Hansjörg Bäzner

Anticoagulant Reversal, Blood Pressure Levels, and Anticoagulant Resumption in Patients With Anticoagulation-Related Intracerebral Hemorrhage

IMPORTANCE Although use of oral anticoagulants (OACs) is increasing, there is a substantial lack of data on how to treat OAC-associated intracerebral hemorrhage (ICH). OBJECTIVE To assess the association of anticoagulation reversal and blood pressure (BP) with hematoma enlargement and the effects of OAC resumption. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study at 19 German tertiary care centers (2006-2012) including 1176 individuals for analysis of long-term functional outcome, 853 for analysis of hematoma enlargement, and 719 for analysis of OAC resumption. EXPOSURES Reversal of anticoagulation during acute phase, systolic BP at 4 hours, and reinitiation of OAC for long-term treatment. MAIN OUTCOMES AND MEASURES Frequency of hematoma enlargement in relation to international normalized ratio (INR) and BP. Incidence analysis of ischemic and hemorrhagic events with or without OAC resumption. Factors associated with favorable (modified Rankin Scale score, 0-3) vs unfavorable functional outcome. RESULTS Hemorrhage enlargement occurred in 307 of 853 patients (36.0%). Reduced rates of hematoma enlargement were associated with reversal of INR levels <1.3 within 4 hours after admission (43/217 [19.8%]) vs INR of ≥1.3 (264/636 [41.5%]; P < .001) and systolic BP <160 mm Hg at 4 hours (167/504 [33.1%]) vs ≥160 mm Hg (98/187 [52.4%]; P < .001). The combination of INR reversal <1.3 within 4 hours and systolic BP of <160 mm Hg at 4 hours was associated with lower rates of hematoma enlargement (35/193 [18.1%] vs 220/498 [44.2%] not achieving these values; OR, 0.28; 95% CI, 0.19-0.42; P < .001) and lower rates of in-hospital mortality (26/193 [13.5%] vs 103/498 [20.7%]; OR, 0.60; 95% CI, 0.37-0.95; P = .03). OAC was resumed in 172 of 719 survivors (23.9%). OAC resumption showed fewer ischemic complications (OAC: 9/172 [5.2%] vs no OAC: 82/547 [15.0%]; P < .001) and not significantly different hemorrhagic complications (OAC: 14/172 [8.1%] vs no OAC: 36/547 [6.6%]; P = .48). Propensity-matched survival analysis in patients with atrial fibrillation who restarted OAC showed a decreased HR of 0.258 (95% CI, 0.125-0.534; P < .001) for long-term mortality. Functional long-term outcome was unfavorable in 786 of 1083 patients (72.6%). CONCLUSIONS AND RELEVANCE Among patients with OAC-associated ICH, reversal of INR <1.3 within 4 hours and systolic BP <160 mm Hg at 4 hours were associated with lower rates of hematoma enlargement, and resumption of OAC therapy was associated with lower risk of ischemic events. These findings require replication and assessment in prospective studies. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01829581.

Relationship between baseline white-matter changes and development of late-life depressive symptoms: 3-year results from the LADIS study.

BACKGROUND Growing evidence suggests that cerebral white-matter changes and depressive symptoms are linked directly along the causal pathway. We investigated whether baseline severity of cerebral white-matter changes predict longer-term future depressive outcomes in a community sample of non-disabled older adults. METHOD In the Leukoaraiosis and Disability in the Elderly (LADIS) study, a longitudinal multi-centre pan-European study, 639 older subjects underwent baseline structural magnetic resonance imaging (MRI) and clinical assessments. Baseline severity of white-matter changes was quantified volumetrically. Depressive outcomes were assessed in terms of depressive episodes and depressive symptoms, as measured by the Geriatric Depression Scale (GDS). Subjects were clinically reassessed annually for up to 3 years. Regression models were constructed to determine whether baseline severity of white-matter changes predicted future depressive outcomes, after controlling for confounding factors. RESULTS Baseline severity of white-matter changes independently predicted depressive symptoms at both 2 (p<0.001) and 3 years (p=0.015). Similarly, white-matter changes predicted incident depression (p=0.02). Over the study period the population became significantly more disabled (p<0.001). When regression models were adjusted to account for the influence of the prospective variable transition to disability, baseline severity of white-matter changes no longer predicted depressive symptoms at 3 years (p=0.09) or incident depression (p=0.08). CONCLUSIONS Our results support the vascular depression hypothesis and strongly implicate white-matter changes in the pathogenesis of late-life depression. Furthermore, the findings indicate that, over time, part of the relationship between white-matter changes and depression may be mediated by loss of functional activity.

