Publications by authors named "Jan Claudius Schwitalla"

16 Publications

  • Page 1 of 1

Capillary microscopy in Europeans with idiopathic Moyamoya angiopathy.

Microcirculation 2020 07 16;27(5):e12616. Epub 2020 Mar 16.

Department of Neurology, Alfried Krupp Hospital, Essen, Germany.

Objective: In Europe, MMA is a very rare non-inflammatory vasculopathy. MMA is an important differential diagnosis of cerebral vasculitis. Systemic manifestations, such as livedo racemosa or renal artery stenosis, associated with Moyamoya variants suggest the involvement also of non-cerebral vessels. Hypothetically, capillary microscopy could be a promising non-invasive screening method to visualize microcirculation, for example prior to cerebral angiography.

Methods: Standardized capillary microscopic images were taken in European patients with MMA and subsequently evaluated in a blinded analysis, using data obtained from a large NP cohort and a large SLE cohort by the same blinded Investigator as controls.

Results: Twenty-four European MMD patients and 14 healthy accompanying controls were included in this study. The results were compared to 116 SLE patients and 754 NP subjects. In MMD patients, no capillary morphological differences were found in comparison with NP, in particular no density reduction or increased neoangiogenesis. The pattern observed in the SLE cohort was clearly distinct from NP and MMD with regard to vascular density, vascular damage, and neoangiogenesis.

Conclusions: MMD is not associated with microvascular changes of the nailfold capillaries. In this respect, it is clearly distinct from SLE.
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http://dx.doi.org/10.1111/micc.12616DOI Listing
July 2020

Reelin signaling modulates GABA receptor function in the neocortex.

J Neurochem 2021 Mar 13;156(5):589-603. Epub 2020 Mar 13.

Department of Neuroanatomy and Molecular Brain Research, Ruhr University Bochum, Medical Faculty, Bochum, Germany.

Reelin is a protein that is best known for its role in controlling neuronal layer formation in the developing cortex. Here, we studied its role for post-natal cortical network function, which is poorly explored. To preclude early cortical migration defects caused by Reelin deficiency, we used a conditional Reelin knock-out (Reln ) mouse, and induced Reelin deficiency post-natally. Induced Reelin deficiency caused hyperexcitability of the neocortical network in vitro and ex vivo. Blocking Reelin binding to its receptors ApoER2 and VLDLR resulted in a similar effect. Hyperexcitability in Reln organotypic slice cultures could be rescued by co-culture with wild-type organotypic slice cultures. Moreover, the GABA receptor (GABA R) agonist baclofen failed to activate and the antagonist CGP35348 failed to block GABA Rs in Reln mice. Immunolabeling of Reln cortical slices revealed a reduction in GABA R1 and GABA R2 surface expression at the plasma membrane and western blot of Reln cortical tissue revealed decreased phosphorylation of the GABA R2 subunit at serine 892 and increased phosphorylation at serine 783, reflecting receptor deactivation and proteolysis. These data show a role of Reelin in controlling early network activity, by modulating GABA R function. Cover Image for this issue: https://doi.org/10.1111/jnc.15054.
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http://dx.doi.org/10.1111/jnc.14990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442713PMC
March 2021

Lamprey Parapinopsin ("UVLamP"): a Bistable UV-Sensitive Optogenetic Switch for Ultrafast Control of GPCR Pathways.

Chembiochem 2020 03 30;21(5):612-617. Epub 2019 Oct 30.

Department of General Zoology and Neurobiology, Ruhr University Bochum, ND7/31, Universitätsstasse 150, 44780, Bochum, Germany.

Optogenetics uses light-sensitive proteins, so-called optogenetic tools, for highly precise spatiotemporal control of cellular states and signals. The major limitations of such tools include the overlap of excitation spectra, phototoxicity, and lack of sensitivity. The protein characterized in this study, the Japanese lamprey parapinopsin, which we named UVLamP, is a promising optogenetic tool to overcome these limitations. Using a hybrid strategy combining molecular, cellular, electrophysiological, and computational methods we elucidated a structural model of the dark state and probed the optogenetic potential of UVLamP. Interestingly, it is the first described bistable vertebrate opsin that has a charged amino acid interacting with the Schiff base in the dark state, that has no relevance for its photoreaction. UVLamP is a bistable UV-sensitive opsin that allows for precise and sustained optogenetic control of G protein-coupled receptor (GPCR) pathways and can be switched on, but more importantly also off within milliseconds via lowintensity short light pulses. UVLamP exhibits an extremely narrow excitation spectrum in the UV range allowing for sustained activation of the G pathway with a millisecond UV light pulse. Its sustained pathway activation can be switched off, surprisingly also with a millisecond blue light pulse, minimizing phototoxicity. Thus, UVLamP serves as a minimally invasive, narrow-bandwidth probe for controlling the G pathway, allowing for combinatorial use with multiple optogenetic tools or sensors. Because UVLamP activated G signals are generally inhibitory and decrease cellular activity, it has tremendous potential for health-related applications such as relieving pain, blocking seizures, and delaying neurodegeneration.
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http://dx.doi.org/10.1002/cbic.201900485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079062PMC
March 2020

