Stefanie Behnke

Stent-Assisted Mechanical Recanalization for Treatment of Acute Intracerebral Artery Occlusions

Background and Purpose— The purpose of this study was to demonstrate a new approach to the use of a self-expanding stent in the treatment of acute ischemic stroke. Methods— Twenty-two consecutive patients with acute intracerebral artery occlusions were treated with a self-expandable intracranial stent, which was withdrawn in its unfolded state. For this technique, we used the Solitaire AB/FR, which is the only intracranial stent that is fully recoverable. Eight patients had an occlusion of the basilar artery, 12 had a middle cerebral artery occlusion, and 2 had terminal carotid artery occlusions; 6 of these had to be treated first for an acute occlusion originating in the internal carotid artery. Recanalization results were assessed by follow-up angiography immediately after the procedure. Neurologic status was evaluated before and after treatment (90-day follow-up) according to the National Institutes of Health Stroke Scale and modified Rankin scale. Results— Successful revascularization was achieved in 20 of 22 (90.9%) patients (thrombolysis in cerebral infarction [TICI] 2a/b and 3), a TICI 3 state was accomplished in 12 patients, and partial recanalization or slow distal branch filling with filling of more than two-thirds of the vessel territory was achieved in 8 patients (TICI 2b). There was immediate flow restoration in 21 of 22 (95.4%) cases after deployment of the device. The stent was removed in its unfolded state in all patients. The mean time from stroke symptom onset to recanalization was 277 minutes, with a standard deviation of 118 minutes. Mean National Institutes of Health Stroke Scale score on admission was 19.4, with a standard deviation of 5.7. Almost two-thirds of the patients (63.6%) improved by >10 points on the National Institutes of Health Stroke Scale at discharge, and 50% showed a modified Rankin scale score of ≤2 at 90 days (59% with a modified Rankin scale ≤3). Mortality was 18.1%. In 1 case, an asymptomatic intracranial hemorrhage was detected on control computed tomography, and 2 patients had a symptomatic intracranial hemorrhage. Conclusion— Withdrawal of an unfolded, fully recoverable, intracranial stent yielded very promising angiographic and clinical results. It combines the advantages of prompt flow restoration and mechanical thrombectomy.

Differentiation of Parkinson’s disease and atypical parkinsonian syndromes by transcranial ultrasound

Neuroimaging is known to complement clinical findings in the diagnostic work up of parkinsonian syndromes. Recently, transcranial ultrasound was reported to have a high diagnostic yield in differentiating idiopathic Parkinson’s disease (IPD) from atypical parkinsonian syndromes. This report summarises the sonographic findings of 102 patients with IPD, 34 patients with multiple system atrophy, and 21 patients with progressive supranuclear palsy. Increased echogenicity of the substantia nigra is predictive for IPD whereas a low echogenic substantia nigra, particularly when combined with a hyperechogenic lentiform nucleus, strongly suggests an atypical Parkinsonian syndrome. The underlying causes for the differential echo pattern of the substantia nigra remain unknown.

Enlarged Substantia Nigra Hyperechogenicity and Risk for Parkinson Disease: A 37-Month 3-Center Study of 1847 Older Persons

OBJECTIVE To evaluate whether enlarged substantia nigra hyperechogenicity (SN+) is associated with an increased risk for Parkinson disease (PD) in a healthy elderly population. DESIGN Longitudinal 3-center observational study with 37 months of prospective follow-up. SETTING Individuals 50 years or older without evidence of PD or any other neurodegenerative disease. PARTICIPANTS Of 1847 participants who underwent a full medical history, neurological assessment, and transcranial sonography at baseline, 1535 could undergo reassessment. MAIN OUTCOME MEASURE Incidence of new-onset PD in relation to baseline transcranial sonography status. RESULTS There were 11 cases of incident PD during the follow-up period. In participants with SN+ at baseline, the relative risk for incident PD was 17.37 (95% confidence interval, 3.71-81.34) times higher compared with normoechogenic participants. CONCLUSIONS In this prospective study, we demonstrate for the first time a highly increased risk for PD in elderly individuals with SN+. Transcranial sonography of the midbrain may therefore be a promising primary screening procedure to define a risk population for imminent PD.

