The 255th ENMC workshop on Muscle Imaging in Idiopathic Inflammatory myopathies (IIM) aimed at defining recommendations concerning the applicability of muscle imaging in IIM. The workshop comprised of clinicians, researchers and people living with myositis. We aimed to achieve consensus on the following topics: a standardized protocol for the evaluation of muscle images in various types of IIMs; the exact parameters, anatomical localizations and magnetic resonance imaging (MRI) techniques; ultrasound as assessment tool in IIM; assessment methods; the pattern of muscle involvement in IIM subtypes; the application of MRI as biomarker in follow-up studies and clinical trials, and the place of MRI in the evaluation of swallowing difficulty and cardiac manifestations. The following recommendations were formulated: In patients with suspected IIM, muscle imaging is highly recommended to be part of the initial diagnostic workup and baseline assessment. MRI is the preferred imaging modality due to its sensitivity to both oedema and fat accumulation. Ultrasound may be used for suspected IBM. Repeat imaging should be considered if patients do not respond to treatment, if there is ongoing diagnostic uncertainty or there is clinical or laboratory evidence of disease relapse. Quantitative MRI is established as a sensitive biomarker in IBM and could be included as a primary or secondary outcome measure in early phase clinical trials, or as a secondary outcome measure in late phase clinical trials. Finally, a research agenda was drawn up.
- MeSH
- biologické markery MeSH
- kosterní svaly patologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- myozitida * diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- konzilia MeSH
- Geografické názvy
- Nizozemsko MeSH
- MeSH
- Leighova nemoc * genetika terapie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- konzilia MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Nizozemsko MeSH
We report the case of a patient suffering from duplicity of myotonic dystrophy type 1 and ulcerative colitis whose treatment for ulcerative colitis included repeated administrations of descending doses of methylprednisolone and in whom we found an association between methylprednisolone dosing and cessation of myotonia. Myotonia severity was expressed as relaxation time after voluntary contraction and as a patient-reported outcome using the Czech version of the Myotonia Behavior Scale. The patient was being treated for a flare of ulcerative colitis, starting with 32 mg of methylprednisolone and reducing the dose by 4 mg a week. The symptoms of myotonia began to wear off three weeks after starting methylprednisolone and had totally disappeared by four weeks after starting methylprednisolone. The first symptoms of myotonia returned about a month after the last dose of methylprednisolone and reached a peak of severity more than two months after the final dose.
- MeSH
- dospělí MeSH
- hormony kůry nadledvin aplikace a dávkování MeSH
- lidé MeSH
- methylprednisolon aplikace a dávkování MeSH
- myotonická dystrofie farmakoterapie MeSH
- myotonie farmakoterapie MeSH
- ulcerózní kolitida farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
The association of GNB4 with Charcot-Marie-Tooth (CMT) has recently been described in a publication by Soong et al. (Soong, et al., 2013). Here we present a patient with CMT in whom whole exome sequencing identified the mutation p.Lys57Glu in the GNB4 gene (NM_021629.3:c.169A>G). The patient, now 41 years old, is a sporadic case in the family. At the age of 35 he presented with severe disability (CMT neuropathy score 29), profound muscle atrophies, pes cavus and scoliosis. Previously, the patient was tested for PMP22 duplications/deletions and later also with 64 CMT gene panel, with no causal variant found. Subsequently, whole exome sequencing was performed. The p.Lys57Glu in the GNB4 gene was identified as the most probable causal variant, the mutation is not present in the patient's parents, neither in his unaffected sister, therefore we assume that the mutation arose de novo. Taken together, these findings support the causal and pathogenic character of the variant. Our report provides important evidence that GNB4 should become an established CMT gene and our findings confirm the original publication by Soong et al. (2013).
- MeSH
- Charcotova-Marieova-Toothova nemoc genetika patologie patofyziologie MeSH
- dospělí MeSH
- lidé MeSH
- mutace MeSH
- proteiny vázající GTP - beta-podjednotky genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Geografické názvy
- Česká republika MeSH
We report two brothers with mild intellectual deficiency, exercise intolerance, rhabdomyolysis, seizures and no hemolysis. Phosphoglycerate kinase (PGK) activity was strongly decreased in their red blood cells. Subsequent molecular analysis of PGK1 revealed hemizygosity for a novel mutation c.756 + 3A > G, in intron 7. Analysis of the effect of this mutation on pre-mRNA processing demonstrated markedly decreased levels of normal PGK1 mRNA. In addition, the c.756 + 3A > G change resulted in abnormally spliced transcripts. If translated, these transcripts mostly encode for C-terminally truncated proteins. The consequences of the c.756 + 3A > G mutation is discussed, as well as the genotype-to-phenotype correlation with regard to previously described mutations (PGK Fukuroi and PGK Antwerp), which also result in C-terminal truncated proteins.
