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Status epilepticus (SE) is frequently observed in epileptic patients. We reviewed a series of video-EEG documented SE to define the characteristics of SE in this population.
Materials and methods
Retrospective evaluation of 50 epileptic patients with SE, revision of the electro-clinical data and therapies, and definition of the semeiological subtypes, aetiology, outcome and related epileptic syndromes.
Results
We identified 28 convulsive (19 focal and 9 generalized) and 22 non-convulsive (8 focal and 14 generalized) SE patients. In 13 patients, SE was situation-related (poor compliance, AED reduction, worsening seizures).
In the remaining 37 patients, SE was related to the natural history of epilepsy (progression of underlying pathologies or intrinsic expression of epileptic syndromes); in these last cases, our results show a higher occurrence in cryptogenic frontal epilepsy (p = 0.01). We identified two subgroups according to the duration of the event, i.e. SE lasting <12 h and SE lasting >12 h. Our results showed a worse response to therapy in SE lasting >12 h (p = 0.01), a better response to therapy in non-convulsive SE than in convulsive SE (p < 0.05) and a relationship at statistical significance limit between a poor response to therapy/worse outcome and symptomatic epileptic syndromes (p = 0.06).
Conclusion
SE in epileptic patients has a wide spectrum of electro-clinical features. It may be related to the withdrawal or reduction of AEDs, or may even be the expression of the evolution of epileptic syndromes. Response to therapy is dependent on early diagnosis and therapy.
Status epilepticus (SE) is a neurological emergency characterized by the occurrence of a “prolonged seizure or many seizures which present so repetitively as to create a fixed or enduring epileptic condition”.
either as the first ictal manifestation or as a complication in non-compliant patients. Data on the clinical and EEG features in either case are often lacking because a targeted assessment of this condition in the emergency department (ER) setting, which is where SE is usually observed, is considered to be either of little use or too complicated.
Although SE in epileptic patients is often precipitated by specific factors (poor compliance, AED withdrawal/reduction, gastroenteral malfunctioning, and multiple other factors such as fever or intoxications with proconvulsant substances), it may even occur for no apparent reason. In this study we reviewed the clinical and EEG data of 50 epileptic patients with a video-EEG recorded SE in an attempt to define the SE semeiological subtypes, aetiology, outcome as well as any related epileptic syndromes.
Materials and methods
We performed a retrospective study of 50 consecutive epileptic patients with SE who had been referred to the video-EEG laboratory of our Epilepsy Unit between 1996 and 2004. The patients’ video-EEG studies were selected from a total of 6749 recordings performed in our laboratory during the period we considered (average of 750 examinations per year). As our video-EEG laboratory is located within the neurological ward, hospitalised patients promptly undergo, in case of epileptological emergencies, a video-EEG recording to assess electro-clinical findings and to monitor the response to therapy. Our outpatients, especially those suffering from drug-resistant seizures, are usually advised to come directly to our laboratory in case of prolonged seizures. Of the 50 patients we selected, 20 had been referred to our laboratory directly by the ward, 17 by our outpatient service and only 13 by the ER.
Inclusion criteria
The inclusion criteria were: (1) a video-EEG documented SE; according to Gastaut's definition,
SE was defined as any prolonged seizure/cluster of recurrent seizures lasting ≥30 min without intervening recovery of consciousness; (2) a previous, documented diagnosis of epilepsy accompanied by complete clinical data (including general characteristics, seizure type, syndromic classification).
Exclusion criteria
The exclusion criteria were: (1) SE in patients with acute neurological disease or with no previous history of epilepsy; (2) incomplete clinical data, including lack of previous documentation, inability to identify the SE time of onset, its temporal evolution and therapy before our clinical and video-EEG assessment.
