Ictal Fear or Panic Attack, This Is the Question-A Video-EEG Study.

Panic disorder (PD) and focal epilepsy, in particular, temporal lobe epilepsy, often present diagnostic challenges due to overlapping clinical manifestations. This article describes the case of a 25-year-old female, misdiagnosed with PD for 15 years, whose recurring episodes of sudden fear, palpitations, and nausea were later identified as manifestations of focal epilepsy. Initially unresponsive to conventional anti-anxiety medications, the patient's correct diagnosis was only established through comprehensive electro-clinical, neuropsychological, and neuroimaging evaluations during her admission to our research hospital. Long-term video-EEG monitoring (LTVEM) played a pivotal role in identifying the epileptic nature of her episodes, which were characterized by paroxysmal activity in the right temporal and zygomatic regions, consistent with the location of a dysplastic lesion in the right amygdala, as revealed by high-resolution magnetic resonance imaging. These findings underline the importance of considering focal epilepsy in the differential diagnosis of PD, especially in cases refractory to standard psychiatric treatments. The misdiagnosis of epilepsy as PD can lead to significant delays in appropriate treatment, potentially exacerbating the patient's condition and affecting their quality of life. This case emphasizes the necessity of a multidisciplinary approach and the utilization of advanced diagnostic tools like LTVEM in elucidating the underlying causes of paroxysmal psychiatric symptoms.

Awake Craniotomy in Conscious Sedation: The Role of A2 Agonists.

BACKGROUND: In Awake Craniotomy (AC), α2-agonists and remifentanil (clonidine and dexmedetomidine) are used in the preoperative phase and throughout the procedure to combine monitored anesthesia care and local anesthesia. The study aims were to specify the key role of α2-agonists administered and to evaluate complication presence/absence in anesthesiologic management. METHODS: 42 patients undergoing AC in 3 different centers in the south of Italy (Foggia, San Giovanni Rotondo, and Bari) were recruited. Our protocol involves analgo-sedation by administering Dexmedetomidine and Remifentanil in continuous intravenous infusion, allowing the patient to be sedated and in comfort but contactable and spontaneously breathing. During pre-surgery, the patient is premedicated with intramuscular clonidine (2 µg/kg). In the operating setting, Dexmedetomidine in infusion and Remifentanil in Target Controlled Infusion for effect are started. At the end of the surgical procedure, the infusion of drugs was suspended. RESULTS: There were no intraoperative side effects. The mean duration of interventions was 240 ± 62 min. The average quantity of Remifentanil and Dexmedetomidine infused during interventions were 4.2 ± 1.3 mg and 1.0 ± 0.3 mg, respectively. No significant side effects were described in the post-operative phase. A total of 86% of patients and 93% of surgeons were totally satisfied. CONCLUSIONS: Synergy between opioid drugs and α2 agonists plays a fundamental role in ensuring procedure success.

Perioperative Management of a Pediatric Patient with Beckwith-Wiedemann Syndrome Undergoing a Partial Glossectomy According to Egyedi/Obwegeser.

Here, we report the perioperative management of a clinical case of a 6 year, 5 month old girl suffering from Beckwith-Wiedemann syndrome undergoing a partial glossectomy procedure in a patient with surgical indication for obstructive sleep apnea syndrome (OSAS), difficulty swallowing, feeding, and speech. On surgery day, Clonidine (4 µg/kg) was administered. Following this, a general anesthesia induction was performed by administering Sevoflurane, Fentanyl, continuous intravenous Remifentanil, and lidocaine to the vocal cords, and a rhinotracheal intubation with a size 4.5 tube was carried out. Before starting the procedure, a block of the Lingual Nerve was performed with Levobupivacaine. Analgosedation was maintained with 3% Sevoflurane in air and oxygen (FiO2 of 40%) and Remifentanil in continuous intravenous infusion at a rate of 0.08-0.15 µg/kg/min. The surgical procedure lasted 2 h and 32 min. At the end of the surgery, the patient was under close observation during the first 72 h. In the pediatric patient with Beckwith-Wiedemann syndrome submitted to major maxillofacial surgery, the difficulty in managing the airways in the preoperative phase during intubation and in the post-operative phase during extubation should be considered.

Real-Time Neuropsychological Testing (RTNT) and Music Listening during Glioblastoma Excision in Awake Surgery: A Case Report.

