[Doctor reports of a neurological clinic in the view of permanent resident neurologists and nerve doctors]. / Arztbriefe neurologischer Kliniken in der Sicht niedergelassener Neurologen und Nervenärzte.

Eight discharge reports involving five diagnoses (anterior territory ischemic stroke, epilepsy, Parkinson's syndrome, multiple sclerosis, polyneuropathy) from five neurological departments were peer-reviewed by five neurologists working in out-patient (private) practice. The review considered the diagnosis, case history, clinical status, laboratory investigation, differential diagnosis and treatment. Criticism mainly involved the quality of the clinical assessment, lack of clinical status at discharge, narrow or incomplete differential diagnosis and the quality of the neurophysiological investigations for epilepsy and polyneuropathy. Improvement potential was seen for the speed of reporting, better comprehensibility, omission of irrelevant information, greater participation of experienced neurologists in report writing, and standardization.

Frequency and topographical distribution of CD68-positive macrophages and HIV-1 core proteins in HIV-associated brain lesions.

We report the neuropathological and immunohistochemical findings in the brains of 14 AIDS patients with HIV-related encephalopathy. Clinically, half of the patients presented with severe AIDS dementia complex including advanced psychomotor retardation and behavioural dysfunction. These features correlated with striking cerebral atrophy and subcortical lesions visible in CT and/or MRI scans. In 7 cases early signs of impaired memory and concentration and/or psychomotor slowing were apparent accompanied by subcortical lesions in MRI scans and normal CCTs. In order to investigate the topographical distribution of HIV-1-associated features, in every case tissue samples from the frontal, temporal, parietal, occipital cortex and subcortical white matter, the hippocampus, basal ganglia, midbrain, pons, medulla oblongata and cerebellum were studied. In all patients histological examination disclosed the typical cellular constituents of HIV encephalitis (n = 12) or leukoencephalopathy (n = 2). Antibodies against lymphocyte subsets, CD68 antigen, myelin basic protein and GFAP were used to characterize the phenotype of cells and to highlight the white matter gliosis. The distribution and degree of pathological features were analysed in a semiquantitative scale, based on the number of CD68-positive cells, and disclosed great interindividual differences concerning the affected brain regions which only in part correlated with the severity of the clinical picture. It is noteworthy, that the deep gray matter, in particular putamen and thalamus, was involved in every case, independent from the stage of the disease. In addition, quantity and topographical distribution of HIV-1 core protein p24 were studied by use of two monoclonal antibodies. It is noteworthy, that the number of immunoreactive multinucleated giant cells and microglial cells decreased gradually from the deep gray matter, especially putamen and thalamus, and deep white matter to corpus callosum, cerebellar white matter and subcortical cerebral white matter. The topographical predilection of the deep gray matter even in cases with early cognitive decline indicates that the basal ganglia are affected early in the course of the disease. This observation closely resembles the results of highly sensitive quantitative neuropsychological tests which disclosed slowing and impaired coordination of rapid extremity movements indicating basal ganglia lesions even in early stages of HIV dementia.

Neuropathological studies in the brains of AIDS patients with opportunistic diseases.

The brains of 70 fatal cases with AIDS were studied by means of immunohistochemistry and in-situ hybridization in a consecutive autopsy series (1985-July 1992). In addition, the neuropathological changes were correlated with the neurological and neuroimaging findings. Opportunistic infections included toxoplasmosis (15 cases), cytomegalovirus (CMV)-encephalitis (6), progressive multifocal leucoencephalopathy (2) and fungal infections (3). Malignant lymphomas were found in 7 patients; 6 involved primarily the CNS, one was metastatic. In 14 cases the neuropathological changes were consistent with HIV encephalitis and HIV leucoencephalopathy. Non-specific lesions occurred in 31 cases. The clinical diagnosis in patients with opportunistic diseases (n = 27) diverged in 15 cases (55%) from the underlying pathology. Toxoplasma gondii, CMV and JC viruses were identified by immunohistochemistry and in-situ hybridization on serial paraffin sections. In addition, antibodies against lymphocyte subsets, tissue macrophages, the glial fibrillary acid protein (GFAP) and myelin basic protein were used to characterize the phenotype of cells and to highlight the degree of gliosis and demyelination. Our results show that the distribution and degree of morphological changes might be helpful for the differential diagnosis antemortem. Since neurological complications may represent the first or sole manifestation of AIDS and risk factors for AIDS are often not known, it should be taken into account that CNS manifestations of AIDS may contribute to a sudden and unexpected death or accident. Opportunistic diseases should be considered as a possible differential diagnosis in cases mimicking the clinical picture of apoplexia or dementia. Furthermore, CNS lesions may be detected postmortem in patients who were not known to suffer from Neuro-Aids during life, indicating that CNS involvement is more widespread than assumed.

