j.1528-1167.2012.03622.x

7/27/2019 j.1528-1167.2012.03622.x

http://slidepdf.com/reader/full/j1528-1167201203622x 1/12

Causes of status epilepticusEugen Trinka, Julia Hofler, and Alexander Zerbs

Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University Salzburg, Salzburg, Austria

SUMMARY

Status epilepticus (SE) is the most extreme form

of epilepsy. It describes a prolonged seizure that

may occur in patients with previous epilepsy or in

acute disorders of the central nervous system. It is

one of the most common neurologic emergencies,

with an incidence of up to 41 per 100,000 per year

and an estimated mortality is 20%. The three

major determinants of prognosis are the duration

of SE, patient age, and the underlying cause. Com-

mon and easily recognized causes of SE include

cerebrovascular disorders, brain trauma, infec-

tions, and low antiepileptic drug levels in patients

with epilepsy. Less common causes present a clini-

cal and diagnostic challenge, but are major deter-

minants of prognosis. Among them, inflammatory

causes and inborn errors of metabolism have

gained wide interest; recent insights into these

causes have contributed to a better understanding

of the pathophysiology of SE and its appropriate

treatment. This review focuses on the different

etiologies of SE and emphasizes the importance of

prompt recognition and treatment of the underly-

ing causes.

KEY WORDS: Status epilepticus – etiology, Treat-

ment, Prognosis.

Status epilepticus (SE) is a term used to describe a pro-

longed and self-sustaining seizure that may have overt,

subtle, or almost no behavioral manifestations. It may beregarded as the most extreme form of epilepsy, or as an

expression of an acute and often life-threatening brain dis-

order, such as stroke, encephalitis, or trauma. Mortality

associated with SE is up to 20% (Shorvon, 1994; Logroscino

et al., 1997, 2005). Less than 50% of people in SE have

had previous seizures or epilepsy (DeLorenzo et al., 1996;

Hesdorffer et al., 1998; Coeytaux et al., 2000; Knake

et al., 2001; Vignatelli et al., 2003). SE is one of the most

common neurologic emergency, with an overall annual

incidence of 10–41 per 100,000 (DeLorenzo et al., 1996;


et al., 2001; Vignatelli et al., 2003). Up to 287,000 patients

per year are affected in Europe. Not all forms of status are

life-threatening and, given the variety of its clinical pre-

sentations, the management must be tailored according to

the type of SE and the underlying cause. Three major

factors determine an increased risk of mortality and mor-

bidity associated with SE: (1) certain etiologies, (2) age

>60 years, and (3) long duration of SE (Towne et al.,

1994; DeLorenzo et al., 1996; Wu et al., 2002; Rossetti

et al., 2006). This review focuses on the various causes of SE, since etiology is increasingly recognized as one of the

most important factors for prognosis and outcome. There-

fore, identifying and treating the underlying cause of SE is

at least as important as prompt and effective treatment

with early termination of seizures.

Definition andClassification

of Status Epilepticus

Status epilepticus (SE) has been recognized for centu-

ries (Shorvon, 1994; Wolf et al., 2009). Henri Gastaut

(1970) recognized SE as a prolonged seizure with as manyforms as there were types of epileptic seizures. Therefore,

SE classification mirrored exactly the seizure classifica-

tion. In the International League against Epilepsy (ILAE)

1981 Classification, SE was defined as ‘‘a seizure that per-

sists for a sufficient length of time, or repeated frequently

enough that recovery between attacks do [does] not

occur’’ (Commission on Classification, ILAE, 1981).

Generalized tonic–clonic seizures usually do not last

longer than 2–3 min (Theodore et al., 1994); the risk of a

seizure becoming self-sustaining increases as the duration

reaches 5 min or more (Lowenstein et al., 1999). For the

purpose of this review, we use a clinical classification

Address correspondence to Eugen Trinka, Department of Neurology,Christian Doppler Klinik, Paracelsus Medical University, Ignaz HarrerStraße 79, 5020 Salzburg, Austria. E-mail: [email protected]

Wiley Periodicals, Inc.ª 2012 International League Against Epilepsy

Epilepsia, 53(Suppl. 4):127–138, 2012

doi: 10.1111/j.1528-1167.2012.03622.x

SEIZURES IN SPECIAL AND SEVERE SITUATIONS

127

7/27/2019 j.1528-1167.2012.03622.x


along two taxonomic criteria: the presence (or absence) of

motor symptoms and the impairment (or retention) of con-

sciousness. Therefore, one can distinguish (A) SE types

with prominent motor symptoms, such as convulsive SE,

and (B) SE types without prominent motor symptoms,

summarized as nonconvulsive SE (NCSE). NCSE canoccur with or without coma; this has important etiologic

implications and determines its treatment. A third cate-

gory (C) comprises the boundary syndromes, including

epileptic encephalopathies and acute forms of coma with

status-like electroencephalography (EEG) patterns.

Table 1 briefly outlines this tentative classification. For a

more detailed discussion of SE classification, refer to:

(Shorvon, 1994; Walker et al., 2005; Bauer & Trinka,

2006, 2009; Berg et al., 2010). However, the definitions

and classifications are in flux and an ILAE Task force is

currently developing a new draft classification of SE, fol-

lowing the concepts of the ILAE’s new classification pro-posal of seizures and syndromes (Berg et al., 2010).

Causes of Convulsive Status

Epilepticus in Adults

Most population-based studies have used a traditional

30-min duration of SE, and so the numbers given are the

lowest estimates. Using the 5-min definition, determining

the time from onset to starting emergency treatment, the

incidence in clinical practice is much higher than in the

epidemiologic studies. Convulsive SE comprises 37–70%

of all forms of status, and its annual incidence is up to 40

per 100,000 (Waterhouse, 2008). In adults with preexist-

ing epilepsy, the most common etiologies are low antiepi-

leptic drug (AED) levels (accounting for at least one

fourth of SE [Fig. 1]), remote symptomatic etiologies, and

stroke (DeLorenzo et al., 1995, 1996). This subgroup with

epilepsy and low AED levels has a good prognosis, with a

low mortality of 4.0–8.6% (Towne et al., 1994; DeLorenzo

et al., 1995). Overall, acute symptomatic causes are the

most common etiology, accounting for 48–63% of all SE

cases (Hesdorffer et al., 1998; Coeytaux et al., 2000;

Knake et al., 2001). Stroke is the leading cause among theacute symptomatic cases, accounting for 14–22% of SE in

adults (DeLorenzo et al., 1995; Knake et al., 2001). In

older adults, remote stroke is a major cause. Knake et al.

(2001) found that remote stroke caused 36% of SE in

patients older than 56 years. In the Richmond Virginia

Status Epilepticus Study, 41% of adults and 61% of the

elderly had acute or remote ischemic and hemorrhagic

strokes as cause of status (DeLorenzo et al., 1995).

In the context of epilepsy, SE may develop in those with

a previous diagnosis of epilepsy or de novo, as its initial

manifestation. Approximately 15% of patients with epi-

lepsy have had at least one episode of status during theirlifetime. Most often, the SE is due to the epilepsy itself,

triggered by medication nonadherence, resulting in sub-

therapeutic AED levels (Aminoff & Simon, 1980) or by

inappropriate drug treatment (Thomas et al., 2006a,b).

