Radiology Department, University of Medicine and Pharmacy Iuliu Haţieganu, Cluj-Napoca, Romania 2
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1 Original papers Medical Ultrasonography 2010, Vol. 12, no. 4, Sonoelastography contribution in cerebral palsy spasticity treatment assessment, preliminary report: A systematic review of the literature apropos of seven patients Dan Vasilescu 1, Dana Vasilescu 2, Sorin Dudea 1, Carolina Botar-Jid 1, Silviu Sfrângeu 1, Dan Cosma 2 1 Radiology Department, University of Medicine and Pharmacy Iuliu Haţieganu, Cluj-Napoca, Romania 2 Cluj Rehabilitation Hospital, Department of Pediatric Surgery, University of Medicine and Pharmacy Iuliu Haţieganu, Cluj-Napoca, Romania Abstract This paper aims to present our experience of 7 cases of spastic children, using sonoelastography in assessing the muscle spasticity: the relaxed muscle structures appear mostly soft (green-yellow-red), while contracted or degenerated muscle fibers appear hard (blue). Using sonoelastographic findings we established the proper place for injecting the botulinum toxin (20 U/ kg Dysport) into the affected muscle. The result was a precise, guided injection, with positive, therapeutic results. It is important consider several factors that can influence the evolution of the case: gray scale ultrasound appearance of the muscle, the patient age, the dosage and the fractionation of toxin. Keywords: Spasticity, botulinum toxin, sonoelastography Rezumat Lucrarea doreşte să prezinte experienţa colectivului nostru în aplicarea sonoelastografiei pentru evaluarea spasticităţii musculare. Au fost examinati 7 copii cu spasticitate musculară cu diverse localizări: muşchiul relaxat are un aspect moale (verde-galben-roşu) pe când cel contractat sau degenerat apare dur (albastru). Ţinând cont de constatările sonoelastografice s-a stabilit locul de injectare a toxinei botulinice (Dysport 20 U/kg). Rezultatul obţinut a fost o injectare precisă şi implicit un rezultat terapeutic favorabil. Trebuie ţinut cont de mai mulţi factori ce pot influenţa evoluţia cazului: aspectul muşchiului, vârsta pacientului, dozarea şi fracţionarea toxinei. Cuvinte cheie: Spasticitate, toxină botulinică, sonoelastografie Introduction Received Accepted Med Ultrason 2010, Vol. 12, No 4, Address for correspondence: Dan Vasilescu University of Medicine and Pharmacy I. Haţieganu Cluj-Napoca, 8 V. Babeş str., Cluj-Napoca, Romania vasilescu.dan@umfcluj.ro Botulinum toxin is a neurotoxin produced by Clostridium botulinum, a gram-positive anaerobic bacterium. Clinical applications are based on its effect on the neuro-muscular junction, producing neuromuscular paralysis. The use of botulinum toxin for medical purposes is mentioned in the late 80s. Initial experiments were conducted on animals and in the late 90s the first applications in humans were made. Currently known applications are spastic muscle pathology, in dermatology, in dystonic torticollis, injections in the submandibular and parotid glands, and even applications in neurogenic bladder pathology. Known products approved for clinical use are: Onabotulinumtoxin A (Botox), Abobotulinumtoxin A
2 (Dysport), Rimabotulinumtoxin B (Myobloc) [1]. The applications, including the therapy for spastic muscles, implied injecting the toxin in the targeted muscle groups. Until a few years ago, the injections were made only by clinical palpation or by using muscle stimulation or by using electromyography (EMG). In recent years, ultrasound techniques were introduced to help guide the injection. In 2005, Chin et al [2] published a study which showed the accuracy of tracing the target muscle with no guidance. They performed 1,372 separate injections for upper and lower limb spasticity in 226 cases of children with cerebral palsy. The accuracy of manual needle placement when compared to electrical stimulation was satisfactory only for gastro-soleus (>75%); it was not satisfactory for hip adductors (67%), medial hamstrings (46%), tibialis posterior (11%), biceps brachii (62%), and for forearm and hand muscles (13% to 35%). Due to the need for a higher accuracy in needle placement in all muscles, ultrasonography (US) became the method most frequently used in guiding the injections. The average time needed to identify and inject the targeted muscle ranged from 5 s in superficial muscles, such as the gastrocnemius muscle, to 30 s in deep-seated muscles [3]. The use of muscle stimulation and of EMG may produce local pain and increase the stress level. In pediatric patients the use of minimally invasive techniques is required and sedation and analgesia is often needed. In these cases EMG potentials recorded from the targeted muscles are low. Also, due to the contraction of the neighboring muscle, EMG might not always identify the right pathological muscle group. All these reasons recommend the use of ultrasound techniques [4]. Sonoelastography is an ultrasound technique that allows the