Implications for driving based on the risk of seizures after ischaemic stroke.

BACKGROUND: In addition to other stroke-related deficits, the risk of seizures may impact driving ability after stroke. METHODS: We analysed data from a multicentre international cohort, including 4452 adults with acute ischaemic stroke and no prior seizures. We calculated the Chance of Occurrence of Seizure in the next Year (COSY) according to the SeLECT2.0 prognostic model. We considered COSY<20% safe for private and <2% for professional driving, aligning with commonly used cut-offs. RESULTS: Seizure risks in the next year were mainly influenced by the baseline risk-stratified according to the SeLECT2.0 score and, to a lesser extent, by the poststroke seizure-free interval (SFI). Those without acute symptomatic seizures (SeLECT2.0 0-6 points) had low COSY (0.7%-11%) immediately after stroke, not requiring an SFI. In stroke survivors with acute symptomatic seizures (SeLECT2.0 3-13 points), COSY after a 3-month SFI ranged from 2% to 92%, showing substantial interindividual variability. Stroke survivors with acute symptomatic status epilepticus (SeLECT2.0 7-13 points) had the highest risk (14%-92%). CONCLUSIONS: Personalised prognostic models, such as SeLECT2.0, may offer better guidance for poststroke driving decisions than generic SFIs. Our findings provide practical tools, including a smartphone-based or web-based application, to assess seizure risks and determine appropriate SFIs for safe driving.

Immune Checkpoint Inhibitor-Related Cerebellar Toxicity: Clinical Features and Comparison with Paraneoplastic Cerebellar Ataxia.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, and the association with immune-related adverse events (irAEs) is well-established. However, cerebellar irAEs are poorly defined and their relationship with paraneoplastic disorders remains unclear. Our aim was (i) to characterize cerebellar irAE; (ii) to compare it with paraneoplastic cerebellar ataxia (PCA). We performed a multicenter, retrospective, cohort study of patients developing new-onset, immune-mediated, isolated/predominant cerebellar dysfunction after ICI administration. In addition, a systematic review following PRISMA guidelines was performed. Cerebellar irAE cases were compared with a consecutive cohort of patients with PCA. Overall, 35 patients were included, of whom 12 were original cases (males: 25/35 (71%), median age: 65 [range: 20-82]). The most frequent tumor was non-small cell lung cancer (12/35, 34%). Anti-PD1 were adopted in 19/35 (54%). Symptoms developed at a median of 11 weeks after ICI onset. Neuronal antibodies were detected in 15/31 patients tested (48%). Cerebrospinal fluid was inflammatory in 25/30 (83%). Magnetic resonance imaging showed cerebellar hyperintensities in 8/35 (23%). Immunotherapy was applied in 33/35 cases (94%), and most patients improved with residual disability (16/35, 46%). When compared with a series of PCA (n = 15), the cerebellar irAE group was significantly more associated with male sex, lung cancer (rather than gynecological/breast cancers), isolated ataxia, and a better outcome. We provide a detailed characterization of cerebellar irAE. Compared to PCA, differences exist in terms of tumor association, clinical features, and outcome. Clinical presentation-antibody-tumor triad in the ICI group only partially reflects the associations described in paraneoplastic disorders.

Sudden unexpected death in epilepsy and ictal asystole in patients with autoimmune encephalitis: a systematic review.

