Utility of intra-operative consultations for the diagnosis of central nervous system lesions.

The inherent soft nature of the central nervous system (CNS) renders poor-quality frozen sections. Cytology has been shown to be of great value in intra-operative consultations of CNS pathology. The current study was undertaken to examine the utility of intra-operative consultations regarding CNS lesions, comparing the usefulness and limitations of frozen section and cytology techniques. A retrospective study of 103 cases of CNS intra-operative consultations was performed. Concordance between the intra-operative diagnosis and the final diagnosis was seen in 94% of cases. Most discrepancies were due to failure to recognize atypia in meningiomas. The cytology technique was more useful for astrocytomas, small round cell tumors, and certain metastases. The frozen section technique was better for the diagnosis of meningiomas, reactive lesions, ependymomas, and most metastatic lesions. Using a combination of the two techniques is most beneficial.

Clinical, pathologic, and neurochemical studies of an unusual case of neuronal storage disease with lamellar cytoplasmic inclusions: a new genetic disorder?

A child of first-cousin Puerto Rican parents had global developmental delay, failure to thrive, and hypotonia since early infancy. At 1 1/2 years of age, she developed clinical and electrophysiologic evidence of progressive motor and sensory neuropathy. At 2 1/2 years, she developed visual impairment and optic atrophy followed by gradual involvement of the 7th, 9th, 10th, and 12th cranial nerves. Uncontrollable myoclonic seizures began at 4 years and she died at 6 years of age. Motor nerve conduction velocities were initially normal and later became markedly slowed. Sensory distal latency responses were absent. Lysosomal enzyme activities in leukocytes and fibroblasts were normal. Sural nerve and two muscle biopsies showed only nondiagnostic abnormalities. Electron microscopy of lymphocytes, skin, and fibroblasts showed cytoplasmic inclusions. Light microscopy of frontal cortex biopsy showed neuronal storage material staining positively with Luxol fast blue, and electron microscopy showed cytoplasmic membranous bodies in neurons, suggesting an accumulation of a ganglioside. At autopsy, all organs were small but otherwise normal and without abnormal storage cells in the liver, spleen, or bone marrow. Anterior spinal nerve roots showed loss of large myelinated axons. The brain was small and atrophic; cortical neurons showed widespread accumulation of storage material, most marked in the pyramidal cell layer of the hippocampus. Subcortical white matter was gliotic with loss of axons and myelin sheaths. In cortical gray matter there was a 35% elevation of total gangliosides, with a 16-fold increase in GM3, a three- to four-fold increase in GM2 gangliosides, and a 15-fold elevation of lactosyl ceramide. GM3 sialidase activity was normal in gray matter at 3.1 nmols/mg protein per hour and lactosyl ceraminidase I and II activities were 70% to 80% of normal. In white matter, total myelin was reduced by 50% but its composition was normal. Phospholipid distribution and sphingomyelin content were normal in gray matter, white matter, and in the liver. These biochemical findings were interpreted as nonspecific abnormalities. The nature of the neuronal storage substance remains to be determined.

Mesenchymal chondrosarcoma of the cerebellum.

Mesenchymal chondrosarcoma is a rare malignant neoplasm of bone and soft tissues. An unique case is described of an 8-year-old child with a midline cerebellar lesion. Pertinent clinical and radiologic findings along with histopathologic features are described. To our knowledge, this is the first case of mesenchymal chondrosarcoma arising in the cerebellar parenchyma of a child.

Autopsy-proven progressive supranuclear palsy in two siblings.

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder that is generally considered to be nonfamilial. We report a brother and sister with clinical and pathologic findings characteristic of PSP. Both developed parkinsonism in the eighth decade of life and within 5 years exhibited severe postural instability, bradykinesia, rigidity, dystonia, dysarthria, dysphagia, urinary incontinence, pseudobulbar palsy, and supranuclear oculomotor dysfunction but no tremor. Neither responded to levodopa and/or carbidopa. Their mother and, possibly, maternal grandfather reportedly suffered from a parkinsonian syndrome. Essential tremor occurred in the siblings' father and in two of the brother's three children. Autopsy in the brother at age 81 years and sister at age 79 years revealed changes typical of PSP with atrophy and neurofibrillary tangles in the globus pallidus, subthalamic nucleus, and rostral tegmental brainstem. No Lewy bodies were present. These cases are the first pair of relatives reported with autopsy confirmation of PSP in both and raise the question of genetic predisposition to PSP.

Recurrent adenocarcinoma of the fallopian tube presenting as leptomeningeal carcinomatosis.

