CASEGary Oh

Farah, a 26 year old student at the Saint James School of Medicine had spent the weekend at Spice beach eating food and enjoying rejuvenating beverages. The next morning while riding her scooter to school, her vision became blurry, and she was forced to pull over to the side of the road. As she sat on her bike, her vision worsened. She waved down a passing car for help and tried to relax. In a short time, a Bonarian pulled over and approached her. By this time, she was having trouble swallowing and speaking clearly. The polite gentleman helped Farah to his car and rushed her to the emergency room at a nearby hospital.

In the ER, Farah was able to describe her symptoms to a physician. The physician made note of what Farah had eaten during the last 24 hours and knew that Spice beach’s kitchen had a protocol of using local canned sea vegetables. The physician observed that Farah's breathing was becoming labored.

??What are the signs and symptoms???

Farah, a twenty-one year old student at Saint James School of Medicine had spent the weekend at Spice beach eating food and enjoying beverages. The next morning while riding her scooter to school, her vision became blurry, and she was forced to pull over to the side of the road. As she sat on her bike, her vision worsened. She waved down a passing car to attracting help and tried to relax. In a short time, a Bonarian pulled over and approached her. By this time, she was having trouble swallowing and speaking clearly. The polite gentleman helped Farah to his car and rushed her to the emergency room at a nearby hospital.

In the ER, Farah was able to describe her symptoms to a physician. The physician made note of what Farah had eaten during the last 24 hours and knew that Spice beach’s kitchen had a protocol of using local canned vegetables. The physician observed that Farah's breathing was becoming labored.

??What is the dDx???

DIFFERENTIAL DIAGNOSIS

Lambert-Eaton myasthenic syndrome (LEMS) Tick paralysis Guillain-Barré syndrome Myasthenia gravis Poliomyelitis Stroke Heavy metal intoxication. Less likely diagnoses

Tetrodotoxin Shellfish poisoning Antimicrobial-associated paralysis.  

??What is the diagnosis???

The physician ordered Farah's blood sampled, her gastrointestinal tract pumped, and a mechanical respirator prepared for use. Fearing that Farah suffered from a case of botulism, she asked that Spice beach be contacted and samples of the meal retained, if possible, and sent to a local clinic for analysis.

??What further testing do you need???

Serum analysis for toxin by bioassay. Analysis of stool, vomitus, and suspected

food items may also reveal toxin EMG studies may be useful Patients with botulism are alert and do

not have fever, headache, or meningismus. Performing a lumbar puncture to rule out meningitis or encephalitis is therefore not typically indicated.

Botulism Life-threatening neuroparalytic syndrome from

neurotoxin by Clostridium botulinum First investigation occurred in 1820s with

hundreds of patients with "sausage poisoning" in a southern German town.

Several decades later in Belgium, the association was demonstrated between a neuromuscular paralysis and ham infected by a spore-forming bacillus that was isolated from the ham.

The organism was named Bacillus botulinus (Latin for sausage, botulus).

Incidence

110 cases /y in the USA (CDC) Infant 72 % Foodborne 25 % Wound 3 %

Types: Foodborne, Infant, Wound Unknown source Inhalational - The form that would occur

if aerosolized toxin was released in an act of bioterrorism

Iatrogenic - Cosmetic indications

Symptoms and Signs

Usually begins within 12 to 36 hours after ingestion Acute bilateral cranial neuropathies with symmetric

descending weakness. Other Sx: -Nonspecific GI symptoms

-No fever-Symmetric neurologic deficits-The patient remains responsive-Normal or slow heart rate and normal blood pressure-No sensory deficits with the exception of blurred vision

Cranial nerve involvement most commonly marks the onset. Blurred vision (secondary to fixed pupillary dilation

and CN III, IV, VI palsies), diplopia, nystagmus, ptosis Dysphagia, dysarthria, and facial weakness.

Descending muscle weakness from trunk to upper extremities to lower extremities.

Urinary retention, constipation, paresthesias CSF is normal. Variable, ranging from mild complaints to death

within the first 24 hours of developing symptoms.

Pathophysiology

C. botulinum gram-positive, rod-shaped, spore-forming, obligate anaerobic bacteria.

Spores are heat resistant, easily surviving 100ºC at one atmosphere for five or more hours.

However, spores can be destroyed by heating to 120ºC for five minutes

Environmental growth parameters include:● Restricted oxygen exposure● Low acidity (pH >4.6) water● A temperature of 25 to 37ºC for ideal growth

Vasculature disperses toxin widely and binds to a specific receptor (synaptotagmin II) on the presynaptic sides of peripheral cholinergic synapses at ganglia and NMJ.

