Jorge G. Burneo, Arturo Carpio, Alejandra Gonzalez-Duarte, et al.
Subcommittee of the American Academy of Neurology
neurocysticercosis: Report of the Guideline Development
Evidence-based guideline: Treatment of parenchymal
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Jorge G. Burneo, Arturo Carpio, Alejandra Gonzalez-Duarte, et al.
of the Guideline Development Subcommittee of the American Academy of
Evidence-based guideline: Treatment of parenchymal neurocysticercosis: Report
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Robert C. Griggs, MD
Editors’ Note: The AAN’s evidence-based guideline for the
treatment of parenchymal neurocysticercosis generated
several suggestions. WriteClick contributors questioned
the guideline’s relevance to clinical practice, the studies
included and excluded, and the outcomes measured. The
authors respond that the guideline’s shortcomings reflect the
inadequacies found in the literature on neurocysticercosis as
—Megan Alcauskas, MD, and Robert C. Griggs, MD
EVIDENCE-BASED GUIDELINE: TREATMENT OF
REPORT OF THE GUIDELINE DEVELOPMENT
SUBCOMMITTEE OF THE AMERICAN ACADEMY
Jorge G. Burneo, Alejandro L. Escalaya, London,
Canada: The success of a systematic review lies in the
adequate selection of the questions that represent the
daily problems encountered by treating physicians.
NCC is a pleomorphic disease and the clinical behav-
ior of patients harboring one cystic lesion is different
from those with multiple intraparenchymal lesions.
Confounders can also play an important role in the
treatment of NCC including the patient’s concomi-
tant use of other medications (e.g., antiepileptic
drugs) and stage of the lesions. These factors were
not considered in the review by Baird et al.1The
authors should have performed systematic reviews
in each of the following groups independently: single
lesion, multiple lesions, and cysticercotic encephalitis.
Furthermore, the relationship between NCC lesion
and seizures is easy to assess when there is a single
lesion in a case of new-onset seizures. However, it is
more complicated when there are multiple lesions.
Even though NCC-related epilepsy is a well-defined
syndrome, there is a need to confirm the epileptogenic
focus responsible for the seizures in a patient with
NCC.Is itlocatedaroundthe lesion or lesions or other
epileptogenic lesions? This needs to be ruled out. The
authors did not include these types of studies.
Finally, the authors did not define “long-term”
seizure control. The selection of 12 months was made
without data. A better assessment of long-term seizure
control would be more accurate if the analysis was
done in those with “resolution” or “inactivation” of
the lesions. Unfortunately, those studies are scarce in
the medical literature.
Arturo Carpio, Cuenca, Ecuador; Agnes Fleury,
Gustavo Vega-Gama, Felipe Garcia-Pedroza,
Fernando Rueda-Franco, Mexico City: Baird
et al.1demonstrated that there are few evidence-based
studies of antihelminthic treatment for NCC. This
guideline has some limitations. The authors’ procedure
was to evaluate treatment based on the reduction of
number of cysts. This method is misleading because if
only one cyst out of many remains alive after treatment,
it could prompt continued or recurrence of symptoms.
The only valid criterion should be the disappear-
ance of all viable parasites.2The authors’ recommen-
dation of albendazole treatment to reduce seizure
frequency is questionable. The authors studied results
that included patients with vesicular (live parasite) in-
fections and patients with colloidal (degenerative/dead
parasite) infections to evaluate treatment effect on sei-
zures. It may be inaccurate to combine those studies
because—considering the role of inflammation in
seizure generation3—parasite phases reveal important
differences regarding the intensity of associated inflam-
matory reaction.4Evaluating treatment using clinical
is unpredictable, with remissions and exacerbations,
and overestimation of treatment effect may occur.
This study demonstrates the need for further con-
trolled studies to better ascertain the scope of NCC
treatment. Clearly, the most important goal should
Alejandra Gonzalez-Duarte, Mexico City: In the
guideline by Baird et al.,19 of the studies used in
the meta-analysis included patients with single paren-
chymal cysts, while 4 studies included patients with
between 36 and up to 100 cysts. These comparisons
are not appropriate, because single cysts are consid-
ered benign, whereas multiple cysts can be lethal. In
addition, seizure control was used as the only clinical
outcome measurement, despite other common man-
ifestations such as encephalopathy, headache, paresis,
and dementia. Furthermore, seizures may continue
after calcification and so most studies showed a non-
significant reduction in number of total seizures.
Conversely, when the number of active cysts was con-
sidered as a surrogate outcome, most studies found a
1474Neurology 81October 15, 2013
significant reduction in active cysts. More importantly,
the baffling aspect of NCC is the emergence of severe
complications including death while receiving treat-
ment. Steroids are important because it is impossible
to foresee the degree of inflammatory response to the
parasite destruction. Although there is not enough evi-
dence regarding steroid administration, not adminis-
tering them while receiving albendazole is hazardous.5
Optimal albendazole dose and length of treatment are
dation to physicians dealing with NCC is to address
each case individually.6,7
Nitin K. Sethi, New York: I read with interest the
recent AAN evidence-based guideline regarding treat-
ment of parenchymal NCC.1The current practice,
especially in patients who harbor a high parenchymal
NCC load, is to pretreat the patient with steroids (dex-
amethasone or prednisone) for 5–7 days before com-
mencing cysticidal therapywith albendazole.The usual
recommended dose for albendazole is 15 mg/kg/day
while the duration of anthelmintic therapy varies.
