D Ranoux

Centre Hospitalier Universitaire de Limoges, Limages, Limousin, France

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Publications (14)61.71 Total impact

  • D Ranoux
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    ABSTRACT: Botulinum toxin type A (BTX-A) is a potent neurotoxin that blocks acetylcholine release from presynaptic nerve terminals by cleaving the SNARE complex. BTX-A has been reported to have analgesic effects independent of its action on muscle tone. The most robust results have been observed in patients with neuropathic pain. Neuropathic pain due to peripheral lesions has been the most widely studied. BTX-A has shown its efficacy on pain and allodynia in various animal models of inflammatory neuropathic pain. The only randomized, double-blind, placebo-controlled trial in patients with focal painful neuropathies due to nerve trauma or postherpetic neuralgia demonstrated significant effects on average pain intensity from 2 weeks after the injections to 14 weeks. Most patients reported pain during the injections, but there were no further local or systemic side effects. The efficacy of BTX-A in painful peripheral neuropathies has been more recently studied. Results were positive in the only study in an animal model of peripheral neuropathy. One study in patients with diabetic painful peripheral neuropathy demonstrated a significant decrease in Visual Analog Scale. In conclusion, one session of multiple intradermal injection of BTX-A produces long-lasting analgesic effects in patients with focal painful neuropathies and diabetic neuropathic pain, and is particularly well tolerated. The findings are consistent with a reduction of peripheral sensitisation, the place of a possible central effect remaining to define. Further studies are needed to assess some important issues, i.e. BTX-A efficacy in patients with small fiber neuropathies and the relevance of early and repeated injections. Future studies could also provide valuable insights into pathophysiology of neuropathic pain.
    Revue Neurologique 01/2011; 167(1):46-50. DOI:10.1016/j.neurol.2010.11.001 · 0.60 Impact Factor
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    ABSTRACT: The units of different preparations of botulinum neurotoxin type A (BoNT-A) have different potencies, and dosing recommendations for each product are not interchangeable. Historically, there has been debate concerning the dose-equivalence ratio that should be used in clinical practice. Published evidence was considered to establish an appropriate dose-conversion ratio for the two main commercially available preparations of BoNT-A--Dysport (Dp) and Botox (Bx). Four key areas of evidence were identified: nonclinical and preclinical studies; studies exploring the diffusion characteristics and effects of complexing proteins; comparative experimental data from human studies; and clinical studies. Nonclinical data indicate that the principal reasons for differences in unit potency between the two products are dilution artefacts in the mouse assay. Use of saline as a diluent, at high dilutions, results in significant loss of potency in the Bx assay, whereas use of gelatin phosphate buffer in the Dp assay procedure protects the toxin during dilution. The published data on mouse assays show a Dp : Bx unit ratio range of 2.3-2.5 : 1 in saline and 1.8-3.2 : 1 in gelatin phosphate buffer. Data indicate that complexing proteins or size of the complex, which is highly pH sensitive, play no role in toxin diffusion and that Dp and Bx have similar diffusion characteristics when used at comparable doses. Randomized, controlled clinical studies indicate that 3 : 1 is more appropriate than 4 : 1, but the two products are not equivalent at this ratio. Comparative human experimental studies using the extensor digitorum brevis test, facial lines and anhidrotic action halo tests support dose-conversion ratios less than 3 : 1. Data comparing dose equivalence ratios from the non-clinical setting should be extrapolated into the clinical setting with some caution. Dose-conversion ratios between Dp and Bx of 4 : 1 and greater are not supported by the recent literature.
    Current Medical Research and Opinion 08/2009; 25(7):1573-84. DOI:10.1185/03007990903028203 · 2.37 Impact Factor
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    ABSTRACT: Botulinum toxin type A (BTX-A) has been reported to have analgesic effects independent of its action on muscle tone, possibly by acting on neurogenic inflammation. Such a mechanism may be involved in peripheral neuropathic pain. A possible direct analgesic effect of BTX-A pain processing was investigated in 29 patients with focal painful neuropathies and mechanical allodynia using a randomized, double-blind, placebo-controlled design. Patients received a one-time intradermal administration of BTX-A (20-190 units) into the painful area. Outcome measures, evaluated at baseline, then at 4, 12, and 24 weeks, included average spontaneous pain intensity, quantified testing of thermal and mechanical perception and pain, allodynia to brushing (area, intensity), neuropathic symptoms, clinical global impression, and quality of life. BTX-A treatment, relative to placebo, was associated with persistent effects on spontaneous pain intensity from 2 weeks after the injection to 14 weeks. These effects correlated with the preservation of thermal sensation at baseline (p < 0.05). BTX also improved allodynia to brush and decreased pain thresholds to cold, without affecting perception thresholds. There were sustained improvements in the proportion of responders (number needed to treat for 50% pain relief: 3.03 at 12 weeks), neuropathic symptoms, and general activity. Most patients reported pain during the injections, but there were no further local or systemic side effects. These results indicate for the first time that BTX-A may induce direct analgesic effects in patients with chronic neuropathic pain independent of its effects on muscle tone and suggest novel indications for BTX-A in analgesia.
