Are there differences between patients with unifocal nummular headache and those who progress to bifocal nummular headache? A retrospective observational study.

OBJECTIVES: This retrospective observational cohort study aimed to compare clinical characteristics and treatment responses in patients exclusively experiencing unifocal nummular headache (NH) with those who develop the bifocal variant. METHODS: A retrospective study was conducted on patients diagnosed with NH who attended a neurology (headache) outpatient clinic between January 2018 and December 2022. The cohort was divided into two groups: Group 1, exclusive unifocal NH; and Group 2, those developing a secondary focal area of pain, i.e., bifocal NH. Data were collected on demographic characteristics, clinical features, other headache comorbidities, and treatment-related information. RESULTS: A total of 23 patients were included in this study: 12 were categorized as unifocal NH (Group 1) and 11 as bifocal NH (Group 2). There were no differences between the two groups in terms of demographic characteristics, clinical features, or treatment response. Nonetheless, patients with bifocal NH exhibited spontaneous remission rates in the first pain area when compared to the unifocal NH group, with statistically significant differences (36% vs. 0%, p = 0.020). CONCLUSION: In our sample, patients with bifocal NH demonstrated spontaneous remission rates in the initial pain area, a phenomenon not observed in patients with unifocal NH. It is worth noting the limited sample size in the present study, highlighting the need for larger cohorts to validate and further explore our findings.

Headache Phenotypes in Idiopathic Intracranial Hypertension and Its Short-Term Outcomes: A Retrospective Case Series Study.

Background: Idiopathic intracranial hypertension (IIH) presents a complex physiopathology, leading into diverse manifestations, notably variable headache phenotypes. Furthermore, its frequent overlap with migraine complicates the evaluation of treatment benefit for IIH-related headache. Our aim was to investigate if there is any relationship between demographic factors, clinical patterns of headache, treatment response, and headache short-term outcome with the headache phenotype of IIH. Methods: This study was a retrospective analysis of demographic, clinical, and treatment features of patients with idiopathic intracranial hypertension presenting with headache and evaluation of headache outcomes in the first 12 months following treatment. Results: Thirty-two patients were included (median age of onset 29.0 years (interquartile range 25.0 - 38.5), 90% females, median body mass index 32.5 kg/m2; 87.5% (n = 28) with papilledema; median cerebrospinal fluid opening pressure 36.5 cm H2O). Patients presented with migraine (n = 11, 34.4%), tension-type (n = 9, 28.1%), or a not-classifiable headache (n = 12, 37.5%). Regarding treatment and short-term follow-up (12 months), there was a failure of medical treatment in 43.8% (n = 14) and a reduction of headaches (≥ 50%) in 62.5% (n = 20) of the patients. Among headache phenotypes, there were no significant differences regarding demographics, clinical features, clinical patterns, or treatment response at baseline. Also, there were no differences regarding response to treatment or headache outcomes in 1, 3, 6, and 12 months of follow-up. Conclusions: In our study, migraine and unclassifiable types were the most commonly reported headache phenotypes. Headache phenotype does not appear to be an essential factor in allowing clinical distinction, treatment response, or predicting the short-term headache outcome of this intriguing entity.

Are we missing an opportunity? Prehospital delay in patients with acute ischemic stroke and known atrial fibrillation.

INTRODUCTION AND OBJECTIVES: The follow-up of patients with atrial fibrillation (AF) presents an opportunity to alert patients and their families on how to recognize and act in the event of stroke. Our aim was to compare stroke recognition-to-door time and prehospital stroke code activation in patients with known AF (KAF) and AF detected after stroke (AFDAS). METHODS: We performed a retrospective cohort study of consecutive patients receiving acute recanalization treatment for acute ischemic stroke between January 2016 and August 2022, with AF as a potential stroke cause. Patients were divided into KAF and AFDAS, and stroke recognition-to-door time and prehospital stroke code activation were compared. In the KAF subgroup, we assessed whether the use of preadmission anticoagulation was associated with the studied prehospital parameters. RESULTS: We included 438 patients, 290 female (66.2%), mean age 79.3±9.4 years. In total, 238 patients had KAF (54.3%) and 200 (45.7%) had AFDAS. Of those with KAF, 114 (48.1%) were pretreated with anticoagulation. Patients with KAF and AFDAS had no differences in stroke recognition-to-door time (74.0 [55.0-101.0] vs. 78.0 [60.0-112.0] min; p=0.097) or prehospital stroke code activation [148 (64.6%) vs. 128 (65.3%); p=0.965]. In the KAF subgroup, preadmission anticoagulation did not influence stroke recognition-to-door time or mode of hospital admission. CONCLUSION: Stroke recognition-to-door time and prehospital stroke code activation were similar between patients with known or newly diagnosed AF. Preadmission anticoagulation treatment also did not affect the studied parameters. Our findings highlight a missed opportunity to promote stroke knowledge in patients followed due to AF.

