RESEARCH ARTICLE

Clinical Symptoms, Imaging Features and

Cyst Distribution in the Cerebrospinal Fluid

Compartments in Patients with

Extraparenchymal Neurocysticercosis

Rodrigo Bazan1, Pedro Tadao Hamamoto Filho1*, Gustavo José Luvizutto1, Hélio

Rubens de Carvalho Nunes1, Newton Satoru Odashima2, Antônio Carlos dos Santos3,

Jorge Elias Júnior3, Marco Antônio Zanini1, Agnès Fleury4, Osvaldo

Massaiti Takayanagui2

1 Department of Neurology, Psychology and Psychiatry from Botucatu Medical School; Univ Estadual

Paulista. Botucatu, Brazil, 2 Department of Neurosciences and Behavioral Sciences from Ribeirão Preto

School of Medicine; Univ São Paulo. Ribeirão Preto, Brazil, 3 Department of Internal Medicine from Ribeirão

Preto School of Medicine; Univ São Paulo. Ribeirão Preto, Brazil, 4 Institute for Biomedical Investigation;

Universidad Nacional Autónoma de Mexico. Mexico City, Mexico

* pthamamotof@hotmail.com

Abstract

Extraparenchymal neurocysticercosis has an aggressive course because cysts in the cere-

brospinal fluid compartments induce acute inflammatory reactions. The relationships

between symptoms, imaging findings, lesion type and location remain poorly understood.

In this retrospective clinical records-based study, we describe the clinical symptoms, mag-

netic resonance imaging features, and cyst distribution in the CSF compartments of 36

patients with extraparenchymal neurocysticercosis. Patients were recruited between 1995

and 2010 and median follow up was 38 months. During all the follow up time we found that

75% (27/36) of the patients had symptoms related to raised intracranial pressure sometime,

72.2% (26/36) cysticercotic meningitis, 61.1% (22/36) seizures, and 50.0% (18/36) head-

aches unrelated to intracranial pressure. Regarding lesion types, 77.8% (28/36) of patients

presented with grape-like cysts, 22.2% (8/36) giant cysts, and 61.1% (22/36) contrast-

enhancing lesions. Hydrocephalus occurred in 72.2% (26/36) of patients during the follow-

up period. All patients had cysts in the subarachnoid space and 41.7% (15/36) had at least

one cyst in some ventricle. Cysts were predominantly located in the posterior fossa (31

patients) and supratentorial basal cisterns (19 patients). The fourth ventricle was the main

compromised ventricle (10 patients). Spinal cysts were more frequent than previously

reported (11.1%, 4/36). Our findings are useful for both diagnosis and treatment selection

in patients with neurocysticercosis.

PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0005115 November 9, 2016 1 / 14

a11111

OPENACCESS

Citation: Bazan R, Hamamoto Filho PT, Luvizutto

GJ, Nunes HRdC, Odashima NS, dos Santos AC, et

al. (2016) Clinical Symptoms, Imaging Features

and Cyst Distribution in the Cerebrospinal Fluid

Compartments in Patients with Extraparenchymal

Neurocysticercosis. PLoS Negl Trop Dis 10(11):

e0005115. doi:10.1371/journal.pntd.0005115

Editor: Ana Flisser, Universidad Nacional

Autónoma de México, MEXICO

Received: May 25, 2016

Accepted: October 17, 2016

Published: November 9, 2016

Copyright: © 2016 Bazan et al. This is an open

access article distributed under the terms of the

Creative Commons Attribution License, which

permits unrestricted use, distribution, and

reproduction in any medium, provided the original

author and source are credited.

Data Availability Statement: All relevant data are

within the paper and its Supporting Information

files.

Funding: The authors received no specific funding

for this work.

Competing Interests: The authors have declared

that no competing interests exist.

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http://creativecommons.org/licenses/by/4.0/


Author Summary

Neurocysticercosis is caused by the accidental ingestion of eggs from Taenia solium whose
larvae lodge in the central nervous system. In this study we found that cysts within the
cerebrospinal fluid leaded to high rates of raised intracranial pressure, meningitis, seizures
and headache. Imaging studies such as magnetic resonance are useful for diagnosis, identi-
fication of the compromised sites of the central nervous system and, then, for treatment
guidance. The pattern of lesions identified through magnetic resonance in our paper helps
physicians on searching and analyzing some typical findings of extraparenchymal
neurocysticercosis.

Introduction

Neurocysticercosis is the most common parasitic disease of the central nervous system (CNS)
worldwide. It is caused by the accidental ingestion of eggs of the tapeworm Taenia solium.
After hatching from the eggs, some of the larvae lodge themselves in the CNS, where they
induce inflammatory reactions causing various symptoms[1]. Although neurocysticercosishas
potential for eradication, it is a neglected disease that remains endemic in Latin America, Sub-
Saharan Africa, and Southeast Asia [2]. In addition, migratory flows have reintroduced the dis-
ease in Europe and the USA [3, 4], increasing public health expenditure. [5].
There are two main forms of neurocysticercosis, parenchymal and extraparenchymal. Cyst

localization determines the clinical presentation of the patient. Cysts within the brain paren-
chyma are responsible for seizures that generally respond well to antiepileptic drugs. In such
cases, the prognosis is good unless there is a large parasite burden. In contrast, extraparenchy-
mal neurocysticercosishas a very poor course with high rates of mortality and disability [6–8]
Cysts in the cerebrospinal fluid (CSF) compartments elicit inflammatory responses that can

