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Migraine is a common neurovascular disorder characterized by recurrent episodes of headache and associated neurological symptoms. At present, a significant portion of patients do not obtain a satisfactory response to acute pain-relieving therapies, including NSAIDs and triptans. In this context, pharmacogenetics plays a key role in the understanding of such a diverse response. In order to investigate whether functional polymorphisms in proinflammatory cytokine genes (IL-1α, IL-1β, IL-1RN; IL-6 and TNF-α) may influence the response to acute treatment, 313 consecutive patients with episodic migraine without aura were enrolled. Pain relief by administration of NSAIDs or triptans for three consecutive migraine attacks was evaluated. We found a significant association between A allele of the TNF-α promoter (−308 A/G) and a lack of efficacy after NSAID administration (p < 0.01, OR 2.51, 95% CI: 1.33 < OR < 4.75 compared to the G allele). Remaining polymorphisms had no significant effect on pain relief. Our study showed that a functional polymorphism in the TNF-α gene significantly modulates the clinical response to NSAID administration in acute attacks. Patients with higher production of the active cytokine during stress showed a significantly lower anti-migraine effect. Our results further support a role for TNF-α in the pathophysiological mechanisms of migraine attack. [ABSTRACT FROM AUTHOR]

Orexins are hypothalamic neuropeptides that regulate several physiological functions, such as appetite, arousal, cognition, stress, sleep and metabolism. Emerging pieces of evidence suggest an orexinergic dysfunction in several neuropsychiatric disorders, including depression, anxiety and addiction. A syndromic overlap between behavioural variant frontotemporal dementia (bvFTD) and several psychiatric disorders was recently demonstrated. Therefore, we analysed cerebrospinal fluid (CSF) orexin A concentrations of 40 bvFTD and 32 non-demented patients, correlating neuropeptide concentrations with several clinical characteristics. A significant increase of orexin A concentrations was found in bvFTD patients when compared to controls (p<0.001). CSF orexin A concentration showed a correlation with Mini-Mental State Examination scores, drug assumption, history of compulsive behaviour and extrapyramidal signs. Moreover, we found a relationship between CSF markers of neurodegeneration, total tau and Aβ1–42 and CSF orexin A concentrations. Our study provides evidence of an orexinergic dysfunction in bvFTD, correlating with several clinical symptoms. Further larger studies are needed to confirm our data. [ABSTRACT FROM AUTHOR]

In the current work, we present a descriptive fluid-structure interaction computational study of the end-to-side radio-cephalic arteriovenous fistula. This allows us to account for the different thicknesses and elastic properties of the radial artery and cephalic vein. The core of the work consists in simulating different arteriovenous fistula configurations obtained by virtually varying the anastomosis angle, i.e. the angle between the end of the cephalic vein and the side of the radial artery. Since the aim of the work is to understand the blood dynamics in the very first days after the surgical intervention, the radial artery is considered stiffer and thicker than the cephalic vein. Our results demonstrate that both the diameter of the cephalic vein and the anastomosis angle play a crucial role to obtain a blood dynamics without re-circulation regions that could prevent fistula failure. When an anastomosis angle close to the perpendicular direction with respect to the radial artery is combined with a large diameter of the cephalic vein, the recirculation regions and the low Wall Shear Stress (WSS) zones are reduced. Conversely, from a structural point of view, a low anastomosis angle with a large diameter of the cephalic vein reduces the mechanical stress acting on the vessel walls. • Fluid-structure interaction analysis for different configurations of the arteriovenous fistula. • Mismatch of the arterial and venous Young's moduli and different vessel thicknesses. • Real reconstruction of the shape of the anastomosis region. • The diameter of the cephalic vein drastically influences the hemodynamics. [ABSTRACT FROM AUTHOR]

Background: Headache is a frequent symptom of the novel coronavirus 19 disease (COVID-19). To date, there are limited information on how COVID-19 affects migraine and its treatment. Case description: A 47-year-old patient, suffering from chronic migraine and medication-overuse headache, in September 2020 started erenumab at 70 mg once monthly. Two months later, monthly migraine days decreased from 20 to 5. On the third month, the patient developed mild COVID-19 symptoms, experiencing extreme fatigue, hyposmia, and attention deficit, resulting positive for SARS-Cov-2 RNA. A significant increase in migraine attacks frequency was reported. Brain MRI and EEG were normal. Erenumab was increased to 140 mg/month, and attacks decreased to 3 monthly migraine days and remained stable. All the headaches experienced by our patient during the infection fulfilled the criteria of the migraine attacks, without tensive-like features. Conclusion: We report the first case showing the effects of SARS-CoV-2 infection in a patient with chronic migraine and medication-overuse headache treated with erenumab. Our case description suggests that inflammatory processes induced by SARS-CoV-2 infection may increase the frequency of migraine attacks, probably through an activation of the trigeminovascular system. Whether treatment with CGRP receptor antagonist may influence COVID is still debated. Additional studies regarding anti-CGRP monoclonal antibodies in COVID-19 patients are warranted. [ABSTRACT FROM AUTHOR]

