Intraventricular cerebral neuroblastoma. Analysis of subtypes and comparison with hemispheric neuroblastoma.

Two cases of intraventricular neuroblastomas were compared with cases of intraventricular and hemispheric neuroblastomas that have been reported in the published literature. The following order of tumor subtypes was found in patients with increasing age: hemispheric neuroblastoma, intraventricular undifferentiated neuroblastoma, intraventricular differentiated neuroblastoma, and intraventricular neurocytoma; for patients with intraventricular neuroblastomas, this was also the order of increasing cellular maturation and survival. Neuronal morphologic or epitope differentiation was associated with a longer survival time than lack of differentiation by Kaplan-Meier product-limit estimates and with a better survival rate (chi 2) for intraventricular tumors but not for hemispheric tumors. Pathologic distinction of a neurocytoma was confirmed with immunostaining or ultrastructural studies that suggested that a neurocytoma is a matured neuroblastoma of a granule-cell (interneuron) phenotype. Differences among neuroblastoma groups bolster previous suggestions that intraventricular tumors arise differently than do cases of hemispheric tumors and follow a more benign course when neuronal differentiation is present.

In utero brain damage: relationship of gestational age to pathological consequences.

The authors examined the brains of two infants in whom episodes of fetal compromise could be accurately correlated with gestational age. A mother who had sustained hypotensive shock at 16 weeks gestation gave birth at 20 weeks to a stillborn infant whose brain showed cystic necrosis of the lenticular nuclei and multifocal polymicrogyria. The brain of a seven-month-old infant born at 33 weeks gestation to a mother who had experienced respiratory arrest during her 28th week showed thalamic and brainstem necrosis accompanied by diffuse white matter gliosis. Review of the literature yielded 10 similar cases. When the insults occurred before 24 weeks of gestation, bilateral pallidal necrosis was a constant feature. Between 26 and 34 weeks, the common finding was thalamic necrosis, often accompanied by brainstem necrosis. These observations should be of assistance in determining the timing of gestational insults, and therefore possible clinical correlations, in prenatal brain damage.

Intracranial lipomas with teratomatous elements.

We report two cases of patients with intracranial tumors that share features with lipomas and teratomas. Although rare reports of lipomas with "hypertrophic nerves" and "teratoid tumors" have been recorded, these two cases are unusual because they contain mature neuroectoderm (choroid plexus, peripheral nerve) and mesoderm (skeletal muscle). The findings are discussed and modern classification schemes are presented. We believe that the cases are examples of a transition between lipoma and teratoma.

Amyloidoma of the CNS. I. Clinical and pathologic study.

We report a 32-year-old man with a 4-year history of headaches, seizures, and dementia secondary to multifocal amyloidomas in the white matter. Immunohistochemical and electron microscopic analyses suggest that the amyloidomas resulted from processing of plasma-cell-derived amyloidogenic protein by microglial cells.

Immunohistochemical properties of human optic nerve glioma. Evidence of type 1 astrocyte origin.

The peroxidase-antiperoxidase method was used to study ten surgically obtained human optic nerve gliomas (pilocytic astrocytomas). All tissues were formalin fixed and paraffin embedded. Primary antisera included glial fibrillary acidic protein (GFAP), HNK-1 (type 1 astrocyte precursor marker), A2B5 (type 2 astrocyte precursor marker), S-100, vimentin, myelin basic protein (MBP), laminin, keratin, cytokeratin, epithelial membrane antigen (EMA), and neuron-specific enolase (NSE). Neoplastic astrocytes in optic nerve gliomas stained with GFAP, HNK-1, S-100, and vimentin. Oligodendrocytes and myelin sheaths stained for MBP, and NSE stained surviving axons in the tumors. Neoplastic astrocytes did not stain for A2B5, keratin, cytokeratin, EMA, or laminin. These results suggest that human optic nerve gliomas (pilocytic astrocytomas) arise from type 1 astrocytes.

The erythrocyte-type glucose transporter in blood vessels of primary and metastatic brain tumors.

