"De novo" non-convulsive status epilepticus in adults and in the elderly

There is a growing number of publications in the recent literature reporting the incidence of non-convulsive status epilepticus in the elderly, including both absence epilepsy and partial epileptic seizures. Absence status epilepticus creates a diagnostic problem because of its clinical features: confusion ranging from slight disorientation to stupor. Duration of such states may vary from one hour to a few weeks, with fluctuations and epileptic features in EEG recording (a typical pattern of spikes-slow waves, 3 Hz frequency, symmetrical and synchronical) that disappear after an intravenous injection of benzodiazepines. Absence status epilepticus can be evoked by toxic, metabolic or pharmacological factors as well as by convulsive epileptic seizures. Besides absence epileptic states of middle-cerebral origin there is a rising concern about absence status resulting from simple or complex partial seizures. Generalized non-convulsive status epilepticus following either simple partial or simple complex seizures is characterized by the presence of various focal signs associated with confusion, stupor or coma. The latter may be masking the clinical picture of an underlying cerebral pathology (e.g. brain tumor, hemorrhage, etc.), and epileptic changes can be seen in EEG recording only. Absence status epilepticus can occur in various forms of brain pathology, including stroke, brain tumors, traumatic lesions and other conditions, as well as in systemic diseases affecting the central nervous system function. Therefore, the authors emphasize the importance of electroencephalography in severely ill and unconscious patients, as well as the role of proper anti-epileptic treatment, as this may improve the outcome.     

Calculating the Risk Benefit Equation for Aggressive Treatment of Non-convulsive Status Epilepticus

Objective

To address the question: does non-convulsive status epilepticus warrant the same aggressive treatment as convulsive status epilepticus?

Methods

We used a decision model to evaluate the risks and benefits of treating non-convulsive status epilepticus with intravenous anesthetics and ICU-level aggressive care. We investigated how the decision to use aggressive versus non-aggressive management for non-convulsive status epilepticus impacts expected patient outcome for four etiologies: absence epilepsy, discontinued antiepileptic drugs, intraparenchymal hemorrhage, and hypoxic ischemic encephalopathy. Each etiology was defined by distinct values for five key parameters: baseline mortality rate of the inciting etiology; efficacy of non-aggressive treatment in gaining control of seizures; the relative contribution of seizures to overall mortality; the degree of excess disability expected in the case of delayed seizure control; and the mortality risk of aggressive treatment.

Results

Non-aggressive treatment was favored for etiologies with low morbidity and mortality such as absence epilepsy and discontinued antiepileptic drugs. The risk of aggressive treatment was only warranted in etiologies where there was significant risk of seizure-induced neurologic damage. In the case of post-anoxic status epilepticus, expected outcomes were poor regardless of the treatment chosen. The favored strategy in each case was determined by strong interactions of all five model parameters.

Conclusions

Determination of the optimal management approach to non-convulsive status epilepticus is complex and is ultimately determined by the inciting etiology.     

Emergent EEG in clinical practice.

OBJECTIVE: Emergency situations require a rapid and precise diagnostic approach. However, the exact role and value of the electroencephalogram (EEG) in emergent conditions have yet to be clearly defined. Our objective was to determine why clinicians order an emergency EEG, to assess to what extent it helps establish a correct diagnosis and to evaluate the result it has on subsequent patient management. METHODS: We studied all successive emergency EEGs ordered during a 3-month period in our institution. We analyzed the reasons why each EEG was ordered and interviewed the prescribing clinicians in order to determine the impact the result of the EEG had on the diagnosis and subsequent therapeutic management. RESULTS: We prospectively studied a total of 111 consecutive recordings. The main reasons for ordering an emergent EEG were: suspected cerebral death (21%), non-convulsive status epilepticus (19.7%), subtle status epilepticus (14%) and follow-up of convulsive status epilepticus (11.2%). In 77.5% of the cases the clinicians considered that the EEG contributed to making the diagnosis and that it helped confirm a clinically-suspected diagnosis in 36% of the cases. When subtle status epilepticus (SSE) or non-convulsive status epilepticus (NCSE) was suspected, the diagnosis was confirmed in 45% and 43.3% of the cases, respectively. In 22.2% of the requests involving follow-up of convulsive status epilepticus after initial treatment, the EEG demonstrated persistent status epilepticus. It resulted in a change in patient treatment in 37.8% of all the cases. When the EEG helped establish the diagnosis, patient treatment was subsequently modified in 46.6% of the cases. CONCLUSIONS: This prospective study confirms the value of an emergent EEG in certain specific clinical contexts: the management of convulsive status epilepticus following initial treatment or to rule out subtle status epilepticus. An emergent EEG can also be ordered if one suspects the existence of non-convulsive status epilepticus when a patient presents with mental confusion or altered wakefulness after first looking for the specific signs suggesting this diagnostic hypothesis. SIGNIFICANCE: After 50 years of development and use in daily practice, the EEG remains a dependable, inexpensive and useful diagnostic tool in a number of clearly-defined emergency situations.     

