Human Hendra virus infection causes acute and relapsing encephalitis.

AIM: To study the pathology of two cases of human Hendra virus infection, one with no clinical encephalitis and one with relapsing encephalitis. METHODS: Autopsy tissues were investigated by light microscopy, immunohistochemistry and in situ hybridization. RESULTS: In the patient with acute pulmonary syndrome but not clinical acute encephalitis, vasculitis was found in the brain, lung, heart and kidney. Occasionally, viral antigens were demonstrated in vascular walls but multinucleated endothelial syncytia were absent. In the lung, there was severe inflammation, necrosis and viral antigens in type II pneumocytes and macrophages. The rare kidney glomerulus showed inflammation and viral antigens in capillary walls and podocytes. Discrete necrotic/vacuolar plaques in the brain parenchyma were associated with antigens and viral RNA. Brain inflammation was mild although CD68(+) microglia/macrophages were significantly increased. Cytoplasmic viral inclusions and antigens and viral RNA in neurones and ependyma suggested viral replication. In the case of relapsing encephalitis, there was severe widespread meningoencephalitis characterized by neuronal loss, macrophages and other inflammatory cells, reactive blood vessels and perivascular cuffing. Antigens and viral RNA were mainly found in neurones. Vasculitis was absent in all the tissues examined. CONCLUSIONS: The case of acute Hendra virus infection demonstrated evidence of systemic infection and acute encephalitis. The case of relapsing Hendra virus encephalitis showed no signs of extraneural infection but in the brain, extensive inflammation and infected neurones were observed. Hendra virus can cause acute and relapsing encephalitis and the findings suggest that the pathology and pathogenesis are similar to Nipah virus infection.

Intrapartum stillbirths in hospital unrelated to uteroplacental vascular insufficiency.

The aim of this study was to investigate the causes of intrapartum asphyxia and its relationship to placental abnormalities. Twenty intrapartum fetal death autopsies carried out over a 10-year period in one hospital pathology department associated with a large obstetric unit were reviewed. All the intrapartum fetal deaths occurred in the hospital, while the mothers were being monitored during and after labor. On morphologic grounds, all the fetal deaths were thought to be caused by intrapartum asphyxia. Seven of the intrapartum fetal deaths were associated with intrauterine infection causing funisitis, and in 6 of these cases, chorioamnionitis was present as well. Two cases were caused by placental abruption, and 1 case was caused by cord compression. In 8 of the 10 remaining cases in which the placenta was examined, a minor placental abnormality was detected in only 1 case. Five of the 10 cases had a mild astrocytosis in the intracerebral periventricular white matter, suggestive of intrauterine ischemia at least 12 hours before death. Five of the 10 cases were thought by the delivering obstetrician to have umbilical cord abnormalities. The main conclusions from this study are that, except in cases of intrauterine infection, placental vascular abnormalities are unlikely to be associated with intrapartum asphyxia leading to fetal death during labor. The number of cases with umbilical cord abnormalities raises the possibility that cord accidents may be a significant cause of intrapartum stillbirth.

Association studies of neurotransmitter gene polymorphisms in alcoholic Caucasians.

Ethanol enhances mesolimbic/cortical dopamine activity in reward and reinforcement circuits. We investigated the hypothesis that risk for alcoholism may be mediated by genes for neurotransmitters associated with the dopamine reward system as well as genes for enzymes involved in ethanol metabolism. DNA was extracted from brain tissue collected at autopsy from pathologically characterized alcoholics and controls. PCR-based assays showed that alcoholism was associated with polymorphisms of the dopamine D2 receptor (DRD2) TaqI B (P = .029) and the GABAA-beta2 subunit C1412T (P = .012) genes, but not with the glutamate receptor subunit gene NMDAR2B (366C/G), the serotonin transporter gene (5HTTL-PR), the dopamine transporter gene DAT1(SLC6A3), the dopamine D2 receptor gene DRD2 TaqI A, or the GABAA alpha1(A15G), alpha6(T1519C), and gamma2(G3145A) subunit genes. The glial glutamate transporter gene EAAT2 polymorphism G603A was associated with alcoholic cirrhosis (P = .048). The genotype for the most active alcohol dehydrogenase enzyme ADH1C was associated with a lower risk of alcoholism (P = .026) and was less prevalent in alcoholics with DRD2TaqIA2/A2 (P = .047), GABAA-beta2 1412C/C (P = .01), or EAAT2 603G/A (P = .022) genotypes. Combined DRD2TaqI A or B with GABAA-beta2 or EAAT2 G603A genotypes may have a concerted influence in the predisposition to alcoholism.

Consensus neuropathological diagnosis of common dementia syndromes: testing and standardising the use of multiple diagnostic criteria.

