Are the criteria for PD-MCI diagnosis comprehensive? A Machine Learning study with modified criteria.

BACKGROUND: Mild cognitive impairment in Parkinson's disease (PD-MCI) includes deficits in different cognitive domains, and one domain to explore for neurocognitive impairment following the DSM-V is social cognition. However, this domain is not included in current criteria for PD-MCI diagnosis. Moreover, tests vary across studies. It is, therefore, crucial to optimize cognitive assessment in PD-MCI. We aimed to do so by using Machine Learning. METHODS: 275 PD patients were included. Four cognitive batteries were created: two Standard ones (Levels I and II), applying current criteria and "traditional" tests; two Alternative ones (Levels I and II), which incorporated a test of social cognition. These batteries were included in the Random Forest (RF) classifier. To assess RF performance, the AUC was considered, and the Variable Importance Index was estimated to understand the contribution of each test in PD-MCI classification. RESULTS: Standard Level I and II showed an AUC of 0.852 and 0.892, while Alternative Level I and II showed an AUC of 0.898 and of 0.906. Variable Importance Index revealed that TMT B-A, Ekman test, RAVLT-IR, MoCA, and Action Naming were tests that most contributed to PD-MCI classification. CONCLUSION: The Alternative level I assessment demonstrated a similar classification capacity to the Standard level II assessment. This finding suggests that in the cognitive assessment of PD patients, it is crucial to consider the most affected cognitive domains in this clinical population, including social cognition. Taken together, these results suggest to revise current criteria for the diagnosis of PD-MCI.

Is there an immunological cross-reactivity of antibodies to the myelin oligodendrocyte glycoprotein and coronaviruses?

Recent reports indicated that myelin oligodendrocyte glycoprotein antibody-associated disease might be a rare complication after severe acute respiratory syndrome coronavirus 2 infection or vaccination. It is unclear whether this is an unspecific sequel of infection or vaccination or caused by possible immunological cross-reactivity of severe acute respiratory syndrome coronavirus 2 proteins and myelin oligodendrocyte glycoprotein. The aim of this study was therefore to elucidate whether there is an immunological cross-reactivity between severe acute respiratory syndrome coronavirus 2 spike or nucleocapsid proteins and myelin oligodendrocyte glycoprotein and to explore the relation of antibody responses against myelin oligodendrocyte glycoprotein and severe acute respiratory syndrome coronavirus 2 and other coronaviruses. We analysed serum samples from patients with severe acute respiratory syndrome coronavirus 2 infection and neurological symptoms with (myelin oligodendrocyte glycoprotein antibody-associated disease, n = 12) or without myelin oligodendrocyte glycoprotein-antibodies (n = 10); severe acute respiratory syndrome coronavirus 2 infection without neurological symptoms (n = 32); vaccinated patients with no history of severe acute respiratory syndrome coronavirus 2 infection and neurological symptoms with (myelin oligodendrocyte glycoprotein antibody-associated disease, n = 10) or without myelin oligodendrocyte glycoprotein-antibodies (n = 9); and severe acute respiratory syndrome coronavirus 2 negative/naïve unvaccinated patients with neurological symptoms with (myelin oligodendrocyte glycoprotein antibody-associated disease, n = 47) or without myelin oligodendrocyte glycoprotein-antibodies (n = 20). All samples were analysed for serum antibody responses to myelin oligodendrocyte glycoprotein, severe acute respiratory syndrome coronavirus 2, and other common coronaviruses (CoV-229E, CoV-HKU1, CoV-NL63 and CoV-OC43). Based on sample amount and antibody titres, 21 samples were selected for analysis of antibody cross-reactivity between myelin oligodendrocyte glycoprotein and severe acute respiratory syndrome coronavirus 2 spike and nucleocapsid proteins using affinity purification and pre-absorption. Whereas we found no association of immunoglobulin G and A myelin oligodendrocyte glycoprotein antibodies with coronavirus antibodies, infections with severe acute respiratory syndrome coronavirus 2 correlated with an increased immunoglobulin M myelin oligodendrocyte glycoprotein antibody response. Purified antibodies showed no cross-reactivity between severe acute respiratory syndrome coronavirus 2 spike protein and myelin oligodendrocyte glycoprotein. However, one sample of a patient with myelin oligodendrocyte glycoprotein antibody-associated disease following severe acute respiratory syndrome coronavirus 2 infection showed a clear immunoglobulin G antibody cross-reactivity to severe acute respiratory syndrome coronavirus 2 nucleocapsid protein and myelin oligodendrocyte glycoprotein. This patient was also seropositive for other coronaviruses and showed immunological cross-reactivity of severe acute respiratory syndrome coronavirus 2 and CoV-229E nucleocapsid proteins. Overall, our results indicate that an immunoglobulin G antibody cross-reactivity between myelin oligodendrocyte glycoprotein and severe acute respiratory syndrome coronavirus 2 proteins is rare. The presence of increased myelin oligodendrocyte glycoprotein-immunoglobulin M antibodies after severe acute respiratory syndrome coronavirus 2 infection may either be a consequence of a previous infection with other coronaviruses or arise as an unspecific sequel after viral infection. Furthermore, our data indicate that myelin oligodendrocyte glycoprotein-immunoglobulin A and particularly myelin oligodendrocyte glycoprotein-immunoglobulin M antibodies are a rather unspecific sequel of viral infections. Finally, our findings do not support a causative role of coronavirus infections for the presence of myelin oligodendrocyte glycoprotein-immunoglobulin G antibodies.

