[Link]

1590/0004-282X-ANP-2022-S115
NEUROINFECTIOUS DISEASE

Update on the diagnosis and management of

neurocysticercosis
Atualização no diagnóstico e manejo da neurocisticercose
Osvaldo Massaiti TAKAYANAGUI1, Tissiana Marques de HAES1

ABSTRACT
Background: Neurocysticercosis (NCC) is a serious public health problem in several developing countries, including those in Latin America,
Asia, and Africa. NCC is considered to be the main cause of late-onset epilepsy in endemic areas. Objective: This review summarizes recent
advances in diagnosis and therapy of NCC. Methods: Relevant articles and books were reviewed and used as a source of information for
this review. Results: The diagnosis of NCC is based upon neuroimaging studies (MRI and computed tomography) and laboratory analysis of
the cerebrospinal fluid (CSF). Praziquantel and albendazole are considered parasiticidal drugs against NCC, but there is an intense debate
over the value and safety of these drugs. Conclusion: Given the relative scarcity of clinical trials, more comparative interventional studies,
especially randomized controlled trials in long-term clinical evolution, are required in order to clarify the controversy over the validity of
parasitic therapy in patients with NCC.
Keywords: Cysticercosis; Taenia solium; Epilepsy; Magnetic Resonance Imaging; Cerebrospinal Fluid; Albendazole; Praziquantel.

RESUMO
Antecedentes: A neurocisticercose (NCC) é grave problema de saúde pública nos países em desenvolvimento, especialmente na América
Latina, Ásia e África. A NCC é considerada a principal causa de epilepsia de início tardio nas regiões endêmicas. Objetivo: Este artigo pretende
discutir os recentes avanços no diagnóstico e tratamento da NCC. Métodos: Artigos científicos e livros relevantes serviram de fonte de
informação para esta revisão. Resultados: O diagnóstico da NCC é fundamentado nos exames de neuroimagem (ressonância magnética
e tomografia computadorizada) e do líquido cefalorraquiano (LCR). Atualmente, praziquantel e albendazole são considerados eficazes na
terapêutica etiológica da NCC, mas há intenso debate quanto à validade e segurança desses medicamentos. Conclusão: Pela relativa carência
de ensaios clínicos, são necessários novos estudos particularmente randomizados, controlados e com análise de desfechos clínicos a longo
prazo para o esclarecimento da polêmica envolvendo a validade da terapêutica parasiticida na NCC.
Palavras-chave: Cisticercose; Taenia solium; Epilepsia; Imageamento por Ressonância Magnética; Líquido Cefalorraquiano; Albendazol;
Praziquantel.

INTRODUCTION Human cysticercosis is the result of accidental infection

with the embryonic form due to the ingestion of water or food
Neurocysticercosis (NCC), the central nervous system (CNS) contaminated with Taenia solium eggs.
infection caused by the larval form of Taenia solium, is a serious
public health problem in several developing countries, includ- PATHOLOGY
ing those in Latin America, Asia, and Africa. NCC is considered
to be the main cause of late-onset epilepsy in endemic areas1,2. The cysts located in the brain parenchyma may range in size
Dangerous sanitary and poor socioeconomic conditions com- from a few millimeters to several centimeters. Initially, viable
bine to perpetuate its dissemination. cysticerci have a translucent whitish membrane, clear vesicular
The prevalence and mortality of NCC are probably grossly fluid, and an invaginated larva, the scolex, with minimal sur-
underestimated because diagnosis requires neuroimaging rounding inflammation (vesicular stage)3,4 (Figures 1 and 2).
(computed tomography and/or MRI) which is largely unavail- The cysticerci developing in the ventricles (Figure 3) or in the
able in highly endemic regions1. subarachnoid space usually reach a larger size and often take

Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Neurociências e Comportamento, Ribeirão Preto SP, Brazil.
1

Correspondence: Osvaldo M. Takayanagui; Email: omtakay@[Link].

Conflict of interest: There is no conflict of interest to declare.
Authors’ contributions: OMT: wrote the paper; OMT, TMH: revised the paper.
OMT  [Link] TMH [Link]
Received on March 15, 2022; Accepted on April 29, 2022.

