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Clinical Neurophysiology 123 (2012) 244251

Contents lists available at ScienceDirect

Clinical Neurophysiology
journal homepage: www.elsevier.com/locate/clinph

Nonconvulsive status epilepticus in adults: Electroclinical differences


between proper and comatose forms q
Jos L. Fernndez-Torre a,e,f,, Mariano Rebollo b, Agustn Gutirrez c, Francisco Lpez-Espadas d,
Miguel A. Hernndez-Hernndez d,f
a

Department of Clinical Neurophysiology, Marqus de Valdecilla University Hospital, Santander, Cantabria, Spain
Department of Neurology, Marqus de Valdecilla University Hospital, Santander, Cantabria, Spain
Department of Radiology, Marqus de Valdecilla University Hospital, Santander, Cantabria, Spain
d
Department of Intensive Medicine, Marqus de Valdecilla University Hospital, Santander, Cantabria, Spain
e
Department of Physiology and Pharmacology, University of Cantabria (UNICAN), Santander, Cantabria, Spain
f
Instituto de Formacin e Investigacin Marqus de Valdecilla (IFIMAV), Santander, Spain
b
c

a r t i c l e

i n f o

Article history:
Accepted 23 June 2011
Available online 19 July 2011
Keywords:
Nonconvulsive status epilepticus
Absence status epilepticus
Complex partial status epilepticus
Coma
Electroencephalogram
Prognosis

h i g h l i g h t s
 This study supports the utility of differentiating between proper and comatose nonconvulsive status epilepticus (NCSE).
 De novo absence status epilepticus (ASE) induced by nonpsychotropic drugs occurs in a well-dened
clinical scenario.
 Comatose NCSE occurs mainly in individuals with acute symptomatic cerebral pathology.

a b s t r a c t
Objective: Nonconvulsive status epilepticus (NCSE) represents an important percentage of status epilepticus in adults, but detailed studies of both NCSE proper and comatose NCSE are lacking. We retrospectively analyzed a prospectively collected series of 50 adult patients with a diagnosis of NCSE whose
electroencephalograms (EEGs) have been interpreted for a period of 10 years by the same investigator.
Methods: Two groups, NCSE proper and comatose NCSE were considered. All clinical, EEGs, neuroimaging
data, antiepileptic treatment and outcome were analyzed.
Results: Thirty-two patients (64%) had NCSE proper and 18 patients (36%) comatose NCSE. The mean age
was 56 years (range 1989 years). Fourteen (44%) were diagnosed with absence status epilepticus (ASE),
one had simple partial status epilepticus (SPSE) and 17 (53%) had complex partial status epilepticus
(CPSE). The mean episode duration (33.2 13.9 versus 60.6 34.0), mean number of antiepileptic drugs
(AEDs) (1.46 0.5 versus 2.77 1.39) and neuroimaging anomalies (50% versus 16%) was signicantly
greater in the partial/focal NCSE proper subgroup than in the ASE subgroup. The mean age (56.0 19.9
versus 69.4 12.1), number of elderly individuals (46% versus 77%), mean duration of the episode
(49.1 30.4 versus 153.3 142.6), mortality rate (6% versus 61%) and admission at ICU (18% versus
83%) was signicantly higher in the comatose NCSE group than in the NCSE proper group (p < .05).
Conversely, a previous history of chronic epilepsy was signicantly more frequent (62% versus 5.6%) in
the NCSE proper group. The mean duration of comatose NCSE was signicantly greater in the surviving
subgroup (102.5 29.1 versus 233.1 65.3; p < .05).
Conclusions: Our study demonstrates that there are sufcient differences regarding age of onset, history
of previous epilepsy, episode duration, mortality rate and clinical presentation between NCSE proper and
comatose NCSE to recommend adoption in clinical practice. These results should be taken into account
when developing future classications and therapeutic trials on NCSE.
Signicance: A distinction between NCSE proper (ambulatory forms of NCSE) and comatose NCSE is useful
in the clinical practice and, therefore, it should taken in account in the design of future investigations on
this heterogeneous epileptic condition.
2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights
reserved.

This investigation was partially presented as poster at the Innsbruck Colloquium on Status Epilepticus, April 2009.

Corresponding author at: Department of Clinical Neurophysiology, Marqus de Valdecilla University Hospital, Avda. Valdecilla, s/n, 39008 Santander, Cantabria, Spain.
Tel.: +34 942 202520x72674; fax: +34 942 315095.
E-mail addresses: jlfernandez@humv.es, ftorrenfc@hotmail.com (J.L. Fernndez-Torre).
1388-2457/$36.00 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.clinph.2011.06.020

J.L. Fernndez-Torre et al. / Clinical Neurophysiology 123 (2012) 244251

1. Introduction
Nonconvulsive status epilepticus (NCSE) represents one of the
great challenges in neurology (Meierkord and Holtkamp, 2007),
because of its frequently missed diagnosis (Kaplan, 1996; Drislane,
2000), and controversy regarding intensity of, and approaches to
treatment (Walker, 2001). Since the introduction by Treiman
et al. (1984) and Treiman (1993, 1995) of the term subtle generalized convulsive status epilepticus (SGCSE), and the description of
different states of continuous electrographic activity associated
with minimal or absent motor manifestations in severely ill and
comatose patients (Simon and Aminoff, 1986; Celesia et al.,
1988; Krumholz et al., 1988; Treiman et al., 1990; Young et al.,
1990; Lowenstein and Aminoff, 1992; Drislane and Schomer,
1994; Privitera et al., 1994), there has been a push to consider this
patient group as a different type of NCSE (Kaplan, 1999, 2000,
2003; Fujikawa, 2006; Bauer and Trinka, 2010).
The purpose of our study was to describe the electroclinical differences between non-comatose and comatose forms of NCSE in
adults.
2. Patients and methods
2.1. Patients
The Department of Clinical Neurophysiology at Marqus de Valdecilla University Hospital provides adult neurophysiologic service
to 591,886 inhabitants in an urban and rural area of the region of
Cantabria, located in the north of Spain. It is the only neurophysiology department in the area. All patients older than 16 years who
between 2002 and 2008 were diagnosed as having NCSE were included in the study and followed clinically until April 2009. In
addition, six patients (Cases 2, 3, 23, 28, 32 and 44) diagnosed by
the rst author (J.L.F.-T.) during the period 19992002 at Cabuees
Hospital (Gijn, Asturias), a secondary hospital providing adult
neurophysiologic service to 350,000 habitants, were also included.
Eighteen of the patients included in this series have been
previously published in detail individually as case reports
(Fernndez-Torre, 2001; Fernndez-Torre and Daz-Castroverde,
2004; Fernndez-Torre and Martnez-Martnez, 2007; FernndezTorre and Leno, 2008; Fernndez-Torre and Rebollo, 2009;
Fernndez-Torre et al., 2000, 2003a,b, 2004, 2005, 2006a,b,c,
2007a,b, 2009). However, none has been analyzed regarding the
criteria and standpoint of this study. In addition, the full description of all patients may be found in Spanish as a Doctoral Thesis
elsewhere (Fernndez-Torre, 2009).
2.2. Denition and diagnostic criteria
NCSE was dened as a pleomorphic and heterogenous epileptic
condition, lasting more than 30 min, in which continuous or recurrent electrographic seizure activity was responsible for diverse
clinical symptoms including altered mental state, behavioral and
perception abnormalities, vegetative disturbances or reduced level
of consciousness (Drislane, 2000; Kaplan, 2002; Brenner, 2002;
Fernndez-Torre et al., 2003; Meierkord and Holtkamp, 2007;
Maganti et al., 2008; Bauer and Trinka, 2010). All these symptoms
occurred without major convulsive activity.
Differential diagnosis and conrmation of NCSE can be difcult
and depends to a large degree on electroencephalography
(Brenner, 2004). Electroencephalograms (EEGs) were performed
with 21 electrodes placed according to the International 1020
system. Continuous EEG or video-EEG was obtained for at least
30 min including photic, sensory and verbal stimulation in awake
and comatose subjects. All tracings were reviewed by one board-

