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Biomedical subjects

D Gardner-Medwin

Publications and source records attributed to D Gardner-Medwin.

At least 19 recordsLinked to original sources
PubMed2006

Pre- and post-synaptic abnormalities associated with impaired neuromuscular transmission in a group of patients with 'limb-girdle myasthenia'.

The properties of neuromuscular junctions (NMJs) were studied in motor-point biopsy samples from eight patients with congenital myasthenic syndromes affecting primarily proximal limb muscles ['limb-girdle myasthenia' (LGM)]. All had moderate to severe weakness of the proximal muscles, without short-term clinical fatigability but with marked variation in strength over periods of weeks or months, with little or no facial weakness or ptosis and no ophthalmoplegia. Most had a characteristic gait and stance. All patients showed decrement of the compound muscle action potential (CMAP) on repetitive stimulation at 3 Hz, and increased jitter and blocking was detected by SFEMG, confirming the presence of impaired neuromuscular transmission. None of the patients had serum antibodies against acetylcholine receptors (AChRs). Two of the patients had similarly affected siblings. Intracellular recording from isolated nerve-muscle preparations revealed that the quantal content (the number of ACh quanta released per nerve impulse) was only approximately 50% of that in controls. However, the quantal size (amplitude of miniature end-plate currents) and the kinetic properties of synaptic potentials and currents were similar to control values. The area of synaptic contact and extent of post-synaptic folding were approximately 50% of control values. Thus, the quantal content per unit area of synaptic contact was normal. The number of AChRs per NMJ was also reduced to approximately 50% of normal, so the local AChR density was normal. Immunolabelling studies revealed qualitatively normal distributions and abundance of each of 14 proteins normally concentrated at the NMJ, including components of the basal lamina, post-synaptic membrane and post-synaptic cytoskeleton. DNA analysis failed to detect mutations in the genes encoding any of the following proteins: AChR subunits, rapsyn, ColQ, ChAT or muscle-specific kinase. Response of these patients to treatment was varied: few showed long-term improvement with pyridostigmine and some even deteriorated with treatments, while others had intolerable side-effects. Several patients showed improvement with 3,4-diaminopyridine, but this was generally only transient. Ephedrine was helpful in half of the patients. We conclude that impaired neuromuscular transmission in these LGM patients results from structural abnormalities of the NMJ, including reduced size and post-synaptic folding, rather from any abnormality in the immediate events of neuromuscular transmission.

Adolescent↗
PubMed2001

Tethering of the vertebral artery in the congenital arcuate foramen of the atlas vertebra: a possible cause of vertebral artery dissection in children.

Twelve children with vertebrobasilar artery stroke are reported (seven males, five females; aged 6 months to 15 years). Patient 1 showed an arcuate foramen in the posterior arch of the atlas, an anatomical variant occurring in 3 to 15% of the population. It was hypothesized that the presence of the arcuate foramen might cause tethering of the vertebral artery and lead to its dissection by repetitive trauma. Lateral plain films of the cervical spine in cases of posterior circulation stroke were taken. Eight of 11 patients showed aberrant arcuate foramina. Of the remaining three patients, one had normal cervical spine X-rays, one had an absent right posterior arch of the atlas following previous surgery for a cervical meningocele, and one patient had incomplete ossification of the vertebrae. Seven of the nine patients with arcuate foramina had vertebral angiograms. In all cases this showed the vertebral artery passing through the arcuate foramen before entering the brain and an appearance consistent with arterial dissection and occlusion at the same site below the foramen. Most documented cases of posterior circulation stroke in children follow trauma, which may be minimal or repetitive, with thrombotic occlusion of the artery at C1-C2 level. The association with an arcuate foramen and its possible causative role in the genesis of posterior circulation stroke in children has not been previously recognized. There may be a causal association between the presence of an arcuate foramen, tethering of the vertebral artery in the foramen, and dissection from repetitive trauma with movement of the neck.

Adolescent↗
PubMed1997

CSF antigliadin antibodies and the Ramsay Hunt syndrome.

Although the association between celiac disease and progressive myoclonic ataxia is well recognized, in each of the reported cases the neurologic features began in middle adult life and usually in patients who had clinical or laboratory evidence of malabsorption. We report a case of progressive myoclonic ataxia and epilepsy (Ramsay Hunt syndrome) that began in childhood. In this patient there were no features suggestive of gluten intolerance. The presence of antigliadin antibodies in the serum and CSF suggested celiac disease was the cause of the patient's neurologic syndrome. Duodenal morphologic abnormalities reversed with treatment but no major changes were noted in the patient. Celiac disease should be considered in the differential diagnosis of myoclonic ataxia at any age, even in the absence of clinical evidence of gluten-sensitive enteropathy.

Adult↗
PubMed1996

Arthrogryposis multiplex congenita and bilateral parietal polymicrogyria in association with the intrauterine death of a twin.

A case of neurogenic arthrogryposis multiplex congenita (AMC) with associated neuronal migration abnormalities is described. A child with neurogenic AMC and developmental delay presented with late onset of seizures. The first trimester of the mother's pregnancy was marked by an episode of gastro-enteritis and the intrauterine death of a twin fetus. Computer tomography (CT) and magnetic resonance (MR) imaging demonstrated abnormal neuronal migration consisting of bilateral parietal polymicrogyria, and an isolated grey matter heterotopia.

Age of Onset↗
PubMed1996

Co-dominant inheritance of hyperekplexia and spastic paraparesis.

