The localization and lateralization of fear aura and its surgical prognostic value in patients with focal epilepsy.

OBJECTIVE: Fear aura has traditionally been considered relevant to epileptic discharges from mesial temporal areas, and few studies have investigated its effect on surgical outcome in drug-resistant epilepsy. We aim to assess the localizing and lateralizing value as well as prognostic significance of fear aura in patients with focal epilepsy. METHODS: The occurrence of fear aura in relation to epileptogenic origin and its association with postoperative outcome were analyzed in 146 consecutive patients undergoing resective surgery for intractable epilepsy. RESULTS: Ninety-four (64.4%) patients reported auras, and 31 (21.2%) reported fear aura in their seizures. One hundred ten (75.3%) patients had an Engel class I outcome until last follow-up, of whom 24 experienced fear aura preoperatively. Fear aura appeared more frequently during temporal and frontal lobe seizures, but did not lateralize the seizure onset zone. There were no significant baseline differences between patients with and without fear aura. No correlation was found between postoperative outcome and the presence of auras. Occurrence of fear aura failed to show predictive value in surgical outcome whether in pooled or subgroup analysis. INTERPRETATION: This study advances our understanding of the origin of fear aura, and is helpful for presurgical evaluation and outcome prediction. Without lateralizing value, fear aura is more commonly seen with temporal or frontal origin. When taken as a whole, auras do not have a significant impact on seizure outcome in focal epilepsy. Patients with fear aura are no more likely to become seizure-free than those without fear aura.

High signal-intensity abnormalities in susceptibility-weighted imaging for primary intracerebral hemorrhage.

Purpose: To identify the regularity of signal evolution of intracerebral hemorrhage on susceptibility-weighted imaging (SWI) at different stages compared with T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI). Methods: We retrospectively evaluated a series of 365 patients who underwent T1WI, T2WI, and SWI examination simultaneously or sequentially in our hospital from January 2015 to May 2017. Two neuroradiologists assessed the images and discrepancies between their interpretations were resolved by consensus. Statistical analysis was performed using Chi-squared and Kappa tests. Results: Of the 365 patients on SWI sequence, 94 were enrolled. SWI detected the cases at different stages; T1WI detected 89 cases and T2WI detected 91 cases. The signal intensity of intracerebral hemorrhage on SWI was significantly associated with T1WI imaging and T2WI (χ2 = 4.651; p < 0.05; χ2 = 26.396; p < 0.01, respectively), especially at the late subacute stage. There was moderate consistency between the signal intensity of intracerebral hemorrhage on T2WI and SWI (Kappa coefficient = 0.530). Conclusion: Intracerebral hemorrhage has a varied appearance on SWI, and the evolution of signal of intracerebral hemorrhage on SWI sequence is influenced by T1WI and T2WI. Hematoma detection should be closely combined with clinical manifestation.

Inhibition of Acid Sensing Ion Channel 3 Aggravates Seizures by Regulating NMDAR Function.

The existing data about whether acid sensing ion channels (ASICs) are proconvulsant or anticonvulsant are controversial. Particularly, acid sensing ion channel 3 (ASIC3) is the most sensitive to extracellular pH and has the characteristic ability to generate a biphasic current, but few studies have focused on the role of ASIC3 in seizure. Here we found ASIC3 expression was increased in the hippocampus of pilocarpine induced seizure rats, as well as in hippocampal neuronal cultures undergoing epileptiform discharge elicited by Mg2+-free media. Furthermore, ASIC3 blockade by the selective inhibitor APETx2 shortened seizure onset latency and increased seizure severity compared with the control in the pilocarpine induced seizure model. Incubation with APETx2 enhanced the excitability of primary cultured hippocampal neurons in Mg2+-free media. Notably, the aggravated seizure was associated with upregulation of the N-methyl-D-aspartate subtype of glutamate receptors (NMDARs), increased NMDAR mediated excitatory neurotransmission and subsequent activation of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cAMP-response element binding protein (CREB) signaling pathway. Moreover, co-immunoprecipitation confirmed the interaction between ASIC3 and NMDAR subunits, and NMDARs blockade prevented the aggravated seizure caused by ASIC3 inhibition. Taken together, our findings suggest that ASIC3 inhibition aggravates seizure and potentiates seizure induced hyperexcitability at least partly by the NMDAR/CaMKII/CREB signaling pathway, which implies that ASIC3 agonists may be a promising approach for seizure treatment.

Amiloride suppresses pilocarpine-induced seizures via ASICs other than NHE in rats.

BACKGROUND AND PURPOSE: Although recent studies have indicated that acid-sensing ion channels (ASICs) may play an important role in suppressing status epilepticus (SE) in rats, the precise mechanism is unclear. We attempted to investigate the antiepileptic effect of amiloride in SE rats and its mechanism. METHODS: Rats with seizures induced by Li-pilocarpine were randomly divided into four groups, phosphate buffer saline (PBS) group, amiloride group, levetiracetam group and acidic liquid group, respectively. The electroencephalogram (EEG) of each group was recorded. Then rats treated with different drugs (2 h after amiloride or PBS injection or 1 h after PBS injection) and a normal control group was selected for reverse transcription-polymerase chain reaction (RT-PCR). The expression of ASIC1a, ASIC3 and sodium-hydrogen exchanger (NHE) in each group was detected. RESULTS: Amiloride reduced the frequency of discharge in 60~90 min after injection significantly. In acidic liquid group, the epileptic discharge was increased in 0~30 min. Moreover, the expression of ASIC1a, ASIC3 and NHE was obviously increased in the SE groups. Compared with SE groups, the expression of ASIC1a and ASIC3 mRNA in amiloride group decreased significantly. While NHE mRNA expression in the SE groups showed no significant difference. CONCLUSION: Amiloride inhibited pilocarpine-induced SE and the anti-epileptic mechanism was associated with deactivation of the ASIC1a and ASIC3 instead of NHE in rats.

Effects of extracellular Ca(2+) influx and intracellular Ca(2+) release on ethanol-induced cytoplasmic Ca(2+) overload in cultured superior cervical ganglion neurons.

The present research was designed to investigate the interference of Ca(2+) homeostasis by ethanol on the primary cultured superior cervical ganglion (SCG) neurons. (1) Using the whole cell patch clamp recording, the amplitudes of voltage-dependent Ca(2+) channel (VDCC) currents could be reduced by ethanol in a concentration-dependent manner. Ethanol (100mM) inhibited about 25% of Ca(2+) channel current. However, the activation of Ca(2+) channel was not affected by ethanol at those concentrations. (2) The similar extent inhibitions of 100mM ethanol on the increments of intracellular Ca(2+) concentration ([Ca(2+)](i)) induced by 40 mM KCl and 1 microM A23187 were also observed in the fluo-3-AM loaded superior cervical ganglia (SCG) via detecting the change of [Ca(2+)](i) with a laser scanning confocal microscopy. In contrast, the basal [Ca(2+)](i) was significantly increased by ethanol alone in a concentration-dependent manner. These phenomena were also observed even under Ca(2+) free bath solution or the solution added 300 microM cadmium chloride conditions. Together with above results, our data suggest that ethanol increases basal [Ca(2+)](i), but it also inhibits the extracellular Ca(2+) influx through VDCC and ionophore channel. And the augment of basal [Ca(2+)](i) induced by ethanol might attribute to the Ca(2+) releasing from intracellular Ca(2+) pools.