November 25, 2004
Sudden Death Secondary to Fulminant Intracranial Aspegillosis in a Healthy Teenager After Posterior Fossa Surgery: the Role of Corticosteroids and Prophylactic Recommendations/Comments
R. D. DICKERMAN, Q. E. J. STEVENS, S. J. SCHNEIDER
Department of Neurosurgery North Shore University-Long Island Jewish Health System New Hyde Park, NY, USAPostoperative complications from corticosteroids in neurosurgical patients are not uncommon. Too often the deleterious immunosuppressive effects of corticosteroids are overlooked in neurosurgery patients and can lead to serious and lethal infections. Experimental design: case report of a 16-year-old healthy male who presented for elective resection of a recurrent juvile pilocytic astrocytoma of the posterior fossa 4 years after initial resection. Setting: major University institutional practice. Intervention/ results: a standard suboccipital craniotomy with gross total resection. Postoperatively, the patient suffered from posterior fossa syndrome and diminished gag reflex requiring nasogastric feeds with progressive improvement. While awaiting transfer to a rehabilitation center on postoperative day 12 he suffered a sudden temperature spike followed by neurological decline. A stat computed tomography scan of the brain revealed a diffuse miliary process with severe cerebral edema. Sputum and cerebrospinal fluid cultures identified Aspergillus. Despite immediate therapy to combat the malignant cerebral edema, the patient died within 24 hours of onset of the symptoms. Corticosteroids are used routinely in neurosurgery to combat cerebral edema without much consideration for the immunosuppressive effects. This case demonstrates how the immunosuppressive effects of corticosteroids can lead to a fulminant lethal fungal infection. Neurosurgeons should be aware of the anticatabolic medications now available to combat the deleterious side effects of corticosteroids.
Key words: Anabolic - Catabolic - Decadron - Steroids - Immune system - Oxandrin.
Corticosteroids are routinely used in neurosurgery for there ability to decrease cerebral edema.1 Corticosteroids have been shown to have a multitude of other effects on multiple systems both beneficial and deleterious.2, 3 A few cases have been reported on catastrophic immunosuppression occurring with routine doses of Corticosteroids in postoperative patients.4-8 We present a tragic case of rapid neurological decline and death secondary to fulminant Aspergillus infection occurring after successful posterior fossa surgery for resection of brain tumor.
Sixteen-year-old male with history of juvenile pilocytic astrocytoma C)PA) resection 4 years prior at an outside institution was seen in the Neurosurgery Clinic for evaluation of radiographie evidence for recurrent tumor and new growth. The patient was an otherwise healthy male, neurologically intact, developmentally normal and very active in sports. The family requested elective surgery for resection of the recurrent tumor. The patient underwent a standard suboccipital approach, with intraoperative neuronavigation assistance due to recurrent tumor growth occurring in the 4th ventricle and attaching to the dorsal brainstem. The patient tolerated the procedure very well and postoperatively suffered posterior fossa syndrome with akinetic mutism and a diminished gag reflex. The patient was on standard postoperative corticosteroid therapy, Dexamethasone 4 mg every 6 hours with a slow taper. A CT scan of the brain was performed on postoperative day 8 as a routine predischarge scan which demonstrated normal postoperative changes (Figure 1). Due to the diminuished gag reflex the patient was nourished with a nasogastric tube until appropriate swallowing reflexes returned. While the diminished gag reflex persisted, the patient progressively improved over the next 2 postoperative weeks and was preparing for discharge to a rehabilitation facility. On postoperative day 12 the patient developed a temperature of 102.S degrees and a chest X-ray was performed while blood and urine cultures were sent for analysis. A small right middle lobe effusion appeared on the radiograph and the patient began to have labored breathing. He was transferred to the Pdiatrie Intensive Care Unit and intubated for airway protection with a presumptive diagnosis of aspiration pneumonia. Approximately 12 hours later the neurosurgery team was notified that the patient had an abnormal pupillary response and an emergent CT scan of the brain was performed (Figure 2). A diffuse miliary process was evident on the CT scan with a yet to be determined etiology. Based on the head CT, a chest CT was also performed demonstrating a similar process of multiple cavitary lesions. A lumbar puncture was performed which was negative for any organisms. Despite aggressive medical intervention for cerebral edema, ventriculostomy, and prophylactic antifungal coverage, the patient developed malignant cerebral edema and died within 24 hours.
Figure 1.-Postoperative day 8, routine predischarge computed tomography .scan demonstrating no hydrocephalus or postoperative hemorrhage.
Figure 2.-Postoperative day 12, emergent computed tomography scan demonstrating a diffuse miliary process with significant cerebral edema.
Postoperative death from corticosteroid-induced immunosuppression in neurosurgery patients is a rare occurrence but surgeons must be aware of the serious deleterious effects of corticosteroids.4,7-9 The immunosuppressive effects of corticosteroids are well documented and often utilized to treat many autoimmune diseases.1,3 Neurosurgical catastrophies secondary to Aspergillus have thus far involved cerebrovascular events such as aneurysmal rupture and diffuse subarachnoid hemorrhage.9-12 This is the first case of fulminant Aspergillus occurring in a postoperative neurosurgical patient secondary to immunosuppression. It is unlikely that the patient suffered an occult immunosuppressive illness to predispose him to this process, with the history of previous posterior fossa surgery and exposure to corticosteroids. We did not use any synthetic dura/grafts that may have predisposed him to infection. It is possible that the combined immunosuppressive effects of corticosteroids and surgical stress may have allowed a fungal infection to become overwhelming.