Highlights • Deletion of Fgf14 causes a reduction of food intake, climbing, digging and burying novel objects. • Fgf14 knock-out mice have normal spontaneous locomotion in a novel environment, ruling out effects of motor impairment. • Fgf14 knock-out mice show reduced aggressivity and sexual behavior. • Fgf14 knock-out mice show normal sociability. Abstract Sexual disturbances, and aggressivity are a major social problem. However, the molecular mechanisms involved in the control of these behaviors are largely unknown. FGF14, which is an intracellular protein controlling neuronal excitability and synaptic transmission, has been implied in neurologic and psychiatric disorders. Mice with Fgf14 deletion show blunted responses to drugs of abuse. By behavioral tests we show that male Fgf14 knockout mice have a marked reduction of several behaviors including aggressivity and sexual behavior. Other behaviors driven by spontaneous initiative like burying novel objects and spontaneous digging and climbing are also reduced in Fgf14 knockout mice. These deficits cannot be attributed to a generalized decrease of activity levels, because in the open field test Fgf14 knockout mice have the same spontaneous locomotion as wild types and increased rearing. Our results show that Fgf14 is important to preserve a set of behaviors and suggest that fine tuning of neuronal function by Fgf14 is an important mechanism of control for such behaviors. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with both genetic and environmental factors contributing to its pathogenesis. While early-onset AD has well-established genetic determinants, the genetic basis for late-onset AD remains less clear. This study investigates a large Italian family with late-onset autosomal dominant AD, identifying a novel rare missense variant in GRIN2C gene associated with the disease, and evaluates the functional impact of this variant. Methods: Affected and unaffected members from a Northern Italian family were included. Genomic DNA from family members was extracted and initially screened for pathogenic mutations in APP, PSEN1, and PSEN2, and screened for 77 genes associated with neurodegenerative conditions using NeuroX array assay. Exome sequencing was performed on three affected individuals and two healthy relatives. Bioinformatics analyses were conducted. Functional analysis was performed using primary neuronal cultures, and the impact of the variant was assessed through immunocytochemistry and electrophysiology. Results: Pathogenic variants were not identified in APP, PSEN1, or PSEN2, nor in the 77 genes in NeuroX array assay. Exome Sequencing revealed the c.3215C > T p.(A1072V) variant in GRIN2C gene (NM 000835.6), encoding for the glutamate ionotropic receptor N-methyl-D-aspartate receptor (NMDA) type subunit 2C (GluN2C). This variant segregated in 6 available AD patients in the family and was absent in 9 healthy relatives. Primary rat hippocampal neurons overexpressing GluN2CA1072V showed an increase in NMDAR-induced currents, suggesting altered glutamatergic transmission. Surface expression assays demonstrated an elevated surface/total ratio of the mutant GluN2C, correlating with the increased NMDAR current. Additionally, immunocytochemistry revealed in neurons expressing the mutant variant a reduced colocalization between the GluN2C subunit and 14-3-3 proteins, which are known to facilitate membrane trafficking of NMDARs. Discussion: We identified a rare missense variant in GRIN2C associated with late-onset autosomal dominant Alzheimer's disease. These findings highlight the role of GluN2C-containing NMDARs in glutamatergic signaling and their potential contribution to AD pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Spinocerebellar ataxia 17 (SCA17) is a rare autosomal dominant form of inherited ataxia, caused by heterozygous trinucleotide repeat expansions encoding glutamine in the TATA box-binding protein (TBP) gene. Case description: We describe the clinical history, neuropsychological, and neuroimaging findings of a 42-year-old patient who presented for medical attention showing prevalent behavioral and cognitive problems along with progressively worsening gait disturbances. The patient's family history indicated the presence of SCA17 in the maternal lineage. Genetic analysis confirmed a heterozygous 52-CAG pathological expansion repeat in TBP (normal interval, 25–40 CAG. Brain 18-fluorodeoxyglucose positron emission tomography (FDG-PET) showed bilateral hypometabolism in the sensorimotor cortex, with a slight predominance on the right, as well as in the striatal nuclei and thalamic hypermetabolism, a finding similar to what is observed in Huntington's disease. The patient also underwent neuropsychological evaluation, which revealed mild cognitive impairment and difficulties in social interaction and understanding other's emotions (Faux Pas Test and Reading the Mind in the Eyes Test). Conclusion: Our report emphasizes the importance of considering SCA17 as a possible diagnosis in patients with a prevalent progressive cognitive and behavioral disorders, even with a pattern of FDG-PET hypometabolism not primarily indicative of this disease. [ABSTRACT FROM AUTHOR]