cause vasculitis, meningitis, CSF circulation imbalance, and elevated intracranial pressure.
Consequently, such cysts can cause strokes, hydrocephalus, and death [9–12]. Cysts in the sub-
arachnoid space over the convexity of the brain develop and progress similarly to parenchymal
cysts [1]. It is hypothesized that cysts located extraparenchymally may continuously absorb the
CSF and may grow to large sizes, resulting in compression of adjacent structures. This phe-
nomenon is called hydropic degeneration and is implicated in the transformation of the cellu-
lose into the racemose type of cysticerci [13]. Generally, scolices are absent in parasites located
in these regions, and the cysts show a characteristicmorphologywith complex proliferating
membranes resembling a cluster of grapes [14, 15]. In the brain ventricles, the cysts can cause
ependymitis and direct obstruction of the CSF flow, which in turn results in hydrocephalus
and often requires surgical intervention [16, 17].
Computed tomography (CT) and magnetic resonance imaging (MRI) are important tools

for the management of neurocysticercosisused for both diagnosis and treatment decisionmak-
ing. CT provides useful information on the stage of parenchymal parasite development; how-
ever, it lacks accuracy for the identification of cysts in the CSF compartments because CSF and
cyst fluid show similar attenuation on X-rays. MRI enables better visualization of cysts within
the subarachnoid space and ventricles [18]; particularly newMRI sequences with improved
sensitivities allow earlier diagnosis [19].
Althoughmany reports describe and review the clinical and radiological presentations of

neurocysticercosis, there is a dearth of systematic studies of lesion site distribution and its cor-
relations with symptom development. In this study, we describe the symptoms and radiological

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findings with special attention to cyst locations in a cohort of patients with extraparenchymal
neurocysticercosis.

Methods

Ethics statement

This project was approved by the Research Ethics Board from the Hospital das Clínicas da
Faculdade de Medicina de Ribeirão Preto (HCRP 12274/2006). All the patients gave informed
consent and analyzed data were anonymized.
This is a retrospective cohort study conducted at a specialized ambulatory clinic of a third

level hospital in Ribeirão Preto, Southeastern Brazil, an endemic area for neurocysticercosis.
Patients were both from rural and urban areas and were attended by the Brazilian Public
Health System. Rural areas are defined administratively by Brazilianmunicipalities, but the
official calculations results are close to the Organisation for Economic Co-operation and
Development one’s [20].
From 1995 to 2010, a total of 493 patients were evaluated for the suspicious of neurocysti-

cercosis and 340 cases were confirmed.Other diagnosis included brain neoplasms and other
CNS infections. From the 340 confirmed cases, 36 of them (10.6%) had extraparenchymal neu-
rocysticercosis. Fig 1 summarizes the recruitment of participants. Inclusion criteria were:
patients of any age, both sexes, with MRI studies showing characteristic lesions of neurocysti-
cercosis and with a minimum follow up period of six months. Exclusion criteria were: uncer-
tain diagnosis of neurocysticercosis, follow up period lesser than six months. We analyzed the
medical records of the 36 patients diagnosedwith extraparenchymal neurocysticercosis. Symp-
toms presented at admission and during the follow-up were grouped in four clinical syn-
dromes: raised intracranial pressure, cysticercoticmeningitis (meningeal irritation signs ie.
nuchal rigidity and Brudzinski or Kernig signs), seizures and isolated headache. In all patients,
at least one 1.5TMRI examination of the brain was performedwith the pattern sequences of
T1, T2 and FLAIR.An initial MRI was performed for diagnosis purposes and subsequent
examinations were performed on the basis of clinical indications. Patients with symptoms of
spinal or radicular compression also performed a spine MRI according to the clinical needs.
Median follow-up periodwas 38 months (range 8.8 to 156 months). We used the imaging data
to analyze the distribution of the cysts among the subarachnoid cisterns, brain fissures, ventri-
cles, and spine. We also analyzed the size of the cysts, the presence of contrast-enhancement,
the pattern of growth and the association with parenchymal lesions, and occurrence of hydro-
cephalus. Multiple cystic lesions resembling a bunch of grapes were considered “grape-like
lesions”. Cysts that reachedmore than 50mm at the largest dimension were considered giant.
For statistical analysis, we used Fisher’s exact test and the Chi-square test for comparison of

percentage between groups. SPSS (v. 15.0) and GraphPad Prism (v. 4.0) softwares were used.

Results

Clinical findings

The patients were aged from 21 to 65 years (40 ± 9.8 years). Twenty were male (55.5%), and
about 22.0% (8/36) lived in rural areas. By the admission, all patients had a probable diagnosis,
according to Del Brutto’s criteria [21]. By the end of the study, eight patients had a definitive
diagnosis of neurocysticercosis after pathologic confirmation, and 28 maintained the probable
diagnosis, as shown in Fig 1.

Initial clinical presentation. Headache was the most common initial symptom, affecting
77.8% of the patients (28/36). Nausea and vomiting affected 21 patients (58.3%), seizures 16

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Fig 1. Flowchart of participants recruitment. There were included 36 patients. By the end of the follow up, eight

patients had definitive diagnosis of neurocysticercosis by fulfilling the absolute criterion of histological

demonstration of the parasite after surgical removal. Beside the evidence of lesion highly suggestive of

neurocysticercosis on neuroimaging studies and clinical manifestations suggestive of neurocysticercosis, 21

patients had positive ELISA and 7 patients had an epidemiological criterion.

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(44.4%) and fatigue 8 patients (22.2%). On neurological examination, fourteen patients pre-
sented no abnormality (38.9%). Papilledema was present in 17 patients (47.2%), slight motor
deficits in 8 patients (22.2%), signs of meningeal irritation were observed in 7 patients (19.4%),
cranial nerve deficits (VI, VIII and XII) in 5 patients (13.9%), cognitive impairment in 4
patients (11.1%) and ataxia/dysmetria in 2 patients (5.6%).
Combining symptoms and signs, we observed the followingmost common syndromes and

diseases: raised intracranial pressure in 58.3% (21/36); seizures in 44.4% (16/36); headache
(without raised intracranial pressure) in 25.0% (9/36); and cysticercoticmeningitis in 19.4%
(7/36) of the patients.

