Generic Name: Botulinum Toxin Type B
Class: Other Miscellaneous Therapeutic Agents
VA Class: MS900
[UPDATED 08/03/2009] FDA notified healthcare professionals of changes to the established drug names for botulinum toxin Type A (Botox/Botox Cosmetic, Dysport) and botulinum toxin Type B (Myobloc) to reinforce individual potencies and prevent medication errors, and provided recommendations for healthcare professionals to consider, plus information for patients, family members, and caregivers. For more information visit the FDA website at: and .
[Posted 04/30/2009] FDA notified healthcare professionals that after an ongoing safety review initiated in February 2008, the manufacturers of licensed botulinum toxin products [botulinum toxin Type A (Botox and Botox Cosmetic) and botulinum toxin Type B (Myobloc)] will be required by FDA to strengthen warnings in product labeling and add a boxed warning regarding the risk of adverse events when the effects of the toxin spread beyond the site where it was injected.
FDA will also require that manufacturers develop and implement a Risk Evaluation and Mitigation Strategy [REMS], including a communication plan to provide more information regarding the risk for distant spread of botulinum toxin effects after local injection, as well as information to explain that botulinum toxin products cannot be interchanged. The REMS would also include a Medication Guide that explains the risks to patients, their families, and caregivers. FDA is requiring the manufacturers to submit safety data after multiple administrations of the product in a specified number of children and adults with spasticity to assess the signal of serious risk regarding distant spread of toxin effects.
FDA’s evaluation of the data continues to support the recommendations made in the 2008 Early Communication. For more information visit the FDA website at: , and .
FDA approved a REMS for rimabotulinumtoxinb (formerly botulinum toxin b) to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of rimabotulinumtoxinb (formerly botulinum toxin b) and consists of the following: medication guide and communication plan. See the FDA REMS page () or the ASHP REMS Resource Center ().
Neurotoxin produced by Clostridium botulinum;1 2 3 5 31 37 70 73 79 7 structurally similar but antigenically and serologically distinct botulinum toxin serotypes (A, B, C, D, E, F, and G) exist.2 3 31 32 37 70 73 75 79
Botulinum toxin disrupts neurotransmission by inhibiting release of acetylcholine at cholinergic nerve terminals of the peripheral nervous system and at ganglionic nerve terminals of the autonomic nervous system, inducing a chemical denervation and flaccid paralysis and inhibiting glandular secretion.2 3 31 32 37 43 72 73 75 194
Uses for Myobloc
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Botulinum toxin type B (Myobloc) and type A (Botox, Botox Cosmetic) currently are the only botulinum toxin serotypes commercially available in the US;1 2 5 types C and F reportedly under clinical investigation in other countries.4
Management of cervical dystonia (also referred to as spasmodic torticollis) to decrease severity of associated abnormal head position and neck pain;2 3 4 9 14 16 29 30 32 35 37 40 54 65 69 81 85 95 96 122 123 designated an orphan drug by US FDA for this use.81
Considered first-line therapy for cervical dystonia because of efficacy, relatively low incidence of adverse effects, and temporary dose-related therapeutic effects (compared with surgery).3 15 30 33 34 35 54 83 86 90 296 297
Also considered an effective and safe treatment for cervical dystonia in patients who are not responsive to therapy with botulinum toxin type A.3 14 15 16 17 32 35 41 42 60 64 65 79 137 348 350 354 355
Comparative safety and efficacy of botulinum toxin types A and B in cervical dystonia have not been established;14 69 botulinum toxin type B appears to be effective in patients who develop tolerance to type A as well as in those who are responsive to botulinum toxin type A.2 14 17 42 69 123 297 345
Has been used for temporary improvement in the appearance of facial wrinkles associated with hyperactivity of the orbiculus oculi muscle† (lateral canthal wrinkles†, also known as “crow’s feet”†) in a limited number of individuals.152 156 310 337 338
Myobloc Dosage and Administration
Lower doses may be required in patients with preexisting weakness or when there is concern about weakness, in those with milder disease severity, and in women and patients with lower body weights.4
Patients with cervical dystonia who have not previously received botulinum toxin should receive a lower initial dose; very limited experience in patients who have not received prior therapy with botulinum toxin type A.2 296 297
Carefully dispose of all used vials, including expired vials and/or equipment used in preparation and administration, as medical waste.2
Commercially available vials of botulinum toxin type B (Myobloc) are overfilled to ensure delivery of the labeled volume of drug: the vial labeled as containing 2500 units in 0.5 mL actually contains approximately 4100 units in 0.82 mL, the vial labeled as containing 5000 units in 1 mL actually contains approximately 6800 units in 1.36 mL, and the vial labeled as containing 10,000 units in 2 mL actually contains approximately 12,650 units in 2.53 mL.2 156 297 338 Drug solutions should not be diluted in the vial since this may result in a solution with a higher concentration than expected due to overfill.297 338
May be diluted with 0.9% sodium chloride injection to obtain desired concentration; however, since the drug solution does not contain a preservative, use diluted solutions within 4 hours of preparation.2 296 297 Diluted solutions reportedly stable for at least 24 hours at 25°C.157 172
Some clinicians suggest that injection pain (possibly due to acidity of the solution)152 157 286 may be decreased by adding a small amount of sodium bicarbonate to the injection solution†.152 157 However, the compatibility and stability of such solutions remain to be fully elucidated.157 296 297
IM Injection Techniques
Targeting the injection to the appropriate muscle(s) may be facilitated by active electromyography (EMG), ultrasonography, palpation of muscle belly, and/or use of anatomic landmarks (e.g., evidence of muscular hypertrophy, stiffness, tenderness, visible abnormal muscular activity).4 120 147 229
EMG-guided injections often are recommended to ensure optimal placement of toxin for efficacy, particularly in patients who have not responded adequately to previous injections, and to minimize adverse effects on nonaffected tissue.120 140 143 147 296 297
Identify affected muscles by careful clinical evaluation, including physical examination (e.g., for areas of hypertrophy, pain) and palpation.9 33 65 Palpation of contracting muscles while patient’s head is placed in position most favored by dystonic pulling of neck muscles is reportedly helpful.9 65
Cosmesis of Lateral Canthal Wrinkles (“Crow’s Feet”)†
If concurrent cosmetic alteration of the eyebrow† is planned,157 296 297 defer treatment of the lateral eyebrow until after treatment of lateral canthal wrinkles (“crow’s feet”); increased diffusion may accomplish sufficient cosmetic alteration of the eyebrow to eliminate the need for further treatment.157 296 297
Administration Precautions for Facial Cosmesis
Appears to have increased diffusion within the muscle (potentially reducing the number of injections and complications)142 157 301 302 353 354 and a somewhat faster onset of action (e.g., within 24–48 hours) than botulinum toxin type A;142 152 157 160 297 353 however, additional experience needed to establish the optimal dose, number of injection sites, and frequency of treatment for facial cosmesis.142 156 301 310 337
In older individuals, do not inject lower portion of brow (this muscle is used to raise eyebrows in order to see).143
Avoid eyelid ptosis by asking individual to remain upright (e.g., avoid naps in reclining position) for 4 hours following treatment, avoid rubbing or massaging treated area for 4 hours (to prevent excess diffusion and possible weakness of adjacent muscles), and frown and smile repeatedly for at least 1–4 hours143 296 297 following treatment.140 141 143 296 297
Apply digital pressure at border of supraorbital ridge while injecting corrugator muscle to minimize potential for diffusion into levator muscle and resultant weakening.143
Before injection, instruct the individual to accentuate specific facial lines to be treated by squinting (for lateral canthal wrinkles).140
Controlling Injection Pain
Pretreatment with ice packs or topical or local anesthetics (e.g., lidocaine/prilocaine cream [EMLA] and an occlusive dressing, proparacaine hydrochloride ophthalmic drops) has been recommended prior to injection.120 140 275 296
Dilution with 0.9% sodium chloride injection containing a preservative (benzyl alcohol)† has been reported to reduce pain on injection;62 64 138 157 297 344 however, the manufacturer recommends use of 0.9% sodium chloride injection without preservative for reconstitution and/or dilution.1 2 5 298
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Data on several different serotypes (e.g., botulinum toxin types A, B, C, F) and/or formulations of botulinum toxin have been reported;1 2 4 5 255 257 assay methods used to determine potency of these various toxins are specific to each individual manufacturer and/or formulation.1 2 4 5
Unless otherwise noted, all botulinum toxin doses in this monograph refer to units of Myobloc.
Patients With a History of Tolerating Botulinum Toxin TreatmentIM
Titrate initial and subsequent dosage considering previous response, adverse reactions, and severity of dystonia based on head and neck position, localization of pain, mass of target muscles and their proximity to critical toxin-sensitive anatomic structures (e.g., larynx, pharynx), and muscular hypertrophy.56 296 297
Initially, total recommended dose per treatment session is 2500–5000 units divided among affected muscles.2
Cosmesis of Lateral Canthal Wrinkles (“Crow’s Feet”)†
750 units divided among 3 injection sites per side also has been used (total dosage 1500 units if both sides treated); resolution of wrinkles occurred at 7 days.152
Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.296
Cautions for Myobloc
Hypersensitivity to botulinum toxin type B or any ingredient in the formulation.2
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Adherence to Recommended Dosage
Do not exceed recommended dosage or frequency of administration; safety and efficacy of higher dosages have not been evaluated.2 296 Severe adverse effects, including a botulism-like syndrome, have been reported with use of higher than recommended dosages of botulinum toxins and/or unlicensed preparations of botulinum toxins.371 374 376 377 378 379
Increased risk of serious adverse systemic effects, including severe dysphagia, muscle weakness, and/or respiratory compromise, with recommended doses in patients with underlying conditions such as peripheral motor neuropathic diseases (e.g., amyotrophic lateral sclerosis, motor neuropathy) or neuromuscular junction disorders (e.g., myasthenia gravis, Lambert-Eaton syndrome); exercise caution when used in such patients.2 4 18 27 29 37 57 58 140 141 219 259 371 375 376 May be related to use of higher dosages in such patients.374 376
Rarely, extreme sensitivity to systemic effects of usual clinical doses reported in patients with known or unrecognized neuromuscular disorders; some patients experienced several months of severe dysphagia and required a gastrostomy or nasogastric tube.2 9 57 69
Some clinicians state that use for cosmetic treatment of neck wrinkles is contraindicated in patients with amyotrophic lateral sclerosis.141
Serious systemic effects related to distant spread of botulinum toxin reported, more often and with greater severity in children with cerebral palsy receiving such therapy; hospitalizations and deaths have occurred.371 372 373 374
Dysphagia is the most common serious adverse effect reported in patients with cervical dystonia;2 11 14 15 16 17 35 53 57 65 69 95 96 122 261 also can occur in patients receiving botulinum toxin type B for other indications (e.g., torticollis, muscle spasticity associated with cerebral palsy).371 375 376 Results from the diffusion of the toxin to tissues (e.g., posterior pharyngeal muscles) outside the injected muscles.29 30 33 57 58 60 65 83 371 Rarely, dysphagia may require placement of gastric feeding tube.2
Risk increased in patients with cervical dystonia and smaller neck muscle mass (e.g., female) receiving bilateral injections and/or relatively high doses into the sternocleidomastoid muscle.2 9 35 57 86
Risk of Creutzfeldt-Jakob Disease
Formulation contains human albumin derived from blood.2 Theoretical but remote risk of transmission of Creutzfeldt-Jakob disease (CJD) via albumin component; however, no cases of CJD identified to date.2
Systemic Toxicity (Botulism)
Serious systemic toxicity, including respiratory compromise and death, reported during an ongoing FDA safety review of botulinum toxins type A and type B.371 372 373 374 More frequent and severe in children with limb spasticity associated with cerebral palsy.371 372 373 374 Causal relationship not established to date; FDA will review additional safety data from clinical studies, medical literature, and postmarketing adverse event reports to further evaluate risk of systemic toxicity.371 372 374
Botulism also possible after iatrogenic overdose or misinjection of botulinum toxin.1 2 5 51 58 59 60 65 70 87 377 378 Following IM injection of usual therapeutic doses, botulinum toxin type B generally not present in the peripheral blood and generally does not induce systemic effects (e.g., generalized or distant muscle weakness) in patients without predisposing neuromuscular dysfunction.2 14 However, systemic autonomic or anticholinergic effects (e.g., dry mouth, dyspepsia,296 swallowing difficulties, accommodation difficulty, corneal and conjunctival irritation, dryness of nasal mucosa, reduced sweating, and urinary voiding difficulties) reported.160 261 296 340 352
