Recent advances in the diagnosis of malignant hyperthermia susceptibility: how confident can we be of genetic testing?

Malignant hyperthermia (MH) is a condition that manifests in susceptible individuals only on exposure to certain anaesthetic agents. Although genetically heterogeneous, mutations in the RYR1 gene (19q13.1) are associated with the majority of reported MH cases. Guidelines for the genetic diagnosis for MH susceptibility have recently been introduced by the European MH Group (EMHG). These are designed to supplement the muscle biopsy testing procedure, the in vitro contracture test (IVCT), which has been the only means of patient screening for the last 30 years and which remains the method for definitive diagnosis in suspected probands. Discordance observed in some families between IVCT phenotype and susceptibility locus genotype could limit the confidence in genetic diagnosis. We have therefore assessed the prevalence of 15 RYR1 mutations currently used in the genetic diagnosis of MH in a sample of over 500 unrelated European MH susceptible individuals and have recorded the frequency of RYR1 genotype/IVCT phenotype discordance. RYR1 mutations were detected in up to approximately 30% of families investigated. Phenotype/genotype discordance in a single individual was observed in 10 out of 196 mutation-positive families. In five families a mutation-positive/IVCT-negative individual was observed, and in the other five families a mutation-negative/IVCT-positive individual was observed. These data represent the most comprehensive assessment of RYR1 mutation prevalence and genotype/phenotype correlation analysis and highlight the possible limitations of MH screening methods. The implications for genetic diagnosis are discussed.

[Cerebral angiography: a study of complications in 450 consecutive procedures]. / Angiographie cérébrale: étude des complications sur 450 examens consécutifs.

PURPOSE: To evaluate all types of complications, both minor and major, associated with modern cerebral angiography. MATERIALS AND METHODS: A prospective study of 450 consecutive cerebral angiographic procedures is reported. RESULTS: One patient (0.2%) died from a cholesterol embolus. In seven patients (1.6%), thromboembolic events occurred within 24 hours after the procedure, leading to transient ischemic symptoms in six and permanent hemiplegia in one. Two patients suffered from acute renal failure (0.4%). Transient cardiac arrhythmias were observed in three patients without consequence on the clinical outcome. Most complications of angiography occurred in patients referred from the neurology department for work-up of stroke syndrome. CONCLUSION: Our results show that morbidity and mortality rates related to the angiographic procedure did not decrease in spite of major improvement of angiographic materiel. Atherosclerosis is the main risk factor for complication. Most of the complications could be avoided by appropriate selection of indications and by using non-invasive techniques such as magnetic resonance angiography or helical CT angiography.

Early onset pneumonia in neurosurgical intensive care unit patients.

To investigate early onset pneumonia in a neurosurgical intensive care unit, we studied a cohort of patients over a 13-month period and compared neurotrauma (T) with non-neurotrauma (NT) patients. Data were abstracted from the infection surveillance database. Five hundred and sixty-five adults were hospitalized in the neurosurgical intensive care unit. 57.9% had trauma and 129 patients developed 152 episodes of pneumonia. Incidence rates, restricted to the 129 first episodes of pneumonia, were 20.1 versus 15.7/1000 patient days and 34.2 versus 27.9/1000 ventilation days, in the T and NT groups respectively. In both groups, the distribution of risk stratified by hospital days was bimodal, being highest during the first three days. However, the risk was higher for T patients (at day 3, 20/1000 ventilation days versus 10.2/1000 ventilation days). The daily risk peaked again at days 5 and 6, and thereafter remained low. Pneumonia occurring within the first three days, or early onset pneumonia (EOP), was associated with trauma (P = 0.036) and, in the NT group only, with a Glasgow coma scale score lower than 9 (P = 0.062). EOP was caused by Staphylococcus aureus (33%), Haemophilus spp. (23%), other Gram-positive cocci (22%), and other Gram-negative bacilli (GNB) (19%); whereas after the third day GNB other than Haemophilus spp. accounted for 45.4% of isolates (P = 0.11). This large series confirms the high incidence of EOP in neurosurgical intensive care units, particularly among trauma patients, in relation to risk factors different from those seen in other intensive care patients. Further studies are needed to elaborate specific preventive measures during early care.

Compatibility of enflurane and adrenaline--experiments in the dog.

Anaesthetised, intubated dogs were ventilated with 1, 2, 3, 4 and 5% enflurane and received adrenaline, 1.4 microgram/kg/min, by intravenous infusion for 5 min. No further adrenaline was given if cardiac arrhythmias occurred. Depth of anaesthesia was controlled by measurement of enflurane levels in arterial blood by an original method. No relationship was observed between the inspired enflurane concentrations and the onset of cardiac arrhythmias.