Buccal midazolam or rectal diazepam for treatment of residential adult patients with serial seizures or status epilepticus

Nakken KO, Lossius MI. Buccal midazolam or rectal diazepam for treatment of residential adult patients with serial seizure or status epilepticus.
Acta Neurol Scand: 2011: 124: 99–103.
© 2011 John Wiley & Sons A/S. Objectives – To compare the efficacy and tolerability of buccal midazolam with rectal diazepam as emergency treatment in residential adults with convulsive or non‐convulsive serial seizures or status epilepticus (SE), and ascertain the preference between the two treatment options among the patients and the nursing staff. Materials and methods – The nursing staff of our residential epilepsy centre treated 80 episodes of serial seizures or SE lasting more than 5 min alternating with rectal diazepam or buccal midazolam. The dose of each study drug was tailored individually. The primary outcome measure was defined as cessation of seizure activity within 10 min without seizure relapse within 2 h. Results – Convulsive SE was treated promptly, after a mean of 6.2 min, and terminated faster with buccal midazolam than with rectal diazepam; i.e. after a mean of 2.8 vs 5.0 min, respectively (n = 0.012). The other subcategories of emergency situations were treated after a mean of 25.0 min, and the seizure activity ceased after a mean of 7.4 min in the diazepam group and 7.6 min in the midazolam group (NS). The success rate was 83.3% in the diazepam group and 74.4% in the midazolam group (NS). The difference was mostly due to slightly more seizure relapses during the first 2 h in the midazolam group. Both treatment options were well tolerated, temporary tiredness being the most frequently occurring adverse effect. All the nursing staff and six of the seven patients who gained experience with both treatment options favoured the buccal route. Conclusions – Buccal midazolam appeared to be at least as effective as rectal diazepam with little or no side effects. The buccal administration was easy to handle and socially more acceptable than the rectal route.     

Non-convulsive status epilepticus associated with tiagabine therapy in children

A case of a 7-year-old male with epilepsy who developed non-convulsive status epilepticus (NCSE) with electroclinical features consistent with those of atypical absence seizures after adjunctive antiepileptic therapy of tiagabine (TGB) is reported. The patient had frequent generalised and rare partial seizures with generalised epileptic discharges on prior electroencephalogram (EEG) recordings. NCSE was developed when rapid dosage increase and high dose of TGB was given. This case emphasises the need for close monitoring of children with epilepsy taking TGB for exacerbation of seizures or development of NCSE.     

Non convulsive status epilepticus following intrathecal fluorescein injection

We report a case of non convulsive status epilepticus after an intrathecal injection of fluorescein. The clinical presentation was a confusional state--the epileptic origin of which was confirmed by the electroencephalogram. This rare and relatively benign complication should not bring about worry concerning the fluorescein test used for the diagnosis of a dural defect and the identification of the site of a CSF leak.     

Good outcome is possible after months of refractory convulsive status epilepticus: lesson learned

Determining a prognosis for functional recovery after prolonged status epilepticus can be difficult. Prior case studies have shown that despite seizure control, functional outcomes are typically poor unless a reversible cause is identified. Herein we present a case of idiopathic status epilepticus with a surprisingly good outcome after a 125-day drug-induced coma.     

Panayiotopoulos syndrome with convulsive status epilepticus at the onset: A long-term study

PurposeTo better define the convulsive status epilepticus (CSE) as a possible manifestation at the onset of Panayiotopoulos syndrome (PS) and to assess its prognostic value in these children.MethodsChildren with CSE and diagnostic criteria of PS were identified, followed clinically and compared with a group of patients with PS without CSE from 1993 to 2012.ResultsWe identified 37 patients with CSE at the onset of PS. During the same period we identified 72 children with autonomic symptoms of PS without CSE. The first episode of CSE occurred at a mean age of 6.5 years. Generalized clonic seizures were the most common ictal event and one-third of the patients required admission to Intensive Care Units. Interictal EEGs showed occipital spike activity in 31 (83.7%) subjects. Only 14 (37.8%) patients were treated with valproic acid and for two of them (5.40%) it was necessary to administer other drugs. There were no intractable cases. The overall prognosis was excellent. After the first event, 15 subjects (40.54%) experienced at least another typical PS seizure, but all patients were seizure free at the last follow-up.ConclusionCSE is not uncommon in PS and it may occur at the onset of benign childhood epilepsy, without leading to a poor prognosis.     

