Functional seizures and binge eating disorder: A cross-sectional study.

OBJECTIVE: Functional seizures (FS) are brief, involuntary changes in behaviour or consciousness, distinct from epileptic seizures, potentially associated with psychological dissociation. Binge eating disorder (BED) was linked to psychological and somatic dissociation also. However, any connection between FS and BED is insufficiently explored. We aimed to assess BED prevalence in individuals with FS, anxiety/depression (AD), and healthy subjects (HS), to investigate dissociation's link to binge eating, and to explore psychological characteristics of FS individuals. METHOD: Participants underwent evaluations based on ILAE guidelines and DSM-5 criteria, including questionnaires assessing binge eating, dissociation, anxiety, depression and personality traits. Inclusion criteria were age > 18 years, no history of substance abuse, no history of epilepsy, and no use of medications inducing eating disorders. RESULTS: We found significantly more frequent and severe binge-eating symptoms in individuals with FS and AD compared to HS. Depression and dissociation correlated with binge-eating symptoms in both AD and FS groups. The PID-5 facet 'Perseveration' predicted binge-eating attitudes only in FS individuals; they reported more childhood emotional neglect and increased disinhibition compared do AD people. DISCUSSION: This study underscores the commonality of binge-eating symptoms in FS individuals, emphasizing its association with dissociation symptoms. This finding support the hypothesis of a link between dissociation and eating disorders. Unique clinical characteristics in individuals with FS were identified, as a compulsive dimension related to binge-eating symptoms, providing a comprehensive understanding of their psychological profile and guiding targeted therapeutic interventions.

Efficacy of an oral suspension containing xyloglucan and pea proteins on a murine model of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is the most common foregut disease, affecting about 20% of the adult population. Esophageal epithelial barrier plays a fundamental role in the pathophysiology of GERD; however, pharmacological therapies mainly aim to reduce the acidity of the gastroesophageal environment rather than to protect esophageal tissue integrity. This study aims to evaluate the efficacy of an oral solution containing xyloglucan and pea proteins (XP) in reestablishing gastroesophageal tissue integrity and biochemical markers. To induce GERD, C57BL/6 mice were alternatively overfed and fasted for 56 days and then treated with XP, sodium alginate, omeprazole, or omeprazole+XP twice daily for 7 days. Gastric pain and inflammatory markers were evaluated after 3 and 7 days of treatment. After sacrifice, the esophagi and stomachs were surgically removed for macroscopic and histological examination. Gastric pain was significantly reduced at days 3 and 7 by XP, omeprazole, and omeprazole+XP, while alginates were ineffective at day 3. XP was able to diminish gastric macroscopic damage and demonstrated the same efficacy as omeprazole in reducing esophageal damage. XP significantly reduced histological damage, with an efficacy comparable to that of omeprazole, but superior to alginates. Inflammatory markers were significantly reduced by XP, with superior efficacy compared with alginates at day 7. Interestingly, XP was also able to significantly increase gastric pH. This study demonstrated that XP restored gastric homeostasis, improved esophageal integrity, and decreased inflammation and pain with a similar efficacy to omeprazole and greater than alginates.

Neuroprotective effects of GSK-343 in an in vivo model of MPTP-induced nigrostriatal degeneration.

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic nigrostriatal neurons, which causes disabling motor disorders. Scientific findings support the role of epigenetics mechanism in the development and progression of many neurodegenerative diseases, including PD. In this field, some studies highlighted an upregulation of Enhancer of zeste homolog 2 (EZH2) in the brains of PD patients, indicating the possible pathogenic role of this methyltransferase in PD. The aim of this study was to evaluate the neuroprotective effects of GSK-343, an EZH2 inhibitor, in an in vivo model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic degeneration. Specifically, nigrostriatal degeneration was induced by MPTP intraperitoneal injection. GSK-343 was administered intraperitoneally daily at doses of 1 mg/kg, 5 mg/kg and 10 mg/kg, mice were killed 7 days after MPTP injection. Our results demonstrated that GSK-343 treatment significantly improved behavioral deficits and reduced the alteration of PD hallmarks. Furthermore, GSK-343 administration significantly attenuated the neuroinflammatory state through the modulation of canonical and non-canonical NF-κB/IκBα pathway as well as the cytokines expression and glia activation, also reducing the apoptosis process. In conclusion, the obtained results provide further evidence that epigenetic mechanisms play a pathogenic role in PD demonstrating that the inhibition of EZH2, mediated by GSK-343, could be considered a valuable pharmacological strategy for PD.

bFGF-like Activity Supported Tissue Regeneration, Modulated Neuroinflammation, and Rebalanced Ca2+ Homeostasis following Spinal Cord Injury.

