Painful Tonic Spasms with Multifocal Dystonia After Cardiac Arrest Showing Emigration-like Pattern Changes During Long-term Botulinum Toxin Type A Therapy A Case Report

Painful Tonic Spasms with Multifocal Dystonia After Cardiac Arrest Showing Emigration-like Pattern Changes During Long-term Botulinum Toxin Type A Therapy A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Painful Tonic Spasms with Multifocal Dystonia After Cardiac Arrest Showing Emigration-like Pattern Changes During Long-term Botulinum Toxin Type A Therapy A Case Report Taro Ogawa, Kazutoshi Yokogushi, Yasunori Mito, Shigeki Hashimoto This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8826724/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction. Secondary dystonia may result from various disorders, including cardiac arrest, and has been reported to be successfully treated with botulinum toxin type A (BoNT-A) injections. However, the long-term clinical course following repeated BoNT-A therapy remains largely undocumented, particularly with respect to pattern changes in dystonic contractions in non-cervical forms of dystonia. Case Presentation. A woman in her 40s developed multifocal dystonia after cardiac arrest caused by thyroid storm. She exhibited involuntary movements in her left arm and both legs. Paroxysmal painful muscle spasms occurred in the left arm more than one hundred times daily, each lasting less than one minute and accompanied by excruciating pain. Brain MRI revealed bilateral low-intensity signals in the basal ganglia consistent with hypoxic encephalopathy. She was diagnosed with painful tonic spasms (PTS) overlapping with multifocal dystonia. Oral pharmacological therapies, including tiapride, clonazepam, and levodopa, were insufficiently effective. BoNT-A injections reduced spasm frequency but provided limited pain relief. Over sixteen BoNT-A injection sessions spanning eight years, both painful and painless dystonic muscle contractions demonstrated dynamic redistribution, and the severity of involuntary movements and pain burden gradually improved. Conclusion. To our knowledge, this is the first report of PTS overlapping with multifocal dystonia following cardiac arrest. We observed an emigration-like redistribution of dystonic muscle contractions during long-term BoNT-A therapy. While pattern changes after BoNT-A injections are well documented in cervical dystonia, such changes have rarely been described in multifocal dystonia. In this case, dystonic activity shifted away from BoNT-A–injected sites to adjacent and distant muscle groups. Figures Figure 1 Figure 2 Figure 3 Introduction Cardiac arrest refers to the cessation of cardiac mechanical activity with absent signs of circulation. Even when resuscitation is successful, patients may suffer hypoxic encephalopathy with neurological sequelae such as persistent vegetative states, seizures, cognitive impairment, and movement disorders. Post-hypoxic myoclonus, often termed Lance–Adams syndrome, is well recognized, and various other movement disorders have been reported following cardiac arrest, including parkinsonism, dystonia, chorea, tics, tremor, ballism, and athetosis.( 1 , 2 ) Scheibe et al. reported a case series of 72 patients with adult-onset cardiac arrest, of whom seven developed dystonia.( 2 ) However, the clinical phenotypes and longitudinal evolution of post-anoxic dystonia, particularly in relation to treatment response, have not been described in detail. Pharmacological treatment for dystonia involves oral medications and botulinum neurotoxin type A (BoNT-A) injections. BoNT-A is particularly effective for focal and segmental dystonia.( 3 ) Generalized dystonia may also be treated with BoNT-A by targeting particularly problematic features.( 3 ) Pattern changes in dystonic symptoms during repeated BoNT-A therapy have been documented in patients with cervical dystonia.( 4 , 5 ) However, whether similar pattern changes occur in other forms of dystonia has not been well established. The scarcity of information regarding these evolving clinical features may hinder clinicians in making treatment decisions for dystonia patients. On the other hand, tonic spasms are characterized by sustained increases in muscle tone affecting a single muscle group and are generally considered distinct from dystonia, although clinical overlap may occur.( 6 ) When these spasms are accompanied by significant pain, they are referred to as painful tonic spasms (PTS). PTS has been well described in spinal cord disorders, including neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD).( 6 ) Other spinal cord conditions, such as Sjögren’s syndrome,( 7 ) have also been associated with PTS, but they have rarely been reported after brain lesions. We report the first case of multifocal dystonia overlapping with painful tonic spasms (PTS) following cardiac arrest and describe the eight-year clinical course of BoNT-A therapy, focusing on emigration-like pattern changes, in which dystonic muscle contractions shifted away from BoNT-A–injected sites. Case Presentation We present this case in accordance with the CARE reporting guideline. A woman in her 40s with no significant past medical history or relevant family history was admitted to a tertiary hospital and diagnosed with thyroid storm due to Graves' disease. On the following day, she experienced cardiac arrest and was successfully resuscitated after 25 minutes. She subsequently underwent radioactive iodine therapy for Graves' disease and was discharged after 54 days with no apparent neurological or cognitive deficits. However, she developed progressive limb dysfunction and speech disturbances. Fifty-three days after discharge, she presented to the neurology department of the same hospital. Neurological examination revealed slow speech, rigid-spastic tone in all limbs, athetoid involuntary movements, increased tendon reflexes in the upper extremities, absence of pathological reflexes, bradykinesia, and a shuffling gait, without pain or cognitive impairment. Brain MRI demonstrated bilateral low-intensity signals in the globus pallidus, consistent with hypoxic encephalopathy (Fig. 1 ). Laboratory investigations including thyroid function tests, autoimmune markers, and cerebrospinal fluid analysis were unremarkable, excluding neuromyelitis optica spectrum disorder, multiple sclerosis, Sjögren's syndrome, and paraneoplastic disorders. Electroencephalography showed no epileptiform activity or features suggestive of Lance-Adams syndrome. She was diagnosed with involuntary movements due to hypoxic encephalopathy following cardiac arrest and was treated with tiapride, clonazepam, and levodopa, but with limited efficacy. Nine months after the cardiac arrest, she was referred to our hospital for outpatient rehabilitation to address gait disturbance due to involuntary movements. The most distressing symptom at that time was severe painful muscle contractions in her left arm. At the first visit, she was fully alert and oriented, speaking slowly in a gravelly voice. Cranial nerve examination revealed no abnormalities except for slowed tongue movements without atrophy or paresis. Motor examination showed normal deep tendon reflexes and no pathological reflexes. The left elbow flexors exhibited intermittent, involuntary contractions accompanied by excruciating pain. These paroxysmal painful spasms were triggered by specific actions such as speaking, standing, yawning, or laughing, but were absent at rest. The patient reported that episodes occurred more than one hundred times per day, each lasting less than one minute, and could not be voluntarily suppressed. During these spasms, muscle contractions were so intense that they resisted passive extension, whereas muscle tone normalized between episodes. Involuntary movements occasionally extended beyond elbow flexion to include reaching motions, finger extension in the left upper limb, and toe extension in both feet. Muscle strength in the right arm and both legs was preserved, but movement of the left leg was impaired and uncoordinated. Sensory and autonomic functions were normal, and no apparent cognitive deficits were observed. She was able to walk indoors by holding onto furniture or walls and remained independent in activities of daily living. The involuntary movements initially appeared consistent with dyskinesia, as they manifested as non-patterned, paroxysmal episodes of gross movement. During follow-up, however, dyskinetic features diminished, and sustained movements became more prominent, while painful intermittent spasms continued to represent the most disabling symptom affecting her quality of life. We therefore considered the movement disorder to be painful tonic spasms (PTS) overlapping with multifocal dystonia, characterized by both painful paroxysmal contractions and sustained painless dystonic postures. Treatment and Clinical Course Figure 2 summarizes the eight-year clinical course. The referring neurologist continued to manage the patient with oral medications throughout the follow-up period. We initiated botulinum toxin type A (BoNT-A) therapy as an additional treatment modality to address the disabling involuntary movements. Clinical severity was assessed using the Movement scale of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), a validated tool for evaluating dystonia.