Prothrombotic immune thrombocytopenia after COVID-19 vaccination.

We report 5 cases of prothrombotic immune thrombocytopenia after exposure to the ChAdOx1 vaccine (AZD1222, Vaxzevria) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients presented 5 to 11 days after first vaccination. The spectrum of clinical manifestations included cerebral venous sinus thrombosis, splanchnic vein thrombosis, arterial cerebral thromboembolism, and thrombotic microangiopathy. All patients had thrombocytopenia and markedly elevated D-dimer. Autoantibodies against platelet factor 4 (PF4) were detected in all patients, although they had never been exposed to heparin. Immunoglobulin from patient sera bound to healthy donor platelets in an AZD1222-dependent manner, suppressed by heparin. Aggregation of healthy donor platelets by patient sera was demonstrated in the presence of buffer or AZD1222 and was also suppressed by heparin. Anticoagulation alone or in combination with eculizumab or intravenous immunoglobulin (IVIG) resolved the pathology in 3 patients. Two patients had thromboembolic events despite anticoagulation at a time when platelets were increasing after IVIG. In summary, an unexpected autoimmune prothrombotic disorder is described after vaccination with AZD1222. It is characterized by thrombocytopenia and anti-PF4 antibodies binding to platelets in AZD1222-dependent manner. Initial clinical experience suggests a risk of unusual and severe thromboembolic events.

The potential role of diffusion weighted imaging in the diagnosis of early carotid and vertebral artery dissection.

PURPOSE: To investigate the role of the diffusion weighted imaging (DWI) in the acute dissection of internal carotid artery (ICA) and vertebral artery (VA) and assessing the length of intramural hematoma (IMH), caused by dissection. METHODS: We analyzed 28 patients presenting with a dissection of the ICA and/or VA with respect to the presence of high signal intensity areas on DWI suggestive of dissection and 20 control subjects without arterial dissection, some with and some without atherosclerotic lesions. ICA or VA dissection was defined by clinical and imaging, computed tomography angiography (CTA), MR angiography (MRA), and digital subtraction angiography (DSA) findings. The length of DWI hyperintensity was compared to length of the occlusion or stenosis on the angiographic examination. RESULTS: In 28 patients, 30 dissected arteries were analyzed. Time intervals from the onset of the first clinical symptoms to the radiological evaluation ranged from 1.5 h to 42 days. In 28 (93%) of the dissections, a high signal intensity of the affected artery was present on DWI. The measurement of the dissection length on DWI compared to DSA showed a mean deviation of 2.7 mm and a standard deviation of 3.7 mm. CONCLUSION: DWI is a highly sensitive and valuable pulse sequence for the detection of dissected cervical arteries even in the first hours after symptom onset. In contrast to CTA and MRA, DWI can be a potential tool for a reliable measurement of the dissection length.

Gain-of-function STAT1 mutations are associated with intracranial aneurysms.

Chronic mucocutaneous candidiasis, characterized by persistent or recurrent fungal infections, represents the clinical hallmark in gain-of-function (GOF) signal transducer and activator of transcription 1 (STAT1) mutation carriers. Several cases of intracranial aneurysms have been reported in patients with GOF STAT1 mutation but the paucity of reported cases likely suggested this association still as serendipity. In order to endorse this association, we link the development of intracranial aneurysms with STAT1 GOF mutation by presenting the two different cases of a patient and her mother, and demonstrate upregulated phosphorylated STAT4 and IL-12 receptor ß1 upon stimulation in patient's blood cells. We also detected increased transforming growth factor (TGF)-ß type 2 receptor expression, particularly in CD14+ cells, and a slightly higher phosphorylation rate of SMAD3. In addition, the mother of the patient developed disseminated bacille Calmette-Guérin disease after vaccination, speculating that GOF STAT1 mutations may confer a predisposition to weakly virulent mycobacteria.

Neurological involvement in children with E. coli O104:H4-induced hemolytic uremic syndrome.

