- Email: [email protected]
185. Disassociation mechanism of progenitor complex of botulinum neurotoxin serotype E
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Abstracts / Toxicon 93 (2015) S2eS67
184. PRIMARY SPEECH-INDUCED LINGUAL DYSTONIA: A RARE FOCAL DYSTONIA e TWO FURTHER CASES OF ILLNESS Andrea Stenner*, Gerhard Reichel Paracelsus Clinic, Saxony, Germany
and X-ray diffraction. We will discuss the disassociation mechanism by which BoNT/E enters the general circulation at neutral pH. We also show that both partners change their molecular conformation on separation. Keywords: Clostridium botulinum; CryoEM; Non-toxin-non hemagglutinin; (NTNH); Progenitor complex; Serotype E; X-ray diffraction
*Corresponding author: Werdauer Str. 68, Zwickau, Saxonia D-08060, Germany. E-mail address: [email protected]
186. APPLIED ANATOMY FOR FACIAL INJECTIONS
Introduction and Objectives: Primary speech-induced lingual dystonia (SILD) occurs very rarely. In this disorder, dystonic lingual movements are triggered only during speech. For this reason, speech is clearly impaired, as words cannot be articulated due to involuntary movements of the tongue, usually with curling of the tongue upward or downward. To date, only 6 cases have been described in the literature. Methods: Two women (ages 16 and 44 years) fell ill with SILD within 1 to 2 years. The overall neurologic and clinical status indicated slight right hemidystonia undiagnosed to date in the 16-year-old woman. The 44year-old woman could reduce tongue movements somewhat by chewing gum. No such trick helped the other patient. In both cases, there was upward curling of the tongue. Results and treatments: Electromyographic (EMG) testing of the intrinsic tongue musculature showed dense patterns of action potentials of motoric units. Attempted treatment with levodopa (L-dopa) produced no effect in the 44-year-old. Surprisingly, in the younger woman, there was a clear improvement in speech with L-dopa treatment, leading to abandonment of a planned treatment with botulinum neurotoxin (BoNT). Her dystonia symptoms worsened when she inadvertently forgot to take L-dopa. An EMG-guided injection of 0.25 mL botulinum neurotoxin type A ([BoNT/ A] 12.5 U Xeomin [incobotulinumtoxinA]) into each of the mm. transversi linguae was performed in the 44-year-old woman. For 4 years now, she has gotten along very well with BoNT treatment at intervals of 6 to 8 weeks. Conclusions: Even with the rare disorder SILD, an L-dopa test should always be performed. EMG-guided BoNT treatment can be an effective therapy; 2 such cases have already been reported in the literature (Degirmenci 2011; Budak 2013). References Budak F, Aydin E, Koçkaya A, Ilbay G. Botulinum toxin in the treatment of lingual dystonia induced by speaking. Case Rep Neurol. 2013;5(1):18-20. Degirmenci Y, Ors CH, Yilmaz U, Karaman HI. Isolated lingual dystonia induced by speaking: a rare form of focal dystonia. Acta Neurol Belgiq. 2011;111(4):360-361. 185. DISASSOCIATION MECHANISM OF PROGENITOR COMPLEX OF BOTULINUM NEUROTOXIN SEROTYPE E Subramanyam Swaminathan a, *, S. Eswaramoorthy a, J. Sun a, H. Li a, B.R. Singh b a Biosciences Department, Brookhaven National Laboratory, Upton, NY, USA; b Botulinum Research Center, Institute of Advanced Sciences, Dartmouth, MA, USA *Corresponding author: Brookhaven National Laboratory, Upton, NY 11973, USA. E-mail address: [email protected]
Botulinum neurotoxin (BoNT), produced by Clostridium botulinum, the most potent protein toxin known to humans, is released as a progenitor toxin complex (PTC), with at least 1 nontoxic nonhemagglutinin protein (NTNH) and several other neurotoxin-associated proteins (NAPs) held together by noncovalent interactions. Depending on the number of proteins forming the complex, 3 kinds of complexes, LL, L, and M, are formed with molecular masses of 900, 500, and 300 kDa, respectively. When ingested by mouth, the components of the progenitor toxin complexes protect the neurotoxin from the harsh conditions of low pH and proteases present in the gastrointestinal tract, enabling its release into the blood circulation. However, the structural arrangement of NAPs and the mechanism by which they protect the BoNT is not yet well understood. Knowledge of the three-dimensional organization of these proteins, their individual structures, and mutual interactions with other components of the PTC will lead to an understanding of the role of NAPs in transcytosis and protecting the BoNT from degradation. We have examined the structure of the M progenitor toxin complex of BoNT serotype E (M-PTC/E), consisting of BoNT/E and NTNH-E, by cryo-electron microscopy (Cryo-EM)