( 8 ) We specifically used the Movement scale component, which assessed dystonia across nine body regions, with total scores ranging from 0 to 120.( 8 ) The Disability scale was not adopted because functional impairment was influenced by multiple non-dystonic factors including falls, trauma, and weight loss from dysphagia. All retrospective BFMDRS Movement scale scoring was performed by the first author (T.O.) based on detailed clinical and rehabilitation records. We tracked the left arm subscore for two reasons: first, retrospective scoring was incomplete for other body regions; second, lower limb function was influenced by the same non-dystonic factors, making the leg subscores less reliable for reflecting dystonia severity. Body weight was also monitored as an indicator of general condition. OnabotulinumtoxinA, a preparation of botulinum neurotoxin type A (BoNT-A), was diluted with physiological saline to a concentration of 20 units/mL. The sites and doses of injections were determined at each session based on the patient’s symptoms and physical findings. Ultrasonography was used to guide injections into deep muscles such as the iliopsoas muscles. Electromyographic guidance was not available at our hospital. At the first injection session, we primarily targeted muscles in the left arm, including the biceps brachii, brachialis, and brachioradialis. We also injected the extensor hallucis longus of the left great toe, which exhibited painless dystonic contractions (Table 1 and Fig. 3 A). Table 1 Muscle targets, doses, and treatment timeline across 16 sessions of botulinum neurotoxin type A injection. Session number 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Months from first visit 3 8 14 20 25 31 35 42 52 58 63 68 72 77 81 85 93 Deep Brain Stimulation R. UE Del. 30 TB 12.5 L. UE PM 25 12.5 30 40 50 25 50 30 25 40 40 30 30 30 Del. 20 LD 20 10 30 75 50 20 40 40 30 30 30 TM 5 BB 15 7.5 15 20 30 30 30 40 25 25 Bra 10 5 20 20 20 20 BR 10 10 25 15 15 TB 10 25 30 20 30 30 45 45 45 60 100 120 90 ECR 10 10 ECU 15 20 20 20 FPL 12.5 5 5 FDS 30 50 30 15 EDC 5 FDI 5 10 10 10 5 5 10 Lu. I 2.5 5 10 Lu. II-IV 12.5 20 R. LE EDL 10 15 10 10 10 10 10 EHL 10 15 10 10 10 10 10 L. LE IP 5 10 AM 5 5 VL 5 EDL 15 15 10 10 10 10 10 EHL 25 5 5 15 15 10 10 10 10 10 The “Deep Brain Stimulation” row marks the start and end of therapy, and grey shading indicates the period during which stimulation was ongoing. Numbers in each muscle row indicate the units of onabotulinumtoxinA injected per session. Blank cells indicate no injection. Abbreviations (listed in order of appearance in the table) : Del, deltoid; TB, triceps brachii; PM, pectoralis major; LD, latissimus dorsi; TM, teres major; BB, biceps brachii; Bra, brachialis; BR, brachioradialis; ECR, extensor carpi radialis; ECU, extensor carpi ulnaris; FPL, flexor pollicis longus; FDS, flexor digitorum superficialis; EDC, extensor digitorum communis; FDI, first dorsal interosseous; Lu, lumbricals; EDL, extensor digitorum longus; EHL, extensor hallucis longus; IP, iliopsoas; AM, adductor magnus; VL, vastus lateralis. Over sixteen BoNT-A injection sessions spanning eight years, the distribution of painful and painless dystonic contractions gradually evolved. The distribution of painful tonic spasms (PTS) initially shifted to adjacent muscle groups, then spread to remote muscles, and eventually returned to the left elbow flexors, as illustrated in Figs. 3 B-D. Although injections consistently reduced the frequency of spasms, pain relief was often insufficient. Because BoNT-A injections alone did not achieve adequate symptom control, additional oral medications—including dantrolene, tizanidine, and diazepam—were attempted, but none provided clinical benefit. Deep brain stimulation (DBS) targeting the bilateral globus pallidus internus (GPi) was performed five years after symptom onset (between the eighth and ninth BoNT-A sessions, as shown in Table 1 and Fig. 2 ). However, it failed to provide clinical benefit and the DBS system was removed two years later at the patient’s request. Although the left arm subscore of the BFMDRS Movement scale decreased transiently after BoNT-A injections, it remained relatively stable at baseline for several years before temporarily worsening. Body weight declined due to dysphagia, likely resulting from recurrent laryngeal nerve palsy diagnosed 56 months after the cardiac arrest. Following the introduction of home suction equipment to manage excessive saliva, the patient's oral intake improved and body weight gradually recovered. As shown in Fig. 2 , the temporal patterns of body weight and baseline BFMDRS Movement left arm subscores appeared to change inversely. Treatment was generally well-tolerated. The only notable adverse event was transient weakness of finger extension following the ninth injection session, which resolved spontaneously. No serious adverse events occurred throughout the eight-year treatment period. Neuropsychometric testing confirmed intact cognitive function, and she was cleared to drive based on driving simulator and on-road assessments. However, her functional independence gradually deteriorated due to evolving dystonic symptoms, recurrent falls with trauma, and deconditioning during the period of weight loss. Despite subsequent weight recovery, physical function did not fully return, and she eventually required partial assistance with activities of daily living. Discussion This case report presents two novel clinical observations in post-anoxic movement disorders: the first documented case of painful tonic spasms (PTS) coexisting with multifocal dystonia following cardiac arrest, and emigration-like pattern changes of dystonic muscle contractions away from botulinum toxin-injected sites over an eight-year treatment course. PTS is well-established as a characteristic symptom of neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD).( 6 ) In contrast, PTS following primary brain lesions has rarely been documented, with only one reported case of putaminal infarction.( 9 ) Our patient presented with coexisting PTS and multifocal dystonia. Differentiating these conditions is challenging because both can be painful. In cervical dystonia, pain arises from musculoskeletal and myofascial factors without necessarily correlating with the extent of dystonic posturing or muscle tone.( 10 ) In contrast, PTS is characterized by its paroxysmal nature, shorter duration (seconds to minutes), and prominence of pain.( 6 , 11 ) Jabbari et al. described this overlap in a case of Sjögren's syndrome, using the term "painful/dystonic" spasms.( 7 ) Similarly, our patient demonstrated features of both conditions: multifocal dystonia involving the left arm and both legs, and localized, paroxysmal, painful contractions characteristic of PTS. Pharmacological treatments for PTS include antiepileptic agents such as carbamazepine, oxcarbazepine, gabapentin, clonazepam, phenytoin, levetiracetam, and topiramate, as well as benzodiazepines, barbiturates, baclofen, pregabalin, and duloxetine.( 11 ) Botulinum neurotoxin type A (BoNT-A) has also been reported to be beneficial.( 12 ) We observed dynamic migration of involuntary movements irrespective of pain over sixteen sessions of BoNT-A treatment spanning eight years. To our knowledge, this is the first report documenting pattern changes of dystonic muscle contractions in multifocal dystonia during BoNT-A therapy. Pattern changes following BoNT-A injections have been well-documented in cervical dystonia.