Johannes Trenkler

In-Hospital Complication Rates After Stent Treatment of 388 Symptomatic Intracranial Stenoses Results From the INTRASTENT Multicentric Registry

Background and Purpose— Stenting is increasingly used as an adjunct to medical therapy in symptomatic intracranial stenoses. High periprocedural adverse event rates are one of the limitations of endovascular treatment. Data from the INTRASTENT multicentric registry should demonstrate in-hospital complications at the current stage of clinical development of the stent procedure. Methods— Participating centers entered the records of all their consecutive intracranial stent procedures into the database. To determine the clinical outcome in the acute phase, we distinguished transient ischemic attack/nondisabling stroke (modified Rankin Scale <2), disabling stroke, death, and intracranial hemorrhage as clinical complications and analyzed whether they were associated with patient- or stenosis-related risk factors. Results— Data from 372 patients with 388 stenoses proved 4.8% disabling strokes and 2.2% deaths. Transient or minor events were detected in 5.4% of the cases. Hemorrhagic events (3.5%) occurred more frequently after treatment of middle cerebral artery stenoses (P=0.004) and were associated with significantly higher morbidity and mortality rates. Ischemic strokes by compromise of perforating branches were detected mainly in the posterior circulation. However, the overall rate of severe adverse events was not dependent from location, degree, and morphology of the stenosis or from patients age, gender, vascular risk factors, or type of qualifying event. Conclusion— The complication rates within the registry are within the limits of previously published data. Severe adverse events were equally distributed between potential risk groups with similar rates but different types of main complications in the anterior and posterior circulation.

Complication rates using balloon-expandable and self-expanding stents for the treatment of intracranial atherosclerotic stenoses : analysis of the INTRASTENT multicentric registry.

IntroductionUsing balloon-expandable stents (BES) for treatment of intracranial stenoses, high inflation pressures and rigidity of the device are regarded as major drawbacks limiting feasibility and safety of the procedure. Self-expanding stents (SES) were developed to facilitate lesion access and to allow for less aggressive dilatation. We analyzed data of the INTRASTENT multicentric registry to assess whether self-expanding stents significantly reduced peri-interventional complication rates.MethodsRecords of intracranial stent procedures were entered consecutively into the registry. Datasets were divided into two groups according to the type of stent used. For outcome measurement, we chose three categories: TIA/minor stroke [modified Rankin score (mRS) <2], disabling stroke, and patient death. Clinical outcome was compared between BES and SES. We analyzed types of adverse events occurring in each group in addition.ResultsOf 409 atherosclerotic lesions, 254 were treated with BES and 155 with SES. Technical success rates were 97.6% and 98.7%, respectively. Adverse event rates were 4.9%, 3.7%, and 0.8% for TIA/nondisabling stroke, disabling stroke, and death in the BES group compared with 5.3%, 6.0%, and 4.0% in the SES group. The differences were not statistically significant. We observed more perforator strokes after use of BES, but thromboembolic events occurred more often in the SES treatment group.ConclusionData of the INTRASTENT registry do not support the hypothesis that introduction of SES lowered the overall complication rate of intracranial stent procedures. There might be an advantage using self-expanding stents in vessel segments with important perforating arteries.

Interactive knowledge discovery with the doctor-in-the-loop: a practical example of cerebral aneurysms research

Established process models for knowledge discovery find the domain-expert in a customer-like and supervising role. In the field of biomedical research, it is necessary to move the domain-experts into the center of this process with far-reaching consequences for both their research output and the process itself. In this paper, we revise the established process models for knowledge discovery and propose a new process model for domain-expert-driven interactive knowledge discovery. Furthermore, we present a research infrastructure which is adapted to this new process model and demonstrate how the domain-expert can be deeply integrated even into the highly complex data-mining process and data-exploration tasks. We evaluated this approach in the medical domain for the case of cerebral aneurysms research.

A case of variably protease-sensitive prionopathy treated with doxycyclin.

