Correspondence
Unité des Maladies Infectieuses Tropicales
et Hygiène, Centre hospitalier Andrée Rosemon,
97300 Cayenne, French Guiana, France, and
EA 3595, Université des Antilles et de la Guyane,
Cayenne, France (AM, PA, MD, FD); and Service
d’Imagerie Médicale, Centre hospitalier Andrée
Rosemon, Cayenne, French Guiana, France (DJ)
1 Del Brutto OH. Clinical management of
neurocysticercosis. Expert Rev Neurother 2014;
14: 389–96
2 White AC Jr. New developments in the
management of neurocysticercosis. J Infect Dis
2009; 199: 1261–62.
3 Garcia HH, Gonzales I, Lescano AG, for the
Cysticercosis Working Group in Peru. Efficacy
of combined antiparasitic therapy with
praziquantel and albendazole for
neurocysticercosis: a double-blind, randomised
controlled trial. Lancet Infect Dis 2014;
14: 687–95.
We read the Article by Hector Garcia
and colleagues1 reporting the efficacy
and safety of combined anthelmintic
treatment for parenchymal neur-
cysticercosis with great interest. The
efficacy of albendazole and prazi-
quantel monotherapy has largely been
suboptimum, leading to complete
disappearance of active cysts in only
a minority of patients after initial
treatment.2 We celebrate the results of
Garcia and colleagues, which showed
that the combination of albendazole
and praziquantel has greatly improved
efficacy compared with albendazole
monotherapy in patients with
parenchymal neurocysticercosis.1 An
important attribute of this trial is the
primary endpoint of complete cyst
resolution, which allows comparison
with previous placebo-controlled trials
of anthelmintic monotherapy.3
Nevertheless, this trial shows some
important issues in treatment of neuro-
cysticercosis. Patients were included
if they had “epilepsy secondary to
neurocysticercosis” rather than new-
onset seizures. Because these patients
had prevalent seizures, the causal
relation between these events and
neurocysticercosis cysts is more dif-
ficult to ascertain than with new-
onset seizures. Inclusion of patients
with incident seizures (ie, new-
onset seizures) would be preferable
because one can be more certain that
these events are directly related to
www.thelancet.com/infection Vol 15 March 2015
degenerating cysts that are seen on
imaging. Inclusion of these patients is
also more likely to be representative
of clinical practice where new-onset
symptoms are the reason that patients
seek care. Furthermore, a clear
distinction should be made between
seizures and epilepsy because acute
symptomatic seizures and unprovoked
seizures are associated with different
risks of seizure recurrence.4 This trial
also shows that diagnostic criteria for
neurocysticercosis remain open to
interpretation because validated criteria
do not exist.5
Garcia and colleagues state that, to
their knowledge, their study provides
“the first evidence that complete
cyst resolution is associated with
fewer seizure relapses”. In a previous
prospective cohort study of 77 patients
with parenchymal neurocysticercosis
and new-onset seizures,6 disappearance
of cysts was predictive of seizure
recurrence irrespective of anthelmintic
treatment. Despite finding a reduction
in seizure rate comparing patients with
and without cyst resolution, Garcia and
colleagues did not find a significant
difference in the proportion of patients
with at least one seizure during follow-
up in the three treatment groups. Thus,
findings from this trial do not show
that combined treatment has any
effect on seizure recurrence.
Many unmet needs of evidence-
based treatment of neurocysticercosis
remain. Extraparenchymal neuro-
cysticercosis is associated with worse
prog nosis than is parenchymal
disease, and anthelmintic treatment
has not been associated with greater
disappearance of active cysts com-
pared with placebo.3 Future trials
are needed to see if combination
treatment would be efficacious in
patients with extraparenchymal
disease.
We declare no competing interests.
*Arturo Carpio, Matthew L Romo
arturocarpio@etapanet.net
School of Medicine, University of Cuenca, PO Box
0101-719, Cuenca, Ecuador, and Gertrude H
Sergievsky Center, College of Physicians and
Surgeons, Columbia University, New York, NY, USA
(AC); and City University of New York School of Public
Health, New York, NY, USA (MLR)
1 Garcia HH, Gonzales I, Lescano AG, et al, for the
Cysticercosis Working Group in Peru. Efficacy of
combined antiparasitic therapy with
praziquantel and albendazole for
neurocysticercosis: a double-blind, randomised
controlled trial. Lancet Infect Dis 2014;
14: 687–95.