OBJECTIVE: As autoimmune encephalitis (AE) often involves the mesial temporal structures which are known to be involved in both sudden unexpected death in epilepsy (SUDEP) and ictal asystole (IA), it may represent a good model to study the physiopathology of these phenomena. Herein, we systematically reviewed the occurrence of SUDEP and IA in AE. METHODS: We searched 4 databases (MEDLINE, Scopus, Embase, and Web of Science) for studies published between database inception and December 20, 2022, according to the PRISMA guidelines. We selected articles reporting cases of definite/probable/possible/near-SUDEP or IA in patients with possible/definite AE, or with histopathological signs of AE. RESULTS: Of 230 records assessed, we included 11 cases: 7 SUDEP/near-SUDEP and 4 IA. All patients with IA were female. The median age at AE onset was 30 years (range: 15-65), and the median delay between AE onset and SUDEP was 11 months; 0.9 months for IA. All the patients presented new-onset seizures, and 10/11 also manifested psychiatric, cognitive, or amnesic disorders. In patients with SUDEP, 2/7 were antibody-positive (1 anti-LGI1, 1 anti-GABABR); all IA cases were antibody-positive (3 anti-NMDAR, 1 anti-GAD65). Six patients received steroid bolus, 3 intravenous immunoglobulin, and 3 plasmapheresis. A pacemaker was implanted in 3 patients with IA. The 6 survivors improved after treatment. DISCUSSION: SUDEP and IA can be linked to AE, suggesting a role of the limbic system in their pathogenesis. IA tends to manifest in female patients with temporal lobe seizures early in AE, highlighting the importance of early diagnosis and treatment.

Dissociations in white matter tracts and neuropsychological findings in a 17 years old patient with Subacute sclerosing panencephalitis.

The present multimodal diffusion tensor imaging and neuropsychological study investigated the integrity of the white matter fascicles in a 17 years-old patient diagnosed with subacute sclerosing panencephalitis (SSPE). A brief neuropsychological testing showed that word and pseudoword repetition, naming, semantic and phonological fluency, long-term memory, working memory were impaired. A review of the literature on Diffusion weighted imaging (DWI) and Diffusion Tensor Imaging (DTI) evidenced that, studies investigating the integrity of white matter in this condition being a rare disease, are very few. Significant differences (p < 0.05) were found between the fractional anisotropy (FA) values of the controls and the patient in the Superior Longitudinal fasciculus, the Inferior Longitudinal Fasciculus, the Inferior Fronto-Occipital Fasciculus, the Uncinate Fasciculus, and the Arcuate Fasciculus with lower values in the patient. No differences were found for the corticospinal tract. The number of streamlines was significantly lower in the patient, compared to controls, for the left Superior Longitudinal fasciculus, and for the left Uncinate fasciculus while for all the other fascicles, the number did not significantly differ from controls. DTI results were consistent with the patient's cognitive profile showing impairments at repetition, at tasks tapping lexical-semantics and long-term memory / retrieval. Diffusion tensor imaging results indicate that there were diffuse alterations of the degree of anisotropic diffusion along the white matter tracts distributed in posterior-anterior direction. Differently, a selective sparing of this measure was observed along the white matter tract distributed in inferior-superior direction (the corticospinal fascicle).

Hyperdense middle cerebral artery sign predicts favorable outcome in patients undergoing mechanical thrombectomy.

Non-contrast computer tomography detects the presence of hyperdense middle cerebral artery sign (HMCAS). Studies on the prognostic value of HMCAS among patients undergoing mechanical thrombectomy (MT) are conflicting. A retrospective analysis of consecutive patients with acute ischemic stroke due to middle cerebral artery occlusion, presenting with or without HMCAS, who underwent MT, was performed. We enrolled 191 patients (HMCAS +, n = 140; HMCAS -, n = 51). Prevalence of successful recanalization was significantly higher in patients with HMCAS than in those without HMCAS (92.1% versus 74.5%, p = 0.001). Patients with HMCAS had a better clinical outcome than those HMCAS - (54.3% versus 37.3%, p = 0.037, for three-month favorable outcome; 62.9% versus 39.3%, p = 0.004, for major neurological improvement at discharge; 8.6% versus 19.6%, p = 0.035, for in-hospital mortality; 14.3% versus 27.5%, p = 0.035, for intracranial hemorrhage; 2.9% versus 17.6%, p = 0.001, for symptomatic intracranial hemorrhage). Multivariate analyses confirmed that HMCAS represents an independent predictor of three-month favorable outcome (OR 2.48, 95% CI 1.10-5.58, p = 0.028), major neurological improvement at discharge (OR 2.40, 95% CI 1.09-5.20, p = 0.030), in-hospital mortality (OR 0.29, 95% CI 0.010-0.81, p = 0.018), presence of ICH (OR 0.49, 95% CI 0.25-0.97, p = 0.042) and presence of SICH (OR 0.16, 95% CI 0.04-0.63, p = 0.009). HMCAS presence predicts favorable outcome in patients undergoing MT. This result may indicate that hyperdense clots are more likely to respond to MT than isodense ones. This effect is mediated by reduction in hemorrhagic transformation.