Immune-Related Adverse Events Due to Cancer Immunotherapy: Immune Mechanisms and Clinical Manifestations.

The landscape of cancer treatment has undergone a significant transformation with the introduction of Immune Checkpoint Inhibitors (ICIs). Patients undergoing these treatments often report prolonged clinical and radiological responses, albeit with a potential risk of developing immune-related adverse events (irAEs). Here, we reviewed and discussed the mechanisms of action of ICIs and their pivotal role in regulating the immune system to enhance the anti-tumor immune response. We scrutinized the intricate pathogenic mechanisms responsible for irAEs, arising from the evasion of self-tolerance checkpoints due to drug-induced immune modulation. We also summarized the main clinical manifestations due to irAEs categorized by organ types, detailing their incidence and associated risk factors. The occurrence of irAEs is more frequent when ICIs are combined; with neurological, cardiovascular, hematological, and rheumatic irAEs more commonly linked to PD1/PD-L1 inhibitors and cutaneous and gastrointestinal irAEs more prevalent with CTLA4 inhibitors. Due to the often-nonspecific signs and symptoms, the diagnosis of irAEs (especially for those rare ones) can be challenging. The differential with primary autoimmune disorders becomes sometimes intricate, given the clinical and pathophysiological similarities. In conclusion, considering the escalating use of ICIs, this area of research necessitates additional clinical studies and practical insights, especially the development of biomarkers for predicting immune toxicities. In addition, there is a need for heightened education for both clinicians and patients to enhance understanding and awareness.

Introduction and overview of immunopathological mechanisms and future directions.

Paraneoplastic neurological disorders represent a significant part of the field of autoimmune neurology. Most neural autoantibodies discovered to date are associated with underlying malignancy and in that context are considered paraneoplastic antibody biomarkers. These autoantibodies can be divided into two major categories: those that target intracellular proteins (not pathogenic) and those that target plasma membrane proteins (pathogenic). Disorders accompanied by the former are mediated primarily by neural peptide-specific cytotoxic T-cells, are commonly associated with cancer, and are poorly responsive to immunotherapy. Disorders accompanied by the latter represent antibody-mediated diseases and are generally more responsive to immunotherapy. Areas of significant unmet need in the context of paraneoplastic neurological disorders include novel therapeutic options, as FDA-approved therapies are lacking. This chapter provides a brief overview of immunopathological mechanisms and potential future therapeutic targets. Our contributing authors and their chapters are also introduced.

Artificial intelligence of imaging and clinical neurological data for predictive, preventive and personalized (P3) medicine for Parkinson Disease: The NeuroArtP3 protocol for a multi-center research study.

