Multisensory mental imagery of fatigue in patients with multiple Sclerosis. Preliminary evidence from a fMRI study.

Fatigue, defined as a subjective lack of physical and/or mental energy, is a clinical symptom highly characterizing multiple sclerosis (MS). The present study utilized a novel approach to the study of fatigue, examining first person-mental imagery of the symptom. Eighteen right-handed patients with MS (14F, 4 M, mean age 45.8 ± 8.15 years) were evaluated and were compared to nineteen healthy controls (10F, 9 M, mean age 43.15 ± 8.34 years) Patients were all in relapsing remitting form and no patient had presented relapses in the 6 months prior to inclusion in the study. We evaluated their behavioral performance and fMRI activations. We used an fMRI paradigm used to trigger first person-mental imagery of fatigue, through short sentences describing the principal manifestations of fatigue. 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. They made a vividness rating by pressing the corresponding button. Behaviorally, we found that patients' mean scores at the Multidimensional Fatigue Symptom Inventory for the general scale, physical scale, and mental scale were significantly higher than healthy controls (p = 0.05, p = 0.002, p = 0.006 respectively), but not for the emotional scale and for vigor scale (p = 0.207, n.s., p = 0.06, n.s.). In the imagery fMRI task, patients were significantly slower (mean reaction times and standard deviation: 2.24 s ± 0.33) than controls (mean reaction times and standard deviation: 1.918 s ± 0.455) for the SI task (Z=-2.058, p = 0.040), while no significant difference was found for the VI task. Regarding brain mapping, our main result is a group by task interaction. The SI task (vs. VI task) in healthy controls (relative to patients) increased activation in the left inferior parietal lobule. These preliminary results indicate that fatigue is related to dysfunctions in higher-order aspects of motor control, given the role of the posterior parietal lobe in motor planning and multisensory integration.

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.

Current and emerging pharmaceutical strategies for the treatment and management of restless legs syndrome.

INTRODUCTION: Restless legs syndrome (RLS) is a sensory-motor sleep disorder that affects up to 13% of adults in the Western world and 2-4% of children. It impairs night sleep with an impact on daily performances and life quality. Thus, moderate-to-severe RLS requires pharmacological treatment. AREAS COVERED: In the present review, which is based on PubMed searches with no time limits, the authors discuss the recommended pharmacotherapy for RLS in addition to other emerging treatment options. The authors provide coverage to the current recommendations for both adults and pediatric patients with RLS. EXPERT OPINION: Current evidence suggests removing all causes of secondary RLS, including iron deficiency, chronic renal failure, drugs, and treating other sleep disorders that may worsen symptoms. Also, intermittent RLS should be addressed with behavioral measures and on-demand therapy. For chronic persistent RLS, α2δ calcium channel ligands are a first-line pharmacological approach, whereas dopamine agonists are associated with increased risk and should be spared. When RLS is refractory to first-line treatment, polytherapy, or opioid monotherapy should be considered. Nonetheless, some patients may not reach sustained symptom relief. Further research is needed to better understand the pathophysiology of RLS and to develop newer more effective drugs.

Safety and Outcomes of Mechanical Thrombectomy in Acute Ischemic Stroke Attributable to Cardiological Diseases: A Scoping Review.