Pathophysiology of Stroke Rehabilitation: The Natural Course of Clinical Recovery, Use-Dependent Plasticity and Rehabilitative Outcome

Even though the disruption of motor activity and function caused by stroke is at times severe, recovery is often highly dynamic. Recuperation reflects the ability of the neuronal network to adapt. Next to an unmasking of latent network representations, other adaptive processes, such as excitatory metabolic stress, an imbalance in activating and inhibiting transmission, leading to salient hyperexcitability, or the consolidation of novel connections, prime the plastic capabilities of the system. Rehabilitative interventions may modulate mechanisms of neurofunctional plasticity and influence the natural course after stroke, both positively, but potentially also acting detrimentally. Though routine rehabilitative procedures are an integral part of stroke care, evidence as to their effectiveness remains equivocal. The present review describes the natural course of motor recovery, focusing on ischemic stroke, and discusses use- and training-dependent adaptive effects. It complements a prior article which highlighted the pathophysiology of plasticity. Though the interaction between rehabilitation and plasticity remains elusive, an attempt is made to clarify how and to what extent rehabilitative therapy shapes motor recovery.

Long-Term Clinical Outcome in Meige Syndrome Treated with Internal Pallidum Deep Brain Stimulation

Deep brain stimulation of the globus pallidus internus (GPi DBS) is effective in the treatment of primary segmental and generalized dystonia. Although limb, neck, or truncal dystonia are markedly improved, orofacial dystonia is ameliorated to a lesser extent. Nevertheless, several case reports and small cohort studies have described favorable short‐term results of GPi DBS in patients with severe Meige syndrome. Here, we extend this preliminary experience by reporting long‐term outcome in a multicenter case series, following 12 patients (6 women, 6 men) with Meige syndrome for up to 78 months after bilateral GPi DBS. We retrospectively assessed dystonia severity based on preoperative and postoperative video documentation. Mean age of patients at surgery was 64.5 ± 4.4 years, and mean disease duration 8.3 ± 4.4 years. Dystonia severity as assessed by the Burke–Fahn–Marsden Dystonia Rating Scale showed a mean improvement of 45% at short‐term follow‐up (4.4 ± 1.5 months; P < 0.001) and of 53% at long‐term follow‐up (38.8 ± 21.7 months; P < 0.001). Subscores for eyes were improved by 38% (P = 0.004) and 47% (P < 0.001), for mouth by 50% (P < 0.001) and 56% (P < 0.001), and for speech/swallowing by 44% (P = 0.058) and 64% (P = 0.004). Mean improvements were 25% (P = 0.006) and 38% (P < 0.001) on the Blepharospasm Movement Scale and 44% (P < 0.001) and 49% (P < 0.001) on the Abnormal Involuntary Movement Scale. This series, which is the first to demonstrate a long‐term follow‐up in a large number of patients, shows that GPi DBS is a safe and highly effective therapy for Meige syndrome. The benefit is preserved for up to 6 years.

Assessment of gait in subcortical vascular encephalopathy by computerized analysis: a cross-sectional and longitudinal study.

Abstract In subcortical vascular encephalopathy (SVE) gait disturbance is a common and early clinical sign which might be used to monitor disease progression. In the absence of reliable scales and with regard to the equivocal results of highly complex gait imaging devices we assessed the natural course of SVE in a prospective study, using a new straight forward technique to quantify and compare sequential gait studies. We report the results of 300 computerized gait analyses in 119 patients with SVE and 63 age-matched controls. Thirty-nine SVE patients were re-evaluated to monitor the natural course of the disease and to study the correlation of gait disturbances with MRI changes and neuropsychological findings. The system consists of a set of shoes containing 16 load sensors and a measuring-unit reading each sensor at 20-ms intervals. By off-line analysis we graded each recording on a Gait Disorder Score (GDS) with six variables indicating gait steadiness: step frequency, length of gait lines (which represent the movement of the centre of gravity during heel to toe movement), length of single support lines, variability of single and of double support lines, and double support time. In cross-sectional analysis, patients with SVE showed cadence (steps/min) to be reduced at 87.3±19.5 (96.4±7.8 in controls, P < 0.05). Length of gait lines was significantly less: 0.70±0.13 vs. 0.80±0.05 in controls, with length of single support gait lines reduced at 0.42±0.14 in SVE (0.58±0.06 in controls, P < 0.05). Variability of both single support lines (5.69±1.90%; 4.24±1.07% in controls, P < 0.05) and double support lines was elevated (3.59±1.62% vs. 2.54±0.59%), while duration of double support phases was increased (0.19±0.10 s vs. 0.13±0.02 s in controls, P < 0.05). The progressive character of the disease was demonstrated by increasing GDS values in 39 SVE patients with a frontal gait disorder who were re-investigated after a mean interval of 26 months (5.4±4.5 vs. 8.4±5.5, P < 0.05). This study shows the value of a new and practicable gait analysis system for the evaluation of gait disorders and it quantifies the deterioration of gait in SVE patients.

Pathophysiology of Stroke Rehabilitation: Temporal Aspects of Neurofunctional Recovery

Stroke almost always causes an impairment of motor activity and function. Clinical recovery, though usually incomplete, is often highly dynamic and reflects the ability of the neuronal network to adapt. Mechanisms that underlie neurofunctional plasticity are now beginning to be understood. Albeit the enormous efforts undertaken to support the natural course of reconvalescence through rehabilitation, little has been done to relate possible effects of these therapeutic approaches to mechanisms of adaptive pathophysiology. The review presented here focuses on these mechanisms during the course of recovery poststroke. Next to an unmasking of latent network representations, other adaptive processes, such as excitatory metabolic stress, an imbalance in activating and inhibiting transmission, leading to salient hyperexcitability or mechanisms that consolidate novel connections prime the system’s plastic capabilities. These pathophysiological processes potentially interact with rehabilitative interventions. They therefore form the foundation of positive, but possibly also negative recuperation under therapy.

Pipeline embolization device for the treatment of intra- and extracranial fusiform and dissecting aneurysms: initial experience and long-term follow-up.

BACKGROUND Flow-diverting stents offer a promising treatment option for complex aneurysms. OBJECTIVE To evaluate the safety and efficacy of the Pipeline embolization device (PED) in the treatment of fusiform and dissecting aneurysms. METHODS Sixty-five consecutive patients with 69 fusiform and dissecting aneurysms underwent endovascular treatment with the use of the PED. Target vessels included the internal carotid artery (n = 28), middle cerebral artery (n = 2), anterior cerebral artery (n = 1), vertebral artery (n = 20), basilar artery (n = 17), and posterior cerebral artery (n = 1). An average of 3.0 PEDs per target vessel were deployed. RESULTS Exclusion of the aneurysm(s) immediately after PED deployment was not observed. Angiographic follow-up examinations were performed in 63/65 patients (67/69 lesions). They showed complete cure of the target lesion in the first follow-up angiography (3.4 months mean interval) in 24 (36%) cases, partial elimination in 30 (45%), and no improvement in 13 (19%). After the latest follow-up (>1 digital subtraction angiography, n = 49, 27.4 months mean interval) complete cure of the target lesion was observed in 33 (67%), partial elimination in 14 (29%), and no change in 2 (4%). Taking all follow-up examinations together, 39/67 (58%) aneurysms were cured. The morbidity and mortality in the entire series were 5% and 8%, respectively. CONCLUSION Flow diverters offer a promising treatment option in fusiform and dissecting aneurysms. The introduction of flow diverters with different densities might help to identify the optimal amount of coverage needed given different anatomic presentations of fusiform and dissecting aneurysms.

