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BACKGROUND AND PURPOSE: Although there is extensive evidence about the safety of monoclonal antibodies against calcitonin gene-related peptide (anti-CGRP mAbs) in combination with traditional drugs, scarce data are available on the safety of their combination with other mAbs. This study aimed to evaluate the 6-month effectiveness and tolerability of anti-CGRP mAbs in combination with other mAbs for different diseases. METHODS: Patients included in the Italian Headache Registry and treated concomitantly with an anti-CGRP mAb and another mAb were included. Effectiveness outcomes for migraine included reduction from baseline of monthly headache days (MHDs), Migraine Disability Assessment (MIDAS) score, Headache Impact Test-6 (HIT-6) scores, and Patients' Global Impression of Change (PGIC) scale. Adverse events (AEs) were recorded. RESULTS: Thirty-eight patients were included. In 27 patients (71.1%), the anti-CGRP mAb was added to a previously ongoing mAb. Nine patients (23.7%) discontinued one of the two mAbs before the end of treatment (seven discontinued the anti-CGRP mAb and two the other mAb). One patient discontinued for AEs. Anti-CGRP mAbs were discontinued due to ineffectiveness (n = 5, 55.5%) and one each (11.1%) for clinical remission and lost to follow-up. MHDs significantly decreased from baseline to 3 months (p < 0.0001) and 6 months (p < 0.001), as did the MIDAS and the HIT-6 scores at 3 and 6 months (p < 0.001). For anti-CGRP mAbs, 27.4% of patients reported PGIC ≥ 5 at 3 months and 48.3% at 6 months. Mild AEs associated with introduction of a second mAb were detected in six patients (15.8%). CONCLUSIONS: In this real-world study, anti-CGRP mAbs showed safety and effectiveness when administered concomitantly with other mAbs.

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INTRODUCTION: Status Epilepticus (SE) can occur in patients without a previous epilepsy diagnosis, a condition identified as "new-onset status epilepticus" (NOSE). Treatment with benzodiazepine may fail in NOSE termination, requiring anti-seizure medication (ASM) employment. The term "established NOSE" (eNOSE) is generally employed in this context. This study aims to describe the main clinical characteristics of a large sample of patients suffering from eNOSE, compare the ASM efficacy, and explore the risk factors associated with ASM treatment unresponsiveness and eNOSE-associated mortality. METHODS: Adult patients diagnosed with eNOSE were retrospectively selected between January 2016 and December 2022. We reviewed demographics, clinical data, diagnostic work-up, and treatment. We considered the last ASM introduced before the eNOSE termination as effective. RESULTS: 123 patients were included (age: 67.9 ± 17.3). eNOSE acute etiology was mostly reported. In the overall cohort, phenytoin showed the highest response rate (p = 0.01). In the pairwise comparisons, valproate was superior to levetiracetam (p = 0.02) but not to lacosamide (p = 0.50). Phenytoin had a significantly higher resolution rate than levetiracetam (p = 0.001) but not lacosamide (p = 0.14). Thirty patients were refractory to ASM treatment. No predictors of refractoriness were identified. Thirty-nine patients died. Age and GCS were identified as eNOSE-related mortality risk factors. CONCLUSION: eNOSE frequently has an acute etiology with several associated syndromes. Phenytoin is more effective in managing eNOSE, even though lacosamide, valproate, and levetiracetam can represent further therapeutic options. Age and GCS are the main risk factors for eNOSE-associated mortality.

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A 52-year-old man experienced two seizures in January and June 2021. In October, the neurological examination did not reveal sensory/motor deficits. Brain magnetic resonance imaging (MRI) showed hyperintense lesions with contrast enhancement (CE) involving white matter bilaterally, brainstem, and cerebellum. Spine MRI showed hyperintense C2-C3 and C4-C6 lesions with CE. Anti-aquaporin-4 (AQP4) antibodies were detected, confirming the diagnosis of neuromyelitis optica spectrum disorder (NMOSD). The patient experienced a status epilepticus compatible with Epilepsia Partialis Continua treated with antiseizure medications. He was also treated with methylprednisolone, plasma exchange, and rituximab. Status epilepticus can be a rare manifestation of NMOSD, heightening the broad spectrum of AQP4 autoimmunity.

