Case studies in cerebral anoxia. I. Cerebral changes incident to hyperinsulinism (hypoglycemia).
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BACKGROUND AND PURPOSE: Diffuse cerebral anoxia is a devastating event, and its acute findings, as revealed by conventional MR imaging and CT scanning, may be subtle. We analyzed diffusion-weighted and conventional MR images of patients with diffuse cerebral anoxia to determine their usefulness in establishing the diagnosis during the acute period and in determining the age of insult. METHODS: We reviewed 11 MR imaging studies of 10 patients who had experienced prolonged cardiac arrest. All of the patients underwent echo-planar diffusion-weighted imaging with low- and high-strength B values and multiplanar unenhanced MR imaging. We considered bright areas on the high-strength diffusion-weighted images to be abnormal when compared with low-strength images. Special attention was given to the cortex, basal ganglia, thalami, hippocampi, cerebellum, and white matter. Conventional MR studies also were reviewed, and abnormalities noted. The medical records of all of the patients were reviewed. RESULTS: Four patients who underwent imaging during the acute period (<24 hours) had bright basal ganglia (n = 2), bright cerebellum (n = 3), and bright cortex (n = 1) shown on their diffusion-weighted images. For these patients, conventional MR images showed questionable increased T2-weighted signal intensity in the basal ganglia (n = 1), and the results of two studies were judged to be normal. During the early subacute period (24 hours-13 days), four patients were studied, and were determined to have an abnormal cortex (n = 3) and basal ganglia (n = 2). For two of these patients, conventional MR images showed similar abnormalities, and the results of one study were normal. For two patients who underwent imaging during the late subacute period (14-20 days), diffusion-weighted images showed abnormalities mostly confined to white matter. Two patients who underwent imaging during the chronic phase (>21 days) had normal results of their diffusion-weighted imaging and one had evidence of laminar necrosis revealed by conventional MR imaging. CONCLUSION: During the acute period, high-strength diffusion-weighted images showed the abnormal basal ganglia, cerebellum, and cortex to a better extent than did conventional MR images. During the early subacute period, gray matter abnormalities were seen on diffusion-weighted images. During the late subacute period, diffusion-weighted images showed mostly white matter abnormalities. During the chronic stage, the results of diffusion-weighted imaging were normal. Our findings suggest that diffusion-weighted images are helpful for evaluating and dating diffuse cerebral anoxia, and therefore aid in the determination of prognosis and management of these patients.
OBJECTIVES: To describe the sequelae of cerebral anoxia following out-of-hospital cardiac arrest, to study the functional outcome and to seek a link between the acute stage and the disability. METHOD: A retrospective study was performed. The initial findings and the neurological and neuropsychological status are recorded of 12 patients admitted to the rehabilitation unit for after-effects of cerebral anoxia following out-of-hospital cardiac arrest. RESULTS: After clinical and neuropsychological assessment, all patients displayed cognitive impairment. Two groups of patients appeared: seven patients were severely disabled with a dysexecutive and behavioural frontal lobe syndrome and memory deficit; five out of the seven also presented an extra-pyramidal syndrome; the other five patients presented behavioural dysfunction related to frontal lobe disorder but were independent in daily life activities. No correlation was found between the acute stage data and the outcome. CONCLUSION: Neurological and neuropsychological impairment after cerebral anoxia may be severe but seems difficult to predict. A dysexecutive syndrome was noted in all 12 patients.
Three victims of severe cerebral anoxia developed the apallic syndrome, and clinical neurophysiological examinations documented slow evolution of a diurnal behavior pattern. Marked EEG attenuation was the primary finding, but all the patients exhibited clustering of quiescent periods at night, during which EEG waves were generated, and two stages suggested REM and non-REM sleep. The results seemed to confirm the notions that brain-stem mechanisms control occurrence of REM and non-REM sleep, and that forebrain mechanisms are required for development of differential EEG features of non-REM sleep stages (I through IV). It is also suggested that an extreme degree of attenuation resulting from EEG desynchronization in certain patients may closely resemble ECS.
Phosphorylation of nuclear protein was investigated in cerebral anoxia up to 30 min with rabbit brain and in cerebral ischemia up to 6 h with gerbil brain in vitro. Isolated nuclei were incubated in the presence of [gamma-32P]ATP and were then fractionated into the NaCl-soluble, HCl-soluble, and phenol-soluble protein fraction. Each protein fraction was further separated by gel electrophoresis, and profiles of 32P incorporation were evaluated in these pathophysiological conditions. 32P incorporation of the acidic phenol-soluble nonhistone chromatin protein became significantly suppressed in cerebral anoxia after 15 min, and there were decreases of 32P incorporation in protein with high molecular weight and increase in protein with low molecular weight on gel electrophoresis. With gerbil brain nuclei, 32P incorporation into the NaCl-soluble and HCl-soluble fraction was increased without significant decrease in the phenol-soluble fraction after an ischemic period of 3 h. However, further separation of the phenol-soluble fraction demonstrated decrease of 32P incorporation in protein with high molecular weight and increase in protein with low molecular weight. At present, the significance of these findings, particularly in relation to chromatin template activity or irreversibility of these pathophysiological conditions, is not clear.
