Roman Herzig

Modulation of Cortical Activity in Patients Suffering from Upper Arm Spasticity following Stroke and Treated with Botulinum Toxin A: An fMRI Study

Botulinum toxin (BTX) treatment can relieve focal arm spasticity after stroke, presumably through dynamic changes at multiple levels of the motor system, including the cerebral cortex. However, the neuroanatomical correlate of BTX spasticity relief is not known and should be reflected in changes of cortical activation during motor tasks assessed using repeated functional magnetic resonance imaging (fMRI).

Troponin T in Acute Ischemic Stroke

Multiple interactions are considered to occur among the various forms of cardiovascular and cerebrovascular diseases. The aim of this study was to assess the serum level profile of cardiac troponin T (cTnT) in patients with acute ischemic stroke (AIS) to evaluate factors associated with increased serum levels of cTnT. Patients with AIS enrolled in this prospective observational study were admitted to the hospital <12 hours after stroke onset. At admission, and 4 hours later, all patients were subjected to neurologic examinations and brain computed tomography or magnetic resonance imaging; standard laboratory tests, including cTnT and other cardiac markers; and repeated electrocardiography. Correlations between cTnT and several baseline parameters were tested, and multivariate regression analysis was used to assess the predictors of cTnT elevation. In total, 107 consecutive patients with AIS (65 men, mean age 67.2 ± 14.2 years) were enrolled. Thirty-nine patients (36.4%) presented with elevated cTnT above the upper limit of normal. The cTnT levels were correlated significantly with age (r = 0.448) and the levels of N-terminal pro-brain natriuretic peptide (r = 0.528), cystatin C (r = 0.457), creatine kinase-MB mass (r = 0.253), urea (r = 0.281), and albumin (r = -0.219). Multiple logistic regression analysis found creatinine >90 μmol/L (odds ratio 3.45, 95% confidence interval 1.09 to 10.85), N-terminal pro-brain natriuretic peptide (odds ratio 100 μg/L increase 1.09, 95% confidence interval 1.03 to 1.16), and creatine kinase-MB mass (odds ratio per 1 μg/L increase 1.45, 95% confidence interval 1.04 to 2.04) were associated with cTnT elevation in patients with AIS. In conclusion, elevated cTnT can be frequently detected in patients with AIS. To reliably identify patients with current acute myocardial impairment, more in-depth clinical investigation is needed.

Correlation Between Substantia Nigra Features Detected by Sonography and Parkinson Disease Symptoms

Objective. The aim of this study was to assess the correlation between substantia nigra (SN) echogenic features and area and the clinical symptoms in patients with Parkinson disease (PD). Methods. Clinical examinations and transcranial sonographic evaluations of the SN were performed in 115 consecutive patients with PD. The presence of tremors, rigidity, bradykinesia, gait disorders, speech disorders, and hypomimia was evaluated according to the motor portion of the Unified Parkinson Disease Rating Scale. The Mann‐Whitney U test, the Kruskal‐Wallis test, analysis of variance, and multivariate analysis were applied when assessing statistical significance. Results. An enlarged and hyperechoic SN existed in 84.0% of patients with bilateral rigidity but in only 70.6% of patients with unilateral rigidity (P < .05). Similarly, 85.0% of patients with bilateral bradykinesia in comparison with 65.7% of patients with unilateral bradykinesia had an enlarged and hyperechoic SN (P < .05). A significant correlation was shown between the SN echogenicity and area (r = 0.705; P < .01). Conclusions. An enlarged and hyperechoic SN seems to be a marker of structural involvement of the SN in patients with PD. This structural involvement is expressed more in patients with bilateral rigidity and bradykinesia.

