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Abstract Despite some evidence of a possible link between epileptogenesis and tumorigenesis in glioblastoma, the prognostic value of epilepsy at presentation has been debated over the years. We performed a systematic review and meta-analysis to summarize all published data evaluating the prognostic significance of seizures as a presenting manifestation of glioblastoma. A comprehensive search of five databases from inception to December 2023 was conducted. Included studies underwent meta-analysis, with subgroup analyses performed to identify sources of heterogeneity. Fifteen studies were included in the analysis. Seizures were considered a favorable prognostic factor in seven studies, while eight studies found no differences in overall survival between patients with seizures and those with other presenting symptoms. Eleven studies were included in the meta-analysis. The overall pooled analysis indicated a potentially favorable prognostic impact of seizures at the clinical onset of glioblastoma (HR 0.73; 95% CI 0.61–0.87). However, subgroup analysis within studies focusing on IDH-wild type cases showed no discernible impact from preoperative seizures. Retrospective design, poor quality in reporting results, and heterogeneity in tumor characteristics and therapies are the main limitations of included studies. Future prospective studies on large, homogeneous cohorts of patients with IDH-wild type glioblastoma are warranted. Overall, these findings suggest that while seizures may hold some prognostic value, further research is essential to clarify their role. Understanding the true prognostic role of seizures at clinical onset may enhance our ability to predict patient outcomes and guide clinical decision-making.

Glioblastoma (GBM) displays significant gender disparities, being 1.6 times more prevalent in men, with a median survival time of 15.0 months for males compared to 25.5 months for females. These differences may be linked to gonadal steroid hormones, particularly testosterone, which interacts with the androgen receptor (AR) to promote tumor proliferation. Conversely, estrogen (E2), progesterone (P4), and P4 metabolites exert more complex effects on GBM. Despite these insights, the identification of reliable hormonal tumor markers remains challenging, and studies investigating hormone therapies yield inconclusive results due to small sample sizes and heterogeneous tumor histology. Additionally, genetic, epigenetic, and immunological factors play critical roles in sex disparities, with female patients demonstrating increased O6-Methylguanine-DNA methyltransferase promoter methylation and greater genomic instability. These complexities highlight the need for personalized therapeutic strategies that integrate hormonal influences alongside other sex-specific biological characteristics in the management of GBM. In this review, we present the current understanding of the potential role of sex hormones in the natural history of GBM.

Some authors use the term cortical–subcortical myoclonus to identify a specific type of myoclonus, which differs from classical cortical myoclonus in that the abnormal neuronal activity spreads between the cortical and subcortical circuits, producing diffuse excitation. The EEG shows generalized spike-and-wave discharges that correlate with the myoclonic jerks. We report the case of a 79-year-old patient with a history of right thalamic deep hemorrhagic stroke, with favorable evolution. Fifteen years later, he was readmitted to the emergency department for episodes characterized by sudden falls without loss of consciousness. An EEG with EMG recording channel on the right deltoid muscle was performed, which documented frequent diffuse spike–wave and polyspike–wave discharges, temporally related to myoclonic jerks in the lower limbs. Brain MRI showed the persistence of a small right thalamic hemosiderin residue at the site of the previous hemorrhage. Antiseizure treatment with levetiracetam was started, with rapid clinical and electroencephalographic improvement. Our case may represent a lesion model of generalized epilepsy with myoclonic seizures. Furthermore, it highlights that lower limb myoclonus of cortical–subcortical origin may be an underestimate cause of gait disturbances and postural instability. Then, it may be reasonable to include the EEG in the diagnostic work-up of patients with recurrent falls.

