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BACKGROUND: Traditionally, non-contrast computed tomography (CT) alone was used in the initial assessment of acute ischaemic stroke patients mainly to exclude haemorrhage or alternative pathology. SUMMARY: Late-window (beyond 6 hours) and recent large-volume endovascular mechanical thrombectomy (MT) trials integrated CT Perfusion (CTP) imaging to guide MT and/or intravenous thrombolysis (IVT) decision-making in stroke patients. KEY MESSAGES: In current clinical practice, many patients are being excluded from reperfusion therapy due to a lack of data from urgent investigations to assess cerebral vasculature and perfusion. Here, we explore the potential benefits of CTP incorporated into the initial CT protocol assessment of stroke patients.
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Stroke is one of the most common acute neurological disorders and a leading cause of disability worldwide. Evidence-based treatments over the last two decades have driven a revolution in the clinical management and design of stroke services. We need a highly skilled, multidisciplinary workforce that includes neurologists as core members to deliver modern stroke care. In the UK, the dedicated subspecialty training programme for stroke medicine has recently been integrated into the neurology curriculum. All neurologists will be trained to contribute to each aspect of the stroke care pathway. We discuss how training in stroke medicine is evolving for neurologists and the opportunities and challenges around practising stroke medicine in the UK and beyond.
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Sickle cell disease (SCD) is the most common type of hereditary anaemia and genetic disorder worldwide. Cerebrovascular disease is one of its most devastating complications, with consequent increased morbidity and mortality. Current guidelines suggest that children and adults with SCD who develop acute ischaemic stroke should be transfused without delay. Those with acute ischaemic stroke aged over 18 years who present within 4.5 hours of symptom onset should be considered for intravenous thrombolysis; older patients with conventional vascular risk factors are the most likely to benefit. Endovascular thrombectomy should be considered carefully in adults with SCD as there are few data to guide how the prevalence of cerebral vasculopathy may confound the expected benefits or risks of intervention. We present a practical approach to cerebrovascular disease in sickle cell patients based on the available evidence and our experience.
Subject(s)
Anemia, Sickle Cell , Brain Ischemia , Ischemic Stroke , Stroke , Child , Adult , Humans , Middle Aged , Stroke/epidemiology , Stroke/etiology , Stroke/therapy , Brain Ischemia/complications , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/epidemiology , Anemia, Sickle Cell/therapy , Ischemic Stroke/complications , Risk FactorsABSTRACT
Spontaneous spinal cord infarction is significantly less common than cerebrovascular disease. Because of the tight anatomical distribution of pathways in the cord, small spinal cord infarcts usually give more obvious symptoms and signs than similar lesions in the brain. Large epidemiological stroke studies have generally not included spinal cord stroke and so the incidence of vascular syndromes in the spinal cord is unknown. Management and prevention strategies for spontaneous spinal cord infarcts stem from small case series and case reports. Patient outcomes from spinal cord infarction are better with prompt recognition, timely management and prevention of associated medical complications arising from paraplegia, tetraplegia, neurogenic bladder and bowel dysfunction. The process of rehabilitation following spinal cord infarction is an evolving area.
Subject(s)
Spinal Cord Injuries , Stroke , Humans , Spinal Cord/diagnostic imaging , Spinal Cord/blood supply , Paraplegia , Infarction/diagnostic imaging , Infarction/etiology , Stroke/complicationsABSTRACT
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.
Subject(s)
Lymphocytes/metabolism , Monocytes/metabolism , Neutrophils/metabolism , Stroke/blood , Stroke/surgery , Thrombectomy/trends , Aged , Aged, 80 and over , Female , Humans , Lymphocyte Count/trends , Male , Middle Aged , Prospective Studies , Retrospective Studies , Treatment OutcomeABSTRACT
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 (nâ¯=â¯80), mimic syndromes (nâ¯=â¯219), and absent LDL-C, or non-HDL-C testing (nâ¯=â¯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 (nâ¯=â¯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.
Subject(s)
Anticholesteremic Agents/therapeutic use , Cholesterol, LDL/blood , Dyslipidemias/drug therapy , Eligibility Determination , Ischemic Attack, Transient/therapy , PCSK9 Inhibitors , Serine Proteinase Inhibitors/therapeutic use , Stroke/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Anticholesteremic Agents/adverse effects , Biomarkers/blood , Dyslipidemias/complications , Dyslipidemias/diagnosis , Dyslipidemias/enzymology , Female , Humans , Ischemic Attack, Transient/complications , Ischemic Attack, Transient/diagnosis , Male , Middle Aged , Patient Admission , Patient Selection , Proprotein Convertase 9/metabolism , Retrospective Studies , Risk Assessment , Risk Factors , Serine Proteinase Inhibitors/adverse effects , Stroke/complications , Stroke/diagnosis , Young AdultABSTRACT
OBJECTIVES: 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. METHODS: 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. RESULTS: Among 21 studies of 4312 IS/TIA patients treated with clopidogrel, the pooled prevalence of HCPR was 28% (95%CI: 24-32%; high heterogeneity: I2â¯=â¯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 (RRâ¯=â¯2.09, 95%CI: 1.61-2.70; pâ¯=â¯0.036; low heterogeneity across studies: I2â¯=â¯27.4%, pâ¯=â¯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 (RRâ¯=â¯1.69, 95%CI: 1.47-1.95; p < 0.001; I2â¯=â¯0.01%, pâ¯=â¯0.475). CONCLUSIONS: 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.