2 Carpio A, Romo ML. Epilepsy and
neurocysticercosis: an endless debate.
Arq Neuropsiquiatr 2014; 72: 383–90.
3 Carpio A, Kelvin E, Bagiella E, et al, for the
Ecuadorian Neurocysticercosis Group. The
effects of albendazole treatment on
neurocysticercosis: a randomized controlled
trial. J Neurol Neurosurg Psychiatry 2008;
79: 1050–55.
4 Hesdorffer DC, Benn EK, Cascino GD,
Hauser WA. Is a first acute symptomatic
seizure epilepsy? Mortality and risk for
recurrent seizure. Epilepsia 2009; 50: 1102–08.
5 Machado LR. The diagnosis of
neurocysticercosis: a closed question?
Arq Neuropsiquiatr 2010; 68: 1–2.
6 Carpio A, Hauser WA. Prognosis for seizure
recurrence in patients with newly diagnosed
neurocysticercosis. Neurology 2002; 59: 1730–34.
Hector Garcia and colleagues,1 in a
double-blind, randomised, controlled
trial, reported that combined
treat ment with albendazole and
praziquantel resulted in an increased
antiparasitic efficacy in patients
with multiple brain cysticercosis
cysts without increased side-effects.
This study is a big advance towards
treatment of neurocysticercosis.
However, Chinese scientists have
substantial experience in treatment of
cerebral cysticercosis with albendazole
plus praziquantel. In a randomised
clinical trial recruiting 864 patients
with definite diagnosis of cerebral
cysticercosis, 2 two albendazole–
praziquantel combination regimens
(96% and 98% total effective
rate) were noted to be more
efficacious than was treatment with
albendazole (55% total effective
rate) or praziquantel (68% total
effective rate) alone (p<0·0001 for all
comparisons between combined and
monotherapy regimens), whereas
no significant differences in efficacy
were detected between the two
combined or monotherapy regimens
(p=0·2130 for combined; p=0·3523
for monotherapy). Of 156 patients
265
 Correspondence
with high intracranial pressure,
epileptic seizures disappeared in 86 of
93 patients (92%) who used to have
epileptic seizures after treatment with
20 mg/kg albendazole daily for 12 days
followed by 15 mg/kg praziquantel
daily for 12 days. CT follow-up showed
36% of patients returned to having no
seizures and 61% only having some
separated calcified foci, whereas 3%
still had some low-density, calcified
foci, but the focus areas shortened.3 In
China, a consensus virtually exists that
the combination of albendazole and
praziquantel increases the therapeutic
efficacy for cerebral cysticercosis.4
Additionally, the study by Garcia
and colleagues 1 has a limitation
that treatment-associated adverse
effects are not described in detail. To
our knowledge, very severe adverse
events can develop after praziquantel
treatment, notably in large doses or
at the early stage of the first course of
treatment. 87% of the 450 patients
with cerebral cysticercosis had adverse
reactions during the first course of
treatment with praziquantel, including
9% with epileptic seizures, 18% with
high intracranial pressure, 3% with
mental symptoms, 2% with coma,
and 1% with cerebral hernia.5 Because
praziquantel treatment causes more
adverse events than does albendazole,
Chinese clinicians recommend
administration of albendazole first,
followed by praziquantel with simul-
taneous administration of steroids
for treat ment of neuro cysticer-
cosis, notably in the first course
of treatment.4 Further large-scale,
multicentre, randomised, controlled
trials with rigorous design might be
needed to validate the efficacy of the
albendazole–praziquantel combination
regimen for neurocysticercosis.
This study was supported by the Natural Science
Foundation of Jiangsu Province (BK20141105). We
declare no competing interests.
