developmental disabilities symposium chapter
DESCRIPTION
Ross Finesmith MDTRANSCRIPT
Community Based Anti-Epileptic Treatment in theDevelopmentally Disabled
Ross FineSmith, MDClinical Instructor of NeurologyNYU School of Medicine Medical
2
Introduction
This chapter reviews the unique factors associated with the
management of epilepsy and antiepileptics drugs (AED) in the
community based population of individuals with developmental
disabilities (DD).
Many of the same principles that are established for AED therapy
in the non-handicapped population can be applied to the individual
with a DD. These principles can be used as guidelines when making
decisions about initiating drug therapy or determining the most
appropriate AED 1. These guidelines are listed in Table 1-1. There are
additional specific challenges to the physician in the community
treating patients with epilepsy and a moderate to profound DD. These
factors include; a higher incidence of difficult to control seizure
disorders, individual cognitive disability may limit feasibility of
neurodiagnostic testing, adverse effects are difficult to assess in those
with limited communicative ability and patients with a DD are more
likely to experience adverse effects from
AED’s 2.
The Relocation of Persons with Disabilities
In the past, most patients with severe disabilities and epilepsy were
treated by pediatricians or pediatric neurologists and were often
admitted to long term care
3
facilities in late childhood or as young adults where staff physicians
provided
their medical and neurological care. The current trend of
deinstitutionalization of individuals with moderate to profound DD’s
has “relocated” this group to a variety of community settings
including; group homes, sponsored living, supported living
arrangements and supervised apartment living. Their medical and
neurological care is now the responsibility of physicians located in
these regions. Unlike the staff physicians in the developmental
centers, most physicians in the community have limited experience or
exposure to persons with significant DD’s. This is not a result of
discrimination, but one simply of demographics. These patients were
institutionalized and typically did not receive treatment from outside
physicians. The relocating process has resulted in a marked increase
in medical consumers with DD’s requiring medical care in our
communities.
In the state of New Jersey there were 5,841 people in
developmental centers in 1986 and as of March 1999, there were
3,623. These 2000 persons have been relocated and are now living in
many communities throughout New Jersey. The number of individuals
residing in group homes has tripled in the last 8 years and, in addition,
there are 2,900 persons on the urgent waiting list and 1,000 on a non-
4
urgent waiting list 3,4. This is a national trend and is not specific to one
state5.
The relocation has been especially challenging to those
physicians treating patients with epilepsy. There is a 30-50%
incidence of epilepsy in individuals with DD’s 6 and as many as 45% of
those have medically refractory epilepsy (MRE)7-9. Patients with MRE
require significantly more of the physicians practice time, than other
patients in the community with epilepsy. This group of patients needs
more aggressive management and treatment and often requires the
use of recently approved AED’s, novel therapies such as the vagal
nerve stimulator and the ketogenic diet, and when appropriate, a
referral for evaluation for epilepsy surgery.
The remainder of this paper is designed to familiarize and aid in
the development of a community-based program to more effectively
treat patients with epilepsy and moderate to profound DD’s.
Legal Guardians and Family Members
Approximately 50% of individuals that are approved and eligible for
services from the Division of Developmental Disabilities (DDD) are
residing with parents or family members3. Many of these persons are
on the waiting lists for group home placement. These individuals will
frequently be seen by the same family physician that has cared for
them most of their lives. Referral to a neurologist may occur if there is
5
an initial seizure or a change in seizure status in those with pre-
existing epilepsy.
Family members have a personal interest in the care of a relative
and this may reflect in the accuracy of the interval history,
management of medication and vigilance in reporting undesirable side
effects. However, aging parents may have difficulty remembering to
give medications, accurately count seizures and recognize side effects.
Parents may have difficulty physically transporting their child to the
office or hospital. This especially problematic if the child has a physical
handicapping condition, such as cerebral palsy.
