@article{GolombeckWessigMonoranuetal.2013, author = {Golombeck, Stefanie Kristin and Wessig, Carsten and Monoranu, Camelia-Maria and Sch{\"u}tz, Ansgar and Solymosi, Laszlo and Melzer, Nico and Kleinschnitz, Christoph}, title = {Fatal atypical reversible posterior leukoencephalopathy syndrome: a case report}, series = {Journal of Medical Case Reports}, volume = {7}, journal = {Journal of Medical Case Reports}, number = {14}, doi = {10.1186/1752-1947-7-14}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135517}, year = {2013}, abstract = {Introduction: Reversible posterior leukoencephalopathy syndrome - a reversible subacute global encephalopathy clinically presenting with headache, altered mental status, visual symptoms such as hemianopsia or cortical blindness, motor symptoms, and focal or generalized seizures - is characterized by a subcortical vasogenic edema symmetrically affecting posterior brain regions. Complete reversibility of both clinical signs and magnetic resonance imaging lesions is regarded as a defining feature of reversible posterior leukoencephalopathy syndrome. Reversible posterior leukoencephalopathy syndrome is almost exclusively seen in the setting of a predisposing clinical condition, such as pre-eclampsia, systemic infections, sepsis and shock, certain autoimmune diseases, various malignancies and cytotoxic chemotherapy, transplantation and concomitant immunosuppression (especially with calcineurin inhibitors) as well as episodes of abrupt hypertension. We describe for the first time clinical, radiological and histological findings in a case of reversible posterior leukoencephalopathy syndrome with an irreversible and fatal outcome occurring in the absence of any of the known predisposing clinical conditions except for a hypertensive episode. Case presentation: A 58-year-old Caucasian woman presented with a two-week history of subacute and progressive occipital headache, blurred vision and imbalance of gait and with no evidence for raised arterial blood pressure during the two weeks previous to admission. Her past medical history was unremarkable except for controlled arterial hypertension. Cerebral magnetic resonance imaging demonstrated cortical and subcortical lesions with combined vasogenic and cytotoxic edema atypical for both venous congestion and arterial infarction. Routine laboratory and cerebrospinal fluid parameters were normal. The diagnosis of reversible posterior leukoencephalopathy syndrome was established. Within hours after admission the patient showed a rapidly decreasing level of consciousness, extension and flexion synergisms, bilaterally extensor plantar responses and rapid cardiopulmonary decompensation requiring ventilatory and cardiocirculatory support. Follow-up cerebral imaging demonstrated widespread and confluent cytotoxic edematous lesions in different arterial territories, global cerebral swelling, and subsequent upper and lower brainstem herniation. Four days after admission, the patient was declared dead because of brain death. Conclusion: This case demonstrates that fulminant and fatal reversible posterior leukoencephalopathy syndrome may occur spontaneously, that is, in the absence of any of the known predisposing systemic conditions.}, language = {en} } @article{EhlingGoebBittneretal.2013, author = {Ehling, Petra and G{\"o}b, Eva and Bittner, Stefan and Budde, Thomas and Ludwig, Andreas and Kleinschnitz, Christoph and Meuth, Sven G.}, title = {Ischemia-induced cell depolarization: does the hyperpolarization-activated cation channel HCN2 affect the outcome after stroke in mice?}, series = {Experimental \& Translational Stroke Medicine}, volume = {5}, journal = {Experimental \& Translational Stroke Medicine}, number = {16}, doi = {10.1186/2040-7378-5-16}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131887}, year = {2013}, abstract = {Background Brain ischemia is known to include neuronal cell death and persisting neurological deficits. A lack of oxygen and glucose are considered to be key mediators of ischemic neurodegeneration while the exact mechanisms are yet unclear. In former studies the expression of two different two-pore domain potassium \((K_{2P})\) channels (TASK1, TREK1) were shown to ameliorate neuronal damage due to cerebral ischemia. In neurons, TASK channels carrying hyperpolarizing \(K^+\) leak currents, and the pacemaker channel HCN2, carrying depolarizing \(I_h\), stabilize the membrane potential by a mutual functional interaction. It is assumed that this ionic interplay between TASK and HCN2 channels enhances the resistance of neurons to insults accompanied by extracellular pH shifts. Methods In C57Bl/6 (wildtype, WT), \(hcn2^{+/+}\) and \(hcn2^{-/-}\) mice we used an in vivo model of