assessment of tissue elasticity. Its application in the musculoskeletal field includes the evaluation of the muscle contraction status. On sonoelastographic images a relaxed muscle structure will appear mostly soft (greenyellow-red), while contracted or degenerated muscle fiber will appear hard (blue) [5,6]. The purpose of this paper is to present our preliminary experience in using ultrasound techniques to guide the injection of botulinum toxin in the muscles of spastic children. Method In our practice we used 20 U/kg botulinum toxin (Dysport). Seven patients were included in the study Medical Ultrasonography 2010; 12(4): until now, who were clinically and US pre-injection evaluated and thereafter on various time intervals. Patients were selected from Cluj Rehabilitation Hospital, Department of Pediatric Surgery after orthopedic and neurological examination, having indication for the use of botulinum toxin in relaxing the spastic muscles. Injections were administered in the upper and lower limb. The study was approved by the local Ethics Committee and all the patients or the patients parents gave the consent to participate to the study. The ultrasound examination was performed in Cluj County Emergency Hospital, in Radiology Department, using a Hitachi Ultrasound EUB 8500 with MHz linear transducer. The examination consisted of two-dimensional comparative study of the muscle groups indicated by the orthopedist and elastography was used for an accurate assessment and identification of the contracted muscle groups. The ultrasonographic description of the pathological muscle groups included muscular fibers ecogenicity, ecogenicity of the fibroadipose septe and the muscle diameter (the criteria for atrophy included increased ecogenicity of the muscles and reduced diameter of the fibers when compared to the opposite site). Sonolastography had been applied on muscle groups previously identified by two-dimensional ultrasound examination. As described before, relaxed muscle structure would appear mostly soft (green-yellow-red), while contracted or degenerated muscle fiber would appear hard (blue) on sonoelastographic images [6]. Sonoelastographic images obtained were analysed using a dedicated software with the purpose of obtaining objective and quantifiable data, useful in establishing an exact imaging diagnosis and in monitoring this disease. The decision where to administer the Dysport was made according to the US findings. The distance to the pathologic muscle, perpendicular to the skin was measured using points marked on the surface of the skin at the end of US examination. Case 1 Five year old boy with cerebral palsy with spasticity predominantly affecting the lower limb muscles. Clinical and US assessment was performed in calf and thigh bilaterally previous injection (fig 1, fig 2). Evident improvement seen on ultrasound images was confirmed by the parents and by the clinical examination
3 308 Dan Vasilescu et al Sonoelastography contribution in cerebral palsy spasticity treatment assessment Fig 1. a) Left thigh and b) right thigh before injection (gray scale US and sonoelastography). Hard aspect (contracted) of the medial gastrocnemius muscle. Fig 2. a) Left thigh and b) right thigh 6 months after from injection (gray scale US and sonoelastography). Gastrocnemius muscle looks softer (less contracted). Fig 3. a) Right pronator teres muscle before injection (gray scale US and sonoelastography) predominantly contracted; b) right pronator teres muscle 4 weeks after injection. The aspect is softer, less contracted Fig 4. Right abductor policis muscle a) before injection contracted aspect of the muscle; b) 4 weeks after injection. The aspect is softer, less contracted
4 Medical Ultrasonography 2010; 12(4): Fig 5. a) Initial contracted aspect of left medial gastrocnemius muscle (gray scale US and sonoelastography); b) unchanged aspect at 2 weeks after injection based on clinical palpation Fig 6. The same case as in fig 5. a) US reassessment followed by marking the points for injection; b) US control after 3 weeks. Improved appearance, the muscle looks softer this time Case 2 Seven year old boy. Cerebral palsy predominantly affecting the upper limb muscles. Clinical and ultrasound evaluation was performed on the arm and forearm, bilaterally (fig 3, fig 4). Ultrasound appearance was confirmed also by clinical examination. Case 3 Seven year old girl. Cerebral palsy with predominant spasticity of the lower limb muscles. First injection was administered after clinical palpation of the muscle group indicated by a previous US exam. The failure in clinical response imposed a new injection, this time with US control (marking points on the patient s skin and indicating the depth of the pathological muscle) (fig 4, fig 5). This case is a good example of repeating the toxin administration if there is no favorable response, before considering that the case as resistant to the therapy. The incorrect