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Antibiotic neurotoxicity

Laboratory and clinical study

Martin H. Weiss, Theodore Kurze, and Frank E. Nulsen

✓ By ventriculocisternal perfusion, a series of newer antibiotics were circulated through the central nervous system to ascertain the potential toxicity of these drugs to the nervous parenchyma. Ampicillin, carbenicillin, gentamycin sulfate, and polymyxin B sulfate appear to be well tolerated whereas cephalexin monohydrate and penicillin G caused a repeated pattern of significant CSF pleocytosis, histological evidence of periventricular perivascular infiltrates, and evidence of clinical toxicity. A regime for treatment of central nervous system infections is presented, derived from the data presented above. Preliminary experience in a clinical series appears to support this program.

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Michael L. J. Apuzzo, Milton D. Heifetz, Martin H. Weiss, and Theodore Kurze

✓ The authors report their application of the Hopkins telescope to various neurosurgical procedures, and describe the technique and advantages of its employment.

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Theodore Kurze, Michael L. J. Apuzzo, Martin H. Weiss, and James S. Heiden

✓ The authors discuss the properties, use, and advantages of collagen sponge as a microneurosurgical adjunct. Experience with the material in over 300 operative cases has demonstrated its value for protecting the surface of the brain during exposure and retraction in neurosurgical procedures.

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Theodore Kurze, Michael L. J. Apuzzo, Martin H. Weiss, and James S. Heiden

✓ Experiments were conducted to assess the feasibility of both paraformaldehyde and ethylene oxide gas sterilization of the operating microscope. From these experiments and practical experience, it is concluded that ethylene oxide sterilization of the operating microscope is a feasible and desirable alternative to cumbersome draping techniques.

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Michael L. J. Apuzzo, Khalid M. A. Sheikh, James S. Heiden, Martin H. Weiss, and Theodore Kurze

✓ Cellular immune responses to brain antigens in patients with head injury were studied by applying the leukocyte adherence inhibition (LAI) assay. The investigation was conducted in three phases. 1) In the initial phase, evaluation of a series of 22 test and 25 control cases obtained at random during a 2- to 6-week time frame following a traumatic event indicated significant non-adherence of leukocytes (NAL) in 77% of the test group and 20% of the control group in the presence of brain antigen. 2) In a second phase, a larger test population was divided into four groups of different posttraumatic intervals. This study measured NAL in the presence of normal heart or normal brain antigen. Assays revealed an initial significant NAL in the presence of both antigens; however, after the first week following injury the majority of cases manifested significant NAL only with brain antigen. These values of NAL persisted over a 6- to 8-week period. 3) As a final phase of investigation, analysis of a sequential series of assays in 12 patients over a 90-day period indicated significant NAL in the presence of brain antigen within the first week of injury, this was followed by a drop in NAL in most of the cases. Studies at 7 to 60 days posttrauma demonstrated significant NAL with brain antigen alone, with a subsequent drop by 90 days. These observations are interpreted to represent sensitization of leukocyte subgroups to brain proteins that are immunologically recognized following the traumatic event.

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James S. Heiden, Martin H. Weiss, Alan W. Rosenberg, Michael L. J. Apuzzo, and Theodore Kurze

✓ Acute cervical spinal cord injuries were reviewed in 356 patients treated by the neurosurgical community in Southern California. Neurological recovery was compared in operated and nonoperated patients with complete and incomplete cervical myelopathies. The complications of nonsurgical and surgical therapy are identified. No neurological improvement was noted in any patient with a complete lesion who underwent early surgical decompression. In those with incomplete sensorimotor paralysis, it was difficult to document any effect of surgical decompression on neurological recovery. Patients with some degree of sensory preservation had a similar incidence of motor recovery in both surgical and nonsurgical groups. With complete sensorimotor paralysis, anterior cervical fusion within the first week of injury was associated with increased pulmonary morbidity.

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James S. Heiden, Martin H. Weiss, Alan W. Rosenberg, Theodore Kurze, and Michael L. J. Apuzzo

✓ The authors present a series of 38 civilian patients with cervical gunshot injuries, and compare neurological recovery in patients with complete lesions and patients with incomplete lesions according to whether therapy was surgical or nonsurgical. In patients with incomplete injury, ultimate recovery was a function of the initial injury more than surgical or nonsurgical therapy; nor did patients with complete lesions show significant change in outcome with either mode of therapy. Cord pathology at laminectomy rarely provided a clue about neurological recovery, and dural decompression did not alter neurological outcome. The authors conclude that the sole indication for routine surgical intervention appears to be progressive neurological deficit.

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Acute fractures of the odontoid process

An analysis of 45 cases

Michael L. J. Apuzzo, James S. Heiden, Martin H. Weiss, Truman T. Ackerson, J. Paul Harvey, and Theodore Kurze

✓ Between 1969 and 1974, 45 cases of acute odontoid fracture were diagnosed and treated at this institution. The group consisted of 35 men and 10 women; 24 were between 19 and 40 years of age, and 21 were over 40 years old. Detectable myelopathy was appreciated in eight cases (18%). Diagnosis was established within 72 hours of the traumatic event. Initial evaluation disclosed displacement of the fracture in 17 cases (38%). Following reduction, the initial treatment was posterior fusion in three cases, and external immobilization in 42 cases. Excluding two deaths within the first week of treatment, 40 cases were available for follow-up analysis. Bone union failed to occur following periods of immobilization ranging from 4 to 6 months in 13 cases (33%). Fibrous union with no evidence of instability was apparent in two cases. Nonunion in displaced fractures was seen in 60%, with a rate of 88% in those displaced more than 4 mm. The rate of nonunion in undisplaced fractures was 16%. The rates of incidence of displacement (53% vs 26%) and nonunion (78% vs 33%) in those displaced were higher in individuals over 40 years of age than in those under 40 years. The incidence of nonunion in individuals aged under 40 with nondisplaced fractures was 12%; it was 25% for individuals over 40 years old. A total of 13 patients underwent posterior fusion. All eventually manifested stability at the C1–2 level. However, 69% failed to show bone union at the fracture site in a 6- to 18-month follow-up period.

This review indicates that in consideration of the fracture, external immobilization is the initial treatment of choice in all nondisplaced fractures. Displaced fractures occurring in patients over 40 years old, and those displaced more than 4 mm are candidates for internal stabilization and fusion as a primary mode of treatment.

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Michael L. J. Apuzzo, Martin H. Weiss, Viesturs Petersons, R. Baldwin Small, Theodore Kurze, and James S. Heiden

✓ This study was designed to define the effect of positive end expiratory pressure (PEEP) ventilation on intracranial pressure (ICP). In 25 patients with severe head trauma with and without associated pulmonary injury the following parameters were simultaneously monitored under mechanical ventilation with and without PEEP: ICP, arterial blood pressure, central venous pressure, arterial blood gases, and cardiac rate. In addition, the volume-pressure response (VPR) was evaluated in each patient to assess cerebral elastance. The results indicate a significant increase in ICP with the application of PEEP only in the 12 patients who manifested increased cerebral elastance by VPR. Half of this latter group manifested impairment of cerebral perfusion pressure to levels less than 60 mm Hg. Return to baseline ICP levels was observed with termination of PEEP. No significantly consistent changes in other parameters were noted.