Ischaemic brain tissue salvaged from infarction with alteplase.
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Aged↗
Biomedical subjects
W D Heiss
Publications and source records attributed to W D Heiss.
Impaired episodic memory retrieval in a case of probable psychogenic amnesia.
A patient with severe, selective retrograde amnesia for personal material diagnosed as probable psychogenic amnesia, was investigated intensively neuropsychologically with cranial computed tomography (CCT), magnetic resonance imaging (MRI), and single photon emission tomography (SPECT). The patient was of average intelligence and memory with no anterograde amnesia. No evidence for structural brain damage was detected in CCT and MRI. SPECT, performed about 3 weeks after the onset of symptoms, demonstrated reduced perfusion in right temporal and frontal areas, that is, in areas which have been suggested as critical for episodic memory retrieval. To study episodic memory retrieval, positron-emission-tomography (PET) blood flow (rCBF) measurements were performed 6 months after the onset of symptoms. During episodic memory retrieval bilateral neuronal activations were observed in the precuneus, the lateral parietal and the right dorsolateral and polar prefrontal cortex. Compared to the results of previous functional imaging studies on episodic memory retrieval, our findings suggest an underlying functional disturbance of brain areas previously demonstrated to be involved in episodic memory retrieval.
Adult↗
MRI- and MRA-guided therapy of carotid and vertebral artery dissections.
A high sensitivity and specificity has been shown for magnetic resonance imaging (MRI) and angiography (MRA) in the diagnosis of internal carotid (ICAD) and vertebral (VAD) artery dissections, where arteriography has been and still is the gold standard. Five patients (three with ICAD, two with VAD; age range 42-56 years) are presented, in whom diagnosis and follow-up management were exclusively based on non-invasive measures. In all patients, MRI demonstrated a typical intramural hematoma and MRA in 3D phase contrast technique showed loss or diminished flow. After anticoagulation (heparin) for 3 to 4 weeks follow-up, MRI showed a regression of the mural hematoma and MRA revealed reperfusion or improvement of flow. Depending on the extent of MRI-/MRA-pathology, three patients were put on antiplatelet therapy and two on Coumadin until normalization of MRI and MRA findings, which are assessed in 3-months intervals. We suggest, that with, (I) a suspicious history, symptoms and signs for cervical artery dissection (CAD), (II) typical MR-findings proven to indicate CAD, (III) improving or resolving at follow-up, (IV) in unusual location for atherosclerotic involvement, (V) in the absence of coexisting atherosclerotic lesions, the diagnosis has not to be confirmed with conventional arteriography. Therefore, safe MRI- and MRA-guided anticoagulation and antiplatelet therapy during serial follow-up measurements are possible.
Adult↗
[Polyneuropathies in monoclonal gammopathy of undetermined significance: initial manifestation of a lymphoma].
BACKGROUND: Monoclonal gammopathies-including so-called monoclonal gammopathies of undetermined significance-MGUS-may cause polyneuropathies, even if immunoglobulin concentrations are within a normal range. CASE REPORT: We report on a patient with a rapidly progressive polyneuropathy with severe motor disturbances in whom a small amount of a monoclonal IgM kappa cryoglobulin was found. Only by extensive, repeatedly performed diagnostic procedures could scattered lymphoma cells be detected. Nonspecific immunosuppression had been unsuccessful but eventually a more specific chemotherapy led to an almost complete, sustained recovery. CONCLUSION: This case shows that in patients with a polyneuropathy of uncertain etiology monoclonal immunoglobulins should be looked for and that a MGUS can precede a lymphoma. Therefore these, patients with a MGUS and clinical deterioration despite conventional immunosuppressive treatment should undergo large-scale diagnostic check-up to make sure that the chance for an adequate chemotherapy is taken.
Aged↗
Speech-induced cerebral metabolic activation reflects recovery from aphasia.
Six stroke patients with clinically significant aphasia were studied 4 weeks and again 12-18 months after their first left hemispheric ictus. The regional cerebral metabolic rate of glucose (rCMRglc) was measured repeatedly by PET at rest and during word repetition, and severity of speech impairment was assessed by a neuropsychologic test battery. The patterns of speech-associated activation of glucose metabolism were related to improvement in language performance as measured by the Token test. Three patients experienced significant recovery from aphasia (Token test: 47 to 3, 45 to 12, and 37 to 5 points, respectively), whereas 3 patients had poor outcome (Token test from 48 to 45, and from 47 to 39 and 24, respectively). Good recovery was related to activation of left hemispheric speech areas surrounding the infarct, especially left superior temporal gyrus. In contrast, the 3 patients with persistent aphasia showed rCMRglc recruitment in right hemispheric regions and were unable to activate left hemispheric speech areas on follow-up. These results indicate that favorable outcome is related to partial sparing of speech areas of the dominant hemisphere that can be (re-) activated. Predominant recruitment of contralateral areas is not efficacious for a considerable recovery from aphasia. It rather indicates unspecific involvement of widespread networks in the effort to perform a complex task.
