Letter to the Editor
Received: June 6, 2012
Accepted after second revision: November 9, 2012
Published online: $ $ $
Stereotact Funct Neurosurg very concerned with the message this report sends to the neuro-
DOI: 10.1159/000342782 surgical community regarding (1) the surgical treatment of ag-
gressiveness disorder and (2) the standards in scientific and ethi-
Surgery for Aggressive Behavior Disorder cal rigor in the study of neuromodulation of mood disorders.
We believe it is premature to be performing bilateral, ablative,
Marc Lévêquea , Alexander G. Weilb, Jean Régisa
irreversible lesions in these patients with aggressive behavior dis-
a
Service de Neurochirurgie Fonctionnelle et Stéréotaxique order. There are no studies, and no rationale in the literature, nei-
CHU, Hôpital d’adulte de la Timone, Marseille, France; ther in humans nor in animals, that have shown the efficacy of
b
Department of Surgery, Section of Neurosurgery, capsulotomy and cingulotomy in the treatment of aggressive be-
Centre Hospitalier de l’Université de Montréal, havior except for a highly questionable publication [2]. Regarding
Hôpital Notre-Dame, Montréal, Qué., Canada cingulotomy alone, the same can be said, except for a publication
from a congress proceeding in 1970 in which the authors mention
5 ‘poor results’ in 10 patients [3]. The combination of these two
We read with interest the article published in the last issue of types of surgeries, as is the case in this study, has never been de-
Stereotactic and Functional Neurosurgery, entitled ‘Bilateral ante- scribed in the treatment of aggression.
rior capsulotomy and cingulotomy applied to patients with ag- We also read with interest the previous report by the same
gressiveness’ [1]. The authors report on a retrospective series of 10 group published 1 year ago of very similar structure [4] and con-
patients treated with combined stereotactic bilateral cingulotomy tent to the present article [1]. That previous paper reported on a
and anterior capsulotomy for the treatment of refractory aggres- series of patients operated on for the same condition, with the
sive disorder. This is the largest series in the literature of patients same procedure, by the same surgeons, at the same institution,
treated for such a condition. The authors found that aggressive- during the same time interval. We were surprised that there is no
ness and functioning, as measured by the Overt Aggression Scale mention of this previous work in the present paper. We invite the
and Global Assessments of Functioning, respectively, were im- authors to clarify several significant discrepancies observed be-
proved at 6 months in 10 patients but not in the long term in the tween their previous report [4] and the current article published
4 patients followed up for 4 years. The procedure allowed some of in Stereotactic and Functional Neurosurgery [1].
the patients to be reintegrated into certain social situations. The initial population diagnosed with a ‘neuroagressive’ dis-
Although aggressiveness disorder, albeit difficult to define, order during the same period (1997–2004) decreased from 25 to
can be a debilitating condition with few good solutions, we are 23 from the first to second publication (fig. 1). What happened to
Color version available online
Cir Cir 2011 Stereotact Funct Neurosurg 2012
25 Initial population 23 Initial population
Excluded due to aggressiveness,
Excluded according to response
0 19 6 R 6 0 17 6 R 6 improvement with pharmacotherapy
to pharmacological treatment
adjustments
19 Candidates with inclusion criteria 17 Met inclusion criteria
Excluded according to negative
0 14 5 R 7 for families or failure to 0 13 4 R 7 Excluded due to refusal of procedure
complete consultations
12 Final sample included in the study 10 Final sample included in the trial
0 10 2 R 0 6 4 R
Bilateral cingulotomy and anterior capsulotomy Bilateral cingulotomy and anterior capsulotomy
Postoperative follow-up (3, 6 months) Postsurgical follow-up
Fig. 1. Differences in the patient populations of both studies by Jimenez et al. [1, 4].
© 2012 S. Karger AG, Basel Marc Lévêque, MD
1011–6125/12/0000–0000$38.00/0 Service de Neurochirurgie Fonctionnelle et Stéréotaxique
Fax +41 61 306 12 34 CHU, Hôpital d’adulte de la Timone, 264, bvd Saint-Pierre
E-Mail karger@karger.com Accessible online at: FR–13385 Marseille (France)
www.karger.com www.karger.com/sfn E-Mail marclevequemd @ gmail.com
SFN342782.indd 1 20.12.2012 11:01:48
Cir Cir 2011 Stereotact Funct Neurosurg 2012
Adverse effect Frequency Side effect Frequency
n %
Hyperphagia 4 31 Hyperphagia 4 (40%)
Sonmolence 3 23 Somnolence 3 (30%)
Disinhibition 2 15 Disinhibition 2 (20%)
Hypersexuality 2 15 Hypersexuality 1 (10%)
Infection 1 8 Infection 1 (10%)
Paraparesis 1 8 Death 1 (10%)
Total 13 100
Five patients (41.6%) presented on a Unfortunately, 1 patient died as an
transitory basis (1 day to 4 weeks). Note outcome of anesthetic hypersensitivity
that in 80% of patients who reported complications before stereotactic sur-
complications, hyperphagia was a re- gery. We also found that in 80% of the
current symptom. No severe adverse patients who reported complications,
Fig. 2. Complication profile of both stud- effects were seen. hyperphagia was a recurrent symptom.
ies by Jimenez et al. [1, 4].
the 2 omitted patients? Four men who were operated on and who
appeared in the 2011 paper [4] were not reported in the present
paper (6 instead of 10), while 2 new women operated on were add-
ed (4 instead of 2). Also, regarding complications, despite the fact
that only 4 patients are common to both publications, we see that
the number of binge eating, drowsiness, disinhibition, hypersex-
uality and infection remains, nevertheless, exactly the same
(fig. 2). We invite the authors to clarify these discrepancies for the
readers.