Neurosteroids are pleiotropic molecules involved in various neurodegenerative diseases with neuroinflammation. We assessed neurosteroids’ serum levels in a cohort of Parkinson’s Disease (PD) patients with heterozygous glucocerebrosidase (GBA) mutations (GBA-PD) compared with matched cohorts of consecutive non-mutated PD (NM-PD) patients and healthy subjects with (GBA-HC) and without (NM-HC) GBA mutations. A consecutive cohort of GBA-PD was paired for age, sex, disease duration, Hoehn and Yahr stage, and comorbidities with a cohort of consecutive NM-PD. Two cohorts of GBA-HC and HC were also considered. Clinical assessment included the Movement Disorder Society revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Montreal Cognitive Assessment (MoCA). Serum samples were processed and analyzed by liquid chromatography coupled with the triple quadrupole mass spectrometry. Twenty-two GBA-PD (males: 11, age: 63.68), 22 NM-PD (males: 11, age: 63.05), 14 GBA-HC (males: 8; age: 49.36), and 15 HC (males: 4; age: 60.60) were studied. Compared to NM-PD, GBA-PD showed more hallucinations and psychosis (p < 0.05, Fisher’s exact test) and higher MDS-UPDRS part-II (p < 0.05). Most of the serum neurosteroids were reduced in both GBA-PD and NM-PD compared to the respective control cohorts, except for 5α-dihydroprogesterone. Allopregnanolone was the only neurosteroid significantly lower (p < 0.01, Dunn’s test) in NM-PD compared to GBA-PD patients. Only in GBA-PD, allopregnanolone, and pregnanolone levels correlated (Spearman) with a more severe MDS-UPDRS part-III. Allopregnanolone levels also negatively correlated with MoCA scores, and pregnanolone levels correlated with more pronounced bradykinesia. This pilot study provides the first observation of changes in neurosteroid peripheral levels in GBA-PD. The involvement of the observed changes in the development of neuropsychological and motor symptoms of GBA-PD deserves further attention.

IntroductionPituitary metastases are very rare in cancer patients and often originate from lung or breast tumors. They usually occur in patients with known metastatic disease, but rarely may be the first presentation of the primary tumor.MethodsWe present the case of a 58 years-old-man who reported a three-month history of polyuria-polydipsia syndrome, generalized asthenia, panhypopituitarism and bitemporal hemianopsia. Brain-MRI showed a voluminous pituitary mass causing posterior sellar enlargement and compression of the surrounding structures including pituitary stalk, optic chiasm, and optic nerves.ResultsThe patient underwent neurosurgical removal of the mass. Histological examination revealed a poorly differentiated adenocarcinoma of uncertain origin. A total body CT scan showed a mass in the left kidney that was subsequently removed. Histological features were consistent with a clear cell carcinoma. However, endoscopic examination of the digestive tract revealed an ulcerating and infiltrating adenocarcinoma of the gastric cardia. Total body PET/CT scan with 18F-FDG confirmed an isolated area of accumulation in the gastric cardia, with no hyperaccumulation at other sites.ConclusionTo the best of our knowledge, there are no reports of pituitary metastases from gastric cardia adenocarcinoma. Our patient presented with symptoms of sellar involvement and without evidence of other body metastases. Therefore, sudden onset of diabetes insipidus and visual deterioration should lead to the suspicion of a rapidly growing pituitary mass, which may be the presenting manifestation of a primary extracranial adenocarcinoma. Histological investigation of the pituitary mass can guide the diagnostic workup, which must however be complete.

(1) Background: Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is characterized by late-onset cerebellar ataxia, bilateral vestibulopathy, and sensory neuronopathy mostly due to biallelic RFC1 expansion. (2) Objectives: The aim of this case series is to describe vestibular, gait, and speech alterations in CANVAS via a systematic approach. (3) Methods: All patients (n = 5) underwent a standardized clinical–instrumental examination, including the perceptual and acoustic analysis of speech, instrumental gait, and balance analysis (posturographic data were acquired using a force plate [Kistler, Winterthur, Switzerland] while 3D gait analysis, inclusive of surface electromyography, was acquired using a motion capture system [SMART DX, BTS Bioengineering, Milan, Italy], a wireless electromyograph [FreeEMG, BTS Bioengineering, Milan, Italy]), and vestibular assessment with video-oculography. (4) Results: Five patients were included in the analysis: three females (patients A, B, C) and two males (patients D and E) with a mean age at evaluation of 62 years (SD ± 15.16, range 36–74). The mean age of symptoms’ onset was 55.6 years (SD ± 15.04, range 30–68), and patients were clinically and instrumentally evaluated with a mean disease duration of 6.4 years (SD ± 0.54, range 6–7). Video-Frenzel examination documented spontaneous downbeat nystagmus enhanced on bilateral gaze in all patients, except for one presenting with slight downbeat nystagmus in the supine position. All patients exhibited different degrees of symmetrically reduced VOR gain for allsix semicircular canals on the video-head impulse test and an unexpectedly normal (“false negative”) VOR suppression, consistent with combined cerebellar dysfunction and bilateral vestibular loss. Posturographic indices were outside their age-matched normative ranges in all patients, while 3D gait analysis highlighted a reduction in ankle dorsiflexion (limited forward rotation of the tibia over the stance foot during the stance phase of gait and fatigue of the dorsiflexor muscles) and variable out-of-phase activity of plantar flexors during the swing phase. Finally, perceptual-acoustic evaluation of speech showed ataxic dysarthria in three patients. Dysdiadochokinesis, rhythm instability, and irregularity were observed in the oral diadochokinesis task. (5) Conclusions: CANVAS is a recently discovered syndrome that is gaining more and more relevance within late-onset ataxias. In this paper, we aimed to contribute to a detailed description of its phenotype.

