Study on the efficacy of and adverse reactions to high-dose dexamethasone therapy for neurological symptoms of spinal cord compression due to malignant tumors

✓ In order to assess the clinical and biological effects of glucocorticoids in the therapy of epidural spinal cord compression, the T8–10 epidural space of 50 rats was implanted with Walker 256 tumor. The rats were studied 10 to 20 days later when they became paraparetic. The regional blood-spinal cord transport constant (K, a function of the blood-spinal cord barrier) of 14Carbon-labeled aminoisobutyric acid was measured with quantitative autoradiography 6 hours after intravenous injection of low-dose (0.1 mg/kg), intermediate dose (1 mg/kg), and high-dose (10 mg/kg) dexamethasone. The effects of dexamethasone in these doses on the clinical signs and water content of the compressed cord were also evaluated 40 hours after treatment began. The K factor increased 730% in compressed compared with noncompressed spinal cords (p < 0.001). Dexamethasone induced a dose-related reduction of both K (p = 0.007) and water content of the compressed cord (p < 0.0001). Stabilization or, more rarely, improvement of weakness at 24 and 40 hours posttreatment correlated with the dose of dexamethasone (r = 0.88, p < 0.001). This study demonstrates that dexamethasone has a dose-related beneficial clinical effect associated with an improvement of blood-spinal cord barrier breakdown and a reduction of the water content of the compressed cord. This study supports the use of high-dose dexamethasone for the initial treatment of epidural spinal cord compression.

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Spinal Cord Compression as an Initial Symptom in Childhood Acute Lymphoblastic Leukemia: Rapid Decompression with High Dose Dexamethasone and Chemotherapy Alone

Annals of Saudi Medicine ◽

10.5144/0256-4947.2003.179 ◽

2003 ◽

Vol 23 (3-4) ◽

pp. 179-180 ◽

Cited By ~ 3

Author(s):

Yasir Iqbal ◽

Reem Al-Sudairy ◽

Mohammed F. Abdullah ◽

Talal Rafaie ◽

Ali Al-Omari

Keyword(s):

Spinal Cord ◽

Acute Lymphoblastic Leukemia ◽

Spinal Cord Compression ◽

Lymphoblastic Leukemia ◽

Cord Compression ◽

Childhood Acute Lymphoblastic Leukemia ◽

High Dose ◽

Initial Symptom ◽

High Dose Dexamethasone ◽

Rapid Decompression

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Effect of high-dose dexamethasone in carcinomatous metastatic spinal cord compression treated with radiotherapy: a randomised trial

European Journal of Cancer ◽

10.1016/s0959-8049(05)80011-5 ◽

1994 ◽

Vol 30 (1) ◽

pp. 22-27 ◽

Cited By ~ 231

Author(s):

P.S. Sørensen ◽

S. Helweg-Larsen ◽

H. Mouridsen ◽

H.H. Hansen

Keyword(s):

Spinal Cord ◽

Spinal Cord Compression ◽

Randomised Trial ◽

Cord Compression ◽

Metastatic Spinal Cord Compression ◽

High Dose ◽

High Dose Dexamethasone

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Treatment of experimental spinal cord compression caused by extradural neoplasms

Journal of Neurosurgery ◽

10.3171/jns.1977.47.3.0380 ◽

1977 ◽

Vol 47 (3) ◽

pp. 380-390 ◽

Cited By ~ 62

Author(s):

Yukitaka Ushio ◽

Roslyn Posner ◽

Jae-Ho Kim ◽

William R. Shapiro ◽

Jerome B. Posner

Keyword(s):

Spinal Cord ◽

Radiation Therapy ◽

Spinal Cord Compression ◽

Clinical Signs ◽

Cord Compression ◽

Neurological Function ◽

Neurological Symptoms ◽

High Dose ◽

Human Spinal Cord ◽

Hind Limbs

✓ Epidural spinal cord compression was produced in rats by injection of Walker 256 carcinoma cell suspension anterior to the T-12 or T-13 vertebral body. The tumor grows through the intervertebral foramina to compress the spinal cord and produce paraplegia in 3 to 4 weeks. The effect of several treatments upon clinical signs was assessed. Dexamethasone caused a significant but transient improvement in neurological function. Radiation therapy likewise improved neurological function, and was more effective when given by a high-dose protracted course than when given either in a single dose or a low-dose protracted course. Laminectomy was not helpful in relieving neurological symptoms. Dimethyl sulfoxide did not relieve neurological symptoms. Cyclophosphamide was most effective in relieving neurological symptoms, and most of the animals that were treated with that drug when they were severely weak but still able to move their hind limbs recovered fully. Some animals that were totally paraplegic when treatment began recovered function after radiation therapy or cyclophosphamide treatment, but recovery was better if treatment was started when animals could still move their hind limbs. This animal model appears to be a useful way of studying the treatment of human spinal cord compression produced by epidural neoplasms.

