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.

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.

Extensive corpus callosum ischemia after coronary artery bypass grafting on extracorporeal circulation.

INTRODUCTION: Heart surgery can be associated with adverse ischemic brain events. CASE REPORT: Here, we describe two patients who presented extensive infarction of the corpus callosum and of other brain watershed areas following coronary artery bypass grafting (CABG) on extracorporeal circulation (ECC). DISCUSSION: Infarction of the corpus callosum is an extremely rare condition due to its abundant blood supply. Our findings are noteworthy since they diverge from classical brain watershed infarcts and from other cases of corpus callosum involvement. This suggests that in some cases, CABG surgery on ECC may be associated to a profound impairment of intracerebral circulation. However, it is also possible that the corpus callosum is particularly vulnerable to yet unknown metabolic modifications connected to ECC. CONCLUSIONS: Further studies are needed in order to investigate the complex response of brain circulation and metabolism during heart surgery with ECC.

Serum-Circulating microRNAs in Sporadic Inclusion Body Myositis.

BACKGROUND: Sporadic inclusion body myositis (s-IBM) represents a unique disease within idiopathic inflammatory myopathies with a dual myodegenerative-autoimmune physiopathology and a lack of an efficacious treatment. Circulating miRNA expression could expand our knowledge of s-IBM patho-mechanisms and provide new potential disease biomarkers. To evaluate the expression of selected pre-amplified miRNAs in the serum of s-IBM patients compared to those of a sex- and age-matched healthy control group, we enrolled 14 consecutive s-IBM patients and 8 sex- and age-matched healthy controls. By using two different normalization approaches, we found one downregulated and three upregulated miRNAs. hsa-miR-192-5p was significantly downregulated, while hsa-miR-372-3p was found to be upregulated more in the s-IBM patients compared to the level of the controls. The other two miRNAs had a very low expression levels (raw Ct data > 29). hsa-miR-192-5p and hsa-miR-372-3p were found to be significantly dysregulated in the serum of s-IBM patients. These miRNAs are involved in differentiation and regeneration processes, thus possibly reflecting pathological mechanisms in s-IBM muscles and potentially representing disease biomarkers.

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.

Autonomic dysfunction in non-critically ill COVID-19 patients during the acute phase of disease: an observational, cross-sectional study.

INTRODUCTION: Evidence is emerging about an extra-pulmonary involvement of SARS-CoV-2, including the nervous system. Autonomic dysfunction in patients recovering from acute coronavirus disease 2019 (COVID-19) has been recently described. Dysautonomic symptoms have been reported in the acute phase of the disease, but clear evidence is lacking, especially in the non-critical forms of the infection. OBJECTIVE: The aim of this study is to assess the prevalence of dysautonomia in acute, non-critically ill COVID-19 patients. METHODS: In this observational, cross-sectional study, we compared 38 non-critically ill patients with acute COVID-19 (COVID + group) to 38 healthy volunteers (COVID - group) in order to assess the prevalence of signs and symptoms of dysautonomia through the administration of the composite autonomic symptom score 31 (COMPASS-31) and an active standing test. Comparisons between groups were performed by means of both univariate and multivariate analyses. RESULTS: The prevalence of orthostatic hypotension was significantly higher in the COVID + group. Higher total scores of COMPASS-31 were observed in the COVID + group than controls. Significant differences between groups emerged in the secretomotor, orthostatic intolerance, and gastrointestinal COMPASS-31 domains. All these results maintained the statistical significance after the adjustment for concomitant drugs with a known effect on the autonomic nervous system assumed by the study participants, except for the differences in the gastrointestinal domain of COMPASS-31. CONCLUSION: Our results suggest that an autonomic dysfunction could be an early manifestation of COVID-19, even in the contest of mild forms of the infection.

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.

Mechanical thrombectomy in acute ischemic stroke due to large vessel occlusion in the anterior circulation and low baseline National Institute of Health Stroke Scale score: a multicenter retrospective matched analysis.