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Multiple sclerosis (MS) is a chronic inflammatory and degenerative demyelinating disease of the central nervous system of unknown etiology, which affects individuals in their early adulthood. However, nearly 5-10% of people with MS can be diagnosed at ages above 50 years old, referred to as late-onset multiple sclerosis (LOMS). Some studies have reported a distinctive presentation, clinical course, and prognosis for LOMS, implicating a different diagnostic and therapeutic approach for this population. Furthermore, similar manifestations between LOMS and other age-related conditions may lead to potential misdiagnosis and diagnostic delays, and a higher burden of multimorbidity associated with aging can further complicate the clinical picture. This review aims to explore the clinical characteristics, the disease course, and the differential diagnosis of LOMS and addresses therapeutic considerations for this population.

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OBJECTIVE: Soluble CD27 is a promising cerebrospinal fluid inflammatory biomarker in multiple sclerosis. In this study, we investigate relevant immune and neuro-pathological features of soluble CD27 in multiple sclerosis. METHODS: Protein levels of soluble CD27 were correlated to inflammatory cell subpopulations and inflammatory cytokines and chemokines detected in cerebrospinal fluid of 137 patients with multiple sclerosis and 47 patients with inflammatory and non-inflammatory neurological disease from three independent cohorts. Production of soluble CD27 was investigated in cell cultures of activated T and B cells and CD27-knockout T cells. In a study including matched cerebrospinal fluid and post-mortem brain tissues of patients with multiple sclerosis and control cases, levels of soluble CD27 were correlated with perivascular and meningeal infiltrates and with neuropathological features. RESULTS: We demonstrate that soluble CD27 favours the differentiation of interferon-γ-producing T cells and is released through a secretory mechanism activated by TCR engagement and regulated by neutral sphingomyelinase. We also show that the levels of soluble CD27 correlate with the representation of inflammatory T cell subsets in the CSF of patients with relapsing-remitting multiple sclerosis and with the magnitude of perivascular and meningeal CD27 + CD4 + and CD8 + T cell infiltrates in post-mortem central nervous system tissue, defining a subgroup of patients with extensive active inflammatory lesions. INTERPRETATION: Our results demonstrate that soluble CD27 is a biomarker of disease activity, potentially informative for personalized treatment and monitoring of treatment outcomes.

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High-grade gliomas (HGGs) constitute the most common malignant primary brain tumor with a poor prognosis despite the standard multimodal therapy. In recent years, immunotherapy has changed the prognosis of many cancers, increasing the hope for HGG therapy. We conducted a comprehensive search on PubMed, Scopus, Embase, and Web of Science databases to include relevant studies. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Fifty-two papers were finally included (44 phase II and eight phase III clinical trials) and further divided into four different subgroups: 14 peptide vaccine trials, 15 dendritic cell vaccination (DCV) trials, six immune checkpoint inhibitor (ICI) trials, and 17 miscellaneous group trials that included both "active" and "passive" immunotherapies. In the last decade, immunotherapy created great hope to increase the survival of patients affected by HGGs; however, it has yielded mostly dismal results in the setting of phase III clinical trials. An in-depth analysis of these clinical results provides clues about common patterns that have led to failures at the clinical level and helps shape the perspective for the next generation of immunotherapies in neuro-oncology.