    Annals of Neurology 09/2008; 64(3):274-83. DOI:10.1002/ana.21427 · 11.91 Impact Factor
  • Journal of palliative care 02/2008; 24(3):190-1. · 0.80 Impact Factor
  • Revue Neurologique 01/2008; 164:30-30. DOI:10.1016/S0035-3787(08)70046-8 · 0.60 Impact Factor
  • K R Aoki, D Ranoux, J Wissel
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    ABSTRACT: When using botulinum toxin-based products, the physician must decide the optimal location and dose required to alleviate symptoms and improve the patient's quality of life. To deliver effective treatment, the physician needs to understand the importance of accurate target muscle selection and localization and the implications of each product's migration properties when diluted in different volumes. Pre-clinical mouse models of efficacy and safety have been utilized to compare local and distal muscle relaxation effects following defined intramuscular administration. Data from the model allow the products to be ranked based on their propensity for local efficacy versus their distal migration properties. Using standardized dilutions, the non-parallel dose-response curves for the various formulations demonstrate that they have different efficacy profiles. Distal effects were also noted at different treatment doses, which are reflected in the different safety and/or therapeutic margins. Based on these pre-clinical data, the safety and therapeutic margin rankings are ordered, largest to smallest, as BOTOX, Dysport and Myobloc. The results of subsequent clinical trials are variable and dose comparisons are inconclusive, thus supporting the regulatory position that the dose units of the individual preparations are unique and cannot be simply converted between products.
    European Journal of Neurology 01/2007; 13 Suppl 4:10-9. DOI:10.1111/j.1468-1331.2006.01649.x · 3.85 Impact Factor
  • D Ranoux, M Zuber, C Gury
    Journal of Neurology Neurosurgery & Psychiatry 11/2002; 73(5):604-604. · 5.58 Impact Factor
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    ABSTRACT: Leber's hereditary optic neuropathy is a mitochondrial disease caused by point mutations in mitochondrial DNA. It usually presents as severe bilateral visual loss in young adults. We report on a neurological disorder resembling Leigh syndrome, which complicated Leber's hereditary optic neuropathy in three unrelated male patients harboring mitochondrial DNA mutations at nucleotide positions 3460, 14459, and 14484, respectively. This Leigh-like encephalopathy appears to be associated with a much more severe outcome than isolated Leber's hereditary optic neuropathy.
    Annals of Neurology 10/2002; 52(3):374-7. DOI:10.1002/ana.10299 · 11.91 Impact Factor
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    ABSTRACT: Botulinum toxin type A is a potent neuromuscular paralyzing agent used in various disorders including cervical dystonia. Two preparations of botulinum toxin are now commercially available ( Dysport and Botox), but much controversy remains about their respective potencies. The aim of the study was to compare the efficacy of Botox with two different ratios of Dysport. A double blind, randomised, three period cross over study involving 54 patients with cervical dystonia was performed. The patients received the following treatments in a randomised order: Botox at the usually effective dose, Dysport at a dose of 1:3 (conversion factor of 3 between Botox and Dysport units-that is, one Botox unit=three Dysport units) and at a dose of 1:4 (conversion factor of four). The improvement of the Tsui (primary outcome criteria) and of the TWSTRS pain scales between baseline and a control visit 1 month after each of the three injections, as well as the incidence of adverse events, were assessed. Comparison of the Tsui scores and of the TWSTRS pain scores showed a better effect on impairment and pain with Dysport 1:3 (p=0.02 and 0.04, respectively) and 1:4 (p=0.01 and 0.02, respectively) than with Botox. The number of adverse events was higher with both Dysport treatments. The most frequent adverse event was dysphagia, found in 3%, 15.6%, and 17.3% (Botox, Dysport 1:3 and 1:4, respectively) of the patients. No adverse event required withdrawal of therapy or specific management. Dysport 1:3 (and Dysport 1:4 to a greater extent) is more efficient than Botox for both impairment and pain in cervical dystonia although with a somewhat higher incidence of minor adverse effects. This strongly suggests that the most appropriate conversion factor between Botox and Dysport units is less than 3 in cervical dystonia.
    Journal of Neurology Neurosurgery & Psychiatry 05/2002; 72(4):459-62. · 5.58 Impact Factor
  • La Revue de Médecine Interne 06/1998; 19. DOI:10.1016/S0248-8663(98)80249-X · 1.32 Impact Factor
