Journal of Pediatric Neurology 2023; 21(04): 320-327
DOI: 10.1055/s-0041-1727140
Review Article

Aristaless-Related Homeobox (ARX): Epilepsy Phenotypes beyond Lissencephaly and Brain Malformations

Bruna Scalia
1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Valeria Venti
1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Lina M. Ciccia
1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Roberta Criscione
1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Manuela Lo Bianco
1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Laura Sciuto
1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Raffaele Falsaperla
2   Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy
3   Neonatal Intensive Care unit and Neonatology, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy
,
Antonio Zanghì
4   Department of Medical and Surgical Sciences and Advanced Technology “G.F. Ingrassia,” University of Catania, Catania, Italy
,
5   Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
› Author Affiliations

Abstract

The Aristaless-related homeobox (ARX) transcription factor is involved in the development of GABAergic and cholinergic neurons in the forebrain. ARX mutations have been associated with a wide spectrum of neurodevelopmental disorders in humans and are responsible for both malformation (in particular lissencephaly) and nonmalformation complex phenotypes. The epilepsy phenotypes related to ARX mutations are West syndrome and X-linked infantile spasms, X-linked myoclonic epilepsy with spasticity and intellectual development and Ohtahara and early infantile epileptic encephalopathy syndrome, which are related in most of the cases to intellectual disability and are often drug resistant. In this article, we shortly reviewed current knowledge of the function of ARX with a particular attention on its consequences in the development of epilepsy during early childhood.



Publication History

Received: 20 February 2021

Accepted: 21 February 2021

Article published online:
13 April 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Bienvenu T, Poirier K, Friocourt G. et al. ARX, a novel Prd-class-homeobox gene highly expressed in the telencephalon, is mutated in X-linked mental retardation. Hum Mol Genet 2002; 11 (08) 981-991
  • 2 Miura H, Yanazawa M, Kato K, Kitamura K. Expression of a novel aristaless related homeobox gene ‘ARX’ in the vertebrate telencephalon, diencephalon and floor plate. Mech Dev 1997; 65 (1-2): 99-109
  • 3 Meijlink F, Beverdam A, Brouwer A, Oosterveen TC, Berge DT. Vertebrate aristaless-related genes. Int J Dev Biol 1999; 43 (07) 651-663
  • 4 Ekşioğlu YZ, Pong AW, Takeoka M. A novel mutation in the aristaless domain of the ARX gene leads to Ohtahara syndrome, global developmental delay, and ambiguous genitalia in males and neuropsychiatric disorders in females. Epilepsia 2011; 52 (05) 984-992
  • 5 Tapie A, Pi-Denis N, Souto J. et al. A novel mutation in the OAR domain of the ARX gene. Clin Case Rep 2017; 5 (02) 170-174
  • 6 Giordano L, Sartori S, Russo S. et al. Familial Ohtahara syndrome due to a novel ARX gene mutation. Am J Med Genet A 2010; 152A (12) 3133-3137
  • 7 Sirisena ND, McElreavey K, Bashamboo A, de Silva KS, Jayasekara RW, Dissanayake VH. A child with a novel de novo mutation in the aristaless domain of the aristaless-related homeobox (ARX) gene presenting with ambiguous genitalia and psychomotor delay. Sex Dev 2014; 8 (04) 156-159
  • 8 Fullston T, Brueton L, Willis T. et al. Ohtahara syndrome in a family with an ARX protein truncation mutation (c.81C>G/p.Y27X). Eur J Hum Genet 2010; 18 (02) 157-162
  • 9 Ruggieri M, McShane MA. Parental view of epilepsy in Angelman syndrome: a questionnaire study. Arch Dis Child 1998; 79 (05) 423-426