The Role of Neurohospitalism in a Specialized Cardiovascular Hospital.

INTRODUCTION: Cardiology and cardiothoracic surgery are among the specialties that most commonly require neurology inpatient consultations. We aimed to study the neurology referrals by the cardiovascular-specialized hospital included in our tertiary hospital center. METHODS: Retrospective study of consecutive patients referred for neurology inpatient consultation between January 1, 2020, and December 31, 2022. We analyzed referrals, patients' characteristics, and the approach taken. A detailed subanalysis was performed for patients diagnosed with acute ischemic stroke (AIS). RESULTS: 143 patients were observed (mean age 67.3 years, 46 [32.2%] females). Most frequent referral reasons were suspected AIS deficits (39.2%), altered mental status (19.6%), suspected seizures (13.3%), and neuroprognostication (11.9%). Mean referral-to-consult time was 2.7 days, and 117 (81.8%) consults were in-person. Additional investigation, treatment changes, and outpatient clinic referral were proposed, respectively, in 79.7%, 60.1%, and 19.6% of patients. Most common diagnoses were AIS (45.5%), hypoxic-ischemic encephalopathy (18.9%), and delirium (7.0%). Regarding patients with AIS (n = 62), most common stroke causes were post-cardiac procedure (44.6%), infective endocarditis (18.5%), aortic dissection (10.8%), acute myocardial infarction (10.8%), and anticoagulant withdrawal in patients with atrial fibrillation (6.2%). Thirty-four AIS patients were diagnosed less than 24 h since last seen well, of which four (6.2%) were treated (three with thrombolysis and one with mechanical thrombectomy). CONCLUSION: AIS is the most common reason for referral in our cardiovascular hospital. Our results highlight the importance of the availability of a neurologist/neurohospitalist with stroke expertise for consultation of inpatients admitted in a specialized cardiovascular hospital.

Thermodynamic Guidelines for the Mechanosynthesis or Solid-State Synthesis of MnFe2O4 at Relatively Low Temperatures.

Herein, thermodynamic assessment is proposed to screen suitable precursors for the solid-state synthesis of manganese ferrite, by mechanosynthesis at room temperature or by subsequent calcination at relatively low temperatures, and the main findings are validated by experimental results for the representative precursor mixtures MnO + FeO3, MnO2 + Fe2O3, and MnO2 +2FeCO3. Thermodynamic guidelines are provided for the synthesis of manganese ferrite from (i) oxide and/or metallic precursors; (ii) carbonate + carbonate or carbonate + oxide powder mixtures; (iii) other precursors. It is also shown that synthesis from metallic precursors (Mn + 2Fe) requires a controlled oxygen supply in limited redox conditions, which is hardly achieved by reducing gases H2/H2O or CO/CO2. Oxide mixtures with an overall oxygen balance, such as MnO + Fe2O3, act as self-redox buffers and offer prospects for mechanosynthesis for a sufficient time (>9 h) at room temperature. On the contrary, the fully oxidised oxide mixture MnO2 + Fe2O3 requires partial reduction, which prevents synthesis at room temperature and requires subsequent calcination at temperatures above 1100 °C in air or in nominally inert atmospheres above 750 °C. Oxide + carbonate mixtures, such as MnO2 +2FeCO3, also yield suitable oxygen balance by the decomposition of the carbonate precursor and offer prospects for mechanosynthesis at room temperature, and residual fractions of reactants could be converted by firing at relatively low temperatures (≥650 °C).

Proteomics to Identify New Blood Biomarkers for Diagnosing Patients With Acute Stroke.

