Jing Jane Tsai

Terminating prolonged refractory status epilepticus using ketamine.

Refractory status epilepticus (RSE) is an emergent and difficult neurologic problem that is not uncommon in clinical practice. In this report, we describe a 23-year-old man whose RSE was refractory to standard antiepileptic drugs and barbiturates; it was successfully terminated only with intravenous ketamine. In this report, we evaluated and discuss the clinical and electroencephalographic effects under ketamine. This case and the rare cases of ketamine experience in RSE reported in the literature show that ketamine is potentially effective to use when treating patients with RSE. Further clinical trials are warranted, however.

Comparative cognitive effects of levetiracetam and topiramate in intractable epilepsy

Aim:  Anti‐epileptic drugs (AED) may cause cognitive impairment. Because intractable epilepsy (IE) represents a distinct group, the purpose of the present study was to study the comparative cognitive effects of the two efficacious AED, levetiracetam (LEV) and topiramate (TPM), on IE.

Characterizing the effects of Eugenol on neuronal ionic currents and hyperexcitability

RationaleEugenol (EUG, 4-allyl-2-methoxyphenol), the main component of essential oil extracted from cloves, has various uses in medicine because of its potential to modulate neuronal excitability. However, its effects on the ionic mechanisms remains incompletely understood.ObjectivesWe aimed to investigate EUG’s effects on neuronal ionic currents and excitability, especially on voltage-gated ion currents, and to verify the effects on a hyperexcitability-temporal lobe seizure model.MethodsWith the aid of patch-clamp technology, we first investigated the effects of EUG on ionic currents in NG108-15 neuronal cells differentiated with cyclic AMP. We then used modified Pinsky–Rinzel simulation modeling to evaluate its effects on spontaneous action potentials (APs). Finally, we investigated its effects on pilocarpine-induced seizures in rats.ResultsEUG depressed the transient and late components of INa in the neurons. It not only increased the degree of INa inactivation, but specifically suppressed the non-inactivating INa (INa(NI)). Its inhibition of INa(NI) was reversed by tefluthrin. In addition, EUG diminished L-type Ca2+ current and delayed rectifier K+ current only at higher concentrations. EUG’s effects on APs frequency reduction was verified by the simulation modeling. In pilocarpine-induced seizures, the EUG-treated rats showed no shorter seizure latency but a lower seizure severity and mortality than the control rats. The EUG’s effect on seizure severity was occluded by the INa(NI) antagonist riluzole.ConclusionThe synergistic blocking effects of INa and INa(NI) contributes to the main mechanism through which EUG affects the firing of neuronal APs and modulate neuronal hyperexcitability such as pilocarpine-induced temporal lobe seizures.

Lamotrigine-related skin rashes in adults

Skin rash is a common adverse effect of lamotrigine (LTG) in both add-on and monotherapy trials and is also the most common adverse event causing LTG withdrawal. From our series of 254 prospectively registered adult patients treated with LTG at a dosage of 25-100 mg/ day, the incidence of allergic and non-allergic skin reactions was 5.1% (13/254) and 1.9% (5/254), respectively. Meanwhile, the rate of allergic skin rashes causing LTG withdrawal was 3.9% (10/254). Co-medication with valproic acid (9.1%) resulted in a higher risk than co-medication with enzyme-inducing antiepileptic medications (2.8%). Moreover, another risk factor was higher initiation and relatively rapid dosage escalation. Among the 13 patients with allergic skin reaction, skin rash appeared during the initiation phase in 12 patients. All the allergic skin lesions were mild, except one presenting with Stevens-Johnson syndrome (0.4%). The patient was an 85-year-old female treated with LTG monotherapy. Three of 13 patients with allergic skin responses were maintained on LTG with concomitant use of anti-allergic medications, and their rashes gradually disappeared. Another three patients agreed on rechallenge with LTG with a smaller dose of no more than 12.5 mg/day after the disappearance of their skin rashes and there was no recurrence of allergic reaction. In conclusion, the incidence and risk factors of LTG-related skin rashes in the present study of adults with epilepsy were comparable to findings from clinical trials in Western countries.