cerebral ischemia (transient middle cerebral artery occlusion (tMCAO)) to depict a functional impact of HCN2 in stroke formation. Subsequent analyses comprise behavioural tests and hcn2 gene expression assays. Results After 60 min of tMCAO induction in WT mice, we collected tissue samples at 6, 12, and 24 h after reperfusion. In the infarcted neocortex, hcn2 expression analyses revealed a nominal peak of hcn2 expression 6 h after reperfusion with a tendency towards lower expression levels with longer reperfusion times. Hcn2 gene expression levels in infarcted basal ganglia did not change after 6 h and 12 h. Only at 24 h after reperfusion, hcn2 expression significantly decreases by ~55\%. However, 30 min of tMCAO in hcn2-/- as well as hcn2+/+ littermates induced similar infarct volumes. Behavioural tests for global neurological function (Bederson score) and motor function/coordination (grip test) were performed at day 1 after surgery. Again, we found no differences between the groups. Conclusions Here, we hypothesized that the absence of HCN2, an important functional counter player of TASK channels, affects neuronal survival during stroke-induced tissue damage. However, together with a former study on TASK3 these results implicate that both TASK3 and HCN2 which were supposed to be neuroprotective due to their pH-dependency, do not influence ischemic neurodegeneration during stroke in the tMCAO model.}, language = {en} } @article{GolombeckWessigMonoranuetal.2013, author = {Golombeck, Stefanie Kristin and Wessig, Carsten and Monoranu, Camelia-Maria and Sch{\"u}tz, Ansgar and Solymosi, Laszlo and Melzer, Niko and Kleinschnitz, Christoph}, title = {Fatal atypical reversible posterior leukoencephalopathy syndrome: a case report}, series = {Journal of Medical Case Reports}, volume = {7}, journal = {Journal of Medical Case Reports}, number = {14}, doi = {10.1186/1752-1947-7-14}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129456}, year = {2013}, abstract = {Introduction: Reversible posterior leukoencephalopathy syndrome - a reversible subacute global encephalopathy clinically presenting with headache, altered mental status, visual symptoms such as hemianopsia or cortical blindness, motor symptoms, and focal or generalized seizures - is characterized by a subcortical vasogenic edema symmetrically affecting posterior brain regions. Complete reversibility of both clinical signs and magnetic resonance imaging lesions is regarded as a defining feature of reversible posterior leukoencephalopathy syndrome. Reversible posterior leukoencephalopathy syndrome is almost exclusively seen in the setting of a predisposing clinical condition, such as pre-eclampsia, systemic infections, sepsis and shock, certain autoimmune diseases, various malignancies and cytotoxic chemotherapy, transplantation and concomitant immunosuppression (especially with calcineurin inhibitors) as well as episodes of abrupt hypertension. We describe for the first time clinical, radiological and histological findings in a case of reversible posterior leukoencephalopathy syndrome with an irreversible and fatal outcome occurring in the absence of any of the known predisposing clinical conditions except for a hypertensive episode. Case presentation: A 58-year-old Caucasian woman presented with a two-week history of subacute and progressive occipital headache, blurred vision and imbalance of gait and with no evidence for raised arterial blood pressure during the two weeks previous to admission. Her past medical history was unremarkable except for controlled arterial hypertension. Cerebral magnetic resonance imaging demonstrated cortical and subcortical lesions with combined vasogenic and cytotoxic edema atypical for both venous congestion and arterial infarction. Routine laboratory and cerebrospinal fluid parameters were normal. The diagnosis of reversible posterior leukoencephalopathy syndrome was established. Within hours after admission the patient showed a rapidly decreasing level of consciousness, extension and flexion synergisms, bilaterally extensor plantar responses and rapid cardiopulmonary decompensation requiring ventilatory and cardiocirculatory support. Follow-up cerebral imaging demonstrated widespread and confluent cytotoxic edematous lesions in different arterial territories, global cerebral swelling, and subsequent upper and lower brainstem herniation. Four days after admission, the patient was declared dead because of brain death. Conclusion: This case demonstrates that fulminant and fatal reversible posterior leukoencephalopathy syndrome may occur spontaneously, that is, in the absence of any of the known predisposing systemic conditions.