Clinical presentation during follow up. During the follow-up period the patients
changed their clinical pictures and presented new symptoms and syndromes. The mean dura-
tion of time from the initial diagnosis to the onset of new syndromes was 6.0 months for men-
ingitis, 27.3 months for seizures, 36.3 months for raised intracranial pressure, and 55.6 months
for chronic headache.
In the entire observational period, themost common syndromes and diseaseswere raised intra-

cranial pressure (75.0% of the cohort, 27/36), cysticercoticmeningitis (72.2%, 26/36), seizures
(61.1%, 22/36), and isolated headache (50.0%, 18/36). Prompt treatment was offered to patients as
soon as new symptoms or complications appeared. Painful radiculopathy and sudden deficit symp-
toms related to stroke were also found, albeit less frequently (11.1%, 4/36; and 8.3%, 3/36 respec-
tively). Raised intracranial pressure was more common inmen than in women (90.0% vs. 56.2%,
p = 0.049). Isolated headachewasmore common in women than inmen (75.0% and 30.0%, respec-
tively; p = 0.017). Among the patients with headaches,migrainewas found in 44.4% (8/18), tension
headache in 38.9% (7/18), and chronic daily headache in 16.7% (3/18) of the patients.
Twenty two patients (61.1%) were treated with anti-parasitic drugs (21 of them with Alben-

dazole). Corticosteroidswere administered to 28 patients (77.8%). Twenty four patients
(66.7%) had at last one surgical procedure (the most frequent was ventriculoperitoneal shunt
[VPS], in 23). Microsurgical removal of cysts was performed in seven patients (19.4%) and
endoscopic surgery for cyst removal and third ventriculostomy was performed in other seven
patients. Among the patients with VPS, 65.2% (15/23) presented shunt malfunction sometime,
and 26.1% (6/23) presented a shunt-related infection. Table 1 summarizes the clinical findings.
Four patients (11.1%; all male) died during the observational period. These four patients pre-
sented seizures sometime, had increased intracranial pressure and died after decompensation
of hydrocephalus. On neuroimaging studies, all had cysts in the posterior fossa and in the basal
cisterns. From the 32 remaining patients, twelve had good outcome, without permanent defi-
cits, and twenty had unfavorable outcome, with some sequel.

Imaging findings

Types and developmental stages of parasites. Grape-like lesions were observed in 77.8%
(28/36) of the patients (Fig 2A–2C). Eight patients (22.2%) had giant cysts (Fig 2D), and 6
(16.7%) had both grape-like and giant cysts. In 22 patients (61.1%), there was contrast
enhancement near the cyst membranes (Fig 2E). Twelve patients presented a cyst mass (com-
pression) effect; in 10 of them, the brainstem was compressed. In the other 2 patients, the com-
pressed regions were the optic chiasm and the pituitary stalk. Associated parenchymal cysts
were found in 27 patients (75%). Twenty-three patients (63.9%) had calcified lesions, 7 cysts at
the vesicular stage, and 6 colloidal cysts. Four patients had both calcified and colloidal cysts,
three patients had calcified and vesicular cysts, and one patient had calcified, colloidal and
vesicular cysts. Twenty-six patients (72.2%) presented hydrocephalus sometime during the
observational period (Fig 2F).

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Cyst distribution in the CNS. Regarding the distribution of cysts among the CSF com-
partments, all patients had cysts in the subarachnoid space. 31 patients (86.1%) had lesions in
the cisterns of the posterior fossa near the brainstem. Nineteen patients (52.8%) presented
cysts in the supratentorial basal cisterns (i.e., the perimesencephalic cisterns and supraselar cis-
terns near the optic chiasm and carotid artery). Fifteen patients (41.7%) had cysts in the Sylvian
fissure (either right or left), 9 (25%) in the choroidal fissure, and 5 (13.9%) in the interhemi-
spheric fissure. Four patients (11.1%) had spine cysts, 3 of them at the lumbosacral level and 1
at the cervical level (Fig 3). Only 1 patient presented cysts in the cortical sulci.
Fifteen patients (41.7%) had at least one cyst within the ventricles: the fourth ventricle con-

tained a cyst in 10 patients, the lateral ventricles in 7 patients, and the third ventricle in 4
patients (Figs 4 and 5). Twelve patients (33.3%) had an enlarged fourth ventricle, indepen-
dently of the presence of cysts within it. In 4 patients, the cyst inside the ventricles displaced
adjacent structures. No patient had cysts only in the ventricles (without subarachnoid space
involvement). Fig 4 summarizes the observed frequencies of cyst occurrences in the CSF com-
partments, including the ventricles.

Table 1. –Clinical findings of the cohort of patients studied from 1995 to 2010.

Demographic data

Age at diagnosis (mean, sd) 40 years, 9.8

Sex 20 men (55.5%); 16 female (45.5%)

Habitation 28 urban (78%); 8 rural (22%)

Initial clinical symptoms and signs

Headache 28 (77.8%)

Nausea/vomiting 21 (58.3%)

Seizures 16 (44.4%)

Fatigue 8 (22.2%)

Papilledema 17 (47.2%)

Motor deficits 8 (22.2%)

Meningeal irritation 7 (19.4%)

Cranial nerve deficits 5 (13.9%)

Cognitive impairment 4 (11.1%)

Ataxia/dysmetria 2 (5.6%)

Initial clinical syndromes

Raised intracranial pressures 21 (58.3%)

Seizures 16 (44.4%)

Headache (w/o raised intracranial pressure) 9 (25%)

Cysticercotic meningitis 7 (19.4%)

Clinical syndromes during all the follow-up period

Raised intracranial pressure 27 (75%)

Cysticercotic meningitis 26 (72.2%)

Seizures 22 (61.1%)

Headache (w/o raised intracranial pressure) 18 (50%)