Serum neuron-specific enolase in the major subtypes of status epilepticus

OBJECTIVES: To determine the relative magnitudes of neuron-specific enolase (NSE) levels after complex partial status epilepticus (SE), absence SE, generalized convulsive SE, and subclinical generalized convulsive SE (frequently referred to as acute symptomatic myoclonic status epilepticus). BACKGROUND: NSE is a marker of acute brain injury and blood-brain barrier dysfunction, which is elevated in SE. METHODS: Serum NSE levels were drawn in 31 patients 1, 2, 3, and 7 days after SE. Patients were classified as acute symptomatic or remote symptomatic, and the duration and outcome of SE were determined and correlated with the peak NSE level. RESULTS: NSE was elevated significantly in all four subtypes of SE, but NSE levels were highest in complex partial and subclinical SE. The mean peak NSE level for the complex partial SE group was 23.88 ng/mL (n = 12), 21.5 ng/mL for absence SE (n = 1), 14.10 ng/mL for the generalized convulsive SE group (n = 12), and 37.83 ng/mL for the subclinical SE group (n = 6), all of which was significantly higher than normal control subjects (5.02 ng/mL). Outcome was significantly different between the three groups (p = 0.0007), and was significantly worse for subclinical SE (p = 0.0005, subclinical versus generalized convulsive SE). CONCLUSION: Serum NSE levels were highest in complex partial and subclinical generalized convulsive SE. The extremely high levels of NSE in subclinical SE reflect the severity of the acute neurologic insults and poor outcome common to subclinical SE. High NSE levels in complex partial SE reflects the long duration of SE in this subgroup, and potential for brain injury.     

Treatment of seizure emergencies: convulsive and non-convulsive status epilepticus

Status epilepticus (SE), defined as recurrent epileptic seizures without complete recovery between seizures, is one of the most serious manifestations of epilepsy. Generalized convulsive status epilepticus (GCSE) is the most common and most life-threatening form of SE, and aging increases the mortality risk. In a recent study of treatment of GCSE, 226 of 518 evaluable patients (43.6%) were of age 65 or older. In the 157 elderly patients with overt GCSE, phenobarbital was successful as first-line treatment in 71.4%, lorazepam in 63%, diazepam and phenytoin in 53.3%, and phenytoin alone in 41.5%. Phenobarbital and lorazepam were more successful than phenytoin alone. In the 69 elderly patients with subtle GCSE, success as the first treatment was 30.8% for phenobarbital, 14.3% for lorazepam, 11.8% for phenytoin, and 7.7% for diazepam and phenytoin. Overall, the results were similar to those reported for the entire study. Lorazepam, because of ease of use, is probably the best drug for the initial treatment of overt GCSE in the elderly; phenobarbital may be the best drug for subtle GCSE in this group, but more data are needed. The term "nonconvulsive SE" has been used to include complex partial SE and absence SE - both of which present as an "epileptic twilight state" - and SE in comatose patients. The diagnosis can be challenging, particularly in the elderly, as overlapping clinical features and electroencephalogram patterns can be seen in SE and in a variety of encephalopathic conditions. There is a suggestion that aggressive treatment of elderly patients with nonconvulsive SE may worsen prognosis. Clearly, there is a need for more data to better understand management of elderly patients with both convulsive and nonconvulsive SE.     

