Muscle weakness botulinum toxins

Botulinum toxin induces weakness of striated muscles by inhibiting transmission of motor neurons at the neuromuscular junction. This has led to its use in conditions with muscular overactivity, such as dystonia. Transmission is also inhibited at y neurons in muscle spindles, which may alter reflex overactivity. 

Botulinum toxin Descending muscle weakness/paralysis 18 to 36 hours... 

Injection site Use caution when botulinum toxin type A treatment is used in the presence of inflammation at the proposed injection site(s) or when excessive weakness or atrophy is present in the target muscle(s). 

An antitoxin is available in the event of immediate knowledge of an overdose or misinjection. In the event of overdosage or injection into the wrong muscle, additional information may be obtained by contacting Allergan at (800) 433-8871 from 8 am to 4 pm Pacific Time, or at (714) 246-5954 for a recorded message at other times. The antitoxin will not reverse any botulinum toxin-induced muscle weakness effects already apparent by the time of antitoxin administration. 

Botulinum toxin is used clinically in the treatment of blepharospasm, writer s cramp, spasticities of various origins, and rigidity due to extrapyramidal disorders. It is also used to treat gustatory sweating and cosmetically to decrease facial wrinkles. Botulinum toxin A Botox, Oculinum) injected intramuscularly produces functional denervation that lasts about 3 months. Clinical benefit is seen within 1 to 3 days. Adverse effects range from diplopia and irritation with blepharospasm to muscle weakness with dystonias. 

A randomized, double-blind, placebo-controlled crossover trial of botulinum toxin for the treatment of simple motor tics was conducted in 20 patients, ages 15-55, 18 of whom completed the study (Marras et al., 2001) (Table 40.2). As rated blindly on a 12-minute videotape sample, the proportional change in treated tics per minute was —39% during the botulinum toxin phase in contrast to an increase of +5.8% during the placebo phase. Half of the patients noted weakness of the injected muscles that was not functionally disabling. Two patients reported inner restlessness, accompanied by an increased urge to perform the treated tic. Two others felt that the decrease in the treated tic prompted a new replacement tic. Despite improvement in the treated tic, there was no significant evidence of overall improvement. 

After synaptic transmission is blocked by botulinum toxin, the muscles become clinically weak and atrophic. The affected nerve terminals do not degenerate, but the blockage of neurotransmitter release is irreversible. Function can be recovered by the sprouting of nerve terminals and formation of new synaptic contacts this usually takes 2 to 3 months. 

The effects of curare develop rapidly after it enters the body. Victims develop rapid weakness of voluntary muscles followed by paralysis, respiratory failure, and death. The cause is a blockade of nicotinic cholinergic receptors at the neuromuscular junctions in skeletal muscle. Unlike botulinum toxin, release of acetylcholine by the cholinergic nerve terminals is not affected. When curare is present, however, the acetylcholine that is released cannot bind to the receptors because they are reversibly occupied by the curare. As a consequence, nerve-muscle communication fails and paralysis ensues. 

Botulinum toxin is one of several toxins produced by the bacterium Clostridium botulinum. The toxin binds with high affinity to peripheral cholinergic nerve endings, such as those at the neuromuscular junction and in the autonomic nervous system, preventing the release of the neurotransmitter acetylcholine (1). This action at the neuromuscular junction can cause weakness and even paralysis of the muscles supplied by the affected nerves. Sprouting of the terminal nerves eventually results in re-innervation of the muscles and return of function. Doses are measured in mouse units (MU), IMU being the LD50 in Swiss-Webster mice. 

While the exact cause of muscle weakness was unclear, this case argues against the use of botulinum toxin in patients with myasthenic syndromes. When the margin of safety is reduced with regard to neuromuscular transmission, botulinum toxin can result in increased morbidity or even mortality. Generalized muscle weakness after botulinum toxin has also been reported in patients with other neuromuscular disorders (18). In addition, it should be remembered that both dysphagia and muscle weakness can occur after botulinum toxin injection, even in patients who do not suffer from generalized neuromuscular disorders (19). 

Chemical Abstracts Service Registry Number CAS 93384-43-1. Botulinum toxins comprise a series of seven related protein neurotoxins that prevent fusion of synaptic vesicles with the presynaptic membrane and thus prevent release of acetylcholine. Exposure in a battlefield or terrorist setting would most likely be to inhaled aerosolized toxin. The clinical presentation is that of classical botulism, with descending skeletal muscle weakness (with an intact sensorium) progressing to respiratory paralysis. A toxoid vaccine is available for prophylaxis, and a pentavalent toxoid can be used following exposure its effectiveness wanes rapidly, however, after the end of the clinically asymptomatic latent period. Because treatment is supportive and intensive (involving long-term ventilatory support), the use of botulinum toxin has the potential to overwhelm medical resources especially at forward echelons of care. 