Most individuals with a moderate to profound DD with cognitive
impairment are evaluated and assessed not to be competent to make
discussions for their own well-being. A legal gaurdian must therefore
be appointed. Parents and other family members may live nearby and
be involved with the DD person’s care and elect not to be the legal
guardian. In addition, many individuals have no close family members
involved and legal guardianship is assigned to a legal representative
within the DDD. It is good practice to routinely obtain the name and
address of the legal guardian and contact them by phone to establish a
relationship. It is necessary to call if there are any questions regarding
the need for written consent for a given procedure. Changing
medications, laboratory blood work, non-invasive radiological and
electrophysiological studies usually do not require consent. However,
6
conscious sedation and general anesthesia are occasionally required to
perform a test or procedure, and since this involves additional medical
risk, written consent should be obtained in advance. The risks and
benefits of any invasive procedure should be discussed with the legal
guardian. There are few individuals with moderate DD’s who are their
own guardian. Whether the person has a legal guardian or not, all
medical discussions should be attempted to be explained to the
patient personally. There are also laws governing the enrollment of
persons with DD’s into research protocols. The research protocol must
be approved by a regional Institutional Review Board and the states
DDD research committee. This was established to ensure that these
patients are not unnecessarily enrolled in higher risk protocols.
The primary caregivers for individuals with DD’s are often group
home staff and this can frequently result in the family being
overlooked in the medical treatment process. Family members are
occasionally present, but due to parental age, health and living
arrangements, parents are unable to be present for many visits.
Health care providers are strongly encouraged to contact the next of
kin to introduce themselves and obtain additional medical information.
Relatives are usually happy to hear from a medical provider and will
supply additional medical information. If family members express
interest in the treatment plan, they should be encouraged to be
present at office visits. This can be invaluable information, as the
7
following account will describe. An individual with Autism and a history
of epilepsy was evaluated by a neurologist and was requested to
provide on-going neurological care. The patient was accompanied by a
staff member that has known the him for the 2 months he has resided
at the group home. A discharge summary from the developmental
center reported that were no seizures observed in the 4 years he
resided there. An EEG and MRI were unremarkable and the patient
was considered a relatively low risk for seizure relapse if the AED was
discontinued, based on this history. His legal guardian was a DDD
representative and the next of kin was a sister that resided in the next
state. The sister was contacted by phone at the time of the office visit
and she reported that over the past nine years, three separate
neurologists attempted to wean her nephew off Tegretol because he
had been seizure free for up to 4 years at a time. All three occasions
resulted in status epilepticus and during one hospitalization he
developed a severe pneumonia and required a prolong hospitalization.
The neurologist elected not pursue this option, the patient has been
followed for three years and continues to be seizure free on Tegretol.
Group Home Structure and Staff
Group home staff, sponsors and personal aids are of great importance
in the execution of the medical treatment plan for persons with DD’s.
A staff member will accompany the patient to the office and are often
times the only source of information at that time. Most persons
8
relocating from developmental centers should have a brief medical
discharge summary. The level of experience, motivation and
competence of the staff varies significantly. Staff names should always
be noted in the margins of the chart adjacent to the medical note. This
will allow for tracking and resolving many problems. It will benefit the
health care provider to educate the accompanying staff and discuss
what is needed each visit. Community or agency presentations and “in-
services” can helpful in educating care providers.
Group home managers oversee the care and treatment of each
of the residents and are typically very reliable and dedicated. It may
be helpful to deal directly with manager on the more difficult to
manage individuals with epilepsy.
Physicians can develop a seizure record form that the staff must
complete after each seizure. The form can be tailored by the physician
to obtain pertinent information describing the event which will allow for
more accurate documentation of the number of seizures and
characterization of the seizure type. This type of form is especially
helpful since the staff member that witnessed a seizure may not be the
same staff that accompanies the patient to the office visit. This seizure
record form can be quickly reviewed at each visit. This will also allow
for a more accurate assessment of the current treatment and more
effective medication adjustments can be made. These seizure logs
should be kept in the person’s medical folder were the medication
9
schedule and medical information is keep. The folder should
accompany the patient to the each visit.
Most group homes keep accurate medication records and log
books. In addition, many now have prescriptions filled at pharmacies
that offer “bubble packs”. Each dose is individually encased in a small
air bubble on a sheet with multiple rows of individual doses. After the
dose is given, a mark is made at the corresponding time in the
person’s medication log. This leaves much less chance of missed
doses. Not all group home staff is allowed to administer and dispense
medications. Each staff allowed to preform this duty must be “med
trained”.
