Potential beneficial effects of granulocyte colony-stimulating factor therapy for spastic paraparesis in a patient with kyphoscoliosis: a case report.

Congenital kyphosis and kyphoscoliosis are much less common than congenital scoliosis and more serious because these curves can progress rapidly and can lead to spinal cord compression and paraplegia. A 15-year-old boy presented with congenital kyphoscoliosis along with spastic paraparesis (American Spinal Injury Association Impairment Scale grade C). We examined the safety and effectiveness of a low dose of analog granulocyte colony-stimulating factor (G-CSF) in this patient. G-CSF 5 µg/kg was given subcutaneously, daily for 5 days per month for 3 months. Laboratory tests, including blood, biochemical tests, and CD34+ cells (marker hematopoietic progenitor cells) were performed, in addition to clinical examination. Clinical examination revealed an increase of muscle strength in the upper limbs and decrease spasticity in the lower limbs between baseline and day 90 and day 180. We found no serious adverse event, drug-related platelet reduction, or splenomegaly. Leukocyte levels remained below 21,000/µL. CD34+ increased significantly at day 5 of G-CSF administration. Low-dose G-CSF was safe and well tolerated by the patient. A significant increase in muscle strength in this patient with spastic paraparesis after 3 months of treatment may indicate beneficial effects of G-CSF factor in this disorder. These results are inspiring and warrant further studies.

Biochemical Changes in Blood of Patients with Duchenne Muscular Dystrophy Treated with Granulocyte-Colony Stimulating Factor.

INTRODUCTION: In addition to the "gold standard" of therapy-steroids and gene therapy-there are experimental trials using granulocyte-colony stimulating factor (G-CSF) for patients with Duchenne muscular dystrophy (DMD). The aim of this study was to present the biochemical changes in blood after repeating cycles of granulocyte-colony stimulating factor G-CSF therapy in children with DMD. MATERIALS AND METHODS: Nineteen patients, aged 5 to 15 years, with diagnosed DMD confirmed by genetic tests, participated; nine were in wheelchairs, and ten were mobile and independent. Patients had a clinical assessment and laboratory tests to evaluate hematological parameters and biochemistry. G-CSF (5µg/kg/day) was given subcutaneously for five days during five nonconsecutive months over the course of a year. RESULTS: We found a significant elevation of white blood cells, and the level of leucocytes returned to norm after each cycle. No signs of any inflammatory process were found by monitoring C-reactive protein. We did not detect significant changes in red blood cells, hemoglobin, and platelet levels or coagulation parameters. We found a significant elevation of uric acid, with normalization after finishing each treatment cycle. A significant decrease of the mean value activity of aspartate transaminase (AST) and alanine transaminase (ALT) of the G-CSF treatment was noted. After each five days of therapy, the level of cholesterol was significantly lowered. Also, glucose concentration significantly decreased after the fourth cycle. CONCLUSIONS: G-SCF decreased the aminotransferases activity, cholesterol level, and glucose level in patients with DMD, which may be important for patients with DMD and metabolic syndrome.

Seasonal Variations in Cerebral Palsy Births.

INTRODUCTION: Previous studies of cerebral palsy (CP) suggest that it seasonal variations in the incidence of CP. The purpose of this paper was to compare seasonal variations in the incidence of cerebral palsy (CP) in Podlaskie Province, Poland, between 1990-1999 (study 2005) and 2000-2014 (study 2017) in a retrospective case-controlled study. MATERIALS AND METHODS: Data were obtained from the hospital database. We compared CP births between January 1, 1990, and December 31, 1999, n = 212 (116 boys, 96 girls) and January 1, 2000, and December 31, 2014, n = 205 (114 boys, 91 girls). We used Cosinor analysis to examine the seasonality of CP births. RESULTS: The highest number of CP births occurred in spring and the lowest in winter, with intermediate values in summer and autumn. This seasonal pattern was significant for spring vs. winter. The peaks in the numbers of CP births occurred in May and August; the lowest numbers of CP births occurred in February, December, and November. In the 2017 study, we observed a slight increase in spastic tetraplegia and a decrease in mixed CP. No significant corrections between mean temperature and Apgar score, low birth weight, and asphyxia were found. CONCLUSIONS: Our study confirmed the existence of seasonal patterns for CP births.

Efficacy and the Safety of Granulocyte Colony-Stimulating Factor Treatment in Patients with Muscular Dystrophy: A Non-Randomized Clinical Trial.