In this case report, real-time neuropsychological testing (RTNT) and music listening were applied for resections in the left temporal-parietal lobe during awake surgery (AS). The case is based on a 66-year-old with glioblastoma and alterations in expressive language and memory deficit. Neuropsychological assessment was run at baseline (2-3 days before surgery), discharge from hospital (2-3 days after surgery), and follow-up (1 month and 3 months). RTNT was started before beginning the anesthetic approach (T0) and during tumor excision (T1 and T2). At T0, T1, and T2 (before performing neuropsychological tests), music listening was applied. Before AS and after music listening, the patient reported a decrease in depression and anxiety. During AS, an improvement was shown in all cognitive parameters collected at T0, T1, and T2. After the excision and music listening, the patient reported a further decrease in depression and anxiety. Three days post surgery, and at follow-ups of one month and three months, the patient reported a further improvement in cognitive aspects, the absence of depression, and a reduction in anxiety symptoms. In conclusion, RTNT has been useful in detecting cognitive function levels during tumor excision. Music listening during AS decreased the patient's anxiety and depression symptoms.

Anesthetic Management for Awake Craniotomy Applied to Neurosurgery.

Our anesthetic technique proposed for awake craniotomy is the monitored anesthesia care (MAC) technique, with the patient in sedation throughout the intervention. Our protocol involves analgo-sedation through the administration of dexmedetomidine and remifentanil in a continuous intravenous infusion, allowing the patient to be sedated and in comfort, but contactable and spontaneously breathing. Pre-surgery, the patient is pre-medicated with intramuscular clonidine (2 µg/kg); it acts both as an anxiolytic and as an adjuvant in pain management and improves hemodynamic stability. In the operating setting, dexmedetomidine in infusion and remifentanil in target controlled infusion (TCI) for effect are started. The purpose of the association is to exploit the pharmacodynamics of dexmedetomidine which guarantees the control of respiratory drive, and the pharmacokinetics of remifentanil characterized by insensitivity to the drug. Post-operative management: at the end of the surgical procedure, the infusion of drugs was suspended. Wake-up craniotomy is associated with reduced hospital costs compared to craniotomy performed in general anesthesia, mainly due to reduced costs in the operating room and shorter hospital stays. Greater patient satisfaction and the benefits of avoiding hospital stay have led to the evolution of outpatient intracranial neurosurgery.

Vascular Schizophrenia-like Psychosis in Older Adults.

BACKGROUND: The aims of this study were to analyze prevalence and severity of vascular risk factors in older patients referred to our clinic due to onset of Very Late-Onset Schizophrenia-Like Psychosis (VLOSLP) and to create a specific phenotype based on pathophysiological insight rather than age of onset. METHODS: In a longitudinal study, 103 (M = 39, F = 64; mean age of 80.32 ± 7.65 years) patients were evaluated with cognitive, neuropsychiatric, and functional assessment scales. Blood concentration of hemoglobin (Hb), mean corpuscular volume (MCV), platelets, total protein test (TPT), creatinine, azotemia, glycemia, total cholesterol (TC), triglycerides (TG), uric acid (UA), sodium (Na), potassium (K), chlorine (Cl), calcium (Ca), folate, vitamin B12 (Vit-B12), and homocysteine were measured. Presence/absence of tobacco use, alcohol consumption, psychoactive substance use, hypertension, hyperlipidemia, diabetes mellitus, and history of vascular disease were collected. RESULTS: Females were more apathetic than males (NPI-Apathy: p = 0.040). Males had a significantly higher level of Hb (p = 0.019) and UA (p = 0.001), and a lower level of platelets (p = 0.004) and Ca (p = 0.003), and used more tobacco (p = 0.046) and alcohol (p = 0.024) than females. Comparing patients < 80 and ≥80 years, we found differences in frequency of vascular risk factors among men (p = 0.027). In total, 102 patients were treated for psychosis (59.16% of them were using atypical antipsychotics). CONCLUSIONS: The results of this study could be useful for a progressive demonstration of the causal relationship between cardiac and cerebral vascular events and VLOSLP.

Emotion Recognizing by a Robotic Solution Initiative (EMOTIVE Project).