Main clinical and EEG findings
In accordance with previous documentation, the clinical characteristics (age at seizure onset, seizure type, risk factors, neurological examination, neuroimaging and interictal EEG) were defined and a epilepsy syndromic classification was drawn up. In the syndromic context, lobar definition was defined according to ictal semeiology, interictal and ictal EEG and neuroimaging features. According to the ILAE classification,
epileptic syndromes not clearly defined as generalized or partial were considered as undetermined. On the basis of the video-EEG documentation, SE semeiological features, EEG findings, temporal evolution, therapeutic management (drug used, route and timing of its administration, loading and maintenance dose) and short-term outcome were analyzed. According to the inclusion criteria, SE duration was defined as the interval between the onset of symptoms (identified on the basis of the information reported by the patients’ relatives or by medical staff) and video-EEG-documented SE resolution (established according to the disappearance of or significant reduction in epileptiform abnormalities).
Although several SE classifications have been proposed in the past
(revised according to specific concepts regarding different subtypes of CSE, with particular attention being paid to focal motor SE, which is usually difficult to classify
) because we deemed it more suitable for the purposes of the present work (it envisages both clinical and instrumental findings).
As regards SE aetiology we adopted a clinically oriented classification with the aim to avoid any terminological confusion between SE and epilepsy aetiology.
Given the retrospective design of the study, only short-term outcome (defined as the patients’ condition in the 30 days following the SE resolution) was evaluated.
Statistical analysis
The statistical analyses were performed by means of χ2-test, with Fisher's correction when required. The values of p ≤ 0.05 were considered statistically significant. All analyses were performed with SPSS (Version 12.0).
Results
General characteristics of the patients
This study included 50 patients, 23 men and 27 women, aged 6–79 years (mean age 36.9 years). The mean age at seizure onset was 15 years, the mean age at first recorded SE was 37 years. The clinical, neurophysiologic and neuroimaging findings of the patients included in the present study are shown in Table 1.
Table 1General characteristics of the patients and SE electro-clinical, aetiological and therapeutical findings
Pt
Seizure type
Epilepsy syndrome
MRI
Interictal EEG
SE semeiological subtypes
SE aetiology
SE EEG findings
SE clinical pattern
1
SPS, CPS
Cryptogenic FLE
Normal
L Frontal spikes, 4 Hz generalized SW-PSW discharges
Simple partial NCSE (experiential)
Epilepsy evolution
4 Hz generalized SW-PSW activity
Slight confusional state, sensation of “feeling cold, a thrill inside”, bil subtle perioral myoclonic jerks
SE was subdivided in convulsive and non-convulsive (CSE and NCSE), with both groups including focal and generalized subtypes. The specific semeiological subtypes are shown in Fig. 1.
Figure 1Classification of SE population according to a recently published proposal.
Definite precipitating factors or conditions were identified in 13 patients. This group, referred to as patients with situation-related SE, included poor compliance in three cases, planned AEDs reduction in eight cases and AED-related seizure worsening in two cases. In the remaining 37 patients, SE was related to epileptic syndrome evolution: a progression of the underlying cerebral pathologies was documented in 4 cases (high grade glioma in 1 case, undetermined encephalopathy in 1 case and late-onset Rasmussen Encephalitis in 2 cases); in the other 33 cases in which no apparent precipitating factors were discovered, SE was presumed to be an intrinsic condition of the epileptic syndrome (in these cases we preferred not to use the term “cryptogenic” so as to avoid any confusion between the aetiologies of epilepsy and SE). This last group of 33 patients contained a large number of patients with a history of recurrent episodes of SE.
SE and related epileptic syndromes
Thirty-three of the 50 patients had partial epilepsy (symptomatic in 14 cases, cryptogenic in 19 cases), 8 patients had generalized epilepsy (idiopathic in 3 cases, symptomatic in 5 cases), 7 patients had undetermined syndromes (whether focal or generalized), 2 patients had a diagnosis of late-onset Rasmussen Encephalitis. Table 2 shows the main clinical characteristics of SE and the related epileptic syndromes. When assessing a possible relationship between epileptic syndromes and SE aetiology, statistical analysis revealed a statistically significant relationship between the forms of cryptogenic partial epilepsy and SE aetiology (p = 0.01).