}, language = {en} } @article{FluriHeinenKleinschnitz2013, author = {Fluri, Felix and Heinen, Florian and Kleinschnitz, Christoph}, title = {Intravenous Thrombolysis in a Stroke Patient Receiving Rivaroxaban}, series = {Cerebrovascular Disease Extra}, volume = {2013}, journal = {Cerebrovascular Disease Extra}, number = {3}, doi = {10.1159/000355839}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128816}, pages = {153-155}, year = {2013}, abstract = {No abstract available.}, language = {en} } @article{LinkerMagnusKornetal.2013, author = {Linker, Ralf A. and Magnus, Tim and Korn, Thomas and Kleinschnitz, Christoph and Meuth, Sven G.}, title = {Report on the 5'th scientific meeting of the "Verein zur F{\"o}rderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Motzen, Germany, Oct. 25th - Oct. 27th, 2013}, series = {Experimental \& Translational Stroke Medicine}, volume = {5}, journal = {Experimental \& Translational Stroke Medicine}, number = {15}, doi = {10.1186/2040-7378-5-15}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129230}, year = {2013}, abstract = {From october 25th - 27th 2013, the 5th NEUROWIND e.V. meeting was held in Motzen, Brandenburg, Germany. This year more than 60 doctoral students and postdocs from over 25 different groups working in German university hospitals or research institutes attended the meeting to discuss their latest findings in the fields of neuroimmunology, neurodegeneration and neurovascular research. All participants appreciated the stimulating environment in Motzen, Brandenburg, and people took the opportunity for scientific exchange, discussion about ongoing projects and already started further collaborations. Like in the previous years, the symposium was regarded as a very well organized platform to support research of young investigators in Germany. According to the major aim of NEUROWIND e.V. to support younger researchers in Germany the 3rd NEUROWIND YOUNG SCIENTIST AWARD for experimental neurology was awarded to Ruth Stassart working in the group of Klaus Armin Nave and Wolfgang Br{\"u}ck (MPI G{\"o}ttingen and Department of Neuropathology, G{\"o}ttingen Germany). The successful work was published in Nature Neuroscience entitled "A role for Swann cell-derived neuregulin-1 in remyelination". This outstanding paper deals with the function of Schwann cell neuregulin as an endogenous factor for myelin repair. The award is endowed with 20.000 Euro sponsored by Merck Serono GmbH, Darmstadt, Germany (unrestricted educational grant). This year's keynote lecture was given by Albert Ludolph, Head of the Department of Neurology at the University Clinic of Ulm. Dr. Ludolph highlighted the particular role of individual scientists for the development of research concepts in Alzheimer´s disease (AD) and frontotemporal dementia (FTD).}, language = {en} } @article{EhlingGoebBittneretal.2013, author = {Ehling, Petra and G{\"o}b, Eva and Bittner, Stefan and Budde, Thomas and Ludwig, Andreas and Kleinschnitz, Christoph and Meuth, Sven G.}, title = {Ischemia-induced cell depolarization: does the hyperpolarization-activated cation channel HCN2 affect the outcome after stroke in mice?}, series = {Experimental \& Translational Stroke Medicine}, volume = {5}, journal = {Experimental \& Translational Stroke Medicine}, number = {16}, doi = {10.1186/2040-7378-5-16}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129240}, year = {2013}, abstract = {Background Brain ischemia is known to include neuronal cell death and persisting neurological deficits. A lack of oxygen and glucose are considered to be key mediators of ischemic neurodegeneration while the exact mechanisms are yet unclear. In former studies the expression of two different two-pore domain potassium \((K_{2P})\) channels (TASK1, TREK1) were shown to ameliorate neuronal damage due to cerebral ischemia. In neurons, TASK channels carrying hyperpolarizing \(K^+\) leak currents, and the pacemaker channel HCN2, carrying depolarizing Ih, stabilize the membrane potential by a mutual functional interaction. It is assumed that this ionic interplay between TASK and HCN2 channels enhances the resistance of neurons to insults accompanied by extracellular pH shifts. Methods In C57Bl/6 (wildtype, WT), \(hcn2^{+/+}\) and \(hcn2^{-/-}\) mice we used an in vivo model of cerebral ischemia (transient middle cerebral artery occlusion (tMCAO)) to depict a functional impact of HCN2 in stroke formation. Subsequent analyses comprise behavioural tests and hcn2 gene expression assays. Results After 60 min of tMCAO induction in WT mice, we collected tissue samples at 6, 12, and 24 h after reperfusion. In the infarcted neocortex, hcn2 expression analyses revealed a nominal peak of hcn2 expression 6 h after reperfusion with a tendency towards lower expression levels with longer