Nanotechnology application in cancer treatment is promising and is likely to quickly spread worldwide in the near future. To date, most scientific studies on nanomaterial development have focused on deepening the attitudes of end users and experts, leaving clinical practice implications unexplored. Neuro-oncology might be a promising field for the application of nanotechnologies, especially for malignant brain tumors with a low-survival rate such as glioblastoma (GBM). As to improving patients’ quality of life and life expectancy, innovative treatments are worth being explored. Indeed, it is important to explore clinicians’ intention to use experimental technologies in clinical practice. In the present study, we conducted an exploratory review of the literature about healthcare workers’ knowledge and personal opinions toward nanomedicine. Our search (i) gives evidence for disagreement between self-reported and factual knowledge about nanomedicine and (ii) suggests the internet and television as main sources of information about current trends in nanomedicine applications, over scientific journals and formal education. Current models of risk assessment suggest time-saving cognitive and affective shortcuts, i.e., heuristics support both laypeople and experts in the decision-making process under uncertainty, whereas they might be a source of error. Whether the knowledge is poor, heuristics are more likely to occur and thus clinicians’ opinions and perspectives toward new technologies might be biased.

Abstract Background Glioblastoma (GBM) is known for its devastating intracranial infiltration and its unfavorable prognosis, while extracranial involvement is a very rare event, more commonly attributed to IDH wild-type (primary) GBM evolution. Case presentation We present a case of a young woman with a World Health Organization (WHO) grade II Astrocytoma evolved to WHO grade IV IDH mutant glioblastoma, with subsequent development of lymphatic and bone metastases, despite the favorable biomolecular pattern and the stability of the primary brain lesion. Conclusions Our case highlights that grade II Astrocytoma may evolve to a GBM and rarely lead to a secondary metastatic diffusion, which can progress quite rapidly; any symptoms referable to a possible systemic involvement should be carefully investigated.

Abstract Aims The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan reduces mortality and hospitalizations in patients with heart failure and reduced ejection fraction (HFrEF). Favourable effects on haemodynamic and functional parameters have been observed in patients with HFrEF undergoing ARNI therapy, using standard transthoracic echocardiography. Global longitudinal strain (GLS) assessment uses a semi‐automatic procedure to provide a reliable and repeatable method that improves the detection of early changes of contractile function. We aimed to assess the effects of ARNI on GLS and myocardial mechanics in patients with HFrEF. Methods and results Thirty patients with New York Heart Association class II–III HFrEF were treated with ARNI and monitored using standard echocardiographic examination and GLS measurements at baseline, 3 months, and 6 months. ARNI therapy resulted in a significant reduction of ventricular volumes and a significant increase in left ventricular ejection fraction at 6 months but not 3 months by standard transthoracic echocardiography (left ventricular ejection fraction from 28 ± 8% at baseline to 34 ± 12% at 6 months, P

Abstract Objective To evaluate clinical outcomes and treatment effectiveness of status epilepticus finally resolved by nonbenzodiazepine antiepileptic drugs (AEDs). Methods All consecutive SE episodes observed from September 1, 2013, to September 1, 2018, and resolved by AEDs were considered. Diagnosis and classification of SE followed the 2015 ILAE proposal. Nonconvulsive status (NCSE) diagnosis was confirmed according to the Salzburg EEG criteria. The modified Rankin Scale and deaths at 30 days from onset were used to evaluate outcomes. Results A total of 277 status episodes (mean age 71 years; 61% female) were treated and resolved by antiepileptic drugs after 382 treatment trials. 68% of the SE resolved after AED use as first/second treatment line, while subsequent trials with AEDs gave an additional 32% resolution. A return to baseline conditions was observed in 48% of the patients, while overall mortality was 19% without significant changes across the study years. Mortality was higher in NCSE than in convulsive SE (22.5% vs 12.9%; P

