Clinical Uses of Botulinum Toxins

Half-title......Page 3
Title......Page 5
Copyright......Page 6
Contents......Page 7
Contributors......Page 9
1.1.1 History of BoNT......Page 13
1.1.2 History of BoNT as a therapeutic agent......Page 14
1.2 Why write this book?......Page 15
1.3 Outline of the book......Page 16
REFERENCES......Page 19
2.1 Introduction......Page 21
2.3 BoNT/A binds to ‘productive’ ecto-acceptors on motor and autonomic nerves: such targeting underlies its peripheral cholinergic specificity......Page 22
2.4 I-BoNT undergoes acceptor-mediated endocytosis in cholinergic nerves: enhancement by stimulation and acceleration of neuromuscular paralysis......Page 26
2.5 Intra-neuronal inhibition by BoNT/A of the release of numerous transmitters from SSVs and LDCVs highlights an ubiquitous target essential for regulated exocytosis......Page 27
2.7 Prolonged neuromuscular paralysis and associated nerve sprouting induced by BoNT/A contrasts with the transient effect of type E: differences…......Page 29
2.8 Therapeutic applications: present success and unique properties of BoNTs offer encouraging prospects for further advancement......Page 33
REFERENCES......Page 34
3.1 Product development......Page 41
3.2 Product assay......Page 44
3.3 Production of botulinum toxins for clinical use......Page 45
3.4 Organisms used for clinical toxin manufacture......Page 47
3.5 Formulation of therapeutic toxin products......Page 48
3.6 Therapeutic ratio of toxin products......Page 49
3.7.2 Exploitation of engineered neurotoxin fragments......Page 50
Exploitation of the light chain......Page 51
Therapeutics for the treatment of chronic pain......Page 52
3.7.3 Exploitation of the heavy chain......Page 53
REFERENCES......Page 54
4.1 Introduction......Page 59
4.2 Primary resistance......Page 60
4.4 Developing resistance......Page 61
4.5 Detecting antibodies......Page 64
4.6 Overcoming resistance......Page 67
REFERENCES......Page 68
5.1 Introduction......Page 72
5.2 Botulinum toxin serotypes......Page 73
5.3 Commercial production......Page 76
5.5 Storage issues......Page 80
5.6.1 Drawing up......Page 81
5.6.2 Dilution......Page 82
5.6.3 Patient preparation......Page 83
5.6.4 Target organ location......Page 84
5.7 Repeated injections......Page 86
5.8.1 General......Page 87
5.9 Safety and adverse events......Page 88
5.11 Training issues......Page 89
REFERENCES......Page 90
6.1 Introduction......Page 94
6.4 Clinical features......Page 95
6.4.4 Social embarrassment......Page 96
6.6 Provocative and palliative factors......Page 97
6.9 Diagnosis......Page 98
6.10 Treatment of cervical dystonia......Page 100
6.11 Pharmacologic therapy......Page 101
6.11.2 GABA mimetic agents......Page 102
6.12.1 Peripheral surgery......Page 103
6.12.2 Central surgical approaches......Page 104
6.13.1 Review and clinical evidence of therapeutic efficacy......Page 105
6.13.2 Non-responders to botulinum toxin treatment......Page 106
6.14.1 Dysphagia......Page 107
6.14.6 Other minor side effects......Page 108
6.15.2 Commencement of botulinum toxin treatment......Page 109
6.15.4 Process of muscle selection......Page 110
6.15.6 Injection techniques......Page 111
Toxin dose......Page 112
Follow-up visits......Page 113
Sternocleidomastoid......Page 114
Semispinalis capitis......Page 115
REFERENCES......Page 116
7.2 Laryngeal dystonia/spasmodic dysphonia......Page 125
Abductor laryngeal dystonia......Page 126
Fibreoptic examination......Page 127
7.2.3 Treatment of spasmodic dysphonia......Page 128
7.2.4 Treatment of adductor laryngeal dystonia with botulinum toxin......Page 129
7.3 Tongue dystonia......Page 130
7.3.2 Tongue protrusion......Page 131
7.4.2 Side effects......Page 132
7.6 The slewed jaw......Page 133
REFERENCES......Page 134
8.1 Introduction......Page 136
8.2 Pathophysiology......Page 137
8.4 Epidemiology......Page 141
8.5 Management principles......Page 142
8.6.1 Patient assessment......Page 145
8.6.2 Aims of treatment......Page 147
8.7 Medical interventions in the treatment for spasticity......Page 148
Baclofen......Page 149
Dantrolene sodium......Page 150
Gabapentin......Page 151
8.7.2 Intrathecal baclofen......Page 152
Phenol nerve blockade......Page 153
8.7.4 Botulinum toxin......Page 155
Electromyography and muscle stimulation......Page 156
The clawed hand and flexed wrist......Page 157
Hip flexor and thigh adductor spasticity......Page 158
Talipes equino-varus foot......Page 159
8.8 Post-injection care......Page 160
8.8.2 Outcome measures......Page 161
Ashworth scale......Page 162
Other measures of spasticity......Page 164
Clinical measures......Page 165
