[Comparability of different data sources on stroke care in Germany]. / Vergleichbarkeit unterschiedlicher Datenquellen zur Schlaganfallversorgung in Deutschland.

This article reviews different methodological approaches for determining treatment reality of ischemic stroke patients in acute care hospitals. Considering specific advantages and disadvantages of two different epidemiologic approaches, a specific comparison was carried out of cases from a structured analysis of the nationwide German diagnosis-related groups (DRG) statistics and data from the acute stroke treatment in Hesse (SA_HE) for 2018 collated by the office for quality management. According to the DRG statistics and the SA_HE data, 16,267 and 15,643 acute ischemic stroke patients (ICD code I63) were treated in Hesse in 2018, with 53.7% and 54.5% males, respectively. The overall age distribution did not show significant differences between the two data sources; however, stroke patients over the age of 70 years were registered significantly more often in the DRG statistics. The rates of systemic thrombolysis were 16.5% in both data sources and the rates of mechanical thrombectomy were 5.6% and 5.9%, respectively. The analysis shows that after a rational limitation of the included cases and based on the place of treatment, there were no statistically significant differences concerning the number of hospitalized patients with ischemic stroke, distribution of gender and age as well as the documented rates of systemic thrombolysis and mechanical thrombectomy. It can therefore be concluded that the well-controlled stroke quality register examined is able to capture a sufficient number of hospitalized acute ischemic stroke cases and treatment rates. Therefore, it appears to be recommendable to adopt the strict Hessian guidelines for data acquisition and control nationwide. In this way a nationwide combined analysis of data from the working group of German stroke registers and the DRG statistics would be possible.

The German trial on Aciclovir and Corticosteroids in Herpes-simplex-virus-Encephalitis (GACHE): a multicenter, randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Comprehensive treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major clinical challenge. The current therapy gold standard is aciclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains around 20% and a majority of survivors suffer from severe disability. Experimental research and recent retrospective clinical observations suggest a favourable therapy response to adjuvant dexamethasone. Currently there is no randomized clinical trial evidence, however, to support the routine use of adjuvant corticosteroid treatment in HSVE. METHODS: The German trial of Aciclovir and Corticosteroids in Herpes-simplex-virus-Encephalitis (GACHE) studied the effect of adjuvant dexamethasone versus placebo on top of standard aciclovir treatment in adult patients aged 18 up to 85 years with proven HSVE in German academic centers of Neurology in a randomized and double blind fashion. The trial was open from November 2007 to December 2012. The initially planned sample size was 372 patients with the option to increase to up to 450 patients after the second interim analysis. The primary endpoint was a binary functional outcome after 6 months assessed using the modified Rankin scale (mRS 0-2 vs. 3-6). Secondary endpoints included mortality after 6 and 12 months, functional outcome after 6 months measured with the Glasgow outcome scale (GOS), functional outcome after 12 months measured with mRS and GOS, quality of life as measured with the EuroQol 5D instrument after 6 and 12 months, neuropsychological testing after 6 months, cranial magnetic resonance imaging findings after 6 months, seizures up to day of discharge or at the latest at day 30, and after 6 and 12 months. RESULTS: The trial was stopped prematurely for slow recruitment after 41 patients had been randomized, 21 of them treated with dexamethasone and 20 with placebo. No difference was observed in the primary endpoint. In the full analysis set (n = 19 in each group), 12 patients in each treatment arm achieved a mRS of 0-2. Similarly, we did not observe significant differences in the secondary endpoints (GOS, mRS, quality of life, neuropsychological testing). CONCLUSION: GACHE being prematurely terminated demonstrated challenges encountered performing randomized, placebo-controlled trials in rare life threatening neurological diseases. Based upon our trial results the use of adjuvant steroids in addition to antiviral treatment remains experimental and is at the decision of the individual treating physician. Unfortunately, the small number of study participants does not allow firm conclusions. TRIAL REGISTRATION: EudraCT-Nr. 2005-003201-81.

Tryptophan immunoadsorption for the treatment of autoimmune encephalitis.

