Full text of DOI:10.1017/S0317167100001748

ORIGINALARTICLE
Convulsive Status Epilepticus in Children
with Intractable Epilepsy is Frequently
Focal in Origin
Mohammed M.S. Jan, Brian G.R. Neville, Timothy C. Cox, Rod C. Scott
ABSTRACT: Background: Convulsive status epilepticus (CSE) is a common neurological emergency. Our objectives were to study
children with recurrent nonfebrile CSE to assess the evidence for focal origin. Methods: Series of 18 children with recurrent CSE and
intractable epilepsy were identified by chart review. Clinical, radiological, and EEG data were reviewed. Focal structural abnormalities
were identified on MRI and CT images by one neuroradiologist who was unaware of the clinical details. Results: The patient’s ages
ranged between 6-22 years (mean 15.3, SD 4), and 67% were males. Most children (89%) had a severe cognitive and / or behavioural
disorder. Most patients (89%) had multiple seizure types and 95% of these were partial seizures. Twelve (67%) children had at least one
episode of CSE with focal features identified clinically. Focal brain abnormalities were detected on 18% and 55% of CTand MRI films
respectively. Overall, 53% had a focal abnormality on structural neuroimaging. Interictal EEG revealed focal or multifocal abnormalities
on at least one occasion in 94% and 22% of patients respectively. Overall, 17 patients had focal features on at least one EEG. Thirteen
ictal EEGs were recorded on 11 (61%) patients. Ten (91%) of these recordings revealed a focal onset. Conclusions: Many handicapped
children with recurrent CSE have focal clinical, radiological, or electrographic features. This supports a focal origin for CSE in most
children with intractable epilepsy.
RÉSUMÉ: Status epilepticus convulsif chez les enfants qui ont une épilepsie réfractaire au traitement a souvent une origine focale.
Introduction: Le status epilepticus convulsif (SEC) constitue une urgence neurologique fréquente. Nos objectifs étaient d’étudier les enfants qui
présentent un SEC non fébrile récurrent et d’évaluer les données en faveur d’une origine focale.Méthodes: Un groupe de 18 enfants présentant un SEC
récurrent et une épilepsie réfractaire au traitement ont été identifiés au moyen d’une revue de dossiers. Les observations cliniques, radiologiques et
électroencéphalographiques ont été révisées. Des anomalies structurales focales ont été identifiées à la RMN et au CTscan par un neuroradiologiste qui
ne connaissait pas les données cliniques pertinentes à chaque patient. Résultats: L’âge des patients variait de 6 à 22 ans (15,3 ± 4), et 67% étaient des
garçons. La plupart des enfants (89%) avaient des troubles cognitifs et/ou comportementaux sévères. La plupart (89%) avaient plusieurs types de crises
et 95% de ces crises étaient des crises partielles. Douze (67%) des enfants avaient eu au moins un épisode de SEC où on avait identifié des
manifestations focales au point de vue clinique. Des anomalies focales ont été détectées sur 18% des images au CTet 55% à la RMN. Dans l’ensemble,
53% avaient une anomalie focale à la neuroimagerie structurale. L’ÉEG interictal a montré des anomalies focales ou multifocales à au moins une
occasion chez 94% et 22% des patients respectivement. En tout, 17 patients avaient des anomalies focales sur au moins un tracé ÉEG. Treize ÉEG ictaux
ont été enregistrés chez 11 patients (61%). Sur dix (91%) de ces enregistrements on a observé un début focal. Conclusions: Plusieurs enfants
handicappés qui ont des SECs récurrents ont des manifestations focales en clinique, à l’imagerie ou à l’électroencéphalographie. Ceci appuie l’origine
focale du SEC chez la plupart des enfants présentant une épilepsie réfractaire au traitement.