The association between seizure clustering and convulsive status epilepticus in patients with intractable complex partial seizures

PURPOSE: We examined the association between seizure clustering and convulsive status epilepticus (SE) in patients with intractable complex partial seizures, to identify whether patients whose seizures typically cluster are at high risk for convulsive SE (CSE). METHODS: Seventy-six patients with intractable complex partial epilepsy who underwent presurgical evaluation in the Montefiore Epilepsy Management Unit from 1993 to 1997 were contacted and interviewed about typical seizure frequency and distribution and history of CSE. Seizure clustering was defined as three or more complex partial seizures within a 24-h period, with return to baseline between seizures. RESULTS: Of the 76 patients contacted, 21 (28%) had experienced at least one episode of CSE, and 36 (47%) typically experienced clustered seizures. SE occurred in 16 (44%) of 36 patients with clustered seizures, and in five (12.5%) of 40 patients with nonclustered seizures (p < 0.002). Of 53 patients with temporal lobe epilepsy, CSE occurred in 13 (50%) of 26 patients with clustered seizures, and four (14.8%) of 27 patients with nonclustered seizures (p < 0.006). CONCLUSIONS: Patients with intractable complex partial or localization-related epilepsy who typically experience seizure clustering are at a significantly higher risk for CSE than are patients with nonclustered seizures.     

Serum prolactin response to metoclopramide during status epilepticus.

Transient elevation of serum prolactin frequently follows generalised tonic-clonic and complex partial seizures. However, the levels of prolactin during status epilepticus are not increased above the normal range. Exhaustion of central prolactin supplies has been proposed as a possible mechanism for the absence of prolactin increase during status epilepticus. To test this hypothesis we injected intravenous metoclopramide (10 mg) in eight consecutive patients with status epilepticus. One patient had generalised tonic-clonic status epilepticus. Seven patients had EEG-verified non-convulsive status epilepticus, consisting of one typical absence status, one atypical absence status and five complex partial status epilepticus. Metoclopramide raised the mean (SD) prolactin levels at least five-fold in all patients, from 5.8 (8.0) micrograms/l to 87.0 (39.0) micrograms/l, within 60 minutes after the injection. Thus the mechanism for low prolactin values in status epilepticus is not cellular depletion of stored prolactin, but more likely an altered regulation, presumably induced by prolonged seizure activity.     

Électroencéphalographie dans les états de mal épileptiques : glossaire, protocole et interprétation

Electroencephalography is a useful tool in the diagnosis and management of status epilepticus (SE) and it can also give prognostic information. It can help to confirm that an episode of SE has ended. It can identify the patients who have unsuspected subclinical seizures. There is a wide range of presentations of SE. Nearly all types of seizures have the potential of occurring in a repeated or continuous form. The polymorphic EEG patterns in SE reflect this wide variety. But controversial patterns also exist in the form of periodic epileptiform discharges. While some authors considered these patterns to be interictal or postictal, others postulate that these patterns are ictal. In these cases, clinical features are very important in order to conclude. Generalized convulsive SE is a medical emergency and the EEG is not necessary to make a diagnosis. Convulsive generalized SE requires immediate treatment and in this case, EEG is used in guiding treatment especially in refractory SE that may evolve into subtle SE. In non-convulsive SE, diagnosis is not obvious on the basis of clinical signs and symptoms alone and the diagnosis must be confirmed by urgent EEG. EEG can also be used to distinguish SE from psychogenic seizures, movement disorders and in patients who have causes of persistent loss of consciousness (metabolic encephalopathy, postanoxic encephalopathy). This article proposes a protocol for the use of the EEG in SE, guidelines and simple vocabulary for a good interpretation and comprehension of the EEG.     

Persistent Nonconvulsive Status Epilepticus After the Control of Convulsive Status Epilepticus

Summary: Purpose: Convulsive status epilepticus (CSE) is a major medical and neurological emergency that is associated with significant morbidity and mortality. Despite this high morbidity and mortality, most acute care facilities in the United States cannot evaluate patients with EEG monitoring during or immediately after SE. The present study was initiated to determine whether control of CSE by standard treatment protocols was sufficient to terminate electrographic seizures. Methods: One hundred sixty-four prospective patients were evaluated at the Medical College of Virginia/VCU Status Epilepticus Program. Continuous EEG monitoring was performed for a minimum of 24 h after clinical control of CSE. SE and seizure types were defined as described previously. A standardized data form entry system was compiled for each patient and used to evaluate the data collected. Results: After CSE was controlled, continuous EEG monitoring demonstrated that 52% of the patients had no after-SE ictal discharges (ASIDS) and manifested EEG patterns of generalized slowing, attenuation, periodic lateralizing epileptiform discharges (PLEDS), focal slowing, and/or burst suppression. The remaining 48% demonstrated persistent electrographic seizures. More than 14% of the patients manifested nonconvulsive SE (NCSE) predominantly of the complex partial NCSE seizure (CPS) type (2). These patients were comatose and showed no overt clinical signs of convulsive activity. Clinical detection of NCSE in these patients would not have been possible with routine neurological evaluations without use of EEG monitoring. The clinical presentation, mortality, morbidity, and demographic information on this population are reported. Conclusions: Our results demonstrate that EEG monitoring after treatment of CSE is essential to recognition of persistent electrographic seizures and NCSE unresponsive to routine therapeutic management of CSE. These findings also suggest that EEG monitoring immediately after control of CSE is an important diagnostic test to guide treatment plans and to evaluate prognosis in the management of SE.     