Botulinum toxin A is a simple protein comprising a single polypeptide chain, readily detoxified by heat, mechanical stress, and oxygen (Stevenson et al., 1947 Lamanna, 1959). In contaminated water, it remains highly toxic for several days but decays rapidly in open air. This toxin inhibits the release of acetylcholine at sites needed to transmit nerve impulse to muscles. Botulinum toxin by ingestion produces nausea and diarrhea, followed by headache, dizziness, fatigue, weakness, vertigo, extreme constipation, convulsions, and death due to paralysis of respiratory muscles. 

The botulinum neurotoxins (BoNTs) comprise a family of seven distinct neurotoxic proteins (A-G) produced by immunologically discrete strains of the anaerobic bacterium Clostridium botulinum and in rare cases by Clostridium baratii and Clostridium butyricum (Habermann and Dreyer, 1986 Harvey et ah, 2002 Simpson, 2004). These toxins act on peripheral cholinergic synapses to inhibit spontaneous and impulse-dependent release of acetylcholine (ACh) (Brooks, 1956 Kao et al., 1976). Intoxication by BoNT results in muscle weakness, which can be fatal when the diaphragm and intercostal muscles become sufficiently compromised to impair ventilation (Dickson and Shevky, 1923). The BoNTs are the most potent substances in nature, and exposure to as httle as 1-3 ng/kg may be sufficient to cause human lethahty (GUI, 1982 Middlebrook and Franz, 1997 Amon et al., 2001). 

Adler, M., Scovill, J., Parker, G., Lebeda, F.J., Piotrowski, J., and Deshpande, S.S. 1995. Antagonism of botulinum toxin-induced muscle weakness by 3,4-diaminopyridine in rat phrenic nerve-hemidiaphragm preparations. Toxicon 33 527-537. 

A. Botulism is caused by a heat-labile neurotoxin (botulin) produced by the bacteria Clostridium botulinum. Different strains of the bacterium produce seven distinct exotoxins A, B, C, D, E, F, and G types A, B, and E are most frequently involved in human disease. Botulin toxin irreversibly binds to cholinergic nerve terminals and prevents acetylcholine release from the axon. Severe muscle weakness results, and death is caused by respiratory failure. The toxin does not cross the blood-brain barrier. 

Botulinum toxins Toxin aerosolized or added to food or virater. Exposed to food orvirater. Exposed surfaces may be contaminated vifith toxin. Toxic dose 0.01 mcg/kg for Inhalation and 70 meg for Ingestion. Hours to a few days See p 136. Symmetric, descending flaccid paralysis with Initial bulbar palsies (ptosis, diplopia, dysarthria, dysphagia) progressing to diaphragmatic muscle weakness and respiratory arrest. Dry mouth and blurred vision due to toxin blockade of muscarinic receptors. Toxin cannot penetrate intact skin but is absorbed across mucous membranes or wounds. Treatment botulinum antitoxin (see p 420). 

Kim KS, Byun YS, Kim YJ, Kim ST. Muscle weakness after repeated injection of botulinum toxin type A evaluated according to bite force measurement of human masseter muscle. Dermatol Surg 2009 35 (12) 1902-6. 

Yuxingcao injection, 772 muscle cramps eplerenone, 344 immunoglobulins, intravenous, 516 phenol, 381 muscle fasdculations suxamethonium, 221 muscle/joint pains naltrexone, 168 muscle rigidity morphine, 160 muscle spasms fenoflbrate, 724 rosuvastatin, 724 simvastatin, 724 muscle vein thrombosis polidocanol, 795 muscle weakness botulinum toxins, 226-7 musculoskeletal pain codeine, 152 cyclobenzaprine, 227 methylnaltrexone, 152 mutagenicity lamivudine, 456 methylphenidate, 5-6... 

Neuromuscular function Long-term data on the use of botulinum toxin type A in the treatment of hyperhidrosis are required in order for the implications to be fully appreciated. Muscle weakness has been reported during long-term therapy [52 ]. 

Methods Muscle weakness was produced in one year old, female New Zealand white rabbits by injecting botulinum toxin type-A (BTXA) into the quadriceps musculature for times ranging from 1-6 months [7]. Contralateral limbs served as saline injected controls while other animals served as normal controls. Strength, muscle mass, muscle structure and knee histology (Mankin score) were evaluated to determine if muscle weakness caused joint degeneration. 

Longino, D. Botulinum toxin and a new animal model of muscle weakness. 2003. University of Calgary, Calgary, AB, Canada, MSc Thesis. 

Botulism is a disease caused by ingestion of foods contaminated with Clostridium botulinum (food-borne botulism) or, very rarely, by wound infection (wound botulism) or colonization of the intestinal tract with Clostridium botulinum (infant botulism). The toxins block the release of acetylcholine. Botulism is characterized by generalized muscular weakness, which first affects eye and throat muscles and later extends to all skeletal muscles. Flaccid paralysis can lead to respiratory failure. 

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