BACKGROUND AND PURPOSE: The benefit of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) and baseline mild neurological symptoms remains unclear. The purpose of this study was to evaluate the effectiveness of MT in this subgroup of patients. METHODS: The databases of 9 high-volume Italian stroke centers were retrospectively screened for patients with LVO in the anterior circulation and a baseline National Institute of Health Stroke Scale (NIHSS) score ≤ 5 that received either immediate MT or best medical management (BMM) with the possibility of rescue MT upon neurological worsening. Primary outcome measure was a modified Rankin Scale score of 0-1 at 90 days. Propensity score matching (PSM) analysis was used to estimate the treatment effect of immediate MT compared to BMM/rescue MT. RESULTS: Two hundred and seventy-two patients received immediate MT (MT group). The BMM/rescue MT group included 41 patients. The primary outcome was achieved in 78.6% (n = 246) of overall patients, with a higher proportion in the MT group (80.5% vs. 65.9%, p = 0.03) in unadjusted analysis. After PSM, patients in the MT group had a 19.5% higher chance of excellent outcome at 90 days compared to the BMM/Rescue MT group with a similar risk of death from any cause. CONCLUSIONS: Our experience is in favor of a potential benefit of MT also in patients with LVO and a NIHSS score ≤ 5 at the time of groin puncture. Nonetheless, this issue waits for a clear-cut recommendation in a dedicated clinical trial.

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.

Effect of the COVID-19 pandemic and the lockdown measures on the local stroke network.

INTRODUCTION: The COVID-19 outbreak highly impacted the acute ischemic stroke care management. The primary end point of the study was to evaluate the impact of the COVID-19 outbreak and the following lockdown measures on our hub-and-spoke network; the secondary end point was to evaluate if the impact of the COVID-19 outbreak was different in hub-and-spoke centers. METHODS: This was a retrospective multicenter observational study conducted at the Stroke Units of Policlinico Gemelli, Ospedale San Filippo Neri, Ospedale di Belcolle, and Ospedale San Camillo de Lellis. We collected clinical reports of all consecutive patients admitted with diagnosis of acute ischemic stroke or transient ischemic attack (TIA) during the phase 1 of the lockdown period (11 March 2020-4 May 2020). As controls, we used all consecutive patients admitted for acute ischemic stroke or TIA in the same period of the previous year. RESULTS: A total of 156 and 142 clinical reports were collected in 2019 and 2020, respectively. During the COVID-19 outbreak, we observed a reduction of number of thrombolysis, a reduction of the length of hospitalization, and an increase of pneumonia. Regarding performance indicators, we observed an increase in onset-to-door time and in door-to-groin time. We did not observe any statistically significant interaction between year (2019 vs 2020) and facility of admission (hub vs spoke) on all variables analyzed. DISCUSSION: Our observational study, involving hub-and-spoke stroke network of a wide regional area, indicates that the COVID-19 outbreak impacted on the acute stroke management. This impact was equally observed in hub as well as in spoke centers.

Mechanical thrombectomy in patients with stroke due to large vessel occlusion in the anterior circulation and low baseline NIHSS score.

We sought to verify the benefit of mechanical thrombectomy in patients with acute ischemic stroke due to large vessel occlusion in the anterior circulation and low National Institute of Health stroke scale score at presentation. The prospective database of our stroke center was screened for patients with acute ischemic stroke due to large vessel occlusion and a baseline National Institute of Health stroke scale score ≤5 that had undergone mechanical thrombectomy. Outcome measures were the modified Rankin Scale (mRS) score at 90 days, brain bleeding events and death at 90 days. Out of 459 patients, 17 (12 females, mean age 70 ± 14 years) with occlusion of M1 or M2 segment of middle cerebral artery and baseline National Institute of Health stroke scale score ≤5 underwent mechanical thrombectomy. Eight patients (47%) were treated within 6 hours from the onset, 5 (29%) were treated beyond 6 hours, and 4 (24%) were wake-up strokes. Effective mechanical thrombectomy was achieved in 16 patients (94%) and associated with excellent functional outcomes at 3 months (mRS 0-1) in 13 (76%). The asymptomatic brain-bleeding event was observed in one patient 4 days after effective mechanical thrombectomy concerning safety issues. One patient died 1 month after mechanical thrombectomy of a cause unrelated to stroke. Our findings favor a potential benefit of mechanical thrombectomy in patients with stroke due to large vessel occlusion and low National Institute of Health stroke scale score at presentation. These patients may also benefit from a prolonged time window for treatment.

Effect of lockdown on the management of ischemic stroke: an Italian experience from a COVID hospital.