BACKGROUND: The aim of this study was to analyze the neurological involvement and outcome in pediatric patients with hemolytic uremic syndrome (HUS) during the 2011 epidemic caused by Escherichia coli O104:H4. METHODS: Clinical data and data from magnetic resonance imaging (MRI) scans and electroencephalography (EEG) during the acute phase of the disease and during follow-up at 3 and 6 months were analyzed in 50 patients. Twenty-five of these patients underwent neuropsychological testing (WISC IV) during follow-up. RESULTS: Neurological involvement (stupor or coma, seizures, visual disturbances, paresis, myocloni) was initially observed in 14/50 (28%) patients. One patient died. EEG abnormalities were more frequent in patients with neurological involvement than in those without (12/14 vs. 13/25, respectively). Cranial MRI scans were analyzed in nine patients with neurological involvement, of whom five showed abnormal findings. At the 3- and 6-month follow-ups, EEG abnormalities were found in 14/40 (35%) and 7/36 (19%) patients, respectively, whereas 28/42 (67%) and 17/39 (44%) patients, respectively, complained about on-going reduced performance. Neuropsychological testing showed a slightly lower global intelligence quotient in patients with neurological involvement versus those without (113.4 ± 2.8 vs. 119.4 ± 1.8, respectively). CONCLUSIONS: Neurological involvement was frequent in our cohort. Accordingly, the incidence of pathological EEG findings was high, even in patients without clinical signs of neurological involvement. Nevertheless, major neurological sequelae were rare, and neuropsychological outcome was favorable after 6 months.

Temporal pattern of cytotoxic edema in the perihematomal region after intracerebral hemorrhage: a serial magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Knowledge about cytotoxic edema (CE) in intracerebral hemorrhage is still limited. We aimed to analyze its presence, temporal pattern, and prognostic meaning. METHODS: Twenty-one patients with primary intracerebral hemorrhage underwent magnetic resonance imaging at days 1, 3, and 7 after symptom onset. CE was identified using diffusion-weighted imaging. Hematoma and perihematomal edema volumes were measured on fluid-attenuated inversion recovery images. National Institutes of Health Stroke Scale score was assessed at admission and with each magnetic resonance imaging. Clinical outcome was assessed by modified Rankin scale at 90 days. RESULTS: CE appeared in half of the patients within the first 24 hours. The apparent diffusion coefficient values decreased until day 3 and were significantly reversed from days 3 through 7 (P<0.01). Patients with CE showed significantly faster perihematomal edema growth from day 0 to 1 (P=0.036) than those without. Larger 3-day perihematomal edema volume (P=0.02) and presence of CE on day 3 (P=0.07) were associated with poor clinical outcome. CONCLUSIONS: CE is associated with stroke severity, perihematomal edema volume, and poor outcome. It is considered to indicate ongoing neuronal injury and, thus, might emerge as new treatment target.

Epstein-Barr virus-associated smooth muscle tumours after transplantation, infection with human immunodeficiency virus and congenital immunodeficiency syndromes.

Smooth muscle tumours (SMT) after transplantation (PTSMT) or associated with congenital immunodeficiency syndromes (CI-SMT) and human immunodeficiency virus (HIV-SMT) are rare. The majority of PTSMT and CI-SMT are associated with Epstein-Barr virus (EBV), while some HIV-SMT can be EBV-negative. SMT in immunodeficient states may present with unspecific symptoms which are mainly related to tumour localisation. In PTSMT, >50% of tumours manifest in the liver/transplant liver, but in general PTSMT, HIV-SMT and CI-SMT can occur at any site as single or multiple tumours. Multiple tumour manifestations do not define metastatic disease as PTSMT can occur synchronously and/or metachronously. PTSMT can originate from the recipient as well as from the donor. Morphologically, most tumours, in particular PTSMT, lack marked histological atypia or tumour necrosis, while some HIV-SMT and CI-SMT can present as sarcoma-like variants, but histomorphology does not predict clinical aggressiveness or tumourbiological behaviour. In PTSMT, surgery and reduced immunosuppression show comparable overall survival rates, while poor prognosis is mainly associated with intracranial manifestation and non-resectable tumours. In HIV-SMT and CI-SMT, surgery should be performed. In all 3 tumour types, adverse prognosis is mainly related to comorbidities associated with immunosuppression but not with the extent of histological atypia or tumour size.

Quantitative MRI shows cerebral microstructural damage in hemolytic-uremic syndrome patients with severe neurological symptoms but no changes in conventional MRI.

