Biomedical subjects

Götz Thomalla

Publications and source records attributed to Götz Thomalla.

13 recordsLinked to original sources

PubMed2007

Two tales: hemorrhagic transformation but not parenchymal hemorrhage after thrombolysis is related to severity and duration of ischemia: MRI study of acute stroke patients treated with intravenous tissue plasminogen activator within 6 hours.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage represents the most feared complication of treatment with intravenous tissue plasminogen activator. We studied whether perfusion-weighted imaging and diffusion-weighted imaging has the potential to identify patients at risk of severe intracerebral hemorrhage after treatment with intravenous tissue plasminogen activator. METHODS: We analyzed data of prospectively studied MRI selected acute ischemic stroke patients treated with intravenous tissue plasminogen activator within 6 hours. All patients were examined by perfusion- and diffusion-weighted imaging < or =6 hours. Perfusion- and diffusion-weighted imaging lesion volumes were calculated. Hemorrhagic transformation was assessed on follow-up CT or MRI and diagnosed as hemorrhagic transformation, parenchymal hemorrhage, or symptomatic intracerebral hemorrhage according to ECASS II criteria. RESULTS: Of 152 patients, hemorrhagic transformation was seen in 60 (39.5%), parenchymal hemorrhage in 15 (9.9%), and symptomatic intracerebral hemorrhage in 4 (2.6%). Multiple logistic regression analysis identified onset to treatment time after 3 to 6 hours (P<0.001), a larger perfusion-weighted imaging lesion volume (P=0.002), and, as a tendency, a higher score on the National Institutes of Health Stroke Scale on admission (P=0.068) as independent predictors of hemorrhagic transformation. Neither MRI lesion volumes nor severity of symptoms, but rather only an older age tended to be associated with parenchymal hemorrhage (P=0.087). CONCLUSIONS: Our results further support the concept of a different pathogenesis for hemorrhagic transformation and parenchymal hemorrhage. Whereas hemorrhagic transformation should be regarded as a clinically irrelevant epiphenomenon of ischemic damage and reperfusion, parenchymal hemorrhage appears to be related to biologic effects of tissue plasminogen activator and other pre-existing pathologic conditions, which deserve further investigation.

Adult↗

PubMed2006

Characterizing physiological heterogeneity of infarction risk in acute human ischaemic stroke using MRI.

Viable tissues at risk of infarction in acute stroke patients have been hypothesized to be detectable as volumetric mismatches between lesions on perfusion-weighted (PWI) and diffusion-weighted magnetic resonance imaging (DWI). Because tissue response to ischaemic injury and to therapeutic intervention is tissue- and patient-dependent, changes in infarct progression due to treatment may be better detected with voxel-based methods than with volumetric mismatches. Acute DWI and PWI were combined using a generalized linear model (GLM) to predict infarction risk on a voxel-wise basis for patients treated either with non-thrombolytic (Group 1; n = 11) or with thrombolytic therapy (Group 2; n = 27). Predicted infarction risk for both groups was evaluated in four ipsilateral regions of interest: tissue acutely abnormal on DWI (Core), tissue acutely abnormal on PWI but normal on DWI that either infarcts (Recruited) or does not (Salvaged), and tissue normal on both DWI and PWI that does not infarct (Normal) by follow-up imaging > or = 5 days. The performance of the models was significantly reduced for the thrombolysed group compared with the group receiving standard treatment, suggesting an alteration in natural progression of the ischaemic cascade. Average GLM-predicted infarction risk values in the four regions were different from one another for both groups. GLM-predicted infarction risk in Salvaged tissue was significantly higher (P = 0.02) for thrombolysed patients than for non-thrombolysed patients, suggesting that thrombolysis rescued tissue with higher infarction risk than typically measured in tissue that spontaneously recovered. The observed spatial heterogeneity of GLM-predicted infarction risk values probably reflects the varying degrees of tissue injury and salvageability that exist after stroke. MRI-based algorithms may therefore provide a more sensitive means for monitoring therapeutic effects on a voxel-wise basis.

