Neurologic Syndromes Predict Higher In-Hospital Mortality in COVID-19.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is protean in its manifestations, affecting nearly every organ system. However, nervous system involvement and its effect on disease outcome are poorly characterized. The objective of this study was to determine whether neurologic syndromes are associated with increased risk of inpatient mortality. METHODS: A total of 581 hospitalized patients with confirmed SARS-CoV-2 infection, neurologic involvement, and brain imaging were compared to hospitalized non-neurologic patients with coronavirus disease 2019 (COVID-19). Four patterns of neurologic manifestations were identified: acute stroke, new or recrudescent seizures, altered mentation with normal imaging, and neuro-COVID-19 complex. Factors present on admission were analyzed as potential predictors of in-hospital mortality, including sociodemographic variables, preexisting comorbidities, vital signs, laboratory values, and pattern of neurologic manifestations. Significant predictors were incorporated into a disease severity score. Patients with neurologic manifestations were matched with patients of the same age and disease severity to assess the risk of death. RESULTS: A total of 4,711 patients with confirmed SARS-CoV-2 infection were admitted to one medical system in New York City during a 6-week period. Of these, 581 (12%) had neurologic issues of sufficient concern to warrant neuroimaging. These patients were compared to 1,743 non-neurologic patients with COVID-19 matched for age and disease severity admitted during the same period. Patients with altered mentation (n = 258, p = 0.04, odds ratio [OR] 1.39, confidence interval [CI] 1.04-1.86) or radiologically confirmed stroke (n = 55, p = 0.001, OR 3.1, CI 1.65-5.92) had a higher risk of mortality than age- and severity-matched controls. CONCLUSIONS: The incidence of altered mentation or stroke on admission predicts a modest but significantly higher risk of in-hospital mortality independent of disease severity. While other biomarker factors also predict mortality, measures to identify and treat such patients may be important in reducing overall mortality of COVID-19.

Compulsivity in Alcohol Use Disorder and Obsessive Compulsive Disorder: Implications for Neuromodulation.

Alcohol use Disorder (AUD) is one of the leading causes of morbidity and mortality worldwide. The progression of the disorder is associated with the development of compulsive alcohol use, which in turn contributes to the high relapse rate and poor longer term functioning reported in most patients, even with treatment. While the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines AUD by a cluster of symptoms, parsing its heterogeneous phenotype by domains of behavior such as compulsivity may be a critical step to improve outcomes of this condition. Still, neurobiological underpinnings of compulsivity need to be fully elucidated in AUD in order to better design targeted treatment strategies. In this manuscript, we review and discuss findings supporting common mechanisms between AUD and OCD, dissecting the construct of compulsivity and focusing specifically on characteristic disruptions in habit learning and cognitive control in the two disorders. Finally, neuromodulatory interventions are proposed as a probe to test compulsivity as key pathophysiologic feature of AUD, and as a potential therapy for the subgroup of individuals with compulsive alcohol use, i.e., the more resistant stage of the disorder. This transdiagnostic approach may help to destigmatize the disorder, and suggest potential treatment targets across different conditions.

Diagnostic Issues in Early-Onset Obsessive-Compulsive Disorder and their Treatment Implications.

BACKGROUND: The lifespan approach and recent shift in the conceptualization of Obsessive- Compulsive Disorder (OCD) promoted by the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM5) along with novel insights into the pathogenesis of this heterogeneous disorder are driving the development of new outcome measures and new treatments for a disease that, on the other hand, is characterized by high rates of refractoriness. OBJECTIVE AND METHODS: The aim of this review is to provide a discussion of the translational evidence about Early Onset OCD (EO) in compliance with a neurodevelopmental and RdoC perspective. RESULTS AND CONCLUSION: EO might be considered the neurodevelopmental subtype of OCD. Indeed there is evidence that different clusters of symptoms and dimensions at an early stage predict different trajectories in phenotype and that distinct neurocircuit pathways underpin the progression of the disorder. Despite the development of high refractoriness in the course of the disorder, evidence suggests that EO may be particularly treatment responsive in the early stages, thus showing the need for early recognition and additional recovery oriented studies in this subgroup. Consistent with the neurodevelopmental perspective, immunity and glutamate neurotransmission are emerging as novel pathways for parsing out the neurobiology of OCD, the EO form, in particular, supporting the implementation of new multisystemic models of the OCD phenotype. Brain connectivity patterns, immune and microbiome profiles are standing out as promising areas for biomarkers with the potential for targeted personalized therapies in EO.

From Treatment Response to Recovery: A Realistic Goal in OCD.

Despite longitudinal studies reporting symptomatic remission rates ranging from 32% to 70%, Obsessive-Compulsive Disorder is considered a persistent and very disabling disorder. However, these studies suggest that recovery can be a realistic goal for a subgroup of the Obsessive-Compulsive Disorder population and that a clear definition of recovery is timely in Obsessive-Compulsive Disorder. The aim of this paper is to discuss the dimensions of and propose an operational definition of recovery in Obsessive-Compulsive Disorder. Considering the impact generated by the definition of recovery for other mental disorders, this article discusses how this concept may shape the future of research and clinical practice in Obsessive-Compulsive Disorder. Ultimately, the hope is that the management of Obsessive-Compulsive Disorder may parallel, and expand upon, some of the current approaches implemented in the care of schizophrenia, so that early diagnosis, stepped-care techniques, and a personalized approach can be used to create recovery-oriented treatment programs and influence policy making for Obsessive-Compulsive Disorder.

Antibiotics for PANDAS? Limited Evidence: Review and Putative Mechanisms of Action.

OBJECTIVE: Antibiotics have been used extensively by clinicians to treat patients with PANDAS or PANS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and pediatric acute-onset neuropsychiatric syndrome, respectively). This review examines the best-quality evidence supporting the practice-based use of antibiotics in these psychiatric conditions. DATA SOURCES: PubMed was searched for English-language articles published between January 1994 and July 2017 using the search terms [PANDAS OR PANS OR new-onset pediatric OCD] AND [antibiotics OR macrolides OR beta-lactams]. STUDY SELECTION: Randomized clinical trials, observational studies, and case reports concerning antibiotic use in PANDAS/PANS were reviewed. Four publications were included in the quantitative synthesis. DATA EXTRACTION: The evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) method. RESULTS: Although the single studies conveyed no statistically significant results, there is some evidence for efficacy of antibiotic therapy in reducing neuropsychiatric symptoms in the PANDAS/PANS population. CONCLUSIONS: Whereas the use of eradicating antibiotic therapy during active infections in PANDAS/PANS is well established, there is still a need for studies that improve the quality of evidence supporting use of antibiotics in this population independent of ongoing infections. Studies that compare antibiotics with other therapies, as well as studies that assess safety and efficacy of long-term use of antibiotic therapy in PANDAS/PANS, are still lacking. However, the available research supports evidence of a subgroup in the pediatric OCD population that is sensitive to antibiotic treatment and immunomodulatory therapy, independent of ongoing infectious conditions. Thus, more studies are warranted in the overall OCD spectrum.