- MeSH
- fenotyp MeSH
- fosfoglycerátkinasa nedostatek genetika ultrastruktura MeSH
- genetické nemoci vázané na chromozom X komplikace diagnóza genetika MeSH
- genotyp MeSH
- hemolýza MeSH
- kosterní svaly patologie MeSH
- lidé MeSH
- mentální retardace komplikace MeSH
- mladiství MeSH
- mutace MeSH
- myoglobinurie komplikace MeSH
- sourozenci MeSH
- vrozené poruchy metabolismu komplikace diagnóza genetika MeSH
- záchvaty komplikace MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
This study evaluates primary and secondary clinical outcome measures in Charcot-Marie-Tooth disease type 1A (CMT1A) with regard to their contribution towards discrimination of disease severity. The nine components of the composite Charcot-Marie-Tooth disease Neuropathy Score and six additional secondary clinical outcome measures were assessed in 479 adult patients with genetically proven CMT1A and 126 healthy controls. Using hierarchical clustering, we identified four significant clusters of patients according to clinical severity. We then tested the impact of each of the CMTNS components and of the secondary clinical parameters with regard to their power to differentiate these four clusters. The CMTNS components ulnar sensory nerve action potential (SNAP), pin sensibility, vibration and strength of arms did not increase the discriminant value of the remaining five CMTNS components (Ulnar compound motor action potential [CMAP], leg motor symptoms, arm motor symptoms, leg strength and sensory symptoms). However, three of the six additional clinical outcome measures - the 10m-timed walking test (T10MW), 9 hole-peg test (9HPT), and foot dorsal flexion dynamometry - further improved discrimination between severely and mildly affected patients. From these findings, we identified three different composite measures as score hypotheses and compared their discriminant power with that of the CMTNS. A composite of eight components CMAP, Motor symptoms legs, Motor symptoms arms, Strength of Legs, Sensory symptoms), displayed the strongest power to discriminate between the clusters. As a conclusion, five items from the CMTNS and three secondary clinical outcome measures improve the clinical assessment of patients with CMT1A significantly and are beneficial for upcoming clinical and therapeutic trials.
- MeSH
- antioxidancia terapeutické užití MeSH
- Charcotova-Marieova-Toothova nemoc diagnóza farmakoterapie genetika terapie MeSH
- chůze MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- hodnocení výsledků zdravotní péče * MeSH
- kohortové studie MeSH
- kyselina askorbová terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- měření bolesti MeSH
- mladiství MeSH
- mladý dospělý MeSH
- progrese nemoci MeSH
- psychomotorický výkon fyziologie MeSH
- shluková analýza MeSH
- stupeň závažnosti nemoci * MeSH
- svalová síla MeSH
- věkové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- klinické zkoušky, fáze III MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
We assessed pulmonary function in hereditary motor and sensory neuropathy. Fourteen neuropathy patients without spinal deformity (group 1), 14 with spinal deformity (group 2), and 16 individuals with idiopathic spinal deformity (group 3) matched to group 2 for age, height and Cobb angle, were included. Hereditary motor and sensory neuropathy severity was measured with Charcot-Marie-Tooth Neuropathy Score. All participants exhibited mild decrease in maximal inspiratory pressure at the mouth. One-way analysis of variance yielded significant main effects for lung volumes - slow vital capacity, forced expiratory volume in 1s, and total lung capacity (p's<.01), attributable to greater volumes in group 1 compared to groups with spinal deformity - and transfer factor for carbon monoxide (p=.013), reflecting differences between groups 1 vs. 2. Slow vital capacity and total lung capacity correlated with maximal inspiratory pressure at the mouth in group 2, whereas slow vital capacity correlated with muscle work in group 3 (p's<.05). Decreased lung volume may be due to impaired respiratory muscle strength in hereditary motor and sensory neuropathy with spinal deformity and due to spinal deformity in idiopathic patients.