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Incidence, Presentation, and Outcome of Spinal Cord Disease in Children With Systemic Cancer

PEDIATRICS ◽

10.1542/peds.78.3.438 ◽

1986 ◽

Vol 78 (3) ◽

pp. 438-443

Author(s):

Donald W. Lewis ◽

Roger J. Packer ◽

Beverly Raney ◽

Ihor W. Rak ◽

Jean Belasco ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Compression ◽

Delayed Diagnosis ◽

Cord Compression ◽

High Dose ◽

Spinal Cord Disease ◽

Satisfactory Outcome ◽

First Relapse ◽

Age Range ◽

Neurologic Emergency

During a 40-month period, in 24 of 643 (4%) newly diagnosed patients with systemic cancer younger than 18 years of age (range: 3 months to 17 years) spinal cord disease developed. Patients with spinal cord disease included 21 children with metastatic spinal cord compression, two with treatment-related transverse myelopathies, and one with an anterior spinal artery stroke. Spinal cord disease occurred in 13 of 102 children (12%) with sarcomas, six of 82 (7%) with neuroblastomas, and four of 94 (4%) with lymphomas. Spinal cord compression occurred as the presenting sign of malignancy in six children (four with sarcomas and two with lymphomas). In the remaining 15 patients, cord compression occurred a median of 13 months after initial diagnosis, and in four patients it occurred at the time of first relapse. Symptoms of metastatic cord compression included back pain in 17 patients (80%), weakness in 14 (67%), sphincter dysfunction in 12 (57%), and sensory abnormalities in three (14%). Findings on plain radiographs of the spine were abnormal in only seven of 20 patients with cord compression, and myelography was needed to differentiate compression from other causes of spinal cord disease. Treatment included high-dose corticosteroids followed by operation (seven patients) or radiotherapy (14 patients). After treatment, nine of 15 nonambulatory patients became ambulatory, and five of 10 incontinent patients regained sphincter control. None of the patients with nonmetastatic spinal cord disease had a satisfactory outcome. Incorrect and delayed diagnosis was frequent in children with spinal cord disease (median time from onset of symptoms to diagnosis, 2 weeks) and 12 children were paraplegic and ten had loss of sphincter control at diagnosis. Spinal cord disease is a relatively common neurologic emergency in children with cancer, especially in those with sarcoma, and requires immediate investigation and intervention.

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Corticosteroid Treatment for Metastatic Spinal Cord Compression: A Review

Global Spine Journal ◽

10.1177/2192568217699189 ◽

2017 ◽

Vol 7 (3) ◽

pp. 272-279 ◽

Cited By ~ 11

Author(s):

Gordon D. Skeoch ◽

Matthew K. Tobin ◽

Sajeel Khan ◽

Andreas A. Linninger ◽

Ankit I. Mehta

Keyword(s):

Spinal Cord ◽

Spinal Cord Compression ◽

Clinical Symptoms ◽

Treatment Strategies ◽

Cord Compression ◽

Metastatic Spinal Cord Compression ◽

Treatment Modalities ◽

High Dose ◽

Dexamethasone Treatment ◽

Corticosteroid Administration

Study Design: Narrative review. Objective: Metastatic spinal cord compression (MSCC) is a very frequent complication among cancer patients. Presenting commonly as nocturnal back pain, MSCC typically progresses to lower extremity paresis, loss of ambulatory capabilities, and paraplegia. In addition to standard treatment modalities, corticosteroid administration has been utilized in preclinical and clinical settings as adjunctive therapy to reduce local spinal cord edema and improve clinical symptoms. This article serves as a review of existing literature regarding corticosteroid management of MSCC and seeks to provide potential avenues of research on the topic. Methods: A literature search was performed using PubMed in order to consolidate existing information regarding dexamethasone treatment of MSCC. Of all search results, 7 articles are reviewed, establishing the current understanding of metastatic spine disease and dexamethasone treatment in both animal models and in clinical trials. Results: Treatment with high-dose corticosteroids is associated with an increased rate of potentially serious systemic side effects. For this reason, definitive guidelines for the use of dexamethasone in the management of MSCC are unavailable. Conclusions: It is still unclear what role dexamethasone plays in the treatment of MSCC. It is evident that new, more localizable therapies may provide more acceptable treatment strategies using corticosteroids. Looking forward, the potential for more targeted, localized application of the steroid through the use of nanotechnology would decrease the incidence of adverse effects while maintaining the drug’s efficacy.

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