Epileptic seizures can be difficult to distinguish from other etiologies that cause cerebral hypoxia, especially cardiac diseases. Long QT syndrome (LQTS), especially LQTS type 2 (LQT2), frequently masquerades as seizures because of the transient hypoxia caused by ventricular arrhythmia. Early and correct diagnosis of LQTS effectively prevents inappropriate treatment with anti-epileptic drugs (AEDs) and sudden death. We report a case of congenital LQT2 with potassium voltage-gated channel subfamily H member 2 gene (KCNH2) mutation misdiagnosed as refractory epilepsy and treated with various AEDs for 22 years. The possibility of cardiac arrhythmia was suspected after the electrocardiograph (ECG) monitor in emergency room showed paroxysmal ventricular tachycardia during attacks. Atypical seizure like attacks with prodromal uncomfortable chest sensation and palpitation, triggered by auditory stimulation, and typical ventricular tachycardia monitored by ECG raised suspicion for LQT2, which was confirmed by exome sequencing. Although the patient rejected implantation of an implantable cardioverter defibrillator, β-blocker was given and the syncope only attacked 1-2 per year when there was an incentive. Our case illustrates how long LQTS can masquerade convincingly as epilepsy and be treated wrongly with AEDs, putting the patient at high risk of sudden death. Careful ECG evaluation is recommend for both patients with first seizure and those with refractory epilepsy.
Aim: To determine the risk factors of valproic acid (VPA)-induced tremor, with particular attention on characterizing cerebellar atrophy and identifying tremor-susceptible gene mutations. Methods: Epileptic patients taking VPA were divided into two groups, a tremor and a non-tremor group, based on self-reported or clinically assessed tremors. A mutation of rs9652490 in the leucine-rich repeat and immunoglobulin domain-containing Nogo-receptor-interacting protein 1 (LINGO-1) gene was determined by Sanger sequencing. Cerebellar atrophy was assessed and various cerebellar dimensions were measured on magnetic resonance imaging (MRI) scans. Results: Among 200 subjects enrolled, 181 were included for analysis (mean age 33.28±11.78 years old, male:female=2.77:1). In the tremor group, the percentage of females (p=0.036), positive tremor family history (p=0.001), and incidence of polytherapy (p=0.034), treatment duration (>12 months [p=0.013] or >24 months [p=0.008]), and daily dosage (>1,000 mg/d; p=0.003) of VPA, were significantly higher than in the non-tremor group. Treatment with VPA magnesium (p=0.030), alone or in combination with carbamazepine (p=0.040), reduced the incidence of tremor. Furthermore, 176 gene sequencing results ruled out any significant difference between the two groups in the mutation of rs9652490 within LINGO-1 (p=0.443); 86 subjects’ MRI scans indicated no significant differences in the ratio of cerebellar atrophy or the cerebellar-dimension values (p>0.05). However, mutation of rs9652490 within LINGO-1 was correlated with increased cerebellar atrophy (p=0.001), reduced cerebellar-hemisphere thickness (p=0.025), and right-cerebellar-hemisphere longitudinal diameter (p=0.047). Conclusion: Our cohort indicated risk and protective factors of VPA-induced tremor. Although mutation of rs9652490 within LINGO-1 correlated with cerebellar atrophy, neither was correlated with VPA-induced tremors.