A spinal cord injury (SCI) is a well-defined debilitating traumatic event to the spinal cord that usually triggers permanent changes in motor, sensory, and autonomic functions. Injured tissue becomes susceptible to secondary mechanisms caused by SCIs, which include pro-inflammatory cytokine release, the activation of astrocytes and microglia, and increased neuronal sensibility. As a consequence, the production of factors such as GFAP, IBA-1, TNF-α, IL-1ß, IFN-γ, and S100-ß slow down or inhibit central nervous system (CNS) regeneration. In this regard, a thorough understanding of the mechanisms regulating the CNS, and specifically SCI, is essential for the development of new therapeutic strategies. It has been demonstrated that basic fibroblast growth factor (bFGF) was successful in the modulation of neurotrophic activity, also promoting neurite survival and tissue repair, thus resulting in the valuable care of CNS disorders. However, bFGF therapeutic use is limited due to the undesirable effects developed following its administration. Therefore, the synthetic compound mimetic of bFGF, SUN11602 (with chemical name 4-[[4-[[2-[(4-Amino-2,3,5,6-tetramethylphenyl)amino]acetyl]methylamino]-1-piperidinyl]methyl]benzamide), has been reported to show neuroprotective activities similar to those of bFGF, also demonstrating a good pharmacokinetic profile. Here, we aimed to investigate the neuroprotective activity of this bFGF-like compound in modulating tissue regeneration, neuroinflammation, and Ca2+ overload by using a subacute mouse model of SCI. SUN11602 (1, 2.5, and 5 mg/kg) was administered orally to mice for 72 h daily following the in vivo model of SCI, which was generated by the extradural compression of the spinal cord. The data obtained demonstrated that SUN11602 treatment considerably decreased motor alteration and diminished the neuroinflammatory state through the regulation of glial activation, the NF-κB pathway, and kinases. Additionally, by controlling Ca2+-binding proteins and restoring neurotrophin expression, we showed that SUN11602 therapy restored the equilibrium of the neuronal circuit. Because of these findings, bFGF-like compounds may be an effective tool for reducing inflammation in SCI patients while enhancing their quality of life.

SUN11602, a bFGF mimetic, modulated neuroinflammation, apoptosis and calcium-binding proteins in an in vivo model of MPTP-induced nigrostriatal degeneration.

BACKGROUND: Parkinson's disease (PD) is the second most frequent neurodegenerative disease. PD etiopathogenesis is multifactorial and not yet fully known, however, the scientific world advised the establishment of neuroinflammation among the possible risk factors. In this field, basic fibroblast growth factor/fibroblast growth factor receptor-1 (bFGF/FGFR1) could be a promising way to treat CNS-mediated inflammation; unfortunately, the use of bFGF as therapeutic agent is limited by its side effects. The novel synthetic compound SUN11602 exhibited neuroprotective activities like bFGF. With this perspective, this study aimed to evaluate the effect of SUN11602 administration in a murine model of MPTP-induced dopaminergic degeneration. METHODS: Specifically, nigrostriatal degeneration was induced by intraperitoneal injection of MPTP (80 mg/kg). SUN11602 (1 mg/kg, 2.5 mg/kg, and 5 mg/kg) was administered daily by oral gavage starting from 24 h after the first administration of MPTP. Mice were killed 7 days after MPTP induction. RESULTS: The results obtained showed that SUN11602 administration significantly reduced the alteration of PD hallmarks, attenuating the neuroinflammatory state via modulation of glial activation, NF-κB pathway, and cytokine overexpression. Furthermore, we demonstrated that SUN11602 treatment rebalanced Ca2+ overload in neurons by regulating Ca2+-binding proteins while inhibiting the apoptotic cascade. CONCLUSION: Therefore, in the light of these findings, SUN11602 could be considered a valuable pharmacological strategy for PD.