296
Figure 1. MRI intraparenchymal viable cysticercus with scolex. Figure 2. MRI multiple intraparenchymal viable cysticerci.

on the form of racemose cysticerci, which are characterized by

a membrane of irregular thickness and the absence of a sco-
lex. These are usually clustered into multiple interconnected
vesicles, resembling a cluster of grapes3,4.
The cysticerci located in the brain parenchyma undergo
a natural evolutionary process which culminates with their
degeneration within a period of approximately three to six
years. Replacement of the clear fluid with a jelly-like whitish
material occurs and the parasite is surrounded by host inflam-
matory cells (colloidal stage). At a more advanced stage, the
cyst begins to be reduced in size, the walls become thicker
and its contents, due to mineralization with calcium salts, are
transformed into coarse granules (granular stage). The final
stage is when the cyst attains complete mineralization (calci-
fied nodular stage)3.

CLINICAL FEATURES

The clinical manifestations of NCC largely depend on the

number, type, size, localization, and stage of development of
cysticerci, as well as on the host immune response against
Figure 3. MRI intraventricular cysticercosis.
the parasite. There are no pathognomonic features of a typi-
cal NCC syndrome5,6.
Intraparenchymal NCC is usually associated with a good Seizures are widely reported to be the most common symp-
prognosis. Frequently, patients with few intraparenchymal tom, occurring in 70-90% of patients and NCC is considered
cysts remain asymptomatic7, although some patients develop to be the main cause of late-onset epilepsy in endemic areas1.
seizures. On the other hand, in patients with massive cerebral Partial seizures, with or without secondary generalization,
infection, uncontrolled seizures and cognitive deficit may predominate in most cases. Seizures are thought to occur
develop5. from parenchymal irritation because of active inflammation

Takayanagui OM, et al. Diagnosis and management of neurocysticercosis. 297

 occurring with the death of the cysticercus or from gliosis
associated with end-stage calcified lesions. In many patients,
as the cysticercus calcifies, seizures tend to become less fre-
quent although patients usually require continuous treatment
with anti-seizure medication.
When cysticerci lodge within the ventricular system a
life-threatening acute intracranial hypertension secondary to
hydrocephalus may develop, directly related to obstruction of
the flow of CSF by the cyst or by inflammatory reaction of the
ependyma. Although the cysts may be found anywhere within
the ventricular system, the fourth ventricle is most commonly
involved8.
Acute intermittent hydrocephalus, with violent headaches,
attacks of positional vertigo or loss of consciousness induced
by abrupt movements of the head (Bruns’ syndrome), or even
sudden death, may result if a mobile ventricular cyst is present4.
Cysts in the subarachnoid space may invade the Sylvian
fissure and grow to large sizes, reaching several centimeters in
diameter (giant cysts) (Figure 4), causing intracranial hyperten-
sion with hemiparesis, partial seizures or other focal neurological
signs. Subarachnoid cysts may also invade the basal cisterns; ini-
tially the growing membranes resemble a bunch of grapes, hence Figure 4. MRI multiple giant cysticerci.
this form of disease is called “racemose” cysticercosis (Figure 5).
It is associated with an intense inflammatory reaction, fibrosis
and progressive thickening of the leptomeninges at the base
of the brain. In approximately 50-60% of the cases, there is an
obstruction of the CSF circulation, resulting in hydrocephalus
and progressive intracranial hypertension and mortality over
20% of cases4. Signs of arachnoiditis, cognitive and psychiatric
dysfunction, cranial nerve palsy, chiasmatic syndrome, cere-
bellopontine-angle syndrome, and cerebral infarcts secondary
to occlusive endarteritis may develop8-11. When hydrocephalus
secondary to cysticercotic meningitis is present, mortality is
high (50%), and most patients die within two years after CSF
shunting12. Therefore, ventricular and basal cisternal locations
are considered to be malignant forms of neurocysticercosis13.
Intracranial hypertension also occurs in patients with cys-
ticercal encephalitis as the result of a massive infection of the
brain parenchyma inducing an intense immune response and
diffuse brain edema14.
Some patients with NCC present with psychiatric and cog-
nitive impairment15,16.
The natural history of NCC is largely unknown and most
Figure 5. MRI subarachnoid racemose cysticercosis, involving
data are based on retrospective and uncontrolled studies, mainly
basal cisterns.
from neurological hospital settings. Prospective and properly
designed studies are keenly awaited to help clarify the natural
history of the disease5. standard for diagnosis of NCC. Early in the infection, a viable
cyst appears as a spherical hypodense lesion on CT scan and
DIAGNOSIS as a CSF-like signal on MRI. Both CT and MRI are able to show
the invaginated scolex. In the degenerative phase, the cyst
The diagnosis of NCC is based upon neuroimaging stud- shows a ring-like or a nodular contrast enhancement, with or
ies and antibody/antigen detection in the serum and the CSF. without perilesional edema. A final stage is observed when the
Neuroimaging with either computed tomography (CT) scan cyst dies and a process of mineralization and resorption takes
or magnetic resonance imaging (MRI) is considered the gold place, resulting in a calcified nodule.

