Correspondence
A Case of Recovery After Delayed Intracranial
Hemorrhage After Deep Brain Stimulation for
Treatment-Resistant Depression
To the Editor:
Deep brain stimulation (DBS) is an invasive neuromodulation
treatment that has been employed for treatment-resistant
depression (TRD) during the last decade (1–3). The safety
and tolerability of DBS have been established in neurological
disorders and might not present greater risks in psychiatric
conditions (1). The most feared complication of this surgery is
an intracerebral hemorrhage (ICH) due to the electrode
placement, with the average risk varying between 0.2% and
5.6% in the literature (4). Here, we report a case of a delayed
ICH after DBS for TRD and discuss possible causes and
outcome comparing with previous literatures.
The patient was a 54-year-old French Caucasian man with
a 9-year history of major depressive disorder. He presented
with high severity associated with impaired global functioning
(Hamilton Depression Rating Scale (17 items) score: 22; Global
Assessment Functioning: 30/100) and severe TRD [stage V
of the classification of Thase and Rush (5)]. Indeed, he
received numerous and adequate traditional methods,
including a combination of pharmacological treatments, psychotherapy, 40 repetitive transcranial magnetic stimulation
sessions, and a course of 12 electroconvulsive therapies,
without improvement.
Our multidisciplinary team hypothesized that this patient
could benefit from DBS. He provided his written informed
consent to participate in a multicenter randomized controlled
trial to assess the therapeutic value of nucleus accumbens (N
Acc)-DBS (registered NCT01973478).
Perioperatively, medical assessment showed moderate
obesity (body mass index = 33), stabilized hypertension, and
hyperlipidemia, treated with amlodipine (5 mg/day), valsartan
(160 mg/day), and rosuvastatin (5 mg/day), respectively, for 4
years. Pharmacotherapy was used as maintenance treatment
(duloxetine [180 mg/day] and quetiapine [300 mg/day]) and
was kept constant during follow-up.
At day 0, a Leksell stereotactic frame (Elekta Instrument,
Stockholm, Sweden) was applied under local anesthesia.
Nonstereotactic anatomical magnetic resonance images were
coregistered on the stereotactic images. According to the
Yelnik and Bardinet atlas (6), the stereotactic coordinates of
the target were defined using SurgiPlan software (Elekta Instrument) as 5 mm below, 4.5 mm anterior, and 9 mm lateral to
the anterior commissure. Two quadripolar DBS electrodes
(Medtronic model 3389; Medtronic, Minneapolis, MN) were
implanted bilaterally. According to the local vascularization, the
cerebral enter point was chosen at the gyral crown with no
sulcal or ventricular incursion. The electrode trajectory was
calculated to pass through the anterior part of the middle
frontal gyrus (Brodmann area 9/46) and the anterior limb of the
internal capsule before ending in the ventral striatum, N Acc
(Figure 1A, B). An immediately postoperative cranial computed

