The autosomal dominant myopathy facioscapulohumeral muscular dystrophy (FSHD1, OMIM 158900) is caused by contraction of the D4Z4 repeat array on 4qter. We show that this contraction causes marked hypomethylation of the contracted D4Z4 allele in individuals with FSHD1. Individuals with phenotypic FSHD1, who are clinically identical to FSHD1 but have an unaltered D4Z4, also have hypomethylation of D4Z4. These results strongly suggest that hypomethylation of D4Z4 is a key event in the cascade of epigenetic events causing FSHD1.

CXCL13 in cerebrospinal fluid (CSF) could be an important component for diagnosing Lyme neuroborreliosis (LNB). Levels of intrathecal CXCL13 were determined for 58 LNB patients and 210 controls; sensitivity was 88% and specificity was 89% (cutoff, 250 pg of CXCL13/ml of CSF). Elevated levels of CXCL13 can aid in the diagnosis of LNB, but levels should be interpreted with care.Diagnosing Lyme neuroborreliosis (LNB) is difficult because one of the most specific markers, the antibody index (AI), is negative in 21 to 45% of patients (1). Intrathecal levels of CXCL13 have been suggested to be a potential biomarker for LNB. CXCL13 is produced by antigen-presenting cells and is a selective chemoattractant for B cells and B-helper T cells. It has been shown that CXCL13 is expressed at high levels in cerebrospinal fluid (CSF) from LNB patients, while levels were barely detectable in CSF from subjects with noninflammatory neurological disease. Overall sensitivity for LNB ranged from 96 to 100%, and specificity ranged from 63 to 98% (3,6,11,12). Case reports describing early diagnosis of LNB using CXCL13 levels in CSF have already been published (5, 9).Our aim was to determine the diagnostic potential of levels of intrathecal CXCL13 to distinguish acute and late LNB from other central nervous system diseases in the pediatric and adult population.Patients were identified retrospectively using the OLVG Hospital laboratory information management system. CSF and serum samples from 58 LNB patients before treatment were included. Criteria for diagnosing LNB patients were that their meningitis had no other cause and that they had three of the following four characteristics: positive serology at presentation, pleocytosis, positive AI with an Ideia Lyme neuroborreliosis kit (Oxoid, Cambridge, United Kingdom), and objective neurological complaints with clinical improvement after treatment. From this group, definite LNB patients (n ϭ 45) were those who had a pleocytosis and a positive AI, and probable LNB patients (n ϭ 13) were those who had either pleocytosis (n ϭ 12) or a positive AI (n ϭ 1) (4). Ninety-one percent of the LNB patients presented within 6 months of the start of complaints; the range was 7 days to 48 months. Forty-one percent of LNB patients were children. Most LNB patients presented with a facial nerve paralysis (60%) or meningoradiculitis (26%). Seventeen percent of LNB patients reported experiencing erythema migrans (EM) before or at presentation.As controls, we included 36 patients with Lyme borreliosis that did not meet the criteria for LNB, 93 patients with an infectious cause of meningitis/encephalitis, 62 patients with neurological inflammatory diseases, and 12 patients with noninflammatory neurological complaints. Furthermore, seven HIV patients with no neurological complaints or evidence of an intrathecal infection were tested. For patient characteristics, see Table S1 in the supplemental material.CSF samples were tested with a Quantikine human CXCL13/BLC/BCA-1 immunoassay (R&D Systems, Minneapolis, MN).Resu...

This questionnaire is accurate and reliable in diagnosing migraine aura among self-reported migraineurs and enables detection of more aura cases with low false-positive rate.

Profiling of metabolites is increasingly used to study the functioning of biological systems. For some studies the volume of available samples is limited to only a few microliters or even less, for fluids such as cerebrospinal fluid (CSF) of small animals like mice or the analysis of individual oocytes. Here we present an analytical method using in-liner silylation coupled to gas chromatography/mass spectrometry (GC/MS), that is suitable for metabolic profiling in ultrasmall sample volumes of 2 microL down to 10 nL. Method performance was assessed in various biosamples. Derivatization efficiencies for sugars, organic acids, and amino acids were satisfactory (105-120%), and repeatabilities were generally better than 15%, except for amino acids that had repeatabilities up to about 35-40%. For endogenous sugars and organic acids in fetal bovine serum, the response was linear for aliquots from 10 nL up to at least 1 microL. The developed GC/MS method was applied for the analysis of different sample matrixes, i.e., fetal bovine serum, mouse CSF, and aliquots of the intracellular content of Xenopus laevis oocytes. To the best of our knowledge, we present here the first comprehensive GC/MS metabolite profiles from mouse CSF and from the intracellular content of a single X. laevis oocyte.

Using an exploratory H-NMR metabolomics analysis we identified metabolites that were able to discriminate hemiplegic migraine patients from healthy controls. The lower levels of 2-hydroxybutyrate found in patients with hemiplegic migraine could indicate a dysregulation of the brain's energy metabolism. An experimental confirmation in vitro or in animal models will be required to confirm or discard this hypothesis. Migraine with and migraine without aura patients did not reveal a metabolic profile different from healthy controls.