Taenia solium is endemic in low-income countries in Latin American, sub-Saharan Africa, and Asia
including India and China.[1]
[2] Cysticercosis is an infection by the larval stage of T. solium that affects both humans and pigs. Humans can become infected by the adult parasite
(Taenia) and by the larval stage (cysticercus) by eating improperly cooked pork infected
with larvae, or food contaminated with feces harboring Taenia eggs, respectively. Pigs are likewise infected after ingesting Taenia eggs. Cysts in human hosts are commonly acquired from a tapeworm carrier in the same
household.[3] Neurocysticercosis (NCC), the central nervous system infection, is associated with
nearly one-third of seizure disorders in endemic areas, and an estimated 50 million
people worldwide have the infection.[4]
In the United States, ∼2% of all emergency department visits for seizures are attributable
to NCC.[5] NCC is more common in immigrants or travelers from endemic areas, particularly from
Latin America.[5]
[6]
[7] A study by O'Keefe et al showed that 45% of subjects admitted to US hospitals due
to NCC between 1998 and 2011 were women and 60% were between 18 and 44 years old,
coinciding with their child bearing age.[5] Transmission of NCC has been reported within the United States through contact with
immigrant workers with taeniasis.[8]
[9]
Obstetricians–gynecologists and general practitioners may encounter patients with
NCC in their practice, particularly in areas with large immigrant populations.[10]
[11] A recent survey among practicing physicians in this specialty suggested significant
gaps in the knowledge about NCC epidemiology and transmission.[12] Only 15% of the obstetrician–gynecologists interviewed in that study were able to
correctly identify the transmission route of cysticercosis and 35% knew how to make
the diagnosis.
In this article, we report two cases of NCC during pregnancy and early postpartum
that presented in two different settings and review the literature from developed
and developing countries about this disease. We discuss aspects of the presentation,
diagnosis, and management of NCC in pregnant women to inform the general practitioner.
Cases
Case 1
A 25-year-old female G7P4024 emigrated from Honduras to the United States during the
6th month of her pregnancy. She had a history of encephalitis 1 year prior, while
in Honduras, which was treated with antibiotics for 10 days. She subsequently experienced
one to two seizures like episodes monthly and intermittently took anticonvulsants
during the pregnancy. A key component of her story is the personal, social, and family
history. In Honduras, she worked in agriculture harvesting coffee beans and fruits.
Her family practiced subsistence farming and raised free roaming pigs for consumption.
A 7-year-old relative in the same household had recently been diagnosed with seizures.
She underwent an uncomplicated spontaneous vaginal delivery at term with a tubal ligation.
However, on postpartum day 4 she complained of dizziness and shakiness of her right
upper extremity followed by generalized seizure activity and loss of consciousness
by postpartum day 6. The patient was transferred to a tertiary care center.
On admission, her physical exam was unremarkable. The computed tomography (CT) scan
of the brain showed scattered intracranial calcifications and the magnetic resonance
imaging (MRI) showed scattered foci of T2/fluid-attenuated inversion recovery signal
hyperintensity in the bilateral cerebral white matter. She was diagnosed with NCC
and deemed to have nonviable parasites. The patient was prescribed divalproex sodium
for seizure control.
Case 2
A 29-year-old female G6 P5005 at 17 weeks estimated gestational age presented to a
rural clinic in Cusco-Peru with a headache. Evaluations were unremarkable and outpatient
management was continued. Six days later when fatigue and anorexia accompanied a severe
headache, the patient was admitted with concerns for sepsis. During observation, a
witnessed tonic–clonic seizure prompted her transfer to a tertiary care center.
Again, the personal, social, and family history were a key component of her diagnosis.
She lived in a rural community known to perform pork household husbandry, and she
was a homemaker with five other children. Upon admission to the tertiary care center,
she was noted to have tachycardia and neck stiffness. A white blood cell of 11,200
cells/μL (93% neutrophils), hemoglobin of 12.1 g/dL (altitude adjustment 9.7 g/dL),
platelets of 218,000 cells/μL, and an urinalysis was normal. An ultrasound showed
a viable 17-week fetus. A brain CT scan showed hydrocephalus and other findings suggesting
intraventricular NCC. No lumbar puncture was performed. She was treated with phenytoin,
dexamethasone, and mannitol. A ventriculoperitoneal shunt was planned but before it
could be placed she developed increasingly severe headaches, mental status changes,
and had a cardiac arrest. In spite of heroic measures, both the mother and fetus succumbed
to her disease within 21 days of the initial presentation of headache.