To date, botulism not reported after IM injections of botulinum toxin type B;2 however, generalized muscle weakness and a generalized botulism-like syndrome, including respiratory arrest, reported rarely after IM injections of therapeutic doses of another botulinum toxin serotype (type A).14 26 32 33 38 52 58 142 293
Maximum safe dose that does not produce toxicity is not known.37 Serious systemic toxicity has been reported during postmarketing experience with doses of 388–625 units/kg in children and doses of 10,000–20,000 units in adults.371
Manifestations of overdose (botulism) include diplopia, ptosis, blurred vision, photophobia, dry mouth, difficulty speaking and swallowing, autonomic dysfunction such as bowel stasis, and generalized muscle weakness that can progress to a symmetric, descending flaccid paralysis;70 87 89 250 manifestations not apparent immediately after the drug is injected.2
If accidental injection or ingestion occurs, closely monitor patient for up to several weeks for manifestations of systemic weakness or muscle paralysis.2 If botulism suspected, hospitalization may be required to monitor closely for systemic weakness, paralysis, and incipient respiratory failure.2 Recovery occurs through neurogenesis of axonal sprouts and motor end plates; can require weeks or months.32 37 79 70
In event of an overdose or misinjection (i.e., wrong muscle), contact manufacturer immediately for additional information and state health department to obtain botulinum antitoxin through CDC;2 if state health department is not available, contact CDC by telephone at 404-639-2206 or 404-639-2888 (after hours).70 Antitoxin will not reverse botulinum toxin-induced muscle weakness already evident at the time of antitoxin administration but may stabilize the deficits.2 265
Botulinum Toxin-naive Patients
Initiate treatment of botulinum toxin-naive patients with lower doses from the recommended dosage range.2
Experience of Clinician
The manufacturer states that the drug should be administered to patients with cervical dystonia only by clinicians familiar with and experienced in the assessment and management of this condition.2
Thorough knowledge of diagnosis, management, and regional anatomy of the treated disorder, careful dose selection, and accomplished injection techniques are critical to obtaining therapeutic benefit and minimizing adverse effects.2 54 56 Some experts recommend limiting use to clinicians with specialized training.37 65 66 296 297
Working knowledge of EMG techniques useful for accurate injection of target muscles in patients with cervical dystonia,35 particularly when palpation is inadequate or adequate relief not obtained with conventional administration.9 35 83
Local spread of toxin may result in weakness to adjacent muscles.9 10 11 12 13 18 30 31 32 33 34 35 37 65 142 371 Systemic spread of botulinum toxin also is possible and can cause a botulism-like syndrome (e.g., dysphagia, muscle weakness, ptosis, respiratory failure).371 372 373 374 Condition treated determines muscles injected and therefore proximate muscles possibly affected by infiltration and resultant undesired weakness.29 37
Systemic autonomic or anticholinergic effects (e.g., dry mouth, dyspepsia,296 swallowing difficulties, accommodation difficulty, corneal and conjunctival irritation, dryness of nasal mucosa, reduced sweating, and urinary voiding difficulties) reported; incidence not fully elucidated.160 261 296 340 352 369
Incidence of autonomic effects (e.g., anticholinergic effects such as dry mouth, ptosis, accommodation difficulty) may be higher with botulinum toxin type B than with type A, possibly because of diffusion characteristics and systemic distribution of type B and/or different relative affinities of toxin serotypes for neuromuscular and autonomic nerve endings.142 160 261 296 320 340 345 352
Incidence of dry mouth appears dose-related in cervical dystonia after injections in the splenius capitis, trapezius, and sternocleidomastoid muscles.2
Monitor patients for possible systemic effects including dysphagia, dysphonia, respiratory compromise, and generalized weakness following administration of botulinum toxin type B.371
Antibody Formation and Tolerance
Clinical importance has not been determined.2 It is not known if patients with neutralizing antibodies to botulinum toxin type A are at increased risk of developing tolerance to the type B toxin.345 351
Neutralizing antibodies generally not detected until after 6 months of treatment.2
Patients who develop tolerance to botulinum toxin type A may respond to botulinum toxin type B or other botulinum toxin serotypes (e.g., botulinum toxin type F);3 32 35 41 42 60 64 65 79 137 348 350 however, long-term response to other serotypes in such patients has not been fully elucidated.14 32 33 41 359
Ensure accuracy of dosing information; units of biologic activity for different serotypes or formulations of botulinum toxin cannot be compared with or converted to units of other botulinum toxins.2 4
Dosing errors reported;32 76 77 157 173 296 297 use care in evaluating medical literature on different toxin serotypes (e.g., botulinum toxin types A, B, C, F) since assay methods used to determine potency of different serotypes are specific to each individual manufacturer and/or formulation.1 2 4 5 255 257
Serious systemic toxicity resembling botulism (e.g., dysphagia, respiratory failure) reported during postmarketing experience in children <16 years of age.371 Such effects were observed with botulinum toxin type B doses of 388–625 units/kg.371 Severe cases involving death or hospitalization or requiring use of gastric feeding tubes and/or mechanical ventilation have occurred, principally in children with cerebral palsy-associated limb spasticity.371 372 373 374 No deaths or serious complications requiring intubation or ventilatory support reported among such cases of botulism in adults.371 374
Safety and/or efficacy in those ≥65 years of age similar to that in younger adults.2
Safety and efficacy data in patients ≥75 years of age insufficient for any comparison to that in younger adults.2
Common Adverse Effects
Interactions for Myobloc
Potential for prolonged paralytic effect of toxin297
Other botulinum toxin serotypes
Possible increased paralytic effect with concurrent or sequential use within several months of administration of type B2
Concurrent or sequential use has not been evaluated2
Anti-infective agents interfering with neuromuscular transmission (aminoglycosides, lincosamides, polymyxins)
Magnesium salts (magnesium sulfate)
Potential for prolonged paralytic effect of toxin297
Neuromuscular blocking agents (e.g., atracurium, succinylcholine)
Potential for prolonged paralytic effect of toxin297
Formal pharmacokinetic studies with botulinum toxin type B have not been performed; the manufacturer states that the drug is not expected to be present in peripheral circulation in measurable concentrations following IM or intradermal injection of recommended doses.2
For information on systemic interactions resulting from concomitant use, see Interactions.
Some clinicians suggest that the addition of a small amount of sodium bicarbonate to the botulinum toxin type B solution may decrease pain on injection;152 157 however, use of such buffering agents reportedly may destabilize the toxin and/or alter its diffusion characteristics.157 296 297
Induces chemical denervation and flaccid paralysis by disruption of neurotransmission; inhibits release of acetylcholine at presynaptic cholinergic nerve terminals of the peripheral nervous system and at ganglionic nerve terminals of the autonomic nervous system.2 3 16 31 32 37 72 73 75 194
At therapeutic doses, muscular paralysis limited to injected muscle; however, weakness or paralysis of adjacent muscles may occur as a result of local diffusion.31
Response in autonomic disorders involving excessive glandular secretion (e.g., hyperhidrosis) may be longer than in conditions involving overactivity of striated or smooth muscle;4 296 297 additional study needed to elucidate mechanism in glandular and non-muscle tissue.4
Advice to Patients
Inform patients with cervical dystonia of possibility of dysphagia (typically mild to moderate);9 14 57 69 rarely, severe dysphagia occurs, sometimes associated with aspiration, dyspnea, pneumonia, and need to reestablish an airway.2
Importance of informing patients of possible systemic effects (e.g., weakness, shortness of breath, respiratory complications, swallowing difficulties) following local injection.371
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., neuromuscular disorders).
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.2
Importance of informing patients of other important precautionary information.2 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
5000 units/mL (of Clostridium botulinum Toxin Type B)
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
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AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Allergan. Botox (botulinum toxin type A) purified neurotoxin complex prescribing information. Irvine, CA; 2006 Oct.
2. Solstice Neurosciences. Myobloc (botulinum toxin type B) injectible solution prescribing information. South San Francisco, CA; 2008 Sep.
3. Bell MS, Vermeulen LC, Sperling KB. Pharmacotherapy with botulinum toxin: harnessing nature’s most potent neurotoxin. Pharmacotherapy. 2000; 20:1079-91. [IDIS 453589] [PubMed 10999501]
4. Munchau A, Bhatia KP. Uses of botulinum toxin injection in medicine today. BMJ. 2000; 320:161-5. [IDIS 441486] [PubMed 10634738]
5. Allergan. Botox Cosmetic (botulinum toxin type A) purified neurotoxin complex prescribing information. Irvine, CA; 2008 Apr.
6. Arthurs B, Flanders M, Codere F et al. Treatment of blepharospasm with medication, surgery and type A botulinum toxin. Can J Ophthalmol. 1987; 22:24-8. [PubMed 3815152]
7. Jankovic J, Orman J. Botulinum A toxin for cranial-cervical dystonia: double-blind, placebo-controlled study. Neurology. 1987; 37:616-23. [IDIS 228452] [PubMed 3561773]
8. Wang YC, Burr DH, Korthals GJ et al. Acute toxicity of aminoglycoside antibiotics as an aid in detecting botulism. Appl Environ Microbiol. 1984; 48:951-55. [PubMed 6508309]
9. Jankovic J, Brin MF. Therapeutic uses of botulinum toxin. N Engl J Med. 1991; 324:1186-94. [IDIS 279793] [PubMed 2011163]
10. Greene P, Kang U, Fahn S et al. Double-blind, placebo-controlled trial of botulinum toxin injections for the treatment of spasmodic torticollis. Neurology. 1990; 40:1213-8. [IDIS 269215] [PubMed 2199847]
11. Jankovic J, Schwartz K. Botulinum toxin injections for cervical dystonia. Neurology. 1990; 40:277-80. [PubMed 2300249]
12. Tsui JK, Calne DB. Botulinum toxin in cervical dystonia. Adv Neurol. 1988; 49:473-8. [PubMed 3344637]
13. Tsui JK, Eisen A, Stoessl AJ et al. Double-blind study of botulinum toxin in spasmodic torticollis. Lancet. 1986; 2:245-7. [IDIS 219431] [PubMed 2874278]
14. Figgit DP, Noble S. Botulinum toxin B: A review of its therapeutic potential in the management of cervical dystonia. Drugs. 2002; 62:705-2. [PubMed 11893235]
15. Lew MF, Adornato BT, Duane DD et al. Botulinum toxin type B: a double-blind, placebo-controlled, safety and efficacy study in cervical dystonia. Neurology. 1997; 49:701-7. [IDIS 395277] [PubMed 9305326]
16. Brashear A, Lew MF, Dykstra DD et al. Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia. Neurology. 1999; 53:1439-46. [IDIS 436526] [PubMed 10534248]
17. Brin MF, Lew MF, Adler CH et al. Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia. Neurology. 1999; 53:1431-8. [IDIS 436525] [PubMed 10534247]
18. Blackie JD, Lees AJ. Botulinum toxin treatment in spasmodic torticollis. J Neurol Neurosurg Psychiatry. 1990; 53:640-3. [PubMed 2213040]
19. Patrinely JR, Whiting AS, Anderson RL. Local side effects of botulinum toxin injections. Adv Neurol. 1988; 49:493-500. [PubMed 3278553]
20. Chen RS, Lu CS, Tsai CH. Botulinum toxin A injection in the treatment of hemifacial spasm. Acta Neurol Scand. 1996; 94:207-11. [PubMed 8899054]
21. Lingua RW. Sequelae of botulinum toxin injection. Am J Ophthalmol. 1985; 100:305-7. [IDIS 204218] [PubMed 4025471]
22. Kalra HK, Magoon EH. Side effects of the use of botulinum toxin for treatment of benign essential blepharospasm and hemifacial spasm. Ophthalmic Surg. 1990; 21:335-8. [PubMed 2381655]
23. Anderson TJ, Rivest J, Stell R et al. Botulinum toxin treatment of spasmodic torticollis. J R Soc Med. 1992; 85:524-9. [PubMed 1433117]
24. Dutton JJ, Buckley EG. Long-term results and complications of botulinum A toxin in the treatment of blepharospasm. Ophthalmology. 1988; 95:1529-34. [PubMed 3211461]
25. Schnider P, Brichta A, Schmied M et al. Gallbladder dysfunction induced by botulinum A toxin. Lancet. 1993; 342:811-2. [IDIS 320391] [PubMed 8103904]
26. Bhatia KP, Munchau A, Thompson PD et al. Generalised muscular weakness after botulinum toxin injections for dystonia: a report of three cases. J Neurol Neurosurg Psychiatry. 1999; 67:90-3. [PubMed 10369829]
27. Mezaki T, Kaji R, Kohara N et al. Development of general weakness in a patient with amyotrophic lateral sclerosis after focal botulinum toxin injection. Neurology. 1996; 46:845-6. [IDIS 364614] [PubMed 8618702]
28. Sheean GL, Murray NM, Marsden CD. Pain and remote weakness in limbs injected with botulinum toxin A for writer’s cramp. Lancet. 1995; 346:154-6. [IDIS 349836] [PubMed 7603232]
29. Anon. Assessment: the clinical usefulness of botulinum toxin-A in treating neurologic disorders. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 1990; 40:1332-6. [PubMed 2202925]
30. Mahant N, Clouston PD, Lorentz IT. The current use of botulinum toxin. J Clin Neurosci. 2000; 7:389-94. [PubMed 10942658]
31. Johnson EA. Clostridial toxins as therapeutic agents: benefits of nature’s most toxic proteins. Annu Rev Microbiol. 1999; 53:551-75. [PubMed 10547701]
