Latency of poststroke epilepsy can predict drug resistance.

BACKGROUND AND PURPOSE: The progressive nature of epileptogenesis raises the question of whether the latent period may already carry information about the characteristics of the subsequent epilepsy. This study aimed to explore whether the time from stroke to epilepsy onset was related to the risk of drug resistance in patients with poststroke epilepsy (PSE). METHODS: Patients with epilepsy secondary to cerebral infarct or spontaneous intracerebral hemorrhage were included. Study outcome was the occurrence of drug resistance defined as failure of adequate trials of two tolerated and appropriately chosen and used antiseizure medication schedules to achieve sustained seizure freedom. RESULTS: One hundred fifty-nine patients with PSE and a median follow-up of 5 (interquartile range [IQR] = 3-9) years were included. In the study cohort, 29 (18.2%) participants were drug resistant. The median length of the time interval between stroke and PSE onset was 13 (IQR = 7-15) months in drug-resistant patients and 19 (IQR = 14-42) months (p < 0.001) in patients with seizure control. According to multivariable regression analysis, the time from stroke to PSE was an independent predictor of drug resistance (p < 0.001). The risk of drug resistance was highest when the onset of PSE occurred within the first months from stroke and decreased progressively with a steeper decline over the first 12 months. CONCLUSIONS: Substantial variability may exist in the pathways leading to PSE and distinguish patients with a variable risk of drug resistance.

Late epileptic seizures following cerebral venous thrombosis: a systematic review and meta-analysis.

BACKGROUND: Identifying late epileptic seizures (LS) following cerebral venous thrombosis (CVT) can be useful for prognosis and management. We systematically reviewed the literature to identify risk factors for LS due to CVT. METHODS: We systematically searched PubMed, Scholar, and Scopus databases (May 2021) to identify studies reporting data on prevalence and risk factors for CVT-LS. The methodological quality was assessed with the Ottawa-Newcastle Scale. The risk of developing CVT-LS was summarized in meta-analyses and expressed as odds ratio (OR) and corresponding 95% confidence intervals (CIs) using random-effects models. RESULTS: Out of the 332 records retrieved, four studies were eventually included with a total of 1309 patients with CVT and 142 (11%) with CVT-LS. The most relevant predictors of CVT-LS were symptomatic seizures (OR 5.66, 95% CI 3.83-8.35), stupor/coma (OR 6.81, 95% CI 1.18-39.20), focal neurologic signs (OR 6.81, 95% CI 1.18-39.2), hemorrhagic component (OR 3.52, 95% CI 2.45-5.06), and superior sagittal sinus involvement (OR 1.52, 95% CI 1.04-2.21). CONCLUSION: There are several risk factors for CVT-LS that should be considered in clinical practice. Further high-quality studies are warranted to develop predictive models for individualized risk stratification and prediction of CVT-LS.

Patent Foramen Ovale and Cryptogenic Stroke or Transient Ischemic Attack: To Close or Not to Close? A Systematic Review and Meta-Analysis.

BACKGROUND: The optimal strategy of secondary stroke prevention in patients with patent foramen ovale (PFO) is controversial. This study was performed to evaluate the efficacy and safety of the device closure (DC) versus the medical therapy (MT) in patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO. SUMMARY: Randomized controlled trials with active and control groups receiving the DC plus MT and MT alone in patients with history of cryptogenic stroke/TIA and diagnosis of PFO were systematically searched. The main efficacy outcome was stroke recurrence. Subgroup-analyses were performed according to age, shunt size, and presence of atrial septal aneurysm (ASA). Safety endpoints included any serious adverse event (SAE), atrial fibrillation (AF), and major bleeding complications. Risk ratios (RRs) and hazard ratios (HRs) with 95% CIs were estimated. Five trials were included, involving 3,440 participants (DC = 1,829, MT = 1,611). There was a protective effect of closure in the risk of recurrent stroke (RR 0.43 [0.21-0.90]; p = 0.024; HR = 0.39 [0.19-0.83]; p = 0.014). The benefit of PFO closure was significant in patients with PFO associated with substantial right-to-left shunt or ASA. There were no differences in the risks of SAEs and major bleedings between the groups. The rate of new-onset AF was higher in the DC than in the MT arm (RR 4.46 [2.35-8.41]; p < 0.001). Successful device implantation and effective PFO closure were achieved in 96 and 91% of the patients respectively. Key Messages: In selected adult patients with PFO and history of cryptogenic stroke, the DC plus MT is more effective to prevent stroke recurrence and is associated with an increased risk of new-onset AF compared to the MT alone.