Why we prefer levetiracetam over phenytoin for treatment of status epilepticus

Over last fifty years, intravenous (iv) phenytoin (PHT) loading dose has been the treatment of choice for patients with benzodiazepine‐resistant convulsive status epilepticus and several guidelines recommended this treatment regimen with simultaneous iv diazepam. Clinical studies have never shown a better efficacy of PHT over other antiepileptic drugs. In addition, iv PHT loading dose is a complex and time‐consuming procedure which may expose patients to several risks, such as local cutaneous reactions (purple glove syndrome), severe hypotension and cardiac arrhythmias up to ventricular fibrillation and death, and increased risk of severe allergic reactions. A further disadvantage of PHT is that it is a strong enzymatic inducer and it may make ineffective several drugs that need to be used simultaneously with antiepileptic treatment. In patients with a benzodiazepine‐resistant status epilepticus, we suggest iv administration of levetiracetam as soon as possible. If levetiracetam would be ineffective, a further antiepileptic drug among those currently available for iv use (valproate, lacosamide, or phenytoin) can be added before starting third line treatment.     

Non-convulsive status epilepticus secondary to valproic acid-induced hyperammonemic encephalopathy

BACKGROUND: Valproic acid (VPA) may induce hyperammonemic encephalopathy. On the other hand, seizure-inducing effects of antiepileptic drugs (AEDs) may be a paradoxical reaction or a result of AED-induced encephalopathy (commonly induced by VPA). METHODS: We present the case of a 19-year-old male who developed acute mental status changes consistent with encephalopathy evolving into repetitive seizures with oral automatisms induced by relatively small doses of VPA. RESULTS: Although serum hepatic enzymes, such as AST and ALT, were normal, serum ammonia concentration was high, i.e. 70 micromol/l (normal range 9-33 micromol/l). Administration of VPA was discontinued immediately after admission. The patient's condition improved during the second week of hospitalization and ammonium levels returned to normal. CONCLUSION: In conclusion, although uncommon, a possible induction of non-convulsive status epilepticus by valproate-induced hyperammonemic encephalopathy should be taken into account and properly managed by discontinuation of the drug.     

Intravenous lacosamide as treatment option in post-stroke non convulsive status epilepticus in the elderly: A proof-of-concept,observational study

PurposeTo evaluate the efficacy and safety of intravenously administered lacosamide (iv LCM) in post-stroke non convulsive status epilepticus (NCSE) in elderly patients.MethodsWe enrolled 16 patients (7 M/9 F; 77 ± 7 years of age) with NCSE. iv LCM was used in all the patients as initial treatment (i.e. patients were directly started on LCM) at a loading dose of 400 mg over 30 min, followed by a mean maintenance dose of 400 mg per day. iv LCM was considered as effective in patients who experience no NCSE for 24 h following treatment, as evaluated by EEG recording and clinical observation.ResultsLCM was effective in treating NCSE in eight of the sixteen patients in whom epileptic activity disappeared (7/8) or was significantly reduced (1/8) within 45–60 min after administration. None of these patients relapsed in the following 24 h. No adverse events were observed. A partial anterior circulation syndrome (PACS) was present in 10 patients while a total anterior circulation syndrome (TACS) in six.ConclusionsThis pilot study suggests that LCM exhibits safety and efficacy profiles which make it an optimal candidate as a first-choice drug against post-stroke NCSE in elderly patients. A prospective comparative trial is needed to confirm these preliminary data.     

