Cognitive function in adult epileptic patients established on anticonvulsant monotherapy

A battery of psychometric tests was administered to 110 patients with epilepsy and to 24 non-epileptic controls. Eighty-four patients had been established on treatment with a single anticonvulsant drug (35 carbamazepine (CBZ), 30 sodium valproate (VPA), 19 phenytoin (PHT)) at unaltered dosage for the previous 3 months. The remaining 26 patients were untreated at the time of study. No individual test discriminated between the groups. Tests were converted to standard scores and summated to give overall psychomotor, memory and side-effect assessments. There were no important differences between the performances of untreated epileptic patients and non-epileptic controls. The CBZ-treated patients had poorer psychomotor scores than both control groups and the VPA-treated patients (all P less than 0.05). The PHT patients scored less well on the composite memory scale than did VPA patients and non-epileptic controls (both P less than 0.05). There were no significant differences in subjective side-effects among the groups. This study demonstrated that anticonvulsant monotherapy has little effect on overall cognitive function in patients tolerating treatment. Psychomotor performance appeared to be selectively influenced by CBZ and memory impaired by PHT. VPA may be the drug to chose when cognitive function is an important consideration. Different cognitive modalities can be affected by different first-line anticonvulsants and this should be taken into account when choosing the most appropriate drug for an individual patient.     

Retinal electrophysiological results in patients receiving lamotrigine monotherapy

PURPOSE: To evaluate the effects on vision in patients receiving lamotrigine (LTG) monotherapy. METHODS: Twenty-four consecutive patients taking LTG for partial seizures were referred for a routine ophthalmologic examination including visual acuity testing, tonometry, slit lamp, and fundus examination. Automated kinetic perimetry, electrooculogram (EOG), and electroretinogram were performed after informed consent was obtained. RESULTS: In 18 patients finally included, the clinical ophthalmologic examination showed no abnormality. Four patients complained of blurring; among them, one patient had a visual field constriction in both eyes, which, however, was of unclear clinical significance (poor compliance) and a reduced light/dark ratio of the electrooculogram. One other patient with blurred vision had a reduced EOG, but the visual field was normal. Two patients had a reduced EOG but no visual symptoms. Considering the whole group of patients receiving LTG therapy, the light/dark ratio of the EOG was reduced in a dose-dependent fashion (p < 0.0001). The electroretinogram was normal in all patients. CONCLUSIONS: No irreversible visual field impairment in patients treated with LTG was encountered, although a dose-dependent retinal toxicity may have been present. The exact cellular mechanism of the electrophysiologic changes in patients taking LTG remain to be explained.     

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. Methods: Daytime vigilance was assessed in 14 consecutive, newly diagnosed and never medicated adult patients with focal epilepsy, receiving monotherapy with TPM. At baseline and 2 months after slowly titrated therapy with TPM, 200 mg/day, patients underwent the Multiple Sleep Latency Test (MSLT), visual simple and choice reaction times (VRT), and self‐rated their own degree of sleepiness with the Epworth Sleepiness Scale. A group of 14 age‐ and gender‐matched healthy volunteers served as controls. Results: At baseline, mean daytime sleep latencies on the MSLT were comparable in patients and in controls. Two months after TPM monotherapy, MSLT scores did not significantly change in patients as compared with pretreatment values. Accordingly, subjective daytime sleepiness and VRTs, which were comparable in controls and in untreated patients at baseline, did not change in patients after TPM monotherapy. Conclusions: Study results suggest that an initial short‐course monotherapy with TPM, 200 mg/day, does not impair daytime vigilance in newly diagnosed adult patients with partial seizures.     

Serum hormones in male epileptic patients receiving anticonvulsant medication

Circulating sex and thyroid hormones, as well as the pituitary function, were assessed in 63 male patients with epilepsy receiving either a single medication of carbamazepine, phenytoin, or valproate or a combination of carbamazepine plus phenytoin or carbamazepine plus valproate. All therapeutic regimens, including carbamazepine and/or phenytoin were associated with low levels of circulating thyroxine (T4), free thyroxine (FT4), and dehydroepiandrosterone sulfate, and with low values for the free androgen index, and phenytoin and carbamazepine plus phenytoin were associated with high serum concentrations of sex hormone-binding globulin. These hormone parameters were unaffected by valproate monotherapy. It seems probable that accelerated hormone metabolism is responsible for the hormonal changes found in patients treated with carbamazepine and/or phenytoin. However, every drug regimen studied also had depressant and/or stimulatory effects on the function of the hypothalamic-pituitary axis. The diverse endocrine effects of different antiepileptic drug regimens should be considered when starting antiepileptic drug therapy.     