32. Brin MF. Botulinum toxin: chemistry, pharmacology, toxicity, and immunology. Muscle Nerve Suppl. 1997; 6:S146-68.
33. Anon. Clinical use of botulinum toxin. NIH Consensus Statement Online 1990 Nov 12-14 [cited 2002 March 26]; 8:1-20.
34. Wheeler AH. Therapeutic uses of botulinum toxin. Am Fam Physician. 1997; 55:541-5, 548. [IDIS 380674] [PubMed 9054223]
35. Jankovic J, Brin MF. Botulinum toxin: historical perspective and potential new indications. Muscle Nerve Suppl. 1997; 6:129-45.
36. Jankovic J, Schwartz K, Clemence W et al. A randomized, double-blind, placebo-controlled study to evaluate botulinum toxin type A in essential hand tremor. Mov Disord. 1996; 11:250-256. [PubMed 8723140]
37. Tsui JK. Botulinum toxin as a therapeutic agent. Pharmacol Ther. 1996; 72:13-24. [PubMed 8981568]
38. Cobb DB, Watson WA, Fernandez MC. Botulism-like syndrome after injections of botulinum toxin. Vet Hum Toxicol. 2000 Jun; 42:163.
39. Callaway JE, Oregozo P, Gore N et al. Long-term stability of a new liquid formulation of botulinum toxin type b (BoNT-B). Neurology. 2001; 56(suppl 3): A346.
40. Lindeboom R, Brans JW, Aramideh M et al. Treatment of cervical dystonia: a comparison of measures for outcome assessment. Mov Disord. 1998; 13:706-12. [PubMed 9686779]
41. Greene PE, Fahn S. Use of botulinum toxin type F injections to treat torticollis in patients with immunity to botulinum toxin type A. Mov Disord. 1993; 8:479-83. [PubMed 8232357]
42. Jankovic J, Schwartz K. Response and immunoresistance to botulinum toxin injections. Neurology. 1995; 45:1743-6. [IDIS 353598] [PubMed 7675238]
43. Heckmann M, Ceballos-Baumann AO, Plewig G. Botulinum toxin A for axillary hyperhidrosis (excessive sweating). N Engl J Med. 2001; 344:488-93. [IDIS 459726] [PubMed 11172190]
44. Naumann M, Lowe NJ. Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis: randomised, parallel group, double blind, placebo controlled trial. BMJ. 2001; 323:596-9. [IDIS 471135] [PubMed 11557704]
45. Naumann M, Hofmann U, Bergmann I et al. Focal hyperhidrosis: effective treatment with intracutaneous botulinum toxin. Arch Dermatol. 1998; 134:301-4. [PubMed 9521028]
46. Heckmann M, Breit S, Ceballos-Baumann A et al. Side-controlled intradermal injection of botulinum toxin A in recalcitrant axillary hyperhidrosis. J Am Acad Dermatol. 1999; 41:987-90. [IDIS 439951] [PubMed 10570385]
47. Cheshire WP, Abashian SW, Mann JD. Botulinum toxin in the treatment of myofascial pain syndrome. Pain. 1994; 59:65-9. [PubMed 7854804]
48. Glogau RG. Botulinum A neurotoxin for axillary hyperhidrosis. No sweat Botox. Dermatol Surg. 1998; 24:817-9. [PubMed 9723044]
49. Shelley WB, Talanin NY, Shelley ED. Botulinum toxin therapy for palmar hyperhidrosis. J Am Acad Dermatol. 1998; 38:227-9. [IDIS 402095] [PubMed 9486678]
50. Laccourreye O, Akl E, Gutierrez-Fonseca R et al. Recurrent gustatory sweating (Frey syndrome) after intracutaneous injection of botulinum toxin type A: incidence, management, and outcome. Arch Otolaryngol Head Neck Surg. 1999; 125:283-6. [PubMed 10190799]
51. Garner CG, Straube A, Witt TN et al. Time course of distant effects of local injections of botulinum toxin. Mov Disord. 1993; 8:33-7. [PubMed 8380486]
52. Bakheit AM, Ward CD, McLellan DL. Generalised botulism-like syndrome after intramuscular injections of botulinum toxin type A: a report of two cases. J Neurol Neurosurg Psychiatry. 1997; 62:198. [PubMed 9048725]
53. Williams A. Consensus statement for the management of focal dystonias. Br J Hosp Med. 1993; 50:655-9. [PubMed 8124547]
54. Anon. Consensus statement on physician training for the treatment of dystonia with botulinum toxin. The Canadian Movement Disorders Group. Can J Neurol Sci. 1992; 19:522. [PubMed 1423051]
55. Pagni CA. Guidelines for the therapeutic use of botulinum toxin in movement disorders. Ital J Neurol Sci. 1998; 19:189-90. [PubMed 10933476]
56. Training guidelines for the use of botulinum toxin for the treatment of neurologic disorders. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 1994; 44:2401-3. [PubMed 7991136]
57. Thobois S, Broussolle E, Toureille L et al. Severe dysphagia after botulinum toxin injection for cervical dystonia in multiple system atrophy. Mov Disord. 2001 Jul; 16:764-5.
58. Erbguth F, Claus D, Engelhardt A et al. Systemic effect of local botulinum toxin injections unmasks subclinical Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry. 1993; 56:1235- 6. [PubMed 8229041]
59. Lange DJ, Rubin M, Greene PE et al. Distant effects of locally injected botulinum toxin: a double-blind study of single fiber EMG changes. Muscle Nerve. 1991; 14:672-5. [PubMed 1922173]
60. Klein AW. Complications and adverse reactions with the use of botulinum toxin. Semin Cutan Med Surg. 2001; 20:109-20. [PubMed 11474743]
61. Argov Z, Mastaglia F L. Disorders of neuromuscular transmission caused by drugs. N Engl J Med. 1979; 301:40-413.
62. Alam M, Dover JS, Arndt KA. Pain associated with injection of botulinum A exotoxin reconstituted using isotonic sodium chloride with and without preservative: a double-blind, randomized controlled trial. Arch Dermatol. 2002; 138:510-4. [IDIS 479681] [PubMed 11939813]
63. Alam M, Arndt KA, Dover JS. Severe, intractable headache after injection with botulinum A exotoxin: report of 5 cases. J Am Acad Dermatol. 2002; 46:62-5. [IDIS 475206] [PubMed 11756947]
64. Anon. Botulinum toxin (Botox Cosmetic) for frown lines. Med Lett Drugs Ther. 2002; 44:47-8. [PubMed 12045752]
65. Berardelli A, Abbruzzese G, Bertolasi L et al. Guidelines for the therapeutic use of botulinum toxin in movement disorders. Italian Study Group for Movement Disorders, Italian Society of Neurology. Ital J Neurol Sci. 1997; 18:261-9. [PubMed 9412849]
66. Matarasso SL, Matarasso A. Treatment guidelines for botulinum toxin type A for the periocular region and a report on partial upper lip ptosis following injections to the lateral canthal rhytids. Plast Reconstr Surg. 2001; 108:208-14,215-7. [PubMed 11420526]
67. Grimalt R, Moreno-Arias GA, Ferrando J. Multi-injection plate for botulinum toxin application in the treatment of axillary hyperhidrosis. Dermatol Surg. 2001; 27:543-4. [PubMed 11442589]
68. Anon. Cosmetic use of botulinum toxin. Med Lett Drugs Ther. 1999; 41:63-4. [PubMed 10436771]
69. Anon. Botulinum toxin for cervical dystonia. Med Lett Drugs Ther. 2001; 43:63-4. [PubMed 11468603]
70. Arnon SS, Schechter R, Inglesby TV et al for the Working Group on Civilian Biodefense. Botulinum toxin as a biologic weapon: medical and public health management. JAMA. 2001; 285:1059-70. [IDIS 459764] [PubMed 11209178]
71. Simpson LL. Kinetic studies on the interaction between botulinum toxin type A and the cholinergic junction. J Pharmacol Exp Ther. 1980; 212:16-21. [PubMed 6243359]
72. Kao I, Drachman DB, Price DL. Botulinum toxin: mechanism of presynaptic blockade. Science. 1976; 193:1256-8. [PubMed 785600]
73. Lamanna C. The most poisonous poison. Science. 1959; 130:763-72. [PubMed 14413547]
74. Simpson LL, Maksymowych AB, Hao S. The role of zinc binding in the biologic activity of botulinum toxin. J Biol Chem. 2001; 276:27034-41. [PubMed 11358966]
75. Hambleton P. Clostridium botulinum toxins:a general review of involvement in disease, structure, mode of action and preparation for clinical use. J Neurol. 1992; 239:16-20. [PubMed 1311751]
76. Krack P, Deuschl G, Benecke R et al. Dose standardization of botulinum toxin. Mov Disord. 1998; 13:749-51. [PubMed 9686787]
77. Dressler D, Rothwell JC. Electromyographic quantification of the paralysing effect of botulinum toxin in the sternocleidomastoid muscle. Eur Neurol. 2000; 43:13-6. [PubMed 10798896]
78. Scott AB. Antitoxin reduces botulinum side effects. Eye. 1988; 2:29- 32. [PubMed 3410138]
79. Huang W, Foster JA, Rogachefsky AS. Pharmacology of botulinum toxin. J Am Acad Dermatol. 2000; 43:249-59. [IDIS 461974] [PubMed 10906647]
80. Scott AB, Suzuki D. Systemic toxicity of botulinum toxin by intramuscular injection in the monkey. Move Dis. 1988; 3:333-5.
81. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P. L. 97 414). Rockville, MD; 2001 May. From FDA web site; accessed March 7, 2002.