The clinical features of SE in these patients depend on the

underlying epilepsy syndrome. In the context of idiopathic

generalized epilepsy, status is most often nonconvulsive

(Shorvon & Walker, 2005); in the context of juvenile

myoclonic epilepsy it may be myoclonic (Thomas et al.,

2006a,b; Larch et al., 2009). Myoclonic status may also

develop in progressive myoclonic epilepsy, Lennox-

Gastaut syndrome, or epilepsy with myoclonic absences.

Table 1. Proposed classification of seizure

types according to their semiology, along two

taxonomic criteria: motor symptoms and

impairment of consciousness

With prominent motor symptoms

Convulsive SE (syn.: tonic–clonic SE)

Myoclonic SE (prominent epileptic myoclonic jerks)

Focal motor (including EPC )

Tonic SE

Hyperkinetic SE

Without prominent motor symptoms (i.e., NCSE)

NCSE with coma

NCSE without coma

Generalized

Focal

Boundary syndromes

Epileptic encephalopathy

Acute forms of coma with status-like EEG pattern

Epileptic behavioral disturbance and psychosis

Confusional states, or delirium with epileptiform EEG changes

Figure 1.

Etiology of status epilepticus in adults, with associatedmortality for each category. Based on data from

DeLorenzo et al., 1995. AED, antiepileptic drugs; CNS,central nervous system.Epilepsia ILAE

Epilepsia, 53(Suppl. 4):127–138, 2012doi: 10.1111/j.1528-1167.2012.03622.x

128

E. Trinka et al.

7/27/2019 j.1528-1167.2012.03622.x


However, the precise incidence of convulsive status or

myoclonic status in these syndromes is not known.

Approximately 12% of patients who eventually develop

epilepsy have presented with SE as their first clinical man-

ifestation (Hauser, 1990; Hesdorffer et al., 1998). In these

patients, SE may be an intrinsic manifestation of disease,sometimes with recurrent episodes, or the epilepsy may be

the consequence of a prolonged SE, with neuronal death

and alteration of networks causing recurrent seizures after

the initial event. During a 10-year follow-up, epilepsy

developed in 42% of patients who had acute symptomatic

SE and in 14% of patients who had acute symptomatic

seizures (Hesdorffer et al., 1998). The development of

subsequent epilepsy is more likely if the status is refrac-

tory to treatment (Holtkamp et al., 2005), supporting the

hypothesis that SE contributes to epileptogenesis by

enhancing hyperexcitable networks.

Nonconvulsive Status

Epilepticus

NCSE may be defined as ‘‘an enduring epileptic condi-

tion with reduced or altered consciousness, behavioral and

vegetative abnormalities, or merely subjective symptoms

without major convulsive movements’’ (Drislane, 2000).

This umbrella term includes a wide spectrum of disorders,

ranging from benign conditions, such as absence status in

idiopathic generalized epilepsy, to severe life-threatening

conditions, such as subtle SE or coma with generalized

epileptiform discharges (coma-GEDs). Therefore, it is

important to subdivide this category according to thedegree of unresponsiveness or to the depth of coma

(Fig. 2). Consciousness, which notoriously resists defini-

tion, becomes a taxonomic criterion for subdividing

NCSE (Bauer & Trinka, 2009). Consciousness itself can

be categorized into quantitative and qualitative conscious-

ness. The quantitative element depends upon the patient’s

level of consciousness and arousability, which in turn

depends upon the integrity of the ponto-mesodiencephalic

reticular pathways and the thalamocortical projections.

Qualitative consciousness, on the other hand, depends

upon the content of consciousness, experience, emotions,

and sensations, known only to patients themselves. Itreflects the inner monologue and it is essential for any

meaningful interaction with the environment. Qualitative

consciousness is associated with awareness, enabling the

patient either to focus on and interact with the environ-

ment or to engage in an inner monologue. Table 2

describes the different types of NCSE.

The incidence of NCSE, based on epidemiologic stud-

ies, ranges from 40.0 to 66.9% (DeLorenzo et al., 1995;


et al., 2001; Vignatelli et al., 2003). Like convulsive sta-

tus, NCSE may occur in acute central nervous system

(CNS) disorders or may be a part of certain electroclinical

syndromes. We do not know the precise incidence of

NCSE in the epilepsy population. In our own audit (1975

to 2003) at the University Hospital Innsbruck, 220 patients

with epilepsy (140 women, median age 45 years [range 2–

89]) had at least one episode of NCSE either during their

Figure 2.

Relationship between depth and coma (x-axis), prog-nosis (x-axis), degree of structural brain damage (red y-

axis), and epileptic brain dysfunction (blue y-axis) dueto status epilepticus. Clinical entities depicted in theupper part of the graph are arranged along the x-axiswithout distinct positions, in recognition that largeborder zones and overlaps between the conditionsmay exist. With permission from Bauer & Trinka, 2009.AS, absence status epilepticus; EPC, epilepsia partialiscontinua; GEDs, generalized epileptiform discharges;IGE, idiopathic generalized epilepsy; LEDs, lateralizedepileptiform discharges; NCSE, nonconvulsive statusepilepticus.Epilepsia ILAE

Table 2. Categories of NCSE, classified

according to the degree of disturbed

consciousness

NCSE with coma

NCSE withoutcoma

Generalized

Typical absence status

Atypical absence status

Myoclonic absence status

Focal

Aura continua

With vegetative symptoms

With sensory symptoms

With visual symptoms

With olfactory symptoms

With gustatory symptoms

With emotional symptoms

AphasicSE

SE with dyscognitive symptoms


129

Causes of Status Epilepticus

7/27/2019 j.1528-1167.2012.03622.x


disease or at their initial presentation (Bauer G, Trinka E,

unpublished data). The cause of NCSE was remote symp-

tomatic in 47%, idiopathic in 45%, and remained

unknown (cryptogenic) in 48%. Forty-six percent had

focal SE, 21% had a generalized NCSE in the context of

idiopathic (or genetic) generalized epilepsies, and 22%

had atypical absence status in the context of Lennox-Gas-

taut syndrome. Table 3 details their different types of sta-

tus epilepticus.

Causes of Absence Status

Epilepticus

Absence status (AS) is best described as ‘‘a confusional

state of variable intensity, ranging from simple cognitive

slowing to catatonic stupor, lasting for hours to days or

weeks’’ (Andermann & Robb, 1972). The EEG shows

bilateral rhythmic, synchronous, and mostly symmetric

paroxysmal activity, which can be continuous or discon-

tinuous (Bauer & Trinka, 2010; Fig. 3). It is important to

recognize that AS is a heterogeneous condition, whichmay occur in patients with preexisting idiopathic general-

ized epilepsy (‘‘typical’’ AS) or during the course of

chronic symptomatic generalized epilepsy, such as Len-

nox-Gastaut syndrome (‘‘atypical’’ AS). Of interest, some

Table 3. Types of NCSE in 220 patients with

epilepsy and a history of NCSE (Bauer &

Trinka, data on file)

n %

Generalized (106 = 48.2%)

Typical absence SE 57 25.9

Atypical absence SE 49 22.3

Localized/lateralized (100 = 45.5%)

Focal simple (58 = 26.4%)

Aura continua 11 5.0

Vegetative 8 3.6

Aphasic 27 12.3

Pure frontal 9 4.1

Psychosis 3 1.4

Focal complex (42 = 19.1%)

Continuous 30 13.7

Discontinuous 12 5.5

Unclassified 14 6.3

Total 220 100.1

Figure 3.

