[Potential Impact of Public Communication on Emergency Presentations due to Headache during the Covid-19 Pandemic]. / Epidemiologische Untersuchung zu möglichen Auswirkungen öffentlicher Kommunikation im Rahmen der COVID-19-Pandemie auf Notfallvorstellungen von Kopfschmerzpatient*innen.

Headache is a frequent presenting symptom in the emergency department. While most cases are of benign aetiology, it is crucially important to identify potentially dangerous underlying disorders. We hypothesized an increase in headache-related emergency presentations after venous thrombosis of cerebral sinuses had been identified as a rare side effect of vaccination with adenovirus vector-based Coronavirus-disease 2019 (COVID-19) vaccines and that information had been publicly communicated by the Paul Ehrlich Institute. Data from patients with the diagnosis of primary headache disorders or unspecified headache presenting to the Interdisciplinary Emergency Department of the University Medicine Mannheim were retrospectively analysed. Based on vaccination dashboard data published by the Federal Ministry of Health, calendar weeks 14-30 and 47-48, on the one hand, and 1-13 and 31-46, on the othe, were categorized into a variable "vaccination epoch" (14-30, 47-48: high vaccination activity if≥3 million weekly vaccinations in Germany; 1-13, 31-46: low vaccination activity if<3 million weekly vaccinations). The number of patients with headache was the dependent variable. A Poisson regression was performed to analyze whether the frequency of events, i. e., patient presentations, was a function of year (2019, 2021), epoch (high, low) and an interaction of year and epoch - the latter reflecting an impact of vaccination activity during the pandemic and expressed as incidence rate ratio. Compared to 2019, there was a more than 70% increase in presentations due to headache during periods of high vaccination activity in 2021 (p<0.001; 95% confidence interval 1.272-2.316), in 25% of presentations in 2021, patients considered their headache as vaccination-associated. Public communication and resulting nocebo effects may, among other factors, have contributed to our observation of increased numbers of emergency headache presentations, illustrating the impact of public distribution of medical information on practical aspects of emergency care during crises.

Use of Prognostication Instruments in Prognostication Procedures of Postanoxic Coma Patients over Time: A Retrospective Study.

BACKGROUND: Many survivors of cardiovascular arrest remain in a postanoxic coma. The neurologist's task is to provide the most accurate assessment of the patient's neurologic prognosis through a multimodal approach of clinical and technical tests. The aim of this study is to analyze differences and developments in the concept of neurological prognosis assessment and in-hospital outcome of patients over a five year-period. METHODS: This retrospective observational study included 227 patients with postanoxic coma treated in the medical intensive care unit of the University Hospital, Mannheim from January 2016 to May 2021. We retrospectively analyzed patient characteristics, post-cardiac arrest care, and the use of clinical and technical tests for neurological prognosis assessment and patient outcome. RESULTS: Over the observation period, 215 patients received a completed neurological prognosis assessment. Regarding the multimodal prognostic assessment, patients with poor prognosis (54%) received significantly fewer diagnostic modalities than patients with very likely poor (20.5%), indeterminate (24.2%), or good prognosis (1.4%; p = 0.001). The update of the DGN guidelines in 2017 had no effect on the number of performed prognostic parameters per patient. The finding of bilaterally absent pupillary light reflexes or severe anoxic injury on CT contributed most to a poor prognosis category (OR 8.38, 95%CI 4.01-7.51 and 12.93, 95%CI 5.55-30.13, respectively), whereas a malignant EEG pattern and NSE > 90 µg/L at 72 h resulted in the lowest OR (5.11, 95%CI 2.32-11.25, and 5.89, 95%CI 3.14-11.06, respectively) for a poor prognosis category. Assessment of baseline NSE significantly increased over the years (OR 1.76, 95%CI 1.4-2.22, p < 0.001), and assessment of follow-up NSE at 72 h trended to increase (OR 1.19, 95%CI 0.99-1.43, p = 0.06). In-hospital mortality was high (82.8%), remained unchanged over the observation period, and corresponded to the number of patients in whom life-sustaining measures were discontinued. CONCLUSIONS: Among comatose survivors of cardiac arrest, the prognosis remains poor. Prognostication of a poor outcome led nearly exclusively to withdrawal of care. Prognostic modalities varied considerably with regard to their contribution to a poor prognosis category. Increasing enforcement of a standardized prognosis assessment and standardized evaluation of diagnostic modalities are needed to avoid false-positive prognostication of poor outcomes.

