Refractory status epilepticus: A prospective observational study

Purpose: Status epilepticus (SE) that is resistant to two antiepileptic compounds is defined as refractory status epilepticus (RSE). In the few available retrospective studies, estimated RSE frequency is between 31% and 43% of patients presenting an SE episode; almost all seem to require a coma induction for treatment. We prospectively assessed RSE frequency, clinical predictors, and outcome in a tertiary clinical setting. Methods: Over 2 years we collected 128 consecutives SE episodes (118 patients) in adults. Clinical data and their relationship to outcome (mortality and return to baseline clinical conditions) were analyzed. Results: Twenty‐nine of 128 SE episodes (22.6%) were refractory to first‐ and second‐line antiepileptic treatments. Severity of consciousness impairment and de novo episodes were independent predictors of RSE. RSE showed a worse outcome than non‐RSE (39% vs. 11% for mortality; 21% vs. 63% for return to baseline clinical conditions). Only 12 patients with RSE (41%) required coma induction for treatment. Discussion: This prospective study identifies clinical factors predicting the onset of SE refractoriness. RSE appears to be less frequent than previously reported in retrospective studies; furthermore, most RSE episodes were treated outside the intensive care unit (ICU). Nonetheless, we confirm that RSE is characterized by high mortality and morbidity.     

Predictors of outcomes and refractoriness in status epilepticus: A prospective study

ObjectiveThe objective of this study was to determine the predictors of outcomes and refractoriness in status epilepticus (SE).MethodsThis is a prospective study of 59 adult patients with SE who were admitted to the Emergency Department between February 2012 and December 2013. The effects of clinical, demographic, and electrophysiologic features of patients with SE were evaluated. To evaluate outcome in SE, STESS, mSTESS, and EMSE scales were used.ResultsLogistic regression analysis showed that being aged ≥ 65 years (p = 0.02, OR: 17.68, 95% CI: [1.6–198.4]) for the short term and having potentially fatal etiology (p = 0.027, OR: 11.7, 95% CI: [1.3–103]) for the long term were the only independent predictors of poor outcomes; whereas, the presence of periodic epileptiform discharges (PEDs) in EEG was the only independent predictor of refractoriness (p = 0.032, OR: 13.7, 95% CI: [1.3–148.5]). The patients with ≥ 3 Status Epilepticus Severity Score (STESS) did not have poorer outcomes in the short- (p = 0.157) and long term (p = 0.065). There was no difference between patients with 0–2, 3–4, and ≥ 4 mSTESS in the short- and long term in terms of outcome (p = 0.28 and 0.063, respectively). Also, there was no difference between subgroups (convulsive SE [CSE], nonconvulsive SE [NCSE], and epilepsia partialis continua [EPC]) in terms of STESS and mSTESS. When patients with EPC were excluded, both STESS and mSTESS scores of the patients correlated with poorer long-term outcomes (p = 0.025 and 0.017, respectively). The patients with ≥ 64 points in the Epidemiology-based Mortality in SE-Etiology, age, comorbidity, EEG (EMSE-EACE) score and those with ≥ 27 points in EMSE-Etiology, age, comorbidity (EMSE-EAC) score did not have poorer outcomes in the short term (p = 0.06 and 0.274, respectively) while they had significantly poorer outcome in the long term (p < 0.001 and 0.002, respectively). In subgroup analysis, patients with CSE with ≥ 64 points in EMSE-EACE had significantly poorer outcome in the both short- and long term (p = 0.014 and 0.012, respectively), and patients with CSE with ≥ 27 points in EMSE-EAC had significantly poorer outcome in the long term (p = 0.03) but not in the short term (p = 0.186). Outcomes did not correlate with EMSE scores in patients with NCSE and EPC. Status epilepticus was terminated with intravenous (IV) levetiracetam (LEV) in 68.75% of patients and with IV phenytoin (PHT) in 83.3% of patients. No statistically significant difference was found between the two groups in terms of efficacy (p = 0.334).ConclusionBeing aged ≥ 65 years predicts poor short-term outcomes, and having potentially fatal etiology predicts poor long-term outcomes, which highlight the importance of SE treatment management in the elderly. Both STESS and mSTESS are not predictive for poor outcomes in EPC. Excluding patients with EPC, STESS, and mSTESS could predict poor long-term outcomes but not in the short term in SE. Epidemiology-based Mortality in Status Epilepticus score could predict poor outcome in the long term better than STESS and mSTESS. Specifically, EMSE scores correlated with poor outcome in patients with CSE but not with NCSE and EPC. New scales are needed to predict outcome especially in patients with NCSE and EPC. The presence of PEDs in EEG is a predictor of RSE, and EMSE score can also be used to predict RSE. There was no difference in the efficacy of IV LEV and IV PHT in SE. This study is significant for having one of the longest follow-up periods in the literature.     

Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study

BACKGROUND: Episodes of childhood convulsive status epilepticus (CSE) commonly start in the community. Treatment of CSE aims to minimise the length of seizures, treat the causes, and reduce adverse outcomes; however, there is a paucity of data on the treatment of childhood CSE. We report the findings from a systematic, population-based study on the treatment of community-onset childhood CSE. METHODS: We collected data prospectively on children in north London, UK, who had episodes of CSE (ascertainment 62-84%). The factors associated with seizure termination after first-line and second-line therapies, episodes of CSE lasting for longer than 60 min, and respiratory depression were analysed with logistic regression. Analysis was per protocol, and adjustment was made for repeat episodes in individuals. RESULTS: 182 children of median age 3.24 years (range 0.16-15.98 years) were included in the North London Convulsive Status Epilepticus in Childhood Surveillance Study (NLSTEPSS) between May, 2002, and April, 2004. 61% (147) of 240 episodes were treated prehospital, of which 32 (22%) episodes were terminated. Analysis with multivariable models showed that treatment with intravenous lorazepam (n=107) in the accident and emergency department was associated with a 3.7 times (95% CI 1.7-7.9) greater likelihood of seizure termination than was treatment with rectal diazepam (n=80). Treatment with intravenous phenytoin (n=32) as a second-line therapy was associated with a 9 times (95% CI 3-27) greater likelihood of seizure termination than was treatment with rectal paraldehyde (n=42). No treatment prehospital (odds ratio [OR] 2.4, 95% CI 1.2-4.5) and more than two doses of benzodiazepines (OR 3.6, 1.9-6.7) were associated with episodes that lasted for more than 60 min. Treatment with more than two doses of benzodiazepines was associated with respiratory depression (OR 2.9, 1.4-6.1). Children with intermittent CSE arrived at the accident and emergency department later after seizure onset than children with continuous CSE did (median 45 min [range 11-514 min] vs 30 min [5-90 min]; p<0.0001, Mann-Whitney U test); for each minute delay from onset of CSE to arrival at the accident and emergency department there was a 5% cumulative increase in the risk of the episode lasting more than 60 min. INTERPRETATION: These data add to the debate on optimum emergency treatment of childhood CSE and suggest that the current guidelines could be updated.     

The etiology and diagnosis of status epilepticus

Status epilepticus (SE) is a common, serious, potentially life-threatening, neurologic emergency characterized by prolonged seizure activity. Generalized convulsive status epilepticus (GCSE) is the most widely recognized form of SE. Direct consequences of convulsive movements from SE can result in injury to the body and brain. Nonconvulsive status epilepticus (NCSE) is underrecognized, with controversy surrounding the consequences and treatment. High mortality rates with GCSE have been noted in the past. New treatments for SE are emerging with new parenteral drug formulations as well as new agents for refractory SE, offering an opportunity to improve outcome. Special drug delivery systems, drug combinations, and neuroprotective agents that prevent the subsequent development of epilepsy may soon emerge as future options for treating SE.     

