Investigation of asymptomatic persistent hyper-CK-emia

Fifty four consecutive adult patients with persistent elevated serum creatine kinase (CK) levels and no muscle weakness were studied during a three-year period using a uniform diagnostic protocol. The aim of the study was to investigate a possible underlying neuromascular disease and to evaluate the usefulness of electrophysiological study, muscle biopsy and genetic testing in the management of persistent hyperokemia. Electrophysiological findings were abnormal in 64% and histopathological lesions were detected in 65.3%. CK values were significant higher (p=0.006) in cases of abnormal electrophysiological study and marginally higher in cases of abnormal muscle biopsy (p=0.051). The sensitivity and specificity of electrophysiological study for abnormal muscle biopsy were 79.31% and 62.5% respectively. Definitive diagnosis was made in 16 cases (29.62%). Histochemical and immunohistochemical study led to diagnosis in 12 patients and genetic testing in 4. A probabe diagnosis was achieved in 4 cases (7.4%). Abnormal electrophysiological study and abnormal muscle biopsy were significantly more common (p<0.001) in cases of definitive or probable diagnosis.Μελετήθηκαν 54 ενήλικες ασθενείς με επίμονα αυξημένα επίπεδα κρεατινικής κινάσης ορού (CK) και χωρίς μυϊκή αδυναμία μέσα σε περίοδο 3 ετών, χρησιμοποιώντας ενιαίο και συμπαγές διαγνωστικό πρωτόκολλο. Ο στόχος της μελέτης ήταν η διερεύνηση πιθανής υποκείμενης νευρομυϊκής νόσου και η εκτίμηση της χρησιμότητας του ηλεκτροφυσιολογικού ελέγχου της βιοψίας μυός και του γενετικου ελέγχου στην διαγνωστική προσέγγιση της επίμονης υπερ-CK-αιμίας. Τα ηλεκτροφυσιολογικά ευρήματα ήταν παθολογικά σε 64% των περιπτώσεων και ιστοπαθολογικές αλλοιώσεις ανιχνεύτηκαν σε 65.3%. Οι τιμές CK ήταν σημαντικά υψηλότερες (p=0.006) στις περιπτώσεις με παθολογική ηλεκτροφυσιολογική μελέτη και οριακά υψηλότερη στις περιπτώσεις παθολογικής βιοψίας μυός (p=0.051). Η ευαισθησία και η ειδικότητα της ηλεκτροφυσιολογικής μελέτης για ανίχνευση παθολογικής βιοψίας μυός ήταν 79.31% και 62.5% αντίστοιχα. Βέβαιη διάγνωση τέθηκε σε 16 περιπτώσεις (29.62%). Η ιστοχημική και ανοσοϊστοχημική μελέτη του μυός οδήγησε σε διάγνωση σε 12 ασθενείς και ο γενετικός έλεγχος σε 4. Πιθανή διάγνωση τέθηκε σε 4 περιπτώσεις (7.4%). Η παθολογική ηλεκτροφυσιολογική μελέτη και η παθολογική βιοψία μυός ήταν σημαντικά συχνότερα (p<0.001) σε περιπτώσεις με βέβαιη ή πιθανή διάγνωση

Facio-scapulo-humeral muscular dystrophy with early joint contractures and rigid spine

Early joint contractures in childhood or adolescence irrespective of muscle weakness are usually found in Emery-Dreifuss muscular dystrophy and collagen-VI related diseases and only rarely in the early stages of other progressive muscular dystrophies. We report a patient presenting severe elbow contractures and a rigid-spine since his early childhood without any evident muscle weakness, who was diagnosed with facioscapulohumeral muscular dystrophy later in life. This case is interesting since there has been no report, to date, of patients with a phenotype resembling facioscapulohumeral muscular dystrophy also in association with early and prominent elbow contractures and spinal rigidity, since childhood, resembling Emery-Dreifuss muscular dystrophy. Our case further confirmed the phenotypic variability often observed in carriers of D4Z4 reduce allele, and highlights the complexity of a definitive diagnosis in these cases

Corticosteroids for spontaneous intracranial hypotension: a case-report and critical review focusing on pathophysiology and treatment