Typical absence status epilepticus in an older patient (V.J., female, 74 years. tc 0.3 F30). This patient had scatteredgeneralized tonic–clonic seizures since age of 54 years. Her EEG showed periodically repeated generalized 3/s spikeand wave, with no major diffuse slow activity between periods (note the reduced time calibration). EEG kindlyprovided by Prof. Dr. G. Bauer, Innsbruck. The patient displayed discontinuous psychic functions, and was amnesicfor the abnormal condition. Recovery was immediate after intravenous diazepam.Epilepsia ILAE


130

E. Trinka et al.

7/27/2019 j.1528-1167.2012.03622.x


patients develop AS later in life, occasionally de novo

(Andermann & Robb, 1972; Thomas et al., 1992), or it

may occur as a late exacerbation of an idiopathic general-

ized epilepsy syndrome (Bauer et al., 2007). There may

also be a fourth group of AS, comprising ‘‘absences’’ with

very clear focal characteristics. This group may be consid-ered as a transitional form between AS and dyscognitive

focal SE of frontal origin (Bauer et al., 2006; Thomas,

2011).

Many cases of AS have nonspecific precipitating fac-

tors. The most important are antiepileptic drug (AED)

withdrawal or impaired adherence, alcohol, sleep depriva-

tion, and sleep–wake cycle disturbance. Other nonspecific

factors include stress, fatigue, fever, mild head trauma, or

metabolic derangement after surgery (Thomas & Zifkin,

2008; Thomas & Gelisse, 2009).

Several idiopathic generalized epilepsy syndromes may

be aggravated by inappropriate AEDs: carbamazepine,phenytoin, tiagabine, or other c-aminobutyric acid

(GABA)ergic medications (Snead & Hosey, 1985; Knake

et al., 1999; Thomas et al., 2006a,b; Trinka et al., 2002).

Thomas et al. reported 14 patients with idiopathic general-

ized epilepsy treated with either carbamazepine alone or

with other potentially aggravating drugs, for example,

phenytoin, vigabatrin, or gabapentin. Ten of these cases

developed AS; in half, the AS was atypical. All their

patients had a clear seizure aggravation, with development

of new seizure types before AS developed (Thomas et al.,

2006a,b). The prognosis was invariably good with full sei-

zure control in all patients after switching to appropriate

drugs.In late-onset AS, other drug-related factors play an

important clinical role (Thomas et al., 1992; Thomas &

Andermann, 1994). Most importantly, psychotropic medi-

cation — or its withdrawal — may provoke late-onset AS

(Fernandez-Torre, 2001). In addition, many other drugs,

for example, theophylline, baclofen, metformin, and

cimetidine, may exacerbate absences later in life (for a

review see Thomas & Snead, 2007).

There are metabolic and toxic factors in many patients,

although the precise incidence is not known. Examples

include hyponatremia, hypoglycemia decompensated

chronic renal failure, hepatic failure, and hypocalcemia(for review see Thomas & Snead, 2007). There have been

several cases of AS following the use of contrast-enhanc-

ing products during myelography or carotid angiography

(Pritchard & O’Neil, 1984; Vollmer et al., 1985; Coeytaux

et al., 2000). Some cases of transient global amnesia after

angiography may in fact also be epileptic in nature (Bauer

et al., 2005).

AS probably occurs most frequently in the context of

electroclinical syndromes. Aside from childhood

absence epilepsy, juvenile absence epilepsy, and juve-

nile myoclonic epilepsy, there are other syndromes asso-

ciated with AS as a key clinical feature: AS may occur

in eyelid myoclonia with absences (Jeavons syndrome)

(Yang et al., 2008), idiopathic generalized epilepsy with

phantom absences (Panayiotopoulos et al., 2001), per-

ioral myoclonias with absences (Agathonikou et al., 1998),

or absences status epilepsy (Genton et al., 2008). The

prognosis in these syndromes (not yet fully accepted inthe ILAE classification) is generally good, and patients

respond well to appropriate AEDs — valproate in most

cases. However, this is not true of AS associated with

ring chromosome 20, where prolonged confusional

states are notoriously resistant to AEDs and there have

been lethal cases (Jacobs et al., 2008). The EEG shows

bilateral high-voltage slow waves, sometimes with inter-

mingled spikes and frontal accentuation. There is no

typical clinical picture, except for mild cognitive impair-

ment (Fig. 4).

Causes of FocalNonconvulsiveStatus Epilepticus

Focal NCSE (as with AS) encompasses a wide range of

clinical symptoms. Previously the term ‘‘complex focal or

complex partial’’ SE was used, which may be replaced in

future by ‘‘dyscognitive SE.’’ These forms usually have

structural abnormalities and clinical focal signs that must

be identified to guide appropriate drug treatment (Fig. 2).

Most of the published literature concerns patients with

temporal or extratemporal lobe epilepsy of remote symp-

tomatic cause, whose NCSE is either as the presenting

symptom or develops during the course of the disease

(Tomson et al., 1992, Kaplan et al., 1996; Scholtes et al.,

1996). As with AS, there are often nonspecific risk factors,

but more often status occurs in these patients without spe-

cific provoking factors. In a review of 70 patients with

focal NCSE of frontal origin, more than one fourth had no

history of epilepsy. Forty-five percent had a focal frontal

Figure 4.

Clinical course of convulsive status epilepticus.Epilepsia ILAE


131


7/27/2019 j.1528-1167.2012.03622.x


lesion. The etiology was most often a brain tumor (benign

or malignant), or a posttraumatic or a postsurgical lesion

(Thomas & Zifkin, 2008).

Rare causes of focal NCSE include intravenous contrast

media, or drugs such as ciprofloxacin, lithium intoxica-

tion, theophylline, vigabatrin, tiagabine, or crack cocaine(Thomas et al., 2006b). Mesial temporal focal NCSE can

also be the presenting symptom of the increasingly recog-

nized nonparaneoplastic limbic encephalitis, related to

voltage-dependent potassium channels (VGKC/LGI1)

(Irani et al., 2010), NMDA receptors (Vincent & Bien,

2008), or antibodies against glutamic acid decarboxylase

(Malter et al., 2010). Some of them lead to a specific sei-

zure type (e.g., faciobrachial dystonic seizures associated

with anti-VGKC/LGI1 antibodies), preceding the onset of

the limbic encephalitis (Irani et al., 2011a,b). It is impor-

tant to note that paraneoplastic limbic encephalitis may

also present with focal NCSE (Dalmau et al., 2008), indi-cating the need for a comprehensive search and rigorous

treatment of any underlying primary neoplasm. We do not

yet know the full spectrum of this new group of immune-

mediated encephalopathies (Table 4).

The outcome for focal NCSE is less favorable than that

for AS. Long-lasting focal status, especially of temporal

lobe origin, may cause brain edema identifiable on mag-

netic resonance imaging (MRI) (Bauer et al., 2006). These

patients may also have severe and prolonged amnesia

(Engel et al., 1978; Treiman et al., 1981). However, many

patients presenting with focal NCSE have acute or remote

symptomatic epileptogenic lesions, making it difficult to

disentangle the dysfunction due to the epileptic activityfrom the effect of the structural lesion (Hilkens & De

Weerd, 1995; Kaplan, 1996; Trinka et al., 2002). How-

ever, focal NCSE occurring with an acute lesion most

likely contributes substantially to the associated neuro-

logic dysfunction (Hilkens & De Weerd, 1995; Bauer &

Trinka, 2010). Therefore, patients with focal NCSE need

prompt and vigorous treatment, tailored to the underlying

cause.