  • 10 Brancati F, Travaglini L, Zablocka D. et al; International JSRD Study Group. RPGRIP1L mutations are mainly associated with the cerebello-renal phenotype of Joubert syndrome-related disorders. Clin Genet 2008; 74 (02) 164-170
  • 11 Ruggieri M, Iannetti P, Pavone L. Delineation of a newly recognized neurocutaneous malformation syndrome with “cutis tricolor”. Am J Med Genet A 2003; 120A (01) 110-116
  • 12 Pavone P, Briuglia S, Falsaperla R. et al. Wide spectrum of congenital anomalies including choanal atresia, malformed extremities, and brain and spinal malformations in a girl with a de novo 5.6-Mb deletion of 13q12.11-13q12.13. Am J Med Genet A 2014; 164A (07) 1734-1743
  • 13 Pavone P, Praticò AD, Ruggieri M. et al. Acquired peripheral neuropathy: a report on 20 children. Int J Immunopathol Pharmacol 2012; 25 (02) 513-517
  • 14 Pavone P, Falsaperla R, Ruggieri M, Praticò AD, Pavone L. West syndrome treatment: new roads for an old syndrome. Front Neurol 2013; 4: 113
  • 15 Kato M, Koyama N, Ohta M, Miura K, Hayasaka K. Frameshift mutations of the ARX gene in familial Ohtahara syndrome. Epilepsia 2010; 51 (09) 1679-1684
  • 16 Shoubridge C, Fullston T, Gécz J. ARX spectrum disorders: making inroads into the molecular pathology. Hum Mutat 2010; 31 (08) 889-900
  • 17 McKenzie O, Ponte I, Mangelsdorf M. et al. Aristaless-related homeobox gene, the gene responsible for West syndrome and related disorders, is a Groucho/transducin-like enhancer of split dependent transcriptional repressor. Neuroscience 2007; 146 (01) 236-247
  • 18 Colasante G, Sessa A, Crispi S. et al. ARX acts as a regional key selector gene in the ventral telencephalon mainly through its transcriptional repression activity. Dev Biol 2009; 334 (01) 59-71
  • 19 Friocourt G, Kanatani S, Tabata H. et al. Cell-autonomous roles of ARX in cell proliferation and neuronal migration during corticogenesis. J Neurosci 2008; 28 (22) 5794-5805
  • 20 Fullenkamp AN, El-Hodiri HM. The function of the Aristaless-related homeobox (ARX) gene product as a transcriptional repressor is diminished by mutations associated with X-linked mental retardation (XLMR). Biochem Biophys Res Commun 2008; 377 (01) 73-78
  • 21 Salpietro V, Polizzi A, Bertè LF. et al. Idiopathic intracranial hypertension: a unifying neuroendocrine hypothesis through the adrenal-brain axis. Neuroendocrinol Lett 2012; 33 (06) 569-573
  • 22 O'Connor KC, Lopez-Amaya C, Gagne D. et al. Anti-myelin antibodies modulate clinical expression of childhood multiple sclerosis. J Neuroimmunol 2010; 223 (1-2): 92-99
  • 23 Salpietro V, Polizzi A, Di Rosa G. et al. Adrenal disorders and the paediatric brain: pathophysiological considerations and clinical implications. Int J Endocrinol 2014; 2014: 282489
  • 24 Colombo E, Galli R, Cossu G, Gécz J, Broccoli V. Mouse orthologue of ARX, a gene mutated in several X-linked forms of mental retardation and epilepsy, is a marker of adult neural stem cells and forebrain GABAergic neurons. Dev Dyn 2004; 231 (03) 631-639
  • 25 Vogt D, Hunt RF, Mandal S. et al. Lhx6 directly regulates ARX and CXCR7 to determine cortical interneuron fate and laminar position. Neuron 2014; 82 (02) 350-364
  • 26 Sandberg M, Flandin P, Silberberg S. et al. Transcriptional networks controlled by NKX2–1 in the development of forebrain gabaergic neurons. Neuron 2016; 91 (06) 1260-1275
  • 27 Poirier K, Van Esch H, Friocourt G. et al. Neuroanatomical distribution of ARX in brain and its localisation in GABAergic neurons. Brain Res Mol Brain Res 2004; 122 (01) 35-46
  • 28 Collombat P, Hecksher-Sørensen J, Broccoli V. et al. The simultaneous loss of ARX and Pax4 genes promotes a somatostatin-producing cell fate specification at the expense of the alpha- and beta-cell lineages in the mouse endocrine pancreas. Development 2005; 132 (13) 2969-2980
