Reduced serum level of THDOC, an anticonvulsant steroid, in women with perimenstrual catamenial epilepsy.

PURPOSE: Seizure exacerbation in catamenial epilepsy (CE) is associated with the decrease in progesterone secretion and increase in estradiol secretion during the premenstrual period. Moreover, experimental evidence suggests that tetrahydrodeoxycorticosterone (THDOC), a positive modulator of the type A receptor for gamma-aminobutyric acid (GABA), and dehydroepiandrosterone sulfate (DHEAS), a negative modulator of this receptor, might play a crucial role in modulating seizure frequency during the menstrual cycle. Following these studies it seems of interest to investigate possible variations, among other hormonal parameters, of THDOC and DHEAS in CE patients. METHODS: The serum concentrations of progesterone (P4), pregnenolone, allopregnanolone (AP), THDOC, DHEAS, cortisol, and DHEAS/cortisol ratio were measured throughout the menstrual cycle at the 7th, 11th, 15th, 19th, 23rd, and 27th day from the onset of spontaneous menstrual blood loss in young premenopausal women with CE (n = 17) and age-matched controls (n = 13). RESULTS: At each time of the study, the serum concentration of THDOC and the DHEAS/cortisol ratio were lower (p < 0.05) in women with CE than in control women. The concentrations of P4, pregnenolone, and AP did not differ between the two groups of subjects. CONCLUSIONS: The reduced serum concentration of THDOC and the reduced DHEAS/cortisol ratio detected throughout the menstrual cycle in women with CE might play a role in CE. Moreover, the peculiar pattern of CE seizure exacerbation might suggest that these neuroendocrine variations are worth investigating in other epileptic syndromes, particularly in those characterized by relevant and uncontrolled variations in seizure frequency.

Activation of GABA(B) receptors reverses spontaneous gating deficits in juvenile DBA/2J mice.

RATIONALE: Gamma-amino-butyric acid (GABA)(B) receptors play a key role in the pathophysiology of psychotic disorders. We previously reported that baclofen, the prototypical GABA(B) agonist, elicits antipsychotic-like effects in the rat paradigm of prepulse inhibition (PPI) of the startle, a highly validated animal model of schizophrenia. OBJECTIVES: We studied the role of GABA(B) receptors in the spontaneous PPI deficits displayed by DBA/2J mice. MATERIALS AND METHODS: We tested the effects of baclofen (1.25-5 mg/kg, intraperitoneal [i.p.]) in DBA/2J and C57BL/6J mice, in comparison to the antipsychotic drugs haloperidol (1 mg/kg, i.p.) and clozapine (5 mg/kg, i.p.). Furthermore, we investigated the expression of GABA(B) receptors in the brain of DBA/2J and C57BL/6J mice by quantitative autoradiography. RESULTS: Baclofen dose-dependently restored PPI deficit in DBA/2J mice, in a fashion similar to the antipsychotic clozapine (5 mg/kg, i.p.). This effect was reversed by pretreatment with the GABA(B) antagonist SCH50211 (50 mg/kg, i.p.). In contrast, baclofen did not affect PPI in C57BL/6J mice. Finally, quantitative autoradiographic analyses assessed a lower GABA(B) receptor expression in DBA/2J mice in comparison to C57BL/6J controls in the prefrontal cortex and hippocampus but not in other brain regions. CONCLUSIONS: Our data highlight GABA(B) receptors as an important substrate for sensorimotor gating control in DBA/2J mice and encourage further investigations on the role of GABA(B) receptors in sensorimotor gating, as well as in the pathophysiology of psychotic disturbances.

Levetiracetam attenuates spontaneous spike-and-wave discharges in DBA/2J mice.

Recent evidence highlights levetiracetam (LEV) as an advantageous treatment of absence epilepsy (AE). Thus, we investigated the effects of this drug in DBA/2J mice, a murine model of AE. Similarly to ethosuximide (200 mg/kg, intraperitoneal, i.p.) and sodium valproate (250 mg/kg, i.p.), two classic antiabsence agents, LEV (50-200 mg/kg, i.p.) reduced the occurrence of spike-and-wave discharges, AE's typical electroencephalographic patterns. Our results confirm LEV's efficacy in AE treatment.

Cardiovascular modulation during vagus nerve stimulation therapy in patients with refractory epilepsy.

To evaluate the effects of permanent vagal stimulation on cardiovascular system, 10 patients, affected by drug-resistant epilepsy with no primitive cardiovascular pathologies, were assessed prior to VNS surgery. A complete echocardiographic study [conventional and tissue Doppler imaging (TDI)], 24-h blood pressure (BP) monitoring and HRV evaluation were performed. The above mentioned parameters were investigated without any substantial changes to drug treatment during a check-up subsequent to VNS activation [mean: 7.7 months]. The results obtained show that while the anthropometrical data and both conventional and TDI echocardiography were unvaried compared to baseline, BP showed a significant increase of both systodiastolic values. Moreover, a close scrutiny of the most affected period of the BP increase (zenith between 16:31 and 17:30 pm) (systolic BP 114.7 mmHg vs 95.3 mmHg, P < 0.0001; diastolic BP 70.9 mmHg vs 56.9 mmHg, P < 0.001) showed a significant increase of the high frequencies components (HF) (28.4 ± 2.7 vs 36 ± 5.3, P < 0.05) and a significant reduction in low frequency/HF ratio (2.3 ± 0.3 vs 1.7 ± 0.3, P < 0.0001). The present study confirms the intrinsic cardiovascular safety and reliability of VNS procedures on both BP and HF and LF profiles and suggests that a primitive VNS-mediated central impingement on vagal efferents, independently by the antiepileptic mechanism, correlated to an moderate increase of parasympathetic activity, which in turn might play a protective role in seizure-triggered alterations of cardiovascular dynamic.

Combined EEG/fMRI recording in musicogenic epilepsy.

Seizures induced by musical stimulation are usually correlated to temporal epilepsy, although the precise localization of their epileptogenic networks are not well characterized. Brain imaging studies show that regional cerebral blood flow (rCBF) recorded during musicogenic seizures is increased in putative epileptogenic foci, as well as in other brain regions not directly related to seizure activity. These studies, however, afford only a virtual temporal relation between ictal discharges and rCBF changes, given that brain images are correlated with off-line EEG recordings. To obviate this problem, the simultaneous multimodal recording of the episode of musicogenic epilepsy is mandatory. The present study describes the EEG-fMRI co-recording of musicogenic elicited seizures in a case of simple partial epilepsy. Our results show that EEG features recorded in epileptogenic areas are largely coupled with rCBF increase. Furthermore, rCBF modifications in other regions suggest that additional aspects of musical processing are also elicited during musicogenic seizures.