John W. Walsh

A Randomized Trial of Surgery in the Treatment of Single Metastases to the Brain

To assess the efficacy of surgical resection of brain metastases from extracranial primary cancer, we randomly assigned patients with a single brain metastasis to either surgical removal of the brain tumor followed by radiotherapy (surgical group) or needle biopsy and radiotherapy (radiation group). Forty-eight patients (25 in the surgical group and 23 in the radiation group) formed the study group; 6 other patients (11 percent) were excluded from the study because on biopsy their lesions proved to be either second primary tumors or inflammatory or infectious processes. Recurrence at the site of the original metastasis was less frequent in the surgical group than in the radiation group (5 of 25 [20 percent] vs. 12 of 23 [52 percent]; P less than 0.02). The overall length of survival was significantly longer in the surgical group (median, 40 weeks vs. 15 weeks in the radiation group; P less than 0.01), and the patients treated with surgery remained functionally independent longer (median, 38 weeks vs. 8 weeks in the radiation group; P less than 0.005). We conclude that patients with cancer and a single metastasis to the brain who receive treatment with surgical resection plus radiotherapy live longer, have fewer recurrences of cancer in the brain, and have a better quality of life than similar patients treated with radiotherapy alone.

Carotid and vertebral artery injury in survivors of atlanto-occipital dislocation : case reports and literature review

Atlanto-occipital dislocation (AOD) usually results in immediate death from transection of the upper cervical spinal cord near the spinomedullary junction. However, over the last several decades increasing numbers of AOD survivors have been identified. Although many of these patients initially demonstrate profound neurologic deficits, a number who survive have regained most or all neurologic functions, indicating that they did not suffer mechanical disruption of the spinal cord at the time of AOD. In the survivors, a growing body of evidence indicates that many of the initial neurologic deficits are related to vascular injury to the carotid or vertebral arteries and their branches. We recently encountered three AOD survivors with no evidence of mechanical injury to the spinal cord in which angiography demonstrated vascular injury to the internal carotid artery in the form of vasospasm in one case and to the vertebral arteries in the forms of focal stenosis at the site of dural penetration, focal stenosis and distal vasospasm, and focal stenosis with distal intimal flap and dissection in one case each. Autopsy after one of the three died after cardiac arrest demonstrated diffuse infarction of the cerebrum, cerebellum, midbrain, brainstem, and upper cervical spinal cord without evidence of mechanical laceration or transection of the spinal cord. Recovery of neurologic function in two cases following prompt immobilization and angiography suggests that neurologic deficits secondary to vascular injury are potentially reversible.

Use of anal sphincter electromyography during operations on the conus medullaris and sacral nerve roots.

The mechanical activity of the anal sphincter can be translated into electrical activity and recorded on graph paper or an oscilloscope. The activity of the anal sphincter may be extrapolated to activity of the external urethral sphincter because both are striated muscles innervated by the pudendal nerve that arises from S-2, S-3, and S-4. Stimulation of these nerves causes contraction of the sphincter muscles, and a deflection of the recording device occurs. This technique was employed intraoperatively in monitoring operations on the conus medullaris and sacral nerve roots in 10 patients with spinal dysraphism (age range, 3 weeks to 15 years). Their diagnoses were tethered conus, 4; lipomeningocele, 3; spinal hamartoma, 1; syringocele, 1; and sacral arachnoiditis, 1. With general anesthesia, and the patient in the prone position, an electrode-containing anal plug was inserted or two needle electrodes were inserted into the anal sphincter muscle. The electrodes were connected to the electromyography recording stylus of the urodynamic bladder diagnostic unit. During the spinal operation, whenever a structure could not be identified clearly, it was stimulated with the disposable electrical stimulator and, if oscillations of the stylus occurred (indicating contraction of the anal sphincter), the structure was preserved. This technique permitted spinal operations in these 10 patients without changes in neurological or urological function.

Urologic aspects of tethered cord.

