Electrophysiologic testing aids diagnosis and subtyping of myoclonus

OBJECTIVE: To determine the contribution of electrophysiologic testing in the diagnosis and anatomical classification of myoclonus. METHODS: Participants with a clinical diagnosis of myoclonus were prospectively recruited, each undergoing a videotaped clinical examination and battery of electrophysiologic tests. The diagnosis of myoclonus and its subtype was reviewed after 6 months in the context of the electrophysiologic findings and specialist review of the videotaped clinical examination. RESULTS: Seventy-two patients with myoclonus were recruited. Initial clinical anatomical classification included 25 patients with cortical myoclonus, 7 with subcortical myoclonus, 2 with spinal myoclonus, and 15 with functional myoclonic jerks. In 23 cases, clinical anatomical classification was not possible because of the complexity of the movement disorder. Electrophysiologic testing was completed in 66, with agreement of myoclonus in 60 (91%) and its subtype in 28 (47%) cases. Subsequent clinical review by a movement disorder specialist agreed with the electrophysiologic findings in 52 of 60; in the remaining 8, electrophysiologic testing was inconclusive. CONCLUSIONS: Electrophysiologic testing is an important additional tool in the diagnosis and anatomical classification of myoclonus, also aiding in decision-making regarding therapeutic management. Further development of testing criteria is necessary to optimize its use in clinical practice

Low prevalence of non-typable Methicillin-resistant Staphylococcus aureus in meat products in The Netherlands

Recently, a new clone of methicillin resistant Staphylococcus (S.) aureus (MRSA) emerged in the Netherlands that was related to pigfarming. A survey in pigs showed that nearly 40% carried this new clone. This new type is characterised by bemg untypable with pulsed field gel electrophoresis (PFGE). This study was undertaken to determme the prevalence and genetic relationship of S.aureus and MRSA in meal products

Pontocerebellar hypoplasia due to bi-allelic variants in MINPP1

Pontocerebellar hypoplasia (PCH) describes a group of rare heterogeneous neurodegenerative diseases with prenatal onset. Here we describe eight children with PCH from four unrelated families harboring the homozygous MINPP1 (NM_004897.4) variants; c.75_94del, p.(Leu27Argfs*39), c.851 C > A, p.(Ala284Asp), c.1210 C > T, p.(Arg404*), and c.992 T > G, p.(Ile331Ser). The homozygous p.(Leu27Argfs*39) change is predicted to result in a complete absence of MINPP1. The p.(Arg404*) would likely lead to a nonsense mediated decay, or alternatively, a loss of several secondary structure elements impairing protein folding. The missense p.(Ala284Asp) affects a buried, hydrophobic residue within the globular domain. The introduction of aspartic acid is energetically highly unfavorable and therefore predicted to cause a significant reduction in protein stability. The missense p.(Ile331Ser) affects the tight hydrophobic interactions of the isoleucine by the disruption of the polar side chain of serine, destabilizing the structure of MINPP1. The overlap of the above-mentioned genotypes and phenotypes is highly improbable by chance. MINPP1 is the only enzyme that hydrolyses inositol phosphates in the endoplasmic reticulum lumen and several studies support its role in stress induced apoptosis. The pathomechanism explaining the disease mechanism remains unknown, however several others genes of the inositol phosphatase metabolism (e.g., INPP5K, FIG4, INPP5E, ITPR1) are correlated with phenotypes of neurodevelopmental disorders. Taken together, we present MINPP1 as a novel autosomal recessive pontocerebellar hypoplasia gene

Pontocerebellar hypoplasia due to bi-allelic variants in MINPP1.

