570626
research-article2015
CPJXXX10.1177/0009922815570626Clinical PediatricsPaccione et al
Resident Rounds
Diffuse Muscle Weakness in an Infant
Clinical Pediatrics 1–2 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/0009922815570626 cpj.sagepub.com
Rose Paccione, MD, MA, MBA1, Paul Remedios, MD1, Jessica Gautreaux, MD1, and Robin English, MD1
Case Report A developmentally appropriate 7-month-old male with no past medical history was transferred to our facility after being evaluated at an outside hospital for suspected meningoencephalitis. His family noted that on awakening earlier that day, he was lethargic, was unable to control his head movement, had a weak cry, poor suck, and seemed generally weak. Associated symptoms included several days of cough and decreased oral intake. The family denied fevers, seizure activity, or recent travel. Additionally, they denied the administration of honey or canned foods. Immunizations were up to date, and the patient was taking no medications except for an overthe-counter homeopathic cold remedy for the past week. Our physical examination revealed an afebrile infant with normal vital signs. He was nontoxic appearing and crying, while intermittently sucking on a pacifier. His oropharynx and tympanic membranes were clear. Cardiovascular, respiratory, and abdominal exams were normal. Neurological exam findings included normal cranial nerves and profound hypotonia. He had proximal > distal muscle weakness and arreflexia. He had no head control, but was moving his extremities spontaneously. His toes were down-going on Babinski maneuver. He had lost the ability to sit and roll over and though he could move arms and legs against gravity, most movement was distal, and there was a paucity of movement overall. He showed fatigability throughout the exam, resisting initially, but losing the ability to resist as the exam went on. The diagnostic evaluation at the outside facility included a normal complete blood count, normal coagulation studies, and a normal complete metabolic panel. Cerebrospinal fluid analysis revealed normal cell counts, protein, glucose, and gran stain. A chest radiograph and computed tomography of the head were normal. Blood cultures had been drawn, and he had been given one dose each of intravenous vancomycin, rocephin, and acyclovir. At our facility, we continued empiric antibiotic coverage until cultures were negative, but because of the lower motor neuron signs, we doubted the diagnosis of meningoencephalitis. Further evaluation included a head magnetic
resonance imaging, electroencephalogram, and electromyogram, all of which were normal. Nerve conduction studies did not show any evidence of demyelination, ruling out Guillain–Barre syndrome. However, repetitive stimulation showed facilitation of compound muscle action potentials, indicative of presynaptic neuromuscular junction disorder and consistent with botulism. Lambert–Eaton antibodies were negative and botulism stool tests were sent. Further investigation revealed that the homeopathic remedy he had received contained honey. He was transferred to the intensive care unit for close monitoring and was treated for suspected botulism with Botulism Immune Globulin (BIG-IV). He demonstrated immediate improvement over the next 2 days and never developed respiratory symptoms. He continued to have gradual improvement over the next several weeks, although central hypotonia was still present on the day of discharge. On follow-up 3 months later, the patient was back to baseline with no associated weakness.
Final Diagnosis The final diagnosis was botulism.
Discussion Infant botulism, though rare, is the most common form of human botulism in the United States. The incidence is 2 cases in 100 000 live births. It was first described in 1976 and is caused by swallowed spores of Clostridium botulinum. In particular, 15% to 30% of cases have been linked to ingestion of contaminated honey.1 C botulinum is a gram-positive, spore-forming organism that is commonly found in soil and agricultural products.2 Human contamination with this organism can occur via contact with an open wound or ingestion. The spores are able to resist temperatures greater than 212°F (100°C); the toxins are 1
Children’s Hospital of New Orleans, New Orleans, LA, USA
Corresponding Author: Rose Paccione, 1401 Saint Andrew St, Apt 114, New Orleans, LA 70130, USA. Email: [email protected]
Downloaded from cpj.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 27, 2015
2
Clinical Pediatrics
