Evaluation and Management of Drug Resistant Epilepsy in Children

ARTICLE IN PRESS
Evaluation and management of

drug resistant epilepsy in
children
Gogi Kumar, MD
Epilepsy is one of the most common neurological conditions in drugs (AEDs)’. DRE is associated with serious consequences
children. Most children with epilepsy respond to anti- epileptic including higher mortality and worse cognitive outcomes. DRE
drugs (AEDs) but approximately 30% of children develop drug impacts several aspects of the child’s and the caregiver’s life.
resistant epilepsy (DRE) defined as ‘the failure of adequate trials
of two tolerated, appropriately chosen and used anti-epileptic Curr Probl Pediatr Adolesc Health Care 2021; 000:101035
rug resistant epilepsy Patient and families should be

D (DRE) is defined as
‘the failure of ade-
Drug resistant epilepsy (DRE) is counseled regarding the risk for
defined as ‘the failure of ade- Sudden Unexplained Death in
quate trials of two tolerated, quate trials of two tolerated, Epilepsy (SUDEP) and co-mor-
appropriately chosen and used bidities including mood disor-
anti-epileptic drugs (AEDs)’ appropriately chosen and used ders, sleep problems, cognitive
Management of DRE includes anti-epileptic drugs (AEDs)’ and memory decline, and an
early identification of this condi- overall decline in the quality of
tion. Multi-modality testing life. A seizure action plan for
including video EEG study, MRI of the brain and genetic rescue medication, in case of prolonged seizures,
testing are essential to establish the etiology and confirm should be initiated for all children with DRE. Collabo-
the diagnosis. The patient should be referred to an epi- ration with the child’s school and day care centers is
lepsy center where comprehensive evaluation and man- essential. The care team should be easily accessible to
agement is available Treatment includes use of carefully the family and should proactively educate all involved
chosen AEDs based on synergism, mechanism of action in the care of the patient about the condition and its
and side effect profile. Around 30 AEDs are available co-morbidities.
worldwide at present. Genetic diagnosis can inform man- Epilepsy is one of most common neurological condi-
agement and target precision therapy for children with tions in children.
epilepsy. If the child has focal seizures, evaluation for epi- In 2015, approximately 3 million US adults and
lepsy surgery should be undertaken. Dietary therapies 470,000 children had active epilepsy.1 The global esti-
such as the ketogenic diet and modified Atkins diet have mate of prevalence of epilepsy is 0.9% for 2.6 billion
been found to be useful in DRE. Neurostimulation devi- children.2
ces including Vagus Nerve Stimulator (VNS) i are often Epilepsy is a clinical diagnosis defined by an endur-
used for the treatment of DRE. ing predisposition to generate epileptic seizures.3 To
diagnose epilepsy, epileptic seizures must be differen-
tiated from provoked seizures.
From the Dayton Children Hospital, Wright State University Boonshoft
Most children with epilepsy will respond to medica-
School of Medicine, 1 Children’s Plaza, Dayton Ohio 45404. tions and become seizure free.4 However, some chil-
E-mail: kumarg@childrensdayton.org dren will continue to have seizures despite adequate
Conflict of Interest statement: There are no conflicts of interest related medical management.5 They develop drug resistant
to this article.
Funding: I did not receive any funding for preparation of this epilepsy defined by the International League against
manuscript. Epilepsy (ILAE) as ‘the failure of adequate trials of
Curr Probl Pediatr Adolesc Health Care 000;000101035 two tolerated, appropriately chosen and used anti-epi-
1538-5442/$ - see front matter
leptic drugs (AEDs)’.6
Ó 2021 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.cppeds.2021.101035
Curr Probl Pediatr Adolesc Health Care, & &&&& 1
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ARTICLE IN PRESS
This definition is based on the observation that if It is important to identify children with drug resis-
complete seizure control is not achieved with trials of tant epilepsy early, so that appropriate evaluation and
two appropriate antiepileptic drugs, the likelihood of management of the condition can be initiated and
success with subsequent regimens is much reduced.4,7 many of the negative consequence of recurrent seiz-
Childhood onset epilepsy has long term consequen- ures on the health related QOL for the patient and the
ces and impacts several aspects of the child’s life QOL of the caregivers can be mitigated.
