Transverse myelitis following COVID-19: Insights from a multi-center study and systematic literature review.

INTRODUCTION: We aimed to provide insights into transverse myelitis (TM) following COVID-19 by analyzing cases treated at tertiary care neurology centers and a systemic review of the literature. METHODS: The retrospective observational multi-center study was conducted at the four university neurology departments in Croatia, Slovenia, Serbia, and Austria. We searched for acute myelitis cases that occurred during or after COVID-19. A systemic review of the literature on COVID-19 and transverse myelitis was performed. RESULTS: We identified 76 persons with TM associated with COVID-19, 13 from the multi-center study and 63 from the literature review. Most of the participants (55.6%) had an intermediate latency, 25.4% had short and 19% long latency from COVID-19 symptoms to TM. The clinical presentation consisted of the typical TM signs. More than half of the participants had inflammatory changes in the CSF, with rare patients having intrathecal OCB synthesis and positive serology for anti-MOG or anti-AQP4 antibodies. Persons with autonomic symptoms and CSF pleocytosis were significantly more common to have an intermediate latency of 8 to 21 days from COVID-19 to TM (p = 0.005 and p = 0.003; respectively). According to logistic regression analysis, only participants with lesions evident on spinal cord MRI compared to normal spinal cord MRI had reduced risks for poor recovery. >80% of participants were treated with a combination of corticosteroids and intravenous immunoglobulins or plasma exchange with 73% having incomplete recovery. CONCLUSION: Our study further characterizes clinical, laboratory, and MRI features, as well as treatment of TM associated with COVID-19.

Diroximel Fumarate as a Novel Oral Immunomodulating Therapy for Relapsing Forms of Multiple Sclerosis: A Review on the Emerging Data.

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disorder of the central nervous system. Disease-modifying drugs (DMDs) and subsequent adherence are crucial for preventing reversible episodes of neurological dysfunction and delayed onset of progressive accumulation of irreversible deficits. Yet, side effects may limit their usage in clinical practice. Gastrointestinal (GI) side effects are a significant limitation of the use of dimethyl fumarate (DMF), the most frequently prescribed oral DMD in MS worldwide. Diroximel fumarate (DRF) is a second-generation oral fumaric acid ester (FAE) that was developed as a formulation with better GI tolerability. The improved tolerability is assumed to be related to a lower synthesis of gut-irritating methanol. Other explanations for DRF's lower extent of GI irritation include a more modest off-target activity due to its chemical structure. The superior GI tolerability of DRF compared to DMF could be proven in clinical trials and lead to approval of DRF for the treatment of relapsing forms of MS/relapsing-remitting MS (United States Food and Drug Administration and European Medicines Agency, respectively). Here, we summarize the mode of action of oral FAE and compare the chemical and physiological characteristics of DMF and DRF. Moreover, we discuss the adverse effects of FAE and introduce the emerging preclinical and trial data leading to the approval of DRF in MS. This article additionally reviews our current understanding of coronavirus disease 2019 (COVID-19) and the efficacy of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination in people treated with FAE.

Embolic Stroke Following Ingestion of Liquid Nicotine Refill Solution.

The use of e-cigarettes is gaining popularity despite knowing about cardiovascular health risks. Cases of intentional or accidental intoxication following ingestion of the refill solution are also a growing concern. Most of these cases were fatal and related to cardiac arrest and hypoxic brain injury. We report the case of a 54-year-old woman who developed bilateral acute ischemic stroke in the anterior and posterior cerebral circulation following intentional oral intake of e-liquid nicotine refill solution. The diagnostic work-up concluded an etiology of embolic stroke of undetermined source, most likely of cardiac origin. We assume that sympathetic overactivation lead to temporary cardiac arrhythmia and subsequent thrombi formation. Moreover, we discuss several additional pathogenic aspects of oral intake of e-liquid refill solution for the development of central nervous system pathology. This case expands the clinical spectrum of health hazards associated with the introduction of e-cigarettes and raises awareness of the need for preventive measures.

Systematic review of cases of acute myelitis in individuals with COVID-19.