The Pivotal Role of Protein Phosphatase 2A (PP2A) in Brain Tumors.

Protein phosphatase 2A (PP2A) is a highly complex heterotrimeric Ser/Thr phosphatase that regulates many cellular processes. PP2A is dysregulated in several human diseases, including oncological pathology; interestingly, PP2A appears to be essential for controlling cell growth and may be involved in cancer development. The role of PP2A as a tumor suppressor has been extensively studied and reviewed. To leverage the potential clinical utility of combination PP2A inhibition and radiotherapy treatment, it is vital that novel highly specific PP2A inhibitors be developed. In this review, the existing literature on the role of PP2A in brain tumors, especially in gliomas and glioblastoma (GBM), was analyzed. Interestingly, the review focused on the role of PP2A inhibitors, focusing on CIP2A inhibition, as CIP2A participated in tumor cell growth by stimulating cell-renewal survival, cellular proliferation, evasion of senescence and inhibition of apoptosis. This review suggested CIP2A inhibition as a promising strategy in oncology target therapy.

Rebalancing NOX2/Nrf2 to limit inflammation and oxidative stress across gut-brain axis in migraine.

Migraine is one of the most common neurological illnesses, and it is characterized by complicated neurobiology. It was confirmed the influence of inflammation and oxidative stress in migraines and also in distal organs such as the intestine. Indeed, the constant bidirectional communication between the Central Nervous System (CNS) and the gastrointestinal (GI) tract, known as the gut-brain axis, has become an attractive target involved in different human disorders. Herein, we explored the role of NADPH oxidase 2 (NOX2) in nitroglycerin (NTG)-induced migraine in mice models to discover the mechanism by which, during migraine attack, oxidative stress is sustained within trigeminal neurons and GI. Considering the inverse relationship between NOX2 and Nrf2, Nrf2 upregulation seems to be a promising approach to decrease NOX2 expression and consequently limit oxidative stress and inflammation spread in neurological and non-neurological diseases. With this aim, we exploited tempol's Nrf2-inducer ability to better understand the involvement of Nrf2/NOX2 axis in migraine and associated GI comorbidities. Behavioral tests confirmed that tempol, in a dose-dependent manner, moderated clinical signs of migraine and abdominal pain. Moreover, we demonstrated that the decrease in migraine-related symptomatology was strongly linked to the modulation of Nrf2/NOX2 signaling pathway in the brain and colon. In the brain, the rebalancing of Nrf2/NOX2 prevented neuronal loss, decreased glia reactivity while inhibiting NF-κB and NLRP3 inflammasome activation. In the colon, Nrf2 upregulation and consequent NOX2 decrease reduced the histological damage, mast cells infiltration as well as tumor necrosis factor (TNF)-α and interleukin (IL)-1ß release. Furthermore, the attenuation of inflammation and oxidative stress led to the restoration of the intestinal barrier through TJs replacement. Taken as a whole, data suggested that the regulation of Nrf2/NOX2 balance is a successful way to reduce neurological and related intestinal impairments during migraine and could be of relevance for migraine-like attacks in humans.

EZH2 Inhibition to Counteract Oral Cancer Progression through Wnt/ß-Catenin Pathway Modulation.

Oral squamous cell carcinoma (OSCC) is one of the most common human malignancies worldwide. The molecular mechanisms of OSCC pathogenesis are still unknown; however, in recent years, several reports have focused on the role of enhancer of zeste homolog 2 (EZH2) in OSCC. Therefore, in this study we aimed to investigate the effects of GSK343, a selective EZH2 inhibitor, and its impact on the signaling pathways in OSCC, using an in vitro and in vivo orthotopic model. In the in vitro model, GSK343 (1, 10, and 25 µM) significantly decreased OSCC cell viability and cell migration through EZH2 inhibition, modulating NF-κB/IκBα pathway activation and eNOS, VEGF, and TGFß expression, important markers of angiogenesis. In the in vivo model, GSK343 (5 mg/kg and 10 mg/kg) restored tongue tissue architecture and reduced tumor progression through EZH2 inhibition and Wnt/ß-catenin signaling pathway modulation. Moreover, GSK343 reduced the expression of inflammatory mediators; eNOS and TGFß, markers of angiogenesis; and CD31 and CD34, markers of micro vessel density, respectively. In conclusion, our data demonstrate that GSK343 counteracts oral cancer progression through EZH2/Wnt/ß-catenin pathway modulation, suggesting that it could be a promising therapeutic approach for OSCC management.

