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Revision of the diagnostic criteria of alternating hemiplegia of childhood

2021; Elsevier BV; Volume: 32; Linguagem: Inglês

10.1016/j.ejpn.2021.05.004

1532-2130

Mohamad A. Mikati, Eleni Panagiotakaki, Alexis Arzimanoglou,

Ion Transport and Channel Regulation

Alternating Hemiplegia of Childhood (AHC) is a severe pediatric neurological disorder [ 1 Bourgeois M. Aicardi J. Goutières F. Alternating hemiplegia of childhood. J. Pediatr. 1993; 122: 673-679 Abstract Full Text PDF PubMed Scopus (168) Google Scholar , 2 Mikati M.A. Maguire H. Barlow C.F. Ozelius L. Breakefield X.O. Klauck S.M. Korf B. O'Tuama S.L. Dangond F. A syndrome of autosomal dominant alternating hemiplegia: clinical presentation mimicking intractable epilepsy; chromosomal studies; and physiologic investigations. Neurology. 1992 Dec; 42 (PMID: 1361034): 2251-2257https://doi.org/10.1212/wnl.42.12.2251 Crossref PubMed Scopus (73) Google Scholar , 3 Mikati M.A. Kramer U. Zupanc M.L. Shanahan R.J. Alternating hemiplegia of childhood: clinical manifestations and long-term outcome. Pediatr. Neurol. 2000; 23: 134-141 Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar , 4 Panagiotakaki E. Gobbi G. Neville B. et al. Evidence of a non-progressive course of alternating hemiplegia of childhood: study of a large cohort of children and adults. Brain. 2010; 133: 3598-3610 Crossref PubMed Scopus (118) Google Scholar , 5 Vuillaumier-Barrot S. Panagiotakaki E. Le Bizec C. El Baba C. Fontaine B. Arzimanoglou A. Seta N. Nicole S. ENRAHs for SME ConsortiumAbsence of mutation in the SLC2A1 gene in a cohort of patients with alternating hemiplegia of childhood (AHC). Neuropediatrics. 2010 Dec; 41 (Epub 2011 Mar 28. PMID: 21445818): 267-269https://doi.org/10.1055/s-0031-1271767 Crossref PubMed Scopus (13) Google Scholar , 6 Fons C. Campistol J. Panagiotakaki E. Giannotta M. Arzimanoglou A. Gobbi G. Neville B. Ebinger F. Nevšímalová S. Laan L. Casaer P. Spiel G. Ninan M. Sange G. Artuch R. Schyns T. Vavassori R. Poncelin D. ENRAH ConsortiumAlternating hemiplegia of childhood: metabolic studies in the largest European series of patients. Eur. J. Paediatr. Neurol. 2012 Jan; 16 (Epub 2011 Sep 25. PMID: 21945173): 10-14https://doi.org/10.1016/j.ejpn.2011.08.006 Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar , 7 Heinzen E.L. Swoboda K.J. Hitomi Y. et al. De novo mutations in ATP1A3 cause alternating hemiplegia of childhood. Nat. Genet. 2012; 44: 1030-1034 Crossref PubMed Scopus (296) Google Scholar , 8 Heinzen E.L. Arzimanoglou A. Brashear A. et al. Distinct neurological disorders with ATP1A3 mutations. Lancet Neurol. 2014; 13: 503-514 Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar , 9 Masoud M. Prange L. Wuchich J. Hunanyan A. Mikati M.A. Diagnosis and treatment of alternating hemiplegia of childhood. Curr. Treat. Options Neurol. 2017; 19: 8 Crossref PubMed Scopus (45) Google Scholar ]. It manifests a spectrum of manifestations some of which occur in most or all patients and the others occurring less frequently. These manifestations include paroxysmal events of hemiplegia, quadriplegia, dystonia, abnormal eye movements, autonomic dysfunction, altered awareness and epilepsy. AHC has an estimated prevalence of 1/1,000,000 children although this could be ten times higher [ [10] Hoei-Hansen C.E. Dali C.Í. Lyngbye T.J. Duno M. Uldall P. Alternating hemiplegia of childhood in Denmark: clinical manifestations and ATP1A3 mutation status. Eur. J. Paediatr. Neurol. 