In a study on neuromodulation of the mood and mind disor-
ders, such as this one, scientific rigor is essential. We encourage
the authors to publish the size and anatomical location/distribu-
tion of capsulotomy/cingulotomy in all 10 of their patients rather
than just 1 representative image (fig. 3). Although the authors sug-
gest that all lesions were correctly located, the right-sided capsu-
lotomy lesion in the illustrative CT scan image seems to be lo-
cated far lateral to the anterior limb of the internal capsule. Also,
we encourage the authors to address the significant selection bias
in their study. It would be preferable for the authors to provide
information regarding the 6 patients who could not be assessed at
4 years. Were they lost to follow-up? Did they survive? The results
are possibly biased and skewed towards a positive result bias, as Fig. 3. Example of bilateral capsulotomy in which the right-sided
poor outcomes could be lost to follow-up. We also encourage the lesion seems to be located lateral to the anterior limb of the inter-
authors to report the current psychotropic treatment of the 4 pa- nal capsule.
tients evaluated at 4 years, as this may affect the interpretation of
the procedure-related efficacy.
Ethical rigor is also integral to any study evaluating the psy-
chosurgery of mood and mind disorders like severe neuroaggres- sent to perform this type of intervention is essential. Because of
sive disorder. Although the ethics committee of their establish- the ‘neuroaggressive’ disorder, consent could not be given by the
ment agreed to the protocol and procedure in each case, it would patients and was obtained by their family. This transfer of consent
be important for the authors to clarify if psychiatrists indepen- raises the question of a possible conflict of interest and therefore
dent of their team performed the recruitment of patients, and may threaten the principle of patient autonomy. This is even more
agreed to the indication of surgery and postoperative evaluation. crucial in the context that the patients have undergone, for eco-
As Jimenez et al. [1] correctly state, obtaining an informed con- nomic reasons, an irreversible lesional technique rather than a
2 Stereotact Funct Neurosurg Lévêque/Weil/Régis
SFN342782.indd 2 20.12.2012 11:02:21
reversible deep brain stimulation technique, which may have been References
more appropriate in this setting. 1 Jimenez F, Soto JE, Velasco F, Andrade P, Bustamante JJ, Gomez P, et
Surgical treatment of aggressive disorders and addiction is un- al: Bilateral cingulotomy and anterior capsulotomy applied to patients
doubtedly among the most controversial topics today in medicine. with aggressiveness. Stereotact Funct Neurosurg 2012;90:151–160.
Its possible social and political implications make it an issue for 2 del Valle R$ $ $ , Garnica SR, Aguilar E, Pérez-Pastenes M: Radio-
which public opinion is, suitably, extremely vigilant. One may re- cirurgia psiquiatrica con gammaknife. Salud Mental 2006;29:18–27.
3 Mingrino S, Schergna E: Stereotaxic anterior cingulotomy in the treat-
call the scandal created by the publication of the polemic Violence
ment of severe behavior disorders; in $ $ $ $ $ $ $ (ed): International
and the Brain by Mark and Ervin in the 1970s [5]. In recent years, Conference on Psychosurgery, 1970, Copenhagen, Denmark. Spring-
because of the reversible nature of deep brain stimulation, psycho- field, Thomas, 1970, pp xxvii, 437.
surgery has earned a second chance as a hope for patients with 4 Jimenez-Ponce F, Soto-Abraham JE, Ramirez-Tapia Y, Velasco-Cam-
severe psychiatric disorders. This new, highly scrutinized, thera- pos F, Carrillo-Ruiz JD, Gomez-Zenteno P: Evaluation of bilateral cin-
peutic hope is made possible because researchers now follow strict gulotomy and anterior capsulotomy for the treatment of aggressive be-
scientific rules, which was not always the case in the past [6]. For havior. Cir Cir 2011;79:107–113.
this last reason, we must be very vigilant about the transparency 5 Mark VH, Ervin FR: Violence and the Brain, ed 1. New York, Medical
and scientific and ethical rigor of new studies involving surgical Department, 1970.
6 Valenstein ES: Great and Desperate Cures: The Rise and Decline of
treatment of disorders of the mood and mind [7]. If patients with Psychosurgery and Other Radical Treatments for Mental Illness. New
pharmacoresistant aggressive disorder are to benefit from neuro- York, Basic Books, 1986.
modulation procedures in the future, it is imperative that evi- 7 Beauchamp TL, Childress JF: Principles of Biomedical Ethics. New
dence of safety and efficacy come first from basic research in an- York, Oxford University Press, 1979.
imal models and well-designed, prospective, preferably random-
ized clinical trials.
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