Renato Galli

Alteration of Cardiac Function in Patients with Temporal Lobe Epilepsy: Different Roles of EEG-ECG Monitoring and Spectral Analysis of RR Variability

Summary: Purpose: Because several reports have described the relation between epilepsy and cardiac arrhythmias and suggest that changes in autonomic neural control of the heart could be involved in the pathogenesis of sudden unexplained death in patients with epilepsy, the aim of this study was to evaluate cardiac function in patients with temporal lobe epilepsy.

Citalopram as treatment of depression in patients with epilepsy.

Objectives:To assess the safety of citalopram as a treatment of depression in patients with epilepsy. Methods:This is an open, multicentered, uncontrolled study. Depressed epileptic patients on antiepileptic drugs (AEDs) took part in the study. Patients who had a mild frequency of seizures in the 4 previous months underwent treatment with citalopram (20 mg/d) for 4 consecutive months. A change in seizure frequency from the baseline was chosen as the primary measure for the safety of citalopram and efficacy against depressive symptoms was taken as secondary measure. Depression was rated using the Montgomery–Åsberg and Zung depression rating scales. Clinical assessments were performed at baseline, and at 2 and 4 months of citalopram therapy. Results:Forty-five patients were enrolled. Six patients dropped out of the study early: none of them because of a deterioration of seizure frequency. An overall improvement in seizure frequency was observed in the 39 patients who completed the study. Plasma AED concentrations were unchanged during therapy, and depressive symptoms improved markedly. Twenty-two patients complained of adverse effects, mainly headache, nausea, dizziness, somnolence, and fatigue. Conclusions:In this open, multicentered, uncontrolled study, 4 months’ of treatment with citalopram (20 mg/d) were associated with an improvement in depressive symptoms and reduction in seizure frequency.

Analysis of RR variability in drug-resistant epilepsy patients chronically treated with vagus nerve stimulation

Vagus nerve stimulation (VNS) has been suggested as an adjunctive treatment for drug-resistant epilepsy when surgery is inadvisable. The overall safety profile of VNS seems to be favorable as only minor adverse effects have been described. The purpose of this study was to determine if cardiac vagal tone is eventually modified by short- and long-term VNS. The effects of short- and long-term VNS were evaluated in seven subjects with intractable epilepsy. Autonomic cardiac function has been carried out by means of a 24-h analysis of RR variability at baseline (t(0)), 1 month (t(1), short-term VNS) and 36 months after VNS initiation (t(2), long-term VNS). Frequency- and time-domain parameters were calculated. Periodic cardiological and neurological evaluations were performed.Clinically relevant cardiac effects were not observed throughout the study. Despite the limited number of patients and the variety of data among them, for all the patients, a common trend towards a nocturnal decrease in the high-frequency (HF) component of the spectrum was observed after long-term VNS (mean+/-S.D.: 40+/-18 normalized units (nu) at t(0), 38+/-17 nu at t(1), 18+/-10 nu at t(2); p<0.05 of t(2) vs. either t(0) or t(1)). The day-to-night changes in the power of low-frequency (LF) and HF components were significantly blunted after long-term VNS (LF day-to-night change: +16+/-13 nu at t(0) and +15+/-8 nu at t(1) vs. +3+/-13 nu at t(2), p<0.02; HF day-to-night change: -18+/-13 nu at t(0) and -13+/-11 nu at t(1) vs. +3+/-12 nu at t(2), p<0.003). No significant changes were observed with regard to the time-domain parameters of the heart rate variability. Throughout the neurological follow-up, one subject became seizure-free, three experienced a seizure reduction of >50%, two patients of <50% and one had no changes in his seizure frequency. Our findings suggest that long-term VNS might slightly affect cardiac autonomic function with a reduction of the HF component of the spectrum during night and a flattening of sympathovagal circadian changes, not inducing, however, clinically relevant cardiac side effects.

Daytime Sleepiness in Epilepsy Patients Receiving Topiramate Monotherapy

Summary:  Purpose: Limited research has focused to date on objective neurophysiological evaluation of daytime sleepiness in patients treated with newer antiepileptic drugs (AEDs), especially when used as monotherapy. This study was aimed at assessing occurrence of daytime sleepiness in newly diagnosed, drug‐naïve patients with partial epilepsy receiving initial topiramate (TPM) monotherapy.

Antimyoclonic effect of levetiracetam in MERRF syndrome

The treatment of progressive myoclonic epilepsy (PME) is largely empirical, even though valproic acid (VPA) is usually considered the drug of first choice. However, VPA should be used with caution in PME due to mitochondrial dysfunction, i.e. in MERRF (myoclonic epilepsy with ragged red fibers) syndrome, because of its interaction with mitochondrial respiration and metabolism. Levetiracetam (LEV) treatment was started in combination with VPA in a patient with typical clinical, histological, and biochemical features of MERRF due to a mutation on the tRNA of Phenilalanine gene. The average myoclonus score improved dramatically, as well as the quality of life and no side effects were observed, even after having withdrawn VPA. LEV may benefit myoclonus in PME of mitochondrial origin without altering mitochondrial function, and it could be considered the drug of first choice for the treatment of myoclonus in MERRF.