Enlarged hyperechogenic substantia nigra as a risk marker for Parkinson's disease

SN hyperechogenicity (SN+), determined by transcranial sonography, has been proposed as a risk factor for Parkinsons disease (PD). Recently, we reported a 17.4‐fold increased risk for PD in individuals with SN+ older than 50 years within 3 years.

Carotid Artery Stenting in Acute Stroke

OBJECTIVES The purpose of this study is to demonstrate the technical success of carotid artery stenting in acute extracranial internal carotid artery (ICA) occlusion as well as the benefit in clinical outcome. BACKGROUND Stroke caused by acute occlusion of the ICA is associated with a significant level of morbidity and mortality. For this type of lesion, treatment with standard intravenous thrombolysis alone leads to a good clinical outcome in only 17% of the cases, with a death rate as high as 55%. Recanalization of the occluded ICA can lead to an improvement in acute symptoms of stroke, prevent possible deterioration, and reduce long-term stroke risk. At present, there is no consensus treatment for patients with acute ischemic stroke presenting with severe clinical symptoms due to atherosclerotic occlusion of the extracranial ICA. METHODS Carotid artery stenting was performed in 22 patients with acute atherosclerotic extracranial ICA occlusion within 6 h of stroke symptom onset. In 18 patients, there was an additional intracranial occlusion at the level of the terminal segment of the ICA (n = 4) and at the level of the middle cerebral artery (n = 14). Intracranial occlusions were either treated with the Penumbra system or the Solitaire stent-based recanalization system, or a combination of mechanical recanalization and intra-arterial thrombolysis. Recanalization results were assessed by angiography immediately after the procedure. The neurologic status was evaluated before and after the treatment with a follow-up as long as 90 days using the National Institutes of Health Stroke Scale and the modified Rankin Scale. RESULTS Successful revascularization of extracranial ICA with acute stent implantation was achieved in 21 patients (95%). There was no acute stent thrombosis. After successful recanalization of the origin of the ICA, the intracranial recanalization with Thrombolysis In Myocardial Infarction flow grade 2/3 was achieved in 11 of the 18 patients (61%). The overall recanalization rate (extracranial and intracranial) was 14 of 22 patients (63%). Nine patients (41%) had a modified Rankin Scale score of ≤2 at 90 days. The mortality rate was 13.6% at 90 days. CONCLUSIONS Carotid artery stenting in acute atherosclerotic extracranial ICA occlusion with severe stroke symptoms is feasible, safe, and useful within the first 6 h after symptom onset.

Reproducibility and diagnostic accuracy of substantia nigra sonography for the diagnosis of Parkinson's disease

Objective Transcranial sonography (TCS) shows characteristic hyperechogenicity of the substantia nigra (SN) in patients with Parkinsons disease (PD). Although this feature is well established, sufficient observer reliability and diagnostic accuracy are prerequisites for advancements of this method. Methods The authors investigated both aspects in a cross-sectional study with four blinded TCS raters in 22 PD patients and 10 healthy controls. Results As expected, the authors found significant bilateral SN hyperechogenicity in PD patients. Quantitative computerised SN planimetry had a substantial intra- (intraclass correlation coefficient (ICC) 0.97 and 0.93 respectively for both hemispheres) and inter-rater reliability (ICC 0.84 and 0.89), while visual semiquantitative echogenicity grading of the SN revealed a moderate intrarater (weighted kappa 0.80 ipsilateral and 0.74 contralateral) and slight (0.33) to fair (0.51) inter-rater reliability only. Diagnostic accuracy measured as the area under the curve of receiver-operating characteristics plots was highest in TCS of the SN opposite the clinically most affected body side (planimetry 0.821, echogenicity grading 0.792) with a hyperechogenic area of 0.24 cm2 as the optimum cut-off value for the differentiation between PD and controls (sensitivity 79%, specificity 81%). Conclusions The data demonstrate that the observer variability of SN planimetry is low in the hands of experienced investigators. This approach also offers adequate diagnostic accuracy. The authors conclude that reliable SN TCS data on PD can be achieved in clinical routine and multicentre trials when standardised analysis protocols and certain quality criteria of brain parenchyma sonography are met.

