History

Fact Explanation
A history of suspicious food ingestion 12-36 hours ago. Clostridium botulinum is a gram-positive, spore forming, anaerobic bacteria on plant roots, soil, water and in the intestinal tracts of animals. [1] The spores retain viability for 6 hours at 100'C [2]. Infection is encountered with canned, smoked food. As C.botulinum is a gas forming organism, the cans appear "swollen". [6] [7] The spores germinate in favorable conditions and the resulting rods secrete toxins. [1] The onset of symptoms depend on the incubation period, which is dependent on the preformed toxin dose. [3] [6] Longer incubation periods equal milder clinical features. [1] The botulinum exotoxins are polypeptide chains complexed with other proteins, and of seven subtypes: A,B,C,D,E,F,G. [5] Types A,B, and E are commonly affect humans. The toxin is absorbed through the gut mucosa and binds to nerve terminals, blocks acetylcholine release [1] and causes the clinical features.
A history of traumatic injury, with soil contamination Clostridium botulinum are saprophytes.[1] Wound botulism is rare but should be considered in patients with wounds contaminated with potential bacterial media.[5] In this type of botulism, gastrointestinal symptoms are usually not evident and the incubation period is longer. [26]
Inhalation of the toxin Rare route of infection, pure toxin and progenitor toxin are both inhalation poisons. [27]
Nausea, vomitting In about 90% of the cases, the initial presentation is an acute gastrointestinal syndrome. [4] [6] [8] There can be associated abdominal pain, cramps and heartburn. [6] In most cases nausea and vomiting precedes neurological symptoms. [14]
Difficulty in swallowing/ dysphagia. This is due to blocking action of the toxins on acetylcholine-associated neurotransmission at bulbar muscles. [6], [9] Its onset is early, and is rapidly progressive. [10] Dysarthria is an associated symptom.
Double vision/ diplopia with blurred vision. Due to the neurotoxin acting on cranial nerve six, and it is usually bilateral, symmetrical and progressive, even though rarer atypical presentations have been noted. [6],[11]
Extremely dry mouth and dry eyes. Due to synapse toxicity of the botulinum toxin. [1],[12] . The secretory function in glandular tissues (e.g. sweat glands, lacrimal glands, gastric glands) is mediated via acetylcholine associated neurotransmission. [20] Antagonist action of the botulism toxin on the synapses cause reduced secretions, which is evident as dry eyes and dry mouth. [6] The patients can have coexistent sore eyes, sore throat also. [21], [22]
Weakness with paralysis Due to the antagonist action of acetylcholine release at the neuromuscular junction. [5] It is bilateral, symmetrical, and descending. Is rapidly progressive. [9],[13]
Breathing difficulty that may lead to respiratory failure Due to paralysis of respiratory muscles. It's descending, symmetrical and rapidly progressive. Respiratory symptoms indicate a severe illness. [7] Patients who had longer incubation period, without urine retention are unlikely to go into respiratory failure. [14] [15]
Progressive constipation Toxemia causes constipation as a feature of the botulism syndrome. [13], [16],[17]
Orthostatic dizziness. Botulism is a rare but important suspicion in acute or isolated autonomic dysfunction. [18] Heart failure with diastolic dysfunction also has been reported. The patients were known to attain previous cardiovascular stability with time. [19]
Urine retention. This is due to dysautonomia caused by the neurotoxin. [6] Likewise, botulinum toxin has proved useful in treating hyperactive bladder. [23]
Sudden death Sudden deaths have been reported and botulinum toxicity has been found later in the postmortem. Sudden death is commoner with infantile botulism compared to adults. [6] [24]
References
  1. DAVIS, L.E. Botulinum Toxin: From Poison to Medicine. West J Med [online] 1993 Jan; 158:25-29 [viewed April 17, 2014] Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1021932/pdf/westjmed00077-0027.pdf
  2. REDDY NR, MARSHALL KM, MORRISSEY TR, LOEZA V, PATAZCA E, SKINNER GE, KRISHNAMURTHY K and LARKIN JW. Combined high pressure and thermal processing on inactivation of type A and proteolytic type B spores of Clostridium botulinum. J Food Prot. [online] 2013 Aug;76(8):1384-92. [viewed April 17, 2014] Available at doi: 10.4315/0362-028X.JFP-12-538.
  3. NISHIURA H. Incubation period as a clinical predictor of botulism: analysis of previous izushi-borne outbreaks in Hokkaido, Japan, from 1951 to 1965. Epidemiol Infect. [online] Jan 2007; 135(1): 126–130. [viewed April 17, 2014] Available at doi: 10.1017/S0950268806006169.
  4. CHERINGTON M. Clinical spectrum of botulism. Muscle Nerve. [online] 1998 Jun;21(6):701-10. [viewed April 17, 2014] Avail;able at DOI: 10.1002/(SICI)1097-4598(199806)21:6<701::AID-MUS1>3.0.CO;2-B.
  5. NIGAM P.K. and NIGAM A. Botulinum Toxin. Indian J Dermatol. [online] 2010 Jan-Mar; 55(1): 8–14. [viewed April 17, 2014] Available at doi: 10.4103/0019-5154.60343.
  6. LOUTFY, Mona R, John W. AUSTIN, Burke BLANCHFIELD and Ignatius W. FONG. An outbreak of foodborne botulism in Ontario. Can J Infect Dis. [online] 2003 Jul-Aug; 14(4): 206–209. [viewed April 17, 2014] Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2094941/pdf/JID14206.pdf.