including school, and later in life affects employment, Drug Resistant Epilepsy: prevalence and risk
marriage, and parenthood.8-10 Long term cognitive factors
outcomes in childhood onset epilepsy are worse in The prevalence of DRE among epilepsy patients was
those with poorly controlled epilepsy.11 Children with 30% in a recent study and the pooled incidence was
epilepsy are also at a higher risk of mortality12,13 chil- 15%.23 Risk factors for developing drug resistant epi-
dren with symptomatic epilepsy have a 20-fold greater lepsy have been elucidated in many studies. Age at
mortality compared to the general population.14 onset, symptomatic epilepsy, abnormal neuroimaging
Patients with epilepsy are at risk for SUDEP which findings, abnormal electroencephalography results,
claims 1% of patients’ lives per decade, and is the sec- history of mental retardation, neuropsychiatric disor-
ond leading neurologic cause of lost potential life- ders, febrile seizure, and status epilepticus increased
years.15 Individual risk varies substantially and is risk for DRE. Early age at onset of epilepsy was asso-
highest in those with DRE who have recent and fre- ciated with a higher risk for developing drug resistant
quent generalized tonic clonic seizures (GTCS), espe- epilepsy in a meta-analysis.23
cially during sleep.16 Other risk factors for developing drug resistance
Obviously, drug resistant epilepsy is associated with include a high number or frequency of seizures in the
serious consequences. early phase of the disorder and the presence of a
Epilepsy affects many other aspects of the child and known, often structural cause of the epilepsy, particu-
the caregiver’s life. larly hippocampal sclerosis.7,24
Patients with epilepsy can often suffer from stigma In a study looking at a sample of children with epi-
and discrimination.17 lepsy, half of DRE occurred in children with idiopathic
From the child's perspective, epilepsy-specific qual- focal epilepsy and frequent seizures at the onset of the
ity of life (QOL) is strongly related to their mental epilepsy. However the absolute number of seizures and
health and social support but not to their unprovoked or febrile status epilepticus were not asso-
seizures. Caregivers of children with epilepsy often ciated with a higher risk of developing DRE.25
have compromised quality of life specifically poorer
mental health related quality of life compared to popu-
lation norms or control groups.18
Diagnosis
It has been noted that parents of children with drug Diagnosis of epilepsy is based on confirming that the
resistant epilepsy and accompanying neurodevelop- seizure was epileptic in nature and there is a tendency to
mental problems fare worse in the mental health have recurrent seizures. Diagnosis is a multi- dimen-
related quality of life than those of healthy children.19 sional process that includes a careful description of the
Adolescents with epilepsy express that ingredients of event by eye-witnesses. The use of smart phones has
a good life (e.g. social and self-acceptance) are more helped tremendously in recording the events and provid-
difficult to attain when growing up with epilepsy due ing high quality evidence for the clinician to analyze.26
to the uncertainty caused by seizures and potential iso- A careful history that includes birth and prenatal his-
lation that results from others' reactions.20 tory, developmental milestones, age of onset of the
Psychiatric and behavior co-morbidities are com- seizures, description of the events, school perfor-
mon in children with epilepsy.21 Almost a third of mance and family history is essential. A 12 lead EKG
people with epilepsy can have a diagnosis of depres- to examine for cardiac abnormalities may be required
sion or anxiety and many can have somatic com- in some patients if the clinical history suggests a car-
plaints.22 Behavioral disturbances are up to 4.8 times diac cause. Blood tests, lumbar puncture, and other
higher in children with epilepsy than the general popu- investigations can be helpful when specific causes are
lation. suspected.26
2 Curr Probl Pediatr Adolesc Health Care, & &&&&
reserved.
ARTICLE IN PRESS
In children with DRE, video EEG studies and ambu- Genetic diagnosis can inform management and tar-
latory EEG studies are often required to capture the get precision therapy for children with epilepsy
different seizure types and characterize them so that
the therapy can be targeted appropriately.