245

certied clinical neurophysiologist (J.L.F.-T.), and the discharge


type, frequency, distribution (generalized or focal) and localization
(hemisphere, lobe) were analyzed.
Particular interest was focused on accurately determining the
level of consciousness and patients mental status, and the response to the acute administration of intravenous benzodiazepines
(IVBZDs) when used for diagnosis. The clinical effect of IVBZDs was
evaluated during the EEG recording for 510 min after its administration. Resolution of the clinical and EEG anomalies after treatment with antiepileptic drugs (AEDs) was considered necessary
to determine denite NCSE (Kaplan, 2005). Not all patients were
treated with acute IVBZDs due to physiologic considerations.
2.3. Classication
In practical terms, the subjects were divided into: (i) NCSE proper and; (ii) Comatose NCSE (Bauer and Trinka, 2010). NCSE proper included patients with generalized NCSE or absence status
epilepticus (ASE), and partial, focal or localization-related NCSE,
which was also divided into simple partial (SPSE) and complex partial status epilepticus (CPSE) (Treiman, 1995; Kaplan, 1996;
Drislane, 2000). All were ambulatory and came to the emergency
department with relatives, and immediate transfer to the intensive
care unit (ICU) was unnecessary. NCSE proper patients remained in
this group for analysis despite being transferred to the ICU because
of refractory NCSE. Comatose NCSE included all subjects with severe
and profound impairment of consciousness (coma state). The
majority of these patients were diagnosed in the ICU; however,
three subjects in this group (Cases 33, 34 and 44) remained on
the hospital ward.
2.3.1. NCSE proper group
ASE was further subdivided into four categories: (i) typical
ASE (or petit mal status epilepticus); (ii) atypical ASE (or
spike-wave stupor); (iii) situation-related ASE and; (iv) ASE with
focal features (Thomas et al., 2006). In addition, we distinguished
two subtypes of situation-related ASE, those with de novo ASE of
late onset (Thomas et al., 1992; Thomas and Andermann, 1994),
precipitated by the use or withdrawal of psychotropic drugs, and
those with de novo ASE induced by nonpsychotropic drugs, toxics, electroconvulsive therapy or metabolic disturbances. CPSE
was also subclassied into two subtypes (Ballenger et al.,
1983; Kaplan, 1996; Williamson, 1997): (i) cyclic CPSE (type I)
with recurrent complex partial seizures without recovery of consciousness between seizures and; (ii) continuous CPSE (type II)
showing continuous seizure activity.
2.3.2. Comatose NCSE group
Among comatose patients, those criteria for the diagnosis of
NCSE proposed by Young and colleagues (1996), and subsequently
modied by Chong and Hirsch (2005) were used. All EEGs in comatose NCSE patients were assessed and found to t into three patterns: (i) generalized, (ii) focal, partial or lateralized, and (iii)
focal secondarily generalized (FSG).
2.4. Data collection
This investigation is a retrospective analysis of a prospectively
collected series. Between 1999 and 2008, we prospectively identied all those patients with a denitive diagnosis of proper and
comatose NCSE. All clinical data were gathered from chart review,
EEG reports and protocols, discharge summaries, and resident
sign-out notes. Baseline demographic data (age, gender), past medical history, and the location of the patient at the time of the EEG
(hospital oor, ICU, emergency) were recorded. All patients and
recordings were examined by the same neurophysiologist

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J.L. Fernndez-Torre et al. / Clinical Neurophysiology 123 (2012) 244251

Table 1
Demographic, clinical characteristics, classication and neuroimaging features of patients with NCSE proper.
Patients

Sex/
age

Clinical presentation

Epilepsy
history

Precipitating factors

NCSE type

Neuroimaging

1 AAB
2 BDG
3 EAR

M/43
F/79
F/74

No
No
Yes

Cefepime
LZP withdrawal

De novo
De novo
Typical

CT: parietal ischemic infarct


CT: normal
CT: normal

4 FPR

M/76

Yes

Typical

CT normal

5 JGT
6 JTM

F/74
M/29

No
Yes

Cefepime

De novo
Atypical

CT: normal
ND

7 JTR

M/50

Yes

AED low levels

Typical

CT: normal

8 MCR
9 PCG
10 POO
11 RRA

F/39
M/57
F/27
M/33

Mutism/stupor
Confusion/incontinence
Somnolence/slowed
thinking
GTCS/slowed thinking/
stupor
Mutism/myoclonias
Slowed thinking/
myoclonias
Slowed thinking/
desorientation
Slowed thinking/stupor
GTCS/confusion
GTCS/mutism
GTCS/confusion

No
No
Yes
Yes

De novo
De novo
Typical
Typical

MR: normal
MR: white matter lesions
ND
CT: normal

12 RSV
13 USV

F/68
M/73

GTCS/slowed thinking
GTCS/slowed thinking

Yesa
No

Typical
De novo

MR: white matter lesions


MR: white matter lesions

14 YRG
15 PGR

F/19
M/44

GTCS/confusion/stupor
Posturing

Yes
Yes

Atypical
Frontal SPSE

MR: diffuse cortical atrophy


CT: right hemispheric atrophy

16 ARL
17 CSV

M/69
F/67

Slowed thinking
Stupor

No
Yes

Parietal CPSE
Temporal CPSE

18
19
20
21

DPC
ESV
FOF
JCM

M/48
M/80
F/43
M/55

Stupor
Stupor
Slowed thinking
Confusion

Yes
Yes
Yes
No

CT: bilateral parietal atrophy


CT: diffuse atrophy; periventricular hypodense
lesions
CT: right temporo-parietal atrophy
CT: left parieto-occipital atrophy
MR: left temporal atrophy
MR: left hyperintense frontal/insular lesions

