Super‐refractory status epilepticus in autoimmune encephalitis treated with interleukin‐1 receptor antagonist, anakinra

Choi, Chun‐Ho; Ma, S.K.; Ky., Karen; Leung, Howan; Mok, Vincent

doi:10.1684/epd.2021.1283

Cited by 14 publications

(9 citation statements)

References 13 publications

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“…This hypothesis was corroborated by 8 (out of 11) subsequent case reports 37–42,45,46 . Anakinra was initiated at a median of 30 days (range = 12 days–12 weeks) after the onset of seizures.…”

Section: Acute Phasementioning

confidence: 62%

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Second‐line immunotherapy in new onset refractory status epilepticus

Hanin,

Muscal,

Hirsch

2024

Epilepsia

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Several pieces of evidence suggest immune dysregulation could trigger the onset and modulate sequelae of new onset refractory status epilepticus (NORSE), including its subtype with prior fever known as febrile infection‐related epilepsy syndrome (FIRES). Consensus‐driven recommendations have been established to guide the initiation of first‐ and second‐line immunotherapies in these patients. Here, we review the literature to date on second‐line immunotherapy for NORSE/FIRES, presenting results from 28 case reports and series describing the use of anakinra, tocilizumab, or intrathecal dexamethasone in 75 patients with NORSE. Among them, 52 patients were managed with anakinra, 21 with tocilizumab, and eight with intrathecal dexamethasone. Most had elevated serum or cerebrospinal fluid cytokine levels at treatment initiation. Treatments were predominantly initiated during the acute phase of the disease (92%) and resulted, within the first 2 weeks, in seizure control for up to 73% of patients with anakinra, 70% with tocilizumab, and 50% with intrathecal dexamethasone. Cytokine levels decreased after treatment for most patients. Anakinra and intrathecal dexamethasone were mainly initiated in children with FIRES, whereas tocilizumab was more frequently prescribed for adults, with or without a prior febrile infection. There was no clear correlation between the response to treatment and the time to initiate the treatment. Most patients experienced long‐term disability and drug‐resistant post‐NORSE epilepsy. Initiation of second‐line immunotherapies during status epilepticus (SE) had no clear effect on the emergence of post‐NORSE epilepsy or long‐term functional outcomes. In a small number of cases, the initiation of anakinra or tocilizumab several years after SE onset resulted in a reduction of seizure frequency for 67% of patients. These data highlight the potential utility of anakinra, tocilizumab, and intrathecal dexamethasone in patients with NORSE. There continues to be interest in the utilization of early cytokine measurements to guide treatment selection and response. Prospective studies are necessary to understand the role of early immunomodulation and its associations with epilepsy and functional outcomes.

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Section: Acute Phasementioning

confidence: 62%

“…This hypothesis was corroborated by 8 (out of 11) subsequent case reports. [37][38][39][40][41][42]45,46 Anakinra was initiated at a median of 30 days (range = 12 days-12 weeks) after the onset of seizures. All patients except one still had ongoing seizures when anakinra treatment commenced.…”

Section: Anakinramentioning

confidence: 99%

Second‐line immunotherapy in new onset refractory status epilepticus

Hanin,

Muscal,

Hirsch

2024

Epilepsia

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“…Its administration led to a substantial benefit in a patient with seronegative limbic encephalitis characterized by new-onset refractory status epilepticus. Improvement was noted soon after the last dose of anakinra and progressed over the next 2 weeks [28]. These results were not confirmed in a heterogeneous case series of autoinflammatory nervous system disorders, where improvement was noted in patients with an acute disseminated encephalomyelitislike phenotype but not in one case of seronegative autoimmune encephalitis [29,30].…”

Section: Anakinramentioning

confidence: 72%

Treatment Options in Refractory Autoimmune Encephalitis

2022

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Autoimmune encephalitis represents a potentially treatable immune-mediated condition that is being more frequently recognized. Prompt immunotherapy is a key factor for the management of autoimmune encephalitis. First-line treatments include intravenous steroids, plasma exchange, and intravenous immunoglobulins, which can be combined in most severe cases. Rituximab and cyclophosphamide are administered as second-line agents in unresponsive cases. A minority of patients may still remain refractory, thus representing a major clinical challenge. In these cases, treatment strategies are controversial, and no guidelines exist. Treatments proposed for refractory autoimmune encephalitis include (1) cytokine-based drugs (such as tocilizumab, interleukin-2/basiliximab, anakinra, and tofacitinib); (2) plasma cell-depleting agents (such as bortezomib and daratumumab); and (3) treatments targeting intrathecal immune cells or their trafficking through the blood-brain barrier (such as intrathecal methotrexate and natalizumab). The efficacy evidence of these drugs is mostly based on case reports or small case series, with few reported controlled studies or systematic reviews. The aim of the present review is to summarize the current evidence and related methodological issues in the use of these drugs for the treatment of refractory autoimmune encephalitis.

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“…The effect of anakinra has shown effective prevention in the development of epilepsy following inflammation-associated epileptic seizures in animal models [ 192 , 193 ]. One case involving a patient suffering from super refractory status epilepticus in AIE reported a reasonable recovery upon treatment with anakinra [ 194 ]. However, no clinical studies in AIE exist to date.…”

Section: Pharmacological Treatmentmentioning

confidence: 99%

Immune Mechanisms in Epileptogenesis: Update on Diagnosis and Treatment of Autoimmune Epilepsy Syndromes

Flammer

Neziraj

Rüegg

et al. 2023

Drugs

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Seizures and epilepsy can result from various aetiologies, yet the underlying cause of several epileptic syndromes remains unclear. In that regard, autoimmune-mediated pathophysiological mechanisms have been gaining attention in the past years and were included as one of the six aetiologies of seizures in the most recent classification of the International League Against Epilepsy. The increasing number of anti-neuronal antibodies identified in patients with encephalitic disorders has contributed to the establishment of an immune-mediated pathophysiology in many cases of unclear aetiology of epileptic syndromes. Yet only a small number of patients with autoimmune encephalitis develop epilepsy in the proper sense where the brain transforms into a state where it will acquire the enduring propensity to produce seizures if it is not hindered by interventions. Hence, the term autoimmune epilepsy is often wrongfully used in the context of autoimmune encephalitis since most of the seizures are acute encephalitis-associated and will abate as soon as the encephalitis is in remission. Given the overlapping clinical presentation of immune-mediated seizures originating from different aetiologies, a clear distinction among the aetiological entities is crucial when it comes to discussing pathophysiological mechanisms, therapeutic options, and long-term prognosis of patients. Moreover, a rapid and accurate identification of patients with immune-mediated epilepsy syndromes is required to ensure an early targeted treatment and, thereby, improve clinical outcome. In this article, we review our current understanding of pathogenesis and critically discuss current and potential novel treatment options for seizures and epilepsy syndromes of underlying or suspected immune-mediated origin. We further outline the challenges in proper terminology.

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Super‐refractory status epilepticus in autoimmune encephalitis treated with interleukin‐1 receptor antagonist, anakinra

Cited by 14 publications

References 13 publications

Second‐line immunotherapy in new onset refractory status epilepticus

Second‐line immunotherapy in new onset refractory status epilepticus

Treatment Options in Refractory Autoimmune Encephalitis

Immune Mechanisms in Epileptogenesis: Update on Diagnosis and Treatment of Autoimmune Epilepsy Syndromes

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