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Nigerian J Paediatrics 2016 vol 43 issue 3

Nigerian J Paediatrics 2016 vol 43 issue 3

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7Seizure related death in children with epilepsy
Niger J Paediatr 2016; 43 (4): 269 – 272
ORIGINAL
Asindi AA
Seizure-related death in children
Eyong KI
with epilepsy
DOI:http://dx.doi.org/10.4314/njp.v43i4.7
Accepted: 16th August 2016
Abstract : Children with epilepsy
pliance to antiepileptic drugs
have a significantly higher rate of
(AED),
poorly
controlled
Asindi AA (
)
death than the general population.
(intractable and refractory) sei-
Eyong KI
The cause of premature death
zures, impaired cognition, struc-
Department of Paediatrics,
College of Medical Sciences,
among epileptics is contributed by
tural/metabolic aetiology and an-
University of Calabar, Nigeria.
the underlying cause, coexisting
tiepileptic drug polypharmacy tend
Email: asindi.asindi@yahoo.com
neurologic compromise and the
to carry poor prognosis. Therefore,
epilepsy itself. Mortality directly
parents need to be appropriately
related to seizures in paediatric
advised about the risk of seizure-
epilepsy is the subject of this re-
related premature death. Early
view. Seizure-related deaths in
identification, compliance with
epileptics arise from status epilep-
AED prescription, and treatment of
ticus, aspiration pneumonia, as
comorbid conditions can reduce
well as sudden and unexpected
mortality risk and improve health
death in epilepsy (SUDEP). Epi-
outcomes in children with epi-
lepsy per se enhances the risks of
lepsy. Children with intractable
accidents and suicide. Children
types of epilepsy may benefit from
with epilepsy who are otherwise
medical marijuana and neurosur-
neurologically intact and with
gery.
normal neuroimaging findings
have an exceedingly low risk of
Key Words: Childhood epilepsy,
seizure-related death. Poor com-
seizure-related death, prevention
Introduction
to report to hospital hence the statistics of death related
to epilepsy are rare in Africa. This communication fo-
Epilepsy is a common childhood neurologic disorder
cuses on the mortality risk due to the direct effect of
and children with epileptic convulsions have an in-
seizures in children with epilepsy. The rationale is to
creased risk of premature death compared with children
create an awareness among medical personnel and par-
without epilepsy. A multicentre survey in the USA
1-5
ents on the dangers posed by every seizure episode.
showed that among children with epilepsy in South
Doctors should not fail to adequately educate parents
Carolina during 2000 – 2011, the overall mortality rate
about the risks of death. Though it is controversial if the
was 8.8 deaths per 1,000 person-years and the annual
child should be told concerning the death aspect, an
risk for death was 0.84 percent compared with 0.22 per-
awareness of the increased risk for premature death as-
cent among children of the same ages without epilepsy.
4
sociated with epilepsy may enhance patients' and par-
Children with epilepsy who are otherwise neurologically
ents' cooperation with therapy.
normal tend to have an exceedingly low risk of seizure-
related death. Symptomatic forms of epilepsy - those
Death from Status epilepticus
with a known cause — generally have poorer outcomes
than idiopathic forms. The term "cryptogenic" has been
Status epilepticus (SE) is a medical emergency associ-
ated with significant morbidity and mortality.
1-5
used to describe epilepsy believed to be symptomatic
The
but for which the cause is unknown. The prognosis for
duration of a seizure appears to be the single major pre-
dictor of mortality.
3-5
these cases is poorly understood.
Status epilepticus is defined as a
Associated congenital malformations, chromosomal
continuous seizure lasting more than 30 minutes, or two
abnormalities, syndromic disorders, cerebral palsy and
or more seizures without full recovery of consciousness
cardiovascular anomalies do boost the mortality rate in
between any of them. There is the non-convulsive type
children with epilepsy. Invariably, increased mortality
of status epilepticus (NCSE) whereby the prolonged
rate may occur due to progression of the underlying dis-
seizure manifests primarily as altered mental state with-
out convulsive movements.
3-5
ease.
GABAergic mechanisms
play a crucial role in terminating seizures but in SE the
In Nigeria most deaths in individuals with epilepsy oc-
innate inhibitory mechanisms in the brain that put a halt
cur at home with no documentation. The stigma of epi-
6
to the seizure are no longer effective. Since only a small
lepsy may dwarf the wish of the parents and the patient
fraction of seizures go on to become SE, the probability
270
that a given seizure will proceed to SE is small at the
human and cow urine are common native concoctions
start of the seizure but increases as the seizure duration
for convulsions in some Nigerian communities. Bacte-
increases. Most seizures cease within a minute or two
rial pneumonia, lipoid pneumonia and chemical pneu-
and if the seizure is prolonged beyond a few minutes, it
monitis are the expected consequences of such unortho-
is unlikely to stop by itself. If a seizure lasts > 5 min,
dox and undesirable treatment. Being in the prone posi-
clinical experience suggests that the likelihood of spon-
tion is a risk factor for aspiration pneumonia. Turning
taneous termination decreases.