22 JMG
23 LGD
24 LMF

F/53
F/47
M/66

Confusion/mutism
Slowed thinking
Confusion

Yes
Yes
No

25 MCA
26 MHM

M/67
F/89

Confusion, disphasia
Stupor

Yes
No

Cefepime
Alcohol

AED low levels,


alcohol

Levooxacin,
LZP, Morne
PME Lafora type
AED low levels;
sleep deprivation
GTCS
AED low levels;
GTCS
GTCS; infection
PB intoxication
GTCS
Alcohol
withdrawal;
GTCS
GTCS
None
Alcohol
withdrawal;
GTCS
AED low levels
Brain infarct

27 MVL

F/23

Yes

Brain infarct

28 PFM

F/75

Confusion,
metamorphosia
Confusion

Yes

CJD

29 SPP

M/50

Slowed thinking

Yes

30 TBM
31 TRD
32 VMS

M/74
F/20
F/81

Confusion
Slowed thinking
Confusion

No
Yes
No

GTCS, sleep deprivation,


alcohol
Brain infarct
GTCS
GTCS

Occipital CPSE
Occipital CPSE
Temporal CPSE
Frontal CPSE

Frontal CPSE
Temporal CPSE
Temporal CPSE

CT: normalb
MR: left hypocampal sclerosis
MR: hyperintense lesions in corona radiata/right
temporal lobe

Temporal CPSE
Fronto-temporal
CPSE
Parietal CPSE

MR: white matter lesions


CT: left basal ganglia ischemic infarct

Indeterminate
CPSE
Parieto-temporal
CPSE
Parietal CPSE
Frontal CPSE
Parietal CPSE

MR: right parietal ischemic infarct; diffuse


cerebral atrophy
MR: diffuse cerebral atrophy
MR: left parietal cavernous angioma
CT: left parietal ischemic infarct
MR: normal
MR: right parietal meningioma

AED: antiepileptic drugs; CJD: CreutzfeldtJakob disease; CPSE: complex partial status epilepticus; CT: computerized tomography; GTCS: generalized tonicclonic seizures;
LZP: lorazepam. MR: magnetic resonance; ND: no done. PME: Progressive Myoclonus Epilepsy; SPSE: simple partial status epilepticus.
a
There was no previous diagnosis of epilepsy but there was history of seizures in infancy.
b
There was a previous history of left frontal hemorrhage.

(J.L.F.-T.) who determined the patient neurologic status at the time


of diagnosis. In all cases subsequent follow-up EEGs were done.
This protocol was approved by the local Ethics Committee. When
we had 50 consecutive patients, we retrospectively analyzed all
our data.
Duration of NCSE could not be determined precisely because
none of our patients had continuous EEG monitoring throughout
the illness. The onset of NCSE was considered as being the moment
at which the rst EEG conrmed the presence of ongoing seizures.
The end-point of NCSE was determined to be when the mental
state normalized and the EEG changes regressed. In all patients
the termination of the episode of NCSE was conrmed with EEG.
NCSE duration may have been underestimated because in some
cases several hours may precede EEG evaluation. An advantage,
however, is that the assessed period by EEG corresponds to denite NCSE. In comatose patients, the number of hours taken to
control NCSE was dened as the lapsed time from diagnosis of ictal

epileptiform discharges (EDs) on the patients EEG until a followup EEG showed seizure resolution with or without changes in
the level of consciousness. The number of EEGs studies ranged
from one to 34 records.

2.5. Statistical analysis


Data were analyzed using commercially available statistical
software SPSS 10.0; (Chicago, IL). Chi-square and Fishers Exact
tests were used for categorical data. For comparison of means between non-normally distributed variables, the MannWhitney
U test was performed. Values of p < .05 for these tests were considered statistically signicant. The grade of agreement or congruence
was performed using a Pearson correlation coefcient.

J.L. Fernndez-Torre et al. / Clinical Neurophysiology 123 (2012) 244251

247

3. Results
In all, 50 patients were identied with both clinical and EEG evidence of NCSE. Thirty-two patients (64%) had NCSE proper and 18
patients (36%) comatose NCSE.
3.1. NCSE proper
Thirty-two patients were included in this group. All demographic, clinical characteristics, classication and neuroimaging
features are summarized in Table 1. There were 16 men and 16 women. The mean age was 56 years (range 1989 years). Five of these
patients (Cases 6, 14, 15, 20 and 31) had mental retardation. Five
patients (Cases 14, 16, 20, 22 and 29) were transferred to the ICU
by refractory NCSE. Two patients, one with Progressive Myoclonus
Epilepsy (PME) of Lafora type (Case 14) and other with sporadic
CreutzfeldtJakob disease (sCJD) (Case 28) died during the episode
of NCSE.
In 20 patients (62.5%), there was previous history of epilepsy. The
syndromic classication included: (a) six patients (Cases 3, 4, 7, 10,
11, and 14) with diagnosis of idiopathic generalized epilepsy (IGE);
(b) one (Case 6) with symptomatic generalized epilepsy (SGE); (c)
six (Cases 15, 17, 25, 27, 28 and 31) with probably symptomatic/
cryptogenic partial epilepsy and; (d) six (Cases 18, 19, 20, 22, 23,
and 29) with symptomatic partial epilepsy (SPE). In one patient
(Case 12), ASE occurred as late complication of an unrecognized picture of IGE (Fernndez-Torre and Rebollo, 2009). In the patient with
PME of Lafora disease, there was a previous misdiagnosis of Juvenile
Myoclonic Epilepsy (JME).
In all subjects except for one (Case 15), the clinical presentation
was an alteration in mental status. In 17 (53%), one or several generalized tonicclonic seizures (GTCSs) occurred at the onset of the
episode. Myoclonias were observed at onset or during the picture
of NCSE in three (Cases 5, 6 and 14).
All ictal EEG features, duration of the episode, treatment and
outcome are summarized in Supplementary Table S1. In 12
patients (37.5%), IVBZDs were administrated during the EEG
recording. The mean duration of NCSE was 49.1 h (range 12
20 h). The data from the patient with PME of Lafora type were
excluded for this statistical analysis because of the exceptional
long duration in this case (86 days). Fifteen patients (46.9%) were
elderly (age P 65 years). Recurrence of NCSE occurred in 10 patients (31%).
3.1.1. Absence status epilepticus (ASE)
Fourteen patients were included in this category. All
characteristics of these patients are summarized in Table 1 and
Supplementary Table S1. There were seven men and seven women.
The mean age was 52.9 years (range 1979 years). All patients were
mentally normal except for two (Cases 6 and 14).
All patients except for one (Case 14) with typical or atypical ASE
had a previous diagnosis of epilepsy. No of subjects with situationrelated ASE had history of previous seizures. The mean duration of
ASE was 33.2 h (range 2472 h; SD, 13.9). There was recurrence in
ve patients (Cases 3, 6, 7, 8 and 11).
Neuroimaging was normal in seven patients and revealed diverse
abnormalities in other ve (Cases 1, 9, 12, 13 and 14). In two (Cases 6
and 10) neuroimaging was not performed (Table 1).
Ictal EEG features are summarized in Supplementary Table S1.
An example of characteristic EEG is shown in Fig. 1a. In eight patients (Cases 2, 3, 4, 5, 8, 9, 10 and 14) accounting for 57%, IVBZDs
were administrated during the EEG. In all of them, a signicant
diminution of EDs was observed, and in ve (Cases 4, 8, 9, 10
and 14) there was clinical improvement (Supplementary Table
S1). In one patient (Case 14), generalized EDs were only abolished

