Towards a Treatment for Neuroinflammation in Epilepsy: Interleukin-1 Receptor Antagonist, Anakinra, as a Potential Treatment in Intractable Epilepsy
Abstract
:1. Introduction
2. Materials and Methods
3. Clinical Findings
3.1. Anakinra for FIRES
3.1.1. Case Study
3.1.2. Cohort Study
3.1.3. FIRES Cases Refractory to Anakinra
3.1.4. Adverse Events of Anakinra
3.2. Anakinra for DRE
4. Scientific Findings
4.1. Cytokine Analysis of Clinical Cases
4.2. IL-1RA-Mediated Regulation of Epileptogenesis
4.3. Potential Indicator of Anakinra Administration
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Ethical Considerations
References
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Case * /Ref. | Onset Age (Years)/Sex | ASM | Special Additions | Sz Onset to Anakinra (Days) | Anakinra Dose (mg/kg/Day) | Anakinra Duration (Days) |
---|---|---|---|---|---|---|
4/[44] | 5/M | PB, MDZ, TH, KETA, CBD | KD CMN-DBS | 22 | titrated up to 10 mg/kg/day | 90 |
6/[40] | 6/M | LEV, PHT, PB, MDZ, KE, PENT, VPA, TPM, CBD, LZP | IVIg, steroid, Tocilizumab, KD | 6 | titrated to 20 mg/kg/day | 15 |
9/[43] | 9/M | MDZ, PENT, LID, CBD, DBS | IVIg, steroid, PE, KD | 42 | 4 mg/kg/day | >114 |
10/[43] | 5/M | MDZ, PENT, LID, KE, CBD, DBS | IVIg, steroid, PE, KD | 21 | 10 mg/kg/day | >124 |
24/[43] | 8/M | MDZ, PENT, CBD | IVIg, steroid, HYPO | 6 | 3.8 mg/kg/day | 9 |
32/[43] | 4/M | MDZ, PENT, KE, CBD | IVIg, steroid, PE, rituximab | 33 | 5 mg/kg/day | 5 |
Case/Ref. | Clinical Diagnosis of Epilepsy | Onset Age (Years)/Sex | ASM */Special Additions | Sz Onset to Anakinra (Years) | Anakinra Dose (mg/kg/Day) | Clinical Findings | Developmental Prognosis |
---|---|---|---|---|---|---|---|
1/[34] | (1) focal onset impaired awareness (2) unknown onset tonic -clonic | 13/M | IVIG, VNS | 4 | 2 mg/kg/day → 4 mg/kg/day | decreased grand mal seizures from 1–2x/week to 1x/3–4 weeks | More alert, expressive, and attentive, with improved social interactions and three-dimensional vision. |
2/[34] | (1) focal onset impaired awareness (2) unknown onset tonic -clonic | 8/F | IVIG, Steroid | 2 | 3 mg/kg/day | seizure-free for 1 year while receiving 100 mg of anakinra. When reduced to 75 mg, cluster seizures occurred. | ND |
3/[34] | Landau-Kleffner syndrome | 6/M | IVIG, Steroid, VNS | 4 | 3 mg/kg/day | Thalidomide and VNS reduced seizure frequency until discontinuation due to adverse reactions. Seizures resolved with addition of anakinra for over 4 years | Improvement in motor skills and cognitive skills. Photophobia and persistently dilated pupils also resolved. |
4/[34] | ND | 9/M | IVIG, Steroid | 1 | 1.5 mg/kg/day | decreased grand mal seizure once a year | Improved cognitive skills (more attentive and focused), reduced irritability, and hyperactivity. |
5/[35] | Generalized onset absence | 14/F | dexamethasone | ND | 100 mg daily → 100 mg/day twice daily | 100 mg of anakinra once daily, 80% reduction in seizure frequency 100 mg twice daily, no clinically evident seizures for two months. | Profound improvements in her fatigue, general malaise, quality of life, and academic performance |
6/[36] | ESES (nocturnal seizure) | 6/M | IVIG, Steroid, mTOR | 2 | 100 mg/day | reduced behavioural symptoms, but not the ESES pattern (N60% SWI in all areas). Adding Sirolimus for 7 weeks improved the ESES pattern on EEG. | Hyperlexia and echolalia remained |
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Yamanaka, G.; Ishida, Y.; Kanou, K.; Suzuki, S.; Watanabe, Y.; Takamatsu, T.; Morichi, S.; Go, S.; Oana, S.; Yamazaki, T.; et al. Towards a Treatment for Neuroinflammation in Epilepsy: Interleukin-1 Receptor Antagonist, Anakinra, as a Potential Treatment in Intractable Epilepsy. Int. J. Mol. Sci. 2021, 22, 6282. https://doi.org/10.3390/ijms22126282
Yamanaka G, Ishida Y, Kanou K, Suzuki S, Watanabe Y, Takamatsu T, Morichi S, Go S, Oana S, Yamazaki T, et al. Towards a Treatment for Neuroinflammation in Epilepsy: Interleukin-1 Receptor Antagonist, Anakinra, as a Potential Treatment in Intractable Epilepsy. International Journal of Molecular Sciences. 2021; 22(12):6282. https://doi.org/10.3390/ijms22126282
Chicago/Turabian StyleYamanaka, Gaku, Yu Ishida, Kanako Kanou, Shinji Suzuki, Yusuke Watanabe, Tomoko Takamatsu, Shinichiro Morichi, Soken Go, Shingo Oana, Takashi Yamazaki, and et al. 2021. "Towards a Treatment for Neuroinflammation in Epilepsy: Interleukin-1 Receptor Antagonist, Anakinra, as a Potential Treatment in Intractable Epilepsy" International Journal of Molecular Sciences 22, no. 12: 6282. https://doi.org/10.3390/ijms22126282