Neonatal intracranial choriocarcinoma.

A 1-month-old infant died from extensive intracerebral hemorrhage due to a metastatic choriocarcinoma to the brain that presumably originated in the placenta. The clinical course was characterized by hyperbilirubinemia, repeated episodes of seizures, and intracranial hemorrhage. A computed tomographic scan revealed a large vascular mass in the left parieto-occipital region and a small lesion in the left frontal lobe. The placenta was expelled during the delivery and was not examined. In view of the high level of maternal human chorionic gonadotropic hormone and the autopsy finding of metastasis, we presumed that the mass was a metastatic choriocarcinoma that had originated in the maternal placenta. To our knowledge, only one previous instance of this phenomenon has been reported.

Abundant REM sleep in a patient with Alzheimer's disease.

In patients with Alzheimer's disease (AD), greatly diminished REM sleep might be expected because of the cholinergic deficit in this disease and because cholinergic agonists stimulate REM sleep in humans and animals. We present here an unusual case of neuropathologically verified AD with abundant REM sleep. We suggest 4 possible explanations for this phenomenon: (1) selective cell loss in caudal midbrain/rostral pontine structures known to control sleep; (2) development of narcolepsy; (3) unrecognized affective disorder; (4) disruption of circadian timekeeping system.

Studies of malformation syndromes of humans XXXIIIC: the FG syndrome - further studies on three affected individuals from the FG family.

The brain findings at autopsy of an 18-year-old male with FG syndrome were megalencephaly, midline fusion of mammillary bodies, heterotopia of neuroglial tissue in the 7th and 8th nerves, and ependymal cell replacement by neuroglial tissue as well as a diffuse defect of neuronal cell migration evidenced from pachygyria of many gyri, dysgenesis of cerebral cortex, and heterotopia of neurons in the white matter of the centrum ovale. A cousin, studied at 20 weeks' gestational age, had gross turridolichocephaly with enlarged cranium and also multiple minor external and internal anomalies. An affected brother of this fetus died at 17 months of complications of a congenital heart defect and CNS dysfunction. X-linked inheritance of the FG syndrome is confirmed.

Niemann-Pick disease type C. Pathological, histochemical, ultrastructural and biochemical studies.

Two sisters with Niemann-Pick Disease Type C suffered from a progressive CNS degenerative disease which ended with death at 8 and 7 years. Light microscopic and histochemical studies revealed storage of lipid (principally sphingomyelin) in the viscera and in the central nervous system (predominantly ganglioside). Complex lipid cytosomes containing stacked membranes, concentric laminated bodies with central dense cores and pleomorphic profiles were seen. Biochemical analysis showed an elevation of sphingomyelin in liver and spleen with normal total sphingomyelinase levels. However, by isoelectric focusing, there was a marked reduction of sphingomyelinase activity in the range of pI 4.6--5.2, whereas normal amounts of more acidic components were found. These data are compatible with autosomal recessive inheritance of a sphingomyelin lipidosis associated with deficiency of isoelectric forms of sphingomyelinase.

Culture of human glomeruli from patients with metabolic or genetic diseases.

Glomeruli from two patients with metabolic disease were cultured and examined ultrastructurally. One patient with neuronal ceroid lipofuscinosis showed intracellular membrane alterations that we have never seen in normal glomerular cells. In contrast, ultrastructural features of glomerular cells from a patient with nonketotic hyperglycinemia did not differ significantly from normal. These initial findings led us to successfully culture glomeruli from a patient with Alport's syndrome (hereditary nephritis). The results of our studies suggest that several metabolic or genetic diseases that affect the kidney could be studied through culture of tissue.

The composition of tuberous sclerosis grey matter.

The chemical analysis of grey matter from a tuberous sclerosis subject indicated the presence of two different types of grey matter based on two distinctly different ganglioside concentrations. Both samples had gangliosides of reduced concentration with an abnormal composition compared to normal grey matter as evidenced from their thin-layer chromatography profiles. Analyses of the glycoprotein fraction from both samples revealed increased glycoprotein content, particularly in total carbohydrate. This observation was consistent with previous studies of angiofibromas and angiomyolipomas.

Idiopathic hydrops fetalis report of 4 patients including 2 affected sibs.

We report four patients with idiopathic hydrops fetalis (IHF), two being affected sibs; the latter represent the first reported familial occurrence. A review identified 45 additional cases that seem to represent 1/3 to 2/3 of all cases of hydrops fetalis of nonimmunologic origin (NIHF). Our patients and the other adequately documented cases permit delineation of "idiopathic" fetal hydrops; ie, that form of the condition which is not associated with any detectable fetal or maternal disorders. These fetuses are usually premature, often the product of a gestation complicated by pre-eclampsia, occasional maternal anemia, and most often polyhydramnios. The fetuses have striking edema of most tissues with effusions into serous cavities, but no other specific anatomic abnormalities. They are often hypoproteinemic, but not anemic and do not manifest signs of accelerated hematopoiesis. Results of fetal and maternal immunohematological examination are normal. Fetal mortality rates approach 100% but recent data suggest that salvage rates can be significantly improved with early diagnosis. This requires accurate diagnosis and all factors and conditions known to be associated with other types of NIHF should be excluded. A relationship between fetal hypoalbuminemia and IHF may exist and needs further investigation, IHF is sporadic in most instances; however, recessive inheritance may be indicated by occurrence in two sibs. IHF represents a distinct, frequently unrecognized and relatively common entity in need of further study and increased recognition.