There is limited evidence on the outcomes and safety of mechanical thrombectomy (MT) among patients with acute ischemic stroke (AIS) in the context of cardiac diseases. Our study reviews MT in AIS within the context of cardiac diseases, aiming to identify existing and emerging needs and gaps. PubMed and Scopus were searched until December 31, 2023, using a combination of cardiological diseases and "mechanical thrombectomy" or "endovascular treatment" as keywords. Study design included case reports/series, observational studies, randomized clinical trials, and meta-analyses/systematic reviews. We identified 943 articles, of which 130 were included in the review. Results were categorized according to the cardiac conditions. MT shows significant benefits in patients with atrial fibrillation (n=139) but lacks data for stroke occurring after percutaneous coronary intervention (n=2) or transcatheter aortic valve implantation (n=5). MT is beneficial in AIS attributable to infective endocarditis (n=34), although functional benefit may be limited. Controversy surrounds the functional outcomes and mortality of patients with AIS with heart failure undergoing MT (n=11). Despite technical challenges, MT appears feasible in aortic dissection cases (n=4), and in patients with left ventricular assist device or total artificial heart (n=10). Data on AIS attributable to congenital heart disease (n=4) primarily focus on pediatric cases requiring technical modifications. Treatment outcomes of MT in patients with cardiac tumors (n=8) vary because of clot consistency differences. After cardiac surgery stroke, MT may improve outcomes with early intervention (n=13). Available data outline the feasibility of MT in patients with AIS attributable to large-vessel occlusion in the context of cardiac diseases.

Predictors of futile recanalization in nonagenarians treated with mechanical thrombectomy: a multi-center observational study.

BACKGROUND: There is a lack of data regarding patients aged 90 years or older undergoing mechanical thrombectomy and their predictors of futile recanalization. AIMS: We sought to evaluate the predictors of futile recanalization in patients ≥ 90 years with large vessel occlusion undergoing mechanical thrombectomy. METHODS: This multi-center observational retrospective study included patients ≥ 90 years consecutively treated with mechanical thrombectomy in four thrombectomy capable centers between January 1st, 2016 and 30th March 2023. Futile recanalization was defined as large vessel occlusion patients experiencing a 90-day poor outcome (mRS 3-6) despite successful recanalization (mTICI ≥ 2b) after mechanical thrombectomy. RESULTS: Our cohort included 139 patients ≥ 90 years with acute ischemic stroke due to anterior circulation large vessel occlusion treated with mechanical thrombectomy. One hundred seventeen of one hundred thirty-nine patients ≥ 90 years who achieved successful recanalization were included in the analysis (seventy-six female (64.9%)), of whom thirty-one (26.49%) experienced effective recanalization and eighty-six (73.51%) experienced futile recanalization. Patients with futile recanalization had higher NIHSS on admission (p < 0.001); they were less frequently treated with intravenous thrombolysis (p = 0.048), had more often general anesthesia (p = 0.011), and longer door to groin puncture delay (p = 0.002). Univariable regression analysis showed that use of intravenous thrombolysis (0.29, 95% CI 0.02-0.79, p = 0.034) and site of occlusion distal vs proximal (0.34, 95% CI 0.11-0.97, p = 0.044) were associated with reduced probability of futile recanalization while NIHSS on admission (1.29, 95% CI 1.16-1.45, p < 0.001), NIHSS at 24 h (1.15, 95% CI 1.07-1.25, p = 0.002), type of anesthesia used (4.18, 95% CI 1.57-11.08, p = 0.004), and door to groin puncture time (1.02, 95% CI 1.00-1.05, p = 0.005) were associated with increased probability of futile recanalization. Multivariable regression analysis showed that use of intravenous thrombolysis (0.44, 95% CI 0.09-0.88, p = 0.039) was associated with reduced probability of futile recanalization. CONCLUSION: Our study seems to suggest that mechanical thrombectomy with intravenous thrombolysis is associated with reduced probability of futile recanalization in a multi-center cohort of patients aged 90 years or older.

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.

Stress hyperglycemia is associated with futile recanalization in patients with anterior large vessel occlusion undergoing mechanical thrombectomy.

