瞬目反射的正常值及其在周围性面瘫所见

本文对５０例健康人及２３例周围性面瘫患者作了瞬目反射（ＢＲ）的检测。刺激一侧眶上神经，于两侧下眼轮匝肌记录。同侧的两个波为Ｒ１、Ｒ２，对侧的一个波为Ｒ＇２。结果各成份的正常值在左右侧、性别以及各年龄组之间的差异均无显著性。Ｒ１的平均潜伏时为１０ｍｓ，Ｒ２Ｒ２为２９ｍｓ，波幅绝对值变异大、意义相对较小，但两侧的比率有一定的价值。刺激频率不能过快，以减少晚成份的适应并保持波形的重复性。病人的ＢＲ均表现为典型的传出性异常，即无论哪侧刺激，均表现为病侧所记录的ＢＲ的异常，或阻滞、延迟、或波幅异常。结论：（１）ＢＲ可为临床上评价面肌麻痹提供另外一种客观和无创的检查手段。（２）结合临床，ＢＲ可客观判断面肌麻痹的病变部位，提示病变范围和异常程度；（３）ＢＲ可反映面瘫病人的预后情况。     

Cognitive Function and Time-of-Day Variation in Serum Carbamazepine Concentration in Epileptic Patients Treated with Monotherapy

Different parameters of antiepileptic drug (AED) treatment have been shown to affect cognitive function. The drug, dose, and duration of treatment have been studied. The present study assessed cognitive function in relation to time-of-day variation in serum carbamazepine (CBZ) concentration in epileptic patients treated with monotherapy. We studied 10 males and 12 females with a mean age of 36 years and a mean duration of CBZ-therapy of 4.4 years. Patients had been seizure-free for at least 1 month and took two daily CBZ doses. The test battery included tests of motor speed, reaction time, attention, and memory. In the experimental design, the subjects were tested twice at times close to expected daily maximum and minimum serum CBZ concentration. They were studied in two balanced blocks (block 1 tested at 8 a.m. and noon, block 2 tested at noon and 8 p.m.). Blood samples were collected every 2 hr from 8 a.m. to 8 p.m. The subjects showed significant differences in serum CBZ concentration between testing times, with suggested maximum concentration between 10 a.m. and noon. The test battery showed no consistent differences between performance at times of high versus low serum concentration. A supplementary analysis of correlations between mean performance level on cognitive tests and variables related to CBZ treatment did not show consistent trends.     

Antiepileptic Drug Treatment After Temporal Lobe Epilepsy Surgery: A Randomized Study Comparing Carbamazepine and Polytherapy

Temporal lobectomy is an effective treatment in selected patients with medically intractable temporal lobe epilepsy (TLE). Postoperative antiepileptic drug (AED) treatment guidelines have not been established, and patients are often treated with polytherapy postoperatively. We prospectively randomized 40 patients undergoing temporal lobectomy to monotherapy with carbamazepine (CBZ, 20) or to continuation of their presurgical polytherapy (20) to assess the efficacy and safety of each regimen during the first year after operation. No significant differences between groups were noted with respect to seizure recurrence rate and type or time of recurrence. Patients in the polytherapy group had a 30% incidence of drug-related side effects as compared with only 10% in the CBZ group. These results suggest that after temporal lobectomy for intractable epilepsy, patients can be safely treated with CBZ monotherapy and that treatment with multiple AEDs is not necessary.     

Tiagabine Monotherapy in the Treatment of Partial Epilepsy

Summary: Three studies were conducted to assess tiagabine (TGB) hydrochloride monotherapy in patients with partial seizures. The first was a double-blind, placebo-controlled trial of 11 patients (seven TGB, four placebo) undergoing evaluation for epilepsy surgery. Baseline antiepileptic drug (AED) therapy was discontinued abruptly before monotherapy. Although 24-h seizure rates increased during monotherapy in both groups, patients receiving TGB experienced fewer seizures than placebo patients. Subsequent studies (an open-label, dose-ranging study; n = 31 and a double-blind, randomized comparison of 6 and 36 mg/day TGB; n = 102 and 96, respectively) involved discontinuation of baseline AEDs. In the dose-ranging study, 19 of 31 patients (61%) converted to TGB monotherapy, with a mean final dose of 38.4 mg/day (range 24–54 mg/day) in those who completed the study ( n = 12). In the low- vs. high-dosage study, median 4-week complex partial seizure rates decreased significantly in patients from both dose groups who completed the monotherapy period ( p <0.05 compared with baseline). In the intent-to-treat analysis, significantly more patients in the high-dose group experienced a reduction in seizures of at least 50% compared with the low-dose group ( p = 0.038). Overall, the types of adverse events with TGB monotherapy were similar to those observed in add-on trials. These initial trials in difficult-to-treat epilepsy patients indicate that TGB monotherapy may provide a new approach to the treatment of patients with partial seizures refractory to other AEDs.     

