment with posterior fossa decompression, C1 laminectomy and partial excision of cerebellar tonsils the patient had a clear improvement in symptoms. Postsurgical the width of cervical syrinx decreases. Now somatosensory evoked potentials of the left ulnar and tibial nerves show amplitude-reduced cortical responses with a normal latency.

Evoked otoacoustic emissions (EOAE) and brainstem acoustic evoked potentials (BAEP) were recorded from 78 children following neonatal intensive care. In 23% no EOAE could be obtained. Hearing impairment in the BAEP was found in 9%. In 22% negative EOAE were found in spite of normal BAEP. According to the latency-intensity function of waves I and V all children with abnormal BAEP were classified having a conductive hearing loss. In accordance in no case a narrowing of the emission spectrum could be found in the EOAE. In both methods the rate of hearing impairment was highest in children with birth weights of less than 1000 g. A screening of all infants after neonatal intensive care using EOAE is recommended. BAEP should be done additionally in cases with deficient EOAE.

Brainstem acoustic evoked responses were recorded from 37 infants with cleft palate. Only 35% presented normal auditory thresholds. 27% had a bilateral 22% a unilateral hearing deficit of more than 30 dB. Controls after operative closure of the cleft showed no improvement of the conductive hearing loss.

Familial hemiplegic migraine (FHM) and alternating hemiplegia of childhood (AHC) are severe neurological disorders that share clinical features. Therefore, FHM genes are candidates for AHC. We performed mutation analysis in the CACNA1A gene in a monozygotic twin pair with clinical features overlapping with both AHC and FHM and identified a novel de novo CACNA1A mutation. We provide the first evidence that a CACNA1A mutation can cause atypical AHC, indicating an overlap of molecular mechanisms causing AHC and FHM. These results also suggest that CACNA1A mutation scanning is indicated in patients with a severe neurological phenotype that includes paroxysmal (alternating) hemiplegia.

Viewing pictures activates the human brain in a complex manner. Stimulated brain areas can be identified by electrophysiological methods even in children.Event related potentials (ERP) were recorded with EEG-surface electrodes in children and adolescents who were shown pictures of increasing complexity. Pictures were categorized into morphologic features such as brightness, color and pattern as well as semantic content.Presentation of comics and unstructured pictures, similar in color and brightness, revealed ERP with nearly identical early components (P 100). However, substantial differences were found in frontocentral brain areas. A negative wave at approximately 400 ms was recorded only when comics were shown.Semantic scenes provoked significant different ERP, which indicate an early involvement of complex neuronal networks. These results could be applied in the research of pediatric cognitive disturbances.

Enteroviruses are common with infections of the CNS, such as encephalitis and myelitis, but they may cause various diseases in different organ systems, particulary with fatal outcome. Pleconaril is a new orally acting antiviral drug with broad anti-picornavirus activity, which provides to treat rhinoviral and enteroviral infections. To explain the importance for clinical use, we report a case of severe enteroviral infections of the CNS, treated by Pleconaril. A 14 year old girl presented with a severe polio- like myelitis including flaccid paraparesis and urinary incontinence due to Coxsackievirus-infection. Because of prolonged course and virus persistence we treated with Pleconaril, after treatment a remarkable improvement could be noticed, continency and the ability to walk without aid were regained within a few weeks. With the development of new antiviral substances we are now given more opportunities to treat infectious conditions of the central nervous system. We suggest to include enteroviruses in diagnostic procedures since there is an effective treatment with the new drug Pleconaril available.

The Chiari-syndrome Type I being a malformation of the posterior cranial fossa often leads to syringomyelia. The disease becomes apparent in adolescence with kyphoscoliosis, headache, vertigo, ataxy, hearing loss, partial paralysis and other neurological disorders. The onset is typically characterized by dissociated anesthesia, due to the frequent localization of the syrinx in the neighborhood of the posterior column of the spinal cord. It is reported a case of an 15-years-old-girl suffering from intensive headache, recurrent left-sided paresthesias and progredient scoliosis. Somatosensory evoked potentials of left ulnar and tibial nerves revealed a complete loss of cortical response. Diagnostic imaging showed an Chiari-malformation I with herniation of cerebellar tonsils and secondary syringomyelia of the cervical spinal cord. After surgical treatment with posterior fossa decompression, C1 laminectomy and partial excision of cerebellar tonsils the patient had a clear improvement in symptoms. Postsurgical the width of cervical syrinx decreases. Now somatosensory evoked potentials of the left ulnar and tibial nerves show amplitude-reduced cortical responses with a normal latency.

