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Time course of downbeat positioning nystagmus in familial hemiplegic migraine type 1 treated with acetazolamide

2016; Elsevier BV; Volume: 368; Linguagem: Inglês

10.1016/j.jns.2016.07.020

1878-5883

Masanobu Suzuki, Keishi Fujiwara, Takashi Tsubuku, Ichiro Yabe, Hidenao Sasaki, Satoshi Fukuda,

Genetic Neurodegenerative Diseases

Familial hemiplegic migraine (FHM) is a rare autosomal dominant genetic disorder that is classified into 3 types: FHM 1, FHM 2 and FHM 3. Mutations in the calcium channel gene CACNA1A are responsible for FHM 1 [ [1] Ophoff R.A. Terwindt G.M. Vergouwe M.N. van Eijk R. Oefner P.J. Hoffman S.M. Lamerdin J.E. Mohrenweiser H.W. Bulman D.E. Ferrari M. Haan J. Lindhout D. van Ommen G.J. Hofker M.H. Ferrari M.D. Frants R.R. Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell. 1996; 87: 543-552 Abstract Full Text Full Text PDF PubMed Scopus (2117) Google Scholar ]. A unique missense mutation in the CACNA1A gene results in extreme clinical diversity and variability [ [2] Barros J. Damasio J. Tuna A. Alves I. Silveira I. Pereira-Monteiro J. Sequeiros J. Alonso I. Sousa A. Coutinho P. Cerebellar ataxia, hemiplegic migraine, and related phenotypes due to a CACNA1A missense mutation: 12-year follow-up of a large Portuguese family. JAMA Neurol. 2013; 70: 235-240 Crossref PubMed Scopus (22) Google Scholar ]. The mutation in CACNA1A gene is also associated with spinocerebellar ataxia type 6 (SCA 6). The main symptoms are migraine with aura and hemiplegia, while progressive cerebellar ataxia and nystagmus are also present. Ducros et al. reported permanent cerebellar signs in 68 of 105 subjects with mutations in CACNA1A, with nystagmus detected in 45% of the subjects [ [3] Ducros A. Denier C. Joutel A. Cecillon M. Lescoat C. Vahedi K. Darcel F. Vicaut E. Bousser M.G. Tournier-Lasserve E. The clinical spectrum of familial hemiplegic migraine associated with mutations in a neuronal calcium channel. N. Engl. J. Med. 2001; 345: 17-24 Crossref PubMed Scopus (467) Google Scholar ]. Downbeat positioning nystagmus (DPN), in particular, was observed as a common clinical feature in one FHM 1 pedigree [ [4] Yabe I. Kitagawa M. Suzuki Y. Fujiwara K. Wada T. Tsubuku T. Takeichi N. Sakushima K. Soma H. Tsuji S. Niino M. Saitoh S. Sasaki H. Downbeat positioning nystagmus is a common clinical feature despite variable phenotypes in an FHM1 family. J. Neurol. 2008; 255: 1541-1544 Crossref PubMed Scopus (11) Google Scholar ]. DPN is observed when the patient's head position changes, especially when adopting a supine position from a sitting position [ [5] Yabe I. Sasaki H. Takeichi N. Takei A. Hamada T. Fukushima K. Tashiro K. Positional vertigo and macroscopic downbeat positioning nystagmus in spinocerebellar ataxia type 6 (SCA6). J. Neurol. 2003; 250: 440-443 Crossref PubMed Scopus (64) Google Scholar ]. As DPN lasts for 10–40 s, it is considered to be positioning rather than positional [ [5] Yabe I. Sasaki H. Takeichi N. Takei A. Hamada T. Fukushima K. Tashiro K. Positional vertigo and macroscopic downbeat positioning nystagmus in spinocerebellar ataxia type 6 (SCA6). J. Neurol. 2003; 250: 440-443 Crossref PubMed Scopus (64) Google Scholar ]. The effectiveness of acetazolamide, which is thought to ameliorate ion channel function in FHM, in treating headaches associated with FHM was demonstrated previously [ [6] Battistini S. Stenirri S. Piatti M. Gelfi C. Righetti P.G. Rocchi R. Giannini F. Battistini N. Guazzi G.C. Ferrari M. Carrera P. A new CACNA1A gene mutation in acetazolamide-responsive familial hemiplegic migraine and ataxia. Neurology. 1999; 53: 38-43 Crossref PubMed Google Scholar ][ [7] Garcia-Baro-Huarte M. Iglesias-Mohedano A.M. Slocker-Barrio M. Vazquez-Lopez M. Garcia-Morin M. Miranda-Herrero M.C. Castro-Castro P. Phenotypic variability in a four generation family with a p.Thr666Met CACNA1A gene mutation. Pediatr. Neurol. 2014; 51: 557-559 Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar ]. Although acetazolamide was reported to decrease the frequency of attacks, there have been no reports on the effects of acetazolamide in the treatment of central vestibular disturbances, such as cerebellar dysfunction in FHM 1. Here, we report a case of FHM 1 in which disequilibrium and DPN were improved by treatment with oral acetazolamide. In this report, we focus on the time course of nystagmus during treatment with acetazolamide. This case was presented in part in a previous report [ [4] Yabe I. Kitagawa M. Suzuki Y. Fujiwara K. Wada T. Tsubuku T. Takeichi N. Sakushima K. Soma H. Tsuji S. Niino M. Saitoh S. Sasaki H. Downbeat positioning nystagmus is a common clinical feature despite variable phenotypes in an FHM1 family. J. Neurol. 2008; 255: 1541-1544 Crossref PubMed Scopus (11) Google Scholar ].