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BACKGROUND: Among university students, migraine is notably prevalent and is linked to compromised academic performance and daily functioning. Medical students are a particularly vulnerable category due to the demanding nature of their training, as they are often exposed to headache trigger factors. We therefore aimed to determine the prevalence, characteristics, and healthcare-seeking practices of primary headaches among Italian medical students. METHODS: We conducted a cross-sectional study among medical students attending the Università Cattolica del Sacro Cuore in Rome who completed a self-administered questionnaire designed following the International Classification of Headache Disorders-3 criteria. The questionnaire assessed sociodemographic and headache features, healthcare utilization, the use of symptomatic and preventive treatment, and headache trigger factors. RESULTS: Five hundred thirty-six students filled out the questionnaire. The lifetime and last-year prevalence of headache in this cohort was 76.7% (n = 411). Among the students surveyed, migraine had a prevalence of 26.9%, probable migraine of 12.9%, and tension-type headache (TTH)/probable TTH of 36.9%. Two hundred and forty-six students (59.8%) reported that their headache worsened after starting university. All students reporting headache had at least one trigger factor. In students fulfilling the criteria for migraine (n = 144), 137 (95.1%) had previously used acute non-prescription treatments, and eight concurrently used a preventive treatment. Thirty-five students fulfilling the criteria for migraine underwent a brain MRI scan (24.3%), 43 performed a neurological evaluation (29.9%), 36 received a diagnosis of migraine (25%), and 20 (13.9%) accessed the emergency room. DISCUSSION: Migraine and TTH are common among medical students in Italy despite low healthcare resource utilization. These results support the need to promote public health policies and strategies in order to reduce the disability and burden associated with primary headaches among medical students.

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Multiple sclerosis (MS) is a chronic, inflammatory, degenerative demyelinating disease of the central nervous system (CNS) of unknown etiology that affects individuals in their early adulthood. In the last decade, life expectancy for people with MS (PwMS) has almost equaled that of the general population. This demographic shift necessitates a heightened awareness of comorbidities, especially the ones that can be prevented and modified, that can significantly impact disease progression and management. Vascular comorbidities are of particular interest as they are mostly modifiable health states, along with voluntary behaviors, such as smoking and alcohol consumption, commonly observed among individuals with MS. Vascular risk factors have also been implicated in the etiology of cerebral small vessel disease. Furthermore, differentiating between vascular and MS lesion load poses a significant challenge due to overlapping clinical and radiological features. This review describes the current evidence regarding the range of preventable and modifiable comorbidities and risk factors and their implications for PwMS.

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Post-acute neurological sequelae of COVID-19 affect millions of people worldwide, yet little data is available to guide treatment strategies for the most common symptoms. We conducted a scoping review of PubMed/Medline from 1/1/2020-4/1/2023 to identify studies addressing diagnosis and treatment of the most common post-acute neurological sequelae of COVID-19 including: cognitive impairment, sleep disorders, headache, dizziness/lightheadedness, fatigue, weakness, numbness/pain, anxiety, depression and post-traumatic stress disorder. Utilizing the available literature and international disease-specific society guidelines, we constructed symptom-based differential diagnoses, evaluation and management paradigms. This pragmatic, evidence-based consensus document may serve as a guide for a holistic approach to post-COVID neurological care and will complement future clinical trials by outlining best practices in the evaluation and treatment of post-acute neurological signs/symptoms.

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Multiple sclerosis (MS) is a chronic, inflammatory, and degenerative disease of the central nervous system (CNS). Inflammation is observed in all stages of MS, both within and around the lesions, and can have beneficial and detrimental effects on MS pathogenesis. A possible mechanism for the neuroprotective effect in MS involves the release of brain-derived neurotrophic factor (BDNF) by immune cells in peripheral blood and inflammatory lesions, as well as by microglia and astrocytes within the CNS. BDNF is a neurotrophic factor that plays a key role in neuroplasticity and neuronal survival. This review aims to analyze the current understanding of the role that inflammation plays in MS, including the factors that contribute to both beneficial and detrimental effects. Additionally, it explores the potential role of BDNF in MS, as it may modulate neuroinflammation and provide neuroprotection. By obtaining a deeper understanding of the intricate relationship between inflammation and BDNF, new therapeutic strategies for MS may be developed.

