Cognitive dysfunction in SLE: An understudied clinical manifestation

Mizrachi, Mark; Anderson, Erik; Carroll, Kaitlin; Tehrani, Nazila; Volpe, Bruce T.; Diamond, Betty

doi:10.1016/j.jaut.2022.102911

Cited by 16 publications

(13 citation statements)

References 235 publications

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“…Finally, functional imaging such as functional MRIs, blood-brain barrier permeability neuroimaging assessment through dynamic contrast-enhanced MRI or fluorine-18 fluorodeoxyglucose-PET scans or MRIs might provide promising additional tools to investigate j-SLE. 36,37 All our j-NPSLE patients had a partial or complete resolution of NP features after treatment, without any reported death. Early j-NPSLE diagnosis allowing prompt appropriate immunosuppressive treatments may explain such positive evolution.…”

Section: Discussionmentioning

confidence: 87%

Juvenile neuropsychiatric systemic lupus erythematosus: A specific clinical phenotype and proposal of a probability score

Labouret,

Trebossen,

Ntorkou

et al. 2024

Lupus

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Objective Juvenile systemic lupus erythematosus (j-SLE) is a rare chronic auto-immune disease involving several organs. Neuropsychiatric (NP) SLE (NPSLE) is frequent in j-SLE and associated with increased morbidity/mortality. Although NPSLE classification criteria exist, attributing NP features to j-SLE remains a major challenge. The study objective is to thoroughly describe j-NPSLE patients and assist in their diagnosis. Methods This is a 4-year retrospective monocentric study of j-SLE patients. NP events were attributed to j-SLE using standardised diagnostic criteria and multidisciplinary paediatric clinical expertise. Clinical features, brain magnetic resonance imaging (MRI)s and samples analysis including cerebrospinal fluid were assessed. A risk of j-NPSLE score was developed based on multivariable logistic regression analysis. Results Of 39 patients included, 44% were identified as having j-NPSLE. J-NPSLE diagnosis was established at the onset of j-SLE in 59% of patients. In addition to frequent kidney involvement (76%) and chilblains (65%), all j-NPSLE patients displayed psychiatric features: cognitive symptoms (82%), hallucinations (76%), depressed mood (35%), acute confused state (18%) and catatonia (12%). Neurological involvement was often mild and nonspecific, with headache (53%) in about half of the patients. The main features reported on brain MRI were nonspecific T2/FLAIR white matter hyperintensities (65%), and cerebral atrophy (88%). Upon immunosuppressive treatment, clinical improvement of NP features was observed in all j-NPSLE patients. The score developed to attribute j-NPSLE probability, guide further investigations and appropriate treatments is based on hallucinations, memory, sleep and renal involvement (Sensitivity: 0.95 Specificity: 0.85). Cerebrospinal fluid (CSF) neopterin assessment increases the score sensitivity and specificity. Conclusion Physicians should carefully and systematically assess the presence of NP features at diagnosis and early stages of j-SLE. For j-NPSLE patients with predominant psychiatric features, a multidisciplinary collaboration, including psychiatrists, is essential for the diagnosis, management and follow-up.

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Section: Discussionmentioning

confidence: 87%

Juvenile neuropsychiatric systemic lupus erythematosus: A specific clinical phenotype and proposal of a probability score

Labouret,

Trebossen,

Ntorkou

et al. 2024

Lupus

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“…Moreover, elevated levels of CSF albumin, haptoglobin, β-2 macroglobulin, and α-2 macroglobulin are found in NPSLE, correlating with the development of diffuse NPSLE. 26 Increased levels of proinflammatory cytokines including IL-6, TNF-α, CXCL8 and IL-8, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and IL-12p70 were observed in newonset status epilepticus patients, highlighting the importance of innate immunity-related inflammation in the pathogenesis of neuropsychiatric syndromes, although causality has not been established, and seizure activity itself may also contribute to this inflammatory response. 27 Complement pathway activation is implicated in subsequent tissue damage in various organs via complement-mediated cytotoxicity as well as neutrophil chemotaxis.…”

Section: Overview Of Cns Symptoms In Cslementioning

confidence: 97%

“…In a mouse model in which the BBB is disrupted, these autoantibodies are found to cause excitotoxic neuronal death in the hippocampus, 25 suggesting that they are likely pathogenic in NPSLE. Moreover, elevated levels of CSF albumin, haptoglobin, β‐2 macroglobulin, and α‐2 macroglobulin are found in NPSLE, correlating with the development of diffuse NPSLE 26 . Increased levels of proinflammatory cytokines including IL‐6, TNF‐α, CXCL8 and IL‐8, monocyte chemoattractant protein‐1, macrophage inflammatory protein‐1α, and IL‐12p70 were observed in new‐onset status epilepticus patients, highlighting the importance of innate immunity‐related inflammation in the pathogenesis of neuropsychiatric syndromes, although causality has not been established, and seizure activity itself may also contribute to this inflammatory response 27 …”

Section: Introductionmentioning

confidence: 98%

Implications of Inflammatory Processes on a Developing Central Nervous System in Childhood‐Onset Systemic Lupus Erythematosus

van der Heijden,

Rameh,

Golden

et al. 2024

Arthritis & Rheumatology

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, increasingly affecting pediatric and adult populations. Neuropsychiatric manifestations (i.e., cognitive dysfunction and mood disorders) appear to occur with greater severity and poorer prognosis in childhood vs adult‐onset SLE, negatively impacting school function, self‐management, and psychosocial health, as well as lifelong health‐related quality of life. In this review, we describe pathogenic mechanisms active in childhood‐onset SLE (cSLE) such as maladaptive inflammatory processes and ischemia, which are hypothesized to underpin central phenotypes in cSLE cases, while the role of alterations in protective central nervous system (CNS) barriers (i.e., the blood‐brain barrier) are also discussed. Recent findings derived from novel neuroimaging approaches are highlighted as the methods employed in these studies hold potential for identifying CNS abnormalities that would otherwise remain undetected with conventional MRI studies (e.g., T2‐weighted/ FLAIR sequences). Furthermore, we propose that a more robust presentation of neuropsychiatric symptoms in childhood‐onset SLE (cSLE) is in part due to the harmful impact of a chronic inflammatory insult on a developing central nervous system (CNS). Although the immature status of the CNS may leave cSLE patients more vulnerable to harboring neuropsychiatric manifestations, the same property may represent greater urgency to reverse the maladaptive effects associated with a pro‐neuroinflammatory state, provided that effective diagnostic tools and treatment strategies are available. Finally, considering the crosstalk between the CNS and other organ systems affected in cSLE, we postulate that a finer understanding of this interconnectivity and its role in the clinical presentation in cSLE is warranted.image

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“…These difficulties are collectively referred by the patients as "brain fog." 4 CD is one of 19 neurological and psychiatric syndromes of SLE proposed by the American College of Rheumatology (ACR), 5,6 and it is defined as "significant deficits in any or all of the following main cognitive functions: memory (learning and recall), complex attention, simple attention, executive skills (planning, organizing, and sequencing), visual-spatial processing, language (e.g., verbal, fluency), reasoning/problem solving and psychomotor speed." 5,6 Patients with SLE who experience a stroke and seizure may have CD in up to 50% of the cases, but patients without neurological manifestations or an active disease may also complain of these symptoms.…”

Section: Introductionmentioning

confidence: 99%

“…3 It causes difficulties keeping up with conversations, poor concentration, and confusion and troubles finding words, problem-solving and planning, localization of travel routes and objects localization. These difficulties are collectively referred by the patients as “brain fog.” 4…”

Section: Introductionmentioning

confidence: 99%

Cognitive dysfunction in patients with systemic lupus erythematosus. A cross-sectional study in a Brazilian sample

Borba

Dias

Vanzin

et al. 2023

Lupus

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Background Cognitive dysfunction (CD) is frequently found in patients with systemic lupus erythematosus (SLE) and contributes to impairment in the patient’s quality of life. Aim To study CD in a sample of patients and the possible associations with cumulative damage, disease activity, clinical/serological profile, and cumulative glucocorticoid dose. Methods Included in this study are 103 patients with SLE and 95 controls for cognitive performance through MoCA (Montreal Cognitive Assessment) and MMSE (Mini-Mental State Examination). Disease activity was measured by SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) and cumulative organ damage by SLICC/ACR/DI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index). CES-D (Center for Epidemiological Studies-Depression) scale was used to evaluate depression. Data on clinical and serological profile, treatment, and cumulative glucocorticoid dose were also collected. Results Patients with SLE had worse performance in the MoCA ( p = 0.009) and MMSE ( p = 0.01) than controls. The MoCA results showed that visuospatial and abstraction domains ( p = 0.03 and p = 0.002, respectively) were impaired, and the MMSE results showed that language and spatial orientation were reduced ( p = 0.002 and p = 0.01, respectively) when compared to controls. Both questionnaires (MoCA with r = −0.29 and MMSE r = −0.21) correlated negatively with SLICC/ACR/DI and the MoCA with SLEDAI (r = −0.22). No associations were found with cumulative glucocorticoid dose, degree of depression, and clinical or serological profile. Conclusions According to the MoCA, visuospatial cognition and abstraction were impaired, and according to the MMSE, spatial orientation and language were impaired in patients with SLE. The CD was correlated with cumulative damage and disease activity. These findings demonstrate that both disease-activity and disease-injury associated CD is found broadly in SLE patients in a Brazilian population, supporting the prior reports of CD in other regional SLE populations.

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Cognitive dysfunction in SLE: An understudied clinical manifestation

Cited by 16 publications

References 235 publications

Juvenile neuropsychiatric systemic lupus erythematosus: A specific clinical phenotype and proposal of a probability score

Juvenile neuropsychiatric systemic lupus erythematosus: A specific clinical phenotype and proposal of a probability score

Implications of Inflammatory Processes on a Developing Central Nervous System in Childhood‐Onset Systemic Lupus Erythematosus

Cognitive dysfunction in patients with systemic lupus erythematosus. A cross-sectional study in a Brazilian sample

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