Ocrelizumab is an effective anti-CD20 therapy approved for Relapsing Remitting (RRMS) and Primary Progressive Multiple Sclerosis (PPMS). In clinical trials, a proportion of patients developed hypogammaglobulinemia which could contribute to infection risk. This study aimed to identify hypogammaglobulinemia and its risk factors and evaluate potentially associated serious infection risk in a real-world cohort of patients.

All MS patients treated with ocrelizumab in a Quebec City MS clinic from January 2017 to August 2021 were included and detailed patient characteristics were collected by chart review. Levels of immunoglobulins (IgM, IgA and IgG) were assessed prior to each treatment. Serious infection was defined as an infection requiring hospitalization or emergency room treatment. Association between hypogammaglobulinemia and serious infection was analyzed.

A total of 266 patients (average follow-up 2.05 years) were included (87% RRMS). After 6 infusions, 32.8%, 3.5% and 4.2% of patients had at least one IgM, IgA and IgG hypogammaglobulinemia event respectively. Aside from pre-treatment hypogammaglobulinemia, there were no variables associated with on-treatment hypogammaglobulinemia. There was a total of 21 serious infections (3.36 and 12.33 per 100-person-years in RRMS and PPMS). Developing hypogammaglobulinemia during treatment was not associated with serious infection. A regression analysis did not show associations between serious infection and key disease characteristics.

Similar to ocrelizumab extension studies, our cohort demonstrated a significant rate of hypogammaglobulinemia over time, mostly with IgM. No association was found between hypogammaglobulinemia and serious infection.

Cognitive sequelae are reported in 20-25% of patients following SARS-CoV-2 infection. It remains unclear whether post-infection sequelae cluster into a uniform cognitive syndrome. In this cohort study, we characterized post-COVID neuropsychological outcome clusters, identified factors associated with cluster membership, and examined 6-month recovery trajectories by cluster.

The Mayo Clinic Institutional Review Board approved study protocols. Informed consent was obtained from all participants. Participants (> 18 years old) were recruited from a hospital-wide registry of Mayo Clinic Florida patients who tested positive for SARS-CoV-2 infection from July 2020 to Feb 2022. We abstracted participant health history and COVID-19 disease severity (NIAID score) from the electronic health record and retrieved Area Deprivation Index (ADI) scores as a measure of neighborhood socioeconomic disadvantage. We assessed objective cognitive performance with the CNS Vital-Signs (CNSVS) and subjective neuropsychological symptoms with the Neuropsych Questionnaire-45 (NPQ-45). Results were used as input features in a K-means clustering analysis to derive neurophenotypes. Chi-square and analysis of variance (AnOvA) tests were used to identify clinical and sociodemographic factors associated with cluster membership. Participants repeated the CNS Vital Signs, NPQ-45, as well as the Medical Outcomes Survey (MOS SF-36) and a posttraumatic stress disorder (PTSD) checklist (PCL-C 17) 6 months following initial testing. Repeated-measures ANOVA was used to assess change in neurocognitive performance over time by cluster. Significance was set at P < 0.05.

Our cohort consisted of 205 participants (171 ambulatory, 34 hospitalized) who completed post-acute outcome assessment a mean of 5.7 (± 3.8) weeks following testing positive for SARS-CoV-2. K-means clustering with elbow method fitting identified three subgroups (see figure). The first cluster (N = 31) is characterized by executive dysfunction, greater socioeconomic disadvantage, and higher rates of obesity. The second cluster (N = 32) is characterized by memory and speed impairment, higher COVID severity, prevalent anosmia (70%), and greater severity of memory complaints, depression, anxiety, and fatigue. The third and largest cluster (N = 142) is absent cognitive impairment. Approximately 39% of participants completed the 6-month outcome assessment (N=79). Regardless of cluster membership, verbal memory, psychomotor speed, and reaction time scores improved over time. Regardless of timepoint, cluster 1 (dysexecutive) showed lower scores on cognitive flexibility and complex attention and cluster 2 (memory-speed impaired) showed lower scores on verbal memory, psychomotor speed, and reaction time. Modeling of cluster by timepoint interactions showed a steeper slope of improvement in complex attention and cognitive flexibility in cluster 1 (dysexecutive). Cluster 3 (normal) showed significant improvement in fatigue while cluster 2 (memory-speed impaired) continued to report moderate-severe fatigue, worse medical outcomes, and higher PTSD symptom severity scores at six months.

Most participants were cognitively normal or experienced cognitive recovery following SARS-CoV-2 infection. The 25-30% of participants who showed cognitive impairment cluster into two different neurophenotypes. The dysexecutive phenotype was associated with socioeconomic factors and medical comorbidities that are non-specific to COVID-19, while the amnestic phenotype was associated with COVID-19 severity and anosmia. These results suggest that cognitive sequelae following SARS-CoV-2 infection are not uniform. Deficits may be influenced by distinct patient- and disease-specific factors, necessitating differentiated treatment approaches.

Childhood ischemic and hemorrhagic stroke is often associated with neuropsychological and cognitive deficits. Stroke induces an inflammatory response in the central and peripheral nervous systems. High levels of inflammatory markers in the plasma have been associated with poorer cognitive outcomes. The role of inflammation in neurological prognosis of stroke has been studied previously; however, there is a limited understanding of the association between inflammatory markers and neuropsychological outcome post-stroke. The present review examined the existing literature on the association between inflammatory markers and post-stroke functioning.

Data bases (PsycINFO, PubMed, Web of Science, and Ovid) were reviewed in October 2020. Articles were restricted to English-language literature. Articles were included regardless of recruitment setting, number of strokes, mechanism of stroke, timing of blood collection and outcome assessment. The articles focused on patients with stroke (between the ages of 0 to 95), measured post-stroke outcome by neurological and cognitive outcome measures (i.e., it included findings on any aspect of cognition such as memory, information processing, or attention), and on pro-inflammatory cytokines and c-reactive proteins as measures of inflammation. The systematic literature search retrieved 954 articles to review against inclusion criteria. Descriptive statistics were performed using IBM SPSS 27.0 Statistics Software.

A total of 18 articles were included in this review. The population age ranged from 21 to 95, and, when reported (n=17), mean participant age was 66.31. Among stroke patient populations, ischemic stroke was most researched (n=15). The most widely investigated biomarkers were CRP (n=9), IL-6 (n=8), TNF- a (n=7), IL-1 b (n=5), and IL-10 (n=5). The time of initial blood collection ranged from on admission to within 3 months poststroke. Equal number of studies used both neurological and cognitive tests (n=7), or only neurological (n=7), 2 studies only used cognitive tests, and one study used all three types of measures. The most commonly used cognitive test was the Mini Mental State Examination, MMSE (n=7). The next commonly used cognitive test was the Montreal Cognitive Assessment (MoCA), (n=4). Only two studies used a comprehensive neuropsychological battery.

There is a lack of research into diverse stroke populations. All the studies examined the association between inflammatory markers and the post-stroke outcomes in adult populations and mostly in patients with ischemic stroke. The lack of research on pediatric and young adult stroke represents a significant gap in understanding predictors of neurological and cognitive outcomes. Further, the review revealed a lack of comprehensive neurocognitive assessment post stroke, with most studies measuring neuropsychological outcome using brief cognitive instruments. Our findings highlight a critical need for addressing the above gaps to help elucidate the role of inflammatory markers in the neuropsychological prognosis of stroke in younger populations.

Non-suicidal self-injurious behavior (NSSI) is rather widespread in adolescents, especially in females, and is an important risk factor for future suicide. The search for neurobiological markers of NSSI is therefore an actual medical and social problem.

The aim of the study was to determine the relationships between pre-treatment quantitative clinical, EEG, and neuroimmunological parameters in female depressive adolescents with NSSI.

40 female depressive patients (all right-handed, 16–25 years old, mean 17.6±2.2 years old) were included in the study. Total HDRS-17 scores varied from 14 to 38 (mean 26.0±6.9). Multichannel eyes closed resting EEG was recorded with subsequent spectral power (SP) measurements in narrow frequency sub-bands. Enzymatic activities of leukocyte elastase (LE) and its antagonist α-1 proteinase inhibitor (α1-PI), as neuroinflammation markers, and the levels of autoantibodies to S100b protein (AAB-S100b) and to basic myelin protein (AAB-BMP), as neuroplasticity markers, were measured in the blood plasma. Spearman’s rank correlations were calculated between clinical, EEG, and neuroimmunological parameters.

HDRS-17 scores correlated positively (p<0.05) with beta2 (20-30 Hz) SP in the right anterior and mid-temporal leads. AAB-S100b values correlated positively with alpha2 (9-11 Hz) and alpha3 (11-13 Hz) SP in central-temporal-parietal-occipital leads, and correlated negatively with beta1 (13-20 Hz) and beta2 SP in the right anterior temporal lead.

The structure of clinical–neurobiological correlations obtained indicates that processes of neuroinflammation in depressive adolescents with NSSI are relatively mild and/or compensated by anti-inflammatory mechanisms. The study supported by RBRF grant No.20-013-00129a.

No significant relationships.