Cerebral microemboli and cognitive impairment.

Transcranial Doppler Ultrasound (TCD) may be used to detect cerebral microemboli in patient groups with an increased stroke risk and during invasive cardiovascular examinations and operations. Although these microemboli do not cause immediate symptoms, there is growing evidence which suggests that they may cause cognitive impairment if they enter the cerebral circulation in significant numbers. This has been studied in detail in patients who have had coronary artery bypass surgery. In these patients, an association has been found between the number of intraoperative cerebral microemboli detected by transcranial Doppler and postoperative neuropsychological outcome. It is also possible that cerebral microemboli may be the cause of cognitive impairment in patients with cerebrovascular disease. Cerebral microemboli are often found in patients with atherosclerosis, especially of the carotid arteries and aortic arch, and in patients with heart disease. There is also an increased risk for silent strokes and cognitive impairment in these patients. Prospective clinical studies are therefore required to determine if continuous cerebral microembolization to the brain will lead to progressive cognitive impairment.

Deficits of motor intention following parietal lesions.

Patients with lesions to the right parietal lobe were tested on their ability to reach to targets, or to respond verbally to targets. The targets occurred at the same two spatial locations--to the left and right of the patient--with the task being cued by the color of the target. Patients were able to perform both tasks separately rapidly and without error. However, when the two tasks were interleaved, they had difficulty making a response in the left (contralesional) field when this was different to a response that they had just made. These results suggest that lesions to the parietal cortex may cause a deficit in the coding for motor intention, as well as attention in the contralesional field.

Utilities for major stroke: results from a survey of preferences among persons at increased risk for stroke.

BACKGROUND: Patient beliefs, values, and preferences are crucial to decisions involving health care. In a large sample of persons at increased risk for stroke, we examined attitudes toward hypothetical major stroke. METHODS AND RESULTS: Respondents were obtained from the Academic Medical Center Consortium (n = 621), the Cardiovascular Health Study (n = 321 ), and United Health Care (n = 319). Preferences were primarily assessed by using the time trade off (TTO). Although major stroke is generally considered an undesirable event (mean TTO = 0.30), responses were varied: although 45% of respondents considered major stroke to be a worse outcome than death, 15% were willing to trade off little or no survival to avoid a major stroke. CONCLUSIONS: Providers should speak directly with patients about beliefs, values, and preferences. Stroke-related interventions, even those with a high price or less than dramatic clinical benefits, are likely to be cost-effective if they prevent an outcome (major stroke) that is so undesirable.

Neuropsychological deficits in asymptomatic atrial fibrillation.

OBJECTIVE: To assess the preclinical effects on cognitive functions of nonrheumatic atrial fibrillation (NRAF) in patients with negative history for cerebrovascular disease. MATERIALS AND METHODS: The study included 37 consecutive patients with chronic (n=16, mean age 65.3+/-6.6 years) or paroxysmal (n=21, mean age 58.3+/-9.5 years) NRAF and an equal number of control subjects in sinus rhythm, who were matched for age, education and presence of hypertension. A comprehensive neuropsychological battery including tests of attention, memory, language and visuospatial skills was administered. RESULTS: Patients with chronic NRAF showed significantly poorer performances in tasks exploring attention and verbal memory functions, while the paroxysmal group was significantly impaired in a long-term memory task. The neuropsychological findings were confirmed excluding from both groups patients with CT evidence of cerebrovascular damage. A small subgroup of patients was also submitted to cerebral MRI. CONCLUSION: Neurologically asymptomatic NRAF is related to a subclinical but significant impairment in attention and memory. These deficits could be produced by minor ischemic lesions due to microembolization, or by diffuse hypoxic damage due to hypoperfusion.

[Treatment of patients with thromboses of the basilar artery and locked-in syndrome. An ethical dilemma]. / Die Behandlung von Patienten mit Thrombosen der Arteria basilaris und Locked-in-Syndrom. Ein ethisches Dilemma.

