A Case of Intermittent Ataxia Associated with Migraine Headaches Teaching Case Report

Practice

Teaching Case Report Box 1: Possible diagnoses in a A case of intermittent ataxia associated with migraine patient with ataxia Primary intermittent ataxia headaches syndromes (often not progressive) With headaches The case: A previously healthy 42-year- or dysarthria and did not display any • Episodic ataxia type 2 old woman had presented to our neu- myokymia about the eyes, lips or fin- • Basilar migraines rology service 1 year earlier with left- gers. She recalled experiencing similar • Episodic ataxia with paroxysmal sided temporal headaches that she mild attacks since the age of 25 that in- choreoathetosis and spasticity said typically lasted from a few hours volved clumsiness and occasional falls • Familial hemiplegic migraines to all day. They were associated with and that lasted from a few hours to a Without headaches* nausea but not with vomiting. Begin- day. These attacks were not associated • Episodic ataxia type 1 ning at age 13 years, these headaches with diplopia, hearing loss, weakness, • Periodic vestibulocerebellar had occurred at a frequency of once a choreiform movements, abnormal pos- ataxia month to once every 2–3 months. The turing, fatigable weakness, cognitive • Spinocerebellar ataxia type 6 woman did not experience visual deficits, seizures, stiffness or myotonia. Secondary intermittent ataxias* auras, such as scintillation photopsias The attacks were not related to head (often progressive) (flashes of light), migrating scotomata position or change of posture. Her mi- • Hartnup’s disease (patches of blurred or absent vision) graine headaches occurred both with • Pyruvate decarboxylase deficiency or fortification spectra (wavy linear and without episodes of ataxia. Simi- • Leigh’s disease “zig-zag” patterns that resemble the larly, ataxic episodes occurred without • Hereditary hyperammonemias battlements of a medieval fort). She migraine headaches. An electroenceph- had no history of vertigo or seizures. alogram appeared normal, as were the Primary ataxia syndromes* (sometimes progressive) The headaches tended to occur results of routine blood tests, including • Spinocerebellar ataxia around the time of her menses. She blood count, electrolyte levels and rated the pain at 3 on a scale of 1–10 serum glucose level. The patient pro- • Multiple system atrophy (10 being most severe), but she noted vided a detailed family history, describ- • Celiac disease that on occasion the headaches could ing intermittent clumsiness in her fa- • Antiphospholipid syndrome be severe enough to wake her from ther and migraine headaches in 2 of 4 • Paroxysmal psychosis sleep and merit a pain rating of 8 or 9. siblings. • Seizures Clinical examination was unremark- A provisional diagnosis of episodic • Drugs (e.g., anticonvulsants) able during each of her visits. Ten ataxia type 2 was made in view of the • Toxins (e.g., alcohol) years earlier, atypical migraine had patient’s history of migraine, episodes “Pseudoataxia”* been diagnosed and treated sympto- of ataxia with normal examination be- • Paroxysmal kinesigenic matically; no migraine prophylaxis tween episodes and a strong family dyskinesias 1,2 had been given in view of her infre- history. The patient responded to ac- *Headaches may occur incidentally. quent and mild headaches. Magnetic etazolamide, 250 mg 3 times a day, resonance imaging scans of the brain but experienced relapses of ataxia were unremarkable. The diagnosis of once or twice a year when she did not atypical migraine was not altered at take her medication. With amelio- 19p13, which codes for the main trans- this time. ration of her ataxic episodes, she membrane component of the neuronal One year after her initial visit to our became bothered by her migraine calcium channel.2 neurology service, the patient was ad- headaches, which responded to pro- mitted to hospital because of unsteadi- phylaxis with amitriptyline and in- ness of gait, gaze-evoked nystagmus domethacin for analgesia. Sumatrip- Ataxia can be progressive, stable or and truncal ataxia (see video of typical tan was efficacious for more severe episodic and can occur with or with-

1 episode, available online at www.cmaj migraine headaches. out headaches (Box 1). Our patient 0 0

0 .ca/cgi/content/full/177/6/565/DC1). She The patient underwent genetic had migraine headaches and episodes 7 0 . j a did not report experiencing headaches counselling and testing. None of the of ataxia, with normal clinical findings m c / at the time. Her condition resolved known mutations that cause episodic between attacks. Her ataxic episodes 3 0 5

1 spontaneously after about 18 hours, ataxia was detected in exons 23, 26, 28, and migraines may have been distinct . 0 1

: and findings on clinical examination 29, 32 and 35 of the calcium-channel but coincidental clinical entities or I O

D were normal. She had no hearing loss gene (CACNA1A) on chromosome manifestations of a single disease. A

