Movement disorders following mechanical thrombectomy resulting in ischemic lesions of the basal ganglia: An emerging clinical entity.

BACKGROUND AND PURPOSE: Post-stroke movement disorders (PMDs) following ischemic lesions of the basal ganglia (BG) are a known entity, but data regarding their incidence are lacking. Ischemic strokes secondary to proximal middle cerebral artery (MCA) occlusion treated with thrombectomy represent a model of selective damage to the BG. The aim of this study was to assess the prevalence and features of movement disorders after selective BG ischemia in patients with successfully reperfused acute ischemic stroke (AIS). METHODS: We enrolled 64 consecutive subjects with AIS due to proximal MCA occlusion treated with thrombectomy. Patients were clinically evaluated by a movement disorders specialist for PMDs onset at baseline, and after 6 and 12 months. RESULTS: None of the patients showed an identifiable movement disorder in the subacute phase of the stroke. At 6 and 12 months, respectively, 7/25 (28%) and 7/13 (53.8%) evaluated patients developed PMDs. The clinical spectrum of PMDs encompassed parkinsonism, dystonia and chorea, either isolated or combined. In most patients, symptoms were contralateral to the lesion, although a subset of patients presented with bilateral involvement and prominent axial signs. CONCLUSION: Post-stroke movement disorders are not uncommon in long-term follow-up of successfully reperfused AIS. Follow-up conducted by a multidisciplinary team is strongly advisable in patients with selective lesions of the BG after AIS, even if asymptomatic at discharge.

Clinical characteristics and treatment approach of established New-Onset status epilepticus (eNOSE): A Real-World multicenter experience.

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.

A systematic review of immunotherapy in high-grade glioma: learning from the past to shape future perspectives.

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.

Treatment of benzodiazepine-refractory status epilepticus: A retrospective, cohort study.

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.

Stroke and endocarditis: Reversing the point of view. A retrospective, cohort study.

STUDY OBJECTIVES: The primary objective of our study is to assess the endocarditis prevalence in patients admitted to the emergency department (ED) for a primary diagnosis of acute stroke (AS). Secondary objectives are the identification of early markers of endocarditis in AS patients and the analysis of the short-term outcome of this population. METHODS: In this observational, retrospective, cohort study we enrolled consecutive adult patients with a primary diagnosis of AS admitted to the Stroke Unit or to the Neurological Intensive Care Unit of our hospital who were then discharged with a diagnosis of endocarditis. These patients were then compared with age and sex-matched controls with a diagnosis of AS and atrial fibrillation. RESULTS: Endocarditis prevalence in patients admitted to the Stroke Unit or Neurological Intensive Care Unit with a primary diagnosis of AS is 1.0% (95% confidence interval 0.61-1.55). Fever on ED admission, concomitant cancer, low hemoglobin, low lymphocyte levels, a high neutrophils count and erythrocyte sedimentation levels could early differentiate among AS patients, those with endocarditis from those with atrial fibrillation. A moderate-to-severe valvular regurgitation is strongly suggestive of endocarditis. The short term-outcome is markedly worse in endocarditis patients compared to patients with atrial fibrillation, in terms of in-hospital mortality and discharge disability. CONCLUSIONS: Endocarditis prevalence in patients admitted for a primary diagnosis of AS is low, but this etiology leads to a poor outcome. Some laboratory, clinical-epidemiological and echocardiographic parameters may help the physician to early recognize this condition and, consequently, to promptly start an antibiotic therapy.

Sleep and Stroke: Opening Our Eyes to Current Knowledge of a Key Relationship.

PURPOSE OF REVIEW: To elucidate the interconnection between sleep and stroke. RECENT FINDINGS: Growing data support a bidirectional relationship between stroke and sleep. In particular, there is strong evidence that sleep-disordered breathing plays a pivotal role as risk factor and concur to worsening functional outcome. Conversely, for others sleep disorders (e.g., insomnia, restless legs syndrome, periodic limb movements of sleep, REM sleep behavior disorder), the evidence is weak. Moreover, sleep disturbances are highly prevalent also in chronic stroke and concur to worsening quality of life of patients. Promising novel technologies will probably allow, in a near future, to guarantee a screening of commonest sleep disturbances in a larger proportion of patients with stroke. Sleep assessment and management should enter in the routinary evaluation of stroke patients, of both acute and chronic phase. Future research should focus on the efficacy of specific sleep intervention as a therapeutic option for stroke patients.

Preventive migraine treatment in mitochondrial diseases: a case report of erenumab efficacy and literature review.