A one-year prospective study of refractory status epilepticus in Modena,Italy

Refractory status epilepticus (RSE) is a particular critical condition characterized by seizures that continue despite the use of first- and second-line therapies and by high mortality. To date, only one prospective study investigated clinical features and prognostic factors in RSE. In this study, we performed a one-year prospective survey to identify clinical features, outcomes, and variables associated with the development of RSE in the adolescent and adult population of Modena, northern Italy. We observed 83 episodes of SE in 83 patients. In 31% of the cases, third-line therapy (anesthetic drug) was needed. Among this group, 14% resolved and were classified as RSE, while, in 17%, seizures recurred at withdrawal of anesthetics and were classified as super-RSE. The development of RSE/super-RSE was associated with a stuporous/comatose state at presentation and with the absence of a previous history of epilepsy. Refractory status epilepticus/super-refractory status epilepticus showed a worse outcome compared with responsive SE: 54% versus 21% for 30-day mortality; 19% versus 56% for a return to baseline condition.This prospective study confirms stupor/coma at onset as a relevant clinical factor associated with SE refractoriness. We observed a rate of RSE comparable with previous reports, with high mortality and morbidity. Mortality in the observed RSE was higher than in previous studies; this result is probably related to the low rate of a previous epilepsy history in our population that reflects a high incidence of acute symptomatic etiologies, especially the inclusion of patients with postanoxic SE who have a bad prognosis per se.This article is part of a Special Issue entitled “Status Epilepticus”.     

Complex partial status epilepticus: a depth-electrode study

Of 87 patients with complex partial epilepsy who were evaluated with depth electrodes, 8 developed complex partial status epilepticus (CPSE). Seizures originated extratemporally in all 8 patients. Frontal lobe onset was established in 4 patients and was probable in 1 more. Medial parietal onset was documented in 1 patient. Medial occipitoparietal onset occurred in another, and 1 patient had multifocal onsets. Even when seizures did not begin frontrally, the frontal lobes were prominently involved during CPSE. CPSE did not occur in 60 patients with seizures originating in the temporal lobe. Both recurrent clinical seizures and continuous altered behavior were observed. Some patients exhibited both clinical patterns at different times during the same episode. Depth recording consistently demonstrated recurrent isolated seizure discharges throughout episodes. The clinical patterns were related, in part, to electroencephalographic seizure frequency, duration, and intensity. Episodes of CPSE were not associated with intellectual deterioration.     

Nonconvulsive status epilepticus in the elderly: a case-control study

BACKGROUND: Nonconvulsive status epilepticus (NCSE) is a usually underdiagnosed and potentially treatable cause of altered awareness in the elderly. To assess etiologies, associations with other medical problems, and prognosis of NCSE in a population aged >75 years we performed a nested case-control study. METHODS: We retrospectively evaluated the clinical manifestations and EEG findings in 19 consecutive elderly patients (mean age 83.3 years) presenting with NCSE and compared them with 34 elderly patients (mean age 83.3 years) with altered mental status but without EEG evidence of NCSE. The variables compared included brain lesions on CT or MRI, number of concomitant chronic active diseases, previous neurological disorders, acute medical problems, the use and withdrawal of medications, and outcome. Statistical analysis was performed using chi-square test, t-test, Fisher's exact two-tailed test, and Wilcoxon rank sum test. RESULTS: The etiology of NCSE was epilepsy in 2, acute medical disorders in 14, and a cryptogenic cause in 4. The NCSE group had a more frequent history of epilepsy, 35% versus 8.8% (p = 0.028); tramadol use, 31% versus 0% (p = 0.00151); longer hospitalization, 25 days versus 7 days (p = 0.0004); and unfavorable outcome, 50% versus 5.8% (p = 0.00031). No significant differences were found in the other variables. Unfavorable outcome was associated with a higher number of comorbidities (>2) and to a severely altered mental status. CONCLUSIONS: NCSE is a serious cause of altered mental status in the elderly. Although its direct role in brain damage is controversial, elderly patients with NCSE have higher morbidity and worst prognosis than those with altered mental status without NCSE.     

