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.

Temporalis muscle thickness as a predictor of functional outcome after reperfusion therapies for acute ischemic stroke: a retrospective, cohort study.

BACKGROUND: Sarcopenia, defined as the loss of skeletal muscle mass, has been associated with a worse functional outcome after stroke. Measurement of temporal muscle thickness (TMT) has been introduced as an easily obtainable surrogate marker to identify patients with sarcopenia. Our study aims to investigate the correlation between pre-stroke sarcopenia, measured by TMT assessment, and functional outcome in patients treated with revascularization procedures for acute ischemic stroke. METHODS: We included consecutive adult patients who underwent thrombolysis, endovascular thrombectomy or both for acute ischemic stroke at our Centre from January 2020 to June 2022. Besides collecting baseline clinical and neuroradiological features, TMT was measured on brain computed tomography scans according to a standardized protocol. Modified Rankin Scale (mRS) scores at 3 months represented the main endpoint of functional outcome. RESULTS: A total of 261 patients were available for the analysis. In univariate models, patients with excellent outcomes (mRS = 0-1) were younger, had higher TMT values and lower pre-event disability and stroke severity. In multivariate models higher TMT values resulted independently associated with reduced mortality (Odds Ratio 0.708, 95% Confidence Interval 0.538-0.930, p = 0.013). Age, diabetes, brain bleeding events and stroke severity were found to be predictors of mortality, too. CONCLUSIONS: Our retrospective analysis shows that in patients who underwent revascularization treatments for ischemic stroke TMT is as an independent predictor of survival easily obtainable from the baseline CT scan. Further investigation is required to confirm the role of sarcopenia assessment and TMT measurement in the prognostication toolkit of this disease.

Intranasal human-recombinant NGF administration improves outcome in children with post-traumatic unresponsive wakefulness syndrome.

BACKGROUND: Severe traumatic brain injury (TBI) is one of the most dramatic events in pediatric age and, despite advanced neuro-intensive care, the survival rate of these patients remains low. Children suffering from severe TBI show long-term sequelae, more pronounced in behavioral, neurological and neuropsychological functions leading to, in the most severe cases, an unresponsive wakefulness syndrome (UWS). Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. In experimental animal models, human- recombinant Nerve Growth Factor (hr-NGF) promotes neural recovery supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated processes. Only a few studies reported the efficacy of intranasal hr-NGF administration in children with post- traumatic UWS. METHODS: Children with the diagnosis of post-traumatic UWS were enrolled. These patients underwent a treatment with intranasal hr-NGF administration, at a total dose of 50 gamma/kg, three times a day for 7 consecutive days. The treatment schedule was performed for 4 cycles, at one month distance each. Neuroradiogical evaluation by Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG), and Power Spectral Density (PSD) was determined before the treatment and one month after the end. Neurological assessment was also deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale. RESULTS: Three children with post-traumatic UWS were treated. hr-NGF administration improved functional (PET and SPECT) and electrophysiological (EEG and PSD) assessment. Also clinical conditions improved, mainly for the reduction of spasticity and with the acquisition of voluntary movements, facial mimicry, attention and verbal comprehension, ability to cry, cough reflex, oral motility, and feeding capacity, with a significant improvement of their neurological scores. No side effects were reported. CONCLUSION: These promising results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from severe TBI and in patients with better baseline neurological conditions, to explore more thoroughly the benefits of this new approach on neuronal function recovery after traumatic brain damage.

Exploring the emotional and behavioural profile in paediatric narcolepsy type 1: A case-control study.