Migraine is a common condition in mitochondrial diseases, with a higher prevalence than in the general population. Although several clinical studies support the hypothesis that mitochondrial dysfunction plays a central role in the pathophysiology of migraine, currently there are few data in the literature regarding the efficacy and safety of drugs for the treatment and prophylaxis for this condition in patients with primary mitochondrial disorders. We report a 37-year-old woman affected by mitochondrial disease with progressive external ophthalmoplegia phenotype (PEO) associated with POLG mutation effectively treated with erenumab, in the absence of side effects. Monoclonal antibodies against the calcitonin gene-related peptide (CGRP) or against its receptor are innovative and specific therapies for migraine prophylaxis. This class of drugs is particularly suitable for subjects, such as those suffering from genetically determined mitochondrial dysfunction, in which pharmacological management can represent a challenge due to the nature of these neurogenetic disorders and/or the frequently associated comorbidities.

Heart rate variability and delirium in acute non-cardioembolic stroke: a prospective, cross-sectional, cohort study.

OBJECTIVES: Delirium is an acute fluctuating disorder of attention and awareness. It is associated with autonomic dysfunction and increased mortality. The primary endpoint of our study was to measure autonomic activity in acute stroke patients, by means of heart rate variability analysis, in order to identify autonomic modifications that can predispose to delirium. METHODS: Patients were consecutively enrolled from the stroke unit. Inclusion criteria were age ≥ 18 years and diagnosis of stroke with onset within the previous 72 h confirmed by neuroimaging. Exclusion criteria were atrial fibrillation, congestive heart failure, and conditions requiring intensive care unit. Patients were evaluated by means of Richmond Agitation Sedation Scale (RASS) and Confusion Assessment Method-Intensive Care Unit (CAM-ICU) at baseline, after 72 h, or when symptoms suggesting delirium occurred. For each patient, ECG was recorded at baseline assessment and HRV analysis was conducted on five consecutive minutes of artifact-free ECG traces. RESULTS: Fifty-six ECGs were available for analysis. During the study period, 11 patients developed delirium. Patients with and without delirium did not differ for sex, age, severity of stroke, and comorbidities. The delirium group had greater standard deviation of the heart rate (DLR - :9.16 ± 8.28; DLR + : 14.36 ± 5.55; p = 0.026) and lower power spectral density of the HF component (DLR - : 38.23 ± 19.23 n.u.; DLR + : 25.75 ± 8.77 n.u.; p = 0.031). CONCLUSIONS: Acute non-cardioembolic stroke patients with increased variability of heart rate and decreased vagal control are at risk for delirium.

Impact of COVID-19 vaccine on epilepsy in adult subjects: an Italian multicentric experience.

OBJECTIVES: To investigate the safety and tolerability of COVID-19 vaccines in people with epilepsy (PwE). METHODS: In this multicentric observational cohort study, we recruited adult patients (age > 18 years old) with epilepsy who attended the Outpatient Epilepsy Clinic from 1st July to 30th October 2021. We administered to the patients a structured questionnaire and interview on demographic and epilepsy characteristics, current treatment, previous SARS-CoV-2 infection, vaccine characteristics, post-vaccine seizure relapse, other side effect, variation of sleep habits, caffeine, or alcohol intake. Seizure frequency worsening was defined as a ratio between mean monthly frequency post-vaccination and mean monthly frequency pre-vaccination superior to 1. Patients were categorized in two groups: patients with seizure frequency worsening (WORSE) and patients with seizure stability (STABLE). RESULTS: A total of 358 people participated with a mean age of 47.46 ± 19.04. Focal seizure (79.1%), generalized epilepsy (20.4%), and unknown types of epilepsy (0.5%) were detected among participants. In total, 31 (8.7%) people expressed that they were not willing to receive a COVID-19 vaccine; 302 patients (92.35%) did not experience an increase in the seizure frequency (STABLE-group) whereas 25 patients (7.65%) had a seizure worsening (WORSE-group). Post-vaccine seizures occurred mainly in the 7 days following the administration of the vaccine. Patients in the WORSE-group were treated with a mean higher number of anti-seizure medication (ASMs) (p = 0.003) and had a higher pre-vaccine seizure frequency (p = 0.009) compared with patients in the STABLE-group. Drug-resistant epilepsy was also associated with seizure worsening (p = 0.01). One-year pre-vaccination seizure frequency pattern demonstrated that patients in the WORSE-group had a higher frequency pattern (p < 0.001). Multivariate analysis of the vaccinated group showed that only the seizure frequency pattern (confidence interval [CI] = 1.257-2.028; p < 0.001) was significantly associated with seizure worsening. CONCLUSION: In our cohort of vaccinated PwE, only a little percentage had a transient short-term increase of seizure frequency. The present study demonstrates that COVID-19 vaccines have a good safety and tolerability profile in the short term in PwE.

Headache onset after vaccination against SARS-CoV-2: a systematic literature review and meta-analysis.