BACKGROUND AND PURPOSE: Detection of autoantibodies against neuronal surface antigens and their correlation with the pattern and severity of symptoms led to the definition of new autoimmune-mediated forms of encephalitis and was essential for the initiation of immunotherapies including plasma exchange. The elimination of autoantibodies using selective immunoadsorption (IA) is a pathophysiologically guided therapeutic approach but has not yet been evaluated in a separate analysis. METHODS: A retrospective analysis was performed of patients with autoimmune encephalitis who were treated with tryptophan IA in six neurological clinics between 2009 and 2013. The modified Rankin scale (mRS) was used to evaluate neurological status before and after IA. RESULTS: Data on 13 patients were documented. Twelve patients were positive for specific autoantibodies (NMDA-R, GABA, GAD, Lgl1). Patients received a series of a median of six IA treatments. Median mRS of all patients was 3.0 before IA and 2.0 after IA (P < 0.001). Eleven patients improved by at least one point in mRS after IA. CONCLUSION: For autoimmune-mediated forms of encephalitis rapid elimination of autoantibodies with selective IA seems to be an effective therapeutic option as part of multimodal immune therapy.

Providing systematic detailed information on medication upon hospital discharge as an important step towards improved transitional care.

WHAT IS KNOWN AND OBJECTIVE: Good communication between hospital and primary care physicians (PCPs) is important for the continuity of patient care in the transition phase following hospital treatment. Drug-related problems and medication errors may occur at that interface. Discharge letters often lack a structured medication report at the end and therefore may not provide the reasons for medication changes, resulting in low adherence rates. The objectives were to develop a structured medication report as part of the discharge letter, to evaluate the impact of the medication report in ischaemic stroke patients and to identify the most important issues in the transitional care process of stroke patients. METHODS: First, a structured medication report was developed. Thereafter, the impact of this new medication report on clinical practice was evaluated with an open, prospective, interventional two-phase study conducted at the Klinikum Fulda gAG (Germany), which included patients with ischaemic stroke and >2 drugs in the discharge medication. In the control group (CG), the neurologist included the current medication in the discharge letter. In the intervention group (IG), the clinical pharmacist added the detailed information to a medication report. To evaluate adherence to discharge medication, the PCP was interviewed 3 months after hospital discharge about the medication. Adherence was measured with respect to the entire medication regimen, antithrombotic and cholesterol-lowering drugs and discontinued medication. The most important issues in the transitional care for patients with ischaemic stroke were identified on the basis of the secondary stroke prevention and cardiovascular risk factors. RESULTS AND DISCUSSION: Overall, 312 patients were enrolled in the study with 156 patients in each group. By providing detailed information in the newly developed discharge letter, adherence increased significantly from 83·3% (CG) to 90·9% (IG; P = 0·01). Significant differences between the CG and IG were found with regard to adherence to both antithrombotic drugs [83·8% CG vs. 91·9% IG (P = 0·033)] and statin therapy [69·8% CG vs. 87·7% IG (P < 0·001)]. WHAT IS NEW AND CONCLUSION: The use of a structured medication report as part of the discharge letter leads to improved adherence to hospital discharge medication.

[Cerebral venous thrombosis and subdural haematoma: complications of spontaneous intracranial hypotension]. / Sinus-/Hirnvenenthrombose und Subduralhämatome als Komplikationen eines spontanen Liquorunterdrucksyndroms.

We report on the case of a spontaneous intracranial hypotension with subdural hygroma, as well as cerebral venous thrombosis (CVT), both known complications of intracranial hypotension. The 45-year-old patient was subsequently treated - according to current guidelines for CVT - with anticoagulation, but developed subdural haematoma (SDH), which required neurosurgical treatment. Our case highlights the complex pathophysiological sequelae of intracranial hypotension, as well as the occasionally difficult treatment decisions. Subdural hygroma probably predisposes patients to SDH during anticoagulation. Thus, the potential benefit of anticoagulation needs to be weighed against the risk of SDH on an individual basis.

Age-related changes of cerebral autoregulation: new insights with quantitative T2'-mapping and pulsed arterial spin-labeling MR imaging.

BACKGROUND AND PURPOSE: Cerebral perfusion and O(2) metabolism are affected by physiologic age-related changes. High-resolution motion-corrected quantitative T2'-imaging and PASL were used to evaluate differences in deoxygenated hemoglobin and CBF of the gray matter between young and elderly healthy subjects. Further combined T2'-imaging and PASL were investigated breathing room air and 100% O(2) to evaluate age-related changes in cerebral autoregulation. MATERIALS AND METHODS: Twenty-two healthy volunteers 60-88 years of age were studied. Two scans of high-resolution motion-corrected T2'-imaging and PASL-MR imaging were obtained while subjects were either breathing room air or breathing 100% O(2). Manual and automated regions of interest were placed in the cerebral GM to extract values from the corresponding maps. Results were compared with those of a group of young healthy subjects previously scanned with the identical protocol as that used in the present study. RESULTS: There was a significant decrease of cortical CBF (P < .001) and cortical T2' values (P < .001) between young and elderly healthy subjects. In both groups, T2' remained unchanged under hyperoxia compared with normoxia. Only in the younger but not in the elderly group could a significant (P = .02) hyperoxic-induced decrease of the CBF be shown. CONCLUSIONS: T2'-mapping and PASL in the cerebral cortex of healthy subjects revealed a significant decrease of deoxygenated hemoglobin and of CBF with age. The constant deoxyHb level breathing 100% O(2) compared with normoxia in young and elderly GM suggests an age-appropriate cerebral autoregulation. At the younger age, hyperoxic-induced CBF decrease may protect the brain from hyperoxemia.