Objective: In this systematic review and meta-analysis, we critically evaluate available evidence regarding the association between primary headaches and subsequent decline of cognitive function and dementia. Background: Recent studies suggested that headache disorders may increase the risk for dementia. However, available studies are conflicting. Methods: To identify qualifying studies, we searched scientific databases, including Pubmed, Scopus, Web of Science, Science Direct and BMC, screening for relevant papers. In order to reduce the heterogeneity between different studies, the analyses were further subdivided according to the clinical diagnoses and the study methodologies. Results: We identified 23 studies investigating the association between primary headaches and the risk of dementia. Of these, 18 met our inclusion criteria for meta-analysis (covering 924.140 individuals). Overall effect-size shows that primary headaches were associated with a small increase in dementia risk (OR = 1,15; CI 95%: 1,03–1,28; p = 0,02). Analyzing subgroups, we found that migraine was associated with both a moderate increased risk of all-cause dementia (OR = 1,26; p = 0,00; 95% CI: 1,13–1,40) as well as a moderate increased risk of Alzheimer's disease (OR = 2,00; p = 0,00; 95% CI: 1,46–2,75). This association was significant in both case–control and retrospective cohort studies but not in prospective studies. Conclusions: Our study supports the presence of a link between primary headaches and dementia. However, in the subgroup analysis, only patients with migraine showed a moderate increase risk for all-cause dementia and for Alzheimer's disease. Additional rigorous studies are needed to elucidate the possible role of primary headaches on the risk of developing cognitive impairment and dementia. [ABSTRACT FROM AUTHOR]

Background: Synaptic disruption precedes neuronal death and correlates with clinical features of Alzheimer's disease (AD). The identification of fluid biomarkers of synaptic damage is emerging as a goal for early and accurate diagnosis of the disease. Objective: To perform a systematic review and meta-analysis to determine whether fluid biomarkers of synaptic damage are impaired in AD. Methods: PubMed, Scopus, EMBASE, and Web of Science were searched for articles reporting synaptic proteins as fluid biomarkers in AD and cognitively unimpaired (CU) individuals. Pooled effect sizes were determined using the Hedge G method with random effects. Questions adapted from the Quality Assessment of Diagnostic Accuracy Studies were applied for quality assessment. A protocol for this study has been previously registered in PROSPERO (registration number: CRD42021277487). Results: The search strategy identified 204 articles that were assessed for eligibility. A total of 23 studies were included in the systematic review and 15 were included in the meta-analysis. For Neurogranin, 827 AD and 1,237 CU subjects were included in the meta-analysis, showing a significant increase in cerebrospinal fluid of patients with AD compared to CU individuals, with an effect size of 1.01 (p < 0.001). A significant increase in SNAP-25 and GAP-43 levels in CSF of patients with AD was observed. Conclusion: Neurogranin, SNAP-25, and GAP-43 are possible biomarkers of synaptic damage in AD, and other potential synaptic biomarkers are emerging. This meta-analysis also revealed that there are still relatively few studies investigating these biomarkers in patients with AD or other dementias and showed wide heterogeneity in literature. [ABSTRACT FROM AUTHOR]

The identification of reliable biomarkers in biological fluids is paramount to optimizing the diagnosis of Alzheimer's disease (AD). Measurement of Aβ42, t-tau, and p-tau in cerebrospinal fluid (CSF) is the most accepted method to support the diagnosis of AD. However, lumbar puncture represents an invasive investigation, whereas saliva is one of the most accessible body fluids. The aim of our study was to investigate salivary concentrations in AD and evaluate the correlation between salivary and CSF Aβ42 concentrations in AD patients, patients with non-AD dementias, and controls. We recruited 100 subjects: 18 AD patients, 64 patients with non-AD dementias, and 18 controls. The mean saliva Aβ42 concentrations in AD patients were higher than in controls (p < 0.001), and to patients with non-AD dementias (p = 0.001). A significant negative correlation between salivary and CSF Aβ42 concentrations was found in the overall group (r = −0.562, p < 0.001) and in non-AD patients (r = −0.443, p < 0.001). Salivary Aβ42 concentrations positively correlated with CSF t-tau (r = 0.321, p = 0.001) and p-tau (r = 0.297, p = 0.001). Our study showed that in AD patients' saliva, Aβ42 concentrations are specifically increased, and we found an interesting negative correlation between CSF and salivary Aβ42 concentrations that warrants further investigation. [ABSTRACT FROM AUTHOR]