Decisions regarding the extent of treatment of severely ill patients can be an ethical dilemma when life-prolonging intensive care contradicts the goal of avoiding unnecessary suffering on the part of the patient. Here we present the results of a written survey of physicians on neurological intensive care units in Germany regarding the treatment of patients with basilar artery thrombosis and locked-in syndrome. 52% of the 93 physicians who replied advocated not treating severe infections with antibiotics, 38% were in favor of stopping intensive care. In contrast, 55% recommended intubating the patient in the presence of swallowing disturbances and imminent aspiration. 58% were in favor of discussing these problems in detail with the patient, and 87% advocated discussing them with relatives. Nearly all physicians (97%) recommended using adequate amounts of opiates and benzodiazepines. In very rare cases, 99% would agree to the use of passive euthanasia and 19% to active euthanasia. These findings illustrate the current disagreement on some of the important treatment decisions among physicians on neurological intensive care units. An open exchange of views on these questions could facilitate the appropriate consideration of ethical matters in the treatment of these patients.

Effect of ischemic cerebral volume changes on behavior.

Ischemia causes long-term effects on brain volume and neurologic function but the relationship between the two is poorly characterized. We studied the relationships between brain volume and three measures of rodent behavior after cerebral ischemia was induced by injecting several thousand microspheres into the internal carotid arteries of rats. Forty eight hours later, each subject was rated using a global neurologic rating scale. Several weeks later, the subjects were tested for open field activity and visual spatial learning. Post-mortem we measured the volume of the cerebral hemispheres and estimated the volume densities of cortex, white matter, hippocampus, basal ganglia, thalamus, ventricle, and visible infarction. Ischemia caused significant impairment, as measured by the global rating scale; the probability of an abnormal rating was correlated with the number of microspheres trapped in the brains. Visual spatial learning was significantly impaired by ischemia, but this deficit was independent of the count of microspheres, whether the subject was abnormal at 48 h, and whether the left or right hemisphere was embolized. Cerebral hemisphere volume was reduced from 430 mm3 to 376 mm3 (P < 0.05). The cortex was reduced from 22 to 19% of cerebrum (P < 0.05) and the white matter compartment was reduced to similar degree. The lesion volume was 6% of cerebrum, comparable to that seen with other ischemia methods. The global outcome rating was significantly related to total cerebral volume, but not to volume changes in any single compartment. On the other hand, visual spatial learning was significantly influenced by volume changes in the cortex and white matter, but not by the topography of the visible infarctions. Open field activity was not altered by infarction. Our data suggests that the total volume of brain tissue lost to infarction may partially determine global neurological rating independently of the topography of the volume loss. Integrative functions such as learning may depend more on the integrity of specific compartments and less on the total volume of intact brain. The volume of visible cystic infarction was not related to long term behavioral outcome. These results should be confirmed using another method of inducing ischemia.

Failure in learning task and loss of cortical cholingergic fibers in microsphere-embolized rats.

The present study was undertaken to elucidate the pathological changes in learning and memory functions and in the metabolism of cortical cholinergic neurons following microsphere embolism in the rat. Microspheres (48 microm) were injected into the right internal carotid artery of rats. Learning and memory functions were measured 7 or more days after the embolism by active and passive avoidance, and water maze tasks. In the biochemical study, cortical acetylcholine and choline contents, and choline acetyltransferase activity were measured. Cortical acetylcholinesterase-containing fibers were quantitatively estimated in the embolized rat. The active and passive avoidance, and water maze tasks were impaired in the microsphere-embolized rat. In the histochemical study, the density of cortical acetylcholinesterase-containing fibers of the ipsilateral hemisphere of the microsphere-embolized rat was decreased, but cell density was unchanged. Furthermore, microsphere embolism decreased the cortical acetylcholine concentration and choline acetyltransferase activity and increased the choline concentration. The results suggest that microsphere embolism causes severe damage to cortical cholinergic neurons, which may be, at least in part, related to the impairment of learning and memory functions in the sustained brain ischemia.

EEG changes during cardiopulmonary bypass surgery and postoperative neuropsychological deficit: the effect of bubble and membrane oxygenators.