A State-of-Art Review of the Vicious Circle of Sleep Disorders, Diabetes and Neurodegeneration Involving Metabolism and Microbiota Alterations.

In the context of neurodegenerative disorders, cognitive decline is frequently reported in older population. Recently, numerous metabolic pathways have been implicated in neurodegeneration, including signaling disruption of insulin and other glucose-regulating hormones. In fact, Alzheimer's disease has now been considered as "type-3 diabetes". In this review, we tried to clarify the role of sleep impairment as the third major player in the complex relationship between metabolic and neurodegenerative diseases. Altered sleep may trigger or perpetuate these vicious mechanisms, leading to the development of both dementia and type 2 diabetes mellitus. Finally, we analyzed these reciprocal interactions considering the emerging role of the gut microbiota in modulating the same processes. Conditions of dysbiosis have been linked to circadian rhythm disruption, metabolic alterations, and release of neurotoxic products, all contributing to neurodegeneration. In a future prospective, gut microbiota could provide a major contribution in explaining the tangled relationship between sleep disorders, dementia and diabetes.

2:1 ketogenic diet and low-glycemic-index diet for the treatment of chronic and episodic migraine: a single-center real-life retrospective study.

AIMS: The evidence supporting the efficacy of dietary preventive therapy in migraine is rising, particularly regarding the ketogenic diet. However, less evidence exists for the Low-Glycemic Index Diet and the 2:1 KD. This retrospective single-center real-life study aims to evaluate the efficacy of a 2:1 ketogenic diet and a Low-Glycemic-index Diet in chronic and high-frequency episodic migraine. METHODS: Sixty patients with high-frequency episodic and chronic migraine were treated with either a Low-Glycemic-index diet (39 patients) or a 2:1 (21 patients) ketogenic diet for three months. We collected data on the migraine frequency and intensity and the MIDAS and HIT-6 scores through the headache diary. Anthropometric measurements (BMI, fat mass, free fat mass, and weight) were also collected and analyzed similarly. Data obtained at the baseline and after three months of each diet were compared. RESULTS: Migraine intensity, frequency, MIDAS and HIT-6 scores, fat mass, weight, and BMI improved in both diet groups. CONCLUSIONS: Both diets are effective in reducing migraine symptoms and migraine-related disability.

The Possible Precipitating Role of SARS-CoV-2 in a Case of Late-Onset Hemichorea Due to a Hyperosmolar Hyperglycemic State: Case Report and Brief Literature Review.

Case report: An 83-year-old Italian female developed postural instability and gait disturbance associated with a concomitant hyperosmolar hyperglycemic state. Brain CT and MRI scans detected a lesion in the right putamen due to metabolic derangement. A month later, the patient started suffering from choreic movements along the left side of the body with brachio-crural distribution, approximately three weeks after SARS-CoV-2 infection. She was treated with tetrabenazine with complete resolution of the aberrant movements. Any attempt to reduce tetrabenazine caused a relapse of the symptoms. Discussion: In diabetic patients, choreic syndrome should be considered a rare event with a benign prognosis and favorable response to treatment. It is the result of a condition known as "diabetic striatopathy". The association of new-onset choreic movements, an episode of hyperglycemia, and a basal ganglia lesion is suggestive of this condition. Its pathophysiology remains unclear, and a lot of hypotheses are still debated. SARS-CoV-2 might have played a role in triggering the patient's motor symptoms. Conclusions: Our case report agrees with the general features of those reported in the literature about movement disorders in diabetic patients. The late onset of symptoms and the poor response to treatment seem to be atypical characteristics of the syndrome. Although speculative, we cannot exclude the role of SARS-CoV-2. This case can be added to the literature for further studies and reviews.

Impact of Disease-Modifying Therapies on Gut-Brain Axis in Multiple Sclerosis.