BACKGROUND AND PURPOSE: An incremental number of cases of acute transverse myelitis (ATM) in individuals with ongoing or recent coronavirus disease 2019 (COVID-19) have been reported. METHODS: A systematic review was performed of cases of ATM described in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by screening both articles published and in preprint. RESULTS: Twenty cases were identified. There was a slight male predominance (60.0%) and the median age was 56 years. Neurological symptoms first manifested after a mean of 10.3 days from the first onset of classical, mostly respiratory symptoms of COVID-19. Overall, COVID-19 severity was relatively mild. Polymerase chain reaction of cerebrospinal fluid for SARS-CoV-2 was negative in all 14 cases examined. Cerebrospinal fluid findings reflected an inflammatory process in most instances (77.8%). Aquaporin-4 and myelin oligodendrocyte protein antibodies in serum (tested in 10 and nine cases, respectively) were negative. On magnetic resonance imaging, the spinal cord lesions spanned a mean of 9.8 vertebral segments, necrotic-hemorrhagic transformation was present in three cases and two individuals had additional acute motor axonal neuropathy. More than half of the patients received a second immunotherapy regimen. Over a limited follow-up period of several weeks, 90% of individuals recovered either partially or near fully. CONCLUSION: Although causality cannot readily be inferred, it is possible that cases of ATM occur para- or post-infectiously in COVID-19. All identified reports are anecdotal and case descriptions are heterogeneous. Whether the condition and the observed radiological characteristics are specific to SARS-CoV-2 infection needs to be clarified.

Cerebral venous thrombosis and severe acute respiratory syndrome coronavirus-2 infection: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection predisposes patients to arterial and venous thrombosis. This study aimed to systematically review the available evidence in the literature for cerebral venous thrombosis (CVT) in association with coronavirus disease-2019 (COVID-19). METHODS: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases to identify cases of COVID-19-associated CVT. The search period spanned 1 January 2020 to 1 December 2020, and the review protocol (PROSPERO-CRD42020214327) followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Identified studies were evaluated for bias using the Newcastle-Ottawa scale. A proportion meta-analysis was performed to estimate the frequency of CVT among hospitalized COVID-19 patients. RESULTS: We identified 57 cases from 28 reports. Study quality was mostly classified as low. CVT symptoms developed after respiratory disease in 90%, and the mean interval was 13 days. CVT involved multiple sites in 67% of individuals, the deep venous system was affected in 37%, and parenchymal hemorrhage was found in 42%. Predisposing factors for CVT beyond SARS-CoV-2 infection were present in 31%. In-hospital mortality was 40%. Using data from 34,331 patients, the estimated frequency of CVT among patients hospitalized for SARS-CoV-2 infection was 0.08% (95% confidence interval [CI]: 0.01-0.5). In an inpatient setting, CVT accounted for 4.2% of cerebrovascular disorders in individuals with COVID-19 (cohort of 406 patients, 95% CI: 1.47-11.39). CONCLUSIONS: Cerebral venous thrombosis in the context of SARS-CoV-2 infection is a rare, although there seems to be an increased relative risk. High suspicion is necessary, because the diagnosis of this potentially life-threatening condition in COVID-19 patients can be challenging. Evidence is still scarce on the pathophysiology and potential prevention of COVID-19-associated CVT.

A global view of comorbidity in multiple sclerosis: a systematic review with a focus on regional differences, methodology, and clinical implications.

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system which is associated with numerous comorbidities. These include cardiovascular disease, psychiatric and neurologic disturbances, restless leg syndrome, migraine, cancer, autoimmune diseases, and metabolic disorders. Comorbid disease is an important consideration for clinicians treating patients with MS; early presentation of comorbidities can obscure or delay MS diagnosis, as well as significantly impacting the disease course. Improved understanding of comorbidities and their emergence in MS populations is important for improving the quality of life and optimizing treatment for patients. Therefore, we evaluated published studies reporting epidemiologic data on comorbidities and their associated impact on disease progression in patients with MS (PwMS). The prevalence of neurologic, cardiovascular, metabolic, and autoimmune comorbidities was elevated in PwMS in general, and furthermore, this adversely affected a broad range of outcomes. Compared with PwMS, cancer rates in people without MS or the general population were lower, which should prompt further studies into the mechanisms of both diseases. Studies were under-represented in many regions owing to the latitudinal gradient of MS and possible underfunding of studies.

Therapy of Dysphagia by Prolonged Pharyngeal Electrical Stimulation (Phagenyx) in a Patient with Brainstem Infarction.