  7. JULIAO PC, MASLANKA S, DYKES J, GAUL L, BAGDURE S, GRANZOW-KIBIGER L, SALEHI E, ZINK D, NELIGAN RP, BARTON-BEHRAVESH C, LÚQUEZ C, BIGGERSTAFF M, LYNCH M,OLSON C, WILLIAMS I and BARZILAY EJ. National outbreak of type a foodborne botulism associated with a widely distributed commercially canned hot dog chili sauce. Clin Infect Dis. [online] 2013 Feb;56(3):376-82. [viewed April 17, 2014] Available at doi: 10.1093/cid/cis901.
  8. SOBEL, Jeremy. Botulism. Clin Infect Dis. [online] 2005; 41(8): p1167-1173. [viewed April 17, 2014] Available at doi: 10.1086/444507.
  9. PREUSS S.F, VEELKEN F, GALLDIKS N, KLUSSMANN J.P, NEUGEBAUER P, NOLDEN-HOVERATH S and HUTTENBRINK K.B. A rare differential diagnosis in dysphagia: wound botulism. Laryngoscope. [online] 2006 May;116(5):831-2. [viewed April 17, 2014] Available at DOI: 10.1097/01.mlg.0000214868.76123.a4.
  10. TEISMANN I.K, STEINSTRAETER O, WARNECKE T, ZIMMERMANN J, RINGELSTEIN E.B, PANTEV C and DZIEWAS R. Cortical recovery of swallowing function in wound botulism. BMC Neurol. [online] 2008 May 7;8:13. [viewed April 17, 2014] Available from doi: 10.1186/1471-2377-8-13.
  11. KHAKSHOOR H, MOGHADDAM A.A, VEJDANI A.H, ARMSTRONG B.K and MOSHIRFAR M. Diplopia as the primary presentation of foodborne botulism. Oman J Ophthalmol. [online] 2012 May;5(2):109-11. [viewed April 18, 2014] Available at doi: 10.4103/0974-620X.99375.
  12. MANFREDI M, SCODITTI U, ANGELINI M, DE GIAMPAULIS P, BORRINI BM, MACALUSO GM, PAVESI G and VESCOVI P. Dry mouth as an initial sign of food-borne botulism: a case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. [online] 2011 Apr;111(4):e15-8. [viewed April 18, 2014] Available at doi: 10.1016/j.tripleo.2010.10.044.
  13. ARORA A, SHARMA C.M, KUMAWAT B.L, and KHANDELWAL D. Rare presentation of botulism with generalized fasciculations. Int J Appl Basic Med Res. [online] 2014 Jan-Jun; 4(1): 56–58. [viewed April 18, 2014] Available at doi: 10.4103/2229-516X.125698.
  14. WITOONPANICH R, VICHAYANRAT E, TANTISIRIWIT K, WONGTANATE M, SUCHARITCHAN N, ORANRIGSUPAK P, CHUESUWAN A, NAKARAWAT W, TIMA A, SUWATCHARANGKOON S,INGSATHIT A, RATTANASIRI S. ansd WANANUKUL W. Survival analysis for respiratory failure in patients with food-borne botulism. Clin Toxicol (Phila). [online] 2010 Mar;48(3):177-83. [viewed April 18, 2014] Available at doi: 10.3109/15563651003596113.
  15. WONGTANATE, Manas, Niwatchai SUCHARITCHAN, Kanit TANTISIRIWIT, Petchdee ORANRIGSUPAK, Aphinya CHUESUWAN, Sukumal TOYKEAW and Yupin SUPUTTAMONGKOL. Signs and Symptoms Predictive of Respiratory Failure in Patients with Foodborne Botulism in Thailand. Am J Trop Med Hyg August [online] 2007 vol. 77 no. 2 386-389. [viewed April 17, 2014] Available at http://www.ajtmh.org/content/77/2/386.long
  16. KESHTGAR A.S., Harry C. WARD, Ahmad SANEI and Graham S. CLAYDEN. Botulinum toxin, a new treatment modality for chronic idiopathic constipation in children: long-term follow-up of a double-blind randomized trial. Journal of Pediatric Surgery [online] April 2007; 42(4) p672-680. [viewed April 18, 2014] Available at doi:10.1016/j.jpedsurg.2006.12.045.
  17. HERNÁNDEZ-DE MEZERVILLE M, ROJAS-SOLANO M, GUTIERREZ-MATA A, HERNÁNDEZ-CON L and ULLOA-GUTIERREZ R. Infant botulism in Costa Rica: first report from Central America. J Infect Dev Ctries. [online] 2014 Jan 15;8(1):123-5. [viewed April 18, 2014] Available at doi: 10.3855/jidc.3594.
  18. POTULSKA-CHROMIK, Anna, Beata ZAKRZEWSKA-PNIEWSKA, Elżbieta Szmidt-SAŁKOWSKA, Jacek LEWANDOWSKI, Maciej SIŃSKI, Witold PRZYJAŁKOWSKI and Anna KOSTERA-PRUSZCZYK. Long lasting dysautonomia due to botulinum toxin B poisoning: clinical- laboratory follow up and difficulties in initial diagnosis. BMC Research Notes [online] 2013, 6:438 [viewed April 18, 2014] Available at doi:10.1186/1756-0500-6-438.
  19. SOBEL J, DILL T, KIRKPATRICK C.L, RIEK L, LUEDTKE P and DAMROW T. Clinical recovery and circulating botulinum toxin type F in adult patient. Emerg Infect Dis [online]. 2009 Jun [April 18, 2014]. Available from http://www.cdc.gov/EID/content/15/6/969.htm; doi 10.3201/eid1506.070571.