Long-term outcome after coil embolization of cavernous sinus arteriovenous fistulas.

BACKGROUND AND PURPOSE: Cranial nerve palsies are regularly observed in patients with arteriovenous fistulas of the cavernous sinus. The purpose of our study was to determine the long-term clinical outcome-with a special focus on extra-ocular muscular dysfunctions-in patients who had undergone endovascular treatment of a cavernous sinus fistula with detachable coils. MATERIALS AND METHODS: Sixteen patients were recalled for an ophthalmoneurologic control examination (mean interval of 4.4 years). The mRS and the EQ-5D questionnaire were used for the description of general outcome. Age, duration of symptoms, character of the fistula (direct, dural), and coil volume were tested to assess their relevance for persistent symptoms. RESULTS: All patients displayed complete regression of chemosis, exophthalmus, and pulsating tinnitus with no evidence of recurrences. Oculomotor disturbances persisted in 9 of 13 patients and caused permanent diplopia in 7 patients. In 15 patients a mRS score of 1 or 2 was achieved; however, 7 patients reported some limitations in life quality (EQ-5D). A significant correlation was found between coil volume and persistent diplopia (P = .032) and persistent cranial nerve VI paresis (P = .037). CONCLUSIONS: Coil embolization of the cavernous sinus led to durable closure of AVF and reliable regression of acute symptoms. However, long-term follow-up showed a 44% rate of persistent cranial nerve deficits with disturbances of oculomotor and visual functions. This may be explained by the underlying fistula size itself and/or the space-occupying effect of the coils. As neuro-ophthalmologic outcome is crucial for control of therapeutic success, patients should be routinely examined by ophthalmologists.

[Cortical venous thrombosis after a diagnostic lumbar puncture]. / Kortikale Venenthrombose nach diagnostischer Lumbalpunktion.

We present the case of a 49-year-old female patient who underwent a lumbar puncture in the context of an extended diagnostic work-up after a transient ischemic attack. A few days later the patient who suffered from severe post-lumbar puncture headache, developed a lobar hemorrhage due to a cortical venous thrombosis requiring decompression surgery.

[Diagnosis of cerebral ischemia: when CT and when MRI?]. / Diagnostik der zerebralen Ischämie: Wann CT, wann MRT?

Rapid and effective diagnostic imaging is important for decision-making concerning thrombolysis in patients with acute ischemic stroke. Apart from excluding intracranial hemorrhage, CT and MRI provide multiple methodological options to define the extent of ischemic brain damage and the underlying vascular pathology. The aim of this article is to discuss the value of CT and MRI from a neurologicalneuroradiological point of view and to discuss which of the available imaging tools are really relevant for clinical decision making.

[Neuroimaging evaluation of intracerebral hemorrhage]. / Bildgebende Diagnostik bei intrazerebralen Blutungen.

Spontaneous intracerebral hemorrhage (ICH) is responsible for 10-15% of all strokes. Standard evaluation includes a CT examination, in which ICH is initially hyperdense but gradually decreases in density over days to weeks. In emergency situations, native CT can be supplemented with CT angiography, which reliably shows aneurysms and other vascular abnormalities larger than 2-3 mm. For detecting ICH in hyperacute situations, MRI is as sensitive as CT but signal characteristics are more complex, strongly depending on the oxygenation status of hemoglobin and the redox status of iron. In terms of localization, deep ICH in typical locations with hypertensive etiology is differentiated from atypical lobar ICH. Atypical ICH in elderly patients is often caused by cerebral amyloid angiopathy. Despite advances in noninvasive imaging techniques, today most atypical ICH patients still require digital subtraction angiography for a complete evaluation. In contrast, hypertensive ICH can be assumed in patients with known arterial hyperstension and ICH in a typical location.

Risk of symptomatic intracerebral hemorrhage in patients treated with intra-arterial thrombolysis.

