DWI-FLAIR mismatch guided thrombolysis in patients without large-vessel occlusion: real-world data from a comprehensive stroke centre

A significant proportion of ischaemic stroke patients present with unknown symptom onset time. DWI-FLAIR mismatch on MRI can help to identify those eligible for thrombolysis. We set out to analyse the short-term efficacy and safety of thrombolysis in a real-world setting.A retrospective single-centre observational study was conducted. We collected data between January 2017 and April 2020. Patients with a large vessel occlusion (LVO) were excluded. Outcomes were compared between thrombolysed patients and those who did not receive alteplase due to lack of DWI-FLAIR mismatch or other contraindications. We analysed baseline and discharge NIHSS scores for efficacy and defined good outcome as any neurological improvement (ANI) on the NIHSS. In terms of safety, the presence and severity of intracerebral haemorrhage on follow-up imaging was analysed, and mortality at 90 days assessed.Seventy-one patients were included in this study, of whom 29 received thrombolysis. Significantly more patients had ANI in the thrombolysed group (OR, 3.16; 95% CI, 1.178-8.479; p = 0.020). In a multivariable logistic regression analysis, only thrombolysis correlated with ANI (OR, 3.051; 95% CI, 1.135-8.206; p = 0.027). Two thrombolysed patients suffered intracerebral haemorrhage (6.90%), of whom one was symptomatic and eventually fatal. We did not find a significant difference in 90-day mortality between the two groups (OR, 0.81, 95% CI, 0.134-4.856; p = 1.000).Our real-world data demonstrate that thrombolysis based on DWI-FLAIR mismatch in patients without LVO has an early beneficial effect. The rate of intracerebral haemorrhage was similar to this complication reported in large thrombolysis trials with known onset times

Kynurenic acid and kynurenine aminotransferase are potential biomarkers of early neurological improvement after thrombolytic therapy : A pilot study

Biomarkers for predicting treatment response to thrombolysis in acute ischemic stroke are currently lacking. Both, animal models and clinical studies have provided evidence that the kynurenine (KYN) pathway is activated in ischemic stroke.In our pilot study, we aimed to investigate whether KYN pathway enzymes and metabolites could serve as potential biomarkers for treatment response in the hyperacute phase of ischemic stroke.We included 48 acute ischemic stroke patients who received thrombolysis. Blood samples were taken both before and 12 h after treatment. Concentrations of 11 KYN metabolites were determined using ultra-high-performance liquid chromatography-mass spectrometry. To assess the treatment response, we used early neurological improvement (ENI), calculated as the difference between the admission and discharge National Institutes of Health Stroke Scale (NIHSS) scores. We performed receiver operating characteristic (ROC) analysis for KYN pathway metabolites and enzymes that showed a correlation with ENI.In the samples taken before thrombolysis, significantly lower concentrations of kynurenic acid (KYNA) and kynurenine aminotransferase (KAT) activity were found in patients who had ENI (p = 0.01 and p = 0.002, respectively). According to the ROC analysis, the optimal cut-off value to predict ENI for KYNA was 37.80 nM (sensitivity (SN) 69.2%, specificity (SP) 68.4%) and 0.0127 for KAT activity (SN 92.3%, SP 73.7%).Our research is the first clinical pilot study to analyze changes in the KYN pathway in ischemic stroke patients who received thrombolytic treatment. Based on our results, baseline KYNA concentration and KAT activity could serve as potential biomarkers to predict early treatment response to thrombolysis

Kynurenine System and Multiple Sclerosis, Pathomechanism and Drug Targets with An Emphasis on Laquinimod

Multiple sclerosis is a common chronic, disabling autoimmune neurological disease affecting mainly young adults. In its pathomechanism, neurodegenerative and acute inflammatory characteristics are both involved. Disease-modifying therapies aim to reduce relapse-rate and slow down the deterioration in neurological functions. The currently available therapies fail to exert neuroprotective effects and most of them are associated with potentially toxic side-effects, therefore, ongoing research aims to develop novel drug candidates to cover these therapeutic gaps. The kynurenine pathway has been implicated in both the physiological processes of the central nervous system and in the pathomechanism of several neurological disorders as well. Alterations of the kynurenine pathway metabolites have been detected in multiple sclerosis and a number of potential therapeutic targets related to this metabolic route have been already identified. Laquinimod is a quinoline carboxamide showing structural similarities with kynurenic acid, which proved to have beneficial effects on reduction of brain atrophy and disability progression. The kynurenine pathway is therefore a promising target for the development of future drugs for the treatment of autoimmune diseases such as multiple sclerosis

