Brain death.

Current law in the United States authorizes physicians to diagnose brain death by applying generally accepted neurologic criteria for determining loss of function of the entire brain. This article offers a medical-legal perspective on problems that may arise with respect to the determination of brain death. These include the possibility of diagnostic error, conceptual disagreements that may constrain the use of neurologic criteria to diagnose death, and the conflation of brain death and loss of consciousness. This article also addresses legal aspects of the debate over whether to expand the definition of brain death to include permanent unconsciousness. Although existing laws draw a clear distinction between brain death and the persistent vegetative state, many courts have authorized removal of life support from individuals whose unconsciousness is believed to be permanent on proof that removal accords with preferences expressed before sentience was lost.

Medicolegal aspects of neurodiagnostic tests.

Legal issues that may arise in neurodiagnostic testing are reviewed briefly. This article focuses on applications of medical malpractice law with respect to negligence in selection, conduct, and interpretation of tests. The impact of the doctrine of informed consent is considered both in the context of malpractice law and human subjects research. The article concludes with a short exposition on enterprise liability and diagnostic tests, indicating the ways in which the growing role of corporations in medical practice may prompt changes in how claims for test-related medical injuries are processed. This article aims to convey an appreciation of how the law attempts to reduce test-related harms by imposing liability on individuals and organizations.

Neurologist as expert witness.

Prevailing liberal rules of evidence permit qualified medical and scientific experts to offer opinions designed to help courts decide issues to which their expertise relates. The opinions can be based on direct examinations, review of data assembled by others and data or inferences of a type relied on by other experts in the field. Application of these rules is illustrated through analysis of expert testimony in litigation involving a neurologic syndrome allegedly caused by an immunization and in a case involving controversy over the extent and outcome of major brain injury. Concerns about misuse of expert medical and scientific testimony in litigation are addressed. The article closes with a consideration of approaches designed to improve the reliability of expert testimony.

Transient unresponsiveness in the elderly. Report of five cases.

Five hospitalized elderly patients had one or more self-limited episodes of unresponsiveness that could not be explained by metabolic, structural, convulsive, or psychiatric disorders. They accounted for approximately 2% of cases referred to us for evaluation of coma. Despite some heterogeneity, shared clinical features in these patients suggest an age-related disorder of arousal that may be more common than is generally appreciated.

Immunohistochemical analysis of neural cell adhesion molecules. Differential expression in small round cell tumors of childhood and adolescence.

The neural cell adhesion molecule (NCAM) was discovered in a search for cell surface antigens of chicken neurons that contribute to cell adhesion and pattern formation during development. Homologous adhesion molecules have been identified in several species, including humans. In this immunohistochemical study, the authors examine the role of human NCAM in tumor diagnosis. The authors used a monoclonal antibody (MAb), 5.1H11, to examine NCAM immunoreactivity in frozen sections of more than 450 tumors, including more than 80 small round cell tumors (SRCT) of childhood and adolescence (neuroblastomas, Ewing's sarcomas [ES], peripheral neuroepitheliomas [PN], primitive neuroectodermal tumors [PNET], esthesioneuroblastomas, malignant ectomesenchymoma, medulloblastomas, small cell osteosarcomas, mesenchymal chondrosarcomas, embryonal rhabdomyosarcomas, and lymphomas). The authors show that 1) neuroblastomas and primary brain tumors are NCAM+; 2) ES, most PN/PNETs, and melanomas are NCAM-; 3) embryonal rhabdomyosarcomas and various other sarcomas are NCAM+; 4) neuroendocrine tumors are NCAM+; 5) subsets of carcinomas of kidney, ovary, lung and other organs are NCAM+; and 6) lymphoid tumors are NCAM-. Tests with normal fetal and adult tissues indicate that these findings reflect only in part the NCAM phenotypes of corresponding normal tissues. Notably the NCAM- phenotype of ES and PN/PNET is not explained by current histogenetic models for these tumors, which suggest a primitive neuroectodermal origin. Finally the authors show that NCAM expression among SRCT has an inverse relationship with the expression of p30/32MIC2, a cell surface antigen of ES and PN/PNET detected with MAb HBA71. These results suggest that immunohistochemical assays for NCAM and p30/32MIC2 expression may aid in the further characterization of SRCT of childhood and adolescence.