Moyamoya angiopathy in PHACE syndrome not associated with RNF213 variants.

Childs Nerv Syst 2019 07 29;35(7):1231-1237. Epub 2019 Apr 29.

Department of Neurology, Alfried Krupp von Bohlen und Halbach Hospital, Alfried-Krupp-Str. 21, 45117, Essen, Germany.

Moyamoya angiopathy is a rare vasculopathy with stenosis and/or occlusion of bilateral intracranial parts of internal carotid arteries and/or proximal parts of middle and anterior cerebral arteries. PHACE syndrome is characterized by large segmental hemangiomas in the cervical-facial region. Both conditions are known to be associated in rare cases. Recently, it was discussed in the literature that RNF213 variants could be etiologically involved in this association. Here, we describe a childhood case with this rare co-occurrence in which we did not identify any rare RNF213 variant. The clinical and genetic backgrounds are discussed.
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http://dx.doi.org/10.1007/s00381-019-04145-9DOI Listing
July 2019

Clinical and Molecular Features of 5 European Multigenerational Families With Moyamoya Angiopathy.

Stroke 2019 04;50(4):789-796

Department of Neurology, Alfried Krupp Hospital Essen, Germany (J.C.S., M.K.).

Background and Purpose Moyamoya angiopathy (MMA) is a rare cerebral vasculopathy outside of Asia. In Japanese patients, a vast majority of patients carry the founder p.R4810K variant in the RNF213 gene, and familial cases are around 10%. In European patients, data about familial occurrence are limited. The aim of this study was to characterize the clinical and molecular features of several European families with a parent-to-child transmission of MMA. Methods Out of 126 MMA probands referred, we identified 113 sporadic probands and 13 familial probands. Segregation analysis showed a vertical parent-to-child pattern of inheritance in the families of 5 of these probands. All 5 families were of German or Dutch ancestry. We investigated the clinical features of affected members and used whole-exome sequencing to screen RNF213 and 13 genes involved in Mendelian MMA and to identify genes recurrently mutated in these families. Results Twelve affected MMA patients were identified, including 9 females and 3 males. Age at clinical onset ranged from 11 to 65 years. In 3 of 5 families, associated livedo racemosa was found. We did not detect any deleterious variants in the 13 known MMA genes. RNF213 rare missense variants predicted to be pathogenic were detected in all affected members of 2 of these families, as well as 2 candidate variants of the PALD1 gene. Conclusions Nonsyndromic MMA was identified in 5 European families, including 2 to 3 clinically affected cases segregating with a parent-to-child pattern of inheritance in each family. Molecular screening detected rare deleterious variants within RNF213 and PALD1 in all affected members of 2 of these 5 families, as well as in some clinically unaffected members. Altogether these data raise the difficult and, to date unanswered, question of the medical indication of presymptomatic screening.
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http://dx.doi.org/10.1161/STROKEAHA.118.023972DOI Listing
April 2019

Clinical presentation of Moyamoya angiopathy in Europeans: experiences from Germany with 200 patients.

J Neurol 2019 Jun 13;266(6):1421-1428. Epub 2019 Mar 13.

Department of Neurology, Alfried Krupp Hospital, Alfried-Krupp-Strasse 21, 45130, Essen, Germany.

Introduction: Moyamoya angiopathy (MMA) is a rare vasopathy, especially among European Caucasians. Data about demographics, clinical presentation, comorbid conditions, radiological findings as well as laboratory and cerebral spinal fluid (CSF) data are sparse.

Methods: Patients with MMA treated in the Alfried Krupp Hospital, Essen, Germany, between 2010 and 2017 with focus on demographic, clinical, radiological and laboratory as well as CSF data were evaluated retrospectively. Patients with non-Caucasian family background were excluded from this study.

