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Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal postures, repetitive movements, or both. Research in dystonia has been challenged by several factors. First, dystonia is uncommon. Dystonia is not a single disorder but a family of heterogenous disorders with varied clinical manifestations and different causes. The different subtypes may be seen by providers in different clinical specialties including neurology, ophthalmology, otolaryngology, and others. These issues have made it difficult for any single center to recruit large numbers of subjects with specific types of dystonia for research studies in a timely manner. The Dystonia Coalition is a consortium of investigators that was established to address these challenges. Since 2009, the Dystonia Coalition has encouraged collaboration by engaging 56 sites across North America, Europe, Asia, and Australia. Its emphasis on collaboration has facilitated establishment of international consensus for the definition and classification of all dystonias, diagnostic criteria for specific subtypes of dystonia, standardized evaluation strategies, development of clinimetrically sound measurement tools, and large multicenter studies that document the phenotypic heterogeneity and evolution of specific types of dystonia.

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To better understand the role and reliability of axillary temperature measurements in clinical real life, axillary and rectal measurements in infants presenting in a private pediatric practice because of fever were compared. Prospectively, 169 infants (81 girls), median 9 (interquartile range 6-13) months of age, were examined at room temperature (20-24 °C). Two left and two right axillary, as well as two rectal measurements were taken with a digital thermometer and subsequently averaged. The median and interquartile range for axillary and rectal measurements were 36.9 (36.3-37.6) °C and 38.2 (37.4-38.9) °C, respectively (p < 0.0001). The limits of agreement in the Bland-Altman plots were 0.32 to 1.98 °C, with a mean bias of 1.15 °C. Axillary thermometers showed a good sensitivity for detecting rectal temperature > 38 °C (95%) but limited specificity (75%), with an area-under-the-curve of 0.95.Conclusions: Axillary readings are always lower than rectal ones, the limits of agreement are quite wide. Axillary readings can be used for screening but critical measurements should be confirmed by more reliable methods. What is Known • In infants and toddlers, temperature has been traditionally taken rectally. • Axillary measurements are better accepted and are recommended in current guidelines. What is New • Axillary temperature was always lower than rectal temperature. • The limits of agreement of axillary thermometers are wide. • Axillary thermometers have a good sensitivity but limited specificity and are therefore adequate for fever screening.

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PURPOSE OF REVIEW: The dystonias are a family of related disorders with many different clinical manifestations and causes. This review summarizes recent developments regarding these disorders, focusing mainly on advances with direct clinical relevance from the past 2 years. RECENT FINDINGS: The dystonias are generally defined by their clinical characteristics, rather than by their underlying genetic or neuropathological defects. The many varied clinical manifestations and causes contribute to the fact that they are one of the most poorly recognized of all movement disorders. A series of recent publications has addressed these issues, offering a revised definition and more logical means for classifying the many subtypes. Our understanding of the genetic and neurobiological mechanisms responsible for different types of dystonias also has grown rapidly, creating new opportunities and challenges for diagnosis, and identifying increasing numbers of rare subtypes for which specific treatments are available. SUMMARY: Recent advances in describing the clinical phenotypes and determining associated causes have pointed to the need for new strategies for diagnosis, classification, and treatment of the dystonias.

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With advances in the understanding of the pathophysiology of dystonia, novel therapeutics are being developed. Such therapies will require clinical investigation ranging from exploratory studies to examine safety, tolerability, dosage selection, and preliminary efficacy to confirmatory studies to evaluate efficacy definitively. As dystonia is a rare and complex disorder with clinical and etiological heterogeneity, clinical trials will require careful consideration of the trial design, including enrollment criteria, concomitant medication use, and outcome measures. Given the complexities of designing and implementing efficient clinical trials, it is important for clinicians and statisticians to collaborate closely throughout the clinical development process and that each has a basic understanding of both the clinical and statistical issues that must be addressed. To facilitate designing appropriate clinical trials in this field, we review important general clinical trial and regulatory principles, and discuss the critical components of trials with an emphasis on considerations specific to dystonia. Additionally, we discuss designs used in early exploratory, late exploratory, and confirmatory phases, including adaptive designs.

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This report describes the consensus outcome of an international panel consisting of investigators with years of experience in this field that reviewed the definition and classification of dystonia. Agreement was obtained based on a consensus development methodology during 3 in-person meetings and manuscript review by mail. Dystonia is defined as a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. Dystonia is classified along 2 axes: clinical characteristics, including age at onset, body distribution, temporal pattern and associated features (additional movement disorders or neurological features); and etiology, which includes nervous system pathology and inheritance. The clinical characteristics fall into several specific dystonia syndromes that help to guide diagnosis and treatment. We provide here a new general definition of dystonia and propose a new classification. We encourage clinicians and researchers to use these innovative definition and classification and test them in the clinical setting on a variety of patients with dystonia. © 2013 Movement Disorder Society.