3 T 3T 3TMRI of the brain performed with a seizure
Management
protocol is essential to evaluate It is essential that the clinician
for cortical malformations in Genetic diagnosis can inform confirms that the diagnosis of
children with DRE and to DRE is correct. In children and
examine for tumors, vascular management and target preci- adolescents, conditions that
malformations, traumatic and sion therapy for children with mimic seizures include vasova-
hypoxic injury to the brain. epilepsy gal syncope, cardiac arrhythmias,
The diagnosis of DRE should migraines, stereotypic behaviors,
be confirmed by careful history complex motor tics and inatten-
taking, physical examination and The diagnosis of DRE should be tiveness. These conditions need
multi-modality investigations. to be investigated by a careful
confirmed by careful history tak- clinical history and physical
ing, physical examination and examination as well as ancillary
Genetic studies multi-modality investigations. testing. Video EEG is invaluable
in this process. If the typical epi-
Genetic studies to establish sodes are captured during a video
the etiology for DRE have cre- EEG, the diagnosis can be confirmed or excluded.
ated a new path for diagnosis and treatment of DRE. Pseudoresistance, in which seizures persist because
After carefully excluding secondary causes such as the underlying disorder has not been adequately or
hypoxic ischemic injury, cortical malformations of appropriately treated, must be addressed before drug
the brain and brain tumors, evaluation of the genetic treatment can be considered to have failed.30
basis of DRE is one of the most frequent referral indi- Pseudoresistance can be caused by failure of drug
cations in a neurological clinic. therapy due to the wrong drug being used for the type
The genetic testing consists of karyotyping, chromo- of epilepsy the child has. Phenytoin, carbamazepine,
somal microarray, epilepsy related gene panel and gabapentin, oxcarbazepine, vigabatrin, tiagabine, and
whole exome genome sequencing (WES). pregabalin can worsen absence epilepsy and myo-
Genetic testing is more likely to be performed in clonic seizures. Lamotrigine can worsen some myo-
patients with developmental delay, epileptic encepha- clonic epilepsy syndromes. Dravet’s syndrome is an
lopathy, and generalized epilepsy. In a study on the epileptic encephalopathy of childhood caused by het-
role of genetic studies in pediatric epilepsy the yield erozygous loss-of-function mutations in SCN1A. It is
of specific genetic diagnosis was relatively high: kar- not surprising that sodium channel blocking AEDs,
yotype 14.3%, microarray 16.7%, targeted single gene such as carbamazepine, oxcarbazepine, phenytoin and
sequencing 15.4%, gene panels 46.2%, and WES lamotrigine, are usually ineffective and can even
16.7%. Overall yield of diagnosis from at least one of aggravate seizures in these patients.29
27
the above tests was 34.5%. Inadequate dosing and excessive reliance on thera-
In a similar study, genetic diagnosis was achieved in peutic drug concentrations may also lead to treatment
86 patients (31.5%) and based on the genetic diagno- failure. Chidren or parents might not be reliably
sis to guide therapy, 52.9% (18/34) became seizure- adhering to the treatment regimen due to competing
free and 38.2% (13/34) achieved seizure reduction.28 priorities or their lack of understanding of the medica-
Genetic diagnosis can inform management and tar- tion regimen.This may lead to treatment failure. Life-
get precision therapy for children with epilepsy. Iden- style choices including poor sleep hygiene and use of
tifying the mutated gene or, more precisely, the recreational drugs, especially in teenagers, can cause
specific gene variant permits rational treatment selec- more seizures and may be mistaken as drug resistant
tion, either by prescribing the most appropriate inter- epilepsy.30
vention or by avoiding medications which can Psychogenic non-epileptic seizures (PNES) are
29
paradoxically worsen the disease. common disorders managed by epilepsy centers and
reserved.
ARTICLE IN PRESS
TABLE 1. A list of websites with information related to epilepsy and its management.