EFNS guideline on the management of status epilepticus

The objective of the current paper was to review the literature and discuss the degree of evidence for various treatment strategies for status epilepticus (SE) in adults. We searched MEDLINE and EMBASE for relevant literature from 1966 to January 2005. Furthermore, the Cochrane Central Register of Controlled Trials (CENTRAL) was sought. Recommendations are based on this literature and on our judgement of the relevance of the references to the subject. Recommendations were reached by informative consensus approach. Where there was a lack of evidence but consensus was clear we have stated our opinion as good practice points. The preferred treatment pathway for generalised convulsive status epilepticus (GCSE) is intravenous (i.v.) administration of 4 mg of lorazepam or 10 mg of diazepam directly followed by 15-18 mg/kg of phenytoin or equivalent fosphenytoin. If seizures continue for more than 10 min after first injection another 4 mg of lorazepam or 10 mg of diazepam is recommended. Refractory GCSE is treated by anaesthetic doses of midazolam, propofol or barbiturates; the anaesthetics are titrated against an electroencephalogram burst suppression pattern for at least 24 h. The initial therapy of non-convulsive SE depends on the type and the cause. In most cases of absence SE, a small i.v. dose of lorazepam or diazepam will terminate the attack. Complex partial SE is initially treated such as GCSE, however, when refractory further non-anaesthetising substances should be given instead of anaesthetics. In subtle SE i.v. anaesthesia is required.     

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.     

Status epilepticus severity influences the long-term outcome of neurogenesis in the adult dentate gyrus

Status epilepticus (SE) is characterized by continual seizure activity that can vary widely in the intensity of convulsions. We induced seizures by applying continuous electrical stimulation to the hippocampus in adult rats to explore the effects of three different SE states on neurogenesis and neuronal death in the hippocampus. Rats exhibiting the most severe SE state (fully convulsive) demonstrated profound increases in cell proliferation in the dentate gyrus (DG) at 1 week post-insult, but the majority of the new neurons had died at 4 weeks. In contrast, rats exhibiting less severe SE states (ambulatory or masticatory, partial convulsive) had the same degree of cell proliferation at 1 week, but most new neurons survived at 4 weeks. As compared to partially convulsive SE rats, fully convulsive SE rats had significantly greater DG pathology. Our data indicate that SE of varying severity triggers similar short-term proliferation of neural progenitors, but that the long-term outcome of neurogenesis is influenced by the degree of insult-induced degeneration in the DG tissue environment.     

Status epilepticus: new concepts

Generalized convulsive status epilepticus is a neurological emergency characterized by abnormally prolonged seizures. This review emphasizes recent developments that bear on our understanding of the pathophysiology and management of status epilepticus. Topics include GABAA receptor modulation during prolonged seizures, the role of genetics in susceptibility to status epilepticus, neuron-specific enolas, the Veterans Administration Cooperative Study Group trial comparison of various drug regimens, utility of the electroencephalogram in patient monitoring, emerging drug therapies and patient management in out-of-hospital settings.     

Febrile seizures in patients with complex partial seizures

Febrile seizures occurred in 14 of 155 (9%) out-patients with complex partial seizures. Twelve patients had prolonged or recurrent febrile seizures, convulsive status epilepticus or a transient postictal neurological deficit. Febrile seizures were associated with perinatal abnormalities, an earlier onset of epilepsy and with a poor seizure control. Recurrent febrile seizures or those with complicating features are associated with an unfavourable therapeutic outcome in adult patients with complex partial seizures.     