Clinical manifestations and immunomodulatory treatment experiences in psychiatric patients with suspected autoimmune encephalitis: a case series of 91 patients from Germany.

Autoimmune encephalitis (AE) can rarely manifest as a predominantly psychiatric syndrome without overt neurological symptoms. This study's aim was to characterize psychiatric patients with AE; therefore, anonymized data on patients with suspected AE with predominantly or isolated psychiatric syndromes were retrospectively collected. Patients with readily detectable neurological symptoms suggestive of AE (e.g., epileptic seizures) were excluded. Patients were classified as "probable psychiatric AE (pAE)," if well-characterized neuronal IgG autoantibodies were detected or "possible pAE" (e.g., with detection of nonclassical neuronal autoantibodies or compatible cerebrospinal fluid (CSF) changes). Of the 91 patients included, 21 (23%) fulfilled our criteria for probable (autoantibody-defined) pAE and 70 (77%) those for possible pAE. Among patients with probable pAE, 90% had anti-NMDA receptor (NMDA-R) autoantibodies. Overall, most patients suffered from paranoid-hallucinatory syndromes (53%). Patients with probable pAE suffered more often from disorientation (p < 0.001) and impaired memory (p = 0.001) than patients with possible pAE. Immunotherapies were performed in 69% of all cases, mostly with high-dose corticosteroids. Altogether, 93% of the patients with probable pAE and 80% of patients with possible pAE reportedly benefited from immunotherapies (p = 0.251). In summary, this explorative, cross-sectional evaluation confirms that autoantibody-associated AE syndromes can predominantly manifest as psychiatric syndromes, especially in anti-NMDA-R encephalitis. However, in three out of four patients, diagnosis of possible pAE was based on nonspecific findings (e.g., slight CSF pleocytosis), and well-characterized neuronal autoantibodies were absent. As such, the spectrum of psychiatric syndromes potentially responding to immunotherapies seems not to be limited to currently known autoantibody-associated AE. Further trials are needed.

Exploring joint patterns of brain structure and function in inflammatory bowel diseases using multimodal data fusion.

BACKGROUND: A growing number of neuroimaging studies suggest distinct neural changes in inflammatory bowel diseases (IBDs). Whether such changes may show similar spatial patterns across distinct neural features within and between specific IBD is unclear. To address this question, we used multivariate multimodal data fusion analysis to investigate structure/function modulation in remitted patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Patients with IBD (n = 46; n = 31 with CD, n = 15 with UC) in stable remission and 17 healthy controls (HC) underwent structural magnetic resonance imaging (sMRI) and resting-state functional magnetic resonance imaging (rs-fMRI) as well as cognitive testing. Anxiety, depression, and fatigue were assessed using self-rating questionnaires. sMRI data were analyzed via voxel-based morphometry (VBM) and rs-fMRI data via amplitude of low-frequency fluctuations (ALFFs) and regional homogeneity (ReHo). Detection of cross-information between VBM, ALFF, and ReHo was conducted by means of a joint independent component analysis (jICA), followed by group-inference statistics. KEY RESULTS: Joint independent component analysis detected structural alterations in middle frontal and temporal regions (VBM), and functional changes in the superior frontal gyrus (ReHo) and the medial as well as inferior frontal, inferior temporal, rectal, and subcallosal gyrus (ALFF). One joint component of extracted features of the three modalities differed significantly between IBD patients and controls (p = 0.03), and most distinctly between HC and patients with UC. CONCLUSIONS AND INFERENCES: Using a multivariate data fusion technique, this study provides further evidence to brain alterations in IBD. The data suggest distinct neural differences between CD and UC, particularly in frontotemporal regions.

