Diagnostic and management challenges of intraventricular neurocysticercosis presenting in the third trimester of pregnancy: A case report

Abstract

The diagnosis of neurocysticercosis in pregnancy is challenging, even in endemic areas, as other neurological conditions with similar manifestations are common. Obstetricians and physicians may be reluctant to do neuroimaging in pregnancy and often the availability is limited in endemic areas. Management of neurocysticercosis depends on the symptomatology. In those presenting with features of increased intracranial pressure early treatment is necessary, taking into consideration the gestational age and the maternal condition at presentation. Presence of intraventricular cysts causing obstructive hydrocephalus necessitates their removal due to the risk of intracranial hypertension which could be life-threatening, particularly peripartum. We report a case of a woman with intraventricular neurocysticercosis, who presented in the third trimester, and described the management dilemmas that were encountered. The differential diagnoses and other aspects of the medical and surgical management of neurocysticercosis in pregnancy are also discussed.

Introduction

Neurocysticercosis (NCC) is the infection of the central nervous system with larvae or parasitic cysts of Taenia solium (pork tapeworm), acquired by the ingestion of contaminated food or water containing parasitic eggs (faecal–oral route).^1,2 It is endemic in low- and middle-income countries in Southeast Asia, sub-Saharan Africa and Latin America and is associated with nearly one-third of cases of epilepsy in these areas.¹ Purely extra-parenchymal, intraventricular lesions in NCC are uncommon during pregnancy and such cases can present with features of obstructive hydrocephalus such as headache, vomiting, papilledema and altered mentation.^2–6 We present the case of a 20-year-old woman in her first pregnancy, who presented in the third trimester with vomiting and headaches and diagnosed with intraventricular NCC after imaging. A caesarean section was performed and then the cyst removed using a neuroendoscope. The differential diagnosis of altered mental status in a pregnant woman in low–middle income countries is discussed, with emphasis on the medical and neurosurgical treatment of NCC in pregnancy.

Case

A 20-year-old woman in her first pregnancy presented at 36 weeks and 5 days of gestation with a five-day history of a slowly evolving, frontal headache and vomiting. There was no history of fever, seizures, visual impairment, diplopia, slurring of speech or any other neurological deficits. She had no history of chronic hypertension, migraines, epilepsy, tuberculosis or trauma. On admission, the pulse rate was 96 beats/min, and the blood pressure was 96/52 mmHg. Cardiovascular and respiratory examination was normal and the urine analysis did not show proteinuria or ketonuria. Neurologically, she was drowsy and confused (GCS was 13: eyes 3, verbal 4, motor 6). There was no neck stiffness, no lateralising focal deficits and no papilledema. On obstetric examination, symphysio-fundal height was noted to be 35 cm with a normal fetal heart on auscultation. Renal, liver function, haemoglobin and platelet count were normal, but a neutrophil leukocytosis was noted. No eosinophilia was present. Ultrasound examination showed an appropriately grown baby with normal biophysical profile.

Two hundred milligrams of intramuscular thiamine was administered to prevent Wernicke’s encephalopathy and was started on intravenous promethazine (25 mg every 8 h) as per the hospital protocol for vomiting in pregnancy. Intravenous ondansetron (4 mg every 8 h) was added subsequently. Cerebral venous sinus thrombosis (CVST) was initially suspected because of the persistence of headache. An emergency CT brain was performed (with abdominal lead shield) on the day of admission. This showed obstructive hydrocephalus with a relatively enlarged fourth ventricle containing an ill-defined hyperdense lesion. In view of her symptoms and the finding of hydrocephalus, ventriculoperitoneal (VP) shunt insertion was considered to mitigate the risk of sudden deterioration from brain herniation.

The potential risks of VP insertion including entry of the peritoneal cavity to position the abdominal part of the shunt and the geographical proximity of the gravid uterus, the fetal risks of general anaesthesia and shunt infection after caesarean section were considered and it was recommended that the procedure was undertaken. The neurosurgical team felt that subcostal access to position the shunt would not be a risk to the gravid uterus to mitigate the former risk.