Narcolepsy type 1 (NT1) is a central disorder of hypersomnolence often arising in childhood and adolescence. NT1 has a significant, but poorly defined, psychological impact. We aimed to investigate the psycho-social functioning of children and adolescents with NT1. We performed a cross-sectional, child and parent-reported questionnaire survey in 37 children and adolescents (6-17 years) with NT1, compared with age- and sex-matched controls. Questionnaires (SSHS, ESS-CHAD, CDI, MASC, CBCL, CRS-R, and SNAP-IV) evaluated various aspects of behavioural and emotional profiles, sleep habits, and daytime sleepiness. Subsequently, NT1 intra-group analysis was performed to investigate the effect of sex (males vs females) and pharmacological treatment (treated vs non-treated) on psychological features. The NT1 questionnaires total scores were then correlated with the clinical characteristics (age, body mass index [BMI], ESS-CHAD score, cerebrospinal hypocretin-1 [Hcrt-1] levels, and diagnostic delay). Patients with NT1 showed a higher tendency to depressive symptoms, anxiety, somatisation, inattention, hyperactivity, oppositional/defiant problems, and other maladaptive behaviours compared with controls. Among NT1 patients, females showed a higher propensity to anxiety, and non-treated patients displayed higher depressive symptoms. Psychological symptoms increased with age, BMI, and daytime sleepiness in patients with NT1, while a younger age was associated with more frequent somatisation symptoms. Lower cerebrospinal Hcrt-1 levels correlated with poorer social competencies, daily activities, and inattention. Diagnostic delay was associated with a higher impact of depressive symptoms and behavioural problems. NT1 in children and adolescents is associated with poorer functioning in multiple psychological domains calling for a multidisciplinary approach and monitoring to reduce disease burden and to prevent psychiatric consequences.

Short- vs long-term assessment of heart rate variability: Clinical significance in Dravet Syndrome.

PURPOSE: Heart rate variability (HRV) is a promising prognostic biomarker in Dravet Syndrome (DS), but different studies are not always comparable, limiting its clinical application. In fact, multiple HRV parameters, analyzed over different timescales and in different states are reported. The aim of this study was to assess which HRV parameter is more reproducible and clinically significant, analyzing differences between wake and sleep. METHOD: Patients with DS, with available 24 h-ECG Holter-derived HRV, were screened to evaluate if they had EEG-derived ECG traces available within one month before/after the Holter. A 5-minute period in the awake and sleep state were analyzed and correlated with the 24 h-HRV. Several relevant clinical features such as age, a recent history of status epilepticus (SE), and frequent generalized tonic-clonic seizures (GTCS) were correlated to HRV parameters with multiple linear regression models. RESULTS: Thirty-oneawake recordings and 22 sleep recordings were included. HF was the parameter with the highest correlation in awake (Rho 0.745, p < 0.001) and in sleep (Rho 0.727, p < 0.001). Age was a significant factor in simple models for most of the parameters except RMSSD. A recent history of SE was associated with a significant reduction of HRV, both in simple and multiple regressions for all parameters except for awake LF and for sleep RMSSD and PNN50. Frequent GTCS were associated with a significant decrease in sleep RMSSD, HF, and LF, also when correcting for the effect of age and history of SE. When compared pairwise, a significant increase in sleep was seen for HF (median + 24.45 ms2, IQR -7.51/+172.18 ms2, p = 0.036; increase in 15/22 patients). CONCLUSION: A moderate degree of correlation between long- and short-term HRV was seen both in sleep and in awake, and a strong correlation for awake HF. HF, both in awake and sleep, was significantly associated with high seizure burden, including SE and frequent GTCS.

Basal ganglia ischaemic infarction after thrombectomy: cognitive impairment at acute stage.

BACKGROUND AND PURPOSE: After successful mechanical thrombectomy for middle cerebral artery occlusion, basal ganglia infarction is commonly detectable. Whilst the functional outcome of these patients is often good, less knowledge is available about the cognitive outcome. The aim of our study was to assess the presence of cognitive impairment within 1 week after thrombectomy. METHODS: In all, 43 subjects underwent a general cognitive assessment using the Montreal Cognitive Assessment and an extensive battery of tests. Patients were classified as cognitively impaired (CImp) or not (noCImp) according to a Montreal Cognitive Assessment score below 18. RESULTS: Cognitively impaired and noCImp subjects did not differ either in their National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at admittance, or in their Fazekas score and Alberta Stroke Program Early Computed Tomography Score. At discharge, CImp subjects showed higher scores than noCImp subjects on NIHSS (p = 0.002) and mRS (p < 0.001). The percentage of pathological performances on each neuropsychological test in the whole sample and in CImp and noCImp patients shows a similar cognitive profile between the groups. CONCLUSIONS: Some patients who underwent thrombectomy experienced a detectable cognitive impairment that probably led to worse NIHSS and mRS. The neuropsychological profile of such cognitive impairment at the acute stage consists of wide deficits in numerous cognitive domains, suggesting that basal ganglia damage may lead to complex functional impairments.

