The absence of antibodies in longitudinally extensive transverse myelitis may predict a more favourable prognosis.

BACKGROUND: Isolated first episodes of longitudinally extensive transverse myelitis (LETM) have typically been associated with neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, in some cases, serological testing and screening for other aetiologies are negative, a condition referred to as double seronegative longitudinally extensive transverse myelitis (dsLETM). OBJECTIVE: The objective of this study was to evaluate comparative outcomes of dsLETM, MOGAD-LETM and NMOSD-LETM. METHODS: Cohort study of LETM cases seen in the UK NMOSD Highly Specialised Service between January 2008 and March 2022. RESULTS: LETM = 87 cases were identified (median onset age = 46 years (15-85); median follow-up = 46 months (1-144); 47% NMOSD-LETM = 41 (aquaporin-4 antibodies (AQP4-IgG) positive = 36), 20% MOGAD-LETM = 17 and 33% dsLETM = 29). Despite similar Expanded Disability Status Scale (EDSS) at nadir, last EDSS was higher in AQP4-IgG and seronegative NMOSD-LETM (sNMOSD) (p = 0.006). Relapses were less common in dsLETM compared to AQP4-IgG NMOSD-LETM and sNMOSD-LETM (19% vs 60% vs 100%; p = 0.001). Poor prognosis could be predicted by AQP4-IgG (odds ratio (OR) = 38.86 (95% confidence interval (CI) = 1.36-1112.86); p = 0.03) and EDSS 3 months after onset (OR = 65.85 (95% CI = 3.65-1188.60); p = 0.005). CONCLUSION: dsLETM remains clinically challenging and difficult to classify with existing nosological terminology. Despite a similar EDSS at nadir, patients with dsLETM relapsed less and had a better long-term prognosis than NMOSD-LETM.

Ustekinumab safety and effectiveness in patients with ulcerative colitis: results from a large real-life study.

BACKGROUND: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC) but with limited real-world data. Therefore, we evaluated the effectiveness and safety of UST in patients with UC in a real-world setting. RESEARCH DESIGN AND METHODS: This is a multicenter, retrospective, observational cohort study. The primary endpoints were the clinical remission rate (partial Mayo score, PMS, ≤1) and the safety of UST. Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and fecal calprotectin (FC) reduction at week 24. RESULTS: We included 256 consecutive patients with UC (M/F 139/117, median age 52). The clinical remission and clinical response rates at eight weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 (p = 0.0004) and 24 (p = 0.038). At eight weeks, patients naïve or with one previous biologic treatment showed higher remission (p = 0.002) and clinical >response rates (p = 0.018) than patients previously treated with ≥ 2. Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy. CONCLUSION: This real-world study shows that UST effectively and safely treats patients with UC.

Predictors of azathioprine and mycophenolate mofetil response in patients with neuromyelitis optica spectrum disorder: A cohort study.

BACKGROUND: Relapse rates of 47 % have been reported in patients with neuromyelitis optica (NMOSD) using Azathioprine (AZA) and mycophenolate mofetil (MMF). Prediction of non-responders could help determine which patients are most likely to benefit from newer monoclonal antibody treatments from the outset. OBJECTIVES: To identify predictors of AZA and MMF treatment response in NMOSD. METHODS: Multicenter cohort study of NMOSD patients from Brazil and the United Kingdom, treated with AZA and MMF. An unsatisfactory response was defined as one severe or two non-severe attacks in a year. Cox regression was used to identify predictive factors of unsatisfactory response to AZA and MMF. RESULTS: 103 NMOSD patients, mean age 38 years, 83% female, and 65% of Black ethnic group were included. An unsatisfactory IS response was observed in 42% of patients over 2.5 years (IQR 1.0-8.8) years. A severe preceding attack was more common in non-responders (31.1% x 76.7%, p = <0.001). In multivariable analysis, severe attack (RR 3.13; 95 % CI 1.37-7.18, p = 0.007) or higher annualized relapse rate (RR 4.84; 95 % CI 2.01-11.65, p = < 0.001) predicted an unsatisfactory response. Interestingly, Black NMOSD patients had a lower risk of poor response (RR 0.39, 95 % CI 0.17-0.85, p = 0.019). CONCLUSION: Severe attack and a higher annualized relapse rate before AZA or MMF initiation were associated with an unsatisfactory IS response. In patients with these characteristics, treatment with higher-efficacy drugs should be considered from the outset.

Timing of MOG-IgG Testing Is Key to 2023 MOGAD Diagnostic Criteria.

BACKGROUND AND OBJECTIVES: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a recently identified autoimmune demyelinating disorder of the CNS affecting both adults and children. Diagnostic criteria for MOGAD have recently been published. We aimed to validate the 2023 MOGAD diagnostic criteria in a real-world cohort of patients with atypical CNS inflammation. METHODS: All patients referred to the National neuromyelitis optica spectrum disorder (NMOSD) specialized service at The Walton Center NHS Foundation Trust between 2012 and 2023 with an atypical demyelinating syndrome were evaluated. We systematically applied the 2023 MOGAD diagnostic criteria and previous 2018 International Diagnostic Recommendations for MOG encephalomyelitis to our retrospective cohort. RESULTS: 474 patients were screened and 66 were excluded for lack of clinical information. Preexisting diagnoses within our cohort included the following: MOGAD, n = 127; AQP4-IgG NMOSD, n = 125; seronegative NMOSD, n = 33; multiple sclerosis (MS), n = 10; and other diagnoses, n = 113. Of patients with preexisting MOGAD, 97% (123/127) fulfilled the 2023 MOGAD diagnostic criteria. Three patients with a low-positive MOG-IgG did not meet supportive features though 2/3 had insufficient investigations. Alternative diagnoses could not be excluded in 1 patient with MS-MOGAD overlap. No patients with a non-MOGAD diagnosis were found to fulfill the 2023 diagnostic criteria. The sensitivity and specificity of the 2023 MOGAD diagnostic criteria were 97% and 100% with no false positives, improving on 2018 International Diagnostic Recommendations for MOG encephalomyelitis. Low-positive MOG-IgG results were more often associated with a longer time from disease onset to sampling (p < 0.001). In addition, in patients with a MOG-IgG1 test within 6 months of clinical onset, approximately 25% can become low positive by 6 months. Of patients with preexisting MOGAD, 9% (12/127) had insufficient investigations and examinations to fully evaluate additional supportive features. However, in those who were completely evaluated, supportive features were fulfilled in 97% (111/115). DISCUSSION: The 2023 MOGAD diagnostic criteria were highly sensitive and specific and closely align with historically established cases of MOGAD. However, because additional supportive features are stipulated for patients with a low-positive MOG-IgG result, missed diagnoses may occur due to delayed testing or insufficient investigations.

Do we still need OCBs in MS diagnosis and how many?

BACKGROUND: CSF-specific oligoclonal bands (CSF-OCBs) can be used for dissemination in time (DIT) in the 2017 multiple sclerosis (MS) diagnostic criteria. A cut-off of ≥2 CSF-OCBs was recommended but studies have suggested ≥3 CSF-OCBs may be superior. OBJECTIVES: To assess utility of ≥2 and ≥3 CSF-OCBs as a cut-off for MS diagnosis. METHODS: Paired serum and CSF-OCBs sent to the Walton Centre, UK between July 2018 and June 2020 were included. CSF-OCBs were assessed using isoelectric focussing and reviewed by two blinded raters. Case records were reviewed. RESULTS: Of 1334 paired serum and CSF-OCB requests, 945 cases had sufficient clinical information. More than 1 CSF-OCB was detected in 268/945(28%) cases. Of these, 252 had ≥2 and 230 had ≥3 CSF-OCBs. The sensitivity and specificity for MS with ≥2 and ≥3 CSF-OCBs were 91.7%, 91.2%, 90.2% and 93.8% respectively. Only 3/22 patients with 2 CSF-OCBs had MS. In 25% of patients, CSF-OCBs reduced time to MS diagnosis (median 437.5 days (28-1332)). CONCLUSION: Although cut-offs of ≥2 or ≥3 CSF-OCBs performed similarly well, 2 CSF-OCBs were frequently seen with non-inflammatory pathology. Use of ≥3 CSF-OCBs for MS diagnosis should be considered. CSF analysis reduced time to MS diagnosis by approximately 14 months.

Risk of Hemolytic Anemia in IBD Patients with Glucose-6-Phosphate Dehydrogenase Deficiency Treated with Mesalamine: Results of a Retrospective-Prospective and Ex Vivo Study.

BACKGROUND: Mesalamine is one of the most-used drugs in inflammatory bowel disease (IBD), especially ulcerative colitis. Regulatory agencies have listed mesalamine as an unsafe drug in subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency based on the risk of hemolysis, although scientific evidence is lacking. The occurrence of acute and/or chronic hemolytic anemia in IBD patients with G6PD deficiency exposed to mesalamine was evaluated. METHODS: In this multicenter study, IBD patients with G6PD deficiency (cases) receiving mesalamine were retrospectively evaluated for acute, and prospectively for chronic, hemolysis. The presence of hemolytic anemia was based on red blood cell and reticulocyte count, hemoglobin, lactate dehydrogenase, unconjugated bilirubin, and haptoglobin levels. Cases were compared with controls (IBD patients with normal G6PD). RESULTS: A total of 453 IBD patients (mean age 52.1 ± 16.0 years; 58.5% female) were enrolled. Ulcerative colitis was present in 75% of patients. G6PD deficiency was detected in 17% of patients. Oral mesalamine was used in 67.9% of ulcerative colitis and in 32.4% of Crohn's disease cases. None of the 78 IBD patients with G6PD deficiency receiving mesalamine underwent hospitalization or specific treatment for acute hemolytic anemia. Relevant differences in chronic hemolysis markers were not observed in 30 cases compared with 112 controls receiving mesalamine (≤4500 mg/day). Marker modifications were also observed in mesalamine-free cases, consistent with the basal rate of erythrophagocytosis in G6PD deficiency. Ex vivo experiments showed the release of methemoglobin by G6PD deficient RBCs upon mesalamine challenge, only above 2.5 mg/mL, a concentration never reached in the clinical setting. CONCLUSIONS: This study provides, for the first time, evidence that mesalamine is safe in G6PD deficiency at a dosage of up to 4500 mg/day.

Liver fibrosis-4 score predicts outcome of patients with ischemic stroke undergoing intravenous thrombolysis.

Some evidence suggests a possible influence of liver disease on stroke prognosis. We investigated the association between fibrosis-4 (FIB-4) score, a marker of liver disease, and the 3-month outcome in patients with ischemic stroke undergoing intravenous thrombolysis. We also evaluated the rate of symptomatic intracranial hemorrhage after thrombolysis. In this prospective cohort study, we enrolled consecutive patients with ischemic stroke treated with thrombolysis who had a 3-month follow-up. The FIB-4 score was calculated and the validated cut-off values were used to indicate high/low risk of advanced liver fibrosis. The primary outcome was 3-month poor prognosis estimated as a modified Rankin scale score ≥3. Of the 264 included patients, 131 (49.62%) had a 3-month mRS ≥3, with a significantly higher FIB-4 score, compared to those with a mRS <3 score (adjp <0.001). When adjusted for possible confounders by multivariate logistic regression, FIB-4 score remained a significant predictor of poor outcome (OR 1.894, p = 0.011), along with history of atrial fibrillation (OR 3.488, p = 0.017), admission NIHSS score (OR 1.305, p < 0.001), and low values of hemoglobin (OR 0.730, p < 0.001). Mechanical thrombectomy had a favorable effect on patients' outcome (OR 0.201, p = 0.005). The risk of poor 3-month outcome was significantly higher among the 32 patients (12.1%) with high risk of severe fibrosis (p = 0.007). FIB-4 score values were also related to symptomatic intracranial hemorrhage (p = 0.004), specifically among patients with high probability of advanced hepatic fibrosis (p = 0.037). FIB-4 score can be considered as a promising independent predictor of poor prognosis in patients with acute ischemic stroke undergoing intravenous thrombolysis.

Acute Inflammatory Diseases of the Central Nervous System After SARS-CoV-2 Vaccination.

BACKGROUND AND OBJECTIVES: Acute inflammatory CNS diseases include neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Both MOGAD and acute disseminated encephalomyelitis (ADEM) have been reported after vaccination. Consequently, the mass SARS-CoV-2 vaccination program could result in increased rates of these conditions. We described the features of patients presenting with new acute CNS demyelination resembling NMOSDs or MOGAD within 8 weeks of SARS-CoV-2 vaccination. METHODS: The study included a prospective case series of patients referred to highly specialized NMOSD services in the UK from the introduction of SARS-CoV-2 vaccination program up to May 2022. Twenty-five patients presented with new optic neuritis (ON) and/or transverse myelitis (TM) ± other CNS inflammation within 8 weeks of vaccination with either AstraZeneca (ChAdOx1S) or Pfizer (BNT162b2) vaccines. Their clinical records and paraclinical investigations including MRI scans were reviewed. Serologic testing for antibodies to myelin oligodendrocyte glycoprotein (MOG) and aquaporin 4 (AQP4) was performed using live cell-based assays. Patients' outcomes were graded good, moderate, or poor based on the last clinical assessment. RESULTS: Of 25 patients identified (median age 38 years, 14 female), 12 (48%) had MOG antibodies (MOGIgG+), 2 (8%) had aquaporin 4 antibodies (AQP4IgG+), and 11 (44%) had neither. Twelve of 14 (86%) antibody-positive patients received the ChAdOx1S vaccine. MOGIgG+ patients presented most commonly with TM (10/12, 83%), frequently in combination with ADEM-like brain/brainstem lesions (6/12, 50%). Transverse myelitis was longitudinally extensive in 7 of the 10 patients. A peak in new MOGAD cases in Spring 2021 was attributable to postvaccine cases. Both AQP4IgG+ patients presented with brain lesions and TM. Four of 6 (67%) seronegative ChAdOx1S recipients experienced longitudinally extensive TM (LETM) compared with 1 of 5 (20%) of the BNT162b2 group, and facial nerve inflammation was reported only in ChAdOx1S recipients (2/5, 40%). Guillain-Barre syndrome was confirmed in 1 seronegative ChAdOx1S recipient and suspected in another. DISCUSSION: ChAdOx1S was associated with 12/14 antibody-positive cases, the majority MOGAD. MOGAD patients presented atypically, only 2 with isolated ON (1 after BNT162b2 vaccine) but with frequent ADEM-like brain lesions and LETM. Within the seronegative group, phenotypic differences were observed between ChAdOx1S and BNT162b2 recipients. These observations might support a causative role of the ChAdOx1S vaccine in inflammatory CNS disease and particularly MOGAD. Further study of this cohort could provide insights into vaccine-associated immunopathology.

Impact of Dimethylfumarate on Sleep in Multiple Sclerosis Patients: An Actigraphic Study.

BACKGROUND: Sleep disorders in multiple sclerosis (MS) patients are common. Dimethylfumarate is an oral disease-modifying drug (DMT), whose impact on sleep is unknown. OBJECTIVE: The aim of this study was to characterize actigraphic patterns in MS patients treated with dimethylfumarate. METHODS: Twenty relapsing-remitting MS patients with low to a mild disability, aged 20-50y, treated with dimethylfumarate for more than 6 months, were enrolled. All subjects had no history of sleep disorders. Actigraphy was used to study sleep patterns during a seven-day period. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Twenty healthy subjects served as controls. RESULTS: Our results showed statistically significant differences between some actigraphic patterns in MS patients treated with dimethylfumarate and healthy subjects, but the values for patients were still within normal limits. PSQI score was higher in MS patients compared to controls. CONCLUSION: Our findings suggest that dimethylfumarate, an oral DMT with a favourable benefit-risk profile, does not strongly alter sleep patterns in MS patients with low to mild disability and with no history of sleep disorders. Actigraphy is a simple diagnostic tool, able to support an objective measure of sleep parameters. The simplicity of application may allow considering its use for a screening of sleep disorders in MS patients.

Gastric duplication cyst: a challenging EUS differential diagnosis between subepithelial gastric lesion and exophytic pancreatic cystic neoplasm-a case report and a literature review.

Gastric duplication cysts are rare congenital malformation with a potential neoplastic progression and they may represent a challenge in differential diagnosis with exophytic pancreatic cyst neoplasm. We describe a case of a 38-year old man, complaining of recurrent epigastric pain due to a large abdominal mass, referred to our Hospital for EUS evaluation. Differential diagnosis was between gastric duplication cyst and exophytic pancreatic cyst because of FNA pointed out amylase 1280 UI/L and CEA 593.33 ng/mL. Despite antibiotic prophylaxis, an overinfection of the lesion occurred after the FNA, likely due to the technical failure to drain the cyst completely. Afterwards, the patient was referred to surgery and the pathologist confirmed the diagnosis of gastric duplication cyst. In this setting, EUS procedure has gained a leading play, complementary to traditional imaging tests, although its role has been not yet standardized in the reported literature. Here, we describe and discuss our demanding case, and we propose an algorithm to simplify and standardize the diagnostic workup.

Inflammation markers in moderate and severe obstructive sleep apnea: the influence of sex.

PURPOSE: Obstructive sleep apnea (OSA) is the most prevalent sleep-related breathing disorder, with a negative impact on cardiovascular health. Different OSA symptoms and treatment response in males and females have been reported. The aim of this study was to investigate inflammatory markers in patients with OSA and the relationship of those markers to disease severity in male and female subjects. METHODS: We considered consecutive subjects referred to the outpatient Sleep Disorder Service of the Respiratory Medicine Department, San Marino Hospital. We included patients with a diagnosis of moderate or severe OSAS and an age range of 45-80 years. Concomitant inflammatory conditions were an exclusion criterion. A polygraphic study and a blood draw for inflammatory markers were performed for each subject. RESULTS: Of 110 subjects, 59 were males. Severe OSA affected 72 subjects. We analyzed data through a 4-level categorical variable according to sex and OSA severity (moderate OSA, males; severe OSA, males; moderate OSA, females; severe OSA, females), which showed significant differences for interleukin-6 (IL-6) and C-reactive protein (CRP) levels. A significant difference in IL-6 levels with a significant ascending trend (p = 0.045) from females with moderate OSAS to males with severe OSAS emerged in our pairwise comparison for estimated marginal means. Also, a significant trend (p = 0.0001) for CRP levels from males with moderate OSAS to females with severe OSAS was shown. CONCLUSIONS: OSA and inflammation are interconnected, and both are associated with vascular diseases. Sex-related differences in OSA phenotypes may help the clinicians aim for a more personalized approach.

Sex-Related Differences in Polygraphic Parameters in a Population of Patients with Obstructive Sleep Apnea Syndrome.

BACKGROUND: Sex-related differences in the prevalence and clinical presentation of Obstructive Sleep Apnea Syndrome (OSAS) have been widely documented. The aim of this study was to investigate the influence of patients' sex on polygraphic parameters with particular attention to sleep autonomic changes in a population of OSAS patients. METHODS: Sixty OSAS patients aged 55-65 years (30 men, 30 women) were enrolled. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and daytime sleepiness with the Epworth Sleepiness Scale (ESS). The presence of respiratory events and autonomic changes during the night was investigated by polygraphy. RESULTS: Similar main cardiovascular risk factors prevalence was observed in both men and women. We observed a significant difference in PSQI (higher in women, p=0.0001) and ESS (higher in men, p=0.004) scores. Snoring (p=0.033), supine AHI (p=0.004), T90 (p=0.021), LO2 (p=0.0001), LF/HF ratio and LF (p=0.0001) were significantly higher in men. Sex differences in PSQI mean score and LF/HF ratio variability were preserved in all the subgroups of OSA severity. CONCLUSION: The influence of sex in modulating cardiovascular risk is a widely discussed topic. In our study, men showed more severe polygraphic parameters and an increase in LF/HF ratio compared to women. The results of our investigation suggest the relevance of delivering information about the different expressions of OSAS in men and women in order to improve diagnostic skills and in-depth prevention approaches.

Unraveling the enigma of new-onset refractory status epilepticus: a systematic review of aetiologies.

BACKGROUND AND PURPOSE: New-onset refractory status epilepticus (NORSE) is a clinical presentation, neither a specific diagnosis nor a clinical entity. It refers to a patient without active epilepsy or other pre-existing relevant neurological disorder, with a NORSE without a clear acute or active structural, toxic or metabolic cause. This study reviews the currently available evidence about the aetiology of patients presenting with NORSE and NORSE-related conditions. METHODS: A systematic search was carried out for clinical trials, observational studies, case series and case reports including patients who presented with NORSE, febrile-infection-related epilepsy syndrome or the infantile hemiconvulsion-hemiplegia and epilepsy syndrome. RESULTS: Four hundred and fifty records were initially identified, of which 197 were included in the review. The selected studies were retrospective case-control (n = 11), case series (n = 83) and case reports (n = 103) and overall described 1334 patients both of paediatric and adult age. Aetiology remains unexplained in about half of the cases, representing the so-called 'cryptogenic NORSE'. Amongst adult patients without cryptogenic NORSE, the most often identified cause is autoimmune encephalitis, either non-paraneoplastic or paraneoplastic. Infections are the prevalent aetiology of paediatric non-cryptogenic NORSE. Genetic and congenital disorders can have a causative role in NORSE, and toxic, vascular and degenerative conditions have also been described. CONCLUSIONS: Far from being a unitary condition, NORSE is a heterogeneous and clinically challenging presentation. The development and dissemination of protocols and guidelines to standardize diagnostic work-up and guide therapeutic approaches should be implemented. Global cooperation and multicentre research represent priorities to improve the understanding of NORSE.

Is Ustekinumab Effective in Refractory Crohn's Disease of the Pouch and Chronic Pouchitis? A Systematic Review.

Crohn's disease (CD) of the pouch and chronic pouchitis represent the most common long-term complications of total proctocolectomy and ileal pouch anal anastomosis (IPAA) for refractory ulcerative colitis (UC). These conditions are treated with multiple agents, including antibiotics, immunomodulators, and biologics. Among the latter, ustekinumab is approved for both CD and UC. We performed a systematic review to evaluate the efficacy of this anti-IL12/23 in CD of the pouch and chronic refractory pouchitis. Pubmed, Embase, Ovid, and the Cochrane Controlled Trials Register were searched to identify studies published until August 2020 investigating the use of ustekinumab for these conditions. Eighty-six eligible patients with IPAA-51 with CD of the pouch, 35 with chronic pouchitis-were identified from 2 retrospective studies and 5 case reports. Reported clinical response to ustekinumab was 63 and 85% in chronic pouchitis and CD of the pouch after 4-12 and 4-16 weeks, respectively. Clinical remission was reported in 10% of patients with chronic pouchitis and 27% of patients with CD of the pouch after 8-52 and 4-52 weeks of treatment, respectively. Endoscopic response was reported in 60% and 67% of patients with chronic pouchitis and CD of the pouch after 24-32 and 8-24 weeks of treatment respectively. Small sample sizes and large heterogeneity of therapy protocols/outcome definitions were significant studies limitations. In conclusion, there is a limited and inconclusive body of evidence suggesting that ustekinumab may be a therapeutic option for patients with chronic pouchitis and CD of the pouch refractory to other therapies.

Systemic Inflammatory Response Index and Futile Recanalization in Patients with Ischemic Stroke Undergoing Endovascular Treatment.

Futile recanalization remains a significant challenge for endovascular treatment (EVT) of acute ischemic stroke (AIS). The inflammatory response that occurs after cerebral infarct plays a central role in stroke pathobiology that can influence the outcome of a recanalization procedure. The aim of this study was to evaluate the relationship between the systemic inflammatory response index (SIRI) and futile recanalization in patients with AIS. We retrospectively identified consecutive patients with ischemic stroke due to proximal arterial occlusion in the anterior circulation, who were treated with EVT and achieved near-complete or complete recanalization. Absolute neutrophil count (ANC), absolute monocyte count (AMC), and absolute lymphocyte count (ALC) were collected from admission blood work to calculate SIRI as ANC × AMC/ALC. The study outcome was futile recanalization, defined as poor functional status [modified Rankin scale (mRS) score ≥ 3] at 3 months despite complete or near-complete recanalization. A total of 184 patients were included. Futile recanalization was observed in 110 (59.8%) patients. Older patients (odds ratio (OR) = 1.07, 95% confidence interval (CI): 1.04-1.10, p < 0.001), higher admission National Institutes of Health stroke scale score (OR = 1.10, 95% CI: 1.02-1.19, p = 0.013), and higher admission SIRI (OR = 1.08, 95% CI: 1.01-1.17, p = 0.028) increased the risk of the poor outcome at 3 months despite complete or near-complete recanalization.