Fig. 1. (A) EEG of patient 10 (POO). Note the presence of continuous polyspikewave (PSW) and spike-wave complexes (SW) in keeping with the diagnosis of
typical ASE. LF: 0.53 Hz, HF: 70 Hz; NF: 50 Hz; sensitivity: 150 lV/cm; speed:
15 mm/s; (B) EEG of patient 14 (LRG). Several years before the episode of atypical
ASE a diagnosis of JME has been established. However, she nally developed
Progressive Myoclonus Epilepsy (PME) of Lafora type. Observe as a tactile stimulus
(black arrow) elicited a burst of epileptiform discharges (EDs) in keeping with the
denition of stimulus-induced rhythmic, periodic, ictal discharges (SIRPIDs). LF:
0.53 Hz, HF: 70 Hz; NF: 50 Hz; sensitivity: 100 lV/cm; speed: 30 mm/s.

during profound sedation with propofol (PPF) and thiopental


(THP). All AEDs used in these patients are given in Supplementary
Table S1.
3.1.2. Partial, focal or localization-related NCSE
There were 18 patients in this group. All patient characteristics
are shown in Table 1 and Supplementary Table S1. There were nine
men and nine women. The mean age was 58 years (range 20
89 years). Seventeen patients were categorized as CPSE and only
one (Case 15) was classied as SPSE. All patients were mentally
normal except for three subjects (Cases 15, 20 and 31). There
was a previous diagnosis of epilepsy in 12 patients (66%).The localization of the onset of NCSE is summarized in Table 1. In four patients, IVBZDs were administrated during the EEG recording. In
three of them (Cases 17, 28 and 32), EDs were completely abolished and in one (Case 20) the attenuation was solely transient.
3.1.2.1. Complex partial status epilepticus (CPSE). There were nine
women and eight men in this group. The mean age was 59 years
(range 2089 years). All these patients had signicant medical
antecedents such as epilepsy, alcoholism, CNS surgery, lupus erythematosus, dementia and cerebrovascular disease, valvular cardiac surgery and Parkinson disease.
In 11 individuals (Cases 16, 18, 19, 21, 22, 24, 25, 27, 29, 30 and
32) a cyclic variety of CPSE was identied (Williamson, 1997). Ictal
EEG features are summarized in Supplementary Table S1. In all
subjects with continuous CPSE, frank EDs consisting of spikes (S)
and spike-wave complexes (SW) were seen from the onset of
EEG recording. In four patients (Cases 17, 20, 28 and 32) IVBZDs
were administrated during the EEG, and in only one (Case 32)
was clinical improvement seen.

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J.L. Fernndez-Torre et al. / Clinical Neurophysiology 123 (2012) 244251

Table 2
Demographic, clinical antecedents, NCSE types and neuroimaging features in comatose NCSE.
Patients

Sex/age

Medical history

Precipitating factors

NCSE type

Neuroimaging

33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50

F/88
M/65
M/79
M/65
M/70
M/69
M/55
M/75
M/74
M/73
F/73
F/80
M/85
F/75
M/56
F/75
M/54
F/39

Hypertension
Lung tumor
Cardiopathy
Cardiopathy, OH
Hepatopathy, OH
Cardiopathy
Leukemia (CLL)
Aortic aneurysm
Hypertension, cardiopathy
Hypertension, CVD
Hypertension, cardiopathy
CVD, parkinsonism
CVD, leukoariosis
Hypertension, hepatopathy
Lung transplant
Hypertension, epilepsy
OH
None

ACVD
ACVD, GTCS
Anoxia
Anoxia
Subdural hematoma, GTCS
Anoxia
CNS infection
ACVD, PMS
Anoxia
ACVD
Subdural hematoma
GCSE
CNS infection, GTCS
Sepsis, hepatic failure
ACVD, PMS
ACVD
GCSE, alcohol deprivation
CNS infection

FSG
Focal
Generalized
Focal
Focal
Generalized
Generalized
Focal
FSG
Focal
Focal
Generalized
Generalized
Focal
Focal
FSG
Generalized
Generalized

CT: intraventricular hemorrhage


Infarct in territory both mid cerebral arteriesa
CT: normal
ND
CT: subdural hematoma
ND
CT: right hypodensity in basal ganglia; NLEa
Right parietal infarcta
ND
CT: left infarct in corona radiata
CT: bilateral subdural hematoma
CT: normal
CT: subcortical atrophy, cerebral infarcts
CT: normal
CT: bilateral occipital infarct
CT: left parieto-temporo-occipital hematoma
CT: congenital ventriculomegaly
CT: cerebral edema

ACG
CGC
EAM
EMP
JFG
JGL
JPJ
JRG
JRU
JSL
JTS
MGC
MGF
MRM
MTJ
PHE
SCR
YIS

ACVD: acute cerebrovascular disease; CNS: central nervous system; CLL: chronic lymphoid leukemia; CT: computerized tomography; CVD: cerebrovascular disease; FSG:
focal secondarily generalized; GCSE: generalized convulsive status epilepticus; GTCS: generalized tonicclonic seizures; ND: no done; NLE: necrotizing leukoencephalopathy;
OH: alcoholism; PMS: partial motor seizures.
a
Necropsy nding.

Neuroimaging was normal in only two subjects (Cases 22 and


31) (Table 1). In the majority of patients a combination of several
AEDs was used (Supplementary Table S1). This group was treated
with an average of 2.7 drugs (range 15; SD, 1.3). The mean duration of NCSE was 63.5 h (range 24120 h; SD, 32.7). Four patients
(Cases 16, 20, 22 and 29) were transferred to the ICU as consequence of refractory NCSE. In three patients (Cases 16, 22 and
29) anesthetic management of NCSE was needed.
Recurrence occurred in ve subjects (Cases 16, 20, 23, 24, and
31). In two patients follow-up data were unavailable. Two patients
died during the follow-up.

48, 49 and 50), abolition was only transient. None had signicant
changes in mental status.
The mean duration of NCSE was 153.3 h (range 24480 h; SD,
142.6). Antiepileptic treatment was varied, and patients were treated with an average of 2.7 drugs (range 16; SD, 1.3). The association between etiology and type of comatose NCSE, and number of
AEDs and etiology may be found in Supplementary Fig. S1.
Eleven patients (61%) died and seven (39%) survived to hospital
discharge. Of these seven patients, two had a favorable outcome.
However, ve out seven (Cases 33, 41, 43, 47 and 48) had signicant sequelae. None of the patients in this group had recurrence
on follow-up.