BACKGROUND: The burden of Parkinson Disease (PD) represents a key public health issue and it is essential to develop innovative and cost-effective approaches to promote sustainable diagnostic and therapeutic interventions. In this perspective the adoption of a P3 (predictive, preventive and personalized) medicine approach seems to be pivotal. The NeuroArtP3 (NET-2018-12366666) is a four-year multi-site project co-funded by the Italian Ministry of Health, bringing together clinical and computational centers operating in the field of neurology, including PD. OBJECTIVE: The core objectives of the project are: i) to harmonize the collection of data across the participating centers, ii) to structure standardized disease-specific datasets and iii) to advance knowledge on disease's trajectories through machine learning analysis. METHODS: The 4-years study combines two consecutive research components: i) a multi-center retrospective observational phase; ii) a multi-center prospective observational phase. The retrospective phase aims at collecting data of the patients admitted at the participating clinical centers. Whereas the prospective phase aims at collecting the same variables of the retrospective study in newly diagnosed patients who will be enrolled at the same centers. RESULTS: The participating clinical centers are the Provincial Health Services (APSS) of Trento (Italy) as the center responsible for the PD study and the IRCCS San Martino Hospital of Genoa (Italy) as the promoter center of the NeuroartP3 project. The computational centers responsible for data analysis are the Bruno Kessler Foundation of Trento (Italy) with TrentinoSalute4.0 -Competence Center for Digital Health of the Province of Trento (Italy) and the LISCOMPlab University of Genoa (Italy). CONCLUSIONS: The work behind this observational study protocol shows how it is possible and viable to systematize data collection procedures in order to feed research and to advance the implementation of a P3 approach into the clinical practice through the use of AI models.

Non-lesional white matter in relapsing-remitting multiple sclerosis assessed by multicomponent T2 relaxation.

INTRODUCTION: The purpose of the study is to investigate, by T2 relaxation, non-lesional white matter (WM) in relapsing-remitting (RR) multiple sclerosis (MS). METHODS: Twenty stable RR MS patients underwent 1.5T Magnetic Resonance Imaging (MRI) with 3D Fluid-Attenuated Inversion-Recovery (FLAIR), 3D-T1-weighted, and T2-relaxation multi-echo sequences. The Lesion Segmentation Tool processed FLAIR images to identify focal lesions (FLs), whereas T1 images were segmented to identify WM and FL sub-volumes with T1 hypo-intensity. Non-lesional WM was obtained as the segmented WM, excluding FL volumes. The multi-echo sequence allowed decomposition into myelin water, intra-extracellular water, and free water (Fw), which were evaluated on the segmented non-lesional WM. Correlation analysis was performed between the non-lesional WM relaxation parameters and Expanded Disability Status Scale (EDSS), disease duration, patient age, and T1 hypo-intense FL volumes. RESULTS: The T1 hypo-intense FL volumes correlated with EDSS. On the non-lesional WM, the median Fw correlated with EDSS, disease duration, age, and T1 hypo-intense FL volumes. Bivariate EDSS correlation of FL volumes and WM T2-relaxation parameters did not improve significance. CONCLUSION: T2 relaxation allowed identifying subtle WM alterations, which significantly correlated with EDSS, disease duration, and age but do not seem to be EDSS-predictors independent from FL sub-volumes in stable RR patients. Particularly, the increase in the Fw component is suggestive of an uninvestigated prodromal phenomenon in brain degeneration.

Models of care in emergency neurology: from the Neuro Fast Track to the emergency neurologist-a position paper of the Italian Association for Emergency Neurology (ANEU).

I n the context of an adequate health care organization, the figure of the neurologist as an emergency operator (in the emergency room-ER-and/or in a dedicated outpatient clinic) is crucial for an effective functional connection with the territory (and therefore with general practitioners), a reduction in inappropriate ER accesses, specific diagnostic and therapeutic approaches to neurological emergencies in the ER and a reduction in nonspecific or even unnecessary instrumental investigations. In this position paper of the Italian Association of Emergency Neurology (ANEU: Associazione Neurologia dell'Emergenza Urgenza), these issues are addressed, and two important organizational solutions are proposed: 1) The Neuro Fast Track, as an outpatient organization approach strongly linked to general practitioners and non-neurological specialists and dedicated to cases with deferrable urgency (to be assessed within 72 h) 2) The identification of an emergency neurologist, who is engaged in ER assessments as a consultant and involved in the management of the semi-intensive care unit of the emergency neurology and the stroke unit according to an appropriate rotation, as well as in consultations for patients with neurological emergencies in inpatient wards The possibility of computerizing the screening of patients with deferrable urgency in the Neuro Fast Track is described. A dedicated app represents an important tool that can facilitate the identification of patients for whom deferred assessment is appropriate, the scheduling of neurological examinations and reductions in the booking time through a more rapid approach to specialist assessment and subsequent investigations.