Circulating levels of allopregnanolone, an anticonvulsant metabolite of progesterone, in women with partial epilepsy in the postcritical phase.

Summary:  Purpose: Several lines of evidence indicate that there exists a relation between ovarian hormones and epilepsy. Estrogens decrease seizure threshold and increase brain excitability, whereas progesterone has an inhibitory effect and reduces epileptiform activity. Recently considerable interest has turned to neuroactive steroids, a group of progesterone metabolites, as endogenous modulators of excitability of the central nervous system (CNS). Their ability to alter neuronal firing rapidly occurs through interaction with γ‐aminobutyric acid (GABA) A receptor complex. In a previous experience, serum allopregnanolone (3α‐OH‐5α‐pregnan‐20‐one) levels were measured in 15 women with partial epilepsy in the intercritical phase, and no significant differences were found between patients and control subjects.

A quantitative study of daytime sleepiness induced by carbamazepine and add-on vigabatrin in epileptic patients.

Introduction – The clinical relevance of daytime sleepiness associated with carbamazepine (CBZ) and vigabatrin (VGB) was objectively assessed by the multiple sleep latency test (MSLT) and nocturnal sleep recordings. Material and methods – Twenty‐six patients with partial epilepsy and mean monthly seizure frequency of 4, aged 18 to 48 years, receiving chronic monotherapy with CBZ and subsequent VGB addition for 2 months (14 patients), were compared with a group of healthy subjects. Subjective daytime sleepiness was complained by 13 patients on CBZ monotherapy and 9 patients during VGB add‐on treatment. Results – No differences in nocturnal sleep parameters, but significantly shorter daytime sleep latencies at the MSLT, were detected in CBZ‐treated patients as compared with healthy controls. Addition of VGB therapy did not further enhance objective daytime sleepiness. Conclusion – Some sleepiness occurs in chronically CBZ‐treated epileptic patients, which can be objectively measured by the MSLT, but it is not aggravated by add‐on VGB.

Catamenial epilepsy, progesterone and its metabolites

This study was undertaken to determine plasma allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one, A-PREG) and pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one, PREG) concentrations in the luteal phase (22nd to 24th day of the ovarian cycle) in 15 women with partial epilepsy and catamenial exacerbation of the seizures in the intercritical phase and in 15 healthy women matched for age in order to determine if an impaired metabolism of 3alpha-hydroxymetabolites of progesterone (P) occurs in this convulsive disorder. No significant differences between the two groups were found with respect to the mean plasmatic A-PREG and PREG levels. A significant correlation was found instead between P and A-PREG or PREG concentrations.

Neurophysiological evaluation of vigilance in epileptic patients on monotherapy with lamotrigine

OBJECTIVE Limited research has focused to date on daytime sleepiness in epileptic patients treated with either conventional or newer antiepileptic drugs. We evaluated the level of vigilance in 15 consecutive, newly diagnosed and never medicated adult epileptic patients, receiving initial monotherapy with lamotrigine (LTG). METHODS Patients underwent the Multiple Sleep Latency Test (MSLT), visual reaction times (VRT) and Stanford Sleepiness Scale (SSS) on two separate occasions, i.e. before and 2 months after LTG treatment. A group of 15 age-matched healthy volunteers was taken as control. RESULTS At baseline, mean sleep latencies on the MSLT were comparable in epileptic patients and in controls. In patients, 2 months after monotherapy with LTG 200 mg/day, MSLT scores did not significantly change as compared with pre-treatment values. Accordingly, subjective evaluation of vigilance by the SSS and psychomotor performance by VRT were superimposable in controls and in untreated patients, and did not change in patients after LTG treatment. CONCLUSIONS These results suggest that in adult, newly diagnosed epileptic patients initial monotherapy with LTG does not impair vigilance.

Visual contrast sensitivity in carbamazepine-resistant epileptic patients receiving vigabatrin as add-on therapy

In 40 adult patients with partial epilepsy resistant to carbamazepine (CBZ) monotherapy at the maximum tolerated individual doses, vigabatrin (VGB) was added to reduce seizure frequency further. In an attempt to evaluate potential drug-related visual side effects, visual contrast sensitivity (VCS), i.e., the ability to perceive minimal differences in luminance between adjacent regions of a grating visual pattern, was assessed before and monthly during a 6-month period of VGB add-on therapy and compared with that of a control group of healthy subjects. Twenty-eight patients completed the prescribed 6-month period of trial and were included in the statistical analysis. VCS measured during CBZ treatment showed a clear loss in all explored spatial frequencies. From the second month of VGB treatment on, VCS exhibited a progressive recovery, especially in the medium-frequency range, although only to a partial extent as compared with that in the controls. This effect saturated at the sixth month. Moreover, a different recovery of VCS to vertical and oblique gratings was observed, which likely suggests a drug effect on visual cortex. VGB add-on therapy was both well tolerated and effective in reducing seizure frequency.