Background Blood biomarkers are a potential tool for early stroke diagnosis. We aimed to perform a pilot and exploratory study on untargeted blood biomarkers in patients with suspected stroke by using mass spectrometry analysis. Methods and Results This was a prospective observational study of consecutive patients with suspected stroke admitted within 6 hours of last being seen well. Blood samples were collected at admission. Patients were divided into 3 groups: ischemic stroke (IS), intracerebral hemorrhage (ICH), and stroke mimics. Quantitative analysis from mass spectrometry data was performed using a supervised approach. Biomarker-based prediction models were developed to differentiate IS from ICH and ICH+stroke mimics. Models were built aiming to minimize misidentification of patients with ICH as having IS. We included 90 patients, one-third within each subgroup. The median age was 71 years (interquartile range, 57-81 years), and 49 participants (54.4%) were women. In quantitative analysis, C3 (complement component 3), ICAM-2 (intercellular adhesion molecule 2), PLGLA (plasminogen like A), STXBP5 (syntaxin-binding protein 5), and IGHV3-64 (immunoglobulin heavy variable 3-64) were the 5 most significantly dysregulated proteins for both comparisons. Biomarker-based models showed 88% sensitivity and 89% negative predictive value for differentiating IS from ICH, and 75% sensitivity and 95% negative predictive value for differentiating IS from ICH+stroke mimics. ICAM-2, STXBP5, PLGLA, C3, and IGHV3-64 displayed the highest importance score in our models, being the most informative for identifying patients with stroke. Conclusions In this proof-of-concept and exploratory study, our biomarker-based prediction models, including ICAM-2, STXBP5, PLGLA, C3, and IGHV3-64, showed 75% to 88% sensitivity for identifying patients with IS, while aiming to minimize misclassification of ICH. Although our methodology provided an internal validation, these results still need validation in other cohorts and with different measurement techniques.

Brain perfusion imaging by multi-delay arterial spin labeling: Impact of modeling dispersion and interaction with denoising strategies and pathology.

PURPOSE: Arterial spin labeling (ASL) acquisitions at multiple post-labeling delays may provide more accurate quantification of cerebral blood flow (CBF), by fitting appropriate kinetic models and simultaneously estimating relevant parameters such as the arterial transit time (ATT) and arterial cerebral blood volume (aCBV). We evaluate the effects of denoising strategies on model fitting and parameter estimation when accounting for the dispersion of the label bolus through the vasculature in cerebrovascular disease. METHODS: We analyzed multi-delay ASL data from 17 cerebral small vessel disease patients (50 ± 9 y) and 13 healthy controls (52 ± 8 y), by fitting an extended kinetic model with or without bolus dispersion. We considered two denoising strategies: removal of structured noise sources by independent component analysis (ICA) of the control-label image timeseries; and averaging the repetitions of the control-label images prior to model fitting. RESULTS: Modeling bolus dispersion improved estimation precision and impacted parameter values, but these effects strongly depended on whether repetitions were averaged before model fitting. In general, repetition averaging improved model fitting but adversely affected parameter values, particularly CBF and aCBV near arterial locations in patients. This suggests that using all repetitions allows better noise estimation at the earlier delays. In contrast, ICA denoising improved model fitting and estimation precision while leaving parameter values unaffected. CONCLUSION: Our results support the use of ICA denoising to improve model fitting to multi-delay ASL and suggest that using all control-label repetitions improves the estimation of macrovascular signal contributions and hence perfusion quantification near arterial locations. This is important when modeling flow dispersion in cerebrovascular pathology.

First evidence of microplastic ingestion in the ocean giant sunfish (Mola mola).

Mola mola is the largest teleost inhabiting our ocean and the presence of microplastics (MP) in this flagship species was, before this study, never described. Thus, this investigation focused on analysing MP ingestion in 53 ocean giant sunfish in the Northeast Atlantic Ocean. A total of 116 MP were found in 79% of the specimens, with a median of 1 MP.ind-1, ranging from 0 to 11 MP.ind-1. Seasonal differences were observed, with more fibers registered in specimens caught in autumn. Among the different size classes observed, the smallest category (<300 µm) was the most frequent (43%). Blue (43%) was the most prevalent color, followed by green (29%) and black (10%). The majority of fragments were styrene acrylic copolymer (53%), while most fibers were rayon (78%). These findings emphasize that the ocean sunfish population crossing the southern waters of Portugal is exposed to microplastic pollution and highlight the need for effective management policies to address plastic pollution in marine ecosystems.

Does Ocean Sunfish Mola spp. (Tetraodontiformes: Molidae) Represent a Risk for Tetrodotoxin Poisoning in the Portuguese Coast?

