| The recognition of uncommon pediatric motor unit disorders or unusual clinical presentations of common illnesses, such as guillain-barre syndrome (GBS), have increased the need for electromyography (EMG) in childhood critical care units. There are two different clinical sets, one appropriate to newborns and infants and the other to older children. Some illnesses that present as an acute floppy infant are not found in the differential diagnosis of motor unit disorders in the older child or adult. These include spinal muscular atrophy, postvaccine poliomyelitis, intrauterine GBS, infantile botulism, and severe myopathies, such as myotonia dystrophy, and some glycogen storage diseases. An appreciation of the neurophysiological maturational norms is essential to an effective pediatric EMG consultation for children ages 0-3 years. Additionally, the neuromuscular complications of extended intubation and sepsis in children are gaining broader recognition. An increased dialogue between clinical neurophysiologists and pediatric neurologists and intensivists in both neonatal and pediatric intensive care units is essential. ( info) |
2/5. Loss-of-function EA2 mutations are associated with impaired neuromuscular transmission. OBJECTIVE: To examine the functional consequences of episodic ataxia type 2 (EA2)-causing nonsense and missense mutations in vitro and to characterize the basis of fluctuating weakness in patients with E2A. BACKGROUND: Mutations in CACNA1A encoding the Ca(v)2.1 calcium channel subunit cause EA2 through incompletely understood mechanisms. Although the Ca(v)2.1 subunit is important for neurotransmission at the neuromuscular junction, weakness has not been considered a feature of EA2. methods: The disease-causing mutations in three unrelated patients with EA2 and fluctuating weakness were identified by mutation screening and sequencing. Mutant constructs harboring mutations R1281X, F1406C, R1549X were transfected into COS7 cells and expressed for patch clamp studies. Single-fiber electromyography (SFEMG) was performed in patients to examine synaptic transmission at the neuromuscular junction. RESULTS: Functional studies in COS7 cells of nonsense and missense EA2 mutants demonstrated markedly decreased current densities compared with wild type. SFEMG demonstrated jitter and blocking in these patients with EA2, compared with normal subjects and three patients with SCA-6. CONCLUSION: EA2-causing missense and nonsense mutations in CACNA1A produced mutant channels with diminished whole cell calcium channel activity in vitro due to loss of function. Altered biophysical properties or reduced efficiency of plasma membrane targeting of mutant channels may contribute to abnormal neuromuscular transmission, manifesting as myasthenic syndrome. ( info) |
3/5. Fatigue and abnormal neuromuscular transmission in Kennedy's disease. We describe a patient with Kennedy's disease (X-linked bulbospinal neuronopathy) who experienced leg muscle fatigue with long-distance running. The patient also reported muscle twitching involving the face and extremities and long-standing muscle cramps. Aside from mild facial and tongue weakness (and fasciculations), his examination was normal, including completely preserved muscle strength in the extremities. Electrodiagnostic evaluation revealed evidence for a chronic motor axonopathy/neuronopathy and abnormal sensory nerve action potentials. In addition, repetitive nerve stimulation studies were normal, but neuromuscular jitter tested in the same muscle was markedly abnormal. The normal clinical strength and repetitive nerve stimulation studies in a muscle showing markedly increased neuromuscular jitter suggested a mechanism for this patient's symptoms of muscle fatigue, related to failure of neuromuscular transmission at a critical number of endplates during extremes of physical activity. ( info) |
4/5. acetazolamide acts on neuromuscular transmission abnormalities found in some migraineurs. Mild subclinical impairment of neuromuscular transmission can be detected with single-fibre electromyography (SFEMG) in subgroups of patients suffering from migraine and could be due to dysfunctioning Ca2 -channels on motor axons controlling stimulation-induced acetylcholine release. acetazolamide, which is thought to ameliorate ion channel function, was shown effective in familial hemiplegic migraine and episodic ataxia type 2, both of which are associated with mutations of the neuronal Ca2 -channel gene CACNA1A, as well as in aura status. We treated therefore in an open pilot study five non-hemiplegic migraineurs showing mild SFEMG abnormalities with acetazolamide for several weeks. This was followed by a normalization of SFEMG recordings in all patients and by clinical improvement in four. These results support the assumption that the subclinical impairment of neuromuscular transmission found in certain migraineurs might be due to dysfunctioning Ca2 -channels. ( info) |
5/5. Anesthesia for sickle cell disease and congenital myopathy in combination. We report on the perioperative management of anesthesia and analgesia in a child with sickle cell disease and a congenital myopathy, presenting for corrective orthopedic surgery. The case illustrates two valuable points of interest: the many benefits of regional anesthesia in complex medical cases and the successful use of tourniquets in children with sickle cell disease. ( info) |