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Purpose: Brain tumor-related epilepsy (BTRE) is a condition characterized by the development of seizures in the context of an undergoing oncological background. Levetiracetam (LEV) is a third-generation anti-seizure medication (ASM) widely used in BTRE prophylaxis. The study evaluated LEV neuropsychiatric side effects (SEs) in BTRE prophylaxis. Method: Twenty-eight patients with brain tumors were retrospectively selected and divided into two groups. In one group, we evaluated patients with a BTRE diagnosis using LEV (BTRE-group). The other group included patients with brain tumors who never had epilepsy and used a prophylactic ASM regimen with LEV (PROPHYLAXIS-group). Neuropsychiatric SEs of LEV were monitored using the Neuropsychiatric Inventory Questionnaire (NPI-Q) at the baseline visit and the 6- and 12-month follow-up. Results: Eighteen patients of the BTRE-group and 10 patients of the PROPHYLAXIS-group were included. Compared to the BTRE-group, the PROPHYLAXIS-group showed a higher severity of neuropsychiatric symptoms. According to Linear Mixed Models (LMM), a multiplicative effect was observed for the interaction between group treatment and time. For the caregiver distress score (CDS), only a time-effect was observed. Conclusion: Prophylactic ASM with LEV is associated with an increased frequency of neuropsychiatric SE. Accurate epileptological evaluations in patients with brain tumors are mandatory to select who would benefit most from ASM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dono, Consoli, Evangelista, Ricci, Russo, Carrarini, Di Iorio, Bonanni, Anzellotti, Onofrj and Sensi.)

Consensus criteria on corticobasal degeneration (CBD) include alien limb (AL) phenomena. However, the gist of the behavioral features of AL is still "a matter of debate." CBD-related AL has so far included the description of involuntary movements, frontal release phenomena (frontal AL), or asomatognosia (posterior or "real" AL). In this context, the most frequent symptoms are language and praxis deficits and cortical sensory misperception. However, asomatognosia requires, by definition, intact perception and cognition. Thus, to make a proper diagnosis of AL in the context of CBD, cognitive and language dysfunctions must be carefully verified and objectively assessed. We reviewed the current literature on AL in CBD and now propose that the generic use of the term AL should be avoided. This catchall AL term should instead be deconstructed. We propose that the term AL is appropriate to describe clinical features associated with specific brain lesions. More discrete sets of regionally bound clinical signs that depend on dysfunctions of specific brain areas need to be assessed and presented when posing the diagnosis. Thus, in our opinion, the AL term should be employed in association with precise descriptions of the accompanying involuntary movements, sensory misperceptions, agnosia-asomatognosia contents, and the presence of utilization behavior. The review also offers an overview of functional magnetic resonance imaging-based studies evaluating AL-related phenomena. In addition, we provide a complementary set of video clips depicting CBD-related involuntary movements that should not mistakenly be interpreted as signs of AL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Di Pietro, Russo, Dono, Carrarini, Thomas, Di Stefano, Telese, Bonanni, Sensi, Onofrj and Franciotti.)

Agitation is a behavioral syndrome characterized by increased, often undirected, motor activity, restlessness, aggressiveness, and emotional distress. According to several observations, agitation prevalence ranges from 30 to 50% in Alzheimer's disease, 30% in dementia with Lewy bodies, 40% in frontotemporal dementia, and 40% in vascular dementia (VaD). With an overall prevalence of about 30%, agitation is the third most common neuropsychiatric symptoms (NPS) in dementia, after apathy and depression, and it is even more frequent (80%) in residents of nursing homes. The pathophysiological mechanism underlying agitation is represented by a frontal lobe dysfunction, mostly involving the anterior cingulate cortex (ACC) and the orbitofrontal cortex (OFC), respectively, meaningful in selecting the salient stimuli and subsequent decision-making and behavioral reactions. Furthermore, increased sensitivity to noradrenergic signaling has been observed, possibly due to a frontal lobe up-regulation of adrenergic receptors, as a reaction to the depletion of noradrenergic neurons within the locus coeruleus (LC). Indeed, LC neurons mainly project toward the OFC and ACC. These observations may explain the abnormal reactivity to weak stimuli and the global arousal found in many patients who have dementia. Furthermore, agitation can be precipitated by several factors, e.g., the sunset or low lighted environments as in the sundown syndrome, hospitalization, the admission to nursing residencies, or changes in pharmacological regimens. In recent days, the global pandemic has increased agitation incidence among dementia patients and generated higher distress levels in patients and caregivers. Hence, given the increasing presence of this condition and its related burden on society and the health system, the present point of view aims at providing an extensive guide to facilitate the identification, prevention, and management of acute and chronic agitation in dementia patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Carrarini, Russo, Dono, Barbone, Rispoli, Ferri, Di Pietro, Digiovanni, Ajdinaj, Speranza, Granzotto, Frazzini, Thomas, Pilotto, Padovani, Onofrj, Sensi and Bonanni.)