Subject Website
Information about epilepsy and its types https://www.cdc.gov/epilepsy/groups/parents.htm
https://www.epilepsy.com/living-epilepsy/parents-and-caregivers/about-kids%20
Information for patients with epilepsy and caregivers https://www.ilae.org/patient-care/for-persons-with-epilepsy-and-caregivers
Role of seizure alerts https://www.epilepsy.com/learn/early-death-and-sudep/sudep/role-seizure-alerts
Seizure tracker app https://www.seizuretracker.com/Seizure_Tracker_Mobile.php
Seizure action plan https://www.epilepsy.com/learn/managing-your-epilepsy/seizure-action-plans
Guidelines and Quality measurement set https://www.aan.com/policy-and-guidelines/quality/quality-measures2/quality-
measures/epilepsy-and-seizures/
https://www.aan.com/Guidelines/home/ByTopic?topicId=23
Self-management of epilepsy https://managingepilepsywell.org
Ketogenic diet https://charliefoundation.org
https://www.matthewsfriends.org
https://www.epilepsy.com/learn/treating-seizures-and-epilepsy/dietary-thera
pies/ketogenic-diet
consist of paroxysmal motor, non-motor, or behav- A list of these medications along with their FDA
ioral alterations that resemble epileptic seizures with- indication and pediatric dosing can be found at multi-
out EEG correlates.31 ple websites (Table 1).
About one-quarter of patients who are sent for The choice of medication depends on multiple fac-
video-EEG monitoring in cases of suspected DRE suf- tors including the epilepsy type, age of the patient,
fer from PNES.32 PNES patients can often be misdiag- comorbid conditions and the adverse effect profile of
nosed with DRE and treated inappropriately without the medication. The goal of therapy is adequate sei-
any response to treatment as the underlying disorder is zure control with minimum cognitive and systemic
not being addressed. side effects. It has been difficult to find evidence for
Once the diagnosis of drug resistant epilepsy is con- which combination of medications work best together.
firmed, anti-epileptic drug combinations that are The strongest evidence in favor of synergism comes
effective and have the least cognitive and other side from nonrandomized, controlled studies involving
effects should be initiated. Other non-medication adults who received a combination of sodium val-
options including vagal nerve stimulator(VNS), Keto- proate and lamotrigine for partial-onset and general-
genic diet and epilepsy surgery evaluation should be ized seizures. There is some evidence for a
discussed. The patient should be referred to an epi- combination of efficacy for the combination of val-
lepsy center where comprehensive evaluation and proate with ethosuximide for absence seizures and
management is available. Patient and families should lamotrigine with topiramate for a range of seizure
be counseled about the risk for SUDEP and the co- types.30 Another suggestion is to use drugs with dif-
morbidities including mood disorders, sleep problems, ferent mechanisms of action and there are some ani-
cognitive and memory decline, and an overall decline mal data that support this approach.33
in the quality of life. A seizure action plan for rescue Drug-drug interactions and their effect on the dosing
medication, in case of prolonged seizures, should be and therapeutic action should be monitored carefully,
initiated for all patients. Collaboration with school most children with DRE are on polytherapy.34
and day care centers is essential. The care team should In the last decade the focus on precision drugs like
be easily accessible to the family and the community, Everolimus as an adjunctive therapy for focal seizures
and should proactively educate all involved in the associated with Tuberous sclerosis complex, based on
care of the patient about the condition and its co-mor- mTOR inhibition, has paved the way for a pharmaco-
bidities. genomic approach to the treatment of DRE.35
Repurposing of medications like fenfluramine for
Dravet’s syndrome and Cannabidiol for the treatment
Medications of Dravet’s syndrome and Lennox Gastatut syndrome
There are 30 medications approved for the treatment have also opened new horizons for the treatment of
of seizures in USA. DRE.
reserved.
ARTICLE IN PRESS
Neurostimulation Ketogenic diet

Neurostimulation is described as application of elec- Diets have been used in an attempt to control epilep-
tric current to the central nervous system with the goal tic seizures throughout the centuries, indeed there is a
of reducing seizure frequency and severity.36 biblical reference to prayer and fasting in epilepsy (St
Mark 9: 14-29).41
The classical ketogenic diet (KD) is a high fat diet
Vagus Nerve Stimulation
that uses a 4:1 ratio of total energy from fat (4) to car-
Neurostimulation has become increasingly wide- bohydrate and protein combined (1) . This diet can be
spread since vagus nerve stimulation (VNS) was difficult to tolerate and maintain so other less restric-
approved for epilepsy in the European Union in 1994, tive diets have been developed including those of
the USA in 1997, Canada in 1998, China in 2008, and lower ratios (such as 3:1), the medium-chain triglycer-
Japan in 2010.36 It is also approved for treatment of ide (MCT) KD and the modified Atkins diet (MAD).
