Objective: To report a case of a unique clinical presentation of hemiplegic migraine associated with paroxysmal multifocal dystonia possibly related to a novel CACNA1A mutation.

Background: 59-year-old right-handed Caucasian woman, who developed hemiplegic migraine in her 40s with partial response to acetazolamide and verapamil. At age 56, she began to have episodic multifocal and segmental dystonia during the migraine attacks, including craniocervical and left hemidystonia. Intra-ictal ataxic gait was also reported. The patient’s daughter and son, currently in their 30s, have severe migraine. A year ago, the daughter developed cervical dystonia.

Methods: Case Study.

Results: Interictal neurological examination was unremarkable. Genetic testing for CACNA1A showed previously unreported 3bp insertion of ACC. Testing of ATP1A2 was normal. No further genes were tested. Family members have chosen not to pursue genetic testing. No structural abnormalities were found on MRI. The patient modestly improved on carbamazepine and local botox injections.

Conclusions: CACNA1A gene encodes for the Cav2.1 pore-forming and voltage-sensing subunit of the P/Q-type calcium channel complex. Missense mutation cause Familial Hemiplegic Migraine type 1 (FHM1). Other typical phenotypes include spinocerebellar ataxia type 6, episodic ataxia type 2, and paroxysmal torticollis of infancy. Various other mutations in the gene have rarely been reported in dystonia (1). This is the first report to our knowledge to include adult-onset paroxysmal dystonia in addition to hemiplegic features limited to migraine episodes. The patient’s phenomenology is also unique in the CACNA1A literature in that it features hemidystonia in addition to craniocervial distribution. Although the CACNA1A mutation found in this patient has not been reported previously, there is possibly a genotype-phenotype correlation. To support this, her testing for alternative FMH causes such as ATP1A2 were negative. We therefore present this insertion in CACNA1A as a possible new genetic association with a spectrum of hemiplegic migraine, dystonic, and ataxic features. Further genetic testing of affected and unaffected family members should be undertaken. This case highlights the emerging role of calcium channel signaling in the pathophysiology of dystonia (2).

References: 3. Spacey SD, Matarek LA, Szczygielski BI, Bird TD. Two novel CACNA1A gene mutations associated with episodic ataxia type 2 and interictal dystonia. Arch Neurol. 2005 Feb;62(2):314-6. 4. Domingo A, Erro R, Lohmann K. Novel Dystonia Genes: Clues on Disease Mechanisms and the Complexities of High-Throughput Sequencing. Mov Disord. 2016 Apr;31(4):471-7.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/paroxysmal-multifocal-dystonia-with-hemiplegic-migraine-possibly-related-to-novel-cacna1a-mutation/