[Complications after stroke : Clinical challenges in stroke aftercare]. / Komplikationen nach Schlaganfall : Klinische Herausforderungen in der Schlaganfallnachsorge.

BACKGROUND: Besides the treatment of cardiovascular risk factors, the prevention and treatment of secondary complications is the main focus of outpatient poststroke care. The spectrum of noteworthy complications after a stroke changes during the course of the treatment and constitutes a specific challenge of outpatient poststroke care. OBJECTIVE AND METHODS: This article provides references to the importance, management, diagnosis and treatment of the wide spectrum of nonvascular complications after stroke in the context of outpatient stroke aftercare. RESULTS: Poststroke depression (PSD), anxiety disorders and post-stroke fatigue are common complications after stroke, which require a timely diagnosis and treatment. Furthermore, the incidence of newly diagnosed dementia is 20% within the first 6 months after a stroke. Here too, therapeutic and preventive strategies especially in the early stage can delay the subsequent burden of the disease and the dependency on care. About half of every newly diagnosed epilepsy in patients older than 60 years is the result of a stroke. Falls and subsequent injuries are another important complication and a common reason for rehospitalization after a stroke. Although nearly 50% of patients suffer from chronic pain after a stroke this is often not sufficiently recognized. CONCLUSION: The wide spectrum of secondary complications after a stroke constitutes a complex, sustained and multidisciplinary challenge, which requires a cross-sectoral interaction of various and numerous actors in outpatient poststroke care.

[Stroke aftercare : Treatment reality, challenges and future perspectives]. / Schlaganfallnachsorge : Versorgungsrealität, Herausforderungen und Zukunftsperspektiven.

BACKGROUND: Registry data demonstrate a high risk of recurrent stroke and rehospitalization rates after first-time stroke in Germany compared to the international level. Meanwhile, a report of the Institute for Applied Quality Assurance in the Healthcare System (aQua institute) pointed out the potential for improvement of post-stroke care in Germany. OBJECTIVE: To establish perspectives for improvement of outpatient post-stroke care in Germany. METHODS: Critical discussion of important aspects of post-stroke care, presentation of the current structures of healthcare provision and possibilities for improvement of post-stroke care. RESULTS: Post-stroke care in Germany is predominantly carried out by general practitioners. Currently, standard healthcare procedures do not provide a comprehensive supportive system of structured and cross-sectoral aftercare after ischemic stroke. Special attention must be paid to the treatment of cardiovascular risk factors according to the guidelines, a specific and rapid provision of assist devices and physiotherapy as well as prevention and treatment of stroke-associated complications. Previous investigations have revealed sometimes clear deficits in the provision of treatment. The reasons include but are not limited to sectoral barriers that are difficult to overcome. New concepts of post-stroke care for improvement of these deficits are currently undergoing clinical testing. CONCLUSION: Ischemic stroke should be considered as a complex chronic disease and should be treated accordingly after discharge from acute inpatient treatment. Emphasis should be placed on the optimization of interdisciplinary and cross-sectoral cooperation and support for general practitioners in the outpatient post-stroke care. New concepts of post-stroke care have the potential for improvement of the current healthcare structures.

