Unusual CLIPPERS presentation with a predominant spinal cord involvement: case report and review of the literature.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a discrete nosological entity characterized by punctate and curvilinear gadolinium enhancement "peppering" the pons and a strong response to steroids. MRI images typically show pontine and cerebellar punctate-enhancing lesions, which occasionally spread up to the juxtacortical areas and down to the spinal cord. Interestingly, the more distant the lesion is from the pons, the less intense they become. Herein, we describe an extremely rare case of CLIPPERS presenting with predominant spinal cord involvement; then, we searched in the literature the available cases with a similar presentation. Our case focuses attention on a rare MRI CLIPPERS presentation. Since CLIPPERS has a dramatic response to corticosteroid treatment, it is fundamental to promptly recognize its MRI pattern to start treatment as soon as possible.

Association of Blood Metabolomics Biomarkers with Brain Metabolites and Patient-Reported Outcomes as a New Approach in Individualized Diagnosis of Schizophrenia.

Given its polygenic nature, there is a need for a personalized approach to schizophrenia. The aim of the study was to select laboratory biomarkers from blood, brain imaging, and clinical assessment, with an emphasis on patients' self-report questionnaires. Metabolomics studies of serum samples from 51 patients and 45 healthy volunteers, based on the liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS), led to the identification of 3 biochemical indicators (cortisol, glutamate, lactate) of schizophrenia. These metabolites were sequentially correlated with laboratory tests results, imaging results, and clinical assessment outcomes, including patient self-report outcomes. The hierarchical cluster analysis on the principal components (HCPC) was performed to identify the most homogeneous clinical groups. Significant correlations were noted between blood lactates and 11 clinical and 10 neuroimaging parameters. The increase in lactate and cortisol were significantly associated with a decrease in immunological parameters, especially with the level of reactive lymphocytes. The strongest correlations with the level of blood lactate and cortisol were demonstrated by brain glutamate, N-acetylaspartate and the concentrations of glutamate and glutamine, creatine and phosphocreatine in the prefrontal cortex. Metabolomics studies and the search for associations with brain parameters and self-reported outcomes may provide new diagnostic evidence to specific schizophrenia phenotypes.

Pediatric craniopharyngiomas: magnetic resonance imaging assessment for hypothalamus-pituitary axis dysfunction and outcome prediction.

BACKGROUND: In adamantinomatous craniopharyngiomas, tumor topographical categories, cystic component volume, and magnetic resonance signal intensity may impact prognosis. OBJECTIVE: To identify magnetic resonance imaging (MRI) variables associated with pituitary-hypothalamic axis dysfunction and predictive of outcome in children with cystic adamantinomatous craniopharyngiomas. MATERIALS AND METHODS: We evaluated 40 preoperative MRIs of adamantinomatous craniopharyngiomas to classify tumor topography, volume, and signal intensity of the cystic components and peritumoral edema. Volumes and normalized signal intensity minimum values were extracted from coronal T2-weighted images (nT2min). Radiological variables were compared to pituitary-hypothalamic axis dysfunction-related clinical data and surgical outcomes. RESULTS: Adamantinomatous craniopharyngiomas were categorized into five topographic classes (12 patients, sellar-suprasellar; seven patients, pseudo-intraventricular; six patients, strict intraventricular; 14 patients, secondary intraventricular; one patient, not strict intraventricular). All cases exhibited a predominant (30 patients, 80%) or total (10 patients, 20%) cystic tumor component and displayed low nT2min percentage values compared to cerebrospinal fluid (42.3% [interquartile range 28.4-54.6%]). Significant associations between tumor topographic classes and pituitary dysfunction (P<0.001), and between peritumoral edema and hypothalamic dysfunction (P<0.001) were found. Considering extent of surgical removal and tumor relapse, volume of the cystic tumor component displayed a positive correlation (P=0.002; r=0.48; P=0.02; r=0.36), while nT2min intensity values exhibited a negative correlation (P=0.01; r= - 0.40; P=0.028; r= - 0.34). CONCLUSION: Severe hypothalamic-pituitary axis dysfunction is associated with tumors along the pituitary stalk and peritumoral edema. Tumor invasion of the third ventricle, tight adherence to the hypothalamus, larger volumes, and lower nT2min intensity of the tumor cystic component are independent predictors of extent of adamantinomatous craniopharyngioma excision and recurrence.