( 4 , 5 ) In their case series of 20 patients, Gelb et al. performed electromyographic (EMG) studies to compare muscle activity patterns before and after botulinum toxin injections. While patients showed general depression of EMG activity in injected muscles even after clinical effects had disappeared, there was a tendency for muscles that had not been injected to show increased EMG activity. The authors speculated that torticollis results from an abnormal motor program for head position, and suggested that when the most active muscles are functionally denervated by botulinum toxin, this program may call on other muscles to achieve its ends.( 4 ) The pattern changes observed in our patient share features of Gelb's findings—specifically, reduced dystonic activity at BoNT-A injection sites. However, our patient demonstrated not only compensatory recruitment to replicate the same dystonic movements but also emigration-like pattern changes, in which dystonic contractions shifted away from injection sites to adjacent and remote muscle groups. The gradual redistribution of dystonic activity may reflect central nervous system plasticity induced by repeated peripheral denervation. In their fMRI study, Nevrlý et al. indicated that the first BoNT-A injection was associated with widespread changes in sensorimotor network activation, reducing baseline differences between patients and healthy controls and suggesting cortical modulation following peripheral chemodenervation.( 13 ) They also demonstrated that dystonia involves widespread sensorimotor network abnormalities extending into cortical representations of body regions not clinically affected.( 13 ) One possible explanation is that BoNT-A–induced modulation of these altered networks may suppress dystonic output corresponding to injected sites, thereby allowing pre-existing abnormal activity in non-injected representations to become clinically manifest in other body regions. This mechanistic link has yet to be fully elucidated. Therefore, the observed emigration-like pattern changes should be interpreted cautiously. Alternative explanations—including natural disease evolution in post-hypoxic injury, compensatory motor strategies, cumulative effects of multiple BoNT-A injection sessions, and the effects of concurrent treatments—cannot be excluded. Nevertheless, careful longitudinal observation of symptom distribution during repeated BoNT-A injections may provide useful insights into the evolving phenomenology of multifocal dystonia. We also attempted deep brain stimulation (DBS) targeting the bilateral globus pallidus internus, but this did not result in meaningful improvement. Several factors may have contributed to the poor response in this case. The DBS period coincided with progressive weight loss and clinical deterioration, which may have confounded the assessment of treatment efficacy. Additionally, the efficacy of DBS for secondary dystonia varies( 14 , 15 ), Zhang et al. reported that patients with diffuse basal ganglia damage are suboptimal candidates for DBS,( 15 ) consistent with our patient's extensive bilateral basal ganglia lesions on MRI. They also suggested that STN stimulation might be theoretically superior to GPi due to its upstream position in the basal ganglia motor circuit.( 15 ) However, whether alternative targets such as the STN would have been more effective in our patient remains unknown. This case report has several limitations. First, as a single case report, our findings require validation through larger case series or well-designed studies to establish whether the emigration-like pattern changes are commonly observed in multifocal dystonia. Second, we were unable to perform electrophysiological studies because the necessary equipment was unavailable. Third, we used the left arm subscore of the BFMDRS Movement scale to assess the severity of dystonia, but scores were assigned retrospectively due to incomplete routine clinical assessment, which might affect the reliability of these scores. Fourth, assessment of pain response was challenging: while spasm frequency decreased, the extremely high baseline frequency of PTS episodes (more than 100 times daily before treatment) precluded precise counting, and pain intensity often remained unchanged. Fifth, concurrent treatments including oral medications and DBS may have influenced the observed symptom evolution, making it difficult to isolate the specific effects of BoNT-A. Conclusion Cardiac arrest may lead to various forms of movement disorders. This case highlights the clinical significance of painful tonic spasms as a neurological sequela following cardiac arrest. In addition, this case demonstrated the coexistence of multifocal dystonia, in which long-term botulinum toxin therapy was accompanied by emigration-like pattern changes of dystonic muscle contractions, shifting away from BoNT-A injection sites to adjacent or distant areas. These observations may help clinicians anticipate the need for progressive adjustment of injection sites, optimize long-term treatment planning, and refine injection strategies during extended BoNT-A therapy for multifocal dystonia. Declarations Patient’s perspective I was told that my 25-minute cardiac arrest would likely leave aftereffects. I worked hard in rehab and was able to walk out of the hospital, but I couldn’t jump, which may have been the first sign of what followed.After discharge, I couldn’t put on stockings or fasten a necklace for my son’s graduation—also due to aftereffects. Gradually losing the ability to walk and speak was the hardest part for me. I couldn’t accept that I could no longer do what used to come naturally. I loved exercising and singing, but lost all of it. I was truly happy when painful muscle contractions in my left arm eased with botulinum toxin injections. Now, I rely on a caregiver, but I try to find things I can still do, like cooking and working on the computer. I continue rehabilitation with a positive and hopeful mindset. Patient’s perspective I was told that my 25-minute cardiac arrest would likely leave aftereffects. I worked hard in rehab and was able to walk out of the hospital, but I couldn’t jump, which may have been the first sign of what followed.After discharge, I couldn’t put on stockings or fasten a necklace for my son’s graduation—also due to aftereffects. Gradually losing the ability to walk and speak was the hardest part for me. I couldn’t accept that I could no longer do what used to come naturally. I loved exercising and singing, but lost all of it. I was truly happy when painful muscle contractions in my left arm eased with botulinum toxin injections. Now, I rely on a caregiver, but I try to find things I can still do, like cooking and working on the computer. I continue rehabilitation with a positive and hopeful mindset. Ethics approval This study was approved by the Institutional Review Board of Sapporo Keijinkai Rehabilitation Hospital (approval number 2024-45). The study was performed in line with the principles of the Declaration of Helsinki. Consent to participate Informed consent was obtained from all the individual participants for participation in this study. Consent to publish Written informed consent for publication and accompanying images was obtained from the patient. Competing interests One of the co-authors has received an honorarium from GlaxoSmithKline for serving as a chairperson at a company-sponsored lecture and industry support from GlaxoSmithKline for a medical meeting at which the co-author served as the conference chair. All other authors declare no conflicts of interest. Funding The authors did not receive support from any organization for the submitted work. Author contributions TO: conception of the work, data collection, drafting and revising the manuscript. KY: participated in patient management, documented daily clinical findings and symptoms, and critically reviewed the manuscript. YM: referring neurologist; provided detailed information on the clinical course prior to referral, initial neurological findings, diagnostic test results, and pharmacological treatments; reviewed the manuscript. SH: senior clinician responsible for the patient's care; supervised the writing of the report and approved the clinical content. All authors approved the final version of the manuscript. Data Availability Statement The data underlying this case report consist of clinical information from an individual patient and cannot be made publicly available due to privacy and ethical restrictions. De-identified data may be shared by the corresponding author upon reasonable request and with appropriate institutional approval. References Lu-Emerson C, Khot S. Neurological sequelae of hypoxic-ischemic brain injury. NeuroRehabilitation. 