However, the woman requested postponement of this procedure as she remained very apprehensive about the risk to the fetus during shunt placement, despite counselling by the multidisciplinary team. Equipment for a quick insertion of an external ventricular drain by the emergency neurosurgery team was kept ready, in case she showed any sudden deterioration while awaiting MRI for further evaluation. She was given intravenous dexamethasone (four doses of 6 mg, every 12 h) to accelerate lung maturity of the fetus, as early delivery was anticipated. As she was nearing 37 weeks, the option of delivery and then imaging was also discussed with radiology and neurology team; however, in view of the acute presentation with a suspected lesion in the fourth ventricle and initial features suggestive of intracranial hypertension, it was decided to evaluate with magnetic resonance imaging (MRI) with contrast. MRI of the brain with gadolinium contrast (Gadopentetate dimeglumine) was performed the following day, which showed dilatation of the bilateral lateral ventricle and the superior portion of the fourth ventricle (Figures 1 & 2(a)). It showed mild periventricular hyperintensity around the fourth ventricle, along with enhancement of the walls of the fourth ventricle around a cystic lesion. The lesion had a mural nodule which was indicative of cysticercal cyst and it was causing ependymitis of the walls of the ventricle. There were no parenchymal cysts.

The multidisciplinary team of obstetricians, radiologists, anaesthesiologists and the neurosurgeon decided to perform the caesarean section prior to therapeutic intervention for the cyst. A female infant was delivered by caesarean section at 37 weeks of gestation. She weighed 2500 g and had an APGAR score of 9 at 5 min.

On the third postoperative day, she again experienced severe headaches. Removal of the offending, solitary obstructing cyst seen on MRI was planned, to see if the need for a permanent VP shunt could be avoided. The cysticercus cyst within the fourth ventricle was removed, four days after the caesarean section, via a small sub-occipital incision through the space between the occiput and C1 arch, using a 4 mm, flexible, fibre endoscope (Karl Storz™). Perioperatively, 24 h before endoscopic surgery, levetiracetam was started (500 mg, intravenously, twice a day before surgery and then orally for another seven days) as a short term risk of seizure activity was anticipated as a result of the surgical pneumocephalus. A five-day course of empirical steroids was also given to reduce the inflammation seen around the degenerating cysts. This resulted in a significant reduction in her headache and the serial CT scans showed a decrease in ventricular size. Both the baby and the mother were discharged on the fifth day after the endoscopic procedure. At three weeks’ follow-up she was asymptomatic, and a postoperative MRI did not show a residual lesion (Figure 2(b)).

Figure 1.

(a) Fluid attenuated inversion recovery axial section of MRI of brain shows dilated bilateral lateral ventricles with mild periventricular oedema and (b) post contrast axial T1 weighted MRI of the brain shows mild wall enhancement of the intraventricular cyst with enhancement of the walls of fourth ventricle suggesting ventriculitis.

Figure 2.

(a) T2 weighted para sagittal section of the brain shows hyperintense cyst within the fourth ventricle with thin irregular walls and eccentric hypointense scolex suggestive of intraventricular NCC and (b) shows the image after the removal of the cysts with reduction in the dilatation of the ventricles.

Discussion

Diagnosis of NCC during pregnancy and in the post-partum period is challenging as the neurological signs are non-specific, and the differential diagnosis in this setting is wide. Generally, conditions that are more common and specific to pregnancy such as eclampsia, migraine episodes and CVST receive more attention.^7,8 NCC is endemic in Latin America, Africa and Southeast Asia (especially in India, China and Nepal); these regions also have a high incidence of other CNS infections too, such as bacterial meningitis, tuberculosis and viral encephalitis.⁹ As a relatively costly neuroimaging is required for the diagnosis of NCC, it makes the diagnosis even more difficult in these endemic areas where such facilities are not easily available.¹⁰

