CXCL13 as a biomarker in the diagnostics of European lyme Neuroborreliosis - A prospective multicentre study in Austria.

Background: 'Definite Neuroborreliosis (NB)' is diagnosed with the presence of NB-specific symptoms, cerebrospinal fluid (CSF) pleocytosis and an elevated Borrelia Burgdorferi antibody index. However, some diagnostic uncertainties exist. The B-cell chemokine CXCL13 represents an emerging biomarker for the diagnosis and treatment of NB because its intrathecal concentration rises prior to the Borrelia antibody index and drops rapidly after antibiotic therapy. Nevertheless, due to lacking prospective data, a definite CXCL13 cut-off for the diagnosis of NB is still pending. Objective: Definition of a CSF CXCL13 cut-off for the diagnosis of acute and untreated NB in a prospective study setting. Design and methods: This multicentre prospective study involved 6 neurological departments treating patients in the Lower Austria district (1.7 million inhabitants). The controls were patients scheduled for a spinal tap but not clinically diagnosed with NB. Demographic data, clinical characteristics and blood counts, as well as inflammatory CSF values and CSF CXCL13-concentration were analysed. Results: We recruited 440 adult patients, of whom 42 have been diagnosed as having an acute and untreated 'definite NB'. Three hundred ninety-eight patients were assigned to the control group. The median intrathecal CXCL13 concentration was 2384 pg/ml for patients with NB and 0 pg/ml for controls. The difference was highly statistically significant (P ≤ .001). A CSF CXCL13 cut-off of 271 pg/ml resulted in a sensitivity of 95.2% and a specificity of 97.2% for the confirmation or exclusion of NB. Conclusion: Based on our results, we propose a CSF CXCL13 cut-off of 271 pg/ml with Euroimmun-Elisa for the diagnosis of acute and untreated NB. Due to its high sensitivity and specificity, CXCL13 is a strong candidate biomarker for routine NB assessment, especially in clinically unclear cases.

Anti-Ri paraneoplastic neurological syndrome presenting with bilateral cranial nerve VI palsy and jaw dystonia-a distinctive syndrome within the anti-Ri spectrum? : Case report and literature review.

OBJECTIVE: Paraneoplastic neurological syndromes (PNS) are rare disorders associated with various onconeuronal antibodies. Anti-Ri antibodies (ANNA-2) are typically found in patients with opsoclonus myoclonus syndrome (OMS) and ataxia. CASE REPORT: We present an anti-Ri antibody-positive 77-year-old woman with subacute progressive bilateral cranial nerve VI palsy, gait disturbance and jaw dystonia. MRI of the brain showed hyperintense signals on T2 bitemporal without contrast enhancement. Cerebrospinal fluid (CSF) examination exhibited mild pleocytosis of 13 cells/µl and positive oligoclonal bands. CSF was overall inconspicuous for a malignant or inflammatory etiology. Immunofluorescence analysis revealed anti-Ri antibodies in both serum and CSF. Subsequent diagnostic work up resulted in a newly diagnosed ductal carcinoma of the right breast. PNS in this case partially responded to the anti-tumor therapy. CONCLUSION: This case shows similarities with recently published anti-Ri syndromes, which might form a distinct triad within the anti-Ri spectrum.

Real-time monitoring of intravenous thrombolysis in acute ischemic stroke using rotational thromboelastometry: a feasibility pilot study.

INTRODUCTION: Rotational thromboelastometry (ROTEM) records whole blood coagulation in vitro. Data on dynamic changes of clot patterns during intravenous thrombolysis (IVT) in acute ischemic stroke is scarce. We investigated the feasibility of ROTEM as a potential point-of-care assessment tool for IVT. METHODS: In this prospective pilot study, patients with acute stroke symptoms received IVT. Whole blood coagulation was tracked on the ROTEM analyzer. Blood samples were analyzed before, and then 2, 15, 30 and 60 min after beginning IVT. In vitro clots (iCLs) were described by their maximum clot firmness (MCF), the time needed to reach MCF (MCF-t), as well as the area under the curve (AR10). National Institutes of Health Stroke Scale (NIHSS) was used as early clinical outcome parameter. RESULTS: We analyzed 288 iCLs from 12 patients undergoing IVT. In all iCLs, an early fibrinolysis (91% within the first 10 min) was detected during IVT. Three different curve progression patterns were observed: a low-responder pattern with a continuous clot increase, a high-responder pattern with a sustained clot decrease or total clotting suppression and an intermediate-responder pattern with alternating clot characteristics. There was a difference among these groups in early clinical outcome (AR10 and MCF each p = 0.01, MCF-t p = 0.02, Kruskal-Wallis Test). CONCLUSION: The fibrinolysis patterns determined using ROTEM allow for the monitoring of IVT in patients with acute ischemic stroke. This pilot study found a correlation between the in vitro fibrinolysis patterns and early clinical outcomes. These findings support a potential for individualization of IVT in the future.