BACKGROUND: Emotion recognition skills are predicted to be fundamental features in social robots. Since facial detection and recognition algorithms are compute-intensive operations, it needs to identify methods that can parallelize the algorithmic operations for large-scale information exchange in real time. The study aims were to identify if traditional machine learning algorithms could be used to assess every user emotions separately, to relate emotion recognizing in two robotic modalities: static or motion robot, and to evaluate the acceptability and usability of assistive robot from an end-user point of view. METHODS: Twenty-seven hospital employees (M = 12; F = 15) were recruited to perform the experiment showing 60 positive, negative, or neutral images selected in the International Affective Picture System (IAPS) database. The experiment was performed with the Pepper robot. Concerning experimental phase with Pepper in active mode, a concordant mimicry was programmed based on types of images (positive, negative, and neutral). During the experimentation, the images were shown by a tablet on robot chest and a web interface lasting 7 s for each slide. For each image, the participants were asked to perform a subjective assessment of the perceived emotional experience using the Self-Assessment Manikin (SAM). After participants used robotic solution, Almere model questionnaire (AMQ) and system usability scale (SUS) were administered to assess acceptability, usability, and functionality of robotic solution. Analysis wasperformed on video recordings. The evaluation of three types of attitude (positive, negative, andneutral) wasperformed through two classification algorithms of machine learning: k-nearest neighbors (KNN) and random forest (RF). RESULTS: According to the analysis of emotions performed on the recorded videos, RF algorithm performance wasbetter in terms of accuracy (mean ± sd = 0.98 ± 0.01) and execution time (mean ± sd = 5.73 ± 0.86 s) than KNN algorithm. By RF algorithm, all neutral, positive and negative attitudes had an equal and high precision (mean = 0.98) and F-measure (mean = 0.98). Most of the participants confirmed a high level of usability and acceptability of the robotic solution. CONCLUSIONS: RF algorithm performance was better in terms of accuracy and execution time than KNN algorithm. The robot was not a disturbing factor in the arousal of emotions.

Targeting NF-κB signaling pathway in cancer by dietary polyphenols.

Being a transcription factor, NF-κB regulates gene expressions involving cell survival and proliferation, drug resistance, metastasis, and angiogenesis. The activation of NF-κB plays a central role in the development of inflammation and cancer. Thus, the down-regulation of NF-κB may be an exciting target in prevention and treatment of cancer. NF-κB could act as a tumor activator or tumor suppressant decided by the site of action (organ). Polyphenols are widely distributed in plant species, consumption of which have been documented to negatively regulate the NF-κB signaling pathway. They depress the phosphorylation of kinases, inhibit NF-κB translocate into the nucleus as well as interfere interactions between NF-κB and DNA. Through inhibition of NF-κB, polyphenols downregulate inflammatory cascade, induce apoptosis and decrease cell proliferation and metastasis. This review highlights the anticancer effects of polyphenols on the basis of NF-κB signaling pathway regulation.

Phosphodiesterase inhibitors say NO to Alzheimer's disease.

Phosphodiesterases (PDEs) consisted of 11 subtypes (PDE1 to PDE11) and over 40 isoforms that regulate levels of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP), the second messengers in cell functions. PDE inhibitors (PDEIs) have been attractive therapeutic targets due to their involvement in diverse medical conditions, e.g. cardiovascular diseases, autoimmune diseases, Alzheimer's disease (AD), etc. Among them; AD with a complex pathology is a progressive neurodegenerative disorder which affect mostly senile people in the world and only symptomatic treatment particularly using cholinesterase inhibitors in clinic is available at the moment for AD. Consequently, novel treatment strategies towards AD are still searched extensively. Since PDEs are broadly expressed in the brain, PDEIs are considered to modulate neurodegenerative conditions through regulating cAMP and cGMP in the brain. In this sense, several synthetic or natural molecules inhibiting various PDE subtypes such as rolipram and roflumilast (PDE4 inhibitors), vinpocetine (PDE1 inhibitor), cilostazol and milrinone (PDE3 inhibitors), sildenafil and tadalafil (PDE5 inhibitors), etc have been reported showing encouraging results for the treatment of AD. In this review, PDE superfamily will be scrutinized from the view point of structural features, isoforms, functions and pharmacology particularly attributed to PDEs as target for AD therapy.

Executive Dysfunction Detected with the Frontal Assessment Battery in Alzheimer's Disease Versus Vascular Dementia.

Alzheimer's disease (AD) and vascular dementia (VaD) lead to progressive decline in executive function. We estimated the prevalence of executive dysfunction in AD and VaD patients, investigating cognitive, functional, and clinical correlates and also using a multidimensional approach based on a standardized comprehensive geriatric assessment (CGA). We included 215 patients (115 AD patients and 100 VaD patients) consecutively evaluated with a complete cognitive and affective assessment, a CGA, and the Frontal Assessment Battery (FAB) with six subtests investigating conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. The prevalence of dysexecutive syndrome screened with a FAB score <12 points was high in both AD (97 patients) and VaD (77 patients) (84.3% versus 77.0%, p = 0.171). AD patients were significantly younger, with higher grade of cognitive impairment and less severe comorbidity and polypharmacy than VaD patients. AD patients showed a significantly higher impairment in FAB total score and five FAB subtests (conceptualization, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy) than VaD patients. These findings were largely confirmed in a sub-analysis conducted subdividing the sample in mild and moderate-to-severe demented patients and suggesting that in moderate-to-severe AD there was higher impairment in FAB total score and four FAB subtests (conceptualization, sensitivity to interference, inhibitory control, and environmental autonomy). Executive dysfunction could be greater in AD patients with moderate-to-severe dementia compared to VaD patients, although our groups were also not matched for age, comorbidity or polypharmacy, which could also exert an effect.

Role of CLU, PICALM, and TNK1 Genotypes in Aging With and Without Alzheimer's Disease.

Healthy and impaired cognitive aging may be associated to different prevalences of single-nucleotide polymorphisms (SNPs). In a multicenter case-control association study, we studied the SNPs rs11136000 (clusterin, CLU), rs541458 (phosphatidylinositol binding clatrin assembly protein, PICALM), and rs1554948 (transcription factor A, and tyrosine kinase, non-receptor, 1, TNK1) according to the three age groups 50-65 years (group 1), 66-80 years (group 2), and 80+ years (group 3) in 569 older subjects without cognitive impairment (NoCI) and 520 Alzheimer's disease (AD) patients. In NoCI subjects, a regression analysis suggested a relationship between age and TNK1 genotypes, with the TNK1-A/A genotype frequency that increased with higher age, and resulting in a different distribution of the TNK1-A allele. In AD patients, a regression analysis suggested a relationship between age and PICALM genotypes and TNK1 genotypes, with the PICALM-T/C and TNK1-A/A genotype frequencies that decreased with increasing age. A resulting difference in the distribution of PICALM-C allele and TNK1-A allele was also observed. The TNK1-A allele was overrepresented in NoCI subjects than in AD patients in age groups 2 and 3. These results confirmed after adjustment for apolipoprotein E polymorphism, which suggested a different role of PICALM and TNK1 in healthy and impaired cognitive aging. More studies, however, are needed to confirm the observed associations.

Psychotropic drugs and CYP2D6 in late-life psychiatric and neurological disorders. What do we know?

INTRODUCTION: Late-life psychiatric and neurological disorders (LLPND) are interesting models to understand the potential role of pharmacogenetics in drug management, since several pharmacological approaches for treating LLPND have proven to be ineffective or deleterious, thus resulting in therapeutic failures (TF) and adverse drug reactions (ADR). Common variants in the genes encoding the cytochrome P450 (CYP) enzyme system, the 'engine room' of drug metabolism, together with well-known age-related increased polypharmacy also contributed to the prevalence of TF and ADR observed in these patients, also rising number and time of hospital readmissions and rate of institutionalizations. Areas covered: The genetics of CYP and how it may be used for the management of the outcomes of the most frequent drugs (antidepressants, antipsychotics, anticholinesterase inhibitors, and anxiolytics) used in LLPND. Expert opinion: Tailored CYP-based pharmacological treatments of LLPND will reduce TFs and ADRs, improving patient's life, reducing number and dosage of administered drugs, and the number and duration of hospital readmissions, saving costs for clinical management of LLPND. Pharmacokinetic interactions are less predictable than pharmacodynamic ones and several requests are made to regulatory organisms for the pharmacological management of frail older patients affected by LLPND.

Emerging biomarkers and screening for cognitive frailty.

Physical frailty and cognitive frailty are two important targets of secondary intervention in aging research to narrow the gap between life and health span. The objective of the present narrative review was to examine clinical and epidemiological studies investigating the recently proposed construct of cognitive frailty and its subtypes, with a focus on operational definitions, clinical criteria, and emerging biomarkers potentially useful for the screening of this novel entity. Both physical frailty and frailty indexes with a multidimensional nature were associated with late-life cognitive impairment/decline, incident dementia, Alzheimer's disease (AD), mild cognitive impairment, vascular dementia, non-AD dementias, and AD pathology proposing cognitive frailty as a clinical entity with cognitive impairment related to physical causes with a potential reversibility. The new clinical and research AD criteria established by the National Institute on Aging-Alzheimer's Association and the American Psychiatric Association could improve the differential diagnosis of cognitive impairment within the cognitive frailty construct. The emerging biomarkers of sarcopenia, physical frailty, and cognitive impairment will provide the basis to establish more reliable clinical and research criteria for cognitive frailty, using different operational definitions for frailty and cognitive impairment and useful clinical, biological, and imaging markers for this novel clinical construct.