Treatment modalities

Anti-parasitic drugs 22 (61.1%)

Corticosteroids 28 (77.8%)

Ventriculoperitoneal shunt 23 (63.9%)

Microsurgical removal of cysts 7 (19.4%)

Endoscopic approaches 7 (19.4%)

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Clinico-radiological correlation

Besides sex and clinical syndromes, we also tested the correlation between the presence of ven-
tricular cysts and sex; the presence of ventricular cysts and hydrocephalus; the occurrence of
seizures and the presence of parenchymal cysts; and the presence of calcified cysts and
headache.
Men have presented more ventricular lesions than women (60% vs. 18.8%, p = 0.019). The

association between the presence of ventricular lesions and the occurrence of symptoms related
to elevated intracranial pressure was close to statistical significance (p = 0.051). The other cor-
relations between clinical presentation and lesion topography did not reach statistical signifi-
cance (seizures and parenchymal cysts: p = 0.712; calcified cysts and headache: p = 0.298).

Discussion

Neurocysticercosis is a pleomorphic disease. Its clinical presentation depends on the site, size
and stage of cyst as well as the intensity of the inflammatory reaction generated by host-para-
site interaction. A systematic review of clinical manifestations of neurocysticercosis showed
that seizures and headache are the most common symptoms in patients seen in neurologic

Fig 2. Different presentation patterns of extraparenchymal neurocysticercosis as revealed by brain MRI.

Grape-like lesions in the basal cisterns are evident on T2 axial (A) and sagittal (B) views of a patient’s brain. C, An

axial fluid-attenuated inversion recovery (FLAIR) coronal view of the same patient showing lesions in the Sylvian

and interhemispheric fissures as well as basal cisterns. D, A giant cyst (*) in the right Sylvian fissure and a

parenchymal enhancing cyst (arrow). E, A T1 axial view showing contrast enhancing in the Sylvian fissures

(arrow), mainly on the left, which is associated with intense inflammatory reactions due to degenerating cysts. F.

Ventricle enlargement (*) in a patient with neurocysticercosis-associated hydrocephalus.

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clinics [22]. Our study showed that headache was the commonest symptom on initial presenta-
tion and this is due to the fact that we focused on patients with the extraparenchymal form of
the disease, which has higher rates of raised intracranial pressure.
In the brain parenchyma, seizures are the most frequent symptom, in relation with the epi-

leptogenic properties of the parasite itself and of the local inflammatory response [23]. In our
study, a high proportion of the patients presented seizures (61.1%), and despite the high fre-
quency of parenchymal cysts, seizures did not reach statistical association with parenchymal
cysts (p = 0.712).

Fig 3. Spinal cysts. A spinal cyst (arrows) at the cervical level in a patient with extraparenchymal

neurocysticercosis (A, sagittal view; B, axial view).

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Fig 4. Schematic representation of the distribution of cysts in the study cohort among the CSF

compartments. A, In the subarachnoid space, the posterior fossa cisterns were involved in 86.1% of patients, the

supratentorial basal cisterns in 52.8%, the Sylvian fissures in 41.7%, and the interhemispheric fissure in 13.9% of

patients. B, Among the patients with cysts in the ventricles, 66.7% had cysts in the fourth ventricle, 46.7% in the

lateral ventricles, and 26.7% in the third ventricle. NB: percentages are higher than 100% because a single patient

could have more than one compromised site.

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On the other hand, when parasites are located extraparenchymally, it is clear that raised
intracranial pressure and signs of meningitis are the most frequent symptoms. The induced
inflammatory process and death of the parasites cause basal arachnoiditis, which perturbs the
free circulation of CSF and caused these two types of symptoms [10]. Symptoms of raised intra-
cranial pressure were among the initial findings in 58.3% of our patients; however, 75% had
experienced these symptoms by the end of the follow-up period.

Fig 5. MRI images of cysts inside brain ventricles. The fourth ventricle is the most common site for ventricular

neurocysticercosis. A large cyst (*) in the fourth ventricle (A) resulted in perilesional edema (arrows) in the

patient’s posterior fossa (B). The lateral ventricles are also common sites of cyst location (C). Meningeal

enhancement (arrowheads) is in a patient with a cyst (*) inside the left lateral ventricle. In some patients, multiple

ventricles can be compromised. D, Cysts in the left lateral (arrow) and fourth (*) ventricles of a patient.

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Regardingmeningitis, almost 1 of 5 patients presented symptomatology while in the entire
period of follow-up nearly 2/3 of the patients developed some symptom. Actually, previous
reports have shown a widely variable occurrence of meningeal signs, from 44 to 80% [24–26].
There seems to be a relationship between calcified neurocysticercosis and primary headache

disorders related to a dynamic remodeling process that occurs in the calcified cysts [27]. We
found that 50% of our patients presented with headache unrelated to intracranial pressure
changes but it was not dependent on the presence of calcified cysts (p = 0.298). Probably the
high prevalence of migraine in the general population poses difficulty in understanding the
causes of primary headache in extraparenchymal neurocysticercosis.Also, it is evident that
these forms of severe NCC can produce headaches by multiple mechanisms, principally
inflammatory, weakening the link between calcifications and headaches. Further research is
needed to ascertain a causal link between the disease and the symptom.
The association between neurocysticercosis and cerebrovascular disease is well established

