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.

The presence of glial fibrillary acidic protein in the human pituitary gland.

The presence of glial fibrillary acidic protein (GFAP) was studied in human pituitary glands with the peroxidase-antiperoxidase (PAP) method. Positive reaction was observed in cells and processes of the neurohypophysis, in occasional cells lining the Rathke's cysts of the pars intermedia, and in scattered star-shaped cells and small follicles of the pars distalis. GFAP immunoreactivity was sparse and variable in amount from case to case. An increase in GFAP-immunoreactivity was observed as a reaction to injury. GFAP-positive cells were seen within and around pituitary adenomas regardless of their secretory cell type. Evidence is presented to indicate that these cells do not contain conventional pituitary hormones. It is postulated that the GFAP-positive cells of the pars distalis are nonsecretory elements, identical to the folliculostellate cells. They may become visible by immunostaining following increased synthesis of GFAP. The latter may be a response to cell injury or metabolic changes in adjacent secretory elements. A similar reaction in pituicytes may explain the appearance of immunoreactive GFAP in the neural lobe. The presence of GFAP in the adenohypophysis suggests that some of their cells are neuroectodermal in origin.

The weight of the infratentorial portion of the adult brain and analysis of the infratentorial/whole brain weight ratio.

A direct relationship exists between the weights of the infratentorial portion (ITP) of the brain and the whole brain. With aging, the weight of the ITP decreases, but the decrease begins later and is smaller than for the forebrain. With whole brain weights, there are significant differences in the weight of the ITP between sexes and between the races. The weight of the ITP increases slightly with increase in body weight. The infratentorial/whole brain ratio is stable during adult life and does not vary with body dimensions. The ratio increases after age 80 because of the accelerated loss of mass of the forebrain. The ratio is the same for both races, but it is significantly higher for the females than for the males. The difference is best accounted for by an arrest in the growth of the forebrain in the female during adolescence.

Neuronal and astrocytic differentiation in human neuroepithelial neoplasms. An immunohistochemical study.

Neuroepithelial neoplasms of childhood were examined immunohistochemically using antibodies against a neurofilament polypeptide and glial fibrillary acidic protein. Ninety-one cases, including 11 controls, were examined. Positively reacting cells, indicating neuronal and glial differentiation, were found in 59 of the 80 tumors. The study supports a neuroepithelial origin for medulloblastomas, central neuroblastomas, and primitive neuroectodermal tumors of childhood. The results also indicate that only a small number of the tumor cells differentiate along either neuronal or glial cell lines.

Correlation of perinatal brain growth with age, body size, sex, and race.

This study compares the weight of the human brain to gestational age and body dimensions. A new formula for calculating the rate of growth is proposed. It consists of a second order polynomial function: Y = A0 + A1X + A2X2, in which Y is brain weight, body weight, height, or body surface area; X is gestational age in weeks and A0, A1, and A2 are statistically estimated coefficients. In utero, the growth rate is most rapid for body weight, followed in decreasing order by brain weight, body surface area, and height. Brain growth is the same for both sexes in black and white races; it accelerates between the 20th and 45th weeks of gestation. The size of the newborn infant brain is directly related to gestational age and body size and is not determined by sex or race.

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 "anoxic" myelopathy.

Pathologic changes and distribution of lesions of the spinal cord were studied in 16 patients who suffered from "anoxic" episodes. The lesions were symmetrical and limited to the gray matter. The vulnerability of the spinal cord was most marked in the lumbosacral region, although almost every nucleus throughout the spinal cord was subject to damage.

Respiratory distress and Arnold-Chiari malformation.

Fourteen children with Arnold-Chiari malformation had history of respiratory distress, apnea, vocal cord paralysis or inability to swallow. Postmortem examination in 12 disclosed vascular lesions in the tegmentum of the medulla oblongata. The length of survival of these children was markedly shorter than of those without such history and anatomic findings. It is suggested that the malformation results in changes in the vascular supply of the herniated portion of the brainstem. Stretching of the arteries may result in irreversible damage to the brainstem with subsequent life-threatening disturbance of respiratory function.

Thrombosis of the middle cerebral artery associated with birth trauma.

After birth trauma, an infant had middle cerebral artery thrombosis, proved at autopsy. Unusual forces exerted on the head and neck at the time of attempted high forceps delivery damaged the inner layers of the right middle cerebral artery, which led to thrombosis and infarction.

Central spinal myelinolysis.

A midline lesion of the funiculus gracilis was found in four patients with histories of alcoholism, nutritional disturbance, and repeated episodes of electrolyte imbalance. Histologic and anatomic abnormalities were similar to those of central pontine myelinolysis. Sodium imbalance may play a role in the pathogenesis of both conditions.

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.

Chiasmal apoplexy: hemorrhage from a cryptic vascular malformation in the optic chiasm.

We describe three patients with acute chiasmal visual field loss caused by hemorrhage within an intrachiasmal arteriovenous malformation. One patient had five episodes; vision improved three times without treatment and twice after surgical decompression. Surgical intervention restored vision in two of the three patients. The role for surgery is indefinite, but may be indicated if the visual defect remains static for 1 week or progresses. Decompression is likely to be most effective if done early. The approach to the optic chiasm should be transcranial, not transsphenoidal. A radiologically normal sella turcica favors the diagnosis of chiasmal apoplexy in the acute chiasmal syndrome.

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.

Anaplastic astrocytoma mimicking metastatic carcinoma.

A case of anaplastic astrocytoma mimicking a metastatic carcinoma is presented. This rare type of astrocytoma with epithelial features is compared to cases reported in the literature, and the importance of staining brain tumor biopsies for glial fibrillary acidic protein is emphasized.

Immunofluorescence technique for rapid diagnosis of glial tumors.

A technique for rapid diagnosis of astroglial and ependymal glial neoplasms is presented. Frozen sections are processed for immunofluorescence using anti-serum raised against the glial fibrillary acidic (GFA) protein. The entire procedure requires 10--15 minutes. The technique is useful for the rapid identification of neoplasms of astroglial and ependymal lineage.

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.

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.

Arterial dysplasia with ruptured basilar artery aneurysm: report of a case.

An 11 year old girl died unexpectedly as a result of spontaneous subarachnoid hemorrhage originating from a ruptured giant fusiform aneurysm of the basilar artery. The aneurysm had developed as a long standing complication of arterial fibromuscular dysplasia. This discussion describes the light and electron microscopic findings in the aneurysm and the histologic examination of abnormalities in the muscular arteries of the viscera.

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.

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.