298 Arq Neuropsiquiatr 2022;80(5 Suppl. 1):296-306

 Since the cyst membrane is thin and the fluid is isodense Unfortunately, diagnosis of NCC requires neuroimaging
within the CSF, non-inflamed extraparenchymal (ventricular techniques (CT and/or MRI), immunodiagnostic tests in serum
or subarachnoid) cysticerci are usually not visible on CT and (EITB) and CSF (antibodies and/or antigens) that are not read-
may only reveal subtle, indirect findings on MRI scans. ily available in many setting where the disease is prevalent1,
MRI is more sensitive than CT scans for the diagnosis of due to resource constraints19.
NCC since it improves recognition of the perilesional edema
and degenerative changes of the parasite, as well as small cysts TREATMENT OF NCC
or those located inside the ventricles, brain stem, cerebellum
and the racemose vesicles at the level of the posterior fossae The treatment modalities available to patients with NCC
and basal cisterns. However, CT scans are more sensitive in include surgery, symptomatic therapy and antiparasitic drugs.
the detection of calcifications.
Recently, the development of three-dimensional MRI
sequences, such as Fast Imaging Employing Steady-State Surgery
(FIESTA) and 3D constructive interferences steady state (3D Prior to the advent of anti cysticercal drugs, surgery was
CISS) has improved the sensitivity and specificity of MRI, espe- the primary therapy for NCC – mainly open surgery for exci-
cially for subarachnoid and ventricular cysticerci17-19. sion of large cysts or cysts in the ventricles. The role of surgical
Analysis of CSF samples is an important parameter for the therapy in the management of NCC has significantly decreased
assessment and follow-up of patients with a suspicion of NCC. over time and surgery is now mainly restricted to placement of
The most frequent CSF alterations are mononuclear pleocy- ventricular shunts for hydrocephalus secondary to NCC and
tosis and the presence of eosinophils and specific antibodies
for occasional cases of accessible intraventricular or racemose
detected by enzyme-linked immunosorbent assay (ELISA) or
subarachnoid cysts, mainly by endoscopic approach32.
enzyme-linked immunoelectrotransfer blot assay (EITB). The
presence of pleocytosis and specific antibodies coincides with
the degenerating stage of cysticerci and intensification of the
Symptomatic therapy
host immune-inflammatory response4.
Symptomatic therapy is probably more important in NCC
A number of tests have been developed for the detection
than in any other infectious disease33.
of antigens and anti cysticercal antibodies in CSF. Although
Most patients with NCC present seizures and the adminis-
enzyme-linked immunosorbent assay (ELISA) and enzyme-
linked immunoelectrotransfer blot assay (EITB) in CSF have a tration of standard doses of a single-first-line anti-seizure medi-
high level of sensitivity and specificity, major concerns for the cation such as phenytoin or carbamazepine usually results in
use of EITB are its complexity, time of execution, and cost20,21. adequate seizure control. The optimum length of anti-seizure
Taenia antigens may also be detected in the CSF specially in the medication therapy has not yet been determined, but it has been
clinically active forms of NCC, being a more sensitive marker suggested that it should be continued until serial neuroimaging
than the classic eosinophil presence22. studies show resolution of acute lesions34. After disappearance
Immunodiagnostic tests of serum samples have been widely of the cysts, most patients who have been free of seizures for
used in diagnostic and epidemiological studies of cysticerco- two years can eventually discontinue anti-seizure medication.
sis. The EITB assay is almost 100% sensitive for patients with Since inflammation is the conspicuous accompaniment
either multiple active parenchymal cysts or extraparenchymal in most forms of NCC, corticosteroids represent the primary
NCC. However, the sensitivity is lower for patients with either form for attenuating the inflammatory reaction that may cause
single parenchymal cysts or calcifications alone. New assays are severe recurrent seizures, focal neurological symptoms and
being developed. Studies of monoclonal antibody-based ELISA intracranial hypertension syndrome. Additionally, corticoste-
tests for detection of antigens have shown detection of circu-
roids are fundamental for patients with cysticercal encephalitis,
lating and CSF antigen and may be useful for both diagnosis
arachnoiditis and angiitis. Only scarce controlled data exist to
and post therapeutic monitoring, with a correlation between
determine when and what type of corticosteroids and the treat-
circulating antigen detection and CT scanning results during
ment regime to use. The most frequent regimen is dexametha-
follow-up23,24. Other assays for detection of parasite antigen
sone at doses of 4.5 to 12 mg/day. Prednisone at 1 mg/kg/day,
are under development including polymerase chain reaction25,
quantitative PCR26, recombinant antigens27 and a combination daily or three times a week, may replace dexamethasone when
of EITB banding patterns with antigen-ELISA28. long-term steroid therapy is required. For patients who develop
Because clinical manifestations are pleomorphic, most chronic or recurrent cerebral inflammation, methotrexate may
neuroimaging findings are not pathognomonic, and several be useful as a corticosteroid-sparing or replacement agent35.
immunological tests show low levels of sensitivity and speci- Symptomatic treatment also includes the placement of ven-
ficity, some authors have proposed diagnostic criteria for diag- tricular shunts for hydrocephalus associated with intracranial
nosis NCC29-31. hypertension syndrome.