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    Journal of Neurology Neurosurgery & Psychiatry 12/1996; 61(5):533-4. DOI:10.1136/jnnp.61.5.533 · 5.58 Impact Factor
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    ABSTRACT: A patent foramen ovale has been reported to be significantly more frequent in young stroke patients than in matched control subjects, and paradoxical embolism has been suggested as the main mechanism of stroke in this situation. The present study was designed to test this hypothesis. Sixty-eight consecutive patients under 55 years of age presenting with an ischemic stroke had an extensive workup, including transesophageal echocardiography with contrast. We compared the prevalence of criteria for the diagnosis of paradoxical embolism in patients with and without a patent foramen ovale. A patent foramen ovale was found in 32 patients (47%). A Valsalva-provoking activity was present at stroke onset in six patients with a patent foramen ovale and in eight patients with no patent foramen ovale (chi 2 = 0.1, nonsignificant). Clinical/radiological features suggestive of an embolic mechanism were not more frequent in patients with a patent foramen ovale. Clinical evidence of deep vein thrombosis was present in one patient with a patent foramen ovale and in none of the others. No occult venous thrombosis was found in a subgroup of patients with a patent foramen ovale and no definite cause for stroke who underwent venography (n = 13). Our results do not support the hypothesis that paradoxical embolism is the primary mechanism of stroke in patients with a patent foramen ovale.
    Stroke 02/1993; 24(1):31-4. DOI:10.1161/01.STR.24.1.31 · 6.02 Impact Factor
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    ABSTRACT: Two cases of meningeal sarcoidosis with unusual and misleading presentations are reported. In the first case, CT scan, angiographic, and MRI findings were indistinguishable from those of meningioma. CSF pleiocytosis may help in diagnosing sarcoid pseudo-meningioma. The second patient had transient focal deficits and pachymeningitis of the convexity. The transient deficits were probably of epileptic origin based on their response to antiepileptic treatment. The diagnosis of neurosarcoidosis was made only after meningeal biopsy, despite thorough investigations.
    Journal of Neurology Neurosurgery & Psychiatry 05/1992; 55(4):300-3. DOI:10.1136/jnnp.55.4.300 · 5.58 Impact Factor
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    K R Aoki, D Ranoux, J Wissel
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    ABSTRACT: 30-ти лет ботулиниче-ский токсин используется при различных показаниях, вна-чале при лечении офтальмологических состояний, таких как косоглазие и блефароспазм, а недавно стал использо-ваться при лечении таких заболеваний как спастичность, гипергидроз и мигрень. Использование ботулинического токсина подтверждается достаточным ко личеством до-клинических и клинических данных, результаты которых приводят к высокой степени доверия при современном клиническом применении токсина. На сегодняшний день в Европе доступны три коммер-ческих препарата ботулинического токсина типа А (БT-A) -BOTOX ® (производитель -Allergan Inc., Irvine, California, USA), Dysport ® (производитель -Ipsen Limited, Berkshire, UK), и Xeomin ® (производитель -Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany, на сегодняшний день доступен только в Германии). Единственный одобренный препарат ботулинического токсина типа В известен в Сое-динённых Штатах Америки как Myobloc ® , а за пределами США – как Neurobloc ® . Хотя все они являются препара-тами ботулинического токсина, между ними существуют различия, которые лечащий врач должен понимать, что-бы обеспечить безопасное и эффективное использование каждого из препаратов. На протяжении более десяти лет продолжаются дискуссии относительно сравнительной эффективности этих коммерчески доступных препаратов ботулинического токсина типа А, и возможности уста-новления конверсионного фактора или соотношения до-зировок между препаратами. Причины необходимости создания такого конверсионного фактора двойственны. Во-первых, пациенты могут сами попросить сменить ис-пользуемый препарат на другой, по причине развития по-бочных эффектов или отсутствия эффективности лечения. В этом случае, для пациента будет предпочтительным простая конверсия дозы, чем повторный подбор эффек-тивной дозы (ED 50) нового препарата. Во-вторых, при ис-пользовании фиксированных соотношений дозировок су-ществует коммерческий подтекст, так как использование соотношения доз 4:1 подразумевает, что стоимость лече-ния препаратом BOTOX ® будет ниже, чем стоимость ле-чения препаратом Dysport ® , а соотношение доз 3:1 будет делать стоимость лечения препаратом BOTOX ® дороже, чем препаратом Dysport ® . Данные, которые использовались с целью определе-ния эквивалентного соотношения доз между препаратами BOTOX ® и Dysport ® , были получены из доклинических и клинических источников. Однако до сегодняшнего дня не проводились рандомизированные, контролируемые ис-Использование трансляционной медицины для понимания клинических различий между препаратами ботулинического токсина.

Publication Stats

484 Citations
61.71 Total Impact Points


  • 2008
    • Centre Hospitalier Universitaire de Limoges
      Limages, Limousin, France
  • 2007
    • Centre Hospitalier Sainte Anne
      Lutetia Parisorum, Île-de-France, France
  • 2002
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France