Keywords
type 1 narcolepsy - cataplexy - pregnancy - delivery - obstetric - Ceserean Section
- medications
Narcolepsy affects 0.05% of the U.S. population and 1 in 2,000 people globally. It
is one of the most common causes of disabling daytime sleepiness after obstructive
sleep apnea. There is no variation in gender, and symptoms can start at any point
in life. It is estimated that only 25% of patients are diagnosed and receiving treatment
for narcolepsy.[1] The focus of this case series is on a pregnant patient with type 1 narcolepsy, the
medical management, and method of delivery.
Narcolepsy is a chronic clinical syndrome that affects the ability to regulate the
sleep–wake cycle. Symptoms include hypersomnia, hypnagogic hallucinations, and sleep
paralysis.[2] orexin/hypocretin A and B are neuropeptides that promote normal wakefulness, inhibition
of rapid eye movement sleep occurrence, and regulation of muscle tone. Losing hypocretin-producing
neurons causes narcolepsy in humans.[3]
[4]
The diagnosis is divided into subtypes: type 1 narcolepsy (previously known as narcolepsy
with cataplexy) and type 2 narcolepsy (previously known as narcolepsy without cataplexy).
Type 1 narcolepsy is based on the individual either having low hypocretin levels (<
110 pg/mL) in the lateral hypothalamus or manifesting as cataplexy. Type 2 narcolepsy
patients experience excessive daytime sleepiness but usually do not have muscle weakness
triggered by emotions. They usually also have less severe symptoms and have hypocretin
within a normal range (> 200 pg/mL).[5] The National Institute of Neurological Disorders and Stroke termed cataplexy as
a “sudden loss of muscle tone while the person is awake that leads to feelings of
weakness and a loss of voluntary muscle control.” This can occur with emotions such
as laughter and sadness and in women reported with sexual activity and during labor
and delivery.[6] Narcolepsy is considered autoimmune in origin, but recent research also shows a
genetic component. This is seen with a variation in this gene, called HLA-DQB1*06:02,
which increases the chance of developing narcolepsy, particularly type 1 narcolepsy.[5]
During pregnancy, physiological changes in sleep can exacerbate underlying sleep disorders.
A pregnant patient may experience fatigue and increased awakening during the night.
Cataplexy has been known to worsen with poor sleep and fatigue, both common during
pregnancy and postpartum.[7]
Case
This is a 23-year-old primigravida who presented for prenatal care at 9 weeks of gestation.
She was diagnosed with type 1 narcolepsy 2 years before conceiving by a daytime sleep
study. She was started on armodafinil and venlafaxine by a sleep specialist, which
she discontinued from 9 to 30 weeks of gestation. During this time, she admitted to
three episodes of cataplexy daily. Prior to the pregnancy, she would report up to
30 episodes daily. Her cataplexy would be triggered by excitement, such as when her
husband returned home from work. She would bring herself to safety beforehand and
had managed until the third trimester without any falls. She admitted to depression
and anxiety surrounding her disorder, which worsened her cataplexy. At 30 weeks of
gestation, the patient complained of worsening cataplexy, sometimes reaching more
than 10 episodes daily, accompanied by severe fatigue. After consultation with the
sleep specialists, maternal–fetal medicine, and counseling regarding the risks and
benefits of the medication, she was initiated on the lowest effective dose of methylphenidate,
5 mg, which she continued until delivery. She continued to have one episode of cataplexy
daily.
The patient's medical history was also significant for ulcerative colitis. She was
diagnosed 5 years prior. She was treated with mesalamine 300 mg. She had recurrent
flares before conceiving and active disease during her pregnancy, treated with oral
prednisone, rectal mesalamine, and rectal hydrocortisone. The patient followed up
with her gastroenterologist throughout her pregnancy.
Recommendations were given regarding cesarean delivery due to active rectal involvement
of her ulcerative colitis and the patient's concern about cataplexy during labor.
Patient presented at 37 weeks with spontaneous rupture of membranes. At this time,
the patient was on 25 mg of prednisone. Stress dose steroids were given, and she underwent
a cesarean delivery under spinal anesthesia. She delivered a viable male infant, weighing
3,152 g, with Apgar scores of 9 and 9. The patient and the infant were discharged
home on postoperative day 3. The infant had no signs of amphetamine withdrawal.