[Causes of death in amyotrophic lateral sclerosis : Results from the Rhineland-Palatinate ALS registry]. / Todesursachen bei amyotropher Lateralsklerose : Ergebnisse aus dem ALS-Register Rheinland-Pfalz.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is associated with an increased mortality. Knowledge of possible causes of death could lead to an individualization of the palliative treatment concept and result in a differentiated palliative treatment pathway. Currently, only few systematic data are available on the heterogeneity of causes of death associated with ALS. OBJECTIVE: Analysis of the various causes of death in a prospective population-based German cohort of ALS patients. MATERIAL AND METHODS: Analysis of data of the Rhineland-Palatinate ALS registry in which newly diagnosed patients who had been identified between October 2009 and September 2012 were prospectively enrolled and followed up at regular intervals. From this prospective cohort study the causes of death were elicited based on information provided by the attending physicians, family members and by means of death certificates registered by the regional health authorities in Rhineland-Palatinate. RESULTS: Out of 200 ALS patients registered 148 died between register initiation on 1 October 2009 and the end of follow-up on 30 September 2015 (78 males and 70 females, death rate 74%). The most frequent cause of death was respiratory failure as a consequence of weakness of respiratory muscles (n = 91, 61%). Less frequent causes of death were pneumonia (n = 13, 9%), terminal cachexia (n = 9, 6%) and death from cardiovascular causes including sudden death (n = 9, 6%). Cases of suicide were rare (n = 3, 2%) as were deaths due to concurrent diseases (n = 2). In 21 cases (14%) the exact cause of death could not be clarified. Differences in the causes of death only showed a tendency towards the ALS phenotype. Respiratory failure was the cause of death in all patients with a respiratory phenotype and in 78% of patients with flail arm syndrome. Despite the low number of patients (8%) with additional frontotemporal dementia (FTD) a distinct difference in causes of death between those with and without FTD could be observed. Death due to respiratory failure was less frequent in ALS patients with FTD (33% vs. 65%) while pneumonia was more frequent (27% vs. 7%). CONCLUSION: Respiratory failure was the most frequent cause of death in our cohort of ALS patients. In contrast, pneumonia and nutritional disorders played a less important role as the cause of death. The phenotypic expression of ALS might in part allow the cause of the prospective death to be predicted. Differentiation of ALS phenotypes is an important foundation for patient counseling on the process of dying to be expected and for the determination of an individual palliative concept.

Intracerebral haemorrhage in a population-based stroke registry (LuSSt): incidence, aetiology, functional outcome and mortality.

Data on incidence of intracerebral haemorrhage (ICH) vary widely. Population-based data on predictors of ICH survival and functional outcome are rare. The Ludwigshafen Stroke Study is a prospective, population-based stroke registry which started in January 2006. All residents of the city of Ludwigshafen, Germany, who suffer from acute stroke or transient ischaemic attack are registered. Patients with first-ever primary intracerebral haemorrhage (FE-pICH) between 2006 and 2010 were included in the present analysis. Between January 1st, 2006 and December 31st, 2010, 152 patients suffered a FE-pICH. Crude and age-adjusted incidence rates per 100,000 for FE-pICH were 18.7 (95 % CI 15.9-21.9) and 11.9 (95 % CI 10.2-14.0), respectively, and remained stable over time. Case-fatality rates for FE-pICH were 27.0, 34.9 and 44.1 % at days 28, 90 and 365, respectively. In 21 patients, an (21.3 %) early do-not resuscitate-order was documented. Excluding these patients from multivariate analyses, National Institute of Health Stroke Scale (NIHSS) (OR 1.22, 95 % CI 1.08-1.36), hypercholesterolemia (OR 0.16, 95 % CI 0.05-0.55) and modified Rankin Scale (mRS) prior to stroke (OR 1.56, 95 % CI 1.06-2.3) were independently associated with risk of 1-year mortality, whereas NIHSS (OR 1.41, 95 % CI 1.20-1.66) and leukocyte count on admission (OR 1.48, 95 % CI 1.16-1.89) were independently associated with good or moderate functional outcome (mRS ≤ 3) after 1 year. Incidence of FE-ICH is in the lower range of those reported from other registries and remained stable over the observation period. Higher treatment rates for hypertension might partly account for this. Stroke severity as indicated by NIHSS was independently associated with mortality and functional outcome after 1 year. We found no association between aetiology and outcome in ICH patients.

Etiology of first-ever ischaemic stroke in European young adults: the 15 cities young stroke study.