Aberrant brain structural large-scale connectome in Crohn's disease.

BACKGROUND: Disturbed brain-gut interactions and a bidirectional relationship between inflammation and psychiatric symptoms such as anxiety and depression are being discussed in patients with inflammatory bowel diseases (IBD). Alterations of brain structure and function in IBD have been reported with heterogeneous results. Whether these changes reflect independent localized deficits or rather a systematic disruption in the anatomical organization of large-scale brain networks remains unclear. The present study investigated the gray matter structural connectome in patients with Crohn's disease (CD). METHODS: Sixty participants (30 with quiescent CD and 30 matched healthy controls [HC]) underwent high-resolution brain MRI at 3 Tesla. Well-established graph theoretical metrics were analyzed at the global and regional network level and compared between groups. KEY RESULTS: The networks in both groups followed a small-world organization, that is, an architecture that is simultaneously highly segregated and integrated. However, transitivity, a measure of global network segregation, was significantly reduced in patients (P = 0.003). Regionally, patients showed a reduction of nodal betweenness centrality in the right insula and cuneus and the left superior frontal cortex and reduced nodal degree within the left-hemispheric cingulate and the left lateral and right medial orbitofrontal cortex. CONCLUSION AND INFERENCES: These findings lend support to the hypothesis that CD is accompanied by alterations in both global network organization and regional connectivity. A deeper understanding of neural central networks in IBD may facilitate the development of complementary strategies in the treatment of "extraintestinal" comorbid conditions such as depression or anxiety.

Intrinsic neural network dysfunction in quiescent Crohn's Disease.

Psychological factors and comorbidities play an important role in inflammatory bowel diseases. Such comorbidity could be associated with a specific neural phenotype. Brain regions associated with emotion regulation and self-referential processing, including areas assigned to the "default mode network" (DMN), could be promising candidates in this regard. We investigated the functional integrity of multiple intrinsic neural networks in remitted patients with Crohn's disease (CD) and sought to establish relationships between neural network connectivity and psychiatric symptoms. Fifteen CD patients in remission and 14 controls were investigated. We employed resting-state functional magnetic resonance imaging (fMRI) at 3 Tesla followed by a spatial Independent Component Analysis for fMRI data. Abnormal connectivity in CD patients was observed in DMN subsystems only (p < 0.05, cluster-corrected). Increased connectivity was found in the anterior cingulate and left superior medial frontal gyrus (aDMN) and the middle cingulate cortex (pDMN). Middle cingulate activity showed a significant association with anxiety scores in patients (p = 0.029). This study provides first evidence of selectively disrupted intrinsic neural network connectivity in CD and suggests abnormalities of self-referential neural networks. An increased sensitivity to self-related affective and somatic states in CD patients could account for these findings and explain a higher risk for anxiety symptoms.

Chorea in a patient with cryopyrin-associated periodic syndrome.

OBJECTIVE: To describe a patient with cryopyrin-associated periodic syndrome (CAPS) with an uncommon neurologic phenotype and a rare underlying genetic mutation. RESULTS: Our patient had CAPS with a rare NLPR3 missense mutation (p.Tyr859Cys) in exon 6 with chorea as the major symptom. Clinical symptoms were associated with persistent inflammatory changes of the CSF and serum and included elevated anticardiolipin immunoglobulin G; MRI showed prolonged gadolinium enhancement of 2 chronic inflammatory lesions. Conventional immunosuppressive treatment with prednisolone and hydroxychloroquine was insufficient. Neurologic symptoms, laboratory/chemical measures, and MRI abnormalities almost completely normalized following interleukin (IL)-1ß blockade with anakinra. CONCLUSIONS: This case is unique for its uncommon neurologic phenotype, the rare underlying genetic mutation, and the long course of the disease as well as almost complete recovery following appropriate therapy. In addition, the chronic inflammatory white matter lesions observed on brain MRI and the responsiveness to IL-1ß blockade with anakinra are unusual.

DWI Lesion Patterns in Cancer-Related Stroke--Specifying the Phenotype.