Tremor reduction by subthalamic nucleus stimulation and medication in advanced Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has proved to be effective for tremor in Parkinson’s disease (PD). Most of the recent studies used only clinical data to analyse tremor reduction. The objective of our study was to quantify tremor reduction by STN DBS and antiparkinsonian medication in elderly PD patients using an objective measuring system. Amplitude and frequency of resting tremor and re-emergent resting tremor during postural tasks were analysed using an ultrasound-based measuring system and surface electromyography. In a prospective study design nine patients with advanced PD were examined preoperatively off and on medication, and twice postoperatively during four treatment conditions: off treatment, on STN DBS, on medication, and on STN DBS plus medication. While both STN DBS and medication reduced tremor amplitude, STN DBS alone and the combination of medication and STN DBS were significantly superior to pre- and postoperative medication. STN DBS but not medication increased tremor frequency, and off treatment tremor frequency was significantly reduced postoperatively compared to baseline. These findings demonstrate that STN DBS is highly effective in elderly patients with advanced PD and moderate preoperative tremor reduction by medication. Thus, with regard to the advanced impact on the other parkinsonian symptoms, STN DBS can replace thalamic stimulation in this cohort of patients. Nevertheless, medication was still effective postoperatively and may act synergistically. The significantly superior efficacy of STN DBS on tremor amplitude and its impact on tremor frequency in contrast to medication might be explained by the influence of STN DBS on additional neural circuits independent from dopaminergic neurotransmission.

Health-related quality of life in segmental dystonia is improved by bilateral pallidal stimulation

In contrast to generalized dystonia, reports on the effectiveness of pallidal stimulation on quality of life in patients with segmental dystonia are sparse to date. In ten patients with idiopathic segmental dystonia we prospectively evaluated the effect of pallidal stimulation on quality of life using the SF-36 questionnaire. Parallel to the improvement of motor scores, total SF-36 scores and physical and mental health subscores improved significantly at follow-up to a mean of 17 months postoperatively. Thus, pallidal stimulation should be recognized as a promising treatment option in patients with segmental dystonia.

The transience and nature of cognitive impairments in transient global amnesia: a meta-analysis.

Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of severe amnesia without concomitant focal neurological symptoms. This meta-analysis of the cognitive characteristics of TGA addressed two main issues. First, we examined the hypothesis that the acute phase of TGA is associated with changes of anterograde and retrograde episodic long-term memory sparing semantic and short-term memory, while we had no clear prediction for potential reductions of executive functions due to the relative lack of previous studies addressing this issue. Second, we analyzed the time-course of changes in cognitive functions throughout three time intervals—acute (0–24 hours after TGA onset), postacute (24 hours to 5 days), and long-term phase (5–30 days)—to reveal whether there is a fast versus a delayed recovery. The results of the meta-analysis on 152 effect sizes from 25 studies showed that TGA is characterized by an extraordinarily large reduction of anterograde (d•  =  1.89) and a somewhat milder reduction of retrograde (d•  =  1.28) episodic long-term memory. Moreover, our results indicate the existence of additional, nonamnestic cognitive changes during TGA, because executive functions were also diminished (d•  =  0.79). Reductions in both anterograde episodic long-term memory and executive function recover slowly, as slightly poorer performance in these cognitive domains can be found in the postacute phase (d•s  =  0.32 and 0.44). All cognitive diminutions resolved within the long-term phase, by this calling into question previous reports of poorer performance of TGA patients relative to comparison subjects weeks or months after the attack.