Mitochondrial myopathies with necrotizing encephalopathy of the Leigh type.

Two patients with mitochondrial encephalomyopathy (MEP) serve to emphasize the variability of this group of diseases. Cerebral insults, mitochondrial cardiopathy, relapsing ileus, cerebral angioma, ataxia, and myoclonic seizures characterized the first case of an adult man with similar diseases in his family, interpreted as transitional form between mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and myoclonus epilepsy associated with ragged red fibers (MERRF). The second patient, a floppy infant with cardiomyopathy and myoclonism, statomotoric and mental retardation showed combined defects in mitochondrial respiratory chain at NADH-CoQ reductase and cytochrome c oxidase and a deficiency of carnitine. In both patients neuropathologically criteria of Leigh's syndrome could be demonstrated in the cerebral cortex, in case 2 also clinically. The classificatory problems of the relationships between KSS, MELAS, MERRF, Leigh's as well as Alpers' syndromes are discussed.

Interstitial fluid of isolated perfused rat hearts: glucose and lactate concentration.

Interstitial fluid (IF) emerging at the ventricular surface of isolated perfused rat hearts was collected and assayed for rate of production, protein content, glucose and lactate concentration. The influence of four perfusion media was investigated during an experimental period of 150 min: Krebs-Henseleit solution (KH) containing glucose (5.5 mM); KH containing glucose and pyruvate (2 mM); Hypoxic KH (20% O2), substrates as 2; KH containing isoprenaline (8 X 10(-9) M), substrates as 2. Interstitial fluid was produced at a rate of 20 to 100 microliters/min/gww and contained proteins (0.5 to 3 g/l). Interstitial glucose concentration was lower than venous concentration by up to 50%. Interstitial lactate concentration was higher by up to 600%. Permeability X surface area products of glucose calculated from transcapillary concentration differences and transfer rates were different depending on experimental conditions, but were within the rather large range of P X S values for molecules of similar size obtained by other authors. Those of lactate were higher by a factor of 3 to 9 and can be interpreted to be influenced by the metabolic activity of the endothelium. The results demonstrate that interstitial substrate concentration can differ very markedly from intravascular concentration and cannot be estimated reliably without assay of the interstitial fluid. Capillary permeability seems to be variable under the experimental conditions of this study.

Barriers in cardiac substrate supply.

The capillary wall, due to its diffusional resistance, causes concentration differences between the vascular space and the interstitial space for substances which are released or taken up by the heart. Estimation of capillary transfer and interstitial concentration in isolated hearts, however, indicates a variable diffusional resistance, which in the case of glucose results from an insulin dependent transfer mechanism and in the case of lactate from a dependence of lactate transfer on lactate concentration or direction of transfer. Due to the unpredictable interstitial concentration investigation of sarcolemmal transfer appears to be possible at present only with isolated cardiac myocytes. Sarcolemmal transfer was studied for glucose and lactate. Recent investigations of lactate transfer revealed saturation kinetics, dependence on pyruvate (inhibition at low lactate concentration and enhancement at high lactate concentration) and dependence on pH (linear increase with lowered pH [8.0 to 6.7]).