INTRODUCTION: Mechanical thrombectomy (MT) is the standard treatment for acute ischemic stroke (AIS) due to anterior large vessel occlusion (LVO). Despite successful recanalization, some patients remain disabled after 3 months. Mechanisms that can cause futile recanalization (FR) are still largely unknown. We investigated if stress hyperglycemia might be associated with FR. PATIENTS AND METHODS: This is a retrospective analysis of consecutive patients with successful recanalization treated in four participating centers between January 2021 and December 2022. According to the modified Rankin scale (mRS) status at 3 months, patients were divided into two groups: FR, if mRS score >2, and useful recanalization (UR), if mRS score ⩽2. Stress hyperglycemia was estimated by the glucose-to-glycated hemoglobin ratio (GAR) index. RESULTS: A total of 691 subjects were included. At 3 months, 403 patients (58.3%) were included in the FR group, while the remaining 288 patients (41.7%) were included in the UR group. At the multivariate analysis, variables independently associated with FR were the following: age (OR 1.04, 95% CI 1.02-1.06, p < 0.001), GAR index (OR 1.08, 95% CI 1.03-1.14, p = 0.003), NIHSS at admission (OR 1.16, 95% CI 1.11-1.22; p < 0.001), and procedure length (OR 1.01, 95% CI 1.00-1.02; p = 0.009). We observed that the model combining age, GAR index, NIHSS at admission, and procedure length had good predictive accuracy (AUC 0.78, 95% CI 0.74-0.81). CONCLUSIONS: Stress hyperglycemia predicts FR in patients with successful recanalization after MT. Further studies should explore if managing stress hyperglycemia may reduce futile recanalization. Additionally, we recommend paying close attention to AIS patients with a GAR index greater than 24.8 who exhibit a high risk of FR.

Isolated insular stroke: topography is the answer with respect to outcome and cardiac involvement.

Background and purpose: Isolated insular strokes (IIS) are a rare occurrence due to the frequent concomitant involvement of adjacent territories, supplied by the M2 segment of the middle cerebral artery (MCA), and clinical aspects are sometimes contradictory. We aimed to describe clinical and radiological characteristics of a pure IIS case series, focusing on its functional outcome and cardiac involvement. Methods: We identified 15 isolated insular ischemic strokes from a pool of 563 ischemic strokes occurred between January 2020 and December 2021. Data collection consisted of demographic and baseline clinical characteristics, comorbidities, electrocardiograms, echocardiograms, stroke topography and etiology, reperfusive treatments, and outcome measures. Descriptive statistical analysis was carried out. Results: Newly detected cardiovascular alterations were the prevalent atypical presentation. Cardioembolism was the most frequent etiology. Most of patients had major neurological improvement at discharge and good outcome at 3-months follow-up. Discussion and conclusion: IIS are extremely rare, representing according to our study about 2.6% ischemic strokes cases per year, and patients have peculiar clinical manifestations, such as dysautonomia and awareness deficits. Our data suggest the possibility for these patients to completely recover after acute ischemic stroke notwithstanding the pivotal role of the insula in cerebral connections and the frequent association with MCA occlusion. Moreover, given the central role of the insula in regulating autonomic functions, newly detected cardiac arrhythmias must be taken into consideration, as well as a full diagnostic work-up for the research of cardioembolic sources. To our knowledge, this is the largest monocentric case series of IIS and it might be useful for future systematic reviews.

Predictors of atrial fibrillation detection in embolic stroke of undetermined source patients with implantable loop recorder.

Background: Covert atrial fibrillation (AF) is a predominant aetiology of embolic stroke of undetermined source (ESUS). Evidence suggested that AF is more frequently detected by implantable loop recorder (ILR) than by conventional monitoring. However, the predictive factors associated with occult AF detected using ILRs are not well established yet. In this study we aim to investigate the predictors of AF detection in patients with ESUS undergoing an ILR. Methods: This observational multi-centre study included consecutive ESUS patients who underwent ILR implantation. The infarcts were divided in deep, cortical infarcts or both. The infarction sites were categorized as anterior and middle cerebral artery, posterior cerebral artery with and without brainstem/cerebellum involvement. Multivariable logistic regression analysis was performed to investigate variables associated with AF detection. Results: Overall, 3,000 patients were initially identified. However, in total, 127 patients who consecutively underwent ILR implantation were included in our analysis. AF was detected in 33 (26%) out of 127 patients. The median follow-up was 411 days. There were no significant differences in clinical characteristics and comorbidities between patients with and without AF detected. AF was detected more often after posterior cerebral artery infarct with brainstem/cerebellum involvement (p < 0.001) whereas less often after infarction in the anterior and middle cerebral artery (p = 0.021). Multivariable regression analysis demonstrated that posterior cerebral artery infarct with brainstem/cerebellum involvement was an independent predictor of AF detection. Conclusion: Our study showed that posterior circulation infarcts with brainstem/cerebellum involvement are associated with AF detection in ESUS patients undergoing ILR. Larger prospective studies are needed to validate our findings.