Takayanagui OM, et al. Diagnosis and management of neurocysticercosis. 299

 is an inflammatory reaction produced by the host in response
Anti Cysticercal Drugs
to the death of the parasite36,37,38,44.
Therapy for NCC, formerly restricted to palliative measures,
Occasionally, severe reactions such as brain infarction and
has advanced with the advent of two drugs considered to be
death due to acute intracranial hypertension syndrome may
effective: praziquantel (PZQ) and albendazole (ALB). However,
occur44. Although severe decompensation of intracranial hyper-
pharmacologic therapy should not be used indiscriminately in
tension is a rare occurrence during treatment, this possibility
all cases but individualized on the basis of clinical syndrome,
advises against treatment on an outpatient basis, especially
characteristic of the cysts, and the host immune response.
for patients with massive infection, ventricle cysts and sub-
The precise indication is for symptomatic patients showing
arachnoid racemose cysticercosis. Additionally, these severe
multiple viable brain parenchymal cysticerci. The viability of
complications support the recommendation of the simultane-
cysticerci is characterized by the presence of rounded areas of
ous use of dexamethasone in these cases. However, it should
hypodense lesions on CT scans with a scolex inside the cyst,
be kept in mind that coadministration of dexamethasone
better shown on MRI, without contrast enhancement or sur-
reduces plasma levels of PZQ. Therefore, some authors have
rounding edema1,36-39.
recommended reserving steroids as symptomatic treatment
The goal of anti cysticercal therapy is the simultaneous
for patients who experience headache or vomiting during PZQ
destruction of multiple cysts and then controlling the resulting
therapy for intraparenchymal lesions.
inflammatory reaction with steroids. This strategy of preventing
On the other hand, dexamethasone should not cause
prolongation of brain inflammation due to degeneration of
concern with ALB therapy since simultaneous administra-
multiple cysts at different times would allow better clinical
tion increases plasma levels of ASOX by slowing the rate of
evolution than the natural progression of NCC37,38.
its elimination45,46.
Praziquantel (PZQ)
Praziquantel is an acylated isoquinoline-pyrazine with Albendazole versus Praziquantel
broad anthelmintic activity and strong activity against schis- Most comparative investigations have shown that ALB
tosomes and cestodes. is more effective than PZQ in reducing the number of cysts
Although its exact mechanism of action is not fully under- and in inducing overall clinical improvement, with a lower
stood, it is generally accepted that PZQ changes metabolism frequency of adverse reactions. However, most of these trials
and intracellular calcium with the main effect of inhibition of have been uncontrolled, observational imaging studies and
muscular movements40. The main PZQ-metabolite in plasma none of them was designed to evaluate seizure control. The
is Trans-4-hydroxy praziquantel formed by cytochrome P45041. meta-analyses of comparative trials suggested that ALB is more
The effective dosage used in most studies was three divided effective than PZQ regarding clinically important outcomes in
doses of 50 mg/kg/day for two weeks. patients with NCC47,48.
ALB is considered to be the drug of choice for therapy of NCC
Albendazole (ALB) because of its widespread availability and low cost. ABZ has also
The benzimidazole derivate ALB is a broad spectrum anthel- been shown to be more effective than PZQ, probably because
mintic drug that affects the dynamics of vesicular traffic42. ABZ penetrates into the CNS more efficiently45,49. Nonetheless,
In human liver microsomes, ALB is oxidized to the the effectiveness of these drugs as single antiparasitic agents
active albendazole sulfoxide (ASOX) metabolite by flavin is only partial, with approximately 60% of parasites destroyed
monooxygenases and the cytochrome P450 system. The and only 35% of patients being free of surviving cysts after a
concentration of ASOX varies widely among individuals and first round of treatment50,51.
the drug has a half-life of six to 15 hours. ASOX crosses the
blood-brain barrier and its concentration in CSF varies as a Albendazole plus Praziquantel
pharmacokinetic characteristic of the drug. Recent studies have demonstrated an improved cysticidal
The ALB dosage regimen currently used is 15 mg/kg/day effect of the simultaneous administration of albendazole and
divided into two doses every 12 hours for 1 week. praziquantel, primarily in patients with more than two cysti-
cerci52,53. This schedule is based on the observation that serum
Side effects levels of Albendazole sulfoxide (the active metabolite of ALB)
Between the second and fifth days of the antiparasitic are variable, but levels are higher and more consistent when
therapy, there is usually an exacerbation of neurological symp- the two drugs are combined54,55.
toms, such as headache, vomiting and seizures in 50-80% of The combined schedule is 15mg/kg per day for ALB and
the patients, accompanied by exacerbation of pleocytosis in 50mg/kg per day for PZQ, divided in two or three daily doses
the CSF in 50-75% of cases43,44. These reactions are eliminated while the proposed length of treatment ranges from one to
or minimized by increasing the dose of dexamethasone. This is two weeks for parenchymal and ≥ 1 month for subarachnoid
probably not caused by a toxic reaction to the drugs, but rather lesions1,19

