Episodic ataxia (EA) is a rare neurological condition characterized by recurrent spells of truncal ataxia and incoordination. Five genes (KCNA1, CACNA1A, CACNB4, SLC1A3, and UBR4) have been linked to EA. Despite extensive efforts to genetically diagnose EA, many patients remain still undiagnosed. Whole-exome sequencing was carried out in 39 Korean patients with EA to identify pathogenic mutations of the five known EA genes. We also evaluated 40 candidate genes that cause EA as a secondary phenotype or cerebellar ataxia. Eighteen patients (46%) revealed genetic information useful for establishing a molecular diagnosis of EA. In 11 patients, 16 pathogenic mutations were detected in three EA genes. These included nine mutations in CACNA1A, three in SLC1A3, and four in UBR4. Three patients had mutations in two genes, either CACNA1A and SLC1A3 or CACNA1A and UBR4, suggesting that SLC1A3 and UBR4 may act as genetic modifiers with synergic effects on the abnormal presynaptic activity caused by CACNA1A mutations. In seven patients with negative results for screening of EA genes, potential pathogenic mutations were identified in the candidate genes ATP1A2, SCN1A, TTBK2, TGM6, FGF14, and KCND3. This study demonstrates the genetic heterogeneity of Korean EA, and indicates that whole-exome sequencing may be useful for molecular genetic diagnosis of EA.

To determine the effect of customized vestibular exercise (VE) and optokinetic stimulation (OS) using a virtual reality system in patients with persistent postural-perceptual dizziness (PPPD). Patients diagnosed with PPPD were randomly assigned to the VE group or VE with OS group. All participants received VE for 20 min using a virtual reality system with a head mount display once a week for 4 weeks. The patients in the VE with OS group additionally received OS for 9 min. We analysed the questionnaires, timed up-to-go (TUG) test, and posturography scores at baseline and after 4 weeks. A total of 28 patients (median age = 74.5, IQR 66–78, men = 12) completed the intervention. From baseline to 4 weeks, the dizziness handicap inventory, activities of daily living (ADL), visual vertigo analogue scale, and TUG improved in the VE group, but only ADL and TUG improved in the VE with OS group. Patients with severe visual vertigo improved more on their symptoms than patients with lesser visual vertigo (Pearson’s p = 0.716, p < 0.001). Our VE program can improve dizziness, quality of life, and gait function in PPPD; however, additional optokinetic stimuli should be applied for individuals with visual vertigo symptoms.

We prospectively recruited 10 patients who presented with urinary retention as a neurological deficit that was attributable to lateral medullary infarction. Of these, 9 patients underwent a urodynamic study, which demonstrated detrusor underactivity of the bladder in 7 patients. Urinary retention developed mainly when the lesions involved the lateral tegmentum of the middle or caudal medulla. We concluded that interruption of the descending pathway from the pontine micturition center to the sacral spinal cord in the lateral medulla was responsible for the development of urinary retention.

Idiopathic infantile nystagmus (IIN) is the involuntary oscillation of the eyes with onset in the first few months of life. The most common form of inheritance is X-linked, and mutations in FRMD7 gene are a major cause. To identify the FRMD7 gene mutations associated with X-linked IIN, we performed PCR-based DNA direct sequencing in 4 affected subjects from 2 Korean families. We also assessed structural abnormalities of retina and optic nerve head using optical coherence tomography (OCT). Genetic analysis revealed a A>G transversion at nucleotide c.1, the first base of the start codon. This mutation leads to the loss of the primary start codon ATG for methionine, which is replaced by a triplet GTG for valine. The alternative in-frame start codon is not present around a mutation. OCT revealed the morphological changes within the optic nerve head, including shallow cup depth and small cup-to-disc ratio. In summary, we identified a novel start codon mutation within the FRMD7 gene of 2 Korean families. Our data expands the mutation spectrum of FRMD7 causing IIN. We also demonstrated abnormal developments of afferent system in patients with FRMD7 mutations using OCT, which may help to understand the etiological factor in development of nystagmus.

Dear Sirs,Damage to the cerebellum or brainstem can often cause vestibular dysfunction. Although rare, central rotational vertigo following cerebral cortical lesions has also been reported [1,4,5,7]. However, no report has documented objective nystagmus associated with central rotational vertigo in cortical stroke. We describe a patient with rotational vertigo who showed mixed horizontal and torsional spontaneous nystagmus mimicking peripheral vestibulopathy in isolated insular infarction.A 51-year-old woman presented with sudden onset of word finding difficulty. She had history of Hashimoto thyroiditis. On admission, neurological examinations were unremarkable. Brain magnetic resonance imaging (MRI) revealed an acute infarction in the left insula. Small parts of the frontal operculum were also involved ( Fig. 1a). One day after symptom onset, her word finding difficulty had completely resolved and the Korean version of the Western Aphasia Battery was administered on the same day showed her overall language skills were normal (Aphasia Quotient = 82.0). However, the patient started to complain of rotational vertigo on the same day. Her vertigo occurred regardless of position change, which was not accompanied by nausea or vomiting. Neurological examinations on that day showed spontaneous right beating horizontal nystagmus. The line bisection test conducted on the second day of her vertigo onset showed bisection markers shifting to the left. Video-oculography performed 7 days after onset of vertigo revealed a right beating horizontal nystagmus mixed with a clockwise torsional component, which was augmented by horizontal head-shaking test (Fig. 1b). Head impulse test was normal. Bithermal caloric tests performed 8 days after vertigo onset revealed 18% canal paresis in the left ear. After that, her vertigo gradually resolved and she intermittently experienced rotational vertigo without any other symptoms, lasting 1 or 2 min, five times a month on average. Her electroencephalogram (EEG) taken during the course of the disease was normal. Follow-up bithermal caloric tests 6 months post stroke showed 14% canal paresis in the left ear. Her vertigo completely disappeared after 9 months post stroke. Follow-up computed tomography (CT) scan performed 17 months post stroke confirmed the lesion to be restricted to the left insula (Fig. 1c).The patient was admitted to our hospital, presenting with word finding difficulty, and her brain MRI showed acute infarction in the left insula. While her word finding difficulty disappeared 1 day after onset of stroke, she developed rotational vertigo. Her spontaneous nystagmus, i.e., a right beating horizontal nystagmus with a clockwise torsional component, suggested left vestibular neuritis (VN). However, normal head impulse test and small degree of canal paresis on bithermal caloric tests were not compatible with left VN, since typical unilateral VN shows positive head impulse test, and 25% or more difference of vestibular function between the affected and nonaffected