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Ivermectin for spasticity in spinal-cord injury
by the public world wide. Data analysis may allow more rapid understanding of predisposing factors to some side-effects of medications. Improved regulations and methods5 are needed to avoid silence controlling knowledge. Shmuel Fuchs, Zvi Simon, Mayer Brezis Department of Medicine, Hadassah University Hospital, Mount Scopus, Jerusalem, PO Box 24035, Israel 91420
1 Kassirer JP, Angell M. Financial conflicts of interest in biomedical research. N Engl J Med 1993; 329: 570-71. 2 The ACG committee on FDA-related matters. Hepatic effects of drugs used in the treatment of peptic ulcer disease. Am J Gastroenterol 1987; 82: 987-1003. 3 Wolfson JS, Hooper DC. Overview of fluoroquinolone safety. Am J Med 1991; 91 (suppl): 153-61. 4 Grassmick BK, Lehr VT, Sundareson AS. Fulminant hepatic failure possibly related to ciprofloxacin. Ann Pharmacother 1992; 26: 636-38. 5 Edwards R. Competing in drug safety. Lancet 1993; 342: 631-32.
Ivermectin for spasticity in spinal-cord injury
Table: Ashworth and spasm each patient
injury. Each patient was admitted to hospital and given a single subcutaneous injection of 02 mg/kg ivermectin. Ashworth and spasm scores4 were recorded over the next 24 hours. Two weeks later, an injection of 04 mg/kg ivermectin was given, with scores again recorded over a 24-hour period. Some patients received subsequent injections at weekly or biweekly intervals, with doses up to 1-6 mg/kg. By 2 to 4 hours after each of the first two doses, both the Ashworth and spasm scores decreased, and remained reduced throughout the full 24 hours of observation (figure). The table summarises Ashworth and spasm scores in patients after several weeks of ivermectin. Every patient had decreased spasm scores, and all but 3 reported lower Ashworth scores. No clinical adverse effects were noted in any of the patients, including the one who received ivermectin for 12 weeks. In fact, many reported improved sleep, less depression, and better bowel and bladder function during the trial. These preliminary observations suggest that ivermectin has properties similar to those of baclofen, a GABA-B agonist, which acts to reduce spasticity in spinal-cord injury.5 Further
Figure: Ashworth and spasm scores within 24 h of 02 mg/kg (broken line) and 04 mg/kg (unbroken line) Ivermectln
conclusion of trial for
clinical trials may be warranted in both spinal-cord injury and in other central nervous system disorders such as epilepsy, which is known to improve with GABA agonists. Jonathan L Costa, Jesus A Diazgranados Schwab Rehabilitation Hospital,
SIR-Ivermectin is used extensively for the treatment of onchocerciasis world wide. 1-3 Although it is believed to exert its antiparasitic activity because of agonism at filarial gamma aminobutyric acid (GABA) receptors, the possibility that ivermectin may act as a GABA agonist in human beings has not previously been explored. Given this potential for ivermectin to act in patients as a GABA agonist, as well as its excellent safety profile, we administered the compound in an open-label fashion to 10 patients with severe spasticity after spinal-cord
scores at
Chicago,
IL
60608, USA; and Clinica del Occidente,
Cali, Colombia
1 2
3
4
5
Whitworth JAG, Morgan D, Maude GH, Taylor DW. Communitybased treatment with ivermectin. Lancet 1988; ii: 97-98. DeSole G, Awadzi K, Remme J, et al. A community trial of ivermectin in the onchocerciasis focus of Asubende, Ghana, II: adverse reactions. Trop Med Parasitol 1989; 40: 375-82. Pacqué M, Muñox B, Greene BM, White AT, Dukuly Z, Taylor HR. Safety of and compliance with community-based ivermectin therapy. Lancet 1990; 335: 1377-80. Meythaler JM, Steers WD, Tuel SM, et al. Continuous intrathecal baclofen in spinal cord spasticity: a prospective study. Am J Phys Med Rehabil 1992; 71: 321-27. Coffey RJ, Cahill D, Steers W, et al. Intrathecal baclofen for intractable spasticity of spinal origin: results of a long-term multicenter study. J Neurosurg 1993; 78: 226-32.
Prophylactic coloproctectomy in ulcerative colitis SIR—Bernstein et al (Jan 8, p 71), in their paper on increased risk of colorectal carcinoma in ulcerative colitis, conclude that patients should be informed about the limitations of colonoscopy in preventing colorectal cancer in ulcerative colitis, and they recommend prophylactic coloproctectomy with ileoanal anastomosis for long or very long-standing disease. We agree that surveillance by colonoscopy has its limitations but feel that patients should also be told about the true risk of cancer in ulcerative colitis and about the complications of coloproctectomy. The risk of colorectal cancer in ulcerative colitis differs among various countries and studies. In Langholz and colleagues’ study1 from Denmark, the incidence of colorectal cancer in an unselected cohort of 1161 patients with ulcerative colitis was not different from that in controls. This result was explained by the high rate of colectomy (32% after 25 years of follow-up) despite the fact that colectomy was never indicated for cancer or dysplasia. Langholz et al recommended a colectomy in ulcerative colitis in patients with severe colitis and in patients with intractable disease and they systematically used corticosteroids, sulfasalazine, or 5-aminosalicylate to control inflammation and to decrease the relapse rate. It is likely that the high-risk patients (patients with pancolitis or patients with a chronic course) had a colectomy before dysplasia and cancer could develop. Patients must be advised about the complications of coloproctectomy and ileoanal anastomosis. The failure rate was 5% in a recent study.2 In that series, unexpected Crohn’s disease was present in 8% and chronic pouchitis in 10% of 739
1 Kassirer JP, Angell M. Financial conflicts of interest in biomedical research. N Engl J Med 1993; 329: 570-71. 2 The ACG committee on FDA-related matters. Hepatic effects of drugs used in the treatment of peptic ulcer disease. Am J Gastroenterol 1987; 82: 987-1003. 3 Wolfson JS, Hooper DC. Overview of fluoroquinolone safety. Am J Med 1991; 91 (suppl): 153-61. 4 Grassmick BK, Lehr VT, Sundareson AS. Fulminant hepatic failure possibly related to ciprofloxacin. Ann Pharmacother 1992; 26: 636-38. 5 Edwards R. Competing in drug safety. Lancet 1993; 342: 631-32.