Adult↗
Functional effects of striatal dysfunction in Parkinson disease.
BACKGROUND: Concepts of basal ganglia organization suggest structually and functionally segregated pathways that link putamen and caudate function to motor and cognitive performance, respectively. OBJECTIVE: To investigate whether motor and cognitive impairment in Parkinson disease is attributable to selective disturbance in nigrostriatal, dopaminergic function and regional cerebral glucose metabolism. DESIGN: Twenty patients with probable Parkinson disease underwent positron emission tomographic measurements of dopaminergic, nigrostriatal function (positron emission tomography with fluorodopa F 18), regional glucose metabolism (positron emission tomography with fludeoxyglucose F 18), memory testing, and evaluation of locomotor disability. RESULTS: Memory performance in the patient cohort strongly correlated with the individual disease duration and degree of locomotor disability (P < .05). Striatal uptake rates of fluorodopa F 18 were significantly reduced in all patients (P < .05) compared with those in normal control subjects, and putaminal rates correlated significantly with the patients' degree of locomotor disability (P < .01) but not with memory performance. In the patients with an advanced stage of disease, there was a significant correlation between reduced caudate uptake rates of fluorodopa F 18 and the patients' impairment in delayed recall performance of the memory task (P < .05) but not with the individual degree of locomotor disability. No changes were found for regional glucose metabolic rates in the patients compared with the controls. CONCLUSIONS: The present study provides evidence for the hypothesis that on the level of the striatum, motor impairment in Parkinson disease may be assigned to altered dopamine neuronal integrity in the putamen but not in the caudate, whereas memory impairment in the more advanced cases may be attributed to caudate but not putaminal dysfunction.
Aged↗
Clozapine-induced agranulocytosis and thrombopenia in a patient with dopaminergic psychosis.
In patients with Parkinson' disease and dopaminergic psychosis, clozapine treatment is recommended as the drug is free from extrapyramidal side effects and does not worsen motor symptoms of the underlying disease. The use of clozapine, however, is limited due to its hematotoxic side effects. For treatment of clozapine-induced agranulocytosis, granulocyte colony-stimulating factors (G-CSF) are recommended. We report the case of a 72-years-old male patient with clozapine-induced agranulocytosis and thrombopenia. Neutropenia was successfully treated with G-CSF, but thrombopenia persisted and resolved spontaneously after 14 days. Bone marrow toxicity of clozapine is not restricted to white cell maturation, but may also impair thrombocytopoesis.
Aged↗
Repeat positron emission tomographic studies in transient middle cerebral artery occlusion in cats: residual perfusion and efficacy of postischemic reperfusion.
The wider clinical acceptance of thrombolytic therapy for ischemic stroke has focused more attention on experimental models of reversible focal ischemia. Such models enable the study of the effect of ischemia of various durations and of reperfusion on the development of infarctions. We used high-resolution positron emission tomography (PET) to assess cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral metabolic rate of glucose (CMRglc) before, during, and up to 24 h after middle cerebral artery occlusion (MCAO) in cats. After determination of resting values, the MCA was occluded by a transorbital device. The MCA was reopened after 30 min in five, after 60 min in 11, and after 120 min in two cats. Whereas all cats survived 30-min MCAO, six died after 60-min and one after 120-min MCAO during 6-20 h of reperfusion. In those cats surviving the first day, infarct size was determined on serial histologic sections. The arterial occlusion immediately reduced CBF in the MCA territory to < 40% of control, while CMRO2 was less affected, causing an increase in OEF. Whereas in the cats surviving 24 h of reperfusion after 60- and 120-min MCAO, OEF remained elevated throughout the ischemic episode, the initial OEF increase had already disappeared during the later period of ischemia in those cats that died during the reperfusion period. After 30-min MCAO, the reperfusion period was characterized by a transient reactive hyperemia and fast normalization of CBF, CMRO2, and CMRglc, and no or only small infarcts in the deep nuclei were found in histology. After 60- and 120-min MCAO, the extent of hyperperfusion was related to the severity of ischemia, decreased CMRO2 and CMRglc persisted, and cortical/subcortical infarcts of varying sizes developed. A clear difference was found in the flow/metabolic pattern between surviving and dying cats: In cats dying during the observation period, extended postischemic hyperperfusion accompanied large defects in CMRO2 and CMRglc, large infarcts developed, and intracranial pressure increased fatally. In those surviving the day after MCAO, increased OEF persisted over the ischemic episode, postischemic hyperperfusion was less severe and shorter, and the perfusional and metabolic defects as well as the final infarcts were smaller. These results stress the importance of the severity of ischemia for the further course after reperfusion and help to explain the diverging outcome after thrombolysis, where a relation between the residual flow and the effectiveness of reperfusion was also observed.
