Evaluation of indirect decompression of the lumbar spinal canal following minimally invasive lateral transpsoas interbody fusion: radiographic and outcome analysis.

BACKGROUND: The surgical treatment of lumbar stenosis traditionally includes laminectomy for direct decompression of the spinal canal. Selected patients with spinal stenosis may also require lumbar fusion. Minimally invasive lateral transpsoas interbody fusion has the ability of placing a large interbody cage that can increase disc height and distract the spinal level. The purpose of this study was to examine the concept of indirect decompression of the spinal canal in patients with co-existing lumbar spinal stenosis undergoing lateral transpsoas interbody fusion. MATERIALS AND METHODS: We reviewed 25 consecutive spinal stenosis patients with instability undergoing lateral transpsoas interbody fusion without laminectomy. All patients had relevant symptoms of back pain, leg pain, and/or spinal claudication and met standard criteria for lumbar fusion. Patients were evaluated by outcome analysis scales (VAS scores, Oswestry disability index and treatment intensity scale). Postoperative MRI scans, when available, were evaluated for change in canal dimensions. Statistical significance was assessed by paired t-test, which compares the mean change. There were 25 patients in the study (mean age 61 years). 15 patients had grade I spondylolisthesis. VAS for back pain intensity improved from 7.74 to 2.07 and for frequency from 7.91 to 2.22. VAS for leg pain intensity improved from 7.24 to 1.87 and frequency from 7.41 to 2.35. All improvements were statistically significant (P<0.0001). The Oswestry disability index improved from 55.1 to 16.4 (P<0.0001), and treatment intensity scale improved from 14.6 to 3.7 (P<0.0001). Radiographic evaluation in 20 treated levels (15 patients) found an increase in dural sac dimension of 54% in the anterior-posterior plane and 48% in the medial-lateral plane (P<0.0001). The calculated area of the dural sac increased an average of 143% (range of - 10.4% to + 495%). CONCLUSION: Indirect decompression of spinal stenosis can be achieved with lateral transpsoas interbody fusion with improved clinical outcomes. Pre-op and post-op MRI scans showed a significant increase in dural sac dimensions. The mechanism for this indirect decompression may relate to stretching and unbuckling of the spinal ligaments and a decrease in intervertebral disc bulging. Further studies are needed to determine which stenosis patients undergoing this surgery are most appropriate for indirect decompression alone over laminectomy.

Tension pneumocephalus resulting from iatrogenic subarachnoid-pleural fistulae: report of three cases.

BACKGROUND: Symptomatic pneumocephalus may result from a cerebrospinal fluid leak communicating with extradural air. However, it is a rare event after thoracic surgical procedures, and its management and physiology are not widely recognized. METHODS: During the past 2 years, we have identified 3 patients who developed pneumocephalus after thoracotomy for tumor resection. Only 1 patient had a discernible spinal fluid leak identified intraoperatively. Two patients experienced delayed spinal fluid drainage from their chest tubes and subsequently developed profound lethargy, confusion, and focal neurologic signs. The third patient was readmitted to the hospital with a delayed pneumothorax and altered mental status. Radiographic imaging in all patients showed significant pneumocephalus of the basilar cisterns and ventricles. RESULTS: The first 2 patients were managed by discontinuation of the chest tube suction and bedrest. The third patient underwent surgical reexploration and nerve root ligation. All 3 patients had resolution of their symptoms within 72 hours. CONCLUSIONS: Pneumocephalus is a rare, but serious, complication of thoracotomy. Previous patients reported in the literature have been managed with reoperation to ligate the nerve roots. However, the condition resolved nonoperatively in 2 of our patients. Discontinuation of chest tube suction may be definitive treatment and is always the important initial management to decrease cerebrospinal fluid extravasation into the pleural space and allow normalization of neurologic symptoms.

Practical value of Ki-67 and p53 labeling indexes in stereotactic biopsies of diffuse and pilocytic astrocytomas.