Pathophysiology of bone loss in patients receiving anticonvulsant therapy

Many studies have shown that patients taking antiepileptic drugs (AEDs) are at increased risk for metabolic bone disease and low bone mineral density. Although early reports of bone disease in patients with epilepsy often involved institutionalized patients, who may be at risk because of lack of physical activity, reduced sunlight exposure, and poor nutrition, low bone density has also been reported in well-nourished, ambulatory outpatients with epilepsy. Traditionally, attention to the problem of AED-induced bone loss has been focused on those drugs that induce the hepatic cytochrome P450 enzyme system, thereby increasing the metabolism of vitamin D. However, the mechanisms of AED-induced bone loss appear to be multiple, and all types of AEDs are potentially implicated. Besides hepatic enzyme induction, mechanisms may include direct effects of AEDs on bone cells, resistance to parathyroid hormone, inhibition of calcitonin secretion, and impaired calcium absorption. An understanding of bone biology and the pathophysiology of bone loss can aid in the identification and monitoring of patients at risk and in the planning of appropriate prophylactic and therapeutic measures, by which most of the morbidity associated with AED-induced bone loss can be prevented.     

Alkaline phosphatase and its isoenzyme activity for the evaluation of bone metabolism in children receiving anticonvulsant monotherapy.

This study aimed to investigate whether carbamazepine, sodium valproate or phenobarbital as monotherapy in ambulatory epileptic children with adequate sun exposure have some effect on their bone metabolism based on the determination of total serum alkaline phosphatase (AP) levels and its bone isoenzyme activity. Blood samples were obtained from 118 epileptic children (37 on carbamazepine, 47 on sodium valproate and 34 on phenobarbital) and from corresponding healthy controls matched for age, gender and anthropometric parameters. AP and its liver, bone and intestinal isoenzyme levels, other common biochemical markers of bone and liver metabolism and drug levels were measured in the study participants. Patients on carbamazepine or phenobarbital had significantly elevated AP levels accompanied by increased bone and liver isoenzyme activity compared to controls. An increase of bone AP isoenzyme values, correlated with the duration of treatment ( r= 0.49, P= 0.002), was found in children on sodium valproate without, however, a concomitant significant elevation of total AP values. We conclude that children who receive antiepileptic drugs as monotherapy, even when residing in a Mediterranean country with adequate sunlight, may have their bone metabolism affected as indicated by the elevated levels of bone AP isoenzyme. This isoenzyme, but not total AP values, could therefore be used as a marker for the selection of patients who would be benefited by a thorough evaluation of their bone metabolism profile.     

Allergic skin reactions to anticonvulsant medications in patients receiving cranial radiation therapy

PURPOSE: Erythema multiforme and Stevens-Johnson syndrome have been associated with anticonvulsant medications (AEDs) in patients with brain tumors receiving cranial irradiation. AEDs are also known to cause mild drug rashes. The incidence of these complications has not been well studied among patients with brain tumors. We reviewed the records of patients with brain tumors treated with cranial radiation and AEDs to assess the frequency of both severe and mild skin reactions. METHODS: Retrospective review of 289 radiotherapy records of consecutively treated patients from 1988 to 1993. RESULTS: Only one of 289 patients developed erythema multiforme. Milder rashes, however, occurred in 18% of exposures to AEDs including 22% of exposures to phenytoin, compared with the expected rate of 5-10%. Most of the mild drug rashes occurred before the initiation of radiotherapy, suggesting that radiation was not the cause of these reactions. CONCLUSIONS: Severe skin rashes are rare among patients with brain tumors receiving radiation therapy and AEDs. There is, however, an increased frequency of mild drug rashes among patients with brain tumors that does not appear related to radiation.     

Renal tubular function in patients receiving anticonvulsant therapy: a long-term study

PURPOSE: The goal of the study was to evaluate the tubular renal function in children and adolescents who are undergoing monotherapy with sodium valproate (VPA), carbamazepine (CBZ), and phenobarbital (PB). METHODS: The urinary excretion of N-acetyl-beta-glucosaminidase (NAG), beta-galactosidase (beta-Gal), alanine-amino-peptidase (AAP), and alpha1-microglobulin (alpha1M) was measured in 58 epileptic patients (29 girls and 29 boys), aged 12.6 +/- 3.9 years, who were subdivided into three groups according to their therapy. Fifty healthy sex-and age-matched children served as controls. The measurements were taken before the beginning of therapy and after 6 months, 1 year, and 2 years of therapy. RESULTS: Before the beginning of therapy, there were no significant differences in NAG, beta-Gal, AAP, and alpha1M values between the control group and the three groups of epileptic children. After 6 months of therapy, patients treated with VPA and CBZ showed a significant increase in the urinary excretion of NAG and beta-Gal compared with baseline data and control values. After 1 and 2 years, these patients showed a persistence of the changes found after 6 months of therapy. In patients treated with PB, we did not find any significant variation in NAG, beta-Gal, AAP, and alpha1M urinary excretion. CONCLUSIONS: Our study demonstrates that in patients treated with VPA and CBZ, an impairment of tubular function can be present, whereas PB does not cause any significant change.     

Plasma anticonvulsant concentrations during pregnancy

Plasma anticonvulsant levels were followed during pregnancy in 11 epileptic women taking phenytoin and/or phenobarbital or a drug metabolized in the body to phenobarbital. As judged from the relationship between plasma level and drug dose, phenytoin requirement increased in all 10 women taking this drug during pregnancy. The requirement fell again in the puerperium. Plasma phenobarbital levels decreased during pregnancy in all five women taking a constant daily dose of phenobarbital or a congener. These findings should be borne in mind if epileptics are to be protected against seizures during pregnancy and against anticonvulsant overdosage during the puerperium.     

Cognitive function and anticonvulsant therapy: effect of monotherapy in epilepsy

Introduction – The effect of antiepileptic drugs (AED) on cognitive function was studied in 87 patients with epilepsy. Material and methods – Group A: (n = 52) started AED treatment (carbamazepine, oxcarbazepine, sodium-valproate, phenobarbital or phenytoin). Group B: (n = 27) had AED monotherapy withdrawn (carbamazepine or sodium-valproate). Group C: (n = 8) was switched from phenytoin to carbamazepine monotherapy. The patients were tested before and 4 months after change of the treatment. Results – In group A the test performances were in general unchanged. Patients who had their drug treatment withdrawn (group B) and the patients who were switched from phenytoin to carbamazepine (group C) improved in single tests. The predominant changes in performance seem to be due to practice effect. Conclusion – Cognitive functions are only minimally influenced by AEDs after short-term treatment whereas there is a slight improvement after discontinuation of long-term administration of carbamazepine and valproate. A lack of practice effect might be the first indicator of a negative effect of AED on cognitive function.     

Liver function tests in persons receiving anticonvulsant medications.

Liver function tests were carried out in 206 adults and children taking anticonvulsants to ascertain the prevalence of biochemical abnormalities in asymptomatic patients. It was observed that serum gamma-glutamyl transpeptidase was elevated in 74.6% of patients, alkaline phosphatase in 29.7% and alanine aminotransferase in 25.2% of cases. These figures are similar to those previously reported in the literature and probably reflect hepatic enzyme induction by the anticonvulsants. It is suggested that there is no value in the routine performance of liver function tests in patients with epilepsy. However, such patients should be informed of the symptoms of hepatic dysfunction and asked to report for liver function tests should they have such symptoms.     