2010;26(1):35–45. Scheibe F, Neumann WJ, Lange C, Scheel M, Furth C, Köhnlein M, et al. Movement disorders after hypoxic brain injury following cardiac arrest in adults. Eur J Neurol. 2020;27(10):1937–47. Dressler D, Adib Saberi F, Rosales RL. Botulinum toxin therapy of dystonia. J Neural Transm. 2021;128(4):531–7. Gelb DJ, Yoshimura DM, Olney RK, Lowenstein DH, Aminoff MJ. Change in pattern of muscle activity following botulinum toxin injections for torticollis. Ann Neurol. 1991;29(4):370–6. Kaňovský P, Dufek J, Halačková H, Rektor I. Change in the pattern of cervical dystonia might be the cause of benefit loss during botulinum toxin treatment. Eur J Neurol. 1997;4(1):79–84. Sarin S, Lawal T, Abboud H. Spinal dystonia and other spinal movement disorders. Dystonia. 2023;2:11303. Jabbari B, Salardini A. Painful tonic/dystonic spasms in Sjogren's syndrome. Mov Disord. 1999;14(5):860–4. Burke RE, Fahn S, Marsden CD, Bressman SB, Moskowitz C, Friedman J. Validity and reliability of a rating scale for the primary torsion dystonias. Neurology. 1985;35(1):73–7. Merchut MP, Brumlik J. Painful tonic spasms caused by putaminal infarction. Stroke. 1986;17(6):1319–21. Relja M, Miletić V. When movement disorders hurt: Addressing pain in hyperkinetic disorders. Parkinsonism Relat Disord. 2017;44:110–3. Asseyer S, Cooper G, Paul F. Pain in NMOSD and MOGAD: A Systematic Literature Review of Pathophysiology, Symptoms, and Current Treatment Strategies. Front Neurol. 2020;11:778. Restivo DA, Tinazzi M, Patti F, Palmeri A, Maimone D. Botulinum toxin treatment of painful tonic spasms in multiple sclerosis. Neurology. 2003;61(5):719–20. Nevrlý M, Hluštík P, Hok P, Otruba P, Tüdös Z, Kaňovský P. Changes in sensorimotor network activation after botulinum toxin type A injections in patients with cervical dystonia: a functional MRI study. Exp Brain Res. 2018;236(10):2627–37. Vidailhet M, Jutras MF, Grabli D, Roze E. Deep brain stimulation for dystonia. J Neurol Neurosurg Psychiatry. 2013;84(9):1029–42. Zhang JG, Zhang K, Wang ZC, Ge M, Ma Y. Deep brain stimulation in the treatment of secondary dystonia. Chin Med J (Engl). 2006;119(24):2069–74. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8826724","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":598456842,"identity":"5db8e45c-2d0d-4bc0-9ab5-88f87eab27a5","order_by":0,"name":"Taro Ogawa","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYDACdjB5AMhoANIGFkRoYYZp4TkA0iJBihaJBBCDCC38zTxmH37U3JEzl3x+dcOPAgkG/vbuBLxaJA7zGM/sOfbM2HJ2TtnNHqDDJM6c3YBXiwEzjzEDb8PhxA23c9Ju8AC1GEjkEtbC+Bek5eaZtJt/iNXCDLblBvux20TZInGYrZhZ5thhY4MzOWy3ZQwkeAj6hb+9eTPjm5rDcgbHjz+7+eaPjRx/ey9+LUiAxwBMEqscBNgfkKJ6FIyCUTAKRhAAAMcBRUOkrkcAAAAAAElFTkSuQmCC","orcid":"","institution":"Sapporo Keijinkai Rehabilitation Hospital","correspondingAuthor":true,"prefix":"","firstName":"Taro","middleName":"","lastName":"Ogawa","suffix":""},{"id":598456843,"identity":"bbe27c28-7a10-4547-be9b-1e150c3a1b63","order_by":1,"name":"Kazutoshi Yokogushi","email":"","orcid":"","institution":"Sapporo Keijinkai Rehabilitation Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kazutoshi","middleName":"","lastName":"Yokogushi","suffix":""},{"id":598456844,"identity":"2b30a743-473e-454e-910b-ccd692c30e3f","order_by":2,"name":"Yasunori Mito","email":"","orcid":"","institution":"Sapporo City General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yasunori","middleName":"","lastName":"Mito","suffix":""},{"id":598456845,"identity":"5968febf-f27b-43ae-a6d2-394598056fef","order_by":3,"name":"Shigeki Hashimoto","email":"","orcid":"","institution":"Sapporo Keijinkai Rehabilitation Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shigeki","middleName":"","lastName":"Hashimoto","suffix":""}],"badges":[],"createdAt":"2026-02-09 06:41:39","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8826724/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8826724/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104170081,"identity":"6f8276bf-31e6-4b44-b5a2-e38116ff1379","added_by":"auto","created_at":"2026-03-08 14:43:16","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":467482,"visible":true,"origin":"","legend":"\u003cp\u003eAxial fluid-attenuated inversion recovery (FLAIR) (left) and T2-weighted (right) brain magnetic resonance images. Both images show bilateral low signal intensity lesions in the globus pallidus (arrowheads).\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8826724/v1/cc061d7f1d766827618f388e.png"},{"id":104170078,"identity":"4f269cfa-93b4-473e-bef1-39d36121b4eb","added_by":"auto","created_at":"2026-03-08 14:43:14","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":274220,"visible":true,"origin":"","legend":"\u003cp\u003eTimeline showing the treatment course. The first visit to our hospital (dark yellow inverted triangle) was nine months after cardiac arrest onset. Sixteen sessions of botulinum toxin (BoNT-A) therapy were performed (orange inverted triangles). Deep brain stimulation was administered from month 60 to month 85 (green shading). The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) Movement scale left arm subscores (green circles, solid line) and body weight (blue squares, dashed line) are also presented.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8826724/v1/15e8ef9fcf04809f2910efca.png"},{"id":104170080,"identity":"2e9dee69-10a1-4b67-9bb3-6e544a311c9e","added_by":"auto","created_at":"2026-03-08 14:43:15","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":953004,"visible":true,"origin":"","legend":"\u003cp\u003eTemporal progression of painful tonic spasms (PTS) and painless dystonic contractions in representative muscles.\u003c/p\u003e\n\u003cp\u003eColored ellipses indicate sites of prominent muscle contractions: red denotes muscles with painful tonic spasms, and blue denotes painless involuntary muscle contractions. Only representative muscles from Table 1 are shown.\u003c/p\u003e\n\u003cp\u003e(A) At the time of the first BoNT-A injection, painful tonic spasms (PTS) were confined to the left biceps brachii, whereas painless dystonic contractions were present in the left pectoralis major, latissimus dorsi, triceps brachii, flexor pollicis longus, and extensor hallucis longus bilaterally.\u003c/p\u003e\n\u003cp\u003e(B) By the sixth injection, PTS had spread to include the left pectoralis major, latissimus dorsi, triceps brachii, and first dorsal interosseous; pain in the left biceps brachii had lessened.\u003c/p\u003e\n\u003cp\u003e(C) By the eleventh injection, the most intense pain localized to the left lumbrical muscles. Additional painful spasms were present in the left triceps brachii and in the extensor hallucis longus and extensor digitorum longus bilaterally.\u003c/p\u003e\n\u003cp\u003e(D) By the fifteenth injection, the most severe PTS again centered on the left biceps brachii. PTS in the left triceps brachii had resolved, and both the frequency and intensity of pain had markedly decreased compared with the initial presentation..\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8826724/v1/fecb113c89d4efa6b44ca32c.png"},{"id":105363174,"identity":"bb13fe34-9694-4104-a410-3421551b5784","added_by":"auto","created_at":"2026-03-25 08:13:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2316582,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8826724/v1/34a4e043-1b58-4541-8e9f-c45c5b9877e3.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Painful Tonic Spasms with Multifocal Dystonia After Cardiac Arrest Showing Emigration-like Pattern Changes During Long-term Botulinum Toxin Type A Therapy A Case Report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCardiac arrest refers to the cessation of cardiac mechanical activity with absent signs of circulation. Even when resuscitation is successful, patients may suffer hypoxic encephalopathy with neurological sequelae such as persistent vegetative states, seizures, cognitive impairment, and movement disorders. Post-hypoxic myoclonus, often termed Lance\u0026ndash;Adams syndrome, is well recognized, and various other movement disorders have been reported following cardiac arrest, including parkinsonism, dystonia, chorea, tics, tremor, ballism, and athetosis.