Safety and Efficacy of the Sonographic Acceleration of the Middle Cerebral Artery Recanalization: Results of the pilot Thrombotripsy Study

The aim was to demonstrate the safety and efficacy of continuous ultrasound monitoring of the artery occlusion area (sonothrombotripsy) in patients with acute middle cerebral artery (MCA) occlusion. A total of 52 consecutive patients with acute MCA occlusion were included in the thrombotripsy group. Doppler monitoring of the region of occlusion was performed for up to 45 min. The control group was created from the NAIS study database. Patients were matched for their vascular status, age, sex, artery occlusion, NIHSS at admission, rt-PA treatment and time to the first ultrasound examination. The number of recanalized arteries at 6 and 24 h after the onset of symptoms, the number of independent patients (mRS 0-2 versus 3-6) after 90 d, and the number of serious adverse events were statistically evaluated. In the thrombotripsy group, 19 patients (36.5%) had complete recanalization and 27 (51.9%) patients had partial recanalization at 1 h after the start of the TCCS monitoring. Higher recanalization rates at 6 and 24 h after stoke onset were also seen compared with controls (69.2% versus 7.7% and 92.3% versus 61.5% complete recanalizations, respectively, p < 0.05). Independence (mRS 0-2) at day 90 was achieved by 61.5% of the thrombotripsy patients and 32.7% controls, p < 0.05, odds ratio 1.88 (95% confidence interval = 1.23 - 2.90). In both groups, two symptomatic intracerebral hemorrhages and one symptomatic brain edema occurred. Sonothrombotripsy with diagnostic transcranial duplex technology is safe and may offer benefit in addition to standard of care stroke treatment.

Transcranial Sonography of the Substantia Nigra: Digital Image Analysis

BACKGROUND AND PURPOSE: Increased echogenicity of the substantia nigra is a typical transcranial sonography finding in Parkinson disease. Experimental software for digital analysis of the echogenic substantia nigra area has been developed. The aim of this study was to compare the evaluation of substantia nigra echogenicity by using digital analysis with a manual measurement in patients with Parkinson disease and healthy volunteers. MATERIALS AND METHODS: One hundred thirteen healthy volunteers were enrolled in the derivation cohort, and 50 healthy volunteers and 30 patients with Parkinson disease, in the validation cohort. The substantia nigra was imaged from the right and left temporal bone window by using transcranial sonography. All subjects were examined twice by using different sonographic machines by an experienced sonographer. DICOM images of the substantia nigra were encoded; then, digital analysis and manual measurement of the substantia nigra were performed. The 90th percentile of the derivation cohort values was used as a cut-point for the evaluation of the hyperechogenic substantia nigra in the validation cohort. The Spearman coefficient was used for assessment of the correlation between both measurements. The Cohen κ coefficient was used for the assessment of the correlation between both measurements and Parkinson disease diagnosis. RESULTS: The Spearman coefficient between measurements by using different machines was 0.686 for digital analysis and 0.721 for manual measurement (P < .0001). Hyperechogenic substantia nigra was detected in the same 26 (86.7%) patients with Parkinson disease by using both measurements. Cohen κ coefficients for digital analysis and manual measurement were 0.787 and 0.762, respectively (P < .0001). CONCLUSIONS: The present study showed comparable results when measuring the substantia nigra features conventionally and by using the developed software.

Acute ischaemic stroke in pregnancy: a severe complication of ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of sterility treatment. It is characterised by ovarian enlargement, ascites, electrolyte disturbance, hypovolaemia and haemoconcentration. A case of ischaemic stroke due to right middle cerebral artery (MCA) occlusion in a young female with OHSS after pharmacological treatment of sterility is reported. Left central hemiparesis occurred suddenly within a few days after the embryo transfer. Magnetic resonance imaging diffusion-weighted images showed infarction in the right basal ganglia and magnetic resonance angiography (MRA) revealed the occlusion of the M1 segment of the right MCA. The haemodilution and the anticoagulation therapy were effective. Twenty-four hours after the stroke onset, MRA showed MCA recanalisation. The neurological deficit resolved completely within 3 months. The patient delivered 2 healthy infants at term. This case emphasises that the recent advent of ovulation induction and reproductive techniques is a newly recognised cause of cerebral stroke in otherwise healthy females.

Combination of linkage and association studies for brain arteriovenous malformation.

