Levodopa-Carbidopa-Entacapone Intestinal Gel in Advanced Parkinson Disease: A Multicenter Real-Life Experience.

BACKGROUND: For Parkinson disease (PD) patients who have been diagnosed with advanced disease that can no longer be effectively controlled with optimized oral or transdermal medications, a range of device-aided therapies (DAT) are available, comprising either deep brain stimulation or infusion therapies providing continuous dopaminergic stimulation. Levodopa-entacapone-carbidopa intestinal gel (LECIG) infusion is the latest DAT for advanced PD (APD) that was approved in Romania in 2021. STUDY QUESTION: What is the experience to date in real-world clinical practice in Romania regarding the efficacy and tolerability of LECIG in APD? STUDY DESIGN: A retrospective evaluation of 74 APD patients treated with LECIG at 12 specialized APD centers in Romania. MEASURES AND OUTCOMES: Demographic data and various clinical parameters were recorded, including Mini Mental State Evaluation score or Montreal Cognitive Assessment Test score. Levodopa-equivalent daily dose and the administered doses of levodopa and other PD medications were evaluated at baseline and after starting LECIG treatment. The efficacy of LECIG in reducing daily hours of off time, motor fluctuations, and dyskinesias were assessed. Any percutaneous endoscopic gastrojejunostomy system or device complications after starting LECIG treatment were noted. RESULTS: At baseline, patients were taking oral levodopa for a mean of 5.3 times per day, with a high proportion also taking concomitant add-on therapies (dopamine agonists, 86%, monoamine oxidase type-B inhibitors, 53%; catechol-O-methyltransferase inhibitors, 64%). LECIG treatment significantly reduced daily off time versus baseline from 5.7 h/d to 1.7 hours per day ( P < 0.01). Duration and severity of dyskinesias was also significantly reduced versus baseline, and improvements were observed in Hoehn and Yahr Scale scores. LECIG treatment also allowed a significant reduction in the use of concomitant oral medications. CONCLUSIONS: These findings suggest that LECIG treatment is an effective DAT option in APD that can simplify the treatment regimen.

Predictive MRI Biomarkers in MS-A Critical Review.

Background and Objectives: In this critical review, we explore the potential use of MRI measurements as prognostic biomarkers in multiple sclerosis (MS) patients, for both conventional measurements and more novel techniques such as magnetization transfer, diffusion tensor, and proton spectroscopy MRI. Materials and Methods: All authors individually and comprehensively reviewed each of the aspects listed below in PubMed, Medline, and Google Scholar. Results: There are numerous MRI metrics that have been proven by clinical studies to hold important prognostic value for MS patients, most of which can be readily obtained from standard 1.5T MRI scans. Conclusions: While some of these parameters have passed the test of time and seem to be associated with a reliable predictive power, some are still better interpreted with caution. We hope this will serve as a reminder of how vast a resource we have on our hands in this versatile tool-it is up to us to make use of it.

Pre-Hospital Delay in Acute Ischemic Stroke Care: Current Findings and Future Perspectives in a Tertiary Stroke Center from Romania-A Cross-Sectional Study.

Background and objectives: The time interval between stroke onset and hospital arrival is a major barrier for reperfusion therapies in acute ischemic stroke and usually accounts for most of the onset-to-treatment delay. The present study aimed to analyze the pre-hospital delays for patients with acute ischemic stroke admitted to a tertiary stroke center in Romania and to identify the factors associated with a late hospital arrival. Material and methods: The study population consisted of 770 patients hospitalized with the diagnosis of acute ischemic stroke in the University Emergency Hospital Bucharest during a 6-month period, between 1 January and 30 June 2018. Data regarding pre-hospital delays were prospectively collected and analyzed together with the demographic and clinical characteristics of the patients. Results: In total, 31.6% of patients arrived at the hospital within 4.5 h from stroke onset and 4.4% in time intervals between 4.5 and 6 h from the onset, and 28.7% of the patients reached the hospital more than 24 h after onset of symptoms. Transport to hospital by own means was the only factor positively associated with arrival to hospital > 4.5 h from stroke onset and more than doubled the odds of late arrival. Factors negatively associated with hospital arrival > 4.5 h after stroke onset were prior diagnosis of atrial fibrillation, initial National Institute of Health Stroke Scale (NIHSS) score ≥ 16 points, presence of hemianopsia, facial palsy and sensory disturbance. Factors increasing the odds of hospital arrival after 24 h from stroke onset were living alone and living in rural areas. Conclusions: Almost one in three ischemic stroke patients presenting to our center reaches hospital more than 24 h after onset of symptoms. These findings highlight the need for urgent measures to improve not only stroke awareness but also pre-hospital protocols in order to provide timely and appropriate care for our stroke patients.