[9]. Angiographic studies have demonstrated that almost one half of the patients with sub-
arachnoid neurocysticercosismay have evidence of cerebral arteritis, mainly in the middle and
posterior cerebral arteries [28]. Reduction of cerebral blood flow was also observed in patients
with inflammatory pattern of CSF [29]. Near 10% of our cohort presented stroke, which is in
accordance to the literature [7].
Imaging studies play a key role in diagnosing neurocysticercosis. Its clinical symptoms are

variable and nonspecific, and depend on the localization of the cysts within the CNS. Though
serological tests can help in diagnosis, they may not characterize the CNS involvement in cysti-
cercosis [15]. Therefore, imaging studies are required for the most accurate diagnosis and best
choice of treatment, because both depend on the activity and viability of the parasites in the
CNS.
Before the advent of CT, the diagnosis of neurocysticercosiswas a challenge, and the confir-

mation of the presence of parasites in the brain depended on risky surgical procedures [30]. CT
became a useful tool for diagnosing parenchymal lesions and, to a large extent, for characteriz-
ing the development stage of the cyst. However, CT was inadequate for detecting cysts within
the CSF compartments. Metrizamide CT ventriculography was an option in suspected cases of
ventricular involvement; however, it was invasive and insufficient for diagnosing cysts in the
fourth ventricle and basal cisterns. The higher sensitivity of MRI made it possible to detect
cysts in the CSF compartments [14]. However, small cysts in early stages of development often
escaped detection. Recently, high-resolutionmagnetic resonance cisternography sequences
have improved the identification of such cysts [15, 19].
Studies have reported conflicting rates of cyst distribution in the CNS of patients with neu-

rocysticercosis [14, 31–35]. The likely reason for the discrepant data is that most of the studies
focused on general imaging findings of neurocysticercosis or specific therapeutic modalities for
a given cyst localization. For example, Fleury et al. (2004) found that between the parasites
located in the subarachnoid space, 61.3% of them lie within the basal cisterns and 38.7% in the
cortical sulci [33]. On the other hand, pathological studies show that cortical sulci are probably
the most common location of intracranial cysticerci–up to 69% in asymptomatic patients
according to Sáenz et al. (2008) [36]. In contrast, we found few cysts in the cortical sulci,
although the prevalence of cysts in the basal cisterns was also high in our cohort. This differ-
ence may be related to the fact that we did not include patients without extraparenchymal
cysts, as long as many cortical sulci cysts may resemble cortical cysts on neuroimaging studies.
Reports to date indicate that cysts in the cortical sulci behave biologically similarly to parenchy-
mal cysts as long as they can also calcify [1]. Our findings also show predominant cyst localiza-
tion in the infratentorial cisterns than in the supratentorial ones (86.1% vs. 52.8%).

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Giant cysts in the subarachnoid space are found in 12.9 to 37% of patients [11, 37]. In our
cohort, this proportion was 22.2%. However, the definition of a giant cyst varies. Proaño et al.
(2001) used the cutoff value of 50 mm in diameter to enroll 33 patients with giant cysts out of a
total of 320 patients with neurocysticercosis (10.3%) [12].
Symptomatic spinal neurocysticercosis is not very frequent–it occurs in only 0.25–5.8% of

all neurocysticercosispatients. However, routine spine imaging in patients with intracranial
subarachnoid neurocysticercosis revealed a much higher frequency of spinal involvement [38].
Consistent with these results, we found a relatively high rate of spinal cysts (11.1%), but our
patients did had symptomatic lesions in the spine. In agreement with previous reports, the
lumbar level was the most frequently affected, causing in all of our patients symptoms of pain-
ful radiculopathy.
We also found a higher rate of ventricle-associated cysts (41.7%) than most common esti-

mates. In the series of Fleury et al. (2004), among 75 patients with extraparenchymal cysts only
18 (24%) had ventricular lesions [33]. In accordance with the literature, [32, 35, 39], we found
the most cysts inside the fourth ventricle (66.6%). However, the higher rate of lateral ventricu-
lar involvement compared to that of the third ventricle differs from previous reports [40].
Hydrocephalus occurs in about 30% of patients with neurocysticercosis [6]. In patients with

the extraparenchymal form of the disease, this rate rises to 64% [41]. We found an even higher
rate (72.2%), probably because our patients were followed longer and, consequently, had more
time to develop hydrocephalus during the follow-up period.Hydrocephalus is a major concern
for patients with extraparenchymal neurocysticercosis, because ventricular-peritoneal shunts
have been plagued with high rates of malfunction and risk of infection. The higher the number
of surgical revisions needed, the higher the overall mortality [42, 43].
We found no statistically significant correlation between any of the symptoms and cyst

topography. This may be due to the high rate of co-occurrenceof cysts in different compart-
ments. We did demonstrate a strong association between ventricular lesions and symptoms
related to increased intracranial pressure that was just below the threshold of statistical signifi-
cance (p = 0.051). In a previously described subset of patients who underwent CSF analysis, we
also could not demonstrate statistically significant differences related to sex, other demo-
graphic data, or cyst location [44].
Finally, the high proportion of patients with contrast-enhancing lesions (61.1%) may be due

to medical treatment, as long as we analyzed all MRI examinations during the follow-up time.
Degenerating cysts induce inflammatory response that becomes evident on contrast-medium
MRI sequences. It is important to be able to recognize this imaging pattern, because it poses
risk for the surgical resection of cysts adjacent to vessels, nerves, and parenchymal tissue itself
[45].
In the present study, we offer a systematic analysis of the distribution pattern of extrapar-

enchymal cysts in the CSF compartments in patients with neurocysticercosis.Limitations of
the present work include its retrospective nature and the limited number of patients. Its major
strength is in its focus on a specific cohort of patients with the extraparenchymal form of neu-
rocysticercosis.The presence of a scolex in a lesion is an absolute requirement in Del Brutto’s
proposed criteria for a diagnosis of neurocysticercosis [21]. However, racemose cysts often lack
a scolex or the scolices cannot be visualized in common neuroimaging studies. So in patients
with the extraparenchymal form of the disease, it is very important to look for other criteria of
the set to reach a definite diagnosis.
In our cohort of 36 patients with extraparenchymal neurocysticercosis,we found high prev-

alences of meningitis, seizures, headache, and symptoms related to raised intracranial pressure.
MRI showed most cysts lodged in the basal cisterns, mainly in the posterior fossa. The Sylvian
fissure was another common localization of cysts in general, and the most frequent site for

Clinical and Radiological Features of Extraparenchymal Neurocysticercosis

PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0005115 November 9, 2016 11 / 14



giant cysts. Spinal cysts may be more common than previously believed. Intraventricular cysts
are relatively frequent, especially in the fourth ventricle. Hydrocephalus and contrast-enhanc-
ing lesions are common features in extraparenchymal neurocysticercosis.The limited number
of patients in the study precludes far-reaching generalizations. Nevertheless, our findings will
be of interest for clinicians, epidemiologists and radiologists.

