[Severe noncardiogenic pulmonary edema due to permeability disorder after i.v. administration of CT contrast medium with subsequent venovenous extracorporeal membrane oxygenation]. / Schweres nichtkardiales Lungenödem durch Permeabilitätsstörung nach i.v.-CT-Kontrastmittel-Gabe mit konsekutiver venovenöser extrakorporaler Membranoxygenierung.

Hypersensitivity reactions are one of the most feared side effects associated with the use of CT contrast agents. Bronchospasm and lung edema are known manifestations, whereby the latter occurs much less often. In anaphylaxis, numerous mechanisms can lead to cardiac failure with subsequent lung edema. In contrast, the cardiac function is not impaired in noncardiogenic pulmonary edema (NCPE), which is a rare phenomenon but with potentially fatal outcome. The exact pathophysiology of NCPE remains unknown and characteristically response to conventional anaphylaxis treatment is poor. This article presents the case of a 48-year-old man with NCPE who underwent elective coronary CT as part of the evaluation of recurrent syncope. After administration of iodinated contrast medium the patient developed a fulminant lung edema, which led to severe hypoxemia with cardiac arrest despite immediate treatment by the medical emergency team, including assisted ventilation, prednisolone, dimetindene and adrenaline. An early echocardiographic assessment after ROSC and intubation showed an intact cardiac function and no signs of valvular pathologies. Arterial blood gas analysis revealed a severe global respiratory failure (Horowitz quotient 73), profound acidosis (pH 7.06), elevated lactate and hemoglobin levels (8.9 mmol/l and 23.7 g/dl, respectively). A chest X­ray revealed bilateral inhomogeneous opacities. Nitrous oxide was administered to improve the ventilation-perfusion mismatch. In addition, intravenous hydrocortisone was started to address the severe capillary leak syndrome. Follow-up echocardiography showed consistently stable cardiac function at all times. As the lung function deteriorated despite aggressive countermeasures, venovenous extracorporeal membrane oxygenation (ECMO) was initiated 6 h after the initial event. With the aid of ECMO support the invasiveness of mechanical ventilation could be reduced and volume substitution intensified. In the further course, microcirculatory dysfunction and respiratory function gradually improved and ECMO support could be discontinued after 70 h. The patient was extubated on day 9 and discharged to the normal ward on day 13 without any neurological impairments.

The late-presenting HIV-infected patient 30 years after the introduction of HIV testing: spectrum of opportunistic diseases and missed opportunities for early diagnosis.

OBJECTIVES: The aim of the study was to describe the characteristics of HIV-infected late presenters, opportunistic diseases at diagnosis and missed opportunities to diagnose HIV infection earlier. METHODS: In a retrospective cohort study, we reviewed the medical records of all adults with newly diagnosed HIV infection admitted to the Department of Infectious Diseases of the Vivantes Auguste-Viktoria Hospital, Berlin, Germany. RESULTS: In the 5-year period from 2009 to 2013, 270 late presenters were identified. The most common AIDS-defining conditions were oesophageal candidiasis (n = 136; 51%), wasting syndrome (n = 106; 40%) and pneumocystis pneumonia (n = 91; 34%). Fifty-five patients (21%) had presented with at least one HIV indicator condition on prior contact with health care services without being offered testing for HIV. Female patients and heterosexual men [not men who have sex with men ('non-MSM')] had a significantly higher chance of being among patients previously presenting with indicator conditions and not being tested [odds ratio (OR) 4.7; 95% confidence interval (CI) 2.2-10.0; P < 0.001; and OR 2.4; 95% CI 1.2-5.1; P < 0.01, respectively]. The most commonly missed indicator conditions were leucocytopenia (n = 13; 24%), thrombocytopenia (n = 12; 22%), oral candidiasis (n = 9; 16%), unexplained weight loss (n = 7; 13%), herpes zoster (n = 5; 9%) and cervical dysplasia/cancer (n = 4; 20% of women). The median time between presentation with an indicator condition and the diagnosis of HIV infection was 158.5 days [interquartile range (IQR) 40-572 days]. Patients with oral candidiasis and unexplained weight loss had the shortest time between the "missed opportunity" and the diagnosis of HIV infection. Fifty-five hospital admissions with a total cost of over EUR 500 000 and - most importantly - six in-hospital deaths might have been prevented if HIV testing had been performed in patients with documented indicator conditions. CONCLUSIONS: Indicator conditions are still missed by clinicians. Women and 'non-MSM' are at highest risk of presenting with an indicator condition but not being tested for HIV infection.