Sleep actigraphic patterns and cognitive status.

We performed an actigraphic assessment of sleep characteristics in healthy subjects and patients with cognitive impairment. Thirty subjects were included and classified into controls (10 subjects), mild cognitive impairment (10 patients) and mild-to-moderate Alzheimer's disease (10 patients). Sleep quality was assessed using the Pittsburgh Sleep Quality Index. Participants had a 7-day actigraphic record. Sleep parameters collected were time in bed, total sleep time, sleep efficiency, sleep latency, wakefulness after sleep onset, number of awakenings, and mean motor activity. Significant differences between mild cognitive impairment and controls patients were found for sleep latency (p = 0.05); Alzheimer's disease patients had significantly worse scores for Pittsburgh Sleep Quality Index (p = 0.01), time in bed (p = 0.001), total sleep time (p = 0.04), sleep latency, sleep efficiency, motor activity (p = 0.0001) and wakefulness after sleep onset (p = 0.001) compared to controls. When comparing Alzheimer's disease and mild cognitive impairment, differences were significant for sleep latency (p = 0.01), wakefulness after sleep onset (p = 0.004), sleep efficiency, number of awakenings and motor activity (p = 0.0001). In addition to showing a high prevalence of sleep alterations in subjects with cognitive impairment, our data suggest that they are evident from the earliest stages of cognitive decline. Further studies are needed to assess whether early correction of sleep alterations can positively influence the evolution of cognitive impairment. The opportunity to provide clinically meaningful information with a simple assessment of sleep characteristics based on actigraphy suggests that wider use of the approach in patients with cognitive decline should be considered.

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.

Highly Purified Cannabidiol for Epilepsy Treatment: A Systematic Review of Epileptic Conditions Beyond Dravet Syndrome and Lennox-Gastaut Syndrome.

BACKGROUND: Cannabidiol (CBD), which is one major constituent of the Cannabis sativa plant, has anti-seizure properties and does not produce euphoric or intrusive side effects. A plant-derived, highly purified CBD formulation with a known and constant composition has been approved by the US Food and Drug Administration for the treatment of seizures associated with Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex. In the European Union, the drug has been authorized by the European Medicines Agency for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome, in conjunction with clobazam, and is under regulatory review for the treatment of seizures in patients with tuberous sclerosis complex. OBJECTIVES: This systematic review aimed to summarize the currently available body of knowledge about the use of this US Food and Drug Administration/European Medicines Agency-approved oral formulation of pharmaceutical-grade CBD in patients with epileptic conditions, especially developmental and epileptic encephalopathies other than Dravet syndrome and Lennox-Gastaut syndrome. METHODS: The relevant studies were identified through MEDLINE and the US National Institutes of Health Clinical Trials Registry in October 2020. There were no date limitations or language restrictions. The following types of studies were included: clinical trials, cohorts, case-control, cross-sectional, clinical series, and case reports. Participants had to meet the following criteria: any sex, any ethnicity, any age, diagnosis of epilepsy, receiving plant-derived, highly purified (> 98% w/w) CBD in a sesame oil-based oral solution for the treatment of seizures. Data extracted from selected records included efficacy, tolerability, and safety outcomes. RESULTS: Five hundred and seventy records were identified by database and trial register searching. Fifty-seven studies were retrieved for detailed assessment, of which 42 were eventually included for the review. The participants of the studies included patients of both pediatric and adult age. Across the trials, purified CBD was administered at dosages up to 50 mg/kg/day. In a randomized double-blind controlled trial in patients with tuberous sclerosis complex, CBD was associated with a significantly greater percent reduction in seizure frequency than placebo over the treatment period. Open-label studies suggested the effectiveness of CBD in the treatment of children and adults presenting with other epilepsy syndromes than those addressed by regulatory trials, including CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes, SYNGAP1 encephalopathy, and epilepsy with myoclonic absences. The most common adverse events observed during treatment with CBD included somnolence, decreased appetite, diarrhea, and increased serum aminotransferases. CONCLUSIONS: The currently available data suggest that response to treatment with a highly purified, plant-derived CBD oil-based solution can be seen in patients across a broad range of epilepsy disorders and etiologies. The existing evidence can provide preliminary support for additional research.