Discussion
The principles of management of NCC in pregnant women are similar to nonpregnant patients.
However, considerations about the mother–fetus well-being and illnesses inherent to
pregnancy pose challenges to the general practitioner. As illustrated by our cases,
the presentation of NCC varies significantly between patients. The symptoms of NCC
depend on the stage of infection, location of the cysts, and host response to the
injury. Fully viable cystic lesions usually remain subclinical unless compression
of adjacent structures triggers symptoms, while decaying stages (colloidal cysts)
and dead cysts (granulomas/calcifications) are associated with perilesional inflammation
and seizures.[3] Parenchymal lesions are associated with seizures, ventricular lesions with hydrocephalus,
and subarachnoid lesions with hydrocephalus and strokes. The presentation may vary
from an incidental finding in an otherwise asymptomatic woman to life-threatening
increased intracranial pressure or intractable seizures.
In the general population, the most common symptoms of NCC are headaches and seizures.[3] During pregnancy, focal and generalized seizures and headaches with increased intracranial
pressure seem to be more common ([Table 1]). Altered mentation, coma, and death of the mother and fetus have also been reported.[10]
[11]
[13] The new onset seizure activity associated with NCC can be confused for pre-eclampsia
and eclampsia particularly during the second half of pregnancy.[11]
[14]
[15]
[16] The confusion between these two diagnosis is compounded by the fact that the prevalence
of eclampsia is higher in low-income countries (6 to 157 cases per 10,000 deliveries)
than in high-income countries (1.5–10 per 10,0000 deliveries)[17]
[18]
[19]
[20] and that other common symptoms of NCC such as visual changes and altered mental
status are often attributed to pre-eclampsia and eclampsia. Headache, a very common
symptom reported by almost 60% of young women, may be regarded as “normal” during
pregnancy.[21] A detailed history and physical exam, including travel history and past medical
history, are crucial to arrive at the correct diagnosis in these settings.
Table 1
Presentation and characteristics of NCC in pregnancy among 49 reported cases
|
Author
|
Country
|
Nationality
|
Cases
|
Presentation
|
Perilesional edema
|
Hydrocephalus
|
Prior NCC Dx
|
|
Grondin et al[14]
|
US
|
Mexico
|
1
|
GS, FS
|
Yes
|
No
|
No
|
|
Browne and Birnbach[39]
|
US
|
Ecuador
|
1
|
GS, HA, MS
|
No
|
Yes
|
No
|
|
D'Cruz et al[40]
|
UK
|
India
|
1
|
GS, FD, IICP
|