The Role of Human Pluripotent Stem Cells in Amyotrophic Lateral Sclerosis: From Biological Mechanism to Practical Implications.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder, characterized by progressive loss of both upper and lower motor neurons, resulting in clinical features such as muscle weakness, paralysis, and ultimately, respiratory failure. Nowadays, there is not effective treatment to reverse the progression of the disease, that leads to death within 3-5 years after the onset. Nevertheless, the induced pluripotent stem cells (iPS) technology could be the answer, providing disease modelling, drug testing, and cell-based therapies for this pathology. The aim of this work was to conduct a literature review of the past 5 years about the role of iPS in ALS, to better define the neurobiological mechanisms involved in the pathogenesis and the potential future therapies. The review also deals with advanced and currently available technologies used to reprogram cell lines and generate human motor neurons in vitro, which represent the source to study the pathological processes, the relationship between phenotype and genotype, the disease progression and the potential therapeutic targets of these group of disorders. Specific treatment options with stem cells involve Advance Gene Editing Technology, neuroprotective agents, and cells or exosomes transplantation, aimed to replace dead or damaged nerve cells. In summary, this review comprehensively addresses the role of human pluripotent stem cells (hPSCs) in motor neuron diseases (MND), with a focus on physiopathology, diagnostic and prognostic implications, specific and potential future treatment options. Understanding the biological mechanisms and practical implications of hPSCs in MND is crucial for advancing therapeutic strategies and improving outcomes for patients affected by these devastating diseases.

Pulsed Radiofrequency for Auriculotemporal Neuralgia: A Case Report.

Auriculotemporal neuralgia is a rare facial pain disorder with no therapeutic evidence for refractory cases. We described a male patient with right auriculotemporal neuralgia, refractory to anesthetic nerve blocks and botulinum toxin type A injections, who was successfully treated with pulsed radiofrequency without adverse events. Pulsed radiofrequency may be an effective and safe treatment for refractory auriculotemporal neuralgia.

A comprehensive update on the ADMET considerations for α2δ calcium channel ligand medications for treating restless legs syndrome.

INTRODUCTION: Restless legs syndrome/Willis-Ekbom disease (RLS/WED) is a sleep-related sensory-motor disorder associated with poor sleep quality and impaired daily functioning. In patients affected by chronic RLS/WED, a pharmacological therapy is recommended. International guidelines suggest to start the treatment with a α2δ calcium channel ligand in most cases, unless contraindicated. AREAS COVERED: The present review is based on an extensive Internet and PubMed search from 1986 to 2024. Our purpose is to describe the absorption, distribution, metabolism, and toxicology (ADMET) of the α2δ ligands, with common consideration for the therapeutic class, specificities of different compounds, efficacy, and safety in relation to other treatment options. EXPERT OPINION: α2δ ligands are quite similar in their ADMET profiles, sharing most of the pharmacokinetics and potential adverse effects. However, we highlight the linear kinetic of gabapentin enacarbil and pregabalin, differently from gabapentin. α2δ ligands are safe and effective for the treatment of RLS/WED. Additional benefits can be obtained in comorbid insomnia, chronic pain syndromes, history of impulse control disorder, and comorbid anxiety. The use of α2δ ligands is associated with poor risk of augmentation. We still need new long-term safe and effective treatments, which could be developed along with our knowledge of RLS/WED pathophysiology.