5,7,8
Uncontrolled tonic-
into the prone position after a convulsive seizure can
clonic seizures, especially at night, and children with
definitely be a contributing factor in aspiration. This is
Dravet syndrome, a rare and catastrophic form of intrac-
probably why sleep is considered a risk factor in chil-
table epilepsy, carry a high fatality frequency.
3
dren with epilepsy.
About 9 – 31% of patients with SE may fail to respond to
standard treatment. This subgroup of refractory status
Sudden unexpected death in epilepsy (SUDEP)
epilepticus (RSE) has greater morbidity and mortality.
9
RSE is defined as continuous or repetitive seizures last-
SUDEP is defined as sudden, unexpected, witnessed or
ing longer than 60 min despite treatment with a benzodi-
unwitnessed, non-traumatic and non-drowning death in
azepine (lorazepam or diazepam) plus another standard
a patient with epilepsy, with or without evidence of a
anticonvulsant (usually phenytoin/fosphenytoin) in ade-
seizure and excluding status epilepticus. Autopsy in this
quate loading dose. Suchis treated with inhalational an-
condition does not reveal an anatomical or toxicological
aesthetic agents. Regardless of seizure type, isoflurane
9
cause for the death. This condition is not rare; it contrib-
utes 8-17 percent of deaths in people with epilepsy.
11
and desflurane have consistently stopped epileptic dis-
charges with adequate, sustained electrographic burst
The average age for SUDEP is 28- 35 years but this con-
dition has also been reported in children.
11,12
suppression within minutes of initiation of therapy. Ma-
A Finnish
lignant SE is a severe variant of RSE, in which the sei-
study followed 245 children with epilepsy for 40 years
zure fails to respond to aggressive treatment even with
and found that 24 percent of them died and that 38 per-
cent of the deaths were due to SUDEP.
1
anaesthetic agents. It commonly occurs in children in the
setting of encephalitis.
10
Various pathophysiologic events contribute to SUDEP.
Prolonged SE can lead to cerebral oedema, cardiac dys-
Evaluation of autonomic cardiovascular reflexes in pa-
rhythmia, autonomic dysfunction, and neurogenic pul-
tients with epilepsies indicates a dysfunction of both the
monary oedema. Excessive muscular activities during
sympathetic and parasympathetic components. These
generalised tonic-clonic seizure result in hyperthermia,
include central apnoea, neurogenic pulmonary oedema
metabolic acidosis, hypoglycaemia, and hyperkalaemia
and airway obstruction; others are cardiac arrhythmias
13-17
all of which can grossly compromise cardiorespiratory
leading to acute cardiac failure and arrest.
Cardiac
functions. In developing countries, poverty and igno-
arrhythmias, during the ictal and interictal periods, lead-
rance play a delaying role whereby even the very sick
ing to acute cardiac failure may contribute significantly
children report late for hospital care. It is not uncommon
to SUDEP. The death is not usually as a direct result of
to encounter children who have convulsed all night at
a seizure or status epilepticus but occurs suddenly dur-
home, and some have gone through alternative source of
ing normal or benign circumstances. In a majority of
treatment for hours before reporting to hospital as a last
cases, patients had had a seizure immediately before
resort. Such cases obviously have very slim chance of
death. In all witnessed deaths, seizure had stopped be-
survival. The goal of pharmacologic therapy is to
fore death, and in many cases, the patient had even re-
achieve rapid and safe termination of the seizure and to
gained full consciousness before he dies. In SUDEP the
victim may succumb through a single, brief attack.
15,18
prevent its recurrence, without adverse effects on the
cardiovascular and respiratory systems or alteration of
Repetitive exposure to catecholamines during fits is
the level of consciousness. Based on this recent under-
known to cause myocardial fibrosis. These fibrotic areas
standing of the pathophysiology, it is now considered
act as foci for cardiac arrhythmias. Autopsies following
that any seizure that lasts more than 5 minutes probably
death from SUDEP have demonstrated fibrosis of the
needs to be treated as SE.
5,8
cardiac conducting system in some patients.
18
Frequent and potentially fatal asystole is an indication
Airway obstruction and Pneumonia
for a permanent pacemaker insertion to avoid sudden
unexpected death.
The possibility of aspiration during a seizure is a well-
recognized cause of death in epilepsy and tends to occur
Seizure severity is a risk factor because intractable epi-
in children with coexistent neurological compromise.
4
leptics have a higher rate of SUDEP than patients with
The combination of dysphagia, gastroesophageal reflux,
well-controlled epilepsy do. Epilepsy is said to be in-
poor airway protection, renders the patients vulnerable.
tractable when a patient requires at least two or three
It can also be dangerous if a child has a seizure with
AEDs taken simultaneously to control the attacks. Poor
food in his mouth. Such a child may choke as the food
control of epilepsy, and polytherapy in the management
can go down the airway instead of the stomach. It is not
of patients, render some epileptics vulnerable to
SUDEP.