Reversible myeloneuropathy of nitrous oxide abuse: serial electrophysiological studies.

Detailed electrophysiological studies were performed in 4 patients with myeloneuropathy induced by abuse of nitrous oxide for 1 to 4 years. All presented with paresthesias, weakness, and Lhermitte's phenomena, and exhibited signs of sensorimotor polyneuropathy, ataxia, and arreflexia. Two had subnormal serum vitamin B12 levels. Baseline electrophysiologic testing revealed reduced motor unit potentials, prolonged F wave latencies, absent H reflexes, denervation potentials, and delays in motor and sensory conduction. Three had peripheral and nuchal delay after median nerve stimulation. All were reevaluated after 3 to 12 months' abstinence and treatment with vitamin B12, and all showed substantial clinical improvement. Parallel improvement in electrophysiologic findings occurred, but residual minor conduction delays, loss of H reflexes, electromyographic evidence of denervation, or abnormalities of posterior tibial SEP were noted. These findings confirm the reversibility of myeloneuropathy of nitrous oxide abuse and describe the profile of electrophysiologic recovery in subjects who abstain from further neurotoxic exposure.

Immunohistochemical analysis of the A4 and AO10 (gp110) cell-surface antigens of human astrocytoma.

The A4 and AO10 (110 kd glycoprotein) cell-surface antigens are biochemically distinct markers of cultured human astrocytomas that are expressed by only a limited number of other cultured cell types. To further characterize these two antigens, the authors used immunohistochemical methods to determine their expression in normal human tissues, astrocytomas, and over 100 tumors of other histologic types. They found that A4 is expressed 1) throughout the central (CNS), but not peripheral nervous system (PNS); 2) in smooth muscle and a small number of epithelial tissues; and 3) in reactive glia and in astrocytomas, but not in most tumors of other histologic types. In contrast, the AO10 antigen is expressed 1) in a small subset of CNS neurons, but not in astrocytes, PNS neurons, or other normal tissues; 2) in astrocytomas and reactive glia; and 3) in some additional neuroectodermal tumors, but not melanomas, carcinomas, or sarcomas. These findings show that A4 and AO10 are restricted markers for human astrocytomas in vivo. Furthermore, the antigens show distinct patterns of expression in normal human CNS but appear to be coordinately expressed in astrocytomas and astrocytoma-derived cell lines.

Legal aspects of termination of treatment decisions.

A large body of medical and ethical opinion holds that it is justifiable to terminate medical treatment for permanently unconscious persons. But opponents of particular decisions to withhold or withdraw treatment may argue that the decisions violate laws against homicide, pose a threat to the lives of other less severely afflicted persons, rest on uncertain diagnoses or prognoses, proceed without adequate knowledge of individual preferences or interests, or have an adverse impact on the values of physicians and other health care providers. Although laws differ among the states, decisions that derive from rigorous clinical evaluations and carefully achieved agreements between medical caretakers and lawful proxies of afflicted persons about appropriate levels of care should be defensible against various forms of legal attack.

Cell surface molecules of human melanoma. Immunohistochemical analysis of the gp57, GD3, and mel-CSPG antigenic systems.

The rapidly expanding list of monoclonal antibodies (MAbs) to human cell surface antigens provides reagents to probe the biology of malignant melanoma and to develop new diagnostic and therapeutic approaches to this disease. The criteria used to select MAb-defined antigens as targets for passive immunotherapy or immunolocalization of melanoma include: 1) consistent antigen expression in melanomas, 2) restricted antigen distribution in normal tissues and nonmelanocytic tumors, and 3) cytotoxic activity of the MAb or MAb conjugates. The present study examined the tissue distribution of three prototype melanoma cell surface antigens, the Mr 57,000 glycoprotein (gp57) recognized by MAb A42, the GD3 ganglioside, and the mel-CSPG chondroitin sulfate proteoglycan. The avidin-biotin immunoperoxidase method was used to examine a large panel of normal tissues and over 150 malignant tumors. It was found that A42 has a highly restricted distribution in normal tissues and is expressed in subsets of melanomas and nonmelanocytic tumors. It was also found that GD3 and mel-CSPG are more widely distributed in normal tissues and among tumors than was thought previously. These immunohistochemical patterns provide an essential data base to evaluate the ongoing clinical trials employing MAbs to GD3 and mel-CSPG for the therapy and immunolocalization of melanomas, and they identify gp57 as a potential marker for subsets of normal and transformed melanocytic cells.

