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Edward R. Laws Jr., William F. Taylor, Marvin B. Clifton and Haruo Okazaki

✓ The authors conducted a retrospective review of surgically treated, histologically proven cases of low-grade (Grade 1 or 2) astrocytomas. Follow-up analysis, with survival time as the end-point, was completed using multivariant statistical analysis. In the 461 cases of supratentorial low-grade astrocytoma in this study, age of the patient at the time of surgery was by far the most important variable in predicting length of survival. Other variables correlating with increasing survival times were: gross total surgical removal, lack of major preoperative neurological deficit, long duration of symptoms prior to surgery, seizures as a presenting symptom, lack of major postoperative neurological deficit, and surgery performed in recent decades. The multi-variant regression analysis showed that radiation therapy was of clear benefit, primarily in older patients with incompletely removed tumors.

For purposes of establishing prognosis and testing the results, a “score” was developed to predict survival times, based on the most important variables. The data in this study provide a basis for the analysis of future modes of management of low-grade gliomas.

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Eugene S. Flamm, Wise Young, William F. Collins, Joseph Piepmeier, Guy L. Clifton and Boguslav Fischer

✓ Results of a Phase I trial of the opiate antagonist naloxone for treatment of patients with acute spinal cord injury are reported. Naloxone was administered in doses ranging from 5 to 200 mg/sq m (0.14 to 5.4 mg/kg) for up to 48 hours. The patients ranged in age from 16 to 79 years (mean 37 years). Twenty patients received naloxone as a loading dose of 5 to 50 mg/sq m (0.14 to 1.43 mg/kg), followed by a maintenance dose of 20% of the loading dose given as a continuous infusion hourly for 47 hours (Group 1). Nine patients received a loading dose of 100 to 200 mg/sq m (2.7 to 5.4 mg/kg) and a maintenance dose of 75% of the initial dose hourly for 23 hours (Group 2). These higher doses (2.7 to 5.4 mg/kg) have been found to be effective in experimental spinal cord injury. Neurological examinations were performed and somatosensory evoked potentials (SEP's) were obtained as soon after admission as possible and again 1, 2, 3, and 7 days, 3 weeks, and 6 weeks to 6 months after admission.

The 20 Group 1 patients who received 1.43 mg/kg or less of naloxone showed no improvement in neurological status or SEP's. All but three (15%) of these patients had a complete neurological deficit at the time of admission. Treatment was begun an average of 12.9 hours after injury. Among the nine Group 2 patients treated with 2.7 mg/kg or more, there were five patients (56%) with incomplete deficits. This group received naloxone an average of 6.6 hours after admission. Two of the five Group 2 patients with incomplete lesions showed improvement in their neurological condition and/or SEP's within 36 hours of receiving the drug. One of the four Group 2 patients with a complete lesion at the time of admission was able to localize pressure sensation in his legs 36 hours after completion of the drug infusion. Four Group 2 patients (two with complete and two with incomplete lesions) have shown improvement in their SEP's, suggesting recovery of SEP's in a dose-related fashion. Four patients experienced increased pain after administration of the loading dose and during the maintenance infusion; in only one patient was this severe enough to require discontinuation of the drug. Of the 29 patients treated with naloxone, four died within 6 weeks of admission, for a mortality rate of 13.8%.

This study demonstrates that, in spinal cord-injured patients, naloxone given as an intravenous loading dose of 200 mg/sq m, followed by a continuous infusion of up to 150 mg/sq m/hr for 23 hours, has minimal side effects. The observed improvement in the clinical examination and SEP's at the higher doses, while not statistically verified in this Phase I trial, is encouraging.

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Methylprednisolone and neurological function 1 year after spinal cord injury

Results of the National Acute Spinal Cord Injury Study

Michael B. Bracken, Mary Jo Shepard, Karen G. Hellenbrand, William F. Collins, Linda S. Leo, Daniel F. Freeman, Franklin C. Wagner, Eugene S. Flamm, Howard M. Eisenberg, Joseph H. Goodman, Phanor L. Perot Jr., Barth A. Green, Robert G. Grossman, John N. Meagher, Wise Young, Boguslav Fischer, Guy L. Clifton, William E. Hunt and Nathan Rifkinson

✓ A multi-center double-blind randomized clinical trial was conducted by the National Acute Spinal Cord Injury Study Group to examine the efficacy of high-dose methylprednisolone (1000-mg bolus and 1000 mg daily thereafter for 10 days) compared with that of a standard dose (100-mg bolus and 100 mg daily for 10 days). No significant difference was observed in neurological recovery of motor function, pinprick response, or touch sensation 1 year after injury between the two treatment groups, after adjustment for other potentially confounding factors. Analyses that specifically took into account the patients' total steroid dose and relative weight confirmed the lack of a steroid treatment effect. The case fatality rate was 10.7% during the 1st year after injury, and this was not associated with the steroid treatment protocol or the patient's gender. Deaths did occur significantly more frequently among patients who were completely (15.3%) and partially (8.6%) plegic than among those who were paretic (2.5%, p = 0.0005), and among patients aged 50 years or older (38.6%, p = 0.0001).