  • 29 Marsh ED, Nasrallah MP, Walsh C. et al. Developmental interneuron subtype deficits after targeted loss of ARX . BMC Neurosci 2016; 17 (01) 35
  • 30 Mattiske T, Lee K, Gecz J, Friocourt G, Shoubridge C. Embryonic forebrain transcriptome of mice with polyalanine expansion mutations in the ARX homeobox gene. Hum Mol Genet 2016; 25 (24) 5433-5443
  • 31 Siehr MS, Massey CA, Noebels JL. ARX expansion mutation perturbs cortical development by augmenting apoptosis without activating innate immunity in a mouse model of X-linked infantile spasms syndrome. Dis Model Mech 2020; 13 (03) dmm042515
  • 32 Polling S, Ormsby AR, Wood RJ. et al. Polyalanine expansions drive a shift into α-helical clusters without amyloid-fibril formation. Nat Struct Mol Biol 2015; 22 (12) 1008-1015
  • 33 Marcorelles P, Laquerrière A, Adde-Michel C. et al. Evidence for tangential migration disturbances in human lissencephaly resulting from a defect in LIS1, DCX and ARX genes. Acta Neuropathol 2010; 120 (04) 503-515
  • 34 Salpietro V, Mankad K, Kinali M. et al. Pediatric idiopathic intracranial hypertension and the underlying endocrine-metabolic dysfunction: a pilot study. J Pediatr Endocrinol Metab 2014; 27 (1-2): 107-115
  • 35 Pavone P, Praticò AD, Falsaperla R. et al. Congenital generalized hypertrichosis: the skin as a clue to complex malformation syndromes. Ital J Pediatr 2015; 41: 55
  • 36 Pavone V, Signorelli SS, Praticò AD. et al. Total hemi-overgrowth in pigmentary mosaicism of the (hypomelanosis of) ito type: eight case reports. Medicine (Baltimore) 2016; 95 (10) e2705
  • 37 Beguin S, Crépel V, Aniksztejn L. et al. An epilepsy-related ARX polyalanine expansion modifies glutamatergic neurons excitability and morphology without affecting GABAergic neurons development. Cereb Cortex 2013; 23 (06) 1484-1494
  • 38 Lee K, Ireland K, Bleeze M, Shoubridge C. ARX polyalanine expansion mutations lead to migration impediment in the rostral cortex coupled with a developmental deficit of calbindin-positive cortical GABAergic interneurons. Neuroscience 2017; 357: 220-231
  • 39 Ruggieri M. Cutis tricolor: congenital hyper- and hypopigmented lesions in a background of normal skin with and without associated systemic features: further expansion of the phenotype. Eur J Pediatr 2000; 159 (10) 745-749
  • 40 Ruggieri M, Polizzi A, Pavone L, Musumeci S. Thalamic syndrome in children with measles infection and selective, reversible thalamic involvement. Pediatrics 1998; 101 (1 Pt 1): 112-119
  • 41 Guerrini R, Moro F, Kato M. et al. Expansion of the first PolyA tract of ARX causes infantile spasms and status dystonicus. Neurology 2007; 69 (05) 427-433
  • 42 Kitamura K, Yanazawa M, Sugiyama N. et al. Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans. Nat Genet 2002; 32 (03) 359-369
  • 43 Strømme P, Mangelsdorf ME, Shaw MA. et al. Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy. Nat Genet 2002; 30 (04) 441-445
  • 44 Bonneau D, Toutain A, Laquerrière A. et al. X-linked lissencephaly with absent corpus callosum and ambiguous genitalia (XLAG): clinical, magnetic resonance imaging, and neuropathological findings. Ann Neurol 2002; 51 (03) 340-349
  • 45 Proud VK, Levine C, Carpenter NJ. New X-linked syndrome with seizures, acquired micrencephaly, and agenesis of the corpus callosum. Am J Med Genet 1992; 43 (1-2): 458-466
  • 46 Kato M, Das S, Petras K. et al. Mutations of ARX are associated with striking pleiotropy and consistent genotype-phenotype correlation. Hum Mutat 2004; 23 (02) 147-159
  • 47 Pavone P, Praticò AD, Vitaliti G. et al. Hydranencephaly: cerebral spinal fluid instead of cerebral mantles. Ital J Pediatr 2014; 40: 79
