[Botulinum toxin treatment in children]. / Mitä annettavaa botuliinilla on lapsille?

Botulinum toxin type A treatments in children were started nearly 20 years ago. The first and still most common indication is spastic equinus gait in cerebral palsy, but other indications have emerged, such as idiopathic toe-walking, peri- and post-operative pain, drooling and idiopathic congenital torticollis. The official indication for botulinum toxin treatment is spastic equinus gait in children over 2 years of age. Botulinum toxin is known as the most potent toxin. However, it has proved to be safe and well tolerated among paediatric patients. Adverse events are infrequent, mostly bruising and limited, temporary muscle weakness. With higher doses the risk for generalized adverse events increases.

[Congenital ciliary dysfunction in children]. / Värekarvojen synnynnäiset toimintahäiriöt lapsilla.

Congenital ciliary dysfunctions are recessively inherited disorders. The disorder is poorly recognized, if the patient has no situs inversus. The diagnosis is delayed, being made on the average at the age of over five years. The review deals with a recent European multinational survey of the occurrence, genetics, diagnostics and treatment of congenital ciliary dysfunctions. Data of Finnish pediatric patients under treatment have also been collected for the survey. The number of congenital ciliary dysfunctions found in Finland is approximately one fifth of that found in other Nordic countries.

Attempt to treat congenital pseudarthrosis of the tibia with mesenchymal stromal cell transplantation.

BACKGROUND AIMS: Congenital pseudarthrosis of the tibia (CPT) caused by neurofibromatosis type 1 (NF1) is a refractory disease occurring in childhood. We present two cases that had failed all earlier treatment attempts and, as a last treatment attempt, the patients were chosen to receive mesenchymal stromal cell (MSC) transplantation prior to amputation. METHODS: The MSC from bone marrow (BM) were harvested from the iliac crest and cultured in osteoinductive medium for 3 weeks. The cultured MSC were injected in solution into BM canals of the tibia and around the resection line or bone defect in a 3-dimensional collagen sponge scaffold. After the MSC transplantation, the patients were monitored during a 10-month follow-up period. In both cases, bone formation at the pseudarthrosis site was observed and two of three treated bone defects healed. For clinical reasons not related to cell transplantation, such as new infection and pseudarthrosis and severe shortening of the leg, both extremities were finally amputated and bone samples were analyzed to evaluate MSC therapy effect and safety. RESULTS: MSC transplantation normalized bone remodeling, promoted bone resorption and improved the overall structure of bone. The number of osteoclasts in the cortical bone was 2-fold higher compared with the monitored situation before MSC transfer. In addition, the mineral content of the bone improved after transplantation. We could see no sign of aberrant bone formation or malignant transformation. CONCLUSIONS: Our data suggest that MSC transplantation is a possibility for treatment of CPT caused by NF1 in less severe cases without adjunct defects.

Treatment of congenital pseudarthrosis of the tibia with native bovine BMP: a case report.

Bone morphogenetic proteins (BMP) have been shown to induce bone formation and union in long bone defects and nonunions. We report a case of congenital pseudarthrosis of the tibia treated with a composite implant consisting of a biocoral frame, collagen carrier, and native bovine BMP extract. A six-year-old boy had persisting congenital proximal tibial pseudarthrosis despite six prior operations. At surgery, the sclerotic surfaces of both fragments were excised, fixation was performed using Ilizarov's device, and the composite implant and an autograft were applied to the nonunion site. Three months after the operation, radiographs showed union, and at four months, the Ilizarov device was removed. Two years later, the proximal pseudarthrosis remained clinically and radiologically united. It is concluded that BMP may contribute to the healing of congenital tibial pseudarthrosis of the tibia.

Mitochondrial DNA Depletion and Deletions in Paediatric Patients with Neuromuscular Diseases: Novel Phenotypes.

OBJECTIVE: To study the clinical manifestations and occurrence of mtDNA depletion and deletions in paediatric patients with neuromuscular diseases and to identify novel clinical phenotypes associated with mtDNA depletion or deletions. METHODS: Muscle DNA samples from patients presenting with undefined encephalomyopathies or myopathies were analysed for mtDNA content by quantitative real-time PCR and for deletions by long-range PCR. Direct sequencing of mtDNA maintenance genes and whole-exome sequencing were used to study the genetic aetiologies of the diseases. Clinical and laboratory findings were collected. RESULTS: Muscle samples were obtained from 104 paediatric patients with neuromuscular diseases. mtDNA depletion was found in three patients with severe early-onset encephalomyopathy or myopathy. Two of these patients presented with novel types of mitochondrial DNA depletion syndromes associated with increased serum creatine kinase (CK) and multiorgan disease without mutations in any of the known mtDNA maintenance genes; one patient had pathologic endoplasmic reticulum (ER) membranes in muscle. The third patient with mtDNA depletion was diagnosed with merosine-deficient muscular dystrophy caused by a homozygous mutation in the LAMA2 gene. Two patients with an early-onset Kearns-Sayre/Pearson-like phenotype harboured a large-scale mtDNA deletion, minor multiple deletions and high mtDNA content. CONCLUSIONS: Novel encephalomyopathic mtDNA depletion syndrome with structural alterations in muscle ER was identified. mtDNA depletion may also refer to secondary mitochondrial changes related to muscular dystrophy. We suggest that a large-scale mtDNA deletion, minor multiple deletions and high mtDNA content associated with Kearns-Sayre/Pearson syndromes may be secondary changes caused by mutations in an unknown nuclear gene.

Permanent brachial plexus birth palsy does not impair the development and function of the spine and lower limbs.

Permanent brachial plexus birth palsy (BPBP) impairs the function of the affected upper limb. Avulsion type root injuries may damage the cervical spinal cord. Whether abnormal function of an upper limb affected by BPBP has any observable effects on the development of the locomotion system and overall motor function has not been clarified in depth. A total of 111 patients who had undergone brachial plexus surgery for BPBP in infancy were examined after a mean follow-up time of 13 (5-32) years. Patients' physical activities were recorded by a questionnaire. No significant inequalities in leg length were found and the incidence of structural scoliosis (1.7%) did not differ from that of the reference population. Nearly half of the patients (43%) had asynchronous motion of the upper limbs during gait, which was associated with impaired upper limb function. Data obtained from the completed questionnaires indicated that only few patients were unable to participate in normal activities such as: bicycling, cross-country skiing or swimming. Not surprisingly, 71% of the patients reported problems related to the affected upper limb, such as muscle weakness and/or joint stiffness during the aforementioned activities.