Multiple sclerosis is a chronic, autoimmune-mediated, demyelinating disease whose pathogenesis remains to be defined. In past years, in consideration of a constantly growing number of patients diagnosed with multiple sclerosis, the impacts of different environmental factors in the pathogenesis of the disease have been largely studied. Alterations in gut microbiome composition and intestinal barrier permeability have been suggested to play an essential role in the regulation of autoimmunity. Thus, increased efforts are being conducted to demonstrate the complex interplay between gut homeostasis and disease pathogenesis. Numerous results confirm that disease-modifying therapies (DMTs) used for the treatment of MS, in addition to their immunomodulatory effect, could exert an impact on the intestinal microbiota, contributing to the modulation of the immune response itself. However, to date, the direct influence of these treatments on the microbiota is still unclear. This review intends to underline the impact of DMTs on the complex system of the microbiota-gut-brain axis in patients with multiple sclerosis.

Multisensory mental imagery of fatigue: Evidence from an fMRI study.

Functional imaging experimental designs measuring fatigue, defined as a subjective lack of physical and/or mental energy characterizing a wide range of neurologic conditions, are still under development. Nineteen right-handed healthy subjects (9 M and 10 F, mean age 43.15 ± 8.34 years) were evaluated by means of functional magnetic resonance imaging (fMRI), asking them to perform explicit, first-person, mental imagery of fatigue-related multisensory sensations. Short sentences designed to assess the principal manifestations of fatigue from the Multidimensional Fatigue Symptom Inventory were presented. Participants were asked to imagine the corresponding sensations (Sensory Imagery, SI). As a control, they had to imagine the visual scenes (Visual Imagery, VI) described in short phrases. The SI task (vs. VI task) differentially activated three areas: (i) the precuneus, which is involved in first-person perspective taking; (ii) the left superior temporal sulcus, which is a multisensory integration area; and (iii) the left inferior frontal gyrus, known to be involved in mental imagery network. The SI fMRI task can be used to measure processing involved in mental imagery of fatigue-related multisensory sensations.

Seizures after Ischemic Stroke: A Matched Multicenter Study.

OBJECTIVE: The purpose of this study was to identify risk factors for acute symptomatic seizures and post-stroke epilepsy after acute ischemic stroke and evaluate the effects of reperfusion treatment. METHODS: We assessed the risk factors for post-stroke seizures using logistic or Cox regression in a multicenter study, including adults from 8 European referral centers with neuroimaging-confirmed ischemic stroke. We compared the risk of post-stroke seizures between participants with or without reperfusion treatment following propensity score matching to reduce confounding due to treatment selection. RESULTS: In the overall cohort of 4,229 participants (mean age 71 years, 57% men), a higher risk of acute symptomatic seizures was observed in those with more severe strokes, infarcts located in the posterior cerebral artery territory, and strokes caused by large-artery atherosclerosis. Strokes caused by small-vessel occlusion carried a small risk of acute symptomatic seizures. 6% developed post-stroke epilepsy. Risk factors for post-stroke epilepsy were acute symptomatic seizures, more severe strokes, infarcts involving the cerebral cortex, and strokes caused by large-artery atherosclerosis. Electroencephalography findings within 7 days of stroke onset were not independently associated with the risk of post-stroke epilepsy. There was no association between reperfusion treatments in general or only intravenous thrombolysis or mechanical thrombectomy with the time to post-stroke epilepsy or the risk of acute symptomatic seizures. INTERPRETATION: Post-stroke seizures are related to stroke severity, etiology, and location, whereas an early electroencephalogram was not predictive of epilepsy. We did not find an association of reperfusion treatment with risks of acute symptomatic seizures or post-stroke epilepsy. ANN NEUROL 2021;90:808-820.

Performing real time neuropsychological testing during awake craniotomy: are dexmedetomidine or propofol the same? A preliminary report.