16,17
uncommon to observe adults force liquid concoctions
Epileptic children with severe cognitive
down the throat of children who are actively convuls-
impairment tend to have an increased risk of sudden,
unexplained death. The most likely explanation for this
3
ing. Native herbs, palm kernel oil, olive oil including
271
association is that the more mentally deranged epileptic
Recommendations
children are more likely are they to have intractable sei-
zures.
3,5
Health care and social service providers, advocacy
groups and others interested in improving outcomes for
Seizure-related injury and death
children with epilepsy can work together to assess
whether coordinated care for these children can prevent
Epilepsy enhances the risks of accidents, such as falls
complications associated with epilepsy and reduce their
from heights, burns, traffic injuries and drowning.
19,20,21
risk for premature death. Taking AED medications as
The kitchen, with its ovens, burners, and sharp knives is
prescribed is the key factor in reducing the number of
a potential danger zone. Adjusting how food is prepared,
seizures and therefore the risk of premature death. Par-
cooked, and cleaned up may make the kitchen safer for
ents of epileptic children have the right to know the
children with seizures. Catastrophic burns may occur if a
mortality risks associated with epilepsy. Once the par-
seizure throws a patient into an open fire. This may be
ents or intelligent teenagers know and accept the risks,
common in poor socioeconomic settings where families
they should be able to decide for themselves what pre-
cook with firewood or kerosene stove in the open on
cautions to take. Ensuring appropriate and timely health
ground level where children may be playing around.
care and social services for children with epilepsy, espe-
cially those with complications, might reduce the risk
In some superstitious communities, it is a taboo to touch
for premature death. Patients who have persistent gener-
an actively convulsing person for fear of contagion
alized seizures beyond 5 minutes deserve to be treated as
hence should a convulsing child fall into a burning fur-
SE. It is a recent knowledge that some children with
nace, such may be left to perish. If an epileptic experi-
22
intractable epilepsy types such as Dravet, Doose and
ences an attack while walking across a busy street or
Lennox-Gaustat syndromes, have benefitted from Can-
nabidiol extract from Cannabis.
27,28
while riding a bicycle, instant death may be the out-
It is equally impor-
come. Likewise, drowning episodes have been reported
tant to attend to the general medical condition of the
in streams, swimming pool and even in bathtubs within
patient, even as the AEDs are being administered.
the house.
21
Achieving complete seizure control with epilepsy sur-
Suicide
gery in intractable patients, who are good surgical candi-
dates, reduces the risk of death to a level indistinguish-
It is important to assess the psychological status of ado-
able from that of the general population.
lescents with epilepsy. Epilepsy is often complicated by
Some dogs have been trained to bark or otherwise alert
depression, impulsivity, psychosis, and substance abuse,
families when a child has a seizure while playing out-
all of which increase the risk for suicide among epilep-
side or in another room. Public interest in seizure assis-
tics.
22,23, 24
The authors of this communication have en-
tance dogs has fuelled demand for dogs with these
skills. The term "seizure dog" covers a variety of ac-
29
countered a 14-year old female who had made repeated
attempts to cut into her radial artery. On interrogation,
tivities associated with a service dog's response to an
she confessed it was a deliberate effort to terminate her
epilepsy seizure. Some dogs learn to lie next to someone
life so as to end the embarrassment from frequent fits
having a seizure to prevent injury. Others are said to be
which she had suffered in front of her mates at school.
able to activate alarm systems. Seizure dogs therefore
The patient was referred for psychiatric evaluation and
trigger securing speedy assistance when a seizure occurs
follow up. Some medication used as AED such as
or alerting others for help.
Levetiracetam has been associated with suicidal tenden-
cies.
25
Treatment-related causes
Conclusion
Poor compliance with prescribed antiepileptic drug
Seizure per se can contribute to mortality in childhood
(AED) and antiepileptic polytherapy, constitute risk
epilepsy. Parents, and perhaps the adolescent child,
factors for premature death in epilepsy.
1-5,16,17
Non-
should be enlightened regarding this possibility. Poorly
compliance to appropriate medication is one of the most
controlled (intractable and refractory) seizure frequency
common causes of status epilepticus among children
constitute a major risk factor. It is pertinent that clini-
with epilepsy. In known epileptics the most common
cians should enlighten and warn the parents concerning
cause is a change in medication, This may involve the
medication. Strict compliance with antiepileptic drugs
use of substandard drugs; the change may be directed
and other adjunct preventive measures is the key in re-
by the clinician, or may be due to an abrupt cessation on
ducing premature death in children with epilepsy.
the parent’s part whether intentional or unintentional.­
26
Regarding under-reporting of seizure-related deaths, the
Over-dosage and overzealous administration of an anti-
use of verbal autopsy is being strongly advocated espe-
cially in developing countries.
30
convulsant by intravenous route during the active phase
This involves a stan-
of a seizure, can compromise cardiorespiratory functions
dardized method of collecting data retrospectively from
with a fatal outcome.
parents and siblings of an epileptic who died suddenly
and unexpectedly. The data, when analysed can help in
determining the diagnosis of SUDEP hence its preva-
272
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