How Should We Lower Blood Pressure after Cerebral Hemorrhage? A Systematic Review and Meta-Analysis.

BACKGROUND: The optimal treatment of high blood pressure (BP) after acute intra-cerebral hemorrhage (ICH) is controversial. SUMMARY: The aim of the study was to evaluate the safety and efficacy of early intensive vs. conservative BP lowering treatment in patients with ICH. Randomized controlled trials with active and control groups receiving intensive and conservative BP lowering treatments were identified. The following outcomes were assessed: 3-month mortality and combined death or major disability, 24-h hematoma growth, early neurological deterioration, occurrence of hypotension, severe hypotension, and serious treatment-emergent adverse events. Five trials were included involving 4,350 participants, 2,162 and 2,188 for intensive and conservative treatment groups, respectively. The pooled risk ratio of 3-month death or major disability was 0.96 (0.91-1.01) and the weighted mean difference in absolute hematoma growth was -1.53 (95% CI -2.94 to -0.12) mL in the intensive compared to conservative BP-lowering. There were no differences across the treatments in the incidence rates of 3-month mortality, early neurological deterioration, hypotension, and treatment-related adverse effects other than renal events. Key Messages: The early intensive anti-hypertensive treatment was overall safe and reduced the hematoma expansion in patients presenting with acute-onset spontaneous ICH and high BP levels.

Lacosamide during pregnancy and breastfeeding.

BACKGROUND: The epilepsy treatment during pregnancy represents a balance between teratogenic hazard and seizure control. The aim of the study was to evaluate the safety and efficacy of lacosamide (LCS) during pregnancy and breastfeeding. METHODS: Patients referred to our Epilepsy Center for pregnancy planning who became pregnant while taking LCS were prospectively followed-up. Data on seizure frequency, side effects, pregnancy course, delivery and breastfeeding, birth outcome, congenital malformation and development of newborns were collected. RESULTS: Three cases of maternal exposure to LCS were reported. Treatment with LCS was continued throughout pregnancy and breastfeeding at a median daily dose of 400mg. Lacosamide was used as monotherapy in two patients and as add-on treatment in one woman. Seizure frequency did not change throughout pregnancy and two subjects remained seizure free. The median gestational age at delivery was 39 weeks. The median Apgar scores at 1 and 5min were 9 and 10, respectively; no major or minor congenital malformations were observed in the offspring. Normal developmental milestone were reached by all new-borns. CONCLUSIONS: Worldwide pregnancy registries have provided consistent and increasing information about the efficacy and safety of the older antiepileptic drugs during gestation, while data are lacking for many of the newer generations. These cases could suggest a good level of efficacy and safety for LCS throughout pregnancy and breastfeeding and argue against teratogenic or toxic potentialities.

Neutrophil-to-Lymphocyte Ratio Predicts the Outcome of Acute Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Increasing evidence suggests that inflammatory mechanisms are involved in the intracerebral hemorrhage-induced brain injury. We evaluated the prognostic role of the peripheral leukocyte counts and neutrophil-to-lymphocyte ratio (NLR) in patients with intracerebral hemorrhage. METHODS: Patients with acute spontaneous intracerebral hemorrhage were retrospectively identified. Total white blood cells, absolute neutrophil count, and absolute lymphocyte count were obtained and the NLR computed from the admission blood work. The study end point was the occurrence of death or major disability at 3 months. RESULTS: One hundred seventy-seven subjects were enrolled. Ninety-four (53.1%) had unfavorable outcome. The absolute neutrophil count, absolute lymphocyte count, and NLR were independently associated with the 3-month status. The NLR resulted the best discriminating variable and the best predictive cut-off value was 4.58. CONCLUSIONS: In patients with acute intracerebral hemorrhage, higher neutrophils, lower lymphocytes, and higher NLRs predicted worse 3-month outcome.

Psychiatric comorbidities in patients from seven families with autosomal dominant cortical tremor, myoclonus, and epilepsy.