Cerebral Venous Sinus Thrombosis in COVID-19 Patients: A Multicenter Study and Review of Literature.

BACKGROUND: COVID-19 infection has been known to predispose patients to both arterial and venous thromboembolic events such as deep venous thrombosis, pulmonary embolism, myocardial infarction, and stroke. A few reports from the literature suggest that Cerebral Venous Sinus Thrombosis (CVSTs) may be a direct complication of COVID-19. OBJECTIVE: To review the clinical and radiological presentation of COVID-19 positive patients diagnosed with CVST. METHODS: This was a multicenter, cross-sectional, retrospective study of patients diagnosed with CVST and COVID-19 reviewed from March 1, 2020 to November 8, 2020. We evaluated their clinical presentations, risk factors, clinical management, and outcome. We reviewed all published cases of CVST in patients with COVID-19 infection from January 1, 2020 to November 13, 2020. RESULTS: There were 8 patients diagnosed with CVST and COVID-19 during the study period at 7 out of 31 participating centers. Patients in our case series were mostly female (7/8, 87.5%). Most patients presented with non-specific symptoms such as headache (50%), fever (50%), and gastrointestinal symptoms (75%). Several patients presented with focal neurologic deficits (2/8, 25%) or decreased consciousness (2/8, 25%). D-dimer and inflammatory biomarkers were significantly elevated relative to reference ranges in patients with available laboratory data. The superior sagittal and transverse sinuses were the most common sites for acute CVST formation (6/8, 75%). Median time to onset of focal neurologic deficit from initial COVID-19 diagnosis was 3 days (interquartile range 0.75-3 days). Median time from onset of COVID-19 symptoms to CVST radiologic diagnosis was 11 days (interquartile range 6-16.75 days). Mortality was low in this cohort (1/8 or 12.5%). CONCLUSIONS: Clinicians should consider the risk of acute CVST in patients positive for COVID-19, especially if neurological symptoms develop.

Neutrophil-to-Lymphocyte Ratio as an Independent Predictor of In-Hospital Mortality in Patients with Acute Intracerebral Hemorrhage.

Background and Objectives: Neutrophil-to-lymphocyte ratio (NLR), a very low cost, widely available marker of systemic inflammation, has been proposed as a potential predictor of short-term outcome in patients with intracerebral hemorrhage (ICH). Methods: Patients with ICH admitted to the Neurology Department during a two-year period were screened for inclusion. Based on eligibility criteria, 201 patients were included in the present analysis. Clinical, imaging, and laboratory characteristics were collected in a prespecified manner. Logistic regression models and receiver operating characteristics (ROC) curves were used to assess the performance of NLR assessed at admission (admission NLR) and 72 h later (three-day NLR) in predicting in-hospital death. Results: The median age of the study population was 70 years (IQR: 61-79), median admission NIHSS was 16 (IQR: 6-24), and median hematoma volume was 13.7 mL (IQR: 4.6-35.2 mL). Ninety patients (44.8%) died during hospitalization, and for 35 patients (17.4%) death occurred during the first three days. Several common predictors were significantly associated with in-hospital mortality in univariate analysis, including NLR assessed at admission (OR: 1.11; 95% CI: 1.04-1.18; p = 0.002). However, in multivariate analysis admission, NLR was not an independent predictor of in-hospital mortality (OR: 1.04; 95% CI: 0.9-1.1; p = 0.3). The subgroup analysis of 112 patients who survived the first 72 h of hospitalization showed that three-day NLR (OR: 1.2; 95% CI: 1.09-1.4; p < 0.001) and age (OR: 1.05; 95% CI: 1.02-1.08; p = 0.02) were the only independent predictors of in-hospital mortality. ROC curve analysis yielded an optimal cut-off value of three-day NLR for the prediction of in-hospital mortality of ≥6.3 (AUC = 0.819; 95% CI: 0.735-0.885; p < 0.0001) and Kaplan-Meier analysis proved that ICH patients with three-day NLR ≥6.3 had significantly higher odds of in-hospital death (HR: 7.37; 95% CI: 3.62-15; log-rank test; p < 0.0001). Conclusion: NLR assessed 72 h after admission is an independent predictor of in-hospital mortality in ICH patients and could be widely used in clinical practice to identify the patients at high risk of in-hospital death. Further studies to confirm this finding are needed.

