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      Journal of Pain Research (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on reporting of high-quality laboratory and clinical findings in all fields of pain research and the prevention and management of pain. Sign up for email alerts here.

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      Hematuria following Botox treatment for upper limb spasticity: a case report

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          Abstract

          Hematuria is a documented side effect of botulinum toxin injection and has only been reported when it is used for overactive bladder. Here we report a rare case of hematuria following onabotulinumtoxin A (Botox) injection for upper limb spasticity in a 29-year-old male with a history of traumatic brain injury and hemophilia. Hematuria resolved without further complication after self-injection of factor VIII as recommended by his hematologist. Botulinum toxin binds peripheral cholinergic nerve endings to prevent acetylcholine and norepinephrine exocytosis. Studies have shown that both of these compounds are involved in antifibrinolytic activation, suggesting botulinum toxin may play a role in the coagulation cascade by preventing formation of fibrin. This is further supported by resolution of hematuria in our patient after self-injection of factor VIII. As such, botulinum toxin injection may result in mild spontaneous hemorrhage in patients with underlying hematological deficiencies. Further studies are needed to elucidate its effects in coagulation.

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          Identification of the major steps in botulinum toxin action.

          Botulinum toxin is a uniquely potent substance synthesized by the organisms Clostridium botulinum, Clostridium baratii, and Clostridium butyricum. This toxin, which acts preferentially on peripheral cholinergic nerve endings to block acetylcholine release, is both an agent that causes disease (i.e., botulism) as well as an agent that can be used to treat disease (e.g., dystonia). The ability of botulinum toxin to produce its effects is largely dependent on its ability to penetrate cellular and intracellular membranes. Thus, toxin that is ingested or inhaled can bind to epithelial cells and be transported to the general circulation. Toxin that reaches peripheral nerve endings binds to the cell surface then penetrates the plasma membrane by receptor-mediated endocytosis and the endosome membrane by pH-induced translocation. Internalized toxin acts in the cytosol as a metalloendoprotease to cleave polypeptides that are essential for exocytosis. This review seeks to identify and characterize all major steps in toxin action, from initial absorption to eventual paralysis of cholinergic transmission.
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            Intramuscular injection of botulinum toxin for the treatment of wrist and finger spasticity after a stroke.

            Spasticity is a disabling complication of stroke, and it is uncertain whether intramuscular injections of botulinum toxin type A reduce disability in persons with spasticity of the wrist and fingers after a stroke. We performed a randomized, double-blind, placebo-controlled, multicenter trial to assess the efficacy and safety of one-time injections of botulinum toxin A (200 to 240 units) in 126 subjects with increased flexor tone in the wrist and fingers after a stroke. The primary outcome measure was self-reported disability in four areas: personal hygiene, dressing, pain, and limb position (on a four-point scale ranging from no disability to severe disability) at six weeks; at base line, each subject selected one of these areas in which there was moderate-to-severe disability as the principal target of treatment. Subjects who received botulinum toxin A had greater improvement in flexor tone in the wrist and fingers at all follow-up visits through 12 weeks than did subjects who received placebo (P<0.001 for all comparisons). Subjects treated with botulinum toxin A had greater improvement in the principal target of treatment at weeks 4, 6, 8, and 12 (P<0.001, P<0.001, P=0.03, and P=0.02, respectively); at week 6, 40 of the 64 subjects in the botulinum-toxin group (62 percent), as compared with 17 of the 62 in the placebo group (27 percent), reported improvement of at least one point on the Disability Assessment Scale in the principal target of treatment (P<0.001). There were no major adverse events associated with injection of botulinum toxin A. Intramuscular injections of botulinum toxin A reduce spasticity of the wrist and finger muscles and associated disability in patients who have had a stroke. Copyright 2002 Massachusetts Medical Society
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              Management of spasticity associated pain with botulinum toxin A.

              Lesions of the central nervous system often result in an upper motor neuron syndrome including spasticity, paresis with pyramidal signs, and painful spasms. Pharmacological treatment with oral antispasticity drugs is frequently associated with systemic side effects which limit their clinical use. Botulinum Toxin A (BtxA) injected in spastic muscles has been shown to be effective in reducing muscle tone, but only few studies have reported pain relief as additional benefit. Therefore, we investigated the effects of local BtxA injections in 60 patients with acute (< 12 months) and chronic spasticity and pain in a prospective multicenter study. Target muscles for BtxA were selected on the basis of clinical examination. Intramuscular BtxA injections were placed in muscles exhibiting increased muscle tone in combination with pain during passive joint movement. Patients received a mean total dose of 165.7 +/- 108.2 [30-400] units BOTOX((R)) per treatment session in a mean 3.4 +/- 1.5 muscles. Baseline and follow-up (mean 5.9 weeks) measures included a patient self-assessment of pain and function on a five-level scale, a physician's evaluation of function, and a global rating of response to BtxA. Fifty-four of sixty patients experienced improvement in pain without subjective functional improvement. The effects were comparable in acute (n = 17) and chronic (n = 43) spasticity. Physician's assessment of gain in function increased significantly (p < 0.05) only in patients with chronic spasticity. No serious adverse event was observed. Mild reversible side effects (local pain, hematoma, edema, mild weakness) were observed in four patients. In conclusion, we found that intramuscular BtxA injections are a potent, well-tolerated treatment modality to significantly reduce spasticity-related local pain. This problem may be a main indication, especially in patients with poor response or intolerable side effects to oral medication.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                1178-7090
                2015
                14 September 2015
                : 8
                : 619-622
                Affiliations
                [1 ]Department of Physical Medicine and Rehabilitation and Neurological Surgery, University of California, Irvine, CA, USA
                [2 ]Institute of Memory Impairment and Neurological Disorders, University of California, Irvine, CA, USA
                Author notes
                Correspondence: Eric Y Chang, Department of Physical Medicine and Rehabilitation, University of California, Irvine, 101 The City Drive South, Orange, CA 92868, USA, Tel +1 714 456 6668, Fax +1 714 456 6557, Email ericyaochang@ 123456yahoo.com
                [*]

                These authors contributed equally to this work

                Article
                jpr-8-619
                10.2147/JPR.S88658
                4576889
                98603495-3bd7-4a1a-a908-c49f6e82335a
                © 2015 Lo et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Case Report

                Anesthesiology & Pain management
                hematuria,botulinum toxin,upper limb spasticity,hemophilia
                Anesthesiology & Pain management
                hematuria, botulinum toxin, upper limb spasticity, hemophilia

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