The Twentieth Century and Beyond
Scott M. Jackson in Skin Disease and the History of Dermatology, 2023
How the human race harnessed one of nature's deadliest substances for therapeutic purposes is one of modern medicine's most fascinating tales. The substance, botulinum toxin, is a neurotoxin that was first isolated in 1944 from the gram-positive, rod-shaped anaerobic bacterium known as Clostridium botulinum. The word botulinum is derived from the Latin word botulus, meaning sausage, and that word was chosen for the toxin because the first reports of botulism in the eighteenth century involved several persons who died from the affliction after ingesting undercooked blood sausage. Thus, botulinum toxin was first known as “sausage poison.” By the twentieth century, it was evident that canned foods contaminated with the bacteria could be a source of botulism. In that disorder, a person ingests the toxin and develops difficulty swallowing, dry mouth, blurry vision, respiratory distress, nausea, vomiting, diarrhea, and paralysis. The toxin interferes with neurotransmitter release at the neuromuscular junction, meaning that nerves cannot innervate muscles. Fortunately, the toxin is easily heat-inactivated, and proper processing of foods prior to canning prevents this deadly form of food poisoning.
Systemic, Intrathecal, and Intravesical Pharmacologic Treatment of Neurogenic Lower Urinary Tract Dysfunction
Jacques Corcos, Gilles Karsenty, Thomas Kessler, David Ginsberg in Essentials of the Adult Neurogenic Bladder, 2020
Since its introduction in the year 2000, cystoscopic injection of botulinum toxin into the detrusor has rapidly become a mainstay in the treatment of NLUTD, with resultant increases in bladder storage capacity and decreases in detrusor pressure.27 Botulinum toxin exerts its therapeutic effect by inhibiting the release of acetylcholine vesicles at presynaptic cholinergic neuromuscular junctions in peripheral nerve endings, resulting in temporary muscle paralysis. In addition to the inhibition of detrusor contraction, it is generally thought that botulinum toxin affects sensory nerve conduction as well.28 The commercially available forms of botulinum toxin include onabotulinumtoxinA (Botox), abobotulinumtoxinA (Dysport), incobotulinumtoxinA (Xeomin), and rimabotulinumtoxinB (Myobloc), though only onabotulinumtoxinA (Botox) and abobotulinumtoxinA (Dysport) have adequate clinical data to support their use for the treatment of NLUTD, and only onabotulinumtoxinA (Botox) has been approved for neurogenic detrusor overactivity by the U.S. Food and Drug Administration.29,30
Myasthenia Gravis
George S. Eisenbarth in Immunotherapy of Diabetes and Selected Autoimmune Diseases, 2019
Myasthenia gravis (MG) is an autoimmune disorder affecting the structural integrity and the function of the neuromuscular junction of skeletal muscle. The following factors contribute to the consideration of MG as an autoimmune disease:The presence of circulating antibodies directed against the acetylcholine receptor in most patients.1-3The presence of complement mediating membrane attack at the neuromuscular junction.4,5The presence of abnormalities of the thymus in most patients and the therapeutic response to thymectomy.6,11The increased occurrence of MG with other autoimmune diseases and following bone marrow transplantation therapy for other diseases.12,13The impressive responsiveness of MG to several immunotherapies, including treatment with steroids.14
Ataxia and ophthalmoplegia: an atypical case of Miller Fisher syndrome (MFS) with anti-GAD antibody
Published in International Journal of Neuroscience, 2022
Ali R. Shoraka, Xiang Fang, Diaa Hamouda, Bhanu Gogia, Xiangping Li
Corticosteroids have been tried as the first-line therapy for GAD-Ab associated neurologic disorders. Additional case reports suggest that a combination of IVIG and delayed plasmapheresis show efficacy regarding symptomatic improvement [18]. Our patient received a course of IVIg and had complete recovery in 3 months. Some other disorders that can manifest with similar presentations are Lambert Eaton Myasthenic Syndrome (LEMS), atypical GAD antibody positive cerebellar degeneration, and paraneoplastic syndrome. Lambert-Eaton myasthenic syndrome (LEMS) is a disorder of neuromuscular junction transmission with the primary clinical manifestation of muscle weakness. GAD antibody positive cerebellar degeneration could cause dysmetria, ataxia, and nystagmus. However, neither entity could explain patient’s new onset numbness and length dependent polyneuropathy seen in the exam. CT chest/abdomen and pelvis did not reveal any underlying malignancy. Patient is a 24-year-old male with no history of smoking or risky behavior, and malignancy is unlikely in his age group.