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The major amyloid-beta (Abeta) peptides found in the brain of familial and late onset Alzheimer's disease include the full-length Abeta1-42 and N-terminally truncated, pyroglutamylated peptides Abetap3-42 and Abetap11-42. The biophysical properties of Abeta1-42 have been extensively studied, yet little is known about the other modified peptides. We investigated the aggregation kinetics of brain-specific Abeta peptides to better understand their potential roles in plaque formation. Synthetic peptides were analyzed individually and in mixtures representing various ratios found in the brain. Spectrofluorometric analyses using Thioflavin-T showed that the aggregation of Abeta1-42 was faster compared to Abetap3-42; however, Abetap11-42 displayed similar kinetics. Surprisingly, mixtures of full-length Abeta1-42 and Abetap3-42 showed an initial delay in beta-sheet formation from both equimolar and non-equimolar samples. Electron microscopy of peptides individually and in mixtures further supported fluorescence data. These results indicate that Abeta-Abeta peptide interactions involving different forms may play a critical role in senile plaque formation and maintenance of the soluble Abeta pool in the brain.

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Representative extraction of both RNA and protein from a single biological sample is required for reliable assessment of coordinated changes in gene and protein expression. Such a simultaneous extraction can be performed by using Trizol Reagent. Here, we demonstrate that, as an alternative to SDS, 2% diethylamine is an effective solvent, which can be conveniently used in extraction of Trizol-isolated proteins from various tissues. Diethylamine provides efficient extraction of proteins and compatibility with a variety of common downstream analytical applications.

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Near infrared spectrophotometric (NIRS) algorithms to determine the tissue oxygen saturation (TOI) assume a semi-infinite, homogenous tissue geometry. At the head, the clear cerebrospinal fluid (CSF) layer may violate this assumption. The aim was to estimate the error in the TOI values caused by the CSF layer in vitro and to confirm the results in vivo. The liquid phantom mimicking the neonatal head, consisted of a spherical shell of silicone filled with a liquid solution (1% Intralipid, 60 mumol/l haemoglobin, yeast) and a clear layer imitating CSF. The solution was oxygenated and deoxygenated, while measuring its TOI and pO2. Without clear layer the mean TOI was 90.9 +/- 0.5% at pO2 > 18 kPa and decreased to 26.0 +/- 1.3% at pO2 = 0 kPa. With a clear layer the TOI increased from 27.8 +/- 0.8% at pO2 > 18 kPa to 68.0 +/- 0.8% at pO2 = 0 kPa. The clear layer caused a large error in the TOI. In ten mechanically ventilated infants (postnatal age 0.03 to 8 months) the TOI (at the head) and arterial oxygen saturation (SaO2) were measured while the inspired oxygen fraction was altered. The TOI was always positively correlated with the SaO2 (mean slope linear regression = 0.89, r2 = 0.62). Thus an adverse effect of the CSF layer on TOI measurements can be excluded for infants. The CSF layer is not modelled correctly in the phantom.

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OBJECTIVE: To evaluate the clinical usefulness of near-infrared spatially resolved spectroscopic quantitative assessment of liver tissue oxygenation for simple, non-invasive estimation of global tissue oxygenation in critically ill neonates and children. DESIGN: Prospective observational clinical study. SETTING: A tertiary multidisciplinary neonatal and paediatric intensive care unit (23 beds). PATIENTS: One hundred neonates and children consecutively admitted to the paediatric intensive care unit. MEASUREMENTS AND RESULTS: Near-infrared spectroscopic single-point assessment of liver tissue oxygenation index (TOI(Liver)) was compared with global tissue oxygenation as measured by central venous oxygen saturation (SvO(2)) and derived haemodynamic parameters. Data were compared using linear and multiple regression analysis. Overall correlation between TOI(Liver)and SvO(2) was good ( r=0.72, p<0.0001). Multivariable regression revealed that SvO(2) alone explained 51% of the observed variance of TOI(Liver). However, our data demonstrated large inter-individual differences between SvO(2) and TOI(Liver) values. CONCLUSION: Near-infrared spatially resolved spectroscopic quantitative measurement of liver tissue oxygenation correlates well with SvO(2) in critically ill neonates and children. Large inter-individual SvO(2) to TOI(Liver) differences may prevent its use for non-invasive single-point estimation of global tissue oxygenation. Further clinical studies are required to validate the method with other regional and global haemodynamic parameters and to evaluate its clinical use for continuous non-invasive haemodynamic monitoring.

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