'Time-to-amphotericin B' in cryptococcal meningitis in a European low-prevalence setting: analysis of diagnostic delays.

BACKGROUND: Cryptococcal meningitis is a rare disease in Europe, resulting in delayed recognition and slower initiation of specific treatment. AIM: To analyse the time-to-treatment and the factors that delay the diagnosis and treatment in the low-prevalence setting of a European centre. DESIGN: Retrospective review METHODS: We reviewed full medical records of all adult patients with cryptococcal meningitis referred to an HIV centre in Berlin, Germany in 10-year period between 1st of October 2003 and 31st of September 2013. Multivariant statistics with bootstrap-resampling were performed. RESULTS: We identified 19 patients with a diagnosis of HIV-related cryptococcal meningitis (0.55% of all consecutive HIV-infected patients). In almost half of our patients the diagnosis was not considered initially on admission to the secondary care centre and the first diagnostic clue being an accidental positive blood, cerebrospinal fluid or bronchoalveolar lavage culture growing Cryptococcus neoformans. The median time-to-treatment was 5 days (range: 1-16). Known positive HIV status accelerated the time-to-diagnosis (p < 0.05) by a median of 1.89 days, whereas the CSF cell count ≤ 10/µl delayed diagnosis by a median time of 1.93 days (p < 0.1). CONCLUSIONS: Diagnostic delays could be avoided by encouraging practising physicians (i) to consider cryptococcal meningitis in immunosuppressed HIV-infected patients irrespective of neurological symptoms; (ii) to test for India ink, cryptococcal antigen and fungal cultures in immunosuppressed HIV-infected patients with normal CSF; (iii) to consider a possibility of underlying HIV infection in patients with unknown HIV status presenting with meningitis; and (iv) to consider early targeted HIV testing in persons at risk according to locally validated criteria.

Combined CMV- and HSV-1 brainstem encephalitis restricted to medulla oblongata.

We report a very rare case of a combined CMV- and HSV-1 isolated brainstem encephalitis restricted to medulla oblongata in a patient with advanced HIV disease. Neither limbic nor general ventricular involvement was detected on neuroimaging. The case highlights the importance of testing for HSV-1 and CMV in HIV-infected patients presenting with an isolated brainstem syndrome.

Central pontine myelinolysis in advanced HIV infection with tuberculosis and multicentric Castleman's disease.

We present a case of central pontine myelinolysis (CPM) in a patient with advanced HIV infection and miliary tuberculosis. While hospitalized the patient developed an unusual ataxic variant of CPM with full clinical recovery. Follow-up imaging revealed resolution of pontine lesions. To our knowledge, this is the first report of a clinical and radiological recovery from CPM in advanced HIV disease. Our report extends our knowledge of neurological presentations in patients with advanced HIV infection. It highlights the importance of considering CPM in patients with advanced HIV disease presenting with an ataxic syndrome, even in the absence of an electrolyte derangement.

Infectious vasculopathy of intracranial large- and medium-sized vessels in neurological intensive care unit: a clinico-radiological study.

BACKGROUND: Infections are a well-known cause of cerebral vasculopathy and vasculitis. We aimed to analyze the frequency of intracranial vasculopathy attributable to infection, the spectrum of causative microorganisms, imaging, and cerebrospinal fluid (CSF) characteristics as well as clinical course and outcome. METHODS: We used our institution's medical record system to identify all patients diagnosed with nonatherosclerotic central nervous system vasculopathy from January 1, 1999 through February 28, 2009. We reviewed their clinical charts, imaging data, and results of CSF studies. RESULTS: Twenty-five adult patients with nonatherosclerotic cerebral vasculopathy of large- and medium-sized intracranial vessels were identified. Eight patients had vasculopathy attributable to infection (32%). The underlying pathologies were acute bacterial meningitis (n = 4), varicella zoster virus (VZV) infection (n = 2), borreliosis (n = 1), and syphilis (n = 1). In six patients, magnetic resonance angiography was performed and showed vasculopathic changes in all patients examined (100%). In both patients with VZV-associated vasculopathy, the arterial wall enhanced on magnetic resonance imaging. The CSF examination of the patients with infectious vasculopathy showed a significantly higher white blood cell count. The outcome of the infectious cohort was unfavorable with one death, two patients with locked-in syndrome, and five patients discharged from intensive care with severe neurological deficits. CONCLUSION: In this cohort, one-third of all cases of nonatherosclerotic vasculopathy were due to infectious vasculopathy of large and medium intracranial vessels.