300 Arq Neuropsiquiatr 2022;80(5 Suppl. 1):296-306

 higher than that of the (-) antipode70,71. The clinical significance
Controversies over anti cysticercal therapy
of these findings remains to be tested. Although ALB is useful
Anti cysticercal therapy has been marked by intense con-
for therapy of cysticercosis in the subarachnoid space where
troversy. The descriptions of spontaneous resolution of paren-
CSF (+)-ASOX and (-)-ASOX concentrations would be of para-
chymal cysticercosis with benign evolution, risks of complica-
mount importance, ALB is more effective in brain parenchymal
tions and reports of no long-term benefits have reinforced the
cysticercosis36. However, due to the difficulty in measuring ASOX
debate over the usefulness and safety of anti cysticercal therapy.
enantiomers within the brain parenchyma, CSF sampling is the
Most available data describing the effectiveness of anti cys-
best substitute for CNS drug penetration. In addition, there are
ticercal treatment are from uncontrolled studies with a signifi-
no data in published studies over which ALB metabolite (+)-
cant selection bias. Many studies have documented that anti-
ASOX, (-)-ASOX or both, is actually effective or the respective
parasitic therapy results in death and resolution of viable cysts,
concentrations required for proper treatment of NCC. Future
but the clinical benefit of this treatment has been questioned.
studies concerning CSF enantiomer concentration and the
Randomized controlled trials evaluating the clinical benefit
clinical outcome of NCC would clarify the question over the
of treatment have yielded conflicting data with some studies
therapeutic role of each ALB metabolite against the cysticerci.
indicating a benefit and others failing to show any difference56.
Similarly, PZQ is also a racemic mixture of two stereoiso-
A randomized, double-blind, placebo-controlled trial
mers, of which only the (-)-(R)-isomer possesses activity against
showed that patients who received ALB had fewer general-
schistosomes. Trans-4-hydroxy praziquantel, the major PZQ
ized seizures, although there was no significant difference in
metabolite, is also a chiral compound and the activity seems
the overall number of seizures or the number of patients with
to be related to the (-)-(R)-isomer. PZQ metabolism is enanti-
seizures57.
oselective with accumulation of the (+)-(S)-PZQ and (-)-(R)-4-
A systematic review by the Cochrane Collaboration con-
OHPZQ in human plasma72. To date, there is no study that
cluded that for patients with a single cyst, there was less seizure
analyzes the plasma concentration of PZQ enantiomers during
recurrence in the albendazole group compared to the placebo/
treatment of human NCC.
no anthelmintic group, but it was uncertain whether albenda-
Given that multiple drug therapy is a common therapeu-
zole reduces seizure recurrence of those with multiple cysts
tic practice in patients with NCC, careful evaluation of drug
while albendazole probably increases radiological clearance