Results: Altogether 200 European Caucasian patients with MMA were identified. There was a female predominance of 3.2:1. The mean age at first presentation was 32.9 years and the mean age of diagnosis was 36.0 years. Eleven of 194 index patients (5.7%) showed a familial presentation. In 11.6% posterior cerebral artery was additionally involved, in 4% additionally cerebral aneurysm and in 2.5% dysgenesis of corpus callosum was found. Most patients suffered from transient ischemic attacks (71.5%) and stroke (82%). Cerebral hemorrhage was found in 9.5%. Livedo racemosa was an associated symptom in 12.8% of patients and thyroid diseases were found in 23.8%.

Conclusions: Compared with Asian data, cerebral hemorrhages are infrequent and female predominance is accentuated among European Caucasians. Some former unknown rare features like associated livedo racemosa, dysgenesis of corpus callosum and associated syncope have been discovered systematically for the first time in this huge European Caucasian cohort.
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http://dx.doi.org/10.1007/s00415-019-09277-1DOI Listing
June 2019

Misdiagnoses and delay of diagnoses in Moyamoya angiopathy-a large Caucasian case series.

J Neurol 2019 May 25;266(5):1153-1159. Epub 2019 Feb 25.

Department of Neurology, University Hospital, Medical Faculty Heinrich-Heine-University, Düsseldorf, Germany.

Background: The lacking awareness of healthcare providers bears the risk of delayed or false diagnoses in rare diseases. No systematic data about misdiagnoses of Moyamoya angiopathy (MMA) are available.

Objective: To evaluate the rate and pattern of missed diagnoses in MMA.

Methods: Retrospective analysis of a consecutive case series from a single German referral center. Rates of missed or delayed diagnoses in Caucasian MMA patients were calculated based on discharge letters from other hospitals and systematic chart review.

Results: Out of 192 Caucasian patients eventually diagnosed with MMA at our center, an initial misdiagnosis was identified in 119 patients (62%). The time between onset and diagnosis was 1 year in 24 patients, 2 years in 23 patients, 3 years in 10 patients, and > 3 years in 49 patients (mean 5.28, median 3, standard deviation 5.11, and range 4-26 years). The most common misdiagnoses were cerebral vasculitis (31%), etiologically ill-defined stroke diagnoses (30.2%), and MS (3.6%).

Conclusions: This is the first systematic report which shows that patients with MMA are at high risk to be falsely diagnosed and treated. Depiction of typical vascular abnormalities in angiopathy is essential. Normal CSF cell counts, negative oligoclonal bands, and lack of infratentorial lesions as well as gadolinium-positive T1 lesions on MRI may be red flags differentiating this vasculopathy from vasculitis and MS.
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http://dx.doi.org/10.1007/s00415-019-09245-9DOI Listing
May 2019

Moyamoya angiopathy: early postoperative course within 3 months after STA-MCA-bypass surgery in Europe-a retrospective analysis of 64 procedures.

J Neurol 2018 Oct 17;265(10):2370-2378. Epub 2018 Aug 17.

Department of Neurosurgery, Alfried Krupp Hospital, Alfried-Krupp-Strasse 21, 45130, Essen, Germany.

Background: Despite the consensus on the necessity of revascularizing surgery in Moyamoya angiopathy in Asia, the indication in Caucasian Moyamoya patients is discussed controversially.

Objective: The safety of revascularizing surgery in Europe should be clarified.

Methods: This study retrospectively analyzed the rate of complications as well as clinical symptoms within the first 3 months after bypass surgery between superficial temporal artery and middle cerebral artery (STA-MCA).

Results: 64 direct bypass procedures in 45 patients (95.5% Caucasians) were analyzed. The magnetic resonance imaging at day 6 showed subdural hematoma in 60.3%. The mean diameter of these hematomas on magnetic resonance imaging was 5.1 mm (SD 3.4 mm) and increased in 25% at follow-up. No difference was found between those patients with early (day 1) or late (day 7) restarts of antiplatelet therapy. Magnetic resonance imaging at day 6 revealed hyperperfusion syndrome after six of 64 procedures (9.3%). Three of these six had clinical symptoms; two-thirds were transient within seconds. Magnetic resonance imaging depicted stroke after seven procedures (10.9%). Five of these seven patients had no new symptoms. Altogether, after ten procedures (15%), patients complained about clinical symptoms. These were all transient. No new transient ischemic attacks occurred during the 3 month follow-up and no new lesions were detected in magnetic resonance imaging. Only two patients underwent surgery for asymptomatic subdural hematoma. All other subdural hematomas resolved spontaneously.