Toxin heavy chain binds to the receptors, allowing the light chain to translocate into the nerve cell via receptor-mediated endocytosis 

After gaining entrance to the cell's cytoplasm, the toxin produces an irreversible disruption in stimulation-induced acetylcholine release by that presynaptic nerve terminal.

Return of synaptic function requires sprouting of a new presynaptic terminal with subsequent formation of a new synapse, a process that requires approximately six months.

Adrenergic synapses not affected, toxin does not penetrate BBB

Therefore limited to the peripheral cholinergic nervous system 

Perhaps the most potent known poison. It is estimated that 1g of aerosol botulism toxin could kill at least 1.5 million people.

???What is the recommended treatment??

Treatment

Immediate hospitalization Meticulous monitoring for signs of respiratory failure

(pulse oxymetry, spirometry, arterial blood gas measurement, and clinical evaluation of ventilation, perfusion, and upper airway integrity.

Respiratory failure is the primary cause of death in these patients. Intubation as necessary.

Two botulism antitoxin therapies Equine serum heptavalent botulism antitoxin is used

to treat children older than one year of age and adults;

Human-derived botulism immune globulin is used for infants less than one year of age.

A pentavalent antitoxin is available within the Department of Defense but is not available for public use.

Clinician should contact the State Health Department and/or CDC immediately for assistance with the decision of whether botulism antitoxin is indicated and to obtain a supply of antitoxin.

Antitoxin should be administered as soon as possible and should not be delayed while awaiting results of diagnostic studies.

Antibiotics - unproven by clinical trial but widely used and recommended for wound botulism after antitoxin has been administeredLaxatives, enemas, or other cathartics may be given, provided no significant ileus is present. Wound botulism - extensive debridement even if wound appears unimpressive. Tetanus boosters as well if it has been five or more years since their last immunization.

??What is the prognosis??

Prognosis Hospitalization for one to three months Attention to the impending respiratory

failure Overall, most patients can expect a

complete or nearly complete recovery with return to previous level of functioning within 3 months

Patients with severe disease may experience protracted courses involving years of neurologic deficits, sequelae from extended mechanical ventilation, and nosocomial illness.

ReferencesAmerican Academy of Pediatrics. Botulism and infant botulism (Clostridium botulinum). In: Red Book: 2012 Report of the Committee on Infectious

Diseases, 29th ed, Pickering LK (Ed), American Academy of Pediatrics, Elk Grove Village, IL 2012. p.281.60. Black JD, Dolly JO. Interaction of 125I-labeled botulinum neurotoxins with nerve terminals. II. Autoradiographic evidence for its uptake into motor

nerves by acceptor-mediated endocytosis. J Cell Biol 1986; 103:535 Bleck TP. Clostridium botulinum (botulism). In: Principles and Practice of Infectious Diseases, 6th ed, Mandel, GL, Bennett JE, Dolin R (Eds),

Churchill Livingstone, Philadelphia 2005. p.2822 Centers for Disease Control and Prevention (CDC). Botulism associated with commercial carrot juice—Georgia and Florida, September 2006.

MMWR Morb Mortal Wkly Rep 2006; 55:1098. Centers for Disease Control and Prevention (CDC). Notice of CDC's discontinuation of investigational pentavalent (ABCDE) botulinum toxoid

vaccine for workers at risk for occupational exposure to botulinum toxins. MMWR Morb Mortal Wkly Rep 2011; 60:1454 64. Chai Q, Arndt JW, Dong M, et al. Structural basis of cell surface receptor recognition by botulinum neurotoxin B. Nature 2006; 444:1096.

Mcnally RE, Morrison MB, Berndt JE, et al. Effectiveness of medical defense interventions against predicted battlefield levels of botulinum toxin A, Science Applications International Corp, Joppa 1994

 Sobel J. Botulism. Clin Infect Dis 2005; 41:1167 Sugiyama H. Clostridium botulinum neurotoxin. Microbiol Rev 1980; 44:419 Varma JK, Katsitadze G, Moiscrafishvili M, et al. Signs and symptoms predictive of death in patients with foodborne botulism--Republic of Georgia,

1980-2002. Clin Infect Dis 2004; 39:35743.

Wannemacher, RW Jr, Dinterman, RE, Thompson, WL, et al. Treatment for removal of biotoxins from drinking water. Fort Detrick, Frederick, MD: US Army Biomedical Research and Development Laboratory. Technical report 9120.