Computed tomography quantitative analysis of cranial vault dysmorphology and severity of facial complex changes in posterior synostotic plagiocephaly patients.

BACKGROUND: Posterior synostotic plagiocephaly (PSP) impacts craniofacial skeleton. Study quantifies facial changes in children with PSP to investigate the impact of age and PSP severity at diagnosis on the facial dysmorphology. MATERIAL AND METHODS: High-resolution preoperative CT images of 22 infants with PSP were analyzed. They were divided according to the early or late age at time of diagnosis. Each group was further subdivided according to the severity of PSP evaluated by the cranial vault asymmetry index (CVAI): mild-moderate PSP (CVAI between 3 and 12%) and severe PSP (CVAI > 12%). Analysis of the facial complex was performed. Each group was compared with age-matched healthy subjects. RESULTS: All children exhibited unilateral lambdoid suture synostosis. The "early" diagnosis group consisted of 7 children with mild-moderate PSP while the "late" diagnosis group of 15 children in which 6 children had mild-moderate and 9 children severe PSP. All children showed altered position of glenoid fossae and mandibular asymmetry characterized by reduced mandibular diagonal distance length on the affected side while the subgroup of children with severe PSP detected in "late" diagnosis group had also altered mandibular inclination and reduced midfacial depth on both sides. CONCLUSIONS: PSP causes cranial base dysmorphology which drives changes in facial complex growth; the severity of facial changes mainly depends on the severity of cranial vault dysmorphology detected by CVAI. Mandible reshapes early under the stress of altered biomechanical forces of the skull base while changes in the maxilla are secondary to the asymmetric growth of the mandible and occur only in severe cases.

High-frequency transcranial alternating current stimulation matching individual frequency of somatosensory evoked high-frequency oscillations can modulate the somatosensory system through thalamocortical pathway.

tACS (transcranial alternating current stimulation) is a technique for modulating brain activity through electrical current. Its effects depend on cortical entrainment, which is most effective when transcranial alternating current stimulation matches the brain's natural rhythm. High-frequency oscillations produced by external stimuli are useful for studying the somatosensory pathway. Our study aims to explore transcranial alternating current stimulation's impact on the somatosensory system when synchronized with individual high-frequency oscillation frequencies. We conducted a randomized, sham-controlled study with 14 healthy participants. The study had three phases: Individualized transcranial alternating current stimulation (matching the individual's high-frequency oscillation rhythm), Standard transcranial alternating current stimulation (600 Hz), and sham stimulation. We measured early and late HFO components after median nerve electrical stimulation at three time points: before (T0), immediately after (T1), and 10 min after transcranial alternating current stimulation (T2). Compared to Sham and Standard stimulation Individualized transcranial alternating current stimulation significantly enhanced high-frequency oscillations, especially the early component, immediately after stimulation and for at least 15 min. No other effects were observed for other high-frequency oscillation measures. In summary, our study provides initial evidence that transcranial alternating current stimulation synchronized with an individual's high-frequency oscillation frequency can precisely and time-specifically modulate thalamocortical activity. These insights may pave the way for innovative, personalized neuromodulation methods for the somatosensory system.

A new gene for autosomal dominant facial palsy/migraine identified in a family by whole exome sequencing.

BACKGROUND: Facial palsy manifests as unilateral or bilateral weakness and inability to move some of the facial muscles. The aetiology may be different including idiopathic, trauma, infections or brain tumours or it can be associated with chronic neurological diseases. For instance, in recurrent migraine, an increased risk of idiopathic facial palsy (often unilateral) has been observed. Migraine is a neurovascular disorder characterized by mild to severe intensity of headaches, often associated with neuro-ophthalmological symptoms. METHODS: A family is reported where five members were affected by facial palsy associated with other clinical features including migraine, diplopia, facial swelling, eye conjunctivitis following a vertical transmission. Whole exome sequencing was performed in three members (two affected and one healthy) in order to identify potential variants causative of their phenotype. RESULTS: A missense variant c.304G>A was found leading to the p.(Ala102Thr) substitution in the TRPM8 gene, previously related to migraine by genome wide association studies. This variant was classified as deleterious by several predictor tools, and the mutant residue was predicted to alter the protein structure in terms of flexibility and interactions with the surrounding residues. CONCLUSION: These findings suggest that TRPM8 could be a new causative gene further linking migraine and recurrent facial palsy.