We previously demonstrated that brain microvessels have a high density of the erythrocyte-type glucose transporter and suggested this could be used as a marker of cells with "occluding" junctions. Now, we have studied by immunocytochemistry the tissue distribution of the glucose transporter in a variety of primary and metastatic human brain tumors with a monoclonal antibody to the glucose transporter of human erythrocytes. Microvessels in normal brain tissue distant from the tumor, and in brain surrounding the tumor, immunostained strongly for the glucose transporter. Microvessels in primary and metastatic tumors, however, lacked glucose transporter immunoreactivity. Only in the relatively benign juvenile cerebellar astrocytomas was glucose transporter immunoreactivity retained in some of the tumor microvessels. Because a high glucose transporter density is a marker of vessels with barrier properties, our results indicate that the vast majority of brain tumor microvessels do nc, have an intact blood-brain barrier.

Seasonal distribution of births in Alzheimer's disease.

We obtained season-of-birth data in 727 autopsy-confirmed cases of Alzheimer's Disease (AD) and compared these data with expected general population birth rates. There were no significant differences between quarterly birth rates in the AD group and expected quarterly birth rates. Edward's test for cyclical trends did not establish a peak period of birth in the AD sample. No significant differences between observed and expected quarterly birth rates were found when data were analyzed with regard to either family history of dementia or to gender. Edward's test for peak quarter was significant for AD females, however, with the peak period occurring early in the first quarter. These negative findings between observed and expected quarterly birth rates, based on the large number of autopsy-confirmed AD cases in this study, suggest that a season-of-birth effect in AD is highly unlikely.

Magnetic resonance imaging in cervical cord birth injury.

Three children who sustained cervical cord injury due to birth trauma are described. The clinical and radiological data, and the central nervous system pathology of one child, illustrate the advantages and feasibility of magnetic resonance imaging in ventilator-dependent children with cervical cord lesions.

Malformational complex in an infant with intrauterine influenza viral infection.

An infant with complex malformations of the central nervous system is described. The abnormalities included ependymal damage, aqueduct forking, hydrocephalus, and neuronal heterotopias; agenesis of the cerebellum, pontine, and inferior olivary neutrons; agenesis of the optic and olfactory systems and corpus callosum; and a highly unusual course of the corticospinal fibers in the spinal cord. Immunohistochemical test results showed the presence of influenza virus antigens in the brain. Possible pathogenetic mechanisms are presented.

Congenital absence of the corticospinal fibers: pathologic and clinical observations.

We describe 2 patients with primary absence of corticospinal tracts. Both presented with delayed motor development, head lag, and spasticity of the limbs. We could not identify precentral cortex, and there were no corticospinal fibers below the internal capsules. We postulate that the fibers were displaced or interrupted early in their development.

Imbalanced biphasic electrical stimulation: muscle tissue damage.

The effects of imbalanced biphasic stimulation were studied on cat skeletal muscle to determine if greater charge densities can be safely used than with balanced or monophasic stimulation. The results of the study indicate that imbalanced biphasic stimulation can be tolerated safely by tissue at or below a net dc current density of 35 microA/mm2 and not safely tolerated at or above a net dc current of 50 microA/mm2. Monophasic stimulation has been shown to be safe at or below net dc current levels of 10 microA/mm2 and in these studies we found it was not safe at or above net dc current levels of 20 microA/mm2. Stimuli were applied to muscles via coiled wire intramuscular electrodes using a regulated current source. Since the safe average current density was higher for imbalanced biphasic stimulation than for monophasic stimulation, this suggests that: (a) pH change is not the primary reaction causing tissue damage and (b) the damaging electrochemical process that takes place during a cathodic stimulation pulse can be reversed by an anodic pulse having substantially less charge than its companion cathodic pulse. We conclude that greater cathodic charge densities can be safely employed with imbalanced biphasic stimulation than with either monophasic stimulation or balanced charge biphasic stimulation.

Giant invasive intracerebral dermoid tumor with subependymoma-like reaction: case report.