Can. J. Neurol. Sci. 2002; 29: 65-67
Epilepsy is a common neurologic disorder in children,
which support this hypothesis. Structural focal abnormalities
occurring with a frequency of 4-6 cases per 1,000 children.1
Status epilepticus (SE) is defined as a seizure or series of
seizure origin have been identified with magnetic resonance
suggestive of acute cortical or hippocampal edema at the site of
imaging (MRI) in patients with generalized CSE.5-7 Functional
seizures which continue for at least 30 minutes without return of
consciousness between the seizures.2,3 Status epilepticus can be
classified as nonconvulsive or convulsive (CSE), which is the
most common medical neurological emergency in childhood
with an incidence of 4-6/10,000 population.4 Detailed
assessment of children undergoing investigation for epilepsy
surgery has revealed that some with CSE have focal, lesional
epilepsy and may have a good outcome from epilepsy surgery.
This has led to the hypothesis that even when generalized CSE is
reported, the origin is focal with secondary generalization.
There are imaging and electroencephalographic (EEG) data
From theDepartment of Pediatrics (Neurology), King Abdulaziz University Hospital
and College of Medicine and Allied Health Sciences, Jeddah, Saudi Arabia (MMSJ),
Neurosciences Unit, (BGR, RCS) and Radiology and Physics Unit, (TCC) Institute of
Child Health, University College London, and Great Ormond Street Hospital for
Children NHS Trust, London, United Kingdom.
RECEIVED JANUARY 18, 2001. ACCEPTED INFINALFORM AUGUST 8, 2001.
Reprint requests to: Mohammed M.S. Jan, Department of Pediatrics (Neurology), King
Abdulaziz University Hospital, PO Box 80215, Jeddah 21589, Kingdom of Saudi
Arabia
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imaging studies using single photon emission tomography
(SPECT) and positron emission tomography have also shown
focal perfusion or metabolic abnormalities when used in the
investigation of children and adults with CSE.8-10 Convulsive
status epilepticus is more common in children with focal
background EEG abnormalities and those with partial seizures.11,12
Aprevious study assessing focal origin of seizures in a population
with learning disability revealed focal EEG abnormalities in
65%.13 Collectively, these structural and functional abnormalities
suggest a focal onset to generalized CSE.
Convulsive status epilepticus frequently occurs in the context
of severe epilepsy such as that seen in children with epileptic
encephalopathies. The purpose of this study was to examine the
clinical, radiological, and EEG data from children with
generalized CSE in the context of severe epilepsy, to seek clinical,
structural and functional evidence supporting a focal onset.
which started at a mean of 16 months (range six weeks - six
years, SD 19 months) and continued for a mean duration of 13
years (range 5-21 years, SD 4). Most patients (89%) had multiple
seizure types and 95% of these were simple or complex partial
seizures. Twelve (67%) children had Lennox Gastaut syndrome
and 28% had a history of infantile spasms. All patients had
received multiple antiepileptic drugs (AEDs). Ten (55%) were
on three or more AEDs, eight on two, and one was on a single
AED. A ketogenic diet was used in 33%. Two children
underwent epilepsy surgery; corpus callosotomy in one and
hemispherectomy in one. One child had a vagal nerve stimulator
implanted without success.
A summary of the clinical, radiological and EEG data can be
found in the Table. Twelve (67%) patients had at least one
episode of CSE with focal features identified clinically. Of these,
four had a focal onset, six had focal features during the seizure,
and two had a focal postictal weakness. Fifteen children had
brain CT or MRI. Of the eleven who had CT, two (18%) had
focal abnormalities. Focal abnormalities were identified on MRI
in 6/11 (55%) patients. Overall, 53% had a focal abnormality on
structural neuroimaging. Seven patients had both CT and MRI.
Four of these patients had normal CT imaging, but an
abnormality was detected on MRI. Four children had interictal
SPECT and two had a focal decrease in cerebral perfusion, not
consistently concordant with the neuroimaging abnormalities.
Multiple EEGs were carried out on each patient (mean 4.5,
range 2-7). Interictal EEG revealed focal or multifocal
abnormalities on at least one occasion in 94% and 22% of
patients respectively. Overall, 17 patients had focal features on at
least one EEG. The patient who never had a focal abnormality
had episodes of myoclonic SE. Thirteen ictal EEGs were
recorded on 11 (61%) patients. Ten (91%) of these recordings
revealed a focal onset. The concordance of clinical, radiological,
and EEG focal abnormalities is summarized in the Table.
Overall, 11 (61%) children were concordant on at least two of
these three modalities.