  • 48 Ruggieri M, Milone P, Pavone P. et al. Nevus vascularis mixtus (cutaneous vascular twin nevi) associated with intracranial vascular malformation of the Dyke-Davidoff-Masson type in two patients. Am J Med Genet A 2012; 158A (11) 2870-2880
  • 49 Demos MK, Fullston T, Partington MW, Gécz J, Gibson WT. Clinical study of two brothers with a novel 33 bp duplication in the ARX gene. Am J Med Genet A 2009; 149A (07) 1482-1486
  • 50 Partington MW, Mulley JC, Sutherland GR, Hockey A, Thode A, Turner G. X-linked mental retardation with dystonic movements of the hands. Am J Med Genet 1988; 30 (1-2): 251-262
  • 51 Turner G, Partington M, Kerr B, Mangelsdorf M, Gecz J. Variable expression of mental retardation, autism, seizures, and dystonic hand movements in two families with an identical ARX gene mutation. Am J Med Genet 2002; 112 (04) 405-411
  • 52 Praticò AD, Polizzi A, Salafia R. et al. Megalencephaly capillary malformation syndrome. J Pediatr Neurol 2018; 16: 328-337
  • 53 Scheffer IE, Wallace RH, Phillips FL. et al. X-linked myoclonic epilepsy with spasticity and intellectual disability: mutation in the homeobox gene ARX . Neurology 2002; 59 (03) 348-356
  • 54 Strømme P, Mangelsdorf ME, Scheffer IE, Gécz J. Infantile spasms, dystonia, and other X-linked phenotypes caused by mutations in Aristaless related homeobox gene, ARX . Brain Dev 2002; 24 (05) 266-268
  • 55 Absoud M, Parr JR, Halliday D, Pretorius P, Zaiwalla Z, Jayawant S. A novel ARX phenotype: rapid neurodegeneration with Ohtahara syndrome and a dyskinetic movement disorder. Dev Med Child Neurol 2010; 52 (03) 305-307
  • 56 Kato M, Saitoh S, Kamei A. et al. A longer polyalanine expansion mutation in the ARX gene causes early infantile epileptic encephalopathy with suppression-burst pattern (Ohtahara syndrome). Am J Hum Genet 2007; 81 (02) 361-366
  • 57 Lionetti E, Francavilla R, Maiuri L. et al. Headache in pediatric patients with celiac disease and its prevalence as a diagnostic clue. J Pediatr Gastroenterol Nutr 2009; 49 (02) 202-207
  • 58 Spinosa MJ, Liberalesso PB, Vieira SC, Olmos AS, Löhr Jr A. Lissencephaly, abnormal genitalia and refractory epilepsy: case report of XLAG syndrome. Arq Neuropsiquiatr 2006; 64 (04) 1023-1026
  • 59 Uyanik G, Aigner L, Martin P. et al. ARX mutations in X-linked lissencephaly with abnormal genitalia. Neurology 2003; 61 (02) 232-235
  • 60 Mirzaa GM, Paciorkowski AR, Marsh ED. et al. CDKL5 and ARX mutations in males with early-onset epilepsy. Pediatr Neurol 2013; 48 (05) 367-377
  • 61 Michaud JL, Lachance M, Hamdan FF. et al. The genetic landscape of infantile spasms. Hum Mol Genet 2014; 23 (18) 4846-4858
  • 62 Ruggieri M, Gabriele AL, Polizzi A. et al. Natural history of neurofibromatosis type 2 with onset before the age of 1 year. Neurogenetics 2013; 14 (02) 89-98
  • 63 Gorman KM, Cary H, Gaffney L. et al. Status dystonicus due to missense variant in ARX: diagnosis and management. Eur J Paediatr Neurol 2018; 22 (05) 862-865
  • 64 Poirier K, Eisermann M, Caubel I. et al. Combination of infantile spasms, non-epileptic seizures and complex movement disorder: a new case of ARX-related epilepsy. Epilepsy Res 2008; 80 (2-3): 224-228
  • 65 Shinozaki Y, Osawa M, Sakuma H. et al. Expansion of the first polyalanine tract of the ARX gene in a boy presenting with generalized dystonia in the absence of infantile spasms. Brain Dev 2009; 31 (06) 469-472
  • 66 Kwong AK, Chu VL, Rodenburg RJT, Smeitink J, Fung CW. ARX-associated infantile epileptic-dyskinetic encephalopathy with responsiveness to valproate for controlling seizures and reduced activity of muscle mitochondrial complex IV. Brain Dev 2019; 41 (10) 883-887
  • 67 Ruggieri M, Praticò AD, Serra A. et al. Childhood neurofibromatosis type 2 (NF2) and related disorders: from bench to bedside and biologically targeted therapies. Acta Otorhinolaryngol Ital 2016; 36 (05) 345-367
