Search

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.

Abstract 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: 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 β-thalassemia coinheritance (HbSβ) 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.

Abstract Introduction 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). 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. 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. Conclusion Our data indicate that CAA can be abundant in non‐AD brains and raise a cautionary note regarding interpretation of amyloid PET imaging.

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