3.2. Comatose NCSE

3.3. Statistical analysis

The clinical, neurophysiologic and neuroimaging characteristics


of the 18 patients with comatose NCSE are summarized in Table 2
and Supplementary Table S2. There were 12 men (66%) and six women (34%). The mean age was 69.4 years (range 3988 years). All
of them were neurologically and intellectually normal. Fourteen
patients (78%) were elderly. Fifteen subjects (83%) were diagnosed
in the ICU.
In all subjects, the request for an EEG was made because of signicant alteration in consciousness. Only one patient (5%) had a
previous history of epilepsy.
Eight patients (44%) had partial, focal or lateralized comatose
NCSE, seven (39%) had generalized comatose NCSE and three
(17%) had a FSG comatose NCSE. In six patients (34%), the cause
or precipitating factor was acute cerebrovascular disease (ACVD),
four (22%) had cerebral anoxia, three had a central nervous system
infection (17%), two (11%) had subdural hematoma, two (11%) had
SGCSE and one (5%) was diagnosed with sepsis (Table 2). In ve patients (Cases 34, 37, 44, 45 and 49), one or several GTCSs preceded
or were associated with the symptoms, and in two (Cases 40 and
47) motor partial seizures occurred. Multiple medical problems
were frequent and are summarized in Table 2.
Neuroimaging was normal in only three patients (Cases 35, 44
and 46) (Table 2). All ictal EEG features, duration of the episode,
treatment and outcome are summarized in Supplementary
Table S2.
In six patients (Cases 35, 41, 44, 48, 49 and 50), IVBZDs were
administrated during the EEG recording. In three (Cases 35, 41
and 44), EDs were completely abolished and in other three (Cases

The mean episode duration (33.2 13.9 versus 60.6 34.0),


mean number of AEDs (1.46 0.5 versus 2.77 1.39) and neuroimaging anomalies (50% versus 16%) were signicantly greater in the
partial/focal NCSE proper subgroup than in the ASE subgroup
(Supplementary Table S3). There was a statistically increased tendency to administer IVBZDs during the EEG (57% versus 22%) in the
ASE subgroup. When we compared our patients according to the
clinical scenario (NCSE proper versus comatose NCSE), the mean
age (56.0 19.9 versus 69.4 12.1), number of elderly individuals
(46% versus 77%), mean duration of the episode (49.1 30.4 versus
153.3 142.6), mortality rate (6% versus 61%) and admission to the
ICU (18% versus 83%) was signicantly higher in the comatose NCSE
group than in the NCSE proper group (p < .05) (Supplementary Table
S4). Conversely, a previous history of chronic epilepsy (62% versus
5.6%) was signicantly more frequent in the NCSE proper group.
Unfortunately, multivariate analysis was not applied. When we
analyzed patients with comatose NCSE, we observed that the mean
duration was signicantly greater in the surviving subgroup
(102.5 29.1 versus 233.1 65.3; p < .05) (Supplementary Table
S5).
4. Discussion
This investigation offers the unusual possibility of comparing 50
patients with ambulatory and comatose forms of NCSE in a homogeneous diagnostic, therapeutic and follow-up setting. There are
few studies including more than 50 patients collected consecu-

J.L. Fernndez-Torre et al. / Clinical Neurophysiology 123 (2012) 244251

tively (Shneker and Fountain, 2003). Most studies of NCSE have


analyzed the two principal categories independently. Thus, while
some authors have focused their attention on ambulatory forms
of NCSE (Andermann and Robb, 1972; Guberman et al., 1986; Tomson et al., 1986, 1992; Ballenger et al., 1983; Scholtes et al., 1996;
Kaplan 1996; Agathonikou et al., 1998), others have concentrated
their efforts in comatose and critically ill individuals (Young
et al., 1996; Litt et al., 1998; Towne et al., 2000; Pandian et al.,
2004; Narayanan and Murthy, 2007; Drislane et al., 2008; Alroughani et al., 2009).
In general in the ASE group, clinical presentation, mean duration, existence of recurrence, and precipitating factors were similar to those described in previous series (Andermann and Robb,
1972; Guberman et al., 1986; Scholtes et al., 1996; Agathonikou
et al., 1998). The patient 14 (YRG) was initially misdiagnosed as
JME. This problem is not rare in patients with GTCSs and myoclonus (Striano et al., 2008). The patient experienced an exceptionally prolonged episode of refractory atypical ASE that proved
fatal. Indeed, she died as consequence of bowel ischemia which
has recently been described as a complication of prolonged treatment with THP (Cereda et al., 2009). NCSE is a rare complication
in Laforas disease (Corkill and Hardie, 1999; Lpez-Mesa et al.,
2003). We believe this to be the rst report of refractory atypical
ASE in a subject with PME of Lafora type in which stimulus-induced rhythmic, periodic, ictal discharges (SIRPIDs) have been described (Fig. 1b).
In all patients with typical and atypical subtypes, generalized
polyspike-wave complexes (PSW) and SW ranging from 2 to 6 Hz
were observed. However, in the group of situation-related ASE
there was a predominance of sharp-slow wave complexes (SSW)
and biphasic sharp waves (Sws) at 22.5 Hz.
In our study, the patients with de novo ASE induced by nonpsychotropic drugs had severe concomitant disorders such as leukemia, lymphoma, renal failure, cancer and infection. In three cases,
situation-related ASE was triggered by intravenous cefepime.
Therefore, these episodes of ASE occurred in different clinical scenarios from those classically seen with de novo ASE of late onset
(Thomas et al., 1992, 1993, 2006; Thomas and Andermann, 1994;
Koutroumanidis, 2009).
Seventeen out of 50 patients (34%) were diagnosed with CPSE. If
we consider only the ambulatory group, this number reached 53%,
slightly more than ASE rate (44%). Although traditionally ASE has
been considered more frequent than CPSE, our results replicate
the ndings also obtained by others authors (Scholtes et al.,
1996; Camacho et al., 2001) supporting the observations reported
by Tomsons group (Tomson et al., 1986, 1992) who emphasized
the high prevalence of this partial type of NCSE.
NCSE may occur following GTCSs or controlled convulsive status epilepticus (SE) (Bauer et al., 1982; Fagan and Lee, 1990;
eLorenzo et al., 1998). In 10 of our patients one or several GTCSs
preceded the episode of CPSE. None of our 10 patients was comatose. It is important to emphasize that an excessively long postictal
period following a GTCS may occur in either ASE or CPSE. This issue
has been recently reviewed (Shorvon and Trinka, 2010). ASE can
generally be detected from the onset of the EEG recording. With
cyclic CPSE it is important to remember that it may be necessary
to extend the recording duration so as to increase the change of
capturing a partial seizure.
Three out four CPSE subjects in whom IVBZDs were administered during the EEG had a continuous type of CPSE. The administration of IVBZDs is considered important in making a denitive
diagnosis of NCSE (Kaplan, 1999); however, this diagnostic approach seems to play a more important role in those patients with
CPSE showing continuous EDs. Thus, the demonstration of recurrent partial seizures may be sufcient to reach a diagnosis in the
cyclic variant of CPSE.