Prolonged Secondary Stroke Prevention with Edoxaban: A Long-Term Follow-Up of the SATES Study.

BACKGROUND: Little evidence is available on the long-term efficacy and safety of edoxaban, mainly due to the recent release date. The primary objective of the study was to evaluate the safety of edoxaban, defined by the incidence of major bleedings. We then aimed to evaluate the incidence of thromboembolic events and the persistence of edoxaban therapy in the long-term. METHODS: In this observational cohort study, we included ischemic stroke patients enrolled in a previous study to evaluate the safety and efficacy of long-term edoxaban treatment. Data were collected by a trained investigator through a structured telephone interview. RESULTS: Sixty-three subjects (median age 81.0 (73.5-88.0) years, 38.1% male) were included in the study, with a mean follow-up of 4.4 ± 0.7 years (range: 3.2-5.5 years). Only one patient (1.6%, 0.4%/year) presented a major extracranial bleeding, and none had cerebral hemorrhage. Six thromboembolic events occurred in five patients (7.9%): three recurrent strokes, two transient ischemic attacks, and one myocardial infarction (2.2%/year). Over a follow-up period of more than three years, 13 patients discontinued edoxaban (20.6%). Conclusions: Edoxaban seems to be effective and safe in the long-term. The persistence rate of edoxaban therapy is optimal after more than three years of treatment.

Intracortical and interhemispheric excitability changes in arm amputees: A TMS study.

OBJECTIVE: To evaluate cortical circuits and excitability of the motor cortex in the hemisphere contralateral to the affected (AH) and to the unaffected arm (UH), in upper limb amputees. METHODS: Motor evoked potentials (MEP) were recorded in 17 subjects who had upper limb amputation: 11 trans-radial (TR) and 6 trans-humeral (TH). Motor thresholds (MT), short interval intracortical inhibition (SICI), and interhemispheric inhibition (IHI) in the available arm muscles of the stump were evaluated. RESULTS: There was no significant difference in MT between hemispheres. SICI was preserved in TR but not in TH group. Additionally, in the TR group, the MEP amplitudes in AH were higher than in UH. A significant IHI was observed in the whole sample but not in each hemisphere or patient group. CONCLUSIONS: In our population of TR amputees, we found increased corticospinal excitability in the AH with preserved intracortical inhibition. This finding was not observed in the TH population. SIGNIFICANCE: Understanding the changes in intracortical excitability in amputees may enhance knowledge of the functional reorganization of the brain in the post-amputation phase, bringing useful information for prosthetic rehabilitation.

Transcranial direct current stimulation in semantic variant of primary progressive aphasia: a state-of-the-art review.

The semantic variant of primary progressive aphasia (svPPA), known also as "semantic dementia (SD)," is a neurodegenerative disorder that pertains to the frontotemporal lobar degeneration clinical syndromes. There is currently no approved pharmacological therapy for all frontotemporal dementia variants. Transcranial direct current stimulation (tDCS) is a promising non-invasive brain stimulation technique capable of modulating cortical excitability through a sub-threshold shift in neuronal resting potential. This technique has previously been applied as adjunct treatment in Alzheimer's disease, while data for frontotemporal dementia are controversial. In this scoped review, we summarize and critically appraise the currently available evidence regarding the use of tDCS for improving performance in naming and/or matching tasks in patients with svPPA. Clinical trials addressing this topic were identified through MEDLINE (accessed by PubMed) and Web of Science, as of November 2022, week 3. Clinical trials have been unable to show a significant benefit of tDCS in enhancing semantic performance in svPPA patients. The heterogeneity of the studies available in the literature might be a possible explanation. Nevertheless, the results of these studies are promising and may offer valuable insights into methodological differences and overlaps, raising interest among researchers in identifying new non-pharmacological strategies for treating svPPA patients. Further studies are therefore warranted to investigate the potential therapeutic role of tDCS in svPPA.

Integration of proprioception in upper limb prostheses through non-invasive strategies: a review.