[Post-stroke depression: clinical aspects, epidemiology, therapy, and pathophysiology]. / Poststroke-Depression: Klinik, Epidemiologie, Therapie, pathophysiologische Konzepte.

Post-stroke depression (PSD) is the most frequent psychiatric complication following ischemic stroke, affecting up to 50% of all such patients. Moreover, PSD is associated with increased morbidity and mortality following ischemic stroke. In clinical practice, PSD is underdiagnosed and many affected patients do not receive adequate treatment. This review article summarizes current knowledge regarding epidemiogy, clinical features, risk factors and predisposition, therapy, and prophylaxis of PSD.

Electroconvulsive monotherapy in the treatment of acute confusion psychosis. A case report.

This report focuses on the successful treatment of a most acute case of confusion psychosis according to the concept of Karl Leonhard. The 18-year-old patient was hospitalized three times before the current episode and his case has been characterized as pharmacologically treatment-resistant psychosis since he failed to respond to any psychopharmacological therapy including sufficient clozapine medication. In the patient's history, typical and atypical antipsychotic as well as mood-stabilizing and sedating pharmacological treatments have been conducted. However, only adverse effects could be observed. When receiving electroconvulsive monotherapy (ECT), the patient showed a marked reduction of symptoms while experiencing no adverse effects. The implications of this finding are discussed with regard to Leonhard's diagnostic system.

[Sporadic cerebral amyloid angiopathy with ischemic leukoencephalopathy and microbleeds. Cause for a rapidly progressive dementia syndrome]. / Sporadische zerebrale Amyloidangiopathie mit ischämischer Leukenzephalopathie und Mikroblutungen. Ursache eines rasch progredienten demenziellen Syndroms.

We describe a 72-year-old patient with rapidly progressive dementia and a complex focal seizure. Magnetic resonance (MR) imaging revealed leukoencephalopathy with the involvement of the U-fibers as well as cortical and subcortical microbleeds. Brain biopsy confirmed the diagnosis of cerebral Abeta amyloid angiopathy (CAA). The presented case illustrates the significance of CAA as a cause of rapidly progressive dementia and leukoencephalopathy and points out the importance of T2-weighted MR imaging in the evaluation of dementia.

[Adenocarcinoma-associated nonbacterial thrombotic endocarditis as the cause of recurrent strokes]. / Adenokarzinom-assoziierte nichtbakterielle thrombotische Endokarditis als Ursache rezidivierender Schlaganfälle.

We describe a 60-year-old female patient without vascular risk factors diagnosed with cardioembolic ischemic stroke due to an atrial septal aneurysm with a right-to-left shunt. However, further investigation after recurrent strokes revealed a nonbacterial thrombotic endocarditis (NBTE) caused by a metastatic adenocarcinoma. The presented case illustrates the difficulties in establishing the diagnosis of NBTE premortally and points out the importance of repeated echocardiographic evaluations of cardiac valves and serological examination of tumor markers in patients with recurrent strokes of unknown origin.

Neuroprotective effects of the antifungal drug clotrimazole.

Pretreatment with 10 microM of the antifungal drug clotrimazole potently reduced the death of cultured rat cerebellar granule cells induced by oxygen/glucose deprivation, and the excitotoxic effect of glutamate on cultured hippocampal neurons and cerebellar granule cells. In patch-clamped hippocampal pyramidal neurons, 10-50 microM clotrimazole caused a decrease in the amplitude of N-methyl-D-aspartate (NMDA) receptor-mediated currents. Glutamate induced intracellular Ca(2+) overload, as measured by Fluo-3 confocal fluorescence imaging, while clotrimazole reduced Ca(2+) overload and promoted the recovery of intracellular calcium homeostasis after glutamate treatment. Using tetramethylrhodamine ethyl ester fluorescence as a marker of mitochondrial membrane potential we found that clotrimazole prevented the glutamate-induced loss of mitochondrial membrane potential. Our data provide evidence that the protective effect of clotrimazole against oxygen/glucose deprivation and excitotoxicity is due to the ability of this drug to partially block NMDA receptor-gated channel, thus causing both reduced calcium overload and lower probability of the mitochondrial potential collapse.

Mild cerebral ischemia induces loss of cyclin-dependent kinase inhibitors and activation of cell cycle machinery before delayed neuronal cell death.