249

In our study, antiepileptic treatment was highly variable. This


therapeutic diversity agrees with the conclusions of a recent investigation on the management of refractory SE, which included CPSE
(Holtkamp et al., 2003).
NCSE in comatose subjects is often unsuspected and difcult to
diagnose (Drislane et al., 2008). The most frequent cause of comatose NCSE in our series was an ACVD (34%). Similar results have
been published by other authors (Jaitly et al., 1997; Drislane
et al., 2008). Both ACVD and anoxia were the two more frequent
causes in the present investigation. Some authors avoid including
anoxic causes of comatose NCSE. However, most cases of comatose
NCSE are acute symptomatic with underlying acute brain disorders
and, an additive negative impact of ongoing EDs to the underlying
lesion cannot be excluded (Waterhouse et al., 1998; Bauer and
Trinka, 2010).
Mortality rate (61%) was notably higher than in the NCSE proper
group (6%), which was statistically signicant. This result was expected because the gravity of etiology in these patients. Others
authors have obtained similar numbers (Young et al., 1996; Litt
et al., 1998; Towne et al., 2000; Drislane et al., 2008). SE outcome
is mainly determined by etiology and age (Towne et al., 1994;
Logroscino et al., 2002; Rossetti et al., 2006). It is therefore not surprising that patients with diagnosis of comatose NCSE have a dismal
prognosis. Interestingly, a recent investigation on duration of
refractory SE and outcome, suggested that the prognostic effect
of duration was strongly inuenced by etiology (Drislane et al.,
2009). In a previous similar study, Litt et al. (1998) did not found
differences in mortality relative to the mean number of hours from
diagnosis to control of SE. However, severity of illness was also the
major determinant of poor outcome.
A previous history of chronic epilepsy was observed in only one
patient (5%). The difference was statistically signicant in comparison with the NCSE proper group. Therefore, it seems that comatose
NCSE occurs in individuals with acute symptomatic cerebral
pathology or exacerbation of a chronic pre-existing neurologic process that only in a small percentage includes epilepsy.
The mean duration of comatose NCSE was signicantly longer in
the surviving subgroup (102.5 29.1 versus 233.1 65.3; p < .05).
This result is not surprising since dead patients may have an abbreviated stay. Moreover, a prolonged in-hospital stay (P10 days) in
three survivors contributed to this result. One of these patients
with cryptogenic encephalitis (Case 50) fullled criteria in keeping
with a malignant variant of SE (Holtkamp et al., 2005) (Fig. 2). After
2-year-follow-up the neurological examination is unremarkable,
and her EEG is completely normalized. We conclude that

Fig. 2. EEG of patient 50 (YIS). Note the presence of continuous epileptiform


discharges (EDs) consistent of rhythmic sharp waves (Sws) and sharp-slow wave
complexes (SSW) at 2.53 Hz in keeping with the diagnosis of generalized comatose
NCSE. Neurologic examination and an EEG obtained several months after hospital
discharge were completely normalized. LF: 0.53 Hz; HF: 70 Hz; NF: 50 Hz;
sensitivity: 100 lV/cm, speed: 15 mm/s.

250

J.L. Fernndez-Torre et al. / Clinical Neurophysiology 123 (2012) 244251

exceptionally prolonged episodes of NCSE should not be regarded


as hopeless in terms of successful clinical recovery (Cooper et al.,
2009; Drislane et al., 2009; Fernndez-Torre, 2010; Nagayama
et al., 2005; Robakis and Hirsch, 2006).
Ictal generalized EEG patterns (generalized and FSG) were more
frequent. We did not nd as others have, association between generalized patterns and mortality rate (Litt et al., 1998). Among treated, nonanoxic patients Drislane et al. (2008), found that the
patients with evidence of focal onset in their seizures responded
better to AEDs that did those with generalized EDs. However, the
authors attributed it to the different etiologies. Similarly Shneker
and Fountain (2003) analyzed 100 patients with NCSE and they
did not observe any association between EEG pattern and mortality. Antiepileptic treatment was heterogeneous, and the mean
number of AEDs employed (2.7) was identical to the study by Litt
and colleagues (1998). Interestingly, several of the unequivocal
cases of generalized and FSG comatose NCSE reported here had a
frequency of EDs < 3 Hz (Supplementary Table S2 and Fig. S2), in
contrast to the EEG criteria proposed by Chong and Hirsch (2005)
that required the second criterion (clinical improvement or
appearance of normal EEG) when EDs occurred at frequency
<3 Hz. Therefore, our ndings suggest that we do not have to be
excessively dogmatic in the interpretation of determined EEG patterns, and that an accurate electroclinical correlation and EEG
monitoring are the clue to reach a denitive diagnosis.
In conclusion, our study demonstrates that there are sufcient
differences regarding age of onset, history of previous epilepsy,
episode duration, mortality rate and clinical presentation between
NCSE proper and comatose NCSE to recommend adoption in clinical
practice. These results should be taken into account when developing future classications and therapeutic trials on NCSE.
Conict of interest
None of the authors has any conict of interest to disclose.
Acknowledgments
Dr. Fernndez-Torre is indebted with Professor Peter W. Kaplan
(Baltimore, USA) by his kind revision of the manuscript and invaluable comments and suggestions. Dr. Fernndez-Torre would like to
thank all staff of the Department of Clinical Neurophysiology of
Marqus de Valdecilla University Hospital (Santander) and Cabuees Hospital (Gijn) for your collaboration in the evaluation of
some of the patients included in this study.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.clinph.2011.06.020.
References
Agathonikou A, Panayiotopoulos CP, Giannakodimos S, Koutroumanidis M. Typical
absence status in adults: diagnostic and syndromic considerations. Epilepsia
1998;39:126576.
Alroughani R, Javidan M, Qasem A, Alotaibi N. Non-convulsive status epilepticus;
the rate of occurrence in a general hospital. Seizure 2009;18:3842.
Andermann F, Robb JP. Absence status. A reappraisal following review of thirtyeight patients. Epilepsia 1972;13:17787.
Ballenger CE, King DW, Gallagher BB. Partial complex status epilepticus. Neurology
1983;33:154552.
Bauer G, Aichner F, Mayr U. Nonconvulsive status epilepticus following generalized
tonic-clonic seizures. Eur Neurol 1982;21:4119.
Bauer G, Trinka E. Nonconvulsive status epilepticus and coma. Epilepsia
2010;51:17790.
Brenner RP. Is it status? Epilepsia 2002;43(Suppl. 3):10313.
Brenner RP. EEG in convulsive and nonconvulsive status epilepticus. J Clin
Neurophysiol 2004;21:31931.