OBJECTIVE: The objective of this report was to assess the psychiatric comorbidity in a group of patients affected by autosomal dominant cortical tremor, myoclonus, and epilepsy (ADCME). METHODS: Reliable and validated psychodiagnostic scales including the BDI (Beck Depression Inventory), STAI-Y1 and 2 (State-Trait Anxiety Inventory - Y; 1 and 2), MMPI-2 (Minnesota Multiphasic Personality Inventory - 2), and QoLIE-31 (Quality of Life in Epilepsy Inventory - 31) were administered to 20 patients with ADCME, 20 patients with juvenile myoclonic epilepsy (JME), and 20 healthy controls. RESULTS: There was a higher prevalence of mood disorders in patients with ADCME compared to patients with JME and healthy controls, particularly depression (p=0.035 and p=0.017, respectively) and state anxiety (p=0.024 and p=0.019, respectively). Trait anxiety was not different from JME (p=0.102) but higher than healthy controls (p=0.017). The myoclonus score positively correlated with both state (rho: 0.58, p=0.042) and trait anxiety (rho: 0.65, p=0.011). These psychiatric features were also often associated with pathological traits of personality: paranoid (OR: 25.7, p=0.003), psychasthenia (OR: 7.0, p=0.023), schizophrenia (OR: 8.5, p=0.011), and hypomania (OR: 5.5, p=0.022). Finally, in patients with ADCME, decreased quality of life correlated with these psychiatric symptoms. SIGNIFICANCE: Patients with ADCME show a significant psychiatric burden that impairs their quality of life. A comprehensive psychiatric evaluation should be offered at the time of diagnosis to detect these comorbidities and to treat them.

Blood Pressure Variability and Clinical Outcome in Patients with Acute Intracerebral Hemorrhage.

BACKGROUND: The aim of this study was to evaluate whether fluctuations of blood pressure (BP) levels occurring in the acute stage of spontaneous intracerebral hemorrhage (ICH) affect the 3-month clinical outcome. METHODS: We retrospectively identified consecutive patients hospitalized for acute spontaneous ICH. BP measurements over the first 72 hours from the onset of symptoms were recorded, and standard deviation (SD), coefficient of variation (CV), and maximum-minimum difference (max-min) were determined to characterize both systolic and diastolic BP variability (BPV). The measure of outcome was the 3-month functional status assessed by the modified Rankin Scale following a baseline severity-adjusted analysis. RESULTS: Among the 138 enrolled patients with ICH, 67 (48.6%) were classified as having a poor 3-month functional recovery. A dose-response relationship with poor outcome was found for each measure of systolic BPV--adjusted odds ratios (ORs) for the highest thirds of SD 7.95 (95% confidence interval [CI], 2.88-21.90), CV 7.74 (95% CI, 2.88-20.80), and max-min 8.36 (95% CI, 2.72-25.62; P < .001). The strength of association with diastolic BPV turned out to be weaker and significant only for the higher values (adjusted ORs for the highest thirds of SD 6.74 [95% CI, 2.52-18.04], CV 4.57 [95% CI, 1.77-11.81], and max-min 4.34 [95% CI, 1.72-10.93]). CONCLUSIONS: In patients with acute ICH, BPV was a strong predictor of the 3-month clinical outcome and may represent a still neglected potential therapeutic target.

Individualized Prediction of Drug Resistance in People with Post-Stroke Epilepsy: A Retrospective Study.

BACKGROUND: The study aimed to develop a model and build a nomogram to predict the probability of drug resistance in people with post-stroke epilepsy (PSE). METHODS: Subjects with epilepsy secondary to ischemic stroke or spontaneous intracerebral hemorrhage were included. The study outcome was the occurrence of drug-resistant epilepsy defined according to International League Against Epilepsy criteria. RESULTS: One hundred and sixty-four subjects with PSE were included and 32 (19.5%) were found to be drug-resistant. Five variables were identified as independent predictors of drug resistance and were included in the nomogram: age at stroke onset (odds ratio (OR): 0.941, 95% confidence interval (CI) 0.907-0.977), intracerebral hemorrhage (OR: 6.292, 95% CI 1.957-20.233), severe stroke (OR: 4.727, 95% CI 1.573-14.203), latency of PSE (>12 months, reference; 7-12 months, OR: 4.509, 95% CI 1.335-15.228; 0-6 months, OR: 99.099, 95% CI 14.873-660.272), and status epilepticus at epilepsy onset (OR: 14.127, 95% CI 2.540-78.564). The area under the receiver operating characteristic curve of the nomogram was 0.893 (95% CI: 0.832-0.956). CONCLUSIONS: Great variability exists in the risk of drug resistance in people with PSE. A nomogram based on a set of readily available clinical variables may represent a practical tool for an individualized prediction of drug-resistant PSE.

