Somnath Nair

Malignant astrocytomas treated with iodine-125 labeled monoclonal antibody 425 against epidermal growth factor receptor: A phase II trial☆

Twenty-five patients with primary presentation of malignant astrocytoma, astrocytoma with anaplastic foci, and glioblastoma multiforme were treated with surgical resection and definitive radiation therapy followed by intravenous or intra-arterial administration of Iodine-125 labeled monoclonal antibody-425, which binds specifically to human epidermal growth factor receptor. The patients presented with primary untreated disease, positive contrast enhanced computed tomography scans of the brain, and compatible clinical symptoms. In this Phase II clinical trial, the patients had surgical debulking or biopsy followed by definitively administered external beam radiation therapy and one or multiple doses (35 to 90 mCi per infusion) of radiolabeled antibody. The total cumulative doses ranged from 40 to 224 mCi. The administrations of the radiolabeled antibody were performed in most cases 4-6 weeks following completion of the primary surgery and radiation therapy. Ten patients had astrocytoma with anaplastic foci and 15 had glioblastoma multiforme. No significant life-threatening toxicities were observed during this trial. At 1 year 60% of the patients with astrocytoma with anaplastic foci or glioblastoma multiforme are alive. The median survival for both groups was 15.6 months.

Cerebral uric acid increases following experimental traumatic brain injury in rat

Following traumatic brain injury (TBI), cortical and thalamic areas were analyzed histologically and by high-performance liquid chromatography with electrochemical detection for uric acid at various survival times. Following TBI, cortical uric acid was elevated by ten-fold at 24 and 48 h, but not at 1 h post-TBI. Histological evidence of neurodegeneration was found not only in cortex but also in the anteroventral thalamus. These data suggest that as in stroke, uric acid measurements may be a convenient and sensitive method for measuring peroxidative status in TBI.

Clinical experience with a fiberoptic intracranial pressure monitor

Retrospective clinical experience with our first 46 patients monitored with a fiberoptic intracranial pressure device is described. In 43 of 46 patients, the transducer was introduced into brain parenchyma. A ventriculostomy system was used in 3 of 46 patients. The monitoring system was generally characterized by ease of placement and system maintenance and by technical simplicity. Several problems were encountered, including breakage of system components (12%), erroneous readings requiring transducer repositioning (8.6%), epidural hematoma (3.4%), and infection (1.7%). No infections or hematomas occurred in the 3 cases in which the ventriculostomy system was used. Overall, our experience with the Camino intracranial pressure fiberoptic monitoring system confirms previous reports of its favorable features.

Surgical Management of Radiated Scalp in Patients with Recurrent Glioma

Patients with malignant brain tumors requiring multiple craniotomies and external beam radiotherapy are at risk of scalp wound breakdown secondary to fibrosis and radiation damage. We present three cases to illustrate the nature of the problem and the surgical approaches to scalp repair. When a bicoronal incision has been used for the initial craniotomy, the plastic repair can be performed with a bipedicle visor scalp flap and split-thickness skin graft to cover the pericranium at the donor site. When a curvilinear (U-shaped or horseshoe) flap has been used for the initial craniotomy, a single-pedicle flap may be rotated to achieve closure without tension. In anticipation of the risk of scalp wound breakdown in patients with malignant brain tumors, the planning of the operative incision for the first craniotomy needs to take into account the long-term viability of the scalp. We recommend linear scalp incisions parallel to the arterial distribution instead of the traditional curvilinear (U-shaped or horseshoe) flaps; linear incisions are less likely to break down, and in the event of breakdown, linear wounds offer better therapeutic surgical options for plastic repair.

Implications for the pathogenesis of aneurysm formation: metastatic choriocarcinoma with spontaneous splenic rupture. Case report and a review.

We report a case of ruptured intracranial aneurysm from metastatic choriocarcinoma in a patient presenting with intracerebral hemorrhage. Operative evacuation of the hematoma with clipping of a distal right middle cerebral artery aneurysm was performed. Postoperatively, the patient developed hypovolemic shock from spontaneous splenic rupture. Histopathologic examination of the cerebral aneurysm showed choriocarcinoma invading the vessel wall. Metastatic choriocarcinoma should be considered in the differential diagnosis of intracerebral or subarachnoid hemorrhage in women of child-bearing age.