(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Scheibe et al. reported a case series of 72 patients with adult-onset cardiac arrest, of whom seven developed dystonia.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) However, the clinical phenotypes and longitudinal evolution of post-anoxic dystonia, particularly in relation to treatment response, have not been described in detail.\u003c/p\u003e \u003cp\u003ePharmacological treatment for dystonia involves oral medications and botulinum neurotoxin type A (BoNT-A) injections. BoNT-A is particularly effective for focal and segmental dystonia.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Generalized dystonia may also be treated with BoNT-A by targeting particularly problematic features.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Pattern changes in dystonic symptoms during repeated BoNT-A therapy have been documented in patients with cervical dystonia.(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) However, whether similar pattern changes occur in other forms of dystonia has not been well established. The scarcity of information regarding these evolving clinical features may hinder clinicians in making treatment decisions for dystonia patients.\u003c/p\u003e \u003cp\u003eOn the other hand, tonic spasms are characterized by sustained increases in muscle tone affecting a single muscle group and are generally considered distinct from dystonia, although clinical overlap may occur.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) When these spasms are accompanied by significant pain, they are referred to as painful tonic spasms (PTS). PTS has been well described in spinal cord disorders, including neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD).(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Other spinal cord conditions, such as Sj\u0026ouml;gren\u0026rsquo;s syndrome,(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) have also been associated with PTS, but they have rarely been reported after brain lesions.\u003c/p\u003e \u003cp\u003eWe report the first case of multifocal dystonia overlapping with painful tonic spasms (PTS) following cardiac arrest and describe the eight-year clinical course of BoNT-A therapy, focusing on emigration-like pattern changes, in which dystonic muscle contractions shifted away from BoNT-A\u0026ndash;injected sites.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eWe present this case in accordance with the CARE reporting guideline. A woman in her 40s with no significant past medical history or relevant family history was admitted to a tertiary hospital and diagnosed with thyroid storm due to Graves' disease. On the following day, she experienced cardiac arrest and was successfully resuscitated after 25 minutes. She subsequently underwent radioactive iodine therapy for Graves' disease and was discharged after 54 days with no apparent neurological or cognitive deficits. However, she developed progressive limb dysfunction and speech disturbances. Fifty-three days after discharge, she presented to the neurology department of the same hospital. Neurological examination revealed slow speech, rigid-spastic tone in all limbs, athetoid involuntary movements, increased tendon reflexes in the upper extremities, absence of pathological reflexes, bradykinesia, and a shuffling gait, without pain or cognitive impairment.\u003c/p\u003e \u003cp\u003eBrain MRI demonstrated bilateral low-intensity signals in the globus pallidus, consistent with hypoxic encephalopathy (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Laboratory investigations including thyroid function tests, autoimmune markers, and cerebrospinal fluid analysis were unremarkable, excluding neuromyelitis optica spectrum disorder, multiple sclerosis, Sj\u0026ouml;gren's syndrome, and paraneoplastic disorders. Electroencephalography showed no epileptiform activity or features suggestive of Lance-Adams syndrome. She was diagnosed with involuntary movements due to hypoxic encephalopathy following cardiac arrest and was treated with tiapride, clonazepam, and levodopa, but with limited efficacy.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eNine months after the cardiac arrest, she was referred to our hospital for outpatient rehabilitation to address gait disturbance due to involuntary movements. The most distressing symptom at that time was severe painful muscle contractions in her left arm.\u003c/p\u003e \u003cp\u003eAt the first visit, she was fully alert and oriented, speaking slowly in a gravelly voice. Cranial nerve examination revealed no abnormalities except for slowed tongue movements without atrophy or paresis. Motor examination showed normal deep tendon reflexes and no pathological reflexes. The left elbow flexors exhibited intermittent, involuntary contractions accompanied by excruciating pain. These paroxysmal painful spasms were triggered by specific actions such as speaking, standing, yawning, or laughing, but were absent at rest. The patient reported that episodes occurred more than one hundred times per day, each lasting less than one minute, and could not be voluntarily suppressed. During these spasms, muscle contractions were so intense that they resisted passive extension, whereas muscle tone normalized between episodes. Involuntary movements occasionally extended beyond elbow flexion to include reaching motions, finger extension in the left upper limb, and toe extension in both feet.\u003c/p\u003e \u003cp\u003eMuscle strength in the right arm and both legs was preserved, but movement of the left leg was impaired and uncoordinated. Sensory and autonomic functions were normal, and no apparent cognitive deficits were observed. She was able to walk indoors by holding onto furniture or walls and remained independent in activities of daily living.\u003c/p\u003e \u003cp\u003eThe involuntary movements initially appeared consistent with dyskinesia, as they manifested as non-patterned, paroxysmal episodes of gross movement. During follow-up, however, dyskinetic features diminished, and sustained movements became more prominent, while painful intermittent spasms continued to represent the most disabling symptom affecting her quality of life. We therefore considered the movement disorder to be painful tonic spasms (PTS) overlapping with multifocal dystonia, characterized by both painful paroxysmal contractions and sustained painless dystonic postures.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eTreatment and Clinical Course\u003c/h2\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e summarizes the eight-year clinical course. The referring neurologist continued to manage the patient with oral medications throughout the follow-up period. We initiated botulinum toxin type A (BoNT-A) therapy as an additional treatment modality to address the disabling involuntary movements.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eClinical severity was assessed using the Movement scale of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), a validated tool for evaluating dystonia.(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) We specifically used the Movement scale component, which assessed dystonia across nine body regions, with total scores ranging from 0 to 120.(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) The Disability scale was not adopted because functional impairment was influenced by multiple non-dystonic factors including falls, trauma, and weight loss from dysphagia. All retrospective BFMDRS Movement scale scoring was performed by the first author (T.O.) based on detailed clinical and rehabilitation records. We tracked the left arm subscore for two reasons: first, retrospective scoring was incomplete for other body regions; second, lower limb function was influenced by the same non-dystonic factors, making the leg subscores less reliable for reflecting dystonia severity. Body weight was also monitored as an indicator of general condition.