The Protective Role of Troxerutin (Trox) in Counteracting Anaplastic Thyroid Carcinoma (ATC) Progression.

Anaplastic thyroid carcinoma (ATC) is a rare thyroid neoplasm characterized by aggressiveness and a high mortality rate. Troxerutin (Trox) is a bioflavonoid widely found in various fruits and vegetables with numerous protective effects, including anticancer activities. To evaluate the anti-oxidant and anti-inflammatory effect of Trox, in vitro and in vivo studies were conducted in a model of ATC. Human ATC 8305C cell lines were treated with increasing concentrations of Trox (10 µg/mL, 30 µg/mL, 100 µg/mL, 300 µg/mL), and our results revealed that Trox treatment was able to reduce the viability of ATC cells and migratory capacity, reducing the expression of anti-apoptotic factors, such as B-cell lymphoma (bcl-2), and increasing the expression of pro-apoptotic factors, such as Caspase-3 and BID, activating oxidative stress mediators, such as manganese superoxide dismutase (MnSOD), heme oxygenase-1 (HO-1), glutathione (GSH) and reactive oxygen species modulator 1 (ROMO-1). Furthermore, Trox modulates NF-κB pathway markers, such as NIK and TRAF-6. Further confirmation was obtained through in vivo studies, in which Trox treatment, at doses of 12.5, 25 and 50 mg/kg, reduced morphological alteration, decreasing mast cell accumulation. Therefore, the use of Trox could be considered a promising strategy to counteract the progression of ATC.

The hidden link between late-onset seizures and cerebral amyloid angiopathy: A case-control study.

OBJECTIVE: Epileptic seizures occurring in late adulthood often remain of unknown origin. Sporadic cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease characterized by intracerebral hemorrhage, microhemorrhage and superficial siderosis, occurring mostly in elderly. This observational case-control study aimed to assess the occurrence of CAA in patients experiencing their first seizure in late adulthood. METHODS: We enrolled consecutive patients aged ≥55 years presenting with late-onset seizures (LOS) to the emergency departments or outpatient clinics of two Italian centers, from April 2021 to October 2022. Two age-matched control subjects with neurological symptoms other than epileptic seizure were recruited for each enrolled case. All participants underwent brain MRI (1.5 Tesla) including blood-sensitive sequences and were assessed for probable CAA diagnosis according to Boston criteria 2.0. Chi-squared test was performed to evaluate group differences. Univariate logistic regression analysis tested the association between clinical variables and CAA. RESULTS: We included 65 patients with LOS (27 females; mean age 72.2 ± 8.9 years) and 130 controls (49 females; mean age 70.3 ± 8.9 years). Diagnosis of probable CAA was achieved in 10.8% (7/65) of LOS patients and 2.3% (3/130) controls, with a statistically significant difference (p = 0.011). The OR for CAA in the LOS group was 5.2 as compared to the control group (95% CI = 1.3-20.6, p = 0.02). SIGNIFICANCE: The frequency of CAA is significatively higher in patients with LOS as compared to other neurological diseases, suggesting that a portion of LOS of unknown or vascular origin are associated with CAA. PLAIN LANGUAGE SUMMARY: Late-onset seizures (LOS) are very frequent in the elderly and often have no clear cause. Cerebral amyloid angiopathy (CAA) is a condition where amyloid proteins build up in the blood vessels of the brain, causing them to become weak and prone to bleeding. In this study, we explored the occurrence of CAA in people with LOS. We found that people with LOS were more likely to have a diagnosis of CAA than controls (i.e., people with other neurological diseases).

Efficacy of the Radical Scavenger, Tempol, to Reduce Inflammation and Oxidative Stress in a Murine Model of Atopic Dermatitis.