Several studies have revealed defects in autophagy in neurodegenerative disorders including Alzheimer's disease (AD) and frontotemporal dementia (FTD). SQSTM1/p62 plays a key role in the autophagic machinery and may serve as a marker for autophagic flux in vivo. We investigated the role of p62 in neurodegeneration, analyzing its concentrations in the CSF of AD and FTD patients. We recruited 76 participants: 22 patients with AD, 28 patients with FTD, and 26 controls. CSF p62 concentrations were significantly increased in AD and FTD patients when compared to controls, which persisted after adjusting for age (p = 0.01 and p = 0.008, respectively). In female FTD patients, p62 positively correlated with the neurodegenerative biomarkers t-Tau and p-Tau. A significant correlation between CSF p62 concentrations and several clinical features of AD was found. Our data show that p62 is increased in CSF of AD and FTD patients, suggesting a key role of autophagy in these two disorders. The levels of p62 in CSF may reflect an altered autophagic flux, and p62 could represent a potential biomarker of neurodegeneration. [ABSTRACT FROM AUTHOR]

Background: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to reduce the risk of developing Coronavirus Disease 2019 (COVID-19). Despite the significant benefits in terms of reduced risk of hospitalization and death, different adverse events may present after vaccination: among them, headache is one of the most common, but nowadays there is no summary presentation of its incidence and no description of its main features. Methods: We searched PubMed and EMBASE covering the period between January 1st 2020 and August 6th, 2021, looking for record in English and with an abstract and using three main search terms (with specific variations): COVID-19/SARS-CoV-2; Vaccination; headache/adverse events. We selected manuscript including information on subjects developing headache after injection, and such information had to be derived from a structured form (i.e. no free reporting). Pooled estimates and 95% confidence intervals were calculated. Analyses were carried out by vaccine vs. placebo, by first vs. second dose, and by mRNA-based vs. "traditional" vaccines; finally, we addressed the impact of age and gender on post-vaccine headache onset. Results: Out of 9338 records, 84 papers were included in the review, accounting for 1.57 million participants, 94% of whom received BNT162b2 or ChAdOx1. Headache was generally the third most common AE: it was detected in 22% (95% CI 18–27%) of subjects after the first dose of vaccine and in 29% (95% CI 23–35%) after the second, with an extreme heterogeneity. Those receiving placebo reported headache in 10–12% of cases. No differences were detected across different vaccines or by mRNA-based vs. "traditional" ones. None of the studies reported information on headache features. A lower prevalence of headache after the first injection of BNT162b2 among older participants was shown. Conclusions: Our results show that vaccines are associated to a two-fold risk of developing headache within 7 days from injection, and the lack of difference between vaccine types enable to hypothesize that headache is secondary to systemic immunological reaction than to a vaccine-type specific reaction. Some descriptions report onset within the first 24 h and that in around one-third of the cases, headache has migraine-like features with pulsating quality, phono and photophobia; in 40–60% of the cases aggravation with activity is observed. The majority of patients used some medication to treat headache, the one perceived as the most effective being acetylsalicylic acid. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Cognitive dysfunction, social behavior disorder, cerebellar ataxia, and atypical brain FDG-PET presentation in spinocerebellar ataxia 17: a case report" published in the journal Neurological Sciences. The correction addresses a spelling error in one of the author's names, stating that "Chiara Lombardi" should be corrected to "Chiara Lombardo." The original article has been corrected accordingly. The publisher, Springer Nature, maintains a neutral stance on jurisdictional claims and institutional affiliations. The authors of the article are listed as Alberto Grassini, Aurora Cermelli, Fausto Roveta, Michela Zotta, Adriana Lesca, Andrea Marcinnò, Fabio Ferrandes, Elisa Piella, Silvia Boschi, Chiara Lombardo, Alfredo Brusco, Salvatore Gallone, Elisa Rubino, Amalia Bruni, and Innocenzo Rainero. [Extracted from the article]

Objectives: The study aims to assess the impact of the second COVID-19 pandemic wave on migraine characteristics. Methods: This is an observational cross-sectional study conducted on migraine patients previously interviewed during the first Italian pandemic outbreak. A second structured telephone interview was conducted between 20 November 2020 and 18 January 2021. We compared migraine characteristics among T0 (before pandemic), T1 (during the first pandemic phase), and T2 (during the second pandemic phase). Results: Among the 433 patients interviewed during the first pandemic phase, 304 cases were finally considered. One hundred forty-eight patients had a control visit between March 2020 and December 2020, 120 had an in-person visit, 14 by phone, the remainder used telemedicine software provided by the hospital. Frequency of headache, number of symptomatic drugs and headache intensity worsened during T2, compared to T0 and T1, especially in episodic migraine. Headache intensity increased relating to the negative emotional impact of the pandemic. Migraine management during the pandemic did not influence the clinical outcome. Conclusion: The prolongation of the pandemic seems to have a negative impact on migraine evolution. The arousal and negative psychological behavior toward the COVID-19 outbreak seem to worsen migraine. [ABSTRACT FROM AUTHOR]