Acute Disease↗

PubMed2006

Outcome and symptomatic bleeding complications of intravenous thrombolysis within 6 hours in MRI-selected stroke patients: comparison of a German multicenter study with the pooled data of ATLANTIS, ECASS, and NINDS tPA trials.

BACKGROUND AND PURPOSE: We compared outcome and symptomatic bleeding complications of intravenous tissue plasminogen activator (IV-tPA) within 6 hours of symptom onset in MRI-selected patients with acute middle cerebral artery infarction with the pooled data of the large stroke tPA trials. METHODS: Patients were examined by perfusion-weighted and diffusion-weighted imaging < or =6 hours. Within 3 hours, patients were treated according to Second European-Australasian Acute Stroke Study (ECASS II) criteria. After 3 to 6 hours, treatment with IV-tPA was performed based on MRI findings. Favorable outcome was assessed after 90 days using a dichotomized modified Rankin scale score of 0 to 1. Intracerebral bleeding complications were assessed on follow-up MRI or computed tomography. Data were compared with the pooled placebo and pooled tPA patients of the ATLANTIS, ECASS, and National Institute of Neurological Disorders and Stroke (NINDS) tPA trials. RESULTS: From 174 MRI-selected tPA patients, 62% (n=108) were treated in < or =3 hours and 38% (n=66) after 3 to 6 hours. Favorable outcome was more frequent in MRI-selected tPA patients (48% [95% CI, 39 to 54]) compared with pooled placebo (33% [95% CI, 31 to 36]; P<0.001) and pooled tPA patients (40% [95% CI, 37 to 42]; P=0.046). Odds ratios for favorable outcome in the MRI-selected tPA group were 1.82 (1.32 to 2.51) compared with the pooled placebo and 1.39 (1.01 to 1.92) compared with the pooled tPA group. The rate of symptomatic intracerebral hemorrhage in MRI-selected tPA patients (3% [95% CI, 0 to 5]) was lower than in the pooled tPA group (8% [95% CI, 7 to 10]; P=0.012) and comparable to the pooled placebo group (2% [95% CI, 1 to 3]; P=0.392). CONCLUSIONS: This study supports that it is safe and effective to expand the time window for IV-tPA up to 6 hours in patients with tissue at risk as defined by MRI.

Adolescent↗

PubMed2006

Cerebral vasculitis following oral methylphenidate intake in an adult: a case report.

Methylphenidate is structurally and functionally similar to amphetamine. Cerebral vasculitis associated with amphetamine abuse is well documented, and in rare cases ischaemic stroke has been reported after methylphenidate intake in children. We report the case of a 63-year-old female who was treated with methylphenidate due to hyperactivity and suffered from multiple ischaemic strokes. We consider drug-induced cerebral vasculitis as the most likely cause of recurrent ischaemic strokes in the absence of any pathological findings during the diagnostic work-up. We conclude that methylphenidate mediated vasculitis should be considered in patients with neurological symptoms and a history of methylphenidate therapy. This potential side-effect, though very rare, represents one more reason to be very restrictive in the use of methylphenidate.

Acute Disease↗

PubMed2005

Outcome and severe hemorrhagic complications of intravenous thrombolysis with tissue plasminogen activator in very old (> or =80 years) stroke patients.

