Prediction of Outcome After Endovascular Embolectomy in Anterior Circulation Stroke Using Biomarkers.

Stroke is a major public health problem that can cause a long-term disability or death due to brain damage. Serious stroke is frequently caused by a large vessel occlusion in the anterior circulation, which should be treated by endovascular embolectomy if possible. In this study, we investigated the use of the brain damage biomarkers tau, NFL, NSE, GFAp, and S100B to understand the progression of nervous tissue damage and their relationship to outcome in such stroke after endovascular treatment. Blood samples were taken from 90 patients pre-treatment and 2 h, 24 h, 48 h, 72 h and 3 months after endovascular treatment. Stroke-related neurological deficit was estimated using the National Institute of Health Stroke Scale (NIHSS) at admission and at 24 h. Neurological outcome was evaluated at 3 months. After stroke, tau, NFL, GFAp and S100B increased in a time dependent manner, while NSE remained constant over time. At 3 months, tau and GFAp levels were back to normal whereas NFL was still high. Tau, NFL and GFAp correlated well to outcome, as well as to infarct volume and NIHSS at 24 h. The best time for prediction of poor outcome was different for each biomarker. However, the combination of NIHSS at 24 h with either tau, NFL or GFAp at 48 h gave the best prediction. The use of biomarkers in the early setting after endovascular treatment of stroke will lead to a simplified and standardized way to estimate the nervous tissue damage and possibly complement the clinical judgement in foreseeing the need of rehabilitation measures.

Neurofilaments can differentiate ALS subgroups and ALS from common diagnostic mimics.

Delayed diagnosis and misdiagnosis are frequent in people with amyotrophic lateral sclerosis (ALS), the most common form of motor neuron disease (MND). Neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH) are elevated in ALS patients. We retrospectively quantified cerebrospinal fluid (CSF) NFL, CSF pNFH and plasma NFL in stored samples that were collected at the diagnostic work-up of ALS patients (n = 234), ALS mimics (n = 44) and controls (n = 9). We assessed the diagnostic performance, prognostication value and relationship to the site of onset and genotype. CSF NFL, CSF pNFH and plasma NFL levels were significantly increased in ALS patients compared to patients with neuropathies & myelopathies, patients with myopathies and controls. Furthermore, CSF pNFH and plasma NFL levels were significantly higher in ALS patients than in patients with other MNDs. Bulbar onset ALS patients had significantly higher plasma NFL levels than spinal onset ALS patients. ALS patients with C9orf72HRE mutations had significantly higher plasma NFL levels than patients with SOD1 mutations. Survival was negatively correlated with all three biomarkers. Receiver operating characteristics showed the highest area under the curve for CSF pNFH for differentiating ALS from ALS mimics and for plasma NFL for estimating ALS short and long survival. All three biomarkers have diagnostic value in differentiating ALS from clinically relevant ALS mimics. Plasma NFL levels can be used to differentiate between clinical and genetic ALS subgroups.

Acute symptomatic seizures and epilepsy after mechanical thrombectomy.

PURPOSE: The purpose of this study was to assess the incidence of acute symptomatic seizures and poststroke epilepsy (PSE) in a well-characterized cohort of patients treated with mechanical thrombectomy. In addition, we aimed to describe the dynamics of blood markers of brain injury in patients that developed PSE. METHODS: Participants of the prospective AnStroke Trial of anesthesia method during mechanical thrombectomy were included and acute symptomatic seizures and PSE ascertained by medical records review. Blood markers neurofilament light (NFL), tau, glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), and neuron-specific enolase (NSE) were assessed. RESULTS: A total of 90 patients with acute anterior ischemic stroke were included. Median National Institutes of Health Stroke Scale (NIHSS) at admission to hospital was 18 (IQR 15-22). Recanalization was achieved in 90%. No patients had epilepsy prior to the ischemic stroke. Four patients (4.4%) had acute symptomatic seizures and four patients (4.4%) developed PSE during the follow-up time (to death or last medical records review) of 0-4.5 years (median follow-up 1070 days IQR 777-1306), resulting in a two-year estimated PSE risk of 5.3% (95%CI: 0.2-10.4%). Blood markers of brain injury (NFL, tau, GFAP, S100B, and NSE) were generally above the cohort median in patients that developed PSE. CONCLUSIONS: The incidence of PSE after mechanical thrombectomy was low in our cohort. All blood biomarkers displayed interesting sensitivity and specificity. However, the number of PSE cases was small and more studies are needed on risk factors for PSE after mechanical thrombectomy. The potential of blood markers of brain injury markers to contribute to assessment of PSE risk should be explored further. This article is part of the Special Issue "Seizures & Stroke".

Correlations between serum and CSF pNfH levels in ALS, FTD and controls: a comparison of three analytical approaches.

Background Phosphorylated neurofilament heavy (pNfH), a neuronal cytoskeleton protein, might provide a promising blood biomarker of neuronal damage in neurodegenerative diseases (NDDs). The best analytical approaches to measure pNfH levels and whether serum levels correlate with cerebrospinal fluid (CSF) levels in NDDs remain to be determined. Methods We here compared analytical sensitivity and reliability of three novel analytical approaches (homebrew Simoa, commercial Simoa and ELISA) for quantifying pNfH in both CSF and serum in samples of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and control subjects. Results While all three assays showed highly correlated CSF measurements, Simoa assays also yielded high between-assay correlations for serum measurements (ϱ = 0.95). Serum levels also correlated strongly with CSF levels for Simoa-based measurements (both ϱ = 0.62). All three assays allowed distinguishing ALS from controls by increased CSF pNfH levels, and Simoa assays also by increased serum pNfH levels. pNfH levels were also increased in FTD. Conclusions pNfH concentrations in CSF and, if measured by Simoa assays, in blood might provide a sensitive and reliable biomarker of neuronal damage, with good between-assay correlations. Serum pNfH levels measured by Simoa assays closely reflect CSF levels, rendering serum pNfH an easily accessible blood biomarker of neuronal damage in NDDs.

Neurofilament changes in serum and cerebrospinal fluid after acute ischemic stroke.

BACKGROUND: Neurofilament light (NFL) is a well-validated biomarker for neuronal injury and neurodegeneration. Increased cerebrospinal fluid (CSF) levels have been shown after stroke, as well as in patients with a broad range of neurodegenerative and neuroinflammatory diseases. Neurofilament heavy (NFH) belongs to the same family of structural proteins but it is less extensively studied. The potential of phosphorylated NFH (pNFH) as a stroke biomarker and for the prediction of clinical outcome is unknown. In this study, we aimed to examine the temporal pattern of NFL and pNFH concentrations in serum and CSF after acute ischemic stroke. MATERIALS AND METHODS: A quantitative Enzyme-Linked ImmunoSorbent Assay (ELISA) for pNFH was developed and tested on CSF and serum samples. NFL and pNFH were analysed in serum and CSF of acute ischemic stroke patients, who were followed over time (Day 0-1, Day 2-3, Day 7-9, three weeks, and 3-5 months after stroke). RESULTS: NFL and pNFH concentrations in serum and CSF increased after stroke, peaked during the 3rd week, and then decreased back to almost baseline levels at 3-5 months. CSF-NFL and serum-NFL correlated to the outcome measured by Barthel Index after 3-5 months, whilst no such association was seen for pNFH. DISCUSSION: These findings suggest that NFL and pNFH in both CSF and serum reflect the temporal pattern of the post ischemic axonal injury and that this process does not seem to progress after 3-5 months. CONCLUSION: NFL and pNFH in CSF and serum are promising biomarkers for axonal injury following stroke. Further studies in larger populations are needed to fully understand the progression of the neuronal damage after acute ischemic stroke and to evaluate if these biomarkers can provide additive information and how they relate to outcome.

A new enzyme-linked immunosorbent assay for neurofilament light in cerebrospinal fluid: analytical validation and clinical evaluation.

BACKGROUND: Cerebrospinal fluid (CSF) neurofilament light (NfL) is a reliable marker of neuro-axonal damage in different neurological disorders that is related to disease severity. To date, all recent studies performed in human CSF have used the same enzyme-linked immunosorbent assay (ELISA). To confirm the large body of evidence for NfL, we developed a new ELISA method and here we present the performance characteristics of this new ELISA for CSF NfL in different neurological disorders. METHODS: We produced two monoclonal antibodies (NfL21 and NfL23) directed against the NfL core domain, and developed a novel sandwich ELISA method that we evaluated in patients with: 1) inflammatory demyelinating diseases (IDD; n = 97), including multiple sclerosis (MS; n = 59), clinically isolated syndrome (CIS; n = 32), and radiologically isolated syndrome (RIS; n = 6); 2) Alzheimer's disease (AD; n = 72), including mild cognitive impairment due to AD (MCI-AD, n = 36) and probable AD dementia (AD-dem; n = 36); 3) Parkinson's disease (PD; n = 30); and 4) other neurological noninflammatory and non-neurodegenerative diseases (OND; n = 30). RESULTS: Our new NfL ELISA showed a good analytical performance (inter-plate coefficient of variation (CV) < 13%), with no cross-reactivity with neurofilament medium and heavy (NfM and NfH). With respect to the other available ELISAs, CSF NfL showed the same range of values with a strong correlation (r = 0.9984, p < 0.001) between the two methods. CSF NfL levels were significantly higher in MCI-AD/AD-dem and IDD patients as compared with both PD and OND patients. The highest discriminative power was obtained between IDD and OND patients (area under the curve (AUC) 0.87, 95% confidence interval (CI) 0.80-0.95). Within the IDD group, CSF NfL positively correlated with several clinical and radiological disease severity parameters. CONCLUSIONS: These results show a good analytical performance of the new ELISA for quantification of NfL concentrations in the CSF. CSF NfL is confirmed to be a reliable marker in AD and MS, and a disease-severity marker in MS patients.

Clinical Features, Complications and Autoimmunity in Male Lichen Sclerosus.

Lichen sclerosus is a chronic inflammatory disease associated with substantial morbidity. Knowledge of the aetiology and progression of lichen sclerosus is therefore needed. In this cross-sectional study, 100 male patients diagnosed with lichen sclerosus were interviewed and examined. Since there is a possible link between lichen sclerosus and autoimmunity, blood tests were analysed for thyroid disease, antinuclear antibodies and antibodies to extracellular matrix protein 1, but autoimmunity was found to be infrequent. In 72 participants active genital lichen sclerosis was observed and complications were common; 27 patients had preputial constriction and 12 meatal engagement. In total, 13 patients needed a referral to the Department of Urology, including 1 patient with suspected penile cancer. In conclusion, despite available treatment with ultra-potent steroids and circumcision, lichen sclerosus in males is frequently complicated by phimosis and meatal stenosis. However, the disease can also go into remission, as seen in 27% of our patients.