Conclusion: Revasculating surgery is a safe procedure in Caucasian patients with Moyamoya angiopathy. The observed complications have a good prognosis.
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http://dx.doi.org/10.1007/s00415-018-8997-2DOI Listing
October 2018

Whole exome sequencing identifies MRVI1 as a susceptibility gene for moyamoya syndrome in neurofibromatosis type 1.

PLoS One 2018 12;13(7):e0200446. Epub 2018 Jul 12.

Dipartimento di Medicina di Precisione, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.

Background And Purpose: Moyamoya angiopathy is a progressive cerebral vasculopathy. The p.R4810K substitution in RNF213 has previously been linked to moyamoya disease in Asian populations. When associated with other medical conditions, such as neurofibromatosis type 1, this vasculopathy is frequently reported as moyamoya syndrome. Intriguingly, most cases of moyamoya-complicated neurofibromatosis type 1 have been described in Caucasians, inverting the population ratio observed in Asians, although prevalence of neurofibromatosis type 1 is constant worldwide. Our aim was to investigate whether, among Caucasians, additive genetic factors may contribute to the occurrence of moyamoya in neurofibromatosis type 1.

Methods: Whole exome sequencing was carried out on an Italian family with moyamoya-complicated neurofibromatosis type 1 to identify putative genetic modifiers independent of the NF1 locus and potentially involved in moyamoya pathogenesis. Results were validated in an unrelated family of German ancestry.

Results: We identified the p.P186S substitution (rs35857561) in MRVI1 that segregated with moyamoya syndrome in both the Italian and German family.

Conclusions: The rs35857561 polymorphism in MRVI1 may be a genetic susceptibility factor for moyamoya in European patients with neurofibromatosis type 1. MRVI1 is a functional partner of ITPR1, PRKG1 and GUCY1A3, which are involved in response to nitric oxide. Mutations in GUCY1A3 have been recently linked to a recessive syndromic form of moyamoya with esophageal achalasia.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0200446PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042724PMC
January 2019

Association of primary central nervous system vasculitis with the presence of specific human leucocyte antigen gene variant.

Clin Neurol Neurosurg 2017 Sep 23;160:137-141. Epub 2017 Jun 23.

Department of Neurology, Alfried-Krupp-von Bohlen und Halbach Hospital, Alfried-Krupp-Straße 21, 45130 Essen, Germany.

Objectives: The etiology and genetic susceptibility of primary central nervous system vasculitis (PCNSV) are still unclear.

Patients And Methods: We analyzed the DNA of 25 Caucasian patients with PCNSV for human leucocyte antigen genes HLA-A, HLA-B, HLA-DRB1, and HLA-DQB1, respectively. HLA-frequencies of the 25 patients with PCNSV were compared with HLA-frequencies of matched Caucasian controls.

Results: No statistically significant associations were found for HLA-B, HLA-DR1 and HLA-DQB1 variant. In the PCNSV group, only the HLA-A*69 variant was found more often than expected statistically.

Conclusion: The results of this study indicate a potential association of HLA marker with PCNSV in Caucasian patients. Further studies are needed to elucidate the role of genes within the human major histocompatibility complex in the pathogenesis of this angiopathy.
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http://dx.doi.org/10.1016/j.clineuro.2017.06.009DOI Listing
September 2017

Rare RNF213 variants in the C-terminal region encompassing the RING-finger domain are associated with moyamoya angiopathy in Caucasians.

Eur J Hum Genet 2017 08 21;25(8):995-1003. Epub 2017 Jun 21.

Inserm UMR-S1161, Génétique et Physiopathologie des Maladies Cérébro-vasculaires, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.

Moyamoya angiopathy (MMA) is a cerebral angiopathy affecting the terminal part of internal carotid arteries. Its prevalence is 10 times higher in Japan and Korea than in Europe. In East Asian countries, moyamoya is strongly associated to the R4810K variant in the RNF213 gene that encodes for a protein containing a RING-finger and two AAA+ domains. This variant has never been detected in Caucasian MMA patients, but several rare RNF213 variants have been reported in Caucasian cases. Using a collapsing test based on exome data from 68 European MMA probands and 573 ethnically matched controls, we showed a significant association between rare missense RNF213 variants and MMA in European patients (odds ratio (OR)=2.24, 95% confidence interval (CI)=(1.19-4.11), P=0.01). Variants specific to cases had higher pathogenicity predictive scores (median of 24.2 in cases versus 9.4 in controls, P=0.029) and preferentially clustered in a C-terminal hotspot encompassing the RING-finger domain of RNF213 (P<10). This association was even stronger when restricting the analysis to childhood-onset and familial cases (OR=4.54, 95% CI=(1.80-11.34), P=1.1 × 10). All clinically affected relatives who were genotyped were carriers. However, the need for additional factors to develop MMA is strongly suggested by the fact that only 25% of mutation carrier relatives were clinically affected.
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http://dx.doi.org/10.1038/ejhg.2017.92DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567158PMC
August 2017

Movement symptoms in European Moyamoya angiopathy - First systematic questionnaire study.