Animals↗
Reduction of infarct volume by halothane: effect on cerebral blood flow or perifocal spreading depression-like depolarizations.
Halothane is a strong inhibitor of potassium evoked spreading depression (SD) in cats. In the current study, we investigate halothane effects on induction of perifocal SD-like depolarizations, CBF, and infarct evolution in focal ischemia. Calomel and platinum electrodes measured cortical direct current potential and CBF in ectosylvian, suprasylvian, and marginal gyri. Left middle cerebral artery occlusion (MCAO) induced permanent focal ischemia for 16 hours in artificially ventilated cats (30% oxygen, 70% nitrous oxide) under halothane (0.75%, n = 8) or alpha-chloralose anesthesia (60 mg/kg intravenously, n = 7). Under alpha-chloralose, MCAO induced severe ischemia in ectosylvian and suprasylvian gyri(mean CBF < 10 mL/100 g/min), and direct current potentials turned immediately into terminal depolarization. In marginal gyri, CBF reduction was mild (more than 20 mL/100 g/min), and in six of seven animals, frequent SD-like depolarizations turned into terminal depolarization at a later stage of the experiments. Under halothane, MCAO induced severe ischemia (less than 10 mL/100 g/min) and immediate terminal depolarization only in ectosylvian gyrus. In suprasylvian gyrus, residual CBF remained significantly higher (more than 10 mL/100 g/min) than under alpha-chloralose, whereas in marginal gyri, CBF did not differ between groups. Compared with chloralose, the number of transient depolarizations was significantly reduced in marginal gyrus, and in suprasylvian gyrus transient but significantly longer depolarizations than in marginal gyrus were recorded. Except for one animal, transient depolarizations did not turn into terminal depolarization under halothane, and infarct volume reduction was particularly seen in suprasylvian gyrus. We conclude that halothane, the most commonly used anesthetic in studies of experimental brain ischemia, has protective properties, which may depend on both cerebrovascular and electrophysiologic influences.
Anesthetics, Inhalation↗
Performance of a randomization test for single-subject (15)O-water PET activation studies.
We adapted and implemented a permutation test (Holmes 1994) to single-subject positron emission tomography (PET) activation studies with multiple replications of conditions. That test determines the experimentwise alpha error as well as location and extent of focal activations in each individual. Its performance was assessed in five normal volunteers, using (15)O-H2O-PET data acquired on a high-resolution scanner, with septa retracted (3D mode), during functional activation by repeating words versus resting (four replications each). Calculated alpha errors decreased and the size of activated tissue volumes (voxels with P < or = 0.05) increased with increasing filter kernel size applied to the difference images. At a filter kernel of 12 mm Gaussian full width at half maximum, significant focal activations were seen bilaterally in superior temporal cortex, including Brodmann's areas 41 and 42, in all five subjects. Additional foci were detected in the precentral gyrus, left inferior frontal gyrus, supplementary motor area, and cerebellum of several subjects. The average CBF increase in activated voxels ranged from 17.6% to 28.7%. Activated volumes were smaller than those detected with a standard parametric test procedure. We conclude that the permutation test is a less sensitive procedure, having the advantage of not depending on unproven distributional assumptions, that detects strong activation foci in individual subjects with high reproducibility.
Adult↗
Profiles of cortical tissue depolarization in cat focal cerebral ischemia in relation to calcium ion homeostasis and nitric oxide production.
Cortical depolarization was investigated in a topographic gradient of ischemic density after 1-hour transient middle cerebral artery occlusion in halothane-anesthetized cats. A laser Doppler flow probe, an ion-selective microelectrode, and a nitric oxide (NO) electrode measured regional CBF (rCBF), direct current (DC) potential, extracellular Ca2+ concentration ([Ca2+]o), and NO concentration in ectosylvian and suprasylvian gyri of nine animals. Recordings revealed 12 of 18 sites with persistent negative shifts of the DC potential, severe rCBF reduction, and a drop of [Ca2+]o characteristic for core regions of focal ischemia. Among these sites, two types were distinguished by further analysis. In Type 1 (n = 5), rapid, negative DC shifts resembled anoxic depolarization as described for complete global ischemia. In this type, ischemia was most severe (8.9 +/- 2.5% of control rCBF), [Ca2+]o dropped fast and deepest (0.48 +/- 0.20 mmol/L), and NO concentration increased transiently (36.1 +/- 24.0 nmol/L at 2.5 minutes), and decreased thereafter. In Type 2 (n = 7), the DC potential fell gradually over the first half of the ischemic episode, rCBF and [Ca2+]o reductions were smaller than in Type 1 (16.2 +/- 8.2%; 0.77 +/- 0.41 mmol/L), and NO increased continuously during ischemia (53.1 +/- 60.4 nmol/L at 60 minutes) suggesting that in this type NO most likely exerts its diverse actions on ischemia-threatened tissue. In the remaining six recording sites, a third type (Type 3) attributable to the ischemic periphery was characterized by minimal DC shifts, mild ischemia (37.2 +/- 13.3%), nonsignificant alterations of [Ca2+]o, but decreased NO concentrations during middle cerebral artery occlusion. Reperfusion returned the various parameters to baseline levels within 1 hour, the recovery of [Ca2+]o and NO concentration being delayed in Type 1. An NO synthase inhibitor (N(G)-nitro-L-arginine, 50 mg/kg intravenously; four animals) abolished NO elevation during ischemia. In conclusion, even in the core of focal cerebral ischemia and reperfusion, different ischemic densities produce different types of cortical tissue manifesting distinctive chronological profiles of depolarization, Ca2+ influx, and NO synthesis.
Animals↗
Preoperative activation and intraoperative stimulation of language-related areas in patients with glioma.
OBJECTIVE: Evaluation of the accuracy of preoperative localization of language-related cortex by magnetic resonance imaging-guided positron emission tomography. METHODS: Patients with gliomas in the left dominant hemisphere were examined preoperatively with magnetic resonance imaging-guided positron emission tomography and intraoperatively by electrical stimulation of cortex. RESULTS: A verb generation task yielded more intense and better lateralized local increases of cerebral blood flow in the positron emission tomographic examination than did a naming task. Significant correspondence of preoperative and intraoperative findings was observed for the verb generation task. Cortical sites with aphasic disturbance during electrical stimulation had a significantly higher cerebral blood flow increase during preoperative activation than did sites without intraoperative language impairment. Areas with cerebral blood flow increases above an optimum threshold had 73% sensitivity and 81% specificity to predict aphasic disturbance during intraoperative stimulation. CONCLUSION: The data suggest that with further technical improvements, imaging of language function may become a preoperative diagnostic tool for patients with tumors close to language-related brain structures.
Adult↗
Widespread functional deficits in perception-related networks demonstrated by PET in a case with simple visual seizures.
PURPOSE: To study benzodiazepine receptor (BZR) density and functional deficits in occipital lobe epilepsy. METHODS: A 39-year-old man who had simple partial visual seizures after neurosurgical transtentorial extirpation of a pinealoma was studied by EEG, magnetic resonance imaging (MRI), and positron emission tomography (PET) of [18F]2-fluoro-2-deoxy-D-glucose (FDG) at rest and during visual activation task and[11C]flumazenil (FMZ). RESULTS: Electroencephalographic recordings were nonspecific, and MRI did not reveal any morphologic anomaly in the occipital lobe. Flumazenil-PET demonstrated a small epileptogenic region in the right visual association cortex and FDG-PET showed hypometabolism in a corresponding location and thalamic diaschisis. Stimulation of occipital metabolism by a continuous visual recognition task improved significantly the contrast between the dysfunctional zone and its surround. CONCLUSIONS: As BZR deficits are restricted to a small region, widespread hypometabolism in networks involved in visual information processing indicates an extensive functional deactivation by the epileptogenic focus.
Adult↗
11C-methionine and 18F-2-fluorodeoxyglucose positron emission tomography: a tool for diagnosis of cerebral glioma and monitoring after brachytherapy with 125I seeds.
Forty-six patients with suspected brain tumors were investigated by positron emission tomography (PET). Using 11C-methionine PET, the spatial extent of increased uptake in gliomas was larger than that of contrast enhancement on CT/MR images in 67% or the same in 33%. Ten of 46 patients treated with brachytherapy for low-grade gliomas were also investigated with 18F-2-fluorodeoxyglucose (FDG)-PET. One year after seed implantation, the glucose metabolism had not changed, but the decline of methionine uptake was significant. In conclusion, 11C-methionine PET may improve tumor delineation and, following brachytherapy, provides more information on the therapeutic effects than FDG.