Camacho A, Prez-Martnez D, Villarejo A, Parrilla G, Floriach-Robert M, de la Pea


P, et al. Status epilepticus no convulsivo: experiencia en 33 pacientes.
Neurologa 2001;16:3948.
Celesia GC, Grigg MM, Ross E. Generalized status myoclonicus in acute anoxic and
toxic-metabolic encephalopathies. Arch Neurol 1988;45:7814.
Cereda C, Berger MM, Rossetti AO. Bowel ischemia: a rare complication of
thiopental treatment for status epilepticus. Neurocrit Care 2009;10:3558.
Chong DJ, Hirsch LJ. Which EEG patterns warrant treatment in the critically ill?
Reviewing the evidence for treatment of periodic epileptiform discharges and
related patterns. J Clin Neurophysiol 2005;22:7991.
Cooper AD, Britton JW, Rabinstein AA. Functional and cognitive outcome in
prolonged refractory status epilepticus. Arch Neurol 2009;66:15059.
Corkill RG, Hardie RJ. An unusual case of Lafora body disease. Eur J Neurol
1999;6:24571.
DeLorenzo RJ, Waterhouse EJ, Towne AR, Boggs JG, Ko D, DeLorenzo GA, et al.
Persistent nonconvulsive status epilepticus after the control of convulsive
status epilepticus. Epilepsia 1998;39:83340.
Drislane FW, Schomer DL. Clinical implications of generalized electrographic status
epilepticus. Epilepsy Res 1994;19:11121.
Drislane FW. Presentation, evaluation, and treatment of nonconvulsive status
epilepticus. Epilepsy Behav 2000;1:30114.
Drislane FW, Lopez MR, Blum AS, Schomer DL. Detection and treatment of
refractory status epilepticus in the intensive care unit. J Clin Neurophysiol
2008;25:1816.
Drislane FW, Blum AS, Lopez MR, Gautam S, Schomer DL. Duration of refractory
status epilepticus and outcome: loss of prognostic utility after several hours.
Epilepsia 2009;50:156671.
Fagan KJ, Lee SI. Prolonged confusion following convulsions due to generalized
nonconvulsive status epilepticus. Neurology 1990;40:168994.
Fernndez-Torre JL. De novo absence status of late onset following withdrawal of
lorazepam: a case report. Seizure 2001;10:4337.
Fernndez-Torre JL. Clinical and electroencephalographic characteristics of
nonconvulsive status epilepticus in adults. Doctoral thesis. Spain: University
of Cantabria; 2009.
Fernndez-Torre JL. Prognostic utility of duration in refractory nonconvulsive status
epilepticus. Epilepsia 2010;51:319.
Fernndez-Torre JL, Daz-Castroverde A-G. Non-convulsive status epilepticus in
elderly individuals: report of four representative cases. Age Ageing
2004;33:7881.
Fernndez-Torre JL, Martnez-Martnez M. Nonconvulsive status epilepticus as an
unrecognised cause of acute confusion in alcoholics. Eur J Neurol
2007;14:e145.
Fernndez-Torre JL, Leno C. Simple partial frontal status epilepticus with recurrent
asymmetric tonic seizures. Neurology 2008;70:e301.
Fernndez-Torre JL, Rebollo M. Typical absence status epilepticus as late
presentation of idiopathic generalised epilepsy in an elderly patient. Seizure
2009;18:823.
Fernndez-Torre JL, Agirre-Arrizubieta Z, Casariego Pola F, Gonzlez-Mandly A. SESA
syndrome: a subtype of localisation-related non-convulsive status epilepticus.
Seizure 2009;18:3067.
Fernndez-Torre JL, Agirre Z, Martnez-Martnez M, Rodrguez E. Subacute
encephalopathy with seizures (SESA syndrome) in alcoholics: report of an
unusual case. Clin EEG Neurosci 2006a;37:2158.
Fernndez-Torre JL, Agirre Z, Puchades R, Marco de Lucas E, Oterino A. Nonconvulsive
status epilepticus causing prolonged stupor after intraventricular hemorrhage:
report of a case. Clin EEG Neurosci 2007;38:5760.
Fernndez-Torre JL, Arce F, Martnez-Martnez M, Gonzlez-Rato J, Infante J, Calleja
J. Necrotizing leukoencephalopathy associated with nonconvulsive status
epilepticus
and
periodic
short-interval
diffuse
discharges:
a
clinicopathological study. Clin EEG Neurosci 2006b;37:503.
Fernndez-Torre JL, Figols J, Martnez-Martnez M, Gonzlez-Rato J, Calleja J.
Localisation-related nonconvulsive status epilepticus. Further evidence of
permanent cerebral damage. J Neurol 2006c;253:3925.
Fernndez-Torre JL, Gonzlez C, Snchez JM. Estado epilptico no convulsivo de
origen frontal. Presentacin de un caso. Rev Neurol 2000;30:10404.
Fernndez-Torre JL, Gutirrez-Prez R, Velasco-Zarzosa M. Estado epilptico no
convulsivo. Rev Neurol 2003a;37:74452.
Fernndez-Torre JL, Hernndez-Hernndez JL, Jimnez-Bonilla J, Gonzlez-Mandly
A. Complex partial status epilepticus is an unrecognised feature in SESA
syndrome: new insights on its pathophysiology. Epileptic Disord 2007;9:1349.
Fernndez-Torre JL, Martnez-Martnez M, Gonzlez-Rato J, Maestro I, Alonso I,
Rodrigo E, et al. Cephalosporin-induced nonconvulsive status epilepticus:
clinical and electroencephalographic features. Epilepsia 2005;46:15502.
Fernndez-Torre JL, Snchez JM, Gonzlez C, Fernndez-Guinea O. Complex partial
status epilepticus of extratemporal origin in a patient with systemic lupus
erythematosus. Seizure 2003b;12:2458.
Fernndez-Torre JL, Solar DM, Astudillo A, Cereceda R, Acebes A, Calatayud MT.
CreutzfeldtJakob disease and nonconvulsive status epilepticus: a clinical and
electroencephalographic follow-up study. Clin Neurophysiol 2004;115:3169.
Fujikawa DG. The two faces of electrographic status epilepticus: the waking
wounded and the ictally comatose. In: Wasterlain CG, Treiman DM, editors.
Status epilepticus. Mechanisms and management. London: The MIT Press;
2006. p. 10912.
Guberman A, Cantu-Reyna G, Stuss D, Broughton R. Nonconvulsive generalized
status epilepticus: clinical features, neuropsychological testing, and long-term
follow-up. Neurology 1986;36:128491.