Table 2SE and related epileptic syndromes
SE type
SE aetiology
SE recurrence
CSE
NCSE
Situation related
Syndrome evolution
PCSE
GCSE
PNCSE
GNCSE
Cryptogenic partial epilepsy
Frontal lobe (12)
3
2
3
4
–
12*
12
Temporal lobe (6)
1
–
4
1
2
4
4
Parieto-occipital lobe (1)
1
–
–
–
1
–
0
Symptomatic partial epilepsy
Frontal lobe (8)
6
–
–
2
4
4
4
Temporal lobe (3)
2
–
1
–
1
2
2
Parieto-occipital lobe (3)
2
–
–
1
1
2
2
Idiopathic generalized epilepsy
Juvenile myoclonic epilepsy (1)
–
1
–
–
1
–
0
Juvenile absence epilepsy (2)
–
–
–
2
1
1
0
Symptomatic/cryptogenic generalized epilepsy
Lennox-Gastaut syndrome (5)
2
3
–
–
1
4
5
Undetermined focal or generalized (7)
–
3
–
4
1
6
5
Special syndromes
Late onset Rasmussen Encephalitis (2)
2
–
–
–
–
2
2
CSE, convulsive status epilepticus; NCSE, non-convulsive status epilepticus; PCSE, partial convulsive status epilepticus; GCSE, generalized convulsive status epilepticus; PNCSE, partial non-convulsive status epilepticus; GNCSE, generalized non-convulsive status epilepticus. *p = 0.01 (χ2-test).
We divided our population in two subgroups of patients according to the duration of the SE: in 28 cases, the SE lasted less than 12 h, whereas in the remaining 22 cases it lasted more than 12 h. Our therapeutic approach included a sequential strategy with: (i) a first-line step consisting of i.v. benzodiazepines (Lorazepam 4–8 mg in bolus, maintenance dose of 16 mg/24 h) and (ii) a second-line step consisting of i.v. phenytoin (dose of 15–18 mg/kg) and of thiopental sodium in non-responders (loading dose of 100–250 mg given over 20 s until seizures are controlled, followed by a maintenance dose of 3–5 mg/kg/h); despite of the refractoriness, in two patients with late-onset Rasmussen's Encephalitis no other acute therapy was administered (immunotherapy was planned). Fig. 2 shows the specific therapies used and the relative responder ratios.
Figure 2Algorithm showing therapeutic strategies in the patients with status epilepticus included in the study. SE, status epilepticus; BDZ, benzodiazepines; PHT, phenytoin; TPS, thiopental sodium; i.v., intravenous administration; other, in patients with a late-onset Rasmussen Encephalitis an immunotherapy was planned.
In 41 patients we did not observe any neurological deficits related to SE. In the remaining nine patients only slight sequelae were documented mainly consisting of a mild cognitive impairment and, in just two cases, a slight pyramidal hemisyndrome (both of them with late-onset Rasmussen's Encephalitis).
Response to therapy and short-term outcome related to age, semeiological subtypes, epileptic syndrome, SE aetiology and duration
The statistical analysis showed a statistically significant correlation between a shorter SE duration and a better response to therapy (p = 0.01) and between CSE subtype and a worse response to the first-line therapy (p < 0.05); a relationship at statistical significance limit between epileptic syndromes and response to therapy (p = 0.06) and between epileptic syndromes and outcome (p = 0.06) was also observed (Table 3). Response to therapy and outcome were not influenced by SE age of onset (Table 3).
Table 3Response to therapy and outcome related to age, semeiological subtypes, epileptic syndrome, aetiology and duration
In this study, a video-EEG analysis allowed us to identify a wide spectrum of electro-clinical features in a population almost equally distributed in the two main groups of CSE and NCSE. In disagreement with previously published series and historical data,
in this study we observed a significant percentage of NCSE (44%) and relatively small number of CSE, especially as regards GCSE (18%). These data are amply justified by the selection criteria adopted in this study that specifically focused on SE in patients suffering from pre-existing epilepsy. In particular the evidence of a low proportion of GCSE is unsurprising as most of our patients had been referred to our laboratory from either a ward or outpatient service. Indeed, patients in more critical conditions, such as those with GCSE, are usually referred to emergency departments where prompt therapy is the primary aim, while the definition of the clinical and neurophysiological features becomes secondary. With respect to semeiological definition, this study confirms the central role of the ictal neurological evaluation and EEG data in classifying NCSE, especially when differentiating partial from generalized subtypes.
