Acta Neurol Scand 2015: 132: 1–6 DOI: 10.1111/ane.12336

© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA

Super-refractory status epilepticus in West China Tian L, Li Y, Xue X, Wu M, Liu F, Hao X, Zhou D. Super-refractory status epilepticus in West China. Acta Neurol Scand 2015: 132: 1–6. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objective – This study aims to determine the general frequency, mortality, and risk factors of super-refractory status epilepticus (SRSE) versus non-refractory status epilepticus (NRSE) and refractory status epilepticus (RSE). Methods – This work is a retrospective study. Clinical data of patients who were diagnosed with status epilepticus (SE) in the neurological ward and neuro-intensive care unit of West China Hospital from January 2009 to December 2012 were collected and analyzed. Results – A total of 98 patients were included in the study. The percentages of NRSE, RSE, and SRSE were 67.3%, 20.4%, and 12.2%, respectively. Convulsive SE was the main seizure type among the three groups. The most common cause of NRSE was related to epilepsy (EP). However, 67.7% of SRSE cases were caused by acute encephalitis. Moreover, 47% of SE and 40% of RSE cases had a history of EP, whereas only 8.3% of SRSE cases had such history (P < 0.01). The percentage of patients with STESS ≤2 was lowest in the SRSE group without statistical significance (P > 0.05). The general mortality of SE was 7.1%, whereas that of SRSE was 50%. During follow-up, most SRSE patients who survived have developed symptomatic EP. Conclusions – This study was the first to use the statistical percentage of SRSE. Approximately 12.2% of SE cases will result in SRSE, which is a challenging medical situation for doctors. Patients with first episodes and acute encephalitis were also prone to develop SRSE.

L. Tian1, Y. Li1, X. Xue2, M. Wu2, F. Liu2, X. Hao1, D. Zhou1 1 Neurology, West China Hospital, Sichuan University, Chengdu, China; 2Intensive Care Unit, West China Hospital, Sichuan University, Chengdu, China

Key words: super-refractory status epilepticus; status epilepticus; refractory status epilepticus D. Zhou, Neurology department, West China Hospital, Sichuan University, No 37 Guoxue Lane, Wuhou District, Chengdu, 610041 China Tel./Fax: +86 028 8542 2549 e-mail: [email protected] Accepted for publication September 19, 2014

Introduction

Methods and definition

Over the last two decades, epidemiology of and treatment strategy for status epilepticus (SE) had gradually developed. Super-refractory status epilepticus (SRSE) is a critical medical situation in SE. That is difficult to deal with and has received considerable attention in recent years (1,2). Although some regimens and successful cases were reported (3, 4), the general frequency, mortality, risk factors, therapeutic strategy, and unique characteristics of SRSE versus non-refractory status epilepticus (NRSE) and refractory status epilepticus (RSE) remain unclear. In this article, clinical data of SE patients were collected from West China Hospital from January 2009 to December 2012. The cases were divided into NRSE, RSE, and SRSE to determine the different clinical characteristics of SRSE.

The ethics committee of West China Hospital of Sichuan University approved this retrospective study. SE was defined as the clinical occurrence of ongoing or repeated epileptic seizures without full recovery for more than 5 min. If SE ceased after the first or second anticonvulsant, SE was considered as NRSE. RSE was defined as the clinical failure of first and second antiepileptic treatments to control seizures (5). SRSE is defined as SE that continues or recurs 24 h or more after the onset of anesthetic therapy, including cases where SE recurs upon reduction or withdrawal of anesthesia (1). SE was classified as convulsive (generalized tonic–clonic seizures with loss of consciousness) and non-convulsive SE (absence SE, simple partial and complex partial SE without jerks, and non-convulsive SE in coma). 1

Tian et al. Table 1 Demographics and clinical features of patients NRSE Case Age Male/female Type of SE convulsive SE Non-convulsive SE History of EP History of SE STESS ≤2

66 44.53 37/29 59 7 31 10 31

(67.3%)  19.71 (89.4%) (10.6%) (47%) (15.2%) (47%)

RSE 20 42.55 9/11 19 1 8 3 8

P value

SRSE

(20.4%)  19.53 (95%) (5%) (40%) (15%) (40%)

12 38.08 7/5 11 1 1 0 2

(12.2%)  24.12

Paired t >0.05 k test >0.05

(91.7%) (8.3%) (8.3%)

Fisher’s exact test 0.05 Fisher’s exact test >0.05

(16.7%)

EP, epilepsy; NRSE, non-refractory status epilepticus; RSE, refractory status epilepticus; SRSE, super-refractory status epilepticus; STESS, Status Epilepticus Severity Score.

Clinical data of patients who were diagnosed with SE in the neurological ward and neuro-ICU of West China Hospital from January 2009 to December 2012 were collected. The diagnoses and subgroups were separately confirmed by two clinicians from the Epilepsy Research Center. Cases in which the clinicians have different opinions were discussed and decided by the group. All related clinical data were collected. These data included gender, age, epilepsy (EP) history, seizure type, etiology, prognosis, treatment, electrophysiological findings, neuroimaging, laboratory findings, outcome at discharge, and follow-up. SPSS 13.0 Software for Windows (SPSS, Chicago, IL, USA) was used. Pearson’s chi-square test, Fisher’s exact test, and one-way ANOVA were used as needed. Statistical significance was set at the 0.05 level.

The difference was significant (P < 0.01). SE history was also recorded. Although this history was recorded only in NRSE and RSE, the statistical results were not significant (P > 0.05). Status Epilepticus Severity Score (STESS) was established to assess the severity of SE and the initial treatment intensity. STESS was successfully used in previous studies (6–9). STESS ≤2 generally indicates positive outcomes. In this study, the percentage of patients with STESS ≤2 was lowest in the SRSE group, although the difference was not statistically significant (P > 0.05). The cause of SE was described in detail (Tables 2 and 3). The most common causes of NRSE were related to EP, including irregular therapy and antiepileptic drugs (AEDs) withdrawal. Sequela of various cerebral disorders was an important etiology of NRSE. However, 66.7%

Results

Table 2 Etiology of NRSE, RSE, and SRSE

A total of 107 patients were diagnosed with SE from January 2009 to December 2012 in the neurology ward and neuro-ICU of West China Hospital. A total of 98 patients were included in the study, and 9 patients were excluded because of incomplete data and/or age below 16. On the basis of the definitions of SE, RSE, and SRSE, the cases were divided into three groups (Table 1). The mean age was approximately 40 years old in the three groups. The percentages of NRSE, RSE, and SRSE were 67.3%, 20.4%, and 12.2%, respectively. The three groups exhibited no difference in age and gender. Convulsive SE was the main seizure type among the three groups. Some convulsive SE evolved into nonconvulsive SE. We still identified these cases under convulsive epileptic status in the study to avoid confusion. In this study, 47% of NRSE and 40% of RSE had a history of EP. However, only one SRSE patient (8.3%) was previously diagnosed with EP. 2

Idiopathic/cryptogenic EP with regular treatment Cerebral vascular malformation Dysplasia Late sequela of TBI Late sequela of cerebral infarction Late sequela of viral encephalitis Late sequela of cerebral hemorrhage Idiopathic/cryptogenic EP (irregular treatment or withdrawal) TBI Metabolic encephalopathy Tumor Acute encephalitis Brain surgery (excluding TBI) Cerebral hemorrhage Multiple sclerosis Subdural effusion Transient ischemic attack Not clear Total

NRSE

RSE

21 (31.8%)

4 (20%)

0

1 1 3 2 0 0 3

0 0 0 1 (8.3%) 0 1 (8.3%) 0

3 2 5 4 1 3 6

(4.5%) (3.0%) (7.6%) (6.1%) (1.5%) (4.5%) (9.1%)

2 2 3 7 2 1 1 1 1 0 66

(3.0%) (3.0%) (4.5%) (10.6%) (3.0%) (1.5%) (1.5%) (1.5%) (1.5%)

(5%) (5%) (15%) (10%)

(15%)

0 0 0 4 (20%) 1 (5%) 0 0 0 0 1 (5%) 20

SRSE

0 2 (16.7%) 0 8 (66.7%) 0 0 0 0 0 0 12

EP, epilepsy; NRSE, non-refractory status epilepticus; RSE, refractory status epilepticus; SRSE, super-refractory status epilepticus; TBI, traumatic brain injury.

Super-refractory status epilepticus Table 3 Clinical features of SRSE

No.

Gender/Age

Etiology

Semiology

STESS score

GOS* at discharge

GOS at 3 months

GOS at 6 months

Symptomatic EP after SRSE

1 2 3 4 5 6 7 8 9 10 11 12

M/19 F/81 F/66 F/24 M/28 M/22 M/24 F/20 M/21 F/19 M/72 M/61

Encephalitis Sequela of cerebral hemorrhage Sequela of cerebral infarction Encephalitis Herpes encephalitis Encephalitis Toxoplasmic encephalitis Encephalitis Herpes encephalitis Herpes encephalitis Metabolic encephalopathy Metabolic encephalopathy

Convulsive Convulsive Convulsive Convulsive Convulsive Convulsive Convulsive Complex partial Convulsive Convulsive Convulsive Convulsive