A large, completely intracerebral, dermoid tumor with extensive outgrowth of appendages into brain tissue caused prominent reactive changes in the surrounding white matter, similar to those seen in a typical subependymoma. This case lends support to the notion that some subependymomas are reactive in etiology.

Septo-optic dysplasia (SOD) or DeMorsier syndrome.

The historical evolution of the DeMorsier syndrome is reviewed. As the emphasis shifted from the eye findings to endocrinological defects and as the syndrome was further expanded through more frequent and easier radiological examination, the concept appears to have expanded, raising questions as to the nature of the disease and its clinical expression. To determine pathogenesis and better define the extent of the disease, further observations are needed, including postmortem studies on patients with septo-optic dysplasia and related disorders.

Muscle plasticity: comparison of a 30-Hz burst with 10-Hz continuous stimulation.

The changes in the contractile properties induced by a 30-Hz phasic stimulation paradigm were measured and compared with the changes induced by a 10-Hz continuous stimulation paradigm. The study was performed on the tibialis anterior muscles of cats with one paradigm applied to one hindlimb muscle and the other to the contralateral limb. Both hindlimb muscles received the same number of stimuli in a day, making the average stimulation frequency 10 Hz. Two periods of daily stimulation were studied, 8 and 24 h/day. Muscles stimulated at 30 Hz produced greater overall tetanic tension and, during a prolonged stimulation test, exerted a greater mean tension than muscles stimulated at 10 Hz (50 and 32% increase for animals stimulated for 8 and 24 h/day, respectively). Muscle mass was least reduced and fewer pathological abnormalities were observed in the muscles stimulated at 30 Hz. There were no apparent differences in the histochemistry or biochemistry between muscles stimulated at 10 and 30 Hz, which could account for these differences in muscle properties. These results indicate the 30-Hz paradigm may be better suited than 10 Hz continuous stimulation for applications requiring sustained muscle tension such as correction of scoliosis or muscle conditioning for motor prostheses.

Astrocyte response to perinatal liver disease, hyperammonemia, and hyperbilirubinemia: an immunohistochemical study.

Astrocytic reaction to perinatal brain damage, which is caused by hyperammonemia, liver disease, hyperbilirubinemia, and a few other conditions, was studied using immunohistochemical methods for the demonstration of glial fibrillary acidic protein (GFAP). We found no increase in GFAP expression in those areas where Alzheimer II astrocytes usually proliferate. Diffuse astrocytic proliferation in the white matter and focal reaction in gray matter, which we ascribe to complicating factors, the foremost of which is anoxia, was found in many of the cases.

Large pituitary gland adenomas evaluated with magnetic resonance imaging.

Magnetic resonance imaging (MRI), computed tomographic (CT) scanning, and angiography or digital subtraction angiography (DSA) were used preoperatively to evaluate 16 surgically proven cases of sellar tumor with extrasellar extension. There were 15 pituitary tumors and 1 schwannoma. The capabilities of MRI in evaluating these tumors were compared with CT scanning and angiography. Bone destruction and tumor calcification were better detected by CT scanning than by MRI. MRI was as effective as CT scanning in detecting a cyst or variation in tumor consistency. Neither MRI nor CT scanning was capable of distinguishing specific tumor types. In every case, MRI was superior to CT scanning for delineating spatial relationships of the tumor to the 3rd ventricle, the optic apparatus, adjacent brain, and parasellar vasculature. Vessel encasement by tumor was clearly seen on MRI when there was no direct indication of this on other studies. Cavernous sinus invasion was not demonstrated by CT scanning, but was indicated by MRI in 5 cases and was surgically confirmed in 3. MRI can provide more precise spatial information on extrasellar tumor extension. Vascular encasement and cavernous sinus invasion may be determined preoperatively. Treatment expectations and operative approaches can be guided by this information. When MRI is available, it is the test of choice for the preoperative evaluation of patients with suspected large pituitary gland (sellar region) tumors. Contrast-enhanced CT scanning and angiography can be used as supplementary studies to add information inherently unique to these techniques.

Neuropathology of "septo-optic dysplasia" (de Morsier syndrome) with immunohistochemical studies of the hypothalamus and pituitary gland.