depression, cluster headaches and obesity. The classical diet is based on a ratio of fat to carbo-
VNS is the best-studied and most widely used among hydrate and protein, usually 3:1 or 4:1. The fat compo-
the neuromodulatory modalities for treating childhood nent is provided by long chain triglycerides. Protein
epilepsy. It is safe, effective and FDA-approved.37 VNS is kept to minimum requirements for growth, and car-
is effective in treating epilepsy in children above age 4 bohydrate is very restricted. MCT is an alternative fat
above age 4 and all epilepsy types and may have addi- source that yields more ketones per kilocalorie of
tional benefit by improving cognition and quality of life. energy than long chain triglycerides, it is absorbed
The effect of VNS therapy improves over time.38 more efficiently, and is carried directly to the liver in
In a recent meta-analysis, seizure outcomes in 3474 the portal blood. This increased ketogenic potential
children with DRE, who had undergone VNS inser- means less total fat is needed in the MCT diet, this
tion, were reviewed from 99 studies. The pooled prev- enables the inclusion of more carbohydrate and pro-
alence estimates for 50%-response rate and the tein in the child’s diet.
proportion of seizure free patients, at last follow-up The mechanism of action for the KD is unknown.
(mean 2.5 years), were 56.4% and 11.6% respectively. Ketogenic diet is considered to be useful in treat-
Fewer number of anti-seizure medications tried before ment of DRE in children. A Cochrane review ana-
VNS and later age at onset of seizures were associated lyzed 11 studies that recruited 778 patients; 712
with better seizure outcomes following VNS.39 children and adolescents and 66 adults. Reported rates
VNS is surgically implanted across the left vagus of seizure freedom reached as high as 55% in a classi-
nerve to avoid activation of the sinoatrial node which cal 4:1 KD group after three months and reported rates
is innervated by the right vagus nerve. The surgical of seizure reduction reached as high as 85% in a clas-
procedure is simple and involves overnight stay. Fam- sical 4:1 KD group after three months. Studies assess-
ilies can activate the VNS by swiping the magnet during the efficacy of the MAD reported seizure freedom
ing a seizure in an attempt to stop the seizure. rates of up to 25% and seizure reduction rates of up to
New generation VNS has the ability to deliver 60% in children.41
higher-intensity stimulation in response to elevations Side effects of KD includes most commonly GI side
in heart rate, based upon the observation that 82% of effects namely vomiting, constipation and diarrheas.
epilepsy patients experience ictal tachycardia.40 Weight loss is also a common side effect in some
Common side effects include voice alteration, patients. The side effects seem to be more pronounced
cough, dyspnea, paresthesia, headache and local pain. in the classic KD (4:1) ratio. In one study, children on
Other modalities of neurostimulation include the classical KD had more vomiting and lack of
responsive neurostimulation, deep brain stimulation, energy than children on the medium chain triglyceride
and transcranial magnetic stimulation. Responsive diet.42
neurostimulation and deep brain stimulation are KD and other dietary therapies should be offered to
approved in USA for adults only. Their use in the all children and their families with DRE.
pediatric population may open new frontiers for treat- KD is the first line therapy for children with glucose
ment of drug resistant epilepsy.36 transporter-1 (GLUT-1) deficiency and pyruvate
reserved.