Neuroprotective Effects of Quercetin: From Chemistry to Medicine.

Neurodegenerative diseases are the leading cause of disability in the elderly. Growing evidence suggests that oxidative stress, which is associated with aging, is the basis of most neurodegenerative disorders; and polyphenols, acting as antioxidant agents, reduce the risk of neurodegenerative diseases. Quercetin is a flavonoid occurring in many plant foods commonly consumed as part of a regular diet. It shows a number of biological properties connected to its antioxidant activity. This review assesses the molecular structure of quercetin, its food sources and bioavailability. Moreover, the main results obtained from in vitro studies, observing the mechanisms of action through which quercetin exerts its antioxidant activity, are reported. However, most of these effects have only been observed in vitro and clinical studies are lacking.

FOXO1 locus and acetylcholinesterase inhibitors in elderly patients with Alzheimer's disease.

OBJECTIVE: Acetylcholinesterase inhibitors (AChEIs) may reduce the oxidative stress in brain of Alzheimer's disease (AD) patients. Forkhead box O1 (FOXO1) protein has been reported as the link between oxidative stress and AD. We evaluated a potential association between FOXO1 gene locus and the response to AChEI treatment in patients with sporadic AD. METHODS: In this prospective study, 109 Caucasian AD patients were treated with standard doses of donepezil, galantamine, or rivastigmine for 6 months. Functional and cognitive status were evaluated at baseline and after treatment. Response to therapy was defined according to the National Institute for Health and Clinical Excellence criteria. Genotype analyses, including the APOE polymorphism, were made in blinded fashion. RESULTS: A significantly higher frequency of FOXO1 rs7981045 G/G genotype was observed in nonresponders compared with responders (17.14% versus 2.70%, P=0.010). Age, sex, and APOE-adjusted logistic regression analysis confirmed that patients with the G/G genotype had a significantly higher risk of poor response to AChEI treatment (odds ratio =10.310; 95% confidence interval, 1.510-70.362). Haplotype analysis revealed significant differences in haplotype frequency distribution between these groups. CONCLUSION: FOXO1 may influence the clinical response to AChEIs in AD patients.

Apolipoprotein E-related all-cause mortality in hospitalized elderly patients.

The most common apolipoprotein E (APOE) allelic variation is implicated in many age-related diseases and human longevity with controversial findings. We investigated the effect of APOE gene polymorphism on all-cause mortality in elderly patients taking into consideration the functional disability, cognitive impairment, malnutrition, and the occurrence of common age-related diseases. APOE genotypes were determined in 2,124 geriatric hospitalized patients (46.5% men and 53.5% women; mean age, 78.2 +/- 7.1 years; range, 65-100 years). At hospital admission, all patients underwent a comprehensive geriatric assessment to evaluate functional disability, cognitive status, nutritional status, and comorbidity. The main and secondary diagnoses at hospital discharge were also recorded. Mortality status was evaluated in all patients after a maximum follow-up of 5 years (range, from 1.26 to 5.23 years; median, 2.86 years). During the study period, 671 patients died (32.0%). At hospital admission, these patients showed a significant higher prevalence of cardiovascular diseases (56.3% vs 53.4%; p = 0.007), neoplasias (32.3% vs 13.7%; p < 0.001), and lower prevalence of neurodegenerative diseases (17.7% vs 20.7%; p < 0.001) than survived patients. Moreover, they also showed an higher prevalence of disability (52.0% vs 25.6%; p < 0.001), cognitive impairment (31.0% vs 18.8%; p < 0.001), and malnutrition (74.0% vs 46.1%; p < 0.001) than survived patients. In the overall study population, the APOE epsilon2 allele was significantly associated to neurodegenerative diseases (odds ratio = 0.59; 95% confidence interval (CI), 0.37-0.94). No significant association between the APOE polymorphism and disability, malnutrition, co-morbidity status, and with all-cause mortality was observed. In patients with cardiovascular diseases, however, a decreased risk of all-cause mortality was found in the epsilon2 allele carriers (hazard ratio = 0.56; 95% CI, 0.36-0.88). In this population, APOE allele variants might play a role on cardiovascular disease-related mortality.