Supporting Information

S1 Checklist.
(DOC)

S1 Database.
(XLS)

Author Contributions

Conceptualization:RB OMT.

Data curation:RB PTHF GJL.

Formal analysis:HRdCN.

Investigation: RB GJL NSO.

Methodology:RB NSO ACdS JEJ.

Resources:ACdS JEJ.

Supervision:OMT.

Visualization:MAZAF OMT.

Writing – original draft:RB PTHF.

Writing – review & editing:MAZAF OMT.

References
1. Garcı́a HH, Del Brutto OH. Neurocysticercosis: updated concepts about an old disease. Lancet Neurol

2005; 4:653–661. doi: 10.1016/S1474-4422(05)70194-0 PMID: 16168934

2. Coyle CM, Mahanty S, Zunt JR, Wallin MT, Cantey PT, White AC Jr et al. Neurocysticercosis:

neglected but not forgotten. PLoS Negl Trop Dis 2012; 6:e1500. doi: 10.1371/journal.pntd.0001500

PMID: 22666505

3. Flisser A, Sarti E, Lightowlers M, Schantz P. Neurocysticercosis: regional status, epidemiology, impact

and control measures in Americas. Acta Tropica 2003; 87:43–51. PMID: 12781377

4. Wallin MT, Kurtzke JF. Neurocysticercosis in the United States. Review of an important emerging

infection. Neurology 2004; 63:1559–1564. PMID: 15534236

5. O’Neal SE, Flecker RH. Hospitalization frequency and charges for neurocysticercosis, United States,

2003–2012. Emerg Infect Dis 2015; 21:969–976. doi: 10.3201/eid2106.141324 PMID: 25988221

6. Estañol B, Corona T, Abad P, A prognostic classification of cerebral cysticercosis: therapeutic implica-

tions. J Neurol Neurosurg Psychiatry 1986; 49:1131–1134. PMID: 3783174

7. Fleury A, Carrillo-Mezo R, Flisser A, Sciutto E, Corona T. Subarachnoid basal neurocysticercosis: a

focus on the most severe form of the disease. Expert Rev Anti Infect Ther 2011; 9:123–133. doi: 10.

1586/eri.10.150 PMID: 21171883

8. Garcia HH, Nash TE, Del Brutto OH. Clinical symptoms, diagnosis and treatment of neurocysticerco-

sis. Lancet Neurol 2014; 13:1202–1215. doi: 10.1016/S1474-4422(14)70094-8 PMID: 25453460

9. Cantú C, Barinagarrementeria F. Cerebrovascular complications of neurocysticercosis. Clinical and

neuroimaging spectrum. Arch Neurol 1996; 53:233–239. PMID: 8651876

Clinical and Radiological Features of Extraparenchymal Neurocysticercosis

PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0005115 November 9, 2016 12 / 14

http://journals.plos.org/plosntds/article/asset?unique&id=info:doi/10.1371/journal.pntd.0005115.s001
http://journals.plos.org/plosntds/article/asset?unique&id=info:doi/10.1371/journal.pntd.0005115.s002
http://dx.doi.org/10.1016/S1474-4422(05)70194-0
http://www.ncbi.nlm.nih.gov/pubmed/16168934
http://dx.doi.org/10.1371/journal.pntd.0001500
http://www.ncbi.nlm.nih.gov/pubmed/22666505
http://www.ncbi.nlm.nih.gov/pubmed/12781377
http://www.ncbi.nlm.nih.gov/pubmed/15534236
http://dx.doi.org/10.3201/eid2106.141324
http://www.ncbi.nlm.nih.gov/pubmed/25988221
http://www.ncbi.nlm.nih.gov/pubmed/3783174
http://dx.doi.org/10.1586/eri.10.150
http://dx.doi.org/10.1586/eri.10.150
http://www.ncbi.nlm.nih.gov/pubmed/21171883
http://dx.doi.org/10.1016/S1474-4422(14)70094-8
http://www.ncbi.nlm.nih.gov/pubmed/25453460
http://www.ncbi.nlm.nih.gov/pubmed/8651876


10. Matushita H, Pinto FC, Cardeal DD, Teixeira MJ. Hydrocephalus in neurocysticercosis. Childs Ner

Syst 2011; 27:1709–1721.

11. Colli BO, Carlotti CG Jr, Assirati JA Jr, Machado HR, Valença M, Amato MC. Surgical treatment of

cerebral cysticercosis: long term results and prognostic factors. Neurosurg Focus 2002; 12:e3.

12. Proaño JV, Madrazo I, Avelar F, Lopez-Felix B, Diaz G, Grijalva I. Medical treatment for neurocysticer-

cosis characterized by giant subarachnoid cysts. N Engl J Med 2001; 345:879–885. doi: 10.1056/

NEJMoa010212 PMID: 11565520

13. Escobar A. The pathology of neurocysticercosis. in: Palacios E, Rodriguez-Carbajal J, Taveras JM

(Eds.) Cysticercosis of the central nervous system. Charles C Thomas, Springfield; 1983: 27–54.