Purpose: The temporal lobe, a critical hub for cognition, also plays a central role in the regulation of autonomic cardiovascular functions. Lesions in this area are usually associated with abnormalities in the regulation of heart rate (HR) and blood pressure (BP). The analysis of the heart rate variability (HRV) is useful to evaluate the cardiac parasympathetic nervous system activity. This study aims at comparing HRV changes occurring in two groups of patients suffering from Temporal Lobe Epilepsy (TLE). To that aim, we evaluated patients differentiated by the right or left location of the epileptic foci. Materials and Methods: Fifty-two adult patients with a diagnosis of TLE were enrolled. Each patient underwent a 20-min EEG + EKG recording in resting state. According to the localization of epileptic focus, patients were divided into two subgroups: right TLE (R-TLE) and left TLE (L-TLE). HRV parameters were calculated with a short-lasting analysis of EKG recordings. Time-domain and frequency domain-related, as well as non-linear analysis, parameters, were compared between the two groups. Results: Compared to the R-TLE group, L-TLE subjects showed a significant decrease in low frequency (LF) ( p < 0.01) and low frequency/high-frequency ratio (LF/HF) ( p < 0.001) as well as increased HF values ( p < 0.01), a parameter indicative of the presence of an increased cardiac vagal tone. These results were also confirmed in the subgroup analysis that took into account the seizure types, responses to antiepileptic drugs, seizure frequencies, and etiology. Conclusions: The main finding of the study is that, compared to R-TLE, L-TLE is associated with increased cardiac vagal tone. These results indicate that patients with TLE exhibit a lateralized cardiac autonomic control. L-TLE patients may have a lower risk of developing cardiac dysfunctions and less susceptible to develop Sudden Death for Epilepsy (SUDEP)., (Copyright © 2020 Dono, Evangelista, Frazzini, Vollono, Carrarini, Russo, Ferrante, Di Stefano, Marchionno, De Angelis, Faustino, Bonanni, Onofrj, Sensi and Anzellotti.)

Psychogenic nonepileptic seizures (PNES) are neurobehavioral conditions positioned in a gray zone, not infrequently a no-man land, that lies in the intersection between Neurology and Psychiatry. According to the DSM 5, PNES are a subgroup of conversion disorders (CD), while the ICD 10 classifies PNES as dissociative disorders. The incidence of PNES is estimated to be in the range of 1.4-4.9/100,000/year, and the prevalence range is between 2 and 33 per 100,000. The International League Against Epilepsy (ILAE) has identified PNES as one of the 10 most critical neuropsychiatric conditions associated with epilepsy. Comorbidity between epilepsy and PNES, a condition leading to "dual diagnosis," is a serious diagnostic and therapeutic challenge for clinicians. The lack of prompt identification of PNES in epileptic patients can lead to potentially harmful increases in the dosage of anti-seizure drugs (ASD) as well as erroneous diagnoses of refractory epilepsy. Hence, pseudo-refractory epilepsy is the other critical side of the PNES coin as one out of four to five patients admitted to video-EEG monitoring units with a diagnosis of pharmaco-resistant epilepsy is later found to suffer from non-epileptic events. The majority of these events are of psychogenic origin. Thus, the diagnostic differentiation between pseudo and true refractory epilepsy is essential to prevent actions that lead to unnecessary treatments and ASD-related side effects as well as produce a negative impact on the patient's quality of life. In this article, we review and discuss recent evidence related to the neurobiology of PNES. We also provide an overview of the classifications and diagnostic steps that are employed in PNES management and dwell on the concept of pseudo-resistant epilepsy., (Copyright © 2020 Anzellotti, Dono, Evangelista, Di Pietro, Carrarini, Russo, Ferrante, Sensi and Onofrj.)