PURPOSE: In awake surgery, the patient is sedated, but is also required to be sufficiently alert and collaborative during extensive neurocognitive testing. In the present preliminary report of a retrospective single-center study, a continuous series of 168 patients who underwent awake surgery for brain tumor located near eloquent areas, was investigated to observe the effect of dexmedetomidine (n = 58) compared with propofol (n = 110) on vigilance and collaboration required to perform extensive intra-operatory Real Time Neuropsychological Testing (RTNT). METHODS: We assigned a score to each patient, by using a scale that combines vigilance and collaboration in a 5 levels score (the higher score denoting higher level). RESULTS: The median interquartile range was significantly lower (range 3-5) for the dexmedetomidine group compared to the propofol one (range 4-5, p = .044). Patients with intra-operative seizures (p = .014) and/or electrocorticographic slow/epileptiform activity (p = .042), and patients in the propofol group who showed increased heart rate (p = .032) were those who obtained the lower scores (lower vigilance and collaboration level). CONCLUSION: The study shows that the effect of dexmedetomidine or propofol -based conscious sedation on ability to perform Real Time Neuropsychological Testing during awake surgery for supratentorial tumor resection is different. Although both permit high mean levels of vigilance and collaboration, the patient who received dexmedetomidine was more likely to show lower vigilance and collaboration during RTNT.

New-onset status epilepticus in SARS-CoV-2 infection: a case series.

BACKGROUND: Neurological manifestations of COVID-19 infection are well recognized. Seizures and status epilepticus (SE) have been reported as possible manifestations and/or complications of SARS-CoV-2 infection at different disease stages, but few data are known about the type, severity, treatment response, and recurrence. METHODS: Single-center retrospective case series. RESULTS: This case series describes four COVID-19-positive patients admitted to an Italian University Hospital, who developed status epilepticus during the active phase of disease, independently from the severity of respiratory symptoms. Two of them presented a relapse after resolution of the acute viral infection, a feature that has not been previously reported. CONCLUSIONS: Although a possible association between SE and COVID-19 has been reported, the exact etiopathogenetic mechanism remains still not understood. Our series adds new insights to shed further light on this controversial issue.

Predictive risk factors of phenoconversion in idiopathic REM sleep behavior disorder: the Italian study "FARPRESTO".

Most patients with idiopathic REM sleep behavior disorder (iRBD) will develop an overt α-synucleinopathy over time, with a rate of phenoconversion of 73.5% after 12 years from diagnosis. Several markers of phenoconversion were identified; however, most studies investigated biomarkers separately, with retrospective study designs, in small cohorts or without standardized data collection methods. The risk FActoRs PREdictive of phenoconversion in idiopathic REM sleep behavior disorder: the Italian STudy (FARPRESTO) is a multicentric longitudinal retrospective and prospective study with a cohort of incident (prospective recruitment) and prevalent (retrospective recruitment) iRBD patients, whose primary aim is to stratify the risk of phenoconversion, through the systematic collection by means of electronic case report forms of different biomarkers. Secondary aims are to (1) describe the sociodemographic and clinical characteristics of patients with iRBD; (2) collect longitudinal data about the development of α-synucleinopathies; (3) monitor the impact of iRBD on quality of life and sleep quality; (4) assess the correlation between phenoconversion, cognitive performance, and loss of normal muscle atony during REM sleep; (5) identify RBD phenotypes through evaluating clinical, biological, neurophysiological, neuropsychological, and imaging biomarkers; and (6) validate vPSG criteria for RBD diagnosis. The FARPRESTO study will collect a large and harmonized dataset, assessing the role of different biomarkers providing a unique opportunity for a holistic, multidimensional, and personalized approach to iRBD, with several possible application and impact at different levels, from basic to clinical research, and from prevention to management. The FARPRESTO has been registered at clinicaltrials.gov (NCT05262543).

Clinical characteristics of a large cohort of patients with narcolepsy candidate for pitolisant: a cross-sectional study from the Italian PASS Wakix® Cohort.