Yes
|
No
|
Yes
|
|
Fica et al[41]
|
Chile
|
Chile
|
1
|
HA, AMS, IICP
|
Yes
|
Yes
|
No
|
|
Gardner et al[13]
|
US
|
Unkn
|
1
|
GS, HA, MS
|
Unkn
|
Yes
|
No
|
|
Pandian et al[22]
|
India
|
India
|
30
|
GS (9) - PS (21)
|
Yes (16)
|
No
|
Yes
|
|
Ramus et al[42]
|
US
|
Mexico
|
1
|
HA, AMS
|
No
|
Yes
|
No
|
|
Bazley[43]
|
US
|
Mexico
|
2
|
HA, AMS
|
No
|
Yes
|
No
|
|
Sahai et al[15]
|
India
|
India
|
2
|
GS (1) - PS (1)
|
Yes
|
No
|
No
|
|
Singhal et al[11]
|
India
|
India
|
2
|
GS (2), AMS (1)
|
Yes
|
No
|
No
|
|
Suarez and Iannucci[16]
|
US
|
Hispanic
|
1
|
HA, AMS
|
No
|
Yes
|
No
|
|
Thaker et al[44]
|
UK
|
UK
|
1
|
GS
|
Yes
|
No
|
No
|
|
Kurl and Montella[10]
|
US
|
Guinea-Bissau
|
1
|
GS, HA
|
No
|
No
|
No
|
|
Forsbach et al[45]
|
Mexico
|
Mexico
|
1
|
GS, FD
|
No
|
Yes
|
No
|
|
Torsone and McMahon[46]
|
US
|
Mexico
|
1
|
HA, MS
|
No
|
No
|
No
|
|
Gowri et al[47]
|
Oman
|
India
|
1
|
GS
|
Yes
|
No
|
No
|
|
Paparone and Menghetti[48]
|
US
|
Mexico
|
1
|
GS
|
Yes
|
No
|
Yes
|
|
Author
|
Location of the lesions
|
Stage of the lesions
|
Trimester
|
Outcome
|
Combination anticonvulsants
|
|
Grondin et al[14]
|
Parenchyma
|
Cyst
|
3rd
|
Good
|
Yes
|
|
Browne and Birnbach[39]
|
Parenchyma
|
Cyst
|
Postpartum
|
Unkn
|
No
|
|
D'Cruz et al[40]
|
Parenchyma
|
Calcified
|
2nd
|
Good
|
Yes
|
|
Fica et al[41]
|
Parenchyma, ventricle
|
Cyst
|
3rd
|
Maternal dead
|
NA
|
|
Gardner et al[13]
|
parenchyma, ventricle
|
Cyst, calcified
|
3rd
|
Good
|
Yes
|
|
Pandian et al[22]
|
Parenchyma
|
Calcified (14) Unkn (16)
|
NA
|
Good (Preterm in 2)
|
Yes (8)
|
|
Ramus et al[42]
|
Parenchyma, ventricle
|
Cyst
|
3rd
|
Good
|
No
|
|
Bazley[43]
|
Ventricle
|
Cyst
|
1st
|
Maternal/fetal dead
|
NA
|
|
Sahai et al[15]
|
Parenchyma
|
Cyst
|
2nd
|
Unkn
|
Unkn
|
|
Singhal et al[11]
|
Parenchyma
|
Cyst
|
2nd
|
Good (1), abortion (1)
|
No
|
|
Suarez and Iannucci[16]
|
Parenchyma, ventricle
|
Cyst
|
3rd
|
Good
|
No
|
|
Thaker et al[44]
|
Parenchyma
|
Cyst
|
1st
|
Good
|
Yes
|
|
Kurl and Montella[10]
|
Parenchyma
|
Cyst
|
1st
|
Good
|
No
|
|
Forsbach et al[45]
|
Sub-arachnoid
|
Cyst
|
2nd
|
Good
|
Unkn
|
|
Torsone and McMahon[46]
|
Parenchyma
|
Cysts, calcified
|
3rd
|
Good
|
NA
|
|
Gowri et al[47]
|
Parenchyma
|
Cyst
|
2nd
|
Good
|
No
|
|
Paparone and Menghetti[48]
|
Parenchyma, subarachnoid
|
Cysts, calcified
|
1st
|
Good
|
Yes
|
Abbreviations: AMS, altered mental status; FD, focal deficits; GS, generalized seizures;
HA, headaches; IICP, increased intracraneal pressure; MS, meningeal signs; NCC Dx,
neurocysticercosis diagnosis; PS, partial seizures; Unkn, unknown.