2014 Jan; 18 (Epub 2013 Sep 25. PMID: 24100174): 50-54https://doi.org/10.1016/j.ejpn.2013.08.007 Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar ], and approximately 75% of clinically-diagnosed cases are due to de novo mutations in the ATP1A3 gene. Tens of mutations have been described but the most common are the D801 N, then E815K and then G947R mutations [ 6 Fons C. Campistol J. Panagiotakaki E. Giannotta M. Arzimanoglou A. Gobbi G. Neville B. Ebinger F. Nevšímalová S. Laan L. Casaer P. Spiel G. Ninan M. Sange G. Artuch R. Schyns T. Vavassori R. Poncelin D. ENRAH ConsortiumAlternating hemiplegia of childhood: metabolic studies in the largest European series of patients. Eur. J. Paediatr. Neurol. 2012 Jan; 16 (Epub 2011 Sep 25. PMID: 21945173): 10-14https://doi.org/10.1016/j.ejpn.2011.08.006 Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar , 7 Heinzen E.L. Swoboda K.J. Hitomi Y. et al. De novo mutations in ATP1A3 cause alternating hemiplegia of childhood. Nat. Genet. 2012; 44: 1030-1034 Crossref PubMed Scopus (296) Google Scholar , 8 Heinzen E.L. Arzimanoglou A. Brashear A. et al. Distinct neurological disorders with ATP1A3 mutations. Lancet Neurol. 2014; 13: 503-514 Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar , 9 Masoud M. Prange L. Wuchich J. Hunanyan A. Mikati M.A. Diagnosis and treatment of alternating hemiplegia of childhood. Curr. Treat. Options Neurol. 2017; 19: 8 Crossref PubMed Scopus (45) Google Scholar , 10 Hoei-Hansen C.E. Dali C.Í. Lyngbye T.J. Duno M. Uldall P. Alternating hemiplegia of childhood in Denmark: clinical manifestations and ATP1A3 mutation status. Eur. J. Paediatr. Neurol. 2014 Jan; 18 (Epub 2013 Sep 25. PMID: 24100174): 50-54https://doi.org/10.1016/j.ejpn.2013.08.007 Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar ]. The diagnosis, before the gene discovery in 2012 was based on clinical criteria named after Professor Aicardi who articulated them in his publications and these were used to ascertain patients for the gene discovery work as well as for subsequent studies [ 1 Bourgeois M. Aicardi J. Goutières F. Alternating hemiplegia of childhood. J. Pediatr. 1993; 122: 673-679 Abstract Full Text PDF PubMed Scopus (168) Google Scholar , 2 Mikati M.A. Maguire H. Barlow C.F. Ozelius L. Breakefield X.O. Klauck S.M. Korf B. O'Tuama S.L. Dangond F. A syndrome of autosomal dominant alternating hemiplegia: clinical presentation mimicking intractable epilepsy; chromosomal studies; and physiologic investigations. Neurology. 1992 Dec; 42 (PMID: 1361034): 2251-2257https://doi.org/10.1212/wnl.42.12.2251 Crossref PubMed Scopus (73) Google Scholar , 3 Mikati M.A. Kramer U. Zupanc M.L. Shanahan R.J. Alternating hemiplegia of childhood: clinical manifestations and long-term outcome. Pediatr. Neurol. 2000; 23: 134-141 Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar , 4 Panagiotakaki E. Gobbi G. Neville B. et al. Evidence of a non-progressive course of alternating hemiplegia of childhood: study of a large cohort of children and adults. Brain. 2010; 133: 3598-3610 Crossref PubMed Scopus (118) Google Scholar , 5 Vuillaumier-Barrot S. Panagiotakaki E. Le Bizec C. El Baba C. Fontaine B. Arzimanoglou A. Seta N. Nicole S. ENRAHs for SME ConsortiumAbsence of mutation in the SLC2A1 gene in a cohort of patients with alternating hemiplegia of childhood (AHC). Neuropediatrics. 2010 Dec; 41 (Epub 2011 Mar 28. PMID: 21445818): 267-269https://doi.org/10.1055/s-0031-1271767 Crossref PubMed Scopus (13) Google Scholar , 6 Fons C. Campistol J. Panagiotakaki E. Giannotta M. Arzimanoglou A. Gobbi G. Neville B. Ebinger F. Nevšímalová S. Laan L. Casaer P. Spiel G. Ninan M. Sange G. Artuch R. Schyns T. Vavassori R. Poncelin D. ENRAH ConsortiumAlternating hemiplegia of childhood: metabolic studies in the largest European series of patients. Eur. J. Paediatr. Neurol. 