THE EEGs OF INFANTS WITH CITRULLINEMIA

Abstract

SUMMARY Three female infants with citrullinemia were followed clinically, biochemically and by electroencephalography. All three had episodes of vomiting, lethargy and hyperammonemia shortly after birth. The two more severe cases developed convulsions. They were saved by peritoneal dialysis, or repeated exchange transfusions followed by dietary adjustment. Multifocal spikes or repetitive paroxysmal activity of various kinds were seen in the EEGs at times of crisis. There was a lag in the EEG returning to normal after ammonia levels had returned to normal. Citrulline remained elevated in all cases. Follow‐up over years revealed mild spasticity, mental retardation and, in one case, cortical atrophy. RÉSUMÉ L';EEG au cours de la citrullinémie infantile Trois fillettes présentant une citrullinémie ont été suivies cliniquement, biochimiquement et par electroencéphalographie. Toutes les trois avaient présenté des é isodes de vomissements, de somnolence et d'hyperammoniémie peu de temps après la naissance. Des convulsions étaient apparues dans les deux cas les plus graves. Les fillettes furent sauvées par dyalise péritoneale, ou exsanguinotransfusions suivies par un régime diététique. Des pointes multifocales et des activités paroxistiques répétitives de type varié ont été observées dans les EEG au moment des crises. Il y a eu un intervalle avant le retour de l'EEG à l'état normal, après que les taux d'ammoniémie soient retournés à la normale. La citrulline est restée élevée dans tous les cas. Le suivi au cours des années a révélé une spasticité modérée, un retard mental et dans un cas une atrophie corticale. ZUSAMMENFASSUNG Das EEG bei kindlicher Zitrullinämie Drei weibliche Säuglinge mit Zitrullinämie wurden klinisch, biochemisch und elektroencephalographisch kontrolliert. Alle drei hatten kurz nach der Geburt Anfälle von Erbrechen, Lethargie und Hyperammonämie. Die zwei schwer betroffenen Kinder entwickelten Krampfanfälle. Sie wurden durch Peritonealdialyse oder wiederholte Austauschtransfusionen mit anschliessender Diät gerettet. In kritischen Situationen wurden im EEG multifokale Spikes oder wiederholte verschiedenartige paroxysmale Aktivitäten gesehen. Nach der Normalisierung der Ammoniumspiegel kehrte das EEG verzögert zur Norm zuruck. Das Zitrullin blieb in alien Fällen erhöht. Jahrelange Kontrolluntersuchungen ergaben eine geringe Spastik, eine geistige Retardierung und, in einem Fall, eine kortikale Atrophie. RÉSUMÉN El EEG en el lactante con citrulinemia Tres lactantes hembras con citrulinemia fueron seguidos clínica, bioquímica y electroencefalográficamente. Los tres tenían episodios de vómito, letargia e hiperamoniemia poco después de nacer. Los dos casos más graves desarrollaron convulsiones. Se salvaron gracias a una dialisis peritoneal o por exsanguino transfusión repetidas, seguidas de un ajuste diétético en el EEG en el momento de las crisis se observaron espigas o actividad paroxistíca repetitiva de diversos tipos. Hubo un retraso en el retorno a la normal del EEG despues de la normalizacion de la amo...

Neurological implications of urea cycle disorders

“…Previous reports have documented EEG changes in patients with OTCD, with multifocal independent spike and sharp wave discharges being the most common finding, although a nonspecific pattern consistent with a diffuse encephalopathy is more commonly observed (Batshaw 1984;Bourrier et al 1988;Brunquell et al 1999;Brusilow 1985;Engel and Buist 1985). In addition, EEG abnormalities have been reported in infants with OTCD in the absence of clinical seizures (Bogdanovic et al 2000;Brunquell et al 1999;Engel and Buist 1985;Verma et al 1984) and may be used to explain differential responses to intervention and outcome when the clinical examination appears similar. EEG patterns that fail to respond, either in amplitude or frequency, to noxious, auditory, or visual stimuli predict a poor prognosis for meaningful neurological recovery, whereas similar patterns with preserved reproducible reactivity imply the potential for some recovery and should be compared with recordings repeated several days later.…”

“…In addition, EEG abnormalities have been reported in infants with OTCD in the absence of clinical seizures (Bogdanovic et al 2000;Brunquell et al 1999;Engel and Buist 1985;Verma et al 1984) and may be used to explain differential responses to intervention and outcome when the clinical examination appears similar. EEG patterns that fail to respond, either in amplitude or frequency, to noxious, auditory, or visual stimuli predict a poor prognosis for meaningful neurological recovery, whereas similar patterns with preserved reproducible reactivity imply the potential for some recovery and should be compared with recordings repeated several days laFter.…”

Stroke-like Episodes in Inherited Neurometabolic Disorders

“…Dysfunction of the urea cycle could involve stroke and SLEs. SLEs may be observed in carbamoyl phosphate synthetase I (CPS1) deficiency, ornithine transcarbamylase (OTC) deficiency and citrullinemia [ 3 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ]. The pathogenesis of stroke-like events in patients affected by urea cycle disorders is unclear.…”

“…Urea cycle disorders should always be included in differential diagnoses of unexplained stroke during infancy and childhood. Citrullinemia type I is an autosomal recessive disorder associated with mutations of argininosuccinate synthase and secondary accumulation of ammonia [ 62 , 63 , 64 , 65 , 66 ].…”