METHOD
A series of children and young adults with recurrent episodes
of SE and intractable epilepsy were identified at St Piers,
Lingfield, United Kingdom. This is a large residential unit
offering special education, medical services and care to children
and young adults with severe epilepsy and associated learning
and behavioural difficulties. St Piers is linked to the Institute of
Child Health and Great Ormond Street Hospital for Children
NHS Trust. It is difficult to make detailed assessments of
children with CSE at the time of the acute event and therefore the
strategy for identifying focal elements to CSE was to assess
clinical, radiological, and EEG data collected at other times
during the natural history of the patient’s epilepsy. A retrospective
chart review methodology was used. A detailed seizure chart is
routinely kept by the carers of each individual at St Piers. The
hospital research ethics committee approved the study design.
The notes were examined to identify focal features of each
individual’s epilepsy and to characterize learning and
behavioural difficulties. Evidence for focal onset, focal ictal
features, and focal postictal phenomena was sought. Long
standing focal neurological deficits were also recorded. Focal
structural abnormalities were identified on MRI and CT images,
and focal perfusion abnormalities on SPECT images, by one
neuroradiologist who was unaware of the clinical details. Ictal
and interictal EEG data were also reviewed to identify focal,
multifocal, or regional abnormalities.
DISCUSSION
The study results suggest that many handicapped children
with recurrent CSE have focal clinical, radiological, or
electrographic features. Most of the patients had partial seizures
and two thirds had SE with focal clinical features. Half of the
children had focal features on structural neuroimaging,
particularly MRI which was clearly superior to CTin identifying
focal brain abnormalities. These findings provide structural
evidence of a focal brain abnormality but do not provide the
required functional evidence that the seizures have a focal origin.
This was achieved by analyzing the EEG data. Focal onset was
best supported by the evidence of the ictal EEG which revealed
a focal onset in 91% of patients who had this investigation. Most
patients also had focal interictal EEG abnormalities. A previous
study of intractable epilepsy in mentally handicapped children
with or without recurrent SE found focal EEG abnormalities in
65%.13 Brain lesions were detected on CTand MRI in 70%, with
pure focal lesions in 26%.13 Our results suggest that focal
abnormalities are more common than previously thought.
However, all our patients had recurrent SE, which is known to be
predictive of frequent seizures.11
RESULTS
Eighteen children and adolescents with recurrent CSE and
intractable epilepsy were included. They had a mean age of 15.3
years (range 6-22 years, SD±4). There were 12 (67%) males and
six (33%) females. Most patients (79%) had a severe learning
disability. Behavioural disorders were present in 89%. Five of
those had pervasive developmental disorder and four had
attention deficit hyperactivity disorder. The rest had no formal
psychiatric diagnosis. The etiology of their disabilities was
unknown in nine (50%), post-encephalitis/meningitis in three,
chromosomal abnormalities in two, and one had each of the
following; cerebral palsy, a history of internal carotid injury, a
history of head injury, and tuberous sclerosis.
All children had a long history of difficult to treat epilepsy
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Table: Focal clinical, radiological, and electrographic features (n=18)
Case
1.
2.
3.
4.
Clinical SE
Focal onset
Not documented
Focal ictus
Not documented
Not focal
CT result
Cerebral atrophy
Normal
Not found
Cerebral atrophy
Not found
MRI result
Not found
Normal
Not found
Cerebral atrophy
Cerebellar atrophy
Interictal EEG
Concordance
Clinical and EEG
None
Clinical and EEG
None
Left frontal spikes
Right frontal spikes
Left midtemporal spikes
Right hemispheric spikes
Multifocal spikes
5.
None
6.
Focal postictal weakness
Normal
Abnormal temporal
white matter signal (more on left)
Right hippocampal sclerosis
Left hippocampal sclerosis
Bilateral MTS (more on right)
Multiple tubers (hamartomas)
Asymmetric cortical atrophy
Left frontal spikes
Clinical and EEG
7.
8.
9.
10.
11.
12.
Focal onset
Focal onset
Focal ictus
Not documented
Focal onset
Not focal
Normal
Not found
Normal
Not found
Normal
Left sided
cortical atrophy
Left anterior
Postictal focal delta
Left anterior temporal spikes Clinical, MRI, and EEG
Right hemispheric spikes
Multifocal spikes
Multifocal spikes
Clinical, MRI and EEG
Clinical and EEG
Variable
Variable
Not found
Left hemispheric spikes
CTand EEG
13.