OBJECTIVE: Quantitative electroencephalography was used during cardiopulmonary bypass surgery to determine the point in time of most neuronal functional change which may result in postoperative neuropsychological deficit. It was also used to determine any relationship between quantitative electroencephalography changes and type of oxygenator used in surgery. METHODS: We studied 61 coronary artery bypass graft patients. Anaesthesia included thiopental, fentanyl and N2O. Surgery was performed with hypothermic bypass (28 degrees C), arterial pressure of 50-70 mmHg, and alpha-stat, using bubble (Harvey 1700), or membrane (Cobe CML) oxygenators, both with arterial line filters (Pall 40 microns). RESULTS: The main finding was a significant increase in delta power at the end of perfusion (P < 0.01), which showed a positive association with delta power before the start of perfusion. Marked quantitative electroencephalography change at the end of perfusion was not related to systemic hypotension, temperature, type of oxygenator, bypass time, or patient age. Intraoperative quantitative electroencephalography changes found in most patients were transient and could not be related to postoperative cerebral function. However, 16 of the 18 patients who had neuropsychological deficit 2 months after surgery, also had a significant quantitative electroencephalography change at the end of perfusion. CONCLUSIONS: While no difference in anaesthetic technique was found between patients, the variation in quantitative electroencephalography power before perfusion may indicate a difference in individual response to anaesthetic. Usefulness of quantitative electroencephalography to predict postoperative cerebral functional deficit remains doubtful.

[Microembolizatoins during heart surgery under extracorporeal circulation]. / Mikroembolisation während Herzoperationen unter extrakorporaler Zirkulation.

OBJECTIVE: By means of transcranial Doppler sonography (TCD), microembolic signals (MES) representing embolic events can be registered during cardiac surgery and extracorporeal circulation in a considerable number of patients. We conducted the present study to determine the neuro-psychiatric consequences of MES. METHODS: 25 patients scheduled for elective aorto-coronary bypass grafting (ACBG; n = 10) or aortic valve replacement (AVR; n = 15) were studied pre- and postoperatively with neuropsychiatric testing. Results were related to the number of MES noted intraoperatively. In addition, we registered the intraoperative changes of middle cerebral artery blood flow velocity, mean arterial pressure, arterial blood gases, haemoglobin and haematocrit. Statistics included t-test, two-way analysis of variance, Mann-Whitney-U-test and Spearman correlation with p < 0.05 considered significant. RESULTS: Regarding demographic data and intraoperative parameters, both study groups (ACBG vs. AVR) were comparable except for age. AVR patients showed significantly more MES than those undergoing ACBG (p < 0.012) which was most pronounced in the late state of surgery (aortic clamp off; p < 0.0003). However, MES counts did not correlate with neuropsychiatric test results. CONCLUSIONS: In contrast to recent reports, we were unable to show a deterioration of postoperative neuropsychiatric state related to high intraoperative MES count in our patients. Future TCD studies should focus on the differentiation between gaseous emboli and particles even in the clinical setting, as the latter may well play a major role for the development of cerebral dysfunction following cardiac surgery and extracorporeal circulation.

Long-term prognosis in cerebral venous thrombosis. Follow-up of 77 patients.

BACKGROUND AND PURPOSE: Very little is known about the long-term outcome of patients with cerebral venous thrombosis (CVT), particularly regarding the risk of residual epilepsy and further thrombotic events. We retrospectively studied 77 patients with CVT diagnosed by angiography and/or MRI. METHODS: A cohort of 77 patients aged 18 to 77 (mean, 38.5) years with CVT, evaluated from 1975 through 1990, was followed up for a mean of 77.8 months (range, 14 to 204 months; median, 63 months). Information on death, neurological status, seizures, recurrent CVT, other thrombotic events, and subsequent pregnancies was obtained from direct observation, mail questionnaire, or telephone interviews. RESULTS: Sixty-six of 77 patients (85.7%) had no neurological sequelae during follow-up. Eleven patients (14.3%) remained neurologically impaired. Two who initially presented with isolated intracranial hypertension had blindness due to optic atrophy. The other 9 had focal signs at the time of CVT and were left with various cognitive or focal deficits. Four of 28 (14.3%) patients who had seizures at the acute stage had recurrent seizures. One of the 51 patients with lateral sinus thrombosis developed a dural arteriovenous fistula. Nine of the 77 patients (11.7%) suffered a second CVT, all but one in the first year. Noncerebral thrombotic events occurred in 11 patients (14.3%). No recurrence of CVT occurred during later pregnancies, but 1 patient had a postpartum deep vein thrombosis. CONCLUSIONS: In the present series, CVT has an essentially good long-term prognosis. The frequency of long-standing epilepsy was low, suggesting that long-term anticonvulsant treatment is not necessary in the majority of cases. A second CVT or another thrombotic episode occurred in 20% of patients, stressing the need in a minority of cases for long-term anticoagulation.