Uric acid levels in patients with schizophrenia on clozapine monotherapy

Abstract

Background. We tested the hypothesis that uric acid levels are higher in subjects with schizophrenia treated with clozapine than in healthy control and they correlate with anthropometric measurements, laboratory tests and results of bioimpedance analysis of body composition. Methods. Data for 24 subjects with schizophrenia treated with clozapine and 24 age- and sex-matched healthy volunteers was analyzed. Results. There was no difference of fasting uric acid concentrations between clozapine and control groups (4.5 ± 1.4 vs. 4.3 ± 1.3 mg/dl, P = 0.87). Regarding the whole group, uric acid levels were significantly higher in men (5.2 ± 1.2 vs. 3.6 ± 0.9, P < 0.001). Uric acid levels correlated with weight (R = 0.58, P = 0.003), body mass index (BMI; R = 0.49, P = 0.01), abdominal circumference (R = 0.45, P = 0.03), waist circumference (R = 0.47, P = 0.02), waist-to-hip ratio (R = 0.42, P = 0.04), insulin (R = 0.50, P = 0.01), homoeostasis model assessment of insulin resistance 2 (HOMA2-IR; R = 0.49, P = 0.01), basal metabolic rate (R = 0.56, P = 0.004), lean body mass (R = 0.55, P = 0.005) and body water (R = 0.55, P = 0.005). There were no significant differences of uric acid levels for smoking status, impaired fasting glucose, abdominal obesity, obesity/overweight and dyslipidemia. Uric acid levels did not correlate with age, duration of clozapine treatment, clozapine dose, leg circumference, systolic blood pressure, diastolic blood pressure, total body fat, triglycerides, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), homocysteine, corrected calcium, glucose and homoeostasis model assessment of insulin resistance 1 (HOMA1-IR). Conclusions. We did not find significant differences in blood uric acid levels between subjects with schizophrenia and controls. Association with weight, BMI, abdominal and waist circumferences, insulin levels and insulin resistance may support uric acid role as an important cardiovascular risk factor. Association with lean weight may explain why men have higher levels of uric acid than women.     

多系统萎缩患者血清尿酸水平分析

目的探讨多系统萎缩患者血清尿酸水平及其与病情严重程度的相关性。方法连续选取2012-06—2016-12在北京大学深圳医院神经内科就诊的多系统萎缩患者32例,详细进行病史采集及体格检查,并进行统一多系统萎缩评估量表(UMSARS)评估。另选择同期健康体检者50例为健康对照组,2组均测定空腹血清尿酸水平。结果 MSA-P组及MSA-C组的尿酸水平均低于对照组,差异有统计学意义(P0.05);MSA-P组血清尿酸水平与MSA-C组比较,差异无统计学意义(P0.05);MSA患者尿酸水平与UMSARS评分呈负相关(Pearson r=-0.389,P0.05),但与病程年限无相关性(P0.05)。结论MSA患者血清尿酸水平降低,低尿酸可能与MSA发病有关;尿酸与MSA病情严重程度呈负相关。     

Serum uric acid level in patients with relapsing-remitting multiple sclerosis

Uric acid (UA) is a hydrophilic antioxidant product associated with multiple sclerosis (MS). We conducted a randomized case-control study to evaluate the serum level of UA in different phases of MS in comparison with levels in a healthy control population. Serum UA was checked in 130 patients with relapsing-remitting MS (85 patients in remitting and 45 patients in relapsing phase) and 50 age-matched controls using a quantitative enzyme-linked immunosorbent assay (ELISA). The mean concentrations of UA in serum was 6.41(±3.18) mg/dL in patients with remitting MS, 4.76(±1.66) mg/dL in patients with relapsing MS and 6.33(±2.94) mg/dL in controls. There was a significant difference between mean UA concentration in relapsing MS and remitting MS (p < 0.001), and between patients with relapsing MS and controls (p = 0.002); however, the difference between levels for patients in the remitting phase of MS and the control group was not significant (p = 0.87). It seems probable that UA has a role in the prevention of disease activity in MS.     

Plasma arginine vasopressin concentrations in epileptics under monotherapy

Plasma arginine vasopressin concentrations were determined by radio-immunoassay in 112 adult epileptics who were taking carbamazepine, phenytoin, primidone, or sodium valproate in long-term monotherapy, and in 19 controls. No significant difference was found between the groups, but some epileptics taking carbamazepine and primidone showed low values. Serum concentrations of carbamazepine did not correlate with the concentrations of plasma arginine vasopressin. In conclusion, there was no evidence of a stimulating effect of chronic carbamazepine medication or a special inhibiting effect of phenytoin on the release of vasopressin arginine from the posterior pituitary.