Characteristics and Outcomes in Patients With COVID-19 and Acute Ischemic Stroke: The Global COVID-19 Stroke Registry.

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4-18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4-18] versus 6 [IQR, 3-14]), P=0.03; (odds ratio, 1.69 [95% CI, 1.08-2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2-6] versus 2 [IQR, 1-4], P<0.001) and death (odds ratio, 4.3 [95% CI, 2.22-8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.

Therapeutic Challenges in Patients With Noncardioembolic Acute Ischemic Stroke in Need of Double Antiplatelet Therapy for Coronary Artery Disease.

BACKGROUND: The risk of ischemic stroke (IS) is significant within 6-12 months from the myocardial revascularization for an acute cardiac event. Consequently, we can expect to have patients with an acute IS occurring right in the time frame of dual antiplatelet therapy (DAPT) imposed by the coronary heart disease (CHD). AREAS OF UNCERTAINTY: Until present, there are no evidence-based guidelines for the management of patients with acute IS in need of DAPT for ischemic heart disease. The aim of this article was to go through the available data and to depict the appropriate therapeutic strategy for this category of patients. DATA SOURCES: We have performed a systematic review of the literature through June 2018, using Medline/PubMed database. THERAPEUTIC ADVANCES: DAPT (aspirin and only clopidogrel among all P2Y12 inhibitors) might be maintained or initiated for CHD in patients with minor acute stroke and high-risk transient ischemic attack patient with IS attributable to an important intracranial stenosis, as long as this drug combination proved to be safe for them in the prevention of stroke recurrence. In patients with IS receiving thrombolysis, with increased size of infarction or high National Institute of Health Stroke Score (NIHSS), the risk of hemorrhagic transformation under DAPT must be weighed against the risk of stent thrombosis in the coronary arteries, which, on its turn, depends on the clinical form for which myocardial revascularization was performed, the time interval from the complexity of a certain interventional procedure. CONCLUSIONS: In the acute phase of an IS, maintenance or initiation of DAPT therapy imposed by CHD relies, on one hand, on the risk of hemorrhagic transformation of the brain injury and, on the other hand, on the risk of stent thrombosis in the coronary arteries. The management of these patients must be carried on by a vascular team, on an individualized basis.

Rates and Causes of Death among Adult Diabetes Patients in Romania.

Aims: To study the age and sex-dependent mortality rates and causes of death in a large Romanian diabetes cohort as compared with the general population. Methods: All adult patients aged 20-64 years, receiving a free diabetes prescription in a major urban area during 2001-2008 were included and followed-up for death until December 31, 2011. Crude mortality rates and standardized mortality rate ratios (SMR) against general population (data from the National Institute of Statistics) were calculated. Years lost due to diabetes were computed assuming the general population mortality rates for ages below 20 and above 64 years. Results: During the 11 years study period, 49,328 diabetes patients (mean age at baseline 53.0 ± 8.8 years) contributed 297,370 person-years and 5,053 deaths. All cause mortality rates (per 1000 person years) increased with age and was 3.4 in 20-24 years age group and 25.7 in 60-64 year age group, while the corresponding SMR decreased from 6.0 to 1.5. Diabetes patients aged 20-24 years had a life expectancy of 48.6 years, which was 6.6 years less compared with the corresponding general population (55.2 years). The gap was 7.0 years in women and 5.8 years in men. Diabetes patients aged 20-24 years lost 196 minutes of life daily due to diabetes in women and 182 minutes in men. Conclusions: Mortality rates increased, while mortality rate ratios against general population decreased with age. Men had higher mortality rates, but women had higher mortality rate ratios in the gender analysis.

Stroke Mortality Rates and Trends in Romania, 1994-2017.