Primary adenocarcinoma of the fallopian tube is a rare malignant neoplasm of the female reproductive system. Unusual patterns of metastasis may be observed. Report is made of a patient with recurrent adenocarcinoma of the fallopian tube, which presented as leptomeningeal carcinomatosis, as a first site of distant metastasis three years after initial diagnosis. The diagnosis was made by cytologic examination of the cerebrospinal fluid. No other sites of distant metastasis were present.

Masson's hemangioma of spinal meninges causing cord compression with paraplegia.

Masson's hemangioma is a rare benign pathological entity. A unique case is reported of a 42 year old man with a spinal epidural mass who developed acute cord compression resulting in sudden onset of paraplegia. Histological examination of the resected mass revealed a cystic vascular lesion associated with papillary endothelial cell proliferation, and overlying thrombosis, consistent with Masson's hemangioma. Clinicoradiological correlation is also presented.

Pathological features of virus infections of the central nervous system (CNS) in the acquired immunodeficiency syndrome (AIDS).

Neurological disorders are a common cause of morbidity and mortality in the acquired immunodeficiency syndrome (AIDS). In this report we describe the neuropathological changes associated with both human immunodeficiency virus (HIV) infection and with the major opportunistic virus infections, cytomegalovirus (CMV), JC papovavirus (JCV) and herpes simplex virus (HSV) seen in AIDS. In addition "in situ" hybridization studies have been employed for the detection of virus genomic material in each case and the usefulness of this method in supporting the pathological diagnosis is demonstrated. Mechanisms whereby HIV infection results in leukoencephalopathy and the possible contributing roles of the three opportunistic virus infections are discussed.

Brain tumors in children: a review.

Brain tumors are the second most common malignancy of children. In contrast to adults, childhood brain tumors are usually of glial origin; metastases and meningiomas are rare. Some tumors, i.e., medulloblastomas, are found almost exclusively in children. The posterior fossa is the most frequent site of occurrence. The prognosis for childhood neoplasms tends to be more favorable than in adults, and some lesions are curable. New techniques, including immunostaining, tumor markers, and cytogenetics, have improved diagnostic accuracy. A review of some of the most important brain tumors of children is presented along with an upgrade on recent developments in diagnoses and treatment.

L-tryptophan induced eosinophilia-myalgia syndrome.

We describe the spectrum of clinical and histologic abnormalities of 11 women with L-tryptophan induced eosinophilia-myalgia syndrome. The illness is characterized by musculoskeletal symptoms including myalgias, arthralgias and paresthesias. The physical findings consist of muscle tenderness, neuropathies, rash, peripheral and periorbital edema. Electroneurography performed in 10 patients demonstrated a neuropathy in 5 and myopathic changes in 3. Skin and muscle biopsies showed fascial edema, inflammation and perivascular infiltrates in the skin, whereas perineural infiltrates and venulitis were identified in muscle. Seven patients were treated with prednisone; eosinophilia disappeared promptly although myalgias and neuropathy persisted.

Echinococcal cyst of the liver: diagnosis and surgical management.

The encysted larval form of Echinococcus granulosus may infest man as an incidental host. The liver is the organ most commonly involved, but the lung and brain may be affected. The disease is endemic where sheep are raised with dogs in a pastoral environment. Areas of high endemicity exist in rural North America. Human echinococcal disease is now seen in urban medical centers because of the changing patterns of migration and immigration. An echinococcal cyst of the liver is reported in a resident of the New York City metropolitan area. Details of the life cycle, pathology, diagnostic imaging techniques and surgical management of hydatid cysts are reviewed.

The pathogenesis of hepatic encephalopathy.

Hepatic encephalopathy remains a complex clinicopathological problem. Much is known about the biochemical derangements in liver, blood, and brain. The precise pathogenetic mechanism for central nervous system dysfunction remains to be determined. Ammonia continues to be considered as an important neurotoxin and may act synergistically with other toxic substances. Disturbances of amino acid balance may result in a disproportion of inhibitory and excitatory neurotransmitters in the brain. Alternatively, some amino acids may act as false neurotransmitters. Recent clinical and laboratory data have advanced the hypothesis that gamma-aminobutyric acid (GABA) absorbed from the gut may enter the brain and exert a profound inhibitory effect. Drugs which antagonize the GABA-benzodiazepate receptor may offer symptomatic improvements in hepatic encephalopathy.

The human subfornical organ: an anatomic and ultrastructural study.