82. Jankovic J, Schwartz KS. Longitudinal experience with botulinum toxin injections for treatment of blepharospasm and cervical dystonia. Neurology. 1993; 43:834-6. [IDIS 313034] [PubMed 8469349]
83. Tintner R, Jankovic J. Focal dystonia:the role of botulinum toxin. Curr Neurol Neurosci Rep. 2001; 1:337-45. [PubMed 11898539]
84. Tan EK, Jankovic J. Botulinum toxin A in patients with oromandibular dystonia: long-term follow-up. Neurology. 1999; 53:2102-7. [IDIS 440446] [PubMed 10599789]
85. Brin MF. Botulinum toxin:new and expanded indications. Eur J Neurol. 1997; 4(Suppl 2):S59-65.
86. Jankovic J, Schwartz KS. Clinical correlates of response to botulinum toxin injections. Arch Neurol. 1991; 48:1253-6. [PubMed 1845028]
87. Greenfield RA, Brown BR, Hutchins JB et al. Microbiological, biological, and chemical weapons of warfare and terrorism. Am J Med Sci. 2002; 323:326-40. [PubMed 12074487]
88. Gelb DJ, Lowenstein DH, Aminoff MJ. Controlled trial of botulinum toxin injections in the treatment of spasmodic torticollis. Neurology. 1989; 39:80-4. [IDIS 249499] [PubMed 2642616]
89. Simpson LL. Botulinum toxin: a deadly poison sheds its negative image. Ann Intern Med. 1996; 125:616-7. [PubMed 8815762]
90. Jankovic J, Schwartz K, Donovan DT. Botulinum toxin treatment of cranial-cervical dystonia, spasmodic dysphonia, other focal dystonias and hemifacial spasm. J Neurol Neurosurg Psychiatry. 1990; 53:633-9. [PubMed 2213039]
91. Ranoux D, Gury C, Fondarai J et al. Respective potencies of Botox and Dysport: a double blind, randomised, crossover study in cervical dystonia. J Neurol Neurosurg Psychiatry. 2002; 72:459-62. [PubMed 11909903]
92. Poewe W. Respective potencies of Botox and Dysport: a double blind, randomised, crossover study in cervical dystonia. Clinically appropriate conversion factor may be less than three. J Neurol Neurosurg Psychiatry. 2002; 72:430. [PubMed 11909897]
93. Odergren T, Hjaltason H, Kaakkola S et al. A double blind, randomised, parallel group study to investigate the dose equivalence of Dysport and Botox in the treatment of cervical dystonia. J Neurol Neurosurg Psychiatry. 1998; 64:6-12. [PubMed 9436720]
94. Sampaio C, Ferreira JJ, Simoes F. DYSBOT: a single-blind, randomized parallel study to determine whether any differences can be detected in the efficacy and tolerability of two formulations of botulinum toxin type A—Dysport and Botox—assuming a ratio of 4:1. Mov Disord. 1997; 12:1013-8. [PubMed 9399229]
95. Lew MF. Botulinum toxin type B: an open-label, dose-escalation, safety and preliminary efficacy study in cervical dystonia patients. Adv Neurol. 1998; 78:227-30. [PubMed 9750919]
96. Truong DD, Cullis PA, O’Brien CF et al. BotB (Botulinum toxin type B): evaluation of safety and tolerability in botulinum toxin type A-resistant cervical dystonia patients (preliminary study). Mov Disorders. 1997; 12:772-5.
97. Morre HH, Keizer SB, Os JJ. Treatment of chronic tennis elbow with botulinum toxin. Lancet. 1997; 349:1746. [IDIS 386572] [PubMed 9193392]
98. Kraft SP, Lang AE. Botulinum toxin injections in the treatment of blepharospasm, hemifacial spasm, and eyelid fasciculations. Can J Neurol Sci. 1988; 15:276-80. [PubMed 3208210]
99. Mauriello JA Jr, Coniaris H, Haupt EJ. Use of botulinum toxin in the treatment of one hundred patients with facial dyskinesias. Ophthalmology. 1987; 94:976-9. [PubMed 3658375]
100. Cohen DA, Savino PJ, Stern MB et al. Botulinum injection therapy for blepharospasm: review and report of 75 patients. Clin Neuropharmacol. 1986; 9:415-29. [PubMed 3533250]
101. Tsoy EA, Buckley EG, Dutton JJ. Treatment of blepharospasm with botulinum toxin. Am J Ophthalmol. 1985; 99:176-9. [IDIS 196461] [PubMed 3970122]
102. Shorr N, Seiff SR, Kopelman J. The use of botulinum toxin in blepharospasm. Am J Ophthalmol. 1985; 99:542-6. [IDIS 199765] [PubMed 4003489]
103. Elston JS, Russell RWR. Effect of treatment with botulinum toxin on neurogenic blepharospasm. BMJ. 1985; 290:1857-9. [IDIS 201875] [PubMed 3924284]
104. Brin MF, Fahn S, Moskowitz C et al. Localized injections of botulinum toxin for the treatment of focal dystonia and hemifacial spasm. Movement Dis. 1987; 2:237-54. [PubMed 3504553]
105. McCann JD, Ugurbas SH, Goldberg RA. Benign essential blepharospasm. Int Ophthalmol Clin. 2002; 42:113-21. [PubMed 11914708]
106. Yoshimura DM, Aminoff MJ, Tami TA et al. Treatment of hemifacial spasm with botulinum toxin. Muscle Nerve. 1992; 15:1045- 9. [PubMed 1518513]
107. Scott AB, Magoon EH, McNeer KW et al. Botulinum treatment of childhood strabismus. Ophthalmology. 1990; 97:1434-8. [PubMed 2255516]
108. Scott AB. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. Ophthalmology. 1980; 87:1044-9. [PubMed 7243198]
109. Carruthers JDA. Ophthalmologic use of botulinum A exotoxin. Can J Ophthalmol. 1985; 20:135-41. [PubMed 4052862]
110. Magoon E, Dakoske C. Botulinum toxin injection for vertical strabismus. Am Orthop J. 1985; 35:48-52.
111. Magoon EH. Chemodenervation of strabismic children. Ophthalmology. 1989; 96:931-4. [PubMed 2771359]
112. Scott AB, Magoon EH, McNeer KW et al. Botulinum treatment of strabismus in children. Tr Am Ophth Soc. 1989; 87:174-80. [PubMed 2562519]
113. Biglan AW, Burnstine RA, Rogers GL et al. Management of strabismus with botulinum A toxin. Ophthalmology. 1989; 96:935-43. [PubMed 2771360]
114. Carruthers JDA, Kennedy RA, Bagaric D. Botulinum vs adjustable suture surgery in the treatment of horizontal misalignment in adult patients lacking fusion. Arch Ophthalmol. 1990; 108:1432-5. [IDIS 271987] [PubMed 2222277]
115. Scott AB. Botulinum toxin treatment of strabismus. In: Focal points 1989: clinical modules for ophthalmologists. American Academy of Ophthalmology. Vol. VII, module 12. 1989:1-11.
116. Blitzer A, Brin MF. Laryngeal dystonia: a series with botulinum toxin therapy. Ann Otol Rhinol Laryngol. 1991; 100:85-9. [IDIS 277419] [PubMed 1992905]
117. Brin MF, Blitzer A, Stewart C. Laryngeal dystonia (spasmodic dysphonia): observations of 901 patients and treatment with botulinum toxin. Adv Neurol. 1998; 78:237-52. [PubMed 9750921]
118. Hermanowicz N, Truong DD. Treatment of oromandibular dystonia with botulinum toxin. Laryngoscope. 1991; 101:1216-8. [PubMed 1943423]
119. Blitzer A, Brin MF, Greene PE et al. Botulinum toxin injection for the treatment of oromandibular dystonia. Ann Otol Rhinol Laryngol. 1989; 98:93-7. [IDIS 250468] [PubMed 2916831]
120. Schwartz M, Freund B. Treatment of temporomandibular disorders with botulinum toxin. Clin J Pain. 2002; 18(6 Suppl):S198-203.
121. Klein AW. Dilution and storage of botulinum toxin. Dermatol Surg. 1998; 24:1179-80. [PubMed 9834735]
122. Tsui JKC, Hayward M, Mak EKM et al. Botulinum toxin type B in the treatment of cervical dystonia: a pilot study. Neurology. 1995; 45:2109-10. [IDIS 357435] [PubMed 7501169]
123. Hallett M. One man’s poison—clinical applications of botulinum toxin. N Engl J Med. 1999; 341:118-20. [IDIS 427540] [PubMed 10395637]
124. Fernandez Lopez F, Conde Freire R, Rios Rios A et al. Botulinum toxin for the treatment of anal fissure. Dig Surg. 1999; 16:515-8. [PubMed 10805553]
125. Madoff RD, Fleshman JW. AGA technical review on the diagnosis and care of patients with anal fissure. Gastroenterology. 2003; 124:235-45. [IDIS 492727] [PubMed 12512046]
126. Maria G, Cassetta E, Gui D et al. A comparison of botulinum toxin and saline for the treatment of chronic anal fissure. N Engl J Med. 1998; 338:217-20. [IDIS 400147] [PubMed 9435326]
127. Brisinda G, Maria G, Bentivoglio AR et al. A comparison of injections of botulinum toxin and topical nitroglycerin ointment for the treatment of chronic anal fissure. N Engl J Med. 1999; 341:65-9. [IDIS 427535] [PubMed 10395629]
128. Mentes BB, Irkorucu O, Akin M et al. Comparison of botulinum toxin injection and lateral internal sphincterotomy for the treatment of chronic anal fissure. Dis Colon Rectum. 2003; 46:232-7. [PubMed 12576897]
129. Jost WH, Schimrigk K. Therapy of anal fissure using botulin toxin. Dis Colon Rectum. 1994; 37:1321-4. [PubMed 7995166]
130. WH. One hundred cases of anal fissure treated with botulin toxin: early and long-term results. Dis Colon Rectum. 1997; 40:1029-32. [PubMed 9293930]
131. Minguez M, Melo F, Espi A et al. Therapeutic effects of different doses of botulinum toxin in chronic anal fissure. Dis Colon Rectum. 1999; 42:1016-21. [PubMed 10458124]
132. Jost WH, Schrank B. Repeat botulin toxin injections in anal fissure: in patients with relapse and after insufficient effect of first treatment. Dig Dis Sci. 1999; 44:1588-9. [IDIS 434747] [PubMed 10492136]
133. Madoff RD. Pharmacologic therapy for anal fissure. N Engl J Med. 1998; 338:257-9. [IDIS 400151] [PubMed 9435334]
134. Maria G, Brisinda G, Bentivoglio AR et al. Botulinum toxin injections in the internal anal sphincter for the treatment of chronic anal fissure: long- term results after two different dosage regimens. Ann Surg. 1998; 228:664-9. [IDIS 417872] [PubMed 9833804]
135. Wehrmann T, Schmitt TH, Arndt A et al. Endoscopic injection of botulinum toxin in patients with recurrent acute pancreatitis due to pancreatic sphincter of Oddi dysfunction. Aliment Pharmacol Ther. 2000; 14:1469-77. [PubMed 11069318]
136. Wehrmann T, Seifert H, Seipp M et al. Endoscopic injection of botulinum toxin for biliary sphincter of Oddi dysfunction. Endoscopy. 1998; 30:702- 7. [PubMed 9865560]
137. Markey AC. Botulinum A exotoxin in cosmetic dermatology. Clin Exp Dermatol. 2000; 25:173-5. [PubMed 10844487]
138. Klein AW, Glogau RG. Botulinum toxin: beyond cosmesis. Arch Dermatol. 2000; 136:539-41. [IDIS 445773] [PubMed 10768654]
139. Heckmann M, Heyer GH, Brunner B et al. Botulinum toxin type A injection in the treatment of lichen simplex: an open pilot study. J Am Acad Dermatol. 2002; 46:617-9. [IDIS 479641] [PubMed 11907521]
140. Blitzer A, Binder WJ, Brin MF. Botulinum toxin injections for facial lines and wrinkles: technique. In: Blitzer A, Binder WJ, Boyd JB et al., eds. Management of facial lines and wrinkles. Lippincott Williams & Wilkins, Philadelphia, PA; 2000:303-13.
141. Carruthers JDA, Carruthers A. Botulinum toxin and laser resurfacing for lines around the eyes. In: Blitzer A, Binder WJ, Boyd JB et al., eds. Management of facial lines and wrinkles. Lippincott Williams & Wilkins, Philadelphia, PA; 2000:315-32.