Prostacyclin analogue TTC-909 reduces memory impairment in rats with cerebral embolism.

The effects of the stable prostacyclin analogue TTC-909 on memory impairment in the water maze task and on neuronal damage were studied in rats with cerebral embolism induced by injecting polyvinyl acetate (PVA) into the right internal carotid artery and the ensuing embolism extending out into the right middle cerebral artery. Areas supplied by the lenticulostriate artery were most markedly damaged. In the water maze test, the PVA-embolized rats took longer to reach the platform than did the nontreated control rats. To some extent, repeated administrations of TTC-909 (200 ng/kg, IV) overcame this impairment in water maze learning in the rats. We assume that the vasodilating effects of TTC-909 maintain this blood supply to the ischemic area and that TTC-909 prevents the development of thrombosis around the PVA particles in the arterial capillaries, as a result of antiplatelet aggregative effects. These two mechanisms are likely to be involved in memory improvement. TTC-909 may prove effective for treating subjects with stroke and other cerebrovascular disorders.

The impact of microemboli during cardiopulmonary bypass on neuropsychological functioning.

BACKGROUND AND PURPOSE: Microemboli have been implicated in the etiology of neuropsychological deficits after cardiopulmonary bypass. This study examined the incidence of high-intensity transcranial signals (microemboli) and their relation to changes in neuropsychological performance after surgery. METHODS: Transcranial Doppler ultrasonography was used to measure middle cerebral artery blood flow velocity and detect microemboli. The number of high-intensity transcranial signals was determined and related to a neurological examination and absolute changes in neuropsychological performance as well as the number of patients considered to exhibit a neuropsychological deficit. Data were available on 100 consenting patients undergoing routine cardiopulmonary bypass. Fifty of the patients were randomly assigned to a procedure that included a 40-microns arterial line filter, and 50 had the procedure without any arterial line filter. RESULTS: Significantly more patients were found to have neuropsychological deficits in the group without the arterial line filter at both 8 days (P < .05) and 8 weeks (P < .03) after surgery. In addition, more "soft" neurological signs were found in the nonfiltered group 24 hours after surgery (P < .05). More high-intensity transcranial signals were found in the nonfiltered group, and the number of high-intensity transcranial signals was found to be related to the likelihood of a patient having a neuropsychological deficit at 8 weeks. CONCLUSIONS: These data suggest that neuropsychological deficits after routine cardiopulmonary bypass are related to the number of microemboli delivered during surgery. Furthermore, the numbers of microemboli may be reduced by including a 40-microns filter on the arterial line.

Spatial limitation of eye movements during ocular exploration of simple line drawings in neglect syndrome.

The eye movement behaviour of a patient suffering from a right basal ganglia infarction with left-sided neglect but without any visual field defects was investigated during the ocular exploration of simple line drawings. The eye movements were registered by means of an i.r. light technique. Each line drawing consisted of different figural elements located in the centre and both the left and the right half of the picture. In each case, only the contextual connection of the left and right elements in a drawing allowed the spectator to describe the whole scene consistently and to perceive the correct theme of the drawing. The drawings fell into two categories. The cognitive impact of the elements in the drawings' centre was varied by "pointing" to the elements located in the left and right halves with a different strength of connection. When exploring the two types of drawings (weak vs. strong connective elements in the centre) the patient showed a similar eye movement pattern, exploring exclusively the right halves of the drawings. Irrespective of the cognitive impact of the drawing's central elements in "pointing" towards supplementary information in the picture's left half, exploration of this half took place in neither case. A striking difference between the two categories was, however, found concerning the patient's ability to recognize the general context, i.e. to describe the correct theme of the whole drawing. While the patient could not correctly depict any of the scenes from the drawings with weak connective elements in the centre, he was easily capable of properly describing the themes from the group of drawings with strong connective elements, which implies that he must have analysed and perceived the figural elements of both halves of the picture. Different possibilities are discussed to explain the similarity of the patient's exploratory eye movements but discrepancy in his verbal responses when dealing with the two different types of drawings.