Epileptogenesis and neuropathology after different types of status epilepticus induced by prolonged electrical stimulation of the basolateral amygdala in rats

It has previously been shown that prolonged (60-min) low-intensity electrical stimulation of a kindled focus in the basolateral nucleus of the amygdala (BLA) of Wistar rats resulted in the development of self-sustained status epilepticus (SSSE) with predominantly partial seizures and subsequent brain damage in the ipsilateral hemisphere. In the present study, using high-intensity (700 microA) pulsed-train electrical stimulation of the BLA for 25 min, SSSE was induced in both kindled and non-kindled Wistar rats, demonstrating that under these experimental conditions prior kindling is not necessary to induce SSSE. Thus, all subsequent experiments were done in non-kindled rats of different strains (Wistar, Sprague-Dawley) and genders. Three distinct behavioral types of SSSE were observed: (1) continuous partial seizures; (2) continuous partial seizures, repeatedly interrupted by generalized convulsive seizures; and (3) continuous generalized convulsive seizures. These three forms of SSSE were seen in both strains and genders, although the percentage of rats in each strain and gender developing a specific type of SSSE differed. Rats spontaneously recovered from SSSE after between 3 and 8h on average, the SSSE duration depending on SSSE type, rat strain and gender. Following SSSE, rats were monitored with a video- and EEG-recording system for occurrence of spontaneous recurrent seizures (SRS). Overall, about 80% of the rats developed epilepsy with SRS after SSSE, but the proportion of rats developing SRS depended on the type of SSSE. Only 33% of the rats developed SRS after a partial SSSE, compared to >90% in case of either type 2 or type 3 SSSE with generalized convulsive seizures. Interruption of different forms of SSSE with diazepam after 90 min prevented development of epilepsy, while a generalized SSSE duration of 4h consistently produced epilepsy in >90% of rats. Histologic analysis of rat brains after the different SSSE types indicated that neuronal loss after partial SSSE was much more regionally restricted and less severe compared to neuronal damage after SSSE with generalized convulsive seizures, which was similar to the brain damage seen in the kainate and pilocarpine models of temporal lobe epilepsy. These experiments establish that prolonged electrical stimulation of the BLA induces different forms of SSSE that resemble nonconvulsive and convulsive types of SE in humans. These different forms of SSSE induce epilepsy with SRS and brain pathology reminiscent of temporal lobe epilepsy with hippocampal sclerosis. The rat model provides a new tool to mimic different types of SE and investigate the pathogenesis underlying their long-term complications.     

Interstrain differences in cognitive functions in rats in relation to status epilepticus

Cognitive functions of Long Evans (N=30) and Wistar rats (N=32) were compared using a Morris water maze. Under control conditions the Long Evans rats were more efficient in this test, their average escape latency after 5 days of training (6.4+/-0.1 s, mean+/-S.E.M.) was significantly shorter than that of the Wistar rats (11.0+/-0.1 s). When the training was completed seizures were induced by an intraperitoneal injection of pilocarpine (330 mg/kg in the Long Evans strain and 350 mg/kg in the Wistar rats) 30 min after pretreatment with N-methylscopolamine (1 mg/kg i.p.). Clonazepam (1 mg/kg i.p.) was used to interrupt clonic seizures after 2 hours of continuous activity. Approximately one quarter of rats in both strains did not develop seizures. Severe convulsive status epilepticus was common in Long Evans rats (23 out of 30). In contrast, only 12 Wistar rats generated convulsive status epilepticus and the same number of animals exhibited only bursts of motor seizures separated by periods without convulsions (temporary seizures). Mortality after pilocarpine-induced status epilepticus was considerably higher in the Long Evans rats than in the Wistar rats. After a latency of 2-3 weeks spontaneous recurrent seizures appeared in all animals surviving status. Cognitive memory was tested during the 'silent period' between status and recurrent seizures. The Long Evans rats were unable to find the platform at the 3rd and 6th day after status but then their performance rapidly improved. The performance of the Wistar rats undergoing status epilepticus was seriously deteriorated and it never normalized, whereas the animals with temporary seizures exhibited only a transitory marginal prolongation of latencies. The hippocampal formation was damaged by status epilepticus in rats of both strains - the Long Evans rats exhibited more extensive damage of subfields CA1 and CA3, whereas in the Wistar rats a complete destruction of hilar neurons was observed in addition to partial CA1 and CA3 damage.     

Status Epilepticus and Refractory Status Epilepticus Management

Status epilepticus (SE) describes persistent or recurring seizures without a return to baseline mental status and is a common neurologic emergency. SE can occur in the context of epilepsy or may be symptomatic of a wide range of underlying etiologies. The clinician׳s aim is to rapidly institute care that simultaneously stabilizes the patient medically, identifies and manages any precipitant conditions, and terminates seizures. Seizure management involves “emergent” treatment with benzodiazepines followed by “urgent” therapy with other antiseizure medications. If seizures persist, then refractory SE is diagnosed and management options include additional antiseizure medications or infusions of midazolam or pentobarbital. This article reviews the management of pediatric SE and refractory SE.