A Case of Anti-Leucine-Rich Glioma-Inactivated Protein 1 (Anti-LGI1) Encephalitis With an Unusual Frontomesial Motor Cortex T2 MRI Hyperintensity.

Anti-leucine-rich glioma-inactivated protein 1 (anti-LGI1) encephalitis is a rare autoimmune disorder, classified within limbic encephalitides, and characterized by seizures and subacute cognitive-behavioral impairment, mainly affecting short-term memory and usually involving temporo-mesial lobe structures. We present a case of anti-LGI1 encephalitis characterized by focal right lower limb motor seizures and pyramidal signs and responsive to high-dose methylprednisolone. The patient developed an atypical left frontal lobe parasagittal T2 hyperintense lesion on MRI within one month of hospital admission, which has not been described previously in this disease to the best of our knowledge.

Predictors of Pharmaco-Resistance in Patients with Post-Stroke Epilepsy.

OBJECTIVES: The study aimed to explore the clinical predictors of pharmaco-resistance in patients with post-stroke epilepsy (PSE). METHODS: Patients with epilepsy secondary to cerebral infarct or spontaneous intracerebral hemorrhage were included. The study outcome was the occurrence of pharmaco-resistance defined as the failure of adequate trials of two tolerated and appropriately chosen and used antiseizure medication schedules, whether as monotherapies or in combination, to achieve sustained seizure freedom. RESULTS: One-hundred and fifty-nine patients with PSE and a median follow-up of 5 (3-9) years were included. The mean age of the patients at stroke onset was 56.7 (14.9) years, and 104 (65.4%) were males. In the study cohort, 29 participants were pharmaco-resistant. Age at stroke onset [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.93-0.99; p = 0.044], history of intracerebral hemorrhage (OR 2.95, 95% CI 1.06-8.24; p = 0.039), severe stroke (OR 5.43, 95% CI 1.82-16.16; p = 0.002), status epilepticus as initial presentation of PSE (OR 7.90, 1.66-37.55; p = 0.009), and focal to bilateral tonic-clonic seizures (OR 3.19, 95% CI 1.16-8.79; p = 0.025) were independent predictors of treatment refractoriness. CONCLUSIONS: Pharmaco-resistance developed in approximately 20% of patients with PSE and was associated with younger age at stroke onset, stroke type and severity, status epilepticus occurrence, and seizure types.

Adjunctive Perampanel in Older Patients With Epilepsy: A Multicenter Study of Clinical Practice.

BACKGROUND: Clinical data regarding use of newer antiseizure medications (ASMs) in an older population are limited. In randomized-controlled, placebo-controlled trials, older patients are under-represented, and protocols deviate markedly from routine clinical practice, limiting the external validity of results. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Perampanel is a third-generation ASM and the first and only non-competitive alfa-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor antagonist. OBJECTIVE: The aim of this study was to assess the effectiveness and tolerability of adjunctive perampanel over a 1-year period in a population of older patients with epilepsy treated in a real-world setting. METHODS: Older (≥ 65 years of age) patients prescribed add-on perampanel at 12 Italian epilepsy centers were retrospectively identified. Seizure occurrence, adverse events (AEs), and drug withdrawal were analyzed. Effectiveness outcomes included the rates of seizure response (≥ 50% reduction in baseline monthly seizure frequency), seizure freedom, and treatment discontinuation. Safety and tolerability outcomes were the rate of treatment discontinuation due to AEs and the incidence of AEs. RESULTS: A total of 92 patients with a median age of 69 (range 65-88) years were included. The median daily dose of perampanel at 12 months was 6 mg (interquartile range 4-6 mg). At 12 months, 53 (57.6%) patients were seizure responders, and 22 (23.9%) patients were seizure free. Twenty (21.7%) patients discontinued perampanel; the reasons for treatment withdrawal were insufficient efficacy (n = 6/20; 30.0%), AEs (n = 12/20; 60.0%), and a combination of both (n = 2/20; 10%). The most common AEs included irritability (8.7%), somnolence (4.3%), and dizziness/vertigo (4.3%). The rate of behavioral and psychiatric AEs was higher in patients with history of psychiatric comorbidities (p = 0.044). There were no differences in the occurrence of behavioral and psychiatric AEs according to the concomitant use of levetiracetam (p = 0.776) and history of cognitive decline (p = 0.332). CONCLUSIONS: Adjunctive perampanel was associated with improvement in seizure control and good tolerability in a real-life setting and can represent a viable therapeutic option in older patients with epilepsy.