Wei Wang
wangweijipd@163.com
Jiangsu Institute of Parasitic Diseases,
117 Yangxiang, Meiyuan, Wuxi City, Jiangsu
Province, 214064, China; and Key Laboratory on
Technology for Parasitic Disease Prevention and
266
Control, National Health and Family Planning
Commission, and Jiangsu Provincial Key Laboratory
on Molecular Biology of Parasites, Yangxiang,
Meiyuan, Wuxi City, Jiangsu Province, China
1 Garcia HH, Gonzales I, Lescano AG, et al, for the
Cysticercosis Working Group in Peru. Efficacy of
combined antiparasitic therapy with
praziquantel and albendazole for
neurocysticercosis: a double-blind, randomised
controlled trial. Lancet Infect Dis 2014;
14: 687–95.
2 Xu HX, Zhang QZ, Liu YL, Mao DH, Shi SJ, Xu J.
Effect of praziquantel alone or albendazole
alone or combination of two drugs in
treatment of cysticercosis. J Qiqihar Med College
2001; 22: 999–1000 (in Chinese).
3 Yue JE, Li H, Wu XY, Huo HY, Yang SF. Clinical
study on treatment of cysticercosis patients
with high cranial pressure. Chin Trop Med 2005;
5: 43–44 (in Chinese).
4 Wu W, Jia F, Wang W, Huang Y, Huang Y.
Antiparasitic treatment of cerebral
cysticercosis: lessons and experiences from
China. Parasitol Res 2013; 112: 2879–90.
5 Ma YX, Zhu JH, Liu ZS, et al. A clinical study on
the treatment of cerebral cysticercosis with
praziquantel. Chin Med J 1984; 64: 79–83
(in Chinese).
Authors’ reply
We thank Aba Mahamat and colleagues
for their comments on our Article1 and
patient data illustrating a difficult case
successfully treated with combined
albendazole and praziquantel. We do
not deem use of the combination a
“shift”, rather a refinement in use of
antiparasitic treatment to destroy
viable brain parasites, which has
been in use for more than 25 years.
We certainly agree that antiparasitic
treatment in neurocysticercosis should
be individualised and not used as a
blanket recipe.
Arturo Carpio and Matthew Romo
bring up several points, including
whether seizures in patients with
cerebral cysticercal lesions are actually
due to these lesions, previous evidence
that complete cyst resolution leads to
fewer seizure relapses than without
resolution, and whether combined
treatment really affects seizure
recurrence. We concur that in a few
cases, seizures might just coexist with
brain cysticerci by simple chance.
To assume that chance is the usual
explanation seems quite far-fetched.
Clinicians treating cysticercosis in
endemic regions have, since the intro-
duction of antiparasitic treatment,
www.thelancet.com/infection Vol 15 March 2015
been aware that destruction of cysts
with either albendazole or prazi-
quantel leads to better seizure control
and long-term prognosis than if cysts
are not destroyed. Our study1 is one
of a few masked randomised trials
providing type I evidence to support
this claim. In our study, combined
antiparasitic treatment led to much
higher cyst clearance in patients
with multiple cysts than did single-
drug treatment, and seizures were
significantly less common in patients
who cleared all their cysts after
antiparasitic treatment than in those
with remnant live cysts. These results,
together with the data suggesting
that cyst clearance is predictive of low
seizure recurrence2 cited in Carpio and
Romo’s letter, leads to the conclusion
that antiparasitic treatment results
in fewer seizures in the follow-up of
treated patients than of untreated
patients. Even if we oversimplify this
outcome to whether treated patients
had at least one further seizure in the
follow up, 41% fewer cases occurred in
patients who were free of cysts than
in those with remnant live cysts (11
[18%] of 60 patients vs 15 [26%] of
58 patients), although this difference
was not statistically significant
(p=0·324). Seizures in patients free of
viable cysts might still occur in relation
to their residual calcified scars. An
ideal treatment will destroy the cysts,
avoiding residual calcium deposit in
resolved lesions. In relation to Carpio
and Romo’s claim that antiparasitic
treatment does not help to resolve
extraparenchymal cysts, we do not
endorse or suggest this concept at all
(and we clearly disagree with it).
Finally, Wei Wang adds information
on the use of combined albendazole
plus praziquantel in a clinical trial3
published in a Chinese journal to which
we had had no access, and bring up
their own conclusion that praziquantel
causes more adverse events than
does albendazole. To extract infor-
mation from this publication is
very difficult without knowing the
characteristics of neurocysticercosis in