Working within the regulations the group homes are mandated to
adhere to can be tedious and frustrating to those that are unfamiliar
with the requirements. The regulations are not established by the
group homes, but are state mandated, in an attempt to insure safety.
For example, on prescriptions the physician must write the specific
times medications are to be administered (i.e. q8am and 8pm) instead
of BID. Staff can not administer any medication without these specifics
and the prescription must be re-written. If doses are adjusted over the
phone, it must be followed by a written prescription that is mailed or
faxed so there is appropriate documentation at the group home. This is
problematic when these changes are made during on-call hours.
10
Neurodiagnostic Testing
Persons with significant disabilities and cognitive impairment often do
not fully understand why they having a test performed. It is similar to a
child of the same mental age being unable to participate in a testing
situation. In addition, there is a higher incidence of psychological and
psychiatric conditions that compound the difficulty in obtaining these
studies. MRI of the brain requires the patient to lie very still for
approximately 40 minutes and several different forms of sedation
made are administered. This may simply include oral benzodiazepines
or require conscious sedation provided by the anesthesiologists. An
EEG can be significantly altered or suppressed with many of the
sedating medications, so the utility of this study is limited in some
cases. The determination of the seizure type would then have to be
based on the clinical description of the event, patient history and the
MRI.
Neurodiagnostic studies on our patients can be very time
consuming and often frustrating for busy MRI facilities and EEG labs.
Antiepileptic Medication
After the diagnosis of epilepsy and seizure type has been established,
the AED that is felt to be most effective with the least chance of side
effects is determined. This is based on whether the seizures are
primary generalized, partial, atonic or myoclonic. A careful review of
11
the history is necessary to insure an AED that was used previously with
adverse effects is not reinstituted.
Co-morbid conditions and mode of drug delivery are prominent
issues in the DD. There is a higher incidence of behavioral and
psychiatric conditions in the DD population and AED’s are commonly
used as mood stabilizers to treat these conditions. Psychiatric co-
morbidities have been reported to occur in 25% and severe
maladaptive behavior in up to 55% of those meeting criteria for mental
retardation10. Depakote and Tegretol are the most commonly used
AED’s in the treatment of bipolar disorder, mania, intermittent
explosive disorder and in the management of aggressive behavior.
Therefore, when choosing a medication to treat seizures, the
psychiatric history must also be obtained. If a patient was previously
treated with Depakote or Tegretol as a mood stabilizer and it was
tolerated and effective, the same medication should be considered for
an initial anticonvulsant. This lowers the risk of adverse events since it
was previously tolerated and may also benefit behaviors. Conversely, a
previously documented adverse effect, such as agitation, would
dismiss a medication.
Tegretol (carbamazepine) is a first-line AED for partial onset and
some forms of generalized seizures. Tegretol is an excellent choice in
the treatment of individuals with DD’s because it has minimal adverse
effects on cognition and behavior. Tegretol is also indicated in the
12
treatment of bipolar disorder and trigeminal neuralgia. It can be used
as a single agent to treat the relatively common co-morbidity of mood
disorder and epilepsy11. Adverse behavioral reactions occur
infrequently and may be due to the tricyclic ring structure in Tegretol.
This may result in mild mood elevating properties that would be
problematic in a patient with hypomania that has not been detected or
diagnosed. These patients may become agitated, irritable and
hyperactive. Hyponatremia is a known side effect and can be
exacerbated by patients who drink free water habitually or due to
dryness as a side effect of antidepressants or antipsychotics.
An additional advantage of Tegretol is the multiple formulations
available. The chewable tablets are used in patients unable to swallow
tablets and the extended release tablets allow for less frequent dosing.
Carbatrol is newer form of extended release carbamazepine that is
produced in a capsule that can be opened and sprinkled on food. This
has allowed the use of an extended release form in young children.