Objective: Classic infantile spinal muscular atrophy (SMA) is believed to be a purely motor disorder, affecting neurons of the spinal anterior horn and nuclei of the lower cranial nerves. Other organ malformations or peripheral nerve involvement have been regarded as exclusion criteria for infantile SMA. Whether SMN protein deficiency can also lead to loss of sensory neurons has not been systematically addressed. Methods: The authors evaluated the sural nerve biopsies of 19 patients with infantile SMA of varying severity. The diagnosis of SMA was confirmed by the presence of a homozygous deletion of the SMN1 gene in all patients. Results: In seven unrelated infants with SMA type I, axonal degeneration of the sural nerve was noted. Five patients showed abnormal sensory conduction, thus prompting sural nerve biopsy. Sural nerves showed different degrees of axonal loss: fiber density ranged from 3.482 to 22.076/mm 2 and was markedly reduced in four patients. There was no evidence of primary demyelination: the ratio of total myelinated fiber thickness to axon diameter (g-ratio) was normal in the patients examined. In seven patients with SMA II and five patients with SMA III, no sural nerve alterations were seen, and conduction velocity was normal. In addition to SMN1 gene deletions, homozygous NAIP gene deletions were detected in six out of seven infants with peripheral neuropathy, whereas there was no evidence of a large deletion including the multicopy markers C212 and Ag1-CA in two out of three families tested. Conclusions: In this series of patients with SMA I through III who underwent sural nerve biopsy, there was significant sensory nerve pathology in severely affected patients with SMA type I, whereas there were no sensory nerve alterations clinically or morphologically in patients with milder SMA type II or III.

An 11-year-old girl presented with recurrent vomiting, reduced food and fluid intake, weight loss and dizziness. In an external hospital she was diagnosed as having habitual vomiting and a beginning eating disorder. The physical examination revealed a very thin, malnourished child with abdominal pain on palpation but without neurologic deficits. Laboratory findings, X-rays, endoscopy and ultrasound revealed no pathological results either. Since the EEG and the cranial computed tomography (CT) were normal, we also suspected the beginning of an eating disorder especially due to some psychical peculiarities. The MRI which was done for ultimate exclusion of an infratentorial tumor showed a well defined displacing structure in the dorsal medulla oblongata and in the upper cervical spinal cord. A corresponding prolongation of the central conduction time was found in the median nerve SSEP whereas the BAEPs were normal. The tumor was excised in toto and the histological examination confirmed the suspected diagnosis of cavernous hemangioma (cavernoma). The post operative phase was without any complications and the intiated nutrition was well tolerated. Neurological deficits were not observed.

In a retrospective study brainstem acoustic evoked potentials (BAEP) were evaluated in 222 children with psychomotor retardation or dysmorphic signs. Registrations were done, when no clear response to acoustic stimuli of medium intensity (60-80 dBA) could be obtained during clinical examination. Only 118 children (53%) had normal BAEP. 50 patients (22%) suffered from hearing impairment. 39 children (17%) showed disturbances of neuronal conduction. In 15 cases (7%) a combination of both conditions occurred. The mean age of our children with hearing impairment was 33.1 months, no case having been diagnosed before. In 57% the impairment was of the conductive type with an amount of less than 40 dB nHL This type was predominant in children with skeletal dysplasias (43%), chromosomal aberrations (43%) and malformation syndromes (40%). Severe hearing deficits of the sensorineural type with more than 69 dB nHL were found in children with malformation syndromes (28%), perinatal injuries (23%) and cns malformations (16%). As far as reference data were available, the hearing impairment in the BAEP was confirmed in 92% by our pedaudiologists. As a consequence hearing aids were first prescribed in 10 children, their medium age being 33.6 months. In 18 cases grommets were inserted. 9 children required paracentesis and 4 adenotomy. Disturbances of neuronal conduction with increased interpeak latencies and deformed potentials were predominantly found in the group of children with neurometabolic diseases (67%) and cns malformations (32%). Early diagnosis of hearing impairment in children with psychomotor retardation remains a problem as it is in the general population. More attention in clinical examination and appropriate screening is necessary. BAEP provide a powerful tool for hearing screening and additional information for differential diagnosis especially in children with neurometabolic diseases.

Neurologische Komplikationen bei Patienten mit Hamophilie wurden vor Auftreten von HIV-Infektionen im wesentlichen als Folge intrazerebraler Blutungen beobachtet [1]. In der neueren Literatur wird hingegen v.a. die Wirkung des HIV-Virus auf das zentrale Nervensystem beschrieben, wobei Patienten mit < 200 CD 4+-Zellen nicht selten eine diffuse zerebrale Atrophie aufweisen [2]

Enteroviruses are common with infections of the CNS, such as encephalitis and myelitis, but they may cause various diseases in different organ systems, particulary with fatal outcome. Pleconaril is a new orally acting antiviral drug with broad anti-picornavirus activity, which provides to treat rhinoviral and enteroviral infections. To explain the importance for clinical use, we report a case of severe enteroviral infections of the CNS, treated by Pleconaril. A 14 year old girl presented with a severe polio- like myelitis including flaccid paraparesis and urinary incontinence due to Coxsackievirus-infection. Because of prolonged course and virus persistence we treated with Pleconaril, after treatment a remarkable improvement could be noticed, continency and the ability to walk without aid were regained within a few weeks. With the development of new antiviral substances we are now given more opportunities to treat infectious conditions of the central nervous system. We suggest to include enteroviruses in diagnostic procedures since there is an effective treatment with the new drug Pleconaril available.

