Efficacy of camptothecin in progressive multifocal leucoencephalopathy.
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Adult↗
Biomedical subjects
E B Ringelstein
Publications and source records attributed to E B Ringelstein.
Features, symptoms, and neurophysiological findings in stroke associated with hyperhomocysteinemia.
BACKGROUND: Hyperhomocysteinemia has been shown to be a mild independent risk factor for premature atherosclerosis, and there is evidence of an increased rate of peripheral vascular occlusive disease, myocardial infarction, and stroke. OBJECTIVE: To evaluate clinical, biochemical, and neurophysiological findings in patients with ischemic stroke with and without hyperhomocysteinemia. SUBJECTS: One hundred twenty-five consecutive patients with a history of stroke and 60 healthy control subjects. METHODS: Patients were divided into those with and those without hyperhomocysteinemia, which was defined as blood levels beyond the mean total plasma homocysteine level plus 2 SDs of the healthy control group. History, symptoms, cause, patterns of infarction, biochemical data, continuous and transcranial Doppler sonography, and event-related potentials were recorded in all patients. RESULTS: Twenty-seven patients had hyperhomocysteinemia. Compared with the 98 patients without hyperhomocysteinemia, they had an increased rate of hypertension (odds ratio, 3.5; 95% confidence interval, 1.0-12.6), an increased level of uric acid (P < .007), an increased hematocrit (P < .02), a higher rate of microangiopathy (odds ratio, 2.8; 95% confidence interval, 1.1-7.2), and a trend to a higher rate of multiple infarction. Furthermore, the P3 latency of the event-related potential was significantly increased in hyperhomocysteinemia (P < .004). CONCLUSIONS: Hyperhomocysteinemia is probably an independent risk factor for stroke, with a prevalence of about 20% in all patients with a history of stroke; however, additional factors (eg, hypertension, hyperuricemia) may have an enhancing effect. There are significant differences in stroke patterns between patients with and without hyperhomocysteinemia, with a higher rate of lesions typical of cerebral microangiopathy and a trend to multiple infarctions in the former. Impairment of cognitive processing as measured by visual event-related potential is more pronounced in hyperhomocysteinemia.
Adult↗
Regional cerebral blood flow increases during preparation for and processing of sensory stimuli.
Preparing for and processing of sensory stimuli are energy-requiring processes. We attempted to assess the relative contributions of these processes to increases in regional cerebral perfusion. Nineteen healthy right-handed subjects were examined while they were engaged in detecting tactile stimuli to the index finger 5 s after a cueing tone. Cerebral blood flow velocity (CBFV) modulations in the middle cerebral arteries (MCAs) were continuously measured by bilateral simultaneous transcranial Doppler ultrasonography. Tactile stimuli well above threshold per se did not produce a significant, relative CBFV increase in the contralateral MCA. However, when subjects were expecting a threshold tactile stimulus, there was a significant regional increase in CBFV in the hemisphere contralateral to the attended index finger for approximately 15 s, starting within the first seconds after the cueing. This increase was present even before the tactile stimulus was applied and also in sessions when the stimulus was omitted. We conclude that preparation of the cortex causes a stronger regional cerebral blood flow increase than the processing of the tactile stimulus itself.
Adult↗
[Prolonged muscle weakness in intensive care patients with special attention to the so-called intensive care polyneuromyopathy].
Generalized muscle weakness in critically ill patients can result in prolonged periods of artificial ventilation and longer stays in the intensive care unit. Both neuropathic (critical illness polyneuropathy) and myopathic (critical illness myopathy) abnormalities seem to play an important role for this prolonged weakness. This article reviews its complex differential diagnosis with special emphasis on the current understanding of the neuromuscular syndromes. An efficient diagnostic plan is necessary for the exclusion of other curable causes of prolonged muscle weakness even in the presence of polyneuromyopathic changes. Psychological support of the patient and prophylaxis of secondary complications of prolonged immobilization are crucial when specific therapy is not possible.
Critical Care↗
Refinement of the hereditary neuralgic amyotrophy (HNA) locus to chromosome 17q24-q25.
Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant, recurrent focal neuropathy characterized by episodes of painful brachial plexus neuropathy with muscle weakness and atrophy, as well as sensory disturbances. Single episodes are commonly preceded by unspecific infections or immunization, or are associated with parturition. Minor facial dysmorphic features are present in some pedigrees but do not clearly segregate with the disease. To confirm the recently described HNA locus on distal chromosome 17q, we performed a genetic linkage study in an extended Turkish pedigree. We were able to refine the HNA locus on chromosome 17q24-q25 in a 16-cM region.