The effects of pregnancy on the clinical course of NCC are unknown and have not been
addressed in prospective studies. In the few case reports of NCC during pregnancy,
most women had no prior history of NCC and presented with new onset seizures or increased
intracranial pressure ([Table 1]). An Indian case–control study compared pregnant women enrolled in an epilepsy registry
with and without NCC. This study suggested an increase in seizure activity during
pregnancy in 4 out of 30 participants with NCC. Although seizure control during pregnancy
was significantly worse in women without NCC, the same group also had very poor seizure
control before pregnancy.[22] The local and systemic immune responses during pregnancy progressively shift toward
a T-regulatory environment and decreased cellular immune response favoring immune
tolerance.[23] The same systemic T-regulatory environment has been documented in subjects with
NCC and is believed to promote parasite survival.[24] Inflammation around the decaying cysts or calcified lesions is fundamental for uncontrolled
seizures to occur in NCC. Thus, the systemic immune response during pregnancy does
not support the worsening of seizure activity during this period. However, pregnancy
is not a generalized state of immunosuppression and some local components of the immune
response may be enhanced (i.e., phagocytosis and monocyte and neutrophils numbers)
possibly explaining changes around the cysticerci.[25] Also, it is unclear if other changes, like those seen during some gestational disorders
in which inadequate response to angiogenic stimuli increase blood–brain barrier permeability,
could explain an increase in seizure activity.[26]
There is no evidence that maternal infection with T. solium causes vertical transmission to the fetus. However, cysticercosis can be transmitted
horizontally from the mother to the newborn and screening mothers with NCC for tapeworm
infection is imperative.[27] Most pregnancies in women with NCC are associated with good outcomes and there is
no indication that maternal NCC itself causes fetal malformations or brain damage.([Table 1]) However, sustained seizures may pose a major risk to the fetus due to hypoxia.[13]
The diagnosis of NCC during pregnancy and postpartum is difficult and depends on a
high level of suspicion. Eliciting the history of exposure in endemic areas as well
as the personal, social, and family histories is the key for suspecting the diagnosis
in patients with neurologic symptoms. The same criteria for the diagnosis of NCC in
the general population apply in pregnancy.[28] Imaging studies should be performed early when NCC is suspected in a pregnant woman.
MRI is highly sensitive to identify small noncalcified cysts, edema, or enhancement
around calcifications, and subarachnoid or intraventricular lesions. CT scan is superior
to MRI for the evaluation of calcified lesions but has a lower sensitivity for subarachnoid
or intraventricular lesions. MRI without gadolinium is not associated with teratogenicity
and should be the test of choice during any stage of pregnancy. If CT scan is performed,
narrow collimation, wide pitch, and shielding should be used.
The enzyme-linked immunoelectrotransfer blot (EITB) assay is the test of choice to
detect antibodies to T. solium in serum. The sensitivity of EITB is very high for patients with more than one lesion,
but only 50% to 60% for patients with single lesions. ELISA assays for the detection
of antibodies are available but not recommended due to their low sensitivity and specificity.[29] T. solium antigen detection is considered a major clinical/exposure diagnostic criteria.[28]
[30]
[31] These tests may also be useful to monitoring the response to medical treatment.[32]
[33]
The management of NCC during pregnancy depends on the clinical presentation and should
focus on symptomatic therapy. Most symptoms of NCC are associated with the host response
to the parasite rather than infection itself.[34]
[35] Antiparasitic therapy is associated with early worsening in seizure activity which
should be avoided during pregnancy. While the safety of short courses of low-dose
albendazole and praziquantel during pregnancy has been established in neglected tropical
diseases control programs, the safety of prolonged high-dose treatment for NCC has
not been studied. Benefits and risks of the antiparasitic therapy during pregnancy
should be discussed with the patient, and in most cases therapy should be deferred
until after delivery.
Women with new onset seizures between the second trimester and the postpartum will
often be considered to have preeclampsia/eclampsia. However, in the absence of high
blood pressure or other signs of preeclampsia, a different diagnosis must be suspected
and neuroimaging ordered particularly for women at risk of transmission. Antiepileptic
medication should be started to avoid seizure recurrence during pregnancy. Monotherapy
is preferred since drug combinations, especially those containing valproic acid, are
associated with a higher incidence of malformations when used in the first trimester.[36] However, up to 16% of patients with NCC will not have adequate seizure control with
only one agent.[37] Corticosteroids are used to treat the inflammation associated with NCC lesions especially
in patients with diffuse edema or mass effect from large cysticerci. Corticosteroids
should be avoided in patients with calcified lesions due to worsening of symptoms
after tapering of the medication.[38] Patients with acute hydrocephalus should be evaluated for urgent surgical management
to remove the parasite from the ventricles or to divert cerebrospinal fluid drainage.
In pregnant and postpartum women with taeniasis, a single dose of the nonabsorbable
antitapeworm medication niclosamide associated with a mild laxative should be prescribed
to prevent cysticercosis transmission to the newborn.
Conclusion
NCC is one of the most common etiologies of seizures worldwide and should be considered
in pregnant or postpartum women with compatible presentations, particularly if coming
from endemic areas. Its diagnosis and management during pregnancy can be challenging,
but prompt interventions are crucial for better maternal and fetal outcomes.