  20. GRANT M.P, FRANCIS N.J and LANDIS S.C. The role of acetylcholine in regulating secretory responsiveness in rat sweat glands. Mol Cell Neurosci. [online] 1995 Feb;6(1):32-42. [viewed April 18, 2014] Available at http://dx.doi.org/10.1006/mcne.1995.1004.
  21. BLAKE KD, McCUSPIE J. and CORSTEN G. Botulinum toxin injections into salivary glands to decrease oral secretions in CHARGE syndrome: prospective case study. Am J Med Genet A. [online] 2012 Apr;158A(4):828-31. [viewed April 18, 2014] Available at doi: 10.1002/ajmg.a.33241.
  22. TORRES-URQUIDY MH, WALLSTROM G and SCHLEYER TK. Detection of disease outbreaks by the use of oral manifestations. J Dent Res. [online] 2009 Jan;88(1):89-94. [viewed April18, 2014] Available from doi: 10.1177/0022034508327546.
  23. HARPER M, FOWLER C.J. and DASGUPTA P. Botulinum toxin and its applications in the lower urinary tract. BJU International [online] April 2004; 93(6) p702–706. [viewed April 18, 2014] Available at DOI: 10.1111/j.1464-410X.2003.04714.x.
  24. WANGROONGSARB P, KOHDA T, JITTAPRASARTSIN C, SUTHIVARAKOM K, KAMTHALANG T, UMEDA K, SAWANPANYALERT P, KOZAKI S. and IKUTA K. Molecular Characterization of Clostridium botulinum Isolates from Foodborne Outbreaks in Thailand, 2010. PLoS One. [online] 2014; 9(1): e77792. [viewd April 18, 2014] Available at doi: 10.1371/journal.pone.0077792
  25. SIERADZAN K.A. Wound Botulism. Pract Neurol [online] 2005;5:46-51 [viewed April 18, 2014] Available at doi:10.1111/j.1474-7766.2005.00276.x.
  26. BHIDAYASIRI, R., Y.M. CHOI and R NISHIMURA. Wound botulism. Postgrad Med J [online] 2004;80:240 [viewed April 18, 2014] Available at doi:10.1136/pgmj.2003.011288.
  27. PARK J. and SIMPSON L.L. Inhalational Poisoning by Botulinum Toxin and Inhalation Vaccination with Its Heavy-Chain Component. Infect Immun. [online] Mar 2003; 71(3): 1147–1154. [viewed AQpril 18, 2014] Available from doi: 10.1128/IAI.71.3.1147-1154.2003.

Examination

Fact Explanation
Fever Foodborne botulism is afebrile, since it's a noninflammatory gastroenteritis [1] [2] and the symptoms are due to preformed toxin, not the infection itself. [3] But in wound botulism, there can be fever, and is usually due to wound sepsis. [4] [5]
Dry eyes and dry mouth. The secretory function in glandular tissues (e.g. sweat glands, lacrimal glands, gastric glands) is mediated via acetylcholine associated neurotransmission. [2] Antagonist action of the botulism toxin on the synapses cause reduced secretions, which is evident as dry eyes and dry mouth. [6]
A wound, most probably traumatic and contaminated. Suggests the entry site for the bacteria, since they are saprophytes, the wounds that are contaminated with soil pose a risk for wound botulism. [4] [5]
Blepharoptosis. It is the result of dysfunction of the levator palpebrae superioris which is innervated by the superior division of third cranial nerve and the Mueller muscle of the eyelid. Cranial neuropathy caused by the toxin is evident as symmetrical complete ptosis. [7] [8]
Binocular diplopia This is the subjective vision of one object as two, and a result of breakdown in the fusional capacity of the binocular system (neuromuscular coordination that maintains correspondence of the visual objects on the two retinas). Visual blurring maybe interpreted as diplopia by the patient, it is important to assess the vision accurately . [9] Is a manifestation of cranial neuropathy affecting occulomotor (CN III), trochlear (CN IV) and abducens (CNVI) nerves. [6] [9]
Extraoccular muscle paralysis. Extraocular muscles are supplied by cranial nerves III (occulomotor), IV (trochlear), and VI (abducens). [10] Neuropathy caused by the botulinum toxin is the cause.[11]
Fixed dilated pupils (Mydriasis) Over excitation of radial fibers of the iris which increases the pupillary aperture is referred to as a mydriasis or blown pupil. [12] The circular sphincter muscles of the iris are supplied by cholinergic parasympathetic nervous system, and the radial dilator muscle fibers are supplied by adrenergic sympathetic nervous system. Acetylcholine antagonizes the action of the botulinum toxin and blocks the sphincter function while the dilator function predominates. In botulism, mydriasis is bilateral and symmetrical, and also equally non reactive. [15], [6],[12],[13],[14]
Suppressed gag reflex. In the reflex arc of the gag reflex, sensory limb is mediated predominantly by cranial nerve IX (glossopharyngeal nerve) and the motor limb by cranial nerve X (vagus nerve). One third of normal healthy adults do not have a gag reflex. Absent gag reflex in botulism is symmetrical, and due to neurotoxicity of the cranial nerves, and can be associated with dysphagia. [16], [17]
Symmetrical descending motor weakness. All serotypes of botulinum toxin interfere with neural transmission by blocking the release of acetylcholine, which is the principal neurotransmitter at the neuromuscular junction. [1] [21] Symmetrical bilateral muscle weakness which is descending in nature is a hallmark feature of botulinum toxin, and can progress to fatal respiratory muscle paralysis rapidly. [18], [19],[20]
Deep tendon reflexes, which may be either intact or diminished Unlike expected significantly diminished deep tendon reflexes, absence of pathologic reflexes is observed in botulism. [1] [6]
Incoordination of muscles. It is due to muscle weakness [24] in neuromuscular junction toxicity in botuoinum.
