Early Treatment in Acute Severe Encephalopathy Caused by ATP1A2 Mutation of Familial Hemiplegic Migraine Type 2: Case Report and Literature Review

Abstract

Familial hemiplegic migraine type 2 (FHM2) is an autosomal dominant inheritance disorder caused by ATP1A2 mutation, and the clinical spectrum is heterogeneous even with acute severe encephalopathy. However, up to now, early treatments against acute and severe attacks in FHM2 are still insufficient. Here, we report a 15-year-old female with intellectual disability due to FHM2 caused by a pathogenic ATP1A2 gene mutation, presenting mild-to-moderate headache at the onset, followed by confusion, complete right hemiparalysis, epileptic partial seizures, and conscious disturbance with rapid progression in acute attack. Brain magnetic resonance imaging (MRI) and magnetic resonance spectroscopy have revealed left extensive cerebral cortex edema, slightly decreased N-acetylaspartate for neuronal damage, and mildly increased lactate acid for mitochondrial dysfunction throughout the hemispheric swollen cortex. The patient is diagnosed as severe encephalopathy caused by FHM2. Based on literature review about pathophysiologic mechanism described in FHM2 recently, we use early treatments including prevention of glutamatergic excitotoxicity and protection of mitochondria function, as well as traditional antimigraine drug. The symptoms are all greatly improved and recovered within a short time, and follow-up MRI also shows complete disappearance of edema throughout the left hemispheric cortex. Altogether, the approach in our case may reduce the severity and duration of encephalopathy effectively, expend therapeutic options, and provide helpful references for acute severe encephalopathy in FHM2.

Keywords

familial hemiplegic migraine - ATP1A2 - encephalopathy - glutamate - mitochondrial dysfunction

Financial Disclosure

None.

Ethics Approval and Consent to Participate

The patient's father was normal. We provided patient's father detailed information about the disease, and obtained the consent of the patient's father to further treatment. We have also reported to the Ethical Committee of Tangdu Hospital, Fourth Military Medical University, and obtained the approval from the committee.

Consent to Publish

We obtained written informed consent from the patient for publication of this report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

^* Ying Du and Chuan Li contributed equally to this work.

• References

• 1 Ferrari MD, Klever RR, Terwindt GM, Ayata C, van den Maagdenberg AM. Migraine pathophysiology: lessons from mouse models and human genetics. Lancet Neurol 2015; 14 (01) 65-80
• 2 Marrannes R, Willems R, De Prins E, Wauquier A. Evidence for a role of the N-methyl-D-aspartate (NMDA) receptor in cortical spreading depression in the rat. Brain Res 1988; 457 (02) 226-240
• 3 Murphy OC, Merwick A, O'Mahony O, Ryan AM, McNamara B. Familial hemiplegic migraine with asymmetric encephalopathy secondary to ATP1A2 mutation: a case series. J Clin Neurophysiol 2018; 35 (01) e3-e7
• 4 Roth C, Ferbert A, Huegens-Penzel M, Siekmann R, Freilinger T. Multimodal imaging findings during severe attacks of familial hemiplegic migraine type 2. J Neurol Sci 2018; 392: 22-27
• 5 Jacob A, Mahavish K, Bowden A, Smith ET, Enevoldson P, White RP. Imaging abnormalities in sporadic hemiplegic migraine on conventional MRI, diffusion and perfusion MRI and MRS. Cephalalgia 2006; 26 (08) 1004-1009
• 6 Hermann A, Engelandt K, Rautenstrauss B, Reichmann H, Jacobasch E. Hemiplegic migraine with reversible cerebral vasoconstriction caused by ATP1A2 mutations. J Neurol 2013; 260 (08) 2172-2174
• 7 Schwarz G, Anzalone N, Baldoli C. , et al. Pediatric sporadic hemiplegic migraine (ATP1A2 gene): a case report and brief literature review. Neurol Sci 2018; 39 (Suppl. 01) 69-71
• 8 Martínez E, Moreno R, López-Mesonero L. , et al. Familial hemiplegic migraine with severe attacks: a new report with ATP1A2 mutation. Case Rep Neurol Med 2016; 2016: 3464285
• 9 Merwick A, Fernandez D, McNamara B, Harrington H. Acute encephalopathy in familial hemiplegic migraine with ATP1A2 mutation. BMJ Case Rep 2013; 2013: bcr2013009750
• 10 Gallanti A, Tonelli A, Cardin V, Bussone G, Bresolin N, Bassi MT. A novel de novo nonsense mutation in ATP1A2 associated with sporadic hemiplegic migraine and epileptic seizures. J Neurol Sci 2008; 273 (1-2): 123-126
• 11 Carreño O, Corominas R, Serra SA. , et al. Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies. Mol Genet Genomic Med 2013; 1 (04) 206-222
• 12 Jorgensen PL, Hakansson KO, Karlish SJ. Structure and mechanism of Na,K-ATPase: functional sites and their interactions. Annu Rev Physiol 2003; 65: 817-849
• 13 Pelzer N, Blom DE, Stam AH. , et al. Recurrent coma and fever in familial hemiplegic migraine type 2. A prospective 15-year follow-up of a large family with a novel ATP1A2 mutation. Cephalalgia 2017; 37 (08) 737-755
• 14 Ueda K, Serajee F, Huq AM. Clinical benefit of NMDA receptor antagonists in a patient with ATP1A2 gene mutation. Pediatrics 2018; 141 (Suppl. 05) S390-S394
• 15 Huang L, Wang S, Ma F. , et al. From stroke to neurodegenerative diseases: The multi-target neuroprotective effects of 3-n-butylphthalide and its derivatives. Pharmacol Res 2018; 135: 201-211