Chronic dysphagia, vomiting and gastroesophageal reflux as manifestations of a brain stem glioma: a case report.

Brain stem glioma is the third most common childhood brain tumor, comprising 10-15% of this group of neoplasms. Typical presenting symptoms include ataxia, diplopia and headache, while signs of increased intracranial pressure occur later in the clinical course. Although prolonged failure to thrive, characterized by cachexia and vomiting are rare manifestations of brain stem lesions, in this study we report a 9.5-year-old boy with failure to thrive since infancy which remitted after excision of a brain stem astrocytoma.

Cell-surface glycoproteins of human sarcomas: differential expression in normal and malignant tissues and cultured cells.

Normal differentiation and malignant transformation of human cells are characterized by specific changes in surface antigen phenotype. In the present study, we have defined six cell-surface antigens of human sarcomas and normal mesenchymal cells, by using mixed hemadsorption assays and immunochemical methods for the analysis of cultured cells and immunohistochemical staining for the analysis of normal tissues and greater than 200 tumor specimens. Differential patterns of F19 (Mr, 120,000/95,000 glycoprotein), F24 (Mr, 95,000 glycoprotein), G171 (Mr, 75,000 glycoprotein), G253 (Mr, 90,000 glycoprotein), S5 (Mr, 120,000 glycoprotein), and Thy-1 (Mr, 25,000 glycoprotein) antigen expression were found to characterize (i) subsets of cultured sarcoma cell lines, (ii) cultured fibroblasts derived from various organs, (iii) normal resting and activated mesenchymal tissues, and (iv) sarcoma and nonmesenchymal tumor tissues. These results provide a basic surface antigenic map for cultured mesenchymal cells and mesenchymal tissues and permit the classification of human sarcomas according to their antigenic phenotypes.

Definition of an extracellular matrix protein in rostral portions of the human central nervous system.

We have identified and characterized an extracellular matrix (ECM) glycoprotein of cultured astrocytomas, NEC1, that is expressed in normal human brain parenchyma. Detailed immunohistochemical analysis reveals a region-specific NEC1 pattern along the rostrocaudal axis of the central nervous system (CNS), with strong expression throughout the white matter of telencephalon and diencephalon, scant expression in some areas of mesencephalon, and no expression in pons, cerebellum, medulla, spinal cord, and peripheral nervous system. NEC1 is not co-distributed with any known neural cell type, suggesting that expression of specific ECM proteins in the CNS is segmentally controlled.

Legal implications of epilepsy.

Physicians who care for patients with epilepsy may function as agents or targets of social control. As agents, they may assist in the identification and control of epileptic drivers, may provide information that enables fair and appropriate job placements for epileptic persons, and give testimony that helps the legal system resolve issues relating to the liability of epileptic persons for harm attributed to seizures or interictal behavioral disturbances. As targets, they may be charged with negligent failure to diagnose, treat, or inform about epilepsy or its associated problems, with failure to exercise due care in protecting persons harmed by their patients, or with failure to preserve confidentiality of medical information. Although legislation and judicial decisions have defined some of the physician's legal duties with reasonable clarity, areas of uncertainty remain, particularly regarding the issue of violating medical confidentiality for the benefit of persons other than the patient.

The Brophy case: whose life is it?

A Massachusetts court recently authorized withdrawal of nutrition from an adult in a chronic vegetative state where he had, while healthy, stated that he would not want his life sustained if he were permanently unconscious. The court rejected the view that a decision to withdraw life-supporting treatment could be made on the basis of "quality of life" determinations by persons other than the patient. In this respect, the decision should not be perceived as a step toward arranged deaths for those who lack the capacity to enjoy someone else's version of life or who are seen by others as social burdens.