Seizure recurrence and risk factors after antiepilepsy drug withdrawal in children with brain tumors

Summary:  Purpose: To study seizure outcome after antiepilepsy drug (AED) withdrawal in brain tumor patients and to analyze risk factors for seizure recurrence.
Methods: Brain tumor patients with seizures and at least one attempt at AED discontinuation were identified from the hospital database and neurology clinic records. After defining study variables, patient charts were abstracted for clinical and demographic data. Statistical analyses used log-rank tests and multivariable Cox proportional hazards models.
Results: Sixty-two patients discontinued AEDs at a median time of 5.6 years from the first seizure (range, 1.2–19.6 years). Median time since AED withdrawal was 2.3 years (range, 0.4–15.1 years). Seizures recurred in 17 (27%) patients within a median time of 0.8 years (range, 0.06–7.7 years). Median seizure-free period before AED withdrawal was 1.3 years (range, 0.1–11 years). More than one tumor resection and whole-brain radiation treatment (WBRT) were associated with seizure recurrence, whereas posterior fossa tumor location was correlated with reduced seizure recurrence risk. At seizure recurrence, control was easily reestablished in 10 patients with AED reinstitution and after dose adjustment in five; two patients with poor drug compliance continue to have seizures. In 48 patients who had an EEG before AED withdrawal, spikes or slow waves did not correlate with seizure recurrence.
Conclusions: AED withdrawal can be successfully achieved in majority of carefully selected patients. WBRT and multiple tumor resections seem to be associated with an increased hazard for seizure recurrence.     

颅骨成形术后癫痫发作的危险因素分析

目的 探讨颅骨成形术后癫痫发作的危险因素。方法 回顾性分析2015年12月至2020年12月行颅骨成形术的72例颅骨缺损病人的临床资料。术后随访2个月,依据癫痫发作的临床表现进行术后癫痫评估。结果 72例中,20例颅骨成形术后出现癫痫发作,发生率为27.8%。即刻癫痫发作（≤24 h）6例,早期癫痫发作（24 h～2周）8例,晚期癫痫发作（>2周）6例。随访期间,未出现伤口感染、人工修补材料外露、颅内感染、术区出血、脑疝等。单因素分析显示年龄、去骨瓣减压术后继发癫痫、颅骨缺损原因和直径与颅骨成形术后癫痫发作有关（P<0.05）,多因素logistic回归分析显示颅骨缺损直径是颅骨成形术后癫痫发作的独立危险因素（P<0.05）。结论 颅骨成形术作为神经外科的基础手术之一,手术过程相对简单,但其并发症不容忽视。颅骨成形术后癫痫发作的临床影响因素较多,颅骨缺损直径越大,发生癫痫的风险越高。     

Early epileptic seizures after stroke are associated with increased risk of new-onset dementia

Background

Subclinical vascular or degenerative lesions occur in the brain before the clinical expression of dementia. Those lesions in a brain that just experienced a stroke may have lower thresholds for early epileptic seizures. Therefore, epileptic seizures may be a marker of subclinical brain lesions, which may lead to dementia.

Objective

To test the hypothesis that patients with stroke who have epileptic seizures without dementia have an increased risk of new‐onset dementia.

Methods

169 consecutive patients with stroke without pre‐existing dementia recruited in the Lille Stroke/Dementia Study were investigated (90 men; 150 ischaemic strokes; median age 73 years). Pre‐stroke cognitive functions were evaluated with the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), with a cut‐off of 104 for the diagnosis of dementia. The patients were followed up over a 3‐year period. Dementia was diagnosed with International Classification of Diseases, 10th revision criteria in survivors who underwent neurological visits, and with the IQCODE score in those who could not. The relationship between epileptic seizures and new‐onset dementia was studied within 3 years, using life‐table methods.

Results

9 patients (5.3%; 95% CI 2.9 to 8.7%) had early seizures. Epileptic seizures were independent predictors of new‐onset dementia within 3 years after stroke (HR 3.81; 95% CI 1.13 to 12.82), with increasing age (HR 1.04; 95% CI 1.01 to 1.08), IQCODE scores at admission (HR 1.08; 95% CI 1.02 to 1.13) and diabetes mellitus (HR 3.52; 95% CI 1.46 to 8.47).