OBJECTIVE: To evaluate the impact of the lockdown measures, consequent to the outbreak of COVID-19 pandemic, on the quality of pre-hospital and in-hospital care of patients with acute ischemic stroke. METHODS: This is an observational cohort study. Data sources were the clinical reports of patients admitted during the first month of lockdown and discharged with a confirmed diagnosis of stroke or TIA. Data were collected in the interval ranging from March 11th to April 11th 2020. As controls, we evaluated the clinical reports of patients with stroke or TIA admitted in the same period of 2019. RESULTS: The clinical reports of patients eligible for the study were 52 in 2020 (71.6 ± 12.2 years) and 41 in 2019 (73.7 ± 13.1 years). During the lockdown, we observed a significant increase in onset-to-door time (median = 387 vs 161 min, p = 0.001), a significant reduction of the total number of thrombolysis (7 vs 13, p = 0.033), a non-significant increase of thrombectomy (15 vs 9, p = 0.451), and a significant increase in door-to-groin time (median = 120 vs 93 min, p = 0.048). No relevant difference was observed between 2019 and 2020 in the total number of patients admitted. CONCLUSIONS: Due to the COVID-19 pandemic and lockdown measures, the stroke care pathway changed, involving both pre-hospital and in-hospital performances.

Unprotected stroke management in an undiagnosed case of Severe Acute Respiratory Syndrome Coronavirus 2 infection.

Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this scenario, managing acute medical conditions, such as stroke, requires a timely treatment together with proper strategies that minimize the risk of infection spreading to health care workers and other patients. We report the case of a 79-year-old woman, who was admitted for a wake-up stroke due to occlusion of the left middle cerebral artery. She was treated outside the COVID-19-dedicated track of the hospital because she had no concomitant signs or symptoms suggestive of SARS-CoV-2 infection nor recent contact with other infected individuals. Post-mortem nasal and pharyngeal swab was positive for SARS-CoV-2 infection. We propose that hyperacute stroke patients should be tested for SARS-CoV-2 infection at admission and then managed as having COVID-19 until cleared by a negative result. We are aware that such measure results in some delay of the acute treatment of stroke, which could be minimal using well-exercised containment protocols.

Dysphagia and Obstructive Sleep Apnea in Acute, First-Ever, Ischemic Stroke.

BACKGROUND: Obstructive sleep apnea (OSA) and dysphagia are common in acute stroke and are both associated with increased risk of complications and worse prognosis. The aims of the present study were (1) to evaluate the prevalence of OSA and dysphagia in patients with acute, first-ever, ischemic stroke; (2) to investigate their clinical correlates; and (3) to verify if these conditions are associated in acute ischemic stroke. METHODS: We enrolled a cohort of 140 consecutive patients with acute-onset (<48 hours), first-ever ischemic stroke. Computed tomography (CT) and magnetic resonance imaging scans confirmed the diagnosis. Neurological deficit was measured using the National Institutes of Health Stroke Scale (NIHSS) by examiners trained and certified in the use of this scale. Patients underwent a clinical evaluation of dysphagia (Gugging Swallowing Screen) and a cardiorespiratory sleep study to evaluate the presence of OSA. RESULTS: There are 72 patients (51.4%) with obstructive sleep apnea (OSA+), and there are 81 patients (57.8%) with dysphagia (Dys+). OSA+ patients were significantly older (P = .046) and had greater body mass index (BMI) (P = .002), neck circumference (P = .001), presence of diabetes (P = .013), and hypertension (P < .001). Dys+ patients had greater NIHSS (P < .001), lower Alberta Stroke Programme Early CT Score (P < .001), with greater BMI (P = .030). The association of OSA and dysphagia was greater than that expected based on the prevalence of each condition in acute stroke (P < .001). CONCLUSIONS: OSA and dysphagia are associated in first-ever, acute ischemic stroke.

Hereditary inclusion-body myopathies.

