In-vivo-Konnektivität der menschlichen Colliculi superiores gemessen mit Resting-State fMRT

Im Rahmen dieser Arbeit wurde die Anwendbarkeit einer Analyse der funktionellen Konnektivität mittels Resting-State fMRT (rs-fMRT) in einem Subvolumen des menschlichen Colliculus superior untersucht (superfizielle und intermediäre Schichten = siSC). Um den speziellen Anforderungen einer so kleinen und im Hirnstamm liegenden Seed-Region gerecht zu werden, wurde ein Ansatz gewählt, bei dem Zeitverläufe aus ungeglätteten Daten extrahiert wurden um dann mit diesen die Korrelationen zu den geglätteten Zeitverläufen der Voxel des restlichen Volumens zu berechnen. Auf diese Weise konnte zum einen ein strukturell präzises Seed-Signal und zum anderen ein ausreichendes Signal-Rausch-Verhältnis erreicht werden. Die Validität dieser Methode konnte initial durch ein klares Korrelationsmuster eines Seeds im Precuneus mit den Regionen des Default Mode Networks, welches vielfach in der Literatur beschrieben wurde, bestätigt werden. Zusätzlich zeigte sich, dass es keine systematischen Unterschiede zwischen den Korrelationen von Messungen mit geschlossenen und denen mit geöffneten Augen, in den für diese Studie im Fokus liegenden Regionen, gibt. Weiterhin stellte sich heraus, dass aufgrund von räumlichen Inkonsistenzen in normalisierten Bildern die Verwendung eines für jeden Probanden individuell gesetzten Seeds tendenziell der Verwendung einer für alle Probanden gleichen Seed-Koordinate überlegen ist. Bei der Gruppenanalyse der Korrelationskarten der siSC zeigten sich für beide Seiten konstante Cluster im lateralen und medialen visuellen Kortex. Weiterhin zeigten sich von okzipital nach dorsal parietal aufsteigende Korrelationen, Cluster im frontalen Kortex und ein axial flächiges Korrelationsmuster in Höhe der SC, welches sich nach lateral in apikale Richtung ausbreitete. Diese Ergebnisse der kortikalen Korrelationen decken sich in großen Teilen mit der bekannten anatomischen Konnektivität der SC in Makaken, auch wenn vor allem zu erwartende Korrelationen zu okulomotorischen Arealen nicht gezeigt werden konnten. Es wurde gezeigt, dass eine rs-fMRT-Analyse eines kleinen Subvolumens im Hirnstamm, hier namentlich den siSC, grundsätzlich möglich ist. Außerdem wurden Vorschläge zur Weiterentwicklung der Methodik beschrieben, welche insbesondere Verbesserungen der Messtechnik und der Datenvorverarbeitung beinhalten

Scientific opinion on dietary reference values for thiamin

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derived dietary reference values (DRVs) for thiamin (vitamin B1). The Panel considers that data from depletion\u2013repletion studies in adults on the amount of dietary thiamin intake associated with the erythrocyte transketolase activity coefficient (\u3b1ETK) < 1.15, generally considered to reflect an adequate thiamin status, or with the restoration of normal (baseline) erythrocyte transketolase activity, without a sharp increase in urinary thiamin excretion, can be used to estimate thiamin requirement. In the absence of new scientific evidence, the Panel endorses the average requirement (AR) of 0.072 mg/MJ (0.3 mg/1,000 kcal) for all adults proposed by the Scientific Committee for Food (SCF) in 1993 on the basis of one depletion\u2013repletion study, in which both \u3b1ETK and urinary thiamin excretion were measured. Results from other depletion\u2013repletion studies are in agreement with this value. The Panel agrees on the coefficient of variation of 20% used by the SCF to cover uncertainties related to distribution of thiamin requirements in the general population, and endorses the population reference intake (PRI) of 0.1 mg/MJ (0.4 mg/1,000 kcal) set by the SCF for all adults. The same AR and PRI as for adults, expressed in mg/MJ, are proposed for infants aged 7\u201311 months, children aged 1 to < 18 years, and during pregnancy and lactation, under the assumption that the relationship between thiamin requirement and energy requirement is the same in all population groups

Hemicrania Continua Associated with Classic Scintillating Scotoma

Hemicrania continua (HC) is a rare primary headache disorder, characterized by persistent unilateral pain associated with cranial autonomic symptoms and prompt response to indomethacin. While migrainous features (including aura) have been recognized in cluster headache, there have been only single reports of HC with aura. Here, we report the case of a 53-year-old man with constant right-sided headache and superimposed exacerbations to severe pain lasting for several hours. Secondary etiologies were excluded, and a diagnosis of HC was established after prompt and complete response to treatment with indomethacin. During an episode of pain exacerbation, for the first time the patient experienced an episode of transient visual disturbances compatible with scintillating scotoma. We propose a potential link between HC and visual aura, which parallels similar observations in other trigeminal autonomic cephalalgias and more specifically confirms previous observational data on aura in HC, thus highlighting potentially shared pathophysiological mechanisms