Low respiratory rate The fatal outcome of muscle paralysis in botulism is respiratory muscle weakness. Once started, it progresses rapidly. [18] [22]
Orthostatic hypotension Botulism is a rare but important suspicion in acute or predominant isolated autonomic dysfunction. [15] Heart failure with diastolic dysfunction also has been reported. The patients were known to attain previous cardiovascular stability with time. [23]
Urinary retention with bladder distension It is due to autonomic toxic neuropathy in botulism, when the suspected patients present with abdominal distention and abdominal pain, urinary retention has to be suspected.[6], [26]
References
  1. NIGAM P.K. and NIGAM A. Botulinum Toxin. Indian J Dermatol. [online] 2010 Jan-Mar; 55(1): 8–14. [viewed April 17, 2014] Available at doi: 10.4103/0019-5154.60343.
  2. DAVIS, L.E. Botulinum Toxin: From Poison to Medicine. West J Med [online] 1993 Jan; 158:25-29 [viewed April 17, 2014] Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1021932/pdf/westjmed00077-0027.pdf
  3. SHEPPARD YD, MIDDLETON D, WHITFIELD Y, TYNDEL F, HAIDER S, SPIEGELMAN J, SWARTZ RH, NELDER MP, BAKER SL, LANDRY L, MACEACHERN R, DEAMOND S, ROSS L,PETERS G, BAIRD M, ROSE D, SANDERS G and AUSTIN JW. Intestinal toxemia botulism in 3 adults, Ontario, Canada, 2006-2008. Emerg Infect Dis. [online] 2012 Jan;18(1):1-6. [viewed April 19, 2014] Available at doi: 10.3201/eid1801.110533.
  4. BHIDAYASIRI, R., Y.M. CHOI and R NISHIMURA. Wound botulism. Postgrad Med J [online] 2004;80:240 [viewed April 18, 2014] Available at doi:10.1136/pgmj.2003.011288.
  5. SIERADZAN K.A. Wound Botulism. Pract Neurol [online] 2005;5:46-51 [viewed April 18, 2014] Available at doi:10.1111/j.1474-7766.2005.00276.x.
  6. LOUTFY, Mona R, John W. AUSTIN, Burke BLANCHFIELD and Ignatius W. FONG. An outbreak of foodborne botulism in Ontario. Can J Infect Dis. [online] 2003 Jul-Aug; 14(4): 206–209. [viewed April 17, 2014] Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2094941/pdf/JID14206.pdf.
  7. SOBEL, Jeremy. Botulism. Clin Infect Dis. [online] 2005; 41 (8): p1167-1173. [viewed April 19, 2014] Available at doi: 10.1086/444507.
  8. OMOIGUI S. and IRENE S. Treatment of ptosis as a complication of botulinum toxin injection. Pain Med. [online] 2005 Mar-Apr;6(2):149-51. [viewed April 19, 2014] Available at DOI: 10.1111/j.1526-4637.2005.05029.x.
  9. WALKER HK, HALL WD and HURST JW. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition [online] Chapter 60: Cranial Nerves III, IV, and VI: The Oculomotor, Trochlear, and Abducens Nerves. Butterworth, 1990. Available at http://www.ncbi.nlm.nih.gov/books/NBK406/
  10. REED, Howard. Paralysis of the Extra-ocular Muscles. Can Med Assoc J. [online] Jun 1954; 70(6): 628–631. [viewed April 19, 2014] Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1825417/pdf/canmedaj00693-0022.pdf.
  11. YASKIN, J.C. Paralysis of the Extraoccular Muscles Clinicoanatomic Considerations; Report of Cases of Paralysis of the Oculomotor and Abducens Nerves Due To Unusual Causes. Arch Ophthalmol. [online] 1939;21(6):1010-1020. [viewed April 19, 2014] Available at doi:10.1001/archopht.1939.00860060120008.
  12. THOMAS, P.D. The Differential Diagnosis of Fixed Dilated Pupils; A Case Report and Review. Critical Care and Resuscitation 2000; 2: 34-37 [viewed April 19, 2014] Available at cicm.org.au/journal/2000/march/Case2.pdf‎
  13. WALKER HK, HALL WD and HURST JW. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition [online] Chapter 58: The Pupils. Butterworth, 1990. Available at http://www.ncbi.nlm.nih.gov/books/NBK381/
  14. MATHIAS, C.J. Autonomic diseases: clinical features and laboratory evaluation. J Neurol Neurosurg Psychiatry [online] 2003;74:iii31-iii41 [viewed April 19, 2014] Available at doi:10.1136/jnnp.74.suppl_3.iii31
  15. POTULSKA-CHROMIK, Anna, Beata ZAKRZEWSKA-PNIEWSKA, Elżbieta Szmidt-SAŁKOWSKA, Jacek LEWANDOWSKI, Maciej SIŃSKI, Witold PRZYJAŁKOWSKI and Anna KOSTERA-PRUSZCZYK. Long lasting dysautonomia due to botulinum toxin B poisoning: clinical- laboratory follow up and difficulties in initial diagnosis. BMC Research Notes [online] 2013, 6:438 [viewed April 18, 2014] Available at doi:10.1186/1756-0500-6-438.