NK Cell Levels Correlate with Disease Activity in Patients with Multiple Sclerosis on Ocrelizumab/Rituximab Therapy.

BACKGROUND: Recently, research on the pathogenesis of multiple sclerosis (MS) has focused on the role of B lymphocytes and the possibility of using specific drugs, such as Ocrelizumab and Rituximab, directed toward these cells to reduce inflammation and to slow disease progression. OBJECTIVE: We aimed to evaluate the effect of Ocrelizumab/Rituximab on laboratory immune parameters and identify the predictors of treatment responses. METHODS: A retrospective single-center study was conducted among patients who received infusion therapy with an anti-CD20 drug to treat MS. RESULTS: A total of 64 patients met the inclusion criteria, with 277 total cycles of therapy studied. Compared with the baseline values, anti-CD20 infusions resulted in absolute-value and percentage decreases in B lymphocyte levels and increased the absolute and percentage levels of NK cells 3 and 5 months after therapy (p < 0.001). After multivariate logistic regression analysis, a reduced percentage level of NK cells 3 months after infusion could predict disease activity 6 months after Ocrelizumab/Rituximab administration (p = 0.041). CONCLUSIONS: Lower percentage levels of NK cells 3 months after anti-CD20 infusion correlate with the presence of disease activity 6 months after therapy, confirming a possible protective role of NK cells in MS.

Central nervous system immune-related disorders after SARS-CoV-2 vaccination: a multicenter study.

Background: COVID-19 vaccines have been approved due to their excellent safety and efficacy data and their use has also permitted to reduce neurological complications of SARS-CoV-2. However, clinical trials were underpowered to detect rare adverse events. Herein, the aim was to characterize the clinical spectrum and immunological features of central nervous system (CNS) immune-related events following SARS-CoV-2 vaccination. Methods: Multicenter, retrospective, cohort study (December 1, 2020-April 30, 2022). Inclusion criteria were (1) de novo CNS disorders developing after SARS-CoV-2 vaccination (probable causal relationship as per 2021 Butler criteria) (2); evidence for an immune-mediated etiology, as per (i) 2016 Graus criteria for autoimmune encephalitis (AE); (ii) 2015 Wingerchuk criteria for neuromyelitis optica spectrum disorders; (iii) criteria for myelitis. Results: Nineteen patients were included from 7 tertiary referral hospitals across Italy and France (one of them being a national referral center for AE), over almost 1 year and half of vaccination campaign. Vaccines administered were mRNA-based (63%) and adenovirus-vectored (37%). The median time between vaccination and symptoms onset was 14 days (range: 2-41 days). CSF was inflammatory in 74%; autoantibodies were detected in 5%. CSF cytokine analysis (n=3) revealed increased CXCL-10 (IP-10), suggesting robust T-cell activation. The patients had AE (58%), myelitis (21%), acute disseminated encephalomyelitis (ADEM) (16%), and brainstem encephalitis (5%). All patients but 2 received immunomodulatory treatment. At last follow-up (median 130 days; range: 32-540), only one patient (5%) had a mRS>2. Conclusion: CNS adverse events of COVID-19 vaccination appear to be very rare even at reference centers and consist mostly of antibody-negative AE, myelitis, and ADEM developing approximately 2 weeks after vaccination. Most patients improve following immunomodulatory treatment.

An "epileptic scent": Olfactory auras in tumor-related epilepsy.

