Malignant Cerebral Edema Secondary to Gliadel Wafers in the Early Postsurgical Period ()
1. Introduction
Carmustine wafer (polifeprosan 20 with carmustine, Gliadel Wafers®) is a sterile wafer that contains 192.3 mg of a biodegradable polyanhydride copolymer and 7.7 mg of carmustine (1,3-bis (2-chlor-oethyl)-1-nitrosourea, or BCNU). BCNU wafers has been shown to improve survival in patients with newly diagnosed and recurrent malignant glioma (MG), and this survival benefit is maintained over the long term follow up in patients with newly diagnosed MG, but a variety of complications and adverse effects (AEs) have been associated including cerebral edema, intracranial hypertension, healing abnormalities, cerebral spinal fluid leaks infections seizures, thromboembolic complications hydrocephalus and cyst formation [1] . Following surgical resection, BCNU wafers are implanted into the resection cavity.
According to the literature currently available the overall incidence of cerebral edema in patients with newly diagnosed is 1.1%. Rare cases of profound cerebral edema have been reported with standard doses of carmustine by weight [2] [3] but none has been reported in the early postsurgical period.
We describe a case of malignant cerebral edema unresponsive to aggressive medical and surgical assessment that finally evolved to premature death 3 days after the craniotomy and implantation of Gliadel wafers.
2. Method
59-year-old female was admitted to the hospital with a two week history of motor and sensory deficit on the left side, this increased in severity and a CT and MRI scan showed a mass lesion in the high right frontal-parietal area with minimal edema and greatest diameter of 2.7 - 3 cm (Figure 1). Dexamethasone started 4 mg every 8 h.
10 days after, a right frontal-parietal craniotomy was performed and the tumour was classified as a high-grade glioblastoma. Six Gliadel wafers were implanted on the brain surface. Immediately postoperation, patient pres- ents neurological deterioration and worsens of left hemiparesis. A TC scan demonstrated a marked midline shift with edema throughout the right hemisphere more pronounced than on preoperative images. A drug regimen of 6 mg dexamethasone and 20 g mannitol EV every 6 H respectively, was initiated by improvement of the symptoms. 12 H later, the patient began with a severe headache, a dense left hemiparesis, increased somnolence and she ceased to respond to painful stimuli.
A new CT scan demonstrated increased edema throughout the right hemisphere and further shift of the midline structure. Dexamethasone 10 mg IV, mannitol 20 g every 4 h, and furosemide were given intravenously. Se- condary to suddenly neurological decline and poorly response to aggressive medical treatment the reoperation was required.
Figure 1. MRI scan: Mass lesion in the high right frontal- parietal area.
Figure 2. CT scan: Massive right uncal and subfalcine herniation.
3. Results
1 hour after surgery the patient was alert, oriented and responding appropriately with improvement in physical neurological exam. But in the next day she became progressively more obtunded, pupils became dilated, with Glasgow Coma Scale (GCS) score 2/15 and the patient died. A CT scan demonstrated massive right uncal and subfalcine herniation (Figure 2).
4. Discussion
While the use of Gliadel wafers for treatment of malignant gliomas has been shown in multiple studies to be effective with minimal adverse effects, we describe a early presentation of malignant cerebral edema in the inmediately postsurgical time which fits well with the potencial cytotoxic effects of carmustine. It has been shown that carmustine distributes widely, at least in the ipsilateral hemisphere, during the first several days postimplantation. Thus the inicial vasogenic edema induced by the surgery likely allowed for a situation of convective flow and greater distribution of carmustine with subsequent cytotoxicity. Fung et al. in studies on rats, concluded that carmustine distribution was increased in the first three days secondary to vasogenic edema and bulk flow [4] [5] .
After revised the prior literature, we think that our patient is the first case of early malignant cerebral edema refractory to standard medical and surgical treatment secondary to Gliadel Wafers.