BACKGROUND AND AIM: Romanian national level stroke mortality data is relatively scarce. The current study investigated stroke mortality rates and trends in Romania. METHODS: All individual deaths registered in Romania during 1994-2017 were analyzed using an anonymized database, based on death certificates. Stroke crude mortality rates (CMR) and age-standardized mortality rates (ASMR) were calculated and expressed per 100,000 persons-year. RESULTS: Between 1994 and 2017, 6,281,873 persons died in Romania, stroke being registered as the underlying cause of death in 959,319 cases. The overall stroke CMR was 188.2 (199.3 for women and 176.5 for men). The CMR for hemorrhagic stroke (HEMS) was 32.4 and for ischemic stroke (ISCS) 10.9. There was a significant decrease in stroke ASMR from 344.4 (95% confidence interval [CI] 343.4-345.4) in 1994 to 192.1 (95% CI 191.5-192.7) in 2017, with an annual percent change (APC) of 2.53% per year (95% CI 2.50-2.55, P < .001). Although compared with men, women had higher CMRs, when those rates were age-standardized men had higher ASMR as compared with women. The decline in HEMS ASMR had an APC of 4.65% per year (95% CI 4.59-4.70, P < .001). ISCS ASMR showed an initial increase in ASMR during 1994-2005, with APC 6.39% per year (95% CI 6.09-6.70, P < .001), followed by a significant decrease until 2017, with APC 2.83% per year (95% CI 2.59-3.07, P < .001). CONCLUSION: There was a significant reduction in stroke ASMR during 1994-2017. The decline was slow until 2002 and became steeper after that, with significant differences in gender analysis.

PFO-spectrum disorder: two different cerebrovascular diseases in patients with PFO as detected by AI brain imaging software.

Background: Patent foramen ovale (PFO) is a prevalent cardiac remnant of fetal anatomy that may pose a risk factor for stroke in some patients, while others can present with asymptomatic white matter (WM) lesions. The current study aimed to test the hypothesis that patients with a PFO who have a history of stroke or transient ischemic attack, compared to those without such a history, have a different burden and distribution of cerebral WM hyperintensities. Additionally, we tested the association between PFO morphological characteristics and severity of shunt, and their impact on the occurrence of ischemic cerebral vascular events and on the burden of cerebral WM lesions. Patients and methods: Retrospective, case-control study that included patients with PFO confirmed by transesophageal echocardiography. Right-to-left shunt size was assessed using transcranial Doppler ultrasound. Cerebral MRIs were analyzed for all participants using the semi-automated Quantib NDTM software for the objective quantification of WM lesions. WM lesions volume was compared between patients with and without a history of stroke. Additionally, the anatomical characteristics of PFOs were assessed to explore their relation to stroke occurrence and WM lesions volume. Results: Of the initial 264 patients diagnosed with PFO, 67 met the inclusion criteria and were included in the analysis. Of them, 62% had a history of PFO-related stroke/TIA. Overall burden of WM lesions, including stroke volume, was not significantly different (p = 0.103). However, after excluding stroke volume, WM lesions volume was significantly higher in patients without stroke (0.27 cm3, IQR 0.03-0.60) compared to those with stroke/TIA (0.08 cm3, IQR 0.02-0.18), p = 0.019. Patients with a history of PFO-related stroke/TIA had a tendency to larger PFO sizes by comparison to those without, in terms of length and height, and exhibited greater right-to-left shunt volumes. Discussion: We suggest that PFO may be associated with the development of two distinct cerebrovascular conditions (stroke and "silent" WM lesions), each characterized by unique imaging patterns. Further studies are needed to identify better the "at-risk" PFOs and gain deeper insights into their clinical implications.

OCT and OCT-A biomarkers in multiple sclerosis - review.

Objective: Retinal neuronal and vascular changes have been observed in multiple sclerosis (MS) patients. The aim of this review was to highlight the most current optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) data in MS and to provide information about the possibility of using OCT / OCT-A parameters as biomarkers for screening, diagnosis and monitoring of MS. Methods: To carry out this review, a meticulous literature search was undergone on PubMed between 2014 and the present day, using the following terms: "multiple", "sclerosis", "optical", "coherence", "tomography" and "angiography". Additional studies were found via references, being chosen according to relevance. Results: Retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) were significantly lower in MS patients compared to controls, and correlated with clinical and paraclinical variables, such as visual function, disability, and magnetic resonance imaging (MRI). Retinal capillary plexuses could be higher, lower or the same, and the best OCT-A microvasculature parameter for the detection of MS was the superficial capillary plexus (SCP). The reduced retinal vessel density (VD) was correlated with the disability in MS. Conclusions: OCT and OCT-A parameters could improve the development of retinal biomarkers for screening, early diagnosis and monitoring the disease progression of MS, and they could improve the development of potential future therapies that could slow or stop the course of this incurable disease. Abbreviations: DCP = deep capillary plexus; EDSS = Expanded Disability Status Scale; GCC = ganglion cell complex; GCL = ganglion cell layer; MRI = magnetic resonance imaging; MS = Multiple sclerosis; OCT = optical coherence tomography; OCT-A = optical coherence tomography angiography; ON = optic neuritis; RNFL = retinal nerve fiber layer; SCP = superficial capillary plexus; VD = vessel density.