In four generations of a family with autosomal dominant hyperekplexia (startle disease), untreated affected adult members had pes cavus and extensor plantar responses, as well as hyper-reflexia. Electroencephalography during a startle, electromyography, nerve conduction velocities and somatosensory evoked potentials were normal. Genetic studies showed linkage to the CSF1R locus on chromosome 5q33-q35, which includes the glycine receptor. This either represents a variant of hyperekplexia with spasticity or suggests that genes for hyperekplexia and a form of hereditary spastic paraparesis may be closely linked.

Adult↗
PubMed1996

Pyridoxine-dependent seizures: demographic, clinical, MRI and psychometric features, and effect of dose on intelligence quotient.

A regional population-based survey identified six patients with pyridoxine dependency. Four presented on the first day of life and the other two at 1 and 8 months of age. Apart from multiple seizure types, other presenting features included jitteriness; encephalopathy, at first thought to be hypoxic-ischaemic; hepatomegaly, and abdominal distension with bilious vomiting. Later problems included break-through fits with fever; transient visual agnosia; squint; severe articulatory apraxia; motor delay with later dyspraxia; macrocephaly, and post-haemorrhagic hydrocephalus. Magnetic resonance imaging showed variable structural abnormalities in all the early onset cases. Psychometric assessment revealed a stereotyped pattern of intelligence scale subtest scores, with a specific impairment of expressive verbal ability. In a prospective open study over one year, an increased dose of pyridoxine was associated with an improvement in IQ, particularly in performance subtests. Pyridoxine dependency is more common than has been thought. It has a wider range of clinical features than the classical neonatal seizures and causes specific impairments of higher function, some of which may be reversible. The dosage of pyridoxine should be optimal for IQ as well as seizure control.

Adolescent↗
PubMed1995

Vigabatrin monotherapy in resistant neonatal seizures.

Seizures in a term infant with Ohtahara syndrome, associated with polymicrogyria, and a pre-term neonate with similar clinical features, failed to respond to conventional anticonvulsants, but were controlled with vigabatrin monotherapy. Another infant with Aicardi syndrome improved with vigabatrin. Autopsy in the first infant showed no evidence of intramyelinic oedema. The developmental outcome in the two survivors was better than expected for their condition.

Agenesis of Corpus Callosum↗
PubMed1995

Deletion status and intellectual impairment in Duchenne muscular dystrophy.

The authors collected Verbal, Performance and Full-scale IQs for 74 patients in whom complete analysis of the dystrophin gene for deletions and duplications had been performed. There was a significant difference in the mean Full-scale IQ between patients with deletions at the 5' and 3' ends of the gene, with no patients with 5' deletions having mental retardation. No relationship was established between mental retardation and the presence or absence of deletions or length of deletions, and similar deletions were observed in the presence and absence of mental retardation. Although distal deletions were more commonly associated with mental retardation, there was no clear evidence for a particular region of the dystrophin gene being specifically responsible for IQ. The intellectual deficit seen in DMD may be a consequence of cerebral hypoxia, ue to malfunction of smooth muscle dystrophin.

Child↗
PubMed1995

Winging of the scapula: the underlying biomechanics and an orthotic solution.

Winging of the scapula occurring in muscular disorders (muscular dystrophy and spinal muscular atrophy) or nerve injury has been investigated, resulting in a thorough understanding and presentation of the underlying biomechanics causing this occurrence. This includes a biomechanical explanation of the characteristic prominence of the medial border of the scapula upon attempted elevation, together with the biomechanical reasons for the rotation of the scapula in a direction contrary to the normal scapulohumeral rhythm. Based on these findings, a non-invasive alternative to the surgical technique for scapular stabilization has been devised, using an inflatable orthosis, placed between the scapula and an external restraint (such as a spinal jacket). The device has been tested on one subject using a 3SPACE Isotrak electromagnetic source and sensor system, and gave encouraging results. Elevation increased by up to 35 degrees (37 per cent), and functional improvement in the use of the hand around the head and face has been achieved. The technique needs no aftercare or physiotherapy and is therefore both economical and functionally effective.

Biomechanical Phenomena↗
PubMed1994

The radiological features of hemimegalencephaly including three cases associated with proteus syndrome.

We report the radiological appearances of 5 children with hemimegalencephaly. There are few reports of this rare condition in the radiological literature. Two of the children have hemimegalencephaly as an isolated finding while the other three have Proteus syndrome. Four children have seizures which commenced within the first 6 months of life and two of these subsequently required hemispherectomy. In addition to the typical radiological features of hemimegalencephaly there was a high incidence of other brain anomalies. These include hypoplasia of the corpus callosum and crus cerebri, grey and white matter calcification and cortical migration/organisational disorders.

Brain↗
PubMed1994

Thalamic infarction in childhood due to extracranial vertebral artery abnormalities.

We report two children who developed thalamic infarctions which were demonstrated by CT. Both children had apparently normal angiograms although the extra cranial portions of the vertebral arteries were not demonstrated on the initial examination. Subsequent angiograms demonstrated abnormalities of the cervical portion of the vertebral arteries, dissection and pseudoaneurysm in one case and a large fusiform aneurysm in the other. Both children made full neurological recoveries. The thalamus is supplied by branches from the vertebro-basilar circulation and it is important to study the entire length of the extra cranial vertebral arteries as well as the intracranial vasculature.

Adolescent↗