Background and Purpose— Genetic factors for brain arteriovenous malformation are unexplored because of the low incidence of familial cases, albeit local and familial clustering. We used a combination of a linkage study and an association study to explore the genetic background. Methods— A genome-wide linkage analysis was performed in 12 patients from 6 unrelated families using the GENEHUNTER program. A genome-wide association analysis of 26 cases and 30 controls was performed using a GeneChip 10K mapping array. Significance levels for linkage and single single-nucleotide polymorphism association analyses were set at P<0.05 and P<0.0001, respectively. Genotyping was also performed using 58 960 single-nucleotide polymorphisms for 2 sets of discordant twins. Results— The linkage analysis revealed 7 candidate regions, with the highest logarithm of odds score of 1.88 (P=0.002) at chromosome 6q25. A significant association was observed for 4 single-nucleotide polymorphisms and 2 haplotypes, but none of them overlapped with candidate linkage regions. Genotyping of the twins showed no genetic heterogeneity. Conclusions— The present study failed to identify genetic factors for arteriovenous malformation although the low statistical power may have resulted in such evidence being missed.

Posterior vs. anterior circulation infarction: demography, outcomes, and frequency of hemorrhage after thrombolysis

Background Intravenous thrombolysis is considered to be the standard specific reperfusion therapy in acute ischemic stroke in both anterior and posterior cerebral circulation. Aims Our aim was to evaluate the 90-day outcome and rate of intracranial hemorrhage after recombinant tissue plasminogen activator administration in posterior circulation stroke and to compare the intracranial hemorrhage risk for posterior circulation stroke and anterior circulation stroke. Methods The set consisted of 877 consecutive acute ischemic stroke patients (777 anterior circulation stroke; 100 posterior circulation stroke) who underwent intravenous thrombolysis with recombinant tissue plasminogen activator in a standard dose of 0·9 mg/kg. The role of following factors was assessed: presenting characteristics, intracranial hemorrhage classification according to ECASS I, mortality, and 90-day clinical outcome assessed using the modified Rankin scale. Results Good clinical outcomes (modified Rankin scale 0–2) were noted in 59% of posterior circulation stroke patients, with a mortality rate of 19%. Intracerebral hemorrhage was significantly less frequent in posterior circulation stroke than in anterior circulation stroke patients (5·1 vs. 17·2%; P = 0·002). The risk of large hemorrhage (parenchymal hematoma 1 and 2) was 5·2 times higher in anterior circulation stroke patients (P = 0·007). The following additional statistically significant differences were found between posterior circulation stroke and anterior circulation stroke patients: median age, male gender, presence of atrial fibrillation, hyperlipidemia, median time to treatment, and median blood glucose level on admission. Conclusions Our study suggests that posterior circulation stroke is associated with a lower risk of intracranial hemorrhage than anterior circulation stroke is.

Genomewide association study identifies no major founder variant in Caucasian moyamoya disease

Moyamoya disease (MMD) is an idiopathic cerebrovascular occlusive-stenosis disorder at the terminal portion of internal carotid arteries and its main branches, accompanied by collateral vascular networks at the base of the circle of Willis (Takeuchi and Shimizu 1957; Suzuki and Takaku 1969). MMD has the highest prevalence in East Asian countries and a low prevalence in European countries (Goto and Yonekawa 1992; Kuroda and Houkin 2008). We have found that the p.R4810K variant in the ring finger protein 213 (RNF213) is a major founder susceptibility gene for East Asian MMD (Liu et al. 2010, 2011). In this study, we aimed to test whether there is a major founder susceptibility gene for Caucasian MMD using a genomewide association study (GWAS). We demonstrated that there was no major founder variant in Caucasian MMD as it is in East Asian MMD. We identified several suggestive association regions for Caucasian MMD.

Detection of Intracranial Arterial Stenosis Using Transcranial Color-Coded Duplex Sonography, Computed Tomographic Angiography, and Digital Subtraction Angiography

The aim of this retrospective study was to compare intracranial arterial stenosis in patients with stroke using 3 different methods: transcranial color‐coded duplex sonography, computed tomographic (CT) angiography, and digital subtraction angiography in a common clinical practice.