interactions is essential in understanding the actual effec-
and evolution of lesions58.
tiveness of anti cysticercal drugs73. On the basis of the high
inter-individual variability and the complex pharmacological
Failure of anti cysticercal therapy: possible explanations
interactions, monitoring of plasma concentration of PZQ and
The discrepant data over the efficacy of anti cysticercal
ASOX would be highly recommended in patients receiving anti
therapy may be explained by several factors.
cysticercal therapy.
First, there is considerable inter-individual variability in
the plasma concentration of PZQ and ASOX45,59,60. The exact
mechanism of this variability in the plasma concentration of Management of NCC according to its location
the drugs is not clear but may include gender factor61 – greater
ASOX concentration in women than in men – and the low Parenchymal brain cysticercosis
solubility of ALB in the gastrointestinal tract fluid and the high The weight of a vast amount of literature showing disap-
presystemic elimination62. pearance of brain parenchymal cysticercosis with subsequent
Second, there are important food and drug interactions. clinical benefits should not be overlooked. A few studies sup-
Dexamethasone decreases plasma concentration of PZQ but porting the argument that ALB does not modify the clinical
increases ASOX45,46. Food, a high carbohydrate diet, grapefruit outcome have shown persistence of lesions on neuroimaging
juice and cimetidine increase plasma PZQ concentration40,63-65. studies as a factor for recurrence of seizures. The paucity of
On the other hand, antiepileptic drugs significantly reduce the adequate therapeutic trials is in fact an irrefutable argument
plasma concentrations of both PZQ and ASOX66. Therefore, it but considering the efficacy, good tolerance and the risks of
was suggested that higher doses of ALB would be necessary leaving multiple cysts dying at different times, anti cysticercal
when the agent is co-administered with antiepileptic drugs. therapy should be considered in every patient with multiple
Third, ASOX is a chiral metabolite. After intestinal absorp- viable intraparenchymal cysticerci.
tion, ALB is rapidly converted into the active metabolite ASOX, Nowadays, ALB is the medication of choice for the treat-
a mixture of (+)-ASOX and (-)-ASOX enantiomers67-69. Plasma ment of symptomatic patients presenting multiple viable cysts
concentrations of the (+)-ASOX enantiomer are approximately in the brain parenchyma on neuroimaging studies. Simultaneous
nine times higher than those observed for the (-)-ASOX anti- administration of ALB plus PZQ is an alternative schedule52,53.
pode59. ASOX is also found in the CSF at a high proportion (a The Infectious Diseases Society of America (IDSA) and the
2:1 serum to CSF ratio)45. It demonstrated an accumulation of American Society of Tropical Medicine and Hygiene (ASTMH)
the (+)-ASOX metabolite in the CSF, which was three times recommend ALB monotherapy for patients with one to two