Atopic dermatitis (AD) is the most common chronically relapsing inflammatory skin disease, predominantly common in children; it is characterized by an eczematous pattern generally referable to skin dryness and itchy papules that become excoriated and lichenified in the more advanced stages of the disease. Although the pathophysiology of AD is not completely understood, numerous studies have demonstrated the complex interaction between genetic, immunological, and environmental factors, which acts to disrupt skin barrier function. Free radicals play a key role by directly damaging skin structure, inducing inflammation and weakening of the skin barrier. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) is a membrane-permeable radical scavenger, known to be a stable nitroxide, which exhibits excellent antioxidant effects in several human disorders, such as osteoarthritis and inflammatory bowel diseases. Considering the few existing studies on dermatological pathologies, this study aimed to evaluate tempol, in a cream formulation, in a murine model of AD. Dermatitis was induced in mice via dorsal skin application of 0.5% Oxazolone, three times a week for two weeks. After induction, mice were treated with tempol-based cream for another two weeks at three different doses of 0.5%, 1% and 2%. Our results demonstrated the ability of tempol, at the highest percentages, to counteract AD by reducing the histological damage, decreasing mast cell infiltration, and improving the skin barrier properties, by restoring the tight junction (TJs) and filaggrin. Moreover, tempol, at 1% and 2%, was able to modulate inflammation by reducing the nuclear factor kappa-light-chain-enhancer of the activated B cell (NF-κB) pathway, as well as tumor necrosis factor (TNF)-α and interleukin (IL)-1ß expression. Topical treatment also attenuated oxidative stress by modulating nuclear factor erythroid 2-related factor 2 (Nrf2), manganese superoxide dismutase (MnSOD), and heme oxygenase I (HO-1) expression levels. The obtained results demonstrate the numerous advantages provided by the topical administration of a tempol-based cream formulation, in reducing inflammation and oxidative stress through modulation of the NF-κB/Nrf2 signaling pathways. Therefore, tempol could represent an alternative anti-atopic approach to treating AD, thereby improving skin barrier function.

Role of Basic Fibroblast Growth Factor in Cancer: Biological Activity, Targeted Therapies, and Prognostic Value.

Cancer is the leading cause of death worldwide; thus, it is necessary to find successful strategies. Several growth factors, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF, FGF2), and transforming growth factor beta (TGF-ß), are involved in the main processes that fuel tumor growth, i.e., cell proliferation, angiogenesis, and metastasis, by activating important signaling pathways, including PLC-γ/PI3/Ca2+ signaling, leading to PKC activation. Here, we focused on bFGF, which, when secreted by tumor cells, mediates several signal transductions and plays an influential role in tumor cells and in the development of chemoresistance. The biological mechanism of bFGF is shown by its interaction with its four receptor subtypes: fibroblast growth factor receptor (FGFR) 1, FGFR2, FGFR3, and FGFR4. The bFGF-FGFR interaction stimulates tumor cell proliferation and invasion, resulting in an upregulation of pro-inflammatory and anti-apoptotic tumor cell proteins. Considering the involvement of the bFGF/FGFR axis in oncogenesis, preclinical and clinical studies have been conducted to develop new therapeutic strategies, alone and/or in combination, aimed at intervening on the bFGF/FGFR axis. Therefore, this review aimed to comprehensively examine the biological mechanisms underlying bFGF in the tumor microenvironment, the different anticancer therapies currently available that target the FGFRs, and the prognostic value of bFGF.

Inhibition of LRRK2 Attenuates Depression-Related Symptoms in Mice with Moderate Traumatic Brain Injury.

Moderate traumatic brain injury (mTBI) has been associated with emotional dysregulation such as loss of consciousness, post-traumatic amnesia and major depressive disorder. The gene Leucine-rich repeat kinase 2 (LRRK2) is involved in protein synthesis and degradation, apoptosis, inflammation and oxidative stress, processes that trigger mTBI. The aim of this study was to investigate the role of LRRK2 in reducing depression-related symptoms after mTBI and to determine whether inhibition of LRRK2 mediated by PF-06447475 could have antidepressant effects. Moderate traumatic brain injury was induced by controlled cortical impact (CCI) and mice were treated with PF-06447475 at doses of 1, 2.5 and 5 mg/kg once daily for 14 days. We performed histological, immunohistochemical and molecular analyses of brain tissue 24 days after mTBI. Furthermore, the tissue changes found in the hippocampus and amygdala confirmed the depression-like behavior. PF-treatment with 06447475 significantly reduced the histological damage and behavioral disturbances. Thus, this study has shown that mTBI induction promotes the development of depression-like behavioral changes. LRRK2 inhibition showed an antidepressant effect and restored the changes in the copper/glutamate/N-methyl-D-aspartic acid receptor (Cu/NMDAR) system.