Techniken und Praktiken der Verdatung

Fragen der Verdatung sind Bestandteil der digitalen Diskursanalyse und keine Vorarbeiten. Die Analyse digital(isiert)er Diskurse setzt im Unterschied zur Auswertung nicht-digital repräsentierter Sprache und Kommunikation notwendig technische Verfahren und Praktiken, Algorithmen und Software voraus, die den Untersuchungsgegenstand als digitales Datum konstituieren. Die nachfolgenden Abschnitte beschreiben kurz und knapp wiederkehrende Aspekte dieser Verdatungstechniken und -praktiken, insbesondere mit Blick auf Erhebung und Transformation (Abschnitt 2), Korpuskompilierung (Abschnitt 3), Annotation (Abschnitt 4) und Wege der analytischen Datenerschließung (Abschnitt 5). Im Fazit wird die Relevanz der Verdatungsarbeit für den Analyseprozess zusammengefasst (6)

Natural History of Polymerase Gamma–Related Ataxia

[Background] Mutations in the mitochondrial DNA polymerase gamma are causing a wide phenotypic spectrum including ataxia as one of the most common presentations.[Objective] The objective of this study was to determine the course of disease of polymerase gamma–related ataxia.[Methods] In a prospective natural history study, we assessed 24 adult ataxia patients with biallelic polymerase gamma mutations for (1) severity of cerebellar dysfunction using the Scale for the Assessment and Rating of Ataxia score, (2) presence of nonataxia signs using the Inventory of Non-Ataxia Symptoms, (3) gray- and white-matter changes in brain MRI, and (4) findings in nerve conduction studies.[Results] Assessment included follow-up visits up to 11.6 years. The Scale for the Assessment and Rating of Ataxia showed a mean annual increase of 1.02 ± 0.78 points/year. Disease progression was faster in patients with age at onset ≤ 30 years (1.5 Scale for the Assessment and Rating of Ataxia points/year) than with later onset (0.5 points/year); P = 0.008. The Inventory of Non-Ataxia Symptoms count increased by 0.30 ± 0.4 points/year. External ophthalmoplegia, brain stem oculomotor signs, areflexia, and sensory deficits were the most common nonataxic features. On MRI cerebellar atrophy was mild. T2 signal alterations affected mostly cerebellar white matter, middle cerebellar peduncles, thalamus, brain stem, and occipital and frontal white matter. Within 4 years, progression was primarily observed in the context of repeated epileptic seizures. Nerve conduction studies revealed axonal sensory peripheral neuropathy with mild motor nerve involvement. Exploratory sample size calculation implied 38 patients per arm as sufficient to detect a reduction of progression by 50% in hypothetical interventions within a 1-year trial.[Conclusion] The results recommend the Scale for the Assessment and Rating of Ataxia as a primary outcome measure for future interventional trials in polymerase gamma–related ataxia. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.This work was supported, in part, via the European Union's Horizon 2020 research and innovation program under the ERA-NET Cofund action no. 643578. It was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) no. 441409627, as part of the PROSPAX consortium under the frame of EJP RD, the European Joint Programme on Rare Diseases, under the EJP RD COFUND-EJP no. 825575 (to M.S. and B.v.d.W.) and to the PREPARE consortium (01GM1607; to M.S. and B.v.d.W.).Peer reviewe

A de novo STUB1 variant associated with an early adult-onset multisystemic ataxia phenotype

Background!#!Biallelic STUB1 variants are a well-established cause of autosomal-recessive early-onset multisystemic ataxia (SCAR16). Evidence for STUB1 variants causing autosomal-dominant ataxia (SCA48) so far largely relies on segregation data in larger families. Presenting the first de novo occurrence of a heterozygous STUB1 variant, we here present additional qualitative evidence for STUB1-disease as an autosomal-dominant disorder.!##!Methods!#!Whole exome sequencing on an index patient with sporadic early-onset ataxia, followed by Sanger sequencing in all family members, was used to identify causative variants as well as to rule out alternative genetic hits and intronic STUB1 variants. STUB1 mRNA and protein levels in PBMCs in all family members were analysed using qRT-PCR and Western Blot.!##!Results!#!A previously unreported start-lost loss-of-function variant c.3G>A in the start codon of STUB1 was identified in the index case, occurring de novo and without evidence for a second (potentially missed) variant (e.g., intronic or copy number) in STUB1. The patient showed an early adult-onset multisystemic ataxia complicated by spastic gait disorder, distal myoclonus and cognitive dysfunction, thus closely mirroring the systems affected in autosomal-recessive STUB1-associated disease. In line with the predicted start-lost effect of the variant, functional investigations demonstrated markedly reduced STUB1 protein expression in PBMCs, whereas mRNA levels were intact.!##!Conclusion!#!De novo occurrence of the loss-of-function STUB1 variant in our case with multisystemic ataxia provides a qualitatively additional line of evidence for STUB1-disease as an autosomal-dominant disorder, in which the same neurological systems are affected as in its autosomal-recessive counterpart. Moreover, this finding adds support for loss-of-function as a mechanism underlying autosomal-dominant STUB1-disease, thus mirroring its autosomal-recessive counterpart also in terms of the underlying mutational mechanism