Proprioception plays a key role in moving our body dexterously and effortlessly. Nevertheless, the majority of investigations evaluating the benefits of providing supplemental feedback to prosthetics users focus on delivering touch restitution. These studies evaluate the influence of touch sensation in an attempt to improve the controllability of current robotic devices. Contrarily, investigations evaluating the capabilities of proprioceptive supplemental feedback have yet to be comprehensively analyzed to the same extent, marking a major gap in knowledge within the current research climate. The non-invasive strategies employed so far to restitute proprioception are reviewed in this work. In the absence of a clearly superior strategy, approaches employing vibrotactile, electrotactile and skin-stretch stimulation achieved better and more consistent results, considering both kinesthetic and grip force information, compared with other strategies or any incidental feedback. Although emulating the richness of the physiological sensory return through artificial feedback is the primary hurdle, measuring its effects to eventually support the integration of cumbersome and energy intensive hardware into commercial prosthetic devices could represent an even greater challenge. Thus, we analyze the strengths and limitations of previous studies and discuss the possible benefits of coupling objective measures, like neurophysiological parameters, as well as measures of prosthesis embodiment and cognitive load with behavioral measures of performance. Such insights aim to provide additional and collateral outcomes to be considered in the experimental design of future investigations of proprioception restitution that could, in the end, allow researchers to gain a more detailed understanding of possibly similar behavioral results and, thus, support one strategy over another.

Using TMS-EEG to assess the effects of neuromodulation techniques: a narrative review.

Over the past decades, among all the non-invasive brain stimulation (NIBS) techniques, those aiming for neuromodulatory protocols have gained special attention. The traditional neurophysiological outcome to estimate the neuromodulatory effect is the motor evoked potential (MEP), the impact of NIBS techniques is commonly estimated as the change in MEP amplitude. This approach has several limitations: first, the use of MEP limits the evaluation of stimulation to the motor cortex excluding all the other brain areas. Second, MEP is an indirect measure of brain activity and is influenced by several factors. To overcome these limitations several studies have used new outcomes to measure brain changes after neuromodulation techniques with the concurrent use of transcranial magnetic stimulation (TMS) and electroencephalogram (EEG). In the present review, we examine studies that use TMS-EEG before and after a single session of neuromodulatory TMS. Then, we focused our literature research on the description of the different metrics derived from TMS-EEG to measure the effect of neuromodulation.

Extremely Preterm Infants with a Near-total Absence of Cerebellum: Usefulness of Quantitative Magnetic Resonance in Predicting the Motor Outcome.

This study aims to evaluate in extremely premature infants the severity of brain structural injury causing total absence or near-total absence of cerebellar hemispheres by using MRI visual and volumetric scoring systems. It also aims to assess the role of the score systems in predicting motor outcome. We developed qualitative and quantitative MRI scoring systems to grade the overall brain damage severity in 16 infants with total absence or near-total absence of cerebellar hemispheres. The qualitative scoring system assessed the severity of macrostructural abnormalities of cerebellum, brainstem, supratentorial gray and white matters, ventricles while the quantitative scoring system weighted the loss of brain tissue volumes, and gross motor function classification system (GMFCS) was used to assess motor function at 1- and 5-year follow-ups.Positive correlations between both MRI scores and GMFCS scales were detected at follow-ups (p > 0.05), but only the volumetric score could identify those infants developing higher levels of motor impairment.Brain volumetric MRI offers an unbiassed assessment of prenatal brain damage. The quantitative scoring system, performed at term equivalent age, can be a helpful tool for predicting the long-term motor outcome in extremely preterm infants with a near-total absence of cerebellum.

Feasibility and efficacy of an at-home, smart-device aided mindfulness program in people with Multiple Sclerosis.