Controlled trial of lamotrigine (Lamictal®) for treatment-resistant partial seizures

The antiepileptic effect of lamotrigine (Lamictal®) was assessed in a double-blind, placebo-controlled, crossover trial in 56 adult patients with refractory partial seizures. Lamotrigine or placebo was added to the patients' existing antiepileptic drugs (AEDs). The dose of lamotrigine varied from 75 to 400 mg daily. Thirty-eight patients completed the trial and 7 withdrew because of adverse experiences. There was a statistically significant reduction in seizure counts on lamotrigine compared with placebo for total seizures (30.3% reduction, 95% CI 8.4%, 47.0%), complex partial seizures (29.2.% reduction, 95% CI 3.8%, 47.9%) and secondary generalised seizures (37.9%, CI 18.9%, 52.4%). The analysis of total seizure days showed a similar significant reduction during lamotrigine treatment for the same seizure categories. There was no statistically significant difference in reporting of adverse events between lamotrigine and placebo except for dizziness which was reported more frequently on lamotrigine than on placebo. There were no differences in abnormal haematological or biochemical findings between lamotrigine and placebo, and lamotrigine had no effect on plasma concentrations of concomitant AEDs.     

Safety and efficacy of intravenous valproate in pediatric status epilepticus and acute repetitive seizures

Summary: Purpose: To evaluate the safety and efficacy of intravenous valproate (VPA) loading in children with status epilepticus (SE) or acute repetitive seizures. Methods: Retrospective review was performed on 40 pediatric patients with intravenous VPA loading. Patients were classified into two groups: SE (n = 18) and acute repetitive seizures (n = 22). Thirty‐one patients were VPA naïve and received a full loading dose of 25 mg/kg; nine had subtherapeutic plasma VPA levels and received a partial loading dose. Average infusion rate was 2.8 mg/kg/min. Heart rate and blood pressure were measured before, during, and after infusion. Results: Intravenous VPA loading stopped seizures in 18 patients with SE within 20 min. All 18 patients regained baseline mental status within 1 h of seizure cessation. Among 22 patients with acute repetitive seizures, only one had further seizures after VPA infusion. One patient in the SE group complained of transient tremors. No significant changes in blood pressure or heart rate were found in either group. Postinfusion plasma VPA levels ranged from 51 to 138 μg/ml (mean ± SD = 88 ± 21.5 μg/ml). Conclusions: Intravenous VPA loading is safe and effective for treating acute seizure emergencies in children.     

老年惊厥性癫痫持续状态28例临床分析

目的观察老年惊厥性癫痫持续状态(CSE)的临床特点。方法收集神经重症监护室(NICU)年龄≥60岁的CSE患者28例,回顾性分析其临床特点。结果脑血管病为28例老年CSE的首位病因。接受抗癫痫药物治疗后,CSE症状控制的中位时间为0.9 h,其中16例患者在1 h内症状控制,12例为难治性癫痫持续状态(RSE)。28例患者中,存活16例、死亡12例。死亡者与存活者相比,合并中枢神经系统新发疾病(P=0.027)和RSE的比例显著不同(P=0.027)。结论老年CSE患者基础情况差,病因多样,合并有中枢神经系统新发疾病或有RSE者的死亡率高。     

Treatment gap for convulsive status epilepticus in resource‐poor countries

The magnitude of the treatment gap (TG) for convulsive status epilepticus (CSE) in resource‐poor countries is unknown. Hospital‐based cohort studies from developing countries revealed that the management of CSE was usually suboptimal due to lack of advanced diagnostic and treatment facilities, significant delay in patient's presentation at hospital, and shortages of essential antiepileptic drugs (AEDs). However, there were no significant differences in the proportion of refractory status epilepticus, short‐term mortalities, and morbidities of CSE between the developed and the developing countries. Therefore, the presence of significant TG for CSE in developing countries is still an assumption without evidence. We conducted an expert survey in Asia for potential sources of TG. Experts from 16 Asian countries responded to the questionnaire. An injectable form of diazepam was available in all 16 countries even at the primary care level, but intravenous lorazepam was available only in four countries. Second‐line AEDs were widely available at tertiary care hospitals, but not at primary care hospitals. Lack of second‐line AEDs at primary care hospitals, significant delay in patient transportation to the hospital, shortages of intensive care unit facilities, and absence of trained physicians were important contributing factors to TG in Asia.     