Lacrimal gland botulinum toxin injection for epiphora management
Published in Orbit, 2022
Johnathan Jeffers, Katherine Lucarelli, Sruti Akella, Pete Setabutr, Ted H. Wojno, Vinay Aakalu
Botulinum toxin was first purified in 1897, with seven different serotypes eventually identified.15,16 The toxin works by inhibiting the presynaptic release of acetylcholine at the neuromuscular junction and by autonomic nerve fibers. This ultimately results in a decreased concentration of post-synaptic acetylcholine receptors and subsequent muscle weakening.17 In the field of ophthalmology, botulinum toxin is commonly used to treat strabismus, blepharospasm, and hemifacial spasm. The use of botulinum toxin injection in medical treatments first started in 1970s, with the use of Botulinum Toxin A in animal trials.18 Dr. Allen Scott, an ophthalmologist was one of the first medical professionals to utilize the toxin as a medical treatment.19 The use of botulinum toxin for injection has been proven to be a safe procedure after over 40 years of use. Initial utilization of the purified toxin in ophthalmology included intramuscular injections for cases of strabismus.18 Frueh, Felt, Wojno, and Musch first described the use of botulinum toxin, previously known as oculinum for treatment of benign blepharospasm in 1984.20 There is also interest in using botulinum toxin to treat epiphora by injecting the lacrimal gland.21–23 Here, the inactivation of acetylcholine release from postganglionic parasympathetic secretomotor fibers lead to decreased tearing.16
Subchronic administration of Parastar insecticide induced behavioral changes and impaired motor coordination in male Wistar rats
Published in Drug and Chemical Toxicology, 2022
Antoine Kada Sanda, Akono Edouard Nantia, T. F. Pascal Manfo, Romi T. Toboh, Roxane Essame Abende, Sterling Adaibum, Paul Fewou Moundipa, Pierre Kamtchouing
The grip strength test is a functional method used to evaluate rat limb strength. This test has been used to investigate the effects of drug on neuromuscular disorders. In both Grid Suspension Grip-strength test and Wire Hang tests, Parastar decreased the suspension time, especially at the medium and high doses, and this suggests negative effect of the agrochemical on muscle strength and coordination in rats. Skeletal muscle contraction is mediated by acetylcholine at the neuromuscular junction. Therefore results from this study suggest a possible alteration of cholinergic neurons or acetylcholinesterase system by Parastar leading to neurotoxic effect. Khan et al. (2003) reported inhibition of brain cholinesterase following exposure of frogs to a component of Parastar, Lambda cyhalothrin. Other studies demonstrated the neurotoxic effect of another pesticide, Chlorpyrifos (Yumino et al.2002; Lee et al. 2014), which was attributed to the capacity of Chorpyrifos to enhance hydrogen peroxide levels (ROS), reduce the antioxidant potential of nervous system (Yumino et al.2002; Lee et al. 2014), and interrupt mitochondria activity in brain (Singh et al. 2013; Yamada et al. 2017). Parastar may induce neurotoxic effects through same or similar mechanism.
Related Knowledge Centers
- Action Potential
- Atrophy
- Central Nervous System
- Chemical Synapse
- Motor Neuron
- Muscle Contraction
- Peripheral Nervous System
- Muscle Tone
- Muscle Cell
- Voltage-Gated Calcium Channel