INTRODUCTION: Severe neurological symptoms in Shiga toxin-producing Escherichia coli infection associated hemolytic-uremic syndrome (STEC-HUS) are often accompanied by none or only mild alterations of cerebral magnetic resonance imaging (MRI). This study aims to analyze if quantitative MRI is able to reveal cerebral pathological alterations invisible for conventional MRI. METHODS: In nine patients with STEC-HUS associated severe neurological symptoms but inconspicuous cerebral MRI findings maps of the parameters T2 relaxation time, relative proton density (PD), apparent diffusion coefficient (ADC), and fractional anisotropy (FA) were generated. Quantitative values of these parameters were measured at the basal ganglia, thalamus, and white matter of the frontal and parietal lobe and compared to those of nine age- and sex-matched controls. RESULTS: Significant T2 prolongation (p < 0.01) was found in the basal ganglia of all patients compared to controls. PD and ADC were not significantly altered. A significant reduction of FA in patients was seen at caput nuclei caudati (p < 0.01). CONCLUSION: Prolonged T2 relaxation time indicates cerebral microstructural damages in these patients despite their inconspicuous MRI findings. T2 relaxometry could be used as a complementary tool for the assessment of metabolic-toxic brain syndromes.

Feasibility and safety of ADAPT in acute distal posterior cerebral artery occlusions.

PURPOSE: The direct aspiration first pass technique (ADAPT) is an effective and safe endovascular treatment for distal medium vessel occlusions (DMVO) of the anterior circulation. Clinical experience with ADAPT in the distal posterior circulation, however, is still limited and published data is scarce. In this original work, feasibility, safety and efficacy of ADAPT with distal access catheters (DAC) for treatment of acute distal posterior cerebral artery occlusions (DPCAOs) is evaluated. METHOD: All acute ischemic stroke patients between 2017 and 2022 with primary or secondary DPCAOs in the P2 or P3 segment, that underwent thrombectomy of the DPACO using ADAPT with DACs as frontline therapy, were identified. Demographic data, recanalization rates, procedural safety, and clinical outcome were assessed. RESULTS: Twenty-four patients with primary (n = 6) or secondary (n = 18) DPCAOs (P2: 21/24; P3: 3/24) were included. Median NIHSS score at admission was 14.5 (IQR 9.5). In all cases, the DPCAO could be reached with the DAC. Successful revascularization (DMVO-p-TICI ≥ 2b) with ADAPT was achieved in 79.2% (19/24), including a first pass effect of 62.5% (15/24), leading to complete recanalization (DMVO-p-TICI 3). Median number of passes was 1 (range 1-2). No complications related to distal PCA aspiration thrombectomy occurred. Median NIHSS and mRS scores at discharge were 4 (IQR 8) and 3 (IQR 2), respectively. CONCLUSIONS: ADAPT appears to be feasible, safe and effective for the treatment of acute DPCAOs in the setting of different occlusion patterns. High revascularization rates without procedural complications can be achieved. Further studies are needed to consolidate these results.

Adhesion of vessel wall to stentriever during combined technique for mechanical thrombectomy in acute ischemic stroke: A histomorphological study.

PURPOSE: Detection of vessel wall tissue in thrombus material in patients with ischemic stroke is judged as vascular injury. So far, several studies investigated components of the free clots after mechanical thrombectomy. The aim of this retrospective study was to investigate the involvement and role of the stentriever in vessel wall injury by analysis of the composition of adherent tissue to the stentriever during combined aspiration thrombectomy with stentriever. METHODS: Stentriever with adherent tissue and free clots in aspiration samples from patients undergoing mechanical thrombectomy (aspiration plus stentriever) were separately assessed for the occurrence of parts of vascular tissue together with clinical and interventional data as well as clinical outcome data. Specimens were analyzed histomorphologically and immunohistochemically. Findings, focused on parts of vessel wall were reported together with clinical data. RESULTS: Specimens from 21 identified patients were available. Parts of the vessel wall were detected in 7 out 21 (33%) samples. All specimens revealed fresh thrombus material without signs of organization or atheromatous tissue. In 90% of patients mTICI was greater than 2b without signs of secondary vessel injury. No vascular tissue was found in free clots of the aspiration samples. CONCLUSION: The examination of adherent tissue to the stentriever instead of the examination of free clots may affect the number of detected parts of vessel wall. Further studies in combination with vessel wall imaging may elucidate the origin of remnants of vessel wall.