BACKGROUND AND PURPOSE: Risk factors for IS in young adults differ between genders and evolve with age, but data on the age- and gender-specific differences by stroke etiology are scare. These features were compared based on individual patient data from 15 European stroke centers. METHODS: Stroke etiology was reported in detail for 3331 patients aged 15-49 years with first-ever IS according to Trial of Org in Acute Stroke Treatment (TOAST) criteria: large-artery atherosclerosis (LAA), cardioembolism (CE), small-vessel occlusion (SVO), other determined etiology, or undetermined etiology. CE was categorized into low- and high-risk sources. Other determined group was divided into dissection and other non-dissection causes. Comparisons were done using logistic regression, adjusting for age, gender, and center heterogeneity. RESULTS: Etiology remained undetermined in 39.6%. Other determined etiology was found in 21.6%, CE in 17.3%, SVO in 12.2%, and LAA in 9.3%. Other determined etiology was more common in females and younger patients, with cervical artery dissection being the single most common etiology (12.8%). CE was more common in younger patients. Within CE, the most frequent high-risk sources were atrial fibrillation/flutter (15.1%) and cardiomyopathy (11.5%). LAA, high-risk sources of CE, and SVO were more common in males. LAA and SVO showed an increasing frequency with age. No significant etiologic distribution differences were found amongst southern, central, or northern Europe. CONCLUSIONS: The etiology of IS in young adults has clear gender-specific patterns that change with age. A notable portion of these patients remains without an evident stroke mechanism according to TOAST criteria.

Stroke due to atrial fibrillation in a population-based stroke registry (Ludwigshafen Stroke Study) CHADS(2) , CHA(2) DS(2) -VASc score, underuse of oral anticoagulation, and implications for preventive measures.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is amongst the most important etiologies of ischaemic stroke. In a population-based stroke registry, we tested the hypothesis of low adherence to current guidelines as a main cause of high rates of AF-associated stroke. METHODS: Within the Ludwigshafen Stroke Study (LuSSt), a prospective ongoing population-based stroke register, we analyzed all patients with a first-ever ischaemic stroke (FEIS) owing to AF in 2006 and 2007. We determined whether AF was diagnosed before stroke and assessed pre-stroke CHADS(2) and CHA(2) DS(2) -VASc scores. RESULTS: In total, 187 of 626 patients with FEIS suffered from cardioembolic stroke owing to AF, which was newly diagnosed in 57 (31%) patients. Retrospective pre-stroke risk stratification according to CHADS(2) score indicated low/intermediate risk in 34 patients (18%) and high risk (CHADS(2)  ≥ 2) in 153 patients (82%). Application of CHA(2) DS(2) -VASc score reduced number of patients at low/intermediate risk (CHA(2) DS(2) -VASc score 0-1) to five patients (2.7%). In patients with a CHADS(2) score ≥ 2 and known AF (n = 106) before stroke, 38 (36%) were on treatment with vitamin K antagonists on admission whilst only in 16 patients (15%) treatment was in therapeutic range. CONCLUSIONS: Our study strongly supports the hypothesis that underuse of oral anticoagulants in high-risk patients importantly contributes to AF-associated stroke. CHA(2) DS(2) -VASc score appears to be a more valuable risk stratification tool than CHADS(2) score. Preventive measures should focus on optimizing pre-stroke detection of AF and better implementation of present AF-guidelines with respect to anticoagulation therapy.

Etiology, risk factors and sex differences in ischemic stroke in the Ludwigshafen Stroke Study, a population-based stroke registry.