Multimodal assessment of disease activity in glioblastoma : A single center experience.

BACKGROUND: Assessment of disease activity in glioblastoma (GBM) can be challenging due to several clinical and radiological pitfalls. Besides MRI, FET-PET and neurocognitive assessment (NA) are used in several neuro-oncological centers in order to improve the specificity of response assessment. We performed a retrospective study to investigate whether the assessment by RANO (Response Assessment in NeuroOncology) corresponds to FET-PET imaging and NA results. Moreover, the concordance of RANO with a final recommendation of an interdisciplinary neuro-oncological tumor board recommendation (TBR) was analyzed. METHODS: We enrolled 25 consecutive patients with newly diagnosed histologically confirmed GBM in a pilot study, accounting for 81 multimodal test results. All patients were selected after undergoing consecutive follow-up comprising MRI, FET-PET, and NA with a subsequent TBR. Results were analyzed for correlations between RANO, FET-PET and NA. An additional consistency analysis was performed to elucidate the impact of RANO on decision making. RESULTS: A highly statistically significant correlation was found between RANO and FET-PET and NA results (all P < 0.01); however, 26% of follow-up tests exhibited inconsistent results in multimodal assessment, among which RANO was only 48% in accordance with the final TBR. The concordance of NA and FET-PET with the final TBR was 67% and 86%, respectively. CONCLUSION: The RANO proved its value in the context of multimodal assessment of disease activity in GBM; however, because the implementation of multimodal assessment showed a considerably high percentage of inconsistent results, further studies are required to investigate the relationship between different assessment techniques, in addition to their overall significance to response rating.

ABCD3-I score and the risk of early or 3-month stroke recurrence in tissue- and time-based definitions of TIA and minor stroke.

Changing definition of TIA from time to a tissue basis questions the validity of the well-established ABCD3-I risk score for recurrent ischemic cerebrovascular events. We analyzed patients with ischemic stroke with mild neurological symptoms arriving < 24 h after symptom onset in a phase where it is unclear, if the event turns out to be a TIA or minor stroke, in the prospective multi-center Austrian Stroke Unit Registry. Patients were retrospectively categorized according to a time-based (symptom duration below/above 24 h) and tissue-based (without/with corresponding brain lesion on CT or MRI) definition of TIA or minor stroke. Outcome parameters were early stroke during stroke unit stay and 3-month ischemic stroke. Of the 5237 TIA and minor stroke patients with prospectively documented ABCD3-I score, 2755 (52.6%) had a TIA by the time-based and 2183 (41.7%) by the tissue-based definition. Of the 2457 (46.9%) patients with complete 3-month followup, corresponding numbers were 1195 (48.3%) for the time- and 971 (39.5%) for the tissue-based definition of TIA. Early and 3-month ischemic stroke occurred in 1.1 and 2.5% of time-based TIA, 3.8 and 5.9% of time-based minor stroke, 1.2 and 2.3% of tissue-based TIA as well as in 3.1 and 5.5% of tissue-based minor stroke patients. Irrespective of the definition of TIA and minor stroke, the risk of early and 3-month ischemic stroke steadily increased with increasing ABCD3-I score points. The ABCD3-I score performs equally in TIA patients in tissue- as well as time-based definition and the same is true for minor stroke patients.

The Last 10 Days of Patients With Glioblastoma: Assessment of Clinical Signs and Symptoms as well as Treatment.

BACKGROUND: High-grade gliomas are the most frequent primary brain tumors. Despite improvement in diagnostics and treatment, survival is still poor and quality-of-life issues are of major importance. Little is known regarding the clinical signs and symptoms of dying patients with glioblastoma. OBJECTIVE: The aim of this study was to investigate signs and symptoms as well as therapeutic strategies in patients with glioblastoma in the end-of-life phase in order to improve end-of-life care. METHODS: In this prospective single-center study, clinical data were obtained using a standardized protocol. We descriptively analyzed signs, symptoms, and therapeutic strategies on a daily basis. RESULTS: A total of 57 patients, who died due to glioblastoma in a hospital setting, were included. The most frequent signs and symptoms in the last 10 days before death were decrease in level of consciousness (95%), fever (88%), dysphagia (65%), seizures (65%), and headache (33%). Concerning medication, 95% received opioids. There was a high need for nonsteroidal anti-inflammatory drugs (77%) and anticonvulsants (75%). Steroids were given to 56%. CONCLUSION: Due to a decrease in level of consciousness and cognitive impairment, assessment of clinical signs and symptoms such as headache at the end of life is difficult. Based on the signs and symptoms in the last days before death in patients with glioblastoma, supportive drug treatment remains challenging. Our study emphasizes the importance of standardized guidelines for end-of-life care in patients with glioblastoma.

Haematological toxicity of Valproic acid compared to Levetiracetam in patients with glioblastoma multiforme undergoing concomitant radio-chemotherapy: a retrospective cohort study.