BAY-117082-driven NLRP3 inflammasome inhibition resolves nitro-glycerine (NTG) neuronal damage in in vivo model of migraine.

Migraine is a common neuronal disorder characterized by recurrent episodes of headache associated with a higher prevalence in women than men. Several risk factors have been associated with migraine disease as genetic factors, gender, and age. Although understanding migraine pathophysiology is improved, it has been reported that NOD-like receptor protein 3 (NLRP3) inflammasome pathway overactivation can contribute to migraine progression. Therefore, the aim of this study was to investigate the effect of BAY-117082, an NLRP3 inflammasome inhibitor, in a mouse model of nitroglycerin (NTG)-induced migraine. The in vivo model of migraine was induced by intraperitoneal (i.p) injection of NTG (dose of 10 mg/kg). Mice were treated intraperitoneally with BAY-117082 at doses of 1 mg/kg, 5 mg/kg, and 10 mg/kg, 5 min following NTG injection. After 4 h of NTG injection, the whole brain tissue with the rostral spinal cord were collected and used to perform further analysis. Our results demonstrated that BAY-117082 treatments (5 mg/kg and 10 mg/kg) reduced pain attacks, hyperalgesia and photophobia more in female mice NTG-induced. Moreover, the treatment with BAY-117082 significantly reduced histological damage in the trigeminal nerve nucleus in female mice accordingly to significantly decreased in NLRP3 complex components expression levels such as ASC, IL-1ß, IL-18, caspase-1 and TNF-α levels. Additionally, the treatment with BAY-117082 at both higher doses significantly modulated CREB/Erk/Akt pathways strictly correlated to the expression of neurotrophic factors. Taken together, obtained results confer new insight into the role of the NLRP3 inflammasome pathway in migraine pathogenesis, suggesting that BAY-117082 could be considered a novel strategy therapeutics for migraine treatment despite unconventional drug use.

A Combination of Xyloglucan, Pea Protein and Chia Seed Ameliorates Intestinal Barrier Integrity and Mucosa Functionality in a Rat Model of Constipation-Predominant Irritable Bowel Syndrome.

Irritable Bowel Syndrome is a gastrointestinal disorder that affects the large intestine, which encompasses several symptoms including, but not limited to, abdominal pain, bloating and dysmotility. In particular, IBS associated with constipation (IBS-C) is characterized by hard and dry stools and inadequate evacuation and difficulty in defecation. Although several drugs ameliorate intestinal modifications and constipation-associated features, management of IBS is still a challenge. Natural compounds including Xyloglucan and pea protein (XP) and Chia seed powder (CS) are widely known to possess beneficial effects in counteracting several gastrointestinal disorders. Here, we aimed to assess the combined effects of XP and CS to treat constipation-related alterations in an IBS-C rat model. IBS-C was induced by gastric instillation of 2 mL of cold water (0-4 °C) for 14 days and Xiloglucan, Pea protein and Chia seeds (XP + CS) treatment was orally administered for 7 days. On day 22, colon tissues were collected for histological analysis. Our results showed that XP + CS administration attenuated constipation-related parameters by increasing body weight and food and water intake. Upon XP + CS treatment, from day 14 to 22, stool moisture content was restored to physiological level. Colonic tissues from IBS-C rats depicted a disruption of the organ architecture accompanied by edema. Loss of colonic structure was reflected by the marked reduction of tight junction protein expression, Occludin and zona occludens-1 (ZO-1). Administration of XP + CS treatment in IBS-C rats significantly ameliorated the colonic histological parameters and exerted a positive effect on barrier integrity by restoring the expression of Occludin and zona occludens-1 (ZO-1). Our findings demonstrated that the efficacy of XP and CS in managing constipation in rats is due to the ability of these compounds to form a protective barrier fortifying intestinal integrity and gut functionality.

Psychiatric and Behavioural Side Effects Associated With Perampanel in Patients With Temporal Lobe Epilepsy. A Real-World Experience.