Causes of Comatose

Nonconvulsive Status

Epilepticus

Comatose forms of NCSE need further attention. It is

important from the clinical standpoint (1) to clarifywhether the coma is caused by the epileptic seizure or sta-

tus, or by the brain disorder itself, (2) to assess the contri-

bution of epileptic activity to the depth of coma, (3) to

consider whether treatment improves prognosis in these

patients or not, and (4) to implement an appropriate treat-

ment in these critically ill patients. Unlike in other forms

of NCSE, the cause of the comatose patient’s SE can

sometimes only be identified from the history, the tempo-

ral pattern of coma, and the neurologic signs. The epileptic

etiology is most often confirmed only by the presence of

continuous or discontinuous epileptiform discharges on

the EEG (Lowenstein & Aminoff, 1992; Jordan, 1999;Brenner, 2005). A frequently used, but not universally

accepted, classification of patients in comatose status uses

the dichotomy of generalized versus focal or lateralized

EEG discharges (Brenner, 2004). The EEG is absolutely

necessary to make this distinction. In this review we used

the terms ‘‘coma with generalized epileptiform dis-

charges’’ (or coma-GED) and ‘‘coma with lateralized epi-

leptiform discharges’’ (or coma-LED) (Bauer & Trinka,

2009). The etiology in these patients is almost always

acute symptomatic, encompassing a wide variety of

Table 5. Etiologic factors and EEG pattern in

comatose NSCE

Etiology EEG pattern

coma-GED Diffuse primary or

secondary brain

disturbances (anoxic,

toxic, metabolic,

infectious, degenerative)

Space-occupying lesions

with brainstem

compression (direct or

due to tentorial

herniation)

a

Known epilepsies?

Continuous generalized

spiking

Periodic spiking

Burst suppression pattern

in different variations

Other generalized

periodic abnormalities

Bilateral triphasic waves

comaLED Focal brain lesions (in

most cases acutely

acquired)In rare cases

diffuse abnormalities

(aminophylline,

intoxiation, some forms

of diabeticcoma)

Known epilepsies?

Continuous focal spiking

PLEDs and Bi-PLEDS

Unilateral burst

suppression pattern

unilateral triphasic waves

Bi-PLED, bilateral periodic epileptiform discharges; GEDs,

generalized epileptiform discharges; LED, lateralized epilepti-

form discharges; PLEDs, periodic epileptiform discharges.aMight also present as coma-LED.

Table 4. Immunologic disorders causing

status epilepticus

Paraneoplastic encephalitis

Hashimoto encephalopathy

Anti-NMDA-receptor encephalitis

Anti-VGKC-receptor encephalitis

Rasmussen encephalitis

Cerebral lupus

Adult-onset Still disease

Anti-GAD antibody associated encephalitis

Goodpasture syndrome

Thrombotic thrombocytopenic purpura

Antibody-negative limbic encephalitis

NMDA, N-methyl-D-aspartate; GAD, glutamate acid dec-

arboxylase.


132

E. Trinka et al.

7/27/2019 j.1528-1167.2012.03622.x


Table 6. Causes of epilepsia partialis continua (according to Tan et al., 2010)

Age period EPC type1 (staticcause) Diagnostictest

EPC type 2 (progressive

cause) Diagnostic test

Infancy Hemimegalencephaly Mitochondrial disease

(Alper disease)

Serum and cerebrospinal

fluid lactate, musclebiopsy biopsy,

mitochondrial DNA

(mutation of POLG1)

Childhood Focal corticaldysplasia

Sturge-Weber

syndrome focal cortical

dysplasia

Rasmussen s yndrome Cerebrospinal fl uid

oligoclonal banding,

immunoglobulin G index

Tuberoussclerosis Repeated ski n

examination

Mitochondrial

encephalomyopathy, lactic

acidosis and stroke-like episodes

(MELAS)


fluid lactate, muscle

biopsy, mitochondrial

DNA

Neurocysticerosis Immunoelectrotransfer

blotassay

Delayed type of measles

encephalitis (complication of

measlesin

immunocompromised children)

Immunosuppresive

treatment, contact with

measles

(Tick-borne) encephalitis Cerebrospinal fluid study

serologic test for virus

Gliomatosis cerebri

Other foreign tissue

lesions Nonketotic

(ketotic) hyperglycemia

Serum glucose, urinary

ketones

Adults Cerebrovascular

disorders (stroke;

intracranial bleeding,

cerebral venous

thrombosis, vasculitis)

Adult-onset Rasmussen’s

syndrome

Cerebrospinal fluid

oligoclonal banding,

immunoglobulin G index

Nonketotic (ketotic)

hyperglycemia

Serum glucose Creutzfeldt-Jakob disease 14-3-3 protein in

cerebrospinal fiuid

Focal cortical dysplasia Myoclonus epilepsy with ragged

redfibers (MERRFs)


fluid lactate, musclebiopsy, mitochondrial

DNA

Paraneoplastic limbic

encephalopathy

Cerebrospinal fluid study,

chest computed

tomography, anti-Hu

test

Kuf’s disease Skin or rectal mucosal

biopsy

Neoplasms

Tuberculous meningitis

(tuberculoma)

(Tick-borne) encephalitis

Cerebrospinal fluid study,

chest XR, tuberculin skintest

Cerebrospinal fluid

study,serologictest for

virus

Autoimmune thyroid

encephalopathy

Thyroid function tests,

antithyroglobulin

antibody,antimicrosomal antibody

Behcet di sease Neuroimaging, recurrent

oral and genital

ulceration, skin lesions,

HLA-B5 positivity

Sjogrensyndrome Hypergammaglobulinemia

positive antinuclear

antibody, anti-SSA, SSB,

rheumatoid factor

Multiplesclerosis Cerebrospinal fluid

oligoclonal banding

HIV encephalopathy

Immunoglobulin G index

Serologic test for HIV


133


7/27/2019 j.1528-1167.2012.03622.x


systemic diseases or CNS disorders. Table 5 shows the eti-

ologic factors and EEG patterns found in coma-GED and

coma-LED. Unlike in AS and focal NCSE, these patients

are often resistant to treatment, and the prognosis depends

entirely on the course of the underlying disorder.

Advanced convulsive SE becomes oligosymptomatic withfewer motor symptoms; deep coma is the leading symp-

tom, hence the term ‘‘subtle status’’ (Treiman et al., 1984).

The causes are identical to convulsive SE.

Causes of Epilepsia Partialis

Continua

Epilepsia partialis continua (EPC) is a special type of

focal status epilepticus (Table 1), first described by

Kojewnikov in 1894; he considered it as a ‘‘peculiar form

of cortical epilepsy.’’ EPC is characterized by ‘‘spontane-

ous regular or irregular clonic muscle twitching of cere-bral cortical origin, sometime aggravated by action or

sensory stimuli, confined to one part of the body, and

continuing for a period hours days, or weeks’’ (Obeso

et al., 1985). EPC, also called Kojewnikov syndrome,

occurred in patients with Russian spring–summer tick-

borne encephalitis; EPC typically develops 2–3 weeks

after the end of the acute illness (Zemskaya et al., 1991).

EPC was later recognized to occur in several neurologic

disorders, with age of onset ranging from infancy to adult-

hood, and even in the elderly. The prevalence, based on

the EPC case registry of the British Neurological Surveil-

lance Unit, is <1 per million (Cockerell et al., 1996).

The reported causes of EPC are extremely diverse, and

include metabolic disorders (nonketotic hyperglycemia ormitochondrial encephalopathy), cerebrovascular disor-

ders, inflammation (especially Creutzfeldt–Jakob disease,

progressive multifocal leukoencephalopathy from HIV

infection, multiple sclerosis, neurocysticercosis and oth-

ers), neoplasms (astrocytoma, hemangioma, lymphoma

and metastasis), and cortical dysplasia (focal cortical

dysplasia and hemimegalencephaly) (Oguni et al., 1991;

Veggiotti et al., 1995; Lee et al., 2000; Placidi et al., 2001;

Pandian et al., 2002; Huang et al., 2005; Wieser & Chauvel,

2005; Aydin-Ozdemir et al., 2006; Kinirons et al., 2006;

Sinha & Satischandra, 2007; Bien & Elger, 2008; Yeh &

Wu, 2008; Mameniskiene et al., 2011). The most commonetiologies are cerebrovascular disorders (24–28%), inflam-

matory causes (15–19%), neoplasms (5–16%), and meta-

bolic disorders (6–14%). Despite full neurologic work-up,

19–28% of EPC cases have no identifiable cause (Thomas

et al., 1977; Cockerell et al., 1996; Sinha & Satischandra,

2007). Table 6 gives an overview of the causes of EPC.

Bancaud divided EPC into two types: type 1, caused by

focal static lesions of the sensorimotor cortex, and type 2,

caused by progressive cerebral lesions with neurologic

and intellectual deterioration (Bancaud, 1992). Type 2

most often reflects mitochondrial diseases and inflamma-

tory causes, such as Rasmussen syndrome or Creutzfeldt–

Jakob disease.

UncommonCauses of Status

Epilepticus

The uncommon causes of SE deserve consideration. In

many cases of drug-resistant SE, the underlying disorder

remains untreated, because rare causes may be over-

looked. We do not know the frequency of these rare

Table 8. Uncommon infectious disease causing status epilepticus

Atypical bacterial infections Viral infections Prion disease Other infections

Bartonella/cat-scratch disease HIV and HIV-related infections Creutzfeldt-Jakob disease Paracoccidioidomycosis

Coxiella burnett (Q fever) West Nile encephalitis Paragonimiasis

Neurosyphilis JC virus ( progressive multifocal

leukoencephalopathy)

Mucormycosis

Scrub typhus Parvovirus B19

Shigellosis Varicella encephalitis

Mycoplasmapneumonia Subacutesclerosing panencephalitis

Chl amydophilapsittaci Measles encephalitis

Rubella encephalitis

Rous sarcoma virus

(RSV) associated SE

Polioencephalomyelitis

St. Louis encephalitis

Table 7. Mitochondrial diseases causing

status epilepticus

Alpers disease

Occipital lobe epilepsy/mitochondrial spinocerebellar ataxia and

epilepsy (MSCAE)

Mitochondrial encephalopathy, lacticacidosis, and stroke-like episodes

(MELAS)

Leigh syndrome

Myoclonic encephalopathy with ragged red fibers (MERRF)

Neuropathy, ataxia, and retinitis pigmentosa (NARP)


134

E. Trinka et al.

7/27/2019 j.1528-1167.2012.03622.x


causes, and the available literature is mostly confined to

single case reports or small case series. This overview is

based on a systematic search of all available English liter-

ature between 1990 and 2008 (Tan et al., 2010). The

authors identified 181 causes of SE after reviewing 513

articles. The causes fell into five categorical groups:

1. Immunologically mediated disorders (Table 4).2. Mitochondrial diseases (Table 7).

3. Uncommon infective disorders (Table 8).

4. Genetic disorders (Table 9).

5. Drugs or toxins.

Table 10 lists other uncommon causes of SE. It cannot

be overemphasized that the knowledge of the range of

conditions is important to clinical practice; the underlying

disorder must be treated to achieve full seizure control.

The tables are derived from the article by Tan et al. (2010)

and reflect the current state of knowledge on these causes

of SE.

TherapeuticConsiderations

Given the wide variety of clinical presentations of SE,

ranging from life-threatening conditions to seemingly

harmless ones, it is important to tailor the treatment to the

type of status and to the underlying disorder. The clinical

presentation of SE determines the aggressiveness treat-

ment. All treatment concepts on convulsive SE are based

on a staged approach (Fig. 4). In the early phase of convul-

sive SE, large randomized controlled trials support the use

of intravenous benzodiazepines. Alternatively, the intra-

muscular route is effective in the prehospital setting

(Silbergleit et al., 2012). In stage two, AEDs were used,

but it must be emphasized that there are no clinical trials

to inform the best drug treatment at this stage (Cock and

ESETT Group, 2011). Phenytoin, levetiracetam, and valp-

roic acid are most often used (Shorvon et al,. 2008). The

newer AED lacosamide has also gained acceptance in the

community, but data on its effectiveness in convulsive

Table 9. Status epilepticus due to genetic diseases

Chromosomal aberrations

Inborn errors of

metabolism

Malformations of

cortical development

Neurocutaneous

syndromes Others

Ring chromosome 20 Porphyria Focal cortical

dysplasias

Sturge-Weber

syndrome

Rett’s syndrome

Angelmansyndrome Menke’s disease Hemimegalencephaly Tuberous sclerosis Dravet syndrome and

SCN1A gene mutation

spectrum

Wolf-Hirschhorn s yndrome Wilson’s disease Polymicrogyria Migrating partial seizures

in infancy

Fragile X syndrome Alexander’s disease Heterotopias Pyeridoxine dependency

X-linked mentalretardation

syndrome

Gobalamin C/D

deficiency

Schizencephaly Familial hemiplegic

migraine

Ringchromosome 17 Ornithine transcarbamylase

(OTC) deficiency

Hyperprolinemia

Maple-syrup urine disease

3-Methylcrotonyl CoA

carboxylase deficiency

Lysinuric protein intoleranceHydroxyglutaric aciduria

Metachromatic

leukodystrophy

Kuf’s disease

Late infantile ceroid

lipofuscinosis

Beta-ureidopropionase

deficiency

Lafora’s disease

Dentato-rubro-pallido-luysian

atrophy

Infantile-onset

spinocerebellar ataxia

Wrinkly-skin syndrome

Neurocutaneousmelanomatosis

Neuroserpin mutation

Wolfram syndrome

Autosomal recessive

hyperekplexia

Cockayne syndrome

Cerebral autosomal

dominant arterio-pathy

with subcortical infarcts

and leuko

encephalopathy

(CADASIL)

3-Hydroxyaxyl

CoA dehydrogenase

deficiencyCarnitine

palmitoyltransferase

Succinic semildehyde

dehydrogenase deficiency

Jeavons syndrome

Robinow syndromeLYK5 mutation

MECP2 mutation

Malignant hyperpyrexia


135


7/27/2019 j.1528-1167.2012.03622.x


status are limited (Hçfler et al., 2011; Trinka, 2011). From

stage three onward, intensive care unit treatment and gen-

eral anesthesia are the mainstays of drug treatment. Again,

there are no randomized controlled trials informing the

effectiveness of individual drugs in this stage. Midazolam

seems to be better tolerated than pentobarbital/thiopental

and propofol (Shorvon & Ferlisi, 2012). A fourth stage of

status was recently introduced (Shorvon & Trinka, 2011),

and a treatment protocol was proposed by Shorvon and

Ferlisi (2011). Needless to say, all general measures for

intensive care treatment have to be applied at the begin-

ning of status (Shorvon et al., 2008). There is general

agreement that AS, dyscognitive status and other forms of

focal nonconvulsive SE do not require the same aggres-

sive treatment as convulsive SE. Most patients in AS

respond promptly to a benzodiazepine or valproic acid. In

focal NCSE the potential risks of treatment, especially

intubation and sedation, must be weighed against the ben-

efits of seizure control in preventing neuronal damage and

long-term consequences.