Differential diagnosis

Headaches are common in pregnancy and are often benign.⁷ Migraine, one of the common causes of headache in pregnancy, usually tends to improve during pregnancy, but may often flare after delivery. New-onset headaches and vomiting in the late second or third trimester may suggest premonitory symptoms of eclampsia, especially when associated with high blood pressure. Even though focal neurological signs and seizures might be present in those developing CVST or stroke, some may present only with signs of increased intracranial pressure as in the index patient who presented with vomiting, headache and associated altered mentation.¹¹ High intracranial pressure should be suspected even in the absence of papilledema, as the fundus changes reflecting raised pressure may take weeks to evolve in case of a slow and mild rise of pressure.⁶

Intraventricular NCC is a form of extra-parenchymal NCC that may present with a rapidly progressive clinical course and is reported to be associated with a poor prognosis.^2,3,5 The fourth ventricle is the most common site and can present with subacute hydrocephalus with brain stem dysfunction.^3,5,8 The episodic rise in intracranial pressure, as was seen in this case, can occur due to changes in the position of the cyst producing a ball-valve mechanism of obstruction.

Neuroimaging in pregnancy

As suggested in the review by Negro et al.,¹¹ red flag symptoms and signs including seizures, worsening and persistent headache, neurological signs, trauma, increased risk of infective disease or a history of thrombophilia require neuroimaging during pregnancy. Use of gadolinium contrast at the time of MRI needs to be restricted in pregnancy to situations where the benefits outweigh the potential risks.^12,13 Gadolinium is mainly distributed in extracellular water and is rapidly eliminated by the kidney. The duration of fetal exposure is not known due to the re-entry into the fetal circulation which occurs during the swallowing of amniotic fluid by the fetus. The duration of re-circulation of gadolinium compounds varies according to which type of gadolinium compound is used; linear ionic gadolinium compounds have a longer duration of re-circulation than gadolinium with a macrocyclic structure. In a large retrospective study, the use of gadolinium in late pregnancy was associated with an increase in fetal loss and in early pregnancy there was an increased prevalence of childhood rheumatological conditions. Concerns regarding the possibility of nephrogenic systemic fibrosis developing later in those exposed to gadolinium in utero also need to be considered.¹⁴ In addition to these risks, the cost and non-availability in low- to middle-income countries lead to even more selective use of contrast.¹³

In this case there was an ill-defined lesion in the fourth ventricle identified on CT, so an MRI with contrast (using linear ionic compound which is associated with an increased duration of re-circulation) was undertaken, to further define the lesion. However due to concerns of prolonged fetal exposure to this type of gadolinium, after discussion with the treating multidisciplinary team, a caesarean section was performed and a healthy infant delivered. Retrospectively, however, it was realised that a diagnosis of intraventricular cysticercal cyst could have been made with T2 weighted images alone as the mural nodule of the cyst was characteristic. The contrast served only to reveal the ependymal enhancement of the hyperintense fourth ventricular wall, the likely result of an inflammatory response to the degenerating cyst. Empirical steroids were continued, to treat this inflammation.

NCC in pregnancy

NCC has an insidious natural history, but may present in pregnancy due to physiological changes in intracranial pressure. The blood volume in the intracranial cavity is almost constant despite a rise in the intravascular volume during pregnancy by nearly 40%. Other changes in pregnancy in the brain include selective parenchymal arteriolar remodelling leading to thinner vessels with larger lumina, increased resistance to vasoconstrictor metabolites and reduction in cerebral blood flow velocity. There is a rise in the cerebral perfusion pressure, within the autoregulatory range, along with an increase in CSF volume due to vasodilation, which results in an increase in intracranial pressure.^15,16 The presence of cysts or inflammatory adhesions in the ventricle obstructing CSF drainage along with the physiological changes can lead to the development of obstructive hydrocephalus.^6,8 Colloid cysts of the third ventricle causing intermittent obstruction of the CSF flow can also present with similar findings.