Improvement of impaired brain monoamine metabolism by the cognition-enhancing agent nefiracetam after microsphere-induced cerebral embolism in rats.

Nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide DM-9384, CAS 77191-36-7), a pyrrolidone (cyclic GABA) derivative, is a newly developed cognition-enhancing (nootropic) agent. In the present study, the effects of nefiracetam on cerebral monoamine metabolism in rats after microsphere-induced cerebral embolism have been examined. For cerebral embolization, microspheres were injected into the left internal carotid artery. Nefiracetam (3, 10 and 30 mg/kg p.o.) was administered daily to the animals for 13 days from the 9th day after the operation. The levels of DA, DOPAC and HVA in the control (embolism-induced, but untreated) group were significantly decreased compared with those of the normal (non-operated) group. In animals treated with nefiracetam (3 mg/kg p.o.), these monoamine levels were higher than controls in the cortex and hippocampus, whereas they were not significantly changed in the striatum. 5-HT contents in the control group significantly decreased from normal levels in the cortex and hippocampus, on which nefiracetam at various doses had no effect. The levels of 5-HIAA in the control group also decreased, which were, however, significantly increased by 3 mg/kg of nefiracetam. The results suggest that nefiracetam has improving actions on the dysfunction of the dopaminergic and serotonergic systems induced by cerebral embolism.

Recovery of sensorimotor function after distal middle cerebral artery photothrombotic occlusion in rats.

BACKGROUND AND PURPOSE: The purpose of the present study was to delineate the behavioral correlates of focal thrombotic occlusion of the distal middle cerebral artery in rats and to compare the pattern of deficits and subsequent recovery to that following proximal middle cerebral artery occlusion. METHODS: Ten Sprague-Dawley rats underwent photothrombotic occlusion of the distal middle cerebral artery with tandem occlusion of the common carotid arteries (dMCAO group); 10 animals served as operated controls. Beginning on postischemia day 2, animals were given a battery of five tests that assessed sensorimotor integration, attentional mechanisms, and muscle strength; testing continued twice weekly until day 30. Nine days of cognitive testing on the learning set of the water maze task were then given. Infarct volume and hemispheric atrophy were determined for each dMCAO animal. RESULTS: After ischemia, the dMCAO group exhibited significant behavioral deficits in posture reflex, ability to place a forelimb to various stimuli, limb adduction during rearing, and neglect of contralateral space. These deficits showed variable recovery rates. No deficits were observed in muscle strength or cognitive performance. The deficits and patterns of recovery were related to infarct location and to degree of hemisphere atrophy. CONCLUSIONS: The present study suggests that a battery of tests is necessary to fully characterize the pattern of behavioral deficits after focal cerebral ischemia. Location of infarct damage and associated degree of hemispheric atrophy were important variables in determining behavioral outcome. The present results are compared with those of the more traditional model of electrocoagulation of the proximal middle cerebral artery.

A case of word deafness with preserved span: implications for the structure and function of short-term memory.

Case IJ shows impaired capacity to repeat individual words despite normal hearing as measured by audiometry and tympanometry. She also has difficulty in identifying other environmental sounds. Her phonological memory span for visually-presented material is normal, and her memory span for spoken digits is only slightly impaired. It is suggested that she has a pre-phonological auditory processing deficit; the implications of this for discussion of the role of phonological short-term memory in language processing are discussed.

Phenomenological comparisons of major depression following stroke, myocardial infarction or spinal cord lesions.