Topiramate related reversible erectile dysfunction in temporal lobe epilepsy

Topiramate (TPM) is a newer antiepileptic drug with high efficacy in treating various neurological disorders, especially epilepsy and migraine. The adverse effects of TPM therapy are mainly central nervous system-related somnolence and dizziness. There are rare reports about the role of TPM on sexual effects, but with inconsistent results. In this report, we describe a 31-year-old man who developed erectile dysfunction after several months of TPM use. Complete urological and sexual psychiatric evaluations were done. There was lack of an identifiable organic basis and psychiatric pathology in this patient. The erectile dysfunction improved only after the termination of TPM, documenting the temporal relationship. We reviewed and discussed the clinical aspect of TPM use in erectile dysfunction. This case and the rare cases of erectile dysfunction in TPM use reported in the literature show that TPM is worth to be paid attention to whenever it is prescribed in a wide range of neurological disorders.

Cognitive performance in cryptogenic epilepsy

Cognitive impairment in epilepsy has begun to gain more attention in clinical practice. There is now a considerable amount of research relating to memory functioning in epilepsy, however, few studies specifically focused on cryptogenic epilepsy. We investigated the cognitive performance in cryptogenic epilepsy patients with the aid of cognitive ability screening instrument (CASI), based on cross‐sectional and longitudinal aspects. A total of 100 patients who met the diagnostic criteria of cryptogenic epilepsy were recruited from a national university hospital. The patients with normal CASI scores were compared with those with abnormal ones. We also compared the follow‐up CASI score after 3 years with the previous score in all cryptogenic epilepsy patients. Thirty‐six per cent of cryptogenic epilepsy patients showed cognitive impairment. The variables correlated with higher risks of cognitive impairment were lower educational status, number of seizure types, duration of seizure and polytherapy, especially in the lower educational status. The correlation between CASI and the Mini‐Mental State Examination was excellent. In the follow‐up study, the abnormal group showed significant improvement in total CASI score. The normal group showed no significant change. We suggest that in cryptogenic epilepsy, lower educational status remains the most important factor in determining cognitive performance. Adequate treatment with antiepileptic drugs can improve cognitive performance in previously cognitively impaired patients.

Paroxysmal Dyskinesia with Secondary Generalization of Tonic-clonic Seizures in Pseudohypoparathyroidism

Paroxysmal dyskinesias (PDs) and some motor manifestations of epileptic seizures have been difficult to differentiate clinically. Whether the two disorders are clinically distinct or share common pathophysiologic mechanisms remains undetermined. The classification of PD has been revised according to its precipitating factors as kinesigenic, nonkinesigenic, exertional, or hypnogenic (1). Most sporadic and all familial cases of PD are idiopathic. Symptomatic PD accounts for only a minority of sporadic cases, such as multiple sclerosis, hypoxic encephalopathy, and hypoparathyroidism (2). We report a case of pseudohypoparathyroidism (PHT) with kinesigenic PD and secondary generalization of tonic–clonic seizures.

Somatosensory rub evoked reflex epilepsy of a temporal lobe origin

Somatosensory rub reflex epilepsy, evoked by prolonged or repetitive cutaneous contact of a circumscribed body area, is an unusual form of reflex epilepsy. The peculiar complaints and the negative interictal electroencephalographic (EEG) recordings make it difficult to identify the epileptic origin. Here we report an unusual case whose seizures would be evoked by a touch or rub on a unilateral arm and shoulder, with a contralateral temporal lobe origin, demonstrated in immediate postictal single-photon emission computed tomography (SPECT).