Depakote (valproate) is a major AED that has a broad spectrum
and is effective against primary generalized, partial, myoclonic
seizures and infantile spasms. Depakote is also indicated in the
treatment of mania and migraine headaches. Both of these conditions
commonly occur in patients with epilepsy. Additional uses in the DD
population include; behavioral cycling12, aggressive behaviors 13,14 and
hyperactivity/agitation in Autism15. This medication should be used in a
13
very limited fashion or not at all in children under 2 years of age
because this group of patients has a significant risk of hepatotoxicity.
These patients are at even greater risk if they have a severe
developmental delay, are on additional AED’s or have a
neurometabolic disorder16. Thrombocytopenia is also a known side
effect and is rarely serious, however, if an individual’s DD includes
ataxia with frequent falls caution should be used. Depakote also is
available as a liquid, IV formulation that may be administered through
a gastric tube and sprinkle capsules.
Dilantin (phenytoin) has a very safe profile and is effective in the
treatment of partial and generalized seizures. There does not appear
to be any significant mood or behavioral effects. The advantage of
Dilantin is that it has a long half-life and may be given once a day. This
is helpful in those with compliance problems. It is available in liquid,
chewable and IV formulation. Dilantin is not a first choice AED in
person’s with DD because the side effect profile is especially
problematic in this population. Oral hygiene is commonly a significant
problem in individuals with DD and this is complicated by the known
side effect of gingival hyperplasia in Dilantin use. In addition,
individuals with DD are often susceptible to balance disturbances
which Dilantin can exacerbate17.
Phenobarbital is the oldest and one of the safest AED’s in current
use. It is the drug of choice on children under 2 years and is effective
14
against a wide range of seizure types. It is not commonly used in older
patients because it has been shown to slow cognition and learning and
has adverse effects on mood, including irritability in children and
depression in adults18. However, it is a very good anticonvulsant and
there is patients that respond exceptionally well and is unable to be
changed to other AED’s.
Felbamate (Felabatol) was the first new generation AED and was
widely used and accepted until the post-marketing experience
revealed a high incidence of hepatic failure and aplastic anemia. It had
a favorable side effect profile for many patients with DD’s. It appeared
to have a mild stimulant quality and therefore was beneficial for
psychomotor slowing and reducing appetite. This same effect was
greater in a subgroup and resulted in insomnia and anorexia. Felbatol
has a wide spectrum of anticonvulsant activity and is especially
effective in Lennox-Gastaut syndrome. This medication should be used
only when the risk-benefit ratio has been carefully evaluated by all of
those involved in the person’s care.
Neurontin (Gabapentin) is effective as an adjunctive therapy in
partial seizures. It is widely used for neuropathic pain syndromes and
refractory bipolar disorder, but is only indicated for partial seizures.
Neurontin is available as a capsule only and has no serious medical
side effects. It has minimal protein binding and hepatic metabolism so
15
it has minimal interactions with other medications and can be used
safely in other medical conditions.
Lamictal (Lamotrigine) also has a wide spectrum of
anticonvulsant activity, is effective against Lennox-Gastaut and
effective in monotherapy. Lamictal also appears to have a mild mood
elevating quality and is rarely sedating. It also has mood stabilizing
qualities and is being used in bipolar disorder. This combination gives
Lamictal a very favorable profile for the use in individuals with DD’s
19,20. However, there have been reports of adverse behavioral effects
including marked elevation of mood and agitation in this population of
patients 21,22.
Initially Lamictal was found to be causing a concerning number
of allergic reactions with subsequent development of Stevens-Johnson
syndrome. However, it has since been established that the incidence of
this reaction is directly related to the rate of titration. The slower the
rate of titration, the less likely a reaction will occur. There is little
chance of complications if increased by 2.5-5mg per week for children
and 12.5mg per week for adults. Lamictal is also available in chewable
tablets.
Topamax (Topiramate) is indicated for partial seizures and
Lennox-Gastaut syndrome. It has been very effective in difficult to
manage seizure disorders, is typically well tolerated and is effective in
monotherapy. Many studies have shown cognitive side effects and
16
word finding difficulties. This has not been a significant problem in the
DD population. Topamax is also available in sprinkle formulation.
Gabitril (Tiagabine) is approved for adjunctive treatment of
partial seizures and has been associated with any behavioral effects.