Increasing Plasma Concentration Tolerability Study of Flunarizine in Comedicated Epileptic Patients

Twelve patients with intractable partial seizures [4 receiving carbamazepine (CBZ), 4 phenytoin (PHT), and 4 both] entered a study of the tolerability of flunarizine (FNR) at specified plasma concentrations. After an 8-week baseline period, a single-dose pharmacoki-netic study was performed for each patient to calculate a loading dose and maintenance dosage necessary to achieve a target plasma FNR concentration of 30 ng/ml. The first 8 patients received the loading dose (as divided doses) during a 1-week hospitalization and the maintenance dosage for the ensuing 8 weeks. These patients proceeded to treatment periods with target concentrations of 60 and then 120 ng/ml, using doses based on an assumed linear relation between dose and plasma concentration. The last 4 patients were studied only at the 120-ng/ml target level. Results indicated that this procedure successfully approximated target levels of 30 and 60 ng/ ml, but observed concentrations in the last period exceeded the 120-ng/ml target level and continued to increase with time, often necessitating a dosage reduction owing to intolerability. Calculated doses for a given target concentration varied by a factor of 12. The most frequently reported adverse experiences were sedation and increased fatigue; reports of dizziness, headache, and lethargy were also common. Based on this study, a target concentration of at least 60 but <120 ng/ml is recommended for a controlled clinical trial of the antiepileptic efficacy of FNR.     

Effects of Antiepileptic Drugs on Sperm Motility of Normal Controls and Epileptic Patients with Long-Term Therapy

The in vitro effects of four antiepileptic drugs (AEDs) on human sperm motility were studied with a transmembrane migration method. Sperm motility of epileptic patients receiving chronic AED therapy was also investigated. Sperm motility was measured immediately after semen had been mixed with AED and after a 2-h preincubation at 37 degrees C. Both in vitro and in vivo studies demonstrated that AEDs inhibited sperm motility. When the drug effect was evaluated after the semen-AED mixture had been preincubated for 2 h, sperm motility was inhibited to 50% of control at concentrations of 1.59, 4.23, and 5.00 mM for phenytoin, carbamazepine, and valproate, respectively. Both with and without preincubation, phenobarbital, even up to 12.92 mM, did not inhibit the motility to less than 50% of the control. In the in vivo study, poor sperm motility was noted in epileptic patients with long-term AED therapy despite serum levels within the therapeutic range. Shorter duration of activity of spermatozoa was also observed in these patients. Interference with sperm membrane function by AEDs may be the underlying mechanism.     

Prognosis of Epilepsy in Newly Referred Patients: A Multicenter Prospective Study of the Effects of Monotherapy on the Long-Term Course of Epilepsy

Summary: A cohort of 280 previously untreated epilepsy subjects (159 men and 121 women aged 2–81 years) recruited in 14 Italian centers were treated with antiepileptic drug (AED) monotherapy and followed for a median period of 48 months to investigate the rates of seizure remission (i.e., complete control), in general and with reference to various prognostic factors. The cumulative probability of achieving 1-year remission was 62% by 1 year after onset of treatment, 81% by 2 years, 92% by 3 years, and 98% by 5 years. The corresponding figures for 2- and 3-year remission at 5 years were 92 and 78%, respectively. Sixty-two patients (22.1%) had no remission period with monotherapy. Remission rates were significantly lower among patients with two or more seizure types and were inversely correlated to the number of seizures before treatment. The rate of seizure relapses during the first year of follow-up appear to correlate to the risk of developing refractory epilepsy (i.e., with no remission).     

Computerized Analysis of EEG Background Activity in Epileptic Patients

Background activity was studied in 128 idiopathic epilepsy patients and 30 normal controls using EEG topography and t-statistic significance probability mapping (t-SPM). In epileptic patients, EEG background activity showed a marked increase in delta, theta, alpha 1, and beta 1, and a decrease in alpha 2 activity as compared with controls. Untreated epileptic patients had a significant increase in delta, theta, and alpha 1 as compared with controls. For epileptic patients treated with antiepileptic drugs (AEDs), the most marked slowing was observed in the polytherapy group, followed by the monotherapy group and then the untreated group. Among seizure types, patients with partial seizures (PS) tended to exhibit more slowing than patients with only generalized tonic-clonic seizures (GTC). Moreover, PS had a right-left asymmetry in alpha 2 and beta 1 activities. In a comparison of AEDs, patients receiving carbamazepine (CBZ) and phenobarbital (PB) showed no significant difference as compared with the untreated group. In contrast, patients receiving valproate (VPA) showed a decrease in slow and fast activities. EEG changes associated with each AED were different in GTC and PS. Patients receiving VPA for GTC showed a decrease in theta and beta 1 activities, but those with PS showed a decrease only in delta activity.     

