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Antibodies directed against the voltage-gated potassium channel complex (anti-VGKCs) are implicated in several autoimmune conditions including limbic encephalitis and epilepsy. However, emerging evidence suggests that only specific subtypes of anti-VGKCs are pathogenic. We present the case of a 55-year-old man who initially presented with focal unaware seizures and behavioural changes mimicking anti-VGKC-seropositive encephalitis that further progressed to parkinsonism with evidence of frontotemporal dementia and pre-synaptic dopaminergic deficit. Aggressive treatment with immunotherapy was ineffective, and antibody subtyping later revealed the anti-VGKC antibodies to be negative for leucine-rich glioma-associated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) – the two known pathogenic subtypes. The clinical relevance of so-called “double-negative” anti-VGKCs (i.e., those not directed towards LGI1 or CASPR2) has been called into question in recent years, with evidence to suggest they may be clinically insignificant. Our case emphasises the importance of antibody subtyping in cases of anti-VGKC seropositivity; negative results, particularly when combined with a poor response to immunotherapy, should prompt a rapid reconsideration of the working diagnosis.

Patent foramen ovale (PFO) is the most common anatomical cause of an interatrial shunt. It is usually asymptomatic but may cause paradoxical embolism, manifesting as stroke, myocardial infarction or visceral/peripheral ischaemia. PFO is a risk factor for stroke and may be associated with migraine with aura. New evidence suggests PFO closure reduces the risk of recurrent ischaemic stroke in a highly selected population of stroke survivors: those aged 60 years or younger with a cryptogenic stroke syndrome, a large right-to-left shunt, an atrial septal aneurysm and no evidence of atrial fibrillation. They benefit from percutaneous PFO closure in addition to antiplatelet therapy, rather than antiplatelet therapy alone. Current evidence does not support PFO closure in the treatment of migraine.

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.

Introduction\ud Radiolabeled ligands for fibrillar amyloid beta (Aβ) peptides are used in positron emission tomography (PET) for dementia diagnosis. Current ligands do not discriminate parenchymal amyloid plaques from cerebral amyloid angiopathy (CAA).\ud \ud Methods\ud We undertook neuropathological examination of 65 older people (81.6 ± 7.96 (mean ± SD) years, 27F/38M): 15 with neuropathological diagnosis of AD, 25 with neuropathological diagnosis of other neurodegenerative dementias (Lewy body dementia and Parkinson disease dementia), and 25 without significant neurodegenerative pathology.\ud \ud Results\ud We observed CAA in non‐Alzheimer's dementia (non‐AD dementia) and control brains, of comparable extent to those with neuropathologically confirmed AD. Aβ‐positive vessel density did not differ significantly between non‐AD dementia and control groups. Across all subjects there was a highly significant correlation between vessel Aβ40 density and vessel Aβ42 density (Spearman rho = 0.855, P < .001). CAA was absent or sparse in subcortical white matter across all patient groups.\ud \ud Conclusion\ud Our data indicate that CAA can be abundant in non‐AD brains and raise a cautionary note regarding interpretation of amyloid PET imaging.

Background Almost half of ischemic strokes in young individuals are cryptogenic. Thrombophilia testing is routinely sent despite limited evidence linking to arterial cerebrovascular events. A full blood count may identify underlying hematological disorder. Methods We retrospectively reviewed all patients younger than 60 years with stroke and transient ischemic attack (TIA) presenting to a regional hyperacute stroke unit and daily TIA clinic from January 2015 to August 2016. We examined hematocrit level and platelet count, and whether abnormalities were further investigated. We examined if primary hematological disorders associated with stroke were considered, specifically myeloproliferative diseases (MPDs) and thrombotic thrombocytopenic purpura (TTP). Results Of 609 patients who presented with stroke or TIA, there were 161 abnormalities in hematocrit level or platelet count in 153 patients (25.1%). One hundred sixteen patients had high hematocrit levels (19%), 19 had thrombocytosis (3.1%), 26 had thrombocytopenia (4.3%), and 8 had abnormalities in both lineages (1.3%). A total of 119 patients had repeat testing (74%). Molecular investigations for MPD were warranted in 19 patients (3.1%), performed in 3 patients (.5%) with 2 patients subsequently diagnosed. ADAMTS13 analysis was indicated in 10 patients with thrombocytopenia, performed in 2 patients with 1 diagnosed with TTP thereafter. Conclusions One quarter of our cohort (n = 153) had abnormalities in hematocrit and/or platelets. MPD or TTP was present in 3 of the 5 patients specifically investigated. At least 22 patients (14%) merited further investigation. Although primary hematological disorders are rare in stroke aetiology, the full blood count is important to exclude known causes of arterial cerebrovascular events in young patients.

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 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.

Recombinant tissue plasminogen activator (rtPA) is currently the only approved thrombolytic agent for treating acute ischaemic stroke that is widely used in clinical practice. However, it may cause haemorrhage and hypersensitivity reactions. Orolingual angioedema is an infrequent, usually mild but potentially life threatening, hypersensitivity reaction to rtPA. Our understanding of the basic biology of angioedema has increased in recent years. There is growing evidence that rtPA-induced orolingual angioedema is driven mainly by bradykinin generation rather than it being an anaphylactic response. Monitoring is important because orolingual angioedema may evolve and compromise airways and a small number do have angioedema as part of systemic anaphylaxis. There are no published guidelines for treating rtPA-induced orolingual angioedema, although some evidence suggests that those refractory to standard antianaphylactic agents may resolve with bradykinin B2 receptor antagonists. It is important that responses to orolingual angioedema are proportionate and that patients are closely monitored.

