Article type: Literature Review
Article title: Navigating the Complexity of Alternating Hemiplegia in Childhood: A Comprehensive Review
Journal: Rambam Maimonides Medical Journal
Year: 2024
Authors: Jamir Pitton Rissardo, Nilorfar Murtaza Vora, Yogendra Singh, Sweta Kishore, and Ana Letícia Fornari Caprara
E-mail: jamirrissardo@gmail.com
ABSTRACT
Alternating hemiplegia of childhood (AHC) is a complex neurodevelopmental disorder characterized by paroxysmal and transient events of unilateral or bilateral paresis, usually occurring before 18 months of age. Mutations in the ATP1A3 gene, mainly p.Asp801Asn, p.Glu815Lys, and p.Gly947Arg at the protein level, are found in around 80% of the individuals with AHC. Interestingly, these mutations reflect the degree of severity of the neurological symptoms (p.Glu815Lys > p.Asp801Asn > p.Gly947Arg). Some channels involved in this disorder are N-type voltage-gated calcium channels, ATP-sensitive potassium channels, and the sodium/calcium exchanger. In this context, the management of AHC should be divided into the treatment of attacks, prophylactic treatment, and management of comorbidities commonly found in this group of individuals, including epilepsy, attention-deficit/hyperactivity disorder, aggressive behavior, cognitive impairment, movement disorders, and migraine. The importance of an integrated approach with a multidisciplinary team, such as neuropsychologists and dietitians, is worth mentioning, as well as the follow-up with a neurologist. In the present study, we propose new diagnostic criteria for AHC, dividing it into clinical, laboratory, supporting, and atypical features. Also, we review the location of the mutations in the ATP1A3 protein of individuals with AHC, rapid-onset dystonia-parkinsonism (RDP) variants, and early infantile epileptic encephalopathy (variants with hemiplegic attack). We also include a section about the animal models for ATP1A3 disorders.
Keywords: aicardi; alternating hemiplegia of childhood; ATP1A2; ATP1A3; flunarizine; rare disease
Full text available at:
DOI
Citation
Rissardo JP, Vora NM, Singh Y, Kishore S, Caprara ALF. Navigating the Complexity of Alternating Hemiplegia in Childhood: A Comprehensive Review. Rambam Maimonides Med J 2024;15(3):e0015.
Figure 1. Location of Alternating Hemiplegia of Childhood (AHC) Variants in the ATP1A3 Protein, Including Rapid-onset Dystonia-parkinsonism (RDP) Variants and Early Infantile Epileptic Encephalopathy (EIEE) Variants with Hemiplegic Attack. Light orange = AHC variants; light blue = AHC and RDP variants; white = EIEE variants with hemiplegia.
Figure 3. Overlapping of AHC, CAPOS, and RDP. AHC, alternating hemiplegia of childhood; CAPOS, cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss; RDP, rapid-onset dystonia-parkinsonism.
Figure 5. ATP1A3 Spectrum Disorders. AHC, alternating hemiplegia of childhood; CAPOS, cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss syndrome; COS, childhood-onset schizophrenia; EIEE, early infantile epileptic encephalopathy; FIPWE, fever-induced paroxysmal weakness and encephalopathy; RDP, rapid-onset dystonia-parkinsonism; RECA, relapsing encephalopathy with cerebellar ataxia.
Table 1. Frequency of Alternating Hemiplegia of Childhood Variants in Different Cohorts.
Table 2. Diagnostic Criteria for Alternating Hemiplegia of Childhood Proposed by Rissardo et al.
Table 4. Clinical Features of Atypical Cases of Alternating Hemiplegia of Childhood (AHC).
Table 5. Management of Disorders Commonly Found in Patients with Alternating Hemiplegia of Childhood.
Table 6. Medications Used in the Management of Alternating Hemiplegia of Childhood.
Table 7. Summary of Pre-clinical Mouse Models of ATP1A3-related Disorders.