OBJECTIVE: Stereotactic biopsies are increasingly being used for the diagnosis and grading of astrocytomas, and there is a growing need to obtain maximum information from these tissue samples. In everyday practice, p53 protein and Ki-67 immunohistochemical analyses are the most frequently used ancillary studies to aid in diagnosis and grading, but their exact role is not clearly established. This study was undertaken to evaluate the practical value of these markers in stereotactic biopsy samples from diffuse astrocytomas as well as pilocytic astrocytomas. Methods/Results.-We analyzed the Ki-67 (MIB-1) and p53 labeling indexes in the stereotactic biopsy specimens from 11 pilocytic astrocytomas; 8 grade 2, 15 grade 3, and 16 grade 4 diffuse astrocytomas. Pilocytic astrocytomas and diffuse astrocytomas were evaluated as 2 separate groups. There was a strong correlation with poor outcome when both labeling indexes were higher than 15% in the same tumor for diffuse astrocytomas (P < 0.01). The indexes did not correlate with outcome in pilocytic astrocytomas. CONCLUSION: Combined Ki-67 and p53 labeling indexes higher than 15% indicated a worse outcome than suggested by the histologic grading. The analysis aided or improved histologic evaluation of stereotactic biopsies in our patients. We believe that a realistic prognostic upgrading of diffuse astrocytomas should be made only when labeling indexes for both markers are greater than 15%.

Split calvarial graft cranioplasty for the prevention of headache after retrosigmoid resection of acoustic neuromas.

OBJECTIVE: This study describes the technique and efficacy of split calvarial graft cranioplasty for the reconstruction of retrosigmoid/suboccipital defects following surgery for acoustic neuromas. STUDY DESIGN: A prospective study of the technique of split calvarial graft cranioplasty, its postoperative healing, and incidence of postoperative headache. METHODS: The technique requires splitting of the craniotomy bone flap into outer and inner table bone grafts. The combination of both bony grafts allows the coverage of a wider area of posterior fossa dura. This technique was used in 18 patients. All patients were followed for a minimum of 6 months. Eleven of 18 patients were followed for 1 year or longer. Four patients had three-dimensional computed tomography of their skull and area of split calvarial bone graft. RESULTS: One of 18 patients had a persistent disabling headache at 1 year postoperatively. A natural contour of the retrosigmoid area was achieved in all patients. Three-dimensional computed tomography scan, obtained 6 months postoperatively, showed total coverage of the retrosigmoid area and fusion of the bone flap to the surrounding skull. CONCLUSION: The technique of split calvarial grafting of posterior fossa defects is a feasible, safe, and effective way of separating the nuchal musculature and posterior fossa dura. The technique also allows the restoration of the contour and bony covering of the retrosigmoid area. The technique is a simple alternative to other types of cranioplasties aimed at reducing the incidence of postoperative headache in patients with acoustic neuromas.

Boron neutron-capture therapy (BNCT) for glioblastoma multiforme (GBM) using the epithermal neutron beam at the Brookhaven National Laboratory.

OBJECTIVE: Boron neutron-capture therapy (BNCT) is a binary form of radiation therapy based on the nuclear reactions that occur when boron (10B) is exposed to thermal neutrons. Preclinical studies have demonstrated the therapeutic efficacy of p-boronophenylalanine (BPA)-based BNCT. The objectives of the Phase I/II trial were to study the feasibility and safety of single-fraction BNCT in patients with GBM. MATERIALS AND METHODS: The trial design required (a) a BPA biodistribution study performed at the time of craniotomy; and (b) BNCT within approximately 4 weeks of the biodistribution study. From September 1994 to July 1995, 10 patients were treated. For biodistribution, patients received a 2-hour intravenous (i.v.) infusion of BPA-fructose complex (BPA-F). Blood samples, taken during and after infusion, and multiple tissue samples collected during surgical debulking were analyzed for 10B concentration. For BNCT, all patients received a dose of 250 mg BPA/kg administered by a 2-hour i.v. infusion of BPA-F, followed by neutron beam irradiation at the Brookhaven Medical Research Reactor (BMRR). The average blood 10B concentrations measured before and during treatment were used to calculate the time of reactor irradiation that would deliver the prescribed dose. RESULTS: 10B concentrations in specimens of scalp and tumor were higher than in blood by factors of approximately 1.5 and approximately 3.5, respectively. The 10B concentration in the normal brain was < or = that in the blood; however, for purposes of estimating radiation doses to normal brain endothelium, it was always assumed to be equal to blood. BNCT doses are expressed as gray-equivalent (Gy-Eq), which is the sum of the various physical dose components multiplied to appropriate biologic effectiveness factors. The dose to a 1-cm3 volume where the thermal flux reached a maximum was 10.6 +/- 0.3 Gy-Eq in 9 patients and 13.8 Gy-Eq in 1 patient. The minimum dose in tumor ranged from 20 to 32.3 Gy-Eq. The minimum dose in the target volume (tumor plus 2 cm margin) ranged from 7.8 to 16.2 Gy-Eq. Dose to scalp ranged from 10 to 16 Gy-Eq. All patients experienced in-field alopecia. No CNS toxicity attributed to BNCT was observed. The median time to local disease progression following BNCT was 6 months (range 2.7 to 9.0). The median time to local disease progression was longer in patients who received a higher tumor dose. The median survival time from diagnosis was 13.5 months. CONCLUSION: It is feasible to safely deliver a single fraction of BPA-based BNCT. At the dose prescribed, the patients did not experience any morbidity. To further evaluate the therapeutic efficacy of BNCT, a dose-escalation study delivering a minimum target volume dose of 17 Gy-Eq is in progress.

Biodistribution of p-boronophenylalanine in patients with glioblastoma multiforme for use in boron neutron capture therapy.

OBJECTIVE: The success of boron neutron capture therapy depends on the safety and specificity of the boron delivery agent. As a preface to clinical boron neutron capture therapy of glioblastoma multiforme, a biodistribution study of intravenous p-boronophenylalanine (BPA) in patients undergoing craniotomy for resection of glioblastoma was performed. METHODS: Varying doses of intravenously administered BPA-fructose (130-250 mg BPA per kilogram of body weight) were given to patients 2 to 3 hours prior to the start of craniotomy for either suspected or known glioblastoma multiforme. Blood samples were collected over a 48-hour period for boron assay. At surgery, multiple samples of tumor, brain, and scalp were obtained for boron and histological analysis. RESULTS: Seventeen patients were studied; all but one had glioblastoma multiforme. No adverse effects from the BPA infusions were noted. The boron concentration in the blood reached a maximum at the end of the BPA infusion and was proportional to the administered dose of BPA. Normal brain concentrations of boron generally were equal to or less than that in blood. Tumor-blood boron ratios were highly variable: 1.6 +/- 0.8 (mean +/- standard deviation; n = 187; range, 0.3-3.5). The observed heterogeneity of BPA uptake in glioblastoma samples appears to correlate with the degree of cellularity observed on histological examination. CONCLUSION: Intravenous BPA administration up to a dose of 250 mg/kg is safe and well tolerated. BPA uptake in surgical samples of glioblastoma tissue is variable and may depend on the fraction of viable tumor cells in the individual sample. Further clinical studies using BPA as a boron delivery agent for boron neutron capture therapy of glioblastoma multiforme appear warranted.

Biodistribution of boronophenylalanine in patients with glioblastoma multiforme: boron concentration correlates with tumor cellularity.