Adult-onset KMT2B-related dystonia.

KMT2B-related dystonia (DYT-KMT2B, also known as DYT28) is an autosomal dominant neurological disorder characterized by varying combinations of generalized dystonia, psychomotor developmental delay, mild-to-moderate intellectual disability and short stature. Disease onset occurs typically before 10 years of age. We report the clinical and genetic findings of a series of subjects affected by adult-onset dystonia, hearing loss or intellectual disability carrying rare heterozygous KMT2B variants. Twelve cases from five unrelated families carrying four rare KMT2B missense variants predicted to impact protein function are described. Seven affected subjects presented with adult-onset focal or segmental dystonia, three developed isolated progressive hearing loss, and one displayed intellectual disability and short stature. Genome-wide DNA methylation profiling allowed to discriminate these adult-onset dystonia cases from controls and early-onset DYT-KMT2B patients. These findings document the relevance of KMT2B variants as a potential genetic determinant of adult-onset dystonia and prompt to further characterize KMT2B carriers investigating non-dystonic features.

TWNK in Parkinson's Disease: A Movement Disorder and Mitochondrial Disease Center Perspective Study.

BACKGROUND: Parkinsonian features have been described in patients harboring variants in nuclear genes encoding for proteins involved in mitochondrial DNA maintenance, such as TWNK. OBJECTIVES: The aim was to screen for TWNK variants in an Italian cohort of Parkinson's disease (PD) patients and to assess the occurrence of parkinsonism in patients presenting with TWNK-related autosomal dominant progressive external ophthalmoplegia (TWNK-adPEO). METHODS: Genomic DNA of 263 consecutively collected PD patients who underwent diagnostic genetic testing was analyzed with a targeted custom gene panel including TWNK, as well as genes causative of monogenic PD. Genetic and clinical data of 18 TWNK-adPEO patients with parkinsonism were retrospectively analyzed. RESULTS: Six of 263 PD patients (2%), presenting either with isolated PD (n = 4) or in combination with bilateral ptosis (n = 2), carried TWNK likely pathogenic variants. Among 18 TWNK-adPEO patients, 5 (28%) had parkinsonism. CONCLUSIONS: We show candidate TWNK variants occurring in PD without PEO. This finding will require further confirmatory studies. © 2022 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Agrypnia excitata as the main feature in anti-leucine-rich glioma-inactivated 1 encephalitis: a detailed clinical and polysomnographic semiological analysis.

BACKGROUND AND PURPOSE: The core manifestations of leucine-rich glioma-inactivated 1 (LGI1) autoantibody-mediated encephalitis are limbic encephalitis and faciobrachial dystonic seizures. Agrypnia excitata (AE) is a rare syndrome characterized by sleep-wake cycle disruption, autonomic hyperactivation and episodes of oneiric stupor. Only a few diseases are known to present with AE. An autoimmune etiology must be considered when accompanied by neuromyotonia. A case of anti-LGI1 encephalitis presenting with AE is reported. METHODS: Detailed clinical, video-polysomnographic, laboratory, radiological and long-term follow-up assessments were performed. RESULTS: A previously healthy 58-year-old man was referred for a rapidly progressive change in mental status, characterized by persistent drowsiness and confusion, accompanied by frequent episodes of unconscious gestures ranging from simple stereotyped movements to more complex actions mimicking various daily activities. Other symptoms included tachycardia, hyperhidrosis, mild hyponatremia, rare faciobrachial dystonic seizures, and a single generalized tonic-clonic seizure, but no neuromyotonia. Prolonged video-polysomnography excluded epileptic activity and showed continuous monomorphic slowing of background activity not consistent with a regular wakefulness or sleep state. A brain magnetic resonance imaging scan was unremarkable. Brain fluorodeoxyglucose positron emission tomography revealed hypermetabolism of the hippocampi, amygdala and basal ganglia. Anti-LGI1 antibodies were detected in the cerebrospinal fluid. The sleep disorder resolved progressively after starting immunotherapy. CONCLUSIONS: Agrypnia excitata can be a dominant, treatable manifestation of anti-LGI1 encephalitis. Oneiric stupor episodes are a useful clinical feature for establishing diagnostic suspicion and could provide a window to understanding the mechanisms behind some movement disorders in autoimmune encephalitis.