Focal ictus
circulation infarction Not done
Left frontal spikes
Left temporal spikes
Multifocal spikes
Not focal
Left parasagittal spikes
Left frontotemporal spikes
Clinical, CT, and EEG
Clinical and EEG
Variable
None
Clinical and EEG
Clinical and EEG
14.
15.
16.
17.
18.
Focal ictus
Focal ictus
Myoclonic
Focal postictal weakness
Focal ictus
Not found
Normal
Not found
Normal
Normal
Not found
Not done
Normal
Not found
Not found
MTS = Mesial temporal sclerosis
3. Lowenstein DH, Alldredge BK. Status epilepticus. N Engl J Med
1998;338(14):970-976.
4. DeLorenzo RJ, Hauser WA, Towne AR. A prospective, population-
based epidemiologic study of status epilepticus in Richmond,
Virginia. Neurology 1996;46:1029-1035.
5. Meierkord H, Weishmann U, Niehaus L, Lehmann R. Structural
consequences of status epilepticus demonstrated with serial MRI.
Acta Neurol Scand 1997;96(3):127-132.
6. Tien RD, Felsberg GJ. The hippocampus in status epilepticus:
demonstration of signal intensity and morphologic changes with
sequential fast spin-echo MR imaging. Radiology 1995;194:249-
256.
7. VanLandingham KE, Heinz ER, Cavazos JE, Lewis DV. Magnetic
resonance imaging evidence of hippocampal injury after
prolonged febrile convulsions. Ann Neurol 1998;43(4):413-426.
8. Ichiseki H, Hamamoto M, Miyazaki T, et al. Regional blood flow in
status epilepticus measured by single photon emission computed
tomography (SPECT). Nippon Ika Daigaku Zasshi 1995;62(6):
605-614.
9. Gorman DG, Shields WD, Shewmon DA, et al. Neurosurgical
treatment of refractory status epilepticus. Epilepsia 1992;33(3):
546-549.
There are some limitations to our study. First, the study
sample is relatively small and all patients included had severe
and difficult to treat epilepsy. This group is more susceptible to
recurrent SE. These patients, particularly those with
symptomatic epilepsy, are more likely to have focal lesions and
therefore secondary generalized epilepsy. The selected nature of
the study population would limit the ability to generalize from
our findings. Secondly, the interictal and ictal EEG data were not
recorded during the episodes of SE. Recording during an episode
of SE, although practically difficult, will be ideal to confirm the
focal onset. Further prospective and systematic studies to
characterize CSE in children presenting to the emergency room
or in other settings are needed to test that SE usually requires a
focal generator. However, it is clear that epidemiological studies
would need to be combined with detailed clinical, radiological,
and EEG studies to answer the question.
ACKNOWLEDGMENTS
10. Frank G, Sadot B, Salmon E, et al. Regional cerebral blood flow and
metabolic rates in human focal epilepsy and status epilepticus.
Adv Neurol 1986;44:935-948.
11. Novak G, Maytal J, Alshansky A, Ascher C. Risk factors for status
epilepticus in children with symptomatic epilepsy. Neurology
1997;49(2):533-537.
We thank the staff of the Medical unit of St Piers for their assistance
and cooperation. The study was sponsored in part by the British Council
and British Aerospace through a generous post-doctoral research award
presented to author MMS Jan (1999 /RIY/260/4).
12. Jaitly R, Sgro JA, Towne AR, et al. Prognostic value of EEG
monitoring after status epilepticus: a prospective adult study. J
Clin Neurophysiol 1997;14(4):326-334.
13. Steffenburg U, Hedstrom A, Lindroth A, et al. Intractable epilepsy
in a population-based series of mentally retarded children.
Epilepsia 1998;39(7):767-775.
REFERENCES
1. Annegers JF. Epidemiology and genetics of epilepsy. Neurol Clin
1994;12:15-29.
2. Treiman DM. Status Epilepticus. Baillieres Clin Neurol 1996;5(4):
821-839.
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