The subfornical organ (SFO), one of the circumventricular organs (CVO) and a thirst-regulating structure, was examined in humans. In 21 autopsy specimens, the SFO was identified as one mm grey nodule on the ventral surface of the fornix at the foramina of Monro. The SFO is a neuronal-vascular organ on a loose glial background, lined by ependyma. Ultrastructural examination reveals deep, narrow invaginations in most neuronal nuclei, characteristically seen in the SFO of other species, but unlike neuronal nuclei in the rest of the human brain. Ovoid, clear vesicles in synaptic complexes and dense-core granules in non-synaptic neuronal process are seen. Ependymal channels are observed. Capillaries have luminal tongue-like projections and pinocytotic vesicles in the endothelial wall, as well as both tight and non-tight junctions between endothelial cells; endothelial fenestrations are not found. These specializations may permit access of macromolecules to receptor sites in the SFO, facilitating its functions as a chemoreceptor organ in drinking behavior. The anatomy of the human SFO is consistent with that of other CVO's and with that of the SFO in other species.

Laboratory diagnosis of the neuromuscular glycogen storage diseases.

Of the 12 known genetic disorders of glycogen metabolism, five consistently involve the neuromuscular system. Pompe's disease is a generalized, fatal, lysosomal storage disease caused by absence of acid maltase. Structurally abnormal glycogen accumulates in Forbes-Cori and Andersen's diseases, resulting from deficient debranching and branching enzymes, respectively. Exercise intolerance, muscle cramps, and myoglobinuria characterize McArdle's syndrome or myophosphorylase deficiency. In Tauri's disease, absence of phosphofructokinase leads to glycogen accumulation indirectly owing to a metabolic block in glycolysis. Diagnosis of the symptomatic patient, antenatal diagnosis, and detection of heterozygous genetic carriers are accomplished using a variety of laboratory methods. Tissue enzyme assays, chemical analysis of glycogen, and studies of carbohydrate metabolism are available. Recent advances in biophysics, such as nuclear magnetic resonance, have opened up a new approach for the study of metabolic diseases.

Paraspinal myxoma with spinal cord compression. Case report.

A patient with thoracolumbar paraspinal muscle myxoma with spinal cord compression presented with a long history of back pain and recent paraparesis. Removal of the tumor and decompression of the spinal cord provided marked improvement of the weakness.

Platelet enzyme abnormalities in neuropsychiatric disease.

Blood platelets accumulate, store and release a variety of biogenic amines including norepinephrine, serotonin and dopamine (DA) which are known to act as neurotransmitter substances. Platelet monoamine oxidase (MAO) shares many biochemical properties with the mitochondrial MAO present in brain tissue. For these reasons it has been suggested that platelets might serve as a diagnostic and research model for nerve cells in a variety of neuropsychiatric diseases. In some patients with schizophrenia and manic depressive phychoses, platelet MAO activity is significantly decreased. Central nervous system inhibition of MAO could lead to excess accumulation of monoamines in the brain; this would be consistent with the DA hypothesis of schizophrenia. Disturbances of monoamines and enzyme kinetics in the hereditary ataxias and in Huntington disease have been described, but these findings are unproven and controversal. If platelet models for human neuropsychiatric disease can be established, they will be immensely important in preclinical diagnosis, therapy and genetic counseling.

Electron microscopy in the diagnosis of pituitary tumors.

The usefulness and limitations of electron microscopy (EM) in pituitary tumor diagnosis are reviewed and illustrated with clinical examples. The traditional classification of chromophil and chromophobe adenomas is often inconsistent with the hormonal activity of the tumors. Virtually all pituitary adenomas contain some secretory granules when viewed with EM. Endocrine inactive chromophobe adenomas contain 150 nm granules with no demonstrable hormone function. Typical growth hormone (GH) secreting eosinophil adenomas contain large 375 nm granules which dominate the cell cytoplasm. GH secreting chromophobic tumors contain secretory granules of abnormal size and concentration which are invisible to the light microscopist. The variability in granule size may indicate the production of abnormal granules or reflect the stage of the cell in a secretory cycle. Because of this wide range in granule size, the identification of tumor cell type or hormone produced is not reliable by granule measurement alone. Some neoplasms in the sella turcica may be so bizzare or undifferentiated as to defy classification. In such instances, EM can reveal ultrastructural details which identify their origin from pituitary tissue. Malignant pituitary tumors may contain minute secretory granules, and rare pituitary oncocytomas are packed with abnormal mitochondria.

Central nervous system aspergillosis in two young adults.

Unusual and unique features were present in the cases of two patients with central nervous system aspergillosis: One had a previously unreported complication of aspergillosis, extracranial internal carotid artery thrombosis documented by angiography, and in the other patient, cerebral granulomas developed from Aspergillus fumigatus in association with intravenous narcotic abuse. The latter etiologic mechanism was suggested once before. Neither of these patients showed other underlying disease. A detailed neuropathologic examination correlated the salient clinical findings with formation of aspergillosis cerebral granulomata, basilar meningitis, and arterial occlusion. Diagnostic and therapeutic methods in this disease are limited.