Background Spontaneous intracranial hypotension (SIH) is characterized by positional headache caused by low CSF pressure, without any major traumatic event. Optimal treatment is still debated; epidural blood patch (EBP) is usually used after unsuccessful conservative treatment with variable efficacy and potentially severe complications. Although steroids have been reported to be beneficial, their effectiveness is still controversial, and more clinical evidence is needed. Case presentation A 37-year-old woman was admitted to the neurology department due to severe orthostatic headache with nausea over the last 5 days. No trauma history or spinal manipulation were mentioned. On arrival, neurological examination, brain CT, and laboratory investigation were normal. Intracranial hypotension was clinically suspected, and lumbar puncture revealed low opening pressure. Brain MRI demonstrated pachymeningeal gadolinium enhancement and distended and rounded dural venous sinuses, while cervicothoracic spine MRI revealed thoracic CSF leakage, leading to SIH diagnosis. The patient was treated with high-dose intravenous methylprednisolone, with complete clinical resolution within 24 h. Conclusions Our case, combined with literature evidence, supports the high-dose intravenous corticosteroids as a reasonable treatment option in selected cases, before trying EBP or surgical repair. Randomized clinical trials are needed, in order to optimize SIH patients&apos; outcomes

MRI evidence of extraocular muscle atrophy and fatty replacement in myasthenia gravis

Purpose The aim of the study was to evaluate extraocular muscle (EOM) atrophy and fatty replacement in ocular myasthenia gravis (OMG) and generalized myasthenia gravis (GMG) patients with chronic and untreated ocular symptoms or with inadequate response to immunotherapy and unprovoked ocular exacerbations despite chronic immunotherapy. Methods Nineteen patients with either OMG or GMG and 19 healthy age-matched controls underwent an orbital MRI. Visually obvious muscle atrophy and muscle fatty replacement were evaluated by two raters independently. Maximum thickness of EOM was measured. Measurements of the muscles of each participant were added up, in order to calculate the total thickness. Results Eleven patients suffered from AChR-positive GMG, and 8 patients from OMG. All patients had chronic ocular symptoms or inadequate response to corticosteroids and unprovoked ocular exacerbations in spite of immunotherapy. Fatty replacement was reported in 6/19 (31.6%) patients and 0/19 (0%) controls (p = 0.02). Obvious atrophy in at least one muscle was reported in 8/19 (42.1%) patients and 1/19 (5.3%) controls (p = 0.019). Statistically significant differences between the two groups were also found in the mean total thickness, as well as in the thickness of superior recti, levator palpebrae, inferior recti, and superior oblique muscles. Conclusion EOM atrophy and fatty replacement were seen frequently in our series of MG patients with treatment difficulties and frequent relapses of ocular involvement

The etiology of cleft palate formation in BMP7-deficient mice

Palatogenesis is a complex process implying growth, elevation and fusion of the two lateral palatal shelves during embryogenesis. This process is tightly controlled by genetic and mechanistic cues that also coordinate the growth of other orofacial structures. Failure at any of these steps can result in cleft palate, which is a frequent craniofacial malformation in humans. To understand the etiology of cleft palate linked to the BMP signaling pathway, we studied palatogenesis in Bmp7-deficient mouse embryos. Bmp7 expression was found in several orofacial structures including the edges of the palatal shelves prior and during their fusion. Bmp7 deletion resulted in a general alteration of oral cavity morphology, unpaired palatal shelf elevation, delayed shelf approximation, and subsequent lack of fusion. Cell proliferation and expression of specific genes involved in palatogenesis were not altered in Bmp7-deficient embryos. Conditional ablation of Bmp7 with Keratin14-Cre or Wnt1-Cre revealed that neither epithelial nor neural crest-specific loss of Bmp7 alone could recapitulate the cleft palate phenotype. Palatal shelves from mutant embryos were able to fuse when cultured in vitro as isolated shelves in proximity, but not when cultured as whole upper jaw explants. Thus, deformations in the oral cavity of Bmp7-deficient embryos such as the shorter and wider mandible were not solely responsible for cleft palate formation. These findings indicate a requirement for Bmp7 for the coordination of both developmental and mechanistic aspects of palatogenesis