Brachial Plexus Neuritis↗
Oxygen inhalation can differentiate gaseous from nongaseous microemboli detected by transcranial Doppler ultrasound.
BACKGROUND AND PURPOSE: Clinically silent circulating microemboli can be detected by transcranial Doppler sonography. The composition of these emboli in different clinical conditions is unclear. METHODS: We performed 1-hour transcranial Doppler sonographic recordings from the middle cerebral or posterior cerebral artery in 20 patients with mechanical prosthetic heart valves, in 78 patients with an arterial embolic source, and in 20 control subjects. During 30 minutes of this recording, the patients inspired room air and 6 L of oxygen per minute via a loosely fitting facial mask; during the remaining 30 minutes, they breathed room air only. RESULTS: There was a significant decline of embolic signals (ES) under oxygen in the patients with mechanical prosthetic cardiac valves (144 ES without oxygen versus 63 ES with oxygen; P = .002) but not in the patients with arterial embolic sources (145 ES without oxygen versus 135 ES with oxygen; P = NS). In the control subjects, no ES were found. CONCLUSIONS: ES in patients with mechanical prosthetic cardiac valves correspond mainly to gas bubbles. Oxygen inhibits the cavitation process of mechanical prosthetic heart valves or speeds up redissolution of gas bubbles generated by cavitation. In contrast, solid microemboli originating from thrombus or atheroma cannot be suppressed by oxygen inhalation. This simple method of oxygen inhalation should help to clarify the composition of microemboli in various clinical and experimental settings.
Administration, Inhalation↗
Spontaneous oscillations in cerebral blood flow velocities in middle cerebral arteries in control subjects and patients with epilepsy.
BACKGROUND AND PURPOSE: Cardiac arrhythmias mediated by the sympathetic nervous system have been implicated in sudden, unexplained deaths in patients with epilepsy. Cerebral blood flow velocities (CBFV) as measured by transcranial Doppler are characterized by slow spontaneous oscillations in part attributed to changes in sympathetic activity (M waves, 3 to 9 cycles per minute) and to discharges of monoaminergic neurons in the brain stem (B waves, 0.5 to 2 cycles per minute). This study was designed to compare spontaneous fluctuations of CBFV in patients with epilepsy with those in normal control subjects. METHODS: Simultaneous registrations of scalp electroencephalograms, with electrodes placed according to the 10-20 System, and transcranial Doppler recordings of both middle cerebral arteries were performed in 27 patients (9 with primary generalized epilepsy, 18 with focal epilepsy). Data analysis of CBFV was based on the envelope curves of the Doppler spectrum. A fast Fourier transformation over the 20-minute CBFV curve was performed, and the amplitudes of B and M waves were calculated and compared with those in 20 normal, age-matched control subjects. RESULTS: While the amplitudes of the B waves in both groups were similar, patients with epilepsy showed significantly increased M waves. Patients with focal epilepsy did not present asymmetries between the normal hemisphere and the side of the epileptic focus with respect to both M and B waves. CONCLUSIONS: Enhanced M waves in epileptic patients may reflect increased sympathetic activity even in the absence of seizures. This study provides further evidence for an autonomic dysfunction as a possible mechanism for sudden unexplained death in patients with epilepsy.
Adult↗
[Are there guidelines for timing readministration of anticoagulation with marcumar in patients with artificial heart valves after intracerebral hemorrhage (stroke, subarachnoid hemorrhage, subdural hematoma)?].
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Anticoagulants↗
Persistent unihemispheric perceptual impairments in humans following focal seizures.
Perception has been linked to a highly coordinated activation of cortical regions whose functional organization and performance is subject to plastic changes. We tested whether chronic repetitive disturbances of the brain by focal epileptic activity have a long-standing detrimental effect on the perceptual performance in the affected hemisphere. Nine patients were examined who had a history of complex partial seizures but no structural cerebral damage on magnetic resonance imaging and no evidence of ongoing epileptic activity on scalp electroencephalography and who had clinically been without seizures for at least 3 days. The side of primary epileptic involvement was determined by seizure semiology (n = 2), focal electroencephalographic slowing (n = 3) or focal abnormality during single photon emission topography (SPECT) (n = 4). The computer controlled psychometric assessment of the somesthetic frequency discrimination revealed that the perception in the hand corresponding to the affected hemisphere was impaired relative to the contralateral hand (P < 0.01), and to the performance of a group of normal controls (P < 0.01). We conclude that mechanisms related to focal epileptic activity can result in regional perceptual decrements even when there is no clinical or surface-electroencephalographic evidence of epileptic discharges. This in turn suggests that somatosensory testing may be of help in localizing, or at least lateralizing an epileptic focus.