Patterns in early diffusion-weighted MRI in children with haemolytic uraemic syndrome and CNS involvement.

OBJECTIVES: Diffusion-weighted imaging (DWI) in children with diarrhoea associated haemolytic uraemic syndrome (D+HUS) and cerebral involvement was evaluated retrospectively. METHODS: DWI within 24 h of onset of neurological symptoms. The apparent diffusion coefficient (ADC) was measured in grey/white matter and correlated with clinical and laboratory findings. RESULTS: DWI was abnormal in all. Abnormal ADC was detected in the supratentorial white matter (6/12) and cortex (1/12), the basal ganglia (5/12), the thalami (4/12), and the cerebellum (1/12). ADC was reduced in 5/12, increased in 4/12, and both in 3/12. Mean serum sodium was lower in patients with DWI abnormalities affecting the white matter (6/12), than in those with basal ganglia/thalamic involvement (6/12). Neurological outcome was normal in 4/11 and abnormal in 7/11, and 1 patient died, outcome did not correlate to either localisation or type of DWI abnormality. CONCLUSIONS: In D+HUS with neurological symptoms, early DWI may reveal abnormal ADC not only in the basal ganglia/thalami, but also in the white matter/cortex. Besides thrombotic microangiopathy, toxic effects of shiga toxin, azotaemia and hyponatraemia / hypoosmolality may be involved in cerebral involvement in children with D+HUS. Findings on early MRI seem not to predict clinical course or outcome. KEY POINTS: • DWI MR imaging may detect early CNS involvement in haemolytic uraemic syndrome • Different pathogenetical mechanisms may contribute to the CNS disease in HUS • Early MRI findings do not seem to allow prediction of clinical outcome.

Interventional stroke treatment - Is it also safe for arteries? Looking at thrombectomy wall damage through clot histology.

BACKGROUND AND PURPOSE: The aim of this study was to investigate whether morphological evidence of intracranial vascular injury can be found in the occluding thrombi of patients with ischemic stroke. METHODS: From 2015 until 2018 specimens of thrombi from patients with large vessel occlusion treated either by stent-assisted aspiration thrombectomy (TE) or by aspiration thrombectomy were prospectively collected. Thrombus specimens were formalin-fixed, paraffin-embedded and stained. Architectural features, presence of parts of vessel wall or atheromatous material, organisation of the thrombi, technique and number of thrombectomy manoeuvers were evaluated. RESULTS: Thrombus specimens from 302 patients were analyzed. 238 (80%) patients were treated with stent-assisted aspiration TE and 64 (20%) patients with aspiration TE only. 286 (95%) had fresh thrombi, 14 (4.6%) showed initial/complete thrombus organisation and multi-staged thrombi were found in 2 (<1%) patients. In 8 patients (2.6%) we found atypical thrombus content after a time interval longer 6 hours after onset and final thrombectomy manoeuvre: 4 with atheromatous material and 4 with parts of a vessel wall. In 1 patient with parts of vessel wall angiographically a dissection was detected. No parts of the vessel wall were found after sole aspiration thrombectomy. CONCLUSIONS: The overall risk of arterial vessel wall injury aspiration thrombectomy was low in our study. Aspiration thrombectomy and the procedure related with a retrieving device together with an ischemia time longer than 6 hours may increase the risk of vessel injury through the thrombectomy procedure. Further investigations are necessary to elucidate the influence of the mentioned aspects.

Varying Patterns of CNS Imaging in Influenza A Encephalopathy in Childhood.