Acute confusional state in HaNDL syndrome.

OBJECTIVE: To assess epidemiological, clinical and neuroimaging features of acute confusional state in the Headache and Neurological Deficits with cerebrospinal fluid Lymphocytosis (HaNDL) syndrome. BACKGROUND: HaNDL is an increasingly recognized syndrome in which migraine-like headache episodes accompanied by hemiparaesthesia and/or hemiparesis and/or dysphasia are associated to CSF lymphocytic pleocytosis. The International Classification of Headache Disorders (ICHD-3) includes HaNDL syndrome in group 7 "headache attributed to non-vascular intracranial disorder" code 7.3.5, and lists the HaNDL-associated signs/symptoms that may be found less frequently. Confusional state is not mentioned in the 7.3.5-ICHD-3 "notes" or "comments" section as part of the HaNDL neurological spectrum. Moreover, the acute confusional state pathogenesis in HaNDL syndrome remains still uncertain and debated. METHODS: Here, we report a 32-year-old male who complained episodes of migraine-like headache and left hemiparaesthesia complicated by confusional state which led to discovering CSF lymphocytosis. Since other workup to determine the cause of his symptoms was otherwise negative, he was diagnosed as having HaNDL syndrome. We also ascertained and reviewed all available reports of HaNDL to assess the significance of confusional state in this syndrome. RESULTS: The search yielded 159 HaNDL cases among single reports and small/large series. Out of 159 patients who fulfilled the inclusion criteria for HaNDL according to the current ICHD at the time of diagnosis, 41 (25.7%) presented with acute confusional state. Among 41 HaNDL patients with confusional state, 16 (66.6%) out of 24 who underwent spinal tap had increased opening pressure. CONCLUSION: We propose that a mention of acute confusional state may be included in the "comments" section of "7.3.5-syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL)," when ICHD-3 diagnostic criteria will be updated. Moreover, we speculate that intracranial hypertension may play a role in the pathogenesis of the acute confusional state associated to HaNDL syndrome. Larger case series are needed to evaluate this hypothesis.

Association of Obstructive Sleep Apnea and Atrial Fibrillation in Acute Ischemic Stroke: A Cross-Sectional Study.

Background: There is a growing body of evidence suggesting a link between obstructive sleep apnea (OSA) and atrial fibrillation (AF). The primary objective of this study is to evaluate the association between OSA and AF in acute ischemic stroke. The secondary objective is to describe the clinical features of patients with acute ischemic stroke and concomitant OSA. Methods: We enrolled consecutive patients with acute ischemic stroke. All patients underwent full-night cardiorespiratory polygraphy. To determine if there is an association between AF and OSA, we compared the observed frequency of this association with the expected frequency from a random co-occurrence of the two conditions. Subsequently, patients with and without OSA were compared. Results: A total of 174 patients were enrolled (mean age 67.3 ± 11.6 years; 95 males). OSA and AF were present in 89 and 55 patients, respectively. The association OSA + AF was observed in 33/174 cases, which was not statistically different compared to the expected co-occurrence of the two conditions. Patients with OSA showed a higher neck circumference and body mass index, a higher prevalence of hypertension and dysphagia, and a higher number of central apneas/hypoapneas. In the multivariate analysis, dysphagia and hypertension were independent predictors of OSA. A positive correlation was observed between OSA severity, BMI, and neck circumference. The number of central apneas/hypoapneas was positively correlated with stroke severity. Conclusions: Our data suggest that OSA and AF are highly prevalent but not associated in acute stroke. Our findings support the hypothesis that OSA acts as an independent risk factor for stroke.

Early neurological deterioration in patients with minor stroke due to isolated M2 occlusion undergoing medical management: a retrospective multicenter study.

