Background-Driving is a complex form of activity involving especially cognitive and psychomotor functions. These functions may be impaired by Parkinson's disease. The relation between Parkinson's disease and driving ability is still obscure and clinicians have to make decisions concerning the driving ability of their patients based on insuYcent information. Until now no studies have compared diVerent methods for evaluating the driving ability of patients with Parkinson's disease. Methods-The driving ability of 20 patients with idiopathic Parkinson's disease and 20 age and sex matched healthy control subjects was evaluated by a neurologist, psychologist, vocational rehabilitation counsellor, and driving instructor using a standard 10 point scale. The patients and controls also evaluated their own driving ability. Cognitive and psychomotor laboratory tests and a structured on road driving test were used for evaluating the subjects' driving ability. Results-The patients with Parkinson's disease performed worse than the controls both in the laboratory tests and in the driving test. There was a high correlation between the laboratory tests and driving test both in the patient group and in the control group. Disease indices were not associated with the driving test. The neurologist overestimated the ability of patients with Parkinson's disease to drive compared with the driving ability evaluated by the structured on road driving test and with the driving related laboratory tests. Patients themselves were not capable of evaluating their own ability reliably. Conclusion-Driving ability is greatly decreased in patients with even mild to moderate Parkinson's disease. The evaluation of patients' driving ability is very diYcult to carry out without psychological and psychomotor tests and/or a driving test. (J Neurol Neurosurg Psychiatry 1998;64:325-330)

Summary:Purpose: Weight gain is an important adverse effect of valproate (VPA) therapy, and it is associated with hyperinsulinemia and hyperandrogenism in women with epilepsy. Leptin is considered a signaling factor regulating body weight and energy metabolism. In human subjects, obesity is in general associated with elevated serum leptin levels, suggesting decreased sensitivity to leptin. The present study aimed at evaluating the role of insulin and leptin in VPA-related obesity.Methods: Body mass index (BMI) was calculated, and serum insulin and leptin levels were measured in 81 patients with epilepsy taking VPA and in 51 healthy control subjects.Results: Forty (49%) of the patients taking VPA and 25 (49%) of the control subjects were obese. The mean insulin levels were higher in VPA-treated patients than in the control subjects despite similar BMI values, when all subjects were included in the comparison. Both obese male and female patients taking VPA had higher serum insulin levels than the respective control subjects with similar BMI values. Serum insulin levels also were higher in lean male and lean female patients compared with the lean control subjects of same sex. Serum leptin levels did not differ between the VPA-treated patients and the control subjects.Conclusions: Both obese and lean patients taking VPA for epilepsy have hyperinsulinemia, suggesting development of insulin resistance. This may be one of the factors leading to weight gain during VPA treatment. However, the results of the present study do not suggest an independent role for leptin in the pathogenesis of VPA-related obesity.

Summary:Purpose: Antiepileptic drugs (AEDs) may affect serum thyroid hormone concentrations. This study aimed to evaluate thyroid function in men taking carbamazepine (CBZ), oxcarbazepine (OCBZ), or valproate (VPA) for epilepsy.Methods: Ninety men with epilepsy (40 taking CBZ, 29 taking OCBZ, and 21 taking VPA monotherapy) and 25 control subjects participated in the study. After clinical examination, a blood sample for hormone, ␥-glutamyl-transferase (GGT) and antibody (ab) assays was obtained.Results: Serum thyroxine (T 4 ) and free thyroxine (FT 4 ) concentrations were low in men taking CBZ or OCBZ. Forty-five percent of men taking CBZ and 24% of men taking OCBZ had serum T 4 and/or FT 4 levels below the reference range. However, no correlations were found between T 4 or FT 4 and GGT concentrations in men taking CBZ or OCBZ. Thirteen percent of men taking CBZ, 17% of men taking OCBZ, and 6% of control men had increased levels of thyroid peroxidase (TPO)-ab and/or thyroglobulin (TG)-ab, but these were not associated with altered serum thyroid hormone concentrations. Serum triiodothyronine and thyrotropin levels in men taking CBZ or OCBZ were normal. In men taking VPA, the concentrations of thyroid hormones, thyrotropin, and antithyroid ab were normal.Conclusions: Serum thyroid hormone concentrations are low in CBZ-or OCBZ-treated men. However, these low levels do not seem to be due to liver enzyme induction or activation of immunologic mechanisms. Therefore, interference with hypothalamic regulation of thyroid function by CBZ and OCBZ seems possible. VPA does not have any significant effects on thyroid function. Key Words: Epilepsy-Thyroid hormonesCarbamazepine-Oxcarbazepine-Valproate.The endocrine effects of carbamazepine (CBZ) have been well documented. A decrease in serum thyroid hormone levels can already be detected in patients 2 months after starting CBZ (1). However, serum thyrotropin concentrations do not change, and the clinical significance of low serum thyroid hormone concentrations is unclear (1-8). The altered thyroid function during CBZ medication has been attributed to induction of the hepatic P-450 enzyme system and the consequent increase in the metabolism of thyroid hormones (9,10).Oxcarbazepine (OCBZ) is a novel antiepileptic drug (AED) that structurally resembles CBZ. However, the metabolic pathway of OCBZ in the liver is different from that of CBZ. OCBZ is mainly reduced, instead of being oxidized. Consequently, OCBZ does not appear to induce the hepatic P-450 enzyme system (11). Therefore, it has been suggested that OCBZ may not have effects on endocrine function equivalent to those of CBZ, and replacing CBZ with OCBZ resulted in deinduction of liver enzyme levels and short-term restoration of normal endocrine function in men with epilepsy (10,12). However, OCBZ may induce the hepatic P-450 enzyme system when given in high doses, and recent studies have shown that high doses of OCBZ may also affect sex hormone metabolism in men with epilepsy (13). Furthermore, OCBZ is well known to decreas...