Long-Term Experience with Topiramate as Adjunctive Therapy and as Monotherapy in Patients with Partial Onset Seizures: Retrospective Survey of Open-Label Treatment

Summary: Because initial studies of new antiepileptic drugs (AEDs) are add-on trials in refractory patient populations, their effectiveness as monotherapy is usually not apparent until relatively later in their development programs. The novel AED topiramate (TPM) has been found efficacious as adjunctive therapy in controlled, randomized trials in adults with partial onset seizures. We report a retrospective analysis of TPM as AED monotherapy in 214 patients from five centers who received TPM in investigational trials. Of this total, 136 (64%) were still receiving TPM at the time of the analysis, with a mean treatment duration of 2.5 years. One-third of the patients have been successfully converted to TPM monotherapy, and 62% of those converted have been seizure-free for at least 3 months. The results of this analysis suggest that TPM may prove to be a valuable new AED for both monotherapy and add-on therapy in partial onset epilepsy.     

Impact of Valproate and Phenytoin on Cognitive Function in Elderly Patients: Results of a Single-Blind Randomized Comparative Study

Summary: Thirty-eight patients (median age 77 years; range 62–88 years) with elderly-onset seizures were entered into a single-blind, randomized study designed to compare the impact of phenytoin (PHT) and valproate (VPA) on cognitive function. A stratified minimization program matched the two groups for age, sex, and seizure type. Attention, concentration, psychomotor speed, and memory were assessed twice before treatment (to minimize practice effects), at 6 weeks and (for patients remaining in the study) at 3 months, 6 months, and 1 year by an extensive battery of psychologic tests. Changes in cognitive function were minor, and some tended toward improvement. Contrary to expectation, there was little difference between PHT and VPA with regard to impact on cognitive function. Frequent noncognitive adverse effects were reported. Thus, we did not replicate the findings of previous literature. We conclude that antiepileptic drug (AED) monotherapy as used in our trial did not produce significant adverse cognitive effects. The choice of AED in the elderly may therefore be more influenced by consideration of other adverse effects.     

Comparison of the Steady-State Pharmacokinetics of Topiramate and Valproate in Patients with Epilepsy During Monotherapy and Concomitant Therapy

Summary: Purpose: The steady-state pharmacokinetics of valproate (VPA) and topiramate (TPM) were compared during VPA monotherapy, concomitant VPA and TPM therapy, and TPM monotherapy to evaluate pharmacokinetic interactions. Methods: After a 3-week baseline period, 12 patients receiving VPA monotherapy (500 to 2,250 mg every 12 h) received TPM at three escalating doses (from 100 to 200 to 400 mg every 12 h), each for 2 weeks. Thereafter, the VPA dose was tapered by 25% weekly. Blood and urine samples were collected over 12-h intervals during VPA monotherapy and at the end of each stage of TPM dose escalation and TPM monotherapy. Results: All patients reached TPM monotherapy, and nine achieved satisfactory seizure control for 2 weeks without VPA. TPM plasma peak concentration (C_max) and area under the concentration-versus-time curve during a 12–h dosing interval (AUC_0–12) were slightly higher (17%; n = 8) during TPM monotherapy than during concomitant VPA therapy. TPM oral and renal clearances (n = 8) were 25.9 ± 4.6 and 11.6 ± 3.2 ml/min during TPM monotherapy and were 29.8 ± 4.2 and 12.4 ± 2.7 ml/min during VPA concomitant therapy. VPA AUC_(0–12) decreased (11.3%; n = 10) with the addition of TPM 400 mg every 12 h. VPA oral clearance was 12.8 ± 4.1 ml/min during monotherapy and was 13.8 ± 4.0,14.1 ± 3.9, and 14.5 ± 5.2 ml/min during coadministration of TPM 100, 200, and 400 mg every 12 h, respectively. Cognitive dysfunction, observed in some patients receiving high doses of VPA with TPM, reversed or improved with VPA dose reduction and discontinuation. The lower-than-normal prestudy platelet count measured in one patient increased to normal levels when VPA was discontinued. Conclusions: Because changes in TPM and VPA pharmacokinetics were small, it is unlikely that their concomitant use will have a significant impact on the clinical condition of the patient.     