BACKGROUND: Patients with minor stroke and M2 occlusion undergoing best medical management (BMM) may face early neurological deterioration (END) that can lead to poor long-term outcome. In case of END, rescue mechanical thrombectomy (rMT) seems beneficial. Our study aimed to define factors relevant to clinical outcome in patients undergoing BMM with the possibility of rMT on END, and find predictors of END. METHODS: Patients with M2 occlusion and a baseline National Institutes of Health Stroke Scale (NIHSS) score≤5 that received either BMM only or rMT on END after BMM were extracted from the databases of 16 comprehensive stroke centers. Clinical outcome measures were a 90-day modified Rankin Scale (mRS) score of 0-1 or 0-2, and occurrence of END. RESULTS: Among 10 169 consecutive patients with large vessel occlusion admitted between 2016 and 2021, 208 patients were available for analysis. END was reported in 87 patients that were therefore all subjected to rMT. In a logistic regression model, END (OR 3.386, 95% CI 1.428 to 8.032), baseline NIHSS score (OR 1.362, 95% CI 1.004 to 1.848) and a pre-event mRS score=1 (OR 3.226, 95% CI 1.229 to 8.465) were associated with unfavorable outcome. In patients with END, successful rMT was associated with favorable outcome (OR 4.549, 95% CI 1.098 to 18.851). Among baseline clinical and neuroradiological features, presence of atrial fibrillation was a predictor of END (OR 3.547, 95% CI 1.014 to 12.406). CONCLUSION: Patients with minor stroke due to M2 occlusion and atrial fibrillation should be closely monitored for possible worsening during BMM and, in this case, promptly considered for rMT.

Deep cerebral venous system involvement in patients with cerebral sinus thrombosis. A proposal of neuroradiological score systems useful for clinical assessment.

PURPOSE: To develop a neuroradiological score in patients with deep cerebral venous thrombosis (DCVT), capable of assessing extension of intracranial changes and venous occlusion at diagnosis; to assess the relationship between neuroradiological and clinical features at follow-up. MATERIAL AND METHODS: In 14 patients with DCVT, we developed 2 score systems on non-enhanced and contrast-enhanced CT: Intracranial Imaging Score (IIS) and Venous Occlusion Imaging Score (VOIS). ISS considers parenchymal venous strokes, hemorrhage, mass effect, and hydrocephalus; VOIS evaluates unilateral or bilateral venous occlusion extension. Modified Rankin Scale (mRS) and vessel recanalization status were assessed at follow-up. RESULTS: At diagnosis, higher IIS was related to bilateral venous thrombosis involvement (p 0,02; r:0,60), but parenchymal strokes were not related to venous occlusion extension (unilateral or bilateral) (p > 0,05). Moreover, the symptoms' onset time did not correlate with the severity scores (p > 0,05). At follow-up, 8 out of 14 patients showed good clinical outcomes with complete recanalization and neurological improvement, 1 patient showed a poor neurological outcome, whereas 5 patients died within 1 week. Positive correlations were found between IIS and mRS (p 0,003, r = 0,73), between IIS and vessels' recanalization status (p 0,002, r = 0,75), and between vessels' recanalization status and mRS (p < 0,001, r = 0,98). CONCLUSION: Neuroradiological scores may enhance diagnostic accuracy, and they may have a predictive significance. In patients with DCVT, although intracranial involvement was not influenced by symptoms' onset time or extension of venous occlusion, clinical outcome was related to both intracranial involvement and venous recanalization state. Collateral venous drainage status may counterbalance the thrombotic process improving prognosis.

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.

Mechanical thrombectomy in minor stroke due to isolated M2 occlusion: a multicenter retrospective matched analysis.

BACKGROUND: The purpose of this study was to evaluate the effectiveness of mechanical thrombectomy (MT) in patients with isolated M2 occlusion and minor symptoms and identify possible baseline predictors of clinical outcome. METHODS: The databases of 16 high-volume stroke centers were retrospectively screened for consecutive patients with isolated M2 occlusion and a baseline National Institutes of Health Stroke Scale (NIHSS) score ≤5 who received either early MT (eMT) or best medical management (BMM) with the possibility of rescue MT (rMT) on early neurological worsening. Because our patients were not randomized, we used propensity score matching (PSM) to estimate the treatment effect of eMT compared with the BMM/rMT. The primary clinical outcome measure was a 90-day modified Rankin Scale score of 0-1. RESULTS: 388 patients were initially selected and, after PSM, 100 pairs of patients receiving eMT or BMM/rMT were available for analysis. We found no significant differences in clinical outcome and in safety measures between patients receiving eMT or BMM/rMT. Similar results were also observed after comparison between eMT and rMT. Concerning baseline predicting factors of outcome, the involvement of the M2 inferior branch was associated with a favorable outcome. CONCLUSION: Our multicenter retrospective analysis has shown no benefit of eMT in minor stroke patients with isolated M2 occlusion over a more conservative therapeutic approach. Although our results must be viewed with caution, in these patients it appears reasonable to consider BMM as the first option and rMT in the presence of early neurological deterioration.