Variably protease-sensitive prionopathy (VPSPr) is a recently described neurodegenerative disorder characterised by the presence of spongiform encephalopathy and an unusual immunostaining and immunoblotting pattern for the disease-associated prion protein (PrPSc).1 This links VPSPr to human prion diseases, which are uniformly fatal disorders. The clinical symptoms and the longer duration of illness make VPSPr distinct from sporadic or idiopathic Creutzfeldt-Jakob disease (sCJD).1 Doxycycline treatment has been evaluated in patients with prion disease, however, there is little evidence that it can reverse the clinical symptoms or reduce the underlying disease progression once established.2 We present a patient with VPSPr who received doxycycline and survived for an extended period of time in an akinetic and mute state. Neuropathological examination was performed using published methods and various anti-PrP antibodies.3 Frozen tissues from selected brain regions were available for biochemical analysis. Tissues were analysed for the presence of protease-resistant PrP (PrPres) as previously described (see online supplementary material).4 In May 2007, a registered psychiatrist suspected an organic affective disorder in a 54-year-old Austrian woman. Two months earlier, medical work-up for presumed weight loss of 16 kg within the past 18 months had been unremarkable. In June 2007, the patient was admitted to a clinic that specialised in disorders of the nervous system. Her family history was negative for neurodegenerative diseases and there was no evidence of exposure to toxins. She reported depressed mood and short-term memory problems, and difficulties with balance, walking, driving and cooking. On neuropsychological examination she was oriented to time, place, person and situation, Mini-Mental State Examination score was 22/30, clock drawing test score was 3/9. She had word-finding difficulties, ideational apraxia, acalculia and visuoconstructive deficits. She displayed affective incontinence with crying fits. She had gait ataxia, and extensor plantar responses were observed with increased tone …

Endovascular thrombectomy for acute ischemic stroke patients anticoagulated with dabigatran.

For the treatment of acute ischemic stroke (AIS), IV recominant tissue plasminogen activator (rtPA) has proven efficacy n eligible patients, but carries an increased risk of intracereral hemorrhage [1]. Preexisting anticoagulation, including the irect thrombin inhibitor dabigatran, usually contraindicates the se of rtPA. This notwithstanding, several single cases of IV tPA treatment in patients with AIS under dabigatran have een reported, with mixed results [2]. Endovascular therapy has merged as a potential, yet still experimental, alternative treatment ption for a number of clinical scenarios with contraindications o IV rtPA [3]. We report successful rescue thrombectomy in two patients who uffered AIS under treatment with dabigatran for atrial fibrillation AF).

The Neuroform Atlas stent to assist coil embolization of intracranial aneurysms: a multicentre experience

Objective To assess the clinical safety and efficacy of the Atlas microstent in stent-assisted coil embolization of wide-necked intracranial aneurysms. Methods Single-center observational study in 36 patients (24 female, 12 male, mean age 56 years) with 37 aneurysms for the endovascular treatment of wide-necked aneurysms. After giving informed consent, patients were included according to the following criteria: aneurysm dome-to-neck ratio <2 or neck diameter >4 mm, and a parent vessel diameter of ≤4.5 mm. Primary endpoint for clinical safety was absence of death, absence of major or minor stroke, and absence of transient ischemic attack. Primary endpoint for treatment efficacy was complete angiographic occlusion according to the Raymond-Roy occlusion classification (RROC) immediately after the procedure. Results In 36/37 (97%) cases, the primary endpoint of safety was reached, one patient had a transitory ischemic attack which completely resolved until discharge. In 31/37 (84%) cases, complete occlusion (RROC 1) was reached, and in 6/36 (17%), a residual neck remained (RROC 2). A sequential approach (first stent, then coiling through the same catheter) was used in 21 cases; the other 16 were treated with the jailing technique. Deployment was technically successful in all cases. Follow-up at a median of 6.1 months was available for 29/37 (78%) aneurysms and showed complete occlusion in 27/29 aneurysms (93%) and a neck remnant in 2 cases (7%). Conclusion Deployment of the Neuroform Atlas microstent is a safe and effective method for the treatment of intracranial wide-necked aneurysms.

Bioptically Confirmed Creutzfeldt-Jakob Disease: Clinical Findings and MRI Characteristics of the Heidenhain Variant