Periodontal Condition of Epileptic Adults Treated Long-Term with Phenytoin or Carbamazepine

The periodontal condition of 40 adult epileptic subjects (mean age 51 years) receiving long-term therapy (mean 18 years) with phenytoin (PHT) or carbamazepine (CBZ) was studied. The subjects completed a questionnaire and underwent clinical and radiologic examination. Patients receiving PHT exhibited the same level of alveolar bone loss as those receiving CBZ. Patients receiving PHT exhibited more units with gingival overgrowth, reflected by the significantly higher number of gingival units with increased probing depth (p < 0.05). The results indicate that long-term PHT does not result in increased risk for alveolar bone loss as compared with CBZ.     

瞬目反射在糖尿病患者脑神经亚临床损害中的应用

目的 探讨瞬目反射对糖尿病患者脑神经亚临床损害的诊断价值。方法检测31例糖尿病患者及35名健康成人 的瞬目反射。结果 糖尿病患者瞬目反射的各期反应即R1、R2和R2’的潜伏期分别为12.22±0.82、33.96±1.11、33.91±1.12ms, 均较对照组延长(P<0.01)。结论 瞬目反射检测有助于糖尿病患者脑神经和脑干受损的早期及亚临床损害的诊断。     

Vigabatrin: Clinical Evidence Supporting Rational Polytherapy in Management of Uncontrolled Seizures

Summary: Monotherapy is the policy for management of patients with epilepsy. With increasing knowledge of the biology of epilepsy and of the modes of action of antiepileptic drugs (AEDs), this concept must be reevaluated. When monotherapy fails to control seizures, subsequent treatment should be based on “rational pharmacology,” taking into consideration the mode of action of the drugs, to provide improved efficacy with maintained tolerance and ease of administration. Introduction of vigabatrin (VGB) as a new AED calls for just such a reevaluation. VGB is an enzyme-activated irreversible inhibitor of γ-aminobutyric acid (GABA)-transaminase that increases brain and cerebrospinal (CSF) GABA concentrations in animals and humans. It has limited efficacy in the classic animal seizure screening tests, but in many clinical studies has halved the incidence of seizures in ～50%of patients, especially those with partial epilepsies. We evaluated the efficacy of VGB in “socially integrated and active outpatients” as a likely subset to demonstrate any advantage of rational polytherapy. The criteria for this evaluation included the effects on seizure frequency, patient tolerability, and cognitive performance in a battery of psychometric tests. Fourteen of the 19 patients (73%) completing the study had >50% réduction in seizure frequency, and 10 of 19 (52%)had >70% réduction in seizure frequency. Tolerability appeared good; somnolence was the most frequent adverse event. Three patients complained of a worsening of their seizures, 1 with an increase in frequency and 2 with development of myoclonic jerks not previously reported. No deleterious effect of VGB on cognitive function was noted, and performance in late recognition tests showed significant improvement by the end of the maintenance period, which may have been due to the réduction in seizure frequency. The efficacy of VGB in this study in controlling seizures as compared with results of earlier published studies of refractory epilepsy may be related to selection of patients with more benign partial epilepsy, but does support the need for further studies in such patients to evaluate the hypothesis of rational polytherapy.     

Blink reflex in facial-hypoglossal anastomosis

Summary The blink reflex was investigated in two patients after a facial-hypoglossal anastomosis had been performed. In each case the first component of the blink reflex could be demonstrated with normal latency on the operated side after ipsilateral supraorbital stimulation. These findings give further evidence that the first component of the blink reflex is not monosynaptic in nature. The second component of the blink reflex was distinctly retarded in the first case and was not seen at all in the second case. The second component of the blink reflex is influenced strongly by alteration of the intrabulbar and efferent part of the reflex circuits; it shows some correlation with voluntary motor activity.Stipendiary of the Humboldt Foundation.     

Effects of Carbamazepine on Auditory Brainstem Response, Middle-Latency Response, and Slow Cortical Potential in Epileptic Patients

Auditory brainstem responses, middle-latency responses, and slow cortical potentials (ABRs, MLRs, SCPs) were recorded in 21 epileptic patients before and during treatment with carbamazepine (CBZ). The peaklatencies, interpeak intervals, and amplitudes were estimated and evaluated statistically. CBZ monotherapy resulted in prolongation of peak latencies of ABR waves I, III, and V as well as of interpeak intervals I–III and I–V. A significant increase in the peak-latencies of MLR components N_a, P_a, and N_b and of interpeak intervals V–P_a and N_a-N_b was also observed along with the systematic N_aP_a amplitude reduction. CBZ also prolonged the peaklatencies of SCP components P₁ and N₁. Based on the obtained results, we suggest that CBZ exerts suppressive influences both on modally specific (lemniscal) and modally nonspecific (extralemniscal) auditory structures.