OrphanAnesthesia

AHC is a very rare neurological disorder first described in 1971 which has received increasing interest recently [1]. It is characterised by hemiplegia of either side of the body, paroxysmal tonic or dystonic spells, oculomotor abnormalities and developmental delay [2-4]. Its onset occurs before 18 months of age. This condition is diagnosed based on the occurrence of the above combination of symptoms, is usually due to de novo pathogenic variant in ATP1A3 and has also been reported in a few families [2-3]. Onset and progression of neurological symptoms have been well characterised. While the course and severity of deficits may vary considerably, there appears to be progression over time, at least in some patients. The differential diagnosis of AHC includes familial hemiplegic migraine (FHM) syndromes (e.g. FHM1-CACNA1A; FHM2-ATP1A2), episodic ataxia type 6, glutamate transporter disorders (SLC1A3), glucose transporter defects, GLUT1 deficiency (SLC2A1), infantile onset epileptic encephalopathies, severe myoclonic epilepsy of infancy (Dravet syndrome), SCN1A mutations, mitochondrial disorders, and disorders of dopamine biosynthesis/neurotransmitter disorders. The prevalence has been estimated at 1:1,000,000 with most cases being due to de novo mutations [4-6]. Triggers in AHC and other ATP1A3-related diseases that can induce paroxysmal episodes in AHC are frequent. They include psychological stress, emotional excitement, environmental stressors (bright light; sunlight or fluorescent lighting), excessive heat or cold, situations associated with excessive noise, crowds, water exposure in the form of bathing, swimming, shampooing, certain foods or odours, missed meals, excessive or atypically strenuous exercise, illness, irregular sleep, missing a nap, and delayed bedtime [5-7]. Flunarizine has remained the most commonly prescribed therapy for prophylaxis of episodic neurologic dysfunction in AHC for more than two decades. However, not all patients respond to flunarizine, the response of the paroxysmal hemiplegia and dystonia is usually only partial and patients continue to have significant developmental and neurological impairments despite this therapy [6-13].

Duke Scholars

Author Mohamad Abdul Mikati Pediatrics, Neurology