Muscle fibrillin deficiency in Marfan's syndrome myopathy.

OBJECTIVE: To report a family with Marfan's syndrome in whom a myopathy was associated with respiratory failure; muscle biopsies from affected individuals were examined to determine whether there were abnormalities in fibrillin. METHODS: 21 family members underwent detailed clinical examination, including neurological and pulmonary assessment. Muscle biopsies in the most severely affected cases were immunostained using monoclonal antibodies to specific fibrillin components. Genomic DNA from all 21 members was analysed for mutations in the fibrillin gene, FBN1, on 15q21. RESULTS: 13 individuals had a C4621T base change in exon 37 of the FBN1 gene, which in four cases segregated with muscle weakness or evidence of respiratory muscle dysfunction or both. Their muscle biopsies revealed an abnormality in fibrillin immunoreactivity. CONCLUSIONS: Abnormalities in fibrillin can be detected in muscle biopsies from patients with Marfan's syndrome who have myopathy. This pedigree, with a point mutation in FBN1, also draws attention to the potential for respiratory failure associated with myopathy.

The histochemistry of reactive masticatory muscle hypertrophy.

There are two types of hypertrophy of the muscles of mastication in man: reactive hypertrophy, the more common form; and nonreactive enlargements-myositic, genetic, myopathic, and idiopathic. Reactive hypertrophy develops when the masticatory muscle workload is increased by local bone and dental disorders; such triggers are not powerful but act over long periods, thus demanding increased endurance. Exercise for endurance has a greater effect on the muscles of mastication than it has on the large muscles of the limbs; these react solely by stimulating the oxidative metabolism of type 1 fibers, whereas masticatory muscle reacts structurally by hypertrophy and progressive type 1 fiber predominance. Eventually enzyme instability of type 1 fibers and end stage atrophy of type 2 fibers may appear. Unexpectedly, lesions have also been found in control masticatory muscle, in particular type 2 fiber specific atrophy like that seen in long-standing acquired autoimmune myasthenia gravis. It is suggested that the adverse lesions in hypertrophied and control masticatory muscle are the consequence of post-activation fatigue.

Malignant hyperpyrexia and sudden infant death syndrome.

This paper reports three investigations of the suggested relationship between sudden infant death syndrome (SIDS) and malignant hyperpyrexia (MH). In the first study 151 MH-susceptible families completed a questionnaire designed to identify the incidence of SIDS within their own pedigree. In the second study 106 SIDS families completed a questionnaire designed to identify the incidence of anaesthetic related problems. In the third study, 14 SIDS parents were subjected to muscle biopsy and in vitro halothane contracture and caffeine contracture screening for susceptibility to MH. From the results of the three studies it can be concluded that there is no association between SIDS and MH.

The work of the Leeds Malignant Hyperpyrexia Unit, 1971-84.

A detailed account of the procedure of muscle biopsy for screening patients suspected of being susceptible to malignant hyperpyrexia is given, together with a review of the results obtained from 1127 patients screened over the last 14 years. The information should help anaesthetists to discuss the investigation fully with probands and other members of their families before referral for further specific investigation.

Cerebral embolism due to non-bacterial thrombotic endocarditis following pregnancy.

A case is reported of cerebral embolism with two very unusual features. Two bilaterally symmetrical haemorrhagic infarcts occurred, due to non-bacterial thrombotic cardiac valvular vegetations precipitated by the puerperium in a previously healthy young woman.

A case of sarcoma of the central nervous system presenting as a Guillain-Barré syndrome.

A case of widespread spinal sarcoma is described with meningeal infiltration, involvement of the anterior cranial fossa complicated by aplastic anaemia and visceral metastases.

Respiratory arrest in familial hemiplegic migraine: a clinical and neuropathological study.

We describe a fatal case of familial hemiplegic migraine. A transient respiratory arrest in this patient led to a persistent "vegetative state," culminating in death four months later. Neuropathological findings included deep microinfarcts in the basal ganglia and a remarkable sparing of brain-stem nuclei associated with the function of respiration.

Ischaemia of peripheral nerve and muscle.

Although skeletal muscle and peripheral nerves are both resistant to ischaemia there are nevertheless many syndromes in which they are affected, either separately or together. It is frequently difficult to distinguish the effects of arterial ischaemia from those of compression, which may operate through vascular occlusion, or, in the case of peripheral nerve, by mechanical deformation of nerve fibres. A great deal has been learned from experimental models, but not all of it is applicable to the complexity of human neuromuscular ischaemia which requires further study.

A comparison of the fine structure of motor end-plates in Duchenne dystrophy and in human neurogenic diseases.

With the aim of investigating the pathogenesis of Duchenne dystrophy, and in particular the role of denervation, the fine structural features of motor end-plates in the limb muscles of 13 patients with Duchenne dystrophy were compared with those in 26 controls and 50 patients suffering from known neurogenic diseases. The wide variation in control end-plates es emphasised. The sole plates in Duchenne dystrophy tended to retract from the end-plate, and shared only sprout formation, enclodure of terminals in Schwann cell cytoplasm and (in one instance) close packing of neurofilaments in the terminal with the changes in denervating end-plates. In these latter, withdrawal of terminals from the sole and various degenerative figures were the rule. It was concluded that there is no adequate morphological evidence in motor end-plates to support the concept of Duchenne dystrophy as a neurogenic disease.

Evaluation of creatinine phosphokinase in screening patients for malignant hyperpyrexia.

Evidence is presented that serum creatinine phosphokinase (CPK) activity is of no direct value in screening patients for susceptibility to malignant hyperpyrexia and does not correlate with halothane-induced muscle contracture or the presence of myopathy. Widely differing CPK values were found at different times in the same people. In most "malignant hyperpyrexia" families the susceptible patients had either normal or inconsistently raised CPK values.