Dysphagia after stroke impacts quality of life and is a risk factor for respiratory infections. Patients frequently require prophylactic measures including nasogastric tube or percutaneous endoscopic gastrostomy. Until recently, therapy for dysphagia was limited to training with a speech and language specialist. Intraluminal pharyngeal electrical stimulation (PES) is a new technique that stimulates the pharyngeal sensory afferents to the higher swallowing center in cortex. The clinical trials published to date involved stimulation for 10 minutes over three days. We present a case of brainstem infarction with severe dysphagia in a 53-year-old woman with preserved cognitive functions. For airway protection, she had a surgical tracheotomy. The initial swallowing training achieved slight improvements, but stagnated after three months so PES was tried. Under good PES tube tolerance, a prolonged and repeated stimulation protocol was administered, with the main purpose of relieving her of the tracheal tube. Although the swallowing improved, she stayed tube-dependent with minimal attempts with puréed food during therapy, and could not be decannulated. Further studies are required to assess the value of this promising approach for the treatment of dysphagia.

Functional Magnetic Resonance Imaging in the Final Stage of Creutzfeldt-Jakob Disease.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare fatal degenerative disease of the central nervous system. The clinical course is characterized by rapid progression of neurological and neuromuscular symptoms. The late stage with loss of consciousness is not well characterized. We report a 62-year-old male patient with sCJD with the clinical picture of a vegetative state/apallic syndrome, in whom we studied cortical responses using a vibration paradigm. The functional magnetic resonance imaging (fMRI) investigation demonstrated a clear response within the sensorimotor cortex, the cerebellum, the parietal cortex, the insular, and frontal inferior region. The finding of persistent cortical activity on fMRI in a patient with CJD in a state of unconsciousness has implications for the clinical management and for ethical considerations.

Cerebral HSV-1 Vasculitis as a Fatal Complication of Immunosuppression in Non-Hodgkin´s Lymphoma: A Case Report and Review of the Literature.

Patients with lymphoma are predisposed to infection because of the immunocompromised state related to the disease itself and as a consequence of chemo-/radiotherapy. Here, we report a case of Herpes-simplex virus encephalitis (HSE) in an immunosuppressed patient with splenic marginal zone lymphoma (SMZL), a rare indolent variant of non-Hodgkin´s lymphoma (NHL). The course was complicated febrile neutropenia and HSV-1-related cerebral vasculitis causing progressive ischemic stroke. This case illustrates the expanding spectrum of atypical clinical and radiological manifestations of HSE in patients treated with myelotoxic drugs. Moreover, we summarize the few central nervous system manifestations of SMZL reported in the literature and discuss distinct causes of neurological deterioration in patients with NHL.

Vitamin D Supplementation in Multiple Sclerosis: A Critical Analysis of Potentials and Threats.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). In recent years, vitamin D has gained attention, as low serum levels are suspected to increase the risk for MS. Cholecalciferol supplementation has been tested in several clinical trials, since hypovitaminosis D was linked to higher disease activity and may even play a role in long-term outcome. Here, we review the current understanding of the molecular effects of vitamin D beyond calcium homeostasis, the potential beneficial action in MS and hazards including complications of chronic and high-dose therapy. In clinical trials, doses of up to 40,000 IU/day were tested and appeared safe as add-on therapy for short-term periods. A recent meta-analysis of a randomized, double-blind, placebo-controlled clinical trial investigating vitamin D as add-on therapy in MS, however, suggested that vitamin D had no therapeutic effect on disability or relapse rate. We recognize a knowledge gap for chronic and high-dose therapy, which can lead to life-threatening complications related to vitamin D toxicity including renal failure, cardiac arrythmia and status epilepticus. Moreover, vitamin D toxicity may manifest as fatigue, muscle weakness or urinary dysfunction, which may mimic the natural course of progressive MS. Given these limitations, vitamin D supplementation in MS is a sensitive task which needs to be supervised by physicians. While there is strong evidence for vitamin D deficiency and the development of MS, the risk-benefit profile of dosage and duration of add-on supplementation needs to be further clarified.

Intracranial Vertebrobasilar Calcification in Patients with Ischemic Stroke is a Predictor of Recurrent Stroke, Vascular Disease, and Death: A Case-Control Study.