A fetus with upper limb amelia, "caudal regression" and Dandy-Walker defect with an insulin-dependent diabetic mother.

We describe the fetus delivered to an insulin-dependent diabetic woman who had had a previous large, stillborn, non-malformed male infant and a normal female infant. The present fetus had a most unusual combination of malformations which to date had not been described in diabetic embryopathy. The anomalies include: upper limb amelia, "caudal regression" with bilateral absence of the fibulae, unilateral absence of a femur and ipsilateral oligodactyly; undescended testes; atrial septal defect; multiple vertebral and rib anomalies with cervical scoliosis and right webbed neck; left cleft lip and cleft palate; severe micrognathia; left microtia with atresia of the ear canal; and central nervous system defects including hydrocephalus with the Dandy-Walker malformation, asymmetry of the lateral ventricles, abnormal frontal gyral formation, and ependymal and ganglion cell heterotopias of the spinal cord. The pathogenesis of diabetic embryopathy is discussed.

The G syndrome--additional observations.

We are reporting the second lethal case of G syndrome occurring in a female. The developmental defects in this patient included posteriorly angulated auricles, bifid tip of tongue with a long frenulum, hypoplasia of the epiglottis and larynx, rocker bottom feet, and hypertrophied labia majora and clitoris. Additional anomalies not previously reported in the G syndrome were circumvallate placenta, and incompletely perforated hymen.

Basal ganglia calcification in Kearns-Sayre syndrome.

The Kearns-Sayre syndrome (KSS) appears to be a distinctive disorder characterized by progressive external ophthalmoplegia, pigmentary degeneration of the retina, heart block, and elevated CSF protein levels. Recent reports have suggested that abnormalities of muscle mitochondria may also be a consistent finding in KSS. We recently examined a patient with KSS whose skeletal muscle contained abnormal mitochondria. In addition, a computerized tomographic scan of the head showed cerebellar and brain stem atrophy, as well as calcification in the region of the basal ganglia.

Myocardial infarct in a child with systemic lupus erythematosus.

An unusual case of systemic lupus erythematosus (SLE) in a young child is reported with sudden death from myocardial infarction. The diagnosis of lupus erythematosus in this patient was made by renal biopsy at the age of 3 years. Atherosclerosis of the coronary arteries and aorta was found at autopsy with occlusion of the anterior descending branch of the left coronary artery. It is suggested that the vascular changes in this case were related to hypertriglyceridemia and prolonged prednisone therapy superimposed on a hypersensitivity vasculitis related to SLE.

New neurological findings in trisomy 13.

The patient in this report had many of the classic neuropathologic stigmata of trisomy 13, including retinal dysplasia, arrhinencephaly, holoprosencephaly, single external nare and granular cell heterotopias in the cerebellum and microthalmia. In addition, several new findings apparently were present in this case. The neuropathologic entities were as follows: (1) herniation of the cochlear nuclei into the eighth cranial nerve bilaterally to the transition of central to peripheral myelin; (2) gray matter present in eleventh cranial nerve bilaterally; (3) arteriovenous malformations of letpomeningeal and intracerebral vessels; (4) arachnoid cyst at the cauda equina; and (5) retinal pigment epithelium within the optic nerve.

Defect of cerebellar Purkinje cell histogenesis associated with type I and type II renal cystic disease.

The cerebellar vermises from a 1 day old child who died with cystic dysplastic kidneys (Potter Type II) and from a 28 day old who died with infantile polycystic kidneys (Potter Type I) were studied by the Golgi silver method and electron microscopical procedures. Golgi stains showed that Purkinje cells from both cases had the following abnormal characteristics: (1) they retained perikaryal processes even at 37-42 weeks after conception although these processes are normally absent from the cerebellar vermis after 34 weeks of gestation; (2) The Purkinje cell dendrites had dilations at their numerous branchpoints. Ultrastructural studies indicated that climbing fibers remained in contact with the perikaryon of the Purkinje cell in both cases although they are not normally present on the perikaryon after 33 weeks gestation. The 1 day old child (Type II) had unusual synaptic structures of the dyad and serial type. The concurrence of cerebellar and kidney cell maldevelopment in this and a variety of other conditions suggests that there may be a pathogenetic and causal relationship between the two.

Sudden infant death due to congenital adrenal hypoplasia.

Adrenocortical hypoplasia was found to be the cause of sudden death in a 9-month-old infant. Most sudden infant deaths in the first year of life are related to the sudden infant death syndrome, in which no specific pathologic changes are found at autopsy. Although specific causes for sudden death in infancy are well documented, adrenocortical hypoplasia is not a well-recognized cause of sudden infant death.