Cognitive function in adult epileptic patients on long-term sodium valproate

A battery of psychometric tests was administered to 102 adult patients with epilepsy. Forty-eight were receiving long-term treatment with sodium valproate (VPA) as monotherapy, and 28 took a combination of VPA with either carbamazepine or phenytoin. An additional 26 patients were untreated, and the tests were also administered to 24 nonepileptic controls. The polypharmacy group performed significantly less well than the other groups in 6 of the 11 tests. Overall, there were no differences in performance between the VPA monotherapy patients and both the drug-free groups. However, patients with higher total and free VPA concentrations reported more sedation and scored less well on the threshold detection task. Patients were divided into those “tolerant” and “intolerant” to the drug in terms of these two tests. The “intolerant” group had a significantly earlier age of onset of epilepsy and a lower nonverbal IQ. Monotherapy with VPA is unlikely to impair cognitive function and may be a suitable choice if cognitive function is an important consideration.     

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 Group B: (n = 27) had AED monotherapy withdrawn (carbamazepine or sodium-valproate).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 Patients who had their drug treatment withdrawn (group B) and the patients who were switched from phenytoin to carbamazepine (group C) improved in single tests.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.     

Cognitive functions of epileptic patients on monotherapy with phenobarbitone and healthy controls.

Quantitative measurements have indicated that heredity, cerebral damage, psycho-social aspects, ictal and inter-ictal phenomena and antiepileptic drugs may interfere in the cognitive dysfunction of epileptic patients. In the present study objective methods included immediate and late recall and recognition of pictures, Stroop test and auditory selection. Twenty patients with symptomatic localized epilepsy aged 17-52 years (27 +/- 10, mean +/- sd) were compared to age and socially matched healthy controls. Patients were on therapeutic serum concentrations (25 +/- 12 mu/ml) of phenobarbitone and had active epilepsy with 1.94 generalized tonic-clonic, 0.85 simple partial and 6.28 complex partial seizures monthly (means). Patients performed worse than controls in all 6 tests (p less than 0.05 to p less than 0.001), indicating a generalized cognitive deficit related to seizures and/or barbiturate therapy. We suggest further studies should be carried out in populations with uniform monotherapeutic regimens and epileptic syndromes in order to isolate factors related to the cognitive dysfunction of epileptic patients.     

Plasma uric acid in patients receiving anticonvulsant monotherapy

In newly diagnosed adult patients with epilepsy followed prospectively on monotherapy, carbamazepine and phenytoin were associated with a fall in plasma uric acid, but sodium valproate and phenobarbitone were associated with a rise in plasma uric acid. The mechanisms and significance of these findings are discussed.     

Osteomalacia in institutionalized epileptic patients on long-term anticonvulsant therapy

The occurrence of anticonvulsant osteomalacia was studied in 31 epileptic inpatients, 16 women and 15 men.
Disturbances in biochemical parameters indicating osteomalacia were frequent. Thirty two per cent of the patients were hypocalcemic, 55% had an increase in S-ALP and 26% in U-HOP, and dU-Ca was decreased in 55%. The S-25OHD₃ concentrations were significantly lower in the patients compared with healthy controls. BMD was decreased in females but not in males compared with the controls. Histomorphometric analysis revealed an increase in the amount of osteoid, but the amount of trabecular bone was no lower than in the controls. The amount of resorption surfases was increased in the females, but not in the males. The patients who took less physical activity had a pronounced decrease in BMD.
The conclusion drawn was that osteomalacia is a frequent complication of long-term anticonvulsant medication, especially among institutionalized patients.     

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.     

Adverse effects of carbamazepine,phenytoin, valproate and lamotrigine monotherapy in epileptic adult Chinese patients

Objective

Antiepileptic drugs (AEDs) have been widely used in patients with epilepsy but the adverse effects in adult Chinese patients have not been investigated. This study evaluated the adverse effects of four commonly prescribed AED monotherapies with carbamazepine (CBZ), phenytoin (PHT), valproate (VPA), and lamotrigine (LTG) in adult Chinese patients with epilepsy.

Methods

The prospective open-label clinical trial was conducted at the Chongqing Epilepsy Center. The study enrolled 505 adults with newly diagnosed epilepsy, including generalized tonic–clonic (n = 110), partial and partial secondarily generalized (n = 395) seizures. Patients were evaluated by two clinicians at the Center and were prescribed one type of AED monotherapy with CBZ, PHT, VPA or LTG for a 24-month period. An adverse effect profile, as well as efficacy of monotherapy, was obtained through a face-to-face interview with the patient at each visit. A physical examination and routine laboratory tests were performed during a clinical screening.

Results

A total of 62.6% (316/505) patients successfully completed the AED monotherapy study: 64.3% of those receiving CBZ, 55.9%—PHT, 61.5%—VPA, and 66.2%—LTG. However, 34.7% of the patients discontinued the AED monotherapy because of unsatisfactory seizure control. Overall, 18% of patients experienced adverse effects: for CBZ (25/168; 14.9%), PHT (18/59; 30.5%), VPA (32/192; 16.7%) and LTG (16/86; 18.6%). The most common drug-related adverse events included gastrointestinal disturbances, loss of appetite and nausea, weight gain and fatigue/tiredness. Tremor and nystagmus occurred in some patients receiving PHT and VPA. Two CBZ, one PHT and four LTG patients (n = 7) discontinued the study due to rash.

Conclusion

Adult Chinese patients with epilepsy accepted and tolerated monotherapy with CBZ, PHT, VPA, and LTG. No fatal adverse events occurred. Unsatisfactory seizure control was a primary reason for withdrawal from the AED monotherapy study.     

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.     