Boron-10 (10B) concentrations were measured in 107 surgical samples from 15 patients with glioblastoma multiforme who were infused with 95 atom% 10B-enriched p-boronophenylalanine (BPA) intravenously for 2 h just prior to surgery at doses ranging from 98 to 290 mg BPA/kg body weight. The blood 10B concentration reached a maximum at the end of the infusion (ranging from 9.3 to 26.0 microg 10B/g) and was proportional to the amount of BPA infused. The boron concentrations in excised tumor samples ranged from 2.7 to 41.3 microg 10B/g over the range of administered BPA doses and varied considerably among multiple samples from individual patients and among patients at the same BPA dose. A morphometric index of the density of viable-appearing tumor cells in histological sections obtained from samples adjacent to, and macroscopically similar to, the tumor samples used for boron analysis correlated linearly with the boron concentrations. From that correlation it is estimated that 10B concentrations in glioblastoma tumor cells were over four times greater than concurrent blood 10B concentrations. Thus, in the dose range of 98 to 290 mg BPA/kg, the accumulation of boron in tumor cells is a linear function of BPA dose and the variations observed in boron concentrations of tumor specimens obtained surgically are largely due to differences in the proportion of nontumor tissue (i.e. necrotic tissue, normal brain) present in the samples submitted for boron analysis. The tumor:blood 10B concentration ratio derived from this analysis provides a rationale for estimating the fraction of the radiation dose to viable tumor cells resulting from the boron neutron capture reaction based on measured boron concentrations in the blood at the time of BNCT without the need for analysis of tumor samples from individual patients.

Boron neutron capture therapy for glioblastoma multiforme using p-boronophenylalanine and epithermal neutrons: trial design and early clinical results.

A Phase I/II clinical trial of boron neutron capture therapy (BNCT) for glioblastoma multiforme is underway using the amino acid analog p-boronophenylalanine (BPA) and the epithermal neutron beam at the Brook-haven Medical Research Reactor. Biodistribution studies were carried out in 18 patients at the time of craniotomy using an i.v. infusion of BPA, solubilized as a fructose complex (BPA-F). There were no toxic effects related to the BPA-F administration at doses of 130, 170, 210, or 250 mg BPA/kg body weight. The tumor/ blood, brain/blood and scalp/blood boron concentration ratios were approximately 3.5:1, 1:1 and 1.5:1, respectively. Ten patients have received BNCT following 2-hr infusions of 250 mg BPA/kg body weight. The average boron concentration in the blood during the irradiation was 13.0 +/- 1.5 micrograms 10B/g. The prescribed maximum dose to normal brain (1 cm3 volume) was 10.5 photon-equivalent Gy (Gy-Eq). Estimated maximum and minimum doses (mean +/- sd, n = 10) to the tumor volume were 52.6 +/- 4.9 Gy-Eq (range: 64.4-47.6) and 25.2 +/- 4.2 Gy-Eq (range: 32.3-20.0), respectively). The estimated minimum dose to the target volume (tumor +2 cm margin) was 12.3 +/- 2.7 Gy-Eq (range: 16.2-7.8). There were no adverse effects on normal brain. The scalp showed mild erythema, followed by epilation in the 8 cm diameter field. Four patients developed recurrent tumor, apparently in the lower dose (deeper) regions of the target volume, at post-BNCT intervals of 7,5,3.5 and 3 months, respectively. The remaining patients have had less than 4 months of post-BNCT follow-up. BNCT, at this starting dose level, appears safe. Plans are underway to begin the dose escalation phase of this protocol.

Uncommon lesions presenting as tumors of the internal auditory canal and cerebellopontine angle.

OBJECTIVE: The aim of this study was to identify distinguishing characteristics of uncommon lesions of the cerebellopontine angle (CPA) and internal auditory canal (IAC) in order to attain the correct diagnosis and thus formulate an appropriate therapeutic protocol. STUDY DESIGN: A retrospective chart analysis was performed on all patients with surgically managed lesions of the IAC and CPA referred to neuropathology from January 1985 to April 1996. SETTING: All patients were treated by New York University faculty at a tertiary referral center. PATIENTS: Among 426 surgical cases identified, 384 patients (90.1%) with acoustic neuromas and 18 patients (4.2%) with meningiomas were excluded. The remaining 24 cases, involving 17 women and seven men with a median age of 34 years, were analyzed. INTERVENTION: Most patients underwent audiovestibular evaluations, as well as magnetic resonance imaging (MRI) and computed tomographic (CT) scanning, and all patients underwent neurotologic surgery as part of their management protocol. MAIN OUTCOME MEASURES: Correlating patient presentation, preoperative imaging, and surgical findings often identified distinguishing characteristics of unusual CPA and IAC lesions. RESULTS: Unusual lesions identified at the CPA and IAC included: four epidermoids, four lipomas, two facial neuromas, two arachnoid cysts, two choroid plexus papillomas, two metastatic adenocarcinomas, one metastatic neuroblastoma, one ependymoma, one lymphoma, one cholesterol cyst, one angioleiomyoma, one venous hemangioma, one cavernous angioma, and one pontine glioma. CONCLUSIONS: Preoperative tumor differentiation based on the patient history, physical examination, audiovestibular testing, CT, and MRI help the surgeon to formulate an appropriate treatment protocol.