Conclusion

Patients with stroke who have epileptic seizures may be at increased risk of dementia. Whether cognitive follow‐up should be systematically performed in those patients remains to be validated.Hospital‐based¹ and population‐based² studies have shown that patients with dementia have an increased risk of seizures compared with patients without dementia. We have shown that patients with stroke with pre‐existing dementia are more likely to develop seizures.³ However, the influence of early seizures on outcome after stroke is controversial,^4,5 and no study has evaluated whether epileptic seizures influence the cognitive outcome. Subclinical vascular or degenerative lesions occur in the brain long before the clinical expression of dementia.^6,7 We hypothesised that epileptic seizures after a stroke is a marker of subclinical lesions in the brain. Therefore, we tested the hypothesis that patients with stroke who have epileptic seizures without dementia have an increased risk of new‐onset dementia.     

Risk factors predicting refractoriness in epileptic children with partial seizures

The aim of this retrospective study was to determine the risk factors associated with intractability to therapy in childhood epilepsy. Fifty children with intractable epilepsy as evidenced by at least 1 epileptic fit per month were included in the study group, whereas the control group consisted of children who did not experience any recurrent seizure for at least 1 year at the time of the study. A chi( 2) test was used to evaluate the relationship between the test variables for the 2 groups, and the estimated relative risk (odds ratio) for each variable was calculated. The risk factors were subsequently determined by logistic multiple regression analysis. Univariate analysis showed that mental retardation, neurological abnormality, neuroradiological abnormality, perinatal anoxia, neonatal convulsion, presence of status epilepticus, and symptomatic etiology were significant risk factors for the development of refractory epilepsy (P < .05). For multivariate logistic regression analysis, age at seizure onset, status epilepticus, mixed type of seizures, and history of frequent seizures (more than once a month) were all found to be significant and independent risk factors for refractory epilepsy, and the number of drugs used in the study group was significantly higher than that in the control group (P < .05). In line with these findings, it was concluded that children who present with epilepsy and have these risk factors should be referred to a center where epileptic surgery is carried out without delay.     

Abuse, dependence, and epileptic seizures after zolpidem withdrawal: review and case report

The imidazopyridine zolpidem is a short-acting hypnotic chemically distinct from benzodiazepines (BZs). According to its peculiar neuropharmacologic activity (selectivity for the omega 1-BZ receptors), zolpidem is expected to be a pure hypnotic, without the other effects of BZs. In particular, it has been stressed that zolpidem is well tolerated in adults and in the elderly, and that tolerance, abuse, dependence, rebound insomnia, and other withdrawal effects do not develop in relation to zolpidem administration. However, despite these assumptions, zolpidem abuse, dependence, and withdrawal effects have been recently discussed and reviewed herein. In addition, the case of a 43-year-old woman who had an epileptic attack after abrupt interruption of an abused, high dose of zolpidem (600 mg/d), is reported and discussed. At the clinical level, it is stressed that the subjective effects ofzolpidem are comparable to those of other BZs, and that abuse, dependence, and withdrawal seizures cannot be avoided simply shifting the regimen of a BZ abuser to zolpidem. At the pharmacologic level, it is important to note that zolpidem's clinical effects cannot be explained on the basis of the old distinction between omega I and 2 receptors because this distinction is no longer valid; the new classification ofGABAA receptor subtypes is reported and zolpidem activity at this level is discussed herein.     

EEG changes after withdrawal of medication in epileptic patients.

Fifty-five patients with intractable partial seizures whose on-medication EEGs demonstrated either predominantly focal epileptiform lesions or absence of paroxysmal activity, were studied, and the effect of withdrawing all anticonvulsive drugs on their EEGs was observed. Four types of response were encountered: (1) no effect (20%); (2) specific (focal) activation (25%); (3) complex activation (29%) with widespread of the initial on-medication focus or appearance of the additional independent epileptogenic foci; and (4) "non-specific" activation (63%), consisting of bursts of either bilaterally synchronous and frontally dominant spike and waves, triphasic waves, or sharp slow complexes, or smaller amplitude rapid and diffuse spike-and-wave complexes. This latter effect is thought to be secondary to metabolic derangements resulting from the withdrawal of neurotropic agents and not directly related to the specific epileptogenic process. No association was found between type of effect and any of the following parameters: topography of on-medication focus, duration of therapy, type of anticonvulsant used, suspected underlying etiopathology, or median age when medication was withdrawnn. Furthermore no evidence could be found that the development of a "complex" or "non-specific" EEG effect carried with it a bad prognosis for surgical cure following focal cortical excision. Performing off-medication tracings seems to be of greatest value in patients with partial seizures and EEGs revealing either a relative paucity of definite absence of epileptiform discharges. The occurrence of a "non-specific" response in a questionable epileptic during the off-medication period, on the other hand, should be interpreted with caution.     

Late epileptic seizures after cerebral infarction

OBJECTIVES: To determine the profile of late epileptic seizures following cerebral infarcts and the predictive clinical and radiological factors associated with their development. METHODS: We compared 86 patients who developed late seizures after cerebral infarction with 285 similar patients who did not develop seizures for at least 1 year after their stroke. Patients who had seizures only at the onset of the stroke were excluded. Odds' ratios were used for statistical analysis. RESULTS: Simple partial, and mainly motor seizures, with or without secondary generalization, accounted for 80% of the classifiable seizures but it was not possible to determine the seizure type in half of the cases. Factors that appeared to be predictive of seizure development were the presence of large cortical infarcts and the presence of apparently preserved cerebral tissue within the infarcted area. Seizures were rare in patients with lacunar infarction but the presence of associated leukoaraiosis increased the risk. The risk was also increased in patients with other medical problems known to lower seizure threshold, such as renal failure.     

Cerebrospinal fluid findings after epileptic seizures

We aimed to evaluate ictally‐induced CSF parameter changes after seizures in adult patients without acute inflammatory diseases or infectious diseases associated with the central nervous system. In total, 151 patients were included in the study. All patients were admitted to our department of neurology following acute seizures and received an extensive work‐up including EEG, cerebral imaging, and CSF examinations. CSF protein elevation was found in most patients (92; 60.9%) and was significantly associated with older age, male sex, and generalized seizures. Abnormal CSF‐to‐serum glucose ratio was found in only nine patients (5.9%) and did not show any significant associations. CSF lactate was elevated in 34 patients (22.5%) and showed a significant association with focal seizures with impaired consciousness, status epilepticus, the presence of EEG abnormalities in general and epileptiform potentials in particular, as well as epileptogenic lesions on cerebral imaging. Our results indicate that non‐inflammatory CSF elevation of protein and lactate after epileptic seizures is relatively common, in contrast to changes in CSF‐to‐serum glucose ratio, and further suggest that these changes are caused by ictal activity and are related to seizure type and intensity. We found no indication that these changes may have further‐reaching pathological implications besides their postictal character.     

Relapse of seizure after withdrawal of antiepileptic drug treatment in childhood epilepsy: age-dependent factors

In 556 epileptic children, clinical and encephalographic factors concerning the discontinuation of antiepileptic drugs (AED) were studied, with emphasis on age-related factors. Seizures relapsed in 80 patients (14.4%), the incidence being high in idiopathic generalized epilepsy with onsets in adolescence or adulthood (juvenile absence epilepsy, juvenile myoclonic epilepsy, grand mal on awakening), symptomatic partial epilepsy and symptomatic generalized epilepsy. The age distribution at the relapse showed two peaks; 9 to 11 and 17 to 19 years. The first peak represented patients with school-age onset epilepsies, and the second those with the adolescent or adult onset epilepsies. The age at discontinuation of AED depended on each epileptic syndrome, and the relapse rate was significantly higher when the AED was discontinued after adolescence. In 56 patients, seizure relapsed during the withdrawal phase or less than 1 year after the discontinuation. The type of the relapsing seizure was the same as the previous ones. On the other hand, in 16 out of 24 patients whose relapse occurred 1 year or more after the discontinuation, the seizure type was different from the previous ones. These results suggest the relevance of age-dependent factors to the discontinuation of therapy.     