Tetrodotoxin (TTX) is a potent neurotoxin naturally occurring in terrestrial and marine organisms such as pufferfish. Due to the risk of TTX poisoning, fish of Tetraodontidae family and other puffer-related species must not be placed in the EU markets. This restriction applies to fish of the family Molidae even though no data on toxins' occurrence is available. In this study, the presence of TTX and its analogues was investigated in the main edible tissue (the white muscle) and the main xenobiotics storage organ (the liver) of ocean sunfish Mola spp. (n = 13) from the South Portuguese coast. HILIC-MS/MS analyses did not reveal TTX in the analyzed samples, suggesting an inexistent or very limited risk of TTX poisoning.

Effects of Hypoxia on Coral Photobiology and Oxidative Stress.

Global ocean oxygen (O2) content is decreasing as climate change drives declines in oxygen solubility, strengthened stratification of seawater masses, increased biological oxygen consumption and coastal eutrophication. Studies on the biological effects of nocturnal decreased oxygen concentrations (hypoxia) on coral reefs are very scarce. Coral reefs are fundamental for supporting one quarter of all marine species and essential for around 275 million people worldwide. This study investigates acute physiological and photobiological responses of a scleractinian coral (Acropora spp.) to overnight hypoxic conditions (<2 mg/L of O2). Bleaching was not detected, and visual and physical aspects of corals remained unchanged under hypoxic conditions. Most photobiological-related parameters also did not show significant changes between treatments. In addition to this, no significant differences between treatments were observed in the pigment composition. However, hypoxic conditions induced a significant decrease in coral de-epoxidation state of the xanthophyll cycle pigments and increase in DNA damage. Although the present findings suggest that Acropora spp. is resilient to some extent to short-term daily oxygen oscillations, long-term exposure to hypoxia, as predicted to occur with climate change, may still have deleterious effects on corals.

Clinical pattern and response to treatment of primary stabbing headache: Retrospective case series study from a Portuguese tertiary hospital.

OBJECTIVES: This retrospective case series study aimed to investigate the demographic and clinical patterns of primary stabbing headache (PSH). In addition, we tried to identify subgroups of treatment responses in a neurology outpatient consultation at a Portuguese tertiary hospital. METHODS: Clinical records were retrospectively reviewed and patients meeting the International Classification of Headache Disorders, 3rd edition, criteria for PSH were identified from January 2014 to December 2020. We collected data regarding demographic characteristics, clinical features of the headache, primary headache comorbidities, and information about treatment-related do PSH. RESULTS: Of 1857 patients, 32 (1.7%; mean [SD] age of onset 56 [3.5] years) had the final diagnosis of PSH. Regarding headache characteristics, 20 patients (62.5%) reported episodes of stabbing in fixed locations and 12 (37.5%) in multiple areas; the duration of each attack was between ≤5 s (seven [21.9%]), 5-60 s (20 [62.5%]), and ≥60 s (five [15.6%]). In all, 18 patients (56.3%) had an episodic course (vs. six of 32 [18.8%] an acute course and eight of 32 [25%] a chronic course). In all, 17 patients started medical treatment (53.1%), with total or partial improvement in 10 (58.8%) of them. It was found that patients with pain in fixed locations had a better response to treatment when compared to patients with multiple locations, in a statistically significant way (eight of 11 vs. two of six, p = 0.023). CONCLUSION: In our sample, the mean age of onset of PSH was >50 years and there was a wide range of PSH duration. The duration of each attack (>5 s), the pain in fixed locations, non-daily episodes of the pain in each attack, and the intermittent course of headache were the most prevalent clinical features. Finally, patients with stabbing in localized areas had a better response to treatment.

Pilot study in human healthy volunteers on the mechanisms underlying remote ischemic conditioning (RIC) - Targeting circulating immune cells and immune-related proteins.

Remote ischemic conditioning (RIC) is a novel promising therapy for treatment of neurological diseases, including ischemic stroke. RIC consists of short cycles of ischemia in a distant non-vital organ that may protect other organs against ischemia. Extensive experimental data and some few clinical trials support the neuroprotective role of RIC in ischemic stroke. Nevertheless, the circulating factors involved in this inter-organ communication and neuroprotection are not clarified. This pilot study in humans characterized the innate and adaptive circulating immune cell populations following RIC. This analysis has a particular focus at 24 h after RIC to avoid circadian influence. In silico functional analysis of mass spectrometry data identified 15 immune-related proteins. Our results reveal an immune response following RIC.