142. Matarasso A, Deva AK. Botulinum toxin. Plast Reconstr Surg. 2002; 109:1191-7. [PubMed 11884859]
143. Klein AW. Treatment of wrinkles with Botox. Curr Probl Dermatol. 2002; 30:188-217. [PubMed 12471713]
144. Carruthers JA, Lowe NJ, Menter MA et al. A multicenter, double-blind, randomized, placebo-controlled study of the efficacy and safety of botulinum toxin type A in the treatment of glabellar lines. J Am Acad Dermatol. 2002; 46:840-9. [IDIS 483024] [PubMed 12063480]
145. Pribitkin EA, Greco TM, Goode RL et al. Patient selection in the treatment of glabellar wrinkles with botulinum toxin type A injection. Arch Otolaryngol Head Neck Surg. 1997; 123:321-6. [PubMed 9076240]
146. Garcia A, Fulton JE Jr. Cosmetic denervation of the muscles of facial expression with botulinum toxin. A dose-response study. Dermatol Surg. 1996; 22:39-43. [PubMed 8556256]
147. Lowe NJ, Maxwell A, Harper H. Botulinum A exotoxin for glabellar folds: a double-blind, placebo-controlled study with an electromyographic injection technique. J Am Acad Dermatol. 1996; 35:569-72. [PubMed 8859286]
148. Guyuron B, Huddleston SW. Aesthetic indications for botulinum toxin injection. Plast Reconstr Surg. 1994; 93:913-8. [PubMed 8134483]
149. Keen M, Blitzer A, Aviv J et al. Botulinum toxin A for hyperkinetic facial lines: results of a double-blind, placebo-controlled study. Plast Reconstr Surg. 1994; 94:94-9. [PubMed 8016257]
150. Carruthers JD, Carruthers JA. Treatment of glabellar frown lines with C. botulinum-A exotoxin. J Dermatol Surg Oncol. 1992; 18:17-21. [PubMed 1740562]
151. Ahn MS, Catten M, Maas CS. Temporal brow lift using botulinum toxin A. Plast Reconstr Surg. 2000; 105:1129-35; discussion 1136-9. [PubMed 10724275]
152. Matarasso SL. Comparison of botulinum toxin types A and B: a bilateral and double-blind randomized evaluation in the treatment of canthal rhytides. Dermatol Surg. 2003; 29:7-13.
153. Guerrissi JO. Intraoperative injection of botulinum toxin A into orbicularis oculi muscle for the treatment of crow’s feet. Plast Reconstr Surg. 2000; 105:2219-25; discussion 2226-8. [PubMed 10839423]
154. Sposito MM. New indications for botulinum toxin type A in cosmetics: mouth and neck. Plast Reconstr Surg. 2002; 110:601-11; discussion 612- 3. [PubMed 12142684]
155. Boyd RN, Hays RM. Current evidence for the use of botulinum toxin type A in the management of children with cerebral palsy: a systematic review. Eur J Neurol. 2001; 8 (Suppl 5):1-20.
156. Ramirez AL, Reeck J, Maas CS. Botulinum toxin type B (MyoBloc) in the management of hyperkinetic facial lines. Otolaryngol Head Neck Surg. 2002; 126:459-67. [PubMed 12075218]
157. Glogau RG. Review of the use of botulinum toxin for hyperhidrosis and cosmetic purposes. Clin J Pain. 2002; 18(6 Suppl):S191-7. [PubMed 12569968]
158. Atkins JL, Butler PEM. Hyperhidrosis: a review of current management. Plast Reconstr Surg. 2002; 110:222-8. [PubMed 12087259]
159. Tögel B, Greve B, Raulin C. Current therapeutic strategies for hyperhidrosis: a review. Eur J Dermatol. 2002; 12:219-23. [PubMed 11978559]
160. Dressler D, Adib Saberi F, Benecke R. Botulinum toxin type B for treatment of axillar hyperhidrosis. J Neurol. 2002; 249:1729-32. [PubMed 12529798]
161. Odderson IR. Long-term quantitative benefits of botulinum toxin type A in the treatment of axillary hyperhidrosis. Dermatol Surg. 2002; 28:480- 3. [PubMed 12081675]
162. Bushara KO, Park DM, Jones JC et al. Botulinum toxin—a possible new treatment for axillary hyperhidrosis. Clin Exp Dermatol. 1996; 21:276-8. [PubMed 8959898]
163. Odderson IR. Hyperhidrosis treated by botulinum A exotoxin. Dermatol Surg. 1998; 24:1237-41. [PubMed 9834745]
164. Naver H, Swartling C, Aquilonius SM. Palmar and axillary hyperhidrosis treated with botulinum toxin: one-year clinical follow-up. Eur J Neuro. 2000; 7:55-62.
165. Vadoud-Seyedi J, Heenen M, Simonart T. Treatment of idiopathic palmar hyperhidrosis with botulinum toxin. Report of 23 cases and review of the literature. Dermatology. 2001; 203:318-21. [PubMed 11752820]
166. Boyd RN, Morris ME, Graham HK. Management of upper limb dysfunction in children with cerebral palsy: a systematic review. Eur J Neurol. 2001; 8 (Suppl 5):150-66.
167. Naumann M, Flachenecker P, Brocker EB et al. Botulinum toxin for palmar hyperhidrosis. Lancet. 1997; 349:252. [IDIS 380461] [PubMed 9014916]
168. Drobik C, Laskawi R. Frey’s syndrome: treatment with botulinum toxin. Acta Otolaryngol. 1995; 115:459-61. [PubMed 7653272]
169. Love SC, Valentine JP, Blair EM et al. The effect of botulinum toxin type A on the functional ability of the child with spastic hemiplegia: a randomized controlled trial. Eur J Neurol. 2001; 8 (Suppl 5):50-8.
170. Wollina U, Karamfilov T, Konrad H. High-dose botulinum toxin type A therapy for axillary hyperhidrosis markedly prolongs the relapse-free interval. J Am Acad Dermatol. 2002; 46:536-40. [IDIS 479634] [PubMed 11907503]
171. Dykstra DD, Sidi AA. Treatment of detrusor-sphincter dyssynergia with botulinum A toxin: a double-blind study. Arch Phys Med Rehabil. 1990; 71:24-6. [PubMed 2297305]
172. Callaway JE, Arezzo JC, Grethlein AJ. Botulinum toxin type B: an overview of its biochemistry and preclinical pharmacology. Semin Cutan Med Surg. 2001; 20:127-36. [PubMed 11474745]
173. Pearce LB, Borodic GE, Johnson EA et al. The median paralysis unit: a more pharmacologically relevant unit of biologic activity for botulinum toxin. Toxicon. 1995; 33:217-27. [PubMed 7597725]
174. Cole R, Hallett M, Cohen LG. Double-blind trial of botulinum toxin for treatment of focal hand dystonia. Mov Disord. 1995; 10:466-71. [PubMed 7565828]
175. Pacchetti C, Albani G, Martignoni E et al. “Off” painful dystonia in Parkinson’s disease treated with botulinum toxin. Mov Disord. 1995; 10:333-6. [PubMed 7651452]
176. Karp BI, Cole RA, Cohen LG et al. Long-term botulinum toxin treatment of focal hand dystonia. Neurology. 1994; 44:70-6. [IDIS 324159] [PubMed 8290095]
177. Tsui JKC, Bhatt M, Calne S et al. Botulinum toxin in the treatment of writer’s cramp. Neurology. 1993; 43:183-5. [IDIS 308721] [PubMed 8423882]
178. Cohen LG, Hallett M, Geller BD et al. Treatment of focal dystonias of the hand with botulinum toxin injections. J Neurol Neurosurg Psychiatry. 1989; 52:355-63. [PubMed 2926421]
179. Molloy FM, Shill HA, Kaelin-Land A et al. Accuracy of muscle localization without EMG: implications for treatment of limb dystonia. Neurology. 2002; 58:805-7. [PubMed 11889247]
180. Lennerstrand G, Nordbo OA, Tian S et al. Treatment of strabismus and nystagmus with botulinum toxin type A. An evaluation of effects and complications. Acta Ophthalmol Scand. 1998; 76:27-7. [PubMed 9541431]
181. Tomsak RL, Remler BF, Averbuch-Heller L et al. Unsatisfactory treatment of acquired nystagmus with retrobulbar injection of botulinum toxin. Am J Ophthalmol. 1995; 119:489-96. [IDIS 345790] [PubMed 7709974]
182. Repka MX, Savino PJ, Reinecke RD. Treatment of acquired nystagmus with botulinum neurotoxin A. Arch Ophthalmol. 1994; 112:1320-4. [IDIS 336520] [PubMed 7945034]
183. Carruthers A, Carruthers J, Cohen J. A prospective, double-blind, randomized, parallel- group, dose-ranging study of botulinum toxin type a in female subjects with horizontal forehead rhytides. Dermatol Surg. 2003; 29:461-7. [PubMed 12752512]
184. Pasricha PJ, Ravich WJ, Hendrix TR et al. Intrasphincteric botulinum toxin for the treatment of achalasia. N Engl J Med. 1995; 332:774-8. [IDIS 344315] [PubMed 7862180]
185. Cohen S, Parkman HP. Treatment of achalasia—from whalebone to botulinum toxin. N Engl J Med. 1995; 332:815-6. [IDIS 344320] [PubMed 7862188]
186. Blitzer A, Binder WJ, Aviv JE et al. The management of hyperfunctional facial lines with botulinum toxin. A collaborative study of 210 injection sites in 162 patients. Arch Otolaryngol Head Neck Surg. 1997; 123:389-92. [PubMed 9109785]
187. Pasricha PJ, Rai R, Ravich WJ et al. Botulinum toxin for achalasia: long- term outcome and predictors of response. Gastroenterology. 1996; 110:1410-5. [PubMed 8613045]
188. Bhutani MS. Gastrointestinal uses of botulinum toxin. Am J Gastroenterol. 1997; 92:929-33. [PubMed 9177504]
189. Fishman VM, Parkman HP, Schiano TD et al. Symptomatic improvement in achalasia after botulinum toxin injection of the lower esophageal sphincter. Am J Gastroenterol. 1996; 91:1724-30. [PubMed 8792688]
190. Wehrmann T, Kokabpick H, Jacobi V et al. Long-term results of endoscopic injection of botulinum toxin in elderly achalasic patients with tortuous megaesophagus or epiphrenic diverticulum. Endoscopy. 1999; 31:352-8. [PubMed 10433043]
191. Annese V, D’Onofrio V, Andriulli A. Botulinum toxin in long-term therapy for achalasia. Ann Intern Med. 1998; 128:696. [PubMed 9537951]
192. Gordon JM, Eaker EY. Prospective study of esophageal botulinum toxin injection in high-risk achalasia patients. Am J Gastroenterol. 1997; 92:1812-7. [PubMed 9382042]
193. Storr M, Allescher HD, Rosch T et al. Treatment of symptomatic diffuse esophageal spasm by endoscopic injection of botulinum toxin: a prospective study with long term follow-up. Gastrointest Endosc. 2001; 54:754-9. [PubMed 11726856]
194. Modugno N, Priori A, Berardelli A et al. Botulinum toxin restores presynaptic inhibition of group Ia afferents in patients with essential tremor. Muscle Nerve. 1998; 21:1701-5. [PubMed 9843072]
195. Trosch RM, Pullman SL. Botulinum toxin A injections for the treatment of hand tremors. Movement Dis. 1994; 9:601-9. [PubMed 7845399]
196. Jankovic J, Schwartz K. Botulinum toxin treatment of tremors. Neurology. 1991; 41:1185-8. [PubMed 1866001]
197. Gordon K, Cadera W, Hinton G. Successful treatment of hereditary trembling chin with botulinum toxin. J Child Neurol. 1993; 8:154-6. [PubMed 8505478]
198. Snow BJ, Tsui JK, Bhatt BH et al. Treatment of spasticity with botulinum toxin: a double blind study. Ann Neurol. 1990; 28:512-5. [IDIS 272868] [PubMed 2252363]
199. Wheeler JS Jr, Walter JS, Chintam RS et al. Botulinum toxin injections for voiding dysfunction following SCI. J Spinal Cord Med. 1998; 21:227-9. [PubMed 9863933]
200. Dykstra DD, Sidi AA, Scott AB et al. Effects of botulinum A toxin on detrusor-sphincter dyssynergia in spinal cord injury patients. J Urol. 1988; 139:919-22. [PubMed 3361663]
201. Schurch B, Hauri D, Rodic B et al. Botulinum-A toxin as a treatment of detrusor-sphincter dyssynergia: a prospective study in 24 spinal cord injury patients. J Urol. 1996; 155:1023-9. [PubMed 8583552]
202. Gallien P, Robineau S, Verin M et al. Treatment of detrusor sphincter dyssynergia by transperineal injection of botulinum toxin. Arch Phys Med Rehabi. 1998; 79:715-7.