Opinion, knowledge, and clinical experience with functional neurological disorders among Italian neurologists: results from an online survey.

BACKGROUND: Functional neurological disorders (FND) are disabling medical conditions commonly seen in neurological practice. Neurologists play an essential role in managing FND, from establishing a diagnosis to coordination of multidisciplinary team-based treatment for patients. With this study, we investigated the knowledge and the clinical experience of Italian neurologists in managing patients with FND. METHODS: Members of the Italian Society of Neurology were invited via e-mail to participate in this ad hoc online survey; 492 questionnaires were returned completed. RESULTS: The term "Functional neurological disorders" in reference to FND was used more frequently than other psychological (e.g., psychogenic or conversion), or descriptive terms (e.g., non-organic or stress-related). When speaking with patients, the respondents stated that they preferred explaining symptoms based on abnormal functioning of the nervous system than discussing mental illness and that they would refer their patient to a psychologist rather than to a psychiatrist. Few considered that physiotherapy and psychiatric interventions are useful approaches to treating FND. Some believed that patients simulate their symptoms. CONCLUSIONS: Overall, the responses suggest that knowledge about scientific advances in FND is somewhat sparse. A psychiatric-centered view of FND opens the way to an approach in which neurobiological and psychological aspects constitute essential factors of the condition. In this context, professional education could improve understanding of FND and optimize patient management.

Characterization and management of neurological adverse events during immune-checkpoint inhibitors treatment: an Italian multicentric experience.

BACKGROUND: Neurological immune-related adverse events (nirAEs) are rare toxicities of immune-checkpoint inhibitors (ICI). With the increase of ICI oncological indications, their incidence is growing. Their recognition and management remain nevertheless challenging. METHODS: A national, web-based database was built to collect cases of neurological symptoms in patients receiving ICI and not attributable to other causes after an adequate workup. RESULTS: We identified 27 patients who developed nirAEs (20 males, median age 69 years). Patients received anti-PD1/PDL1 (78%), anti-CTLA4 (4%), or both (19%). Most common cancers were melanoma (30%) and non-small cell lung cancer (26%). Peripheral nervous system was mostly affected (78%). Median time to onset was 43.5 days and was shorter for peripheral versus central nervous system toxicities (36 versus 144.5 days, p = 0.045). Common manifestations were myositis (33%), inflammatory polyradiculoneuropathies (33%), and myasthenia gravis (19%), alone or in combination, but the spectrum of diagnoses was broad. Most patients received first-line glucocorticoids (85%) or IVIg (15%). Seven patients (26%) needed second-line treatments. At last follow-up, four (15%) patients were deceased (encephalitis, 1; myositis/myasthenia with concomitant myocarditis, 2; acute polyradiculoneuropathy, 1), while seven (26%) had a complete remission, eight (30%) partial improvement, and six (22%) stable/progressing symptoms. ICI treatment was discontinued in most patients (78%). CONCLUSIONS: Neurological irAEs are rare but potentially fatal. They primarily affect neuromuscular structures but encompass a broad range of presentations. A prompt recognition is mandatory to timely withheld immunotherapy and administrate glucocorticoids. In corticoresistant or severely affected patients, second-line treatments with IVIg or plasmapheresis may result in additional benefit.

Paraneoplastic Neuropathies: What's New Since the 2004 Recommended Diagnostic Criteria.

