Clinical Neurology and Neurosurgery 111 (2009) 900–903 Contents lists available at ScienceDirect Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro Case report Pseudohypoxic brain swelling after elective clipping of an unruptured anterior communicating artery aneurysm Hiroshi Yokota ∗ , Kazuhiro Yokoyama, Kazunori Miyamoto, Toshikazu Nishioka Department of Neurosurgery, Higashiosaka City General Hospital, 3-4-5 Nishiiwata, Higashiosaka, Osaka, 578-8588, Japan a r t i c l e i n f o Article history: Received 11 February 2009 Received in revised form 12 June 2009 Accepted 9 August 2009 Available online 5 September 2009 Keywords: Basal ganglia Brain swelling Complication Craniotomy Intracranial hypotension Pseudohypoxic Subgaleal drainage a b s t r a c t A case of pseudohypoxic brain swelling, a newly defined entity, is described. The patient experienced generalized seizures and did not awake initially after a seemingly uneventful elective craniotomy for clipping of an unruptured anterior communicating artery aneurysm. Neuroimaging findings demonstrated diffuse brain swelling, especially in the bilateral basal ganglia and thalami. The rarity of this postoperative complication is addressed and the pathogenesis discussed. © 2009 Elsevier B.V. All rights reserved. 1. Introduction Van Roost et al. were the first to define pseudohypoxic brain swelling (PHBS), which is presented as consciousness disturbance, brainstem dysfunction, and generalized seizures in patients following uneventful brain surgery [1]. Diffuse brain swelling, especially that involving the bilateral basal ganglia and thalami, is a typical finding on computerized tomography (CT) and magnetic resonance (MR) images, with over-drainage of cerebrospinal fluid (CSF), especially with the use of suction drainage, suggested to contribute to the pathogenesis of this condition. We present an additional case of PHBS that developed after an uneventful elective craniotomy for clipping of an unruptured anterior communicating artery aneurysm. Neuroimaging findings and pathogenic factors are also discussed. 2. Case report History and examination: A 56-year-old man was diagnosed with an asymptomatic unruptured anterior communicating artery aneurysm, which was confirmed by cerebral angiography. The patient had hypertension, diabetes, and chronic hepatitis C, however, no complaints and, notably, no orthostatic headache. Neurological examinations were normal. CT scans as well as MR ∗ Corresponding author. Tel.: +81 6 6781 5101; fax: +81 6 6781 2194. E-mail address: h-yokota@higashiosaka-hosp.jp (H. Yokota). 0303-8467/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2009.08.007 imaging showed asymptomatic lacunar infarctions in the basal ganglia and deep white matter bilaterally. Operation: The patient underwent a right frontotemporal craniotomy. The sylvian fissure was opened from a distal site via a pterional approach, and neck clipping of the aneurysm was performed after subfrontal exposure, which was uneventful. Lumbar CSF and external ventricular drainage were not used during the procedure. Anti-edematous agents such as mannitol were not administered. At the end of surgery, the brain was slack and the dura was closed in a water-tight fashion, with a drain without suction placed in the subgaleal space. Postoperative course: Following the operation, the subgaleal drain was opened and drained by gravity, while administration of propofol was continued as a sedative agent from the operation. However, generalized seizures occurred 45 min after the end of surgery, when the total amount of drainage was about 70 ml. Despite a bolus infusion of propofol and intramuscular phenobarbital, a second set of generalized seizures occurred 5 h after the first, when the total amount of drainage had reached about 130 ml. An additional bolus infusion of propofol and intramuscular phenobarbital resulted in freedom from further seizures. No significant reductions of systemic blood pressure or hypoxia were observed, and no pupillary abnormalities were noted. Arterial blood gas analyses did not demonstrate abnormal values. The drain was removed 17 h after the operation, with a total of 235 ml of fluid collected. Despite discontinuation of sedation, the patient did not awaken. A CT scan revealed diffuse abnormal hypodensity regions, especially in the basal ganglia and thalami bilaterally (Fig. 1A). H. Yokota et al. / Clinical Neurology and Neurosurgery 111 (2009) 900–903 901 Fig. 1. CT scans showing diffuse brain swelling with prominent hypodensity areas in the basal ganglia and thalami bilaterally (A), with tight cerebral cisterns (B) and effacement of the sulci (A and B). Fig. 2. MR images obtained 5 days after the operation showing extensive hyperintense signals in the bilateral basal ganglia and thalami, which are especially prominent in the lenticular nuclei. (A) T2-weighted image. (B) FLAIR image. (C) DW image demonstrating heterogeneous signal changes, including isointensity and hyperintensity. (D) ADC map showing signal changes concomitant with hyperintensity, isointensity, and hypointensity in the area of the lesion. 