Intracranial artery calcification can be detected on nonenhanced brain computer tomography (NECT) and is a predictor of early vascular events. Here, we assessed the impact of vertebrobasilar artery calcification (VBC) on the long-term risk for recurrent stroke and vascular events. We performed a case-control trial of all consecutive stroke patients admitted to the University Hospital of Maribor, Slovenia over a period of 14 months. VBC was defined as presence of a hyperdense area within vertebrobasilar arteries that exceeds > 90 Hounsfield units as seen on NECT. Clinical follow-up information was obtained from the hospital documentation system and mortality registry of the district and included recurrent stroke, subsequent vascular events (myocardial infarction, heart failure, peripheral arterial occlusive disease), and death. We followed a total of 448 patients for a median of 1505 days (interquartile range, IQR 188-2479). Evidence for VBC was present in 243 (54.2%) patients. Median age was 76 years, recurrent stroke occurred in 33 (7.4%), any vascular events in 71 (15.8%), and death in 276 (61.6%). VBC was associated with a higher risk of recurrent stroke (hazard ratio, HR 3.13, 95% confidence interval (CI 1.35-7.20)) and vascular events (HR 2.05, 95% CI 1.21-3.47). Advanced age, male gender, and ischemic stroke involving the entire anterior circulation raised the likelihood for death. We conclude that the presence of VBC in patients with ischemic stroke is a short- and long-term prognostic factor for stroke recurrence and subsequent manifestation of acute vascular disease. Further understanding of the pathophysiology of VBC is warranted.

Clinical Challenges in a 49-Year-Old Patient with Severe Tick-Borne Myeloradiculitis Despite Complete Active Vaccination.

Vaccination is an effective means to prevent infectious diseases including tick-borne encephalitis (TBE), an emerging Flavivirus infection. There is, however, only limited knowledge about risk of vaccination failure, the disease course and the challenges for work-up and care. Of note, there is evidence that patients with breakthrough disease experience a more severe disease course. We report the case of a previously healthy 49-year-old woman who developed severe myeloradiculitis caused by the TBE virus despite receiving a complete cycle of primary immunization and booster vaccinations within the recommended timeframe. The disease course was characterized by progressive tetraparesis, pain and bladder dysfunction and necessitated intensive care unit admission (ICU) and the escalation of pain management. This case raises awareness for the recognition of breakthrough disease in younger patients and reinforces the need to develop measures to identify patients with insufficient protection.

Cardiac Autonomic Dysfunction in Multiple Sclerosis: A Systematic Review of Current Knowledge and Impact of Immunotherapies.

Cardiac autonomic dysfunction (CAD) has been reported in patients with multiple sclerosis (MS). This systematic review summarizes the evidence for the types and prevalence of CAD in MS patients, as well as its association with MS type, disease characteristics, fatigue and immunotherapies used to treat MS. The analysis revealed that CAD is correlated with pathophysiological processes of MS, can trigger serious cardiovascular complications that may reduce life expectancy, and may have implications for treatment with immunotherapies, especially fingolimod. Numerous mainly small case-control or cohort studies have reported various measures of CAD (particularly heart rate variation) in MS patients, showing higher rates of abnormality versus controls. A smaller number of studies have reported on cardiac autonomic symptoms in MS, including orthostatic intolerance/dizziness in around 50% of patients. CAD also appears to be associated with disease duration and to be more common in progressive than relapsing-remitting MS. However, although a substantial evidence base suggests that assessing CAD in people with MS may be important, standardised methods to evaluate CAD in these patients have not yet been established. In addition, no studies have yet looked at whether treating CAD can reduce the burden of MS symptoms, disease activity or the rate of progression.

Effects of repetitive transcranial magnetic stimulation on nicotine consumption and craving: A systematic review.

We performed a systematic review of the studies employing repetitive transcranial magnetic stimulation (rTMS) in subjects with smoking addiction. High-frequency (HF) rTMS over the prefrontal cortex (PFC), in particular the left dorsolateral PFC (DLPFC), might represent a save and innovative treatment tool for tobacco consumption and craving in nicotine-dependent otherwise healthy people. rTMS can be effective for this indication also in patients with schizophrenia, but the results are conflicting and sufficient evidence from large-scale trials is still lacking. Promising results have been obtained using particular techniques for brain stimulation, such as deep rTMS and theta burst stimulation. Multiple-target HF rTMS can also have a potential in smoking cessation. fMRI and EEG recordings have proven to be useful for objectively assessing the treatment effects. TMS is likely to be most effective when paired with an evidence-based self-help intervention, cognitive-behavioral interventions and nicotine replacement therapy. However, the most recent studies employed different protocols and yielded heterogeneous results, which should be replicated in further controlled studies with larger sample sizes and rigorous standards of randomization. To date, no recommendation other than that a possible efficacy of HF-rTMS of the left DLPFC can be made for alternative rTMS procedures in nicotine craving and consumption.

