Hypothyreose bei Frühgeborenen - Retrospektive Analyse der Thyreotropin- und freien Thyroxin-Werte einer 7 Jahreskohorte Frühgeborener < 32 SSW

Bei transienten Hypothyreosen im Rahmen von Frühgeburtlichkeit (THOP) ist weiterhin Diskussionsgegenstand, ob eine Hormonersatztherapie zur Verbesserung kognitiver Einschränkungen beitragen kann. Vorliegende Dissertation hatte es zum Ziel, zunächst Schilddrüsenreferenzwerte speziell für das Tübinger Patientenkollektiv zu generieren sowie im Sinne der Qualitätssicherung die Therapieergebnisse der Tübinger Schilddrüsenleitlinie aus dem Jahr 2005 auszuwerten. In der Folge sollte, unter Berücksichtigung resultierender Ergebnisse sowie der aktuellen Literatur, eine Überarbeitung der Tübinger Leitlinie und Formulierung neuer Therapierichtlinien erfolgen. In diese retrospektive, beobachtende Analyse wurden alle Frühgeborenen mit einem Gestationsalter unter 32 Schwangerschaftswochen eingeschlossen, welche während des Auswertezeitraums zwischen 01.01.2007 und 20.09.2014 im Perinatalzentrum Tübingen zur Welt kamen oder direkt nach einer externen Geburt dorthin verlegt wurden. Insgesamt wurden 822 Frühgeborene (408 weiblich) entsprechend o.g. Kriterien eingeschlossen. Aus vorliegenden Analysen ließen sich folgende Kernempfehlungen für die Generierung einer neuen Leitlinie der Tübinger Neonatologie ableiten: Kontrollen von TSH und FT4 im chronologischen Alter von 2 Wochen, im postmenstruellen Alter (PMA) von 32 und 36 Wochen sowie im Rahmen einer ambulanten Kontrolle im korrigierten Alter von 4 Monaten. Unter L-Thyroxin (LT4) Therapie zusätzliche Kontrollen 2 und 4 Wochen nach Therapiestart zur Dosisanpassung und dann in 4-6 Wochen-Intervallen. Eine prophylaktische Routinesupplementierung bei Frühgeborenen ist nicht empfohlen, die Indikationsstellung für eine Therapie erfolgt anhand des FT4-Werts bei 12 mU/l unter 36 Wochen PMA, > 8 mU/l zwischen 36 Wochen PMA und korrigiert 4 Monaten und > 6 mU/l für ein korrigiertes Alter von über 4 Monaten. Die LT4-Startdosis beträgt (4)-5-(8) µg/kg/d, eine probatorische Dosisreduktion und Schilddrüsen-Funktionstestung kann bei einer LT4-Dosis von < 3,3 µg/kg/d im chronologischen Alter von 12 Monaten oder bei Borderline-Befunden nach 3 Jahren erfolgen. Aufgrund des retrospektiv-beobachtenden Designs vorliegender Studie lassen sich keine kausalen Zusammenhänge ableiten, sondern lediglich Assoziationen beschreiben. Insbesondere hinsichtlich der Fragestellungen Einfluss von Störfaktoren, neurologisches Outcome bei THOP durch verschiedene Therapieformen, Unterscheidungsmerkmale zwischen kongenitaler und transienter Hypothyreose wäre die Durchführung großer, multizentrischer, prospektiver, ggf. interventioneller Studien notwendig

Atypical language organization following perinatal infarctions of the left hemisphere is associated with structural changes in right-hemispheric grey matter.

AIM To assess how atypical language organization after early left-hemispheric brain lesions affects grey matter in the contralesional hemisphere. METHOD This was a cross-sectional study with between-group comparisons of 14 patients (six female, 8-26 years) with perinatal left-hemispheric brain lesions (two arterial ischemic strokes, 11 periventricular haemorrhagic infarctions, one without classification) and 14 typically developing age-matched controls (TDC) with functional magnetic resonance imaging (fMRI) documented left-hemispheric language organization (six female, 8-28 years). MRI data were analysed with SPM12, CAT12, and custom scripts. Language lateralization indices were determined by fMRI within a prefrontal mask and right-hemispheric grey matter group differences by voxel-based morphometry (VBM). RESULTS FMRI revealed left-dominance in seven patients with typical language organization (TYP) and right-dominance in seven patients with atypical language organization (ATYP) of 14 patients. VBM analysis of all patients versus controls showed grey matter reductions in the middle temporal gyrus of patients. A comparison between the two patient subgroups revealed an increase of grey matter in the middle frontal gyrus in the ATYP group. Voxel-based regression analysis confirmed that grey matter increases in the middle frontal gyrus were correlated with atypical language organization. INTERPRETATION Compatible with a non-specific lesion effect, we found areas of grey matter reduction in patients as compared to TDC. The grey matter increase in the middle frontal gyrus seems to reflect a specific compensatory effect in patients with atypical language organization

