Role of atherosclerosis, clot extent, and penumbra volume in headache during ischemic stroke

ABSTRACT

Objective: To investigate the role of large vessel atherosclerosis, blood clot extent, and penumbra volume in relation to headache in ischemic stroke patients.

Methods: In this cross-sectional study, we performed noncontrast CT, CT angiography (CTA), and CT perfusion (CTP) in 284 participants from the Dutch Acute Stroke Study and Leiden Stroke Cohort within 9 hours after ischemic stroke onset. We collected headache characteristics prospectively using a semi-structured questionnaire. Atherosclerosis was assessed by evaluating presence of plaques in extracranial and intracranial vessels and by quantifying intracranial carotid artery calcifications. Clot extent was estimated by the clot burden score on CTA and penumbra volume by CTP. We calculated risk ratios (RRs) with adjustments (aRR) for possible confounders using multivariable Poisson regression.

Results: Headache during stroke was reported in 109/284 (38%) participants. Headache was less prevalent in patients with than in patients without atherosclerosis in the extracranial anterior circulation (35% vs 48%; RR 0.72; 95% confidence interval [CI] 0.54–0.97). Atherosclerosis in the intracranial arteries was also associated with less headache, but this association was not statistically significant. Penumbra volume (aRR 1.08; 95% CI 0.63–1.85) and clot extent (aRR 1.02; 95% CI 0.86–1.20) were not related with headache.

Conclusions: Headache in the early phase of ischemic stroke tends to occur less often in patients with atherosclerosis than in patients without atherosclerosis in the large cerebral arteries. This finding lends support to the hypothesis that vessel wall elasticity is a necessary contributing factor in the occurrence of headache during acute ischemic stroke

Neurology 2016

Zoonotic bacterial meningitis in human adults

ABSTRACT

Objective: To describe the epidemiology, etiology, clinical characteristics, treatment, outcome, and prevention of zoonotic bacterial meningitis in human adults.

Methods: We identified 16 zoonotic bacteria causing meningitis in adults.

Results: Zoonotic bacterial meningitis is uncommon compared to bacterial meningitis caused by human pathogens, and the incidence has a strong regional distribution. Zoonotic bacterial meningitis is mainly associated with animal contact, consumption of animal products, and an immunocompromised state of the patient. In a high proportion of zoonotic bacterial meningitis cases, CSF analysis showed only a mildly elevated leukocyte count. The recommended antibiotic therapy differs per pathogen, and the overall mortality is low.

Conclusions: Zoonotic bacterial meningitis is uncommon but is associated with specific complications. The suspicion should be raised in patients with bacterial meningitis who have recreational or professional contact with animals and in patients living in regions endemic for specific zoonotic pathogens. An immunocompromised state is associated with a worse prognosis. Identification of risk factors and underlying disease is necessary to improve treatment.

Neurology 2016

Lenalidomide long-term neurotoxicity Clinical and neurophysiologic prospective study

ABSTRACT

Objective: To evaluate long-term lenalidomide neurotoxicity and correlation with cumulative dose and hematologic response.

Methods: Nineteen myeloma patients (7 men, mean age 63.2 years) underwent clinical and neurophysiologic assessment at baseline and at 2 (8 patients, group A) or 5 years (11 patients, group B) after starting lenalidomide therapy for relapsed/refractory multiple myeloma. Neuropathy was scored with Total Neuropathy Score clinical version (TNSc). Lenalidomide cumulative dose was correlated with severity of neuropathy and hematologic response.

Results: At enrollment, 7/19 patients (3 in group A, 4 in group B) had neurophysiologic signs of neuropathy secondary to previous chemotherapy, in 2 of them subclinical. Neurophysiologic evidence of sensory axonal neuropathy occurred in 4/8 patients at 2 years follow-up (group A) and in 3/11 patients at 5 years follow-up (group B). Dorsal sural nerve sensory action potential amplitude was the earliest neurophysiologic abnormality. No relevant (≥4) clinical changes were found in TNSc score. Hematologic overall response was 62% in group A and 100% in group B. No correlation was found between lenalidomide cumulative dose and neuropathy or between neuropathy and hematologic response.

Conclusions: In our study, up to 50% of myeloma patients on long-term lenalidomide therapy developed sensory axonal neuropathy. Reduced dorsal sural nerve sensory action potential amplitude was the first neurophysiologic alteration. Neuropathy was usually subclinical or mild, however. Neurotoxicity was independent of lenalidomide cumulative dose and hematologic response.

Neurology 2016

Article Predicting Alzheimer disease from a blood-based biomarker profile A 54-month follow-up

ABSTRACT

Objective: We assessed a blood-based signature, which previously demonstrated high accuracy at stratifying individuals with high or low neocortical β-amyloid burden (NAB), to determine whether it could also identify individuals at risk of progression to Alzheimer disease (AD) within 54 months.

Methods: We generated the blood-based signature for 585 healthy controls (HCs) and 74 participants with mild cognitive impairment (MCI) from the Australian Imaging, Biomarkers and Lifestyle Study who underwent clinical reclassification (blinded to biomarker findings) at 54-month follow-up. The individuals were split into estimated high and low NAB groups based on a cutoff of 1.5 standardized uptake value ratio. We assessed the predictive accuracy of the high and low NAB groupings based on progression to mild cognitive impairment or AD according to clinical reclassification at 54-month follow-up.