Ivermectin for spasticity in spinal-cord injury
Table: Ashworth and spasm each patient
injury. Each patient was admitted to hospital and given a single subcutaneous injection of 02 mg/kg ivermectin. Ashworth and spasm scores4 were recorded over the next 24 hours. Two weeks later, an injection of 04 mg/kg ivermectin was given, with scores again recorded over a 24-hour period. Some patients received subsequent injections at weekly or biweekly intervals, with doses up to 1-6 mg/kg. By 2 to 4 hours after each of the first two doses, both the Ashworth and spasm scores decreased, and remained reduced throughout the full 24 hours of observation (figure). The table summarises Ashworth and spasm scores in patients after several weeks of ivermectin. Every patient had decreased spasm scores, and all but 3 reported lower Ashworth scores. No clinical adverse effects were noted in any of the patients, including the one who received ivermectin for 12 weeks. In fact, many reported improved sleep, less depression, and better bowel and bladder function during the trial. These preliminary observations suggest that ivermectin has properties similar to those of baclofen, a GABA-B agonist, which acts to reduce spasticity in spinal-cord injury.5 Further
Figure: Ashworth and spasm scores within 24 h of 02 mg/kg (broken line) and 04 mg/kg (unbroken line) Ivermectln
conclusion of trial for
clinical trials may be warranted in both spinal-cord injury and in other central nervous system disorders such as epilepsy, which is known to improve with GABA agonists. Jonathan L Costa, Jesus A Diazgranados Schwab Rehabilitation Hospital,
SIR-Ivermectin is used extensively for the treatment of onchocerciasis world wide. 1-3 Although it is believed to exert its antiparasitic activity because of agonism at filarial gamma aminobutyric acid (GABA) receptors, the possibility that ivermectin may act as a GABA agonist in human beings has not previously been explored. Given this potential for ivermectin to act in patients as a GABA agonist, as well as its excellent safety profile, we administered the compound in an open-label fashion to 10 patients with severe spasticity after spinal-cord
scores at
Chicago,
IL
60608, USA; and Clinica del Occidente,
Cali, Colombia
1 2
3
4
5
Whitworth JAG, Morgan D, Maude GH, Taylor DW. Communitybased treatment with ivermectin. Lancet 1988; ii: 97-98. DeSole G, Awadzi K, Remme J, et al. A community trial of ivermectin in the onchocerciasis focus of Asubende, Ghana, II: adverse reactions. Trop Med Parasitol 1989; 40: 375-82. Pacqué M, Muñox B, Greene BM, White AT, Dukuly Z, Taylor HR. Safety of and compliance with community-based ivermectin therapy. Lancet 1990; 335: 1377-80. Meythaler JM, Steers WD, Tuel SM, et al. Continuous intrathecal baclofen in spinal cord spasticity: a prospective study. Am J Phys Med Rehabil 1992; 71: 321-27. Coffey RJ, Cahill D, Steers W, et al. Intrathecal baclofen for intractable spasticity of spinal origin: results of a long-term multicenter study. J Neurosurg 1993; 78: 226-32.
Prophylactic coloproctectomy in ulcerative colitis SIR—Bernstein et al (Jan 8, p 71), in their paper on increased risk of colorectal carcinoma in ulcerative colitis, conclude that patients should be informed about the limitations of colonoscopy in preventing colorectal cancer in ulcerative colitis, and they recommend prophylactic coloproctectomy with ileoanal anastomosis for long or very long-standing disease. We agree that surveillance by colonoscopy has its limitations but feel that patients should also be told about the true risk of cancer in ulcerative colitis and about the complications of coloproctectomy. The risk of colorectal cancer in ulcerative colitis differs among various countries and studies. In Langholz and colleagues’ study1 from Denmark, the incidence of colorectal cancer in an unselected cohort of 1161 patients with ulcerative colitis was not different from that in controls. This result was explained by the high rate of colectomy (32% after 25 years of follow-up) despite the fact that colectomy was never indicated for cancer or dysplasia. Langholz et al recommended a colectomy in ulcerative colitis in patients with severe colitis and in patients with intractable disease and they systematically used corticosteroids, sulfasalazine, or 5-aminosalicylate to control inflammation and to decrease the relapse rate. It is likely that the high-risk patients (patients with pancolitis or patients with a chronic course) had a colectomy before dysplasia and cancer could develop. Patients must be advised about the complications of coloproctectomy and ileoanal anastomosis. The failure rate was 5% in a recent study.2 In that series, unexpected Crohn’s disease was present in 8% and chronic pouchitis in 10% of 739