✓ A controlled, prospective, randomized study evaluated the use of mithramycin in the treatment of anaplastic glioma compared to a similar group of patients receiving best conventional care. From a total of 116 patients in the study, 96 were within the valid study group. All patients were operated on, had histological confirmation of anaplastic glioma, and received radiotherapy at the discretion of the principal investigator. Fifty-two patients received mithramycin at a dose of 25 µg/kg/day for 21 days, while 44 patients were in the control group. There was no significant difference in the median survival from time of randomization in those receiving mithramycin (21 weeks) as compared to those not receiving mithramycin (26 weeks). There was no significant difference between the two groups in relation to age distribution, sex, location, diagnosis, tumor characteristics, signs or symptoms, or radiotherapy received. Duration of symptoms correlates positively with survival and was also significantly longer in the control group than in the treated group. This, however, did not account for the failure of mithramycin to be found an effective agent. Although the study was not designed to evaluate the efficacy of radiotherapy, patients who were so treated had a significant improvement in survival. The toxic complications of mithramycin included gastrointestinal symptoms, dermatological involvement, anemia, and liver dysfunction, indicating the need for close supervision.
Michael D. Walker, Eben Alexander Jr., William E. Hunt, Carl M. Leventhal, M. Stephen Mahaley Jr., John Mealey, Horace A. Norrell, Guy Owens, Joseph Ransohoff, Charles B. Wilson and Edmund A. Gehan
Joe M. McWhorter, Eben Alexander Jr., Courtland H. Davis Jr. and David L. Kelly Jr.
✓ Six cases of posterior cervical fusion with rib grafts in children are reported. Four of the children had sustained cervical spine injuries in accidents, and two had congenital absence of the odontoid. Three-level fusions (C1–3) were done in four children, and four-level fusions (C1–4) in two. One child died of unrelated causes 3 months after the operation. The other five children have been followed for 5 to 13 years. All are doing well and each has a remarkably supple, stable neck and no neurological deficit.
A cooperative clinical trial
Michael D. Walker, Eben Alexander Jr., William E. Hunt, Collin S. MacCarty, M. Stephen Mahaley Jr., John Mealey Jr., Horace A. Norrell, Guy Owens, Joseph Ransohoff, Charles B. Wilson, Edmund A. Gehan and Thomas A. Strike
✓ A controlled, prospective, randomized study evaluated the use of 1,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) and/or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma. A total of 303 patients were randomized into this study, of whom 222 (73%) were within the Valid Study Group (VSG), having met the protocol criteria of neuropathology, corticosteroid control, and therapeutic approach. Patients were divided into four random groups, and received BCNU (80 mg/sq m/day on 3 successive days every 6 to 8 weeks), and/or radiotherapy (5000 to 6000 rads to the whole brain through bilateral opposing ports), or best conventional care but no chemotherapy or radiotherapy. Analysis was performed on all patients who received any amount of therapy (VSG) and on the Adequately Treated Group (ATG), who had received 5000 or more rads radiotherapy, two or more courses of chemotherapy, and had a minimum survival of 8 or more weeks (the interval that would have been required to have received either the radiotherapy or chemotherapy). Median survival of patients in the VSG was, best conventional care: 14 weeks (ATG: 17.0 weeks); BCNU: 18.5 weeks (ATG: 25.0 weeks); radiotherapy: 35 weeks (ATG: 37.5 weeks); and BCNU plus radiotherapy: 34.5 weeks (ATG: 40.5 weeks). All therapeutic modalities showed some statistical superiority compared to best conventional care. There was no significant difference between the four groups in relation to age distribution, sex, location of tumor, diagnosis, tumor characteristics, signs or symptoms, or the amount of corticosteroid used. An analysis of prognostic factors indicates that the initial performance status (Karnofsky rating), age, the use of only a surgical biopsy, parietal location, the presence of seizures, or the involvement of cranial nerves II, III, IV, and VI are all of significance. Toxicity included acceptable, reversible thrombocytopenia and leukopenia.
Harold P. Smith, John M. Russell, William H. Boyce and Eben Alexander Jr.