- MeSH
- celková kapacita plic fyziologie MeSH
- dospělí MeSH
- dýchací svaly patofyziologie MeSH
- hereditární motorické a senzitivní neuropatie komplikace patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- plíce patofyziologie MeSH
- poranění míchy komplikace patofyziologie MeSH
- respirační funkční testy metody MeSH
- skolióza patofyziologie MeSH
- svalová síla fyziologie MeSH
- usilovný výdechový objem fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Charcot-Marie-Tooth neuropathies (CMT) are a group of clinically and genetically heterogeneous disorders of the peripheral nervous system. Selection of candidate disease genes for mutation analysis is sometimes difficult since more than 40 genes and loci are known to be associated with CMT neuropathies. Hence a Czech family Cz-CMT with demyelinating type of autosomal dominant CMT disease was investigated by genome-wide linkage analysis by means of single-nucleotide polymorphism (SNP) arrays. Among 35 regions with linkage, five carried known CMT genes. In the final result a novel early growth response 2 - missense mutation c.1235 A>G, p.Glu412Gly was found. Surprisingly, the more severely affected proband carried an additional heterozygous myelin protein zero variant p.Asp246Asn detected previously, which may modify the phenotype. However, this MPZ variant is benign in heterozygous state alone, because it is also carried by the patient's healthy father.
- MeSH
- celogenomová asociační studie MeSH
- Charcotova-Marieova-Toothova nemoc etnologie genetika MeSH
- fenotyp * MeSH
- genetická vazba * MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace genetika MeSH
- protein 2 časné růstové odpovědi genetika MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
The pathogenesis of myotonic dystrophy type 2 includes the sequestration of MBNL proteins by expanded CCUG transcripts, which leads to an abnormal splicing of their target pre-mRNAs. We have found CCUG(exp) RNA transcripts of the ZNF9 gene associated with the formation of ribonuclear foci in human skeletal muscle and some non-muscle tissues present in muscle biopsies and skin excisions from myotonic dystrophy type 2 patients. Using RNA-FISH and immunofluorescence-FISH methods in combination with a high-resolution confocal microscopy, we demonstrate a different frequency of nuclei containing the CCUG(exp) foci, a different expression pattern of MBNL1 protein and a different sequestration of MBNL1 by CCUG(exp) repeats in skeletal muscle, vascular smooth muscle and endothelia, Schwann cells, adipocytes, and ectodermal derivatives. The level of CCUG(exp) transcription in epidermal and hair sheath cells is lower compared with that in other tissues examined. We suppose that non-muscle tissues of myotonic dystrophy type 2 patients might be affected by a similar molecular mechanism as the skeletal muscle, as suggested by our observation of an aberrant insulin receptor splicing in myotonic dystrophy type 2 adipocytes.
- MeSH
- aktiny metabolismus MeSH
- analýza rozptylu MeSH
- antigeny CD34 metabolismus MeSH
- endotel metabolismus patologie MeSH
- konfokální mikroskopie MeSH
- kosterní svaly metabolismus MeSH
- kůže metabolismus patologie MeSH
- lidé MeSH
- myotonické poruchy diagnóza genetika metabolismus patologie MeSH
- neurofilamentové proteiny metabolismus MeSH
- proteiny S100 metabolismus MeSH
- proteiny vázající RNA genetika metabolismus MeSH
- receptor inzulinu genetika MeSH
- repetitivní sekvence nukleových kyselin genetika MeSH
- RNA metabolismus MeSH
- sestřih RNA genetika MeSH
- transport proteinů fyziologie MeSH
- tukové buňky metabolismus patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Distal hereditary motor neuropathy is a heterogeneous group of disorders characterised by a pure motor axonal neuropathy. It is occasionally associated with additional signs such as facial weakness, vocal cord paralysis, weakness of the diaphragm, and pyramidal signs. Although predominantly the inheritance is autosomal dominant, all types of inheritance have been described. Here we report a Czech family with cranial nerves palsy as an initial feature of a non progressive infantile onset dominant distal hereditary motor neuropathy. This family may represent a new subtype of distal hereditary motor neuropathy.
- MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- elektromyografie MeSH
- fenotyp MeSH
- kojenec MeSH
- lidé MeSH
- nemoci kraniálních nervů etiologie MeSH
- nervové vedení MeSH
- onemocnění motorického neuronu diagnóza komplikace MeSH
- progrese nemoci MeSH
- rodina MeSH
- věk při počátku nemoci MeSH
- Check Tag
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH