Cognitive impact of neuronal antibodies: encephalitis and beyond

Gibson, Lucy; McKeever, Anna; Coutinho, Estér; Finke, Carsten; Pollak, Thomas A

doi:10.1038/s41398-020-00989-x

Cited by 38 publications

(34 citation statements)

References 143 publications

(264 reference statements)

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“…An excellent overview of cognitive impairment in the acute and post-acute phases of different auto-antibody defined subtypes of LE is provided by Gibson et al [4]. The overview indicates that confusion can be another relevant symptom in the acute phase in all subtypes of LE but predominantly in LGI1 and gamma-aminobutyric acidB-receptor (GABAbR) associated LE.…”

Section: Which Neuropsychological Functions Are Affected?mentioning

confidence: 99%

“…Accordingly, cognitive and behavioral alterations can be dynamic and reversible or chronic and irreversible. The type and extent of the impairments depend on several etiological factors including (1) the underlying autoimmune process (type of auto-antibodies [4], B-and T-cell activity [5]) (2) the inflammatory-driven functional and/or structural changes [2,6,7], (3) if applicable, epileptic seizures and interictal epileptic discharges [8], (4) immunomodulatory or anti-epileptic treatment effects [9][10][11]. Finally, (5) pre-existent psychiatric comorbidities or (6) psychiatric symptoms caused by LE may also have a negative impact on cognitive performance.…”

Section: Introductionmentioning

confidence: 99%

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Neuropsychological Evaluations in Limbic Encephalitis

Helmstaedter

2021

Brain Sciences

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Limbic encephalitis (LE) can cause dynamic and permanent impairment of cognition and behavior. In clinical practice, the question arises as to which cognitive and behavioral domains are affected by LE and which assessment is suited to monitor the disease progress and the success of treatment. Current findings on cognition and behavior in LE are reviewed and discussed based on current guidelines and consensus papers. In addition, we outline approaches for the neuropsychological monitoring of LE and its treatment. Dependent on disease acuity and severity, LE leads to episodic long-term memory dysfunction in different variants (e.g., anterograde memory impairment, accelerated long-term forgetting, and affection of autobiographical memory) and executive deficits. In addition, affective disorders are very common. More severe psychiatric symptoms may occur as well. In the course of the disease, dynamic phases with functional recovery must be differentiated from residual defect states. Evidence-based neuropsychological diagnostics should be conducted ideally before treatment initiation and reassessments are indicated when any progress is suggested, and when decisive anti-seizure or immunomodulatory treatment changes are made. Cognition and behavior may but must not run in synchrony with seizures, MRI pathology, or immune parameters. Cognitive and behavioral problems are integral aspects of LE and represent important biomarkers of disease acuity, progress, and therapy response beyond and in addition to parameters of immunology, neurological symptoms, and brain imaging. Thus, evidence-based neuropsychological assessments are essential for the diagnostic workup of patients with suspected or diagnosed limbic encephalitis, for treatment decisions, and disease and treatment monitoring.

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Section: Which Neuropsychological Functions Are Affected?mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neuropsychological Evaluations in Limbic Encephalitis

Helmstaedter

2021

Brain Sciences

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“…In the acute stage, in anti‐NMDAR Ab‐mediated AE, the NMDAR system is significantly interrupted through the reversible antibody‐mediated capping and internalization of the receptor, possibly leading to the observed amnestic syndrome. In addition, NMDARs are highly concentrated in the frontal cortex, likely explaining the deficits in executive function and psychiatric presentations of this patient population 49 . The literature of the hypothesized mechanisms inducing cognitive deficits in anti‐AMPARs, anti‐CASPR2 and anti‐GABA A Rs Ab‐mediated AE is very limited and is summarized by Gibson et al 49 …”

Section: Neural Systems Of Acute Aementioning

confidence: 99%

“…In addition, NMDARs are highly concentrated in the frontal cortex, likely explaining the deficits in executive function and psychiatric presentations of this patient population 49 . The literature of the hypothesized mechanisms inducing cognitive deficits in anti‐AMPARs, anti‐CASPR2 and anti‐GABA A Rs Ab‐mediated AE is very limited and is summarized by Gibson et al 49 …”

Section: Neural Systems Of Acute Aementioning

confidence: 99%

Cognition and psychopathology in autoimmune encephalitides: A focus on risk factors and patient outcomes

Griffith

Malpas

Kyndt

et al. 2021

Clinical & Exp Neuroim

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Neurocognitive compromise, neuropsychiatric symptoms and psychopathology are all evident in the acute stages of autoimmune encephalitides. These factors considerably affect functional independence after discharge. Drawing on psychometric assessments and qualitative descriptions, this review explores the nature, extent and diagnosis of cognitive disorder in autoimmune encephalitides. Potential pathophysiological and neuroanatomical architecture related to neurocognitive compromise in the acute and chronic stages of this illness is examined. In regard to outcomes, the review highlights clinicodemographic factors currently known to be associated with poorer cognitive outcome. Finally, the review delves into neuropsychiatric symptomology and psychological concerns that should be considered at diagnosis and during follow up of these patients.

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“…Furthermore, both brain regions are main components of the DMN and are involved in memory and executive functions [24,25] -the two cognitive domains most frequently impaired in patients with NMDARE. [4,26,27]…”

Section: Static Functional Network Connectivity Analysismentioning

confidence: 99%

State-dependent signatures of Anti-NMDA Receptor Encephalitis: a dynamic functional connectivity study

Schwanenflug

Krohn

Heine

et al. 2020

Preprint

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IntroductionAnti-N-methyl-d-aspartate receptor encephalitis (NMDARE) is an autoimmune disorder associated with severe neuropsychiatric symptoms. While patients with NMDARE exhibit disrupted functional connectivity (FC), these findings have been limited to static connectivity analyses. This study applies time-resolved FC analysis to explore the temporal variability of large-scale brain activity in NMDARE and to assess the discriminatory power of functional brain states in a supervised classification approach. MethodsResting-state fMRI data from 57 patients with NMDARE and 61 controls was included. To capture brain dynamics, four discrete connectivity states were extracted and state-wise group differences in FC, occurrence, dwell time and transition frequency were assessed. Furthermore, logistic regression models with embedded feature selection were trained for each state to predict group status in a leave-one-out cross validation scheme. ResultsPatients showed FC alterations in three out of four states. Besides a reduction in hippocampalfrontal connectivity, we observed connectivity decreases within the default mode network and between frontal areas and subcortical as well as visual regions, which remained undetected in static FC. Furthermore, patients displayed a shift in dwell time from the weakly connected dominant state to a higher connected, but less frequent state, accompanied by increased transition frequencies. Discriminatory network features and predictive power varied dynamically over states, reaching up to 78.6% classification accuracy. ConclusionPatients showed state-specific alterations in FC along with a shift in dwell time and increased volatility of state transitions. These measures were associated with disease severity and duration, highlighting the potential of spatiotemporal dynamics in FC as prognostic biomarkers in NMDARE.

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Cognitive impact of neuronal antibodies: encephalitis and beyond

Cited by 38 publications

References 143 publications

Neuropsychological Evaluations in Limbic Encephalitis

Neuropsychological Evaluations in Limbic Encephalitis

Cognition and psychopathology in autoimmune encephalitides: A focus on risk factors and patient outcomes

State-dependent signatures of Anti-NMDA Receptor Encephalitis: a dynamic functional connectivity study

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