Parkinson’s disease (PD) is a multifarious neurodegenerative disease. Its pathology is characterized by a prominent early death of dopaminergic neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies with aggregated α-synuclein. Although the α-synuclein pathological aggregation and propagation, induced by several factors, is considered one of the most relevant hypotheses, PD pathogenesis is still a matter of debate. Indeed, environmental factors and genetic predisposition play an important role in PD. Mutations associated with a high risk for PD, usually called monogenic PD, underlie 5% to 10% of all PD cases. However, this percentage tends to increase over time because of the continuous identification of new genes associated with PD. The identification of genetic variants that can cause or increase the risk of PD has also given researchers the possibility to explore new personalized therapies. In this narrative review, we discuss the recent advances in the treatment of genetic forms of PD, focusing on different pathophysiologic aspects and ongoing clinical trials.

(1) Background: Epilepsy is a frequent comorbidity in patients with brain tumors, in whom seizures are often drug-resistant. Current evidence suggests that excess of glutamatergic activity in the tumor microenvironment may favor epileptogenesis, but also tumor growth and invasiveness. The selective non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist perampanel (PER) was demonstrated to be efficacious and well-tolerated in patients with focal seizures. Moreover, preclinical in vitro studies suggested a potential anti-tumor activity of this drug. In this systematic review, the clinical evidence on the efficacy and tolerability of PER in brain tumor-related epilepsy (BTRE) is summarized. (2) Methods: Five databases and two clinical trial registries were searched from inception to December 2022. (3) Results: Seven studies and six clinical trials were included. Sample size ranged from 8 to 36 patients, who received add-on PER (mean dosage from 4 to 7 mg/day) for BTRE. After a 6–12 month follow-up, the responder rate (% of patients achieving seizure freedom or reduction ≥ 50% of seizure frequency) ranged from 75% to 95%, with a seizure freedom rate of up to 94%. Regarding tolerability, 11–52% of patients experienced non-severe adverse effects (most frequent: dizziness, vertigo, anxiety, irritability). The retention rate ranged from 56% to 83%. However, only up to 12.5% of patients discontinued the drug because of the adverse events. (4) Conclusions: PER seems to be efficacious, safe, and well-tolerated in patients with BTRE. Further randomized studies should be conducted in more homogeneous and larger populations, also evaluating the effect of PER on tumor progression, overall survival, and progression-free survival.

The most prevalent and deadly primary malignant glioma in adults is glioblastoma (GBM), which has a median survival time of about 15 months. Despite the standard of care for glioblastoma, which includes gross total resection, high-dose radiation, and temozolomide chemotherapy, this tumor is still one of the most aggressive and difficult to treat. So, it is critical to find more potent therapies that can help glioblastoma patients have better clinical outcomes. Additionally, the prognosis for recurring malignant gliomas is poor, necessitating the need for innovative therapeutics. Immunotherapy is a rather new treatment for glioblastoma and its effects are not well studied when it is combined with standard chemoradiation therapy. We conducted this study to evaluate different glioblastoma immunotherapy approaches in terms of feasibility, efficacy, and safety. We conducted a computer-assisted literature search of electronic databases for essays that are unique, involve either prospective or retrospective research, and are entirely written and published in English. We examined both observational data and randomized clinical trials. Eighteen studies met the criteria for inclusion. In conclusion, combining immunotherapy with radiochemotherapy and tumor removal is generally possible and safe, and rather effective in the prolongation of survival measures.

Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment in advanced Parkinson’s Disease (PD). However, the effects of STN-DBS on freezing of gait (FOG) are still debated, particularly in the long-term follow-up (≥5-years). The main aim of the current study is to evaluate the long-term effects of STN-DBS on FOG. Twenty STN-DBS treated PD patients were included. Each patient was assessed before surgery through a detailed neurological evaluation, including FOG score, and revaluated in the long-term (median follow-up: 5-years) in different stimulation and drug conditions. In the long term follow-up, FOG score significantly worsened in the off-stimulation/off-medication condition compared with the pre-operative off-medication assessment (z = −1.930; p = 0.05) but not in the on-stimulation/off-medication (z = −0.357; p = 0.721). There was also a significant improvement of FOG at long-term assessment by comparing on-stimulation/off-medication and off-stimulation/off-medication conditions (z = −2.944; p = 0.003). These results highlight the possible beneficial long-term effects of STN-DBS on FOG.