J.L. Fernndez-Torre et al. / Clinical Neurophysiology 123 (2012) 244251


Holtkamp M, Masuhr F, Harms L, Einhupl KM, Meierkord H, Buchheim K. The
management of refractory generalised convulsive and complex partial status
epilepticus in three European countries: a survey among epileptologists and
critical care neurologists. J Neurol Neurosurg Psychiatry 2003;74:10959.
Holtkamp M, Othman J, Buchheim K, Masuhr F, Schielke E, Meierkord H. A
malignant variant of status epilepticus. Arch Neurol 2005;62:142831.
Jaitly R, Sgro JA, Towne AR, Daijin K, DeLorenzo RJ. Pronostic value of EEG
monitoring after status epilepticus: a prospective adult study. J Clin
Neurophysiol 1997;14:32634.
Kaplan PW. Nonconvulsive status epilepticus in the emergency room. Epilepsia
1996;37:64350.
Kaplan PW. Assessing the outcomes in patients with nonconvulsive status
epilepticus: nonconvulsive status epilepticus is underdiagnosed, potentially
overtreated, and confounded by comorbidity. J Clin Neurophysiol
1999;16:34152.
Kaplan PW. Prognosis in nonconvulsive status epilepticus. Epileptic Disord
2000;2:18593.
Kaplan PW. Behavioral manifestations of nonconvulsive status epilepticus. Epilepsy
Behav 2002;3:12239.
Kaplan PW. Nonconvulsive status epilepticus. Neurology 2003;61:10356.
Kaplan PW. The clinical features, diagnosis, and prognosis of nonconvulsive status
epilepticus. Neurologist 2005;11:34861.
Koutroumanidis M. Absence status epilepticus. In: Kaplan PW, Drislane FW, editors.
Nonconvulsive status epilepticus. New York: Demos Medical Publishing; 2009.
p. 14566.
Krumholz A, Stern BJ, Weiss HD. Outcome from coma after cardiopulmonary
resuscitation: relation to seizures and myoclonus. Neurology 1988;38:4015.
Logroscino G, Hesdorffer DC, Cascino GD, Annegers JF, Bagiella E, Hauser WA. Longterm mortality after a rst episode of status epilepticus. Neurology
2002;58:53741.
Lpez-Mesa EG, Cerda-Tllez F, Alanis-Guevara IM, Fernndez Gonzlez-Aragn MC,
Ruano-Caldern MA. Estado epilptico no convulsivo asociado a Enfermedad de
Lafora: presentacin de dos casos. Rev Neurol 2003;37:9457.
Lowenstein DH, Aminoff MJ. Clinical and EEG features of status epilepticus in
comatose patients. Neurology 1992;42:1004.
Litt B, Wityk RJ, Hertz SH, Mullen PD, Weiss H, Ryan DD, et al. Nonconvulsive status
epilepticus in the critically ill elderly. Epilepsia 1998;39:1194202.
Maganti R, Gerber P, Drees C, Chung S. Nonconvulsive status epilepticus. Epilepsy
Behav 2008;12:57286.
Meierkord H, Holtkamp M. Non-convulsive status epilepticus in adults: clinical
forms and treatment. Lancet Neurol 2007;26:32939.
Nagayama M, Matsushima K, Nagayama T, Shinohara Y. Persistent but reversible
coma in encephalitis. Neurocrit Care 2005;2:2527.
Narayanan JT, Murthy JMK. Nonconvulsive status epilepticus in a neurological
intensive care unit: prole in a developing country. Epilepsia 2007;48:9006.
Pandian JD, Cascino GD, So EL, Manno E, Fulgham JR. Digital videoelectroencephalographic monitoring in the neurologicalneurosurgical intensive
care unit. Clinical features and outcome. Arch Neurol 2004;61:10904.
Privitera M, Hoffman M, Moore JL, Jester D. EEG detection of nontonicclonic status
epilepticus in patients with altered consciousness. Epilepsy Res
1994;18:15566.
Robakis TK, Hirsch LJ. Literature review, case report, and expert discussion of
prolonged refractory status epilepticus. Neurocrit Care 2006;4:3546.
Rossetti AO, Hurwitz S, Logroscino G, Bromeld EB. Prognosis of status epilepticus:
role of aetiology, age, and consciousness impairment at presentation. J Neurol
Neurosurg Psychiatry 2006;77:6115.

251

Scholtes FB, Renier WO, Meinardi H. Non-convulsive status epilepticus: causes,


treatment, and outcome in 65 patients. J Neurol Neurosurg Psychiatry
1996;61:935.
Shorvon S, Trinka E. Nonconvulsive status epilepticus and the postictal state.
Epilepsy Behav 2010;19:1725.
Shneker BF, Fountain NB. Assessment of acute morbidity and mortality in
nonconvulsive status epilepticus. Neurology 2003;61:106673.
Simon RP, Aminoff MJ. Electrographic status epilepticus in fatal anoxic coma. Ann
Neurol 1986;20:3515.
Striano P, Zara F, Turnbull J, Girard JM, Ackerley CA, Cervasio M, et al. Typical
progression of myoclonic epilepsy of the Lafora type: a case report. Nat Clin
Pract Neurol 2008;4:10611.
Thomas P, Andermann F. Late-onset absence status epilepticus is most often
situation-related. In: Malafosse A, Genton P, Hirsch E, Marescaux C, Broglin D,
Bernasconi R, editors. Idiopathic generalized epilepsies. London: John Libbey
and Company Ltd.; 1994. p. 95109.
Thomas P, Beaumanoir A, Genton P, Dolisi C, Chatel M. De novo absence status of
late onset: report of 11 cases. Neurology 1992;42:10410.
Thomas P, Lebrun C, Chatel M. De novo absence status as a benzodiazepine
withdrawal syndrome. Epilepsia 1993;34:3558.
Thomas P, Zifkin B, Andermann F. Absence status. In: Wasterlain CG, Treiman DM,
editors. Status epilepticus. Mechanisms and management. London: The MIT
Press; 2006. p. 91108.
Tomson T, Lindbom U, Nilsson BY. Nonconvulsive status epilepticus in adults:
thirty-two consecutive patients from a general hospital population. Epilepsia
1992;33:82935.
Tomson T, Svanborg E, Wedlund J-E. Nonconvulsive status epilepticus: high
incidence of complex partial status. Epilepsia 1986;27:27685.
Towne AR, Pellock JM, Ko D, DeLorenzo RJ. Determinants of mortality in status
epilepticus. Epilepsia 1994;35:2734.
Towne AR, Waterhouse EJ, Boggs JG, Garnett LK, Brown AJ, Smith Jr JR, et al.
Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology
2000;54:3405.
Treiman DM, DeGiorgio CM, Salisbury S, Wickboldt C. Subtle generalized status
epilepticus. Epilepsia 1984;25:653.
Treiman DM, Walton NY, Kendrick C. A progressive sequence of
electroencephalographic changes during generalized convulsive status
epilepticus. Epilepsy Res 1990;5:4960.
Treiman DM. Generalized status epilepticus in the adult. Epilepsia 1993;34(Suppl.
1):S2S11.
Treiman DM. Electroclinical features of status epilepticus. J Clin Neurophysiol
1995;12:34362.
Walker MC. Diagnosis and treatment of nonconvulsive status epilepticus. CNS
Drugs 2001;15:9319.
Waterhouse EJ, Vaughan JK, Barnes TY, Boggs JG, Towne AR, Kopec-Garnett L, et al.
Synergistic effect of status epilepticus and ischemic brain injury on mortality.
Epilepsy Res 1998;29:17583.
Williamson PD. Complex partial status epilepticus. In: Engel Jr J, Pedley TA, editors.
Epilepsy: a comprehensive textbook. Philadelphia: Lippincott-Raven
Publishers; 1997. p. 68199.
Young GB, Gilbert JJ, Zochodne DW. The signicance of myoclonic status epilepticus
in postanoxic coma. Neurology 1990;40:18438.
Young GB, Jordan KG, Doig GS. An assessment of nonconvulsive seizures in the
intensive care unit using continuous EEG monitoring: an investigation of
variables associated with mortality. Neurology 1996;47:839.