Article abstract-Background: Recent observations have indicated that reproductive endocrine disorders are common among women taking valproate (VPA) for epilepsy, but it is not known whether respective abnormalities develop in men taking VPA for epilepsy. Carbamazepine (CBZ) may induce endocrine disorders in men with epilepsy, but the endocrine effects of oxcarbazepine (OXC) are not known. Methods: Reproductive endocrine function was evaluated in 90 men taking VPA (n ϭ 21), CBZ (n ϭ 40), or OXC (n ϭ 29) as monotherapy for epilepsy and in 25 healthy control men. Results: Twelve men (57%) taking VPA had increased serum androgen levels. The mean serum level of androstenedione was high in patients taking VPA. Serum levels of dehydroepiandrosterone sulfate were low, and serum concentrations of sex hormonebinding globulin (SHBG) were high in men taking CBZ. The endocrine effects of OXC seemed to be dose-dependent, because serum hormone levels were normal in patients with low OXC doses (Ͻ900 mg/day), but serum concentrations of testosterone, gonadotropins, and SHBG were high in patients with a daily OXC dose Ն900 mg. Conclusions: VPA increases serum androgen concentrations in men with epilepsy. The endocrine effects of CBZ and OXC were different, because CBZ appears to decrease the bioactivity of androgens, whereas OXC does not. NEUROLOGY 2001;56:31-36 Reproductive endocrine disorders and sexual dysfunction have frequently been attributed to epilepsy itself, but antiepileptic drugs (AED) also have various effects on endocrine function.1-7 Valproate (VPA) has been implicated to have only minor effects on the hormonal system in men with epilepsy.3,4 However, there is growing evidence that VPA therapy induces endocrine disorders in women with epilepsy, which are characterized by hyperandrogenism and hyperinsulinemia that are related to obesity. 5,6 Carbamazepine (CBZ) is one of the most widely used first-line AED. The use of CBZ is associated with a progressive increase in circulating levels of sex hormone-binding globulin (SHBG) and, consequently, in a decreased proportion of free, bioactive testosterone, which may result in sexual dysfunction in some men with epilepsy after long-term CBZ treatment.8 CBZ-related endocrine changes have been attributed to the induction of the hepatic P450-enzyme system by the drug. 9,10Oxcarbazepine (OXC), a keto-derivative of CBZ, is a new AED that closely resembles CBZ in structure.11 However, it has a different metabolic pathway in the liver; instead of by oxidation, it is mainly metabolized by reduction, and does not appear to induce the oxidative P450-enzyme system to the same extent as CBZ.12 Previous studies have shown that the CBZ-induced changes in endocrine and metabolic function equilibrate after CBZ is replaced with OXC.13,14 Thus, OXC has been suggested to be a safe AED with regard to endocrine and metabolic effects. However, there is evidence that OXC may also induce liver enzymes when prescribed at higher doses. 15 Endocrine effects of OXC have not been previously assessed...

The aim of this study was to evaluate cardiovascular responses as a marker of autonomic nervous system (ANS) disturbances in patients with untreated Parkinson's disease (PD) and to assess the relationship between them and the clinical characteristics of PD. The ANS functions were investigated in 50 patients with PD and 55 healthy subjects by measuring standard cardiovascular autonomic reflexes and heart rate variability (HRV) at rest using spectral analysis (the autoregressive model and the fast Fourier transformation), the percentage of the counts of beat-to-beat variation greater than 50 ms and the fractal dimension. Significantly attenuated HRV and deficient blood pressure reaction to tilting were found in the PD patient group. The patients with hypokinesia/rigidity as the initial symptom of PD had a more pronounced HRV deficit than those with tremor onset. Untreated PD patients suffer significant failure in cardiovascular nervous system regulation, and in patients with hypokinesia/rigidity as their initial disease manifestation the risk of this ANS dysfunction is high. However, in the early stages of PD these changes did not reach significance at individual level.

The autonomic nervous system (ANS) function of patients with Parkinson’s disease (PD) was investigated in 30 patients with PD, and in 21 healthy subjects of similar age by utilizing cardiovascular reflex measurements as indicators. In deep breathing, in the Valsalva manoeuvre, and in the tilting test the heart rate variability (R-R variation) differed significantly between the patients and the controls: the beat-to-beat variation was clearly decreased in patients with PD. Responses in diastolic pressure to isometric work were also clearly diminished. However, no significant differences in any measured ANS indices were found between the patients who were treated with levodopa and those who were not. Similarly, anticholinergics did not seem to affect the results.

Obese valproate-treated men have high serum insulin levels, indicating insulin resistance. Moreover, some of the valproate-treated men cluster cardiovascular risk factors such as obesity, hyperinsulinemia, and elevated serum triglyceride concentrations. CBZ and OXC do not seem to have any significant effects on serum insulin or lipid levels in men with epilepsy.

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