The de Morsier syndrome, or septo-optic dysplasia, is a developmental anomaly characterized by involvement of the optic system, hypothalamic-pituitary axis and septum pellucidum. Only a few anatomical observations are recorded. We report three new cases and review the pertinent literature. The neuropathological lesions varied as did the clinical features. The hypothalamic nuclei were most commonly involved, followed by the optic system and the septum pellucidum. Other lesions were found in the cerebral cortex, corpus callosum, olfactory system and cerebellum. The hypopituitarism appeared to have been secondary to hypothalamic damage rather than to intrinsic pituitary defect. A virtually normal histology and the usual endocrine cell populations were demonstrated by immunocytochemistry in the adenohypophysis. Damage to the neurophysin-containing cells of the hypothalamus explains the various degrees of clinically observed diabetes insipidus.

Diffuse axonal injury by assault.

A case of diffuse axonal injury (DAI) by assault is reported. The majority of DAI cases documented have been due to traffic accidents and some due to falls from height. DAI is caused by angular or rotational acceleration of the victim's head. The condition is common and is the second most important head injury after subdural hematoma with regard to death. Its clinical picture is characterized by immediate and prolonged coma or demented state. Because of the subtle nature of histological changes in DAI, awareness and intentional search for the lesion is essential. The triad of DAI is as follows: focal lesions (hemorrhages and/or lacerations) in the corpus callosum and brain stem, and microscopic demonstration of axonal damage--retraction balls. The concept of DAI will elucidate and enhance the understanding of many head trauma cases.

Deficiency of the reduced nicotinamide adenine dinucleotide dehydrogenase component of complex I of mitochondrial electron transport. Fatal infantile lactic acidosis and hypermetabolism with skeletal-cardiac myopathy and encephalopathy.

A mitochondrial defect was investigated in an infant with fatal congenital lactic acidosis (3-14 mM), high lactate-to-pyruvate ratio, hypotonia, and cardiomyopathy. His sister had died with a similar disorder. Resting oxygen consumption was 150% of controls. Pathological findings included increased numbers of skeletal muscle mitochondria (many with proliferated, concentric cristae), cardiomegaly, fatty infiltration of the viscera, and spongy encephalopathy. Mitochondria from liver and muscle biopsies oxidized NADH-linked substrates at rates 20-50% of controls, whereas succinate oxidation by muscle mitochondria was increased. Mitochondrial NADH dehydrogenase activity (complex I, assayed as rotenone-sensitive NADH oxidase, NADH-duroquinone reductase, and NADH-cytochrome c reductase) was 0-10% of controls, and NADH-ferricyanide reductase activity was 25-50% of controls in the mitochondria and in skin fibroblasts. Activities of other electron transport complexes and related enzymes were normal. Familial deficiency of a component of mitochondrial NADH dehydrogenase (complex I) proximal to the rotenone-sensitive site thus accounts for this disorder.

Cerebro-ocular dysplasia-muscular dystrophy syndrome. Report of two cases.

Cerebro-ocular dysplasia-muscular dystrophy (COD-MD) syndrome is a rare disorder encompassing a triad of brain, eye, and muscle abnormalities. The principal central nervous system features are cerebral and cerebellar agyria-micropolygyria, cortical disorganization, glial-mesodermal proliferation within the leptomeninges, neuronal heterotopias, hypoplasia of nerve tracts, hydrocephalus, and, occasionally, encephalocele. Ocular abnormalities include microphthalmia, cataract, immature anterior chamber angle, retinal dysplasia with or without retinal detachment, persistent hyperplastic primary vitreous, optic nerve hypoplasia, and coloboma. Skeletal muscle findings include fiber splitting, variable fiber size, and endomysial fibrosis. Recent evidence has shown that COD-MD syndrome may be identical to the Walker-Warburg (also known as Warburg) syndrome. Fukuyama congenital muscular dystrophy is similar to the COD-MD and Walker-Warburg syndromes, although the ocular manifestations are less severe. We report the histopathologic findings in two siblings with multiple features of COD-MD syndrome.