PURPOSE: The brain imaging findings in children with neurological complications associated with influenza A infections are presented and analyzed and pathological imaging changes including atypical intracerebral hemorrhages in these patients are discussed. METHODS: Neuroimaging findings in six children with influenza encephalopathy following influenza A infection between 2012-2017 were retrospectively investigated. Of these five underwent magnetic resonance imaging (MRI) and one computed tomography (CT). Gene analysis was performed in two cases with acute necrotizing encephalitis of childhood (ANEC). RESULTS: The MRI findings of one child were concordant with mild encephalopathy with a reversible splenial lesion (MERS); this patient recovered but remained aphasic. In two cases MRI showed typical bilateral thalamic lesions as a feature of ANEC; genetic testing facilitated the diagnosis in one case. One of the patients died, the other showed little improvement. The remaining three patients had multiple diffuse cerebral hemorrhages predominantly affecting the supratentorial white matter after influenza A infection complicated by pneumonia, rhabdomyolysis and sepsis requiring extracorporeal membrane oxygenation (ECMO). CONCLUSION: Neurological complications in children associated with influenza A infection may include MERS and ANEC. Additionally, atypical disseminated intracerebral hemorrhages as a complication of influenza A infection is reported.

Computed tomography assessment of cerebral perfusion using a distributed parameter tracer kinetics model: validation with H(2)((15))O positron emission tomography measurements and initial clinical experience in patients with acute stroke.

We describe a distributed parameter (DP) model for tracer kinetic analysis in brain and validate the derived perfusion values with positron emission tomography (PET) scans. The proposed model is applied on actual clinical cases of hemispheric stroke. Nine patients with experienced transient ischaemic attack or minor stroke and a stenosis of the internal carotid artery were referred for computed tomography (CT) and PET imaging. The applicability of the DP model in clinical practice was tested in seven patients with acute stroke who received a baseline perfusion CT study and a noncontrast follow-up CT study after 2.4+/-1.8 days. The mean blood flow (F) value for all patients with carotid stenosis in the pooled data (54 regions of interest (ROIs)) was 37.9+/-11.2 mL/min per 100 g in perfusion CT and 35.6+/-9.8 mL/min per 100 g in perfusion PET imaging [r=0.77 (P=0.00)]. Regression analysis of the pooled ROIs for every patient revealed significant correlation between F values in seven patients [r=0.50 to 0.79 (r(2)-values ranged from 0.45 to 0.79), (0.01 < or = P < or = 0.05)]. Parametric maps that corresponded to all physiologic parameters were generated for every perfusion CT in the patients with acute stroke using the DP model. The ischaemic area was better delineated in F, intravascular blood volume and lag time (t(lag)) maps. The correlation coefficient comparing the visually outlined regions of abnormality between the t(lag) parametric map and the follow-up CT scans was 0.81 (P=0.003). In conclusion, DP physiological model using more realistic pharmacokinetics is feasible in dynamic contrast-enhanced CT of the brain in patients with acute and chronic cerebrovascular disease.

Chronic Granulomatous Disease First Diagnosed in Adulthood Presenting With Spinal Cord Infection.

Chronic granulomatous disease (CGD) is a rare genetic immunodeficiency, which is characterized by recurrent severe bacterial and fungal infections caused by a defect in phagocytic cells due to loss of superoxide production. The disease usually manifests within the first years of life. Early diagnosis allows therapeutic intervention to improve the limited life expectancy. Nevertheless, only half of the patients exceed the age of 25. Here, we present the case of a 41-year old female patient who presented with an extensive spinal cord infection and atypical pneumonia mimicking tuberculosis. The medical history with recurrent granulomatous infections and microbiological findings with multiple unusual opportunistic pathogens was the key to the diagnosis of CGD, which is exceptionally rare first diagnosed in patients in the fifth decade of life. The late diagnosis in this case was likely due to the lack of knowledge of the disease by the treating teams before but not because the patient did not have typical CGD infections along her life. The extensive progressive developing granulomas in our patient with fatal outcome raise the question of early immunosuppressive therapy in addition to anti-infectious treatment. We recommend appropriate CGD diagnostics in adult patients with unclear granulomatous diseases of the nervous system.

Effect of the arterial input function on the measured perfusion values and infarct volumetric in acute cerebral ischemia evaluated by perfusion computed tomography.