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Ross C. Puffer, William E. Clifton, Grant W. Mallory and Michelle J. Clarke

OBJECT

Delayed cervical palsy (DCP) is a known complication following cervical spine surgery. While most DCPs eventually improve, they can result in significant temporary disability. Postoperative complications affect hospital length of stay (LOS) as well as overall hospital cost. The authors sought to determine the hospital cost of DCP after cervical spine fusion operations.

METHODS

A retrospective review of patients undergoing cervical fusion for degenerative disease at the Mayo Clinic from 2008 to 2012 was performed. Patients who developed DCPs not attributable to intraoperative trauma were included. All nonoperative-related costs were compared with similar costs in a control group matched according to age, sex, and surgical approach. All costs and services were reflective of the standard costs for the current year. Raw cost data were presented using ratios due to institutional policy against publishing cost data.

RESULTS

There were 27 patients (18 men, 9 women) who underwent fusion and developed a DCP over the study period. These patients were compared with 24 controls (15 men, 9 women) undergoing fusion in the same time period. There was no difference between patients and controls in mean age (62.4 ± 3.1 years vs 63.8 ± 2.5 years, respectively; p = 0.74), LOS (4.2 ± 3.3 days vs 3.8 ± 4.5 days, respectively; p = 0.43), or operating room–related costs (1.08 ± 0.09 vs 1.0 ± 0.07, respectively; p = 0.58). There was a significant difference in nonoperative hospital-related costs between patients and controls (1.67 ± 0.15 vs 1.0 ± 0.09, respectively; p = 0.04). There was a significantly higher utilization of postoperative imaging (CT or MRI) in the DCP group (14/27, 52%) when compared with the matched cohort (4/24, 17%; p = 0.018), and a significantly higher utilization of physiatry services (24/27 [89%] vs 15/24 [63%], respectively; p = 0.046).

CONCLUSIONS

While DCPs did not significantly prolong the length of hospitalization, they did increase hospital-related costs. This method could be further extrapolated to model costs of other complications as well.

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Jack Phan, Courtney Pollard III, Paul D. Brown, Nandita Guha-Thakurta, Adam S. Garden, David I. Rosenthal, Clifton D. Fuller, Steven J. Frank, G. Brandon Gunn, William H. Morrison, Jennifer C. Ho, Jing Li, Amol J. Ghia, James N. Yang, Dershan Luo, He C. Wang, Shirley Y. Su, Shaan M. Raza, Paul W. Gidley, Ehab Y. Hanna and Franco DeMonte

OBJECTIVE

The objective of this study was to assess outcomes after Gamma Knife radiosurgery (GKRS) re-irradiation for palliation of patients with trigeminal pain secondary to recurrent malignant skull base tumors.

METHODS

From 2009 to 2016, 26 patients who had previously undergone radiation treatment to the head and neck received GKRS for palliation of trigeminal neuropathic pain secondary to recurrence of malignant skull base tumors. Twenty-two patients received single-fraction GKRS to a median dose of 17 Gy (range 15–20 Gy) prescribed to the 50% isodose line (range 43%–55%). Four patients received fractionated Gamma Knife Extend therapy to a median dose of 24 Gy in 3 fractions (range 21–27 Gy) prescribed to the 50% isodose line (range 45%–50%). Those with at least a 3-month follow-up were assessed for symptom palliation. Self-reported pain was evaluated by the numeric rating scale (NRS) and MD Anderson Symptom Inventory–Head and Neck (MDASI-HN) pain score. Frequency of as-needed (PRN) analgesic use and opioid requirement were also assessed. Baseline opioid dose was reported as a fentanyl-equivalent dose (FED) and PRN for breakthrough pain use as oral morphine-equivalent dose (OMED). The chi-square and Student t-tests were used to determine differences before and after GKRS.

RESULTS

Seven patients (29%) were excluded due to local disease progression. Two experienced progression at the first follow-up, and 5 had local recurrence from disease outside the GKRS volume. Nineteen patients were assessed for symptom palliation with a median follow-up duration of 10.4 months (range 3.0–34.4 months). At 3 months after GKRS, the NRS scores (n = 19) decreased from 4.65 ± 3.45 to 1.47 ± 2.11 (p < 0.001); MDASI-HN pain scores (n = 13) decreased from 5.02 ± 1.68 to 2.02 ± 1.54 (p < 0.01); scheduled FED (n = 19) decreased from 62.4 ± 102.1 to 27.9 ± 45.5 mcg/hr (p < 0.01); PRN OMED (n = 19) decreased from 43.9 ± 77.5 to 10.9 ± 20.8 mg/day (p = 0.02); and frequency of any PRN analgesic use (n = 19) decreased from 0.49 ± 0.55 to 1.33 ± 0.90 per day (p = 0.08). At 6 months after GKRS, 9 (56%) of 16 patients reported being pain free (NRS score 0), with 6 (67%) of the 9 being both pain free and not requiring analgesic medications. One patient treated early in our experience developed a temporary increase in trigeminal pain 3–4 days after GKRS requiring hospitalization. All subsequently treated patients were given a single dose of intravenous steroids immediately after GKRS followed by a 2–3-week oral steroid taper. No further cases of increased or new pain after treatment were observed after this intervention.

CONCLUSIONS

GKRS for palliation of trigeminal pain secondary to recurrent malignant skull base tumors demonstrated a significant decrease in patient-reported pain and opioid requirement. Additional patients and a longer follow-up duration are needed to assess durability of symptom relief and local control.

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William Clifton