http://dx.doi.org/10.1016/j.biopsych.2017.04.009
ISSN: 0006-3223

Biological
Psychiatry

tomography scan (Figure 1B) was coregistered and fused with
the preoperative magnetic resonance imaging. This immediate
postoperative imaging confirmed the correctness of the final
implantation of the two electrodes in terms of location and the
total absence of hemorrhage. A pacemaker (Activa PC, model
37601, Medtronic) was implanted at day 2, while the medical
device could be activated after randomization at day 30. Vital
signs for surgery were normal. Moreover, no complication
occurred during 7 days after surgery. At day 8, the patient
presented with an acute confusional syndrome with aphasia
and psychomotor retardation without tonic-clonic seizures.
Computed tomography showed a voluminous left frontal hematoma along the electrode (diameter 55 mm) with perihematomal edema, a deletion of cortical sulci, and a mild
deflection of the midline (Figure 1C). His ICH was managed
conservatively, without surgical evacuation, and it resolved
spontaneously. After 1 month, computed tomography showed
a resorption of the hematoma with the presence of a sequellar
hypodense range (Figure 1D). No mass effect or sign of
commitment remained, and the DBS leads did not shift away
from the original target. The ICH caused slurred speech and a
frontal syndrome with predominant apathy, which entirely
recovered after a 3-month rehabilitation course. Because of
persistent depression, programming of the internal pulse
generator was started. During 1 year, we used bipolar contact,
and the amplitude was gradually increased to 4.9 V (130 Hz,
60 ms) without side effects but no improvement. We changed
to a monopolar stimulation with the same frequency and pulse
width by gradually adjusting the amplitude. At 4 V, the patient
improved immediately; after a few seconds, he reported “a puff
of well-being.” The antidepressant effect remains for more than
a year afterward (Hamilton Depression Rating Scale (17 items)
score: 9; Global Assessment Functioning: 65/100).
We first reported the case of ICH 8 days after N Acc-DBS for
TRD. The effectiveness of DBS and the choice of the stimulation site remain debated in the treatment of depression (1).
This case confirms the antidepressant efficacy of N Acc-DBS
suggested in previous studies (3,7). We also found the acute
effect of DBS as described by Schlaepfer et al. when optimal
parameters were determined (3). Thereby, N Acc-monopolar
stimulation seems in this case to be more effective than
bipolar stimulation.
In general, ICH due to DBS surgery is described during
surgery or during the early postoperative phase, that is,
diagnosed during the first 24 hours after surgery (4). The
pathogenesis of delayed ICH remains unclear. Various intervals of ICH after lead implant are 36 hours to 3 months (8).
The use of microelectrode recording, the number of microelectrode recording penetrations, and the sulcal or ventricular
incursion confer significantly greater surgery-related risk (4,9).
Moreover, some patient-related risk factors have been identified as older age, taking antiplatelet or anticoagulation
agents, and history of hypertension (4). Our patient had
presented with one hypertensive crisis 5 years ago and was
stabilized with the same treatment without any other risk
factor.

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Correspondence

Figure 1. (A, B) The electrode trajectory was
calculated to pass through the anterior part of the
middle frontal gyrus (Brodmann area 9/46) and the
anterior limb of the internal capsule before ending in
the ventral striatum, nucleus accumbens. (C)
Computed tomography showed a voluminous left
frontal hematoma along the electrode (diameter 55
mm) with perihematomal edema, a deletion of
cortical sulci, and a mild deflection of the midline. (D)
After 1 month, computed tomography showed a
resorption of the hematoma with the presence of a
sequellar hypodense range.

Finally, ICH related to DBS frequently causes mass effect
and significant displacement of the brain and the leads and
may need surgical evacuation (4). However, as described in
previous reports, when the leads return to near their initial
position, stimulation success may still be achieved (8,10).
Such a rare hemorrhagic event, although not clearly
explained, exists. Awareness is important for proper clinical
management of patients after DBS.
In summary, this case report confirms that with allowed
time, after the hematoma has resolved, an antidepressant
effect from bilateral DBS therapy can occur on follow-up.
Raphaëlle Richieri
Pierre-Yves Borius
Michel Cermolacce
Bruno Millet
Christophe Lançon
Jean Régis

Hospitals, Health, Chronic Diseases and Quality of Life (RR, CL), EA 3279
Research Unit, and Institut de Neurosciences des Systèmes (JR), Institut
National de la Santé et de la Recherche Médicale UMR 1106, Aix Marseille
University, Marseille; Department of Neurosurgery (P-YB) and Department of
Psychiatry (BM), Pitié-Salpétrière University Hospital, Public Assistance
Paris Hospitals, Paris, France.
Address correspondence to Raphaëlle Richieri, M.D., Ph.D., Hôpital
Sainte Marguerite, Pôle Psychiatrie Addictologie et Pédopsychiatrie,
270, Boulevard Sainte Marguerite, 13009 Marseille, France; E-mail:
raphaellemarie.richieri@ap-hm.fr.
Received Apr 19, 2017; accepted Apr 19, 2017.

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Acknowledgments and Disclosures
This trial was supported by a grant from the French Ministry of Health (Grant
No. PHRC 2013).
The authors report no biomedical financial interests or potential conflicts
of interest.

Article Information
From the Department of Psychiatry, Addictology and Child Psychiatry
(RR, MC, CL), La Conception University Hospital, and Department of
Neurosurgery (JR), La Timone Hospital, Public Assistance Marseille

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