Takayanagui OM, et al. Diagnosis and management of neurocysticercosis. 301

 viable parenchymal cysticerci and ALB combined with PZQ repeated courses of ALB, PZQ (50 mg/kg/day for 30 days) and
for those with more than two viable parenchymal cysticerci19. sequential or combined use of both drugs76. Inflammation plays
Concomitant steroids are recommended, particularly dexa- a key role in the pathogenesis of subarachnoid neurocysticer-
methasone38,46. However, the optimal drug, dose, and duration cosis and nearly all of the complications (chronic meningitis,
have yet to be defined74. vasculitis and hydrocephalus) are the result of an inflamma-
ALB is not usually recommended for single enhancing tory reaction to parasite antigen. Thus, concomitant cortico-
lesions (SEL), given that these lesions correspond to degener- steroid therapy is essential to avoid complications due to the
ating cysticerci and are usually resolved spontaneously within ensuing inflammation in the subarachnoid space especially
a couple of months, regardless of therapy36,38 and requires only after the administration of antiparasitic drugs, with a careful
symptomatic treatment (anti-seizure medication - ASM, ste- tapering schedule to avoid cerebrovascular complication and
roids, etc.). Additional corticosteroid treatment was found hydrocephalus19.
to have a beneficial effect both on seizure reduction and cyst
resolution75. FUTURE PERSPECTIVES
Calcified lesions do not require antiparasitic therapy because
the cysticerci are thought to be already dead, even when rem- Adequate experimental models of NCC need to be devel-
nants of scolex are detected by chance. Perilesional edema and oped to test the efficacy of the available and new drugs and
contrast enhancement around calcifications in patients with vaccines for NCC.
seizures activity may require transitory anti-inflammatory Due to high inter-individual variability and complex phar-
medication36. macological interactions, monitoring of plasma concentration
of ASOX and PZQ will be highly recommended in future trials.
The determination of minimal plasma concentrations of ASOX
Extraparenchymal cysticercosis
and PZQ, which is effective against cysticerci, would allow the
Extraparenchymal cysticercosis (subarachnoid, intraven-
optimization of therapy by monitoring the plasma concentra-
tricular and racemose form) is associated with a poor progno-
tion and dose adjustment during treatment.
sis and requires a more aggressive approach. When feasible,
Investigations into which ALB metabolite, (+)-ASOX, (-)-
complete surgical excision of lesions remains the definitive
ASOX or both, is actually effective against cysticerci and the
therapy. In patients with hydrocephalus or intracranial hyper-
respective concentrations required for correct treatment are
tension, the priority is to manage the hypertension problem
also needed. In the future, studies concerning CSF enantio-
before considering any other form of therapy. Hydrocephalus,
mer concentration and clinical outcome of NCC will be able
whether caused by ventricular or cisternal cysts, usually require
to clarify the question over the therapeutic role of each of the
ventricular shunting which may be complemented with exci-
sion of approachable ventricular or cisternal cysts. ALB metabolites against the cysticerci.
Ventricular freely mobile cysts should be treated with Additionally, asymmetric synthesis or purification of ASOX
surgical or, preferably, neuroendoscopic removal9,10,36. There enantiomers, (+)-ASOX and (-)-ASOX, might allow the separate
are, however, contraindications to endoscopic cyst removal. evaluation of the efficacy of each one of them in experimental
Inflamed or degenerating cysticerci are frequently adherent to models or in vitro studies.
the ventricular walls and ependymal and attempted removal Similarly, the role of PZQ stereoisomers should be evaluated
of adherent cysts is associated with a high risk of hemorrhage in future clinical trials. In addition, the pharmacological activ-
and neurologic sequelae19. As antiparasitic drugs may induce ity of trans-4-hydroxy praziquantel, the major PZQ metabolite
cyst inflammation, pre-operative antiparasitic therapy should which is also a chiral compound, should also be determined.
generally be avoided. It is biologically plausible that a combined ALB+PZQ sched-
The optimal treatment of subarachnoid giant cysts with ule may improve clearance of viable cysts and thus provide
local compression or mass effect is surgical-cyst excision via a better cysticidal efficacy as a consequence of a higher concen-
direct approach, or at least cyst evacuation and partial resec- tration of both active metabolites.
tion via a direct or stereotaxic approach. However, in patients Given the relative scarcity of clinical trials, more compara-
with racemose cysticercosis, complete excision of all cysts in tive interventional studies,especially randomized controlled
the basal cisternal is usually impracticable. Most experts have trials in long-term clinical evolution, are required in order to
concluded that there are benefits of cysticidal therapy, but that clarify the controversy over the validity of parasitic therapy in
more intensive therapy may be needed that is traditionally used patients with NCC.
for parenchymal disease. A long course (at least a month) of Given the risks and fallibility of anti cysticercal therapy,
ALB is indicated in association with dexamethasone75. Other only the implementation of control measures will be able to
approaches have included high-dose ALB (30 mg/kg/day), eliminate this serious public health problem.