203. Schurch B, Hodler J, Rodic B. Botulinum A toxin as a treatment of detrusor-sphincter dyssynergia in patients with spinal cord injury: MRI controlled transperineal injections. J Neurol Neurosurg Psychiatry. 1997; 63:474-6. [PubMed 9343126]
204. Ubhi T, Bhakta BB, Ives HL et al. Randomised double blind placebo controlled trial of the effect of botulinum toxin on walking in cerebral palsy. Arch Dis Child. 2000; 83:481-7. [IDIS 456851] [PubMed 11087280]
205. Bielamowicz S, Stager SV, Badillo A et al. Unilateral versus bilateral injections of botulinum toxin in patients adductor spasmodic dysphonia. J Voice. 2002; 16:117-23. [PubMed 12002878]
206. de Seze M, Petit H, Gallien P et al. Botulinum A toxin and detrusor sphincter dyssynergia: a double-blind lidocaine-controlled study in 13 patients with spinal cord disease. Eur Urol. 2002; 42:56-62. [PubMed 12121731]
207. Blitzer A, Brin MF, Stewart C et al. Abductor laryngeal dystonia: a series treated with botulinum toxin. Laryngoscope. 1992; 102:163-7. [PubMed 1738288]
208. Schulte-Baukloh H, Michael T, Schobert J et al. Efficacy of botulinum-A toxin in children with detrusor hyperreflexia due to myelomeningocele: preliminary results. Urology. 2002; 59:325-8. [PubMed 11880062]
209. Mall V, Glocker FX, Frankenschmidt A et al. Treatment of neuropathic bladder using botulinum toxin A in a 1-year-old child with myelomeningocele. Pediatr Nephrol. 2001; 16:1161-2. [PubMed 11793122]
210. Schurch B, Schmid DM, Stohrer M. Treatment of neurogenic incontinence with botulinum toxin A. N Engl J Med. 2000; 342:665. [IDIS 441107] [PubMed 10702067]
211. Schulte-Baukloh H, Michael T. Botulinum-A toxin in the treatment of neurogenic bladder in children. Pediatrics. 2002; 110(2 Part 1):420-1. [PubMed 12165609]
212. Phelan MW, Franks M, Somogyi GT et al. Botulinum toxin urethral phincter injection to restore bladder emptying in men and women with voiding dysfunction. J Urol. 2001; 165:1107-10. [PubMed 11257648]
213. Joo JS, Agachan F, Wolff B et al. Initial North American experience with botulinum toxin type A for treatment of anismus. Dis Colon Rectum. 1996; 39:1107-11. [PubMed 8831524]
214. Hallan RI, Williams NS, Melling J et al. Treatment of anismus in intractable constipation with botulinum A toxin. Lancet. 1988; 2:714-7. [PubMed 2901570]
215. Albanese A, Maria G, Bentivoglio AR et al. Severe constipation in Parkinson’s disease relieved by botulinum toxin. Mov Disord. 1997; 12:764-6. [PubMed 9380063]
216. Langer JC, Birnbaum E. Preliminary experience with intrasphincteric botulinum toxin for persistent constipation after pull-through for Hirschsprung’s disease. J Pediatr Surg. 1997; 32:1059-61. [PubMed 9247234]
217. Stein E. Botulinum toxin and anal fissure. Curr Probl Dermatol. 2002; 30:218-26. [PubMed 12471714]
218. Simpson DM. Clinical trials of botulinum toxin in the treatment of spasticity. Muscle Nerve Suppl. 1997; 6:S1-7.
219. Moore AP. Botulinum toxin A (BoNT-A) for spasticity in adults. What is the evidence? Eur J Neurol.2002; 9(Suppl 1):42-7.
220. Jozefczyk PB. The management of focal spasticity. Clin Neuropharmacol. 2002; 25:158-73. [PubMed 12023570]
221. Brashear A, Gordon MF, Elovic E for the Botox Post-Stroke Spasticity Study Group. Intramuscular injection of botulinum toxin for the treatment of wrist and finger spasticity after a stroke. N Engl J Med. 2002; 347:395- 400. [IDIS 484719] [PubMed 12167681]
222. Rowland LP. Stroke, spasticity, and botulinum toxin. N Engl J Med. 2002; 347:382-3. [PubMed 12167679]
223. Hesse S, Krajnik J, Luecke D et al. Ankle muscle activity before and after botulinum toxin therapy for lower limb extensor spasticity in chronic hemiparetic patients. Stroke. 1996; 27:455-60. [PubMed 8610313]
224. Simpson DM, Alexander DN, O’Brien CF et al. Botulinum toxin type A in the treatment of upper extremity spasticity: a randomized, double-blind, placebo-controlled trial. Neurology. 1996; 46:1306-10. [IDIS 367055] [PubMed 8628472]
225. Bhakta BB, Cozens JA, Chamberlain MA. Use of botulinum toxin in stroke patients with severe upper limb spasticity. J Neurol Neurosurg Psychiatry. 1996; 61:30-5. [PubMed 8676154]
226. Kirazli Y, On AY, Kismali B et al. Comparison of phenol block and botulinus toxin type A in the treatment of spastic foot after stroke. Am J Phys Med Rehabil. 1998; 77:510-5. [PubMed 9862538]
227. Hesse S, Reiter F, Konrad M et al. Botulinum toxin type A and short-term electrical stimulation in the treatment of upper limb flexor spasticity after stroke: a randomized, double-blind, placebo-controlled trial. Clin Rehabil. 1998; 12:381-8. [PubMed 9796928]
228. Carr LJ, Cosgrove AP, Gingras P et al. Position paper on the use of botulinum toxin in cerebral palsy. Arch Dis Child. 1998; 79:271-3. [PubMed 9875028]
229. Koman LA, Smith BP, Balkrishnan R. Spasticity associated with cerebral palsy in children. Pediatr Drugs. 2003; 5:11-23.
230. Corry IS, Cosgrove AP, Walsh EG et al. Botulinum toxin A in the hemiplegic upper limb: a double-blind trial. Dev Med Child Neurol. 1997; 39:185-93. [PubMed 9112968]
231. Sutherland DH, Kaufman KR, Wyatt MP et al. Double-blind study of botulinum A toxin injections into the gastrocnemius muscle in patients with cerebral palsy. Gait Posture. 1999; 10:1-9. [PubMed 10469936]
232. Koman LA, Mooney JF III, Smith BP et al. Management of spasticity in cerebral palsy with botulinum-A toxin: report of a preliminary, randomized, double-blind trial. J Pediatr Orthop. 1994; 14:299-303. [PubMed 8006158]
233. Flett PJ, Stern LM, Waddy H et al. Botulinum toxin A versus fixed cast stretching for dynamic calf tightness in cerebral palsy. J Paediatr Child Health. 1999; 35:71-7. [PubMed 10234640]
234. Corry IS, Cosgrove AP, Duffy CM et al. Botulinum toxin A compared with stretching casts in the treatment of spastic equinus: a randomised prospective trial. J Pediatr Orthop. 1998; 18:304-11. [PubMed 9600553]
235. Yablon SA, Agana BT, Ivanhoe CB et al. Botulinum toxin in severe upper extremity spasticity among patients with traumatic brain injury: an open-labeled trial. Neurology. 1996; 47:939-44. [IDIS 374813] [PubMed 8857723]
236. Palmer DT, Horn LJ, Harmon RL. Botulinum toxin treatment of lumbrical spasticity. Am J Phys Med Rehabil. 1998; 77:348-50. [PubMed 9715926]
237. Anon. FDA approves Botox to treat severe underarm sweating. FDA talk paper. Rockville, MD: Food and Drug Administration; 2004 Jul 20.
238. Loder E, Biondi D. Use of botulinum toxins for chronic headaches: a focused review. Clin J Pain. 2002; 18(6 Suppl):S169-76. [PubMed 12569965]
239. Silberstein S, Mathew N, Saper J et al for the BOTOX Migraine Clinical Research Group. Botulinum toxin type A as a migraine preventive treatment. Headache. 2000; 40:445-50. [PubMed 10849039]
240. Raj PP. Botulinum toxin in the treatment of pain associated with musculoskeletal hyperactivity. Curr Rev Pain. 1997; 1:403- 16.
241. Sheean G. Botulinum toxin for the treatment of musculoskeletal pain and spasm. Curr Pain Headache Rep. 2002; 6:460-9. [PubMed 12413405]
242. Lang AM. Botulinum toxin therapy for myofascial pain disorders. Curr Pain Headache Rep. 2002; 6:355-60. [PubMed 12207848]
243. Smith HS, Audette J, Royal MA. Botulinum toxin in pain management of soft tissue syndromes. Clin J Pain. 2002; 18(6 Suppl):S147-54. [PubMed 12569962]
244. Foster L, Clapp L, Erickson M et al. Botulinum toxin A and chronic low back pain: randomized, double-blind study. Neurology. 2001; 6:1290-3.
245. Difazio M, Jabbari B. A focused review of the use of botulinum toxins for low back pain. Clin J Pain. 2002; 18(6 Suppl):S155-62. [PubMed 12569963]
246. Carruthers J, Carruthers A. Aesthetic botulinum A toxin in the mid and lower face and neck. Dermatol Surg. 2003; 29:468-76. [PubMed 12752513]
247. Troung DD, Rontal M, Rolnick M et al. Double-blind controlled study of botulinum toxin in adductor spasmodic dysphonia. Laryngoscope. 1991; 101(6 Pt 1):630-4. [PubMed 2041443]
248. Pahwa R, Busenbark K, Swanson-Hyland EF et al. Botulinum toxin treatment of essential head tremor. Neurology. 1995; 45:822-4. [IDIS 345749] [PubMed 7723978]
249. Setler PE. Therapeutic use of botulinum toxins: background and history. Clin J Pain. 2002; 18(Suppl):S119-24. [PubMed 12569958]
250. Terranova W, Breman JG, Locey RP et al. Botulism type B: epidemiologic aspects of an extensive outbreak. Am J Epidemiol. 1978; 108:150-6. [PubMed 707476]
252. Brin MF, Vapnek JM. Treatment of vaginismus with botulinum toxin injections. Lancet. 1997; 349:252-3. [IDIS 380462] [PubMed 9014917]
253. Dressler D, Bigalke H. Botulinum toxin antibody type A titres after cessation of botulinum toxin therapy. Mov Disord. 2002; 17:170-3. [PubMed 11835457]
254. Critchfield J. Considering the immune response to botulinum toxin. Clin J Pain. 2002; 18(6 Suppl):S133-41. [PubMed 12569960]
255. Greene PE, Fahn S. Response to botulinum toxin F in seronegative botulinum toxin A-resistant patients. Mov Disord. 1996; 11:181-4. [PubMed 8684389]
256. Davies J, Duffy D, Boyt N et al. Botulinum toxin (Botox) reduces pain after hemorrhoidectomy. Dis Colon Rectum. 2003; 46:1097-1102. [PubMed 12907905]
257. Chen R, Karp BI, Hallett M. Botulinum toxin type F for treatment of dystonia: long-term experience. Neurology. 1998; 51:1494- 6. [IDIS 417620] [PubMed 9818895]
258. Hexsel DM, Trindade de Almeida T, Rutowitsch M et al. Multicenter, double-blind study of the efficacy of injections of botulinum toxin type A reconstituted up to six weeks before application. Dermatol Surg. 2003; 29:523-9. [PubMed 12752522]
259. Schaffner R, Kreyden OP. Complications and side-effects of botulinum toxin A. Curr Probl Dermatol. 2002; 30:141-8. [PubMed 12471708]
260. Wyndaele JJ, Van Dromme SA. Muscular weakness as side effect of botulinum toxin injection for neurogenic detrusor overactivity. Spinal Cord. 2002; 40:599-600. [PubMed 12411968]
261. Dressler D, Benecke R. Autonomic side effects of botulinum toxin type B treatment of cervical dystonia and hyperhidrosis. Eur Neurol. 2003; 49:34- 8. [PubMed 12464716]
262. Papadonikolakis AS, Vekris MD, Kostas JP et al. Transient erectile dysfunction associated with intramuscular injection of botulinum toxin type A. J South Orthop Assoc. 2002; 11:116-8. [PubMed 12741592]
263. Price J, Farish S, Taylor H et al. Blepharospasm and hemifacial spasm. Randomized trial to determine the most appropriate location for botulinum toxin injections. Ophthalmology. 1997; 104:865-8.
