A critical appraisal of the reporting of the National Acute Spinal Cord Injury Studies (II and III) of methylprednisolone in acute spinal cord injury.

From the beginning, the reporting of the results of National Acute Spinal Cord Injury Studies (NASCIS) II and III has been incomplete, leaving clinicians in the spinal cord injury (SCI) community to use or avoid using methylprednisolone in acute SCI on the basis of faith rather than a publicly developed scientific consensus. NASCIS II was initially reported by National Institutes of Health announcements, National Institutes of Health facsimiles to emergency room physicians, and the news media. The subsequent report in the New England Journal of Medicine implied that there was a positive result in the primary efficacy analysis for the entire 487 patient sample. However, this analysis was in fact negative, and the positive result was found only in a secondary analysis of the subgroup of patients who received treatment within 8 hours. In addition, that subgroup apparently had only 62 patients taking methylprednisolone and 67 receiving placebo. The NASCIS II and III reports embody specific choices of statistical methods that have strongly shaped the reporting of results but have not been adequately challenged or or even explained. These studies show statistical artifacts that call their results into question. In NASCIS II, the placebo group treated before 8 hours did poorly, not only when compared with the methylprednisolone group treated before 8 hours but even when compared with the placebo group treated after 8 hours. Thus, the positive result may have been caused by a weakness in the control group rather than any strength of methylprednisolone. In NASCIS III, a randomization imbalance occurred that allocated a disproportionate number of patients with no motor deficit (and therefore no chance for recovery) to the lower dose control group. When this imbalance is controlled for, much of the superiority of the higher dose group seems to disappear. The NASCIS group's decision to admit persons with minor SCIs with minimal or no motor deficit not only enables statistical artifacts it complicates the interpretation of results from the population actually sampled. Perhaps one half of the NASCIS III sample may have had at most a minor deficit. Thus, we do not know whether the results of these studies reflect the severely injured population to which they have been applied. The numbers, tables, and figures in the published reports are scant and are inconsistently defined, making it impossible even for professional statisticians to duplicate the analyses, to guess the effect of changes in assumptions, or to supply the missing parts of the picture. Nonetheless, even 9 years after NASCIS II, the primary data have not been made public. The reporting of the NASCIS studies has fallen far short of the guidelines of the ICH/FDA and of the Evidence-based Medicine Group. Despite the lucrative "off label" markets for methylprednisolone in SCI, no Food and Drug Association indication has been obtained. There has been no public process of validation. These shortcomings have denied physicians the chance to use confidently a drug that many were enthusiastic about and has left them in an intolerably ambiguous position in their therapeutic choices, in their legal exposure, and in their ability to perform further research to help their patients.

Central nervous system tuberculosis: medical management and surgical indications.

BACKGROUND: An increase in the incidence of tuberculosis in industrialized nations has prompted a need for earlier diagnosis, treatment, and isolation of disease. An associated rise in the number of patients with central nervous system tuberculosis (CNS TB) has forced neurosurgical services to reevaluate the indications for operative intervention. METHODS: Seventeen cases of CNS TB were found in a retrospective review of all cases managed on the neurosurgical service between 1989 and 1994. These cases included eight with tuberculous meningitis, seven cases of supratentorial tuberculomas, and two cases of infratentorial tuberculomas. RESULTS: Major permanent neurologic morbidity was seen in one case (6%). Five patients (29.4%) died of complications associated with their primary disease. Eleven patients (64.6%) had excellent outcomes. All patients in the latter group completed an 18-month course of antituberculous therapy. Cerebrospinal fluid shunts were necessary in three cases and emergent craniotomy was performed in three cases. Only four cases had human immunodeficiency virus (HIV) coinfection. CONCLUSION: The neurosurgeon's role in the management of CNS TB has once again become more evident. In the present series it is unclear as to whether this is due to multiple drug-resistant strains of Mycobacterium tuberculosis or HIV coinfection. It is clear, however, that vigilance over patient compliance and serial neurologic evaluation will determine the need for operative intervention.

Cerebral tuberculosis with expansion into brainstem tuberculoma. Report of two cases.

There are only scattered case reports of intracranial tuberculosis in industrialized nations; brainstem tuberculoma is even more unusual, accounting for 2.5% to 8% of all intracranial tuberculoma. In developing nations, however, central nervous system tuberculosis (CNS-TB) is not rare and intracranial tuberculoma may account for 5% to 30% of all intracranial masses. The authors present two cases of CNS-TB with expansion to brainstem tuberculoma in patients who were undergoing treatment and had no known prior exposure to Mycobacterium tuberculosis.

Transoral gunshot wounds to the atlanto-axial complex: report of five cases.

Although there has been a rise in the incidence of gunshot wounds to the spine in the United States, involvement of the upper cervical spine, i.e., the atlanto-axial complex, remains rare. Management strategies for these types of injuries come from wartime as well as civilian experience, however, they are not uniformly agreed upon. Treatment strategies are aimed at both stabilization of bony structures and preservation of neurologic function. This report documents five neurologically intact patients who sustained gunshot wounds to the atlanto-axial complex, their management, and follow-up results.

Electrophrenic respiration after intercostal to phrenic nerve anastomosis in a patient with anterior spinal artery syndrome: technical case report.

Long-term positive pressure mechanical ventilation has been the standard of care for patients with respiratory insufficiency caused by high cervical spine injury. Stimulation of the phrenic nerves, and thus the diaphragm, with an implanted phrenic nerve pacemaker has provided adequate ventilation and an alternative to the standard. Diaphragmatic pacing, also known as electrophrenic respiration, requires an intact phrenic nerve to act as a conduit for the applied stimulus. Propagation of the stimulus is impossible if the injury sustained has led to axonal loss in the phrenic nerve. This may be expected if the damage to the spinal cord is at the C3-C5 level. If the cell bodies of the motor neurons in this region have been damaged, or direct injury to the phrenic nerve has occurred, then diaphragmatic pacing is not feasible by the traditional method. Microsurgical repair of peripheral nerves and nerve grafting have provided the impetus for research into anastomosis of a viable intercostal nerve to a nonfunctional phrenic nerve, with subsequent reinnervation of the diaphragm. Once successful axonal regeneration and diaphragmatic reinnervation have occurred, the distal phrenic nerve may then be paced. This case documents the first successful institution of electrophrenic respiration after intercostal to phrenic nerve anastomosis.