Evoked otoacoustic emissions (EOAE) and brainstem acoustic evoked potentials (BAEP) were recorded from 78 children following neonatal intensive care. In 23% no EOAE could be obtained. Hearing impairment in the BAEP was found in 9%. In 22% negative EOAE were found in spite of normal BAEP. According to the latency-intensity function of waves I and V all children with abnormal BAEP were classified having a conductive hearing loss. In accordance in no case a narrowing of the emission spectrum could be found in the EOAE. In both methods the rate of hearing impairment was highest in children with birth weights of less than 1000 g. A screening of all infants after neonatal intensive care using EOAE is recommended. BAEP should be done additionally in cases with deficient EOAE.

Early and late acoustic evoked responses were simultaneously recorded from 42 children aged 3–17 years by means of a computer-based device using self-developped software. Filling the interstimulus intervals of late acoustic evoked potentials with clicks leads to an increase of latencies and a decrease of amplitudes on N1 and P2 components. Agedependent normal values for various recording conditions are given.

Brainstem acoustic evoked responses were recorded from 37 infants with cleft palate. Only 35% presented normal auditory thresholds. 27% had a bilateral 22% a unilateral hearing deficit of more than 30 dB. Controls after operative closure of the cleft showed no improvement of the conductive hearing loss.

Die Behandlung von Medulloblastomen wird um so kritischer gesehen, je junger die Patienten sind. Chirurgisch soll eine weitestgehende Tumorresektion vorgenommen und eine Shuntimplantation vermieden werden, um Erfolge der onkologischen Therapie und die Lebensqualitat der Patienten zu begunstigen.

Akustisch evozierte Hirnstammpotentiale (AEHP) werden in zunehmendem Mas zur Objektivierung von Storungen im Stammhirnbereich auch bei Patienten unter Intensivtherapie eingesetzt [1,2,3,4]. In der vorliegenden Arbeit soll der Wert dieser Methode fur Prognose und Verlaufsbeobahctung komatoser Kinder, auch im Vergleich zu EEG und dopplersonographischen Flusmessungen untersucht werden.

Ein Hirnodem tritt im Kindesalter hauptsachlich als Folge asphyktischer Ereignisse oder eines Schadel-Hirn-Traumas auf. Pathophysiologisch konnen zwei Formen des Hirnodems voneinander abgegrenzt werden: das zytotoxische und das vasogene Hirnodem. Das vasogene Hirnodem wird v.a. bei Vaskulitiden im Zusammenhang mit einer Meningitis gefunden. Das zytotoxische Odem tritt v.a. postasphyktisch auf [2, 6, 10].

BAEPs were recorded from 92 healthy children with a gestational age of 35 weeks up to 16 years. The maturation kinetic of I-III and I-V interpeak latency can well be approximated by the exponential regressions I-V : y = 0.9588 x e -0.9215 x x + 3.9728; r = 0.87; I-III : y = 0.6182 x e -1.1737 x x + 2.1759; r = 0.81; Adult values are reached by about two years of life. In contrast to this immaturity of the central auditory pathways the slopes of latency--intensity functions of waves I and V show no significant differences between premature infants and neonates versus older children over three years. Caused by the prolonged I-V IPL wave V latency is about 1 ms longer in the first group, whereas wave I is only slightly prolonged (0.2 ms) within the first three months of life.

Es werden die Wirkungsweise und die Anwendungsmoglichkeiten einer Drehstrommaschine beschrieben, deren Lauferstrome in Abhangigkeit vom Polradwinkel durch Regler und Stromrichterstellglieder eingepragt werden. Eine solche Anordnung verhalt sich vom Netz her gesehen wie eine Synchronmaschine, jedoch ist die bei einer ublichen Synchronmaschine bestehende Verknupfung des Motormomentes mit dem Polradwinkel bzw. der Drehzahl nicht vorhanden.

An adapted cow's milk formula with or without supplemental taurine (480 μmol/l) was fed for 16 weeks to 20 low-birth-weight infants. In the 2nd and 16th, weeks of life, respectively, the following parameters were determined: growth, sonography of heart and brain, ECG, EEG, neurological development and the taurine concentration of plasma and urine. None of the parameters investigated was influenced by taurine supplementation except the urinary taurine excretion. At least according to these data, the addition of taurine to whey-predominant infant formulae seems to be unnecessary for the development of heart and brain function in low-birth-weight infants.

To investigate the age-dependency of central conduction time somatosensible evoked potentials to median nerve stimulation were recorded in 80 infants and children from the age of one week to 20 years. It is shown that the central conduction time starts at about 14 ms in the neonatal period and then gradually declines until the 7th or 8th year of life to the normal adult value with an upper limit of 7 ms. By dividing the data into several groups with age delimiters at 0.5, 1, 3, 5 and 7 years it shows significant differences of the mean values for the central conduction times according to the Student's t-test. The graph itself can well be approximated by the exponential regression y = 6.099 + 7.55 X e-0.686 X x where y represents the CCT and x the age in years. This slow maturation kinetic is presumably due to the ongoing central myelinisation.