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Objectives The objectives of this study were to determine how hemispheric laterality of seizure activity influences periictal heart rate variability (HRV) and investigate the ability of HRV parameters to discriminate right- and left-sided seizures. Methods Long-term video electroencephalogram-electrocardiogram recordings of 54 focal seizures in 25 patients with focal epilepsy were reviewed. Using linear mixed models, we examined the effect of seizure laterality on linear (standard deviation of R-R intervals [SDNN], root mean square of successive differences [RMSSD], low frequency [LF] and high frequency [HF] power of HRV, and LF/HF) and nonlinear (standard deviation [SD]1, SD2, and SD2/SD1 derived from Poincare plots) periictal HRV parameters, the magnitude of heart rate (HR) changes, and the onset time of increased HR. Receiver operating characteristics (ROC) were used to determine the ability of these parameters to discriminate between right- and left-sided seizures. Results Postictal SDNN, RMSSD, LF, HF, SD1, and SD2 were higher in right- than left-sided seizures. Root mean square of successive difference and HF were decreased after left- but not right-sided seizures. Standard deviation of R-R intervals, LF, and SD1 were increased after right- but not left-sided seizures. Increased ictal HR was earlier and larger in right- than left-sided seizures. Postictal HF showed the greatest area under the ROC curve (AUC) (0.87) for discriminating right- and left-sided seizures. Conclusions Our data suggest that postictal parasympathetic activity is higher, whereas ictal HR increase is greater, in right- than left-sided seizures. Involvement of the right hemisphere may be associated with postictal autonomic instability. Postictal HRV parameters may provide useful information on hemispheric laterality of seizure activity.

We report the case of a 17-year-old woman with paroxysmal sympathetic storm (PSS), which was successfully treated with clonidine hydrochloride. The patient was hospitalized for acute disseminated encephalomyelitis in June 2006. Dysphagia led to severe aspiration pneumonia in September 2006, and she suffered cardiopulmonary arrest. She survived but had severe brain damage, with her brain MRI showing diffuse hypoxic encephalopathy. From October 2006, she had several episodes of profound tachypnea (> 60/min), tachycardia (160 to 170 beats/min), hypertension (> 140 mmHg), hyperthermia (39°C), and decerebrate posturing. During the attacks, the levels of catecholamines in the patient's blood and urine were markedly elevated. Accordingly, a diagnosis of PSS associated with hypoxic encephalopathy was made. Her PSS clearly improved after the administration of clonidine hydrochloride (900 μg/day). This case suggests that clonidine hydrochloride, an α2 blocker, may be one therapeutic option for PSS.

Epilepsy is a frequent comorbidity in patients with focal cortical dysplasia (FCD). Recent studies utilizing massive sequencing data identified subsets of genes that are associated with epilepsy and FCD. AKT and mTOR-related signals have been recently implicated in the pathogenic processes of epilepsy and FCD. To clarify the functional roles of the AKT-mTOR pathway in the hippocampal neurons, we generated conditional knockout mice harboring the deletion of Pten (Pten-cKO) in Proopiomelanocortin-expressing neurons. The Pten-cKO mice developed normally until 8 weeks of age, then presented generalized seizures at 8-10 weeks of age. Video-monitored electroencephalograms detected paroxysmal discharges emerging from the cerebral cortex and hippocampus. These mice showed progressive hypertrophy of the dentate gyrus (DG) with increased expressions of excitatory synaptic markers (Psd95, Shank3 and Homer). In contrast, the expression of inhibitory neurons (Gad67) was decreased at 6-8 weeks of age. Immunofluorescence studies revealed the abnormal sprouting of mossy fibers in the DG of the Pten-cKO mice prior to the onset of seizures. The treatment of these mice with an mTOR inhibitor rapamycin successfully prevented the development of seizures and reversed these molecular phenotypes. These data indicate that the mTOR pathway regulates hippocampal excitability in the postnatal brain.

Epilepsy is a frequent comorbidity in patients with focal cortical dysplasia (FCD). Recent studies utilizing massive sequencing data identified subsets of genes that are associated with epilepsy and FCD. AKT and mTOR-related signals have been recently implicated in the pathogenic processes of epilepsy and FCD. To clarify the functional roles of the AKT-mTOR pathway in the hippocampal neurons, we generated conditional knockout mice harboring the deletion of Pten (Pten-cKO) in Proopiomelanocortin-expressing neurons. The Pten-cKO mice developed normally until 8 weeks of age, then presented generalized seizures at 8–10 weeks of age. Video-monitored electroencephalograms detected paroxysmal discharges emerging from the cerebral cortex and hippocampus. These mice showed progressive hypertrophy of the dentate gyrus (DG) with increased expressions of excitatory synaptic markers (Psd95, Shank3 and Homer). In contrast, the expression of inhibitory neurons (Gad67) was decreased at 6–8 weeks of age. Immunofluorescence studies revealed the abnormal sprouting of mossy fibers in the DG of the Pten-cKO mice prior to the onset of seizures. The treatment of these mice with an mTOR inhibitor rapamycin successfully prevented the development of seizures and reversed these molecular phenotypes. These data indicate that the mTOR pathway regulates hippocampal excitability in the postnatal brain.

A 44-year-old man with a bilateral hand tremor suffered from a decline in concentration and abnormal vision for several months. He also complained of easily falling down because of muscle stiffness and cramps in his lower limbs. On admission, he demonstrated lower limb stiffness, muscle cramps, diplopia, hyperhidrosis, left upper limb ataxia and dysesthesia in all limbs. Laboratory examination showed a marked elevation in his serum creatine kinase level (26,890 U/l), and needle electromyography demonstrated myokymic discharges in the muscles of his lower extremities. Isaacs' syndrome was diagnosed based on a positive voltage-gated potassium channel antibody titer of 1,007 pM. Administration of an anticonvulsant (phenytoin, 200 mg/day) did not resolve his symptoms; however, high-dose intravenous methylprednisolone therapy (1 g/day for 3 days) resulted in marked clinical improvement. This case suggests that high-dose intravenous methylprednisolone therapy for Isaacs' syndrome might be as effective as other immunosuppressive therapies such as plasma exchange or intravenous immunoglobulin.