Johannes C. Wöhrle

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.

Gamma activity and reactivity in human thalamic local field potentials

Depth recordings in patients with Parkinson’s disease on dopaminergic therapy have revealed a tendency for oscillatory activity in the basal ganglia that is sharply tuned to frequencies of ∼70 Hz and increases with voluntary movement. It is unclear whether this activity is essentially physiological and whether it might be involved in arousal processes. Here we demonstrate an oscillatory activity with similar spectral characteristics and motor reactivity in the human thalamus. Depth signals were recorded in 29 patients in whom the ventral intermediate or centromedian nucleus were surgically targeted for deep brain stimulation. Thirteen patients with four different pathologies showed sharply tuned activity centred at ∼70 Hz in spectra of thalamic local field potential (LFP) recordings. This activity was modulated by movement and, critically, varied over the sleep–wake cycle, being suppressed during slow wave sleep and re‐emergent during rapid eye movement sleep, which physiologically bears strong similarities with the waking state. It was enhanced by startle‐eliciting stimuli, also consistent with modulation by arousal state. The link between this pattern of thalamic activity and that of similar frequency in the basal ganglia was strengthened by the finding that fast thalamic oscillations were lost in untreated parkinsonian patients, paralleling the behaviour of this activity in the basal ganglia. Furthermore, there was sharply tuned coherence between thalamic and pallidal LFP activity at ∼70 Hz in eight out of the 11 patients in whom globus pallidus and thalamus were simultaneously implanted. Subcortical oscillatory activity at ∼70 Hz may be involved in movement and arousal.

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.

Rapid Response of Parkinsonian Tremor to STN-DBS Changes: Direct Modulation of Oscillatory Basal Ganglia Activity?

Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) has proved to be effective for tremor and other cardinal symptoms in Parkinsons disease (PD), the precise mechanisms of action of DBS are still unclear. We analyzed the time course of resting tremor amplitude and frequency during discontinuation and subsequent reinitiation of STN‐DBS in nine PD patients, using a computerized three‐dimensional motion analysis combined with surface electromyography. Following discontinuation of STN‐DBS, resting tremor amplitude rapidly increased, reaching maximum amplitude after 2 min (mean ± 95%CI: 34.3 ± 13.8 mm; P < 0.01), subsequently stabilizing at a medium level. Reinitiation of stimulation after 30 min resulted in rapid, nearly complete suppression of tremor activity within 1 min (1.4 ± 1.3 mm; P < 0.01) and, furthermore, increased tremor frequency within a few seconds in seven of nine patients. These findings support the hypothesis that STN‐DBS acts by direct interference with the neurotransmission of basal ganglia networks involved in tremor.

Posttraumatic peripherally-induced dystonia and multifocal deep brain stimulation : Case report

OBJECTIVE:We report on the effect of multifocal deep brain stimulation for the treatment of posttraumatic peripherally-induced dystonia. CLINICAL PRESENTATION:A 34-year-old woman presented with an 8-year history of painful tonic dystonia starting in her left leg after injury of the third metatarsal bone. She did not benefit from right-sided pallidal stimulation by an electrode misplaced in the globus pallidus externus in another hospital. INTERVENTION:Quadripolar deep brain stimulation electrodes were placed in the globus pallidus internus and the ventrolateral thalamus by computed tomographic-guided stereotactic surgery and microelectrode recording contralateral to the side of dystonia. The Burke-Fahn-Marsden motor score of 34 did not improve with chronic pallidal or thalamic stimulation. CONCLUSION:Although deep brain stimulation is received with great enthusiasm, it is important to identify its limitations in certain subtypes of dystonia.