BACKGROUND AND PURPOSE: Information on safety and efficacy of intravenous thrombolysis with tissue plasminogen activator (tPA) (IV-tPA) in very old acute ischemic stroke (AIS) patients is scarce. We studied outcome and severe hemorrhagic complications in patients aged 80 and older. METHODS: We analyzed data of AIS patients, treated with IV-tPA, in 3 German stroke centers. Neurologic deficit on admission was assessed using the National Institutes of Health Stroke Scale (NIHSS). Outcome was assessed after 90 days using the Modified Rankin Scale (MRS), and favorable outcome was defined as a MRS score of 0 to 1. Severe intracerebral bleeding complications were assessed on follow-up magnetic resonance imaging or cranial computed tomography. Data were compared between patients <80 years of age and patients aged > or =80 years. RESULTS: A total of 228 patients were treated with IV-tPA; 38 (16%) were 80 years or older. There was no difference in NIHSS on admission or onset to treatment time between younger and older patients. Less patients > or =80 years of age achieved a favorable outcome (26.3 versus 46.8%, P=0.021), and mortality was higher in older patients (21.1 versus 5.3%, P=0.004). There was no difference in the rate of parenchymal hemorrhage (6.3%<80 years versus 5.3%> or =80 years, P=1.000) and symptomatic intracerebral hemorrhage (2.6%<80 years versus 2.6%> or =80 years, P=1.000) between both groups. CONCLUSIONS: There is no increase in severe intracerebral hemorrhage after IV-tPA in very old patients, but outcome is worse as compared with younger patients. There is no evidence to exclude ischemic stroke patients from thrombolysis based on a predefined age threshold.

Age Factors↗

PubMed2005

Aggressive therapy with intravenous abciximab and intra-arterial rtPA and additional PTA/stenting improves clinical outcome in acute vertebrobasilar occlusion: combined local fibrinolysis and intravenous abciximab in acute vertebrobasilar stroke treatment (FAST): results of a multicenter study.

BACKGROUND AND PURPOSE: A combined therapy of local recombinant tissue plasminogen activator (rtPA) fibrinolysis and intravenous Abciximab platelet inhibition with additional percutaneous transluminal angioplasty (PTA)/stenting may improve recanalization and neurological outcome in patients with acute vertebrobasilar occlusion. METHODS: Combined FAST therapy consisted on intravenous bolus of Abciximab (0.25 mg/kg) followed by a 12-hour infusion therapy (0.125 microg/kg per minute) and low-dose intra-arterial rtPA (median dosage: 20 mg, FAST cohort: N=47). The results were compared with a retrospective cohort, treated by intraarterial rtPA monotherapy (median dosage: 40 mg, rtPA cohort, N=41). Additional PTA/stenting was performed in case of severe residual stenosis. Recanalization success was classified according to the Trials in Myocardial Infarction (TIMI) criteria: TIMI0/1, failed recanalization; TIMI2/3, successful recanalization. Bleeding complications were evaluated according to severe extracerebral hemorrhage (ECH), asymptomatic intracerebral hemorrhage (AIH), and symptomatic intracerebral hemorrhage (SIH). RESULTS: Overall bleeding rate was higher under the combined therapy, but the SIH rate did not differ (FAST versus rtPA: ECH, 3% versus 0%; AIH, 32% versus 22%; SIH 13% versus 12%). Additional PTA/stenting was performed in 14 (FAST) versus 5 (rtPA) patients. TIMI2/3 recanalization rate was similar (FAST, 72%; rtPA, 68%), but TIMI3 rate was remarkably higher under combined therapy (FAST, 45%; rtPA, N=22%). Neurologic outcome appeared better under combined therapy (FAST versus rtPA: favorable outcome rate: 34% versus 17%) with a significantly lower mortality rate (FAST versus rtPA: 38% versus 68%; P=0.006). These results were consistent for embolic and atherothrombotic occlusions. CONCLUSIONS: Combined therapy of intravenous Abciximab and half dose intra-arterial rtPA with additional PTA/stenting appears to improve neurologic outcome in acute vertebrobasilar occlusion despite an increase of overall bleeding complications.

Abciximab↗

PubMed2005

Reperfusion after severe local perfusion deficit precedes hemorrhagic transformation: an MRI study in acute stroke patients.