  • 68 Falsaperla R, Perciavalle V, Pavone P. et al. Unilateral eye blinking arising from the ictal ipsilateral occipital area. Clin EEG Neurosci 2016; 47 (03) 243-246
  • 69 Incorpora G, Pavone P, Castellano-Chiodo D, Praticò AD, Ruggieri M, Pavone L. Gelastic seizures due to hypothalamic hamartoma: rapid resolution after endoscopic tumor disconnection. Neurocase 2013; 19 (05) 458-461
  • 70 Marsh E, Fulp C, Gomez E. et al. Targeted loss of ARX results in a developmental epilepsy mouse model and recapitulates the human phenotype in heterozygous females. Brain 2009; 132 (Pt 6): 1563-1576
  • 71 Wallerstein R, Sugalski R, Cohn L, Jawetz R, Friez M. Expansion of the ARX spectrum. Clin Neurol Neurosurg 2008; 110 (06) 631-634
  • 72 Friocourt G, Parnavelas JG. Mutations in ARX result in several defects involving GABAergic neurons. Front Cell Neurosci 2010; 4: 4
  • 73 Friocourt G, Poirier K, Rakić S, Parnavelas JG, Chelly J. The role of ARX in cortical development. Eur J Neurosci 2006; 23 (04) 869-876
  • 74 Okazaki S, Ohsawa M, Kuki I. et al. Aristaless-related homeobox gene disruption leads to abnormal distribution of GABAergic interneurons in human neocortex: evidence based on a case of X-linked lissencephaly with abnormal genitalia (XLAG). Acta Neuropathol 2008; 116 (04) 453-462
  • 75 Bettella E, Di Rosa G, Polli R. et al. Early-onset epileptic encephalopathy in a girl carrying a truncating mutation of the ARX gene: rethinking the ARX phenotype in females. Clin Genet 2013; 84 (01) 82-85
  • 76 Kwong AK-Y, Ho AC-C, Fung C-W, Wong VC-N. Analysis of mutations in 7 genes associated with neuronal excitability and synaptic transmission in a cohort of children with non-syndromic infantile epileptic encephalopathy. PLoS One 2015; 10 (05) e0126446
  • 77 Gécz J, Cloosterman D, Partington M. ARX: a gene for all seasons. Curr Opin Genet Dev 2006; 16 (03) 308-316
  • 78 Ruggieri M, Polizzi A, Spalice A. et al. The natural history of spinal neurofibromatosis: a critical review of clinical and genetic features. Clin Genet 2015; 87 (05) 401-410
  • 79 Ruggieri M, Polizzi A. Segmental neurofibromatosis. J Neurosurg 2000; 93 (03) 530-532
  • 80 Fullston T, Finnis M, Hackett A. et al. Screening and cell-based assessment of mutations in the Aristaless-related homeobox (ARX) gene. Clin Genet 2011; 80 (06) 510-522
  • 81 Wu G, Hao L, Han Z. et al. Maternal transmission ratio distortion at the mouse Om locus results from meiotic drive at the second meiotic division. Genetics 2005; 170 (01) 327-334
  • 82 Shoubridge C, Gardner A, Schwartz CE, Hackett A, Field M, Gecz J. Is there a Mendelian transmission ratio distortion of the c.429_452dup(24bp) polyalanine tract ARX mutation?. Eur J Hum Genet 2012; 20 (12) 1311-1314
  • 83 Reish O, Fullston T, Regev M, Heyman E, Gecz J. A novel de novo 27 bp duplication of the ARX gene, resulting from postzygotic mosaicism and leading to three severely affected males in two generations. Am J Med Genet A 2009; 149A (08) 1655-1660
  • 84 Poirier K, Abriol J, Souville I. et al. Maternal mosaicism for mutations in the ARX gene in a family with X linked mental retardation. Hum Genet 2005; 118 (01) 45-48
  • 85 Ruggieri M, Tigano G, Mazzone D, Tiné A, Pavone L. Involvement of the white matter in hypomelanosis of Ito (incontinentia pigmenti achromiens). Neurology 1996; 46 (02) 485-492
  • 86 Moey C, Topper S, Karn M. et al. Reinitiation of mRNA translation in a patient with X-linked infantile spasms with a protein-truncating variant in ARX . Eur J Hum Genet 2016; 24 (05) 681-689
  • 87 Ruggieri M, Huson SM. The neurofibromatoses. An overview. Ital J Neurol Sci 1999; 20 (02) 89-108