Medical treatment

The effect of pregnancy on the course of NCC is unknown and the management is based on the expert opinion available as case series or case reports in the literature.¹⁷ Management in pregnancy is determined by the symptoms at presentation. Medical therapy with albendazole or praziquantel for a prolonged period may be considered in women with (i) inflamed or adherent ventricular cysticerci which are technically difficult to remove or (ii) when complete surgical removal of isolated intraventricular cysts is not possible following a shunt procedure. This is usually advised after starting a course of corticosteroids to reduce the inflammatory response and brain oedema. Those receiving anthelmintic therapy should be monitored for hepatotoxicity and leukopenia and for drug interaction with anti-seizure drugs, especially for praziquantel.^2,3 In addition, ocular cysticercosis should be ruled out prior to starting anti-helminthic therapy. As the symptoms are predominantly due to the host response to the parasite than the infection itself, anti-helminthic therapy can lead to worsening of the symptoms initially. Current recommendations suggest its use to be deferred until delivery due to concerns of adverse fetal effects such as fetal loss, birth defects (as observed in animal studies) and low-birth-weight babies, as well as the worsening of the symptoms due to host response.³

Perioperative or prophylactic use of antiepileptic drugs (AEDs) is suggested in the literature, especially in those cases with parenchymal lesions.^17,18 The choice of the agents depends on the gestational age at presentation and the concerns regarding their effects on the growing fetus. Due to the risk of congenital malformation if used in early pregnancy or risk of cognitive dysfunction, most of the older generation AEDs are not preferred. Levetiracetam has several advantages such as the rapid onset of action, administration by intravenous or oral route, being weight-neutral and because there is excretion through the kidneys. We preferred it to other agents as there are no reported major effects on the cognitive function or risk of fetal malformation.^19,20 Serum levels of levetiracetam in breastfed infants are low and is generally considered safe in lactating mothers.²¹ Since the woman did not have seizure history or the presence of intraparenchymal cysts, we gave only a short duration (seven days) of perioperative antiepileptic prophylaxis.

Surgical treatment

Neurosurgical intervention by microsurgery or endoscopy may be required in cases of obstructive hydrocephalus, ventricular cysticercosis and drug-refractory seizures.^2,3,8,18 In women where removal of the cysts is technically challenging as in case of inflamed or adherent of ventricular cysticerci, or if neurosurgical expertise to do that is lacking, a VP shunt procedure followed by the use of antiparasitic therapy and corticosteroids can be considered. Removal of cysts as in the index case, from the ventricles or an early CSF diversion such as a VP shunt to divert cerebrospinal fluid drainage, is often required in the management of those women who develop hydrocephalus. In the early half of the pregnancy, CSF diversion surgeries to reduce the ICP can be performed, but the benefits and risks of shunt placement in the third trimester must be discussed with the individual and the multi-disciplinary team.^2,3,6,8,18

In women with raised ICP, labour and delivery present further challenges to the treating team as haemodynamic changes and Valsalva manoeuvres during the labour can lead to a further increase in intracranial pressure.^15,16,18 In such women, planned delivery by caesarean section may be preferable, and experienced anaesthetists can avoid the fluctuation in ICP produced during laryngoscopy and intubation.¹⁶ However, in cases where a VP shunt has been inserted to control the ICP, instrumental vaginal delivery can be considered under adequate labour analgesia to blunt the physiological changes induced by labour.¹⁵

Conclusion

In conclusion, the differential diagnosis of altered mentation in pregnancy is wide, and in this setting includes neurosurgical emergencies such as high intracranial pressure from NCC. A high index of suspicion and an appreciation of red flag symptoms should prompt neuroimaging, and where this is unavailable a referral to a higher centre should be made. An appreciation of risks and benefits of various forms of intervention around delivery is required, and joint decision making between members of the multidisciplinary team and an understanding of the woman’s wishes are paramount.