Seizures and epilepsy secondary to viral infection in the central nervous system

Zhang, Peng; Yang, Yuting; Zou, Jialin; Yang, Xinrui; Liu, Qiankun; Chen, Yangmei

doi:10.1186/s42494-020-00022-0

Cited by 15 publications

(17 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, HSV encephalitis has a predisposition to affect epileptogenic areas within the frontotemporal region and in autoimmune encephalitis, the antibodies associated with neuronal cell-surface antigens, that are highly expressed in this region, are themselves often directly involved in the disease process. [16][17][18] The differential disease mechanisms observed in specific aetiologies of encephalitis may influence seizure risk, however, there was inadequate power in this analysis to establish factors associated with seizures within aetiological subgroups. Certain clinical features were less common in patients with seizures, specifically, stiff neck, photophobia, lethargy and any focal deficit on neurological examination.…”

Section: Discussionmentioning

confidence: 99%

Acute seizure risk in patients with encephalitis: development and validation of clinical prediction models from two independent prospective multicentre cohorts

et al. 2022

View full text Add to dashboard Cite

ObjectiveIn patients with encephalitis, the development of acute symptomatic seizures is highly variable, but when present is associated with a worse outcome. We aimed to determine the factors associated with seizures in encephalitis and develop a clinical prediction model.MethodsWe analysed 203 patients from 24 English hospitals (2005–2008) (Cohort 1). Outcome measures were seizures prior to and during admission, inpatient seizures and status epilepticus. A binary logistic regression risk model was converted to a clinical score and independently validated on an additional 233 patients from 31 UK hospitals (2013–2016) (Cohort 2).ResultsIn Cohort 1, 121 (60%) patients had a seizure including 103 (51%) with inpatient seizures. Admission Glasgow Coma Scale (GCS) ≤8/15 was predictive of subsequent inpatient seizures (OR (95% CI) 5.55 (2.10 to 14.64), p<0.001), including in those without a history of prior seizures at presentation (OR 6.57 (95% CI 1.37 to 31.5), p=0.025).A clinical model of overall seizure risk identified admission GCS along with aetiology (autoantibody-associated OR 11.99 (95% CI 2.09 to 68.86) and Herpes simplex virus 3.58 (95% CI 1.06 to 12.12)) (area under receiver operating characteristics curve (AUROC) =0.75 (95% CI 0.701 to 0.848), p<0.001). The same model was externally validated in Cohort 2 (AUROC=0.744 (95% CI 0.677 to 0.811), p<0.001). A clinical scoring system for stratifying inpatient seizure risk by decile demonstrated good discrimination using variables available on admission; age, GCS and fever (AUROC=0.716 (95% CI 0.634 to 0.798), p<0.001) and once probable aetiology established (AUROC=0.761 (95% CI 0.6840.839), p<0.001).ConclusionAge, GCS, fever and aetiology can effectively stratify acute seizure risk in patients with encephalitis. These findings can support the development of targeted interventions and aid clinical trial design for antiseizure medication prophylaxis.

show abstract

Section: Discussionmentioning

confidence: 99%

Acute seizure risk in patients with encephalitis: development and validation of clinical prediction models from two independent prospective multicentre cohorts

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In this context, seizures which appeared approximately 6 months after PrV‐∆UL21/US3∆kin infection may result from either chronic or autoimmune encephalitis. Epilepsy has been described in chronic herpes encephalitis, but autoimmunity may also play an important role in the development of seizures [ 40 , 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical, neuropathological, and immunological short‐ and long‐term feature of a mouse model mimicking human herpes virus encephalitis