Discussion
Treatment for type 1 narcolepsy involves behavioral modifications, proper sleep hygiene,
and medications geared toward alleviating symptoms. Behavioral modifications involve
regularly scheduled naps and exercising. Sleep hygiene consists of maintaining regular
sleep and wake times and getting appropriate sleep each night. Medications include
modafinil, stimulants, antidepressants, and sodium oxybate.
There are significant challenges during pregnancy and childbirth in women with type
1 narcolepsy. These challenges include decisions about medications, risk of trauma,
increased risk of adverse perinatal outcomes, and determination regarding mode of
delivery.
The potential teratogenicity of medications available for narcolepsy has not been
fully established. The risks and benefits should be discussed in detail prior to the
initiation or continuation of these medications during pregnancy[8] ([Table 1]). In the literature, Pascoe et al conducted a survey assessing pregnant narcolepsy
patients. The survey assessed prescription narcolepsy medication use and discontinuation
during pregnancy. The survey results indicate that 33.3% of women discontinued medication
during pregnancy. A total of 82.9% of women discontinued due to fears of harming the
fetus, and 58.5% discontinued due to the recommendation of a provider. Alternative
management was recommended, such as sleep extension, increased caffeine intake, discontinuing
work, and discontinued driving.[9] Our patient resumed medication during her third trimester because the risk of trauma
secondary to her increased cataplectic episodes outweighed the potential risks of
the medication.
Table 1
Medications used in the treatment of narcolepsy and cataplexy[13]
[14]
[15]
[16]
|
Medication
|
Indication
|
Pregnancy category
|
Adverse events
|
Adverse events reported in neonates
|
|
Modafinil
|
Excessive daytime sleepiness
|
C
|
Headache, nervousness, syncope, Steven– Johnson syndrome with higher incidence in
pediatric patients
|
In June 2019, manufacturers stated to not give Modafinil to pregnant patients, as
postmarketing data showed 15% of congenital malformations detected in children exposed
to Modafinil during pregnancy compared with 3% in the general population.[14]
A total of 13% of 102 live births had major congenital malformations (MCMs) such as
congenital heart disease, congenital torticollis, and hypospadias. Since there was
no specific organ malformation pattern identified There cannot be an established association
between use of modafinil and/or armodafinil and MCMs.[13]
May be excreted in breast milk.
|
|
Atomoxetine
|
Cataplexy
|
C
|
Dry mouth, xerostomia, headache, abdominal pain, decreased appetite, cough, somnolence,
vomiting
|
No adequate controlled studies done in humans. Excreted in breast milk
|
|
Dextroamphetamine
|
Excessive daytime sleepiness
|
C
|
Loss of appetite, insomnia, abdominal pain, vomiting, fatigue, dizziness
|
Increased risk of premature delivery and low birth weight. May experience withdrawal
symptoms. Excreted into breast milk.
|
|
Methylphenidate
|
Excessive daytime sleepiness
|
C
|
Headache, insomnia, abdominal pain
|
No controlled studies in humans. Excreted in breast milk. Associated with higher rates
of prematurity, growth restriction, and neonatal withdrawal
|
|
Selective serotonin reuptake inhibitors (SSRIs)
|
Cataplexy
|
C-D
|
Headache, nausea, insomnia, anorexia, anxiety, asthenia, diarrhea, decreased libido
|
Neonatal abstinence syndrome. Six-fold increase of persistent pulmonary hypertension
in the newborn. Possible increase in frequency of pregnancy loss. Excreted in breast
milk
|
|
Serotonin– norepinephrine reuptake inhibitors (SNRIs)
|
Cataplexy
|
C
|
Headache, nausea, insomnia, asthenia, dizziness, somnolence, dry mouth, sweating
|
No controlled studies in humans. Possible drug discontinuation syndrome. Possibly
associated with spontaneous abortion, low birth weight, prematurity, serotonin syndrome,
and persistent pulmonary hypertension. Excreted in breast milk
|
|
Tricyclic antidepressants (TCAs)
|
Cataplexy
|
C-D
|
Xerostomia, headache, constipation, fatigue, nausea, impotence, weight gain, mania,
tremor
|
Associated with possible cardiac defects. Withdrawal symptoms: respiratory distress,
cyanosis, tremor, and seizures. Excreted in breast milk.