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566 CMAJ • September 11, 2007 • 177(6) Practice

discussion of the differential diagno- Channelopathies, such as paroxys- sis of recurrent and relapsing ataxia mal kinesigenic dyskinesias, can be as- REFERENCES follows. sociated with migraine and can mimic 1. Gordon N. Episodic ataxia and channelopathies. Brain Dev 1998;20:9-13. Episodic ataxias are characterized by episodic ataxias. Clinical examination 2. Kullmann DM. The neuronal channelopathies. spontaneous paroxysmal periods of during the attack (see online video, Brain 2002;125(pt 6):1177-95. 3. Headache Classification Subcommittee of the In- ataxia that typically last from minutes available at www.cmaj.ca/cgi/content ternational Headache Society. The international to hours or days. Between episodes, the /full/177/6/565/DC1) confirmed the classification of headache disorders, 2nd edition. Cephalalgia 2004;24(Suppl 1):S9-160. patient is normal, except for the pres- presence of truncal ataxia rather than 4. Manto MU. The wide spectrum of spinocerebellar ence of gaze-dependent or downbeat dyskinesia. ataxias (SCAs). Cerebellum 2005;4:2-6. 1,2 5. Harno H, Hirvonen T, Kaunisto MA, et al. Acetazo- nystagmus. Migraine is associated Migrainous headaches have also lamide improves neurotological abnormalities in a with episodic ataxia in a variety of con- been reported to occur incidentally in family with episodic ataxia type 2 (EA-2). J Neurol ditions, such as basilar type migraine; patients who have ataxia because of 2004;251:232-4. 6. Lee H, Wang H, Jen JC, et al. A novel mutation in episodic ataxia types 1 and 2; episodic other diseases, such as spinocerebellar KCNA1 causes episodic ataxia without myokymia. ataxia with paroxysmal choreoathetosis ataxia type 6, celiac disease, antiphos- Hum Mutat 2004;24:536. and spasticity; periodic vestibulocere- pholipid syndrome, paroxysmal psy- bellar ataxia; and familial hemiplegic chosis and seizures. Similarly, they migraine.1 The clinical characteristics can occur in patients with cerebellar See an online video and distinguishing features of these dysfunction or acutely from drugs showing an episode conditions are summarized in Table 1. (e.g., anticonvulsants) or toxins (e.g., of moderately severe Our patient likely had episodic alcohol). truncal ataxia (avail- ataxia type 2 in view of her history of Finally, ataxia may be seen intermit- able at www.cmaj.ca/cgi/content migraine, fairly long ataxic episodes tently as part of several recessively /full/177/6/565/DC1). The patient (lasting minutes to hours), good clini- inherited diseases, such as Hartnup’s did not have a migraine headache cal response to acetazolamide therapy disease, pyruvate decarboxylase defi- during this episode. and relevant family history. CACNA1A ciency, Leigh’s disease and hereditary encodes the α-1A subunit of the volt- hyperammonemias. These conditions age-dependent P/Q-type calcium chan- are usually associated with other signs, nel, mainly expressed in the Purkinje such as mental retardation, seizures cells of the cerebellum. Calcium chan- and pyramidal dysfunction. nelopathy is thought to lead to alter- Episodic ataxia type 2 is treated with ations in intracellular pH, which alters carbonic anhydrase inhibitors, such as the transmembrane potential. Acetazo- acetazolamide, as well as migraine pro- Canadian Adverse lamide is thought to normalize intra- phylaxis and therapy with analgesics. Reaction Newsletter cellular pH and thus restore Purkinje Magnetic resonance spectroscopy stud- cell function.5 The patient’s negative ies have demonstrated an increase in Bulletin canadien genetic screen for episodic ataxia type 2 cerebellar pH in affected patients, des effets indésirables does not rule out the possibility that which returns to normal on consump- she has the condition, since we tion of acetazolamide. The disease runs To receive the Newsletter and health screened for only 6 of the mutations a relatively benign course, although product Advisories free by email, join described to date. It is also possible, of progression to severe persistent cere- Health Canada’s MedEffect mailing list. course, that our patient carries a novel bellar ataxia has been described in Go to www.healthcanada.gc.ca/medeffect mutation in the CACNA1A gene or car- some cases.2 Our patient has remained ries a mutation in some other gene. For well 6 years after initiation of therapy. Inscrivez-vous à la liste MedEffet de Santé Canada pour recevoir example, a family whose members have gratuitement par courriel le Bulletin et the phenotype for episodic ataxia type 2 Raymond C.S. Seet MBBS MMed les Avis au sujet des produits de santé. but who carry the genotype for episodic (IntMed) Rendez-vous à l’adresse ataxia type 1 has been described.6 Erle C.H. Lim MBBS MMed (IntMed) www.santecanada.gc.ca/medeffet We ruled out basilar type migraine3 Yong Loo Lin School of Medicine on the basis of the temporal dissocia- National University of Singapore Department of Medicine Report adverse reactions toll free to tion between migrainous and ataxic Health Canada • Signaler sans frais des National University Hospital episodes, as well as the patient’s fa- effets indésirables à Santé Canada Singapore vourable response to acetazolamide. Tel./Tél. : 866 234-2345 We also excluded episodic ataxia with This article has been peer reviewed. Fax/Téléc. : 866 678-6789 paroxysmal choreoathetosis and spasticity as well as familial hemiplegic Competing interests: None declared. migraine because of the absence of Acknowledgements: We thank Soh-Eng Chew and chorea, stiffness and hemiplegia dur- Professor Jean-Marc Burgunder for performing the ing the headaches. genetic analysis of the CACNA1A gene mutations.

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