The major pathway by which the brain obtains essential omega-3 fatty acids from the circulation is through a sodium-dependent lysophosphatidylcholine (LPC) transporter (MFSD2A), expressed in the endothelium of the blood-brain barrier. Here we show that a homozygous mutation affecting a highly conserved MFSD2A residue (p.Ser339Leu) is associated with a progressive microcephaly syndrome characterized by intellectual disability, spasticity and absent speech. We show that the p.Ser339Leu alteration does not affect protein or cell surface expression but rather significantly reduces, although not completely abolishes, transporter activity. Notably, affected individuals displayed significantly increased plasma concentrations of LPCs containing mono- and polyunsaturated fatty acyl chains, indicative of reduced brain uptake, confirming the specificity of MFSD2A for LPCs having mono- and polyunsaturated fatty acyl chains. Together, these findings indicate an essential role for LPCs in human brain development and function and provide the first description of disease associated with aberrant brain LPC transport in humans.
Background and aim: Neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR) are associated with clinical outcomes in malignancy, cardiovascular disease and stroke. Here we investigate their association with outcome after acute ischaemic stroke treated by mechanical thrombectomy (MT). Methods: Patients were selected using audit data for MT for acute anterior circulation ischaemic stroke at a UK centre from May 2016-July 2017. Clinical and laboratory data including neutrophil, lymphocyte and monocyte count tested before and 24 h after MT were collected. Poor functional outcome was defined as modified Rankin Scale (mRS) of 3-6 at 3 months. Multivariable logistic regression analyses were performed to explore the relationship of NLR and LMR with functional outcome. Results: One hundred twenty-one patients (mean age 66.4 ± 16.7, 52% female) were included. Higher NLR (adjusted OR 0.022, 95% CI, 0.009-0.34, p = 0.001) and lower LMR (adjusted OR − 0.093, 95% CI (− 0.175)−(− 0.012), p = 0.025) at 24-h post-MT were significantly associated with poorer functional outcome when controlling for age, baseline NIHSS score, infarct size, presence of good collateral supply, recanalisation and symptomatic intracranial haemorrhage on multivariate logistic regression. Admission NLR or LMR were not significant predictors of mRS at 3 months. The optimal cut-off values of NLR and LMR at 24-h post-MT that best discriminated poor outcome were 5.5 (80% sensitivity and 60% specificity) and 2.0 (80% sensitivity and 50% specificity), respectively on receiver operating characteristic curve analysis.Conclusion: NLR and LMR tested at 24 h after ictus or intervention may predict 3-month functional outcome.
Catheter-based angiography is an important but invasive procedure in vascular neurology. It is used mainly for diagnosis and for planning treatment in patients with a suspected underlying vascular abnormality. It is often performed as a semiurgent, planned investigation or linked to an interventional procedure. Cerebral angiography provides high-resolution, three-dimensional, pathoanatomical data about the cerebral vasculature and also allows real-time analysis of blood flow. Contrast injections can be repeated to identify subtleties. A physical intervention may also follow angiography. For these reasons, angiography remains the gold standard for delineating vascular lesions of the brain (and spine). Permanent neurological complications are rare, approximately 1%, but become increasingly common in patients aged over 55 years. The main complications are embolic stroke, groin haematoma and contrast-induced nephropathy. In the new era of thrombectomy, it may transpire that other specialists including neurologists may learn to perform the procedure and to manage its complications.
IntroductionApproximately 40% of strokes in young adults are cryptogenic. The diagnostic yield of thrombophilia screening remains controversial. We aimed to determine utility of current thrombophilia testing for young patients with stroke and transient ischaemic attack (TIA).MethodsWe present a retrospective review of all patients with stroke and TIA ≤60 years presenting to University College London Hospital stroke unit and daily TIA clinic from 1 January 2015 to 1 August 2016. Consecutive clinical records and thrombophilia tests, including factor V Leiden (FVL), prothrombin G20210A mutation (PGM), antiphospholipid antibody (APA), and protein S, C and antithrombin (AT) levels, were reviewed.ResultsThe mean age of 628 patients with stroke and TIA was 49.1 years (SD 9.2). Thrombophilia testing was performed in 360 (57%) patients, including 171 with stroke and 189 with TIA. Positive tests were found in 50 (14%) patients, of whom 24 patients were <50 years. Positive results were found in 36 (10%) with acute ischaemic stroke, 4 (1%) with haemorrhagic stroke and 10 (3%) with TIA. Thirteen patients (4%) had homozygous/heterozygous FVL or PGM, and 27 (7.5%) had positive APA (anticardiolipin antibody, anti-β2 glycoprotein antibody or lupus anticoagulant). Of 27 (7.5%) patients with protein C, S or AT deficiency, 10 (2.8%) had primary deficiency, presumed hereditary with other secondary causes excluded. 9% of patients with protein C, S or AT and 27% with APA were followed by confirmatory testing.ConclusionThrombophilia testing was positive in only 14% of cases overall. Thrombophilia mutations and protein C, S or AT abnormalities were found rarely and were very uncommon in patients with TIA. Follow-up of abnormal results was generally poor for all groups, which further limited the impact of the thrombophilia testing policy.
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