14. Martinez HR, Rangel-Guerra R, Elizondo G, Todd LE, Ancer J, Prakash SS. MR Imaging in neurocysti-

cercosis: a study of 56 cases. Am J Neuroradiol 1989; 10:1011–1019. PMID: 2505513

15. Lerner A, Shiroishi MS, Zee CS, Law M, Go JL. Imaging of neurocysticercosis. Neuroimaging Clin N

Am 2012; 22:659–676. doi: 10.1016/j.nic.2012.05.004 PMID: 23122261

16. Cuetter AC, Andrews RJ. Intraventricular neurocysticercosis: 18 consecutive patients and review of

the literature. Neurosurg Focus 2002; 12:e5.

17. Rangel-Castilla L, Serpa JA, Gopinath SP, Graviss EA, Diaz-Marchan P, White AC Jr. Contemporary

neurosurgical approaches to neurocysticercosis. Am J Trop Med Hyg 2009; 80:373–378. PMID:

19270284

18. Kimura-Hayama ET, Higuera JA, Corona-Cedillo R, Chávez-Macı́as L, Perochena A, Quiroz-Rojas LY

et al. Neurocysticercosis: radiologic-pathologic correlation. Radiographics 2010; 30:1705–1719. doi:

10.1148/rg.306105522 PMID: 21071384

19. Carrilo Mezo R, Garcı́a JL, Arroyo M, Fluery A. Relevance of 3D magnetic resonance imaging

sequences in diagnosing basal subarachnoid neurocysticercosis. Acta Tropica 2015; 152:60–65. doi:

10.1016/j.actatropica.2015.08.017 PMID: 26327445

20. Braga GB, Remoaldo PC, Fiúza ALC. A methodology for definition of rural spaces: an implementation

in Brazil. Cienc Rural 2015; 46:375–380.

21. Del Brutto OH, Rajshekhar V, White AC Jr, Tsang VC, Nash TE, Takayanagui OM, Schantz PM,

Evans CA, Flisser A, Correa D, Botero D, Allan JC, Sarti E, Gonzalez AE, Gilman RH, Garcia HH. Pro-

posed diagnostic criteria for neurocysticercosis. Neurology 2001; 57:177–183. PMID: 11480424

22. Carabin H, Ndimubanzi PC, Budke CM, Nguyen H, Qian Y, Cowan LD et al. Clinical manifestations

associated with neurocysticercosis: a systematic review. PLoS Negl Trop Dis 2011; 5:e1152. doi: 10.

1371/journal.pntd.0001152 PMID: 21629722

23. Carpio A, Romo ML. The relationship between neurocysticercosis and epilepsy: and endless debate.

Arq Neuropsiquiatr 2014; 72:383–390. PMID: 24863516

24. Venkataraman S, Roy AK, Dhamija RM, Sanchetee PC. Cysticercal meningoencephalitis: clinical pre-

sentation and autopsy findings. J Assoc Physicians India. 1990; 3 8:763–763.

25. Bonametti AM, Baldy SJL, Bortoliero AL, Maio CM, Passso JN, Takata PK, Pauli DS, Guimarãres JC,

Anzai ET, Elisbão MC. Neurocysticercosis with initial clinical picture of acute meningitis. Rev Inst Med

Trop Sao Paulo. 1994; 36:27–27. PMID: 7997770

26. Cárdenas G, Jung H, Rı́os C, Fleury A, Soto-Hernández JL. Severe Cysticercal Meningitis: Clinical

and Imaging Characteristics. Am J Trop Med Hyg. 2010; 82:121–125 doi: 10.4269/ajtmh.2010.09-

0347 PMID: 20065006

27. Del Brutto OH, Del Brutto VJ. Calcified neurocysticercosis among patients with primary headache.

Cephalalgia 2011; 32:250–254. doi: 10.1177/0333102411433043 PMID: 22174352

28. Barrinagarrementeria F, Cantú C. Frequency of cerebral arteritis in subarachnoid cysticercosis. An

angiographic study. Stroke 1998; 29:123–125. PMID: 9445339

29. Góngora-Rivera F, Soto-Hernández JL, Guevara P, Sotelo-Morales J. In neurocysticercosis, CSF

cytokines correlate with cerebral blood flow velocities. Neurology 2008; 71:1119–1122. doi: 10.1212/

01.wnl.0000326961.34868.5b PMID: 18824677

30. Minguetti G, Ferreira MV. Computed tomography in neurocysticercosis. J Neurol Neurosurg Psychia-

try 1983; 46:936–942. PMID: 6644318

31. Del Brutto OH, Sotelo J. Neurocysticercosis: an update. Rev Infect Dis 1988; 106:1075–1087.

32. Garcia HH, Del Brutto OH. Taenia solium cysticercosis. Infect Dis Clin North Am 2000; 14:97–119.

PMID: 10738675

33. Fleury A, Dessei A, Preux PM, Dumas M, Tapia G, Larralde C, Sciutto E. Symptomatic human neuro-

cysticercosis. Age, sex and exposure factors relating with disease heterogeneity. J Neurol 2004;

251:830–837. doi: 10.1007/s00415-004-0437-9 PMID: 15258785

Clinical and Radiological Features of Extraparenchymal Neurocysticercosis

PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0005115 November 9, 2016 13 / 14