INTRODUCTION: Narcolepsy is a chronic and rare hypersomnia of central origin characterized by excessive daytime sleepiness and a complex array of symptoms as well as by several medical comorbidities. With growing pharmacological options, polytherapy may increase the possibility of a patient-centered management of narcolepsy symptoms. The aims of our study are to describe a large cohort of Italian patients with narcolepsy who were candidates for pitolisant treatment and to compare patients' subgroups based on current drug prescription (drug-naïve patients in whom pitolisant was the first-choice treatment, switching to pitolisant from other monotherapy treatments, and adding on in polytherapy). METHODS: We conducted a cross-sectional survey based on Italian data from the inclusion visits of the Post Authorization Safety Study of pitolisant, a 5-year observational, multicenter, international study. RESULTS: One hundred ninety-one patients were enrolled (76.4% with narcolepsy type 1 and 23.6% with narcolepsy type 2). Most patients (63.4%) presented at least one comorbidity, mainly cardiovascular and psychiatric. Pitolisant was prescribed as an add-on treatment in 120/191 patients (62.8%), as switch from other therapies in 42/191 (22.0%), and as a first-line treatment in 29/191 (15.2%). Drug-naive patients presented more severe sleepiness, lower functional status, and a higher incidence of depressive symptoms. CONCLUSION: Our study presents the picture of a large cohort of Italian patients with narcolepsy who were prescribed with pitolisant, suggesting that polytherapy is highly frequent to tailor a patient-centered approach.

Specialized Pro-Resolving Mediators in Neuroinflammation: Overview of Studies and Perspectives of Clinical Applications.

Specialized pro-resolving mediators (SPMs) are lipid mediators derived from poly-unsaturated fatty acids (PUFAs) which have been demonstrated to have an important role in the inflammation environment, preventing an overreaction of the organism and promoting the resolution of inflammation. Our purpose was to point out the current evidence for specialized pro-resolving mediators, focusing on their role in neuroinflammation and in major neurological diseases.

Fine-Mapping of SNCA in Rapid Eye Movement Sleep Behavior Disorder and Overt Synucleinopathies.

OBJECTIVE: Rapid eye movement sleep behavior disorder (RBD) is a prodromal synucleinopathy, as >80% will eventually convert to overt synucleinopathy. We performed an in-depth analysis of the SNCA locus to identify RBD-specific risk variants. METHODS: Full sequencing and genotyping of SNCA was performed in isolated/idiopathic RBD (iRBD, n = 1,076), Parkinson disease (PD, n = 1,013), dementia with Lewy bodies (DLB, n = 415), and control subjects (n = 6,155). The iRBD cases were diagnosed with RBD prior to neurodegeneration, although some have since converted. A replication cohort from 23andMe of PD patients with probable RBD (pRBD) was also analyzed (n = 1,782 cases; n = 131,250 controls). Adjusted logistic regression models and meta-analyses were performed. Effects on conversion rate were analyzed in 432 RBD patients with available data using Kaplan-Meier survival analysis. RESULTS: A 5'-region SNCA variant (rs10005233) was associated with iRBD (odds ratio [OR] = 1.43, p = 1.1E-08), which was replicated in pRBD. This variant is in linkage disequilibrium (LD) with other 5' risk variants across the different synucleinopathies. An independent iRBD-specific suggestive association (rs11732740) was detected at the 3' of SNCA (OR = 1.32, p = 4.7E-04, not statistically significant after Bonferroni correction). Homozygous carriers of both iRBD-specific SNPs were at highly increased risk for iRBD (OR = 5.74, p = 2E-06). The known top PD-associated variant (3' variant rs356182) had an opposite direction of effect in iRBD compared to PD. INTERPRETATION: There is a distinct pattern of association at the SNCA locus in RBD as compared to PD, with an opposite direction of effect at the 3' of SNCA. Several 5' SNCA variants are associated with iRBD and with pRBD in overt synucleinopathies. ANN NEUROL 2020;87:584-598.

Comprehensive Analysis of Familial Parkinsonism Genes in Rapid-Eye-Movement Sleep Behavior Disorder.