BACKGROUND: We applied magnetic resonance imaging to analyze the degree of local diffusion and perfusion abnormalities and the status of reperfusion in regions with subsequent hemorrhagic transformation (HT). METHODS: 51 patients with acute ischemic stroke were studied by diffusion- and perfusion-weighted imaging within 3.0 +/- 0.8 h, on day 1 and days 5-8. After realignment of the image data sets, the parameter maps of the apparent diffusion coefficient (ADC), cerebral blood flow (CBF) and cerebral blood volume (CBV), and mean transit time were analyzed in the area of subsequent HT. The degree of local diffusion and perfusion impairment in the HT area was compared with the entire diffusion and perfusion abnormality. Reperfusion status was separately assessed for the entire perfusion abnormality and the HT area. RESULTS: HT was observed in 19/51 patients (37.2%) within 8 days after symptom onset. Areas destined for HT revealed a more severe decrease in ADC (to 70 +/- 13%; p < 0.01), CBV (to 31 +/- 26%; p < 0.001) and CBF (to 28 +/- 19%; p < 0.001) compared to the entire perfusion abnormality. Local reperfusion in the HT area was seen in 18/19 patients. The presence of HT did not coincide with a worse clinical outcome. DISCUSSION: HT is the result of reperfusion in the region with the most severe local perfusion impairment and does not influence the neurological outcome.

Age Factors↗

PubMed2005

Vascular occlusion sites determine differences in lesion growth from early apparent diffusion coefficient lesion to final infarct.

BACKGROUND AND PURPOSE: Occlusion of major cerebral arteries is the primary source of tissue damage in ischemic stroke and the target of thrombolytic therapy. We hypothesized that large infarcts in more proximal vascular occlusions correspond with substantially increased ischemic lesions shown on initial apparent diffusion coefficient (ADC) maps. METHODS: Initial ADC lesions in 120 patients with acute ischemic stroke were analyzed within 6 hours of stroke onset. Patients were categorized on the basis of vascular occlusion, as shown on MR angiography. Lesion volumes were determined by using manual delineation (ADC(man)) and a threshold method for ADC values (<550 x 10(-9) mm(2)/s(-1), ADC(<550)). Infarct volumes were analyzed by using T2-weighted (n = 109) or CT (n = 11) images obtained on days 5-8. RESULTS: Median lesion volumes for ADC(<550), ADC(man), and infarcts, respectively, were as follows: proximal internal carotid artery (ICA)/middle cerebral artery (MCA) occlusions, 10, 23, and 32 cm(3); carotid-T occlusions, 11, 37, and 138 cm(3); MCA trunk occlusions, 11, 27, and 44 cm(3)); and MCA branch occlusions 8, 27, and 21 cm(3). Initial ADC lesion volumes were different only between the carotid T and the MCA branch (P < .05). On days 5-8, infarct volumes decreased from proximal to distal sites (P < .05), with the exception of MCA trunk versus proximal ICA/MCA occlusions. Recanalization rate in carotid-T occlusion was significantly lower than those of all other occlusion types. CONCLUSION: Initial ADC lesions can be small, even in patients with proximal vascular occlusions. These patients develop considerably large infarctions, suggesting a high potential for infarct growth. This growth might be averted with improved early recanalization of proximal vascular occlusions.

Arterial Occlusive Diseases↗

PubMed2004

Are there time-dependent differences in diffusion and perfusion within the first 6 hours after stroke onset?