Adult↗
Successive activation of both cerebral hemispheres during cued word generation.
Most humans have a left hemispheric dominance for language. However, during diagnostic language testing there also is activation of the right hemisphere, which is probably related to attention. To investigate further the role of attention during language production we monitored cerebral blood flow velocities in the middle cerebral arteries by continuous bilateral transcranial Doppler ultrasonography (TCD) in nine right-handed subjects. During cued word generation, a successive activation of the right hemisphere in the preparatory phase, and of the left hemisphere during word searching was demonstrated. These findings indicate that attentional processes precede verbal activation and that the two procedures can be separated by comparative blood flow velocity measurement.
Acoustic Stimulation↗
Detectability of cerebral hemisphere ischaemic infarcts by CT within 6 h of stroke.
To determine how early and how reliably ischaemic brain infarcts can be detected on CT within 6 h of the onset of cerebral hemisphere strokes, 44 such studies were interpreted by an experienced neuroradiologist blinded to clinical signs, but aware that the cohort was a stroke population. He was asked to detect and localise an area of parenchymal low density and/or focal brain swelling. A follow-up study showing the definite infarct served as a reference in each case. In 38 patients areas of slightly low density were seen, and in 36 follow-up CT confirmed infarcts in the locations indicated. In 2 patients the reading was false positive. In 6 patients no low density focus could be detected. In these 8 patients examined by CT within 180 min of the stroke, no low density could be identified, even in retrospect with the knowledge of the findings on follow-up. Thus, 42 readings (95%) were true positive or true negative; 2 were false positive; and none was a false negative. CT within 6 h of the onset of symptoms has a mean sensitivity of 82% (36/44) for ischaemic cerebral hemisphere infarcts. By contrast, its sensitivity to ischaemic parenchymal low density is low during the initial 2 h. The early development of hemispheric infarcts can be detected reliably if the radiologist is familiar with the signs.
Adult↗
Transcranial Doppler during neurocardiogenic syncope.
The purpose of the present study was to investigate changes in cerebral circulation during neurocardiogenic syncope (NCS). Twenty patients with a history of unexplained syncopes were studied over a 45 min period in a tilted position. Heart rate and arterial blood pressure were recorded non-invasively using Finapres. Cerebral blood flow velocity of both middle cerebral arteries was measured with transcranial Doppler (TCD). Ten patients (50%) developed a NCS during the tilt test, with a strong reduction in blood pressure (mean, 48/34 mmHg) and heart rate (mean, 54 beats/min). Simultaneously, diastolic blood flow velocities dropped to values close to zero. However, systolic blood flow velocities did not decrease. In consequence, the pulsatility index (PI) increased considerably from 0.93 to 2.01. The increase in PI suggests that there is a constriction of cerebral resistance vessels during NCS. Despite the drop in blood pressure and the putative increase in cerebrovascular resistance, systolic blood flow velocities remained unchanged in the TCD records. This fact can be explained by a lumen narrowing of the middle cerebral artery at the site of insonation. In conclusion, the typical changes in cerebral blood flow velocity during NCS are probably due to a strong constriction of both the proximal and the peripheral segments of cerebral arteries. It is clear that, in addition to vasodepression and cardiac inhibition, cerebral vasoconstriction is a further mechanism in the pathogenesis of a NCS.
Adult↗
[Genetics of migraine].
Several historical reports focusing on the heredity of migraine, as well as recent studies on its epidemiology and molecular biology, have revealed evidence for a decisive role of genetic factors in the aetiopathogenesis of familial migraine. Indeed, family studies, segregation analyses and twin studies have shown that genetic factors play an important role in disposition towards migraine but could not explain the entire aetiopathogenesis. The influence of extragenetic factors, however, remains mostly unknown. Recent linkage analyses have provided evidence for genetic heterogeneity. A locus for Familial Hemiplegic Migraine (FHM), the only known type of migraine that follows autosomaldominant transmission, has been linked to chromosome 19p13 but genetic heterogeneity has also been shown, i.e., different types of migraine could be excluded from this locus. Further investigations should concentrate on identifying the FHM gene on chromosome 19p13, on linkage analyses with markers for different susceptibility genes, and on genomic analyses of highly informative pedigrees. This would lead to further clues to the pathogenesis underlying migraine and, thus, to therapeutic developments.