2012 Jan; 16 (Epub 2011 Sep 25. PMID: 21945173): 10-14https://doi.org/10.1016/j.ejpn.2011.08.006 Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar , 7 Heinzen E.L. Swoboda K.J. Hitomi Y. et al. De novo mutations in ATP1A3 cause alternating hemiplegia of childhood. Nat. Genet. 2012; 44: 1030-1034 Crossref PubMed Scopus (296) Google Scholar , 8 Heinzen E.L. Arzimanoglou A. Brashear A. et al. Distinct neurological disorders with ATP1A3 mutations. Lancet Neurol. 2014; 13: 503-514 Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar , 9 Masoud M. Prange L. Wuchich J. Hunanyan A. Mikati M.A. Diagnosis and treatment of alternating hemiplegia of childhood. Curr. Treat. Options Neurol. 2017; 19: 8 Crossref PubMed Scopus (45) Google Scholar ] There were subsequent laudable adaptations of these criteria [ [11] Rosewich H. Sweney M.T. DeBrosse S. Ess K. Ozelius L. Andermann E. Andermann F. Andrasco G. Belgrade A. Brashear A. Ciccodicola S. Egan L. George Jr., A.L. Lewelt A. Magelby J. Merida M. Newcomb T. Platt V. Poncelin D. Reyna S. Sasaki M. Sotero de Menezes M. Sweadner K. Viollet L. Zupanc M. Silver K. Swoboda K. Research conference summary from the 2014 international task force on ATP1A3-related disorders. Neurol. Genet. 2017 Mar 2; 3 (PMID: 28293679; PMCID: PMC5335249): e139https://doi.org/10.1212/NXG.0000000000000139 Crossref PubMed Scopus (38) Google Scholar , [12] IHS Classification ICHD-3. International Headache Society, London2019ichd-3.org/appendix/a1-migraine/a1-6-episodic-syndromes-that-may-be-associated-with-migraine/a1-6-5-alternating-hemiplegia-of-childhood/ Google Scholar ]. However, the understanding of the spectrum of the clinical manifestations of AHC has been evolving suggesting that revisiting these criteria is warranted [ 13 Panagiotakaki E. De Grandis E. Stagnaro M. et al. Clinical profile of patients with ATP1A3 mutations in Alternating Hemiplegia of Childhood—a study of 155 patients. Orphanet J. Rare Dis. 2015; 10: 123 Crossref PubMed Scopus (107) Google Scholar , 14 Uchitel J. Helseth A. Prange L. et al. The epileptology of alternating hemiplegia of childhood. 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Fernández-Alvarez E. Willemsen M.A.A.P. Benign nocturnal alternating hemiplegia of childhood: a clinical and nomenclatural reappraisal. Eur. J. Paediatr. Neurol. 2018 Nov; 22 (Epub 2018 Aug 15. PMID: 30194039): 1110-1117https://doi.org/10.1016/j.ejpn.2018.07.012 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar , 25 Stagnaro M. Pisciotta L. Gherzi M. Di Rocco M. Gurrieri F. Parrini E. Prato G. Veneselli E. De Grandis E. ATP1A3 spectrum disorders: a video-documented history of 7 genetically confirmed early onset cases. Eur. J. Paediatr. Neurol. 2018 Mar; 22 (0.1016/j.ejpn.2018.01.010) (Epub 2018 Jan 31. PMID: 29396171): 264-271 Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar ]. Also, the presence of the ATP1A3 mutations is important to include in a revision of the AHC diagnostic criteria. In addition, there is often confusion in the literature in which patients who have had episodes of hemiplegia on either side and are children are considered to have AHC. The point is that not every alternating hemiplegia during childhood is alternating hemiplegia of childhood. The first i.e. hemiplegia that alternates sides, is a symptom the second, i.e. AHC, is a disorder.