Botulism

Toxic
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Diagnosis and reasoning

At first glance, this previously healthy lady has presented with a frighteningly complex set of signs and symptoms; however, a careful analysis allows us to make order out of chaos by creating intelligible groupings. First of all, note that the clinical findings are almost completely neurological in nature; a closer look shows these to be confined to the motor and autonomic systems, with sensation apparently unaffected. Further analysis of the motor symptoms show that the motor cranial nerves (III, IV, V, VI, VII, IX, XI and XII) are severely affected, while the flexors of the neck and upper limbs are much less so; note also that the weakness is both bilateral and symmetric. When the above are considered together, they suggest that a bilateral, symmetric, descending paralysis in association with dysautonomia. This is a relatively unusual neurological pattern, with a somewhat limited differential diagnosis; key possibilities include Botulism, Miller-Fisher syndrome (MFS) and Lambert–Eaton myasthenic syndrome (LEMS) . It is important to appreciate that while Myasthenia Gravis (MG) can give rise to virtually any type of motor symptoms, this is not associated with autonomic findings. Note that a friend of hers has already been admitted with similar symptoms after eating out together. This suggests that a 'cluster' of cases is present - making this Botulism until proven otherwise. At this point, Botulinum antitoxin should be administered without delay (after sensitivity testing, as allergic reactions may occur); this is a highly time-critical intervention which should not be delayed pending investigations. The sole exception is sending a Botulinum toxicology screen for stools and serum, as the antitoxin will otherwise neutralize all toxins in the circulation and provide the test meaningless. Note that the toxicology screen results will take several days to arrive, making them of little utility in the acute management; these are mainly of use for epidemiological and medical legal purposes. Electrodiagnostic studies can provide valuable supportive evidence in the acute setting; the incremental response to repetitive nerve stimulation seen here is compatible with the clinical diagnosis. On a side, a similar response is also seen in patients with LEMS (although this is highly unlikely in this specific patient). Given the overwhelming likelihood of Botulism, CSF analysis or an anti-GQ1b antibody assay (both of which are of use in excluding MFS) are probably not indicated here. This patient should be managed in a critical care environment. It is particularly important to note that she is at high risk for progression into respiratory failure, and should be kept under careful observation in this regard. Antibiotics are not indicated in her current management; it should be further noted that IV clindamycin is contraindicated in these patients, as this may exacerbate the neuromuscular blockade. Botulism is a public health emergency - thus, it is important to notify the relevant authorities immediately; this information may also be of use to the medical staff in the hospital where the other affected patient was admitted.