Objectives\ud To assess the prevalence of high on-clopidogrel platelet reactivity (HCPR) in patients with ischaemic stroke or transient ischaemic attack (IS/TIA), their outcome and genetic basis of on-treatment response variability in IS/TIA patients.\ud \ud Methods\ud We conducted a comprehensive search of PubMed and EMBASE from their inceptions to March 9, 2019. Studies that reported absolute numbers/percentages of HCRP at any time point after IS/TIA onset evaluated with any type of platelet function tests, clinical outcomes and genotyping data were included.\ud \ud Results\ud Among 21 studies of 4312 IS/TIA patients treated with clopidogrel, the pooled prevalence of HCPR was 28% (95%CI: 24–32%; high heterogeneity: I2 = 88.2%, p < 0.001). Heterogeneity degree diminished across groups defined by the HCPR testing method. Clopidogrel non-responder IS/TIA patients had poorer outcome compared to responders (RR = 2.09, 95%CI: 1.61–2.70; p = 0.036; low heterogeneity across studies: I2 = 27.4%, p = 0.210). IS/TIA carriers of CYP2C19*2 or CYP2C19*3 loss of function alleles had a higher risk of HCPR compared to wild type (RR = 1.69, 95%CI: 1.47–1.95; p < 0.001; I2 = 0.01%, p = 0.475).\ud \ud Conclusions\ud This systematic review shows a high prevalence of clopidogrel resistance in IS/TIA and poor outcome in these patients. CYP2C19 polymorphisms may potentially influence clopidogrel resistance.

Background Protein convertase subtilisin–kexin type 9 (PCSK9) inhibitors effectively clear low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). We evaluated stroke admissions potentially eligible for more intensive cholesterol treatment. Methods Retrospective analysis of consecutive admissions to a hyperacute stroke unit over 5 months in 2017. Records were individually searched. Data were collected on diagnosis, risk factors, and stroke work-up. European Society of Cardiology and European Atherosclerosis Society guidelines for the management of dyslipidaemias were used for screening patients eligible for PCSK9 inhibitors. Results Of 650 patient admissions: 351 (54%) had acute ischemic stroke or transient ischemic attack (TIA), 80 (12%) hemorrhage, and 219 (34%) mimic syndromes. Patients with hemorrhage (n = 80), mimic syndromes (n = 219), and absent LDL-C, or non-HDL-C testing (n = 27) were subsequently excluded. 324 patients with acute ischemic stroke and TIA were further screened for PCSK9-inhibitor treatment eligibility. Forty-one (13%) patients with LDL-C greater than or equal to 1.8mmol/L (≥70 mg/dL) on maximal tolerated statin dose and with concomitant “very high vascular risk” were identified. “Very high vascular risk” was defined as a documented history of cardiovascular disease and/or peripheral arterial disease. Of 41 patients eligible for PCSK9 inhibitors, median age was 82 years (range 53-96); median vascular risk factors were 2 (range 1-5); 7 (17%) had TIA; 13 (31%) had history of preceding cerebrovascular events, 13 (31%) diabetes mellitus, 17 (42%) cardioembolic events, 9 (22%) lacunar syndrome, 11 (22%) symptomatic internal carotid artery stenosis (n = 9 were >70%), and 4 (10%) undetermined aetiology. Eighty-three percent patients eligible for PCSK9 inhibitors also had non-HDL-C values greater than or equal to 2.6 mmol/L. Conclusions Up to 13% of unselected acute ischemic stroke or TIA patients admitted to a hyper-acute stroke unit were potentially suitable for more intensive cholesterol treatment. Our data may act as a useful guide for sample size selection in future stroke trials testing PCSK9 inhibitors.

Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy in adults, is an autosomal dominant disorder with a wide phenotypic spectrum ranging from oligosymptomatic forms to a life-threatening, multisystem disease. People with DM1 overall have a reduced life expectancy, mainly due to respiratory or cardiac causes. There is no cure but prompt, appropriate symptom management is essential to limit disease-related complications. We present a case of DM1, unrecognised when the patient presented with recurrent type 2 respiratory failure, and initially misdiagnosed as Guillain-Barré syndrome. This misdiagnosis subsequently led to unnecessary investigation and treatment before further detailed neurological examination and collateral family history gave the diagnosis. This case highlights the importance of considering a chronic neuromuscular disorder in patients presenting with acute respiratory failure and an unusual pattern of weakness.

Current national guidelines advocate intravenous thrombolysis to treat patients with acute ischaemic stroke presenting within 4.5 hours from symptom onset, and thrombectomy for patients with anterior circulation ischaemic stroke from large vessel occlusion presenting within 6 hours from onset. However, a substantial group of patients presents with acute ischaemic stroke beyond these time windows or has an unknown time of onset. Recent studies are set to revolutionise treatment for these patients. Using MRI diffusion/FLAIR (fluid-attenuated inversion recovery) mismatch, it is possible to identify patients within 4.5 hours from onset and safely deliver thrombolysis. Using CT perfusion imaging, it is possible to identify subjects with a middle cerebral artery syndrome who have an extensive area of ischaemic brain but as yet have only a small area of infarction who may benefit from urgent thrombectomy in up to 24 hours. Here, we highlight the recent advances in late window stroke treatment and their potential contribution to clinical practice.

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.