The term hereditary inclusion-body myopathies (HIBMs) defines a group of rare muscle disorders with autosomal recessive or dominant inheritance and presence of muscle fibers with rimmed vacuoles and collection of cytoplasmic or nuclear 15-21 nm diameter tubulofilaments as revealed by muscle biopsy. The most common form of HIBM is due to mutations of the GNE gene that codes for a rate-limiting enzyme in the sialic acid biosynthetic pathway. This results in abnormal sialylation of glycoproteins that possibly leads to muscle fiber degeneration. Mutations of the valosin containing protein are instead responsible for hereditary inclusion-body myopathy with Paget's disease of the bone and frontotemporal dementia (IBMPFD), with these three phenotypic features having a variable penetrance. IBMPFD probably represents a disorder of abnormal cellular trafficking of proteins and maturation of the autophagosome. HIBM with congenital joint contractures and external ophthalmoplegia is due to mutations of the Myosin Heavy Chain IIa gene that exerts a pathogenic effect through interference with filament assembly or functional defects in ATPase activity. This review illustrates the clinical and pathologic characteristics of HIBMs and the main clues available to date concerning the possible pathogenic mechanisms and therapeutic perspectives of these disorders. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.

Risk factor and etiology analysis of ischemic stroke in young adult patients.

BACKGROUND: Approximately 10%-14% of ischemic strokes occur in young adults. AIMS: To investigate risk factors and etiologies of strokes of young adults admitted to the "stroke unit" of Policlinico "Gemelli" of Rome from December 2005 to January 2013. METHODS: In all, 150 consecutive patients younger than 50 years diagnosed with ischemic stroke were enrolled. Clinical evaluation consisted of a complete neurologic examination and the National Institutes of Health Stroke Scale. Diagnostic workup consisted of anamnesis, extensive laboratory, radiologic, and cardiologic examination. Stroke etiologies were classified according to the Trial of Org 10172 in Acute Stroke Treatment. RESULTS: Patients' mean age was 41 ± 8.0 years. The most common risk factors were dyslipidemia (52.7%), smoking (47.3%), hypertension (39.3%), and patent foramen ovale (PFO, 32.8%). Large-artery atherosclerosis was diagnosed as the cause of stroke in 17 patients (11.3%). Cardioembolism was presumed in 36 patients (24%), most of them presented a PFO at transesophageal echocardiography. Small-vessel occlusion was diagnosed in 12 patients (8%); all of them were hypertensive and most of them presented additional risk factors. Forty-one patients (27.3%) presented a stroke of other determined etiology and 44 (29.3%) presented a stroke of undetermined etiology. The 3-year survival was 96.8% and recurrent strokes occurred in only 3 cases. CONCLUSIONS: Traditional vascular risk factors are also very common in young adults with ischemic stroke, but such factors increase the susceptibility to stroke dependent to other causes as atherosclerosis and small-artery occlusion represent less than 20% of cases. Prognosis quoadvitam is good, being characterized by low mortality and recurrence rate.

Automated Pupillometry Is Able to Discriminate Patients with Acute Stroke from Healthy Subjects: An Observational, Cross-Sectional Study.

BACKGROUND: Automated pupillometry (AP) is a handheld, non-invasive tool that is able to assess pupillary light reflex dynamics and is useful for the detection of intracranial hypertension. Limited evidence is available on acute ischemic stroke (AIS) patients. The primary objective was to evaluate the ability of AP to discriminate AIS patients from healthy subjects (HS). Secondly, we aimed to compute a predictive score for AIS diagnosis based on clinical, demographic, and AP variables. METHODS: We included 200 consecutive patients admitted to a comprehensive stroke center who underwent AP assessment through NPi-200 (NeurOptics®) within 72 h of stroke onset and 200 HS. The mean values of AP parameters and the absolute differences between the AP parameters of the two eyes were considered in the analyses. Predictors of stroke diagnosis were identified through univariate and multivariate logistic regressions; we then computed a nomogram based on each variable's ß coefficient. Finally, we developed a web app capable of displaying the probability of stroke diagnosis based on the predictive algorithm. RESULTS: A high percentage of pupil constriction (CH, p < 0.001), a low constriction velocity (CV, p = 0.002), and high differences between these two parameters (p = 0.036 and p = 0.004, respectively) were independent predictors of AIS. The highest contribution in the predictive score was provided by CH, the Neurological Pupil Index, CV, and CV absolute difference, disclosing the important role of AP in the discrimination of stroke patients. CONCLUSIONS: The results of our study suggest that AP parameters, and in particular, those concerning pupillary constriction, may be useful for the early diagnosis of AIS.