The long-term negative impact of childhood stroke on language.

OBJECTIVES This study aims to investigate the long-term language outcome in children with unilateral childhood stroke in comparison to those with perinatal strokes and typically developing individuals and to explore the impact of lesion-specific modifiers. METHODS We examined nine patients with childhood stroke, acquired between 0;2 and 16;1 years (CHILD; 3 female, median = 13.5 years, 6 left-sided), 23 patients with perinatal strokes (PERI; 11 female, median = 12.5 years, 16 left-sided), and 33 age-matched typically developing individuals (CONTROL; 15 female, median = 12.33 years). The language outcome was assessed using age-appropriate tasks of the Potsdam Illinois Test of Psycholinguistic Abilities (P-ITPA) or the Peabody Picture Vocabulary Test (PPVT). For group comparisons, study-specific language z-scores were calculated. Non-verbal intelligence was assessed using the Test of Non-verbal Intelligence (TONI-4), language lateralization with functional MRI, and lesion size with MRI-based volumetry. RESULTS All four patients with childhood stroke who initially presented with aphasic symptoms recovered from aphasia. Patients with childhood stroke showed significantly lower language scores than those in the control group, but their scores were similar to those of the patients with perinatal stroke, after adjusting for general intelligence (ANCOVA, language z-score CHILD = -0.30, PERI = -0.38, CONTROL = 0.42). Among the patients with childhood stroke, none of the possible modifying factors, including lesion side, correlated significantly with the language outcome. CONCLUSION Childhood stroke, regardless of the affected hemisphere, can lead to chronic language deficits, even though affected children show a "full recovery." The rehabilitation of children and adolescents with childhood stroke should address language abilities, even after the usually quick resolution of clear aphasic symptoms

Non-verbal Intelligence in Unilateral Perinatal Stroke Patients With and Without Epilepsies

Background: The risk factors for impaired cognitive development after unilateral perinatal stroke are poorly understood. Non-verbal intelligence seems to be at particular risk, since language can shift to the right hemisphere and may thereby reduce the capacity of the right hemisphere for its originary functions. Pharmaco-refractory epilepsies, a frequent complication of perinatal strokes, often lead to impaired intelligence. Yet, the role of well-controlled epilepsies is less well-understood. Here, we investigated whether well-controlled epilepsies, motor impairment, lesion size, lesion side, and lateralization of language functions influence non-verbal functions. Methods: We recruited 8 patients with well-controlled epilepsies (9–26 years), 15 patients without epilepsies (8–23 years), and 23 healthy controls (8–27 years). All underwent the Test of Non-verbal Intelligence, a motor-independent test, which excludes biased results due to motor impairment. Language lateralization was determined with functional MRI, lesion size with MRI-based volumetry, and hand motor impairment with the Jebson-Taylor Hand Function-Test. Results: Patients with epilepsies showed significantly impaired non-verbal intelligence [Md = 89.5, interquartile range (IQR) = 13.5] compared with controls (Md = 103, IQR = 17). In contrast, patients without epilepsies (Md = 97, IQR = 15.0) performed within the range of typically developing children. A multiple regression analysis revealed only epilepsy as a significant risk factor for impaired non-verbal functions. Conclusion: In patients with unilateral perinatal strokes without epilepsies, the neuroplastic potential of one healthy hemisphere is able to support the development of normal non-verbal cognitive abilities, regardless of lesion size, lesion side, or language lateralization. In contrast, epilepsy substantially reduces this neuroplastic potential; even seizure-free patients exhibit below-average non-verbal cognitive functions