BACKGROUND: There is only partial overlap in the genetic background of isolated rapid-eye-movement sleep behavior disorder (iRBD) and Parkinson's disease (PD). OBJECTIVE: To examine the role of autosomal dominant and recessive PD or atypical parkinsonism genes in the risk of iRBD. METHODS: Ten genes, comprising the recessive genes PRKN, DJ-1 (PARK7), PINK1, VPS13C, ATP13A2, FBXO7, and PLA2G6 and the dominant genes LRRK2, GCH1, and VPS35, were fully sequenced in 1039 iRBD patients and 1852 controls of European ancestry, followed by association tests. RESULTS: We found no association between rare heterozygous variants in the tested genes and risk of iRBD. Several homozygous and compound heterozygous carriers were identified, yet there was no overrepresentation in iRBD patients versus controls. CONCLUSION: Our results do not support a major role for variants in these genes in the risk of iRBD. © 2020 International Parkinson and Movement Disorder Society.

Stress hyperglycemia is predictive of worse outcome in patients with acute ischemic stroke undergoing intravenous thrombolysis.

No study investigated the possible detrimental effect of stress hyperglycemia on patients affected acute ischemic stroke (AIS) undergoing intravenous thrombolysis (IVT). A new index, the glucose-to-glycated hemoglobin ratio (GAR), has been developed for assessing stress hyperglycemia. We retrospectively analyzed data from a prospectively collected database of consecutive patients admitted to the Udine University Hospital with AIS that were treated with IVT from January 2015 to December 2019. Four hundred and fourteen consecutive patients with AIS undergoing IVT entered the study. The patients were then stratified into four groups by quartiles of GAR (Q1-Q4). The higher GAR index was, the more severe stress hyperglycemia was considered. Prevalence of 3 months poor outcome (37.7% for Q1, 34% for Q2, 46.9% for Q3, and 66.7% for Q4, p for trend = 0.001), 3 months mortality (10.5% for Q1, 7.5% for Q2, 11.2% for Q3, and 27.1% for Q4, p for trend = 0.001), and symptomatic intracranial hemorrhage (0.9% for Q1, 0.9% for Q2, 5.1% for Q3, and 17.7% for Q4, p for trend = 0.001) was significant different among the four groups. AIS patients with severe stress hyperglycemia had a significantly increased risk of 3 months poor outcome (OR 2.43, 95% CI 1.14-5.22, p = 0.02), 3 months mortality (OR 2.38, 95% CI 1.01-5.60, p = 0.04), and symptomatic intracranial hemorrhage (OR 16.76, 95% CI 2.09-134.58, p = 0.008) after IVT. In conclusion, we demonstrated that stress hyperglycemia, as measured by the GAR index, is associated to worse outcome in AIS patients undergoing IVT.

Clinical and neurophysiological characterization of muscular weakness in severe COVID-19.

OBJECTIVE: To report clinical and electroneuromyographic (ENMG) characteristics of patients affected by severe COVID-19 infection, evaluated for muscular weakness. MATERIALS AND METHODS: ENMGs performed for evaluation of diffuse weakness in patients who could not be discharged from semi-intensive care COVID unit because of difficulties in ventilation weaning were reviewed. Patients with severe COVID-19 infection who had undergone endotracheal intubation and able to co-operate were considered. ENMG protocol was focused on neurophysiological items that excluded or confirmed critical illness polyneuropathy (CIP), myopathy (CIM), or polyneuromyopathy (CIPM). Standardized clinical evaluation was performed using Medical Research Council (MRC) sum score. RESULTS: Eight patients were included in the study. All presented known risk factors for intensive care unit-acquired weakness (ICU-AW), and none of them had history of underlying neuromuscular disorders. ENMG findings were normal in two patients, while only two patients had an altered MRC sum score (< 48). Neuromuscular involvement was diagnosed in 6/8 patients (75%): 2 had CIP, 1 had possible CIM, 1 had CIPM, while 1 patient, with clinically evident weakness but equivocal ENMG findings, was classified as ICU-AW. Finally, 1 patient was diagnosed with acute demyelinating neuropathy. Patients with neuromuscular involvement were those with longer intubation duration and higher levels of IL-6 at admission. CONCLUSION: Neuromuscular complications are frequent in severe COVID-19 and cannot be excluded by MRC sum scores above 48. Standardized ENMG is helpful in guiding diagnosis when clinical evaluation is not reliable or possible. Elevated IL-6 at admission may be a predictor biomarker of ICU-AW in COVID-19.