Urban M. Fietzek

Clinical impact of antibody formation to botulinum toxin A in children

We studied the clinical impact of neutralizing antibodies to botulinum toxin A that occurred during long‐term treatment of children between 1993 and 2001. Antibodies were found in high titers in 35 of 110 (31.8%) samples from individual patients. Antibody formation correlated with secondary nonresponse (p < 0.001). The most significant risk factors for antibody formation were the frequency of treatments (p = 0.0001) and the injection of a higher weight‐adapted maximum dose per treatment (p = 0.001).

Sonography-guided injection of botulinum toxin in children with cerebral palsy

Visual identification of muscles and depth control of needle placement are the key features of sonography-guided injection that lead to improved targeting and safety of BoNT/A injections. This method may be especially helpful to validate already established injection techniques or when learning the correct injection technique. We recommend sonography-guided injection as a simple and painless add-on to the currently used standard procedure of palpation. The additional expenditure for sonography-guided injection is more than offset by the improved reliability in correct needle placement.

When it comes to botulinum toxin, children and adults are not the same: Multimuscle option for children with cerebral palsy

to be palatopharyngeal myoclonus/tremor and posited a direct relationship to metoclopramide. The drug was stopped and her symptoms subsided over approximately 8 hours. Palatopharyngeal myoclonus is typically a slow form of tremor at 1 to 4 Hz. It can involve the pharynx, larynx, diaphragm, and extend to involve even eye muscles. The rhythmic movement can occur both during phonation and at rest. Voice tremor and clicking or popping sounds can be associated with the movement. The disorder is usually secondary to an interruption in the central tegmental tract from brainstem infarct or from idiopathic degeneration. Treatment may include serotonin precursors, carbamazepine, and clonazepam, but in general the condition is resistant to treatment. Previously described adverse reactions to metoclopramide include several conditions associated with more typical neuroleptic agents: acute dystonias, parkinsonian symptoms, including perioral, jaw, and extremity rest tremors, akathisia, tardive dyskinesia in several clinical forms, and neuroleptic malignant syndrome.1,2 The risk of developing metoclopramide-induced movement disorders has been found to increase with age, female sex, and some coexistent illnesses.1,3 Diabetes mellitus appears to confer additional risk for extrapyramidal symptoms.4 There is a 2:1 risk ratio for tardive dyskinesia in diabetics compared to nondiabetics.5 Diabetics who have been treated with metoclopramide also have a significantly greater severity of tardive dyskinesia than nondiabetics who have been treated with metoclopramide.5 We alert colleagues to our observation because we have not found other reports of metoclopramide-induced palatopharyngeal myoclonus/tremor, and because the patient responded fully and promptly to metoclopramide cessation.

Maturation of inhibitory and excitatory motor cortex pathways in children

OBJECTIVEnTo study intracortical inhibition and facilitation with paired-pulse transcranial magnetic stimulation in children, adolescents and adults.nnnMETHODSnPaired-pulse transcranial magnetic stimulation (interstimulus intervals (ISI): 1, 3, 5, 10 and 20 ms) was applied over the primary motor cortex (M1) in 30 healthy subjects (range 6-30 years, median age 15 years and 8 months, SD 7,9) divided in three groups: adults (>or=18 years), adolescents (> 10 and < 18 years) and children (<or=10 years).nnnRESULTSnWe observed significantly less intracortical inhibition (SICI) in childrens M1 compared to that of adults. Adolescents showed significantly less SICI at the 5 ms interval than did adults. No significant differences were apparent in intracortical facilitation (ICF).nnnCONCLUSIONnWe postulate that, as in adults, the maturing M1 possesses horizontal glutamatergic cross-links that represent the neuronal substrate of excitatory intracortical pathways. GABAergic interneurons, the neuronal substrate of inhibitory intracortical pathways, mature between childhood and adulthood. Reduced GABAergic inhibition may facilitate neuronal plasticity and motor learning in children.

Grafikgestützter Konsensus für die Behandlung von Bewegungsstörungen bei Kindern mit bilateralen spastischen Zerebralparesen (BS-CP)

