BOTULISM had been recognized by the 18th century, but the observation that a toxin produced by an anaerobic organism might be responsible for food poisoning was not made until 1897.1 Although seven immunologically distinct toxins have since been identified, only types A, B, and E have been linked to cases of botulism in humans.2 , 3 Botulinum toxin type A (hereafter referred to as botulinum toxin), one of the most lethal biologic toxins, has been found to be of therapeutic value in the treatment of a variety of neurologic and ophthalmologic disorders.4 The Food and Drug Administration recently approved botulinum toxin (Oculinum) . . .

Therapeutic uses of botulinum toxin

We studied the effect of botulinum-A toxin on spasticity of the leg adductors in 9 patients who were either chair-bound or bed-bound with chronic stable multiple sclerosis. We injected botulinum toxin (400 mouse units) or placebo into the adductor muscles in a randomized, crossover, double-blind design. Two physicians, who were unaware of the treatment order, used an objective rating scale and independently assessed the patients; interobserver correlation was excellent (r = 0.93-0.81). We found that botulinum toxin produced a significant reduction in spasticity (p = 0.009) and a significant improvement in the ease of nursing care (p = 0.009). There were no adverse effects during this short-term trial. This is the first demonstration of the beneficial effect of botulinum toxin on focal spastic muscle contractions.

Treatment of spasticity with botulinum toxin: a double-blind study.

In the past five years, 477 patients with various focal dystonias and hemifacial spasm received 3,806 injections of botulinum A toxin for relief of involuntary spasms. A definite improvement with a global rating greater than or equal to 2 on a 0-4 scale, was obtained in all 13 patients with spasmodic dysphonia, 94% of 70 patients with blepharospasm, 92% of 13 patients with hemifacial spasm, 90% of 195 patients with cervical dystonia, 77% of 22 patients with hand dystonia, 73% of 45 patients with oromandibular dystonia, and in 90% of 21 patients with other focal dystonia who had adequate follow up. While the average duration of maximum improvement lasted about 11 weeks after an injection (range seven weeks in patients with hand dystonia to 15 weeks in patients with hemifacial spasm), some patients benefited for over a year. Only 16% of the 941 treatment visits with follow up were not successful. Except for transient focal weakness, there were very few complications or systemic effects attributed to the injections. This study supports the conclusion that botulinum toxin injections are a safe and effective therapy for patients with focal dystonia and hemifacial spasm.

https://jnnp.bmj.com/content/jnnp/53/8/633.full.pdf

Botulinum toxin treatment of cranial-cervical dystonia, spasmodic dysphonia, other focal dystonias and hemifacial spasm.

Objectives: This paper reviews a 12-year experience in more than 900 patients with spasmodic dysphonia who have been treated with botulinum toxin. Study Design: This is a retrospective analysis of patients with adductor spasmodic dysphonia (strainstrangled voice), abductor spasmodic dysphonia (whispering voice), and adductor breathing dystonia (paradoxical vocal fold motion), all of whom have been treated with botulinum toxin injections for relief of symptom. Methods: All of the patients were studied with a complete head and neck and neurologic examination; fiberoptic laryngostroboscopy; acoustic and aerodynamic measures; and a speech evaluation including the Universal spasmodic dysphonia rating scale. Some were given electromyography. All patients received botulinum toxin injections into the affected muscles under electromyographic guidance. Results: The adductor patients had an average benefit of 90% of normal function lasting an average of 15.1 weeks. The abductor patients had an average benefit of 66.7% of normal function lasting an average of 10.5 weeks. Adverse effects included mild breathiness and coughing on fluids in the adductor patients, and mild stridor in a few of the abductor patients. Conclusion: Botulinum toxin A injection of the laryngeal hyperfunctional muscles has been found over the past 12 years to be the treatment of choice to control the dystonic symptoms in most patients with spasmodic dysphonia. Laryngoscope, 108:1435–1441, 1998

Botulinum toxin management of spasmodic dysphonia (laryngeal dystonia): A 12-year experience in more than 900 patients