OBJECTIVES: We sought to evaluate the accuracy of the perfusion computed tomography (PCT) deconvolution-based brain perfusion measurements and the lesions' (infarct and penumbra) volumetric with regard to arterial input function (AIF) selection in patients with acute stroke. MATERIALS AND METHODS: Eighteen consecutive patients with symptoms of acute stroke underwent PCT at admission. Follow-up magnetic resonance imaging was obtained in all patients after 3.6 +/- 1.7 days (range, 1.5-6 days). PCT maps were generated focusing on the anterior cerebral artery (ACA) and branches of the middle cerebral artery (MCA) ipsilateral and contralateral to the ischemic lesion as AIFs. Infarct, penumbra, and total ischemic lesion were delineated on cerebral blood flow (CBF) maps. CBF, cerebral blood volume (CBV), and mean transit time (MTT) were calculated in the ischemic regions as provided by the 3 different AIFs, the normality test was applied for the obtained parameters, and the values were correlated (Pearson's correlation coefficient). Volumes of the ischemic regions (as obtained by the different AIFs) also were correlated and compared (paired t test) to the follow-up infarct volume. RESULTS: The CBF and CBV values obtained by the different AIFs in the infarct, penumbra, and total ischemic lesion were significantly correlated (r=0.94-0.96, P

ADMA increases arterial stiffness and decreases cerebral blood flow in humans.

BACKGROUND AND PURPOSE: Preclinical studies have revealed that the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine (ADMA), increases vascular tone in cerebral blood vessels. Marked elevations of ADMA blood levels were found in patients with diseases characterized by decreased cerebral perfusion, such as ischemic stroke. Arterial stiffness is an independent predictor of stroke and other adverse cardiovascular events. The aim of this study was to investigate the influence of a systemic subpressor dose of ADMA on arterial stiffness and cerebral perfusion in humans. METHODS: Using a double-blind, vehicle-controlled study design, we allocated 20 healthy men in random order to infusion of either ADMA (0.10 mg ADMA/kg per min) or vehicle over a period of 40 minutes. Arterial stiffness was assessed noninvasively by pulse wave analysis. All volunteers underwent measurement of cerebral perfusion by dynamic contrast-enhanced perfusion magnetic resonance imaging of the brain. RESULTS: Infusion of ADMA significantly decreased total cerebral perfusion by 15.1+/-4.5% (P=0.007), whereas blood flow in the vehicle group increased by 7.7+/-2.8% (P=0.02). ADMA also increased arterial stiffness as assessed by measurement of the augmentation index (-12.6+/-1.9 to -9.6+/-1.5, P=0.007). CONCLUSIONS: Our results document for the first time that subpressor doses of ADMA increase vascular stiffness and decrease cerebral perfusion in healthy subjects. Thus, ADMA is an important endogenous modulator of cerebral vascular tone and may be involved in the pathogenesis of cerebrovascular disease.

Feasibility of central cannabinoid CB1 receptor imaging with [124I]AM281 PET demonstrated in a schizophrenic patient.

We studied central cannabinoid CB1 receptors in a schizophrenic patient using the pyrazole derivative AM281 labelled with the positron-emitting nuclide iodine-124. A dynamic positron emission tomography (PET) acquisition with simultaneous blood sampling was performed up to 1.5 h post-injection. The classical Logan plot analysis was applied to generate a three-dimensional map of distribution volume (DV). The map was spatially normalised into the Montreal Neurological Institute stereotactic space. Using a volume of interest (VOI) template, mean values of DV were extracted from multiple grey matter regions and white matter (as a reference). As a measure of regional receptor availability, ratios of DV in grey matter to DV in white matter minus one (DVR-1) were calculated. The highest receptor binding was observed in the striatum and the pallidum (DVR-1: 0.35-0.37). Binding in basal ganglia regions was lower on the left than the right side. Moderately high binding was seen in the frontal cortex (0.22), the temporal cortex (0.18) and the cerebellum (0.15). In conclusion, 124I-AM281 PET can be used to reveal areas with prominent CB1 receptor binding. Nevertheless, limited image contrast and relatively high radiation exposure (physical half-life of 124I: 4 days) have to be taken into account. Asymmetric receptor binding may possibly reflect pathologic changes in schizophrenia.

CSF Levels of Angiopoietin-2 Do Not Differ between Patients with CSF Fluid Leakage Syndrome and Controls.