http://dx.doi.org/10.1056/NEJMoa010212
http://dx.doi.org/10.1056/NEJMoa010212
http://www.ncbi.nlm.nih.gov/pubmed/11565520
http://www.ncbi.nlm.nih.gov/pubmed/2505513
http://dx.doi.org/10.1016/j.nic.2012.05.004
http://www.ncbi.nlm.nih.gov/pubmed/23122261
http://www.ncbi.nlm.nih.gov/pubmed/19270284
http://dx.doi.org/10.1148/rg.306105522
http://www.ncbi.nlm.nih.gov/pubmed/21071384
http://dx.doi.org/10.1016/j.actatropica.2015.08.017
http://www.ncbi.nlm.nih.gov/pubmed/26327445
http://www.ncbi.nlm.nih.gov/pubmed/11480424
http://dx.doi.org/10.1371/journal.pntd.0001152
http://dx.doi.org/10.1371/journal.pntd.0001152
http://www.ncbi.nlm.nih.gov/pubmed/21629722
http://www.ncbi.nlm.nih.gov/pubmed/24863516
http://www.ncbi.nlm.nih.gov/pubmed/7997770
http://dx.doi.org/10.4269/ajtmh.2010.09-0347
http://dx.doi.org/10.4269/ajtmh.2010.09-0347
http://www.ncbi.nlm.nih.gov/pubmed/20065006
http://dx.doi.org/10.1177/0333102411433043
http://www.ncbi.nlm.nih.gov/pubmed/22174352
http://www.ncbi.nlm.nih.gov/pubmed/9445339
http://dx.doi.org/10.1212/01.wnl.0000326961.34868.5b
http://dx.doi.org/10.1212/01.wnl.0000326961.34868.5b
http://www.ncbi.nlm.nih.gov/pubmed/18824677
http://www.ncbi.nlm.nih.gov/pubmed/6644318
http://www.ncbi.nlm.nih.gov/pubmed/10738675
http://dx.doi.org/10.1007/s00415-004-0437-9
http://www.ncbi.nlm.nih.gov/pubmed/15258785


34. Takayanagui OM. Therapy for neurocysticercosis. Expert Rev Neurother 2004; 4:129–139. doi: 10.

1586/14737175.4.1.129 PMID: 15853623

35. Takayanagui OM, Odashima NS. Clinical aspects of neurocysticercosis. Parasitol Int 2006; 55:S111–

115. doi: 10.1016/j.parint.2005.11.016 PMID: 16330240

36. Sáenz B, Ramı́rez J, Aluja A, Escobar A, Fragoso G, Morales J et al. Human and porcine neurocysti-

cercosis: differences in the distribution and developmental stages of cysticerci. Trop Med Int Health

2008; 13:697–702. doi: 10.1111/j.1365-3156.2008.02059.x PMID: 18384482

37. Del Brutto OH. Albendazole therapy for subarachnoid cysticerci: clinical and neuroimaging analysis of

17 patients. J Neurol Neurosurg Psychiatry 1997; 62:659–661. PMID: 9219761

38. Callacondo D, Garcia HH, Gonzales I, Escalante D, Nash TE, Cysticercosis Working Group in Peru.

High frequency of spinal involvement in patients with basal subarachnoid neurocysticercosis. Neurol-

ogy 2012; 78:1394–1400. doi: 10.1212/WNL.0b013e318253d641 PMID: 22517102

39. Garcia HH, Gonzalez AE, Evans CA, Gilman RH. The Cysticercosis Working Group in Peru. Taenia

solium cysticercosis. Lancet 2003; 361:547–556.

40. Zee CS, Go JL, Kim PE, DiGiorgio CM. Imaging of neurocysticercosis. Neuroimaging Clin N Am 2000;

10:391–407. PMID: 10775958

41. Figueroa JJ, Davis LE, Magalhaes A. Extraparenchymal neurocysticercosis in Albuquerque, New

Mexico. J Neuroimaging 2011; 21:38–43. doi: 10.1111/j.1552-6569.2009.00452.x PMID: 20002970

42. Kelley R, Duong DH, Locke GE. Characteristics of ventricular shunt malfunctions among patients with

neurocysticercosis. Neurosurgery 2002; 50:757–762. PMID: 11904026

43. Agapejev S, Souza AFP, Bazan R, Faleiros ATS. Clinical and evolutive aspects of hydrocephalus in

neurocysticercosis. Arq Neuropsiquiatr 2007; 65:674–680. PMID: 17876413

44. Bazan R, Odashima NS, Luvizutto GJ, Hamamoto Filho PT, Zanini MA, Takayanagui OM. Analysis of

cerebrospinal fluid in racemose form of neurocysticercosis. Arq Neuropsiquiatr 2015; 73:852–855.

doi: 10.1590/0004-282X20150120 PMID: 26291994

45. Garcia HH, Evans AW, Nash TE, Takayanagui OM, White AC Jr, Botero D et al. Current consensus

guidelines for treatment of neurocysticercosis. Clin Microbiol Rev 2002; 15:747–756. doi: 10.1128/

CMR.15.4.747-756.2002 PMID: 12364377

Clinical and Radiological Features of Extraparenchymal Neurocysticercosis

PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0005115 November 9, 2016 14 / 14

http://dx.doi.org/10.1586/14737175.4.1.129
http://dx.doi.org/10.1586/14737175.4.1.129
http://www.ncbi.nlm.nih.gov/pubmed/15853623
http://dx.doi.org/10.1016/j.parint.2005.11.016
http://www.ncbi.nlm.nih.gov/pubmed/16330240
http://dx.doi.org/10.1111/j.1365-3156.2008.02059.x
http://www.ncbi.nlm.nih.gov/pubmed/18384482
http://www.ncbi.nlm.nih.gov/pubmed/9219761
http://dx.doi.org/10.1212/WNL.0b013e318253d641
http://www.ncbi.nlm.nih.gov/pubmed/22517102
http://www.ncbi.nlm.nih.gov/pubmed/10775958
http://dx.doi.org/10.1111/j.1552-6569.2009.00452.x
http://www.ncbi.nlm.nih.gov/pubmed/20002970
http://www.ncbi.nlm.nih.gov/pubmed/11904026
http://www.ncbi.nlm.nih.gov/pubmed/17876413
http://dx.doi.org/10.1590/0004-282X20150120
http://www.ncbi.nlm.nih.gov/pubmed/26291994
http://dx.doi.org/10.1128/CMR.15.4.747-756.2002
http://dx.doi.org/10.1128/CMR.15.4.747-756.2002
http://www.ncbi.nlm.nih.gov/pubmed/12364377