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Background. Anifrolumab is a biologic agent approved for the treatment of Systemic Lupus Erythematosus (SLE). Clinical trials evaluating its efficacy (TULIP-1 and TULIP-2) excluded patients with active neuropsychiatric manifestations (NPSLE). The aim of this study was to review the published cases of NPSLE treated with Anifrolumab (ANI) and to describe a clinical case from our cohort. Materials and Methods. A literature search was conducted on Medline/PubMed and Embase for reports of NPSLE patients treated with ANI. In addition, we describe a case from our local cohort. Results. The literature review identified seven published cases of NPSLE successfully treated with ANI, including two with confusional states, one with acute psychosis, one with headache, one with cerebral vasculitis, one with aseptic meningitis, and one with demyelinating polyneuropathy. The data are summarized in Table 1. We also report the case of a 63-year-old woman with a 26-year history of SLE and antiphospholipid syndrome (APS), who initially presented with polyarthritis, lymphopenia, an ischemic stroke, and positivity for ANA, anti-dsDNA, anti-Ro/SSA, lupus anticoagulant, anti-cardiolipin IgG, and hypocomplementemia. Over the years, she experienced a relapsing-remitting course characterized by cutaneous vasculitis of the hands and feet, thrombocytopenia, leukopenia, and epileptic seizures with spatiotemporal disorientation. Electroencephalography revealed left-hemispheric irritative electrical abnormalities, interpreted as secondary to ischemic damage. The patient’s treatment history included several immunosuppressants—cyclophosphamide, azathioprine, mycophenolate mofetil, belimumab, and hydroxychloroquine (discontinued due to gastrointestinal intolerance, INR abnormalities, and arrhythmia). Levetiracetam was escalated to 2500 mg/day due to worsening seizures, without achieving clinical remission (DORIS). In 2022, following prednisone tapering to 5 mg/day, disease flare occurred with hand vasculitis, malar rash, alopecia, leukopenia (1700/µl), and thrombocytopenia (95,000/µl). Anifrolumab was initiated, and prednisone was increased to 10 mg/day. At the 3-month follow-up, mucocutaneous and hematologic manifestations had resolved, and seizure frequency had decreased (from 2/week to 1 every 8 weeks). After 6 months of ANI treatment, the patient achieved complete clinical remission (CLASI = 0, cSLEDAI-2K = 0) with prednisone tapered to 2.85 mg/day. Conclusions. The results from both the literature review and our clinical case suggest that Anifrolumab may be effective in managing neuropsychiatric manifestations of SLE. In our experience, a remarkable improvement was also observed in the hematologic domain. Although these findings are encouraging, they warrant confirmation in dedicated clinical trials, emphasizing the need for personalized therapeutic strategies in SLE management.

Background Caregiver burden is related to personal factors and patient characteristics and is greater when neuropsychiatric symptoms (NPSs) are present. Objective: Estimate the prevalence of burden among caregivers of dementia patients and its association with NPSs and identify NPSs causing greater caregiver distress according to dementia stage. Methods A cross-sectional observational study in caregivers of noninstitutionalized dementia patients was conducted. Caregiver variables were sociodemographic, time of care, NPS-associated distress based on the Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D) and burden based on the Zarit Burden Interview (ZBI). Patient variables were time since disease onset, Global Deterioration Scale (GDS) disease stage, functional assessment and NPS presence and intensity according to the Neuropsychiatric Inventory (NPI). The mean ZBI score, prevalence of burden and NPI-D score with 95% CIs at each dementia stage were estimated. Factors associated with burden were identified by multivariate analysis. Results Of the 125 caregivers included, 77.6% were women, with a mean age of 60.7 (± 14.3) years; 78.4% (95%CI: 71.0; 86.0) experienced burden. The mean ZBI score was 12.3 (95%CI: 11.6; 12.9) and increased according to NPS number (p = 0.042). The NPSs causing the most burden were disinhibition (93.5%), irritability (87.3%) and agitation (86.1%). Agitation, apathy, and sleep disorders were the NPSs generating the greatest overall caregiver distress; depression (max NPI-D 1.9), hyperactivity (max NPI-D 2.1), and psychosis symptoms (max NPI-D 1.6) generated the greatest distress at stage GDS 3, stages GDS 4–5, and stages GDS 6–7, respectively. The NPI score (OR = 1.0, 95%CI 1.0; 1.1), intensity of irritability (OR = 1.2, 95%CI 1.0; 1.6), disinhibition (OR = 2.6, 95%CI 1.1; 5.8) and hyperactivity subsyndrome (OR = 1.1, 95%CI 1.0; 1.2) were associated with caregiver burden. Other associated factors were female gender (OR = 6.0, 95%CI 1.6; 22.8), ≥ 8 h daily care (OR = 5.6, 95%CI 1.4; 22.8), working outside the home (OR = 7.6, 95%CI 1.8; 31.8), living with the patient (OR = 4.5, 95%CI 1.1; 19.6), kinship (OR = 5.4, 95%CI 1.0; 28.2) and lower patient education (OR = 8.3, 95%CI 2.3; 30.3). Conclusions The burden on caregivers of dementia patients is high and associated with NPS presence and intensity. Disinhibition and irritability caused the highest burden. Depression, hyperactivity and psychosis produce more distress in mild, mild-moderate and severe dementia, respectively.

Post-stroke depression (PSD) is one of common and serious sequelae of stroke. Approximately, one in three stroke survivors suffered from depression after stroke. It heavily affected functional rehabilitation, which leaded to poor quality of life. What is worse, it is strongly associated with high mortality. In this review, we aimed to derive a comprehensive and integrated understanding of PSD according to recently published papers and previous classic articles. Based on the considerable number of studies, we found that within 2 years incidence of PSD has a range from 11 to 41%. Many factors contribute to the occurrence of PSD, including the history of depression, stroke severity, lesion location, and so on. Currently, the diagnosis of PSD is mainly based on the DSM guidelines and combined with various depression scales. Unfortunately, we lack a unified mechanism to explain PSD which mechanisms now involve dysregulation of hypothalamic–pituitary–adrenal (HPA) axis, increased inflammatory factors, decreased levels of monoamines, glutamate-mediated excitotoxicity, and abnormal neurotrophic response. At present, both pharmacotherapy and psychological therapies are employed in treating PSD. Although great advance has been made by researchers, there are still a lot of issues need to be addressed. Especially, the mechanism of PSD is not completely clear.

The gut-brain axis is a complex, bidirectional network of communication systems that integrates neural, endocrine, and immune pathways, as well as metabolic processes, to regulate homeostasis and maintain physiological and cognitive equilibrium. Central to this axis is the gut microbiota, which exerts a profound influence on brain function through microbial metabolites, including short-chain fatty acids, tryptophan metabolites, and bile acids. Disruption of this microbial balance, known as dysbiosis, has been implicated in the onset and progression of major neuropsychiatric and neurodegenerative disorders, including depression, Alzheimer's disease, and Parkinson's disease. This review critically examines the mechanistic underpinnings of the gut-brain axis, emphasizing metabolic, immunological, and neuroendocrine signaling as key mediators. Furthermore, it explores how dietary components, particularly fiber, polyphenols, and fermented foods, modulate gut microbial composition and function to influence brain health. Emerging therapeutic strategies, such as probiotics, prebiotics, and fecal microbiota transplantation, are discussed, along with the potential of personalized targeted intervention. By integrating current findings, this review underscores the gut-brain axis as a dynamic interface that not only influences neurological and psychiatric outcomes but also represents a promising target for therapeutic intervention.

Neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD) affect up to 97% of AD patients, with an estimated 80% of current AD patients experiencing these symptoms. Common AD-associated NPS include depression, anxiety, agitation, aggression, and apathy. The severity of NPS in AD is typically linked to the disease’s progression and the extent of cognitive decline. Additionally, these symptoms are responsible for a significant increase in morbidity, mortality, caregiver burden, earlier nursing home placement, and greater healthcare expenditure. Despite their high prevalence and significant impact, there is a notable lack of clinical research on NPS in AD. In this article, we explore and analyze the prevalence, symptom manifestations, challenges in diagnosis, and treatment options of NPS associated with AD. Our literature review reveals that distinguishing and accurately diagnosing the NPS associated with AD remains a challenging task in clinical settings. It is often difficult to discern whether NPS are secondary to pathophysiological changes from AD or are comorbid psychiatric conditions. Furthermore, the availability of effective pharmaceutical interventions, as well as non-pharmacotherapies for NPS in AD, remains limited. By highlighting the advance and challenges in diagnosis and treatment of AD-associated NPS, we aspire to offer new insights into the complexity of identifying and treating these symptoms within the context of AD, and contribute to a deeper understanding of the multifaceted nature of NPS in AD.

The human microbiota has a fundamental role in host physiology and pathology. Gut microbial alteration, also known as dysbiosis, is a condition associated not only with gastrointestinal disorders but also with diseases affecting other distal organs. Recently it became evident that the intestinal bacteria can affect the central nervous system (CNS) physiology and inflammation. The nervous system and the gastrointestinal tract are communicating through a bidirectional network of signaling pathways called the gut-brain axis, which consists of multiple connections, including the vagus nerve, the immune system, and bacterial metabolites and products. During dysbiosis, these pathways are dysregulated and associated with altered permeability of the blood-brain barrier (BBB) and neuroinflammation. However, numerous mechanisms behind the impact of the gut microbiota in neuro-development and -pathogenesis remain poorly understood. There are several immune pathways involved in CNS homeostasis and inflammation. Among those, the inflammasome pathway has been linked to neuroinflammatory conditions such as multiple sclerosis, Alzheimer’s and Parkinson’s diseases, but also anxiety and depressive-like disorders. The inflammasome complex assembles upon cell activation due to exposure to microbes, danger signals, or stress and lead to the production of pro-inflammatory cytokines (interleukin-1β and interleukin-18) and to pyroptosis. Evidences suggest that there is a reciprocal influence of microbiota and inflammasome activation in the brain. However, how this influence is precisely working is yet to be discovered. Herein, we discuss the status of the knowledge and the open questions in the field focusing on the function of intestinal microbial metabolites or products on CNS cells during healthy and inflammatory conditions, such as multiple sclerosis, Alzheimer’s and Parkinson’s diseases, and also neuropsychiatric disorders. In particular, we focus on the innate inflammasome pathway as immune mechanism that can be involved in several of these conditions, upon exposure to certain microbes.

Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) and its subset, pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS), are emerging autoimmune encephalopathies of childhood. Management guidelines are needed. This article, from the PANS/PANDAS Consortium, presents a consensus management guideline for the infection components. Accompanying papers from the Consortium discuss psychiatric and immunomodulatory management. Methods: Literature was reviewed and integrated with the clinical experience of the authors to provide a set of practical guidelines. This article was submitted to all members of the PANS/PANDAS Consortium, and their additional comments were added. Results: The relationships between PANS and infections are reviewed. An approach to the retrospective diagnosis of group A streptococcal infection for an operational definition of PANDAS is proposed. An initial course of anti-streptococcal treatment is proposed for all newly diagnosed PANS cases. Chronic secondary antimicrobial prophylaxis is suggested for children with PANDAS who have severe neuropsychiatric symptoms or recurrent group A Streptococcus-associated exacerbations. Guidelines for children with non-streptococcal PANS include vigilance for streptococcal pharyngitis or dermatitis in the patient and close contacts. All patients with PANS or PANDAS should also be closely monitored for other intercurrent infections, including sinusitis and influenza. Intercurrent infections should be diagnosed and treated promptly according to current standard guidelines. A guideline for the assessment of infection at initial onset or during neuropsychiatric exacerbations is also presented. Standard immunizations and attention to vitamin D are encouraged. Data indicating limited utility of adenotonsillectomy and probiotics are presented. Conclusion: A working guideline for the management of infection issues in PANS and PANDAS, based on literature and expert opinion, is provided.

Increasing evidence implies a possible causal link between periodontitis and neuropsychiatric disorders, such as Alzheimer’s disease (AD) and major depression (MD). A possible mechanism underlying such a link can be explained by neuroinflammation induced by chronic systemic inflammation. This review article focuses on an overview of the biological and epidemiological evidence for a feasible causal link of periodontitis to neuropsychiatric disorders, including AD, MD, Parkinson’s disease, and schizophrenia, as well as the neurological event, ischemic stroke. If there is such a link, a broad spectrum of neuropsychiatric disorders associated with neuroinflammation could be preventable and modifiable by simple daily dealings for oral hygiene. However, the notion that periodontitis is a risk factor for neuropsychiatric disorders remains to be effectively substantiated.