Spontaneous movement of bullets in the brain.

We report two patients in whom bullets in the brain migrated into the adjacent lateral ventricle and moved freely as a consequence of gravity. A review of the literature suggests that the spontaneous migration of intracerebral bullets is influenced by cerebral softening, the specific gravity of the bullet compared with brain tissue, and the sink function of the cerebral ventricles. In patients undergoing the surgical removal of intracerebral or intraventricular bullets, it is recommended that an x-ray be obtained after the final positioning of the head.

Cerebral metabolic interactions between thyroid state and imipramine in the rat.

Local rates of cerebral glucose metabolism were determined in four groups of adult rats 4 weeks after surgery: sham-operation + saline; thyro-parathyroidectomy (TX) + saline; sham-operation + imipramine; or TX + imipramine. Daily i.p. injections, imipramine at 10 mg/kg or saline at 1 ml/kg b.w., were given during the 2 weeks before the deoxyglucose experiment. TX reduced glucose utilization in the limbic, motor, endocrine and auditory systems. Imipramine reduced glucose metabolism in the median eminence, both habenular nuclei and several limbic regions including the amygdala, hippocampus and parietal cortex. Five structures showed significant interactions between TX and imipramine. In three of these regions, the supraoptic nucleus, central amygdala and lateral habenula; TX and/or imipramine individually reduced metabolism and the combined treatment raised it back to within the normal range. In the dorsal raphe, TX and imipramine tended to increase metabolism and the combined treatment resulted in a decrease to within normal range. The neurohypophysis, unaffected by TX alone, showed a significant increase in activity when TX was combined with imipramine. These data indicate, in part, that both hypothyroidism and imipramine treatment alone depress metabolism in limbic forebrain and the major limbic-brainstem relay nuclei. Combined treatment normalizes metabolism in many of these limbic pathways. Hypothetically, hypothyroidism may alter central catecholamine function in such a way that the metabolic response to imipramine is reversed or altered.

Effect of traumatic injury on membrane phosphatase activity in cat spinal cord.

The enzymatic activities of the spinal cord membrane phosphatases, (Na,K)ATPase, KpNPPase, 5'-nucleotidase, MgATPase, and MgpNPPase, were determined following contusion injury. Within 30 min after injury, the activities of (Na,K)ATPase, KpNPPase, and 5'-nucleotidase were suppressed at the injury site and remained suppressed for 24 h. Considerable loss of (Na,K)ATPase and KpNPPase activity was seen along the longitudinal axis of the spinal cord for the first 4 h after injury, whereas at 24 h after injury, there was almost complete restitution in the activity of those enzymes. No similar changes in activity were observed for the MgATPase, whereas the activity of the MgpNPPase progressively worsened with time at the injury site. The deduce the pathobiochemical process that accounts for the loss of spinal membrane phosphatase activity, spinal cord membranes were incubated in vitro in the presence of a superoxide anion-generating system, as well as in the presence of trypsin and lysolecithin. It was found that superoxide anions inhibited only the activity of transport phosphatase, KpNPPase, whereas trypsin inhibited the activity of both KpNPPase and MgpNPPase. No inhibition of 5'-nucleotidase was observed by superoxide anions; however, the activity of 5'-nucleotidase was enhanced by trypsin, lysolecithin, or both in concert. These results suggest that the pathobiochemical process that accounts for the loss of spinal membrane phosphatase activity that follows injury can be attributed to the concerted effects of free radical attack as well as the activation of proteolytic and lipolytic enzymes. Inactivation of spinal membrane phosphatase can occur by direct attack of these processes on the membrane or by loss of membrane material, e.g., solubilization.