\u003c/p\u003e \u003cp\u003eOnabotulinumtoxinA, a preparation of botulinum neurotoxin type A (BoNT-A), was diluted with physiological saline to a concentration of 20 units/mL. The sites and doses of injections were determined at each session based on the patient\u0026rsquo;s symptoms and physical findings. Ultrasonography was used to guide injections into deep muscles such as the iliopsoas muscles. Electromyographic guidance was not available at our hospital.\u003c/p\u003e \u003cp\u003eAt the first injection session, we primarily targeted muscles in the left arm, including the biceps brachii, brachialis, and brachioradialis. We also injected the extensor hallucis longus of the left great toe, which exhibited painless dystonic contractions (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMuscle targets, doses, and treatment timeline across 16 sessions of botulinum neurotoxin type A injection.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"19\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c17\" colnum=\"17\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c18\" colnum=\"18\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c19\" colnum=\"19\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSession number\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c15\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c16\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c17\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c18\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c19\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMonths from first visit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c15\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c19\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDeep Brain Stimulation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR. UE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDel.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL. UE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c15\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDel.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c15\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBra\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c15\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eECR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eECU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c15\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFPL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c15\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEDC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFDI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLu. I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLu. II-IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e12.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR. LE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEDL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c15\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEHL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c15\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL. LE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEDL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c15\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEHL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c15\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c18\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"19\"\u003eThe \u0026ldquo;Deep Brain Stimulation\u0026rdquo; row marks the start and end of therapy, and grey shading indicates the period during which stimulation was ongoing. Numbers in each muscle row indicate the units of onabotulinumtoxinA injected per session. Blank cells indicate no injection.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"19\"\u003eAbbreviations (listed in order of appearance in the table) : Del, deltoid; TB, triceps brachii; PM, pectoralis major; LD, latissimus dorsi; TM, teres major; BB, biceps brachii; Bra, brachialis; BR, brachioradialis; ECR, extensor carpi radialis; ECU, extensor carpi ulnaris; FPL, flexor pollicis longus; FDS, flexor digitorum superficialis; EDC, extensor digitorum communis; FDI, first dorsal interosseous; Lu, lumbricals; EDL, extensor digitorum longus; EHL, extensor hallucis longus; IP, iliopsoas; AM, adductor magnus; VL, vastus lateralis.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOver sixteen BoNT-A injection sessions spanning eight years, the distribution of painful and painless dystonic contractions gradually evolved. The distribution of painful tonic spasms (PTS) initially shifted to adjacent muscle groups, then spread to remote muscles, and eventually returned to the left elbow flexors, as illustrated in Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB-D. Although injections consistently reduced the frequency of spasms, pain relief was often insufficient.\u003c/p\u003e \u003cp\u003eBecause BoNT-A injections alone did not achieve adequate symptom control, additional oral medications\u0026mdash;including dantrolene, tizanidine, and diazepam\u0026mdash;were attempted, but none provided clinical benefit. Deep brain stimulation (DBS) targeting the bilateral globus pallidus internus (GPi) was performed five years after symptom onset (between the eighth and ninth BoNT-A sessions, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). However, it failed to provide clinical benefit and the DBS system was removed two years later at the patient\u0026rsquo;s request.\u003c/p\u003e \u003cp\u003eAlthough the left arm subscore of the BFMDRS Movement scale decreased transiently after BoNT-A injections, it remained relatively stable at baseline for several years before temporarily worsening. Body weight declined due to dysphagia, likely resulting from recurrent laryngeal nerve palsy diagnosed 56 months after the cardiac arrest. Following the introduction of home suction equipment to manage excessive saliva, the patient's oral intake improved and body weight gradually recovered. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, the temporal patterns of body weight and baseline BFMDRS Movement left arm subscores appeared to change inversely.\u003c/p\u003e \u003cp\u003eTreatment was generally well-tolerated. The only notable adverse event was transient weakness of finger extension following the ninth injection session, which resolved spontaneously. No serious adverse events occurred throughout the eight-year treatment period.\u003c/p\u003e \u003cp\u003eNeuropsychometric testing confirmed intact cognitive function, and she was cleared to drive based on driving simulator and on-road assessments. However, her functional independence gradually deteriorated due to evolving dystonic symptoms, recurrent falls with trauma, and deconditioning during the period of weight loss.\u003c/p\u003e \u003cp\u003eDespite subsequent weight recovery, physical function did not fully return, and she eventually required partial assistance with activities of daily living.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case report presents two novel clinical observations in post-anoxic movement disorders: the first documented case of painful tonic spasms (PTS) coexisting with multifocal dystonia following cardiac arrest, and emigration-like pattern changes of dystonic muscle contractions away from botulinum toxin-injected sites over an eight-year treatment course.\u003c/p\u003e \u003cp\u003ePTS is well-established as a characteristic symptom of neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD).(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) In contrast, PTS following primary brain lesions has rarely been documented, with only one reported case of putaminal infarction.(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eOur patient presented with coexisting PTS and multifocal dystonia. Differentiating these conditions is challenging because both can be painful. In cervical dystonia, pain arises from musculoskeletal and myofascial factors without necessarily correlating with the extent of dystonic posturing or muscle tone.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) In contrast, PTS is characterized by its paroxysmal nature, shorter duration (seconds to minutes), and prominence of pain.