BACKGROUND: Stroke etiology in ischemic stroke guides preventive measures and etiological stroke subgroups may show considerable differences between both sexes. In a population-based stroke registry we analyzed etiological subgroups of ischemic stroke and calculated sex-specific incidence and mortality rates. METHODS: The Ludwigshafen Stroke Study is a prospective ongoing population-based stroke registry. Multiple overlapping methods of case ascertainment were used to identify all patients with incident stroke or transient ischemic attack. Modified TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria were applied for subgroup analysis in ischemic stroke. RESULTS: Out of 626 patients with first-ever ischemic stroke in 2006 and 2007, women (n = 327) were older (73.5 ± 12.6 years) than men (n = 299; 69.7 ± 11.5 years; p < 0.001). The age-adjusted incidence rate of ischemic stroke was significantly higher in men (1.37; 95% CI 1.20-1.56) than in women (1.12; 95% CI 0.97-1.29; p = 0.04). Cardioembolism (n = 219; 35.0%), small-artery occlusion (n = 164; 26.2%), large-artery atherosclerosis (n = 98; 15.7%) and 'probable atherothrombotic stroke' (n = 84; 13.4%) were common subgroups of ischemic stroke. Stroke due to large-artery atherosclerosis (p = 0.025), current smoking (p = 0.008), history of smoking (p < 0.001), coronary artery disease (p = 0.0015) and peripheral artery disease (p = 0.024) was significantly more common in men than in women. Overall, 1-year survival was not different between both sexes; however, a significant age-sex interaction with higher mortality in elderly women (>85 years) was detected. CONCLUSIONS: Cardioembolism is the main source for ischemic stroke in our population. Etiology of ischemic stroke differs between sexes, with large-artery atherosclerotic stroke and associated diseases (coronary artery disease and peripheral artery disease) being more common in men.

Neurologic complications of Churg-Strauss syndrome--a prospective monocentric study.

BACKGROUND: Churg-Strauss syndrome (CSS) is a rare systemic vasculitis. Case series with a focus on neurologic involvement are not common. With this study, we intended to evaluate the frequency and types of neurologic manifestations and complications at time of diagnosis and during follow-up of patients with CSS. METHODS: In this monocentric study, consecutive patients of our hospital with first diagnosis of CSS based on the criteria of the American College of Rheumatology were included between 2001 and 2007. Each patient underwent a periodic follow-up with clinical and electrophysiologic examination. Data were obtained prospectively. RESULTS: Fourteen patients were included. All patients had a hypereosinophilia and a history of asthma. Twelve of 14 patients had a neurologic involvement, mainly as an acute or subacute multiplex mononeuropathy (eight patients) or an axonal polyneuropathy (three patients). Three patients suffered from a neuropathy of cranial nerves, and two patients had a cerebral infarct. Mean follow-up period was 31 months. With immunosuppressive therapy, 13 patients had no additional neurologic complications, one patient suffered from a cerebral infarct. Initial neurologic symptoms as a result of peripheral neuropathy improved, but sequelae of axonal damage were persistently detectable. CONCLUSIONS: Even at time of diagnosis of a CSS, neurologic manifestations are common, especially as a multiplex mononeuropathy. With a consequent immunosuppressive therapy, new neurologic complications can be avoided for the most part.

Leukocyte-platelet aggregates in acute and subacute ischemic stroke.

BACKGROUND: Leukocyte-platelet aggregates appear to be a stable and sensitive marker of platelet activation as suggested by studies in coronary heart disease. We tested the hypothesis that leukocyte-platelet aggregates are increased after ischemic stroke and investigated the contribution of different leukocyte subtypes to such increase. METHODS: We serially determined granulocyte-, lymphocyte- and monocyte-platelet aggregates, using flow cytometry at days 1, 2, 3, 5, 7, 10, and 90 in patients with ischemic stroke (n = 45) and in age- and sex-matched healthy control subjects (n = 30). RESULTS: Granulocyte-platelet aggregates (granulocytes with > or =1 platelet/microl) were more common in patients than control subjects from day 1 through day 10 (p < 0.04, respectively), but not on day 90 after stroke. The percentage of granulocytes forming aggregates was increased on days 1-3 after stroke but not at other time points. Lymphocyte-platelet aggregates were not more common at any time point after stroke. Total numbers and percentages of monocytes forming platelet aggregates were significantly increased on day 2 (p = 0.003), but not at other time points after stroke. CONCLUSION: The 3 leukocyte subtypes showed different kinetics regarding aggregate formation with platelets after ischemic stroke. Increase of monocyte-platelet aggregates is short-lived and may reflect an acute reaction to cerebral ischemia, whereas granulocyte-platelet aggregate formation persists into the subacute phase, suggesting that they are a particularly sensitive parameter reflecting both prothrombotic and inflammatory processes after stroke.