Developmental brain damage after chemically induced epileptic seizures.

25 Wistar rats were subjected twice daily to epileptic seizures induced by the convulsant gaz Flurothyl. Compared with littermates of the same sex and birth weight, the brain of seizure-treated rats showed a reduction of 6% (5.2 million cells) after 5 days and 17.6% (33.4 million cells) after 10 days of treatment.     

The safety of antiepileptic drug withdrawal in patients with non-epileptic seizures

BACKGROUND: To determine whether withdrawal of anticonvulsant drugs (AED) can be carried out safely in patients with non-epileptic seizures (NES). METHODS: Prospective evaluation of safety and outcome in 78 patients with NES who satisfied a standardised set of criteria for excluding the diagnosis of coexisting or underlying epilepsy.Findings: The patients were taking from one to three AED. Sixty four patients were withdrawn as outpatients, 14 as inpatients. Five patients stopped their drugs abruptly, and two had AED restarted and had to be withdrawn again. Otherwise all patients adhered to withdrawal schedules. A new type of attack in addition to NES was seen in three patients (complex partial seizures in all three cases). NES frequency declined in the group as a whole over the period of the study (follow up 6-12 months) in all individuals except for eight patients in whom there was a transient increase. Fourteen patients reported new physical symptoms after withdrawal; however, no serious adverse events were reported. CONCLUSIONS: With appropriate diagnostic investigation and surveillance during follow up withdrawal of AED can be achieved safely in patients with NES.     

Progressive facial hemiatrophy after epileptic seizures

Intractable complex partial seizures developed in a 3-year-old female with normal intracranial findings on computed tomography. Frontal paramedian band-like depression of the skin gradually developed thereafter, and progressive facial hemiatrophy (Parry-Romberg syndrome) was diagnosed. Computed tomography scanning at 5 years of age revealed multiple parenchymal calcifications and low-density areas in the white matter of the frontoparietal lobes. Epileptic seizures, one of the major neurologic complications of progressive facial hemiatrophy, could precede the succeeding neurocutaneous changes.     

Nap polygraphic recordings after partial sleep deprivation in patients with suspected epileptic seizures.

A review of the literature shows that nap recordings make a significant contribution to epilepsy studies, providing evidence of specific EEG findings in patients suspected of having epilepsy. In addition, sleep deprivation can cause paroxysmal EEG activity and clinical seizures. We studied retrospectively 686 patients, 51.8% males and 48.2% females, who had experienced at least one episode classified from the clinical point of view as epileptic in origin. They were divided into six age groups. Patients underwent a two-hour (1 P.M.-3 P.M.) nap-video-polygraphic recording (EEG 13 channels using the standard 10-20 system, EOG, ECG, EMG and respiration), following a partial sleep deprivation (1 to 3 h) the night before. A second recording was made in 40 patients. In 35.3% of patients, a complete sleep cycle was obtained; in 64.6% sufficient light and deep NREM sleep was obtained, but not REM stage; in 9.3%, we only observed drowsiness and stage 1 of sleep, and this group was excluded from the analysis. Interictal and/or ictal epileptic discharges were observed during the first nap recording in 245 patients (40.4% of the sample). In addition, in 40 patients (11%) with normal or inconclusive first nap EEG, a second recording was able to demonstrate epileptic abnormalities in 35% of cases. Because of its good cost/benefit ratio and availability in most western laboratories, we consider the 'nap plus partial sleep deprivation' method as advantageous over other activation procedures.     

Reduction of antiepileptic drug dosage for monitoring epileptic seizures

Eleven epileptic patients, candidates for surgical treatment, were examined in order to localize epileptic foci. The daily doses of antiepileptic drugs (AEDs) were reduced by fifty per cent or less, and the reduced dosages were maintained until a seizure had occurred. The reduction resulted in seizures within five days among all patients, and the number of seizures increased significantly in comparison with the five-day period before AED reduction. The seizures so provoked were typical for each patient, as confirmed by clinical observation and video-EEG telemetry. No status epilepticus or withdrawal psychosis occurred. The AED concentrations at the time of the seizures were generally within the reference values.