BACKGROUND: Multiple Sclerosis (MS) is a chronic disease with a high prevalence of neuropsychiatric symptoms. Mindfulness is a practice that encourages individuals to cultivate a present-focused, acceptance-based approach for managing psychological distress. Its positive effect on MS has been demonstrated, but learning such technique is expensive and time-consuming. In this study, we investigated the feasibility and efficacy of an 8-week, at-home, smart-device aided mindfulness program in a cohort of MS patients. Specifically, we explored the role of a brain-sensing headband providing real-time auditory feedback as supportive tool for meditation exercises. METHODS: The study included two visits, one at baseline and another after the mindfulness program. We measured adherence to the proposed mindfulness treatment and its effect on questionnaires investigating different psychological domains, cognition, fatigue, quality of life and quantitative EEG parameters. All participants received a smart biofeedback device to be used during the therapeutic program consisting of daily meditative exercises. RESULTS: Twenty-nine patients were recruited for the present study. Among them, 27 (93%) completed the entire program and 17 (63%) completed more than 80% of the scheduled sessions. We observed a statistically significant reduction of the Ruminative Response Scale score and a significant increase of the Digit Span Backward. Regarding neurophysiological data, we found a significant reduction of the whole-scalp beta and parieto-occipital theta power post intervention. CONCLUSION: Our results show that an at-home, smart-device aided mindfulness program is feasible for people with MS. The efficacy in terms of reappraisals of stress, cognitive and emotional coping responses is also supported by our neurophysiological data. Further studies are warranted to better explore the role of such approaches in managing the psychological impact of MS diagnosis.

Melkersson-Rosenthal Syndrome and Migraine: A New Phenotype Associated with SCN1A Variants?

Peripheral facial palsy rarely occurs as part of Melkersson-Rosenthal syndrome (MRS), which is characterized by the classical triad of tongue cheilitis, recurrent episodes of orofacial swelling, and palsy. MRS is a disorder with variable expressivity and clinical as well as genetic heterogeneity; however, the causative gene remains to be identified. Migraine is a common neurological disorder, presenting with or without aura, which may be associated with neurological symptoms. The classical example of monogenic migraine is familial hemiplegic migraine (FHM), which has phenotypic variability in carriers of variants in the same gene or even carriers of the same variant. We present a family in which two sisters displayed recurrent migraines, one of which presented recurrent facial palsy and had clinical diagnosis of MRS. We performed WES and Sanger sequencing for segregation analysis in the available family members. We identified a c.3521C>G missense heterozygous variant in SCN1A carried only by the affected sister. Variants in the SCN1A gene can cause a spectrum of early-onset epileptic encephalopathies, in addition to FHM; therefore, our finding reasonably explains the proband phenotype, in which the main symptom was recurrent facial palsy. This report also adds knowledge to the clinical spectrum of SCN1A alterations and suggests a potential overlap between MRS and FHM.

A smart devices based secondary prevention program for cerebrovascular disease patients.

Background: Commercially available health devices are gaining momentum and represent a great opportunity for monitoring patients for prolonged periods. This study aimed at testing the feasibility of a smart device-based secondary prevention program in a cohort of patients with cryptogenic stroke. Methods: In this proof-of-principle study, patients with non-disabling ischemic stroke and transient ischemic attacks (TIA) in the subacute phase were provided with a smartwatch and smart devices to monitor several parameters - i.e., oxygen saturation, blood pressure, steps a day, heart rate and heart rate variability - for a 4-week period (watch group). This group was compared with a standard-of-care group. Our primary endpoint was the compliance with the use of smart devices that was evaluated as the number of measures performed during the observation period. Results: In total, 161 patients were recruited, 87 in the WATCH group and 74 in the control group. In the WATCH group, more than 90% of patients recorded the ECG at least once a day. In total, 5,335 ECGs were recorded during the study. The median blood pressure value was 132/78 mmHg and the median oxygen saturation value was 97%. From a clinical standpoint, although not statistically significant, nine atrial fibrillation episodes (10.3%) in the WATCH group vs. 3 (4%) in the control group were detected. Conclusion: Our study suggests that prevention programs for cerebrovascular disease may benefit from the implementation of new technologies.

Subclavian artery revascularization with subclavian-carotid transposition for TEVAR and non-TEVAR patients.