The PRIPS study: screening battery for subjects at risk for Parkinson's disease

Screening batteries to narrow down a target‐at‐risk population are essential for trials testing neuroprotective compounds aiming to delay or prevent onset of Parkinsons disease (PD).

Functional relevance of ceruloplasmin mutations in Parkinson’s disease

Increased iron levels of the substantia nigra and the discovery of ceruloplasmin mutations in patients with Parkinsons disease (PD) imply impaired iron metabolism in this neurodegenerative disorder. Ceruloplasmin has ferroxidase activity oxidizing iron(II) to iron(III). In the present study, we analyzed the amount of ceruloplasmin, iron, ferritin, and transferrin and the ceruloplasmin ferroxidase activity in serum of patients with the diagnosis of PD carrying the ceruloplasmin mutations I63T, D544E, and R793H. The impact of these missense mutations on the biosynthesis of holo‐ceruloplasmin was investigated in cell culture experiments. Functional relevance was found for the ceruloplasmin mutations I63T and D544E. In vivo, the I63T mutation resulted in half the normal ceruloplasmin concentration and markedly reduced ferroxidase activity in serum from a heteroallelic PD patient. In cell culture, the I63T glycosylphosphatidylinositol (GPI)‐linked ceruloplasmin isoform was retained in the endoplasmatic reticulum of human embryonic kidney cells. Furthermore, the D544E polymorphism resulted in significantly reduced serum ceruloplasmin levels and ferroxidase activity in heteroallelic patients and in expression of mainly apo‐ceruloplasmin in cell culture. Our studies indicate that altered activity of ceruloplasmin may present a vulnerability factor for iron induced oxidative stress in PD.

Hyperechogenicity of the substantia nigra in healthy controls is related to MRI changes and to neuronal loss as determined by F-Dopa PET.

Transcranial ultrasound (TCS) has been shown to reveal hyperechogenicity of the substantia nigra (SN) in Parkinsonian patients and in about 10% of healthy controls. It is hypothesized that SN hyperechogenicity in healthy subjects is a vulnerability marker for idiopathic Parkinsons disease (IPD). Although there is strong evidence that the echomarker results from increased local iron content, the exact pathophysiological mechanisms remain incompletely understood. Thus, prognostic impact can only be estimated. We examined 14 subjects with SN hyperechogenicity (SN+) (7 IPD patients and 7 controls) and 7 healthy controls without the echomarker (SN-) by a magnetic resonance imaging method (MRI; T2 relaxation times) known to reveal tissue inhomogeneity following abnormal iron content and by F-Dopa PET to assess nigrostriatal function.

Cross-sectional study discloses a positive family history for Parkinson’s disease and male gender as epidemiological risk factors for substantia nigra hyperechogenicity

SummaryHyperechogenicity of the substantia nigra (SN) has been proposed to be a typical finding in Parkinson’s disease (PD) and a marker of vulnerability to nigrostriatal dysfunction in healthy subjects. This large cross-sectional study including 1120 subjects older than 50 years without any signs of PD was performed to evaluate the association of SN hyperechogenicity and other proposed epidemiological risk factors for PD. Among all variables assessed only family history of PD and male gender proved to be significantly associated with SN hyperechogenicity, indicating a genetic predisposition for the ultrasound marker.