Subject(s)
Blood Platelets/drug effects , Clopidogrel/therapeutic use , Drug Resistance , Ischemic Attack, Transient/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation/drug effects , Stroke/drug therapy , Blood Platelets/metabolism , Clopidogrel/adverse effects , Clopidogrel/pharmacokinetics , Cytochrome P-450 CYP2C19/genetics , Cytochrome P-450 CYP2C19/metabolism , Drug Resistance/genetics , Humans , Ischemic Attack, Transient/blood , Ischemic Attack, Transient/diagnosis , Pharmacogenomic Variants , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/pharmacokinetics , Polymorphism, Genetic , Risk Factors , Stroke/blood , Stroke/diagnosis , Treatment OutcomeABSTRACT
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.
Subject(s)
Echocardiography, Transesophageal/methods , Foramen Ovale, Patent/diagnostic imaging , Foramen Ovale, Patent/epidemiology , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/epidemiology , Atrial Fibrillation/prevention & control , Decompression Sickness/diagnostic imaging , Decompression Sickness/epidemiology , Decompression Sickness/prevention & control , Foramen Ovale, Patent/surgery , Humans , Migraine Disorders/diagnostic imaging , Migraine Disorders/epidemiology , Migraine Disorders/prevention & control , Risk Factors , Stroke/diagnostic imaging , Stroke/epidemiology , Stroke/prevention & control , Watchful Waiting/methodsABSTRACT
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.
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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.
Subject(s)
Drug Hypersensitivity/diagnosis , Drug Hypersensitivity/therapy , Recombinant Proteins/adverse effects , Tissue Plasminogen Activator/adverse effects , Angioedema/chemically induced , Angioedema/diagnosis , Angioedema/therapy , Drug Hypersensitivity/etiology , HumansABSTRACT
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.
Subject(s)
Diffusion Magnetic Resonance Imaging/trends , Stroke/diagnostic imaging , Stroke/therapy , Thrombolytic Therapy/trends , Time-to-Treatment/trends , Tomography, X-Ray Computed/trends , Diffusion Magnetic Resonance Imaging/methods , Disease Management , Humans , Thrombolytic Therapy/methods , Tomography, X-Ray Computed/methodsABSTRACT
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.
Subject(s)
Blood Cell Count , Ischemic Attack, Transient/blood , Stroke/blood , Cerebral Hemorrhage/blood , Humans , Middle Aged , Retrospective StudiesABSTRACT
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.
Subject(s)
Cerebral Angiography/adverse effects , Cerebral Angiography/methods , Cerebrovascular Disorders/diagnostic imaging , Cerebrovascular Disorders/surgery , Thrombectomy/methods , Central Nervous System/diagnostic imaging , HumansABSTRACT
BACKGROUND: The deletion of the chromosome 4p16.3 Wolf-Hirschhorn syndrome critical region (WHSCR-2) typically results in a characteristic facial appearance, varying intellectual disability, stereotypies and prenatal onset of growth retardation, while gains of the same chromosomal region result in a more variable degree of intellectual deficit and dysmorphism. Similarly the phenotype of individuals with terminal deletions of distal chromosome 3p (3p deletion syndrome) varies from mild to severe intellectual deficit, micro- and trigonocephaly, and a distinct facial appearance. METHODS AND RESULTS: We investigated a large Indian five-generation pedigree with ten affected family members in which chromosomal microarray and fluorescence in situ hybridization analyses disclosed a complex rearrangement involving chromosomal subregions 4p16.1 and 3p26.3 resulting in a 4p16.1 deletion and 3p26.3 microduplication in three individuals, and a 4p16.1 duplication and 3p26.3 microdeletion in seven individuals. A typical clinical presentation of WHS was observed in all three cases with 4p16.1 deletion and 3p26.3 microduplication. Individuals with a 4p16.1 duplication and 3p26.3 microdeletion demonstrated a range of clinical features including typical 3p microdeletion or 4p partial trisomy syndrome to more severe neurodevelopmental delay with distinct dysmorphic features. CONCLUSION: We present the largest pedigree with complex t(4p;3p) chromosomal rearrangements and diverse clinical outcomes including Wolf Hirschorn-, 3p deletion-, and 4p duplication syndrome amongst affected individuals.