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OBJECTIVE: The aim of this study was to evaluate the microvasculature of the macula and the optic nerve in patients affected by migraine with aura (MA) and without aura (MO) by optical coherence tomography angiography (OCTA), comparing the findings with healthy controls (HC). METHODS: We collected data from ocular and orthotic examinations, including eye motility, intraocular pressure measurement, best-corrected visual acuity (BCVA) measurement, objective refraction measurement, fundus examination, macular and optic disk OCTA examination. All subjects were imaged with solix fullrange OCT. The following OCTA parameters were recorded: macular vessel density (VD), inside disc VD, peripapillary VD, disc whole image VD, fovea choriocapillaris VD, fovea VD, parafovea VD, peripapillary thickness, fovea thickness, parafovea thickness, macular full retinal thickness, and foveal avascular zone (FAZ) parameters. Clinical and demographical data about migraine patients were collected by a neurologist. RESULTS: We included 56 eyes from 28 patients with a diagnosis of MO, 32 eyes from 16 patients with a diagnosis of MA, and 32 eyes from 16 HC subjects. The FAZ area was 0.230 ± 0.099 mm2 in the MO group, 0.248 ± 0.091 mm2 in the MA group and 0.184 ± 0.061 mm2 in the control group. The FAZ area was significantly larger in the MA group than in the HC group (p = 0.007). The foveal choriocapillaris VD was significantly lower in MA patients (63.6 ± 2.49%) when compared with MO patients (65.27 ± 3.29%) (p = 0.02). CONCLUSION: An impairment of retinal microcirculation can be detected in patients with MA, as demonstrated by the enlargement of FAZ. Moreover, the study of choroid circulation may reveal microvascular damage in patients with migraine with aura. OCTA is a useful non-invasive screening tool for the detection of microcirculatory disturbance in patients with migraine.

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BACKGROUND: To assess the ability of the 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) clinical criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) to include within their classification the whole spectrum of clinical heterogeneity of the disease and to define the clinical characteristics of the unclassifiable clinical forms. METHODS: The 2021 EAN/PNS clinical criteria for CIDP were applied to 329 patients fulfilling the electrodiagnostic (and in some cases also the supportive) criteria for the diagnosis of CIDP. Clinical characteristics were reviewed for each patient not strictly fulfilling the clinical criteria ('unclassifiable'). RESULTS: At study inclusion, 124 (37.5%) patients had an unclassifiable clinical presentation, including 110 (89%) with a typical CIDP-like clinical phenotype in whom some segments of the four limbs were unaffected by weakness ('incomplete typical CIDP'), 10 (8%) with a mild distal, symmetric, sensory or sensorimotor polyneuropathy confined to the lower limbs with cranial nerve involvement ('cranial nerve predominant CIDP') and 4 (1%) with a symmetric sensorimotor polyneuropathy limited to the proximal and distal areas of the lower limbs ('paraparetic CIDP'). Eighty-one (65%) patients maintained an unclassifiable presentation during the entire disease follow-up while 13 patients progressed to typical CIDP. Patients with the unclassifiable clinical forms compared with patients with typical CIDP had a milder form of CIDP, while there was no difference in the distribution patterns of demyelination. CONCLUSIONS: A proportion of patients with CIDP do not strictly fulfil the 2021 EAN/PNS clinical criteria for diagnosis. These unclassifiable clinical phenotypes may pose diagnostic challenges and thus deserve more attention in clinical practice and research.

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BACKGROUND: The Cluster Headache Impact Questionnaire (CHIQ) is a specific and easy-to-use questionnaire to assess the current impact of cluster headache (CH). The aim of this study was to validate the Italian version of the CHIQ. METHODS: We included patients diagnosed with episodic CH (eCH) or chronic CH (cCH) according to the ICHD-3 criteria and included in the "Italian Headache Registry" (RICe). The questionnaire was administered to patients through an electronic form in two sessions: at first visit for validation, and after 7 days for test-retest reliability. For internal consistency, Cronbach's alpha was calculated. Convergent validity of the CHIQ with CH features and the results of questionnaires assessing anxiety, depression, stress, and quality of life was evaluated using Spearman's correlation coefficient. RESULTS: We included 181 patients subdivided in 96 patients with active eCH, 14 with cCH, and 71 with eCH in remission. The 110 patients with either active eCH or cCH were included in the validation cohort; only 24 patients with CH were characterized by a stable attack frequency after 7 days, and were included in the test-retest cohort. Internal consistency of the CHIQ was good with a Cronbach alpha value of 0.891. The CHIQ score showed a significant positive correlation with anxiety, depression, and stress scores, while showing a significant negative correlation with quality-of-life scale scores. CONCLUSION: Our data show the validity of the Italian version of the CHIQ, which represents a suitable tool for evaluating the social and psychological impact of CH in clinical practice and research.