Immunological Aspects of Approved MS Therapeutics.

Multiple sclerosis (MS) is the most common neurological immune-mediated disease leading to disability in young adults. The outcome of the disease is unpredictable, and over time, neurological disabilities accumulate. Interferon beta-1b was the first drug to be approved in the 1990s for relapsing-remitting MS to modulate the course of the disease. Over the past two decades, the treatment landscape has changed tremendously. Currently, more than a dozen drugs representing 1 substances with different mechanisms of action have been approved (interferon beta preparations, glatiramer acetate, fingolimod, siponimod, mitoxantrone, teriflunomide, dimethyl fumarate, cladribine, alemtuzumab, ocrelizumab, and natalizumab). Ocrelizumab was the first medication to be approved for primary progressive MS. The objective of this review is to present the modes of action of these drugs and their effects on the immunopathogenesis of MS. Each agent's clinical development and potential side effects are discussed.

Effects of Repetitive Transcranial Magnetic Stimulation over Prefrontal Cortex on Attention in Psychiatric Disorders: A Systematic Review.

Repetitive transcranial magnetic stimulation (rTMS) may be effective for enhancing cognitive functioning. In this review, we aimed to systematically evaluate the effects of rTMS on attention in psychiatric diseases. In particular, we searched PubMed and Embase to examine the effectiveness of rTMS administered to the dorsolateral prefrontal cortex (DLPFC) on this specific cognitive domain. The search identified 24 articles, 21 of which met inclusion and exclusion criteria. Among them, nine were conducted in patients with depression, four in patients with schizophrenia, three in patients with autism spectrum disorder (ASD), two in patients with attention deficit hyperactivity disorder, one each in patients with Alzheimer's disease and in patients with alcohol or methamphetamine addiction. No evidence for cognitive adverse effects was found in all the included rTMS studies. Several studies showed a significant improvement of attentional function in patients with depression and schizophrenia. The beneficial effects on attention and other executive functions suggest that rTMS has the potential to target core features of ASD. rTMS may influence the attentional networks in alcohol-dependent and other addicted patients. We also reviewed and discussed the studies assessing the effects of rTMS on attention in the healthy population. This review suggests that prefrontal rTMS could exert procognitive effects on attention in patients with many psychiatric disorders.

Transcranial magnetic stimulation in subjects with phantom pain and non-painful phantom sensations: A systematic review.

Several studies have applied transcranial magnetic stimulation (TMS) in the attempt to further explore the pathophysiological mechanisms of phantom-limb pain (PLP) and non-painful phantom sensations (PS). We performed a systematic review of available evidence of this emerging technology in this indication. We identified studies which report a reduced intracortical inhibition and increased intracortical facilitation in the hemisphere contralateral to the PLP. TMS mapping revealed a significant lateralization of the center of gravity and an enlargement of the excitable area on the hemisphere contralateral to the amputation. N-Methyl-d-Aspartate-mediated mechanisms influence the changes of intracortical inhibition and facilitation occurring after limb amputation; however, these cortical excitability changes and PLP are independent of each other. TMS can also influence brain function if applied repetitively. A few studies have begun to therapeutically use repetitive TMS (rTMS) to relief PLP and non-painful PS. rTMS of the contralateral parietal cortex lead to a transient reduction in pain intensity. High frequency rTMS applied over the contralateral motor cortex (M1) or low frequency rTMS over the unaffected hemisphere might also induce significant clinical improvement in PLP. On the other hand, serum beta-endorphin increased significantly after real stimulation over contralateral M1. This systematic review illustrates that TMS technique is an emerging tool to gain insights to pathophysiological aspects of pain and non-painful phantom phenomena. Moreover, TMS could support appropriate patient selection for different therapies and may also have therapeutic utility in subjects with PLP or PS, though the evidence is still very preliminary and well-designed studies in larger cohort of patients are warranted.

Hypertrophic chronic pachymeningitis associated with Epstein-Barr virus reactivation: a case report.