Psychiatric and behavioural side effects are common, undesirable effects associated with antiseizure medication use. Temporal lobe epilepsy is the most common focal epilepsy in adults and it is frequently associated with drug resistance. Patients with intractable epilepsy are more likely to have psychiatric and behavioural side effects when taking antiseizure medications and seem to be at higher risk for psychiatric comorbidities. Perampanel is a novel anti-seizure medication approved for focal and generalised epilepsies as add-on therapy. This is a 12-week short-term observational prospective study on people with focal epilepsy consecutively recruited from an Italian tertiary epilepsy centre, aimed to compare incidence and severity of psychiatric and behavioural side effects associated with perampanel use in patients with temporal lobe epilepsy as compared to other focal epilepsies. All patients received add-on perampanel according to indication and clinical judgement. Incidence and severity of psychiatric and behavioural side effects were rated by Neuropsychiatric Inventory Questionnaire. All patients enrolled answered the questionnaire before starting perampanel and after 12 weeks of treatment. We found no significant difference in terms of incidence and severity of psychiatric and behavioural side effects associated with perampanel in patients with temporal lobe epilepsy as compared to other focal epilepsies. In line with the literature, the most common adverse effects were "irritability" for both groups and "aggression" for patients with other focal epilepsies.

Adenosine Targeting as a New Strategy to Decrease Glioblastoma Aggressiveness.

Glioblastoma is the most commonly malignant and aggressive brain tumor, with a high mortality rate. The role of the purine nucleotide adenosine and its interaction with its four subtypes receptors coupled to the different G proteins, A1, A2A, A2B, and A3, and its different physiological functions in different systems and organs, depending on the active receptor subtype, has been studied for years. Recently, several works have defined extracellular adenosine as a tumoral protector because of its accumulation in the tumor microenvironment. Its presence is due to both the interaction with the A2A receptor subtype and the increase in CD39 and CD73 gene expression induced by the hypoxic state. This fact has fueled preclinical and clinical research into the development of efficacious molecules acting on the adenosine pathway and blocking its accumulation. Given the success of anti-cancer immunotherapy, the new strategy is to develop selective A2A receptor antagonists that could competitively inhibit binding to its endogenous ligand, making them reliable candidates for the therapeutic management of brain tumors. Here, we focused on the efficacy of adenosine receptor antagonists and their enhancement in anti-cancer immunotherapy.

Diagnostic and therapeutic approach to drug-resistant juvenile myoclonic epilepsy.

INTRODUCTION: Juvenile myoclonic epilepsy (JME), also known as Janz syndrome, is a common form of generalized epilepsy of presumed genetic origin representing up to 10% of all epilepsy cases. Despite adequate anti-seizure medication (ASM) treatment, seizures persist in one-third of JME patients. AREAS COVERED: A literature search was conducted using Pubmed search on the topics of drug-resistant JME. EXPERT OPINION: About 30% of JME patients are drug-resistant. Valproate (VPA) is considered the first-choice drug. In women of childbearing potential, levetiracetam (LEV) should represent the first-choice treatment. Alternative monotherapy or add-on therapy should be considered in subjects with resistant seizures after the exclusion of pseudo-drug resistance. The choice of the add-on ASM depends on the predominant seizure type. In subjects with persistent bilateral tonic-clonic seizures, LEV or lamotrigine should be firstly considered. In patients with difficult-to-treat myoclonic seizures, clonazepam or LEV are recommended. In case of persistent absences, ethosuximide should be considered. With appropriate selection and safeguards in place, VPA should remain available as an option in women of childbearing potential whose seizures are resistant to other treatments.

Gadoxetate disodium-enhanced magnetic resonance cholangiography for the noninvasive detection of an active bile duct leak after laparoscopic cholecystectomy.

We report a case of an endoscopically confirmed biliary leak of the common hepatic duct after laparoscopic cholecystectomy that was prospectively diagnosed on gadoxetate disodium-enhanced magnetic resonance cholangiography. Whereas dynamic contrast-enhanced magnetic resonance images during the early vascular phases helped to rule out the causes of possible complications such as seroma, hematoma, or abdominal abscess, delayed hepatobiliary phase imaging was crucial for unequivocal diagnosis and location of the biliary leak. The diagnosis prompted therapeutic endoscopic retrograde cholangiography whereby a polytetrafluoroethylene-covered nitinol stent graft was successfully placed to repair the biliary injury.