BACKGROUND: In intra-arterial (IA) thrombolysis trials, higher rates of symptomatic intracerebral haemorrhage (sICH) were found than in trials with intravenous (IV) recombinant tissue plasminogen activator (tPA); this observation could have been due to the inclusion of more severely affected patients in IA thrombolysis trials. In the present study, we investigated the rate of sICH in IA and combined IV + IA thrombolysis versus IV thrombolysis after adjusting for differences in clinical and MRI parameters. METHODS: In this multicenter study, we systematically analyzed data from 645 patients with anterior-circulation strokes treated with either IV or IA thrombolysis within 6 h following symptom onset. Thrombolytic regimens included (1) IV tPA treatment (n = 536) and (2) IA treatment with either tPA or urokinase (n = 74) or (3) combined IV + IA treatment with either tPA or urokinase (n = 35). RESULTS: 44 (6.8%) patients developed sICH. sICH patients had significantly higher scores on the National Institutes of Health Stroke Scale (NIHSS) at admission and pretreatment DWI lesions. The sICH risk was 5.2% (n = 28) in IV thrombolysis, which is significantly lower than in IA (12.5%, n = 9) or IV + IA thrombolysis (20%, n = 7). In a binary logistic regression analysis including age, NIHSS score, time to thrombolysis, initial diffusion weighted imaging lesion size, mode of thrombolytic treatment and thrombolytic agent, the mode of thrombolytic treatment remained an independent predictor for sICH. The odds ratio for IA or IV + IA versus IV treatment was 3.466 (1.19-10.01, 95% CI, p < 0.05). CONCLUSION: In this series, IA and IV + IA thrombolysis is associated with an increased sICH risk as compared to IV thrombolysis, and this risk is independent of differences in baseline parameters such as age, initial NIHSS score or pretreatment lesion size.

[Stroke MRI for risk assessment of intracerebral hemorrhage associated with thrombolytic therapy]. / Schlaganfall-MRT zur Abschätzung des Blutungsrisikos bei thrombolytischer Therapie.

This article summarizes recent developments concerning MRI-based risk assessment of symptomatic intracerebral hemorrhage (sICH) associated with thrombolytic therapy for acute stroke. Special attention is paid to three imaging parameters: cerebral microangiopathy, lesion size on diffusion weighted imaging (DWI), and the role of cerebral microbleeds. Both severe cerebral microangiopathy and increasing lesion size on DWI are now established risk factors for sICH following thrombolysis, while the presence of a single or few microbleeds is not associated with a substantially elevated sICH risk.

Combined 1H and 31P MR spectroscopic imaging: impaired energy metabolism in severe carotid stenosis and changes upon treatment.

OBJECT: To evaluate if combined (1)H and (31)P MR spectroscopic imaging (MRSI) before and after treatment of severe internal carotid artery (ICA) stenosis detects significant changes in energy metabolism in the basal ganglia of both hemispheres. MATERIALS AND METHODS: A group of 14 patients with high-grade ICA stenosis and 11 healthy control subjects were examined with 2D (1)H MRSI and 3D (31)P MRSI at 3 T before and after treatment of severe ICA stenosis. Spectroscopic data were processed with LCModel and jMRUI software. Changes of the phosphorylated metabolites, pH, N-acetyl-acetate, creatine and choline-containing compounds prior/post intervention were analyzed and patients' data were compared with that of control subjects. RESULTS: Untreated patients had significantly higher Adenosindiphosphate (ADP) in basal ganglia ipsi- and contralateral to the side of ACI stenosis compared to controls. After treatment, ADP of both hemispheres significantly decreased by approximately 20% compared to the pre-treatment values. Further, significant decreases of phosphorylated metabolites prior/post intervention were found for patients compared to controls. CONCLUSION: This spectroscopic study reveals that unilateral high-grade ICA stenosis has an effect on cerebral high-energy metabolism of both hemispheres, which is at least partially reversible after treatment. Therefore the restoration of blood flow in high-grade ICA stenosis recovers the impaired energy balance of the brain.

Treatment of symptomatic high-grade intracranial stenoses with the balloon-expandable Pharos stent: initial experience.

INTRODUCTION: We report our first clinical experience with a CE-marked flexible monorail balloon-expandable stent for treatment of high-grade intracranial stenoses. METHODS: Between April 2006 and November 2007 21 patients with symptomatic intracranial stenoses (>70%) were treated with the PHAROS stent. In seven patients, the procedure was performed during acute stroke intervention. Procedural success, clinical complication rates and mid-term follow-up data were prospectively recorded. RESULTS: During a median follow-up period of 7.3 months one additional patient died of an unknown cause 3 months after the intervention. A patient with a significant residual stenosis presented with a new stroke after further progression of the residual stenosis. None of the successfully treated patients experienced ipsilateral stroke. CONCLUSION: Recanalization of intracranial stenoses with the balloon-expandable Pharos stent is technically feasible. The periprocedural complication rate and mid-term follow-up results were in the range of previously reported case series. This pilot study was limited by the small sample size and severe morbidity of the included patients. Final evaluation of the efficacy of Pharos stent treatment demands further investigation.