Pregabalin Attenuates Excitotoxicity in Diabetes

Diabetes can exacerbate seizures and worsen seizure-related brain damage. In the present study, we aimed to determine whether the standard antiepileptic drug pregabalin (PGB) protects against pilocarpine-induced seizures and excitotoxicity in diabetes. Adult male Sprague-Dawley rats were divided into either a streptozotocin (STZ)-induced diabetes group or a normal saline (NS) group. Both groups were further divided into subgroups that were treated intravenously with either PGB (15 mg/kg) or a vehicle; all groups were treated with subcutaneous pilocarpine (60 mg/kg) to induce seizures. To evaluate spontaneous recurrent seizures (SRS), PGB-pretreated rats were fed rat chow containing oral PGB (450 mg) for 28 consecutive days; vehicle-pretreated rats were fed regular chow. SRS frequency was monitored for 2 weeks from post-status epilepticus day 15. We evaluated both acute neuronal loss and chronic mossy fiber sprouting in the CA3 area. In addition, we performed patch clamp recordings to study evoked excitatory postsynaptic currents (eEPSCs) in hippocampal CA1 neurons for both vehicle-treated rats with SRS. Finally, we used an RNA interference knockdown method for Kir6.2 in a hippocampal cell line to evaluate PGBs effects in the presence of high-dose ATP. We found that compared to vehicle-treated rats, PGB-treated rats showed less severe acute seizure activity, reduced acute neuronal loss, and chronic mossy fiber sprouting. In the vehicle-treated STZ rats, eEPSC amplitude was significantly lower after PGB administration, but glibenclamide reversed this effect. The RNA interference study confirmed that PGB could counteract the ATP-sensitive potassium channel (KATP)-closing effect of high-dose ATP. By opening KATP, PGB protects against neuronal excitotoxicity, and is therefore a potential antiepileptogenic in diabetes. These findings might help develop a clinical algorithm for treating patients with epilepsy and comorbid metabolic disorders.

Lamotrigine-induced hypersensitivity syndrome in a Han Chinese patient with the HLA-B*5801 genotype

Antiepileptic drug (AED) therapy is the mainstay for treating epilepsy. Most of the adverse effects in AED therapy are mild, predictable, and dose-dependent. Cutaneous eruptions, which lead to drug withdrawal and hospitalization, are the most frequent idiosyncratic adverse reactions. Severe cutaneous adverse reactions (SCARs) with high morbidity and mortality, including Stevens– Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity syndrome, are not uncommon in AED therapy. A strong association between the allele of human leukocyte antigen HLA-B*1502 and carbamazepine-induced SJS has been found in Han Chinese [1]. The lower incidence of carbamazepine-induced SJS in Caucasians, in contrast to its higher incidence in Han Chinese, suggests that there is an ethnic difference in susceptibility. Lamotrigine, one of the newer AEDs, has been reported as a risk factor for skin rashes. We previously [2] identified the risk factors of skin rashes in the patients treated with an initially high dose and rapid escalation of the dose of lamotrigine, and co-medicated with valproic acid. The role of HLA B*1502 in lamotrigine-induced SJS has been investigated and no definite association was found in the studied Han Chinese population [3], which is the same as in Caucasians. In contrast, there seems to be a weak association between HLA B*5801 and lamotrigineinduced SCARs in Caucasians [4]. We report a female Han Chinese patient with epilepsy and lamotrigine-induced SCARs; a genetic study identified the HLA-B*5801 allele as a risk factor. A 32-year-old Han Chinese woman with epilepsy, treated in a special epilepsy clinic in National Cheng Kung University Hospital for years, had been given regular valproic acid therapy (400 mg/day) and had a seizure frequency of around once a month. As the frequency had increased to around once a week, lamotrigine (starting at 20 mg/day, with a 20 mg/week increase) was added. Four weeks later, with the lamotrigine dose at 100 mg/day, she was admitted because of a high fever, generalized erythema, and jaundice. The patient’s blood test revealed high levels of AST (413 U/L), GPT (496 U/L), total bilirubin (17.7 mg/dL), LDH (790 IU/L), alkaline phosphate (582 IU/L), and gamma-GT (821 U/L). Combined with the high fever and a generalized rash, the patient was diagnosed with drug hypersensitivity syndrome. A skin biopsy (Fig. 1) showed mild spongiosis and scattered necrotic keratinocytes in the spinous layer, and vacuolar interface alteration of the basal layers with an infiltration of small lymphocytes. She also showed a perivascular infiltrate of small lymphocytes with scattered neutrophils in the upper dermis. These findings are consistent with maculopapular drug eruption. Under the diagnosis of lamotrigine-induced SCARs, we performed genotyping for this patient and the results showed the J. C. Chow Y.-J. Wu J.-J. Tsai Department of Pediatrics, Chi-Mei Foundation Medical Center, Tainan, Taiwan