Dissociative episode and panic attacks triggered by pitolisant in a narcoleptic patient.

Pitolisant is a histamine 3-receptor antagonist/inverse agonist effective and safe for the treatment of excessive daytime sleepiness and cataplexy in narcolepsy. We report a 19-year-old woman affected by narcolepsy type 1 who presented panic attacks and dissociative symptoms induced by pitolisant. The patient medical history was unremarkable except that for familiarity for anxiety disorder and chronic insomnia. Moreover, a detailed psychometric evaluation revealed a profile of low resilience, a severe grade of depression, an anxiety trait and a propension to dissociative symptoms. Our report suggests that caution should be used in patients with predisposing factors to psychiatric disorders, especially during the first period of treatment with pitolisant. In consideration of the high prevalence of psychiatric comorbidities in narcolepsy, it seems worth to carefully investigate psychiatric background of narcoleptic patients.

COVID-19 Vaccination Is Associated with a Better Outcome in Acute Ischemic Stroke Patients: A Retrospective Observational Study.

Background: It is unclear whether and how COVID-19 vaccination may affect the outcome of patients with acute ischemic stroke (AIS). We investigated this potential association in a retrospective study by comparing previously vaccinated (VAX) versus unvaccinated (NoVAX) stroke patients. Methods: We collected clinical reports for all consecutive AIS patients admitted to our hospital and evaluated the outcome predictors in VAX and NoVAX groups. Adjustments were made for possible confounders in multivariable logistic regression analysis, and adjusted hazard ratios were calculated. Results: A total of 466 AIS patients (287 VAX and 179 NoVAX) were included in this study. The NIHSS score at discharge and mRS score at a 3-month follow-up visit were significantly lower in VAX patients compared to NoVAX patients (p < 0.001). Good outcomes (mRS 0−2) were significantly associated with COVID-19 vaccination before AIS (adjusted hazard ratio, 0.400 [95% CI = 0.216−0.741]). Conclusions: The observation that COVID-19 vaccination can influence the outcome of AIS provides support for further studies investigating the role of immunity in ischemic brain damage.

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.

Th1/Th2 polarization of peripheral immune response in atherothrombotic and cardioembolic stroke: a prospective study.

Compelling evidence suggest a key role of immune system in the development and progression of ischemic stroke. Although the balance between proinflammatory CD4 + T helper (Th)-1 lymphocytes, expressing T-bet transcription factor, and anti-inflammatory Th2 cells expressing GATA3 seems to influence the outcome in experimental stroke, the role of peripheral immune response in acute stroke patients is poorly understood. We aimed to evaluate the peripheral Th1/Th2 balance in acute atherothrombotic (ATHS) and cardioembolic stroke (CES) patients and in age- and sex-matched healthy subjects. Using flow cytometry, we analyzed the percentage of CD4 + T-bet + T cells and CD4 + GATA3 + T cells from peripheral blood of ATHS and CES patients (2,4 and 7 days after stroke onset). Patients and controls were screened for infectious conditions, autoimmune, inflammatory, or cancerous diseases. On day 2 circulating CD4 + T-bet + T cells were significantly higher in stroke patients compared to controls, and in ATHS compared to CES and controls. On day 7, we observed a significant increase of CD4 + T-bet + T cells in both ATHS and CES patients compared to baseline. No difference was observed in circulating CD4 + GATA3 + T cells among ATHS, CES patients, and controls. These data suggest that circulating CD4 + T-bet + T cells could be useful marker indicating atherothrombotic genesis of stroke and provide new insight into the peripheral adaptive immune response in acute stroke.

Validation Study of the Richards-Campbell Sleep Questionnaire in Patients with Acute Stroke.