Prion diseases: New considerations

The transmissible spongiform encephalopathies, which include Creutzfeldt-Jakob disease, are fatal neurodegenerative disorders caused by the pathological accumulation of abnormal prion protein. The diagnosis of Creutzfeldt-Jakob disease is complex. The electroencephalogram, magnetic resonance imaging, lumbar puncture and genetic testing findings can help in the differential diagnosis of rapidly progressive dementia. There has recently been considerable debate as to whether proteins involved in the development of neurodegenerative diseases should be regarded as prions or only share prion-like mechanisms. Two recent reports described the detection of abnormal prion protein in the nasal mucosa and urine of patients with Creutzfeldt-Jakob disease. These findings raise major health concerns regarding the transmissibility of human prion diseases. We set out to address this neurological hot topic and to draw conclusions on the basis of what is known in the literature thus far. © 2016 Elsevier B.V

24-Hour Near-Infrared Spectroscopy Monitoring of Acute Ischaemic Stroke Patients Undergoing Thrombolysis or Thrombectomy

Monitoring of acute ischaemic stroke patients during thrombolysis or thrombectomy is based mostly on frequent physical examinations, since no objective measurement of cerebrovascular haemodynamics is available in routine clinical practice. Near-infrared spectroscopy (NIRS) is a bed-side, noninvasive assessment tool that could help monitor these patients and potentially guide therapeutic interventions. Our goal in this pilot study was to investigate whether NIRS is a suitable method to monitor leptomeningeal collateral circulation via changes in cortical oxygen saturation in the first 24 hours of acute ischaemic stroke.Our study included 5 patients with acute anterior circulation infarcts. All patients received thrombolytic therapy and 1 had thrombectomy. 24-hour continuous NIRS monitoring was performed on all participants.We aimed to give a detailed description of each NIRS recording and explain how the observed findings could correlate with changes in anterior watershed territory collateral circulation and clinical outcome.Our pilot study supports the use of NIRS monitoring in acute ischaemic stroke. We believe that this technique could provide real-time information on the dynamic changes of leptomeningeal collateral circulation and help monitor the effects of thrombolysis and thrombectomy

Paraneoplastic neuromyelitis optica spectrum disorder: a case report and review of the literature

Neuromyelitis optica spectrum disorders (NMOSD) are demyelinating, autoimmune diseases affecting the central nervous system. Typically, recurrent optic neuritis and longitudinal extensive transverse myelitis dominates the clinical picture. In most cases NMOSD are associated with autoantibodies targeting the water channel aquaporin-4 (AQP-4). NMOSD usually present in young adults. Clinical findings suggestive of NMOSD in elderly patients should raise the suspicion of a paraneoplastic etiology. To our knowledge, we report the first case of a 66 year-old female patient with paraneoplastic NMOSD that is associated with squamous cell lung carcinoma. Anti-AQP-4 was present in both the serum and cerebrospinal fluid of the patient. However, immunhistological staining of the malignant tissue did not show presence of AQP-4 on the surface of tumour cells. © 2017 Elsevier Ltd

Unilateral thalamic infarction causing downward gaze palsy in a patient with uncorrected tetralogy of Fallot: A case report

Introduction - Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease (CHD). Adults with surgically uncorrected forms of this condition are extremely rare, since operation is recommended in childhood to prevent cyanosis. Cyanotic CHD increases the risk of thromboembolic events. An endothelial dysfunction caused by chronic hypoxia and shear stress due to rheological alterations with a platelet dysfunction appear to be the explanation behind this finding. Paramedian thalamic infarction causing vertical gaze palsy without midbrain involvement is an infrequent finding. We report here a rare case of a patient with untreated TOF, who suffered a left-sided unilateral thalamic infarction presenting as downward gaze palsy and diplopia. Case presentation - A 44-year-old women complained of sudden onset diplopia and vertigo. Neurological examination revealed a downward gaze palsy with other symptoms related to a vertebrobasilar territory circulatory disturbance. The MRI scan revealed an acute infarction, 8 mm in diameter in the left medial thalamic region without midbrain involvement. Discussion - Adults with uncorrected forms of TOF are extremely uncommon, and descriptions of stroke in these patients are therefore rarities. We set out to give a concise survey of the literature regarding TOF patients with stroke. Conclusion - We present a rare case of unilateral thalamic infarction causing downward gaze palsy in an adult patient with uncorrected TOF. Cyanotic CHD is regarded as one of the risk factors of stroke. Besides other pathologic conditions, ischaemic stroke at an early age should raise the suspicion of a cardioembolic origin and, in rare cases, might result from cyanotic CHD