After mild ischemic insults, many neurons undergo delayed neuronal death. Aberrant activation of the cell cycle machinery is thought to contribute to apoptosis in various conditions including ischemia. We demonstrate that loss of endogenous cyclin-dependent kinase (Cdk) inhibitor p16(INK4a) is an early and reliable indicator of delayed neuronal death in striatal neurons after mild cerebral ischemia in vivo. Loss of p27(Kip1), another Cdk inhibitor, precedes cell death in neocortical neurons subjected to oxygen-glucose deprivation in vitro. The loss of Cdk inhibitors is followed by upregulation of cyclin D1, activation of Cdk2, and subsequent cytoskeletal disintegration. Most neurons undergo cell death before entering S-phase, albeit a small number ( approximately 1%) do progress to the S-phase before their death. Treatment with Cdk inhibitors significantly reduces cell death in vitro. These results show that alteration of cell cycle regulatory mechanisms is a prelude to delayed neuronal death in focal cerebral ischemia and that pharmacological interventions aimed at neuroprotection may be usefully directed at cell cycle regulatory mechanisms.

Differential mechanisms of neuroprotection by 17 beta-estradiol in apoptotic versus necrotic neurodegeneration.

The major goal of this study was to compare mechanisms of the neuroprotective potential of 17 beta-estradiol in two models for oxidative stress-independent apoptotic neuronal cell death with that in necrotic neuronal cell death in primary neuronal cultures derived from rat hippocampus, septum, or cortex. Neuronal apoptosis was induced either by staurosporine or ethylcholine aziridinium (AF64A), as models for necrotic cell death glutamate exposure or oxygen-glucose deprivation (OGD) were applied. Long-term (20 hr) pretreatment (0.1 microm 17 beta-estradiol) was neuroprotective in apoptotic neuronal cell death induced by AF64A (40 microm) only in hippocampal and septal neuronal cultures and not in cortical cultures. The neuroprotective effect was blocked by the estrogen antagonists ICI 182,780 and tamoxifen and the phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002. In glutamate and OGD-induced neuronal damage, long-term pretreatment was not effective. In contrast, short-term (1 hr) pretreatment with 17 beta-estradiol in the dose range of 0.5-1.0 microm significantly reduced the release of lactate dehydrogenase and improved morphology of cortical cultures exposed to glutamate or OGD but was not effective in the AF64A model. Staurosporine-induced apoptosis was not prevented by either long- or short-term pretreatment. The strong expression of the estrogen receptor-alpha and the modulation of Bcl proteins by 17 beta-estradiol in hippocampal and septal but not in cortical cultures indicates that the prevention of apoptotic, but not of necrotic, neuronal cell death by 17 beta-estradiol possibly depends on the induction of Bcl proteins and the density of estrogen receptor-alpha.

Protective effects of PJ34, a novel, potent inhibitor of poly(ADP-ribose) polymerase (PARP) in in vitro and in vivo models of stroke.

Focal cerebral ischemia activates the nuclear protein poly(ADP-ribose) polymerase (PARP) by single DNA strand breaks which leads to energy depletion and cell necrosis. Deletion or inhibition of PARP protects against ischemic brain injury. Here we examined the neuroprotective effect of PJ34, a novel potent inhibitor of PARP in vitro and in vivo. Serum-free primary neuronal cultures derived from rat cortex (E15-17) and kept in culture for 10 days were exposed to oxygen glucose deprivation (OGD) in vitro. Neuronal injury was quantified by LDH release after 24 h. Pretreatment with 30-1000 nM PJ34 significantly protected from OGD-induced cell injury in a dose-dependent manner. For in vivo experiments SV/129 mice were treated with PJ34 (50 microg) by intraperitoneal injection 2 h before 1 h middle cerebral artery occlusion (MCAo) and again 6 h later. Twenty-three h after reperfusion ischemic injury was significantly decreased compared to vehicle-treated controls (infarct volume reduction of 40%, p<0.05). Similarly, in a rat model of MCAo (2 h occlusion followed by up to 22 h reperfusion), PJ34 administration (10 mg/kg i.v.) significantly reduced infarct size, and the effect of the drug was maintained even if it was given as late as 10 min prior to reperfusion time. PJ34 significantly protected in a 4 h, but not in a 24 h permanent occlusion model. In conclusion, PJ34, a novel, potent inhibitor of PARP exerts massive neuroprotective agents, with a significant therapeutic window of opportunity. The present work strengthens the concept that pharmacological PARP inhibition may be a suitable approach for the treatment of acute stroke in man.