Results: Twelve percent of HCs with estimated high NAB progressed in comparison to 5% of HCs with estimated low NAB (odds ratio = 2.4). Forty percent of the participants with MCI who had estimated high NAB progressed in comparison to 5% of the participants with MCI who had estimated low NAB (odds ratio = 12.3). These ratios are in line with those reported for Pittsburgh compound B–PET results. Individuals with estimated high NAB had faster rates of memory decline than those with estimated low NAB.

Conclusion: These findings suggest that a simple blood-based signature not only provides estimates of NAB but also predicts cognitive decline and disease progression, identifying individuals at risk of progressing toward AD at the prodromal and preclinical stages.

Neurology 2016

Probiotics and prebiotic fiber for constipation associated with Parkinson disease An RCT

ABSTRACT

Objectives: Our objective was to evaluate the efficacy of probiotics and prebiotics in patients with Parkinson disease (PD) and constipation.

Methods: We conducted a tertiary setting, randomized, double-blind, placebo-controlled trial in patients with PD with Rome III–confirmed constipation based on 2-week stool diary data at baseline. Patients (n = 120) were randomly assigned (2:1) to either a fermented milk, containing multiple probiotic strains and prebiotic fiber, or placebo, once daily for 4 weeks. The primary efficacy endpoint was the increase in the number of complete bowel movements (CBMs) per week. The key secondary endpoints were 3 or more CBMs and an increase by one or more CBMs per week during weeks 3 and 4.

Results: For the primary endpoint, the consumption of a fermented milk containing probiotics and prebiotics resulted in a higher increase in the number of CBMs (mean 1.2, 95% confidence interval [CI] 0.8–1.6) than placebo (0.1, 95% CI −0.4% to 0.6%) (mean difference 1.1, 95% CI 0.4–1.8; p = 0.002). For the key secondary endpoints, a higher number of patients in the probiotics–prebiotics group vs the placebo group reported 3 or more CBMs (p = 0.030; 58.8% vs 37.5%; odds ratio = 2.4, 95% CI 1.1–5.2) and an increase by one or more CBMs (p = 0.004; 53.8% vs 25.0%; odds ratio = 3.5, 95% CI 1.8–8.1) during weeks 3 and 4.

Conclusions: The consumption of a fermented milk containing multiple probiotic strains and prebiotic fiber was superior to placebo in improving constipation in patients with PD.

ClinicalTrials.gov identifier: NCT02459717.

Classification of evidence: This study provides Class I evidence that for patients with PD who have constipation, fermented milk containing probiotics and prebiotics increases the frequency of CBMs.

Neurology 2016

New diagnostic criteria for neurocysticercosis: Reliability and validity

Objective

The diagnosis of neurocysticercosis (NCC) remains problematic because of the heterogeneity of its clinical, immunological, and imaging characteristics. Our aim was to develop and assess a new set of diagnostic criteria for NCC, which might allow for the accurate detection of, and differentiation between, parenchymal and extraparenchymal disease.

Methods

A group of Latin American NCC experts developed by consensus a new set of diagnostic criteria for NCC. A multicenter, retrospective study was then conducted to validate it. The reference standard for diagnosis of active NCC was the disappearance or reduction of cysts after anthelmintic treatment. In total, three pairs of independent neurologists blinded to the diagnosis evaluated 93 cases (with NCC) and 93 controls (without NCC) using the new diagnostic criteria. Mixed-effects logistic regression models were used to estimate sensitivity and specificity.

Results

Inter-rater reliability (kappa) of diagnosis among evaluators was 0.60. For diagnosis of NCC versus no NCC, the new criteria had a sensitivity of 93.2% and specificity of 81.4%. For parenchymal NCC, the new criteria had a sensitivity of 89.8% and specificity of 80.7% and for extraparenchymal NCC, the new criteria had a sensitivity of 65.9% and specificity of 94.9%.

Interpretation

These criteria have acceptable reliability and validity and could be a new tool for clinicians and researchers. An advantage of the new criteria is that they consider parasite location (ie, parenchymal or extraparenchymal), which is an important factor determining the clinical, immunological, and radiological presentation of the disease, and importantly, its treatment and prognosis. 

Ann Neurol 2016;

Myeloid cells — targets of medication in multiple sclerosis

Discussions of multiple sclerosis (MS) pathophysiology tend to focus on T cells and B cells of the adaptive immune response. The innate immune system is less commonly considered in this context, although dendritic cells, monocytes, macrophages and microglia — collectively referred to as myeloid cells — have prominent roles in MS pathogenesis. These populations of myeloid cells function as antigen-presenting cells and effector cells in neuroinflammation. Furthermore, a vicious cycle of interactions between T cells and myeloid cells exacerbates pathology. Several disease-modifying therapies are now available to treat MS, and insights into their mechanisms of action have largely focused on the adaptive immune system, but these therapies also have important effects on myeloid cells. In this Review, we discuss the evidence for the roles of myeloid cells in MS and the experimental autoimmune encephalomyelitis model of MS, and consider how interactions between myeloid cells and T cells and/or B cells promote MS pathology. Finally, we discuss the direct and indirect effects of existing MS medications on myeloid cell

Nature Reviews Neurology 2016