Myoclonic status epilepticus: a clinical and electroencephalographic study

We reviewed the clinical features and ictal EEGs in 23 adults with myoclonic status epilepticus (MSE). Anoxic encephalopathy was the most common cause of MSE, occurring in 15 patients; 8 developed MSE within 14 hours following the anoxic insult. Metabolic encephalopathies were present in 4 patients, while 2 had degenerative CNS disorders. In 2 patients with generalized epilepsy, MSE developed during a medication change. Five types of EEG patterns were associated with MSE. Generalized periodic complexes (usually spikes, polyspikes, or sharp waves), often with attenuation of background activity between complexes (11 patients) or a burst-suppression pattern (4 patients), were the most common types. Outcome was poor: 20 patients died without regaining consciousness, while 1 remains in a vegetative state. The 2 patients with generalized epilepsy, both of whom were conscious during MSE, survived without sequelae.     

Sodium valproate vs phenytoin in status epilepticus: a pilot study

Sixty-eight patients with convulsive status epilepticus (SE) were randomly assigned to two groups to study the efficacy of sodium valproate (VPA) and phenytoin (PHT). Seizures were aborted in 66% in the VPA group and 42% in the PHT group. As a second choice in refractory patients, VPA was effective in 79% and PHT was effective in 25%. The side effects in the two groups did not differ. Sodium valproate may be preferred in convulsive SE because of its higher efficacy.     

Electroencephalographic study of status epilepticus

The authors have reported EEG findings during attacks of status epilepticus and clinical symptoms in four cases which were considered as temporal lobe status or its marginal group.     

Role of MR imaging in the evaluation of etiology of status epilepticus

PURPOSE: MRI helps in detecting the etiology of epilepsy, which may assist in better management. However its role in emergency situations like status epilepticus (SE) is still not clear. We analyzed the MRI findings in various subtypes of SE and tried to find out if etiological diagnosis improves by doing MRI over and above that provided by clinical evaluation, CT scan and CSF and other laboratory data. METHOD: This prospective study involved 34 patients (M:F:: 23:11, mean age: 25.8+/-17.2 years; range=1-60 years) of SE. Patients were chosen irrespective of type of SE, etiology of SE, duration of SE, or treatment received. MRI was performed using standard parameters and sequences. Details of clinical, laboratory, EEG, and CT/MRI scan data were recorded. RESULTS: While 23 patients had received some treatment prior to admission, the rest did not receive any treatment. Eight patients had past history of seizures and 3 of them had history of SE. EEG revealed background slowing (22) and epileptiform discharges (15). CT scan (n=32) observations were: normal (25), inconclusive (2), diagnostic (3). MRI improved the diagnosis in 32.4% (11/34) patients over and above that provided by clinical examination, EEG, other laboratory investigations and CT scan. Seizures could be controlled with recommended treatment in 29 patients, while in 5 (Generalized Convulsive SE: 3, Epilepsia Partialis Continua: 2), it remained uncontrolled. At discharge, all but eight scored '0' on modified Rankin Scale. CONCLUSIONS: MRI is an important diagnostic tool even in emergency situation like SE. Detection of proper etiology assists in appropriate treatment and hence improves the outcome of SE.     

Efficacy of intravenous lacosamide as an add-on treatment in refractory status epilepticus: A multicentric prospective study

ObjectiveTreatment of status epilepticus (SE) has not changed in the last few decades, benzodiazepines plus phenytoin or valproate being the most common treatment. Once this first and second line treatment has failed SE is considered refractory (RSE). This study aimed to assess the efficacy and tolerability of intravenous (iv) lacosamide (LCM) in RSE.MethodPatients with RSE who were treated with ivLCM in six Spanish centers were prospectively included. Efficacy was defined as cessation of seizures after starting ivLCM, with no need for any further antiepileptic drug. All patients had been unsuccessfully treated following the standard protocol (benzodiazepines plus phenytoin or valproate) before ivLCM was added.ResultsThirty-four patients were included, 52.9% men, with mean age of 60.15 years. In 58.9% of patients the etiology was symptomatic, and the most common type of SE was focal convulsive (82.4%). Mean initial bolus dose of LCM was 323.53 mg. ivLCM was effective in more than half of patients (64.7%), with termination of SE before 12 h in 50% of them. ivLCM was used as a fourth or later option in 76.5% of patients. No serious adverse events attributable to LCM were reported.ConclusionsLCM might be a fast, effective and safe add-on treatment in RSE.     