The aim of this study was to assess the variation between neuropathologists in the diagnosis of common dementia syndromes when multiple published protocols are applied. Fourteen out of 18 Australian neuropathologists participated in diagnosing 20 cases (16 cases of dementia, 4 age-matched controls) using consensus diagnostic methods. Diagnostic criteria, clinical synopses and slides from multiple brain regions were sent to participants who were asked for case diagnoses. Diagnostic sensitivity, specificity, predictive value, accuracy and variability were determined using percentage agreement and kappa statistics. Using CERAD criteria, there was a high inter-rater agreement for cases with probable and definite Alzheimer's disease but low agreement for cases with possible Alzheimer's disease. Braak staging and the application of criteria for dementia with Lewy bodies also resulted in high inter-rater agreement. There was poor agreement for the diagnosis of frontotemporal dementia and for identifying small vessel disease. Participants rarely diagnosed more than one disease in any case. To improve efficiency when applying multiple diagnostic criteria, several simplifications were proposed and tested on 5 of the original 20 cases. Inter-rater reliability for the diagnosis of Alzheimer's disease and dementia with Lewy bodies significantly improved. Further development of simple and accurate methods to identify small vessel lesions and diagnose frontotemporal dementia is warranted.

A case of myoepithelial carcinoma displaying biallelic inactivation of the tumour suppressor gene APC in a patient with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by mutation of the APC gene. It is characterised by the appearance of hundreds to thousands of colorectal adenomas in adolescence and the subsequent development of colorectal cancer. Various extracolonic malignancies are associated with FAP, including desmoids and neoplasms of the stomach, duodenum, pancreas, liver, and brain. We present a family affected by FAP with an exon 14 APC mutation displaying two rare extracolonic lesions, a hepatoblastoma and a myoepithelial carcinoma. The hepatoblastoma was found in a male patient aged 2 years. The second lesion, a myoepithelial carcinoma of the right cheek, was found in a female patient aged 14 years. Inactivation of the normal APC allele was demonstrated in this lesion by loss of heterozygosity analysis, thus implicating APC in the initiation or progression of this neoplasm. This is the first reported case of this lesion in a family affected by FAP.

Transoral resection of retro-odontoid disc sequestration: case report and review of the literature.

A rare case of retro-odontoid disc sequestration causing significant cord compression and progressive neurological deterioration is presented. The clinical history, radiology, treatment and pathogenesis of the case are described, along with a review of the relevant literature.

Australian bat lyssavirus infection: a second human case, with a long incubation period.

In December 1998, a 37-year-old Queensland woman died from a rabies-like illness, 27 months after being bitten by a flying fox (fruit bat). Molecular techniques enabled diagnosis of infection with Australian bat lyssavirus (ABL), the second human case to be recognised and the first to be acquired from a flying fox. It must be assumed that any bat in Australia could transmit ABL; anyone bitten or scratched by a bat should immediately wash the wounds thoroughly with soap and water and promptly seek medical advice.

Rasmussen's syndrome in a 54 year old female: more support for an adult variant.

Rasmussen's syndrome, a syndrome of chronic focal encephalitis, is usually considered to be a disease of childhood. Typical features include intractable focal seizures and progressive unilateral neurological deficits with radiological evidence of focal cortical atrophy. This report documents the case of the oldest patient yet described in the literature with Rasmussen's syndrome. Magnetic resonance imaging revealed gadolinium enhancing tissue, not previously described in this condition.

Considerations in the treatment of patients with renal disease.

Renal function includes maintenance of fluid pH, electrolyte and fluid balance, influence on blood pressure, excretion of fluid and metabolic soluble wastes after filtration or reabsorption, and production of erythrocyte stimulating factor and the active form of vitamin D. These processes involve sensory mechanisms in the kidney, as well as the ability to respond to sensed changes, to maintain body homeostasis. Decrease in or failure of renal function induces abnormalities in many other systems, requiring a modified approach that is individual to each patient, and includes alteration of medications used and a re-evaluation of their doses. Some patients may require a regimen of dialysis or eventual renal transplantation, each with attendant advantages and risks. Careful evaluation and consultation with a nephrologist is required when local or systemic treatment is contemplated.

Regional development of glutamate-N-methyl-D-aspartate receptor sites in asphyxiated newborn infants.

The N-methyl-D-aspartate (NMDA) subclass of glutamate receptors was examined in newborn infants dying between 25 weeks' gestation and term, either from acute cerebral hypoxia, or from other noncerebral conditions incompatible with life. Frontal, occipital, temporal, and motor cortex tissue samples were obtained at autopsy (post mortem delay: median, 45.9 hr; range, 24-96 hr) and frozen for subsequent [3H]MK801 homogenate binding assays. Whereas no significant variation was observed in ligand affinity (KD), in all cases receptor density (BMAX) increased with gestational age, in occipital cortex (27 weeks, BMAX = 222 +/- 44 fmol x mg protein(-1); 39 weeks, 439 +/- 42 fmol x mg protein[-1]), but not in motor or temporal cortex. The gestational-age increase also occurred in control frontal cortex (27 weeks, 284 +/- 80; 39 weeks, 567 +/- 40 fmol x mg protein[-1]), but was significantly less marked in frontal cortex in hypoxia cases (27 weeks, 226 +/- 90; 39 weeks, 326 +/- 47 fmol x mg protein[-1]). In all cortical areas except temporal, the maximal response to glutamate did not vary across case groups. Hypoxia cases showed an increased response to glutamate enhancement selectively in temporal cortex. Binding site density did not correlate with degree of hypoxia as assessed pathologically, suggesting that receptor differences preceded the hypoxic episode. Regional differences in glutamate-NMDA receptor sites may underlie increased vulnerability to hypoxia at birth.