ZusammenfassungUnter der Federführung der Gesellschaft für Neuropädiatrie erarbeiteten die Fachgesellschaften für Neuropädiatrie, Sozialpädiatrie und Kinderorthopädie eine grafikgestützte Empfehlung für die Behandlung von Bewegungsstörungen bei Kindern mit bilateralen spastischen Zerebralparesen (BS-CP). Der vorliegende Konsensus wurde unter Einbindung der Neurowissenschaften und Rehabilitationsmedizin fertiggestellt. Der Konsensus „Therapiekurven-CP-Motorik“ hat das Ziel, alters- und schweregradbezogen Therapieoptionen zur Behandlung motorischer Störungen für Kinder mit BS-CP darzustellen. Als Grundlage dienen die GMFCS-Entwicklungskurven der Gruppe um Peter Rosenbaum, Kanada (www.canchild.ca). Die Therapie bedarf eines interdisziplinären, multimodalen Teams, das die individualisierten Therapiewege formuliert und umsetzt. Die Therapiekurven-CP-Motorik sollen den Ärzten, Therapeuten und Eltern helfen, die adäquaten Therapieoptionen auszuwählen und die Frage zu beantworten, welche Therapieoptionen wann, wie lange und in welchem Umfang begründet sind.AbstractAn interdisciplinary group of German experts in the field of movement disorders was assembled under the auspices of the Society for Neuropediatrics to develop a graphically based guideline for a multidisciplinary treatment regime in the management of motor dysfunction in children with bilateral spastic cerebral palsy (BS-CP). The present consensus was accomplished by a cooperation including neuroscience and rehabilitation medicine. The aim of the “motor treatment curves in CP” is to present age- and severity-specific therapy options for the treatment of motor dysfunction in children with BS-CP on the basis of the GMFCS development curves from Peter Rosenbaum’s group in Canada (www.canchild.ca). An interdisciplinary team is required to set up and implement an optimal treatment plan for each individual patient. The motor treatment curves in CP are designed to help physicians, therapists and parents to choose the best therapy options and to decide when, for how long and to what extent therapy should be administered.

Muscle Atrophy Beyond the Clinical Effect After a Single Dose of OnabotulinumtoxinA Injected in the Procerus Muscle: A Study with Magnetic Resonance Imaging

Background Botulinum toxin is a powerful and often used agent to treat dynamic rhytides. Focal and reversible neurogenic atrophy is considered to be the relevant mechanism of action. Objective To investigate the loss and regain of muscular volume in relation to clinical wrinkle severity as assessed using standardized scales. Methods The facial procerus and corrugator supercilii muscles were injected in two drug‐naïve men with 20 U of onabotulinumtoxinA at five injection points (onA). Two men served as controls (one with the same volume of placebo injection using saline solution, one without any intervention). All subjects underwent 3 Tesla magnetic resonance imaging before and after the injection and 1, 4, 6, 10, and 12 months after the injection. Standardized photographs were taken at each test point. Results Volumetric muscle analysis revealed a 46% to 48% reduction in procerus muscle volume lasting for 12 months after a single dose of onA; glabellar line severity returned to the drug‐naïve status after 6 to 10 months. Conclusion The gap between long‐term focal muscular atrophy and regained function remains to be elucidated. Future studies will be needed to investigate the complex interaction between focal neurogenic atrophy and potential compensatory functional muscle changes.

Canalicular magnetic stimulation lacks specificity to differentiate idiopathic facial palsy from borreliosis in children.

OBJECTIVEnTo investigate the role of transcranial magnetic stimulation (TMS) to differentiate between idiopathic facial nerve palsy (iFNP) and facial nerve palsy due to borreliosis (bFNP).nnnPATIENTS AND METHODSnTranscranial and intracanalicular magnetic and peripheral electrical stimulation of the facial nerve together with clinical grading according to the House and Brackmann scale were performed in 14 children and adolescents with facial palsy (median age 11.5 yr, range 4.6-16.5 yr). Serum and cerebrospinal fluid (CSF) were evaluated for antibodies against Borrelia burgdorferi and CSF cell count, glucose and protein content were screened with methods of routine laboratory testing. Data of patients were compared with normal values established in 10 healthy subjects (median age 10.2 yr, range 5.1-15.3 yr).nnnRESULTSnPatients with iFNP showed a significant decrease in MEP amplitude to canalicular magnetic stimulation compared with healthy controls (p=0.03). However, MEP amplitude did not discriminate sufficiently between the two groups, because the ranges of dispersion of MEP amplitudes overlapped. Patients with bFNP had normal MEP amplitudes to canalicular magnetic stimulation compared with normal subjects.nnnCONCLUSIONnDiagnostic assessment by TMS failed to provide a reliable diagnostic criterion for distinguishing between iFNP and bFNP in children and adolescents.

Zerebralparese - Klassifikation und Therapie

Cerebral palsy is the most common etiology of a spastic movement disorder in childhood. The present paper gives an introduction to the classification, the phenomenology, the diagnosis and current pathophysiological concepts of the cerebral palsies. It focusses on the interdisciplinary therapy approach of the motor disorder, especially on the functional therapies and the treatment with botulinum toxin.