8.8.3 Evidence for the use of BoNT in spasticity......Page 167
REFERENCES......Page 169
9.1 Introduction......Page 189
9.2 Hyperhidrosis......Page 190
9.3 Measuring hyperhidrosis......Page 193
9.4 Therapy......Page 194
9.6 Axillary hyperhidrosis......Page 196
9.7 Palmar hyperhidrosis......Page 198
9.8 Plantar hyperhidrosis......Page 202
9.9 Facial hyperhidrosis......Page 203
9.10 Other indications......Page 205
9.11 Botulinum toxin type B......Page 206
9.12 Complications......Page 207
9.13 Future directions......Page 208
REFERENCE......Page 209
10.2 Background and clinical description......Page 215
10.2.1 The salivary glands......Page 216
10.2.2 Drooling......Page 218
Evaluation of drooling......Page 219
10.3.1 Anticholinergic drugs......Page 221
10.3.2 Surgical treatment......Page 222
10.3.3 Radiotherapy......Page 223
10.3.5 Acupuncture......Page 224
10.4.2 Efficacy......Page 225
10.4.3 Injection techniques......Page 227
10.4.4 Dosage guidelines......Page 233
10.4.5 Side effects......Page 234
REFERENCES......Page 235
Drooling rating scale......Page 239
Drooling rating scale......Page 240
11.1 Introduction......Page 243
11.3 Episodic migraine......Page 245
11.4 Chronic daily headache......Page 247
11.6 Tolerability......Page 250
11.7 Injection strategy......Page 251
REFERENCES......Page 253
12.1 Introduction......Page 257
12.3 Clinical management......Page 258
12.5.2 Bed rest......Page 259
Compound analgesics......Page 260
Anticonvulsants......Page 261
Multidisciplinary programmes......Page 262
12.5.9 Surgical interventions......Page 263
Botulinum toxin in low back pain......Page 264
Botulinum toxin in the management of whiplash associated disorder......Page 266
12.6.1 Identification and injection of trigger points......Page 267
12.10 Injection technique......Page 269
REFERENCES......Page 271
13.1.1 Introduction......Page 276
13.2 Strabismus......Page 277
Infantile esotropia......Page 279
Specific syndromes......Page 281
13.4.2 Adult......Page 282
13.5 Facial movement disorders......Page 287
13.5.1 Idiopathic blepharospasm......Page 288
13.5.2 Apraxia of eye opening......Page 289
13.5.3 Hemifacial spasm......Page 290
13.5.5 Other facial movement disorders......Page 291
Eyelid position......Page 292
Facial scars......Page 293
REFERENCES......Page 294
14.2.1 Anatomy and physiology of micturition......Page 296
14.2.2 Detrusor-sphincter dyssynergia......Page 298
14.2.3 Neurogenic detrusor overactivity......Page 303
14.2.4 Idiopathic detrusor overactivity or sensor urge......Page 305
14.3.1 Chronic prostatic pain......Page 306
14.3.2 Benign prostatic hyperplasia (BPH)......Page 308
14.5.1 Anatomy and physiology of anal sphincters......Page 312
Functional organization of the ENS......Page 314
Smooth muscle contraction......Page 316
14.6.1 Chronic anal fissure......Page 317
Pathophysiology of chronic fissure......Page 319
Results of BoNT treatment......Page 320
Pelvic floor dysfunction......Page 325
Chronic idiopathic anal pain......Page 329
14.7.1 Sphincter of Oddi......Page 330
Available treatments......Page 331
REFERENCES......Page 332
15.1.1 Dilution of the toxin for cosmetic purposes......Page 342
15.2.1 General tips......Page 343
15.3.1 General tips for treatment of the glabella......Page 344
15.3.2 Glabellar anatomy......Page 345
15.3.3 Injection technique for the glabella......Page 347
15.4.2 Anatomy of the forehead musculature......Page 348
15.4.3 Injection technique: forehead......Page 349
15.4.4 Complications: forehead......Page 350
15.5.2 Injection technique for the periorbital areas......Page 351
15.5.5 ‘Bunny lines’......Page 352
15.6.1 General anatomy of the lower face......Page 353
Injection technique for lips......Page 355
15.6.4 ‘Downturned smile’......Page 356
15.6.6 ‘ Vertical neck bands’ and ‘horizontal necklace lines’......Page 357
Radish calf......Page 358
The use of toxins with fillers......Page 359
REFERENCES......Page 361
16.2.1 Background......Page 363
16.2.3 Management......Page 364
16.2.4 The role of botulinum toxin......Page 365
16.3.1 Background......Page 366
16.3.2 Other treatments......Page 367
16.3.3 The role of botulinum toxin......Page 368
16.4.1 Background......Page 369
The role of botulinum toxin......Page 370
16.5.4 Blepharospasm/apraxia of lid opening......Page 371
16.5.7 Freezing......Page 372
16.5.8 Rigidity......Page 373
16.6.1 Background......Page 374
16.6.3 The role of botulinum toxin......Page 375
16.7.2 Focal limb dystonias......Page 379
16.7.3 Occupational task specific dystonia......Page 380
16.7.4 Other treatments......Page 381
16.7.5 The role of botulinum toxin......Page 382
REFERENCES......Page 384
Index......Page 389