et al. 2021

View full text Add to dashboard Cite

Herpes simplex encephalitis (HSE) is one of the most serious diseases of the nervous system in humans. However, its pathogenesis is still only poorly understood. Although several mouse models of predominantly herpes simplex virus 1 (HSV‐1) infections mimic different crucial aspects of HSE, central questions remain unanswered. They comprise the specific temporofrontal tropism, viral spread within the central nervous system (CNS), as well as potential molecular and immunological barriers that drive virus into latency while only rarely resulting in severe HSE. We have recently proposed an alternative mouse model by using a pseudorabies virus (PrV) mutant that more faithfully represents the striking features of human HSE: temporofrontal meningoencephalitis with few severely, but generally only moderately to subclinically affected mice as well as characteristic behavioral abnormalities. Here, we characterized this animal model using 6‐ to 8‐week‐old female CD‐1 mice in more detail. Long‐term investigation over 6 months consistently revealed a biphasic course of infection accompanied by recurring clinical signs including behavioral alterations and mainly mild meningoencephalitis restricted to the temporal and frontal lobes. By histopathological and immunological analyses, we followed the kinetics and spatial distribution of inflammatory lesions as well as the underlying cytokine expression in the CNS over 21 days within the acute phase of infection. Affecting the temporal lobes, the inflammatory infiltrate was composed of lymphocytes and macrophages showing a predominantly lymphocytic shift 15 days after infection. A strong increase was observed in cytokines CXCL10, CCL2, CCL5, and CXCL1 recruiting inflammatory cells to the CNS. Unlike the majority of infected mice, strongly affected animals demonstrated extensive temporal lobe edema, which is typically present in severe human HSE cases. In summary, these results support the validity of our animal model for in‐depth investigation of HSE pathogenesis.

show abstract

“…Experimental corneal inoculation of HSV-1 in BALB/c mice led to increased CA3 pyramidal cell excitability and aberrant mossy fiber sprouting in the hippocampus as well as clinical seizures ( Wu et al, 2003 ). Remarkably, after initial infection, HSV can establish persistent latent infections in the CNS, acting as a continuous source of HSE recurrence ( Zhang et al, 2020 ).…”

Section: Mechanisms Of Seizures and Epilepsy Associated With Viral In...mentioning

confidence: 99%

Molecular Mechanisms in the Genesis of Seizures and Epilepsy Associated With Viral Infection

Löscher

Howe

2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Seizures are a common presenting symptom during viral infections of the central nervous system (CNS) and can occur during the initial phase of infection (“early” or acute symptomatic seizures), after recovery (“late” or spontaneous seizures, indicating the development of acquired epilepsy), or both. The development of acute and delayed seizures may have shared as well as unique pathogenic mechanisms and prognostic implications. Based on an extensive review of the literature, we present an overview of viruses that are associated with early and late seizures in humans. We then describe potential pathophysiologic mechanisms underlying ictogenesis and epileptogenesis, including routes of neuroinvasion, viral control and clearance, systemic inflammation, alterations of the blood-brain barrier, neuroinflammation, and inflammation-induced molecular reorganization of synapses and neural circuits. We provide clinical and animal model findings to highlight commonalities and differences in these processes across various neurotropic or neuropathogenic viruses, including herpesviruses, SARS-CoV-2, flaviviruses, and picornaviruses. In addition, we extensively review the literature regarding Theiler’s murine encephalomyelitis virus (TMEV). This picornavirus, although not pathogenic for humans, is possibly the best-characterized model for understanding the molecular mechanisms that drive seizures, epilepsy, and hippocampal damage during viral infection. An enhanced understanding of these mechanisms derived from the TMEV model may lead to novel therapeutic interventions that interfere with ictogenesis and epileptogenesis, even within non-infectious contexts.

show abstract

Seizures and epilepsy secondary to viral infection in the central nervous system

Cited by 15 publications

References 112 publications

Acute seizure risk in patients with encephalitis: development and validation of clinical prediction models from two independent prospective multicentre cohorts

Acute seizure risk in patients with encephalitis: development and validation of clinical prediction models from two independent prospective multicentre cohorts

Clinical, neuropathological, and immunological short‐ and long‐term feature of a mouse model mimicking human herpes virus encephalitis

Molecular Mechanisms in the Genesis of Seizures and Epilepsy Associated With Viral Infection

Contact Info

Product

Resources

About