Tethered cord syndrome, a form of spinal dysrhaphism, may involve vesical neurologic dysfunction. We present herein 60 cases of tethered cord syndrome, including 24 patients who underwent preoperative urodynamics studies. Preoperative cystometrography revealed areflexic bladders in 71 percent of cases and hyperreflexic bladders in 29 percent. Eight patients had serial pre- and postoperative urodynamics testing. Slight improvement was noted in postoperative urodynamics studies performed on 4 of 6 areflexic bladders and in the only hyperreflexic bladder studied. In addition, of the 3 patients in the serial urodynamics groups who had urinary symptoms preoperatively, 2 noted clinical improvement postoperatively. The urologists role is important in the early detection, evaluation, and treatment of tethered cord syndrome and the neuropathic bladders that may result.

Failure of Prophylactically Administered Phenytoin to Prevent Post-Traumatic Seizures in Children

We report the results of a randomized, double-blind, placebo-controlled study to determine whether phenytoin administered soon after a head injury lessens the incidence of late post-traumatic epilepsy in children. 41 patients were randomized into either a phenytoin or placebo group and followed for 18 months. The patients were administered phenytoin or placebo intravenously or intramuscularly within 24 h of hospital admission. The patients were parenterally administered phenytoin or placebo until oral doses could be tolerated. There was no significant difference in the percentage of children having seizures in the treated and placebo groups (p = 0.25).

Questionnaires and Pocket Spirometers Provide an Alternative Approach for COPD Screening in the General Population

BACKGROUND In response to the Agency for Healthcare Research and Quality statement questioning the usefulness of “screening spirometry,” the National Heart, Lung, and Blood Institute and the COPD Foundation held a consensus conference in June 2008 to establish a procedure to detect cases of COPD in the general population. Conference participants developed a three-stage approach, using a brief questionnaire, peak flow measurement with a pocket spirometer, and diagnostic quality spirometry. The overall objective of this study was to examine the usefulness of a simple questionnaire and peak flow measurement in screening for COPD in a self-selected population. We hypothesized that this combination would efficiently screen for clinically relevant COPD. METHODS We queried individuals attending public events regarding the presence of wheeze and/or asthma, mucus production, dyspnea, exposure to irritants, and tobacco use. Peak expiratory flow (PEF) was then measured with a pocket spirometer. If PEF was < 70% predicted, spirometry was performed. In order to estimate the false-negative rate, a random sample of every 10th participant was also selected for spirometry. RESULTS Between June 2008 and December 2009, 5,761 adults completed the risk assessment questionnaire. The mean age of the respondents was 54 years, 58% were women, and 88% were white. Of these, 5,638 participants completed pocket spirometry, and 315 (5.6%) had PEF < 70% predicted. Of 5,323 with normal PEF, 651 underwent spirometry. The performance of PEF was assessed via positive and negative predictive values relative to a diagnosis of clinically significant airflow obstruction, defined as FEV(1)/FEV(6) < the lower limit of normal and FEV(1) < 60% predicted. Of 4,238 subjects with at least two risk factors, 267 (6.3%) had PEF < 70%, compared with 48 of the 1,400 subjects (3.4%) with fewer than two risk factors (P < .001). Based on 729 participants with acceptable spirometry, 63.1% (113 of 179) of those with abnormal PEF tested positive for clinically significant airflow obstruction, compared with 5.5% (30 of 550) with normal PEF (P < .001). The estimated prevalence of significant COPD among the 5,638 screened was 8.7%, and sensitivity and specificity were 40.7% and 97.7%, respectively. CONCLUSIONS A staged approach to COPD screening in adults is useful for detecting clinically significant airflow obstruction in our study population.

Split-thickness skin grafting of the myelomeningocele defect: a subset at risk for late ulceration.

The appropriate method and timing of the management of the myelomeningocele defect have prompted considerable discussion. Use of split-thickness skin grafts acutely has accomplished wound closure with low morbidity and mortality. This study was designed to address the question of long-term suitability of the technique of split-thickness skin grafting of the myelomeningocele patient. The incidence of late and/or severe skin ulceration and the presence of gibbus deformity were correlated with the method of skin closure. Long-term follow-up revealed a higher incidence of chronic skin ulceration in the split-thickness skin graft group as compared with the primary closure group. All skin breakdowns appeared in the presence of a gibbus deformity, and gibbus deformity was more prevalent in the split-thickness skin graft group. The incidence of skin ulceration and gibbus deformity was site-dependent. A thoracic or thoracolumbar myelomeningocele repair with split-thickness skin graft was significantly more likely to be complicated by skin problems than the defect in the lumbar, lumbosacral, or sacral region. This relationship was secondary to the frequency of gibbus deformity in the more cephalad defects than defects caudad. A treatment plan is outlined that is based on the primary variable of the location of the myelomeningocele and secondarily by defect size.