The diagnostic criteria published by the PNS (Paraneoplastic Neurological Syndromes) Euronetwork in 2004 provided a useful classification of PNS, including paraneoplastic neuropathies. Subacute sensory neuronopathy (SSN) was the most frequently observed peripheral PNS, whereas other forms of neuropathy, as sensory polyneuropathy, sensorimotor polyneuropathy, demyelinating neuropathies, autonomic neuropathies, and focal nerve or plexus lesions, were less frequent. At the time of publication, the main focus was on onconeural antibodies, but knowledge regarding the mechanisms has since expanded. The antibodies associated with PNS are commonly classified as onconeural (intracellular) and neuronal surface antibodies (NSAbs). Since 2004, the number of antibodies and the associated tumors has increased. Knowledge has grown on the mechanisms underlying the neuropathies observed in lymphoma, paraproteinemia, and multiple myeloma. Moreover, other unrevealed mechanisms underpin sensorimotor neuropathies and late-stage neuropathies, where patients in advanced stages of cancer-often associated with weight loss-experience some mild sensorimotor neuropathy, without concomitant use of neurotoxic drugs. The spectrum of paraneoplastic neuropathies has increased to encompass motor neuropathies, small fiber neuropathies, and autonomic and nerve hyperexcitability syndromes. In addition, also focal neuropathies, as cranial nerves, plexopathies, and mononeuropathies, are considered in some cases to be of paraneoplastic origin. A key differential diagnosis for paraneoplastic neuropathy, during the course of cancer disease (the rare occurrence of a PNS), is chemotherapy-induced peripheral neuropathy (CIPN). Today, novel complications that also involve the peripheral nervous system are emerging from novel anti-cancer therapies, as targeted and immune checkpoint inhibitor (ICH) treatment. Therapeutic options are categorized into causal and symptomatic. Causal treatments anecdotally mention tumor removal. Immunomodulation is sometimes performed for immune-mediated conditions but is still far from constituting evidence. Symptomatic treatment must always be considered, consisting of both drug therapy (e.g., pain) and attempts to treat disability and neuropathic pain.

Epidemiology of neuronal surface antibody-mediated autoimmune encephalitis and antibody-based diagnostics.

Epidemiologic data on neuronal surface antibody (NSAb)-associated autoimmune encephalitides (NSAE) are scarce and heterogeneous. We review our 13-year-long biobank-data collection and provide the incidence of NSAE in two Italian provinces (approx. Population of 1,400,000) over a 5-year period (July 2013-June 2018). NSAbs were diagnosed in 75 out of 1179 tested patients (6.4%). The most common NSAbs were anti-LGI1 (30 cases), followed by NMDAR (24). Eleven cases of NSAE were diagnosed in Treviso and Trento provinces with an estimated incidence of 1.54 per 1,000,000 population (LGI1-encephalitis 0.84; C.I. 0.38-1.88). LGI1-E is the most frequent NSAE among adults.

Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes.

OBJECTIVE: The contemporary diagnosis of paraneoplastic neurologic syndromes (PNSs) requires an increasing understanding of their clinical, immunologic, and oncologic heterogeneity. The 2004 PNS criteria are partially outdated due to advances in PNS research in the last 16 years leading to the identification of new phenotypes and antibodies that have transformed the diagnostic approach to PNS. Here, we propose updated diagnostic criteria for PNS. METHODS: A panel of experts developed by consensus a modified set of diagnostic PNS criteria for clinical decision making and research purposes. The panel reappraised the 2004 criteria alongside new knowledge on PNS obtained from published and unpublished data generated by the different laboratories involved in the project. RESULTS: The panel proposed to substitute "classical syndromes" with the term "high-risk phenotypes" for cancer and introduce the concept of "intermediate-risk phenotypes." The term "onconeural antibody" was replaced by "high risk" (>70% associated with cancer) and "intermediate risk" (30%-70% associated with cancer) antibodies. The panel classified 3 levels of evidence for PNS: definite, probable, and possible. Each level can be reached by using the PNS-Care Score, which combines clinical phenotype, antibody type, the presence or absence of cancer, and time of follow-up. With the exception of opsoclonus-myoclonus, the diagnosis of definite PNS requires the presence of high- or intermediate-risk antibodies. Specific recommendations for similar syndromes triggered by immune checkpoint inhibitors are also provided. CONCLUSIONS: The proposed criteria and recommendations should be used to enhance the clinical care of patients with PNS and to encourage standardization of research initiatives addressing PNS.

Seizures, Edema, Thrombosis, and Hemorrhages: An Update Review on the Medical Management of Gliomas.

