Bahman Jabbari’s research while affiliated with Yale-New Haven Hospital and other places

Dysphagia is prevalent in patients with cervical dystonia (CD) and is a potential adverse event in patients treated with botulinum neurotoxin (BoNT) for CD. Real-world studies may provide a better understanding of the incidence and potential risk factors of dysphagia after BoNT administration. This retrospective cohort study used longitudinal patient-level data from Optum’s de-identified Market Clarity Data to evaluate rates of dysphagia in patients with CD exposed and unexposed to BoNT. Patients ≥18 years of age with ≥2 CD diagnoses ≥30 days apart during the study period (1 January 2017–30 September 2021) who had ≥180 days of continuous health plan enrollment prior to the cohort entry date (first CD diagnosis) were included. Overall, the mean (SD) age of all CD patients (Cohort 1; N = 81,884) was 54.00 (16.21) years, and they were mostly female (67.9%) and white (76.96%). BoNT-Exposed patients (Cohort 2; N = 19,244) had a higher incidence of dysphagia (16.3%) and comorbid conditions when compared with BoNT-Unexposed patients (Cohort 3; N = 61,154 [12.1%]). Overall, patients with pre-existing dysphagia, other dystonias, and comorbid neurologic conditions at baseline also had higher proportions of dysphagia. This real-world analysis indicates that comorbid conditions predispose patients with CD to a greater dysphagia risk during treatment.

A literature search on the subject of botulinum toxin treatment in psoriasis found 15 relevant articles, 11 on human subjects and 4 on animal studies. Of the human data, eight were clinical trials and three were single case reports. Seven out of eight clinical trials, all open-label, reported improvement in psoriasis following intradermal or subcutaneous botulinum toxin injections. One double-blind, placebo-controlled study, which used a smaller dose than the open-label studies, did not note a healing effect. Animal studies have shown that injection of botulinum toxins in the skin heals psoriatic skin lesions and can reduce the level of interleukins (ILs) and cytokines as well as inflammatory cells in psoriatic plaques. There is a need for controlled, blinded studies conducted in larger numbers of patients with doses that have shown promise in open-label studies.

A systematic review of the literature found fifteen articles on the effect of a botulinum toxin on neoplastic cell lines and eight articles on in vivo neoplasms. The reported in vitro effects rely on high doses or the mechanical disruption of cell membranes to introduce the botulinum neurotoxin into the cell cytoplasm. The potency of the botulinum neurotoxin to intoxicate non-neuronal cells (even cell lines expressing an appropriate protein receptor) is several orders of magnitude lower compared to that to intoxicate the primary neurons. The data suggest that the botulinum toxin disrupts the progression of cancer cells, with some studies reporting apoptotic effects. A majority of the data in the in vivo studies also showed similar results. No safety issues were disclosed in the in vivo studies. Limited studies have suggested similar anti-neoplastic potential for the clostridium difficile. New modes of delivery have been tested to enhance the in vivo delivery of the botulinum toxin to neoplastic cells. Careful controlled studies are necessary to demonstrate the efficacy and safety of this mode of anti-neoplastic treatment in humans.

Botulinum toxins, after injection into the muscle, block the release of acetylcholine from the neuromuscular junction. Acetylcholine is a chemical neurotransmitter that, upon release from nerve endings, activates the muscles. In disease conditions characterized by presence of overactive muscles with involuntary movements (dystonias, tremors, tics), injection of the botulinum toxin into the affected muscles decreases the involuntary movements substantially and improves the patients’ quality of life.

Animal studies have shown that local injection of botulinum toxins improves pain behavior via blocking the release of pain transmitters and modulators. In human, carefully designed studies comparing the effect of local injection of botulinum toxins with placebo (salt water) have demonstrated efficacy of toxin injection in relieving the pain of chronic osteoarthritis, local pain of tennis elbow, chronic pain after knee surgery and knee pain related to tightness of lateral thigh muscles.

Over the past 35 years, botulinum toxin therapy in adults has been established as a major mode of treatment for a variety of medical conditions. Several of these conditions including involuntary movements, spasticity, chronic migraine, excessive sweating/drooling, and bladder dysfunction have received FDA approval for use in the US. In this chapter, major indications of botulinum toxin therapy in childhood including stiffness of muscles with increased reflexes (spasticity), involuntary movements, strabismus (crossed eyes) and excessive sweating/drooling will be addressed.

This chapter provides information on the history of botulinum toxin development into a powerful therapeutic agent. It explains how through tireless efforts of remarkable basic scientists and clinicians one of deadliest toxins in the nature developed into a widely used treatment with high safety profile. Some of the characteristics of different brands of botulinum toxin in the US market are also briefly discussed in this chapter.

Headache is a common human ailment. Migraine is a recurrent and distressing headache that often impairs the quality of life. Uncontrolled and chronic migraine is a huge financial burden to the individual and to the country’s economy. The data from high quality studies have shown efficacy of botulinum toxin injections in chronic migraine. Based on these data, in 2010, Botox was approved for chronic migraine in Europe and by FDA for use in the US. This chapter discusses the role of botulinum therapy in primary headaches, migraine and tension headache. It also provides information on the limited data published on secondary headaches such as those occurring after head injury. Information on different techniques of botulinum toxin injection for treatment of chronic migraine is also provided. The results of botulinum therapy for migraine are compared with the results of pharmacological therapy in migraine including the newer drugs introduced to the market over the past 10 years.

Over the past 20 years, researchers and clinicians have found different potential indications for the use of botulinum toxin therapy in dentistry. The areas of interest are management of pain in temporomandibular disorder, pain after fracture of jawbone, local persistent pain at the site of tooth extraction, teeth grinding, angular cheilitis and burning mouth syndrome as well as improvement of gummy smile and management of protruded tongue.