**9. Drug-resistant epilepsy and polytherapy**

**8.3. Plants**

may be responsible for this effect.

24 Pharmacology and Nutritional Intervention in the Treatment of Disease

**8.4. Nootropics and anti-oxidants**

Assuming that AEDs can trigger free radical production and lipid peroxidation, Hung-Ming et al. (2002) studied TW970, a modified version of the Chinese herbal specific chaihu-longumuli-tang which has antiepileptic and antioxidant properties. The TW 970 was administered for 4 months to 3 groups of adults: 1) 20 patients with drug-resistant epilepsy (at least 4 seizures a month); 2) 20 patients with mild epilepsy (fewer than 4 seizures a month), and 3) a control group of 20 healthy adults matched for age. The patients were tested prior to the introduction of TW970 and four months after introduction. In the resistant group, seizure frequency dropped from 13.4 ± 3.4 to 10.7 ± 2.5 a month but the difference was not significant (p=0.084). Prior to TW970 introduction, the resistant epilepsy group had significantly higher lipid peroxidation, increased MDA and CuZn-SOD activity, including reduced GSH, compared with the healthy control group. After 4 months of TW970 treatment, levels of MDA and CuZn-SOD normalized in the resistant epilepsy group whereas no significant changes in parameters were found in the mild epilepsy group, either prior to or following TW970 therapy. The authors suggest that TW970 may reduce seizure frequency in resistant epilepsy and that anti-oxidants

Japanise kampo (TJ-960) traditional herbal medicine was used for treatment of epilepsy (Hamada et al., 1993). The authors identified baicalein as one of the several components the most potent scavenger for radicals in FeCl3-induced epilepsy model in rats. It is suggested that

Many Native American plants are valued by local medical practitioners for their positive effects on health and a number of diseases, including epilepsy. *Celastrus paniculatus L.* (CP), *Picrorhiza kurroa (PK)* and *Withania somnifera L. (WS)* were investigated for their free radical scavenging capacity (Russo et al., 2001). It has been observed that methanolic extracts of these plants are dose-dependent free radical scavengers, and that they prevent DNA injury due to oxygen stress. PK extract had a more powerful effect than CP or WS. These favourable biological properties, reported in clinical and animal studies, have been attributed, at least in part, to their anti-stress, immune-modulating, anti-inflammatory and anti-aging effects. A similar anti-oxidant effect was observed using another plant in Ayurvedic medicine, *Bacopa*

It was reported that nootropics (phenotropil) and antioxidants (mexidol) potentiate AEDs in posttraumatic epilepsy treatment (Savenkov et al., 2013).The authors observed in 75 patients significant reduction of epileptic seizure frequency, decrease of epileptic changes in the EEG, improvement of cognitive function and quality of life. Coherent indicators of slow waveactivity were observed after treatment. The authors recommended to use mexidol and

When interpreting clinically, these and the highlighted earlier results, one needs to be careful because the relationships in disease as heterogeneous as epilepsy are complex and multifac‐

baicalein action is based upon radical quenching and anti-oxidant effects.

*monniera L.* (BM), which has free radical scavenging capacity (Russo et al., 2003).

phenotropil with AEDs for complex treatment of posttraumatic epilepsy.

Drug-resistant seizures force physicians to use polytherapy with various AEDs. Polytherapy increases the production of free radicals and disturbs mineral balance to a greater extent than monotherapy, leading to increased oxygen stress. Both, increased free radical production and inhibition of the enzymes which remove scavengers, lead to adverse reactions and aggravation of the morbid process (Maertens et al., 1995; Hamed et al., 2004).

Patients with chronic epilepsy and long-term AED therapy are at greater risk of atherosclerotic changes in the arteries through complex molecular mechanisms that promote atherogenesis (Hamed and Nabeshima, 2005). Metabolic dysfunctions in these patients have been attributed to altered homocysteine, lipid and lipoprotein metabolism and uric acid.

In relevant study, relationship between the carotid artery intima-media thickness (CA-IMT) and lipid profile (MDA, oxidised LDL, total anti-oxidant capacity, GSH-Px and uric acid) were assessed in 225 adult patients with epilepsy (and 60 control subjects) (Hamed et al., 2007). Compared to the control group, the CA-IMT of treated and untreated patients common carotid artery, bifurcation area and internal carotid arteries were significantly thickened in 51.1%, 73.3% and 43.6% of patients, respectively. The study supports the opinion that in patients with epilepsy, various risk factors and CA-IMT become worse, which could be attributed to epilepsy itself and/or AEDs. According to the authors, these dysfunctions are indications for routine anti-oxidant multivitamin supplementation (folic acid, vitamins B12, B6, C, E, and betacarotene). The protective, anti-atheromatic effect of vitamins is based on their anti-oxidant and anti-inflammatory properties. Tupeev et al. (1993) found a positive effect of prolonged vitamin E treatment (600 mg/day) in patients with generalized seizures: seizure frequency was reduced, EEG improved and anti-oxidant activity increased.

In other research highlighted earlier, increased lipid hydroperoxidase concentrations were weakly correlated with the risk factors for vascular changes (triglyceridemia, cholesterolemia) (Mahle and Dasgupta, 1997).