Jonathan M. Sykes Facial Plastic and Reconstructive Surgery, UC Davis Medical Group, 2521 Stockton Blvd., Suite 6206, Sacramento, CA 95817, USA. E-mail address: [email protected]
In order to successfully perform any facial injection, a systematic evaluation of facial aesthetics is essential. In addition, a detailed knowledge of the applied anatomy of the face is necessary. This includes an understanding of topographic landmarks that will allow predictable identification of deeper structures. Specifically, any practitioner who injects botulinum toxin should have a thorough knowledge of all soft-tissue and skeletal structures, from superficial to deep. The location and action of all pertinent facial muscles is important. Additionally, the position of the associated muscle action potentials is critical to maximize the impact of each injection and to minimize the possibility of untoward side effects. The periorbital region is an area where hyperfunction of muscles results in a tired and aged appearance and increased rhytides. The relationship of the eyebrow elevators and depressors is important. Correct placement of appropriate amounts of toxin to minimize rhytides, without negatively affecting eyebrow position, is important. The applied anatomy of the facial muscles as they relate to other anatomic structures, and the depth and topography of the musculature, are reviewed, with an emphasis on promoting efficient injections and avoiding complications. 187. PILOT STUDY TO ESTABLISH PROOF OF PRINCIPLE FOR THE USE OF ONABOTULINUMTOXINA (BOTOX) IN THE TREATMENT OF NOCTURNAL BRUXISM WITH ASSOCIATED CRANIOFACIAL PAIN Deborah R. Syna Northwest Neurological Specialists PC, 1585 SW Marlow #110, Portland, OR 97225, USA. E-mail address: [email protected] Introduction and Objectives: Nocturnal bruxism, the repetitive grinding, clenching, and chewing movements of the jaw during sleep, can occur in both children and adults. Case series and anecdotal reports suggest that botulinum neurotoxin type A injection may provide effective treatment of nocturnal bruxism and its sequelae. Open-label trials for patients with nocturnal bruxism indicate that it may confer reduction in pain medication use and migraine headache frequency. This open-label pilot study sought to establish “proof of principle” for the use of onabotulinumtoxin A (Botox) to treat nocturnal bruxism with associated craniofacial pain. Methods: The primary outcome measure of this study was the change in number of electromyography (EMG) bursts in the temporalis and masseter muscles as measured during nocturnal polysomnography in an accredited sleep laboratory. Polysomnograms were administered once for baseline measurement and at weeks 4 and 8 after injection of 100 to 150 U onabotulinumtoxinA in a fixed site pattern including temporalis and masseter muscles. Results: Five consenting patients with nocturnal bruxism and craniofacial pain who had tried dental prosthetics and failed trials of at least 2 prophylactic headache medications were enrolled. Four patients completed the trial. No serious adverse events were experienced by any patient. Average number of bruxism events decreased through week 4 after treatment. One of 4 participants’ polysomnograph showed consistent decrease in bruxism events in the weeks following treatment, but, overall, the trends did not reach statistical significance. Secondary outcome measures that demonstrated a trend for improvement included bed partner survey of bruxing activity and sleep interruption, daily subject craniofacial pain diary, Headache Impact Test (HIT-6), and Migraine Disability Assessment scores. Sleep efficiency and percentage of rapid eye movement (REM) sleep on polysomnograms also demonstrated a trend toward improvement after injection but did not reach statistical significance.
Abstracts / Toxicon 93 (2015) S2eS67
184. PRIMARY SPEECH-INDUCED LINGUAL DYSTONIA: A RARE FOCAL DYSTONIA e TWO FURTHER CASES OF ILLNESS Andrea Stenner*, Gerhard Reichel Paracelsus Clinic, Saxony, Germany
and X-ray diffraction. We will discuss the disassociation mechanism by which BoNT/E enters the general circulation at neutral pH. We also show that both partners change their molecular conformation on separation. Keywords: Clostridium botulinum; CryoEM; Non-toxin-non hemagglutinin; (NTNH); Progenitor complex; Serotype E; X-ray diffraction
*Corresponding author: Werdauer Str. 68, Zwickau, Saxonia D-08060, Germany. E-mail address: [email protected]
186. APPLIED ANATOMY FOR FACIAL INJECTIONS
Introduction and Objectives: Primary speech-induced lingual dystonia (SILD) occurs very rarely. In this disorder, dystonic lingual movements are triggered only during speech. For this reason, speech is clearly impaired, as words cannot be articulated due to involuntary movements of the tongue, usually with curling of the tongue upward or downward. To date, only 6 cases have been described in the literature. Methods: Two women (ages 16 and 44 years) fell ill with SILD within 1 to 2 years. The overall neurologic and clinical status indicated slight right hemidystonia undiagnosed to date in the 16-year-old woman. The 44year-old woman could reduce tongue movements somewhat by chewing gum. No such trick helped the other patient. In both cases, there was upward curling of the tongue. Results and treatments: Electromyographic (EMG) testing of the intrinsic tongue musculature showed dense patterns of action potentials of motoric units. Attempted treatment with levodopa (L-dopa) produced no effect in the 44-year-old. Surprisingly, in the younger woman, there was a clear improvement in speech with L-dopa treatment, leading to abandonment of a planned treatment with botulinum neurotoxin (BoNT). Her dystonia symptoms worsened when she inadvertently forgot to take L-dopa. An EMG-guided injection of 0.25 mL botulinum neurotoxin type A ([BoNT/ A] 12.5 U Xeomin [incobotulinumtoxinA]) into each of the mm. transversi linguae was performed in the 44-year-old woman. For 4 years now, she has gotten along very well with BoNT treatment at intervals of 6 to 8 weeks. Conclusions: Even with the rare disorder SILD, an L-dopa test should always be performed. EMG-guided BoNT treatment can be an effective therapy; 2 such cases have already been reported in the literature (Degirmenci 2011; Budak 2013). References Budak F, Aydin E, Koçkaya A, Ilbay G. Botulinum toxin in the treatment of lingual dystonia induced by speaking. Case Rep Neurol. 2013;5(1):18-20. Degirmenci Y, Ors CH, Yilmaz U, Karaman HI. Isolated lingual dystonia induced by speaking: a rare form of focal dystonia. Acta Neurol Belgiq. 2011;111(4):360-361. 185. DISASSOCIATION MECHANISM OF PROGENITOR COMPLEX OF BOTULINUM NEUROTOXIN SEROTYPE E Subramanyam Swaminathan a, *, S. Eswaramoorthy a, J. Sun a, H. Li a, B.R. Singh b a Biosciences Department, Brookhaven National Laboratory, Upton, NY, USA; b Botulinum Research Center, Institute of Advanced Sciences, Dartmouth, MA, USA *Corresponding author: Brookhaven National Laboratory, Upton, NY 11973, USA. E-mail address: [email protected]
Botulinum neurotoxin (BoNT), produced by Clostridium botulinum, the most potent protein toxin known to humans, is released as a progenitor toxin complex (PTC), with at least 1 nontoxic nonhemagglutinin protein (NTNH) and several other neurotoxin-associated proteins (NAPs) held together by noncovalent interactions. Depending on the number of proteins forming the complex, 3 kinds of complexes, LL, L, and M, are formed with molecular masses of 900, 500, and 300 kDa, respectively. When ingested by mouth, the components of the progenitor toxin complexes protect the neurotoxin from the harsh conditions of low pH and proteases present in the gastrointestinal tract, enabling its release into the blood circulation. However, the structural arrangement of NAPs and the mechanism by which they protect the BoNT is not yet well understood. Knowledge of the three-dimensional organization of these proteins, their individual structures, and mutual interactions with other components of the PTC will lead to an understanding of the role of NAPs in transcytosis and protecting the BoNT from degradation. We have examined the structure of the M progenitor toxin complex of BoNT serotype E (M-PTC/E), consisting of BoNT/E and NTNH-E, by cryo-electron microscopy (Cryo-EM)