The significance of anti-neuronal antibodies in Alzheimer's disease

Indirect immunofluorescence and cell-type-specific markers were used to determine whether antibodies directed against specific neural cell types were present in patients with Alzheimer's disease (AD), other neurological diseases (OND) and normal controls. Sera and cerebrospinal fluid (CSF) were tested on either frozen sections of rat and human cortex and/or dissociated cell cultures of neonatal rat cerebellum, and human fetal dorsal root ganglia (DRG).All groups of patients and normal subjects were indistinguishable in their pattern of immunoglobulin (Ig) staining. Staining of neurones on frozen sections was predominantly nuclear. In cultures all sera showed weak staining of oligodendrocytes, fibroblasts and Schwann cells. Varying degrees of surface staining of neurones were seen with both sera and CSF within all groups.     

Propofol treatment of refractory status epilepticus: a study of 31 episodes

PURPOSE: Refractory status epilepticus (RSE) is a critical medical condition with high mortality. Although propofol (PRO) is considered an alternative treatment to barbiturates for the management of RSE, only limited data are available. The aim of this study was to assess PRO effectiveness in patients with RSE. METHODS: We retrospectively considered all consecutive patients with RSE admitted to the medical intensive care unit (ICU) between 1997 and 2002 treated with PRO for induction of EEG-monitored burst suppression. Subjects with anoxic encephalopathy showing pathological N20 on somatosensory evoked potentials were excluded. RESULTS: We studied 31 RSE episodes in 27 adults (16 men, 11 women; median age, 41.5 years). All patients received PRO, and six also subsequently thiopental (THP). Clonazepam (CZP) was administered with PRO, and other antiepileptic drugs (AEDs) concomitant with PRO and THP. RSE was successfully treated with PRO in 21 (67%) episodes and with THP after PRO in three (10%). Median PRO injection rate was 4.8 mg/kg/h (range, 2.1-13), median duration of PRO treatment was 3 days (range, 1-9), and median duration of ICU stay was 7 days (range, 2-42). In 24 episodes in which the patient survived, shivering after general anesthesia was seen in 10 episodes, transient dystonia and hyperlipemia in one each, and mild neuropsychological impairment in five. The seven deaths were not directly related to PRO use. CONCLUSIONS: PRO administered with CZP was effective in controlling most of RSE episodes, without major adverse effects. In this setting, PRO may therefore represent a valuable alternative to barbiturates. A randomized trial with these drug classes could definitively assess their respective role in RSE treatment.     

Cortico-thalamic activation in generalized status epilepticus, a PET study

In a patient with a refractory generalized convulsive status epilepticus, the ictal distribution of regional cerebral glucose was assessed with positron emission tomography (PET). Synchronized seizure activity in the EEG was associated with bilateral metabolic activation of medial sensorimotor regions, anterior cingulate cortex, striatum and thalamus. This pattern with focal cortical activation supports the concept that a cortical focus may drive epilepsy, while the thalamus mediates synchronization of neuronal activity as reflected in the EEG.     

Reversible Parkinsonian syndrome associated with anti-neuronal antibodies in acute EBV encephalitis: a case report

We report a case of subacute-onset isolated parkinsonian syndrome in a 16 years old patient. Epstein-Barr infection was diagnosed according to serologic evidences. Parkinson-like syndrome completely recovered after 60 days. Autoantibodies reacting against a 130 Kda antigens expressed in human neuroblastoma cell line were detected. Pathogenesis and differential diagnosis are briefly discussed. EBV testing could be worthwhile in juvenile, acute-onset, parkinsonism.