The Clinical and Radiological Spectrum of Hippocampal Pathology in Amyotrophic Lateral Sclerosis

Hippocampal pathology in Amyotrophic Lateral Sclerosis (ALS) remains surprisingly under recognized despite compelling evidence from neuropsychology, neuroimaging and neuropathology studies. Hippocampal dysfunction contributes significantly to the clinical heterogeneity of ALS and requires structure-specific cognitive and neuroimaging tools for accurate in vivo evaluation. Recent imaging studies have generated unprecedented insights into the presymptomatic and longitudinal processes affecting this structure and have contributed to the characterisation of both focal and network-level changes. Emerging neuropsychology data suggest that memory deficits in ALS may be independent from executive dysfunction. In the era of precision medicine, where the development of individualized care strategies and patient stratification for clinical trials are key priorities, the comprehensive review of hippocampal dysfunction in ALS is particularly timely

Health-related quality of life, assessed with a disease-specific questionnaire, in Swedish adults suffering from well-diagnosed food allergy to staple foods

BACKGROUND: Our aim was to investigate the factors that affect health related quality of life (HRQL) in adult Swedish food allergic patients objectively diagnosed with allergy to at least one of the staple foods cow’s milk, hen’s egg or wheat. The number of foods involved, the type and severity of symptoms, as well as concomitant allergic disorders were assessed. METHODS: The disease-specific food allergy quality of life questionnaire (FAQLQ-AF), developed within EuroPrevall, was utilized. The questionnaire had four domains: Allergen Avoidance and Dietary Restrictions (AADR), Emotional Impact (EI), Risk of Accidental Exposure (RAE) and Food Allergy related Health (FAH). Comparisons were made with the outcome of the generic questionnaire EuroQol Health Questionnaire, 5 Dimensions (EQ-5D). The patients were recruited at an outpatient allergy clinic, based on a convincing history of food allergy supplemented by analysis of specific IgE to the foods in question. Seventy-nine patients participated (28 males, 51 females, mean-age 41 years). RESULTS: The domain with the most negative impact on HRQL was AADR, assessing the patients’ experience of dietary restrictions. The domain with the least negative impact on HRQL was FAH, relating to health concerns due to the food allergy. One third of the patients had four concomitant allergic disorders, which had a negative impact on HRQL. Furthermore, asthma in combination with food allergy had a strong impact. Anaphylaxis, and particularly prescription of an epinephrine auto-injector, was associated with low HRQL. These effects were not seen using EQ-5D. Analyses of the symptoms revealed that oral allergy syndrome and cardiovascular symptoms had the greatest impact on HRQL. In contrast, no significant effect on HRQL was seen by the number of food allergies. CONCLUSIONS: The FAQLQ-AF is a valid instrument, and more accurate among patients with allergy to staple foods in comparison to the commonly used generic EQ-5D. It adds important information on HRQL in food allergic adults. We found that the restrictions imposed on the patients due to the diet had the largest negative impact on HRQL. Both severity of the food allergy and the presence of concomitant allergic disorders had a profound impact on HRQL

S100b in acute ischemic stroke clots is a biomarker for post-thrombectomy intracranial hemorrhages

Background and purposePost-thrombectomy intracranial hemorrhages (PTIH) are dangerous complications of acute ischemic stroke (AIS) following mechanical thrombectomy. We aimed to investigate if S100b levels in AIS clots removed by mechanical thrombectomy correlated to increased risk of PTIH.MethodsWe analyzed 122 thrombi from 80 AIS patients in the RESTORE Registry of AIS clots, selecting an equal number of patients having been pre-treated or not with rtPA (40 each group). Within each subgroup, 20 patients had developed PTIH and 20 patients showed no signs of hemorrhage. Gross photos of each clot were taken and extracted clot area (ECA) was measured using ImageJ. Immunohistochemistry for S100b was performed and Orbit Image Analysis was used for quantification. Immunofluorescence was performed to investigate co-localization between S100b and T-lymphocytes, neutrophils and macrophages. Chi-square or Kruskal-Wallis test were used for statistical analysis.ResultsPTIH was associated with higher S100b levels in clots (0.33 [0.08–0.85] vs. 0.07 [0.02–0.27] mm2, H1 = 6.021, P = 0.014*), but S100b levels were not significantly affected by acute thrombolytic treatment (P = 0.386). PTIH was also associated with patients having higher NIHSS at admission (20.0 [17.0–23.0] vs. 14.0 [10.5–19.0], H1 = 8.006, P = 0.005) and higher number of passes during thrombectomy (2 [1–4] vs. 1 [1–2.5], H1 = 5.995, P = 0.014*). S100b co-localized with neutrophils, macrophages and with T-lymphocytes in the clots.ConclusionsHigher S100b expression in AIS clots, higher NIHSS at admission and higher number of passes during thrombectomy are all associated with PTIH. Further investigation of S100b expression in AIS clots by neutrophils, macrophages and T-lymphocytes could provide insight into the role of S100b in thromboinflammation

Is DAO in serum affected by food challenge with a histamine-rich meal?

