Muscular dystrophies and myopathies: the spectrum of mutated genes in the Czech Republic.

Inherited neuromuscular disorder (NMD) is a wide term covering different genetic disorders affecting muscles, nerves, and neuromuscular junctions. Genetic and clinical heterogeneity is the main drawback in a routine gene-by-gene diagnostics. We present Czech NMD patients with a genetic cause identified using targeted next-generation sequencing (NGS) and the spectrum of these causes. Overall 167 unrelated patients presenting NMD falling into categories of muscular dystrophies, congenital muscular dystrophies, congenital myopathies, distal myopathies, and other myopathies were tested by targeted NGS of 42 known NMD-related genes. Pathogenic or probably pathogenic sequence changes were identified in 79 patients (47.3%). In total, 37 novel and 51 known disease-causing variants were detected in 23 genes. In addition, variants of uncertain significance were suspected in 7 cases (4.2%), and in 81 cases (48.5%) sequence changes associated with NMD were not found. Our results strongly indicate that for molecular diagnostics of heterogeneous disorders such as NMDs, targeted panel testing has a high-clinical yield and should therefore be the preferred first-tier approach. Further, we show that in the genetic diagnostic practice of NMDs, it is necessary to take into account different types of inheritance including the occurrence of an autosomal recessive disorder in two generations of one family.

Successful use of metronomic vinblastine and fluorothymidine pet imaging for the management of intramedullary spinal cord anaplastic oligoastrocytoma in a child.

BACKGROUND: Children with high-grade glioma still have a poor prognosis despite the use of multimodal therapy including surgery, radiotherapy, and chemotherapy. New therapeutic strategies and methods evaluating such therapies are needed. OBSERVATION: Here we describe a child with anaplastic oligodendroglioma of the spinal cord who was unable to tolerate standard chemoradiotherapy and who had still-vital residual tumour during therapy. A good response was obtained with low-dose metronomic treatment containing vinblastine. The treatment was guided according to gradual response assessed using various positron-emission tomography tracers. CONCLUSIONS: Metronomic treatment guided by positron-emission tomography could be a reasonable option in some high-risk pediatric tumours.

Long-term vagus nerve stimulation in children with focal epilepsy.

OBJECTIVES: The aim of the study was to evaluate the long-term efficacy and hospitalization rates in children with refractory focal epilepsy treated by vagus nerve stimulation. MATERIALS AND METHODS: We retrospectively analyzed 15 children with intractable focal epilepsy treated by vagus nerve stimulation (mean age of 14.6 ± 2.5 years at the time of implantation). We analyzed the treatment effectiveness at 1, 2, and 5 year follow-up visits. We counted the average number of urgent hospitalizations and number of days of urgent hospitalization per year for each patient before and after the VNS implantation. RESULTS: The mean seizure reduction was 42.5% at 1 year, 54.9% at 2 years, and 58.3% at 5 years. The number of responders was 7 (46.7%) at 1 year and 9 (60%) at both 2 and 5 years. The mean number of urgent hospitalizations per patient was 1.0 ± 0.6 per year preoperatively and 0.3 ± 0.5 per year post-operatively (P < 0.0001). The mean number of days of urgent hospitalization per patient was 9.3 ± 6.1 per year preoperatively and 1.3 ± 1.8 per year post-operatively ( < 0.0001). CONCLUSIONS: Vagus nerve stimulation is an effective method of treating children with refractory focal epilepsy. It leads to a substantial decrease in the number and duration of urgent hospitalizations.

[Long term outcomes of chronic abducens palsy surgical treatment in children and adults]. / Dlouhodobé výsledky chirurgické lécby chronické obrny n. VI u detí a dospelých.

Abducent nerve palsy is the most frequent of the acquired palsies and occurs rarely on congenital basis. It is widely recommened to wait at least 6 mohths for possible return of sixth nerve function. After this period we consider surgical management. Our retrospective comparative study evaluated long-term results of two methods for surgical treatment of chronic six nerve palsy in 118 pediatric and adult patiens who undergone surgery in the period from January 1990 to December 2005. Group A had 56 patients, in whom we performed a large recession of the medial rectus combined with a supramaximal resection of the lateral rectus. The Hummelsheim transposition procedure with or without resection of transposed half-tendon vertical muscle was performed in 62 patients of the B group. This procedure was always combined with recession of medial rectus. The augmented version of the transposition surgery resulted in a significantly better primary position of eyes postoperatively, than single graded recession-resection procedure of the horizontal muscles. The transposition surgery resulted in visible improvement in head posture and ocular alignment in the primary position, with partial restoration of abduction.

Glaucoma drainage implants in the treatment of refractory glaucoma in pediatric patients.

PURPOSE: The aim of this study is to report the clinical course, effectiveness, and safety of glaucoma drainage implants (Molteno and Baerveldt devices) in primary and secondary childhood glaucomas refractory to conventional surgical treatments and medical therapy. METHODS: This retrospective study included 76 children (76 eyes) younger than 18 years who underwent glaucoma drainage device (GDD) implantation in our clinic between 1990 and 2004. The mean age at time of surgery was 6.9+/-5.3 years (range: 4 months to 17.5 years). Intraocular pressure (IOP), visual acuity, corneal diameter, axial length, intraoperative and postoperative complications, and number of glaucoma medications were evaluated. Criteria for success were defined as IOP between 7 and 22 mmHg with or without glaucoma medications, no further glaucoma surgery, the absence of visually threatening complications, and no loss of light perception. Results were compared for children with primary and secondary glaucomas. The mean follow-up was 7.1+/-6.5 years (range: 1.6 to 15.2 years). RESULTS: Mean preoperative and postoperative IOP was 33.6+/-11.4 mmHg and 17.1+/-6.5 mmHg (p<0.001), respectively. Kaplan-Meier survival analysis showed cumulative probability of success: 93% at 6 months, 91% at 1 year, 82% at 2 years, 76% at 3 years, 71% at 4 years, 67% at 5 years, and 65% at 6 years. There was no difference between patients with primary (n=31 eyes) and secondary glaucoma (n=45 eyes) in terms of cumulative success (p=0.186), final IOP, number of medications, or length of follow-up. On average, the GDI surgery was successful for a mean period of 6.7 years. Fourteen eyes of 76 (18.4%) failed: 10 eyes with uncontrolled IOP, 2 eyes with retinal detachment, and 2 eyes with no light perception. Statistical regression model did not show influence of gender and previous surgery. Lower age at the time of surgery was found to be associated with higher probability of treatment failure. CONCLUSIONS: Molteno and Baerveldt glaucoma drainage implants surgery seems to be safe and effective treatment for primary and secondary pediatric glaucoma refractory to the initial surgical procedure and medical therapy.