Case Report Sporadic hemiplegic migraine and epilepsy associated with CACNA1A gene mutation Andro Zangaladze a, * , Ali A. Asadi-Pooya a , Avi Ashkenazi b , Michael R Sperling a a Jefferson Comprehensive Epilepsy Center, Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA b Jefferson Headache Center, Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA article info Article history: Received 10 November 2009 Accepted 19 December 2009 Available online 13 January 2010 Keywords: Epilepsy Sporadic hemiplegic migraine CACNA1A gene mutation Hemiplegic migraine Status epilepticus S218L mutation abstract Familial hemiplegic migraine (FHM) is a clinically and genetically heterogeneous disease most commonly linked to CACNA1A gene mutation. Epilepsy rarely occurs in FHM and is seen predominantly with specific CACNA1A gene mutations. Here we report a sporadic case of FHM1 linked to S218L CACNA1A gene muta- tion with the triad of prolonged hemiplegic migraine, cerebellar symptoms, and epileptic seizures. Epi- lepsy in this syndrome follows the pattern of isolated unprovoked seizures occurring only during childhood and hemiplegic migraine-provoked seizures occurring during adulthood. Clinical and electro- graphic status epilepticus can occur during prolonged migraine attacks. We suggest that patients with seizures, ataxia, and hemiplegic migraine be genetically tested for FHM. Patients with prolonged hemi- plegic migraine attacks and confusion should be tested with continuous EEG recording to ascertain whether electrographic status is occurring, as intensive antiepileptic treatment not only resolves status but immediately stops hemiplegic migraine and improves associated neurological deficits. Ó 2010 Elsevier Inc. All rights reserved. 1. Introduction Epilepsy and migraine can be related [1,2], and this link is evi- dent in familial hemiplegic migraine (FHM) [3–5]. FHM is a rare, clinically and genetically heterogeneous disease of migraine with aura that is characterized by hemiparesis and occasionally enceph- alopathy during migraine attacks [5]. The spectrum of clinical symptoms depends on specific genetic mutations. About 50% of pa- tients with FHM have a mutation in the CACNA1A gene (FHM1), which is located on chromosome 19p13 and encodes neuronal P/ Q type voltage-gated calcium channels [6–9]. Another 20% of pa- tients with FHM have mutations in the ATP1A2 gene on this chro- mosome, which encodes the transmembrane Na/K-ATPase (FHM2) [10,11]. Far less frequently, FHM has been linked to an SCNA1 gene mutation encoding sodium channels (FHM3) [12]. Epilepsy has been reported in all three FHM types, although with a higher fre- quency in FHM2 and FHM3 because of a higher association of sei- zures with ATP1A2 and SCNA1gene mutations. More than 20 CACNA1A gene mutations are linked to FHM1 [4], which can also cause cerebellar symptoms [8,9], but these rarely cause seizures except in cases related to S218L, I1710T, and W1684R mutations [9,13–15]. In addition to familial cases, there have been reports of sporadic cases of hemiplegic migraine. They share the clinical features and, in some cases, genetic changes of FHM [16]. These individual cases likely represent a first FHM patient in the family. Here we describe a case with a sporadic S218L mutation with somewhat different phenotype than has been previously reported. This patient pre- sented with severe and prolonged hemiplegic migraines associated with status epilepticus during migraine attacks and childhood epi- lepsy independent of migraine headaches. 2. Case report A 37-year-old right-handed woman presented with severe, con- tinuous, right-sided throbbing headache lasting several weeks and accompanied by profound left-sided weakness and mild confusion. She had had similar episodes in the past starting at age 12. At age 4, she had a head trauma and a few months later developed occa- sional secondarily generalized tonic–clonic seizures and complex partial seizures that remitted at age 7. Anticonvulsants were stopped and she did well until age 12, when she experienced se- vere throbbing headaches associated with either left- or right- sided hemiparesis. Most attacks lasted a few hours and occurred up to five times per year. About once a year, the headache and weakness had a protracted course, typically lasting about 2–3 weeks despite treatment, and were associated with fever, confu- sion, visual field deficits, and, on a few occasions, well-documented generalized tonic–clonic seizures. These severe attacks typically 1525-5050/$ - see front matter Ó 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2009.12.017 * Corresponding author. Address: Thomas Jefferson University, 900 Walnut Street, Suite 200, Philadelphia, PA 19107, USA. Fax: +1 215 955 0606. E-mail address: andro.zangaladze@jefferson.edu (A. Zangaladze). Epilepsy & Behavior 17 (2010) 293–295 Contents lists available at ScienceDirect Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh