Improved management of multiple brain abscesses: a combined surgical and medical approach.

Bacterial brain abscesses occur in approximately 1500 to 2500 patients each year in the United States. Multiple abscesses have been noted in 10 to 50% of these patients. The goal of this study was to better define the roles of surgery and medical management in patients harboring multiple brain abscesses and to develop an algorithmic approach to the treatment of these complex patients. Between 1976 and 1992, 16 patients with multiple brain abscesses were treated by a single physician (M.L.R.). The ages of the patients ranged from 1.5 to 73 years (median, 47 yr). In all patients, a diagnosis of multiple abscesses was made by computed tomography (15 patients) or magnetic resonance imaging (1 patient) brain scans. The number of abscesses per patient ranged from 2 to 30, and the abscesses were located in all regions of the brain. Thirteen received a combination of antibiotics and surgical drainage, and three received antibiotics only. Surgery was performed on abscesses larger than 2.5 cm or on those situated in critical areas of the brain or causing significant mass effect. Excision and open aspiration via craniotomy and stereotactic aspiration were analyzed on the basis of the location of the lesion and infecting organism. Any abscess that enlarged after 2 weeks of antibiotics or that failed to shrink after 3 to 4 weeks of antibiotics was again aspirated or excised. Forty-three surgical procedures were performed in 13 patients, and 8 (62%) of the patients operated on required more than one surgical procedure. No significant morbidity was observed in any of the surgical procedures. Antibiotics were administered intravenously for an average of 6 to 8 weeks and were adjusted according to organism type and sensitivity to antibiotics. One patient (6%) died, and the remaining 15 patients had resolution of all abscesses and good neurological recovery within 6 months. On the basis of these results, we propose a combined surgical and medical approach to the treatment of patients with multiple brain abscesses. We recommend the aggressive surgical drainage of all abscesses larger than 2.5 cm in diameter, combined with 6 to 8 weeks of intravenous antibiotics. Biweekly computed tomography or magnetic resonance imaging is necessary to closely monitor patients for evidence of abscess growth or failure to resolve despite antibiotics, prompting another operation. The application of this combined approach should yield cure rates of more than 90% in patients with multiple brain abscesses, a result similar to that expected when treating patients with solitary lesions.

Nocardial brain abscess: treatment strategies and factors influencing outcome.

The successful management of nocardial brain abscess remains problematic. The authors report 11 cases of nocardial brain abscess treated between 1971 and 1993 and review 120 cases reported since 1950. The clinical findings included focal deficits in 55 patients (42%), nonfocal findings in 36 (27%), and seizures in 39 (30%). Extraneural nocardiae were present in 66% of the cases; pulmonary (38%) and cutaneous/subcutaneous (20%) locations were the most frequent. The abscesses were single in 54% of the patients, multiple in 38%, and of unknown number in 8%. Forty-four of 131 patients (34%) were immunocompromised; since 1975, 18 of 40 immunocompromised patients (45%) were transplant recipients and six (15%) had human immunodeficiency virus. The mortality rate was 24% after initial craniotomy and excision (11/45), 50% after aspiration/drainage (17/34), and 30% after nonoperative therapy (7/23); 29 cases (22%) were diagnosed at autopsy. The mortality rate was 33% in patients with single abscesses and 66% in those with multiple abscesses (P < 0.0003). There was no difference in the mortality rates of immunocompromised and nonimmunocompromised patients treated before computed tomography (CT) was available; since the advent of CT, however, the mortality rate has been significantly higher in immunocompromised patients (55% vs. 20%, P < 0.05). Although the mortality rate for nocardial brain abscesses has dropped almost 50% since the advent of CT, it has remained virtually unchanged in immunocompromised patients and is three times higher than that of other bacterial brain abscesses (30% vs. 10%). The authors recommend image-directed stereotactic aspiration for diagnosis; however, craniotomy and total excision are necessary in most cases, because nocardial abscesses are usually multiloculated. Patients with minimal neurological deficits or small abscesses may be treated initially with antibiotics alone. Sulfonamides, alone or in combination with trimethoprim, are most effective and should be continued for at least 1 year. Minocycline, imipenem, or aminoglycoside in combination with a third-generation cephalosporin may be used with reasonably good success as second-line agents in cases of allergy or nonresponsiveness to sulfa agents.

Treatment options and prognosis for multicentric juvenile pilocytic astrocytoma.

Little is known about the risk of developing multicentric disease in patients with juvenile pilocytic astrocytoma (JPA), and even less about its prognosis. Only five cases have been reported. Between 1986 and 1992, the authors treated 90 patients with either primary or recurrent JPA, 11 of whom developed multicentric spread. Ten patients had primary tumors in the hypothalamic region, eight were under 4 years of age at initial diagnosis, all had initially undergone a subtotal resection or biopsy, and 10 received postoperative multiagent chemotherapy or irradiation for residual disease. Multicentric spread was discovered immediately to 108 months after initial diagnosis; nine patients were asymptomatic at the time. Most patients received chemotherapy for the multicentric disease, which was found throughout the craniospinal axis. During 21 to 148 months of follow-up monitoring, seven patients had stabilization or regression of multicentric disease and four died. Patients with hypothalamic region tumors were 23 times more likely to develop multicentric spread than were those with primary tumors located elsewhere (p < 0.001). Based on this review, it is concluded that multicentric spread of JPA occurs more frequently than was previously recognized. In patients with subtotally resected JPA and several years of follow-up review via magnetic resonance imaging, the incidence of recurrence in a site different from the original was 12%. Patients with subtotally resected JPA in the hypothalamic region should be considered to be at high risk for developing multicentric spread. Chemotherapy appears useful in stabilizing multicentric disease. Earlier detection and intervention may result in longer disease-free survival in patients with multicentric spread of JPA.

Resection of dominant opercular gliosis in refractory partial epilepsy. Report of two cases.

Frontal opercular gliosis in the dominant hemisphere caused medically refractory partial epilepsy in two patients. Both patients were aphasic during their seizures, but otherwise had normal speech. Magnetic resonance images showed well-demarcated lesions resembling tumors in each patient; on heavily T2-weighted images, the lesions were hyperintense compared with normal brain. Cortical mapping with subdural grids localized speech to the area of the lesions; therefore, the resections were performed under local anesthesia and speech was tested throughout the procedure. Postoperatively, both patients were seizure-free and had no new neurological deficits. Well-demarcated lesions, even in the dominant operculum, can be safely removed in patients with medically refractory partial epilepsy.

Nonoperative treatment of neurosurgical infections.

The indications for nonsurgical management of CNS infections manifested by collections of pus are very limited. In general, such management is restricted to neurologically intact patients who are unable to undergo the needed surgical procedure and in whom the organism can be identified presumptively from other cultures. In such circumstances, brain abscesses less than 1.5 cm in diameter, small subdural empyemas, some spinal epidural abscesses, and many cases of spinal osteomyelitis can be successfully treated with prolonged intravenous antibiotic therapy. In patients who are unable to tolerate a neurosurgical procedure, the presence of an infectious CNS mass lesion is not hopeless and vigorous medical therapy offers the possibility of cure.

Metastatic juvenile pilocytic astrocytoma. Case report.

The authors report the case of a metastatic juvenile pilocytic astrocytoma of the hypothalamic region in a 10-year-old boy. Eight years after craniotomy and radiation therapy, the tumor spread via cerebrospinal fluid pathways to the left cerebellar tonsil and the lumbosacral region. Histological evaluation of both the original hypothalamic and the new lumbosacral masses showed features of a slow-growing juvenile pilocytic astrocytoma with no evidence of malignant transformation. The clinical implications and possible mechanisms of metastatic spread are discussed.

Ultrasound-guided aspiration of a neonatal brain abscess.

The authors successfully treated a Serratia marcescens brain abscess in the right parieto-occipital region of a newborn infant born at 27 weeks' gestation and weighing 800 g. Bedside ultrasound-guided aspiration techniques and local anesthesia were used to treat the abscess.

A case of Rhodococcus equi brain abscess.

We treated a patient with acquired immunodeficiency syndrome for a brain abscess caused by Rhodococcus equi, an actinomycete that usually infects the lung in immunosuppressed hosts. Rhodococcus equi brain abscess is an extremely rare lesion that has never been reported in a patient with acquired immunodeficiency syndrome. The infection was cured by lengthy therapy with multiple antibiotics after aspiration of the lesion to identify the infective organism and determine its sensitivity to antibiotics.

Epidermoid cysts of the brain stem. Report of three cases.

The authors report the cases of three patients with epidermoid cysts which insinuated themselves into the brain stem. In all three patients, the tumor occupied the pons, although in one it was predominantly located in the medulla. The cyst contents and nonadherent tumor capsule were removed in all three patients, but no attempt was made to remove tumor densely adherent to the brain stem. One patient's cyst was removed in one operation, but maximal resection in the other two required two operations. After surgery, sixth nerve function completely returned in one patient; another patient had a stable pontine gaze palsy but developed new facial weakness; and the third patient had stable cranial nerve deficits with a diminished hemiparesis. The last patient developed a pseudomeningocele and communicating hydrocephalus, and required a lumboperitoneal shunt. In all three patients, computerized tomography scans demonstrated hypodense tumors not enhanced by contrast material. Magnetic resonance imaging was performed on two patients; in both, the tumors showed increased signal intensity relative to brain on T1-weighted images and decreased signal intensity relative to brain on T2-weighted studies. Magnetic resonance imaging, the most accurate modality for localizing these lesions and determining their extent, was also invaluable for postoperative monitoring and follow-up evaluation. Safe and adequate resection includes decompression of cyst contents and removal of nonadherent portions of the cyst capsule. Cyst wall adherent to the brain stem, however, should not be removed.

Antimigraine treatment for slit ventricle syndrome.

Slit ventricle syndrome is characterized by chronic or recurring headaches associated with subnormal ventricular volume in patients who have undergone shunt treatment for hydrocephalus. There appear to be at least three pathophysiological mechanisms that cause this syndrome: 1) intermittent shunt malfunction; 2) intracranial hypotension; and 3) paroxysms of increased intracranial pressure in the presence of normal shunt function. To treat seven patients with slit ventricle syndrome caused by paroxysms of elevated intracranial pressure, we successfully used antimigraine therapy rather than standard calvarial expansion procedures. None of these patients has required shunt revision or calvarial expansion during a mean follow-up period of 2 years. The symptoms of slit ventricle syndrome may be a form of "acquired" migraine in shunt patients. We suggest that, in clinically stable patients with normal shunt function, treatment against migraine may stabilize symptoms resulting from paroxysms of increased intracranial pressure. Such treatment may prevent unnecessary shunt revisions and/or calvarial expansion procedures.

Cerebrospinal fluid rhinorrhea in patients with untreated pituitary adenoma: report of two cases.

We report the cases of two patients with untreated pituitary adenoma who presented with cerebrospinal fluid rhinorrhea. The surgical treatment and mechanisms involved in this rare condition are discussed.

Stroke associated with cocaine use.

We describe eight patients in whom cocaine use was related to stroke and review 39 cases from the literature. Among these 47 patients the mean (+/- SD) age was 32.5 +/- 12.1 years; 76% (34/45) were men. Stroke followed cocaine use by inhalation, intranasal, intravenous, and intramuscular routes. Intracranial aneurysms or arteriovenous malformations were present in 17 of 32 patients studied angiographically or at autopsy; cerebral vasculitis was present in two patients. Cerebral infarction occurred in 10 patients (22%), intracerebral hemorrhage in 22 (49%), and subarachnoid hemorrhage in 13 (29%). These data indicate that (1) the apparent incidence of stroke related to cocaine use is increasing; (2) cocaine-associated stroke occurs primarily in young adults; (3) stroke may follow any route of cocaine administration; (4) stroke after cocaine use is frequently associated with intracranial aneurysms and arteriovenous malformations; and (5) in cocaine-associated stroke, the frequency of intracranial hemorrhage exceeds that of cerebral infarction.

Effect of opiate antagonists on middle cerebral artery occlusion infarct in the rat.

The authors examined the effect of the opiate antagonists naloxone and thyrotropin-releasing hormone (TRH) on neurological outcome and the size of areas of cerebral infarction in a rat model of focal cerebral ischemia. The middle cerebral artery (MCA) was permanently occluded in 66 adult Sprague-Dawley rats. The rats were randomly divided into three groups. In 20 Group I rats, TRH in normal saline was administered initially as a 2-mg/kg bolus followed by continuous infusion of 2 mg/kg/hr for 4 hours. In 20 Group II rats, naloxone in normal saline was administered initially as a 2-mg/kg bolus followed by continuous infusion of 2-mg/kg/hr for 4 hours. In 26 Group III rats, physiological saline was administered as an initial 0.5-cc bolus followed by continuous infusion of 0.5 cc/hr for 4 hours. All solutions were given in volumes of 0.5 cc for the bolus and 0.5 cc/hr for continuous infusion, and all infusions were begun within 10 minutes of MCA occlusion. Twenty-four hours after treatment, the rats underwent a careful neurological examination and were then sacrificed immediately. The size of areas of cerebral infarction was evaluated using 2,3,5-triphenyltetrazolium chloride staining techniques. The neurological grade of the rats correlated with the size of infarcted areas among all grades, irrespective of treatment (p less than 0.01). Neither naloxone nor TRH improved neurological function or reduced the size of infarction compared to saline-treated control rats. Treatment with TRH caused a significant increase in mean arterial blood pressure during infusion, but naloxone had no effect. These results suggest that neither TRH nor naloxone are effective in the treatment of acute focal cerebral ischemia.

Experimental brain abscess development in the chronically immunosuppressed host. Computerized tomographic and neuropathological correlations.

The neuropathological progression of brain abscess formation was studied experimentally in paired immunosuppressed and control dogs. The immunosuppressed animals received azathioprine and prednisone beginning 7 days prior to intracerebral inoculation with alpha streptococcus. Histological findings were correlated with computerized tomography (CT) brain scans. The evolution of brain abscess in the immunosuppressed animals could be divided into three stages based on histological evaluation: cerebritis stage (1 to 11 days), early-capsule stage (12 to 17 days), and late-capsule stage (18 days and later). There was a significant delay in the evolution of alpha streptococcus brain abscess compared to the authors' previous studies. Histologically, abscesses in immunosuppressed dogs were characterized by a decrease and delay in collagen formation, a reduction in polymorphonuclear leukocytes and macrophages, longer persistence of bacterial organisms, and an increase in gliosis. During the cerebritis stage, abscesses in control animals were consistently larger and more edematous than those in immunosuppressed animals and reached their maximum size by Day 8, whereas abscesses in immunocompromised animals reached their maximum size around Day 12. In the late-capsule stage, abscesses in immunosuppressed animals remained larger than those of control animals and continued to show signs of delayed development. This was evidenced by diffusion of contrast medium into the lucent center of ring-enhancing lesions on delayed CT scans. The results suggest that the decreased inflammatory response and edema formation in the immunosuppressed host resulted in less initial mass effect from brain abscess, but that the eventual size and area of the abscess may have become larger due to the less effective host response.

Experimental Staphylococcus aureus brain abscess.

The virulent organism Staphylococcus aureus produced brain abscesses that were quantitatively and qualitatively different from those caused by less virulent organisms. S. aureus abscesses created larger lesions, as earlier ependymitis, delayed progress toward healing, and caused areas of inflammatory escape outside the collagen capsule. Imaging tests revealed similar findings: the abscesses were larger, had more extensive central necrosis, and showed earlier evidence of ependymitis. This virulent organism also demonstrated that white matter is more susceptible than overlying gray matter to destruction by infection. The pattern of spread and other histologic findings suggest that collagen capsule formation has less of an infection "containment" function than was previously thought.

Chronic histological effects of ultrasonic hyperthermia on normal feline brain tissue.

The histopathological changes associated with ultrasonic heating of normal cat brain have been correlated with thermal distributions. Ultrasound energy was applied for 50 min at different intensities to generate tissue temperatures from 42 to 48 degrees C. Animals were sacrificed at various intervals from 1 to 56 days. The organization and resolution of thermal damage was characterized by three stages of histopathological changes within the nervous tissue. The acute stage (Days 1-3) was defined by (1) extensive coagulation necrosis, (2) pyknosis of neuronal elements in the gray matter, (3) edema and vacuolation in the white matter, and (4) polymorphonuclear leukocytes. The subacute stage (Days 3-21) was characterized by (1) the appearance of lipid-laden macrophages, (2) liquefaction of the necrotic regions, (3) fibroblastic proliferation, and (4) vascular proliferation with some perivascular inflammatory infiltration (lymphocytes). Lastly, the chronic stage (Days 21-56) was defined by (1) fibrosis (reticulin and collagen formation) and (2) gliosis (reactive astrocytic proliferation) occurring around the fluid-filled necrotic center. Analysis of these data has also included a study of the lesion size versus the dose (temperature for 50 min) of heating. The results demonstrate a significant linear dose-response correlation. The results of this study indicate that the histological appearance and time course of repair of thermal injury in the normal brain tissue are analogous to acute brain necrosis resulting from cerebral infarction, except the thermal damage does not result in significant hemorrhage.

Experimental anaerobic brain abscess. Computerized tomographic and neuropathological correlations.

The neuropathological progression of brain abscess formation induced by a mixed anaerobic culture of Bacteroides fragilis and Staphylococcus epidermidis was studied experimentally in dogs. Histological findings were correlated with computerized tomographic (CT) brain scans. The evolution of brain abscess formation could be divided into three stages based on histological criteria: early cerebritis (Days 1 to 3); late cerebritis (Days 4 to 9); and capsule formation (Day 10 and later). Capsule formation could not be divided into early and late stages because encapsulation was delayed compared with a previously reported model of alpha-Streptococcus brain abscess. Histologically, there was evidence for a very virulent infection. Leptomeningitis was significant even in the late stages. Early ventricular rupture occurred in 25% of the animals. A pattern of extensive purulent encephalitis was seen in 25% of the animals. In the early cerebritis stage, blood vessels near the necrotic center were engorged and were surrounded by hemorrhage and/or protein-rich fluid. Cerebral edema was extensive. Although fibroblasts appeared in late cerebritis, there was marked delay of capsule formation. Three-week-old lesions still had areas of incomplete capsule formation and foci of uncontrolled infection. In the cerebritis stages, CT scans showed an area of ring enhancement which was incomplete on early scans (at 5 minutes after injection of contrast material) but partially filled in and thickened on delayed scans (at 20 to 45 minutes). On even later delayed scans there was no decrease in intensity of ring enhancement. Lesions in which capsule formation occurred also showed ring enhancement, but delayed scans showed a decrease in the intensity of enhancement. The lesions that ruptured into the ventricular system showed atypical CT findings, with either lack of contrast enhancement (histologically there was minimal cerebritis adjacent to the abscess cavity) or a marked delay in contrast enhancement (cerebritis was more extensive and corresponded to the width of ring of enhancement). This study suggests that Bacteroides fragilis is a virulent organism in the brain. The developing abscesses enlarged quickly, were prone to early ventricular rupture, and showed incomplete and delayed encapsulation.

Short term, high dose corticosteroids in computed tomographic staging of experimental brain abscess.

A short term, high dose corticosteroid treatment protocol was investigated to determine its clinical utility in staging an experimental brain abscess. Corticosteroids were shown to decrease the degree of contrast enhancement of brain abscess 12 h after administration but the magnitude of the effect was not consistent enough to be clinically useful in staging. The corticosteroid effect progressively diminished as the inflammatory lesion encapsulated over time. This effect emphasized that a decreasing ring diameter and not diminished contrast enhancement should be the CT criterion for brain abscess resolution.