BACKGROUND: Subclavian artery revascularization (SAR) has become an increasingly performed technique in patients undergoing thoracic endovascular aortic aneurysm repair (TEVAR), in order to optimize the proximal landing zone, or in patients with significant atherosclerotic diseases. SAR was usually achieved through carotid-subclavian bypass (CSB) which is daunted by graft and patency-related issues, or through subclavian carotid transposition (SCT) which has recently been reconsidered as a potential solution. Nowadays, multiple endovascular strategies including parallel grafts, chimney graft and branch-fenestrated repair, are available in patients unfit for open SAR. However, there is no consensus on the preferable technique in both TEVAR- and non TEVAR-patients. The purpose of this study was to evaluate our experience with SCT in terms of overall postoperative adverse events and mid-term patency rate. METHODS: We performed a retrospective cohort study, including all patients who underwent SCT between June 2014 and March 2020 at our Division. Preoperative risk factors, symptoms, intraoperative details, postoperative outcomes and follow-up data were collected. RESULTS: A total of 27 patients were included in this study. Indications for SCT included aortic arch debranching for TEVAR for thoracic aortic aneurysm and type B dissection and symptomatic subclavian steal syndrome (SSS). There were no major perioperative adverse events or major neurological complications; five minor adverse events occurred (18.5%) (3 Horner' Syndrome, 1 hematoma requiring reoperation,1 pneumothorax). Peripheral nerve injuries and lymphatic lesions were not recorded. On a mean follow-up of 21±16 months, SCT patency was confirmed in all patients and no deaths occurred. Comparison of baseline and operative characteristics and intraoperative details between groups of patients with or without adverse events did not found differences. CONCLUSIONS: SCT should be considered a feasible, effective and safe technique for SAR, with low perioperative complications and optimal mid-term patency. This surgical technique appears to provide a lower risk of neurological events and mortality, particularly in TEVAR patients, reducing the complications caused by the coverage of the left subclavian artery.

Lipid profiles and atrial fibrillation in ischemic stroke patients treated with thrombectomy: experience from a tertiary Italian stroke hospital.

OBJECTIVES: To assess acute lipid profiles, atrial fibrillation and other cardiovascular risk factors in patients undergoing treatments by thrombectomy (EVT) with acute ischemic stroke (AIS). METHODS: We performed a retrospective analysis of the lipid profile and vascular risk factor in 1639 consecutive patients with acute ischemic stroke between January 2016 and December 2021. To assess lipid profiles, laboratory tests, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), were obtained the day after admission. We also examined assessed the association between lipid profile, AF and EVT in multivariate logistic regression analysis. RESULTS: Median age of patients was 74 years, 54.9% were males (95% CI 52.5-57.4%), and 26.8% (95% CI, 24.7-29.0%) had AF. EVT patients (n= 370; 22.57 %; 95% CI, 20.6-24.7) showed no difference in age (median 73 years [IQR; 63-80 ] versus 74 years [ QR; 63-82+ HbA1c levels (median 5.8 [IQR; 5.4-6.2] versus 5.9 [ IQR; 5.4-6.4+TG/HDL ratio (median 2.40 [IQR; 1.65-3.48#43; versus[IQR; 1.73-3.64)] diabetes (OR 0.82; 95% CI 0.61 to 1.08), hypertension (OR 0.87; 95% CI 0.68 to 1.12) and obesity (OR 1.06; 95% CI 0.78 to 1.42) compared to non-EVT patients. Conversely, EVT patients showed lower levels of TC (160 mg/dl[ IQR;139-187] versus 173 mg/dl [ IQR;148-202] P <0.001), LDL-C (105 mg/dl [ IQR; 80-133] versus 113 mg/dl [ IQR; 88-142] ; P <0.01), TG (98 mg/dl [ IQR; 76-126] versus 107 mg/dl [ IQR; 85-139] P <0.001), non-HDL-C (117 mg/dl[ IQR; 94-145] versus 127 mg/dl [ IQR; 103-154] P <0.001), HC (8.3[ mol/l [ IQR; 6-11] versus 10 µ mol/l[ IQR; 7.3-13.5] P <0.001) than non-EVT patients. Multivariate logistic regression analysis showed an independent association of EVT with TC (OR 0.99, 95% CI 0.98-0.99), AF (OR 1.79, 95% CI 1.34-2.38), age (OR 0.98, 95% CI 0.96-0.99), and NIHSS (OR 1.17, 95% CI 0.14-1.19). CONCLUSION: Total cholesterol and all cholesterol-related measures were significantly lower in patients undergoing thrombectomy than in other stroke patients. Conversely, we found that AF was significantly high in patients with EVT, suggesting that hypercholesterolemia could be mainly linked to small-vessel occlusion stroke while large vessel occlusion (LVO) stroke could show different causes. AIS patients may have different pathogenesis and their understanding may improve enhance the discovery of specific and tailored preventive treatments.