Clinical and electrographic effects of acute anticonvulsant withdrawal in epileptic patients

We retrospectively investigated the effects of acute antiepileptic drug (AED) withdrawal on seizure symptomatology--including frequency, clinical features, and electrical onset--by studying 35 patients during evaluation for epilepsy surgery. The highest risk for both partial and secondary generalized seizures occurred during absent or subtherapeutic, and not during rapidly falling, AED levels. AED withdrawal had minimal effect on clinical symptomatology or electrographic onset.     

癫痫患者执行功能损害特点及影响因素研究

目的分析癫痫患者执行功能损害的特点及相关影响因素。方法1999年1月～2006年4月在我院癫痫专病门诊就诊或长期随访的109例成年癫痫患者和75例正常对照者进行神经认知心理测验，包括语义流畅性试验、数字广度测验、数字符号测验、色词干扰测验和连线试验检查。结果癫痫患者组语义流畅性显著差于正常对照组，数字广度、数字符号亦显著低于正常对照组．癫痫组连线时间、Stroop试验反应时显著延长，Stroop试验错误数显著增加（P〈0．01）。颞叶癫痫患者数字广度低于额叶癫痫患者。多元线性回归显示：文化程度高、非颞叶癫痫对语义流畅性有保护作用：文化程度高、单一抗癫痫药物治疗、病程短、年龄大对数字广度有保护作用；病程短、文化程度高和颅内无病灶对数字符号有保护作用。结论癫痫患者在多项执行功能方面均存在损害．文化程度高的患者执行功能相对较好；颞叶癫痫患者语义流畅性差；病程、药物、年龄对数字广度有影响：病程、有无病灶对数字符号有影响。     

Testosterone levels in adult male epileptic patients

Total and free testosterone levels were assayed in 80 epileptic outpatients. The levels were in the low-normal range, and there was no dissociation between free and total levels observable in this sample. No relationships to clinical epilepsy parameters or anticonvulsant levels were found, but significant inverse relationships existed with age and the number of different anticonvulsant medications a patient was taking. The age effect was independent of the medication contribution and raises the question of premature aging of the sexual system in patients with epilepsy. Whether or not this is part of a more general premature decrease in the functions of the pituitary hypothalamic axis needs to be investigated.     

Sister chromatid exchanges in adult epilepsy patients on valproate monotherapy

Sister chromatid exchanges (SCE) were studied in peripheral lymphocyte cultures of 13 adult male patients with epilepsy treated chronically with valproate (VPA) and in their matched controls. No statistically significant differences in SCE level were found between the patient and control groups, indicating a lack of mutagenic potential of VPA within the therapeutic dose range.     

Cognitive function in early adult and adult onset myotonic dystrophy

Introduction - Most studies revealing intellectual deficits in myotonic dystrophy (MyD) involved heterogeneous groups of patients with respect to intelligence and onset of disease. The present study was undertaken to investigate whether patients with early adult and adult MyD show subtle cognitive deficits despite a normal intelligence. Materials and methods - We compared 26 MyD patients of normal intelligence with mild symptoms and early adult and adult onset to 25 matched control subjects (CS) on a range of neuropsychological tests and a number of motor tasks of increasing complexity, which required increasing cognitive control. Results - The groups did not differ as far as the neuropsychological tests were concerned, with the exception of the Stroop Color Word Test. With respect to motor performance, the MyD patients were poorer scorers on simple and automatic motor tasks than CS, but the difference disappeared as the complexity of the tasks increased and required correspondingly more cognitive control. Conclusion - We found hardly any evidence of cognitive dysfunction in our group of MyD patients with early adult and adult onset.     

Psychosocial conditions of adult epileptic patients in Hungary

Authors analyze the possible connections among psychosocial, more important epileptological and social conditions in the population of the Hungarian Epilepsy Database. The inclusion criteria were the presence of repeated epileptic seizures, the strict diagnosis of epilepsy and at least three registered control visits. Four hundred and fifty 30 or more years old patients fulfilled the criteria. Based on the answers to four questions in the database considering some conditions potentially modifying the way of life the patients were scored and distributed into 3 subgroups (good, average and bad) concerning their psychosocial conditions. In contrast to previous expectations they found that the type of epilepsy does not influence the attainable psychosocial conditions. Presence of generalized tonic-clonic or complex partial seizure did not exhibit influence either. Analysis of the seizure frequency showed that generalized convulsions, if occurred rarely were accompanied by good psychosocial level and if occurred frequently they were accompanied by a less acceptable level. Psychopathological symptoms independently from their nature and evidenced brain lesion as etiology also made the psychosocial conditions worse. No difference was found concerning the gender of the population. It contradicts the hypothesis that epilepsy has a greater impact on females. Psychosocial conditions are better in patients with higher education and living in pairs. Based on the study authors support the statements of the literature emphasizing that for achieving the best quality of life and psychosocial level an appropriate medical care is not enough. They need also the relative highest level of education and a stable partnership.     

Reliability of seizure diaries in adult epileptic patients

Daily diaries are used widely in neurologic research and clinical practice to assess alterations in seizure frequency among patients with epilepsy. However, no formal tests of the reliability of this data collection method have been performed. We investigated the reliability of seizure recall in adult patients participating in a longitudinal study of stress, mood and seizure frequency. Patients maintained daily diaries for 10-36 weeks. The reliability study entailed completion of a single additional diary on the evening of a randomly selected day with reference to the preceding day. This design produced two diaries, completed 1 day apart, for the same 24-hour period. Measuring reliability with the Pearson correlation coefficient, overall reliability of seizure recall was 0.95 and was not markedly influenced by the subjects' sociodemographic characteristics, neurological or psychological status. In sum, the assumption in the literature that the daily diary is a reliable method for securing data on seizure counts appears warranted.