Disclosure of Conflict

of Interest

AZ has no conflict of interest to declare. JH has received speaker’shonoraria from UCB and travel grants from UCB, Eisai, and Gerot. EThas acted as a paid consultant to Eisai, Medtronics, Bial, and UCB. Hehasreceived research fundingfrom UCB, Biogen-Idec, and Sanofi-Aven-tis, and speakers’ honoraria from Bial, Cyberonics, Desitin Pharma, Eisai,Gerot, Bçhringer, Sanofi, Medis, and UCB. We confirm that we haveread the Journal’s position on issues involved in ethical publication andaffirm that this report is consistent with those guidelines.

References

Agathonikou A, Panayiotopoulos CP, Giannakodimos S, Koutroumani-dis M. (1998) Typical absence status in adults: diagnostic and syndro-mic considerations. Epilepsia 39:1265–1276.

Aminoff MJ, Simon RP. (1980) Status epilepticus causes, clinical fea-tures and consequences in 98 patients. Am J Med 69:657–666.

Andermann F, Robb JP. (1972) Absence status: a reappraisal followingreview of thirty-eight patients. Epilepsia 13:177–187.

Aydin-Ozdemir Z, Tüzün E, Baykan B. (2006) Autoimmune thyroidencephalopathy presenting with epilepsia partialis continua. ClinEEG Neurosci 37:204–209.

Bancaud J. (1992) Kojewnikov’s syndrome (epilepsia partialis continua)in children. In Roger J, Dravet C, Bureau M, Dreifuss FE, Wolf P(Eds) Epileptic syndromes in infancy, childhood and adolescence.2nd edn.John Libbey Eurotext, London, pp. 363–379.

Bauer G, Trinka E. (2006) Seizures, syndromes and classifications.

Epileptic Disord 8:162–163.

Table 10. Other causes of status epilepticus

Iatrogenic Other medical conditions

Electroconvulsive therapy

Temporal lobectomy and

other neurosurgeryInsertion of intracranialelectrode

Ventriculoperitoneal shunt

Blood transfusion

Carotid angioplasty and stenting

Multiple sclerosis

Hypertension-induced posterior

reversible encephalopathysyndrome

Panayiotopoulos syndrome

Thyroid disease

Pyridoxine-dependent seizure

Neuroleptic malignant syndrome

Ulcerative colitis

Behcet syndrome

Celiac disease

Cobalamin deficiency

Folinicacid responsive seizures

Renal arterystenosis

Pituitary apoplexy

Renal arterydissection

Hypomelanosis of Ito

Cerebral palsyHemophagocytic

lymphohistiocytosis

Anhidrotic ectodermal dysplasia

Methemoglobinemia

Figure 5.

Staged approach to the treatment of convulsive statusepilepticus. *There is currently limited evidence for theuse of lacosamide in SE (see Hofler et al., 2011) Modi-fied after Trinka, 2007; Shorvon et al., 2008.

Epilepsia ILAE

Figure 6.

Treatment algorithm for superrefractory statusepilepticus. Modified after Shorvon & Ferlisi, 2011.Epilepsia ILAE


136

E. Trinka et al.

7/27/2019 j.1528-1167.2012.03622.x


Bauer G, Trinka E. (2010) Nonconvulsive status epilepticus and coma.

Epilepsia 51:177–190.Bauer G, Benke T, Unterberger I, Schmutzhard E, Trinka E. (2005) Tran-

sient global amnesia or transient epileptic amnesia? QJM 98:383;author reply 383–384.

Bauer G, Dobesberger J, Bauer R, Embacher N, Benke T, Unterberger I,Walser G, Luef G, Trinka E. (2006) Prefrontal disturbances as the

sole manifestation of simple partial nonconvulsive status epilepticus.Epilepsy Behav 8:22–225.

Bauer G, Bauer R, Dobesberger J, Benke T, Walser G, Trinka E. (2007)Absence status in the elderly as a late complication of idiopathic gen-eralized epilepsies. Epileptic Disord 9:39–42.

Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van EmdeBoas W, Engel J, French J, Glauser TA, Mathern GW, MoshØ SL,Nordli D, Plouin P, Scheffer IE. (2010) Revised terminology andconcepts for organization of seizures and epilepsies: report of theILAE Commission on Classification and Terminology, 2005–2009.Epilepsia 51:676–685.

Bien CG, Elger CE. (2008) Epilepsia partialis continua: semiology anddifferential diagnoses. Epilept Disord 10:3–7.

BrennerRP. (2004) EEGin convulsiveand nonconvulsive status epilepti-cus. J Clin Neurophysiol 21:319–331.

Brenner RP. (2005) The interpretation of the EEG in stupor and coma.

Neurologist 11:271–284.Cock HR, ESETT Group. (2011) Established status epilepticus treatmenttrial (ESETT). Epilepsia 52(Suppl. 8):50–52.

Cockerell OC, Rothwell J, Thompson PD, Marsden CD, Shorvon SD.(1996) Clinical and physiological features of epilepsia partial con-tinua: cases ascertained in the UK. Brain 119:393–407.

Coeytaux A, Reverdin A, Jallon P, Nahory A. (1999) Non-convulsivesta-tus epilepticus following intrathecal fluorescein injection. Acta Neu-rol Scand 100:278–280.

Coeytaux A, Jallon P, Galobardes B, Morabia A. (2000) Incidence of status epilepticus in French-speaking Switzerland: EPISTAR.

Neurology 55:693–697.Commission on Classification and Terminology of the International

League Against Epilepsy. (1981) Proposal for revised clinicaland electroencephalographic classification of epileptic seizures.Epilepsia 22:489–501.

Dalmau J, Gleichman AJ, Hughes EG. (2008) Anti-NMDA-receptor

encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 7:1091–1098.

DeLorenzo RJ, Pellock JM, Towne AR, Boggs JG. (1995) Epidemiologyof status epilepticus. J Clin Neurophysiol 12:316–325.

DeLorenzo RJ, Hauser WA, Towne AR. (1996) A prospective, popula-tion-based epidemiologic study of status epilepticus in Richmond,Virginia. Neurology 46:1029–1035.

Drislane FW. (2000) Presentation, evaluation, and treatment of noncon-vulsivestatus epilepticus. Epilepsy Behav 1:301–314.

Engel J, Ludwig B, Fetell M. (1978) Prolonged partial complex statusepilepticus: EEG and behavioral observations. Neurology 28:863–869.

Fernandez-Torre JL. (2001) De novo absence status of late onset follow-ing withdrawal of lorazepam: a case report. Seizure 10:433–437.