BACKGROUND: Due to the lack of specific diagnostic markers, the diagnosis of cancer-related stroke strongly depends on its phenotype. Distinct DWI lesion patterns with involvement of multiple vascular territories have been reported repeatedly in cancer-related stroke but have not been addressed in detail in a selected cohort of prospectively recruited cancer patients with emphasis on hypercoagulable conditions. PATIENTS AND METHODS: Ischemic stroke patients with known malignant cancer activity, laboratory evidence of strong plasmatic hypercoagulation (D-dimer levels > 3 µg/ml) and without competing stroke etiologies according to the recently introduced ASCOD (A - atherosclerosis, S - small vessel disease, C - cardiac pathology, O - other cause, and D - dissection) classification of evidence-rated etiology of stroke subtypes were included in the analysis. Cerebral MRI on admission was reviewed with respect to ischemic lesion patterns. RESULTS: Thirty-two patients met the inclusion criteria. The mean D-dimer levels were 15.39 µg/ml (± 10.84). Acute infarction in ≥ 2 vascular territories was present in 27/32 (84%) patients. (Micro-) embolic scattering of infarction was present in 25/32 (78%) patients. Evidence for previous, potentially oligosymptomatic infarction was found in 16 (50%) patients, demonstrated by the additional presence of subacute or chronic ischemic lesions. CONCLUSION: When excluding competing embolic and nonembolic stroke etiologies, the pattern of scattered DWI lesions in multiple vascular supply territories strongly dominates the phenotype of cancer-related stroke. Additionally, evidence of recurrent infarction is frequent in this cohort of patients. This is not only important for the diagnosis of cancer-related stroke itself but may prove helpful for the identification of cancer-related stroke patients with unknown malignancy at the time of stroke manifestation and evaluation of strategies for secondary prevention.

MRI Characteristics of the Evolution of Supratentorial Recent Small Subcortical Infarcts.

OBJECTIVE: Morphological changes of recent small subcortical infarcts are not well defined. The purpose of the present study was to describe the MRI characteristics of the evolution for this stroke subtype. METHODS: We conducted a retrospective review of patients diagnosed with definite supratentorial recent small subcortical infarcts according to the ASCO classification with baseline and follow-up MRI (≥90 days of stroke onset). We investigated the incidence of cavity formation, the infarct volume change, and the positional relationship between infarct lesions and preexisting white matter hyperintensities (WMHs) of presumed vascular origin. RESULTS: We identified 62 patients with a median age of 71 years (range: 30-87). Median follow-up period was 26 months (range: 3-99). Cavity formation was observed in 38 infarct lesions (61%). Eighteen lesions (29%) were partially adjacent to WMHs and 7 (11%) were fused into WMHs. In a multiple logistic regression analysis, age [odds ratio per 5-year increase: 1.34; 95% confidence interval (CI): 1.03-1.80; p = 0.03] and baseline infarct volume (odds ratio per 1-ml increase: 4.7; 95% CI: 1.6-19.7; p = 0.003) were independent predictors of cavity formation. There was a significant volume reduction between baseline and follow-up infarct lesions (median volume reduction rate: 44%). CONCLUSION: More than one-third of recent small subcortical infarcts do not lead to cavity formation and 40% of infarct lesions overlap with WMHs. Our data indicate the continuity between recent small subcortical infarcts and WMHs.

Presumptive progressive multifocal leukoencephalopathy in multiple sclerosis after natalizumab therapy.

BACKGROUND AND PURPOSE: To describe a patient with relapsing remitting MS who was treated with natalizumab for 36 months. First symptoms of presumptive progressive multifocal leukoencephalopathy (PML) appeared 14 weeks after her last natalizumab infusion. METHODS: Neurological examination, MRI and CSF analysis were performed. RESULTS: The lack of anti-inflammatory treatment response, clinical course, and serial MRI examinations showed lesion development typical for PML on diffusion-weighted and FLAIR MRI. CSF analysis for JC virus was tested negative twice. CONCLUSIONS: This case represents a presumptive PML after discontinuation of natalizumab treatment-similar to the definition established for PML in HIV patients.