[Long term follow-up after intracranial vertebro-basilar artery stenting]. / Langzeitergebnisse nach Behandlung intrakranieller vertebrobasilärer Stenosen mit Stents.

PURPOSE: Recurrent ischemic symptoms attributable to intracranial high-grade vertebrobasilar artery stenoses are associated with a high risk of ischemic stroke, particularly if these occur in spite of aggressive medical treatment. Long term efficacy data for endovascular stent angioplasty of symptomatic intracranial stenoses are lacking. The purpose of this prospective study is to determine the rates of deaths, of ischemic events and of restenosis during long-term follow-up. MATERIALS AND METHODS: Between June 2001 and February 2004 twelve patients (11 male, 1 female; median 63 yrs; range, 46 - 75 yrs) with recurrent ischemic symptoms attributed to > or = 70 % intracranial vertebro-basilar artery stenoses, who had failed aggressive medical treatment, were included. Median follow-up was 24 months (range: 6 to 36 months). Intracranial stenoses were measured using 3D rotation angiography data sets and treated with balloon expandable stents. All patients were scheduled for follow-up including clinical (Barthel Index) and transcranial Doppler examinations and intraarterial angiography at 6 months after intervention. Clinical outcome was defined as the rate of stroke in any vascular territory or death during follow-up. Vascular outcome was determined by the rate of in-stent restenosis 50 % on follow-up as examined by intraarterial angiography at 6 months or by transcranial color-coded duplex sonography. RESULTS: Stent placement was technically successful in all patients. No patient had further cerebral ischemic symptoms; two patients died (1 myocardial infarct, 1 sudden death) during follow-up of median 24 months. The degree of stenoses was reduced from median 81 % (range 69 - 94 %) to 19 % (range 10 - 36 %) immediately after stent placement and to 32 % (range 22 - 48 %) after 6 months. No restenosis > or = 50 % occurred during follow-up. CONCLUSION: Based on this limited series, we believe that in patients, with recurrent symptoms despite aggressive medical treatment, endovascular stent placement in intracranial high-grade vertebrobasilar artery stenoses can be an effective and safe treatment option.

Serum glial fibrillary acidic protein as a biomarker for intracerebral haemorrhage in patients with acute stroke.

BACKGROUND: Biomarkers of stroke are an evolving field of clinical research. A serum marker which can differentiate between haemorrhagic and ischaemic stroke in the very early phase would help to optimise acute stroke management. OBJECTIVE: To examine whether serum glial fibrillary acidic protein (GFAP) identifies intracerebral haemorrhage (ICH) in acute stroke patients. METHODS: A pilot study assessing 135 stroke patients admitted within six hours after symptom onset. Diagnosis of ICH (n = 42) or ischaemic stroke (n = 93) was based on brain imaging. GFAP was determined from venous blood samples obtained immediately after admission, using a research immunoassay. RESULTS: GFAP was detectable in the serum of 39 patients (34 of 42 (81%) with ICH, and five of 93 (5%) with ischaemic stroke). Serum GFAP was substantially raised in patients with ICH (median 11 ng/l, range 0 to 3096 ng/l) compared with patients with ischaemic stroke (median 0 ng/l, range 0 to 14 ng/l, p<0.001). Using receiver operating characteristic curve analysis, a cut off point of 2.9 ng/l provided a sensitivity of 0.79 and a specificity of 0.98 for the identification of ICH in acute stroke (positive predictive value 0.94, negative predictive value 0.91; p<0.001). CONCLUSIONS: Serum GFAP can reliably detect ICH in the acute phase of stroke. Further evaluation of the usefulness of GFAP as an early diagnostic marker of ICH is now required, with the aim of optimising cause specific emergency management.

Hemi-spinal cord infarction due to vertebral artery dissection in congenital afibrinogenemia.

Isolated ischemia of the cervical spinal cord is an uncommon but increasingly recognized complication of vertebral artery dissection (VAD). The authors report a young patient with congenital afibrinogenemia, who developed VAD with extensive unilateral spinal cord infarction, probably caused by local compression of spinal radicular feeders at their origin by vertebral artery hematoma.