The protective effect of 1-[2-(2-chlorobenzoyl)-4-nitrophenyl]-2-(diethylaminomethyl) imidazole fumarate (Y-9179) against cerebral anoxia was investigated with a variety of experimental models in mice and rats. Y-9179, at doses lower than 1 mg/kg, showed a consistent protective action against the cerebral anoxia in all of the models studied: hypoxia, ischemia, histotoxic and asphyxic anoxia. The antianoxic activity of Y-9179 was found to be about 100 times greater than that of pentobarbital. This anti-anoxic effect was observed at very small doses at which neither sedation nor motor depression was induced. There was no decrease in the protective effect or no adverse effect even at as high a dose as 30 mg/kg, which corresponded to about 150 times the effective dose. The universal anti-anoxic properties of Y-9179 may be useful both clinically and as a pharmacological tool to elucidate the physiological significance of cerebral anoxia.
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BACKGROUND AND PURPOSE: Early and accurate detection of global cerebral anoxia is important for determination of prognosis and further management. We evaluated whether accuracy in early detection of global cerebral anoxia was improved by high-b-value diffusion-weighted imaging (DWI) with long echo time (TE). METHODS: Routine DWI (b = 1000 s/mm(2); TE = 139 ms), high-b-value DWI (b = 3000 s/mm(2); TE = 190 ms), T2-weighted imaging (T2WI), and fluid-attenuated inversion recovery (FLAIR) imaging were acquired in six patients who experienced cardiopulmonary arrest within 24 hours and six volunteers. Region of interest-based analysis was performed. Regions of interest of patients showing significant decrease in apparent diffusion coefficient (ADC) values than volunteers were considered abnormal. Three neuroradiologists independently assessed images of the patients for conspicuity of hyperintensity within regions of interest. Receiver operating characteristic (ROC) analysis was performed, and the area under the curve (Az) was compared among sequences and observers. Average contrast and contrast-to-noise ratios between abnormal regions of interest and regions of interest of normal surrounding parenchyma were calculated. RESULTS: For all observers, high-b-value DWIs achieved the largest Az, and FLAIR imaging the lowest Az. Az of routine DWI and T2WI were between these values. High-b-value DWI and FLAIR imaging showed no significant interobserver variation in Az, whereas routine DWI and T2WI did. High-b-value DWI also achieved the largest contrast and contrast-to-noise ratios. CONCLUSION: High-b-value DWI with long TE improved accuracy in early detection of global cerebral anoxia. Application of the sequence would facilitate early diagnosis.
To investigate mechanisms of cerebral anoxia tolerance, cerebrocortical intracellular calcium ([Ca2+]i) and pH (pHi) regulation were compared in turtles (Trachemys scripta) and laboratory rats. [Ca2+]i and pHi in living 200 to 300-microns-thick cortical brain slices were measured with the fluorescent indicators fura-2/acetoxymethyl ester (AM) and 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein during exposure to anoxia. Within 5 min, [Ca2+]i increased to > 1,000 nM in rat brain slices exposed to anoxia but [Ca2+]i was normal even after 5 h of anoxia in turtles. ATP levels remained normal in anoxic turtle brain but fell rapidly in rats. During anoxia, pHi fell by 0.25 +/- 0.08 pH units in rats but only 0.10 +/- 0.04 in turtles (P < 0.05). Inhibition of glycolysis in anoxic turtle brain with iodoacetate resulted in large increases in [Ca2+]i but prior exposure of slices to anoxia resulted in greatly attenuated calcium entry. The reduction in calcium flux was greater with increasing exposure to anoxia, suggesting progressive arrest of calcium channel activity. Tolerance of cerebral anoxia in turtles may be related to anaerobic ATP production, arrest of calcium channels, and attenuation of changes in pHi.
In 30 patients, who were all comatose as a result of cerebral anoxia after cardiac arrest, at least one EEG with activity in the alpha frequency range was recorded. Regionally the activity of the above mentioned characteristic was often diffusely distributed or most pronounced occipitally, whereas a tendency to affect other regions was rarely observed. In 50% of the patients, where more than one EEG was recorded, the 'alpha' rhythm was still present in the following record. Only one of the patients survived, and even so, with considerable mental defects. In 4 patients the level of consciousness improved, but 3 of them never reached a definite level of cortical function and died as a result of cerebral anoxia.