Gene expression in human peripheral blood mononuclear cells upon acute ischemic stroke.

BACKGROUND AND PURPOSE: Ischemic stroke provokes a systemic inflammatory response. The purpose of this study was to characterize this response on the gene expression level in circulating mononuclear leukocytes from acute ischemic stroke (AIS) patients. METHODS: RNA from peripheral blood mononuclear cells (PBMCs) of AIS patients (24 + 2 hours after onset of symptoms) was analyzed with Affymetrix U133A GeneChips using a pooled design. We compared the gene expression signature from AIS patients (n = 20), stroke survivors (n = 15), patients with acute traumatic brain injury (ATBI, n = 15) and healthy control subjects without vascular risk factors (n = 15). RESULTS: Expression levels of 9682 probe sets with present calls on each GeneChip were compared. Between AIS patients and stroke survivors or between AIS patients and ATBI patients there were no significant differences in expression values of single genes after correction for multiple testing. However, comparison of the PBMC expression profiles from AIS patients and healthy subjects revealed significantly different expression (p = 0.012) of a single probe set, specific for phosphodiesterase 4 D (PDE4D). In order to detect modest expression differences in multiple genes with a presumed cumulative effect we studied the gene expression of functional groups of genes by global statistical tests. Analysis of 11 gene groups revealed differential expression between AIS patients and healthy subjects for genes involved in the inflammatory response (GeneOntology GO:0006954). Genes encoding the N-formyl peptide receptor-like 1 (FPRL1), interleukin-1 receptor antagonist (IL1RN) and complement component 3a receptor 1 (C3AR1) contributed most to the observed difference. CONCLUSIONS: This transcriptome analysis did not identify significant changes between circulating mononuclear cells from AIS patients 24 hours after stroke and closely matched stroke survivors. However, comparing AIS patients with healthy control subjects revealed measurable differences in PDE4D and in inflammatory response genes when considered as a set.

Factor XII C46T gene polymorphism and the risk of cerebral venous thrombosis.

BACKGROUND: The TT genotype of a functional factor XII (FXII) C46T gene polymorphism was shown to be a risk factor for peripheral venous thrombosis. We tested whether this genetic variant also increases the risk for cerebral venous thrombosis (CVT). METHODS: We performed a case-control study including 78 consecutive patients with proven CVT and 201 healthy population controls from South Germany. The FXII C46T genotype was assessed using a PCR technique. RESULTS: The TT genotype of the FXII C46T polymorphism was more common in patients (16.7%) than in controls (5.5%). A strong association of the TT genotype with CVT was found, which was independent of covariables (adjusted odds ratio 4.57; 95% CI 1.55 to 13.41; p = 0.006). CONCLUSION: The TT genotype of the functional factor XII C46T gene polymorphism may be a new independent risk factor for cerebral venous thrombosis (CVT). Our finding warrants confirmation in an independent study before this genetic variant should be added to the panel of established risk factors for CVT.

[Intracranial bleeding in acquired hemophilia]. / Intrakranielle Blutung bei erworbener Hemmkörperhämophilie.

Acquired hemophilia is a rare complication in autoimmune disorders and malignancies. It can result in bleedings into skin and muscle, whereas intracranial hemorrhage in adults has so far not been described. We report a patient with acute intracerebral hemorrhage due to acquired hemophilia with factor VIII inhibition. The patient was treated with recombinant factor VIIa and open hematoma evacuation followed by administration of cortisone and cyclophosphamide. After good initial recovery, intracerebral rebleeding occurred and the patient died from brainstem compression.

The ICAM-1 E469K gene polymorphism is a risk factor for spontaneous cervical artery dissection.

In a primary study on proinflammatory genetic profiles in stroke, the authors found the E469K polymorphism of the intercellular adhesion molecule 1 (ICAM-1) highly represented in the subgroup with spontaneous cervical artery dissection (sCAD). They further investigated the same genetic variant in a second group of 65 patients with sCAD. An association between sCAD and EE genotype was confirmed (odds ratio 3.16; p < 0.01), indicating that a proinflammatory predisposition is a risk factor for sCAD.