CSF abnormalities have been reported in CSF leakage syndrome. However, the mechanism for these CSF changes is actually unknown and they may indicate impaired CSF flow or blood-CSF barrier. Angiopoietin-2 (Ang-2), a protein which is expressed and released by endothelial cells, has been associated with increased vascular permeability. In the assumption that CSF changes are due to an impaired blood-CSF barrier, we hypothesized that subjects with persistent CSF leakage may have increased CSF Ang-2 levels. We enrolled 10 subjects with a clinically definite diagnosis of persisting CSF leakage syndrome and 10 control subjects. In CSF analyses, CSF to serum albumin ratio (Qalb) was the most frequently increased parameter indicating a disturbed blood-CSF barrier function. Comparison of the mean CSF Ang-2 levels, CSF to serum Ang-2 ratio (QAng-2), and QAng-2/Qalb between the control and CSF leakage patients did not show any significant difference. We suggest that the increase of Qalb results from a low CSF flow. Future studies with phase contrast-MRI in conjunction with CSF analyses before and after epidural blood patch treatment are required to address this question. It would be of particular interest whether Qalb can be used as a marker for successful nontargeted epidural blood patch treatment.

Effect of isovolemic, isothermic hemodialysis on cerebral perfusion and vascular stiffness using contrast computed tomography and pulse wave velocity.

BACKGROUND: Patients undergoing hemodialysis treatment have a six-fold increased risk for stroke relative to the general population. However, the effect of hemodialysis on cerebral blood flow is poorly studied and confounding factors like blood pressure and ultrafiltration as well as temperature changes have rarely been accounted for. The aim of our study was to use state-of-the-art technology to evaluate the effect of a single dialysis session on cerebral perfusion as well as on vascular stiffness. METHODS: Chronic hemodialysis patients (7 male/3 female, mean age 58 years) were recruited. Cerebral blood flow and arterial pulse wave velocity were measured before and immediately after a hemodialysis session. To exclude effects of volume changes we kept ultrafiltration to a minimum, allowing no change in body weight. Isothermic conditions were maintained by using the GENIUS single-pass batch-dialysis system with a high-flux polysulfone dialyser. Cerebral blood flow was measured by contrast-enhanced computed tomography. Pulse wave velocity was measured using the SphygmoCor (AtCor Medical, USA) device by a single operator. RESULTS: This study shows for the first time that isovolemic, isothermic hemodialysis neither affected blood pressure or heart rate, nor total or regional cerebral perfusion. There was also no change in pulse wave velocity. CONCLUSIONS: Mechanisms other than the dialysis procedure itself might be causative for the high incidence of ischemic strokes in this patient population. Moreover, the sole removal of uremic toxins does not lead to short-term effects on vascular stiffness, underlying the importance of volume control in this patient population.

Neurologic manifestations of E coli infection-induced hemolytic-uremic syndrome in adults.

OBJECTIVE: To describe the neurologic and neuroradiologic complications of Shiga toxin producing Escherichia coli infection (STEC)-associated hemolytic-uremic syndrome (HUS) in adults. METHODS: All 52 adult patients with STEC O104:H4 infection cared for at Hannover Medical School during the outbreak in Germany through May-July 2011 are considered in this observational study. Forty-three of the 52 patients underwent a standard neurologic diagnostic procedure including clinical examination, Mini-Mental State Examination, and Glasgow Coma Scale Score. Thirty-six patients underwent EEG, and 26 had cerebral MRI, 9 of them repeatedly. Case records of 9 patients who had not been seen by a neurologist were analyzed retrospectively. RESULTS: Forty-eight of the 52 patients had HUS. All but 1 of these showed neurologic symptoms. Focal neurologic signs like double vision, difficulties in finding words, or hyperreflexia were present in 23, additional deficits in orientation, attention, memory, or constructive abilities in 9, and marked impairment of consciousness in 15. MRI showed brainstem, midbrain, thalamus, corpus callosum, and white matter lesions in half of the patients, predominantly in diffusion-weighted images. The extent of MRI lesions did not correlate with clinical symptoms. General slowing but no focal alteration was found in half of the patients examined by EEG. CONCLUSION: Our findings suggest a toxic-metabolic pathology behind the neurologic impairment instead of multiple infarction due to microthrombosis. Future studies should aim to clarify if early antibiotic therapy or bowel cleansing might help to decrease the rate of neurologic complications in STEC-HUS.