Articles on AHC May-August 2015
SUMMARY OF ORIGINAL ARTICLES ON ALTERNATING HEMIPLEGIA OF CHILDHOOD
MAY - AUGUST 2015
Written by M. Mikati
|1.||Jaffer et al. (2015) analyzed ECG recordings of 52 patients with alternating hemiplegia from nine countries: all had whole-exome, whole-genome, or direct Sanger sequencing of ATP1A3. Half the cohort (26/52) had resting 12-lead electrocardiogram abnormalities: 25/26 had repolarization (T wave) abnormalities. These abnormalities were significantly more common in people with alternating hemiplegia than in an age-matched disease control group of 52 people with epilepsy. The average corrected QT interval was significantly shorter in people with alternating hemiplegia than in the disease control group. J wave or J-point changes were seen in six people with alternating hemiplegia. Additionally over half the affected cohort (28/52) had intraventricular conduction delay, or incomplete right bundle branch block, a much higher proportion than in the normal population or disease control cohort (P = 0.0164). Abnormalities in alternating hemiplegia were more common in those ≥16 years old, compared with those <16 (P = 0.0095), even with a specific mutation (p.D801N; P = 0.045). Dynamic, beat-to-beat or electrocardiogram-to- electrocardiogram, changes were noted, suggesting the prevalence of abnormalities was underestimated. Electrocardiogram changes occurred independently of seizures or plegic episodes.
The authors concluded that electrocardiogram abnormalities are common in alternating hemiplegia, have characteristics reflecting those of inherited cardiac channelopathies and most likely amount to impaired repolarization reserve. The dynamic electrocardiogram and neurological features point to periodic systemic decompensation in ATP1A3-expressing organs. Cardiac dysfunction may account for some of the unexplained premature mortality of alternating hemiplegia. Systematic cardiac investigation is warranted in alternating hemiplegia of childhood, as cardiac arrhythmic morbidity and mortality are potentially preventable.
|2.||Muriel et al. (2015) report a girl of 7 years-old with alternating hemiplegic who underwent testing using the Wechsler Intelligence Scale for Children IV (WISC-IV), the Conners Continuous Performance Test II (CPT-II), the Conners scales for parents (CPRS-48) and teachers (CTRS-28) and the Behavior Rating Inventory Executive Function (BRIEF). They found deficits in sustained attention, reduced speed of information processing, and difficulties in understanding, speaking and working memory. In addition, parents and teachers reported behavioral disturbances, difficulties inhibition capability, in self-control and in regulating emotions.|
|3.||Viollet et al. (2015) identified heterozygous ATP1A3 mutations in 154 of 187 (82%) AHC patients. Of 34 unique mutations, 31 (91%) were missense, and 16 (47%) had not been previously reported. Concordantwith prior studies, more than 2/3 of all mutations are clustered in exons 17 and 18. Of 143 simplex occurrences, 58 had D801N (40%), 38 had E815K (26%) and 11 had G937R (8%) mutations. Patients with an E815K mutation demonstrated an earlier age of onset, more severe motor impairment and a higher prevalence of status epilepticus.
This study further expanded the number and spectrum of ATP1A3 mutations associated with AHC and confirms a more deleterious effect of the E815K mutation on selected neurologic outcomes.
|1.||Jaffer F, Avbersek A, Vavassori R, Fons C, Campistol J, Stagnaro M, De Grandis E, Veneselli E, Rosewich H, Gianotta M, Zucca C, Ragona F, Granata T, Nardocci N, Mikati M, Helseth AR, Boelman C, Minassian BA, Johns S, Garry SI, Scheffer IE, Gourfinkel-An I, Carrilho I, Aylett SE, Parton M, Hanna MG, Houlden H, Neville B, Kurian MA, Novy J, Sander JW, Lambiase PD, Behr ER, Schyns T, Arzimanoglou A, Cross JH, Kaski JP, Sisodiya SM. Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype.
Brain. 2015 Aug 21. pii: awv243. [Epub ahead of print] PubMed PMID: 26297560 [PubMed - as supplied by publisher]
|6.||Muriel V, Garcia-Molina A, Aparicio-Lopez C, Ensenat A, Roig-Rovira T. Neuropsychological deficits in alternating hemiplegia of childhood: a case study.[Article in Spanish]
Rev Neurol. 2015 Jul 1;61(1):25-8. PMID: 26108905 [PubMed - in process]
|7.||Viollet L, Glusman G, Murphy KJ, Newcomb TM, Reyna SP, Sweney M, Nelson B, Andermann F, Andermann E, Acsadi G, Barbano RL, Brown C, Brunkow ME, Chugani HT, Cheyette SR, Collins A, DeBrosse SD, Galas D, Friedman J, Hood L, Huff C, Jorde LB, King MD, LaSalle B, Leventer RJ, Lewelt AJ, Massart MB, Mérida MR 2nd, Ptáček LJ, Roach JC, Rust RS, Renault F, Sanger TD, Sotero de Menezes MA, Tennyson R, Uldall P, Zhang Y, Zupanc M, Xin W, Silver K, Swoboda KJ. Alternating Hemiplegia of Childhood: Retrospective Genetic Study and Genotype-Phenotype Correlations in 187 Subjects from the US AHCF Registry.
PLoS One. 2015 May 21;10(5):e0127045. doi: 10.1371/journal.pone.0127045. eCollection 2015. PMID: 25996915 [PubMed - in process] PMCID: PMC4440742