INTRODUCTION: The current standard treatment for patients with Duchenne muscular dystrophy (DMD) involves corticosteroids. Granulocyte colony-stimulating factor (G-CSF) induces the proliferation of satellite cells and myoblasts and, in turn, muscle regeneration. Beneficial effects of G-CSF were also described for skeletal muscle disorders. AIM: We assessed the safety and effects of using G-CSF to promote muscle strength in patients with DMD. MATERIALS AND METHODS: Inclusion criteria were as follows: patients aged 5-15 years with diagnosed with DMD confirmed by genetic test or biopsy. Fourteen patients were treated with steroids, and their use was not changed in this study. Diagnoses were confirmed by genetic tests: deletions were detected in 11 patients and duplications in 5 patients. Nineteen 5- to 15-year-old patients diagnosed with DMD-9 were in wheelchairs, whereas 10 were mobile and independent-completed an open study. Participants received a clinical examination and performed physiotherapeutic and laboratory tests to gage their manual muscle strength, their isometric force using a hand dynamometer, and aerobic capacity [i.e., 6-min walk test (6MWT)] before and after therapy. Each participant received G-CSF (5 µg/kg/body/day) subcutaneously for five consecutive days during the 1st, 2nd, 3rd, 6th, and 12th month. Laboratory investigations that included full blood count and biochemistry were performed. Side effects of G-CSF treatment were assessed during each visit. During each cycle of G-CSF administration in the hospital, rehabilitation was also applied. All patients received regular ambulatory rehabilitation. RESULTS: The subcutaneous administration of G-CSF improved muscle strength in participants. We recorded a significant increase in the distance covered in the 6MWT, either on foot or in a wheelchair, increased muscle force in isometric force, and a statistically significant decrease in the activity of the muscle enzyme creatine kinase after nearly every cycle of treatment. We observed no side effects of treatment with G-CSF. CONCLUSION: Our findings suggest that G-CSF increases muscle strength in patients with DMD, who demonstrated that G-CSF therapy is safe and easily tolerable.

Effect of Periodic Granulocyte Colony-Stimulating Factor Administration on Endothelial Progenitor Cells and Different Monocyte Subsets in Pediatric Patients with Muscular Dystrophies.

Muscular dystrophies (MD) are heterogeneous group of diseases characterized by progressive muscle dysfunction. There is a large body of evidence indicating that angiogenesis is impaired in muscles of MD patients. Therefore, induction of dystrophic muscle revascularization should become a novel approach aimed at diminishing the extent of myocyte damage. Recently, we and others demonstrated that administration of granulocyte colony-stimulating factor (G-CSF) resulted in clinical improvement of patients with neuromuscular disorders. To date, however, the exact mechanisms underlying these beneficial effects of G-CSF have not been fully understood. Here we used flow cytometry to quantitate numbers of CD34+ cells, endothelial progenitor cells, and different monocyte subsets in peripheral blood of pediatric MD patients treated with repetitive courses of G-CSF administration. We showed that repetitive cycles of G-CSF administration induced efficient mobilization of above-mentioned cells including cells with proangiogenic potential. These findings contribute to better understanding the beneficial clinical effects of G-CSF in pediatric MD patients.

Duchenne muscular dystrophy: current cell therapies.

Duchenne muscular dystrophy is a genetically determined X-linked disease and the most common, progressive pediatric muscle disorder. For decades, research has been conducted to find an effective therapy. This review presents current therapeutic methods for Duchenne muscular dystrophy, based on scientific articles in English published mainly in the period 2000 to 2014. We used the PubMed database to identify and review the most important studies. An analysis of contemporary studies of stem cell therapy and the use of granulocyte colony-stimulating factor (G-CSF) in muscular dystrophy was performed.

Quality of life in children and adolescents with cerebral palsy and myelomeningocele.

The aim of this study was to compare health-related quality of life in children with cerebral palsy and with myelomeningocele. Fifty-seven children with spastic cerebral palsy and 34 patients with myelomeningocele aged 5-16 years were included in the study. Their mothers completed standardized measures on the Revidierter Kinder Lebensqualitätsfragebogen (KINDL-R) parent questionnaire. The 2 groups were demographically comparable. The children with cerebral palsy were classified more frequently into levels II (n = 24) and III (n = 18) of the Gross Motor Function Classification System. Other patients were classified into levels IV (n = 5) and V (n = 10). Three patients with myelomeningocele were community walkers, 10 could walk with assistive devices, and 21 used a wheelchair. Lesion level was thoracic in 13 patients, lumbar in 17, and sacral in 4. Twenty-nine patients (85.3%) with myelomeningocele had hydrocephalus, and 27 had a shunt. Parents in the both studied groups reported similar overall quality of life of their children in the dimensions of physical and emotional well-being, self-esteem, family, friends, and school. No significant correlations between the quality-of-life scores and age, walking ability, and mental development of the studied groups were found.