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Show ORIGINAL CONTRIBUTION Gaze-Evoked and Rebound Nystagmus in a Case of Migrainous Vertigo Sun-Young Oh, MD, Man-Wook Seo, MD, Young-Hyun Kim, MD, Kwang-Dong Choi, MD, Dae-Seong Kim, MD, and Byoung-Soo Shin, MD and hemicranial. It alternated sides and was associated with nausea, vomiting, and rarely photophobia and phonopho-bia. The vertigo was aggravated by body position changes. She had no family history of migraine, vertigo, or episodes of ataxia. Various analgesics had not provided alleviation of symptoms. Results of several electroence-phalograms had been normal as were results of hematologic examinations, including a complete blood cell count, electrolytes, glucose, erythrocyte sedimentation rate, and liver and kidney function tests. During an episode, gaze-evoked nystagmus (GEN) and rebound nystagmus were captured on video (see Supplemental Digital Content 1, http://links.lww.com/A685) and in three-dimensional oculography (Fig. 1) in eccentric positions of gaze under lighted conditions in the horizontal (30-35) plane. In the vertical (25-30) plane and after the patient's symptoms had resolved, GEN and rebound nystagmus were not observed. Although she showed normal findings on finger-to-nose, heel-to-shin, and diadochokinesis tests, we observed disturbed stance and gait during the attack. She could stand and walk with eyes open but could not stand with eyes closed. She was unable to perform a tandem gait. (This impaired gait and balance normalized 2 days later.) During the attack, findings from the rest of the neurologic examination, calorics, bedside head-thrust tests, and audiometry were unremarkable. Results of brain MRI and fluorodeoxyglucose positron emission tomography (FDG-PET) were also normal. (Fig. 2). To exclude the diagnosis of episodic ataxia type 2 (EA-2), we performed a polymerase chain reaction (PCR)- based direct sequence analysis of all coding regions of CACNA1A. Genomic DNA was extracted from the patient's peripheral blood and was amplified using 52 primer pairs covering 47 exons and their neighboring intron sequences (2). The amplified products from the PCR reaction were then separated on 2% agarose gels, purified, cycle-sequenced with PCR primers using a BigDye Terminator Sequencing Kit (PE Applied Biosystems, Foster City, CA), and electrophoresed using an ABI PRISM 3730XL DNA analyzer (PE Applied Biosystems). By visual analysis of Abstract: A patient with migrainous vertigo showed pronounced gaze-evoked and rebound nystagmus during an attack. These findings, which have not been previously documented, suggest that migrainous vertigo is based on central vestibular dysfunction. (J Neuro-Ophthalmol 2009;29:26-28) igrainous vertigo (MV) is an increasingly recognized cause of episodic vertigo and headache (1). How-ever, whether MV is a central or peripheral vestibular sys-tem disorder is not known. As in any paroxysmal disorder, the physical examination during the acute episode is indis-pensable for an understanding of the underlying patho-physiology. We present a patient with MV who showed pronounced gaze-evoked and rebound nystagmus together with gait imbalance during an attack, suggesting that central vestibular dysfunction was the basis of the clinical manifestations. CASE REPORT A 57-year-old woman had episodes of severe headache, nausea and vomiting, and a slight imbalance almost always associated with vertigo. She also experi-enced isolated incidents of spontaneous vertigo without headache and migraine-like headache without vertigo. The headache and vertigo attacks lasted from 30 minutes to several days and had occurred once or twice per month for more than 10 years. The headache was pulsating M Department of Neurology (S-YO, M-WS, Y-HK, B-SS), College of Medicine, Chonbuk National University, Jeonju, Korea; and Department of Neurology (K-DC, D-SK), Pusan National University School of Medicine and Medical Research Institute, Pusan National University, Pusan, Korea. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jneuro-ophthalmology. com). Address correspondence to Byoung-Soo Shin, MD, PhD, Department of Neurology, Chonbuk National University College of Medicine, Jeonju, Korea; E-mail: sbsoo@chonbuk.ac.kr 26 J Neuro-Ophthalmol, Vol. 29, No. 1, 2009 Migrainous Vertigo J Neuro-Ophthalmol, Vol. 29, No. 1, 2009 FIG. 1. Gaze-evoked nystagmus recorded by three-dimensional oculography during an episode of headache, vertigo, and gait imbalance. The eyes were tested under lighted conditions in the horizontal (30°) plane. gel electrophoresis of amplified PCR products and chro-matograms, we were able to exclude a mutation of CACNA1A, including an abnormal CAG expansion at exon 47. A diagnosis of MV was made, and the patient was treated abortively with oral sumatriptan and prophylacti-cally with 80 mg/day propranolol and 50 mg/day top-iramate. Symptoms improved several days later. On examination 6 months after discharge, the patient reported only one attack of headache of relatively decreased intensity. DISCUSSION Our patient experienced episodic spontaneous or positional vertigo with imbalance aggravated by head and body movements. She also experienced migraine according to the criteria of the International Headache Society (3), • w y w ij L$ .9.66 FIG. 2. Normal appearance of brainstem and cerebellum on axial T2 MRI (A) and [18F]fluorodeoxyglucose positron emission tomography (B) performed during the episode described in Figure 1. 27 J Neuro-Ophthalmol, Vol. 29, No. 1, 2009 Oh et al including nausea, vomiting, and photophobia accompanied by vertigo. After appropriate investigations ruled out other causes of her symptoms, we settled on a diagnosis of MV based on the criteria proposed by Neuhauser et al (4). The principal alternative diagnoses in our patient are basilar migraine and transient ischemic attacks. To fulfill the diagnosis of basilar migraine, she would have needed at least two of the following symptoms: dysarthria, diplopia, and tinnitus, which she lacked (5). We excluded transient ischemic attacks because she had had attacks for 10 years without other neurologic manifestations and with normal brain imaging. Between attacks of MV, various ocular motor signs have been reported (1,6-8), including saccadic pursuit, spontaneous or positional nystagmus, vertical nystagmus, GEN, and impaired fixation suppression of vestibulo-ocular reflex (VOR) (1,8). During attacks of MV, there are only a few reports of ocular motor findings (8-10), including spontaneous and positional nystagmus, saccadic pursuit, caloric weakness, and gait ataxia (9). In one report, two patients with MV showed very mild GEN during the acute episode (10). Our patient showed pronounced GEN and rebound nystagmus during an acute episode of MV. These findings suggest a central vestibular origin of MV. GEN is caused by an inadequately sustained eye position signal originating from the neural integrator. This form of nystagmus is associated with cerebellar disorders involving the vestibulocerebellum (flocculonodular lobe) or its connections (11,12) and brainstem lesions affecting the nucleus prepositus hypoglossi (NPH) and medial vestibular nucleus (MVN) (2). Rebound nystagmus is most often encountered in patients with cerebellar lesions involving the flocculus and paraflocculus (13), and it also occurs in monkeys with lesions in the flocculus and paraflocculus (11) and with bilateral lesions restricted to the NPH and MVN (14). The calcium channel gene has been considered a candidate in MV (15,16), This hypothesis relies on findings of involvement of the CACNA1A gene region in some families with non-hemiplegic migraine with and without aura (17). Mutations in the CACNA1A gene of a neuronal Ca2+ channel have been identified in familial hemiplegic migraine (FHM), EA-2, and spinocerebellar ataxia type 6. No such mutations have been found in basilar migraine or migraine with and without aura and only sparsely in hemiplegic migraine (2). These findings suggest that this gene is not associated with the more common migraine syndromes or most cases of hemiplegic migraine. The sequence analysis of the CACNA1A genes in our patient did not show mutations in these genes. Recently, PET with radioactive water (H2 15O) per-formed during acute migraine attacks has identified activa-tion of the locus ceruleus and the dorsal raphe nucleus, which are involved in the initiation of migraine attacks. The vestibular nuclei receive fibers from these structures (18-20). Our lack of apparent brainstem or cerebellar activation might be related to the use of FDG-PET rather than H2 15O-PET in the study of our patient. FDG-PET may not be sufficiently sensitive to pick up changes in brainstem activity during migraine attacks. REFERENCES 1. Kayan A, Hood JD. Neuro-otological manifestations of migraine. 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