Adult↗
Early detection of irreversibly damaged ischemic tissue by flumazenil positron emission tomography in cats.
BACKGROUND AND PURPOSE: Ligands for cerebral benzodiazepine receptors were used in the past to indicate the intactness of cortical neurons in subacute to chronic states after stroke and thus to differentiate among brain regions with complete or incomplete infarction and with functional deactivation. For planning acute interventional therapy, however, a marker of irreversible damage in early ischemia is needed. We studied the applicability of [11C]flumazenil (FMZ) for differentiation between tissue with and without potential of recovery in the first hours after focal experimental ischemia. METHODS: In 11 cats, cerebral blood flow, cerebral metabolic rate for oxygen, oxygen extraction fraction, and FMZ binding were studied repeatedly by positron emission tomography before, during, and up to 12 hours after transient middle cerebral artery occlusion (MCAO) (30 minutes in 2, 60 minutes in 7, and 120 minutes in 2 cats, respectively). Development of the defects in energy metabolism were compared with the defects in FMZ binding (2 to 3 hours and 8 to 9 hours after MCAO), with the pattern of disturbed glucose metabolism (determined 12 hours after MCAO), and with the size of the infarcts (determined approximately 15 hours after MCAO). RESULTS: Irrespective of the level of reperfusion, defects in FMZ binding (2 to 3 hours after MCAO) were closely related to areas with severely depressed oxygen consumption and predicted the size of the final infarcts, whereas preserved FMZ binding indicated intact cortex. Depression of glucose metabolism was in all animals larger than the defects in FMZ binding and the infarcts, indicating functional deactivation of brain areas beyond the permanent morphological damage. In addition, FMZ distribution within 2 minutes after injection was significantly correlated to flow and yielded reliable perfusion images. CONCLUSIONS: The reduction of FMZ binding early after focal ischemia reflects irreversible neuronal damage that otherwise only can be detected by multitracer studies. Our experimental data and first clinical applications suggest that FMZ has potential as an indicator of developing infarction. Since FMZ distribution additionally images perfusion, this tracer might be useful for the selection of patients who would benefit from acute therapeutic intervention.
Animals↗
Interferon gamma producing blood lymphocytes are decreased by interferon beta therapy in patients with multiple sclerosis.
OBJECTIVE: We studied the individual course of interferon gamma producing blood lymphocyte count (IFGC) of 15 multiple sclerosis patients started on 8 MIU beta interferon administered subcutaneously each other day. METHODS: Mononuclear blood cells were prepared before treatment and on day 3, 9, 15, as well as after month 1, 2, 3 and 4 of therapy. After stimulation intracellular interferon gamma was detected with monoclonal fluorescent antibodies and measured by flow cytometry. IFGC is given as percentage of all gated lymphocytes. RESULTS: forty-eight hours after first interferon beta application the mean IFGC dropped significantly from 11.37 to 7.09 (P < 0.05) and to 4.22 within 4 months. Whereas the majority of patients showed a decrease of IFGC from the beginning of therapy, in three of the 15 patients a transient increase of IFGC was seen suggesting a different response to immunomodulatory therapy. CONCLUSIONS: Interferon gamma producing lymphocyte count might be a useful tool to determine the biological effect of interferon beta therapy in multiple sclerosis patients.
Adjuvants, Immunologic↗
Recovery of language after brain damage.
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Aphasia↗
Spontaneous intracerebral hemorrhage. Prognostic factors in 896 cases.
To determine the prognostic value of etiology and localization in spontaneous intracerebral hemorrhage, 896 patients with spontaneous intracerebral hemorrhage, as proven by CT, operation or autopsy, were retrospectively studied using univariate data analysis. Etiologies were hypertension in 63.5%, cerebrovascular malformations in 8.5% and abnormal hemostasis in 15% of the patients. In 23% no etiology was determined. Main localizations were cerebral lobes in 49.2%, basal ganglia in 34.4%, brain stem in 6.9%, cerebellum in 6.7% and primary intraventricular in 2.3% of the patients. Ventricular extension was present in 47.0%. A higher case fatality correlated with: 1) ventricular extension (P < 0.00001), 2) increasing age (P = 0.00005), 3) surgical treatment (P = 0.00010), 4) localization in basal ganglia (P = 0.0108) and 5) hypertension as only etiology (P = 0.01471). A lower case fatality was found in patients with cerebrovascular malformations (P = 0.00006) and when the hemorrhage was localized to the cerebral lobes (P = 0.0050). We conclude that etiology and localization are of prognostic value in spontaneous intracerebral hemorrhage.
Adolescent↗