Combined pallidal and subthalamic nucleus stimulation in sporadic dystonia-parkinsonism

Multifocal deep brain stimulation (DBS) is a new technique that has been introduced recently. A 39-year-old man with dystonia-parkinsonism underwent the simultaneous implantation of subthalamic nucleus (STN) and globus pallidus internus (GPi) DBS electrodes. While bilateral STN DBS controlled the parkinsonian symptoms well and allowed for a reduction in levodopa, the improvement of dystonia was only temporary. Additional GPi DBS also alleviated dystonic symptoms. Formal assessment at the 1-year follow-up showed that both the parkinsonian symptoms and the dystonia were markedly improved via continuous bilateral combined STN and GPi stimulation. Sustained benefit was achieved at 3 years postoperatively.

Movement disorders after intervertebral disc surgery: Coincidence or causal relationship?

It is well known that brain injury or central traumatic lesions may result in the subsequent appearance of movement disorders such as dystonia or tremor. The concept that peripheral lesions to neural structures may be involved in the pathogenesis of movement disorders has been discussed controversely but has gained more widespread acceptance only recently. Here, we report on 6 patients who developed movement disorders after spinal disc surgery. The movement disorders became manifest with a delay of 1 day to 12 months after surgery. Of the six patients, 4 underwent cervical disc surgery, and 2 patients were operated on for lumbar disc herniation; 2 patients presented with paroxysmal kinesigenic segmental dystonia, 1 patient with focal dystonia, 2 with unilateral tremor, and 1 with bilateral tremor. The appearance of the movement disorder was associated with persistent dermatomal or segmental pain. In all patients, the anatomic distribution of the movement disorder was related to the nerve root or spinal segment of the corresponding disc level and the manifestation was in close temporal relation to the surgery. We conclude that spinal disc surgery may be another, thus far neglected, cause for movement disorders. The postoperative pain syndrome in all patients should be considered as an important factor of pathogenesis. Overall, movement disorders associated with disc surgery appear to be rare, yet they may cause significant discomfort to the affected individual.

Early Motor Evoked Potentials in Acute Stroke: Adjunctive Measure to MRI for Assessment of Prognosis in Acute Stroke within 6 Hours

Background: In acute stroke, a magnetic resonance (MR) perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) mismatch (PWI>DWI mismatch) may indicate tissue at risk for infarction and poor prognosis. However, different to early enthusiasm about this surrogate marker, its validity has shown several drawbacks in individual patients. Rather than relying on imaging, we evaluated motor evoked potentials (MEP) as a measure of cerebral function in the acute stroke setting. Methods: Thirteen patients with acute hemiparetic stroke underwent time to peak PWI and DWI within 6 h after onset as well as recordings of early MEP of first dorsal interosseous muscles. Outcome was assessed by the Unified Neurological Stroke Scale and Barthel Index at day 42. Results: Of 8 patients with PWI>DWI mismatch, 4 patients with normal MEP had a good clinical outcome and 4 patients with absent or pathological MEP had an unfavourable outcome (p < 0.05, Fisher’s exact test). In all patients without PWI>DWI mismatch, MEP findings predicted clinical outcome. Normal MEP at day 0 – but not PWI/DWI findings – significantly correlated with a good clinical outcome. Conclusions: Early MEP recordings in acute stroke patients provide valid prognostic information; they may become more useful for specific treatment decisions than presently available MRI surrogate parameters.

Differential pattern of hand-tapping compromise in vascular versus idiopathic parkinsonism: A study based on computerized movement analysis

We tested the characteristics and the differential pattern of upper extremity motor compromise, comparing hand tapping in patients with subcortical vascular encephalopathy (SVE; n = 18), idiopathic Parkinsons disease (PD; n = 18), and in healthy controls (n = 18). Both patient groups showed significant compromise in hand tapping compared with that in controls, with higher coefficients of variability (CV) regarding tapping amplitude and angular velocity, determined using a computerized movement analysis system. A differential tapping pattern in both patient groups could be demonstrated in that patients with PD showed lower tapping amplitudes than patients with SVE. Both patient groups displayed abnormalities in tapping rhythmicity compared with that in the control group.