Clin Neurol Neurosurg 2017 Jan 23;152:52-56. Epub 2016 Nov 23.

Department of Neurology, Alfried-Krupp-von Bohlen und Halbach Hospital, Alfried-Krupp-Straße 21, 45130 Essen, Germany.

Objective: Movement disorders are a rare manifestation of Moyamoya angiopathy (MMA). Data on prevalence and clinical presentation are warranted. Possible involuntary movements include focal motor seizures, tremor, limb-shaking transient ischemic attacks, choreiform and spastic or dystonic movement disorders.

Patients And Methods: We developed a questionnaire to systematically assess movement disorders in MMA. Patients' history of involuntary movements and their clinical presentation were assessed systematically by interview. Additionally, demographic data were assessed as well as localization of movements, possible trigger factors and the presence of other symptoms.

Results: The questionnaire was administered to 63 European patients with MMA. The response rate was high with 93.6% participating patients. Twenty-eight patients (47.4%) reported involuntary movement disorders including periodic tremor, irregular jerks, involuntary movements with loopy or pranced character, stiffness and muscle cramps. From those patients, 16 (57.1%) individuals had the symptoms prior to the diagnosis of MMA. The most common involuntary movements were irregular jerks witnessed by 17 (60.7%) patients, followed by stiffness and muscle cramps in 10 (35.7%). Eight (28.6%) Patients suffered from unintended loopy and pranced character, while 4 individuals (14.3%) remembered periodic tremor. Of the 28 patients who witnessed movement disorders, 23 had undergone revascularization surgery (82.1%). From the latter subgroup, movement disorders were reversed in 7 out of 12 patients (58.3%) with irregular jerks and 4 out of 7 patients (57.1%) with unintended loopy and pranced character.

Conclusions: Our study elucidates the high incidence of movement disorders in an unselected consecutively recruited cohort of European MMA patients.
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http://dx.doi.org/10.1016/j.clineuro.2016.11.017DOI Listing
January 2017

Keeping Our Calcium in Balance to Maintain Our Balance.

Biochem Biophys Res Commun 2017 02 5;483(4):1040-1050. Epub 2016 Jul 5.

Department of Zoology and Neurobiology, ND7/31, Ruhr University Bochum, Universitätsstr. 150, D-44780 Bochum, Germany.

Calcium is a key signaling molecule and ion involved in a variety of diverse processes in our central nervous system (CNS) which include gene expression, synaptic transmission and plasticity, neuronal excitability and cell maintenance. Proper control of calcium signaling is not only vital for neuronal physiology but also cell survival. Mutations in fundamental channels, transporters and second messenger proteins involved in orchestrating the balance of our calcium homeostasis can lead to severe neurodegenerative disorders, such as Spinocerebellar (SCA) and Episodic (EA) ataxias. Hereditary ataxias make up a remarkably diverse group of neurological disorders clinically characterized by gait ataxia, nystagmus, dysarthria, trunk and limb ataxia and often atrophy of the cerebellum. The largest family of hereditary ataxias is SCAs which consists of a growing family of 42 members. A relatively smaller family of 8 members compose the EAs. The gene mutations responsible for half of the EA members and over 35 of the SCA subtypes have been identified, and several have been found to be responsible for cerebellar atrophy, abnormal intracellular calcium levels, dysregulation of Purkinje cell pacemaking, altered cerebellar synaptic transmission and/or ataxia in mouse models. Although the genetic diversity and affected cellular pathways of hereditary ataxias are broad, one common theme amongst these genes is their effects on maintaining calcium balance in primarily the cerebellum. There is emerging evidence that the pathogenesis of hereditary ataxias may be caused by imbalances in intracellular calcium due to genetic mutations in calcium-mediating proteins. In this review we will discuss the current evidence supporting the role of deranged calcium as the culprit to neurodegenerative diseases with a primary focus on SCAs and EAs.
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http://dx.doi.org/10.1016/j.bbrc.2016.07.020DOI Listing
February 2017

Transient inhibition of protein synthesis in the rat insular cortex delays extinction of conditioned taste aversion with cyclosporine A.