Gastaut H. (1970) Clinical and electroencephalographic classification of epileptic seizures. Epilepsia 11:102–113.

Genton P, Ferlazzo E, Thomas P. (2008) Absence status epilepsy: delin-eation of an adult idopathic generalized epilepsy syndrome. Epilepsia49:642–649.

Hauser WA. (1990) Status epilepticus: epidemiology considerations. Neurology 40(Suppl. 2):9–12.

Hesdorffer DC, Logroscino G, Cascino G, Annegers JF, Hauser WA.(1998) Incidence of status epilepticus in Rochester, Minnesota,1965–1984. Neurology 50:735–741.

Hilkens PHE, De Weerd AW. (1995) Non-convulsive status epilepticusas cause for focal neurological deficit. Acta Neurol Scand 92:193–197.

Hçfler J, Unterberger I, Dobesberger J, Kuchukhidze G, Walser G,Trinka E. (2011) Intravenous lacosamide in status epilepticus and sei-zure clusters. Epilepsia 52:e148–e152.

Holtkamp M, Othman J, Buchheim K, Meierkord H. (2005) Predictorsand prognosis of refractory status epilepticus treated in a neurologicalintensive care unit. J Neurol Neurosurg Psychiatry 76:534–539.

Huang CW, Hsieh YY, Pai MC, Tsai JJ, Huang CC. (2005) Nonketotichyperglycemia-related epilepsia partialis continua with ictal unilat-eral parietal hyperperfusion. Epilepsia 46:1843–1844.

Irani SR, Alexander S, Waters P, Kleopa KA, Pettingill P, Zuliani L,Peles E, Buckley C, Lang B, Vincent A. (2010) Antibodies to Kv1potassium channel-complex proteins leucine-rich, glioma inactivated1 protein and contactin-associated protein-2 in limbic encephalitis,

Morvan’s syndrome and acquired neuromyotonia. Brain 133:2734–2748.

Irani SR, Michell AW, Lang B, Pettingill P, Waters P, Johnson MR,Schott JM, Armstrong RJ, S Zagami A, Bleasel A, Somerville ER,Smith SM, Vincent A. (2011a) Faciobrachial dystonic seizuresprecede Lgi1 antibody limbic encephalitis. Ann Neurol 69:892–900.

Irani SR,SchottJM, Vincent A, Smith SJ.(2011b) Tonic seizures: a diag-nostic clue of anti-LGI1 encephalitis? Neurology 77:2140–2141;author reply 2141-3.

Jacobs J, Bernard G, Andermann E, Dubeau F, Andermann F. (2008)Refractory and lethal status epilepticus in a patient with ring chromo-some 20 syndrome. Epileptic Disord 10:254–259.

Jordan KG.(1999)Nonconvulsive status epilepticus in acute brain injury. J Clin Neurophysiol 16:332–340.

Kaplan PW. (1996) Nonconvulsive status epilepticus in the emergencyroom. Epilepsia 37:643–650.

Kinirons P, O’Dwyer JP,Connolly S, HutchinsonM. (2006) Paraneoplas-tic limbic encephalitis presenting as lingual epilepsia partialis con-

tinua. J Neurol 253:256–257.

Knake S, Hamer HM, Schomburg U, Oertel WH, Rosenow F. (1999)Tiagabine-induced absence status in idiopathic generalized epilepsy.

Seizure 8:314–317.Knake S, Rosenow F, Vescovi M, Oertel WH, Mueller HH, Wirbatz A,

Katsarou N, Hamer HM, Status Epilepticus Study Group Hessen(SESGH). (2001) Incidence of status epilepticus in adults in Ger-many: a prospective, population-based study. Epilepsia 40:759–762.

Larch J, Unterberger I, Bauer G, Reichsoellner J, Kuchukhidze G, TrinkaE. (2009) Myoclonic status epilepticus in juvenile myoclonicepilepsy. Epileptic Disord 11:309–314.

Lee K, Haight E, Olejniczak P. (2000) Epilepsia partialis continua inCreuzfeldt-Jacob disease. Acta Neurol Scand 102:398–402.

Logroscino G, Hesdorffer DC, Cascino G, Annegers JF, Hauser WA.

(1997) Short-term mortality after a first episode of status epilepticus.

Epilepsia 38:1344–1349.Logroscino G, Hesdorffer DC, Cascino G, Hauser WA, Coeytaux A,

Galobardes B, Morabia A, Jallon P. (2005) Mortality after a first epi-sode of status epilepticus in the United States and Europe. Epilepsia46(Suppl. 11):46–48.

Lowenstein DH, Aminoff MJ. (1992) Clinical, EEG features of statusepilepticus in comatose patients. Neurology 42:100–104.

Lowenstein DH, Bleck T, Macdonald RL. (1999) It’s time to revisetorevise the definitionof status epilepticus. Epilepsia 40:120–122.

Malter MP, Helmstaedter C, Urbach H, Vincent A, Bien CG. (2010)Antibodies to glutamic acid decarboxylase define a form of limbicencephalitis. Ann Neurol 67:470–478.

Mameniskiene R, Bast T, Bentes C, Canevini MP, Dimova P, Granata T,Høgenhaven H, Jakubi BJ, Marusic P, Melikyan G, Michelucci R,Mukhin KY, Oehl B, Ragona F, Rossetti AO, Rubboli G, Schubert S,Stephani U, Strobel J, Vignoli A, Zarubova J, Wolf P. (2011) Clinical

course and variability of non-Rasmussen, nonstroke motor and sen-sory epilepsia partialis continua: a European survey and analysis of 65 cases. Epilepsia 52:1168–1176.

Obeso JA, Rothwell JC, Marsden CD. (1985) The spectrum of corticalmyclonus: from focal reflex jerks to spontaneous motor epilepsy.

Brain 108:193–224.Oguni H, Andermann F, Rasmussen T. (1991) The natural history of the

syndrome of chronic encephalitis and epilepsy: a study of the MNIseries of forty-eight cases. In Andermann F (Ed.) Chronic encephali-tis and epilepsy: Rasmussens's syndrome. Butterworth-Heinermann,Boston,MA, pp. 7–35.

Panayiotopoulos CP, Ferrie CD, Koutroumanidis M, Rowlinson S, Sand-ers S. (2001) Idiopathic generalized epilepsy with phantom absencesand absencestatusin a child. Epileptic Disord 3:63–66.

Pandian JD, Thomas SV, Santoshkumar B. (2002) Epilepsia partialis

continua: a clinical and electroencephalography study. Seizure11:437–441.


137


7/27/2019 j.1528-1167.2012.03622.x


Placidi F, Floris R, Bozzao A. (2001) Ketotic hyperglycemia and epilep-sia partialis continua. Neurology 57:534–537.

Pritchard PB III, O’Neal DB. (1984) Nonconvulsive status epilepticusfollowing metrizamide myelography. Ann Neurol 16:252–254.

Rossetti AO, Hurwitz S, Logroscino G, Bromfield EB. (2006) Prognosis of status epilepticus: role of aetiology, age, and consciousness impaire-ment at presentation. J Neurol Neurosurg Psychiatry 77:611–615.

Scholtes FB, Renie WO, Meinardi HM. (1996) Non-convulsive statusepilepticus: causes, treatment, outcome in 65 patients. J Neurol

Neurosurg 61:93–95.Shorvon S. (1994) Status epilepticus: its clinical features and treatment

in children and adults. University Press, Cambridge.Shorvon S, Ferlisi M. (2011) The treatment of super-refractory status

epilepticus: a critical review of available therapies and a clinicaltreatment protocol. Brain 134(Pt 10):2802–2818.