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dehydrogenase (PDH) deficiency. Children with The presurgical evaluation for epilepsy surgery aims
Lennox Gastaut syndrome were most commonly to identify the epileptogenic zone (EZ) that must be
started on the KD in the past, however in the last removed to give seizure freedom through the integra-
decade many new conditions including myoclonic- tion of seizure semiology, EEG, neuro- psychological
astatic epilepsy, tuberous sclerosis complex, Rett syn- evaluation, and multimodal imaging. Patients with an
drome, infantile spasms, Dravet syndrome, and chil- identified epileptogenic lesion have 2.5 times higher
dren receiving only formula and having DRE are odds of seizure freedom following surgery than those
treated with KD.43 Children with mitochondrial disor- without an identified focal lesion.46
ders also appear to do very well with KD therapy. The epilepsy surgery team is an inter-professional
The decision to start dietary therapy may depend on team consisting of neurologist with special qualification
the family’s resources, the age of the child, whether in neurophysiology, a pediatric neurosurgeon, a neuro-
the child eats orally or is fed through Gastrostomy radiologist, a neuropsychologist, a social worker and
tube and many other variables because this diet can be nursing coordinators. High resolution MRI scan, video-
difficult to maintain. EEG monitoring, Positron Emission Tomography (PET
After initiation of the KD, a trained dietitian along scan) and neuropsychiatric testing are essential in the
with the primary neurologist should follow up with workup of the child. Functional studies, such as func-
the family frequently to make changes in the diet and tional MRI (fMRI) may be used to study eloquent
monitor blood glucose, ketone levels, lipid profile, regions controlling language, motor, visual, sensory and
electrolytes, levels of zinc, magnesium, phosphorus auditory functions of the brain. Other tests include ictal
and Vitamin D levels at the minimum. For more infor- single-photon emission computed tomography (SPECT)
mation on ketogenic diet, please review the websites and magnetoencephalography (MEG).
in Table 1. Invasive testing is reserved for cases in which localiza-
tion of the epileptogenic zone is not clear or if the rela-
tionship of eloquent cortex to epileptic cortex needs to
be more precisely determined. The choice of invasive
Epilepsy surgery electrodes has included the use of subdural electrodes,
Epilepsy surgery is the most effective way to control depth electrodes, and a combination of both. Many cen-
seizures in patients with drug-resistant focal epilepsy, ters in USA are using stereotactic EEG, that consists of
often leading to improvements in cognition, behavior, stereotactically placed multiple depth electrodes.47
and quality of life. Types of surgical procedures includes temporal lobe
In a single-center trial, children and adolescents with resection, frontal lobe resection, insula resection, parietal
drug-resistant epilepsy who had undergone epilepsy lobe resection, occipital lobe resection, corpus callosot-
surgery had a significantly higher rate of freedom omy, and functional hemispherectomy. The best surgical
from seizures and better scores with respect to behav- outcomes have been noted to be achieved in patients
ior and quality of life than did those who continued who undergo temporal lobectomy (64%-80%).45
medical therapy alone at 12 months. Surgery resulted Epilepsy surgery evaluation should be initiated in every
in anticipated neurologic deficits related to the region child with DRE who has focal seizures.
of brain resection.44 Non-medication options
In the past, there has been a including neurostimulation,
wide gap between the time of Non-medication options includ- dietary therapies and epilepsy
identification of focal DRE and ing neurostimulation, dietary surgery should be considered
referral to an epilepsy center. therapies and epilepsy surgery early in the treatment of DRE.
Patients should be referred to should be considered early in
an epilepsy center as soon as
possible for epilepsy surgery
the treatment of DRE. Complementary and
evaluation because early sur- Alternative medicine
gery provides the best opportu-
nity for seizure remission. Early surgery minimizes
(CAM)
adverse social and psychological consequences as Complementary and alternative medicine (CAM)
45
well as premature death. is used widely by parents/guardians of patients
reserved.
ARTICLE IN PRESS
with epilepsy. In a study of caregivers of children a preceding electrographic or clinical seizure.50 Indi-
admitted to a regional epilepsy monitoring unit vidual risk varies substantially and is highest in those
(EMU) in southeast United States,13% of respond- with treatment-resistant epilepsy who have recent and
ents indicated current use of CAM by their child, frequent GTCS, especially during sleep. Education
16% reported past use, and 43% reported interest about SUDEP should be included as a part of the edu-
in future use, most commonly in marijuana as a cation from the time of the first visit after a diagnosis
potential treatment (23%). Over 25% of respond- of epilepsy is made. Use of seizure alarm systems and
ents expressed interest in CAM use related to side smart devices should be discussed.