Sleep disorders are frequent in acute stroke. The Richards-Campbell Sleep Questionnaire (RCSQ) is a validated scale for the sleep assessment in intensive care unit. The aim of the present study is to validate RCSQ for use in patients with acute stroke. We performed a validation study by comparing the RCSQ with polysomnography (PSG), the standardized measure of sleep. Inclusion criteria were age ≥ 18 years and a radiologically confirmed diagnosis of stroke. Exclusion criteria were global aphasia, extreme severity of clinical conditions and inability to attend PSG. All patients underwent PSG in a stroke unit, the day after a subjective sleep assessment by means of the RCSQ. The RCSQ was compared with PSG parameters to assess the degree of concordance of the two measures. The cohort consisted of 36 patients. Mean RCSQ score was 61.5 ± 24.8. The total score of the RCSQ showed a good degree of concordance with the sleep efficiency index of PSG. Accuracy of the RCSQ was 70%, sensitivity 71% and specificity 68%. The RCSQ is a good tool for screening the sleep quality in the setting of a stroke unit. Therefore, it could be useful to select the patients who might beneficiate from an instrumental sleep evaluation.

Pupillometric findings in ATTRv patients and carriers: results from a single-centre experience.

INTRODUCTION: Hereditary transthyretin amyloidosis (ATTRv) is a treatable multisystemic disease with great phenotypic heterogeneity. Among extra-neurological features, pupillary abnormalities have been reported, either related to amyloid deposition in the eye or to a progressive autonomic neuropathy. OBJECTIVE: To evaluate the role of automated pupillometry, a non-invasive and rapid test able to provide objective and reproducible data on pupil size and reactivity, as a marker of disease severity in late-onset ATTRv patients. PATIENTS AND METHODS: We performed automated pupillometry on a cohort of ATTRv patients and pre-symptomatic TTR mutation carriers and compared results to healthy controls. An exhaustive clinical and instrumental evaluation was performed on all enrolled subjects. RESULTS: A statistically significant difference in most pupillometry parameters was found in ATTRv patients as compared to both carriers and healthy controls. Moreover, in ATTRv patients, we found a significant correlation between many pupillometry findings and disease duration, as well as widely accepted clinical scales and investigations (NIS, Sudoscan from feet, and Norfolk QoL-DN questionnaire). CONCLUSIONS: We suggest pupillometry may play a role as a reliable and non-invasive biomarker to evaluate ATTRv disease severity and monitor its progression.

Impact of delirium on the outcome of stroke: a prospective, observational, cohort study.

INTRODUCTION: Delirium is an acute fluctuating disorder of attention and awareness, which often complicates the clinical course of several conditions, including acute stroke. The aim of the present study was to determine whether delirium occurrence impacts the outcome of patients with acute stroke. METHODS: The study design is single center, prospective, observational. We consecutively enrolled patients admitted to the stroke unit from April to October 2020. Inclusion criteria were age ≥ 18 years and diagnosis of acute stroke. Exclusion criteria were stroke mimics, coma, and terminal conditions. All patients were screened for delirium upon admission, within 72 h, and whenever symptoms suggesting delirium occurred by means of the Confusion Assessment Method for Intensive Care Unit and the Richmond Agitation Sedation Scale. Outcomes were evaluated with the 90-days modified Rankin Scale (mRS) by telephone interview. RESULTS: The final study cohort consisted of 103 patients (62 men; median age 75 years, interquartile range 63-81). Thirty-one patients (30%) developed delirium. In the multivariate ordinal logistic regression, patients with delirium had higher mRS scores at 3 months (DLR + : mRS = 4 (3-6); DLR-: mRS = 1 (1-3); adjusted odds ratio = 4.83; CI = 1.88-12.35; p = 0.006). Delirium was a risk factor for death (mRS = 6) in the univariate logistic regression (OR 4.5, CI = 1.44-14.07; p = 0.010), but not in the adjusted analysis (OR 3.45; CI = 0.66-17.95; p = 0.142). Survival time during 90-days follow-up was shorter in the delirium group (Log Rank χ2 3.89; p = 0.048). CONCLUSION: Delirium negatively impacts the prognosis of patients with acute stroke. Patients with post-stroke delirium have a worse functional outcome and a shorter survival.