Chromosome Aberrations↗
[Molecular biology and genetics of hereditary motor and sensory neuropathies].
Hereditary neuropathies (HMSN) are among the most common genetic diseases in neurology. Various mutations in different genes are known which lead to the most frequent hereditary neuropathies. These mutations concern proteins of the myelin of the peripheral nervous system, as well as a gap-junction protein expressed in peripheral nerves. The molecular mechanisms leading from gene mutation to disease phenotypes are not fully understood. Nowadays, we are able to use DNA analysis for symptomatic, presymptomatic, and prenatal screening. The latter is of questionable value because of the variability in disease severity and outcome. Deeper insights into the molecular pathophysiology will, however, yield new therapeutic strategies in individual patients.
Connexins↗
Hyperinsulinism and cerebral microangiopathy.
BACKGROUND AND PURPOSE: High insulin levels are a recognized risk factor for atherosclerosis. Microvascular endothelium is more susceptible to metabolic and mitogenic effects of insulin than large-vessel endothelium. Besides their atherogenic effect, high insulin levels impair fibrinolysis by enhancing plasminogen activator inhibitor-1. We undertook this study to evaluate the hypothesis that elevated serum insulin and C-peptide levels are related to cerebral small-vessel disease rather than large-vessel pathology. METHODS: One hundred ninety-four consecutive patients presenting with symptomatic cerebrovascular disease were assigned to three subgroups that were differentiated by clinical presentations, brain imaging studies, and extracranial as well as transcranial vascular ultrasound findings: (1) patients with lacunes (n = 20), (2) patients with subcortical arteriosclerotic encephalopathy (n = 35), and (3) patients with strokes due to large-vessel disease (n = 99). Patients who had suffered a cryptogenic (n = 9) or cardioembolic (n = 16) stroke or who showed characteristics of the microangiopathy and macroangiopathy groups (n = 15) were not further evaluated. Thirty patients without manifestations of cerebrovascular disease were also examined. Fasting blood glucose, insulin, and C-peptide levels were determined in all subjects. RESULTS: There were no significant differences in age or sex among the three groups and control patients. Insulin levels were significantly higher in the lacunar group compared with the subcortical arteriosclerotic encephalopathy group, the macroangiopathy group, and the control patients (median [interquartile range]: 103.8 [198.6], 72.0 [103.2], 66.0 [57.0], and 52.2 [57.0] pmol/L, respectively; all P < .05, Mann-Whitney test). There was a statistically significant difference in insulin concentrations between the microangiopathy group (subcortical arteriosclerotic encephalopathy and lacunes) and the macroangiopathy and control groups (81.0 [110.4], 66.0 [57.0], and 55.2 [57.0] pmol/L, respectively; all P < .05, Mann-Whitney). The same was true for the distribution of C-peptide levels and to a minor extent blood glucose values, but these differences failed to reach statistical significance. CONCLUSIONS: Elevated insulin levels potentially represent a pathogenetic factor in the development of cerebral small-vessel disease, predominantly in patients presenting with lacunes. Whether this is due solely to atherosclerotic changes of the small penetrating arteries or whether changes in hemorheology are operative as well remains to be evaluated.
Aged↗
A novel technique for identification of doppler microembolic signals based on the coincidence method: in vitro and in vivo evaluation.
BACKGROUND AND PURPOSE: The applicability of a novel differentiation technique in embolus detection based on the coincidence principle and using a multigate probe was evaluated in this study. METHODS: According to the coincidence method, high-intensity transients should only be classified as microembolic signals if they appear sequentially in the two sample volumes monitored and within a defined time window calculated from the blood velocity and the spatial distance between the insonation depths. Part A: microbubbles were introduced in a continuous flow bench model of the middle cerebral artery to evaluate the accuracy of the multigate probe in embolus detection. Part B: in the subjects and patients, the minimal and maximum time delays in the appearance of microembolic signals in the two middle cerebral artery sample volumes were calculated as 0.01 second and set at 0.1 second, respectively. The multigate probe was used to monitor (1) 5 normal volunteers in whom 1008 artifact signals were produced,(2) 2 patients undergoing aortic valve replacement surgery, and (3) 12 patients with potential cardiac or carotid embolic sources. RESULTS: In the bench model, 95.5% of microembolic signals produced by microbubbles appeared in the two sample volumes with a time delay between 0.02 and 0.05 second, while in the remaining 4.5% a shorter passage time of 0.01 second was measured. A total of 1968 high-intensity signals were recorded in subjects and patients. All but 20 of these (99%) appeared in both monitoring channels within the above time frame. To summarize, 996 (98.8%) of the 1004 artifact signals and 943 (98.1%) of the 961 microembolic signals were correctly classified. CONCLUSIONS: Application of the coincidence theory to distinguish microembolic signals from artifacts provides a promising new technique with high sensitivity and specificity that could decisively improve the validity of embolus detection.