  16. LEDER S.B. Gag reflex and dysphagia. Head & Neck [online] 1996, 18(2):138-141. [viewed April 19, 2014] Available at DOI: 10.1002/(SICI)1097-0347(199603/04)18:2<138::AID-HED5>3.0.CO;2-2.
  17. DANIELS S.K. Neurological disorders affecting oral, pharyngeal swallowing. GI Motility online [online] 2006: May 16. [viewed April 19, 2014] Available at doi:10.1038/gimo34
  18. WITOONPANICH R, VICHAYANRAT E, TANTISIRIWIT K, WONGTANATE M, SUCHARITCHAN N, ORANRIGSUPAK P, CHUESUWAN A, NAKARAWAT W, TIMA A, SUWATCHARANGKOON S,INGSATHIT A, RATTANASIRI S. ansd WANANUKUL W. Survival analysis for respiratory failure in patients with food-borne botulism. Clin Toxicol (Phila). [online] 2010 Mar;48(3):177-83. [viewed April 18, 2014] Available at doi: 10.3109/15563651003596113.
  19. BHATIA K et al.Generalised muscular weakness after botulinum toxin injections for dystonia: a report of three cases. J Neurol Neurosurg Psychiatry. [online] Jul 1999; 67(1): 90–93. [viewed April 19, 2014] Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1736426/
  20. BROOK I. Infant botulism. Journal of Perinatology [online] 2007; 27, 175–180. [viewed April 19, 2014] Available at doi:10.1038/sj.jp.7211651
  21. LONGINO D, FRANK C, LEONARD T.R, VAZ M.A. and HERZOG W. Proposed model of botulinum toxin-induced muscle weakness in the rabbit. J Orthop Res. [online] 2005 Nov;23(6):1411-8. [viewed April 19, 2014] Available at DOI: 10.1016/j.orthres.2005.02.016.1100230625.
  22. WONGTANATE, Manas, Niwatchai SUCHARITCHAN, Kanit TANTISIRIWIT, Petchdee ORANRIGSUPAK, Aphinya CHUESUWAN, Sukumal TOYKEAW and Yupin SUPUTTAMONGKOL. Signs and Symptoms Predictive of Respiratory Failure in Patients with Foodborne Botulism in Thailand. Am J Trop Med Hyg August [online] 2007 vol. 77 no. 2 386-389. [viewed April 17, 2014] Available at http://www.ajtmh.org/content/77/2/386.long
  23. SOBEL J, DILL T, KIRKPATRICK C.L, RIEK L, LUEDTKE P and DAMROW T. Clinical recovery and circulating botulinum toxin type F in adult patient. Emerg Infect Dis [online]. 2009 Jun [April 18, 2014]. Available from http://www.cdc.gov/EID/content/15/6/969.htm; doi 10.3201/eid1506.070571.
  24. BOURBONNAIS D and NOVEN S.V. Weakness in Patients With Hemiparesis. American Journal of Occupational Therapy [online] May 1989 vol. 43 no. 5 313-319. [viewed April 20, 2014] Available at doi: 10.5014/ajot.43.5.313.
  25. KEMPLER P, AMARENCO G, FREEMAN R, FRONTONI S, HOROWITZ M, STEVENS M, LOW P, POP-BUSUI R, TAHRANI A, TESFAYE S, VÁRKONYI T, ZIEGLER D and VALENSI P. Gastrointestinal autonomic neuropathy, erectile-, bladder- and sudomotor dysfunction in patients with diabetes mellitus: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. [online] 2011 Jul 11. [viewed April 20, 2014] Available at doi: 10.1002/dmrr.1223.
  26. KIRBY RS, FOWLER CJ, GOSLING JA and BANNISTER R. Bladder dysfunction in distal autonomic neuropathy of acute onset. J Neurol Neurosurg Psychiatry. [online] 1985 Aug;48(8):762-7. [viewed April 20, 2014] Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1028447/

Differential Diagnoses

Fact Explanation
Hypermagnesemia. Hypermagnesemia causes blockage of neuromuscular transmission by preventing presynaptic acetylcholine release and competitively inhibiting calcium influx into the presynaptic nerve channels via the voltage-dependent calcium channel. One of the earliest symptoms of hypermagnesemia is deep-tendon reflex attenuation, unlike in botulism, where reflexes are normal or slightly diminished. Facial paresthesias also may occur at moderate serum levels. Muscle weakness is a manifestation of more severe forms of hypermagnesemia, , occurring at levels greater than 5 mmol/L. It also can lead to rapid respiratory depression and apnea if left untreated, hence the importance of diagnosing. Higher concentration of magnesium may cause severe symptomatic hypotension, mimicking that of toxic autonomic neuropathy in botulism. The vague initial symptoms of hypermagnesemia such as nausea and vomiting also raises suspicion of botulism. [1] [2] [3] For differentiating both, serum calcium and magnesium assays are necessary.