264. D. Polyradiculoneuritis after botulinum toxin type A therapy for cervical dystonia. Clin Neuropharmacol. 2001; 24:122-4. [PubMed 11307052]
265. Martin CO, Adams HP Jr. Neurological aspects of biological and chemical terrorism: a review for neurologists. Arch Neurol. 2003; 60:21-5. [PubMed 12533084]
266. Pasricha PJ, Miskovsky EP, Kalloo AN. Intrasphincteric injection of botulinum toxin for suspected sphincter of Oddi dysfunction. Gut. 1994; 35:1319-21. [PubMed 7959245]
267. Freund BJ, Schwartz M. Treatment of chronic cervical-associated headache with botulinum toxin A: a pilot study. Headache. 2000; 40:231-6. [PubMed 10759926]
268. Maria G, Brisinda G, Civello IM et al. Relief by botulinum toxin of voiding dysfunction due to benign prostatic hyperplasia: results of a randomized, placebo-controlled study. Urology. 2003; 62:259-65. [PubMed 12893330]
269. Koman LA, Mooney JF III, Smith B et al. Management of cerebral palsy with botulinum-A toxin: preliminary investigation. J Pediatr Orthop. 1993; 13:489-95. [PubMed 8370782]
270. Koman LA, Mooney JF III, Smith BP et al. Botulinum toxin type A neuromuscular blockade in the treatment of lower extremity spasticity in cerebral palsy: a randomized, double-blind, placebo-controlled trial. BOTOX Study Group. J Pediatr Orthop. 2000; 20:108-15. [PubMed 10641699]
271. Graham HK, Aoki KR, Autti-Ramo I et al. Recommendations for the use of botulinum toxin type A in the management of cerebral palsy. Gait Posture. 2000; 11:67-79. [PubMed 10664488]
272. Molenaers G, Desloovere K, Eyssen M et al. Botulinum toxin type A treatment of cerebral palsy: an integrated approach. Eur J Neurol. 1999; 6 Suppl 4:S51-7.
273. Gormley ME, Gaebler-Spira D, Delgado MR. Use of botulinum toxin type A in pediatric patients with cerebral palsy: a three-center retrospective chart review. J Child Neurol. 2001; 16:113-8. [PubMed 11292216]
274. Maria G, Brisinda G, Civello IM et al. Relief by botulinum toxin of voiding dysfunction due to benign prostatic hyperplasia: results of a randomized, placebo-controlled study. Urology. 2003; 62:264-5.
275. Barwood S, Baillieu C, Boyd R et al. Analgesic effects of botulinum toxin A: a randomized, placebo-controlled clinical trial. Dev Med Child Neurol. 2000; 42:116-21. [PubMed 10698329]
276. Grazko MA, Polo KB, Jabbari B. Botulinum toxin A for spasticity, muscle spasms, and rigidity. Neurology. 1995; 45:712-7. [IDIS 345748] [PubMed 7723960]
277. Centeno RF, Boswell CB, Matarasso A. Botulinum toxin for managing focal hyperhidrosis. Aesthetic Surg J. 2003; 23:67-9.
278. Sloop RR, Cole BA, Escutin RO. Reconstituted botulinum toxin type A does not lose potency in humans if it is refrozen or refrigerated for 2 weeks before use. Neurology. 1997; 48:249-53. [IDIS 379261] [PubMed 9008526]
279. Friedman A, Diamond M, Johnston MV et al. Effects of botulinum toxin A on upper limb spasticity in children with cerebral palsy. Am J Phys Med Rehabil. 2000; 79:53-9. [PubMed 10678604]
280. Koman LA, Brashear A, Rosenfeld S et al. Botulinum toxin type A neuromuscular blockade in the treatment of equinus foot deformity in cerebral palsy: a multicenter, open-label clinical trial. Pediatrics. 2001 Nov; 108:1062-71.
281. Sutherland DH, Kaufman KR, Wyatt MP et al. Double-blind study of botulinum A toxin injections into the gastrocnemius muscle in patients with cerebral palsy. Gait Posture. 1999; 10:1-9. [PubMed 10469936]
282. Baumann L, Frankel S, Welsh E et al. Cryoanalgesia with dichlorotetrafluoroethane lessens the pain of botulinum toxin injections for the treatment of palmar hyperhidrosis. Dermatol Surg. 2003; 29:1057-60. [PubMed 12974705]
283. Colosimo C, Chianese M, Giovannelli M et al. Botulinum toxin type B in blepharospasm and hemifacial spasm. J Neurol Neurosurg Psychiatry. 2003; 74:687-91. [PubMed 12700325]
284. Glanzman RL, Gelb DJ, Drury I et al. Brachial plexopathy after botulinum toxin injections. Neurology. 1990; 40:1143. [IDIS 269203] [PubMed 2162501]
285. Molenaers G, Eyssen M, Desloovere K et al. A multilevel approach to botulinum toxin type A treatment of the (ilio)psoas in spasticity in cerebral palsy. Eur J Neurol. 1999; 6(Suppl 4):S59-2.
286. Jost WH. Botulinum toxin type B in the treatment of anal fissures: first preliminary results. Dis Colon Rectum. 2001; 44:1721-2. [PubMed 11719933]
287. Vieregge P, Kömpf D. Brachial plexopathy after botulinum toxin administration for cervical dystonia. J Neurol Neurosurg Psychiatry. 1993; 56: 1338-9.
288. Sampaio C, Castro-Caldas A, Sales-Luis ML et al. Brachial plexopathy after botulinum toxin administration for cervical dystonia. J Neurol Neurosurg Psychiatry. 1993; 56:1339.
289. Vargas H, Galati LT, Parnes SM. A pilot study evaluating the treatment of postparotidectomy sialoceles with botulinum toxin type A. Arch Otolaryngol Head Neck Surg. 2000; 126:421-4. [PubMed 10722021]
290. Guntinas-Lichius O, Sittel C. Treatment of postparotidectomy salivary fistula with botulinum toxin. Ann Otol Rhinol Laryngol. 2001; 110:1162-4. [PubMed 11768708]
291. Dykstra DD, Pryor J, Goldish G. Use of botulinum toxin type B for the treatment of detrusor hyperreflexia in a patient with multiple sclerosis: a case report. Arch Phys Med Rehabil. 2003; 84:1399-400. [PubMed 13680581]
292. Latimer PR, Hodgkins PR, Vakalis AN et al. Necrotising fasciitis as a complication of botulinum toxin injection. Eye. 1998; 12(Part 1):51-3. [PubMed 9614517]
293. Porta M. A comparative trial of botulinum toxin type A and methylprednisolone for the treatment of myofascial pain syndrome and pain from chronic muscle spasm. Pain. 2000; 85:101-5. [PubMed 10692608]
294. Shakespeare DT, Boggild M, Young C. Anti-spasticity agents for multiple sclerosis (Cochrane review). In: The Cochrane Library. Issue 3. Oxford, UK: Update Software, Inc. 2003.
295. Ade-Hall RA, Moore AP. Botulinum toxin type A in the treatment of lower limb spasticity in cerebral palsy (Cochrane review). In: The Cochrane Library. Issue 3. Oxford, UK: Update Software, Inc. 2003.
296. Reviewers’ comments (personal observations).
297. Elan Pharmaceuticals. South San Francisco, CA: Personal communication.
298. Allergan. Irvine, CA: Personal communication on botulinum toxin type B (Botox, Botox Cosmetic).
299. Tintner R, Jankovic J. Botulinum toxin for the treatment of cervical dystonia. Expert Opin Pharmacother. 2001; 2:1985-94. [PubMed 11825330]
300. Zimbler MS, Holds JB, Kokoska MS et al. Effect of botulinum toxin pretreatment on laser resurfacing results: a prospective, randomized, blinded trial. Arch Facial Plast Surg. 2001; 3:165-9. [PubMed 11497500]
301. Sadick NS. Prospective open-label study of botulinum toxin type B (Myobloc) at doses of 2,400 and 3,000 U for the treatment of glabellar wrinkles. Dermatol Surg. 2003; 29:501-7. [PubMed 12752518]
302. Sadick NS. Botulinum toxin type B for glabellar wrinkles: a prospective open-label response study. Dermatol Surg. 2002; 28:817-21. [PubMed 12269875]
303. Blitzer A. Botulinum neurotoxin A for the management of lower facial lines and platysmal bands. In: Lowe N, ed. Textbook of facial rejuvenation. Martin Dunitz, London; 2002:171-177.
304. Matarasso A, Matarasso SL, Brandt FS et al. Botulinum A exotoxin for the management of platysma bands. Plast Reconstr Surg. 2003; 112:127-34S.
305. Sposito MM. New indications for botulinum toxin type a in cosmetics: mouth and neck. Plast Reconstr Surg. 2003; 112:75-85S.
306. Matarasso A, Matarasso SL. Botulinum A exotoxin for the management of platysma bands. Plast Reconstr Surg. 2003; 112:138-140S.
307. Arad-Cohen A, Blitzer A. Botulinum toxin treatment for symptomatic Frey’s syndrome. Otolaryngol Head Neck Surg. 2000; 122:237-40. [PubMed 10652397]
308. Blitzer A, Brin MF, Stewart CF. Botulinum toxin management of spasmodic dysphonia (laryngeal dystonia): a 12-year experience in more than 900 patients. Laryngoscope. 1998; 108:1435-41. [PubMed 9778279]
309. Ron T, Jankovic J. Botulinum Toxin Type A in the Management of Oromandibular Dystonia and Bruxism. In: Brin MF, Hallett M, Jankovic J, ed. Scientific and Therapeutic Aspects of Botulinum Toxin. Lippincott Williams & Wilkins, Philadelphia, PA; 2002.
310. Baumann L, Slezinger A, Vujevich J et al. A double-blinded, randomized, placebo-controlled pilot study of the safety and efficacy of Myobloc (botulinum toxin type B)-purified neurotoxin complex for the treatment of crow’s feet: a double-blinded, placebo-controlled trial. Dermatol Surg. 2003; 29:508-15. [PubMed 12752519]
311. Lowe NJ, Lask G, Yamauchi P et al. Bilateral, double-blind, randomized comparison of 3 doses of botulinum toxin type A and placebo in patients with crow’s feet. J Am Acad Dermatol. 2002; 47:834-40. [IDIS 490926] [PubMed 12451366]
312. McNeer KW, Tucker MG, Spencer RF. Management of essential infantile esotropia with botulinum toxin A: review and recommendations. J Pediatr Ophthalmol Strabismus. 2000; 37:63-7. [PubMed 10779262]
313. Royal MA. The use of botulinum toxins in the management of myofascial pain and other conditions associated with painful muscle spasm. Available at Pain.com. Accessed 2004 Jan 5.
314. Karamfilov T, Konrad H, Karte K et al. Lower relapse rate of botulinum toxin A therapy for axillary hyperhidrosis by dose increase. Arch Dermatol. 2000; 136:487-90. [IDIS 445772] [PubMed 10768647]
315. Russman BS, Tilton A, Gormley ME. Cerebral palsy: a rational approach to a treatment protocol, and the role of botulinum toxin in treatment. Muscle Nerve Suppl. 1997; 6:181-93S.
316. Brisinda G, Civello IM, Albanese A et al. Gastrointestinal smooth muscles and sphincters spasms: treatment with botulinum neurotoxin. Curr Med Chem. 2003; 10:603-23. [PubMed 12678792]
317. Blitzer A, Brin MF, Stewart C., et al. Abductor laryngeal dystonia: a series treated with botulinum toxin. Laryngoscope. 1992; 102:163-7. [PubMed 1738288]
318. Kuo HC. Botulinum A Toxin Urethral Injection for the Treatment of Lower Urinary Tract Dysfunction. J Urol. 2003; 170:1908-12. [IDIS 508891] [PubMed 14532805]
319. Kuo HC. Effect of botulinum a toxin in the treatment of voiding dysfunction due to detrusor underactivity. Urology. 2003; 61:550-4. [PubMed 12639645]
320. Racette BA, Good L, Sagitto S et al. Botulinum toxin B reduces sialorrhea in parkinsonism. Mov Disord. 2003; 18:1059-61. [PubMed 14502678]
321. Fehlings D, Rang M, Glazier J et al. An evaluation of botulinum-A toxin injections to improve upper extremity function in children with hemiplegic cerebral palsy. J Pediatr. 2000; 137:331-7. [IDIS 455122] [PubMed 10969256]
322. Keizer SB, Rutten HP, Pilot P et al. Botulinum toxin injection versus surgical treatment for tennis elbow: a randomized pilot study. Clin Orthop. 2002; 401:125-31. [PubMed 12151889]
323. Gassner HG, Sherris DA. Addition of an anesthetic agent to enhance the predictability of the effects of botulinum toxin type A injections: a randomized controlled study. Mayo Clin Proc. 2000; 75:701-4. [IDIS 450892] [PubMed 10907385]
324. Brin MF, Binder W, Blitzer A et al. Botulinum Toxin Type A Botox for Pain and Headache. In: Brin MF, Hallett M, Jankovic J, ed. Scientific and Therapeutic Aspects of Botulinum Toxin. Lippincott Williams & Wilkins, Philadelphia, PA; 2002.