Endovascular treatment and cognitive outcome after anterior circulation ischemic stroke.

The impact of reperfusion therapies on cognition has been poorly explored and little knowledge exists. We explored the influence of endovascular treatment (EVT) on cognitive outcome in patients with anterior circulation ischemic stroke. Patients presenting with ischemic stroke due to anterior large vessel occlusion who underwent intravenous thrombolysis (IVT) alone or EVT plus IVT were recruited. Cognitive abilities were evaluated at 6 months from stroke through a neuropsychological test battery. A total of 88 patients with a mean age of 66.3 ± 12.9 years were included, of which 38 treated with IVT alone and 50 with IVT plus EVT. Compared to patients treated with IVT alone, patients who received EVT plus IVT performed significantly better at the neuropsychological tests exploring executive functions, attention, abstract reasoning, visuospatial ability, visual and verbal and memory. At multivariable regression analysis, the EVT was independently associated with the 6-month cognitive performance after the adjustment for age, sex, admission National Institutes of Health Stroke Scale score, systolic blood pressure, glucose level, Alberta Stroke Program Early CT score, side of stroke, site of occlusion, and Back Depression Inventory score [Stroop Test Word Reading: adjß = 13.99, 95% confidence interval (CI) 8.47-19.50, p < 0.001; Stroop Test Colour Naming: adjß = 6.63, 95% CI 2.46-10.81, p = 0.002; Trail Making Test-A: adjß = - 92.98, 95% CI - 153.76 to - 32.20, p = 0.003; Trail Making Test-B: adjß = - 181.12, 95% CI - 266.09 to - 96.15; p < 0.001; Digit Span Test Forward: adjß = 1.44, 95% CI 0.77-2.10, p < 0.001; Digit Span Test Backward: adjß = 1.10, 95% CI 0.42-1.77, p = 0.002; Coloured Progressive Matrices: adjß = 5.82, 95% CI 2.71-8.93, p < 0.001; Rey Complex Figure Test-Copy: adjß = 6.02, 95% CI 2.74-9.30, p < 0.001; Rey Complex Figure Test-Immediate recall: adjß = 6.00, 95% CI 2.34-9.66, p = 0.002; Rey Complex Figure Test-Delayed recall: adjß = 5.73, 95% CI 1.95-9.51, p = 0.003; Rey Auditory Verbal Learning Test-Immediate recall: adjß = 12.60, 95% CI 6.69-18.52, p < 0.001; Rey Auditory Verbal Learning Test-Delayed recall: adjß = 1.85, 95% CI 0.24-3.45, p = 0.025]. Patients treated with EVT plus IVT had better cognitive performance than patients treated with IVT alone at 6 months from anterior circulation ischemic stroke.

Neutrophil-to-Lymphocyte Ratio in Acute Cerebral Hemorrhage: a System Review.

Spontaneous intracerebral hemorrhage (ICH) accounts for approximately 10 to 30% of all acute cerebrovascular events, and it is the type of stroke associated with the highest rates of mortality and residual disability. The inflammatory response is early triggered by hematoma components and can enhance the damage within the hemorrhagic brain. Assessment of peripheral biomarkers of inflammation could contribute to increase knowledge about some of the mechanisms involved in the ICH-induced injury and yield information on the disease course. The neutrophil-to-lymphocyte ratio (NLR) integrates information on both the innate and adaptive compartments of the immunity and represents a reliable measure of the inflammatory burden. The aim of the current review is to highlight the available evidence about the relationships between the NLR and clinical outcome in patients with acute ICH and provide critical insights into the underlying pathophysiology. Since no therapy targeting ICH-induced primary injury has yielded conclusive benefits and ICH treatment remains mainly supportive within a framework of general critical care management, these findings could also contribute to identify new potential targets for neuroprotection and develop novel therapeutic strategies.

Predictors of cognitive functioning after carotid revascularization.

PURPOSE: High-grade carotid stenosis can affect cognition, but the relationship between stenosis correction and cognitive outcome is not fully understood, yet. The aim of this study was to evaluate the predictors of post-operative neurocognitive functioning in patients with symptomatic severe internal carotid artery (ICA) stenosis undergoing carotid endarterectomy (CEA). MATERIALS AND METHODS: Patients with history of transient ischemic attack within the past 6 months and ipsilateral high-grade stenosis of ICA undergoing CEA were prospectively enrolled. Cerebral hemodynamics was assessed by means of the cerebral vasomotor reactivity (CVR) to hypercapnia measured through transcranial Doppler ultrasonography. Coloured Progressive Matrices plus Complex Figure Copy Test, and phonemic plus categorical (ca) Verbal Fluency tests were performed to assess right and left hemisphere cognitive functions, respectively. Cerebral hemodynamics and cognitive functions were assessed before and 6 months after CEA. RESULTS: One hundred and eighty-one patients were included. The mean age was 73.2 (6.9) years and 121 (66.9%) were males. At 6 months from CEA, the scores obtained in the cognitive tests exploring the re-vascularized hemisphere's functions and ipsilateral cerebral hemodynamics were improved. At multivariate linear regression analysis, the 6-month change in cognitive performance was inversely associated with age [ß = -0.17, 95% confidence interval (CI) -0.22 to -0.12; p < .001] and CVR value obtained before CEA on the side of ICA stenosis (ß = -6.25, 95% CI -7.40 to -5.10; p < .001). CONCLUSIONS: In patients with symptomatic high-grade ICA stenosis, age and cerebral hemodynamic status before CEA predicted the neurocognitive performance changes after surgical stenosis correction.

Eslicarbazepine acetate in the treatment of adults with partial-onset epilepsy: an evidence-based review of efficacy, safety and place in therapy.

INTRODUCTION: Up to 30% of the patients diagnosed with epilepsy will continue suffering from seizures despite treatment with antiepileptic drugs, either in monotherapy or polytherapy. Hence, there remains the need to develop new effective and well-tolerated therapies. AIM: The objective of this article was to review the evidence for the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive treatment in adult patients with focal onset seizures. EVIDENCE REVIEW: ESL is the newest, third-generation, single enantiomer member of the dibenzazepine family. Following oral administration, ESL is rapidly and extensively metabolized by hepatic first-pass hydrolysis to the active metabolite eslicarbazepine, which has linear, dose-proportional pharmacokinetics and low potential for drug-drug interactions. Eslicarbazepine works as a competitive blocker of the voltage gated sodium channels; unlike carbamazepine (CBZ) and oxcarbazepine (OXC), it has a lower affinity for the resting state of the channels, and reduces their availability by selectively enhancing slow inactivation. Efficacy and safety of ESL have been assessed in four randomized, Phase III clinical trials: the median relative reduction in standardized seizure frequency was 33.4% and 37.8% in the ESL 800 and 1,200 mg daily dose groups, and the responder rates were 33.8% and 43.1%, respectively. The incidence of treatment-emergent adverse events (TEAEs) increased with raising the dosage (ESL 400 mg: 63.8%, ESL 800 mg: 67.0%, ESL 1,200 mg: 73.1%). The TEAEs were generally mild to moderate in intensity, and the most common were dizziness, somnolence, headache and nausea. Open-label studies confirmed the findings from the pivotal trials and demonstrated sustained therapeutic effect of ESL over time and improvement of tolerability profile in patients switching from OXC/CBZ. No unexpected safety signals emerged over >5 years of follow-up. CONCLUSION: Once-daily adjunctive ESL at the doses of 800 and 1,200 mg was effective to reduce the seizure frequency and was fairly well tolerated in adults with focal onset epilepsy. Starting treatment at 400 mg/day, followed by 400 mg increments every 7-14 days, could provide the optimal balance of efficacy and tolerability.

Neutrophil-to-lymphocyte ratio improves outcome prediction of acute intracerebral hemorrhage.

