DOI: 10.5137/1019-5149.JTN.11387-14.1

Case Report

Intraoperative Neurophysiological Evidence of
Hydrogen Peroxide-Induced Stroke in Insular Tumor
Surgery
İnsüla Tümörü Cerrahisinde Hidrojen Peroksitle İndüklenen İnmenin
İntraoperatif Nörofizyolojik Bulguları
Alba León Jorba1, Miguel López Cuıña1, Alessandro Prıncıpe1, Gloria VIllalba Martínez2
1Parc de Salut Mar, Department of Neurology, Barcelona, Spain

2Parc de Salut Mar, Department of Neurosurgery, Barcelona, Spain

Presented in: XVI Congress of the Societat Catalana de Neurologia. Vic. March 15-16 2012 and II Congress of the Sociedad Española de Monitorización
Intraoperatoria. Tenerife. April 27-28 2012
Corresponding Author: Alba Leon Jorba / E-mail: [email-masked]

ABSTRACT
Hydrogen peroxide (H2O2) is commonly used as a haemostatic agent in all type of surgeries. Some adverse effects have been described related
to its use. However, only very few cases are published in the literature of a stroke associated with the application of this agent directly to
the brain. We present the case of a patient operated on for a right insular tumor with the assistance of intraoperative neurophysiological
monitoring who developed a postoperative severe hemiparesis caused by a stroke in left middle cerebral artery territory due to the irrigation
with H2O2. Based on this case, we recommend avoiding the H2O2 irrigation for hemostasis in surgery for brain tumors when vascular structures
are exposed.
Keywords: Brain tumors, Hemostasis, Hydrogen peroxide, Intraoperative neurophysiological monitoring, Stroke

ÖZ
Hidrojen peroksit (H2O2) tüm cerrahi tiplerinde bir hemostatik ajan olarak kullanılır. Kullanımıyla ilişkili bazı yan etkiler tanımlanmıştır. Ancak
literatürde bu ajanın doğrudan beyine uygulanmasıyla ilişkili inmenin bulunduğu sadece birkaç olgu mevcuttur. İntraoperatif nörofizyolojik
monitörizasyon eşliğinde sağ insüla tümörü için ameliyat edilen bir olguda H2O2 ile irrigasyon nedeniyle sol middle serebral arter sulama
bölgesinde inme sonucunda postoperatif şiddetli hemiparezi gelişmesini sunuyoruz. Bu olgu temelinde beyin tümörleri için cerrahi sırasında
vasküler yapılar ortaya konulduğunda hemostaz için H2O2 irigasyonunun kullanılmasından kaçınmayı öneriyoruz.
ANAHTAR SÖZCÜKLER: Beyin tümörleri, Hemostaz, Hidrojen peroksit, İntraoperatif nörofizyolojik izleme, İnme

Introduction
Hydrogen peroxide (H2O2) is widely used as a haemostatic
agent in neurosurgery. Although its mechanism of action is
unknown, several hypotheses have been proposed, among
which are vasoconstriction, platelet aggregation, thrombus
formation and small blood vessel occlusion due to micro
bubbles (4, 5). Although complications have been reported
(3, 8), there are only few descriptions of a stroke after brain
irrigation with H2O2. Despite those reports, H2O2 usage has
not decreased among neurosurgeons.
Insular tumor surgery has been debated for years, due to its
unfavorable anatomical conditions that imply a high risk of
neurological impairment. However, several reports show that
lesions localized in the insula can be resected with acceptable
complication rates and outcomes (2, 14).

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The main cause of a motor deficit after insular tumor surgery
is ischemia caused by the occlusion of the lenticulostriate
perforating arteries (7). Damage to corticospinal tract may
ensue anytime during the resection and even after the end
of the anesthesia (13). For these kind of lesions, intraoperative
neurophysiological monitoring (INM) is a valid method of
detecting and preventing potential neurological deficits, thus
maximizing the extent of the resection and allowing a better
outcome (9).
We describe the case of a patient with a right insular lowgrade glioma operated with the assistance of INM. The subject
developed postoperative hemiplegia caused by an occlusion
of left middle cerebral artery (MCA) perforators after the
irrigation with H2O2.