Available in tablet forms only.
Sabril (vigabatrin) is not approved in this country and it may not
obtain approval. Changes in the white matter in animal studies and
concerns about visual field deficits may prevent its approval. It is
obtained from other countries and is effective and well tolerated in
persons with DD’s 23. Sabril has been most useful in the treatment of
infantile spasms.
Oxcabazepine (Trileptal) will be available soon. It is a variant of
carbamazepine, but metabolically bypasses the problematic epoxide
intermediate that is responsible for many of the side effects of
carbamazepine, including sedation. Patients are therefore able to
tolerate higher doses and this will result in a greater chance of
successful monotherapy. This should be very beneficial for use its use
in individuals with DD’s 24.
I feel reason there are so many conflicting reports concerning the
adverse behavioral effects of AED’s on DD person’s, is due to the fact
that we are unable to consistently recognize pre-existing psychiatric
disorders in handicapped individuals. This results in AED choice that
may not have been used if the condition was recognized and may
17
aggravate a condition. In addition, DD persons often are unable
communicate side effects and may act out only when the side effects
are intolerable.
Individuals recently discharged from developmental centers are
may have had appropriate AED management. Epileptologist are
frequently contracted to aid in the management of patients with
epilepsy residing in developmental centers in New Jersey. This is not
true in all settings and some physicians in the community continue
AED’s indefinitely 25 . Re-evaluation of the patients epilepsy and need
for AED’s are frequently necessary. Monotherapy should be attempted
since it has been shown to be effective in up to 90% of institutionalized
persons with epilepsy 26,27. Withdrawing AED’s, especially Phenobarbital
can result in a marked improvement in alertness and mood. An
increase in muscle tone can be seen in some individuals with cerebral
palsy or acquired hemiplegia after Phenobarbital is withdrawn.
Baclofen is a good treatment for the spastically. Occasionally, an
unpleasant underlying personality or mood will be unmasked when the
AED is withdrawn. Mania can appear as Depakote or Tegretol are
withdrawn28. If there were no signs of side effects of the medication
that was withdrawn, it can simply be restarted to treat the unmasked
psychiatric disorder.
The field of developmental neurology is an evolving field of
study. It includes understanding both the unique medical needs of
18
those with DD’s and the constraints involved in their medical care. Our
ability to successfully incorporate these unique provisions into current
clinical practice depends on the initiative, motivation and cooperation
we have as a medical community. Further collaborative studies are
required to determine the efficacy of alternative therapies, such as
vagal nerve stimulation 29,30 and epilepsy surgery 27 in individuals with
DD’s. Cooperation with diagnostic testing centers and educating our
communities is essential to the successful ongoing implementation of
appropriate neurological care to those with moderate to profound
DD’s.
19
References
1. Coulter DL. Comprehensive management of epilepsy in persons with mental retardation. Epilepsia 1997;38(S4):S24-31.
2. Alvarez N, Besag F, Iivanainen M. Use of antiepileptic drugs in the treatment of epilepsy in people with intellectual disability. Journal of Intellectual Disability Research 1998;42(1):1-15.
3. New Jersey Department of Human Services: Division of Developmental Disabilities. Annual Report to the Constituency. August 21, 1998.
4. The Association for Retarded Citizens. Matrix of Program Services. July 15,1998.
5. Braddock D, Hemp R, Bachelder L, Fujiura G. The state of states in developmental disabilities. 4th ed. Washington. DC. American Association of Mental Retardation, 1995.
6. Sunder TR. Meeting the challenge of epilepsy in persons with multiple handicaps. J Child Neurol 1997;12(1):S38-S43.
7. Steffenberg U, Hedstrom A, Lindroth A, Wilklund LM, Hagberg G, Kyllerman M. Intractable epilepsy in a population-based series of mentally retarded children. Epilepsia 1998;39(7):767-775.
8. Marcus JC. Control of epilepsy in a population with mental retardation: Lack of correlation with IQ, neurologic status, and the electroencephalogram. Am J Ment Retard 1993;(98S)47-51.