BACKGROUND: The inflammatory response plays a role in determining the course of intra-cerebral hemorrhage (ICH) and immune parameters may have prognostic value. The aim of the study was to determine whether the peripheral leukocyte counts and neutrophil-to-lymphocyte ratio (NLR) were associated to 30-day functional status after ICH, and improved the accuracy of outcome prediction when added to the Modified ICH score. METHODS: We retrospectively identified consecutive patients with spontaneous ICH who underwent blood sampling and cranial CT neuroimaging within 24 h from onset. Total white blood cells (WBC), absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) were collected, and the NLR computed as the ANC to ALC ratio. The study endpoint was 30-day functional status; poor outcome was defined as death or major disability (modified Rankin Scale score ≥ 3). RESULTS: Two hundred and eight patients were enrolled, of which 111 (53.4%) had a modified Rankin Scale score ≥ 3 at 30 days from ICH. At multivariate analysis, the WBC (adjusted odd ratio [adjOR] for 1000 leukocytes increase 1.20, 95% confidence interval [CI] 1.05-1.38), ANC (adjOR for 1000 neutrophils increase 1.34, 95% CI 1.14-1.57), ALC (adjOR for 1000 lymphocytes increase 0.34, 95% CI 0.20-0.59) and NLR (adjOR for 1-point increase 1.49, 95% CI 1.24-1.79) were independently associated with 30-day poor outcome. Predictive accuracy of the Modified ICH score was enhanced by adding the NLR. CONCLUSIONS: The NLR was associated with 30-day mortality and morbidity after ICH, and improved the accuracy of outcome prediction when added to the Modified ICH score.

Endovascular treatment of symptomatic vertebral artery stenosis: A systematic review and meta-analysis.

BACKGROUND: The study aim was to evaluate the safety and efficacy of endovascular treatment (EVT) versus medical treatment (MT) in patients with symptomatic vertebral artery (VA) stenosis. METHODS: Randomized controlled trials with active and control groups receiving EVT plus MT and MT alone in patients with vertebro-basilar transient ischemic attack (TIA) or stroke and VA stenosis were identified. Primary endpoints included the occurrence of any stroke, any vertebro-basilar stroke, vertebro-basilar ischemic stroke, and vertebro-basilar TIA. Secondary endpoints were myocardial infarction, vascular death, and composite vascular outcome. All endpoints were assessed at short and long-term. Risk ratios (RRs) with 95% confidence intervals (CIs) have been estimated. RESULTS: Four trials were included involving 370 participants, 194 and 176 for EVT and MT arms, respectively. There was no overall effect of EVT on the occurrence of any stroke [short-term: RR 3.05 (95% CI 0.33-28.49); long-term: RR 0.75 (95% CI 0.40-1.40)], any vertebro-basilar stroke [short-term RR 3.05 (95% CI 0.33-28.49); long-term RR 0.91 (95% CI 0.42-1.99)], vertebro-basilar ischemic stroke [short-term: RR 1.02 (95% CI 0.07-15.88); long-term RR 1.27 (95% CI 0.36-4.50)], vertebro-basilar TIA [short-term: RR 5.00 (95% CI 0.28-90.18); long-term: RR 0.85 (95% CI 0.39-1.81)]. There were no differences across the treatments in any secondary outcome. CONCLUSIONS: There were no clear-cut benefits or harms for EVT versus MT alone in patients with symptomatic VA stenosis.

Efficacy and Safety of Adjunctive Cannabidiol in Patients with Lennox-Gastaut Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: Lennox-Gastaut syndrome (LGS) is a severe developmental epileptic encephalopathy, and available interventions fail to control seizures in most patients. Cannabidiol (CBD) is a major chemical of marijuana, which has anti-seizure properties and different mechanisms of action compared with other approved antiepileptic drugs (AEDs). OBJECTIVE: The aim was to evaluate the efficacy and safety of CBD as adjunctive treatment for seizures in patients with LGS using meta-analytical techniques. METHODS: Randomized, placebo-controlled, single- or double-blinded trials were identified. Main outcomes included the ≥ 50% reduction in baseline drop and non-drop seizure frequency, and the incidence of treatment withdrawal and adverse events (AEs). Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated through the inverse variance method. RESULTS: Two trials were included involving 396 participants. Patients presenting ≥ 50% reduction in drop seizure frequency during the treatment were 40.0% with CBD and 19.3% with placebo [RR 2.12 (95% CI 1.48-3.03); p < 0.001]. The rate of non-drop seizure frequency was reduced by 50% or more in 49.4% of patients in the CBD and 30.4% in the placebo arms [RR 1.62 (95% CI 1.09-2.43); p = 0.018]. The RR for CBD withdrawal was 4.93 (95% CI 1.50-16.22; p = 0.009). The RR to develop any AE during CBD treatment was 1.24 (95% CI 1.11-1.38; p < 0.001). AEs significantly associated with CBD were somnolence, decreased appetite, diarrhea and increased serum aminotransferases. CONCLUSIONS: Adjunctive CBD resulted in a greater reduction in seizure frequency and a higher rate of AEs than placebo in patients with LGS presenting seizures uncontrolled by concomitant AEDs.