Ischaemic cerebral injury, intrauterine growth retardation, and placental infarction.

Two hundred and twenty-five consecutive autopsies performed on fetuses >20 weeks' gestation were reviewed, and 37 growth-retarded stillborn fetuses without multiple congenital abnormalities or evidence of intrauterine infection were identified. Histological evidence of ischaemic cerebral injury was found in 31 of the 37 cases and placental infarction was seen in 26 of 36 placentas. Of the 31 cases with cerebral ischaemia, 24 had placental infarcts. Twenty-six of 27 stillborn fetuses >26 weeks' gestation showed histological evidence of cerebral ischaemia. It was concluded that in the group of growth-retarded fetuses studied, there was a high incidence of both cerebral and placental ischaemic abnormality.

The D178N (cis-129M) "fatal familial insomnia" mutation associated with diverse clinicopathologic phenotypes in an Australian kindred.

Fatal familial insomnia (FFI) is an inherited prion disease characterized by progressive insomnia and dysautonomia with only modest cognitive impairment early in the disease, associated with atrophy and gliosis in the medial thalamus, but without spongiform change. FFI is associated with an aspartic acid to asparagine mutation at codon 178 of the PrP gene (D178N) in conjunction with methionine at the codon 129 polymorphic site on the mutant allele (cis-129M). We report a pedigree with this genotype in which marked clinicopathologic phenotypic heterogeneity occurred including typical Creutzfeldt-Jakob disease, FFI, and what was thought to be an autosomal dominant cerebellar ataxia (ADCA)-like-illness, suggesting that the genotype-phenotype correlation is not as tight for this mutation as is frequently supposed.

Unusual presentation of colloid cyst of the third ventricle.

This case report describes death in a young male, six months after an assault. The death was caused by a colloid cyst, a rare but important malformation in the brain. The possible relationship between the assault and the cyst is discussed.

Fatal familial insomnia: a seventh family.

A 60-year-old woman with a typical history of fatal familial insomnia (FFI) had FFI proven by histologic examination and molecular testing. Her son, who died at the age of 20 in 1978, had a rapidly progressive dementing illness without reported insomnia. He carried the characteristic mutation for FFI and is the youngest patient reported with this condition.

Two cases of maternal antenatal splenic rupture and hypotension associated with Moebius syndrome and cerebral palsy in offspring. Further evidence for a utero placental vascular aetiology for the Moebius syndrome and some cases of cerebral palsy.

UNLABELLED: We wish to report two cases of congenital abnormality after antenatal car accidents resulting in ruptured spleen and severe hypotension in the mothers at 8 and 14 weeks gestation. The first case had the classical Moebius syndrome with 6th and 7th cranial nerve palsy with abnormal brain stem evoked responses, presumably due to hypoxic/ischaemic brain stem damage and the second case had severe retardation and hypertonic cerebral palsy which at post mortem was found to be due to old hypoxic/ischaemic lesions to the caudate nucleus putamen and striatum. CONCLUSION: The cases described provide evidence that severe maternal hypotension during pregnancy can be associated with lesions to the midbrain and brain stem of offspring. The mechanism is probably utero-placental insufficiency, and extrapolation from these two unusual cases would support utero-placental insufficiency as a cause of Moebius syndrome and limb deficiency after chorionic villus sampling.

Iatrogenic Creutzfeldt-Jakob disease and its neurosurgical implications.

Creutzfeldt-Jakob (CJD) disease has been reported after the insertion of dural homografts. Two Australian cases of CJD, both following posterior fossa craniotomies done in 1982, are reported; the incubation periods were 5 and 12 years. It seems highly probable that the association is causal. CJD infective agents (prions) are resistant to many previously accepted means of sterilisation and it is postulated that cadaver dural material was either derived from subjects with CID, or was contaminated during preparation. In Australia the use of dural homografts in neurosurgery was abandoned in 1987; as the mean incubation period (determined from a world-wide review) has been about 65 months, it is now hoped that this cause of CJD will not recur in the Australian population, although it is premature to state this with confidence. However, precautions against case-to-case transmission remain necessary, and guidelines for this purpose should be enforced in theatre practice and in organ donations.

Dementia pugilistica in an alcoholic achondroplastic dwarf.

Dementia pugilistica is classically seen in boxers. We describe the case of a 33-yr-old achondroplastic dwarf who developed the pathological hallmarks of the condition, probably as a result of chronic occupational trauma. Dementia pugilistica has not been previously described in achondroplasia.