OBJECTIVES: To characterize a profile for patients with tumor-related epilepsy presenting olfactory auras. MATERIALS AND METHODS: We conducted a monocentric, retrospective study on patients who underwent surgery in the Neurosurgery Unit of Udine University Hospital (Udine, Italy), between the 1st of January 2010 and the 1st of January 2019, for primary brain tumors (PBTs) involving the temporal lobe and the insula. All patients were affected by tumor-related epilepsy; the study group presented olfactory auras as well. We collected neuroradiological, neuropsychological and neurophysiological data from patients' medical charts. RESULTS: The subtraction analysis of MRI data shows maximum lesion overlay in left olfactory cortex, left and right hippocampus, left amygdala, right rolandic operculum, right inferior frontal gyrus and right middle temporal gyrus. The presence of olfactory auras did not influence seizure outcome (p = 0.500) or tumor recurrence after surgery (p = 0.185). The type of auras (elementary vs. complex), also, did not influence seizure control (p = 0.222). DISCUSSION: In presence of olfactory auras, anterior and mesial temporal regions are mainly involved, such as olfactory cortex, amygdala, and anterior hippocampus, together with right rolandic operculum, right inferior frontal gyrus and right middle temporal gyrus, suggesting their possible role in the genesis of olfactory auras. Post-surgical seizure outcome and disease relapse are not influenced by neither the presence nor the type of olfactory auras. CONCLUSIONS: Olfactory auras are rare event, however they may be often underestimated by the patients and under-investigated by the clinicians, even when their occurrence can represent a useful localizing tool.

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.

Comparison of pharmacokinetic properties of alteplase and tenecteplase. The future of thrombolysis in acute ischemic stroke.

INTRODUCTION: The drug most frequently used for thrombolysis in cases of acute ischemic stroke (AIS) is alteplase. However, there is moderate-to-high-quality evidence that tenecteplase has similar or higher efficacy and safety. With improved pharmacokinetic properties over alteplase, tenecteplase could be a significant advantage in treating AIS. AREAS COVERED: After conducting an extensive search on Scopus and PubMed, this manuscript reviews and compares the pharmacokinetic properties of alteplase and tenecteplase. Additionally, it provides information on pharmacodynamics, clinical efficacy, safety, tolerability, and drug-drug interactions. EXPERT OPINION: The pharmacokinetic profile of alteplase and tenecteplase is derived from studies in patients with acute myocardial infarction. Thanks to its pharmacokinetic properties, tenecteplase is the drug closest to being the ideal fibrinolytic for AIS. Its longer half-life enables a single-bolus administration, which is particularly useful in emergencies. Tenecteplase has proven to have a good efficacy and safety profile in randomized clinical trials. Although we are awaiting the results of the ongoing phase 3 randomized clinical trials, we believe that tenecteplase has the potential to revolutionize the treatment of AIS through thrombolysis.

Intravoxel incoherent motion magnetic resonance imaging in the assessment of brain microstructure and perfusion in idiopathic normal-pressure hydrocephalus.

PURPOSE: To determine the relationship between intravoxel incoherent motion (IVIM) MRI parameters and clinical changes post-tap test (TT) in idiopathic normal-pressure hydrocephalus (iNPH) patients. METHODS: Forty-four probable iNPH patients underwent 3 T MRI before and after TT. IVIM parameters were calculated from eight different bilateral regions of interest in basal ganglia, centrum semiovale, and corona radiata. Patients were categorized based on TT response into positive (group 1) and negative (group 2) groups. A Welch two-sample t-test was used to compare differences in D, D*, f, and ADC between the two groups, while a paired t-test was employed to assess the changes within each group before and after TT. These parameters were then correlated with clinical results. RESULTS: In the lenticular and thalamic nuclei, D value was significantly lower in the group 1 compared to group 2 both pre- and post-TT (p = 0.002 and p = 0.007 respectively). Post-TT, the positive response group exhibited a notably reduced D* value (p = 0.012) and significantly higher f values (p = 0.028). In the corona radiata and centrum semiovale, a significant post-TT reduction in D* was observed in the positive response group (p = 0.017). Within groups, the positive response cohort showed a significant post-TT increase in ADC (p < 0.001) and a decrease in D* (p = 0.007). CONCLUSION: IVIM permits the acquisition of important non-invasive information about tissue and vascularization in iNPH patients. Enhanced perfusion in the lenticular and thalamic nuclei may suggest the role of re-established microvascular and glymphatic pathways, potentially elucidating the functional improvement in motor function after TT in iNPH patients.