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BACKGROUND AND PURPOSE: The aim was to evaluate the risk of relapse after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, and its safety and tolerability, in patients with chronic inflammatory neuropathies. METHODS: In this multicenter, cohort and case-crossover study, the risk of relapse associated with SARS-CoV-2 vaccination was assessed by comparing the frequency of relapse in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) patients who underwent or did not undergo vaccination. Frequency of relapse in the 3 months prior to and after vaccination, and safety and tolerability of SARS-CoV-2 vaccination, were also assessed. RESULTS: In all, 336 patients were included (278 CIDP, 58 MMN). Three hundred and seven (91%) patients underwent SARS-CoV-2 vaccination. Twenty-nine patients (9%) did not undergo vaccination. Mild and transient relapses were observed in 16 (5%) patients (13 CIDP, 3 MMN) after SARS-CoV-2 vaccination and in none of the patients who did not undergo vaccination (relative risk [RR] 3.21, 95% confidence interval [CI] 0.19-52.25). There was no increase in the specific risk of relapse associated with type of vaccine or diagnosis. Comparison with the 3-month control period preceding vaccination revealed an increased risk of relapse after vaccination (RR 4.00, 95% CI 1.35-11.82), which was restricted to CIDP patients (RR 3.25, 95% CI 1.07-9.84). The safety profile of SARS-CoV-2 vaccination was characterized by short-term, mild-to-moderate local and systemic adverse events. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in CIDP and MMN patients does not seem to be associated with an increased risk of relapse at the primary end-point, although a slightly increased risk in CIDP patients was found compared to the 3 months before vaccination.

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INTRODUCTION: Status epilepticus (SE) is a frequent neurological emergency, derived from the failure of mechanisms responsible for seizure termination. The present study aims to compare the efficacy of the most common antiseizure medications (ASMs) employed for the treatment of benzodiazepine-refractory SE. METHODS: We performed a retrospective cohort study of all SE episodes treated in our hospital between January 2016 and December 2020. Inclusion criteria were: age ≥ 18 years; a diagnosis of status epilepticus. Exclusion criteria were: status epilepticus resolved by initial therapy with benzodiazepines; impossibility to retrieve medical records. We considered as effective the ASM that was the last drug introduced or increased in dose before termination of SE and without changes in the co-medication. RESULTS: A total of 244 episodes in 219 patients were included in the study. The mean age of the final study cohort was 63.6 ± 19.2, with 108 (49%) men. In the total cohort, phenytoin (PHT) showed the highest response rate (57.6%), followed by lacosamide (LCM) (40.7%) and valproate (VPA) (39.8%). The comparative efficacy among the different drugs was significantly different (p < 0.001). In the pairwise comparisons, VPA was superior to levetiracetam (LEV) (response rate: 39.75% vs 24.71%; p = 0.004), but not to LCM. Phenytoin had a significantly higher resolution rate compared to VPA (response rate: 57.63% vs 39.75%; p = 0.02) and LEV (response rate: 57.63% vs 24.71; p < 0.001). The clinical predictors of anaesthetics administration were a disorder of consciousness upon clinical presentation, previous diagnosis of epilepsy, and younger age. CONCLUSION: In our cohort of SE, PHT showed higher effectiveness in terminating established SE, as well as refractory SE in the subgroup of patients treated with anaesthetics.

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We present a case of a 61-year-old woman with an atypical non-arteritic anterior ischemic optic neuropathy (NA-AION) as a unique manifestation of COVID-19. Furthermore, the patient worsened after Pfizer-BioNTech COVID-19 vaccine administration. Our findings suggest that NA-AION could result from microangiopathic/thrombotic events that may occur during SARS-CoV-2 infection and/or vaccination against COVID-19. This report sheds light on possible ophthalmologic complications of COVID-19.

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