Hypertrophic pachymeningitis is a rare inflammatory condition characterized by the thickening of the dura mater. We describe a patient who presented with intractable headache and complex cranial nerve palsy. Hypertrophy of the frontal dura was accompanied by pleocytosis and detection of Epstein-Barr virus (EBV) by PCR in cerebrospinal fluid. Clinical symptoms gradually improved after acyclovir and corticosteroid treatment, whereas dural pathology remained unchanged on neuroimaging. This case points at an expansion of the spectrum of neurological manifestations for EBV.

Cerebrovascular manifestations of herpes simplex virus infection of the central nervous system: a systematic review.

BACKGROUND: Intracerebral hemorrhage and ischemic stroke are increasingly recognized complications of central nervous system (CNS) infection by herpes simplex virus (HSV). AIM OF THE STUDY: To analyze clinical, imaging, and laboratory findings and outcomes of cerebrovascular manifestations of HSV infection. METHODS: Systematic literature review from January 2000 to July 2018. RESULTS: We identified 38 patients (median age 45 years, range 1-73) comprising 27 cases of intracerebral hemorrhage, 10 of ischemic stroke, and 1 with cerebral venous sinus thrombosis. Intracerebral hemorrhage was predominantly (89%) a complication of HSV encephalitis located in the temporal lobe. Hematoma was present on the first brain imaging in 32%, and hematoma evacuation was performed in 30% of these cases. Infarction was frequently multifocal, and at times preceded by hemorrhage (20%). Both a stroke-like presentation and presence of HSV encephalitis in a typical location were rare (25% and 10%, respectively). There was evidence of cerebral vasculitis in 63%, which was exclusively located in large-sized vessels. Overall mortality was 21% for hemorrhage and 0% for infarction. HSV-1 was a major cause of hemorrhagic complications, whereas HSV-2 was the most prevalent agent in the ischemic manifestations. CONCLUSION: We found a distinct pathogenesis, cause, and outcome for HSV-related cerebral hemorrhage and infarction. Vessel disruption within a temporal lobe lesion caused by HSV-1 is the presumed mechanism for hemorrhage, which may potentially have a fatal outcome. Brain ischemia is mostly related to multifocal cerebral large vessel vasculitis associated with HSV-2, where the outcome is more favorable.

Contribution of Serum Lipid Profiles to Outcome After Endovascular Thrombectomy for Anterior Circulation Ischemic Stroke.

The contribution of lipids, including low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively) and triglycerides (TG), to stroke outcomes is still debated. We sought to determine the impact of LDL-C concentrations on the outcome of patients with ischemic stroke in the anterior circulation who received treatment with endovascular thrombectomy (EVT). We performed a retrospective analysis of consecutive patients with acute ischemic stroke treated at a tertiary center between 2012 and 2016. Patients treated with EVT for large artery occlusion in the anterior circulation were selected. The primary endpoint was functional outcome at 3 months as measured with the modified Rankin Scale (mRS). Secondary outcome measures included hospital death and final infarct volume (FIV). Blood lipid levels were determined in a fasting state, 1 day after admission. We studied a total of 174 patients (44.8% men) with a median age of 74 years (interquartile range [IQR] 61-82) and median National Institutes of Health Stroke Scale at admission of 18 (14-22). Bridging therapy with intravenous tissue-plasminogen activator (t-PA) was administered in 122 (70.5%). The median LDL-C was 90 mg/dl (72-115). LDL-C demonstrated a U-type relationship with FIV (p = 0.036). Eighty-three (50.0%) patients had an mRS of 0-2 at 3 months. This favorable outcome was independently associated with younger age (OR 0.944, 95% CI 0.90-0.99, p = 0.012), thrombolysis in cerebral infarction 2b-3 reperfusion (OR 5.12, 95% CI 1.01-25.80, p = 0.015), smaller FIV (0.97 per cm3, 95% CI 0.97-0.99, p < 0.001), good leptomeningeal collaterals (OR 5.29, 95% CI 1.48-18.9, p = 0.011), and LDL-C more than 77 mg/dl (OR 0.179, 95% CI 0.04-0.74, p = 0.018). A higher LDL-C concentration early in the course of a stroke caused by large artery occlusion in the anterior circulation is independently associated with a favorable clinical outcome at 3 months. Further studies into the pathophysiological mechanisms underlying this observation are warranted.