Serum Neurofilaments and OCT Metrics Predict EDSS-Plus Score Progression in Early Relapse-Remitting Multiple Sclerosis.

(1) Background: Early disability accrual in RRMS patients is frequent and is associated with worse long-term prognosis. Correctly identifying the patients that present a high risk of early disability progression is of utmost importance, and may be aided by the use of predictive biomarkers. (2) Methods: We performed a prospective cohort study that included newly diagnosed RRMS patients, with a minimum follow-up period of one year. Biomarker samples were collected at baseline, 3-, 6- and 12-month follow-ups. Disability progression was measured using the EDSS-plus score. (3) Results: A logistic regression model based on baseline and 6-month follow-up sNfL z-scores, RNFL and GCL-IPL thickness and BREMSO score was statistically significant, with χ2(4) = 19.542, p < 0.0001, R2 = 0.791. The model correctly classified 89.1% of cases, with a sensitivity of 80%, a specificity of 93.5%, a positive predictive value of 85.7% and a negative predictive value of 90.62%. (4) Conclusions: Serum biomarkers (adjusted sNfL z-scores at baseline and 6 months) combined with OCT metrics (RNFL and GCL-IPL layer thickness) and the clinical score BREMSO can accurately predict early disability progression using the EDSS-plus score for newly diagnosed RRMS patients.

Differences in clinical and biological factors between patients with PFO-related stroke and patients with PFO and no cerebral vascular events.

Background: While stroke is one of the most dissected topics in neurology, the primary prevention of PFO-related stroke in young patients is still an unaddressed subject. We present a study concerning clinical, demographic, and laboratory factors associated with stroke and transient ischemic attack in patients with patent foramen ovale (PFO), as well as comparing PFO-patients with and without cerebrovascular ischemic events (CVEs). Patients and methods: Consecutive patients with PFO-associated CVEs were included in the study; control group was selected from patients with a PFO and no history of stroke. All participants underwent peripheral routine blood analyses, as well as, on treating physician's recommendations, screening for thrombophilia. Results: Ninety-five patients with CVEs and 41 controls were included. Females had a significantly lower risk of CVEs than males (p = 0.04). PFO size was similar between patients and controls. Patients with CVEs had more often hypertension (n = 33, 34.7%), p = 0.007. No significant differences were found between the two groups with regard to routine laboratory tests and thrombophilia status. Hypertension and gender were identified in a binomial logistic regression model as independent predictors for CVEs, but with an area under the ROC curve of 0.531, suggesting a very poor level of discrimination between the two groups. Discussion and conclusions: There is little difference between patients with PFO with and without CVEs in terms of PFO size and routine laboratory analyses. While still a controversial topic in the specialty literature, classic first-level thrombophilic mutations are not a risk factor for stroke in patients with PFO. Hypertension and male gender were identified as factors associated with a higher risk of stroke in the setting of PFO.

Quality of acute stroke care in Romania: Achievements and gaps between 2017 and 2022.

Romania has one of the highest incidences of stroke and one of the highest mortality rates in Europe. The mortality rate due to treatable causes is also very high and is associated with the lowest public spending on healthcare in the European Union. Nonetheless, significant achievements in acute stroke care have been made in Romania in the last 5 years, most notably the increase of the national thrombolysis rate from 0.8% to 5.4%. Numerous educational workshops and constant communication with the stroke centers led to a solid and active stroke network. Due to the joint efforts of this stroke network and the ESO-EAST project, the quality of stroke care has significantly improved. However, Romania still faces many problems: a major lack of specialists in interventional neuroradiology and consequently a low number of stroke patients treated by thrombectomy and carotid revascularization procedures, a low number of neuro-rehabilitation centers and a country-wide lack of neurologists.

Combining retinal structural and vascular measurements improves discriminative power for multiple sclerosis patients.