Discussion

Botulism is a potentially lethal neuroparalytic disease caused by botulinum neurotoxins produced by the anaerobic spore-forming bacterium Clostridium botulinum, and rarely by botulinum toxin producing strains of Clostridium baratii and Clostridium butyricum. The term 'Botulism' hails from the Latin word 'Botulus', meaning 'Sausage'. This is because when botulism was first recognized in Europe, many cases were caused by home-fermented sausages. Even today, the overwhelming majority of cases are secondary to ingestion of contaminated food; however, it should be noted that several other forms of botulism exist; these are respectively wound botulism, infant botulism, adult infectious botulism, and inadvertent botulism (i.e. following botulinum toxin injection). The remainder of this text deals with foodborne botulism only; however, note that the signs and symptoms of the other forms are similar. In the USA, approximately 24 cases of foodborne botulism are reported each year. The disease is very rare in the UK, but more common in Southern and Eastern Europe (where the practice of home preservation is more widespread). C. botulinum is an obligate anaerobe found in soil and aquatic sediments; it is a common contaminant of food which is not washed properly. The bacterial spores are resistant to heat and may survive temperatures below 120°C; thus, they may contaminate canned or packaged foods containing fish and vegetables (particularly those prepared at home) The anaerobic environment of the can allows the spores to germinate; the food is subsequently contaminated by toxins produced by the bacteria. Note that C. botulinum has several subtypes (ranging from A to G); these are distinguished by the antigenic characteristics of the neurotoxins they produce. Types A, B, E and rarely, F, cause disease in humans. The type A and B neurotoxins are usually found in vegetables, fruits and meat products, while Type E botulism is associated with the ingestion of contaminated seafood. The structure and mechanism of action of the neurotoxins is very similar; they are polypeptide sequences which bind irreversibly to presynaptic receptors and inhibit the release of acetylcholine, resulting in neuromuscular weakness and autonomic dysfunction. In foodborne botulism, symptoms most often appear between 12 and 36 hours after consumption of contaminated food; however, these can occur within 8 hours to 8 days, depending on the levels and serotype of toxin. Affected individuals may initially present with a symmetrical motor cranial neuropathy; this then progresses into a descending flaccid paralysis of the motor and autonomic nerves. The symptoms and and signs are mainly related to oculobulbar muscle weakness such as blurring of vision, diplopia, ptosis, ophthalmoplegia, dysarthria, and dysphagia. Note that sensation and intellectual functions are preserved; fever is usually not present. Rarely, these patients can rapidly progress into respiratory failure and death before any other symptoms or signs become apparent. Botulism is a clinical diagnosis made in patients with supportive signs and symptoms; a history of consumption of (potentially) contaminated food substantially enhances the likelihood of the diagnosis, as does the presence of a 'cluster' of cases with similar features. While diagnostic tests based on detection of toxin levels and cultures for the organism exist, these are time consuming and are of little use in the acute management; note that samples should be collected before administering antitoxins. The mouse bioassay test (which literally involves injecting a mouse with serum samples) to detect the presence of toxins is positive in over half of patients if collected within 1 day of onset, but in less than one quarter after 3 days. Stool cultures are positive in over 70% of patients within 2 days of onset, and in over 40% even after 10 days. These patients usually require immediate supportive therapy (including airway protection, careful monitoring of vital capacity and institution of mechanical ventilation if required) in an intensive care setting. IV antitoxin therapy is the only specific treatment for Botulism; note that this only arrests the progression of paralysis (i.e. it does not reverse the established paralysis) - hence the earlier the administration, the better the outcome. Before administration, skin testing should be performed to test for hypersensitivity reactions. Repeat doses are only necessary if the patient continues to deteriorate. Notification to the relevant public health authorities is important and should be done promptly; this will allow public health professionals to take measure to reduce the spread. Note that there is no postexposure prophylaxis for asymptomatic exposed persons; close observation is recommended. If they develop symptoms compatible with the disease, treatment should be initiated immediately. As the Botulinum toxin binds to neuroreceptors in a noncompetitive and irreversible fashion, it takes time for the synapses and axonal branches to regenerate; this may range from weeks to months. Thus, these patients may require extended outpatient rehabilitation therapy. Fortunately, full recovery does occur in the majority of cases; the outcome is directly linked to the timeliness of the diagnosis and initiation of specific treatment. Patients who received antitoxin therapy within the first 24 hours of onset of symptoms have a shorter duration of ventilatory support and hospital stays and a lower fatality rate (10%) than those given antitoxin > 24 hours after onset (15%) or those who do not receive antitoxin at all (46%).


Take home messages

  1. Botulism causes an acute symmetrical cranial motor neuropathy followed by descending flaccid paralysis.
  2. Rapid clinical diagnosis, provision of intensive care and administration of botulinum antitoxin are the fundamentals of management.
  3. Early administration of botulinum antitoxin is essential to prevent the progression of paralysis, reduce the duration of paralysis and reduce the hospital stay.
  4. Even a single incident of suspected botulism considered as a public health emergency therefore urgent notification to public health authorities and action to prevent further spread is essential.

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  1. Clin Infect Dis. 2005 Oct 15;41(8):1167-73. Epub 2005 Aug 29, Botulism, Sobel J.
  2. Clin Microbiol Rev. 2006 April; 19(2): 298–314, doi: 10.1128/CMR.19.2.298-314.2006, Laboratory Diagnostics of Botulism, Miia Lindström and Hannu Korkeala.
  3. Emerg Infect Dis. 2004 Sep;10(9):1606-11, Foodborne botulism in the United States, 1990-2000, Sobel J, Tucker N, Sulka A, McLaughlin J, Maslanka S.
  4. Guidelines for Action in the Event of a Deliberate Release: Botulism, Version 4.5.1 31 March 2009, HPA Centre for Infections.
  5. J Neuroimmunol. 2004 Mar;148(1-2):200-5, Usefulness of anti-GQ1b IgG antibody testing in Fisher syndrome compared with cerebrospinal fluid examination, Nishimoto Y, Odaka M, Hirata K, Yuki N.
  6. J Public Health (Oxf). 2006 Dec;28(4):337-42. Epub 2006 Aug 17, Foodborne botulism in the United Kingdom, McLauchlin J, Grant KA, Little CL.BMJ Case Rep. 2013 Jan 3;2013. pii: bcr0120125678. doi: 10.1136/bcr.01.2012.5678, Clinically and electrophysiologically diagnosed botulinum intoxication, Kotan D, Aygul R, Ceylan M, Yilikoglu Y.
  7. JAMA. 2001 Feb 28;285(8):1059-70, Botulinum toxin as a biological weapon: medical and public health management, Arnon SS, Schechter R, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Fine AD, Hauer J, Layton M, Lillibridge S, Osterholm MT, O'Toole T, Parker G, Perl TM, Russell PK, Swerdlow DL, Tonat K; Working Group on Civilian Biodefense.
  8. Muscle Nerve. 1998 Jun;21(6):701-10, Clinical spectrum of botulism, Cherington M.