Non-pharmacological strategies for the treatment of acute ischaemic stroke.

Early recanalisation and an increase in collateral blood supply are predictors of favourable outcome in acute ischaemic stroke. Since individual responses to intravenous treatment with alteplase are heterogeneous, additional intra-arterial thrombolytic and mechanical endovascular treatment is increasingly given. Despite encouraging findings from single-centre studies, data from randomised clinical trials have not proven the hypothesis that interventional recanalisation leads to a better outcome. Advanced thrombectomy devices, the effect of ultrasound-enhanced thrombolysis, and imaging-guided selection of patients outside the currently approved time-window are all under investigation. Although neuroprotective agents have not shown benefit in clinical trials, non-pharmacological treatment strategies-such as decompressive surgery, therapeutic hypothermia, transcranial laser treatment, or augmentation of cerebral collateral perfusion by different means (eg, partial aortic occlusion or sphenopalatine ganglion stimulation)-are topics of current research. The future of acute stroke therapy relies on evidence for individually tailored, effective, safe, and rapidly accessible treatment probably consisting of combined pharmacological and improved non-pharmacological approaches.

Gender differences in acute ischemic stroke: etiology, stroke patterns and response to thrombolysis.

BACKGROUND AND PURPOSE: Differences between women and men in relation to stroke are increasingly being recognized. METHODS: From July 2004 until June 2007, 237 acute ischemic stroke (AIS) patients were treated with recombinant tissue plasminogen activator (rtPA) within 3 hours after onset of symptoms in our stroke unit. Baseline characteristics, etiology, CT/MRI stroke patterns, clinical outcome, and complications of women were compared to those of men. RESULTS: Of 237 AIS patients (mean age 70.7 years), 111 (46.8%) were women and 126 (53.2%) were men. Women were older (P=0.001), but history of hyperlipidemia (P=0.03), smoking (P=0.03), and coronary heart disease (P<0.001) was less frequent than in men. Internal carotid artery disease occurred more often in men (P=0.02), whereas atrial fibrillation was observed more often in women (P=0.002). In men borderzone/small embolic and lacunar stroke was found more frequently (39.7 versus 27.2%), whereas women showed a higher percentage of large territorial stroke (72.8 versus 60.3%, P=0.09). Baseline National Institute of Health Stroke Scale scores (12.5 versus 11.3), NIHSS score at discharge (11.0 versus 9.5), 3-month-outcome modified Rankin Scale score, thrombolysis-related (17.1% versus 13.5%) or independent complications (32.4% versus 30.2%), and mortality after 3 months (13.5% versus 9.5%) were similar. CONCLUSIONS: Differences of stroke lesion patterns in genders are paralleled by differences in etiology and risk factor profiles (women, cardioembolism; men, large and small vessel disease). Baseline characteristics, rates of rtPA-related and independent complications, as well as clinical outcomes were not different between women and men with AIS.

Modulation of monocyte matrix metalloproteinase-2 by breast adenocarcinoma cells.

INTRODUCTION: The presence of monocyte and macrophage cells in growing breast tumors, and the positive relationship between the degree of immune cell infiltration and tumor growth, suggest a possible paracrine growth regulatory function of immune cells in breast cancer. METHOD: To better understand the interaction between monocytes and breast cancer cells, in vitro matrix metalloproteinase and tissue inhibitor of metalloproteinase activity was assessed from the THP-1 myeloid cell line in response to conditioned media from two breast cancer cell lines, MCF-7 and MDA-MB-231. RESULTS: Enzymography and immunoblotting revealed increased MMP-2 as well as increased levels of TIMP-1 and TIMP-2. Furthermore, a significant increase in the invasive potential of MCF-7 and MDA-MB-231 cells was noted in response to THP-1 cell-conditioned media. CONCLUSION: These data demonstrate that monocyte cells in the breast tumor microenvironment play an important role in the modulation of MMPs, which may have a significant effect on the control of tumor growth and metastatic spread.