In some conditions, a more careful electro-clinical assessment appears to be useful as a means of understanding the role of SE in different epileptic syndromes.
Although epileptic patients account for as many as 50% of the patients in SE population-based studies (predominantly performed in emergency departments), the data available on this subgroup of patients cannot be considered exhaustive because targeted clinical and neurophysiological assessments needed for a thorough definition of the syndrome are lacking.
It is commonly accepted that SE, when recognized in epileptic patients, is often related to AED withdrawal due to either the medical strategy or patient non-compliance. However, the natural evolution of some epileptic syndromes, especially drug-resistant ones, has been known to be characterized by the occurrence of SE or seizure clustering.
a number of cases of SE closely related to AED (non-compliance, planned reduction or worsening seizures), it is noteworthy that SE in a large number of patients was related to epileptic syndrome natural history (37/50 cases). Indeed, with the exception of a few cases in which progression of the underlying cerebral pathologies was documented (4/37 cases), SE, which was often found to recur in the same patient, was presumably an intrinsic condition of the cryptogenic/non-evolving symptomatic epileptic syndrome in the vast majority of the cases (33/37 cases) confirming previously published data.
From a syndromic point of view, this group of “unexplained” recurrent SE, which often occurred in patients with an apparently normal brain, comprised various conditions. While recurrent SE may be expected in the natural history of some of these conditions (e.g. drug-resistant partial epilepsy and Lennox-Gastaut syndrome),
it is more difficult to explain in the remainder (undetermined syndrome, whether focal or generalized, or idiopathic generalized epilepsy with secondary “lennoxization”). In this regard, the higher incidence of SE in patients with frontal lobe epilepsy, particularly in those suffering from a cryptogenic partial syndrome, is worthy of note. Further studies are warranted to shed light on this specific issue.
In the present study, the analysis of the patients’ variables with respect to the patient's response to therapy and short-term outcome yielded some noteworthy findings. Symptomatic epileptic syndromes tend to be related to a worse response to therapy and a less favourable outcome: a very interesting finding was that this group included epilepsies related not only to evolving lesions (in which it is difficult to assess the exact role SE plays in the prognosis) but also to fixed and “remote” conditions, in which a worsening neurological status is related to prolonged activity per se. Moreover, in accordance with published data
we found a close relationship between SE duration and the response to therapy: indeed, SE lasting less than 12 h responded promptly to therapy, whereas SE lasting longer was more likely to be therapy-resistant. As regards the relationship between SE semeiological subtypes and the response to therapy, this study seems to be in agreement with previous studies, confirming that CSE is usually more difficult to manage than NCSE,
especially in epileptic patients. One apparent contradiction was that a longer-lasting SE was not, as would be expected, related to a worse outcome. This last issue which in fact partially confirmed already published data
however appears to be closely related to the intrinsic limitations of this study. Indeed, the small number of patients did not yield statistically significant information on this specific topic; moreover, the retrospective design of the study allowed us to evaluate short-term outcome alone, and not the possible presence of subtle, long-term cognitive consequences, particularly in patients presenting recurrent episodes of SE.
In conclusion, though SE in epileptic patients appears to be a less critical condition than acute symptomatic SE, a long-lasting epileptic condition may reinforce its self-sustaining neurophysiological mechanism, thereby affecting the patient's response to therapy and the time of recovery. As regards the prognosis, if administered promptly, therapy may, as happens in brief, single seizures, help avoid or limit the “cumulative damage” in the long term.
References
Gastaut H.
Clinical and electroencephalographic classification of epileptic seizures.
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