We followed 205 of 232 patients with medically intractable cervical dystonia for at least 3 months and up to 4 years, during which time they received 1,074 injections in 505 visits. One hundred forty-five of the 205 patients (71%) improved substantially (global rating $2; from 0 = no response to 4 = marked improvement in severity and function) after 1 or more visits. Of the 89 patients who reported pain, 68 (76%) had almost complete relief of their pain. While most patients noted improvement within the 1st week after injection, some had a latency of up to 8.5 weeks. Duration of maximum benefit lasted up to 12.5 months in some, but the average was 11.2 weeks. Only 58 of 205 (28%) patients, seen in 76 of 505 visits (15% of all visits), had complications, primarily mild dysphagia (35 patients) or neck weakness (17 patients). We conclude that botulinum toxin is a safe and effective therapy for most patients with cervical dystonia.

Botulinum toxin injections for cervical dystonia.

Adductor spasmodic dysphonia involves an overadduction of the vocal folds during speech causing uncontrolled voice and pitch breaks and slow, effortful speech The disorder is resistant to speech therapy and often recurs following initial benefit from unilateral recurrent laryngeal nerve resection Botulinum toxin injections into multiple sites of the thyroarytenoid muscle on one side were performed in 16 patients Speech was recorded prior to injection and three times post-injection Symptoms were measured by two examiners from speech spectrograms without knowledge of speaker identity or recording session Significant (p less than or equal to 003) reductions in pitch and voice breaks, phonatory aperiodicity, and sentence time occurred only when injections resulted in unilateral vocal fold paralysis Symptoms returned with the restoration of vocal fold movement, 3 months later Reduction in speed of swallowing without aspiration was reported in 80% of cases Although speech volume was reduced, there were no instances of aphonia

Effects of botulinum toxin injections on speech in adductor spasmodic dysphonia

We studied 12 patients with spasmodic dysphonia (SD) and 12 healthy control subjects. The patients, who had no symptomatic involvement of the eyes, were evaluated for increased excitability of blink reflexes, which is characteristic of blepharospasm and generalized dystonia. We measured symptom severity from sound spectrograms of five sentences, including sentence production time, number of pitch phonatory breaks, and percentage of aperiodic phonation. We evoked blink reflexes by electrical and mechanical stimulation, and assessed excitability by obtaining excitability recovery curves and responses to trains of stimuli. Patients and controls differed from each other in test R2 amplitude attenuation across all intervals from 150 to 1,000 msec to electrical and mechanical stimulation. Our results indicate that patients with SD have increased excitability of blink reflexes, which suggests that the dystonia involves not only the larynx but also other anatomical structures.

Blink reflex excitability recovery curves in patients with spasmodic dysphonia.

24 – The pathophysiology of spasmodic dysphonia and its modification by botulinum toxin

The purpose of this study was to determine if botulinum toxin injections into the thyroarytenoid muscle would reduce symptoms in adductor spasmodic dysphonic patients who had experienced symptom recurrence after recurrent laryngeal nerve surgery. Five patients were seen between 3 to 10 years after surgery with a return of speech symptoms and persistent unilateral vocal fold paralysis. Before injection, comparisons with controls on spectrographic measures of pitch and voice breaks, aperiodicity, and sentence length demonstrated significant symptoms of spasmodic dysphonia (p ≤ 0.02). Electromyographic measures demonstrated equal levels of thyroarytenoid muscle activation on the operated and non-operated sides with bipolar needle electrodes, and heightened activity in both muscles relative to normal. Therefore, symptom return was associated with thyroarytenoid innervation after recurrent nerve surgery. In all patients, the thyroarytenoid muscle on the side operated on was injected with type A botulinum toxin...

S. E. Sedory

Papers

Effects of botulinum toxin injections on speech in adductor spasmodic dysphonia

Blink reflex excitability recovery curves in patients with spasmodic dysphonia.

24 – The pathophysiology of spasmodic dysphonia and its modification by botulinum toxin

Spasmodic dysphonia: botulinum toxin injection after recurrent nerve surgery.

Cerebral activation during speech discrimination in temporal lobe epilepsy.