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) Jabbari et al. described this overlap in a case of Sj\u0026ouml;gren's syndrome, using the term \"painful/dystonic\" spasms.(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) Similarly, our patient demonstrated features of both conditions: multifocal dystonia involving the left arm and both legs, and localized, paroxysmal, painful contractions characteristic of PTS.\u003c/p\u003e \u003cp\u003ePharmacological treatments for PTS include antiepileptic agents such as carbamazepine, oxcarbazepine, gabapentin, clonazepam, phenytoin, levetiracetam, and topiramate, as well as benzodiazepines, barbiturates, baclofen, pregabalin, and duloxetine.(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) Botulinum neurotoxin type A (BoNT-A) has also been reported to be beneficial.(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eWe observed dynamic migration of involuntary movements irrespective of pain over sixteen sessions of BoNT-A treatment spanning eight years. To our knowledge, this is the first report documenting pattern changes of dystonic muscle contractions in multifocal dystonia during BoNT-A therapy. Pattern changes following BoNT-A injections have been well-documented in cervical dystonia.(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) In their case series of 20 patients, Gelb et al. performed electromyographic (EMG) studies to compare muscle activity patterns before and after botulinum toxin injections. While patients showed general depression of EMG activity in injected muscles even after clinical effects had disappeared, there was a tendency for muscles that had not been injected to show increased EMG activity. The authors speculated that torticollis results from an abnormal motor program for head position, and suggested that when the most active muscles are functionally denervated by botulinum toxin, this program may call on other muscles to achieve its ends.(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) The pattern changes observed in our patient share features of Gelb's findings\u0026mdash;specifically, reduced dystonic activity at BoNT-A injection sites. However, our patient demonstrated not only compensatory recruitment to replicate the same dystonic movements but also emigration-like pattern changes, in which dystonic contractions shifted away from injection sites to adjacent and remote muscle groups.\u003c/p\u003e \u003cp\u003eThe gradual redistribution of dystonic activity may reflect central nervous system plasticity induced by repeated peripheral denervation. In their fMRI study, Nevrl\u0026yacute; et al. indicated that the first BoNT-A injection was associated with widespread changes in sensorimotor network activation, reducing baseline differences between patients and healthy controls and suggesting cortical modulation following peripheral chemodenervation.(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) They also demonstrated that dystonia involves widespread sensorimotor network abnormalities extending into cortical representations of body regions not clinically affected.(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) One possible explanation is that BoNT-A\u0026ndash;induced modulation of these altered networks may suppress dystonic output corresponding to injected sites, thereby allowing pre-existing abnormal activity in non-injected representations to become clinically manifest in other body regions. This mechanistic link has yet to be fully elucidated. Therefore, the observed emigration-like pattern changes should be interpreted cautiously. Alternative explanations\u0026mdash;including natural disease evolution in post-hypoxic injury, compensatory motor strategies, cumulative effects of multiple BoNT-A injection sessions, and the effects of concurrent treatments\u0026mdash;cannot be excluded. Nevertheless, careful longitudinal observation of symptom distribution during repeated BoNT-A injections may provide useful insights into the evolving phenomenology of multifocal dystonia.\u003c/p\u003e \u003cp\u003eWe also attempted deep brain stimulation (DBS) targeting the bilateral globus pallidus internus, but this did not result in meaningful improvement. Several factors may have contributed to the poor response in this case. The DBS period coincided with progressive weight loss and clinical deterioration, which may have confounded the assessment of treatment efficacy. Additionally, the efficacy of DBS for secondary dystonia varies(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e), Zhang et al. reported that patients with diffuse basal ganglia damage are suboptimal candidates for DBS,(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) consistent with our patient's extensive bilateral basal ganglia lesions on MRI. They also suggested that STN stimulation might be theoretically superior to GPi due to its upstream position in the basal ganglia motor circuit.(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) However, whether alternative targets such as the STN would have been more effective in our patient remains unknown.\u003c/p\u003e \u003cp\u003eThis case report has several limitations. First, as a single case report, our findings require validation through larger case series or well-designed studies to establish whether the emigration-like pattern changes are commonly observed in multifocal dystonia. Second, we were unable to perform electrophysiological studies because the necessary equipment was unavailable. Third, we used the left arm subscore of the BFMDRS Movement scale to assess the severity of dystonia, but scores were assigned retrospectively due to incomplete routine clinical assessment, which might affect the reliability of these scores. Fourth, assessment of pain response was challenging: while spasm frequency decreased, the extremely high baseline frequency of PTS episodes (more than 100 times daily before treatment) precluded precise counting, and pain intensity often remained unchanged. Fifth, concurrent treatments including oral medications and DBS may have influenced the observed symptom evolution, making it difficult to isolate the specific effects of BoNT-A.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eCardiac arrest may lead to various forms of movement disorders. This case highlights the clinical significance of painful tonic spasms as a neurological sequela following cardiac arrest. In addition, this case demonstrated the coexistence of multifocal dystonia, in which long-term botulinum toxin therapy was accompanied by emigration-like pattern changes of dystonic muscle contractions, shifting away from BoNT-A injection sites to adjacent or distant areas. These observations may help clinicians anticipate the need for progressive adjustment of injection sites, optimize long-term treatment planning, and refine injection strategies during extended BoNT-A therapy for multifocal dystonia.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003ePatient\u0026rsquo;s perspective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;I was told that my 25-minute cardiac arrest would likely leave aftereffects. I worked hard in rehab and was able to walk out of the hospital, but I couldn\u0026rsquo;t jump, which may have been the first sign of what followed.After discharge, I couldn\u0026rsquo;t put on stockings or fasten a necklace for my son\u0026rsquo;s graduation\u0026mdash;also due to aftereffects. Gradually losing the ability to walk and speak was the hardest part for me. I couldn\u0026rsquo;t accept that I could no longer do what used to come naturally. I loved exercising and singing, but lost all of it. I was truly happy when painful muscle contractions in my left arm eased with botulinum toxin injections. Now, I rely on a caregiver, but I try to find things I can still do, like cooking and working on the computer. I continue rehabilitation with a positive and hopeful mindset.\u003cbr\u003e \u003cstrong\u003ePatient\u0026rsquo;s perspective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;I was told that my 25-minute cardiac arrest would likely leave aftereffects. I worked hard in rehab and was able to walk out of the hospital, but I couldn\u0026rsquo;t jump, which may have been the first sign of what followed.After discharge, I couldn\u0026rsquo;t put on stockings or fasten a necklace for my son\u0026rsquo;s graduation\u0026mdash;also due to aftereffects. Gradually losing the ability to walk and speak was the hardest part for me. I couldn\u0026rsquo;t accept that I could no longer do what used to come naturally. I loved exercising and singing, but lost all of it. I was truly happy when painful muscle contractions in my left arm eased with botulinum toxin injections. Now, I rely on a caregiver, but I try to find things I can still do, like cooking and working on the computer. I continue rehabilitation with a positive and hopeful mindset.