BACKGROUND AND PURPOSE: Stroke heterogeneity in computed tomography-based studies has been attributed as main cause for missing efficacy of intravenous tissue plasminogen activator (tPA) therapy within 3 to 6 hours. We investigated early time-dependent differences in acute stroke pathophysiology by multiparametric magnetic resonance imaging (MRI). METHODS: Stroke MRI of 112 acute ischemic stroke patients within <6 hours were dichotomized into a <3-hour group (n=52) and a 3- to 6-hour group (n=60). Infarct volume was determined on days 5 to 8. Lesion volumes were determined for apparent diffusion coefficient (ADC_man) and the subregion with ADC values <550x10(-9) mm/s2 (ADC <550), and for the time-to-peak (TTP) delay of 2 to 4 seconds, 4 to 6 seconds, 6 to 8 seconds, and >8 seconds. A subsample analysis was performed for occlusions of the middle carotid artery (MCA) trunk (n=36) and MCA branches (n=30), and for all patients treated by intravenous tPA (n=70). RESULTS: ADC and TTP lesion volumes were not different within <3 hours compared with volumes at 3 to 6 hours. In patients receiving intravenous tPA (n=70), there were no significant differences in ADC_man, TTP >2 seconds, and infarct volume (days 5 to 8) between the 2 groups. There was a greater proportion of ADC <550/ADC_man, which was most pronounced in patients with MCA trunk occlusions after 3 to 6 hours and a larger mismatch in the <3-hour group compared with that of the 3- to 6-hour group. In MCA branch occlusions, there was a less severe TTP delay after 3 to 6 hours. However, all differences missed the significance level (P=0.05) after correction for multiple testing. CONCLUSIONS: We observed no significant time-dependent differences within 6 hours after stroke onset in degree and volume of diffusion and perfusion impairment. An exclusion from intravenous tPA solely based on a rigid 3-hour time window seems unjustified in MRI-confirmed ischemic stroke.

Acute Disease↗

PubMed2004

Predictors of apparent diffusion coefficient normalization in stroke patients.

BACKGROUND AND PURPOSE: We sought to describe the frequency of normalization of apparent diffusion coefficient (ADC) values that are decreased in hyperacute stroke and to identify characteristics of tissue demonstrating normalization. METHODS: Sixty-eight acute ischemic stroke patients underwent MRI examination (including diffusion/perfusion imaging and MR angiography) within 6 hours (mean, 2.8 hours) after symptom onset, after 24 hours, and again 4 to 7 days later. Lesion volumes with decreased ADC and delayed time to peak in perfusion imaging were determined. In patients showing ADC normalization, volumes with ADC decrease graded as <50%, 50% to 60%, 60% to 70%, and 70% to 80% of the contralateral value were determined by thresholding. Patients were categorized as normalizers (demonstrating ADC normalization in >5 mL tissue with initially decreased ADC) or nonnormalizers (demonstrating ADC normalization in <5 mL tissue). RESULTS: Fourteen patients (19.7%) were classified as normalizers. Eleven of 31 patients (35.5%) initially imaged <3 hours after stroke onset and 3 of 37 (7.5%) of those imaged 3 to 6 hours after onset were normalizers. ADC normalization occurred predominantly in the basal ganglia and white matter after thrombolytic therapy in patients with more distal vessel occlusions. All normalizers demonstrated at least partial tissue reperfusion. Tissue with more severe initial decrease in ADC was less likely to demonstrate normalization. CONCLUSIONS: ADC normalization is not a rare event in acute stroke after tissue reperfusion. Brain tissue with initially decreased ADC, especially within 3 hours after stroke onset, may include "tissue at risk."

Acute Disease↗

PubMed2004

Diffusion tensor imaging detects early Wallerian degeneration of the pyramidal tract after ischemic stroke.