Patients with major depression admitted to hospital with acute stroke (n = 44), acute myocardial infarction (n = 25), or acute spinal cord injury (n = 12) were examined for differences in their phenomenological presentation of major depression. Depressed stroke patients were found to have significantly higher scores on the syndrome clusters for generalized anxiety and ideas of reference than depressed cardiac or spinal cord injury patients. In addition, significantly more stroke patients met diagnostic criteria for generalized anxiety disorder compared with the other two groups. Although spinal cord injury patients were younger, more likely to be treated with benzodiazepines, and less likely to be treated with beta-blockers, none of these factors distinguished stroke patients with anxious depression from stroke patients with depression only. These findings are consistent with the hypothesis that the etiology of depression following stroke may be different from that associated with myocardial infarction or spinal cord injury.

Mechanisms for accessing lexical representations for output: evidence from a category-specific semantic deficit.

We report the performance of a neurologically impaired patient, JJ, whose oral reading of words exceeded his naming and comprehension performance for the same words--a pattern of performance that has been previously presented as evidence for "direct, nonsemantic, lexical" routes to output in reading. However, detailed analyses of JJ's reading and comprehension revealed two results that do not follow directly from the "direct route" hypothesis: (1) He accurately read aloud all orthophonologically regular words and just those irregular words for which he demonstrated some comprehension (as indicated by correct responses or within-category semantic errors in naming and comprehension tasks); and (2) his reading errors on words that were not comprehended at all (but were recognized as words) were phonologically plausible (e.g., soot read as "suit"). We account for these results by proposing that preserved sublexical mechanisms for converting print to sound, together with partially preserved semantic information, serve to mediate the activation of representations in the phonological output lexicon in the task of reading aloud. We present similar arguments for postulating an interaction between sublexical mechanisms and lexical output components of the spelling process.

Depression after stroke: the importance of cerebral hemisphere asymmetries.

The pattern of brain asymmetries was visualized on computed tomography (CT) scan in patients with a single acute cerebrovascular lesion. Patients were divided into those with typical or reversed frontal and/or occipital asymmetries. Among patients with a typical occipital asymmetry, those with left frontal or left basal ganglia lesions showed a significantly higher frequency of major depression and significantly higher depression scores than patients with similar lesion location but with reversed occipital asymmetry or those with a typical asymmetry and lesions in other (left or right) brain areas. Among patients with a reversed occipital asymmetry, there was no significant association between left frontal or left basal ganglia lesions and depression. This study demonstrates that the previously reported significant association between post-stroke major depression and lesion location is restricted to patients with a typical occipital asymmetry and is not present in patients with a reversed occipital asymmetry.

[Anterior cerebral artery occlusion clinical analysis of 27 self-experienced cases].

From the years 1977 through 1989, the author experienced 27 cases with only anterior cerebral artery (ACA) occlusion but without any other main cerebral arterial occlusions. These were proven by cerebral angiographies and verified by CT. Two patients showing large infarction in the left frontal lobe on CT but showing no evidence of arterial occlusion by cerebral angiography were also registered in this study because these patients were thought to have recanalized ACA. There were 15 males and 12 females with an age of 61.5 +/- 7.98 (mean +/- SD) and 66.1 +/- 6.45, respectively. Twenty two cases had cerebral thrombosis and 5 had cerebral embolism. There were 4 cases with bilateral ACA occlusions, 8 with right ACA occlusion and 15 with left ACA occlusion. Twenty two patients (81%) were alert on admission and this fact might explain their excellent ADL on discharge: full recovery in 9 patients (33%) and self-management in 12 patients (44%). Seventeen patients (63%) had a CT-proven infarcted area with a correlation to ACA occlusion (s), while 9 patients (33%) showed no correlation between an infarction on CT and an ACA occlusion. One patient showed no abnormal findings on CT. Four patients with right ACA occlusion were incidentally observed, even though their mode of onset was strokes. The symptoms of the other 23 patients were those of anterior cerebral artery syndromes: hemiparesis (74%), urinary incontinence (39%), forced grasping (39%), mutism (30%), indifference (26%) and apraxia (22%) etc.