Adult↗
Clinical relevance of intracranial microembolic signals in patients with left ventricular assist devices. A prospective study.
BACKGROUND AND PURPOSE: The use of left ventricular assist devices has become an established method in bridging patients with end-stage cardiac failure to heart transplantation. Since thromboembolism is one of the major complications, we undertook this study to evaluate the clinical significance of Doppler microembolic signals (MES) in patients with left ventricular assist devices. METHODS: Six patients with left ventricular assist devices were monitored for MES with transcranial Doppler ultrasonography during the first 30 postoperative days. Additionally, repeated (10 per day and patient) and prolonged (3 hours per patient) monitorings were performed to assess the adequacy of the 30-minute recordings. Three observers evaluated 30 randomly assigned monitorings in a blinded fashion to assess the interobserver variability. The relation between MES counts and clinical, radiological, hemostaseological, and pump flow parameters and the predictive value of MES counts regarding the occurrence of embolic events was evaluated. RESULTS: Ten ischemic cerebrovascular accidents and 2 peripheral thromboembolic events occurred during the observation period of 177 days (total incidence, 6.8%). MES were found in 143 of 170 monitorings (84.1%). Their counts were significantly higher on days with clinically manifest embolic events as compared with event-free days (18.5 [3-74] versus 4 [0-52], respectively, median and 95% CI; P < .001, Mann-Whitney). The predictive value of MES counts above 7 per 30 minutes was high (75%). Significant differences in the incidence and counts of MES as well as in the incidence of clinically manifest embolic events were noted among the six patients (all P < .01) without equal differences in anticoagulant treatment or pump flow. Interobserver agreement was high (p = .78 to .89, unpaired Student's t test). Considerable short- and long-term intrapatient variations of MES counts, without consistent pattern, were noted. CONCLUSIONS: Serial monitoring for MES is prognostically superior to single monitorings in patients with left ventricular assist devices. In the future, this new application mode may individually guide anticoagulation strategies and even influence the decision regarding early cardiac transplantation versus long-term use of the assist devices.
Adult↗
Detection of microembolic signals in patients with middle cerebral artery stenosis by means of a bigate probe. A pilot study.
BACKGROUND AND PURPOSE: Middle cerebral artery (MCA) stenosis is a relatively rare occlusive disease with an annual stroke risk of approximately 7% to 8%. However, the frequent coincidence of cardiac or ipsilateral carotid artery disease may lead to difficulties in identifying the relevant embolizing source in symptomatic patients. We undertook this study to evaluate the prevalence of microembolic signals (MES) as well as the potential and limitations of bigate monitoring in patients with MCA stenosis. METHODS: Fourteen patients aged 33 to 87 years with angiographically demonstrated symptomatic (acute, n = 2; chronic, n = 8) or asymptomatic (n = 4) MCA stenosis were examined. Six patients (43%) had additional cardiac (n = 3) or carotid artery (n = 3) disease. By means of a bigate probe, simultaneous insonation of prestenotic and poststenotic vessel segments was attempted. RESULTS: In 10 patients (71%), MES detection could be performed sufficiently at target vessel sites. In the remaining patients, either prestenotic (n = 3) or poststenotic (n = 1) monitoring was not satisfactory due to insufficient transtemporal bone window or the great length or extent of MCA stenosis. Poststenotic MES were detectable in 2 acutely symptomatic and 1 asymptomatic patient (prevalence, 21%). In the latter case, the sequential appearance of MES in both prestenotic and poststenotic channels excluded MCA stenosis but strongly favored coexisting carotid artery stenosis as the active embolic source. CONCLUSIONS: MES are detectable in patients with MCA stenosis. Bigate monitoring in this setting is feasible and allows identification of the active source among "competing" embolizing conditions.
Adult↗