- intestinal production of C. Botulinum toxin results in impaired release of
- spores found in honey, corn syrup, soil
- presents with constipation, poor feeding, bulbar and skeletal
muscle weakness, loss of DTR's
- Dx: isolation of organism in stool
- RX: supportive, specific Ig in proven cases
- Self-limited disease, may last up to 6 weeks
CHLA Board Review 2005
Weakness and hypotonia in newborns can be caused by disorders of the neuromuscular junction. They are characterized by abnormal neuromuscular transmission leading to muscle fatiguability and weakness. Although most of these disorders are transient, congenital forms sometimes may be permanent.
These rare conditions include
- transient acquired neonatal myasthenia gravis
- congenital myasthenia
- elevated levels of magnesium or aminoglycosides
- infantile botulism
Infant botulism results from intestinal colonization by Clostridium botulinum The disease presentation and severity are variable, most likely due to variations in the size of the bacterial inoculum and in host susceptibility.
The initial presentation may involve constipation, shortly followed by weakness, feeding difficulties, descending or global hypotonia, drooling, anorexia, irritability, and weak cry.
For suspected infant botulism occurring in any state, the California Department of Health Services, Infant Botulism Treatment and Prevention Program should be contacted (www.infantbotulism.org/ or 510-231-7600).
- affects infants between one week and 12 months of age.
- Most cases: 2-8 mos
- Median age of onset: 3-4 mos
- Clostridium species that cause infant botulism: types A, B, E, and F;
- Majority: types A or B
- Type A: more prevalent in the western United States
- Type B: more prevalent in the eastern United States.
- occurs more commonly in areas where environmental conditions favor persistence of spores in the soil, including Pennsylvania, Utah, and California in North America
- result from ingestion of environmental dust containing C. botulinum spores, and residence near activities that disturb the soil such as construction or agricultural cultivation may enhance exposure. Food-borne cases can result from ingestion of wild honey or home canned foods contaminated with C. botulinum spores
- Young age and the absence of competitive bowel flora are factors that predispose to vulnerability.
- Colostrum in breast mild offers some protection, but breast fed infants may become susceptible during the transition to formula or solid foods.
Clinical features —
- progressive neuromuscular blockade: mild to severe.
- “Top to bottom”: muscles innervated by the cranial nerves are affected first, followed by those of the trunk, extremities, and diaphragm.
- Infants typically present with constipation and poor feeding
- followed by progressive hypotonia, and weakness.
- Loss of deep tendon reflexes appears to occur more commonly in type B infection
- Cranial nerve dysfunction: decreased gag and suck, diminished range of eye movement, pupillary paralysis, and ptosis
- Autonomic signs: decreased tearing and salivation, fluctuating heart rate and blood pressure, and flushed skin.
- Infant botulism may present with or progress to life-threatening respiratory failure,
- In a clinical trial, most infants required intensive care and about half required mechanical ventilation
- In atypical cases, infants may present with catastrophic collapse or rapid deterioration following brief periods of poor feeding but without the typical initial complaints of constipation, ptosis, or facial weakness.
- Prior to the advent of BIG-IV treatment, the duration of illness was usually one to two months, and occasional infants might relapse. Untreated type A infant botulism was longer in duration and more severe than type B illness.
- Suspect botulism in any infant with acute onset of weak suck, ptosis, inactivity, and constipation. The diagnosis is often missed.
- Therapy should be administered as early as possible.
- A presumptive diagnosis should be made based upon the clinical presentation and electrophysiologic findings while the confirmatory stool studies are pending.
- Serum samples for botulinum toxin are often negative in cases of infant botulism (positive in <10%).
- The diagnosis is supported by the isolation of C. botulinum spores from the stool and is confirmed by the identification of botulinum toxin in stool samples.
- D/t constipation, stool sample collection can be difficult. Consider collection from gastric aspirates.
- Anaerobic cultures take up to 6 days for growth and identification of the organism; initial detection of toxin requires 1 to 4 days
Details of specimen collection and testing
- Mouse bioassay for toxin is the preferred method for diagnosis and results are positive in all likely cases of infant botulism. C. botulinum organisms and toxin have been identified in stool of affected infants as late as 5 months and 4 months, respectively, after onset of symptoms. Fluorescent antibody or enzyme immunosorbent assays for detection of toxin or organism are inferior. Polymerase chain reaction testing is promising as a rapid and less cumbersome test, but is not standardized.