This case study examines the kinetics of the diamine oxidase levels after challenge with a histamine-rich meal in patients with histamine intolerance as an alternative diagnostic tool to conventional tests combined with the dietary intervention

Corticosteroids for spontaneous intracranial hypotension: a case-report and critical review focusing on pathophysiology and treatment

Background Spontaneous intracranial hypotension (SIH) is characterized by positional headache caused by low CSF pressure, without any major traumatic event. Optimal treatment is still debated; epidural blood patch (EBP) is usually used after unsuccessful conservative treatment with variable efficacy and potentially severe complications. Although steroids have been reported to be beneficial, their effectiveness is still controversial, and more clinical evidence is needed. Case presentation A 37-year-old woman was admitted to the neurology department due to severe orthostatic headache with nausea over the last 5 days. No trauma history or spinal manipulation were mentioned. On arrival, neurological examination, brain CT, and laboratory investigation were normal. Intracranial hypotension was clinically suspected, and lumbar puncture revealed low opening pressure. Brain MRI demonstrated pachymeningeal gadolinium enhancement and distended and rounded dural venous sinuses, while cervicothoracic spine MRI revealed thoracic CSF leakage, leading to SIH diagnosis. The patient was treated with high-dose intravenous methylprednisolone, with complete clinical resolution within 24 h. Conclusions Our case, combined with literature evidence, supports the high-dose intravenous corticosteroids as a reasonable treatment option in selected cases, before trying EBP or surgical repair. Randomized clinical trials are needed, in order to optimize SIH patients' outcomes

The Clinical and Radiological Spectrum of Hippocampal Pathology in Amyotrophic Lateral Sclerosis

Hippocampal pathology in Amyotrophic Lateral Sclerosis (ALS) remains surprisingly under recognized despite compelling evidence fromneuropsychology, neuroimaging and neuropathology studies. Hippocampal dysfunction contributes significantly to the clinical heterogeneity of ALS and requires structure-specific cognitive and neuroimaging tools for accurate in vivo evaluation. Recent imaging studies have generated unprecedented insights into the presymptomatic and longitudinal processes affecting this structure and have contributed to the characterisation of both focal and network-level changes. Emerging neuropsychology data suggest that memory deficits in ALS may be independent from executive dysfunction. In the era of precision medicine, where the development of individualized care strategies and patient stratification for clinical trials are key priorities, the comprehensive review of hippocampal dysfunction in ALS is particularly timely

New molecular diagnostic trends and biomarkers for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurodegenerative disorder. Two forms are recognized, familial (FALS) that accounts for 5-10% of ALS cases, and sporadic (SALS) that accounts for the rest. Early diagnosis of ALS is important because it improves their therapeutic efficacy. Current diagnosis is based on clinical assessment and requires approximately 12 months, leading to a significant delay in drug administration. Therefore, new methods are required for the earlier diagnosis of ALS. Screening for pathogenic variants in known ALS-associated genes is already exploited as a diagnostic tool in ALS but cannot be applied for population-based screening. New circulating biomarkers (proteins or small molecules) are needed for initial screening, whereas specific diagnostic methods can be applied to confirm the presence of pathogenic variants in the selected population subgroup. Lipids appear as promising biomarkers for population-based screening and for monitoring disease progression. Genetic analysis can also assist in the prediction of disease progression by analyzing disease-modifying genes, for example, EPHA4 and CHGB. Furthermore, molecular diagnosis will aid the stratification of ALS patients for improved pharmacological approaches. Here, we discuss current and novel diagnostic strategies and how they can be applied to revolutionize the field of ALS molecular diagnosis

The impact of occlusion location and bridging therapy in patients affected by acute ischemic stroke in determining the total number of passes required to remove the clot and the final revascularization outcome

Purpose Our purpose was to assess the impact of occlusion location in patients suffering from Acute Ischemic Stroke (AIS) on the total number of passes (attempts) necessary to retrieve the clot and on final revascularization outcome. Moreover, we analysed the impact of bridging-therapy, i.e. the concomitant use of IV tPA (intravenous tissue plasminogen activator) and mechanical thrombectomy (MT) on the different categories of occlusion locations. Methods 550 mechanically extracted thrombi were collected from four partner hospitals: Beaumont (Dublin) Sahlgrenska (Gothenburg), National Institute of Clinical Neurosciences (Budapest) and Metropolitan Hospital (Piraeus). In the vast majority of the cases (311 patients, 56.5%) the thrombus was located in the Middle Cerebral Artery (MCA), followed by Carotid Terminus/Internal Carotid Artery (ICA) in 89 cases (16.2%) and by vertebral/basilar artery (45 patients, 8.2%). In 65 cases (11.8%) a tandem occlusion, i.e. the occlusion of both ICA and MCA was found, while a dual occlusion occurred in 26 cases (4.7%). 248 patients (45.1%) underwent bridging-therapy, while 291 patients (52.9%) were treated with MT alone. For 11 patients (2%) we have no information whether tPA was administered or not. Recanalization rate was defined by using the modified Thrombolysis In Cerebral Infarction (mTICI) score. Non-parametric Kruskal-Wallis test using IBM SPSS-25 software was used for statistical analysis. Results Occlusion location had a significant impact on the total number of passes required to retrieve the clot as well as on final revascularization outcome. The cases with tandem and dual occlusion showed higher number of procedural passes and lower percentage of complete revascularizations (mTICI=3, Table 1). Bridging-therapy did not significantly reduce the total number of passes or improve the recanalization rates for patients with singular occlusion. On the other hand, bridging-therapy significantly lowered the total number of passes to remove the clot in patients with dual and tandem occlusion (N=87, mean for MT+tPA= 2.63±1.73, MT alone=3.80±2.14, H1=7.608, p=0.006*), but had no statistically significant effect on the final mTICI score (N=87, H1=0.266, p=0.606). Conclusion This study suggests that occlusion location significantly influences the total number of procedural passes in MT procedures as well as the final revascularization outcome. Furthermore, bridging-therapy lowers the number of procedural passes in cases of tandem and dual occlusion without having significant effect on final mTICI score. Funding: Science Foundation Ireland (Grant Number 13/RC/2073) and Cerenovus.Science Foundation Ireland (Grant Number 13/RC/2073) and Cerenovus.non-peer-reviewe