✓ Among 481 children with myelomeningocele seen at the North Carolina Baptist Hospital since 1949, 46 have undergone a urinary diversion procedure, as follows: ileal loop in 43; sigmoid loop in two; and transverse colon conduit in one. The indications for diversion were incontinence in 28, urinary infection or pyelonephritis in 27, and hydronephrosis, pyelocaliectasis, and reflux in 12 patients. No deaths resulted from the diversionary procedures. One patient required early surgical revision and seven patients required late surgical revision. Two patients have since died, 44 have been followed for an average of 7.9 years, 15 for more than 10 years. Overall, of 26 patients with normal prediversionary intravenous pyelograms (IVP's), 88% now have normal or nearly normal IVP's; of 14 patients with abnormal prediversionary IVP's, 79% now have normal, improved, or unaltered IVP's. Renal function has remained normal in all 44 patients, and renal calculi have developed in 10 patients.
Ileal loop diversion appears to convert a high-pressure system into a low-pressure system, thereby helping to prevent further renal damage. This procedure tends to stabilize, rather than improve, urinary-tract function. For these children already so incapacitated by their basic disease, this goal is acceptable, particularly since it also provides continence and independence from parental nursing.
Harold P. Smith, Venkata R. Challa and Eben Alexander Jr.
✓ Cervical spine involvement by rheumatoid arthritis is common; brain-stem compression secondary to vertical subluxation of the odontoid in patients with rheumatoid arthritis is rare. Vertical subluxation results from 1) destruction of the transverse atlantal, apical, and alar ligaments of the atlas and odontoid, and 2) bone resorption in the occipital condyles, lateral masses of the atlas, and basilar processes of the skull. Neurological symptoms result from direct compression of the brain stem or from ischemia secondary to compression of vertebral arteries, anterior spinal arteries, or small perforating arteries of the brain stem and spinal cord. A case is reported in which a slowly progressive neurological deficit developed in a woman with rheumatoid arthritis following a fall from a stretcher. Neurological symptoms represented direct compression of the medulla by the dens, a mechanism confirmed at operation and autopsy.
Recognition of progressive neurological deficit is often difficult in patients with rheumatoid arthritis because of their inactivity and their atrophic and immobile joints, but is essential if appropriate decompressive or stabilizing procedures are to be done. In patients with vertical subluxation of the dens, the transoral approach with removal of the odontoid is recommended. Decompression should be extensive, including the fibrous capsule around the odontoid and overlying synovial tissue as well as the odontoid itself.
Case report with 20-year follow-up results
Eben Alexander Jr., Courtland H. Davis Jr. and Charas Suwanwela
✓ The 20-year follow-up results of a case of extradural aerocele (pneumatocele) are reported.
A review of 50 cases and description of surgical treatment
Eben Alexander Jr., David L. Kelly Jr., Courtland H. Davis Jr., Joe M. McWhorter and William Brown
✓ Over the past 11 years, the authors have treated 50 cases of intact arch spondylolisthesis. There were 38 female and 12 male patients, and all but 11 were older than 60 years of age. Almost all had severe low-back pain made worse by standing or walking. Other common manifestations were unilateral leg pain, numbness or weakness of the leg, and evidence of mild cauda equina compression. Severe cauda equina compression was rare. Myelography invariably showed an extradural dorsal compression. A waist deformity was characteristic in many patients, but 12 had a complete block. In 15 patients (30%) the myelographic impression was that of a herniated intervertebral disc. Most subluxations were of L-4 on L-5. At operation, the facets were found to be thickened, distorted, and irregular. All patients were treated with a wide decompression and laminectomy, which included a medial facetectomy of the inferior and superior facets. An intervertebral disc was removed in 10 patients. Follow-up monitoring of 41 patients (for an average period of 36 months) showed that 26 (63%) were pain-free, 11 had less pain, and four were unimproved. Five other patients with short follow-up periods (average 5 months) were all improved.
Eben Alexander Jr.
✓ The Journal of Neurosurgery, begun in 1944, has successfully fulfilled the purposes of its founders. During the 50 years of its existence it has remained pre-eminent in its field, while evolving in presentation, size, and content in response to the needs of succeeding generations of neurosurgeons and allied specialists. This article draws from the memories of many people, from the minutes of meetings of the Editorial Board, and from reports of successive editors, and touches on some of the knotty problems faced by those dedicated individuals.
Keasley Welch, Frank Turnbull and Eben Alexander Jr.
✓ Three authors, who were all individual contributors to the first volume of the Journal of Neurosurgery, share some thoughts and remembrances of their original published articles. They also speak to the history of the Journal and its relationship to the growth of neurosurgery.