Patients affected with gliomas develop a complex set of clinical manifestations that deeply impact on quality of life and overall survival. Brain tumor-related epilepsy is frequently the first manifestation of gliomas or may occur during the course of disease; the underlying mechanisms have not been fully explained and depend on both patient and tumor factors. Novel treatment options derive from the growing use of third-generation antiepileptic drugs. Vasogenic edema and elevated intracranial pressure cause a considerable burden of symptoms, especially in high-grade glioma, requiring an adequate use of corticosteroids. Patients with gliomas present with an elevated risk of tumor-associated venous thromboembolism whose prophylaxis and treatment are challenging, considering also the availability of new oral anticoagulant drugs. Moreover, intracerebral hemorrhages can complicate the course of the illness both due to tumor-specific characteristics, patient comorbidities, and side effects of antithrombotic and antitumoral therapies. This paper aims to review recent advances in these clinical issues, discussing the medical management of gliomas through an updated literature review.

Immunophenotypical characterization of paraneoplastic neurological syndrome patients: a multicentric study.

Paraneoplastic neurological syndromes (PNS) are a group of rare and severe immune-mediated disorders that affect the nervous system in patients with cancer. The best way to diagnose a paraneoplastic neurological disorder is to identify anti-onconeural protein antibodies that are specifically associated with various cancers. The aim of this multicentric study was to clinically and immunologically characterize patients with PNS and study their association with cancer. Patients suspected to have PNS were enrolled from various clinical centres and were characterized immunologically. This study population consisted of 112 patients. Onset of PNS was mainly subacute (76 %). PNS patients had various neurological disorders and symptoms. PNS developed before the diagnosis of cancer in 28 definite PNS patients and in six suspected PNS patients. The most frequent autoantibodies detected in PNS patients were anti-Hu and anti-Yo. One definite PNS patient with cerebellar syndrome had anti-Tr antibody and seven patients had atypical antibodies. The literature associates these antibodies with various neurological disorders and cancers. Our observations confirm the important role of autoantibodies in PNS and their importance for the early diagnosis of cancer in PNS patients.

Stroke management during the coronavirus disease 2019 (COVID-19) pandemic: experience from three regions of the north east of Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige).

BACKGROUND: Efficiency of care chain response and hospital reactivity were and are challenged for stroke acute care management during the pandemic period of coronavirus disease 2019 (COVID-19) in North-Eastern Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige), counting 7,193,880 inhabitants (ISTAT), with consequences in acute treatment for patients with ischemic stroke. METHODS: We conducted a retrospective data collection of patients admitted to stroke units eventually treated with thrombolysis and thrombectomy, ranging from January to May 2020 from the beginning to the end of the main first pandemic period of COVID-19 in Italy. The primary endpoint was the number of patients arriving to these stroke units, and secondary endpoints were the number of thrombolysis and/or thrombectomy. Chi-square analysis was used on all patients; furthermore, patients were divided into two cohorts (pre-lockdown and lockdown periods) and the Kruskal-Wallis test was used to test differences on admission and reperfusive therapies. RESULTS: In total, 2536 patients were included in 22 centers. There was a significant decrease of admissions in April compared to January. Furthermore, we observed a significant decrease of thrombectomy during the lockdown period, while thrombolysis rate was unaffected in the same interval across all centers. CONCLUSIONS: Our study confirmed a decrease in admission rate of stroke patients in a large area of northern Italy during the lockdown period, especially during the first dramatic phase. Overall, there was no decrease in thrombolysis rate, confirming an effect of emergency care system for stroke patients. Instead, the significant decrease in thrombectomy rate during lockdown addresses some considerations of local and regional stroke networks during COVID-19 pandemic evolution.

Stroke and digital technology: a wake-up call from COVID-19 pandemic.

INTRODUCTION: The pandemic has implemented the need for new digital technologies as useful tools during the emergency and the long recovery phase that will follow. SARS-CoV-2 has strongly impacted stroke care with significant contraction in a number of patients treated. METHODS: This mini-review is an initiative of the "Digital Technologies, Web and Social Media Study Group" of the Italian Society of Neurology and briefly discusses digital tools for managing the acute phase and the rehabilitation after stroke, even considering the new apps that will improve the process of remote monitoring of patients after discharge at home. RESULTS: Telemedicine and digital technologies could play a role in each of the three stroke-belt stages: hyperacute treatment and reperfusion, acute care, etiological classification and secondary prevention and rehabilitation. CONCLUSION: The global emergency represented by the COVID-19 pandemic can be the stimulus to accelerate the digitalization process in the field of stroke for the use of new methods on a large scale.