3 5 2 3 3 3 3 2 3 3 5 3

5 1 1** 1** 2 4 2 2 1** 1** 2 1

5 – – – 4 5 2 5 – – 1 –

– – – – 4 5 3 5 – – – –

Yes

Yes Yes Yes

EP, epilepsy. *Glasgow Outcome Scale (GOS) (10) was categorized as: died (GOS score = 1), not improved (GOS score = 2), improved (GOS score = 3–4), and recovered to baseline condition (GOS score = 5). **Patients who died 24 h after therapy were abandoned.

of SRSE patients had acute encephalitis. The etiology of SRSE is described in Table 3. Antibodies against N-methyl-D-aspartate (NMDA), a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), voltage-gated potassium channel (VGKC), and glutamic acid decarboxylase (GAD) were tested in the SRSE patients with encephalitis. None of these antibodies were found positive. All patients received diazepam as the first therapeutic choice. Diazepam was re-administered if seizures recurred in 5–10 min. For patients who had not experienced any effect, the second choice

was valproate infusion. If the second step failed, midazolam, diazepam, and propofol were used alone or in combination and adjusted according to the symptoms, EEG, blood pressure, complications, and so on. The maximum doses are listed in Table 4. Both symptoms and EEG were monitored while the treatment was adjusted. Oral AEDs were also administered according to the seizure type. Muscle relaxation, mechanical ventilation, and other supportive therapies were applied as necessary. All types of complications were monitored and addressed. Three SRSE patients failed upon anesthesia withdrawal and

Table 4 Course of therapies for SRSE

No

Time-latency of SE treatment

Time-latency AED1–AED2

AED 2 (mg/kg/h)

Time-latency AED2anesthesia

VPA 0.5 VPA 0.6 VPA 1 Unknown VPA 1.5

1h 2h 3.5 h Unknown 1h

1 2 3 4 5

M/19 F/81 F/66 F/24 M/28

0.5 h 20 min 1h Unknown 10 min

1h 5h 1.5 h Unknown 1h

6 7 8 9 10

M/22 M/24 F/20 M/21 F/19

1h 2h 6h Unknown 1h

2 2 2 1 2

11 12

M/72 M/61

Unknown 15 min

Unknown 2h

h day day h day

VPA VPA VPA VPA VPA

1 1 0.8 0.5 0.8

Unknown VPA (1) Mid (0.1)

3 12 1 3 2

h h day h day

Unknown 1 day

Maximum dose used (mg/kg/h) Mid 0.2 Dia 0.4 Mid 0.1 Mid 0.1 + Pro 1 Mid 0.4 + Dia0.4/Mid 0.4 + Pro 4 Pro2 + Dia0.5 Mid0.4 + Pro1 Mid 0.1 Mid0.2 + Pro1 Mid0.2 + Pro3/Pro4 + Dia0.2 Mid0.1/Pro1 Mid0.1 + Pro1

Time-latency anesthesia to SE termination

Therapy failure because of anesthesia withdrawal

9 3 8 6 45

day day* day* day* day

Yes – – Yes –

9 28 2 5 18

day day day day* day*

– – – – –

6 day 2 day*

Yes –

Oral drug (g/day) OXC (0.9), TPM (0.2) LEV (0.5), TPM (0.1) VPA (1.4), TPM (0.1) VPA (0.8), PB (0.3), LEV (1), TPM (0.1) VPA (1.4), PB (0.3), LEV (3), TPM (0.2), OXC (0.9) LEV (1), OXC (0.6) VPA (1.2), PB (0.6), LEV (2), TPM (0.1), VPA (0.6), TPM (0.1), OXC (0.9) VPA (2), PB (0.3), CBZ (0.6) VPA (0.6), PB (0.3), CBZ (0.3), PHT (0.3) VPA (1.2), LEV (1), TPM (0.1) VPA (0.6), PB (0.3)

AEDs, anti-epileptic drugs; CBZ, carbamazepine; Dia, diazepam; LEV, levetiracetam; Mid, midazolam; OXC, oxcarbazepine; PB, phenobarbital; PHT, phenytoin; Pro, propofol; TPM, topiramate; VPA, valproate. *Patient died.

3

Tian et al. Table 5 Outcome at discharge NRSE Outcome at discharge Improvement 65 (98.5%) Death No improvement Hospitalization time

1 (1.5%) 0 8.09  5.18

RSE

20 (100%) 0 0 11.5  9.11

SRSE

5 (41.7%)

P value

Super-refractory status epilepticus in West China.

This study aims to determine the general frequency, mortality, and risk factors of super-refractory status epilepticus (SRSE) versus non-refractory st...
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