Data on how retinal structural and vascular parameters jointly influence the diagnostic performance of detection of multiple sclerosis (MS) patients without optic neuritis (MSNON) are lacking. To investigate the diagnostic performance of structural and vascular changes to detect MSNON from controls, we performed a cross-sectional study of 76 eyes from 51 MS participants and 117 eyes from 71 healthy controls. Retinal macular ganglion cell complex (GCC), retinal nerve fiber layer (RNFL) thicknesses, and capillary densities from the superficial (SCP) and deep capillary plexuses (DCP) were obtained from the Cirrus AngioPlex. The best structural parameter for detecting MS was compensated RNFL from the optic nerve head (AUC = 0.85), followed by GCC from the macula (AUC = 0.79), while the best vascular parameter was the SCP (AUC = 0.66). Combining structural and vascular parameters improved the diagnostic performance for MS detection (AUC = 0.90; p<0.001). Including both structure and vasculature in the joint model considerably improved the discrimination between MSNON and normal controls compared to each parameter separately (p = 0.027). Combining optical coherence tomography (OCT)-derived structural metrics and vascular measurements from optical coherence tomography angiography (OCTA) improved the detection of MSNON. Further studies may be warranted to evaluate the clinical utility of OCT and OCTA parameters in the prediction of disease progression.

Delivery of acute ischaemic stroke treatments in the European region in 2019 and 2020.

INTRODUCTION: We assessed best available data on access and delivery of acute stroke unit (SU) care, intravenous thrombolysis (IVT) and endovascular treatment (EVT) in the European region in 2019 and 2020. PATIENTS AND METHODS: We compared national data per number of inhabitants and per 100 annual incident first-ever ischaemic strokes (AIIS) in 46 countries. Population estimates and ischaemic stroke incidence were based on United Nations data and the Global Burden of Disease Report 2019, respectively. RESULTS: The estimated mean number of acute SUs in 2019 was 3.68 (95% CI: 2.90-4.45) per one million inhabitants (MIH) with 7/44 countries having less than one SU per one MIH. The estimated mean annual number of IVTs was 21.03 (95% CI: 15.63-26.43) per 100,000 and 17.14% (95% CI: 12.98-21.30) of the AIIS in 2019, with highest country rates at 79.19 and 52.66%, respectively, and 15 countries delivering less than 10 IVT per 100,000. The estimated mean annual number of EVTs in 2019 was 7.87 (95% CI: 5.96-9.77) per 100,000 and 6.91% (95% CI: 5.15-8.67) of AIIS, with 11 countries delivering less than 1.5 EVT per 100,000. Rates of SUs, IVT and EVT were stable in 2020. There was an increase in mean rates of SUs, IVT and EVT compared to similar data from 2016. CONCLUSION: Although there was an increase in reperfusion treatment rates in many countries between 2016 and 2019, this was halted in 2020. There are persistent major inequalities in acute stroke treatment in the European region. Tailored strategies directed to the most vulnerable regions should be prioritised.

Real-world operation of multiple sclerosis centres in Central-Eastern European countries covering 107 million inhabitants.

BACKGROUND: In 2018 multiple sclerosis (MS) care unit (MSCU) recommendations were defined. Nevertheless, the information on MS care, and whether MS centres fulfil the international recommendation is limited. Thus our objectives were to assess whether centres meet the MSCU recommendations and gain a comprehensive overview of MS care in Central-Eastern European countries. METHODS: A self-report questionnaire assessing aspects of the MSCU recommendations, disease-modifying therapy (DMT) and registry use and the patient number was assembled and sent to nine Central-Eastern European countries. Furthermore, one Danish and one German centre were contacted as a reference. RESULTS: In 9/9 countries, MS care was pursued in centres by MS neurologists and MS nurses. In Austria and the Czech Republic, management of MS was conducted under strict regulations displaying a referral centre system, fundamentally similar to but independent of the MSCU criteria. Several centres fulfilled all aspects of the MSCU criteria, while others had similar insufficiencies consisting of a speech therapist, continence, pain and spasticity specialist, neuro-ophthalmologist, and oto-neurologist. In 9/9 countries, DMTs were reimbursed. However, some centres did not provide every available DMT. A national registry was available in 4/9 countries with mandatory registry use only in Austria and the Czech Republic. CONCLUSION: In countries where MSCU recommendations are not fulfilled, a strictly regulated centre system similar to the Austrian and Czech model with a registry-based quality control might ensure appropriate care for people with MS.