Subject(s)
Chromosome Disorders/genetics , Chromosomes, Human, Pair 3 , Chromosomes, Human, Pair 4 , Chromosome Disorders/etiology , Developmental Disabilities/genetics , Female , Humans , In Situ Hybridization, Fluorescence , India , Male , Oligonucleotide Array Sequence Analysis , Pedigree , Sequence Deletion , Trisomy , Wolf-Hirschhorn Syndrome/geneticsABSTRACT
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.
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Intravenous thrombolysis with alteplase within 4.5 hours from symptom onset is a well-established treatment of acute ischaemic stroke (AIS). The aim was to compare alteplase for AIS between patients aged >80 and ≤80 years in our registry data, from 2013 to 2018. Mechanical thrombectomy cases were excluded. We assessed clinical outcomes over the six-year period and between patients aged over 80 and ≤80 years, using measures including the discharge modified Rankin Scale (mRS), 24-hour National Institutes of Health Stroke Scale (NIHSS) improvement, and symptomatic intracerebral haemorrhage (sICH) rate. Of a total of 805 AIS patients who received intravenous alteplase, 278 (34.5%) were over 80 years old, and 527 (65%) were younger. 616 (76.5%) received thrombolysis ≤ 3 hours after symptom onset and 189 (23.5%) within 3-4.5 hours. Median baseline mRS and NIHSS of the elderly cohort were 1 (IQR 0-5) and 13 (IQR 2-37), respectively, compared to the younger cohort 0 (IQR 0-5) and 9 (IQR 0-29). The sICH rate was 7.2% in the elderly and 4.6% in those ≤80 years, p = 0.05. NIHSS improved within 24 hours in 34% of the elderly cohort compared to 35% in the younger cohort. At hospital discharge, the mortality rate was 9% in the elderly cohort compared to the 6% in the younger cohort, p = 0.154. 25% of patients aged >80 years had mRS ≤ 2 compared to 47% in the younger patients (p < 0.0001). In conclusion, thrombolysis in elderly patients results in clinical improvement comparable to younger patients.
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Introduction: Risk factors for neurological complications in sickle cell disease differ in the adult and pediatric populations. Here, we focused on neurological complications in adults with sickle cell disease. Methods: Patients were selected using the audit data from the St George's Hospital Red Cell Database. The genotyping, demographics, clinical data, and investigation findings were collected. Results: A total of 303 patients were enrolled in the study: hemoglobin S homozygosity (HbSS) genotype 56%, hemoglobin S and C coinheritance (HbSC) genotype 35%, and hemoglobin S and ß-thalassemia coinheritance (HbSß) thalassemia genotype 9%; the mean age was 38.8 years (±13.5 SD) with 46% males. The most common neurological complication was cerebrovascular disease (n = 37, 12%) including those with ischemic stroke (10%), cerebral vasculopathy (3%), and intracranial hemorrhage (1%). Ischemic stroke was common among the HbSS genotype compared with other genotypes (8 vs. 1.6%, p = 0.001). Comparing the patients with sickle cell disease who had suffered a stroke to those who had not, there was a higher proportion of intracranial vasculopathy (p = 0.001, in particular, Moyamoya) and cognitive dysfunction (p < 0.0001). Conclusion: Our cohort supports previous reports that the most common neurological complication in adult sickle cell patients is cerebrovascular disease. Strategies to prevent cerebral vasculopathy and cognitive impairment should be explored.
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INTRODUCTION: Radiolabeled ligands for fibrillar amyloid beta (Aß) peptides are used in positron emission tomography (PET) for dementia diagnosis. Current ligands do not discriminate parenchymal amyloid plaques from cerebral amyloid angiopathy (CAA). METHODS: 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. RESULTS: We observed CAA in non-Alzheimer's dementia (non-AD dementia) and control brains, of comparable extent to those with neuropathologically confirmed AD. Aß-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 Aß40 density and vessel Aß42 density (Spearman rho = 0.855, P < .001). CAA was absent or sparse in subcortical white matter across all patient groups. CONCLUSION: Our data indicate that CAA can be abundant in non-AD brains and raise a cautionary note regarding interpretation of amyloid PET imaging.
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OBJECTIVE: To elucidate the genetic cause of a large 5 generation South Indian family with multiple individuals with predominantly an upper limb postural tremor and posturing in keeping with another form of tremor, namely, dystonic tremor. METHODS: Whole-genome single nucleotide polymorphism (SNP) microarray analysis was undertaken to look for copy number variants in the affected individuals. RESULTS: Whole-genome SNP microarray studies identified a tandem duplicated genomic segment of chromosome 15q24 present in all affected family members. Whole-genome sequencing demonstrated that it comprised a â¼550-kb tandem duplication encompassing the entire LINGO1 gene. CONCLUSIONS: The identification of a genomic duplication as the likely molecular cause of this condition, resulting in an additional LINGO1 gene copy in affected cases, adds further support for a causal role of this gene in tremor disorders and implicates increased expression levels of LINGO1 as a potential pathogenic mechanism.
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INTRODUCTION: Approximately 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). METHODS: We 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. RESULTS: The 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-ß2 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. CONCLUSION: Thrombophilia 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.