302 Arq Neuropsiquiatr 2022;80(5 Suppl. 1):296-306

PREVENTIVE MEASURES In 1992, a pilot project was launched in Ribeirão Preto, São
Paulo, Brazil. The project included a number of environmental
By the first part of 20th Century, T. solium infections had sanitation measures, compulsory notification, meat inspec-
been almost eliminated in Europe. This process took place tion, monitoring of vegetable crops and commercial concerns,
over several decades and required many changes in economic, and active surveillance of taeniasis among food handlers78-80.
educational and sanitary standards, and improvement in the In conclusion, NCC is the most common cause of acquired
effectiveness of medical and veterinary services, especially epilepsy worldwide, especially in endemic areas.
meat inspection. These are not likely to be duplicated soon Clinical manifestations of NCC are pleomorphic depending
in many parts of the developing world. Therefore, the realistic upon the number, type, size, location and stage of cysticerci
aim of control is to reduce the incidence and prevalence of T. development, as well as on the host immune response, and
solium infections in humans and pigs to the level that human there is not a pathognomonic manifestation.
NCC does not constitute a major public health and economic The diagnosis of NCC is based on neuroimaging studies
problem in a given endemic area77. (CT and MRI), immunodiagnostic tests in serum (EITB) and
The control and elimination of T. solium/cysticercosis is CSF (antibodies and/or antigens) that are not readily avail-
hindered by many factors, including the lack of reliable epi- able in many settings where NCC is prevalent due to resource
demiological data on infection. No national surveillance or constraints.
control program is currently in place, except in China, despite Therapy for NCC has advanced with the advent of two drugs
the endemicity of T. solium and epilepsy in low-and-middle- that are considered to be effective: PZQ and ALB. Most compara-
income countries1. tive studies have shown that ALB is more effective than PZQ in
New cases can be prevented with health and educational
inducing overall clinical improvement. Nowadays, ALB is the
community interventions78-80 and a One Health approach
medication of choice for the treatment of symptomatic patients
involving1:
presenting multiple viable cysts in the brain parenchyma on
neuroimaging studies. However, anti cysticercal therapy has
y vaccination and anthelmintic treatment of pigs to pre-
been marked by an intense controversy and the benefit of this
vent infection with T. solium cysticerci;
treatment has been questioned. Randomized controlled trials
y improved pig management practices to prevent expo-
sure of pigs to human feces; evaluating the clinical benefit have yielded conflicting results
y improved sanitation to prevent contact between pigs with some studies indicating a benefit and others failing to
and humans and T. solium eggs in human feces and in show a difference. The discrepant data over the efficacy of anti
the environment; cysticercal therapy may be explained by high inter-individual
y meat inspection and sufficient cooking of pork to reduce variability in plasma concentration of ALB sulfoxide (ASOX),
the risk of humans becoming infected; the active metabolite of ALB, and the complex interactions of
y treatment of human taeniasis; and several drugs with ASOX.
y health education to promote hand hygiene, food safety, There are several interventions that can be implemented
sanitation and pig management1. for the control of T. solium, and a One-Health approach is the
most effective, efficient, and sustainable control. However,
Considering the differences in cultures, levels of educa- implementation of control measures has been limited due to
tion, socio-economic levels, and sanitary conditions, etc. these a variety of reasons, including the lack of appropriate tools.
control measures should be adapted to the local epidemiologi- Over the last few years, a new set of tools has been developed
cal situation. The prevention strategies must rely on multiple to assist health care providers in appropriate evidence-based
approaches, tailoring each to the specific features of the par- management of NCC, and so assist public health stakeholders
ticular endemic area77. in implementing control measures for T. solium.

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