Introduction Creutzfeldt-Jakob disease (CJD) belongs to the group of transmissible human spongiform encephalopathies. It is a very rare neurodegenerative disease of the brain, which occurs in humans as genetic, transmitted or sporadic form. Mutations in the prion protein gene are the cause of the genetic form of prion disease, which shows an autosomal dominant inheritance with almost 100% penetrance. Besides the familial Creutzfeldt-Jakob disease also Gerstmann-Sträussler-Scheinker syndrome and fatal familial insomnia are counted toward this group of diseases. In contrast to its sporadic form the genetic form of the disease has a longer duration (14 months) and the affected patients are younger. Iatrogenic transmission among humans has so far only been described in cases of direct contact with infectious tissue due to dura mater or corneal grafts or due to the administration of growth hormones or gonadotropins extracted from pituitary glands of corpses [1–3]. In 1996, Will et al. described a new variant of CJD, which cumulatively occurred in Great Britain and is counted toward the group of bovine spongiform encephalopathies (BSE). Today it is assumed that the new variant of Creutzfeldt-Jakob disease (today known as vCJD) has a causal relationship with the consumption of BSE-contaminated beef [4]. Within the rest of Europe CJD shows a consistent incidence of one case per one million population per year, with sporadic CJD being the most common form of occurrence of the disease worldwide. The patients that are mostly affected are elderly persons aged between 60 and 70 who develop rapidly progressing dementia combined with myoclonia, ataxia, extrapyramidal and pyramidal disorders within only a few weeks. The clinical end-stage is usually reached after an average disease duration of 6 months and its clinical picture corresponds largely to that of akinetic mutism. A suspected clinical diagnosis of CJD can be confirmed through additional diagnostic procedures like electroencephalograms (EEG), diagnostic investigations of cerebrospinal fluid (CSF) and magnetic resonance images (MRI). The EEG shows periodic biand triphasic complexes. However, these so-called periodic “sharp-wave” complexes can disappear again during the course of the disease but occasionally, they can be provoked through certain stimuli [5, 6]. CSF samples show inconspicuous standard parameters but an abnormally high concentration of neuronal and astrocytic proteins like protein 14-3-3, tau, NSE, and S100 [7, 8]. Among these proteins protein 14-3-3 represents the most important group because with it the prion disease can be established with a specificity of 93% and a sensitivity of 94%. As regards imaging techniques to establish CJD, computed tomography has no significance due to the usually negative findings [9]. By now, MRI is the investigative method of choice with the FLAIR sequence and the diffusion-weighted sequence having the best sensitivity [10–13]. In T2-weighted pictures of the common form of CJD hyperintensities can

Anti-NMDA receptor encephalitis triggered by epilepsy surgery

We report on a patient diagnosed with anti-NMDA receptor (NMDAR) encephalitis after epilepsy surgery. We argue that the encephalitis was directly induced by brain surgery, which would render it the first such case published. A 40-year-old male had suffered from HSV1-encephalitis (HSVE) at the age of 3 years and subsequently developed drug-resistant frontal lobe epilepsy. Previous partial resection of the left frontal lobe had resulted in incomplete remission. After detailed presurgical evaluation, a frontoopercular part of the left precentral gyrus was resected. PCR for HSV1 performed on the specimen was positive, suggesting latent HSV1 infection. MRI 2 days post-surgery was unremarkable except for postinterventional alterations (Day 2, Fig. 1). On day 3, the patient developed semiologically new seizures and pronounced dysarthria and dysphagia. MRI on day 8 showed vasogenic edema of the left subcentral gyrus and a new small cortical diffusion restriction in the rolandic area of the right hemisphere which remained unchanged on an MRI on day 42. Cerebrospinal fluid (CSF) analysis revealed slight lymphocytic pleocytosis (10 cells/μl). The varicellazoster-IgG-CSF/serum-index (AI) was somewhat elevated (2.49), but VZV-PCR was negative. The HSV1/2-IgG-AI and -PCR were unremarkable. Phenytoin, benzodiazepines and dexamethasone were introduced and the patient was discharged to a rehabilitation unit on day 45. Due to severe progressive dysarthria and dysphagia, the patient was transferred back to our hospital on day 56. Subsequently, the patient developed a new paresis of the right arm. An MRI on day 56 revealed progress of the lesions (Fig. 1). CSF analysis showed 17 cells/μl. The HSV1-IgG-AI was elevated (4.47), HSV-PCR remained negative. Therapy with acyclovir was initiated, but no clinical response ensued. 12 days later, serum and CSF NMDAR antibodies returned positive (1:32 and 1:10). Antibodies against Hu, Yo, Ri, PNMA2, CV2, amphiphysin, PCA2, TR, SOX1, Zic4, recoverin, GAD, and anti-glial nuclear antibodies as well as anti-CASPR2-/GABA B-/LGI1-/AMPA-GluR1/2and DPPX-antibodies were negative. Due to lack of clinical improvement and deterioration of MRI findings after steroid treatment and plasmapheresis (Day 85, Fig. 1), immunosuppressive therapy with rituximab and cyclophosphamide was started (Fig. 1). With this regimen, the patient’s MRI and clinical presentation improved markedly (Day 121, Fig. 1). On day 170, NMDAR antibodies were negative in the serum and significantly reduced in the CSF (1:1). In summary, we present a patient who was diagnosed with anti-NMDAR encephalitis shortly after epilepsy surgery. Two pathomechanisms are feasible:

Brain Tumors: Clinical Applications of Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging

One of the most exciting methodologies in the clinical neurosciences evolving toward the end of the twentieth century was functional magnetic resonance imaging (fMRI). Whereas MRI is used to produce structural images of subjects’ brain the functional component allows an in vivo measurement of brain activity. fMRI has provided new insights into human cognitive functions. Till now it was mainly used for basic scientific questions and has provided foundations for at least five large-scale neurocognitive networks identified in the human brain, namely for spatial attention, language, memory-emotion, executive function, and face and object recognition. In addition, white matter tractography based on diffusion tensor imaging (DTI) has become a well-accepted noninvasive tool for exploring the white matter architecture of the human brain in vivo. These two MR techniques are complementary in describing functional and anatomical components of grey and white matters. Furthermore, fMRI is useful to define the seed regions for DTI, because large interindividual anatomical variations make it difficult to define tracking seed areas based reliably on macroanatomical landmarks. An accurate definition of seed regions for the reconstruction of a specific neuronal pathway becomes even more challenging in patients suffering from space occupying brain lesions due to the displacement of the tissue and the distortion of anatomical landmarks around the lesion. Therefore, fMRI and DTI play a growing role in clinical neuroimaging with increasing applications in neurosurgical planning using neuronavigation. By means of neuronavigational devices both modalities can intuitively be used during surgical procedures. The goal of tumor surgery is to optimize the extent of resection, while minimizing the risk of a permanent neurological deficit. Because the tumor may infiltrate eloquent areas and because of major intersubject anatomical and functional variability, cortical functional organization, subcortical connectivity and brain plasticity can be studied at an individual scale. Presurgical functional neuroimaging and tractography can show the relationships between eloquent regions and the tumor, and consequently the cortical and subcortical structures essential for brain functions can be identified and preserved. In addition, post-operative control and longitudinal neuroimaging studies are important to study adaptive changes in network behaviour and to monitor the effects of brain plasticity.

Intrazerebral lokalisiertes Sarkom NOS – eine interdisziplinäre Herausforderung

Hintergrund:In der Literatur werden nur wenige Fälle eines intrazerebral lokalisierten neurogenen Sarkoms beschrieben. Hinsichtlich der therapeutischen Empfehlungen existieren keine exakten Richtlinien.Fallbericht:Bei einer 28-jährigen Patientin wurde eine Raumforderung links parietal postzentral diagnostiziert. Es erfolgte die Tumorexstirpation. Der Tumor war letztlich keiner rubrizierten Entität zuordenbar und wurde als Sarkom NOS eingestuft. Der Tumor zeigte eine ausgesprochene Rezidivneigung. Zweimal wurde eine Rezidivoperation durchgeführt. Aufgrund des raschen Tumorwachstums wurde die Radiotherapie frühestmöglich begonnen. Insgesamt wurde eine Dosis von 5 400 cGy in 22 Fraktionen verabreicht.Ergebnis:In der magnetresonanztomographischen Kontrolle zeigte sich eine ausgeprägte Tumorregression. Eine außerhalb des Bestrahlungsfeldes liegende Läsion hatte an Größe zugenommen. Bei der Patientin wurden pulmonale Filiae diagnostiziert, und sie erhielt eine Chemotherapie. Unter dieser Therapie nahmen die pulmonalen Filiae an Größe ab. Leider entwickelte die Patientin eine hepatische Enzephalopathie und starb an einem Multiorganversagen.Schlussfolgerung:Beim intrazerebral lokalisierten Sarkom NOS scheint der frühestmögliche Beginn der Radiotherapie post operationem wegen der beobachteten Strahlensensibilität sinnvoll. Hinsichtlich der lokalen Kontrolle zeigt sich ein dokumentiertes ausgezeichnetes Ansprechen dieser Tumorentität auf die Radiotherapie. Die Fernabsiedlung kann erwartungsgemäß nicht beeinflusst werden. Zur Therapieoptimierung ist ein interdisziplinäres Vorgehen unumgänglich.Background:In the literature, surveys of malignant intracerebral nerve sheath tumors are very rare (Table 1). Therapeutic guidelines do not exist.Case Report:A 28-year-old female patient presented with a tumor in the postcentral region of the left parietal lobe (Figures 1 and 2). The specimen could not be categorized into a common tumor entity and was classified as sarcoma NOS. Shortly after surgery, a recurrence occurred (Figures 3 to 5) followed by a further excision. Due to the rapid tumor growth irradiation with CT-aided treatment planning (Figure 6) has been started immediately afterwards. A dose of 5,400 cGy in 22 fractions was administered.Result:2 weeks after treatment, the patient presented with a noticeable tumor regression (magnetic resonance imaging; Figures 7 to 9). She developed pulmonary metastases. A partial remission could be achieved by systemic chemotherapy. Unfortunately, the patient died because of an exacerbation of a hepatic encephalopathy.Conclusion:In cases of intracerebrally localized sarcomas NOS, the earliest possible start of radiotherapy after surgery seems useful because of the noticed radiosensitivity of these tumors. In regard of the local control, this tumor entity shows a documented excellent response to radiotherapy. Expectedly, distant metastases cannot be influenced. Interdisciplinary cooperation is mandatory to enhance the diagnostic process, the treatment decisions, and the results.