Renal Osteodystrophy of the Cervical Spine: Neurosurgical Implications

Renal osteodystrophy describes the changes in bone physiology seen in renal failure. Traditionally, these changes resulted in mild neurological sequelae that were effectively managed medically. Despite the often severe destruction seen on x-ray, surgical therapy has not been reported extensively. With increasing numbers of long-term hemodialysis survivors, however, a newly recognized erosive spondyloarthropathy with extensive bony destruction is seen more frequently. These changes can mimic the radiographic appearance of osteomyelitis, not an uncommon sequela of hemodialysis patients; therefore, this diagnosis must be considered. Although renal osteodystrophy can be seen throughout the spine, reports of significant cervical spine involvement are uncommon. We present our experience with six cases of renal osteodystrophy of the cervical spine requiring surgical intervention for instability or cord compression. Osteomyelitis was present in two of the patients. The pathophysiology and radiographic characteristics of renal osteodystrophy and the incidence of osteomyelitis are discussed. Fusion techniques, including the use of anterior and posterior internal and external stabilization, are presented. These patients represent a therapeutic challenge for the neurosurgeon, given the underlying bone pathology.

NMDA receptors: the first decade

A little over ten years ago, three events occurred which began the story of the N-methyl-D-aspartate (NMDA) receptor, as far as drug discovery was concerned. In a series of publications, Watkins and co-workers marshalled sufficient evidence about the ability of certain antagonists to block the excitatory action of NMDA. This evidence served to convince a majority of scientists that NMDA receptors did indeed exist. The mechanism of action of MK-801 was discovered to be the blockade of ion channels associated with NMDA receptors. Finally, the first competitive NMDA antagonists to be developed for therapeutic purposes, CPP and CGS19755, were discovered. It was the honeymoon for the NMDA receptor, with expected side effects exceeded only by predicted therapeutic applications. Now there has been sufficient time to test many of the original concepts surrounding the NMDA receptor and its antagonists, and to test the first generation of NMDA antagonists in man. At the same time, many other classes of compounds ac...

Management of Infected Laminectomy Wounds

Wound infection after lumbar, thoracic, or cervical laminectomies is a rare but potentially devastating complication. It can range in severity from superficial wound infection to an extensive wound dehiscence. The usual treatment of these wounds consists of intensive local care, debridement, and appropriate antibiotic therapy. Secondary healing can result in chronic, painful wounds that are difficult to manage and can create the potential for osteomyelitis. Seven cases of infected dehiscent laminectomy wounds are presented. Either critical structures were exposed, or the patients did not heal after secondary or delayed primary closures. In each case, full healing was attained by means of reconstruction with a regional muscle flap. We propose that muscle flap reconstruction offers an excellent alternative for the reconstruction of difficult postlaminectomy wounds.

A Novel Microdialysis Probe Designed for Clinical Use: Potential Analytical and Therapeutic Applications

Significant obstacles to the use of microdialysis in the clinic for diagnostic or therapeutic purposes include the production of dedicated entry port through the skull and the formation of a tract by the insertion of a probe into the parenchyma. We have developed a microdialysis probe that is minimally invasive and can be combined with an intracranial pressure probe, recording electrode, or other intracranial probe, that is minimally invasive. Yet the surface area of this probe is very high, permitting high recovery efficiencies even at relatively high flow rates. This probe design makes possible minimally invasive measurement of the peroxidation product, uric acid, and excitatory amino acids, two analytes that increase in experimental traumatic brain injury in animals. Moreover, its large surface area makes therapeutic applications of microdialysis probes in the brain potentially feasible. A pilot evaluation of the ability of microdialysis to have therapeutic benefit in limiting experimental excitotoxin lesions induced in rat striatum by N-methyl-D-aspartate (NMDA) is reported.

MonthlyUpdate—Central & Peripheral Nervous Systems: Pharmacotherapeutic Potential for Compounds Acting at NMDA Receptors: Update 1995

The exciting developments of the past year occurring since our last comprehensive review of NMDA receptor pharmacological agents as drugs [1], not yet appearing in the refereed literature, involve the use of NMDA antagonists in stroke and traumatic brain injury. A year ago, there seemed to be a three way tie in the race for effective ‘brain-attack’ (emergency anti-stroke rescue therapy) and traumatic brain injury therapy between the anti-oxidant tirilazad (Upjohn), the NMDA-antagonist selfotel (Ciba, CGS 19755), and the NMDA-antagonist eliprodil (Synthelabo/Searle/Lorex, SL 82.0715). Unexpected side-effects severely retarded the progress of tirilazad, and the ‘dark horse’ glutamate-release blocker lubeluzole (Janssen) suddenly burst into, possibly, the leading position in this race, with selfotel and eliprodil still jockeying effectively as they move into Phase III trials in stroke. Some attention has also been focused on trials involving drug combinations. Although theoretically this would offer the adva...