Hyperthyroidism. Hyperthyroidism also presents with opthalmophlegia, muscle weakness and relative anhydrosis. As the clinical presentations are variable and patient-dependent, it's important to exclude thyroid dysfunction in a thyroid hormone assay. [4] [5]
Guillain-Barré syndrome. It is a heterogeneous group of immune-mediated acute inflammatory processes generally characterized by motor, sensory, and autonomic dysfunction. The common symptoms are paralysis, and hyporeflexia, progressive symmetric ascending muscle weakness, with or without sensory or autonomic symptoms. The variability of patient complaints make it difficult to separate from other muscle and nerve disorders, hence making it an important differential in botulism. Nerve conduction studies play an important role in diagnosing. [6] [7]
References
  1. JHANG W.K,LEE Y.J. and PARK Y.S. Severe hypermagnesemia presenting with abnormal electrocardiographic findings similar to those of hyperkalemia in a child undergoing peritoneal dialysis. Korean J Pediatr. [online] Jul 2013; 56(7):308-311. [viewed April 20, 2014] Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728451/
  2. YOON HE, KIM YW, HA KS, SIM EH, GO SW and SHIN SJ. Hypermagnesemia accompanied with colonic perforation in a hemodialysis patient. Yonsei Med J. [online] 2013 May 1;54(3):797-800. [viewed April 20, 2014] Available at doi: 10.3349/ymj.2013.54.3.797.
  3. KHAIRI T et al. Severe Symptomatic Hypermagnesemia Associated with Over-the-Counter Laxatives in a Patient with Renal Failure and Sigmoid Volvulus. Case Rep Nephrol. [online] 2014; 2014: 560746. [viewed April 20, 2014] Available at doi: 10.1155/2014/560746
  4. BAHN CHAIR R.S. et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid. [online] 2011 Jun;21(6):593-646. [viewed April 20, 2014] Available at doi: 10.1089/thy.2010.0417.
  5. COOPER, David S. Hyperthyroidism. Lancet. [online] 2003 Aug 9;362(9382):459-68. [viewed April 20, 2014] Available at doi:10.1016/S0140-6736(03)14073-1
  6. VAN DOORNE, P.A. Diagnosis, treatment and prognosis of Guillain-Barré syndrome (GBS). Presse Med. [online] 2013 Jun;42(6 Pt 2):e193-201. [viewed April 20, 2014] Available at doi: 10.1016/j.lpm.2013.02.328.
  7. GONZÁLEZ-SUÁREZ I et al. Guillain-Barré Syndrome: Natural history and prognostic factors: a retrospective review of 106 cases. BMC Neurology [online] 2013, 13:95 [viewed April 20, 2014] Available at doi:10.1186/1471-2377-13-95

Investigations - for Diagnosis

Fact Explanation
Toxicology screen It is an important diagnostic tool in detecting the toxin activity. The conventional method is using Enzyme-linked Immunosorbent Assay. [1] [2] [3] [4] [5]
Culture of gastric aspirates, vomitus or stools Because intestinal carriage is rare, identifying the organism points to a definite diagnosis of botulism. [6] [7] [8]
Wound culture It suggests a definitive diagnosis of wound botulism as it's almost always a pathogenic microbe. [8] [9] [10]
Single-fiber Electromyography (EMG) Abnormalities in EMG are observed in all botulism cases, but repetitive stimulation of a motor nerve showed a characteristic triad, indicating presynaptic block of neuromuscular transmission: the muscle compound action potential amplitude is low. [11] [12]
References
  1. DAVIS, L.E. Botulinum Toxin: From Poison to Medicine. West J Med [online] 1993 Jan; 158:25-29 [viewed April 17, 2014] Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1021932/pdf/westjmed00077-0027.pdf
  2. NIGAM P.K. and NIGAM A. Botulinum Toxin. Indian J Dermatol. [online] 2010 Jan-Mar; 55(1): 8–14. [viewed April 17, 2014] Available at doi: 10.4103/0019-5154.60343.
  3. PEARCE LB, BORODIC GE, FIRST ER and MACCALLUM RD. Measurement of botulinum toxin activity: evaluation of the lethality assay. Toxicol Appl Pharmacol. [online] 1994 Sep;128(1):69-77. [viewed April 20, 2014] Available at http://dx.doi.org/10.1006/taap.1994.1181
  4. DEZFULIAN M and BARTLETT J.G. Detection of Clostridium botulinum type A toxin by enzyme-linked immunosorbent assay with antibodies produced in immunologically tolerant animals. J Clin Microbiol. [online] May 1984; 19(5): 645–648. [viewed April 20, 2014] Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC271147/
  5. SESARDIC D1, LEUNG T, GAINES DAS R.Role for standards in assays of botulinum toxins: international collaborative study of three preparations of botulinum type A toxin. Biologicals. [online] 2003 Dec;31(4):265-76. [viewed April 20, 2014] Available at http://dx.doi.org/10.1016/j.biologicals.2003.08.001
  6. McKEE MT et al. Culture of Clostridium Botulinum type C With Controlled pH. J Bacteriol. [online] Feb 1958; 75(2): 135–142. [viewed April 20, 2014] Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC290049/
  7. DEZFULIAN M and V R DOWELL, JR. Cultural and physiological characteristics and antimicrobial susceptibility of Clostridium botulinum isolates from foodborne and infant botulism cases. J Clin Microbiol. [online] 1980 Jun;11(6):604-9. [viewed April 20, 2014] Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC273469/
  8. LINDSTRÖM M, KORKEALA H. Laboratory diagnostics of botulism. Clin Microbiol Rev. [online] 2006 Apr;19(2):298-314. [viewed April 20, 2014] Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1471988/
  9. KALKA-MOLL W.M. et al. Wound Botulism in Injection Drug Users. Emerg Infect Dis. [online] Jun 2007; 13(6): 942–943. [viewed April 20, 2014] Available at doi: 10.3201/eid1306.061336.