Neurobiol Learn Mem 2016 09 14;133:129-135. Epub 2016 Jun 14.

Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany.

Conditioned responses gradually weaken and eventually disappear when subjects are repeatedly exposed to the conditioned stimulus (CS) in the absence of the unconditioned stimulus (US), a process called extinction. Studies have demonstrated that extinction of conditioned taste aversion (CTA) can be prevented by interfering with protein synthesis in the insular cortex (IC). However, it remained unknown whether it is possible to pharmacologically stabilize the taste aversive memory trace over longer periods of time. Thus, the present study aimed at investigating the time frame during which extinction of CTA can be efficiently prevented by blocking protein synthesis in the IC. Employing an established conditioning paradigm in rats with saccharin as CS, and the immunosuppressant cyclosporine A (CsA) as US, we show here that daily bilateral intra-insular injections of the protein synthesis inhibitor anisomycin (120μg/μl) immediately after retrieval significantly diminished CTA extinction over a period of five retrieval days and subsequently reached levels of saline-infused controls. These findings demonstrate that it is possible to efficiently delay but not to fully prevent CTA extinction during repeated retrieval trials by blocking protein translation with daily bilateral infusions of anisomycin in the IC. These data confirm and extent earlier reports indicating that the role of protein synthesis in CTA extinction learning is not limited to gastrointestinal malaise-inducing drugs such as lithium chloride (LiCl).
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http://dx.doi.org/10.1016/j.nlm.2016.06.008DOI Listing
September 2016

Headache in Caucasian patients with Moyamoya angiopathy - a systematic cohort study.

Cephalalgia 2017 Apr 25;37(5):496-500. Epub 2016 Apr 25.

3 Department of Neurology and Headache Center, University Hospital Essen, University of Duisburg-Essen, Germany.

Background Headache is common in patients with Moyanoya angiopathy (MMA), but usually underestimated in its management and not well characterized. Methods A validated self-administered headache screening questionnaire and a telephone interview were used in order to investigate headache characteristics, frequency and pain intensity in a large cohort of 55 German patients with MMA. Results Thirty-seven patients (67.3%) had suffered from headache in the past year. Headache intensity was rated 3.2 ± 1.3 on a verbal rating scale from 0 to 10. Seventeen patients (47.9%) reported migraine-like headache, 10 patients (27.0%) reported tension type-like headache and 10 patients (27.0%) had a combination of both. The majority of patients with migraine-like headache ( n = 10, 58.8%) described migrainous aura. Headache frequency and intensity improved significantly after revascularization surgery; however, nine patients developed new-onset headache postoperatively. Conclusion Headache is very common in MMA, often with a migraine-like phenotype. Tension type-like headache was also found in 27% of patients, which is a new finding that has not been reported before.
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http://dx.doi.org/10.1177/0333102416643516DOI Listing
April 2017

Pre-exposure to the unconditioned or conditioned stimulus does not affect learned immunosuppression in rats.

Brain Behav Immun 2016 Jan 10;51:252-257. Epub 2015 Sep 10.

Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. Electronic address:

In order to analyze the effects of pre-exposure to either the unconditioned (US) or conditioned stimulus (CS) on learned immunosuppression, we employed an established conditioned taste aversion (CTA) paradigm in rats. In our model, a sweet-tasting drinking solution (saccharin) serves as CS and injection of the immunosuppressive drug cyclosporine A (CsA) is used as US. The conditioned response is reflected by a pronounced CTA and diminished cytokine production by anti-CD3 stimulated splenic T cells. In the present study, experimental animals were exposed either to the US or the CS three times prior to the acquisition phase. On the behavioral level, we found a significantly diminished CTA when animals were pre-exposed to the US or the CS before acquisition. In contrast, US or CS pre-exposure did not affect the behaviorally conditioned suppression of interleukin (IL)-2 production. From the clinical perspective, our data may suggest that conditioning paradigms could be systemically integrated as supportive therapeutic interventions in patients that are already on immunosuppressive therapy or have had previous contact to the gustatory stimulus. Such supportive therapies to pharmacological regimens could not only help to reduce the amount of medication needed and, thus, unwanted toxic side effects, but may also maximize the therapeutic outcome.
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http://dx.doi.org/10.1016/j.bbi.2015.09.005DOI Listing
January 2016