Ictal generalized rhythmic alpha activity during non-convulsive status epilepticus

We investigated the repetitive manifestation of non-convulsive status epilepticus with an uncommon ictal electroencephalographic pattern observed in two patients suffering from epilepsy (aged 29 and 55 years). The patients had suffered from epilepsy since the age of 1 and 40 years, respectively. Interictal and ictal neurological, neuropsychological and electroencephalographic investigations were carried out. Non-convulsive status started and ended abruptly, clinically as well as electroencephalographically. The ictal electroencephalographic pattern was a monomorphic alpha activity with a generalized bilateral distribution. Altered responsiveness, sometimes eyelid myoclonia (in one patient) and amnesia were the most characteristic clinical findings during non-convulsive status. Intellectual development was delayed in the patient with early onset of epilepsy. However, this was not the case in the other patient, who developed memory impairment during the course of the disease. In both patients, lamotrigine added to valproate reduced the frequency of status epileptici significantly. Obviously, these patients suffer(ed) from a type of generalized non-convulsive status epilepticus with an uncommon electroencephalographic pattern.     

Successful treatment for refractory convulsive status epilepticus by non‐parenteral lacosamide

Lacosamide (Vimpat) is a newly licensed novel antiepileptic drug. We report a case of refractory convulsive status epilepticus (CSE) that was successfully controlled with lacosamide. The 38‐year‐old male patient was admitted for a series of complex partial seizures with secondary generalization leading to refractory CSE. During the transport to the hospital the patient was given 22.5 mg diazepam, 12.5 mg etomidate, and 5 mg midazolam without success. An additional dose of 4 mg lorazepam and a dose of 1,500 mg levetiracetam after admission were yet without clinical effect. A further treatment with lacosamide (300 mg via percutaneous gastric fistula) resulted in complete clinical remission of the epileptic activity within 30 min. The application of lacosamide resulted in cessation of CSE and was well tolerated. To our knowledge, this is the first case of successful treatment of refractory CSE with lacosamide. Further studies are needed to evaluate the safety and efficacy of lacosamide in treatment of SE.     

Inadequate benzodiazepine dosing may result in progression to refractory and non‐convulsive status epilepticus

Aims. Status epilepticus (SE) is defined as ongoing seizures lasting longer than five minutes or multiple seizures without recovery. Benzodiazepines (BZDs) are first‐line agents for the management of SE. Our objective was to evaluate BZD dosing in SE patients and its effects on clinical/electrographic outcomes. Methods. A retrospective analysis was conducted from a prospective database of SE patients admitted to a university‐based neurocritical care unit. The initial presentation and progression to refractory SE (RSE) and non‐convulsive SE (NCSE) with coma was evaluated. Outcome measures included length of stay (LOS), rates of intubation, ventilator‐dependent days, and Glasgow outcome scale (GOS). The lorazepam equivalent (LE) dosage of BZDs administered was calculated and we analysed variations in progression if 4 mg or more of LE (adequate BZDs) was administered. Results. Among 100 patients, the median dose of LE was 3 mg (IQR: 2–5 mg). Only 31% of patients received adequate BZDs. Only 18.9% of patients with NCSE without coma received adequate BZDs (p=0.04). Among patients progressing to RSE, 75.4% had not received adequate BZDs (p=0.04) and among patients developing NCSE with coma, 80.6% did not receive adequate BZDs (p=0.07). Escalating doses of BZDs were associated with a decrease in cumulative incidences of RSE (correlation coefficient r=‐0.6; p=0.04) and NCSE with coma (correlation coefficient r=‐0.7; p=0.003). Outcome measures were not influenced by BZD dosing. Conclusion. The majority of our patients were not adequately dosed with BZDs. Inadequate BZD dosing progressed to RSE and had a tendency to lead to NCSE with coma. Our study demonstrates the need to develop a hospital‐wide protocol to guide first responders in the management of SE.