The protective effects of DM-9384 [N-(2,6-dimethylphenyl)-2-(2-oxo- 1-pyrrolidinyl) acetamide] against cerebral anoxia were investigated using various animal models. Oral administration of DM-9384 resulted in a significant prolongation of survival time in mice and rats subjected to the normobaric hypoxia; its minimal effective doses were 30 and 10 mg/kg, respectively. A significant protection by this drug against hypobaric hypoxia, histotoxic anoxia and cerebral ischemia also occurred in mice at a dose of 100 mg/kg, p.o. Bifemelane (100-300 mg/kg, p.o.) was protective against these models except for hypobaric hypoxia, and the effects of piracetam, aniracetam and pramiracetam (1000 mg/kg, p.o.) were variable depending on the type of anoxia model used. DM-9384 (100 mg/kg and lower) attenuated the hypolocomotion and the disturbance of cerebral energy metabolism such as a decrease in ATP, an increase in lactate and lactate/pyruvate ratio induced by hypoxia in rats. The spontaneous motor activity, uptake and utilization of brain glucose in normal animals, however, were not influenced by this drug. Based on these results, DM-9384 is characterized as a broad spectrum anti-anoxic drug with negligible CNS depression, and the cerebral protective effect of this drug may be, at least in part, attributable to its ability to improve the cerebral energy metabolic disturbance.
The effects of scymnol, chimaerol and sodium scymnol sulfate, prepared from the bile of Rhizoprionodon acutus, on cerebral anoxia were investigated in experimental models of hypoxia, ischemia and histotoxic anoxia in mice. Scymnol, at a dose of 100 mg/kg, showed a significant protective action against cerebral anoxia in all of the models studied and significantly increased the partial oxygen pressure of the arterial blood. The anti-anoxic activity of scymnol was found to be slightly greater than that of idevenone. A similar protective effect of sodium scymnol sulfate was seen at doses higher than 100 mg/kg. The survival time on hypoxia was significantly prolonged in the animals pretreated with chimaerol.
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Protective effects of OP-2507 [15-cis-(4-propylcyclohexyl)-16,17,18,19,20-pentanor-9-deoxy -9 alpha, 6-nitrilo-PGF1 methyl ester] against cerebral anoxia and edema were investigated in a variety of experimental models in mice and rats. OP-2507 given s.c. or p.o. led to a consistent and dose-dependent prolongation of survival time against cerebral anoxia in hypobaric and normobaric hypoxia, KCN-induced anoxia and decapitation-induced gasping. Furthermore, treatment with 0.03-0.1 mg/kg s.c. or 0.3 mg/kg p.o. of OP-2507 was found to be effective against the changes of cerebral energy metabolites and cyclic nucleotides in hypoxic brain. In brain ischemia induced by bilateral ligation of common carotid arteries of rats, a reduction in specific gravity of cortex and an increase in water content of brain were observed, in accordance with changes of cerebral energy metabolites. These edematous and biochemical changes were prevented by the treatment with 0.01-0.03 mg/kg s.c. of OP-2507. These results indicate a potential usefulness of OP-2507 in protecting the brain from oxygen insufficiency resulting from cerebral ischemia.
The periodicity of paroxysmal wave complexes in EEG after acute cerebral anoxia with special reference to the dynamics of period duration (alteration of Zeitmass) is described in case 20 hours before isoelectric tracing. The completely asynchronous feature of paroxysmal events within certain limits of period duration in both hemispheres is a rare condition. Late and pure cortical electrogenesis is suggested. Short and long EEG- periods in similar and different pathological processes and functional states are compared with respect to topography of lesions. Subcortical interactions and extraneuronal influences upon periodicty are discussed. The parameters "complex wave and periodicity" in EEG and the dynamics respectively are a matter of serial investigations for better understanding pathophysiology and prognostic value.
The protective effect of Hachimi-jio-gan (HJ) against cerebral anoxia was investigated with various experimental models in mice. Minimal effective dose of HJ which significantly prolonged the survival time was 0.5 g/kg, p.o. for normobaric hypoxia and 0.5 g/kg, p.o. for KCN- (4 mg/kg, i.v.) induced anoxia. HJ reduced the duration of coma induced by a sublethal dose of KCN (1.8 mg/kg, i.v.) in a dose-dependent manner. Furthermore HJ potentiated the anti-anoxic effect of physostigmine and the effect of HJ was diminished by the treatment with atropine.
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