Impact of white-matter mask selection on DTI histogram-based metrics as potential biomarkers in cerebral small vessel disease.

OBJECTIVE: Histogram-based metrics extracted from diffusion-tensor imaging (DTI) have been suggested as potential biomarkers for cerebral small vessel disease (SVD), but methods and results have varied across studies. This work aims to assess the impact of mask selection for extracting histogram-based metrics of fractional anisotropy (FA) and mean diffusivity (MD) on their sensitivity as SVD biomarkers. METHODS: DTI data were collected from 17 SVD patients and 12 healthy controls. FA and MD maps were estimated; from these, histograms were computed on two whole-brain white-matter masks: normal-appearing white-matter (NAWM) and mean FA tract skeleton (TBSS). Histogram-based metrics (median, peak height, peak width, peak value) were extracted from the FA and MD maps. These were compared between groups and correlated with the patients' cognitive scores (executive function and processing speed). RESULTS: White-matter mask selection significantly impacted FA and MD histogram metrics. In particular, significant interactions were found between Mask and Group for FA peak height (p = 0.027), MD Median (p = 0.035) and MD peak width (p = 0.047); indicating that the mask used affected their ability to discriminate between groups. In fact, MD peak width showed a significant 8.8% increase in patients when using TBSS (p = 0.037), but not when using NAWM (p = 0.69). Moreover, the mask may have an effect on the correlations with cognitive measures. Nevertheless, MD peak width (TBSS: r = - 0.75, NAWM: r = - 0.71) and MD peak height (TBSS: r = 0.65, NAWM: r = 0.62) remained significantly correlated with executive function, regardless of the mask. CONCLUSION: The impact of the processing methodology, in particular the choice of white-matter mask, highlights the need for standardized MRI data-processing pipelines.

Remote but not Distant: a Review on Experimental Models and Clinical Trials in Remote Ischemic Conditioning as Potential Therapy in Ischemic Stroke.

Stroke is one of the main causes of neurological disability worldwide and the second cause of death in people over 65 years old, resulting in great economic and social burden. Ischemic stroke accounts for 85% of total cases, and the approved therapies are based on re-establishment of blood flow, and do not directly target brain parenchyma. Thus, novel therapies are urgently needed. In this review, limb remote ischemic conditioning (RIC) is revised and discussed as a potential therapy against ischemic stroke. The review targets both (i) fundamental research based on experimental models and (ii) clinical research based on clinical trials and human interventional studies with healthy volunteers. Moreover, it also presents two approaches concerning RIC mechanisms in stroke: (i) description of the underlying cerebral cellular and molecular mechanisms triggered by limb RIC that promote neuroprotection against stroke induced damage and (ii) the identification of signaling factors involved in inter-organ communication following RIC procedure. Limb to brain remote signaling can occur via circulating biochemical factors, immune cells, and/or stimulation of autonomic nervous system. In this review, these three hypotheses are explored in both humans and experimental models. Finally, the challenges involved in translating experimentally generated scientific knowledge to a clinical setting are also discussed.

Regional patterns of δ 13C and δ 15N for European common cuttlefish (Sepia officinalis) throughout the Northeast Atlantic Ocean and Mediterranean Sea.

Stable isotope compositions of carbon and nitrogen (expressed as δ 13C and δ 15N) from the European common cuttlefish (Sepia officinalis) were measured in order to evaluate the utility of using these natural tracers throughout the Northeast Atlantic Ocean and Mediterranean Sea (NEAO-MS). Mantle tissue was obtained from S. officinalis collected from 11 sampling locations spanning a wide geographical coverage in the NEAO-MS. Significant differences of both δ 13C and δ 15N values were found among S. officinalis samples relative to sampling location. δ 13C values did not show any discernable spatial trends; however, a distinct pattern of lower δ 15N values in the Mediterranean Sea relative to the NEAO existed. Mean δ 15N values of S. officinalis in the Mediterranean Sea averaged 2.5‰ lower than conspecifics collected in the NEAO and showed a decreasing eastward trend within the Mediterranean Sea with the lowest values in the most eastern sampling locations. Results suggest δ 15N may serve as a useful natural tracer for studies on the population structure of S. officinalis as well as other marine organisms throughout the NEAO-MS.