|
|
Sodium oxybate
|
Cataplexy associated with narcolepsy
|
B
|
Headache, nausea, dizziness, pain, somnolence, pharyngitis
Characterized as a schedule III controlled substance
|
No controlled data in human pregnancy
|
A cataplectic episode can lead to falls and trauma to the mother and the fetus. Trauma
in pregnancy can lead to devastating outcomes for the mother and her unborn child,
including maternal injury, placental abruption, and fetal death.
Recent data have emerged to suggest that narcolepsy can increase the risk of adverse
perinatal outcomes, and more so with type 1 narcolepsy as compared with type 2 narcolepsy.
A retrospective cross-sectional analysis was performed using nationwide inpatient
sample data in pregnant women with type 1 and type 2 narcolepsy, revealing that type
1 narcolepsy has an increased risk of gestational hypertension (5.3%), preeclampsia
(4.8%), and cesarean sections (1.1%) than in pregnant patients without narcolepsy.[5]
Mode of delivery can be complex, since there are more obstetric complications seen
and higher rates of cesarean sections in these women. There are cases reported of
cataplexy during vaginal delivery that led to emergency cesarean section. In fact,
the majority of the successful outcomes in the case reports are women who delivered
by cesarean section. Although vaginal delivery is not contraindicated, if there are
multiple narcoleptic and cataplectic episodes during labor and delivery, a cesarean
section may be indicated.[8]
There is a paucity of data and case reports of type 1 narcolepsy in pregnancy ([Table 2]). In their article, Ping et al describe a case of a 32-year-old female with a history
of type 1 narcolepsy triggered by sexual excitement. Her cataplectic episodes were
described as an inability to speak and involved atonia of her limbs. She remained
off of her medications during pregnancy and resumed postpartum. She had an emergency
cesarean section at 39 weeks, secondary to prolonged cataplectic episodes following
each uterine contraction.[10] Williams et al describe a 16-year-old female with narcolepsy, controlled on fluoxetine
and modafinil, and glutaric aciduria during pregnancy. She continued to have episodes
of cataplexy that worsened as she neared her delivery date. Their patient had an elective
cesarean section at 38 weeks with favorable outcomes.[11] Hoque's and Chesson's recommendations to a 25-year-old pregnant patient involved
discontinuing stimulant use unless the risks of narcolepsy substantiated the use of
the medication. They believe a patient with significant cataplexy should also consider
an elective cesarean section due to the risk of labor-induced cataplexy.[12]
Table 2
Medication use, mode of delivery and outcomes of patients with narcolepsy during pregnancy
|
Author
|
Age
|
Medication use in pregnancy
|
Mode of delivery
|
Outcome
|
|
Hoque et al
|
25
|
No
|
Not stated, advised their patient that cesarean may be preferred[2]
|
Not stated
|
|
Ping et al
|
32
|
No
|
Emergency cesarean due to cataplectic episodes during labor
|
Postpartum depression and excessive daytime sleepiness, resumed modafinil postpartum.
Favorable recovery[5]
|
|
Williams et al
|
16
|
Yes: Fluoxetine and modafinil
|
Elective cesarean: due to increased cataplectic episodes
|
No complications, Apgar score of 7 and 9, mother and infant discharged after 3 d[4]
|
|
Our patient
|
23
|
Yes: methylphenidate
|
Elective cesarean: due to active ulcerative colitis and worsening cataplexy
|
No complications, Apgar score of 9 and 9, mother and infant discharged after 3 d
|
We reported a case of a woman with type 1 narcolepsy during pregnancy, controlled
on medication for worsening cataplexy in the third trimester. In total, the literature
describes one other case that continued medication during pregnancy with favorable
outcomes. Comprehensive counseling of the patient regarding the risks and benefits
of the individual medications during pregnancy is recommended. Our patient was successfully
managed with the lowest effective dose of methylphenidate, 5 mg, and had an elective
cesarean section with a successful maternal and neonatal outcome.
