Biochemical mechanisms in pathogenesis of infantile epileptic spasm syndrome. (February 2023)

• Record Type: Journal Article
• Authors: Riikonen, Raili
• Is Part Of: Seizure. Volume 105(2023)
• Page Start: 1
• Page End: 9
• Publication Date: 2023-02
• Subjects: West syndrome -- Infantile spasms -- Infantile epileptic spasms syndrome -- Developmental delay -- Molecular mechanisms -- Brain maturation; Epilepsy -- Periodicals; Epilepsy -- Periodicals; Seizures -- Periodicals; Épilepsie -- Périodiques; Electronic journals; Electronic journals; 616.853
• DOI: 10.1016/j.seizure.2023.01.004
• Languages: English
• ISSNs: 1059-1311

Abstract

Highlights: The molecular mechanisms leading to IESS and developmental delay remain obscure. The current literature and data on Finnish IESS patients are reviewed. IESS is characterized by an imbalance of inhibitory, (NGF, IGF-1, ACTH, GABA), and excitatory (glutamate, nitrites), factors, (2) an abnormality of the hypothalamic-pituitary-adrenal axis, (3) inflammation, (4) altered proliferation, migration, apoptosis, synaptogenesis and myelination of the brain. An interaction between the HPA axis, nerve growth factors and immune system was already shown by the Nobel Prize winner Rita Levi-Montalcini. An altered maturational process limited to a certain sensitive period of infancy could possibly explain why so many, seemingly independent etiological factors lead to the same clinical syndrome and developmental delay. Understanding these factors may lead to novel therapies. Abstract: The molecular mechanisms leading to infantile epileptic spasm syndrome (IESS) remain obscure. The only common factor seems to be that the spasms are restricted to a limited period of infancy, during a certain maturational state. Here the current literature regarding the biochemical mechanisms of brain maturation in IESS is reviewed, and various hypotheses of the pathophysiology are put together. They include: (1) imbalance of inhibitory (NGF, IGF-1, ACTH, GABA) and excitatory factors (glutamate, nitrites) which distinguishes the different etiological subgroups, (2) abnormality of the hypothalamic pituitary adrenal (HPA) axis linking insults and early life stress, (3) inflammation (4) yet poorly known genetic and epigenetic factors, and (5) glucocorticoid and vigabatrin action on brain development, pinpointing at molecular targets of the pathophysiology from another angle. An altered maturational process may explain why so many, seemingly independent etiological factors lead to the same clinical syndrome and frequently to developmental delay. Understanding these factors can provide ideas for novel therapies.