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Purpose of ReviewTo elucidate the interconnection between sleep and stroke.Recent FindingsGrowing 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.SummarySleep 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.

Background and aimsHemiplegic 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.MethodsWe 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.ResultsCACNA1A-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.DiscussionThe 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.

BackgroundVaccines 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.MethodsWe 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.ResultsOut 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.ConclusionsOur 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.

ObjectivesTo investigate the safety and tolerability of COVID-19 vaccines in people with epilepsy (PwE).MethodsIn 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).ResultsA 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.ConclusionIn 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.

Abstract ObjectivesDelirium 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.MethodsPatients 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.ResultsFifty-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).ConclusionsAcute non-cardioembolic stroke patients with increased variability of heart rate and decreased vagal control are at risk for delirium.

Introduction Data on the population-based incidence of primary progressive aphasia (PPA), including all variants and Alzheimer’s disease (AD) biomarker profiles, are scarce. Methods We conducted a 4-year, prospective, population-based study in the Salento region of Southern Italy, identifying incident PPA cases through a territory-wide surveillance network. Clinical diagnoses followed consensus criteria; AD pathology was defined by positive CSF or amyloid PET biomarkers. Results We identified 35 incident PPA cases, yielding an overall incidence of 1.14 (95% CI, 0.79–1.59) per 100,000 person-years. Incidence peaked in the early 60s for men and in the late 70s for women. The logopenic variant was most frequent and invariably associated with AD pathology. Approximately 20% of nonfluent and semantic cases, and the majority unclassified cases, also showed AD biomarkers. Discussion These findings provide real-world epidemiological evidence and underscore the need for systematic biomarker assessment in PPA to guide diagnosis, prognosis, and access to emerging therapies.

Objectives: To investigate clinical and imaging predictors of short- and long-term outcomes in patients with posterior circulation stroke (PCS), with particular focus on infarct topography and ischemic burden. Methods: We conducted a retrospective multicenter observational study including 251 consecutive patients with acute PCS. All patients underwent CT angiography within 24 h and follow-up CT/MRI at 48–72 h. Clinical data, vascular risk factors, stroke severity (NIHSS), and functional outcome assessed by modified Rankin Scale (mRS), were collected. Short-term outcome was defined as mRS at discharge and long-term outcome as mRS at 3 months. Favorable outcome was defined as independence, graded as mRS 0–1. Imaging analysis included pc-ASPECTS, collateral scores, and quantitative ischemic volume assessment. Multivariable logistic regression was performed to identify independent predictors of outcome. Results: Among 251 patients, 105 (41.8%) had LVO. Patients with LVO presented with higher NIHSS scores, larger infarct volumes, and more frequent multiregional involvement. Basilar artery occlusion was associated with the most severe clinical and radiological profile. Infarct location, ischemic volume, baseline NIHSS, and pre-stroke mRS were independently associated with short-term outcome. For long-term outcome, age, infarct location, diabetes, and pre-stroke mRS remained significant predictors. LVO status and treatment variables were not independently associated with outcome. Conclusions: In PCS, outcome is primarily influenced by infarct topography and clinical factors rather than LVO status alone. Multiregional involvement and baseline disability are key determinants of prognosis. These findings underscore the need for PCS-specific prognostic models and highlight the importance of detailed imaging assessment beyond vessel occlusion.

Binaural beats (BB) are a non‐acoustic perception generated when two pure tones with a slight mismatch in frequency are presented separately to each ear. The aims of our study were to analyze the ability of 6‐Hz BB in entraining cortical activity, altering cortical connectivity, and influencing Autonomic Nervous System (ANS) functioning to evaluate, in future studies, their application in improving compliance with Non‐Invasive Ventilation (NIV) in critically ill patients. Twenty healthy volunteers underwent four 10‐min experimental auditory conditions while their electroencephalographic and polygraphic activities were recorded: Resting‐state, 6‐Hz BB, 6‐Hz monaural beats (MB), and random noise (RN). Frequency analysis and analysis of lagged‐phase connectivity were computed through eLORETA. Heart rate variability, respiratory rate, and pulse transit time were analyzed as indicators of ANS activity. 6‐Hpz BB entrained cortical activity at the beat frequency in the left cuneus and precuneus, in contrast with other experimental conditions. All auditory stimuli increased the interhemispheric lagged‐phase connectivity between auditory cortices. Contrary to MB and RN, BB induced only minimal changes in ANS parameters. 6‐Hz BB is effective in entraining cortical activity and induces only minimal changes in ANS parameters. These findings support the future use of BB as tools for increasing NIV compliance.

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 mm 2 in the MO group, 0.248 ± 0.091 mm 2 in the MA group and 0.184 ± 0.061 mm 2 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.