- Specimens for culture should be refrigerated if inoculation is not to be prompt, but no other special handling is required. C. botulinum can be isolated from stool, intestinal contents from autopsy specimens, food specimens, or dust or dirt with the use of enrichment in chopped meat broth and then anaerobic incubation on selective egg yolk agar. Density of organism in stool can be as high as 108 colony-forming units per gram. C. botulinum-producing toxins types A through F produce lipase, which is detected as an iridescent film surrounding colonies.
- Passed stool is the preferred specimen, but effluent obtained after a small-volume enema using sterile, nonbacteriostatic water is acceptable. In the latter instance, subsequent specimens are collected if the initial test result is negative and diagnosis is likely. Specimens for toxin assay should be refrigerated but not frozen pending shipping directions from public health officials.
- Electromyography (EMG) findings consistent with infant botulism are not pathognomonic and may not be present early in the course of the disease. Nevertheless, certain EMG findings support the diagnosis of botulism when coupled with the appropriate clinical presentation:
- Repetitive nerve stimulation at rates of 20 to 50 Hz with an abnormal incremental response. An incremental response to 50 Hz stimulation is seen in 92 percent of infants with botulism poisoning, compared with 20 percent of normal infants
- EMG showing short-duration, low-amplitude motor unit potentials
In clinical practice, spinal muscular atrophy type I and metabolic disorders are the most frequent mimics of infant botulism.
- brainstem encephalitis
- cerebral infarction
- drug ingestion
- Guillain-Barré syndrome, including Miller-Fisher variant
- Lambert-Eaton myasthenic syndrome
- metabolic encephalopathy; metabolic / mitochondrial disorders
- myasthenia gravis
- neuromuscular disorders
- Any infant with clinical signs, symptoms, or history suspicious for botulism should be hospitalized immediately and meticulously monitored for signs of respiratory failure.
- For suspected infant botulism occurring in any state, the California Department of Health Services, Infant Botulism Treatment and Prevention Program should be contacted (www.infantbotulism.org/ or 510-231-7600).
- Botulism immune globulin intravenous (BIG-IV or babyBIG), a human-derived botulinum antitoxin, is safe and effective therapy for infant botulism and should be administered as early as possible. Treatment should not be delayed while awaiting results of confirmatory tests. (See "Botulism immune globulin (intravenous human): Drug information").
- Arnon, SS, Schechter, R, Maslanka, SE, et al. Human botulism immune globulin for the treatment of infant botulism. N Engl J Med 2006; 354:462. Benefits of BIG-IV
- hospital stay (2.6 versus 5.7 weeks)
- intensive care (1.8 versus 5 weeks)
- mechanical ventilation (1.8 versus 4.4 weeks
- tube or intravenous feeding (3.6 versus 10 weeks)
- Mean hospital charges were reduced by $89,000 (in 2004 United States dollars)
- In preplanned subgroup analyses, BIG-IV treatment was beneficial for both type A and type B infant botulism
- No serious adverse events were associated with BIG-IV therapy.
Management of infant botulism is otherwise supportive and includes close monitoring to detect sudden worsening.
There has been concern that antibiotics used to treat secondary bacterial infections could cause lysis of the C. botulinum vegetative cells within the intestine and thereby increase the amount of toxin that can be absorbed. However, this concern is ameliorated by BIG-IV treatment because a single BIG-IV infusion will neutralize all botulinum toxin available for absorption for at least six months
Aminoglycosides should be avoided because they can potentiate the effects of the toxin (Excess aminoglycoside levels, especially in combination with neuromuscular blockers, may lead to prolonged weakness caused by a presynaptic block. Bladder, bowel, and pupillary functions may be depressed. Hypocalcemia accentuates the neurotoxic effects of aminoglycosides and hypermagnesemia.)
UTD (last updated 2009)
Neuromuscular junction disorders in newborns and infants
Olaf A Bodamer, MD, FACMG, PhD
Geoffrey Miller, MD
Marc C Patterson, MD, FRACP
Joseph A Garcia-Prats, MD
John F Dashe, MD, PhD
Last literature review version 16.3: October 2008 | This topic last updated: May 31, 2008
And anecdotally: https://md.sermo.com/medical/ticket/details?nav=on&id=25135