The commonly cited reason for pretreatment with ste-
roids is to quell the inflammatory response that may be
triggered by the dying larvae on initiation of cysticidal
therapy. The inflammatory response is hypothesized to
lead to cerebral edema and often seizures. The AAN
ify some aspects of parenchymal NCC treatment—fails
to address important questions regarding steroid use:
When should they be started, at what dose, and for
how long? A future AAN evidence-based guideline
should also address management issues concerning soli-
tary parenchymal NCC granuloma, which may disap-
pear on its own, an entity commonly reported in the
Author Response: Ruth Ann Baird, Indianapolis;
Sam Wiebe, Calgary, Canada; Joseph R. Zunt,
Seattle; John J. Halperin, Summit, NJ; Karen L.
Roos, Indianapolis: We thank the authors for their
comments on this guideline.1As stated previously,
AAN guidelines require Class I, Class II, or Class III
evidence, as defined by the AAN classification of evi-
dence scheme provided in the publication, to support
recommendations. Our systematic literature search re-
vealed 610 potentially informative abstracts, review of
which identified 123 articles that we then analyzed in
detail. We based recommendations on the literature’s
very limited, high-level evidence. We certainly agree
that more high-level studies addressing the many
important but as yet unanswered clinical questions
would be extremely helpful. A goal of evidence-based
tify gaps in the literature relating to important clinical
questions, as indicated in our suggestions for future
Following are our responses to the authors’
1. Suggestion: Pretreatment with steroids and assessment
of endpoints other than seizures or imaging findings.
Our response: These suggestions are not supported
by any high-level evidence and therefore would not
meet the required criteria for an AAN guideline
2. Suggestion: Use of disappearance of all viable para-
sites as the only valid criterion by which to evaluate
Our response: Given the limitations of the studies
analyzed, we were unable to determine whether all
viable parasites were killed; detailed information
regarding cyst stage and response of cysts to treat-
ment was not provided by most studies, and no
study reported elimination of all viable cysts as an
endpoint. Despite this limitation, as seizure fre-
quency was significantly reduced in patients who
received albendazole, if bias were present in our
analysis due to remaining viable cysts, this would
underestimate rather than overestimate the effect
of treatment on seizure frequency.
3. Suggestion: Performance of systematic reviews in
each of the following groups independently: single
lesion, multiple lesions, cysticercotic encephalitis.
Our response: Although we agree that the proposed
studies would be helpful, they have not been done.
addressed the most relevant questions. We refer the
authors to our recommendations for future research
provided at the end of the guideline, particularly this:
“Neurocysticercosis can be intraventricular or intraoc-
ular or can involve the subarachnoid space.”1
For more information regarding formulation of
AAN guidelines and assessment of quality of evi-
dence, we refer readers to the article by Gronseth
and French, “Invited article: Practice parameters
and technology assessments: What they are, what
they are not, and why you should care.”9
© 2013 American Academy of Neurology
1.Baird R, Wiebe S, Zunt J, et al. Evidence-based guideline:
treatment of parenchymal neurocysticercosis: report of the
Guideline Development Subcommittee of the American
Academy of Neurology. Neurology 2013;80:1424–1429.
2. Carpio A, Fleury A, Hauser WA. Neurocysticercosis: five
new things. Neurol Clin Pract 2013;3:118–125.
3.Singh G, Burneo JG, Sander JW. From seizures to epilepsy and
its substrates: neurocysticercosis. Epilepsia 2013;54:783–792.
4.Vezzani E, Balosso S, Ravizza T. Inflammation and epi-
lepsy. Handb Clin Neurol 2012;107:163–175.
5.Ramos-Zúñiga R, Pérez-Gómez HR, Jáuregui-Huerta F, et al.
Incidental consequences of antihelmintic treatment in the
central nervous system. World Neurosurg 2013;79:149–153.
6.Sotelo J. Clinical manifestations, diagnosis and treatment of
neurocysticercosis. Curr Neurol Neurosci Rep 2011;11:
Neurology 81October 15, 20131475
7.Gonzalez I, Garcia HH. Current status and future perspec- Download full-text
tives on the medical treatment of neurocysticercosis. Pathog
Glob Health 2012;106:305–309.
Kishore D, Misra S. Short course of oral prednisolone on
disappearance of lesion and seizure recurrence in patients of
solitary cysticercal granuloma with single small enhancing
CT lesion: an open label randomized prospective study.
J Assoc Physicians India 2007;55:419–424.
Gronseth G, French J. Invited article: practice parameters
and technology assessments: what they are, what they are
not, and why you should care. Neurology 2008;71:1639–
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