Bahman Jabbari

Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

Objective: To perform an evidence-based review of the safety and efficacy of botulinum neurotoxin (BoNT) in the treatment of autonomic and urologic disorders and low back and head pain. Methods: A literature search was performed including MEDLINE and Current Contents for therapeutic articles relevant to BoNT and the selected indications. Authors reviewed, abstracted, and classified articles based on the quality of the study (Class I–IV). Conclusions and recommendations were developed based on the highest level of evidence and put into current clinical context. Results: The highest quality literature available for the respective indications was as follows: axillary hyperhidrosis (two Class I studies); palmar hyperhidrosis (two Class II studies); drooling (four Class II studies); gustatory sweating (five Class III studies); neurogenic detrusor overactivity (two Class I studies); sphincter detrusor dyssynergia in spinal cord injury (two Class II studies); chronic low back pain (one Class II study); episodic migraine (two Class I and two Class II studies); chronic daily headache (four Class II studies); and chronic tension-type headache (two Class I studies). Recommendations: Botulinum neurotoxin (BoNT) should be offered as a treatment option for the treatment of axillary hyperhidrosis and detrusor overactivity (Level A), should be considered for palmar hyperhidrosis, drooling, and detrusor sphincter dyssynergia after spinal cord injury (Level B), and may be considered for gustatory sweating and low back pain (Level C). BoNT is probably ineffective in episodic migraine and chronic tension-type headache (Level B). There is presently no consistent or strong evidence to permit drawing conclusions on the efficacy of BoNT in chronic daily headache (mainly transformed migraine) (Level U). While clinicians’ practice may suggest stronger recommendations in some of these indications, evidence-based conclusions are limited by the availability of data.

Botulinum toxin A and chronic low back pain A randomized, double-blind study

Objectives: To investigate the efficacy of botulinum toxin A in chronic low back pain and associated disabilities. Methods: Thirty-one consecutive patients with chronic low back pain who met the inclusion criteria were studied: 15 received 200 units of botulinum toxin type A, 40 units/site at five lumbar paravertebral levels on the side of maximum discomfort, and 16 received normal saline. Each patient’s baseline level of pain and degree of disability was documented using the visual analogue scale (VAS) and the Oswestry Low Back Pain Questionnaire (OLBPQ). The authors reevaluated the patients at 3 and 8 weeks (visual analogue scale) and at 8 weeks (OLBPQ). Results: At 3 weeks, 11 of 15 patients who received botulinum toxin (73.3%) had >50% pain relief vs four of 16 (25%) in the saline group (p = 0.012). At 8 weeks, nine of 15 (60%) in the botulinum toxin group and two of 16 (12.5%) in the saline group had relief (p = 0.009). Repeat OLBPQ at 8 weeks showed improvement in 10 of 15 (66.7%) in the botulinum toxin group vs three of 16 (18.8%) in the saline group (p = 0.011). No patient experienced side effects. Conclusion: Paravertebral administration of botulinum toxin A in patients with chronic low back pain relieved pain and improved function at 3 and 8 weeks after treatment.

Botulinum toxin A for spasticity, muscle spasms, and rigidity

Article abstract-We studied the effects of botulinum toxin A in 12 patients with spasticity and in eight patients with rigidity. The study design was a double-blind, placebo-controlled crossover trial with botulinum toxin A versus saline. Using the Ashworth Scale for spasticity and the Unified Parkinsons Disease Rating Scale for rigidity, we gave the patients a tone grade before and 2 weeks after treatment. Improvement in tone by two grades or more was considered clinically significant. In the spasticity group, botulinum toxin A reduced the tone of all patients significantly, improved functionality and nursing care in eight of 12 patients, and alleviated painful spasms in five of five patients. In the rigidity group, muscle tone was decreased in seven of eight patients, functionality improved in four of seven, and joint and muscle pain decreased in four of five. We conclude that botulinum toxin A is effective against the disabling effects of spasticity and rigidity. The treatment was well tolerated. NEUROLOGY 1995;45: 712-717

Treatment of pain attributed to plantar fasciitis with botulinum toxin a: a short-term, randomized, placebo-controlled, double-blind study.

Babcock MS, Foster L, Pasquina P, Jabbari B: Treatment of pain attributed to plantar fasciitis with botulinum toxin A: A short-term, randomized, placebo-controlled, double-blind study. Am J Phys Med Rebabil 2005;84:649–654. Objective: To investigate the effect of botulinum toxin A on associated pain and functional impairment of refractory plantar fasciitis. Design: This is a randomized, double-blind, placebo-controlled study of 27 patients (43 feet) with plantar fasciitis. Block randomization was performed using computer software. In patients with bilateral symptoms of comparable severity, botulinum toxin A was injected in one foot and saline in the other foot. The treatment group received a total of 70 units of botulinum toxin A divided into two sites per foot. One of the two sites was the tender area in the medial aspect of the heel close to the calcaneal tuberosity (40 units), and the other was in the arch of the foot between an inch anterior to the heel and middle of the foot (30 units). The placebo group received the same volume of normal saline. Main outcome measures included: Pain Visual Analog Scale, Maryland Foot Score, Pain Relief Visual Analog Scale, and pressure algometry response. Patients were assessed before injection, at 3 wks, and at 8 wks. Results: The study revealed statistically significant changes in the treatment group. Compared with placebo injections, the botulinum toxin A group improved in all measures: Pain Visual Analog Scale (P < 0.005), Maryland Foot Score (P = 0.001), Pain Relief Visual Analog Scale (P < 0.0005), and pressure algometry response (P = 0.003). No side effects were noted. Conclusions: Botulinum toxin A injection for plantar fasciitis yields significant improvements in pain relief and overall foot function at both 3 and 8 wks after treatment.

Nerve agents: A review

Nerve agents produce neuromuscular blockade and convulsions in exposed humans. Military personnel in areas of potential exposure take prophylactic pyridostigmine. They are instructed to self-administer atropine and pralidoxime at the first sign of nerve agent toxicity. The key to treatment of nerve agent poisoning is the administration of atropine in doses larger than is customary in most other disorders, repeated as often as needed. Mechanical ventilation may be required. Convulsions are treated with diazepam, but only after atropine has been administered.

Deep brain stimulation in Tourette's syndrome.

A 48‐year‐old man with severe, lifelong Tourettes syndrome (TS) characterized by forceful self‐injurious motor tics and obsessive‐compulsive disorder was treated with bilateral deep brain stimulation (DBS). The decision to treat was based on his progressive neurological impairment (left sided weakness secondary to spinal cord injury) because of his relentless, violent head jerks. Electrodes were implanted at the level of the medial part of the thalamus (centromedian nucleus, the substantia periventricularis, and the nucleus ventro‐oralis internus). DBS resulted in a substantial reduction of tics. These data show that bilateral DBS of the thalamus can have a good effect on severe tics in adult patients suffering from intractable TS.

Treatment of Refractory Pain with Botulinum Toxins—An Evidence-Based Review

OBJECTIVES To provide updated information on the role of botulinum toxins in the treatment of refractory pain based on prospective, randomized, double-blind, placebo-controlled studies. DESIGN OF THE REVIEW: Class I and class II articles were searched online through PubMed (1966 to the end of January 2011) and OvidSP including ahead-of-print manuscripts. RESULTS Level A evidence (two or more class I studies-established efficacy): pain of cervical dystonia, chronic migraine, and chronic lateral epicondylitis. Level B evidence (one class I or two class II studies-probably effective and recommended): post-herpetic neuralgia, post-traumatic neuralgia, pain of plantar fasciitis, piriformis syndrome, and pain in total knee arthroplasty. Level C evidence (one class II study-possibly effective, may be used at discretion of clinician): allodynia of diabetic neuropathy, chronic low back pain, painful knee osteoarthritis, anterior knee pain with vastus lateralis imbalance, pelvic pain, post-operative pain in children with cerebral palsy after adductor hip release surgery, post-operative pain after mastectomy, and sphincter spasms and pain after hemorrhoidectomy. Level U evidence (efficacy not proven due to diverse class I and II results): myofascial pain syndrome and chronic daily headaches. Studies in episodic migraine and tension headaches have shown treatment failure (level A-negative). CONCLUSION Evidence-based data indicate that administration of botulinum toxin in several human conditions can alleviate refractory pain. The problems with some study designs and toxin dosage are critically reviewed.