Serum and CSF Biomarkers Predict Active Early Cognitive Decline Rather Than Established Cognitive Impairment at the Moment of RRMS Diagnosis.

(1) Background: Cognitive impairment (CI) begins early in the evolution of multiple sclerosis (MS) but may only become obvious in the later stages of the disease. Little data is available regarding predictive biomarkers for early, active cognitive decline in relapse remitting MS (RRMS) patients. (2) Methods: 50 RRMS patients in the first 6 months following diagnosis were included. The minimum follow-up was one year. Biomarker samples were collected at baseline, 3-, 6- and 12-month follow-up. Cognitive performance was assessed at baseline and 12-month follow-up; (3) Results: Statistically significant differences were found for patients undergoing active cognitive decline for sNfL z-scores at baseline and 3 months, CSF NfL baseline values, CSF Aß42 and the Bremso score as well. The logistic regression model based on these 5 variables was statistically significant, χ2(4) = 22.335, p < 0.0001, R2 = 0.671, with a sensitivity of 57.1%, specificity of 97.4%, a positive predictive value of 80% and a negative predictive value of 92.6%. (4) Conclusions: Our study shows that serum biomarkers (adjusted sNfL z-scores at baseline and 3 months) and CSF biomarkers (CSF NfL baseline values, CSF Aß42), combined with a clinical score (BREMSO), can accurately predict an early cognitive decline for RRMS patients at the moment of diagnosis.

Low Fluctuation of Symptoms May Delay Diagnosis of Myasthenia Gravis: A Case Series.

INTRODUCTION: Myasthenia gravis is an autoimmune disorder affecting neuromuscular transmission, and its hallmark is fluctuating muscular weakness affecting the ocular, bulbar, respiratory, or limb muscles. Our objective is to highlight the difficulties encountered in diagnosing this disorder in patients lacking this characteristic phenomenon. METHODS: Three cases of patients presenting with progressive weakness of bulbar and ocular muscles, in whom a lack of fluctuation delayed the diagnosis of myasthenia gravis, are described. RESULTS: Amyotrophic lateral sclerosis was considered in two of the patients, while cavernous sinus thrombosis was initially diagnosed in the third. Electrodiagnostic, pharmacologic, and serologic testing ultimately established the diagnosis of myasthenia gravis. CONCLUSION: While the typical clinical pattern of myasthenia gravis is well known and easily recognizable, there are cases when the diagnosis, and thus the treatment, is delayed because of low or absent fluctuation of symptoms. The acknowledgment of this probably underestimated presentation is important for expeditious management.

Microvascular changes in the macular and parafoveal areas of multiple sclerosis patients without optic neuritis.

Retinal imaging has been proposed as a biomarker for neurological diseases such as multiple sclerosis (MS). Recently, a technique for non-invasive assessment of the retinal microvasculature called optical coherence tomography angiography (OCTA) was introduced. We investigated retinal microvasculature alterations in participants with relapsing-remitting MS (RRMS) without history of optic neuritis (ON) and compared them to a healthy control group. The study was performed in a prospective, case-control design, including 58 participants (n = 100 eyes) with RRMS without ON and 78 age- and sex-matched control participants (n = 136 eyes). OCTA images of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris (CC) were obtained using a commercial OCTA system (Zeiss Cirrus HD-5000 Spectral-Domain OCT with AngioPlex OCTA, Carl Zeiss Meditec, Dublin, CA). The outcome variables were perfusion density (PD) and foveal avascular zone (FAZ) features (area and circularity) in both the SCP and DCP, and flow deficit in the CC. MS group had on average higher intraocular pressure (IOP) than controls (P < 0.001). After adjusting for confounders, MS participants showed significantly increased PD in SCP (P = 0.003) and decreased PD in DCP (P < 0.001) as compared to controls. A significant difference was still noted when large vessels (LV) in the SCP were removed from the PD calculation (P = 0.004). Deep FAZ was significantly larger (P = 0.005) and less circular (P < 0.001) in the eyes of MS participants compared to the control ones. Neither LV, PD or FAZ features in the SCP, nor flow deficits in the CC showed any statistically significant differences between the MS group and control group (P > 0.186). Our study indicates that there are microvascular changes in the macular parafoveal retina of RRMS patients without ON, showing increased PD in SCP and decreased PD in DCP. Further studies with a larger cohort of MS patients and MRI correlations are necessary to validate retinal microvascular changes as imaging biomarkers for diagnosis and screening of MS.