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Leon Jorba A. et al: Hydrogen Peroxide-Induced Stroke

Case report
A 51-year-old man presented with simple partial seizures.
On admission, the patient’s neurological examination was
unremarkable. Magnetic resonance imaging (MRI) showed
a right insular tumor graded 3B in the Yasargil Classification
consistent with a low-grade glioma (Figure 1). A right frontotemporal craniotomy was performed under total intravenous
anesthesia. Bilateral somatosensory evoked potentials (SEPs)
after posterior tibial nerve and median nerve stimulation, and
motor evoked potentials (MEPs) after transcranial electrical
stimulation (MEPtc) were performed throughout the surgery.
Pairs of subcutaneous needles were inserted in the abductor
pollicis brevis (APB), extensor comunis, tibialis anterior
and abductor hallucis longus (AHL) bilaterally for muscle
recordings. After opening the dura, a 6x1 grid electrode was
placed over the cortex and continuous direct motor cortical
stimulation was performed. Dissection of the sylvian fissure
(trans-sylvian approach) was used to achieve middle cerebral
artery exposure, then its M1 and M2 segments and the
perforators were dissected from the tumor. The tumor was
removed by utilizing an ultrasonic aspirator. Tumoral frontal
and temporal opercula were subpially removed. A monopolar
stimulator was used for continuous subcortical mapping. The
resection was stopped when a threshold of 6 mA was found for
the MEPs of the left upper extremity. During tumor resection,
only mild transient changes in MEPs were observed allowing
the continuation of the intervention until the resection was
apparently complete. Minor bleeding of the deep surgical
field was managed with haemostatic fibrin (surgicelR) (Ethicon,
Johnson and Johnson). Finally, a piece of cotton irrigated with
2% H2O2 solution was left in the surgical bed. A few seconds
later, the left MEPs from upper and lower extremities and
the left median SEPs progressively abated. Although the
cotton was removed and blood pressure increased, irrigation
with saline and local infusion of papaverine was done, the

Figure 1: Axial fluid-attenuated inversion recovery (FLAIR)
image showing the lesion located in the right insula, frontal and
temporal opercula consistent with a low-grade glioma.
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recordings did not change. The dura closure was watertight,
and the bone flap was fixed with craneofixR (Aesculap). At
closing, there was a very poor response in the left AHL and
still no response in the left upper extremity (Figure 2). The
patient woke up with a complete right hemispheric syndrome,
including apraxia of eyelid opening, right oculocephalic
deviation, left homonymous hemianopsia, left hemiplegia,
left anesthesia and anosognosia. A postoperative MRI (24
hours after surgery) showed a complete tumor resection and
an acute stroke in superficial and deep regions of the MCA
(Figure 3, 4). A decrease in collateral vascularization with

Figure 2: Motor evoked potentials (MEPs) recorded in abductor
pollicis brevis (L-APB) and extensor digitorum comunis (L-EXT)
after direct cortical stimulation with an intensity of 13 mA.
The arrow indicates the placement of the cotton with H2O2.
Immediately after, a severe and progressive decrease of
amplitude of MEPs is observed.

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Leon Jorba A. et al: Hydrogen Peroxide-Induced Stroke

permeability of M1 and M2 segments of MCA was noted with
magnetic resonance angiography (MRA). Six months later the
patient was not able to walk on his own and had monoplegia
of the upper left extremity. Only twelve months after the
event we observed an improvement of the impairment, with
mild paresis of the leg that allowed the subject to ambulate
independently.
Discussion
Insular tumor surgery is very complex due to its vascular
relationship. The goal of this type of surgery is not only the
largest resection possible for oncological control, but also
the best tailored one for preserving the functionality and
avoiding catastrophic neurological impairments. Sanai

Figure 3: Postoperative axial diffusion-weighted image (DWI)
showing an acute infarction involving superficial (insular) and
deep (lateral lenticulostriate) branches of the right middle
cerebral artery.

Figure 4: Postoperative axial T2-diffusion image showing a
complete tumor resection.