Patients with glioblastoma multiforme (GBM) and symptomatic seizures are in need of a sufficient antiepileptic treatment. Haematological toxicity is a limiting side effect of both, first line radio-chemotherapy with temozolomide (TMZ) and co-medication with antiepileptic drugs. Valproic acid (VPA) and levetiracetam (LEV) are considered favourable agents in brain tumor patients with seizures, but are commonly reported to induce haematological side effects on their own. We hypothesized, that antiepileptic treatment with these agents has no increased impact on haematological side effects during radio-chemotherapy in the first line setting. We included 104 patients from two neuro-oncologic centres with GBM and standard radio-chemotherapy in a retrospective cohort study. Patients were divided according to their antiepileptic treatment with either VPA, LEV or without antiepileptic drug therapy (control group). Declines in haemoglobin levels and absolute blood cell counts for neutrophil granulocytes, lymphocytes and thrombocytes were analyzed twice during concomitant and once during adjuvant phase. A comparison between the examined groups was performed, using a linear mixed model. Neutrophil granulocytes, lymphocytes and thrombocytes significantly decreased over time in all three groups (all p < 0.012), but there was no significant difference between the compared groups. A significant decline in haemoglobin was observed in the LEV treated group (p = 0.044), but did not differ between the compared groups. As a novel finding, this study demonstrates that co-medication either with VPA or LEV in GBM patients undergoing first line radio-chemotherapy with TMZ has no additional impact on medium-term haematological toxicity.

Neuromyelitis optica in Austria in 2011: to bridge the gap between neuroepidemiological research and practice in a study population of 8.4 million people.

BACKGROUND: In 2008 the Austrian Task Force for Neuromyelitis Optica (NMO) started a nation-wide network for information exchange and multi-centre collaboration. Their aim was to detect all patients with NMO or NMO spectrum disorders (NMO-SD) in Austria and to analyse their disease courses and response to treatment. METHODS: (1) As of March 2008, 1957 serum samples (of 1557 patients) have been tested with an established cell based immunofluorescence aquaporin-4 antibody (AQP4-ab) assay with a high sensitivity and specificity (both >95%). All tests were performed in a single reference laboratory (Clinical Dept. of Neurology of the Innsbruck Medical University). (2) A nation-wide survey with several calls for participation (via email newsletters, articles in the official journal of the Austrian Society of Neurology, and workshops) was initiated in 2008. All collected data will be presented in a way that allows that every individual patient can be traced back in order to ensure transparency and to avoid any data distortion in future meta-analyses. The careful and detailed presentation allows the visualization and comparison of the different disease courses in real time span. Failure and response to treatment are made visible at one glance. Database closure was 31 December 2011. All co-operators were offered co-authorship. RESULTS: All 71 NMO- or NMO-SD patients with AQP4-ab positivity (age range 12.3 to 79.6 years) were analysed in detail. Sex ratio (m:f = 1:7) and the proportion of patients without oligoclonal bands in cerebrospinal fluid (86.6%) were in line with previously published results. All identified patients were Caucasians. CONCLUSIONS: A nationwide collaboration amongst Austrian neurologists with good network communications made it possible to establish a database of 71 AQP4-ab positive patients with NMO/NMO-SD. This database is presented in detail and provides the basis for further studies and international cooperation in order to investigate this rare disease.

Malignant spinal cord compression in cerebral glioblastoma multiforme: a multicenter case series and review of the literature.

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. Compared with other malignancies, remote metastases in GBM are rare. However, multicentric spreading within the central nervous system is common and also metastases to the spinal cord have been reported. Some of these drop metastases may also lead to malignant spinal cord compression (MSCC). We retrospectively identified nine patients from 2001 to 2010 and performed data analysis according to a standardized clinical protocol. We also provide a review of the literature on this rare condition. MSCC from cerebral GBM is rare and is found in approximately 1 % of GBM patients. Median age of 54 years in this case series is comparable with that of GBM patients without MSCC. Treatment regimens for cerebral GBM and overall survival was similar to those for patients without MSCC. Spinal metastasis seems to occur in the advanced state of the disease, and the outcome subsequently is extremely poor. All patients presented with multicentric radiological features of GBM on cerebral MRI when MSCC was diagnosed. Subependymal enhancement is another common radiological finding in GBM patients with spinal drop metastases. Steroids and focal radiotherapy were used to treat all patients, with little clinical benefit. This study is the largest case series of MSCC from cerebral GBM. Multicentric cerebral distribution and subependymal enhancement of GBM are observed on cerebral MRI at the time of MSCC. On the basis of our results, no specific treatment recommendations for MSCC in GBM patients can be given. However, accurate diagnosis of MSCC in GBM patients with spinal signs and symptoms can lead to adequate management of symptoms and improvement of quality of life in terms of best palliative care.