BACKGROUND: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to reduce the risk of developing Coronavirus Disease 2019 (COVID-19). Despite the significant benefits in terms of reduced risk of hospitalization and death, different adverse events may present after vaccination: among them, headache is one of the most common, but nowadays there is no summary presentation of its incidence and no description of its main features. METHODS: We searched PubMed and EMBASE covering the period between January 1st 2020 and August 6th, 2021, looking for record in English and with an abstract and using three main search terms (with specific variations): COVID-19/SARS-CoV-2; Vaccination; headache/adverse events. We selected manuscript including information on subjects developing headache after injection, and such information had to be derived from a structured form (i.e. no free reporting). Pooled estimates and 95% confidence intervals were calculated. Analyses were carried out by vaccine vs. placebo, by first vs. second dose, and by mRNA-based vs. "traditional" vaccines; finally, we addressed the impact of age and gender on post-vaccine headache onset. RESULTS: Out of 9338 records, 84 papers were included in the review, accounting for 1.57 million participants, 94% of whom received BNT162b2 or ChAdOx1. Headache was generally the third most common AE: it was detected in 22% (95% CI 18-27%) of subjects after the first dose of vaccine and in 29% (95% CI 23-35%) after the second, with an extreme heterogeneity. Those receiving placebo reported headache in 10-12% of cases. No differences were detected across different vaccines or by mRNA-based vs. "traditional" ones. None of the studies reported information on headache features. A lower prevalence of headache after the first injection of BNT162b2 among older participants was shown. CONCLUSIONS: Our results show that vaccines are associated to a two-fold risk of developing headache within 7 days from injection, and the lack of difference between vaccine types enable to hypothesize that headache is secondary to systemic immunological reaction than to a vaccine-type specific reaction. Some descriptions report onset within the first 24 h and that in around one-third of the cases, headache has migraine-like features with pulsating quality, phono and photophobia; in 40-60% of the cases aggravation with activity is observed. The majority of patients used some medication to treat headache, the one perceived as the most effective being acetylsalicylic acid.

Delirium in acute stroke: A prospective, cross-sectional, cohort study.

BACKGROUND AND PURPOSE: Delirium is a neuropsychiatric disorder of attention and awareness that develops over a short time and fluctuates in severity. Although delirium has been extensively studied in intensive care units, the incidence of delirium in stroke units and its predictors in stroke patients need further investigation. The endpoints of our study were incidence of delirium in acute stroke and the risk factors that predispose to this condition. METHODS: Patients were consecutively enrolled in a stroke unit from April to October 2020. Inclusion criteria were: age ≥18 years, acute stroke and National Institute of Health Stroke Scale (NIHSS) score ≥1 at the time of clinical assessment of delirium. Exclusion criteria were: transient ischemic attack; absence of neuroimaging evidence of brain lesion; cerebral venous thrombosis; subarachnoid hemorrhage; and clinical conditions requiring intensive care unit treatment. All patients were evaluated by means of Richmond Agitation-Sedation Scale (RASS) and Confusion Assessment Method-Intensive Care Unit (CAM-ICU) scores at baseline, evaluations which were repeated within 72 h or when patients developed symptoms suggesting delirium. RESULTS: The overall incidence of delirium was 36/120 (30%). Delirium was associated with aphasia (odds ratio [OR] 9.77; confidence interval [CI] 1.2-79.6), chronic obstructive pulmonary disease (COPD; OR 16.67; CI 1.1-263.0), deep Fazekas score (OR 5.05; CI 1.7-14.8), and physical restraint (OR 45.02; CI 1.4-1411.5). Diabetes was associated with a lower incidence of delirium (OR 0.04; CI 0.026-0.7). CONCLUSIONS: Nearly one-third of patients (30%) had delirium in the acute phase of stroke. This finding supports the notion that delirium is a common complication of stroke. Delirium was associated with speech disorder, leukoencephalopathy, COPD and early use of physical restraint.

CACNA1A-p.Thr501Met mutation associated with familial hemiplegic migraine: a family report.

BACKGROUND AND AIMS: Hemiplegic migraine (HM) is a rare form of migraine characterized by the presence of a motor and other types of aura. HM can be sporadic or familial. Familial hemiplegic migraine (FHM) is an autosomal dominant disorder, classified into 3 subtypes, based on the gene involved (CACNA1A in FHM1, ATP1A2 in FHM2 and SCN1A in FHM3). The clinical presentation is highly heterogeneous and some attacks may be severe. We report the clinical characteristics and genetic analysis of 12 patients belonging to a family with CACNA1A-p.Thr501Met gene mutation. METHODS: We screened for mutations in CACNA1A gene 15 patients belonging to the same family. The exonic sequences of CACNA1A were analyzed using a Tru-seq® Custom Amplicon (TSCA) (Illumina Inc., San Diego, CA) targeted capture and paired end library kit. Sanger sequencing was used to confirm CACNA1A variants and segregation analysis. RESULTS: CACNA1A-p.Thr501Met mutation was found in 12 of the 15 patients screened, which was compatible with the diagnosis of FHM1. Attacks of hemiplegic migraine were reported by 10 of the 12 subjects (83.33%). Only one subject developed persistent mild cerebellar symptoms and none of the subjects developed cerebellar atrophy. DISCUSSION: The variant p.Thr501Met was described previously in association with episodic ataxia and rarely with FHM related to cerebellar symptoms. FHM1 has a broad clinical spectrum and about half of the families have cerebellar involvement. In our study, only one patient developed persistent cerebellar deficits. These data suggest that CACNA1A-p.Thr501Met mutation can occur prevalently as hemiplegic migraine.

Isotopic, mycotoxin, and pesticide analysis for organic authentication along the production chain of wheat-derived products.

Wheat-based products are staples in diets worldwide. Organic food frauds continuously threaten consumer trust in the agri-food system. A multi-method approach was conducted for the organic authentication and safety assessment of pasta and bakery products along their production chain. Bulk and Compound-Specific (CS) Isotope Ratio Mass Spectrometry (IRMS) suggested the δ15Nbulk, δ15Nleucine and δ15Nproline as promising organic markers, with CS able to distinguish between pairs which bulk analysis could not. Processing significantly affected the values of δ15Nleucine, δ13Cproline and δ13Cleucine. Multi-mycotoxin analysis (HT-2, T-2, DON, ZEN, OTA, AFB1) revealed higher contamination in conventional than organic samples, while both milling and baking significantly reduced mycotoxin content. Lastly, from the evaluation of 400 residues, isopyrazam was present at the highest concentration (0.12 mg/kg) in conventional wheat, exhibiting a 0.12 Processing Factor (PF), while tebuconazole levels remained unchanged in pasta production (90 °C) and reduced below LOQ in biscuits and crackers (180-250 °C).

QuEChERS method combined to liquid chromatography high-resolution mass spectrometry for the accurate and sensitive simultaneous determination of pyrrolizidine and tropane alkaloids in cereals and spices.

Within the last decades, in the EU, there has been an increasing interest in toxic plant alkaloids as food contaminants, especially after the continuous and growing consumption of plant-based foods compared with food of animal origin. In this regard, the once neglected presence of these tropane alkaloids (TAs) and pyrrolizidine alkaloids (PAs) has recently been reconsidered by the European Food Safety Authority, highlighting the lack of data and the need to develop risk assessment strategies. For this reason, the emphasis has been placed on detecting their occurrence in food through the development of accurate and sensitive analytical methods to achieve the determination of these compounds. The present study aims to elaborate and validate an analytical method based on QuEChERS sample preparation approach, exploiting the UHPLC coupled to the HRMS to simultaneously identify and quantify 21 PAs and two TAs in cereals and spices. For TAs, the obtained limit of detection (LOD) is 0.1 µg·kg-1 and the limit of quantification (LOQ) is 0.4 µg·kg-1 , while for PAs, the LODs values ranging between 0.2 to 0.3 µg·kg-1 and the LOQ, between 0.4 and 0.8 µg·kg-1 , ensuring compliance with the recently established European Regulations. Several commercial samples were analysed to further verify the applicability of this comprehensive analytical approach.

Antiseizure Medications for the Prophylaxis of Migraine during the Anti- CGRP Drugs Era.

Migraine and epilepsy are fundamentally distinct disorders that can frequently coexist in the same patient. These two conditions significantly differ in diagnosis and therapy but share some widely- used preventive treatments. Antiseizure medications (ASMs) are the mainstay of therapy for epilepsy, and about thirty different ASMs are available to date. ASMs are widely prescribed for other neurological and non-neurological conditions, including migraine. However, only topiramate and valproic acid/valproate currently have an indication for migraine prophylaxis supported by high-quality evidence. Although without specifically approved indications and with a low level of evidence or recommendation, several other ASMs are used for migraine prophylaxis. Understanding ASM antimigraine mechanisms, including their ability to affect the pro-migraine calcitonin gene-related peptide (CGRP) signaling pathway and other pathways, may be instrumental in identifying the specific targets of their antimigraine efficacy and may increase awareness of the neurobiological differences between epilepsy and migraine. Several new ASMs are under clinical testing or have been approved for epilepsy in recent years, providing novel potential drugs for migraine prevention to enrich the treatment armamentarium and drugs that inhibit the CGRP pathway.

Microvascular involvement in migraine: an optical coherence tomography angiography study.

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.