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e This study was approved by the Institutional Review Board of Sapporo Keijinkai Rehabilitation Hospital (approval number 2024-45). The study was performed in line with the principles of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e Informed consent was obtained from all the individual participants for participation in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish\u003c/strong\u003e Written informed consent for publication and accompanying images was obtained from the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e One of the co-authors has received an honorarium from GlaxoSmithKline for serving as a chairperson at a company-sponsored lecture and industry support from GlaxoSmithKline for a medical meeting at which the co-author served as the conference chair. All other authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e The authors did not receive support from any organization for the submitted work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e TO: conception of the work, data collection, drafting and revising the manuscript. KY: participated in patient management, documented daily clinical findings and symptoms, and critically reviewed the manuscript. YM: referring neurologist; provided detailed information on the clinical course prior to referral, initial neurological findings, diagnostic test results, and pharmacological treatments; reviewed the manuscript. SH: senior clinician responsible for the patient\u0026apos;s care; supervised the writing of the report and approved the clinical content. All authors approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data underlying this case report consist of clinical information from an individual patient and cannot be made publicly available due to privacy and ethical restrictions. De-identified data may be shared by the corresponding author upon reasonable request and with appropriate institutional approval.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLu-Emerson C, Khot S. Neurological sequelae of hypoxic-ischemic brain injury. NeuroRehabilitation. 2010;26(1):35\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScheibe F, Neumann WJ, Lange C, Scheel M, Furth C, K\u0026ouml;hnlein M, et al. Movement disorders after hypoxic brain injury following cardiac arrest in adults. Eur J Neurol. 2020;27(10):1937\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDressler D, Adib Saberi F, Rosales RL. Botulinum toxin therapy of dystonia. J Neural Transm. 2021;128(4):531\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGelb DJ, Yoshimura DM, Olney RK, Lowenstein DH, Aminoff MJ. Change in pattern of muscle activity following botulinum toxin injections for torticollis. Ann Neurol. 1991;29(4):370\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaňovsk\u0026yacute; P, Dufek J, Halačkov\u0026aacute; H, Rektor I. Change in the pattern of cervical dystonia might be the cause of benefit loss during botulinum toxin treatment. Eur J Neurol. 1997;4(1):79\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSarin S, Lawal T, Abboud H. Spinal dystonia and other spinal movement disorders. Dystonia. 2023;2:11303.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJabbari B, Salardini A. Painful tonic/dystonic spasms in Sjogren's syndrome. Mov Disord. 1999;14(5):860\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBurke RE, Fahn S, Marsden CD, Bressman SB, Moskowitz C, Friedman J. Validity and reliability of a rating scale for the primary torsion dystonias. Neurology. 1985;35(1):73\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMerchut MP, Brumlik J. Painful tonic spasms caused by putaminal infarction. Stroke. 1986;17(6):1319\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRelja M, Miletić V. When movement disorders hurt: Addressing pain in hyperkinetic disorders. Parkinsonism Relat Disord. 2017;44:110\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAsseyer S, Cooper G, Paul F. Pain in NMOSD and MOGAD: A Systematic Literature Review of Pathophysiology, Symptoms, and Current Treatment Strategies. Front Neurol. 2020;11:778.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRestivo DA, Tinazzi M, Patti F, Palmeri A, Maimone D. Botulinum toxin treatment of painful tonic spasms in multiple sclerosis. Neurology. 2003;61(5):719\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNevrl\u0026yacute; M, Hlušt\u0026iacute;k P, Hok P, Otruba P, T\u0026uuml;d\u0026ouml;s Z, Kaňovsk\u0026yacute; P. Changes in sensorimotor network activation after botulinum toxin type A injections in patients with cervical dystonia: a functional MRI study. Exp Brain Res. 2018;236(10):2627\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVidailhet M, Jutras MF, Grabli D, Roze E. Deep brain stimulation for dystonia. J Neurol Neurosurg Psychiatry. 2013;84(9):1029\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang JG, Zhang K, Wang ZC, Ge M, Ma Y. Deep brain stimulation in the treatment of secondary dystonia. Chin Med J (Engl). 2006;119(24):2069\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8826724/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8826724/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntroduction. Secondary dystonia may result from various disorders, including cardiac arrest, and has been reported to be successfully treated with botulinum toxin type A (BoNT-A) injections. However, the long-term clinical course following repeated BoNT-A therapy remains largely undocumented, particularly with respect to pattern changes in dystonic contractions in non-cervical forms of dystonia.\u003c/p\u003e \u003cp\u003eCase Presentation. A woman in her 40s developed multifocal dystonia after cardiac arrest caused by thyroid storm. She exhibited involuntary movements in her left arm and both legs. Paroxysmal painful muscle spasms occurred in the left arm more than one hundred times daily, each lasting less than one minute and accompanied by excruciating pain. Brain MRI revealed bilateral low-intensity signals in the basal ganglia consistent with hypoxic encephalopathy. She was diagnosed with painful tonic spasms (PTS) overlapping with multifocal dystonia. Oral pharmacological therapies, including tiapride, clonazepam, and levodopa, were insufficiently effective. BoNT-A injections reduced spasm frequency but provided limited pain relief. Over sixteen BoNT-A injection sessions spanning eight years, both painful and painless dystonic muscle contractions demonstrated dynamic redistribution, and the severity of involuntary movements and pain burden gradually improved.\u003c/p\u003e \u003cp\u003eConclusion. To our knowledge, this is the first report of PTS overlapping with multifocal dystonia following cardiac arrest. We observed an emigration-like redistribution of dystonic muscle contractions during long-term BoNT-A therapy. While pattern changes after BoNT-A injections are well documented in cervical dystonia, such changes have rarely been described in multifocal dystonia. In this case, dystonic activity shifted away from BoNT-A\u0026ndash;injected sites to adjacent and distant muscle groups.\u003c/p\u003e","manuscriptTitle":"Painful Tonic Spasms with Multifocal Dystonia After Cardiac Arrest Showing Emigration-like Pattern Changes During Long-term Botulinum Toxin Type A Therapy A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-08 14:43:10","doi":"10.21203/rs.3.rs-8826724/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a34d3429-4a38-40a5-91e2-ad762cf2f853","owner":[],"postedDate":"March 8th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-25T08:12:56+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-08 14:43:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8826724","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8826724","identity":"rs-8826724","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}