9. Singh BK, Towle PO. Antiepileptic drug status in adult outpatients with mental retardation. Am J of Ment Retard 1993;(98S):41-46.
10. Deb S. Mental disorder in adults with mental retardation and epilepsy. Comp Psych. 1997;(3):179-184.
20
11. Waisburg H, Alvarez N. Carbamazepine in the treatment of epilepsy in people with intellectual disability. Journal of Intellectual Disability Research 1998;42(1):36-40.
12. Kastner T., FineSmith R., and Walsh K. Long-term administration of valproic acid in the treatment of affective symptoms in people with mental retardation. Journal of Psychopharmacology 1993;13(6): 448-451.
13. Mattes JA. Valproic acid for nonaffective aggression in the mentally retarded. J Nerv Ment Dis. 1992;(9):601-602.
14. Wilcox J. Divalproex sodium in the treatment of aggressive behavior. Ann Clin Psychiatry. 1994;6(1):17-20.
15. Pioplys AV. Autism: electroencephalogram abnormalities and clinical improvement with valproic acid. Arch Pediatr Adolesc Med. 1994;(148):220-222.
16. Friis ML. Valproate in the treatment of epilepsy in people with intellectual disability. J Intellec Dis Res. 1998;42(S1):32-35.
17. Iivanainen M. Phenytoin: effective but insidious therapy for epilepsy in people with intellectual disability. Journal of Intellectual Disability Research 1998;42(1):24-31.
18. Alvarez N. Barbiturates in the treatment of epilepsy in people with intellectual disability. Journal of Intellectual Disability Research 1998;(1):16-23.
19. Besag FM. Lamotrigine in the treatment of epilepsy in people with intellectual disability. Journal of Intellectual Disability Research 1998;42(1):50-56.
20. Davanzo PA, King BH. Open trial lamotrigine in the treatment of self-injurious behavior in an adolescent with profound mental retardation. Journal of Child & Adolescent Psychopharmacology 1996;6(4):273-279.
21. Ettinger AB, Weisbrot DM, Saracco J, Dhoon A, Kanner A, Devinsky O. Positive and negative psychotropic effects of lamotrigine in patients with epilepsy and mental retardation. Epilepsia 1998;39(8):874-877.
21
22. Beran RG, Gibson RJ. Aggressive behavior in intellectually challenged patients with epilepsy treated with lamotrigine. Epilepsia 1998;39(9):1018-1019.
23. Ylinen A. Antiepileptic efficacy of vigabatrin in people with severe epilepsy and intellectual disability. Journal of Intellectual Disability Research 1998;(1):46-49.
24. Gaily E, Granstrom ML, Liukkonen E. Oxcarbazepine in the treatment of epilepsy in children and adolescents with intellectual disability. Journal of Intellectual Disability Research 1998;(1):41-45.
25. Baribeault JJ. Clinical advocacy for persons wit epilepsy and mental retardation living in community-based programs. Journal of Neuroscience Nursing 1996;28(6):359-372.
26. Pellock JM, Hunt PA. A decade of modern epilepsy therapy in institutionalized mentally retarded patients. Epilepsy Research 1996;25(3):263-268.
27. Beckung E, Uvebrant P. Impairments, disabilities and handicaps in children and adolescents with epilepsy. Acta Paediatrica 1997;86(3):254-260.
28. Ketter TA, Malow BA, Flamini R, White SR, Post RM, Theodore WH. Anticonvulsant withdrawl-emergent psychopathology. Neurology 1994;(44):55-61.
29. Parker AP, Polkey PE, Binnie CD, Madigan C, Ferrie CD, Robinson RO. Vagal nerve stimulation in epileptic encephalopathies. Pediatrics 1999;103(4):778-782.
30. Uthman BM, Wilder BJ, Hammond EJ, Reid SA. Efficacy and safety of vagus nerve stimulation in patients with complex partial seizures. Epilepsia 1990;3(suppl 2):S44-S50.
22
Table 1-1. Principles of AED therapyAssessment of risk/benefit ratio of starting medication Choosing appropriate medication based on seizure typeIf seizures persist, consider adding or substituting 2nd AED Diligently monitor for medication side effects and QOL
23