Jonathan M. Sykes Facial Plastic and Reconstructive Surgery, UC Davis Medical Group, 2521 Stockton Blvd., Suite 6206, Sacramento, CA 95817, USA. E-mail address: [email protected]
In order to successfully perform any facial injection, a systematic evaluation of facial aesthetics is essential. In addition, a detailed knowledge of the applied anatomy of the face is necessary. This includes an understanding of topographic landmarks that will allow predictable identification of deeper structures. Specifically, any practitioner who injects botulinum toxin should have a thorough knowledge of all soft-tissue and skeletal structures, from superficial to deep. The location and action of all pertinent facial muscles is important. Additionally, the position of the associated muscle action potentials is critical to maximize the impact of each injection and to minimize the possibility of untoward side effects. The periorbital region is an area where hyperfunction of muscles results in a tired and aged appearance and increased rhytides. The relationship of the eyebrow elevators and depressors is important. Correct placement of appropriate amounts of toxin to minimize rhytides, without negatively affecting eyebrow position, is important. The applied anatomy of the facial muscles as they relate to other anatomic structures, and the depth and topography of the musculature, are reviewed, with an emphasis on promoting efficient injections and avoiding complications. 187. PILOT STUDY TO ESTABLISH PROOF OF PRINCIPLE FOR THE USE OF ONABOTULINUMTOXINA (BOTOX) IN THE TREATMENT OF NOCTURNAL BRUXISM WITH ASSOCIATED CRANIOFACIAL PAIN Deborah R. Syna Northwest Neurological Specialists PC, 1585 SW Marlow #110, Portland, OR 97225, USA. E-mail address: [email protected] Introduction and Objectives: Nocturnal bruxism, the repetitive grinding, clenching, and chewing movements of the jaw during sleep, can occur in both children and adults. Case series and anecdotal reports suggest that botulinum neurotoxin type A injection may provide effective treatment of nocturnal bruxism and its sequelae. Open-label trials for patients with nocturnal bruxism indicate that it may confer reduction in pain medication use and migraine headache frequency. This open-label pilot study sought to establish “proof of principle” for the use of onabotulinumtoxin A (Botox) to treat nocturnal bruxism with associated craniofacial pain. Methods: The primary outcome measure of this study was the change in number of electromyography (EMG) bursts in the temporalis and masseter muscles as measured during nocturnal polysomnography in an accredited sleep laboratory. Polysomnograms were administered once for baseline measurement and at weeks 4 and 8 after injection of 100 to 150 U onabotulinumtoxinA in a fixed site pattern including temporalis and masseter muscles. Results: Five consenting patients with nocturnal bruxism and craniofacial pain who had tried dental prosthetics and failed trials of at least 2 prophylactic headache medications were enrolled. Four patients completed the trial. No serious adverse events were experienced by any patient. Average number of bruxism events decreased through week 4 after treatment. One of 4 participants’ polysomnograph showed consistent decrease in bruxism events in the weeks following treatment, but, overall, the trends did not reach statistical significance. Secondary outcome measures that demonstrated a trend for improvement included bed partner survey of bruxing activity and sleep interruption, daily subject craniofacial pain diary, Headache Impact Test (HIT-6), and Migraine Disability Assessment scores. Sleep efficiency and percentage of rapid eye movement (REM) sleep on polysomnograms also demonstrated a trend toward improvement after injection but did not reach statistical significance.