reperfusion times. Hcn2 gene expression levels in infarcted basal ganglia did not change after 6 h and 12 h. Only at 24 h after reperfusion, hcn2 expression significantly decreases by ~55\%. However, 30 min of tMCAO in hcn2-/- as well as hcn2+/+ littermates induced similar infarct volumes. Behavioural tests for global neurological function (Bederson score) and motor function/coordination (grip test) were performed at day 1 after surgery. Again, we found no differences between the groups. Conclusions Here, we hypothesized that the absence of HCN2, an important functional counter player of TASK channels, affects neuronal survival during stroke-induced tissue damage. However, together with a former study on TASK3 these results implicate that both TASK3 and HCN2 which were supposed to be neuroprotective due to their pH-dependency, do not influence ischemic neurodegeneration during stroke in the tMCAO model.}, language = {en} } @article{KleinschnitzMenclGarzetal.2013, author = {Kleinschnitz, Christoph and Mencl, Stine and Garz, Cornelia and Niklass, Solveig and Braun, Holger and G{\"o}b, Eva and Homola, Gy{\"o}rgy and Heinze, Hans-Jochen and Reymann, Klaus G. and Schreiber, Stefanie}, title = {Early microvascular dysfunction in cerebral small vessel disease is not detectable on 3.0 Tesla magnetic resonance imaging: a longitudinal study in spontaneously hypertensive stroke-prone rats}, series = {Experimental \& Translational Stroke Medicine}, journal = {Experimental \& Translational Stroke Medicine}, doi = {10.1186/2040-7378-5-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97056}, year = {2013}, abstract = {Background Human cerebral small vessel disease (CSVD) has distinct histopathologic and imaging findings in its advanced stages. In spontaneously hypertensive stroke-prone rats (SHRSP), a well-established animal model of CSVD, we recently demonstrated that cerebral microangiopathy is initiated by early microvascular dysfunction leading to the breakdown of the blood-brain barrier and an activated coagulatory state resulting in capillary and arteriolar erythrocyte accumulations (stases). In the present study, we investigated whether initial microvascular dysfunction and other stages of the pathologic CSVD cascade can be detected by serial magnetic resonance imaging (MRI). Findings Fourteen SHRSP and three control (Wistar) rats (aged 26-44 weeks) were investigated biweekly by 3.0 Tesla (3 T) MRI. After perfusion, brains were stained with hematoxylin-eosin and histology was correlated with MRI data. Three SHRSP developed terminal CSVD stages including cortical, hippocampal, and striatal infarcts and macrohemorrhages, which could be detected consistently by MRI. Corresponding histology showed small vessel thromboses and increased numbers of small perivascular bleeds in the infarcted areas. However, 3 T MRI failed to visualize intravascular erythrocyte accumulations, even in those brain regions with the highest densities of affected vessels and the largest vessels affected by stases, as well as failing to detect small perivascular bleeds. Conclusion Serial MRI at a field strength of 3 T failed to detect the initial microvascular dysfunction and subsequent small perivascular bleeds in SHRSP; only terminal stages of cerebral microangiopathy were reliably detected. Further investigations at higher magnetic field strengths (7 T) using blood- and flow-sensitive sequences are currently underway.}, language = {en} } @article{GunrebenGeisKleinschnitz2013, author = {Gunreben, Ignaz and Geis, Christian and Kleinschnitz, Christoph}, title = {Acute tetraparesis secondary to bilateral precentral gyral cerebral ischemia: a case report}, series = {Journal of Medical Case Reports}, journal = {Journal of Medical Case Reports}, doi = {10.1186/1752-1947-7-61}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96179}, year = {2013}, abstract = {Introduction Sudden tetraparesis represents a neurological emergency and is most often caused by traumatic spinal cord injury, spinal epidural bleeding or brainstem ischemia and less frequently by medial disc herniation or spinal ischemia. Case presentation Here we report the rare case of an 82-year-old Caucasian man who developed severe tetraparesis four days after radical cystoprostatectomy. An emergency diagnostic study for spinal cord affection was normal. Brain magnetic resonance imaging revealed acute bilateral ischemic strokes in the precentral gyri as the underlying cause. Conclusions This case report underlines the need to also consider unusual causes of tetraparesis in an emergency situation apart from spinal cord or brain stem injury in order not to leave severe symptomatology unclear and possibly miss therapeutic options.}, language = {en} }