administration of the toxin could be another reason for this failure Case 4-6 These 3 patients (age 3, 4, and 7 years) had limb palsy. After US guided toxin administration all presented favorable overall evolution. Case 7 Ten year old boy with cerebral palsy predominant to the lower limb muscles. No improvement was obtained after toxin administration. Results and Discussion The use of Botulinum toxin in pediatric patients requires a complex evaluation: orthopedic, neurological and imaging. One of the reasons of therapeutic failures may be an incomplete evaluation of the case. This suggests the need of teamwork: neurologist-radiologist-orthopedist-physical therapist and that standardized tests are needed to monitor the evolution of cases. The cases presented in this paper show related features regarding the location of muscle groups that were suitable for the injection of botulinum toxin, including upper and/or lower limbs. In our opinion an unsatisfactory therapeutic result after Botulinum toxin injection would be expected if the muscles had structural alterations with the appearance of fibrosis (gray scale US); if the toxin was administrated in other structures than those indicated by the ultrasound examination; in cases of patients older than 7 years; if the treatment was not followed by a proper physical therapy;
5 310 Dan Vasilescu et al Sonoelastography contribution in cerebral palsy spasticity treatment assessment Improvement of protocols for clinical and ultrasound examination could lower the rate of treatment failure. It is also necessary to administer a sufficient dose of toxin to achieve the expected effect and the injection should be followed by a proper physiotherapy. Dosage should be individualized to each patient and suitably fractionated for targeted muscle groups. It should also be considered as an option to inject the muscle in several different points. We appreciated that the use of US had an important contribution in the easiness of a precise tracking of the muscle groups, being the easiest technique in pediatric patients. Schroeder et al [7] concluded that in most aspects ultrasound is superior to EMG (table I). Sonoelastography improves the findings of grayscale US in assessing the degree of muscle contraction, especially in the cases with less information then the ones offered by EMG. Superior therapeutic results seem to be obtained by combining two-dimensional ultrasound with sonoelastography to mark the exact injection site or making the approach ultrasound guided, as it can be seen in the 3-rd presented case. Larger studies are needed to confirm the substantial contribution of sonoelastography, but also to discover new aspects that would improve the therapeutic decision. For a better evaluation of muscle contraction status we need more experience with the benefits of sonoelastography in the musculoskeletal pathology. Table I. Differences between EMG, muscle stimulation and US in guiding the toxine injection [7]. EMG Muscle stimulation US Identification accuracy o + + Time for identify the muscle group o + Availability of technical equipment o o + Pain and stress caused by the method + Dependency on expert experience o Necessary number of stabs + Depth injection control o o + Differentiation of adjacent muscle groups (also contracted) o o + Differentiation of the muscle from surrounding tissues + Dependence on patient cooperation + + The possibility to confirm the correct placement after injection + The possibility of injection documentation + Issues related to sedation analgesia association + + Control of neuro muscular junction proximity + + Control of muscular hyperactivity + o Control of muscle dimension o o + Control of muscle fibrosis o o + Potential for future technology development and research o + -: unfavourable; +: advantageous; o: acceptable References 1. Kedlaya D. Botulinum Toxin, Overview. Emedicine Chin T, Selber P, Graham HK. Accuracy of intramuscular injection of botulinum toxin A: a comparison between manual needle placement and placement guided by electrical stimulation. Pediatr Orthop 2005;25: Berweck S, Schroeder AS, Fietzek UM, Heinen F. Sonography-guided injection of botulinum toxin in children with cerebral palsy. Lancet 2004;363: Berweck S, Wissel J. Sonographic Imaging for Guiding Botulinum Toxin Injections in Limb Muscles. ACNR 2004; 4: Botar-Jid C, Vasilescu D, Dudea S. Ecografia tridimensională şi elastografia în patologia aparatului locomotor. In: Daniela Fodor (ed). Ecografie clinică musculoscheletală. Ed. Medicală Bucureşti 2009: Botar-Jid C, Damian L, Dudea SM, Vasilescu D, Rednic S, Badea R. The contribution of ultrasonography and sonoelastography in assessment of myositis. Med Ultrason 2010; 12: Schroeder AS, Berweck S, Lee SH, Heinen F. Botulinum toxin treatment of children with cerebral palsy a short review of different injection techniques. Neurotox Res 2006;9:
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