  • 88 Ruggieri M, Pavone V, De Luca D, Franzò A, Tiné A, Pavone L. Congenital bone malformations in patients with neurofibromatosis type 1 (Nf1). J Pediatr Orthop 1999; 19 (03) 301-305
  • 89 Ruggieri M, Polizzi A, Marceca GP, Catanzaro S, Praticò AD, Di Rocco C. Introduction to phacomatoses (neurocutaneous disorders) in childhood. Childs Nerv Syst 2020; 36 (10) 2229-2268
  • 90 Kato M. A new paradigm for West syndrome based on molecular and cell biology. Epilepsy Res 2006; 70 (Suppl. 01) S87-S95
  • 91 Marques I, Sá MJ, Soares G. et al. Unraveling the pathogenesis of ARX polyalanine tract variants using a clinical and molecular interfacing approach. Mol Genet Genomic Med 2015; 3 (03) 203-214
  • 92 Krey I, Krois-Neudenberger J, Hentschel J. et al. Genotype-phenotype correlation on 45 individuals with West syndrome. Eur J Paediatr Neurol 2020; 25: 134-138
  • 93 Barbagallo M, Ruggieri M, Incorpora G. et al. Infantile spasms in the setting of Sturge-Weber syndrome. Childs Nerv Syst 2009; 25 (01) 111-118
  • 94 Ruggieri M, Praticò AD, Serra A. et al. Early history of neurofibromatosis type 2 and related forms: earliest descriptions of acoustic neuromas, medical curiosities, misconceptions, landmarks and the pioneers behind the eponyms. Childs Nerv Syst 2017; 33 (04) 549-560
  • 95 Della Mina E, Borghesi A, Zhou H. et al. Inherited human IRAK-1 deficiency selectively impairs TLR signaling in fibroblasts. Proc Natl Acad Sci U S A 2017; 114 (04) E514-E523
  • 96 Vita G, Migliorato A, Baradello A. et al. Expression of cytoskeleton proteins in central core disease. J Neurol Sci 1994; 124 (01) 71-76
  • 97 Ruggieri M, Praticò AD, Scuderi A, Sorge G, Polizzi A. The multiple faces of artwork diagnoses. Lancet Neurol 2017; 16 (06) 417-418
  • 98 Ohya T, Nagai T, Araki Y. et al; Research Group on Adverse Effects of Vaccination in Patients with Neurological Disorders. A pilot study on the changes in immunity after ACTH therapy in patients with West syndrome. Brain Dev 2009; 31 (10) 739-743
  • 99 Partikian A, Mitchell WG. Major adverse events associated with treatment of infantile spasms. J Child Neurol 2007; 22 (12) 1360-1366
  • 100 Hamano S, Yamashita S, Tanaka M, Yoshinari S, Minamitani M, Eto Y. Therapeutic efficacy and adverse effects of adrenocorticotropic hormone therapy in west syndrome: differences in dosage of adrenocorticotropic hormone, onset of age, and cause. J Pediatr 2006; 148 (04) 485-488
  • 101 Praticò AD, Pavone P, Scuderi MG. et al. Symptomatic hypocalcemia in an epileptic child treated with valproic acid plus lamotrigine: a case report. Cases J 2009; 2: 7394
  • 102 Pratico AD, Longo L, Mansueto S. et al. Off-label use of drugs and adverse drug reactions in pediatric units: a prospective, multicenter study. Curr Drug Saf 2018; 13 (03) 200-207
  • 103 Pratico AD, Ruggieri M, Falsaperla R, Pavone P. A probable topiramate-induced limbs paraesthesia and rigid fingers flexion. Curr Drug Saf 2018; 13 (02) 131-136
  • 104 Falsaperla R, D'Angelo G, Praticò AD. et al. Ketogenic diet for infants with epilepsy: a literature review. Epilepsy Behav 2020; 112: 107361
  • 105 Ruggieri M, Rizzo R, Pavone P, Baieli S, Sorge G, Happle R. Temporal triangular alopecia in association with mental retardation and epilepsy in a mother and daughter. Arch Dermatol 2000; 136 (03) 426-427
  • 106 Ruggieri M, Iannetti P, Clementi M. et al. Neurofibromatosis type 1 and infantile spasms. Childs Nerv Syst 2009; 25 (02) 211-216
  • 107 Galanopoulou AS, Moshé SL. Pathogenesis and new candidate treatments for infantile spasms and early life epileptic encephalopathies: a view from preclinical studies. Neurobiol Dis 2015; 79: 135-149
  • 108 Olivetti PR, Maheshwari A, Noebels JL. Neonatal estradiol stimulation prevents epilepsy in ARX model of X-linked infantile spasms syndrome. Sci Transl Med 2014; 6 (220) 220ra12