902 H. Yokota et al. / Clinical Neurology and Neurosurgery 111 (2009) 900–903 Fig. 3. T2-weighted MR image obtained 19 days after the operation showing near disappearance of abnormal signal intensities, while ischemic changes in the basal ganglia and subdural effusion can be seen bilaterally. Furthermore, tight cerebral cisterns (Fig. 1B) and effacement of the sulci were also noted (Fig. 1 A and B). An emergency cerebral angiography revealed a slow circulation flow, though neither occlusion nor stenosis of the main vessels including the arteries and veins was noted. The anterior communicating artery aneurysm was completely obliterated. We made a diagnosis of diffuse cerebral swelling of unknown etiology, with a possible relationship to impairment of deep venous drainage. The patient was treated with an intravenous administration of mannitol, glycerol, and lowmolecular-weight dextran, while intramuscular phenobarbital was also continued. Over the next 5 days, his level of consciousness gradually improved. MR imaging performed 5 days after the operation revealed signal changes in the bilateral basal ganglia and thalami on both T2-weighted and fluid-attenuated inversion recovery (FLAIR) images (Fig. 2 A and B). A diffusion-weighted (DW) image revealed mottled hyperintensity signals in the area of the lesion (Fig. 2C). In addition, an apparent diffusion coefficient (ADC) map showed heterogeneity mixed with hyperintensity, isointensity, and hypointensity in the area of the lesion (Fig. 2D). The findings of DW MR imaging with an ADC map indicated vasogenic edema in the bilateral basal ganglia and thalami, with some degree of progression to cytotoxic edema. MR images obtained 19 days after surgery revealed nearly complete disappearance of abnormal signals, while additional ischemic changes in the basal ganglia and bilateral subdural effusions were noted (Fig. 3). During the follow-up period, the patient suffered from symptomatic epilepsy and cognitive impairment. Ischemic changes in the basal ganglia and para-ventricular region persisted on both MR imaging and CT scan. He died due to an intracerebral hemorrhage 6 years after the operation. cal presentation includes brainstem dysfunction and generalized seizures, which are observed in patients in a comatose state a few hours after an uneventful elective craniotomy surgical procedure. Diffuse brain swelling, especially that involving the bilateral basal ganglia and thalami, is a typical finding on CT and MR images. PHBS is a potentially fatal condition, though patient prognoses vary widely from full recovery to death. The present case is compatible with PHBS clinically as well as radiographically. Hemorrhagic complications following an uneventful craniotomy procedure are well known, with over-drainage of CSF proposed to be the most likely cause [2–4]. Thus, PHBS may be a more specific complication caused by such excessive CSF depletion. Van Roost et al. suggested intracranial hypotension caused by transmission of negative pressure with special attention to use of suction drainage as a possible main pathogenic factor [1]. Indeed, more than 300 ml of subgaleal drainage has been noted in 8 of 12 cases for which data were obtained regarding subgaleal drainage volume. Tight cerebral cisterns, effacement of the sulci, and bilateral subdural effusion in neuroimaging findings may reflect CSF depletion. However, we did not use suction drainage and the volume of CSF drainage was about 70 ml when the first seizures occurred in the present patient. Notably, a case with a drainage volume of 100 ml that showed a rapidly fatal course was included in the series reported by Van Roost et al. [1]. Subgaleal drainage by gravity can, by negative hydrostatic pressure, mimic active suction from a closed skull. Therefore, PHBS may develop in cases with small amounts of CSF drainage, even with use of subgaleal drainage by gravity only. In addition, CSF depletion during the operative procedure may have been a contributing factor in the present case. For example, a wide opening of the sylvian fissure, cerebral cistern, and ventricle can exaggerate acute CSF depletion [2,3]. Findings obtained in pre-operative neurological and neuroimaging examinations in our case do not support another possible cause associated with CSF depletion, such as a preexisting spontaneous spinal CSF leak [5]. Interestingly, MR imaging findings in the present case support vasogenic edema, similar to the pathogenesis of a patient with deep cerebral venous thrombosis [6]. The marked discrepancy between extensive abnormalities seen on FLAIR images and relatively few abnormalities on DW images also supports vasogenic edema concomitant with cytotoxic edema, as in a previously reported case of cerebral venous thrombosis [7]. Brain sag resulting from CSF depletion and subsequent compression of the deep venous system are also possible pathogenic factors. However, angiographic findings revealed neither stenosis nor occlusion in the deep venous system, and only non-specific findings, such as slow circulation time, were noted in the report by Van Roost et al. [1]. A slowed circulation time shown by angiography may reflect a microvascular dysfunction secondary to cerebral swelling. Thus, we could not conclude a venous origin as the mainstay of the pathogenesis of PHBS. Neurosurgeons should be aware of potential fatal postoperative complications, namely PHBS, following uneventful brain surgery, though the pathogenesis remains unknown. In the present case, DW MR imaging with an ADC map demonstrated vasogenic edema in the bilateral basal ganglia and thalami, similar to impairment of deep venous drainage caused by venous sinus thrombosis. However, angiographic findings, such as slow circulation time, were non-specific. Elucidation of the pathogenesis as well as effective treatment for PHBS is needed in further studies. 3. Discussion References In 2003, Van Roost et al. coined PHBS as a newly defined complication after uneventful brain surgery [1]. A typical clini- [1] Van Roost D, Thees C, Brenke C, Oppel F, Winkler PA, Schramm J. Pseudohypoxic brain swelling: a newly defined complication after uneventful brain surgery, probably related to suction drainage. Neurosurgery 2003;53:1315–27. H. Yokota et al. / Clinical Neurology and Neurosurgery 111 (2009) 900–903 [2] Yacubian EM, de Andrade MM, Jorge CL, Valerio RM. Cerebellar hemorrhage after supratentorial surgery for treatment of epilepsy: report of three cases. Neurosurgery 1999;45:159–62. [3] Papanastassiou V, Kerr R, Adams C. Contralateral cerebellar hemorrhagic infarction after pterional craniotomy: report of five cases and review of the literature. 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