325. Binder WJ, Brin MF, Blitzer A et al. Botulinum toxin type A (Botox) for treatment of migraine headaches: an open-label study. Otolaryngol Head Neck Surg. 2000; 123:669-76 [PubMed 11112955]
326. Binder WJ, Brin MF, Blitzer A et al. Botulinum toxin type A (Botox) for treatment of migraine. Semin Cutan Med Surg. 2001; 20:93-100. [PubMed 11474749]
327. Blumenfeld AM, Binder W, Silberstein SD. Procedures for administering botulinum toxin type A for migraine and tension-type headache. Headache. 2003; 43:884-91. [IDIS 504325] [PubMed 12940810]
328. Wheeler AH. Botulinum toxin injection technique for treatment of headaches. Aesthetic Surg J. 2002; 22:65-8.
329. Wheeler AH, Goolkasian P, Gretz SS. A randomized, double-blind, prospective pilot study of botulinum toxin injection for refractory, unilateral, cervicothoracic, paraspinal, myofascial pain syndrome. Spine. 1998; 23:1662-6. [PubMed 9704373]
330. Wheeler AH. Botulinum toxin A, adjunctive therapy for refractory headaches associated with pericranial muscle tension. Headache. 1998; 38:468-71. [PubMed 9664753]
331. Wheeler AH, Goolkasian P, Gretz SS. Botulinum toxin A for the treatment of chronic neck pain. Pain. 2001; 94:255-60. [PubMed 11731062]
332. Guyer BM. Mechanism of botulinum toxin in the relief of chronic pain. Curr Rev Pain. 1999; 3:427-31. [PubMed 10998700]
333. Wheeler AH, Goolkasian P. Open label assessment of botulinum toxin A for pain treatment in a private outpatient setting. J Musculoskeletal Pain. 2001; 9:67-82.
334. Gokani T, Robbins L. Botulinum toxin: Efficacy in migraine, tension-type, and cluster headache. J Pain Management. 2002; 12:79-85.
335. Opida C. Open-label study of Myobloc (botulinum toxin type B) in the treatment of patients with transformed migraine headaches. Arch Pharmacol. 200; 365. Abstract.
336. Freund BJ, Schwartz M. Use of botulinum toxin in chronic whiplash-associated disorder. Clin J Pain. 2002; 18:S163-8.
337. Lowe NJ, Yamauchi PS, Lask GP et al. Botulinum toxins types A and B for brow furrows: preliminary experiences with type B toxin dosing. J Cosmet Laser Ther. 2002; 4:15-8. [PubMed 12079632]
338. Baumann L, Black L. Botulinum toxin type B (Myobloc). Dermatol Surg. 2003; 29:496-500. [PubMed 12752517]
339. Argoff CE. A focused review on the use of botulinum toxins for neuropathic pain. Clin J Pain. 2002; 18(Suppl):S177-S181. [PubMed 12569966]
340. Brashear A, McAfee AL, Kuhn ER et al. Treatment with botulinum toxin type B for upper-limb spasticity. Arch Phys Med Rehabil. 2003; 84:103-7. [PubMed 12589629]
341. O’Brien CF. Treatment of spasticity with botulinum toxin. Clin J Pain. 2002; 18: S182-90.
342. Desloovere K, Molenaers G, Jonkers I et al. A randomized study of combined botulinum toxin type A and casting in the ambulant child with cerebral palsy using objective outcome measures. Eur J Neurol. 2001; 8 Suppl 5:75-87. [PubMed 11851736]
343. Houltram J, Noble I, Boyd RN et al. Botulinum toxin type A in the management of equinus in children with cerebral palsy: an evidence-based economic evaluation. Eur J Neurol. 2001; 8 Suppl 5:194-202. [PubMed 11851748]
344. van Laborde S, Dover JS, Moore M et al. Reduction in injection pain with botulinum toxin type B further diluted using saline with preservative: a double-blind, randomized controlled trial. J Am Acad Dermatol. 2003; 48:875-7. [PubMed 12789177]
345. Dressler D, Bigalke H, Benecke R. Botulinum toxin type B in antibody-induced botulinum toxin type A therapy failure. J Neurol. 2003; 250:967-9. [PubMed 12928917]
346. Greene P, Fahn S, Diamond B. Development of resistance to botulinum toxin type A in patients with torticollis. Mov Disord. 1994; 9:213-7. [PubMed 8196686]
347. Jankovic J, Vuong KD, Ahsan J. Comparison of efficacy and immunogenicity of original versus current botulinum toxin in cervical dystonia. Neurology. 2003; 60:1186-8. [IDIS 499827] [PubMed 12682332]
348. Jankovic J, Schwartz K. Response and immunoresistance to botulinum toxin injections. Neurology. Sep; 45:1743-6.
349. Adler CH, Factor SA, Brin M et al. Secondary nonresponsiveness to botulinum toxin type A in patients with oromandibular dystonia. Mov Disord. 2002; 17:158-61. [PubMed 11835455]
350. Sankhla C, Jankovic J, Duane D. Variability of the immunologic and clinical response in dystonic patients immunoresistant to botulinum toxin injections. Mov Disord. 1998; 13:150-4. [PubMed 9452341]
351. Racette BA, Stambuk M, Perlmutter JS. Secondary nonresponsiveness to new bulk botulinum toxin A (BCB2024). Mov Disord. 2002; 17:1098-100. [PubMed 12360571]
352. Racette BA, Lopate G, Good L et al. Ptosis as a remote effect of therapeutic botulinum toxin B injection. Neurology. 2002; 59:1445-7. [IDIS 489747] [PubMed 12427903]
353. Evers S, Rahmann A, Vollmer-Haase J et al. Treatment of headache with botulinum toxin A--a review according to evidence-based medicine criteria. Cephalalgia. 2002; 22:699-710. [PubMed 12421155]
354. Sataloff RT, Heman-Ackah YD, Simpson LL et al. Botulinum toxin type B for treatment of spasmodic dysphonia: a case report. J Voice. 2002; 16:422-4. [PubMed 12395995]
355. Guntinas-Lichius O. Injection of botulinum toxin type B for the treatment of otolaryngology patients with secondary treatment failure of botulinum toxin type A. Laryngoscope. 2003 Apr; 113:743-5.
356. Kayikcioglu A, Erk Y, Mavili E. Botulinum toxin in the treatment of zygomatic fractures. Plast Reconstr Surg. 2003; 111:341-6. [PubMed 12496600]
357. Arezzo JC, Litwak MS, Gasper CA et al. The spread of paralytic activity in juvenile monkeys: a comparison of botulinum toxin type A and botulinum toxin type B. Paper presented at the World Congress of Neurological Rehabilitation, Venice, Italy: 2002 Apr 2-6.
358. Turkel CC, Dru RM, Simon D et al. Neutralizing antibody formation is rare following repeated injections of a low protein formulation of botulinum toxin type a (BTX-A) in patients with poststroke spasticity. Neurology. 2002; 58(Suppl 3):A316.
359. Aoki KR, Guyer B. Botulinum toxin type A and other botulinum toxin serotypes: a comparative review of biochemical and pharmacological actions. Eur J Neurol. 2001; 8(Suppl 5):21-9. [PubMed 11851731]
360. Yablon SA. Botulinum neurotoxin intramuscular chemodenervation. Role in the management of spastic hypertonia and related motor disorders. Phys Med Rehab Clin NA. 2001; 12:833-74.
361. Jost WH, Kohl A. Botulinum toxin: evidence-based medicine criteria in blepharospasm and hemifacial spasm. J Neruol. 2001; 248 (Suppl 1):I21-24.
362. Park YC, Lim JK, Lee DK et al. Botulinum a toxin treatment of hemifacial spasm and blepharospasm. J Korean Med Sci. 1993; 8:334-40.
363. Food and Drug Administration. Orphan drug regulations. 21 CFR Part 316. [Docket No. 85N-0483] Fed Regist. 1991; 56:3338-51.
364. Food and Drug Administration. Botulinum toxin. Import alert #57-17, 7/31/03, detention without physical examination of unlicensed botulinum toxin. Rockville, MD. From FDA website. Accessed 2005 Feb 18.
365. Jonas M, Speake W, Scholefield JH. Diltiazem heals glyceryl trinitrate-resistant chronic anal fissures: a prospective study. Dis Colon Rectum. 2002; 45:1091-5. [PubMed 12195195]
366. DasGupta R, Franklin I, Pitt J et al. Successful treatment of chronic anal fissure with diltiazem gel. Colorectal Dis. 2002; 4:20-2. [PubMed 12780649]
367. Solstice Neurosciences. South San Francisco, CA: Personal communication.
368. Yablon SA, Jackkson MS, Daggett S et al. Toxin neutralizing antibody formation with botulinum toxin type A (BoNTA) treatment in neuromuscular disorders. Neurology. 2005; 64 (suppl 1); A72. Abstract.
369. Baumann L, slezinger A, Halem M et al. Double-blind, randomized, placebo-controlled pilot study of the safety and efficacy of Myobloc (botulinum toxin type B) for the treatment of palmar hyperhidrosis. Dermatol Surg. 2005; 31:263-70. [PubMed 15841624]
370. Jesitus J. Bogus Botox sounds wake-up call. Cosm Surg Times [online]. March 2005. Available at ModernMedicine website. Accessed 2005 May 8.
371. Food and Drug Administration. Early communication about an ongoing safety review: Botox and Botox Cosmetic (botulinum toxin type A) and Myobloc (botulinum toxin type B). Rockville, MD; 2008 Feb 8. From FDA website.
372. Food and Drug Administration. FDA notifies public of adverse reactions linked to Botox use. FDA News. February 8, 2008. From FDA website.
373. Food and Drug Administration. Botox, Botox Cosmetic (botulinum toxin type A), Myobloc (botulinum toxin type B). Medwatch safety information alerts 2008. Rockville, MD; February 8, 2008. From FDA website.
374. Kuehn BM. Studies, reports say botulinum toxins may have effects beyond injection site. JAMA. 2008; 299:2261-3. [PubMed 18492959]
375. Barbehenn E, Lurie P, Stark S et al. Petition to the FDA requesting regulatory action concerning the possible spread of botulinum toxin (Botox, Myobloc) from the site of injection to other parts of the body. Washington, DC: Public Citizen’s Health Research Group; 2008 Jan.
376. Coté TR, Mohan AK, Polder JA et al. Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases. J Am Acad Dermatol. 2005; 53:407-15. [PubMed 16112345]
377. Chertow DS, Tan ET, Maslanka SE et al. Botulism in 4 adults following cosmetic injections with an unlicensed, highly concentrated botulinum preparation. JAMA. 2006; 296:2476-9. [PubMed 17119144]
378. Souayah N, Karim H, Kamin SS et al. Severe botulism after focal injection of botulinum toxin. Neurology. 2006; 67:1855-6. [PubMed 17130423]
379. Tugnoli V, Eleopra R, Quatrale R et al. Botulism-like syndrome after botulinum toxin type A injections for focal hyperhidrosis. Br J Dermatol. 2002; 147:808-9. [PubMed 12366438]
380. Roche N, Schnitzler A, Genet F F et al. Undesirable distant effects following botulinum toxin type A injection. Clin Neuropharmacol. 2008; 31:272-80. [PubMed 18836345]