A recent study from the National Institutes of Health demonstrated an increasing incidence of Pneumocystis carinii pneumonia in brain tumor patients, without HIV, receiving Decadron and recommended prophylactic antibiotics.6 Previous studies on brain tumor patients receiving corticosteroid therapy have also demonstrated an increased risk for immunocompromised infections and recommended both prophylactic antibiotics and antifungals.2, 8 We recently reported on a 38-year-old male on corticosteroids for systemic sarcoidosis who developed an isolated intracranial infection with Mycobacterium avium which we attributed to corticosteroid immunosuppression.13 Based on these reports and our experience, we are now routinely utilizing an anticatabolic/ anabolic agent Oxandrin (BTG Pharmaceutical, NJ, USA) which is indicated to combat the deleterious effects of corticosteroids.14- 16 Oxandrin has anabolic properties that can assist with protein metabolism essential for proper immune function and postoperative healing while also combating the catabolic effects of corticosteroids. Our experience thus far with Oxandrin has been successful in assisting with wound-healing in patients undergoing neurosurgery in our practice, especially the compromised patients such as elderly and diabetics. We feel that this medication may have been helpful in combating the immunosuppression in this case.
Lastly, nosocomial causes for aspergillosis infections have been implicated in the past, specifically ongoing hospital construction.17 There was no construction occurring during this patients admission and there were no other patients suffering from a pneumonia in the patients vicinity. In addition, no cases of Aspergillus pneumonia have been reported at the hospital since this patients death 18 months ago. A recent study provided the term "immunoparalysis" for patients that are immunocompetent and subsequently succumb to infections that are usually found in chronically immunosuppressed patients.18 The authors reported on 4 immunocompetent patients that acquired invasive aspergillosis and hypothesized that the patients immune system responded to their initial insult with the expected hyperinflammatory phase followed by the anti-inflammatory phase, it is during this anti-inflammatory phase that the patient suffers "immunoparalysis" and is susceptible to the opportunistic infections.18 Thus, it is plausible that corticosteroids enhanced the anti-inflammatory phase in our patient making him more susceptible to opportunistic infections.
The deleterious effects of corticosteroids are too often underestimated in the field of neurosurgery due to there routine use. This case demonstrates that routine utilization of corticosteroids can lead to catastrophe even in a healthy 16-year- old male. Surgeon awareness of the immunosuppressive effects of corticosteroids is imperative along with education on nutritional and pharmaceutical modalities available to prevent/combat immunosuppression in patients receiving corticosteroids.
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18. Hartemink KJ, Paul MA, Spijkstra JJ, Girbes AR, Poklerman KH. Immunoparalysis as a cause for invasive aspergillosis? Intensive Care Med 2003;24:15-20.
Received March 26, 2004.
Accepted for publication July 15, 2004.
Address reprint requests to: R. D. Dickerman, D.O., Ph.D., Department of Neurosurgery, 260-12 74th Avenue, Glen Oaks, NY 11004, USA. E-mail: [email protected]
This report of intracranial aspergillosis alerts us to a very rare complication of surgery, obviously related to the immunosuppressive effect of corticosteroids. Corticosteroids are of course indispensable in neurosurgical practice, but every effort should be made control their side effects. However there is no hard evidence that the use of anabolics, like oxandrolone, as suggested by the authors, reduces the incidence of opportunistic infections. Their help seems to be limited to muscular wasting and wound healing in immunosuppressed patients.
Athens - GR
It seems quite impossible to disagree with the objective and conclusions of the paper of Dickerman et al.: the immunosuppressive effects, often deleterious, of corticosteroids are too frequently overlooked in neurosurgery. The cue for these considerations is represented by the case of a young boy who, after a surgical resection of a pilocytic astrocytoma of the cerebellum and subsequent steroid administration, presented a diffuse intracranial fungal infection rapidly lethal.
Corticosteroids are routinely used in neurosurgery with great benefit so that at the end of the '5Os began the "steroid era". Postoperative courses and the entire management of brain tumors radically changed. But corticosteroids have been shown to have many other effects both beneficial and deleterious: cutaneous effects, electrolyte abnormalities, hypertension, hyperglicemia, pancreatitis, hematologie effects, adrenal insufficiency, gastrointestinal, hepatic, ophthalmologic, immunologie effects, i.e. immunosuppression with patients becoming prone to bacterial and fungine infection.
Surgeon awareness of adverse effects of corticosteroids, the immunosuppressive too, is imperative along with education on nutritional and pharmaceutical modalities to prevent or combat immunosuppression.
A 16-year-old neurologically intact patient underwent surgery owing to progression of growth of a cerebellar pilocytic astrocytoma, that had been (partially?) removed 4 years earlier. Following extirpation of a tumor located in the 4th ventricle and implanted on the dorsal brain stem, a routine corticosteroid therapy (Dexamethasone, 4 mg every 6 hours) was started.
On the 12th postoperative day the patient developed high fever followed by neurological deterioration. Multiple cavitary lesions within the brain and the lungs were revealed by CT scan. On the basis of cultures of sputum and cerebrospinal fluid a diagnosis of aspergillosis was made.
The patient died within 24 hours. It was assumed that the infection was consequent to immunosuppression secondary to corticosteroid therapy.
This article is rather untidy and somewhat confusing, with the results of the cultures being reported only in the summary. Immunological pattern and autopsy records are lacking. The cause- effect relationship is conjectural, owing to the shortage of available findings. However, this case report can be a reminder of possible complications following intracranial surgery.
Genoa - I
Copyright Edizioni Minerva Medica Jun 2004