Increased prevalence of and gene transcription by Chlamydia pneumoniae in cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis.

Microbial agents may play a role in the pathogenesis of multiple sclerosis (MS). C. pneumoniae has been recently associated with MS; however, study results are at variance. We tested the hypothesis that Chlamydia pneumoniae-specific DNA and RNA are more often detected in cerebrospinal fluid (CSF) of patients with multiple sclerosis than patients with other neurological diseases (OND). We investigated CSF samples from 84 patients with definite MS and 89 OND patients (n = 62 with normal CSF; n = 27 with pathological CSF) using a nested polymerase chain reaction (PCR) to detect ompA gene sequences of C. pneumoniae. In subjects with positive PCR, we probed for chlamydial heat shock protein 60-mRNA and 16S-rRNA by reverse transcriptase (rt)-PCR. C. pneumoniae-specific DNA was more often detected in MS patients (50 %) than in all OND patients combined (28.1%, p = 0.003) and in OND patients with normal CSF (24.2%, p = 0.003) but not than in OND patients with pathological CSF (37%, p = 0.24). In relapsing-remitting MS (n = 55), the prevalence of C. pneumoniae DNA was higher (66.7 %) than in both OND subgroups (p

[Niemann-Pick disease type C--a neurometabolic disease through disturbed intracellular lipid transport]. / Morbus Niemann-Pick Typ C. Eine neurometabolische Erkrankung durch Störung des intrazellulären Lipidtransports.

Niemann-Pick disease type C (NPC) is a rare, neurovisceral lipid storage disorder caused by genetic defects in lipid transporting proteins. It is distinct from Niemann-Pick types A and B (sphingomyelin lipidoses) and displays genetic (mutations in the NPC1 or NPC2[=HE1] gene), biochemical, and clinical heterogeneity. Late infantile to juvenile forms of NPC predominate and are characterised by atypical behaviour, ataxia, dysarthria, dysphagia, dystonia, cataplexy, vertical gaze palsy, splenomegaly, and dementia. In adult variants, psychosis and dementia are common, and dysarthria, ataxia, splenomegaly, and vertical gaze palsy are further facultative signs. Routine laboratory results including serum cholesterol are normal. In bone marrow smears, sea-blue histiocytes are often demonstrated and foam cells sometimes seen. The diagnosis is confirmed by detecting free cholesterol accumulation in perinuclear granules (lysosomes) and reduced cholesterol esterification after challenge with exogenous low-density lipoprotein in fibroblasts. Alternatively or additionally, mutational analysis can be performed. Treatment is restricted to symptomatic measures, since there is no specific therapy.

[Fabry's disease: new therapeutic options for this lysosomal storage disorder]. / Morbus Fabry. Eine lysosomale Stoffwechselerkrankung mit neuen therapeutischen Möglichkeiten.

Fabry's disease is an x-linked, recessive, lysosomal storage disorder that results from deficient alpha-galactosidase A activity with pathological sphingolipid deposition mainly in endothelium, smooth muscle cells, kidneys, central and peripheral nervous system, and myocardium. Clinical manifestation mostly occurs during childhood and adolescence with severe pain attacks or chronic pain mainly in hands and feet, hypohydrosis, and skin lesions (angiokeratoma). In more advanced disease stages, renal and cerebrovascular complications develop with proteinuria and later renal failure and cerebral ischemia caused by cerebral microangiopathy, dilatative arteriopathy, or cardiac embolism. Heterozygote female carriers are severely affected more often than was previously considered. The diagnosis is based on the detection of deficient alpha-galactosidase A activity in leukocytes, fibroblasts, or tissue biopsies. Two randomised placebo-controlled studies showed that enzyme replacement is effective by demonstrating either reduced pain or reduced tissue sphingolipid deposition. Early diagnosis of Fabry's disease is important in view of these new causal therapeutic options.