Pontocerebellar hypoplasia (PCH) describes a group of rare heterogeneous neurodegenerative diseases with prenatal onset. Here we describe eight children with PCH from four unrelated families harboring the homozygous MINPP1 (NM_004897.4) variants; c.75_94del, p.(Leu27Argfs*39), c.851 C > A, p.(Ala284Asp), c.1210 C > T, p.(Arg404*), and c.992 T > G, p.(Ile331Ser). The homozygous p.(Leu27Argfs*39) change is predicted to result in a complete absence of MINPP1. The p.(Arg404*) would likely lead to a nonsense mediated decay, or alternatively, a loss of several secondary structure elements impairing protein folding. The missense p.(Ala284Asp) affects a buried, hydrophobic residue within the globular domain. The introduction of aspartic acid is energetically highly unfavorable and therefore predicted to cause a significant reduction in protein stability. The missense p.(Ile331Ser) affects the tight hydrophobic interactions of the isoleucine by the disruption of the polar side chain of serine, destabilizing the structure of MINPP1. The overlap of the above-mentioned genotypes and phenotypes is highly improbable by chance. MINPP1 is the only enzyme that hydrolyses inositol phosphates in the endoplasmic reticulum lumen and several studies support its role in stress induced apoptosis. The pathomechanism explaining the disease mechanism remains unknown, however several others genes of the inositol phosphatase metabolism (e.g., INPP5K, FIG4, INPP5E, ITPR1) are correlated with phenotypes of neurodevelopmental disorders. Taken together, we present MINPP1 as a novel autosomal recessive pontocerebellar hypoplasia gene

Influence of personalized extended interval dosing on the natalizumab wearing-off effect - a sub-study of the NEXT-MS trial

Background and objectives: Wearing-off symptoms during natalizumab treatment in multiple sclerosis are characterized by an increase of MS-related symptoms prior to natalizumab administration. The influence of extended interval dosing (EID) on wearing-off symptoms are important to consider, as this might cause hesitancy in initiating or continuing EID. Methods: Participants of the NEXT-MS trial, in which treatment intervals are adjusted based on drug concentrations, were divided into two groups: an extended group containing participants with at least one week of additional interval extension, and a group with a fixed interval during the trial (range 4–7 weeks). Changes in the occurrence, frequency, onset, and severity of wearing-off symptoms were evaluated. Results: 255 participants were included (extended group n = 171, fixed group n = 84). The odds on occurrence of wearing-off symptoms in the extended group did not increase after extending the treatment interval. Additional analyses for frequency, onset, and severity of wearing-off symptoms showed no changes over time. Mean decrease in natalizumab drug concentration did not influence the frequency of wearing-off symptoms. Discussion: Wearing-off symptoms were not reinforced by further extending the natalizumab interval. Wearing-off symptoms might increase in a minority of patients after EID, although our data support the view that wearing-off symptoms appear to be unrelated to the decrease in natalizumab trough drug concentrations.</p

Gray matter imaging in multiple sclerosis: what have we learned?

At the early onset of the 20th century, several studies already reported that the gray matter was implicated in the histopathology of multiple sclerosis (MS). However, as white matter pathology long received predominant attention in this disease, and histological staining techniques for detecting myelin in the gray matter were suboptimal, it was not until the beginning of the 21st century that the true extent and importance of gray matter pathology in MS was finally recognized. Gray matter damage was shown to be frequent and extensive, and more pronounced in the progressive disease phases. Several studies subsequently demonstrated that the histopathology of gray matter lesions differs from that of white matter lesions. Unfortunately, imaging of pathology in gray matter structures proved to be difficult, especially when using conventional magnetic resonance imaging (MRI) techniques. However, with the recent introduction of several more advanced MRI techniques, the detection of cortical and subcortical damage in MS has considerably improved. This has important consequences for studying the clinical correlates of gray matter damage. In this review, we provide an overview of what has been learned about imaging of gray matter damage in MS, and offer a brief perspective with regards to future developments in this field

Schuldig landschap. Over de toeristische aantrekkingskracht van Baantjer, Wallander en Inspector Morse

De opnamelokaties van tv-detectives genieten een toenemende populariteit onder toeristen. In dit artikel wordt, op basis van een tekstuele analyse van ‘Baantjer’, ‘Inspector Morse’ en ‘Wallander’, onderzocht welke inhoudelijke kenmerken van deze tv-detectives mogelijk als ‘trigger’ fungeren. Uit de analyse blijkt dat plaats en beweging een centrale rol vervullen binnen de narratieve structuur van dit genre. Door zelf de lokaties te bezoeken, kunnen toeristen het spoor nalopen van hun geliefde detective om aldaar, vanuit een veilige positie, tijdelijk op te gaan in het schemergebied tussen fictie en werkelijkheid