  10. TAYLOR, S.M. et al. Wound Botulism Complicating Internal Fixation of a Complex Radial Fracture. J Clin Microbiol. [online] Feb 2010; 48(2): 650–653. [viewed April 20, 2014] Available at doi: 10.1128/JCM.01258-09
  11. PADUA L, APRILE I, MONACO ML, FENICIA L, ANNIBALLI F, PAURI F and TONALI P. Neurophysiological assessment in the diagnosis of botulism: usefulness of single-fiber EMG. Muscle Nerve. [online] 1999 Oct;22(10):1388-92. [viewed April 21, 2014] Available at DOI: 10.1002/(SICI)1097-4598(199910)22:10<1388::AID-MUS8>3.0.CO;2-3
  12. CHAUDHRY V and CRAWFORD TO. Stimulation single-fiber EMG in infant botulism. Muscle Nerve. [online] 1999 Dec;22(12):1698-703. [viewed April 21, 2014] Available at DOI: 10.1002/(SICI)1097-4598(199912)22:12<1698::AID-MUS12>3.0.CO;2-K

Management - General Measures

Fact Explanation
Urgent admission On suspicion of symptoms or known exposure should be hospitalized into emergency settings and closely observed. Once the respiratory muscle paralysis begins, respiratory failure can occur with unexpected rapidity. It's necessary to have emergency resuscitation facilities at hand. [1] [2]
Sequential observation of spirometry, pulse oximetry, vital capacity, and arterial blood gases. In preparation to resuscitate as soon as respiratory failure sets in. [1]
Intubation and mechanical ventilation It should be considered when there are features of impending respiratory failure, with hypoxemia with hypercarbia being present. [1]
Stress ulcer prophylaxis Since the patient is going to be in the intensive care for an extended period of time, stress ulcer prevention is important, though uncommon. [3]
Nasogastric suction and intravenous hydration. If paralytic ileus is present this is a known complication in critical conditions. [4],[5]
Nasogastric feeding for enteral nutritional supplementation Early enteral feeding reduces the intensive care mortality significantly. [6]
Urinary catheterization Consider if urinary retention occurs. This must be monitored conscientiously and changed regularly to prevent catheter-associated urinary tract infections. [7],[8].
Deep venous thrombosis (DVT) prophylaxis Majority of the critically ill patients admitted to intensive care have a tendency to develop deep vein thrombosis, and it's prophylaxis is a must in long term patients. [9] Low-molecular weight heparin, thrombo embolic deterrent (TED) stockings are the management of choice. [10]
Isolation and infection control Universal precautions should always be implemented when evaluating and treating patients. The toxin can be absorbed through mucosal surfaces, the eye, and nonintact skin. Upto now, no case of human-human transmission of botulinum has been described, nevertheless, persons exposed to bodily fluids or stool from patients with botulism should be advised of the early signs of botulism and should report for evaluation if these are noted. [11]
Wound debridement and toilet. In wound botulism. [12]
Cathartics and enemas. To eliminate the yet unabsorbed toxin in the gut. [12]
References
  1. HEMMILA MR and NAPOLITANO LM. Severe respiratory failure: advanced treatment options. Crit Care Med. [online] 2006 Sep;34(9 Suppl):S278-90. [viewed April 21, 2014] Available at doi: 10.1097/01.CCM.0000233788.96388.D8
  2. WITOONPANICH R, VICHAYANRAT E, TANTISIRIWIT K, WONGTANATE M, SUCHARITCHAN N, ORANRIGSUPAK P, CHUESUWAN A, NAKARAWAT W, TIMA A, SUWATCHARANGKOON S,INGSATHIT A, RATTANASIRI S. ansd WANANUKUL W. Survival analysis for respiratory failure in patients with food-borne botulism. Clin Toxicol (Phila). [online] 2010 Mar;48(3):177-83. [viewed April 18, 2014] Available at doi: 10.3109/15563651003596113.
  3. MARIK PE1, VASU T, HIRANI A, PACHINBURAVAN M. Stress ulcer prophylaxis in the new millennium: a systematic review and meta-analysis. Crit Care Med. [online] 2010 Nov;38(11):2222-8. [viewed April 21, 2014] Available at doi: 10.1097/CCM.0b013e3181f17adf.
  4. MOSS G. The etiology and prevention of feeding intolerance paralytic ileus--revisiting an old concept. Ann Surg Innov Res. [online] 2009 Apr 17;3:3. [viewed April 21, 2014] Available at doi: 10.1186/1750-1164-3-3.
  5. SCHWARZ N.T. et al. Pathogenesis of Paralytic Ileus. Ann Surg. [online] Jan 2002; 235(1): 31–40. [viewed April 21, 2014] Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1422393/
  6. ARTINIAN V1, KRAYEM H and DIGIOVINE B. Effects of early enteral feeding on the outcome of critically ill mechanically ventilated medical patients. Chest. [online] 2006 Apr;129(4):960-7. [viewed April 21, 2014] Available at doi:10.1378/chest.129.4.960
  7. SAINT S1, SAVEL RH, MATTHAY MA. Enhancing the safety of critically ill patients by reducing urinary and central venous catheter-related infections. Am J Respir Crit Care Med. [online] 2002 Jun 1;165(11):1475-9. [viewed April 21, 2014] Available at doi: 10.1164/rccm.2110035
  8. CLEC'H C1, SCHWEBEL C, FRANÇAIS A, TOLEDANO D, FOSSE JP, GARROUSTE-ORGEAS M, AZOULAY E, ADRIE C, JAMALI S, DESCORPS-DECLERE A, NAKACHE D, TIMSIT JF,COHEN Y; OUTCOMEREA STUDY GROUP. Does catheter-associated urinary tract infection increase mortality in critically ill patients? Infect Control Hosp Epidemiol. [online] 2007 Dec;28(12):1367-73. [viewed April 21, 2014] Available at DOI: 10.1086/523279
  9. ATTIA J1, RAY JG, COOK DJ, DOUKETIS J, GINSBERG JS and GEERTS WH. Deep vein thrombosis and its prevention in critically ill adults. Arch Intern Med. [online] 2001 May 28;161(10):1268-79. [viewed April 21, 2014] Available at doi:10.1001/archinte.161.10.1268.