effects of anti-epileptic medications and 81% of The American Academy of Neurology Epilepsy
respondents reported that they had not discussed Quality Measurement Set recommends counseling for
CAM use with their doctor.48 all females between 12-44 years of age for the effect
Thus, CAM treatment should be enquired about and of epilepsy and its treatment on contraception and
discussed with families and children with DRE. pregnancy at least annually. It also recommends qual-
Cannabis has been a subject of great interest as an ity of life assessment for patients with epilepsy and
alternative therapy for children with DRE in the past documentation of seizure frequency for patients with
decade. Approval of the Cannabidiol medication Epi- epilepsy for each seizure type. Screening for depres-
diolex for treatment of Dravet’s syndrome, Lennox sion and anxiety should be undertaken on a regular
Gastaut Syndrome and Tuberous Sclerosis Complex basis because psychiatric disorders are a common co-
related seizures has enabled the clinicians to offer morbidity of epilepsy.51 Referral to psychology and
FDA approved cannabis-based therapy.49 psychiatry should be undertaken if the child screens
positive for depression or anxiety.
Education
Management of DRE is a team effort by an interpro-
Transition to adult neurology
fessional team. The Institute of Medicine has provided Transition to an adult neurology service for children
a model of care for patients suffering from epilepsy and adolescents suffering with DRE can be a very diffi-
that relies on the close collaboration among patients cult and traumatizing process for young adults with epi-
and families, the community and the care team lepsy and their families. Many adult neurologists are not
(Figure 1). familiar with medications like cannabidiol, stiripentol
The school system plays a major role in providing and vigabatrin used in pediatric epilepsy.52 Parents and
education and rehabilitative services to children. guardians of children often feel more comfortable within
Close collaboration with the school nurses is impera- the Children’s Hospital settings due to the more personal
tive for optimal outcomes. A seizure action plan and friendly nature of the Children’s Hospital and may
should be formulated for each patient and shared with complain of feeling lost in the ‘adult” world. It is imper-
the family and the school. Patients, families and ative that the care team help young adult patients and
school nurses should be educated on the use of seizure families make this transition smoothly and the clinicians
rescue medication so that these medications can be are available to coordinate care with their adult col-
administered in a timely manner. leagues if the need arises.
Sudden unexpected death in epilepsy (SUDEP) is a Management of DRE is a team effort and close col-
common cause of death among laboration between the school
people with epilepsy (PWE), system, community, patients
claiming 1% of patients’ lives Management of DRE is a team and families, and care team is
per decade, and is the second effort and close collaboration required.
leading neurologic cause of lost between the school system, Conclusion: Drug Resistant
potential life-years. When wit- community, patients and fami- epilepsy is a serious condition
nessed outside the hospital or that has long term consequen-
recorded on video EEG, most lies, and care team is required. ces on a child’s cognition,
SUDEPs follow 1 generalized behavior and health related
tonic-clonic seizures (GTCS) with death during the quality of life and increases the risk of premature
postictal state. However, some SUDEPs occur without death. Early identification of this condition and
reserved.
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Figure 1. Care model for DRE
reserved.
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referral to an epilepsy center, where multi-modality 16. Tomson T, Nashef L, Ryvlin P. Sudden unexpected death in
investigations and therapeutic interventions are epilepsy: current knowledge and future directions. Lancet
employed is critical to optimize the outcomes. Close Neurol 2008;7(11):1021–31.
17. Quintas R, Raggi A, Giovannetti AM, et al. Psychosocial
collaboration among the patients, families, care team difficulties in people with epilepsy: a systematic review of
and the community is essential for optimal functional literature from 2005 until 2010. Epilepsy Behav 2012;25
and clinical outcomes and optimal family adaptation. (1):60–7.
18. Fayed N, Davis AM, Streiner DL, et al. Children's perspective
of quality of life in epilepsy. Neurology 2015;84(18):1830–7.
19. Bompori E, Niakas D, Nakou I, Siamopoulou-Mavridou A,
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Evaluation and Management of Drug Resistant Epilepsy in Children

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Evaluation and management of

rug resistant epilepsy Patient and families should be

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Neurostimulation Ketogenic diet

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Figure 1. Care model for DRE

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