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and colleagues analyzed patients with low and high-grade
gliomas and found that those resected over 90% had a 5-year
survival rate of 100%, whereas those with lesions resected
less than 90% had a 5-year survival rate of 84%. The same
significant difference was found for patients with high-grade
gliomas (10). They concluded that the extent of resection
was a significant predictor of overall survival after surgery of
insular low and high-grade glioma.
One of the main risks of insular surgery is vascular injury. The
resection of the most medial part of the insula may result
in damage to perforating vessels and subcortical ischemia.
Damage of long perforating vessels supplying the corona
radiata and the internal capsule causes postoperative motor
deficits (7, 15). Despite this, retrospective data and also some
prospective analyses support the feasibility of resections of
insular low-grade gliomas by experienced surgeons. The
potential benefits of a tumor resection need to be balanced
against the risk of incurring a new postoperative deficit (10,
11).
In the neurosurgical field, H2O2 is mainly used as a haemostatic
agent, although some complications have been described
in relation to its use. Some adverse effects as air-embolism,
pneumoencephalus and trigeminal cardiac reflex have been
reported (1, 4, 8, 12). Mut and colleagues reported a case
with a H2O2-induced stroke. They observed multiple bubbles
within the lumen of the vessels after the exposure to H2O2 in a
patient. Later, they performed an animal experimental study
and found signs of both local and deep diffusion of H2O2
through brain parenchyma that ensued in gas embolism,
vasoconstriction, platelet aggregation and vascular occlusion
(5). There are very few cases of stroke described after the
application of H2O2 to the brain parenchyma and the agent is
still used for hemostasis in many centers.
In our case, the most probable cause of ischemic damage
was the summation of local mechanisms on the site of H2O2
application that lead to superficial parenchyma infarction,
and distal mechanisms owing to diffusion of H2O2, affecting
deep perforating vessels and other small caliber arteries in a
similar manner, while large caliber MCA was un-affected. This
sequence could explain the postoperative stroke in our patient
and also the significant changes in MEPs and SEPs observed
only a few seconds after irrigation with H2O2, while no major
changes were detected after the complete resection of the
tumor, or during the coagulation, excluding another possible
mechanism of stroke. Moreover, the MRA showed a decrease
in collateral vascularization from M1 and M2 segments, while
the MCA caliber was unaltered, thus suggesting that the
infarct was due to occlusion of small caliber arteries.
MEPs loss in supratentorial surgery is related to a postoperative
motor deficit (13) and indicates a motor cortical or subcortical
lesion, while SEP changes are very sensitive for detecting
cortical perfusion disorders. In our case, the initial decrease
of MEP pointed to an involvement of the lenticulostriate
arteries. The following SEP deterioration on the other hand
heralded as well a cortical implication. At the end of surgery,
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we found an absence of the hand motor response and very
low amplitude of the foot response, suggesting a poor longterm functional outcome (6, 7).

5. Mut M, Yemisci M, Gursoy-Ozdemir Y, Ture U: Hydrogen
peroxide-induced stroke: Elucidation of the mechanism in
vivo. J Neurosurg 110(1): 94-100, 2009

To date, all reports of H2O2-induced strokes are limited
to describing the radiological and clinical findings of a
stroke after a surgery where H2O2 was utilized and was
supposedly, the culprit. Here we bridge the gap, providing
neurophysiological proof that the H2O2 instillation provoked
the tissue damage in our patient given that the temporal gap
between intraoperative neurophysiological changes and the
irrigation with H2O2, once the tumor resection and bipolar
coagulation was already finished, is only of few seconds.
Furthermore, the stroke occurred in absence of any another
possible inducing cause.

6. Neuloh G, Pechstein U, Schramm J: Motor tract monitoring
during insular glioma surgery. J Neurosurgery 106: 582-592,
2007

The INM changes prompted a quick start of maneuvers aimed
at reversing the injury. These measures may have changed the
final postoperative outcome of the patient. We conclude that
INM can be a very useful tool to detect even the most unlikely
mechanisms of neural injury during brain surgery, and to aid
neurosurgeons to change the surgical strategy. Finally, we
recommend being cautious or even avoiding the application
of H2O2 for hemostasis during cranial tumor resection when
vascular structures are exposed.
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