Sudden adult death syndrome in m.3243A>G-related mitochondrial disease: an unrecognized clinical entity in young, asymptomatic adults.

AIMS: To provide insight into the mechanism of sudden adult death syndrome (SADS) and to give new clinical guidelines for the cardiac management of patients with the most common mitochondrial DNA mutation, m.3243A>G. These studies were initiated after two young, asymptomatic adults harbouring the m.3243A>G mutation died suddenly and unexpectedly. The m.3243A>G mutation is present in ∼1 in 400 of the population, although the recognized incidence of mitochondrial DNA (mtDNA) disease is ∼1 in 5000. METHODS AND RESULTS: Pathological studies including histochemistry and molecular genetic analyses performed on various post-mortem samples including cardiac tissues (atrium and ventricles) showed marked respiratory chain deficiency and high levels of the m.3243A>G mutation. Systematic review of cause of death in our m.3243A>G patient cohort showed the person-time incidence rate of sudden adult death is 2.4 per 1000 person-years. A further six cases of sudden death among extended family members have been identified from interrogation of family pedigrees. CONCLUSION: Our findings suggest that SADS is an important cause of death in patients with m.3243A>G and likely to be due to widespread respiratory chain deficiency in cardiac muscle. The involvement of asymptomatic relatives highlights the importance of family tracing in patients with m.3243A>G and the need for specific cardiac arrhythmia surveillance in the management of this common genetic disease. In addition, these findings have prompted the derivation of cardiac guidelines specific to patients with m.3243A>G-related mitochondrial disease. Finally, due to the prevalence of this mtDNA point mutation, we recommend inclusion of testing for m.3243A>G mutations in the genetic autopsy of all unexplained cases of SADS.

Cysticercosis of the fourth ventricle causing sudden death: a case report and review of the literature.

A 15 years old girl of African origin was admitted with a history of headaches and a generalised tonic seizure. Her clinical examination including fundoscopy was normal. She claimed she had been assaulted. Within a few hours of her admission she was found dead in her bed during the ward round. Cardiopulmonary resuscitation was unsuccessful. At post-mortem, the major organs showed no pathological changes and neck dissection showed no abnormality. Neuropathological examination after formalin fixation revealed a cystic lesion in the fourth ventricle, ependymitis and acute hydrocephalus. Histology showed parts of the parasite Taenia solium and the diagnosis was neurocysticercosis. This case highlights the need for forensic and general pathologists as well as forensic medical examiners and paediatricians to be aware of neurocysticercosis as a possible cause of sudden death in the presence of normal clinical findings and negative autopsy, especially in patients from Asian, African or South American countries. As cysticercosis is the commonest cause of seizures in the developing world, neurocysticercosis needs to be considered as a cause of sudden and unexpected death in any patient with a history of headaches and/or seizures.

"Pseudosarcoma" in a pregnant woman.

BACKGROUND: Intravascular fasciitis (IVF) is a rare benign condition characterised by reactive myofibroblastic proliferation arising from the superficial or deep fascia and involving arteries and/or veins. It is a distinct variant of the more common condition of nodular fasciitis, which possesses similar clinical and histological features to IVF, but lacks vascular invasion. A thorough review of the literature revealed 26 reported cases of IVF. CASE PRESENTATION: We report a case of IVF in a 16-week pregnant lady affecting the hypothenar eminence of the hand associated with the ulnar artery. CONCLUSION: The characteristic involvement of muscular arteries and veins by reactive myofibroblastic proliferation in IVF suggests a malignant component and often leads to an inappropriate diagnosis for this benign condition. We propose that hormone-related changes associated with pregnancy may play an important role in the aetiopathogenesis of this myofibroblastic lesion.