Seizures in Thyrotoxicosis

Summary: Over a period of 2 years we have observed 3 thyrotoxic patients who presented with a convulsive encephalopathy. These patients had no history of seizures before and experienced no further seizures after subsidence of the thyroid dysfunction. During the convulsive period, electroencephalograms of 2 patients showed evidence of cerebral hyperexcitability, but in both cases it returned to normal once the thyroid disorder was corrected. We believe that thyrotoxic seizures are not rare. These seizures can be focal as well as generalized and can constitute the presenting symptoms of the disease. Absence of other laboratory abnormalities such as serum electrolytes, or osmolality changes, or hypoglycemia in all patients who reportedly suffered from thyrotoxic seizures, and the data obtained from animal studies, suggest that human thyrotoxic seizures result mainly from the direct effect of thyroid hormones over the cerebral tissue.

Hyperhidrosis: Anatomy, Pathophysiology and Treatment with Emphasis on the Role of Botulinum Toxins

Clinical features, anatomy and physiology of hyperhidrosis are presented with a review of the world literature on treatment. Level of drug efficacy is defined according to the guidelines of the American Academy of Neurology. Topical agents (glycopyrrolate and methylsulfate) are evidence level B (probably effective). Oral agents (oxybutynin and methantheline bromide) are also level B. In a total of 831 patients, 1 class I and 2 class II blinded studies showed level B efficacy of OnabotulinumtoxinA (A/Ona), while 1 class I and 1 class II study also demonstrated level B efficacy of AbobotulinumtoxinA (A/Abo) in axillary hyperhidrosis (AH), collectively depicting Level A evidence (established) for botulinumtoxinA (BoNT-A). In a comparator study, A/Ona and A/Inco toxins demonstrated comparable efficacy in AH. For IncobotulinumtoxinA (A/Inco) no placebo controlled studies exist; thus, efficacy is Level C (possibly effective) based solely on the aforementioned class II comparator study. For RimabotulinumtoxinB (B/Rima), one class III study has suggested Level U efficacy (insufficient data). In palmar hyperhidrosis (PH), there are 3 class II studies for A/Ona and 2 for A/Abo (individually and collectively level B for BoNT-A) and no blinded study for A/Inco (level U). For B/Rima the level of evidence is C (possibly effective) based on 1 class II study. Botulinum toxins (BoNT) provide a long lasting effect of 3–9 months after one injection session. Studies on BoNT-A iontophoresis are emerging (2 class II studies; level B); however, data on duration and frequency of application is inconsistent.

Sialorrhea: Anatomy, Pathophysiology and Treatment with Emphasis on the Role of Botulinum Toxins

Sialorrhea or excessive drooling is a major issue in children with cerebral palsy and adults with neurodegenerative disorders. In this review, we describe the clinical features, anatomy and physiology of sialorrhea, as well as a review of the world literature on medical treatment using Yale University’s search engine; including but not limited to Medline and Erasmus. Level of drug efficacy is defined according to the guidelines of American Academy of Neurology. Current medical management is unsatisfactory. Topical agents (scopolamine and tropicamide) and oral agents (glyccopyrolate) combined render a level B evidence (probably effective); however, this treatment is associated with troublesome side effects. Double-blind and placebo-controlled studies of botulinum toxin (BoNT) provide a level A evidence for type B (two class I studies; effective and established) and both overall and individual B level of evidence for OnabotulinumtoxinA (A/Ona) and AbobotulinumtoxinA (A/Abo); these are probably effective. For IncobotulinumtoxinA (A/Inco), the level of evidence is U (insufficient) due to lack of blinded studies. Side effects are uncommon; transient and comparable between the two types of toxin. A clinical note at the end of this review comments on fine clinical points. Administration of BoNTs into salivary glands is currently the most effective way of treating sialorrhea.