We used diffusion tensor imaging (DTI) to assess Wallerian degeneration of the pyramidal tract within the first 2 weeks after ischemic stroke, and correlated the extent of Wallerian degeneration with the motor deficit. Nine patients with middle cerebral artery stroke were examined 2-16 days after stroke by DTI and T2-weighted MRI. We measured fractional anisotropy (FA), averaged diffusivity (Dav), eigenvalues of the diffusion tensor and T2-weighted signal in the cerebral peduncle and compared these values between the affected and the unaffected side and between patients and six controls. FA was significantly reduced on the affected side compared to the unaffected side and compared to the control group. The largest eigenvalue was reduced, whereas the smallest eigenvalue was elevated on the affected side. There was no significant difference in T2-weighted signal and Dav. The decrease of anisotropy correlated positively with the motor deficit at the time of DTI study and 90 days after stroke. The reduction of anisotropy mirrors the disintegration of axonal structures, as it occurs in the early phase of Wallerian degeneration. DTI detects changes of water diffusion related to beginning pyramidal tract degeneration within the first 2 weeks after stroke that are not yet visible in conventional T2-weighted or orientationally averaged diffusion weighted MRI. We demonstrated for the first time a correlation of early DTI findings of pyramidal tract damage with the motor deficit. DTI can help prognosing recovery of motor function after stroke within the early subacute phase.

Aged↗

PubMed2002

Acute basilar artery occlusion treated with combined intravenous Abciximab and intra-arterial tissue plasminogen activator: report of 3 cases.

BACKGROUND: Acute vertebrobasilar occlusion remains a disease with a high mortality even after treatment by local intra-arterial fibrinolysis. Adjunctive treatment with platelet glycoprotein IIb/IIIa receptor inhibitors such as abciximab may facilitate recanalization and improve the neurological outcome. Results after treatment of 3 patients by combined intravenous abciximab and local intra-arterial tissue plasminogen activator (tPA) are reported. CASE DESCRIPTIONS: Treatment was performed within 6 hours of stroke onset. Angiography revealed embolic occlusion of the basilar artery in 2 patients and atherothrombotic occlusion at the vertebrobasilar junction in 1 patient. Therapy consisted of intravenous abciximab bolus administration (0.25 mg/kg) followed by 12-hour infusion therapy (0.125 microg/kg per minute) and local intra-arterial thrombolysis with tPA (10 mg/h). Heparin was only applied for catheter flushing (500 IU/h). The patient with the atherothrombotic occlusion was treated with additional percutaneous transluminal angioplasty and stenting. Complete recanalization of the basilar artery occurred in 2 patients, whose conditions improved clinically to functional independence. In the third patient only partial recanalization was seen, with only slight clinical improvement. This patient died of cardiac failure 2 months later. Besides a subtle subarachnoid hemorrhage (n=1), no intracranial or extracranial bleeding complication was observed. CONCLUSIONS: The combination of glycoprotein IIb/IIIa receptor inhibitor with local intra-arterial tPA might be a promising therapy for patients with acute vertebrobasilar occlusion. Further studies are necessary to define the clinical benefit and the bleeding rate of this new pharmacological approach.

Abciximab↗

PubMedDate not supplied

[Psychosocial symptoms in children of hemodialysis patients].

Serious somatic illness in a parent represents a risk factor for psychosocial abnormalities in children. In a cross sectional study 24 families with a parent undergoing hemodialysis and at least one child living at home were examined. Patients, their spouses, children up from age 11 as well as the nephrologists in charge of the dialysis treatment were interrogated. In the parental perspective of a symptom checklist (CBCL), the children on average did not have higher scores for psychosocial abnormalities than a normative sample. In the self-reporting perspective (YSR), however, the adolescents averaged clinically abnormal scores. The discrepancy between the parental and the children's self-reporting scores were significant, which indicates an underestimation of children's psychological stress by both parents. Case analysis revealed a concentration of abnormalities within a quarter of the sample. This smaller subgroup showed clinically relevant scores in psychosocial abnormalities in the parental perspective, too. Younger children and children with additional life stressors had higher scores in psychosocial abnormalities. Futhermore, children's problems were correlated with depressive symptoms in one or both parents, which indicates an increased risk for children's psychological maladaptation in cases of depressive maladjustment to the illness in the ill parent or his spouse. It is concluded that children at special risk should be identified as early as possible. When problems are detected, counselling support should be offered to affected families.

Adaptation, Psychological↗