Epilepsy is reported in 29–52% of patients with glioblastoma (GBM) and has an important role in the natural history of this tumor and patients’ life quality. Although GBM is less epileptogenic than lower-grade gliomas, seizures are usually more difficult to control with common antiseizure medications; drug resistance is found in 20% of cases. Recent studies suggest that seizures at the onset of GBM could be a possible favorable independent prognostic factor in patients. Moreover, a growing body of evidence shows that many molecular mechanisms that influence epileptogenesis often regulate GBM growth and invasiveness, sometimes favoring or counteracting the tumor, respectively. The better-characterized players include glutamate, γ-aminobutyric acid, aquaporin-4, and hypoxia-activated molecules. However, currently available data on the molecular basis of epileptogenesis, tumorigenesis, and their relationship is incomplete or discordant and further research is urgently needed on this topic.

Abstract Objective To compare the incidence and clinical features of individuals presenting in emergency rooms (ER) with facial palsy during the Italian COVID‐19 outbreak and in the same period of 2019. Methods We retrospectively reviewed the medical records for all accesses to the six ER in the province of Reggio Emilia, Italy, during the first phase of the COVID‐19 pandemic (27 February‐3 May 2020) to identify all cases of diagnosed facial palsy. Clinical information was retrieved for each patient and compared with that of facial palsy cases presenting in 2019. Result Between 27 February and 3 May 2020, 38 patients presented to provincial ERs for facial palsy; in 2019, there were 22 cases, for an incidence rate ratio of 1.73 (95% CI 1.02–2.92) for the 2020 cohort. Of the 2020 cohort, eight patients (21%) presented with active or recent symptoms consistent with COVID‐19 infection, compared with 2 (9%) in 2019 (p = .299); one was tested and resulted positive for SARS‐CoV‐2. Moreover, patients were younger (−11 years, p = .037) than those of the previous year and manifested a longer lag (+1.1 days, p = .001) between symptoms onset and ER presentation. Conclusion We observed a higher occurrence of facial palsy during the COVID‐19 outbreak compared to the same period of the previous year; 21% of patients presenting with facial palsy had active or recent symptoms consistent with SARS‐CoV‐2 infection, suggesting an excess risk of facial palsy during or after COVID‐19. These patients searched for medical attention later, probably because of the fear of contracting COVID‐19 during assistance.

In this paper, we describe the multimodal MRI findings in a patient with Wilson disease and a seizure disorder, characterized by an electroclinical picture resembling juvenile myoclonic epilepsy. The brain structural MRI showed a deposition of ferromagnetic materials in the basal ganglia, with marked hypointensities in T2-weighted images of globus pallidus internus bilaterally. A resting-state fMRI study revealed increased functional connectivity in the patient, compared to control subjects, in the following networks: (1) between the primary motor cortex and several cortical regions, including the secondary somatosensory cortex and (2) between the globus pallidus and the thalamo-frontal network. These findings suggest that globus pallidus alterations, due to metal accumulation, can lead to a reduction in the normal globus pallidus inhibitory tone on the thalamo-(motor)-cortical pathway. This, in turn, can result in hyperconnectivity in the motor cortex circuitry, leading to myoclonus and tonic-clonic seizures. We suppose that, in this patient, Wilson disease generated a ‘lesion model’ of myoclonic epilepsy.

Background In patients with chronic heart failure, abnormal ventilation at cardiopulmonary testing (expressed by minute ventilation‐to‐carbon dioxide production, or VE/VCO2 slope, and resting end‐tidal CO2 pressure) may derive either from abnormal autonomic or chemoreflex regulation or from lung dysfunction induced by pulmonary congestion. The latter hypothesis is supported by measurement of pulmonary capillary wedge pressure, which cannot be obtained routinely but may be estimated noninvasively by measuring transthoracic conductance (thoracic fluid content 1/kΩ) with impedance cardiography. Methods and Results Preliminarily, in 9 patients undergoing invasive hemodynamics during cardiopulmonary testing, we demonstrated a significant relationship between VE/VCO2 slope and resting end‐tidal CO2 pressure with baseline and peak pulmonary capillary wedge pressure. Later, noninvasive hemodynamic evaluation by impedance cardiography was performed before cardiopulmonary testing in 190 patients with chronic systolic heart failure and normal lung function (aged 67±3 years, 71% with ischemia, ejection fraction 32±7%, 69% with implantable cardioverter‐defibrillator or cardiac resynchronization therapy). In this group, we determined the relationship between abnormal ventilation (VE/VCO2 slope and resting end‐tidal CO2 pressure) and transthoracic conductance. In the whole population, thoracic fluid content values were significantly related to VE/VCO2 slope (R=0.63, P