Evaluation of children and young adults with tethered spinal cord syndrome. Utility of spinal and scalp recorded somatosensory evoked potentials.

The diagnosis of tethered spinal cord syndrome should be considered in young patients with progressive orthopedic deformities, lower extremity weakness, urinary and fecal incontinence, low back pain, or combinations of these symptoms. Myelographic, computed tomographic, and urodynamic studies are useful for establishing a diagnosis, but contribute little to the evaluation of lower extremity sensory function or to the assessment of electrophysiologic impairment of the spinal cord itself. To determine the diagnostic usefulness of the somatosensory evoked potential after posterior tibial nerve stimulation (posterior tibial nerve somatosensory evoked potential) in tethered spinal cord syndrome, 22 consecutive patients with symptoms of tethered spinal cord syndrome (aged 18 months to 22 years) underwent recording of posterior tibial nerve somatosensory evoked potential; results were correlated with clinical, myelographic, and operative findings. In patients with clinical symptoms but no myelographically demonstrable lesions, posterior tibial nerve somatosensory evoked potentials were within normal limits, suggesting normal physiologic function. In patients with myelographically and operatively confirmed tethering dysraphic lesions, posterior tibial nerve somatosensory evoked potential was predictive of the level and laterality of the lesion. Similarly, ranking the severity of neurological impairment and extent of dysraphism at operation, as well as the extent of abnormality of posterior tibial nerve somatosensory evoked potential, revealed a significant (r = 0.81, p less than 0.001) correlation between clinical severity and posterior tibial nerve somatosensory evoked potential abnormalities. Postoperatively, in 8 patients, posterior tibial nerve somatosensory evoked potential also reflected improved function in relation to the level and type of dysraphic lesion present. These findings indicate that posterior tibial nerve somatosensory evoked potential is a sensitive indicator of neurophysiologic status in patients with tethered spinal cord, and is useful for determining the level of the conus medullaris, degree of spinal cord displacement, and severity of neurological impairment associated with this congenital disturbance of neuraxis formation. Recording of posterior tibial nerve somatosensory evoked potential is noninvasive and offers a more sensitive diagnostic tool than the clinical testing of sensation for detection of the development of neurologic deficits in patients with tethered cord syndrome.

Role of viruses in the induction of primary intracranial tumors.

The role of viruses in the induction of primary intracranial tumors is reviewed. Papovaviruses of the simian virus 40 (SV40) group are used as a representative model, and a distillation of the literature on virus induction of intracranial tumors in laboratory animals and neoplastic transformation of cells in culture is presented. The molecular sequence of events during tumor induction and neoplastic cell transformation is also discussed. Recent evidence that the papovaviruses play a role in the formation of human brain tumors is summarized.

Ultrastructural Study of the Medulloblastoma in Tissue Culture

The electron microscopic features of the early phases of growth of the medulloblastoma maintained in vitro are described. The predominant early growth is comprised of small migrating cells with large nucleocytoplasmic ratio, few organelles and prominent neuritic processes containing abundant microtubules. These cells compare favorably with the cells of the primitive external granular layer of the cerebellum and cells cultivated in vitro from the fetal cerebellar cortex previously described. In addition astrocytes containing 70 to 90 A cytoplasmic filaments were commonly found in these cultures. Undifferentiated cells and cells with cilia were present in the explant proper. Cells with processes containing large dense core vesicles were also present in the explant proper suggesting the presence of neuronal differentiation. Our studies support the concept that the medulloblastoma is derived from primitive neuroectodermal cells. In addition it also suggests that astrocytic and neuronal differentiation may occur in this neoplasm in vitro.