  10. DOUKETIS J1, COOK D, MEADE M, GUYATT G, GEERTS W, SKROBIK Y, ALBERT M, GRANTON J, HÉBERT P, PAGLIARELLO G, MARSHALL J, FOWLER R, FREITAG A, RABBAT C, ANDERSON D, ZYTARUK N, HEELS-ANSDELL D and CROWTHER M. Prophylaxis against deep vein thrombosis in critically ill patients with severe renal insufficiency with the low-molecular-weight heparin dalteparin: an assessment of safety and pharmacodynamics: the DIRECT study. Arch Intern Med. [online] 2008 Sep 8;168(16):1805-12. [viewed April 21, 2014] Available at doi: 10.1001/archinte.168.16.1805.
  11. SOBEL J.Botulism. Clin Infect Dis. [online] 2005 Oct 15;41(8):1167-73. [viewed April 21, 2014] Available at doi: 10.1086/444507
  12. ARORA A, SHARMA C.M, KUMAWAT B.L and KHANDELWAL D. Rare presentation of botulism with generalized fasciculations. Int J App Basic Med Res [online] 2014;4:56-8. [viewed April 21, 2014] Available at DOI: 10.4103/2229-516X.125698.

Management - Specific Treatments

Fact Explanation
Antitoxin therapy. It's the only definitive management option in botulism [1] [2] [3] [4]. Antitoxin can arrest the progression of paralysis and decrease the duration of paralysis and dependence on mechanical ventilation. [5] Antitoxin should be given early in the course of illness, ideally before 24 h after onset of symptoms, [6] because antitoxin neutralizes only toxin molecules that are yet unbound to nerve endings. Use of antitoxin is associated with adverse effects, [7] including anaphylaxis, other hypersensitivity reactions, and serum sickness. About 9% of patients treated with equine antitoxins developed hypersensitivity reactions but long lasting immunity is rare since the half-life of the immunoglobulin is short. [8]
Oral antibiotics e.g. Penicillin, Chloramphenicol, Clindamycin C.botulinum rods are susceptible to many antibiotics except a very few ( e.g. gentamycin, trimethoprium). [9] Since the clinical syndrome is not due to the multiplying bacteria themselves, but the pre-formed toxin, it's debatable whether antibiotic administration is necessary, but to prevent further deterioration by bacteremia, antibiotics are important. On the other hand, in wound botulism, antibiotics are a must to prevent sepsis. [5]
References
  1. DEMBEK ZF, SMITH LA and RUSNAK JM. Botulism: cause, effects, diagnosis, clinical and laboratory identification, and treatment modalities. Disaster Med Public Health Prep. [online] 2007 Nov;1(2):122-34. [viewed April 21, 2014] Available at doi: 10.1097/DMP.0b013e318158c5fd.
  2. GUTZWILLER FS, STEFFEN R, MATHYS P, WALSER S, SCHMID H and MÜTSCH M. [Botulism: prevention, clinical diagnostics, therapy and possible threat]. Dtsch Med Wochenschr. [online] 2008 Apr;133(16):840-5. [viewed April 21, 2014] Available at doi: 10.1055/s-2008-1075658.
  3. WERNER S.B. and CHIN J. Botulism—Diagnosis, Management and Public Health Considerations. Calif Med. [online] May 1973; 118(5): 84–88. [viewed April 21, 2014] Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1455058/
  4. SOBEL J. Diagnosis and Treatment of Botulism: A Century Later, Clinical Suspicion Remains the Cornerstone. Clin Infect Dis.[online] 2009; 48 (12): 1674-1675. [viewed April 21, 2014] Available at doi: 10.1086/599030.
  5. SOBEL J.Botulism. Clin Infect Dis. [online] 2005 Oct 15;41(8):1167-73. [viewed April 21, 2014] Available at doi: 10.1086/444507
  6. CHANG GY and GANGULY G. Early antitoxin treatment in wound botulism results in better outcome. Eur Neurol [online] 2003;49:151-3. [viewed April 21, 2014] Available at DOI:10.1159/000069073.
  7. SCOTT A.B. Antitoxin reduces botulinum side effects. Eye [online] 1988; 2, 29–32; [viwed April 21, 2014] Available at doi: 10.1038/eye.1988.7.
  8. DeCUSTOS E.E.V. et al. Equine Botulinum Antitoxin for the Treatment of Infant Botulism. Clin Vaccine Immunol [online] November 2011;18(11) p1845-1849 [viewed April 21, 2014] Available at http://cvi.asm.org/content/18/11/1845.full.
  9. SWENSON JM, THORNSBERRY C, MCCROSKEY LM, HATHEWAY CL and DOWELL VR JR. Susceptibility of Clostridium botulinum to thirteen antimicrobial agents. Antimicrob Agents Chemother. [online] 1980 Jul;18(1):13-9. [viewed April 21, 2014] Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC283932/