Shorvon S, Ferlisi M. (2012) The outcome of therapies in refractory andsuper-refractory convulsive status epilepticus and recommendationsfor therapy. Brain May 9 [Epubahead of print].

Shorvon S, Trinka E. (2011) Status epilepticus – making progress.Epilepsia 52(Suppl. 8):1–2.

Shorvon S, Walker M. (2005) Status epilepticus in idiopathic generalizedepilepsy. Epilepsia 46(Suppl. 9):73–79.

Shorvon S, Baulac M, Cross H, Trinka E, Walker M. (2008) The drug

treatment of status epilepticus in Europe: censensus document from aworkshop at the first London Colloquium on Status Epilepticus.

Epilepsia 49:1277–1285.

Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, PaleschY, Barsan W. (2012) Intramuscular versus intravenous therapy forprehospital status epilepticus. N EnglJ Med 366:591–600.

Sinha S, Satischandra P. (2007) Epilepsia partialis continua over last14 years: experience from a tertiary care center from south India.Epilepsy Res 74:55–59.

Snead OC, Hosey LC. (1985) Exacerbation of seizures in children bycarbamazepine. N EnglJ Med 313:916–921.

Tan R, Neligan A, Shorvon SD. (2010) Uncommon causes of statusepilepticus. Epilepsy Res 91:11–22.

Theodore WH, Porter RJ, Albert P. (1994) The secondarily generalizedtonic-clonic seizure: a videotape analysis. Neurology 44:1401–1407.

Thomas P. (2011) Causes of non-convulsive status epilepticus in adults.

In Shorvon S, Andermann F, Guerrini R (Eds) The causes of epilepsy.

Cambridge University Press,Cambridge, pp. 752–758.Thomas P, Andermann F. (1994) Late-onset absence status epilepticus is

most often situation-related. In Malafosse A, Genton P, Hirsch E,Marescaux C, Broglin D, Bernasconi R (Eds) Idiopahtic generalized epilepsies. John Libbey, London,pp. 95–109.

Thomas P, Gelisse P. (2009) Nonconvulsive status epilepticus. Rev Neurol (Paris). 165:380–389.

Thomas P, Snead OC III. (2007) Absence status epilepticus. In Engel J,Pedley T (Eds) Epilepsy: a comprehensive textbook , 2nd ed. Lippin-cott William and Wilkins, Philadelphia, pp. 693–703.

Thomas P, Zifkin B. (2008) Frontal lobe non convulsive status epilepti-cus. In Kaplan PWA, Dislane F (Eds) Non convulsive status epilepti-cus. Demos Biomedical, New York, pp. 91–101.

Thomas JE, Reagan TJ, Klass DW. (1977) Epilepsia partialis continua:a reviewof 32 cases. Arch Neurol 34:266–275.

Thomas P, Beaumanoir A, Genton P, Dolisi C, Chatel M. (1992) De novo

absence status:reportof 11 cases. Neurology 42:105–110.Thomas P, Valton L, Genton P. (2006a) Absence and myoclonic statusepilepticus precipitated by antiepileptic drugs in idiopathic general-ized epilepsy. Brain 129:1281–1292.

Thomas P, Zifkin B, Andermann F. (2006b) Complex partialstatus epilepticus. In Wasterlain CG, Treiman DM (Eds) Status epi-lepticus: mechanism and management . MIT Press, Cambridge, pp.69–90.

Tomson T, LindbomU, NilssonBY. (1992) Non-convulsve status epilep-ticus in adults: thirty-two consecutive patients from a general hospitalpopulation. Epilepsia 33:829–835.

Towne AR, Pellock JM, Ko D, DeLorenzo RJ. (1994) Determinants of mortality in status epilepticus. Epilepsia 35:27–34.

Treiman DM, Delgado-Escueta AV, Clark MA. (1981) Impairment of memory following complex partial status epilepticus. Neurology31:109.

Treiman DM, DeGiorgio CMA, Salisbury SM, Wickboldt CL.(1984) Subtle generalized convulsive status epilepticus. Epilepsia25:653.

Trinka E. (2007) Notfälle im Bereich der Epilepsien: was tun und waslassen? Nervenheilkunde 26:953–1072.

Trinka E. (2011) What is the evidence to use new intravenous AEDs instatus epilepticus? Epilepsia 52(Suppl. 8):35–38.

Trinka E, Dilitz E, Unterberger I. (2002) Non-convulsive status epilepti-cus after replacement of valproate with lamotrigine. J Neurol249:1417–1422.

Veggiotti P, Colamaria V, Dalla Bernardina B. (1995) Epilepsia partialis

continua in a case of MELAS: clinical and neurophysiological study. Neurophysiol Clin 25:158–166.Vignatelli L, Tonon C, D’Alessandro R. (2003) Incidence and short-term

prognosis of status epilepticus in adults in Bologna, Italy. Epilepsia44:964–968.

Vincent A, Bien CG. (2008) Anti-NMDA-receptor encephalitis: a causeof psychiatric, seizure, and movement disorders in young adults.

Lancet Neurol 7:1091–1098.Vollmer ME, Weiss H, Beanland C, Krumholz A. (1985) Prolonged con-

fusion due to absence status following metrizamide myelography. Arch Neurol 42:1005–1007.

Walker M, Cross H, Smith S. (2005) Nonconvulsive status epilepticus:Epilepsy Research Foundation workshop reports. Epilept Disord 7:253–296.

WaterhouseE. (2008) Theepidemiology of status epilepticus. In DrislaneR, Kaplan P (Eds) Nonconvulsive status epilepticus. Demos Medical

Publishing, New York, pp. 23–40.

Wieser HG, Chauvel P. (2005) Simple partial status epilepticus and epi-lepsia partialis continua of Koshevnikov. In Engel J Jr, Pedley TA(Eds) Epilepsy: a comprehensive textbook . Lippincott-Raven, Phila-delphia, PA,pp. 705–724.

Wolf NI,Rahman S, SchmittB. (2009) Status epilepticus in children withAlpers disease caused by POLG1 mutations: EEG and MRI features.Epilepsia 50:1596–1607.

Wu YW, Shek DW, Garcia PA, Zhao S, Johnston SC. (2002) Incidenceand mortality of generalized convulsive status epilepticus in Califor-nia. Neurology 58:1070–1076.

Yang T, Liu Y, Liu L. (2008) Absence status epilepticus in monozygotictwins Jeavons syndrome. Epileptic Disord 10:227–230.

Yeh SJ, Wu RM. (2008) Neurocysticerosis presenting with epilepsiapartialis continua: a clinicopathologic report and literature review.

J Formos Med Assoc 108:576–581.Zemskaya AG,YatsukSL, Samoilov VI.(1991) Intractable or partial epi-

lepsy of infectious or inflammatory etiology: recent-surgical experi-ence in the USSR. In Andermann F (Ed) Chronic encephaltis and

epilepsy: Rasmussens's syndrome. Butterworth-Heinemann, Boston,MA,pp. 271–279.

Epilepsia 53(Suppl 4):127 138 2012

138

E. Trinka et al.

j.1528-1167.2012.03622.x

Documents

Transcript of j.1528-1167.2012.03622.x