heat-labile and easily inactivated by temperatures above 176°F (80°C).3 Inadequately prepared food, canned foods, honey, and corn syrup are common vectors. The spores germinate, temporarily colonize the lumen of the large intestine, and produce botulinum neurotoxin. The toxin is devastating, as it can cause irreversible binding to the neuromuscular junction. It has no odor or taste and this makes it extremely dangerous.1 Eight neurotoxins have been isolated, but infant botulism is commonly associated with neurotoxin types A and B. Infant botulism appears in children less than a year of age and is more common around 6 months of age. The incubation period ranges from several days to 4 weeks.4,5 There is no association with seasons or gender variation. There have been reports of clustering of cases of infant botulism in regions of the country with high C botulinum spore counts, such as California.2 There has been some concern over breastfed infants, since some studies have reported a greater incidence of botulism in patients who have been breastfed. However, this relationship is unclear, and current recommendations include continuing to breastfeed in infants with suspected botulism.4 Clinical manifestations of botulism include overt weakness or nonspecific symptoms including constipation.6 An infant may be alert, but can present with generalized weakness, poor tone, poor suck, drooling, loss of head control, and diminished or absent reflexes. A thorough history and physical exam are necessary to illicit the diagnosis and to differentiate from various other causes of weakness. Due to the varying degrees of severity, it is necessary to watch these patients closely with frequent monitoring. Respiratory compromise and diaphragmatic paralysis are 2 serious concerns that can have rapid onset. Mechanical ventilation and intensive care unit admission may be warranted depending on the clinical picture. The diagnosis of botulism includes sending stool samples and serum samples. If the patient is constipated, as with many affected, an enema may be required to obtain this sample. Botulinum toxin is detected in the serum or stool in approximately 46% of clinically diagnosed cases.7 The sensitivity of the most commonly used assay ranges from 33% to 44%. This is due to low toxin concentrations and delays in obtaining specimens.8 Furthermore, the toxin is isolated in the serum in only 1% of cases.4 Treatment with BIG-IV has been effective at neutralizing the toxin and improving clinical outcomes, including improved symptoms, shortened hospital stay, and reduced need for mechanical ventilation and tube feedings.4 Administration of BIG-IV should occur
as soon as the diagnosis of botulism is clinically evident and should not be delayed while awaiting confirmatory testing.9 Botulinum toxin is shed in the stool for weeks, so careful handling and disposal of stool is necessary.4
Conclusion Infantile botulism carries a good prognosis for recovery once the diagnosis is made. Among food-borne botulism, the mortality rates are 5% to 10% of cases.7 A high index of suspicion in infants who present with generalized weakness is essential to prevent delay of diagnosis. Infantile botulism is a condition that may be avoided if education regarding the potentially harmful effects of homeopathic remedies that include honey is explained to families. Though honey is often thought to be associated with spore ingestion, commonly the cause of spore ingestion is unknown. A judicious diagnosis is imperative for achieving optimal treatment results and reducing mortality from rapid disease progression. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Muensterer OJ. Infant botulism. Pediatr Rev. 2000;21:427. 2. Glatman-Freedman A. Infant botulism. Pediatr Rev. 1996;17:185-186. 3. Risko W. Infant botulism. Pediatr Rev. 2006;27:36-37. 4. Waseem M, Hussain A, Kang EY 3rd, et al. Index of suspicion. Pediatr Rev. 2004;25:397-403. 5. Brown RH Jr, Grant PE, Pierson CR. Case records of the Massachusetts General Hospital. Case 35-2006. A newborn boy with hypotonia. N Engl J Med. 2006;355:2132-2142. 6. Buetti-Sgouros M, Wilson J. Index of suspicion. Case 1. Autoimmune chronic hepatitis. Pediatr Rev. 1999;20:29-31. 7. Shapiro RL, Hatheway C, Swerdlow DL. Botulism in the United States: a clinical and epidemiologic review. Ann Intern Med. 1998;129:221-228. 8. Vasa M, Baudendistel TE, Ohikhuare CE, et al. Clinical problem-solving. The eyes have it. N Engl J Med. 2012;367:938-943. 9. Arnon SS, Schechter R, Maslanka SE, Jewell NP, Hatheway CL. Human botulism immune globulin for the treatment of infant botulism. N Engl J Med. 2006;354:462-471.
Downloaded from cpj.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 27, 2015
research-article2015
CPJXXX10.1177/0009922815570626Clinical PediatricsPaccione et al
Resident Rounds
Diffuse Muscle Weakness in an Infant
Clinical Pediatrics 1–2 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/0009922815570626 cpj.sagepub.com
Rose Paccione, MD, MA, MBA1, Paul Remedios, MD1, Jessica Gautreaux, MD1, and Robin English, MD1
Case Report A developmentally appropriate 7-month-old male with no past medical history was transferred to our facility after being evaluated at an outside hospital for suspected meningoencephalitis. His family noted that on awakening earlier that day, he was lethargic, was unable to control his head movement, had a weak cry, poor suck, and seemed generally weak. Associated symptoms included several days of cough and decreased oral intake. The family denied fevers, seizure activity, or recent travel. Additionally, they denied the administration of honey or canned foods. Immunizations were up to date, and the patient was taking no medications except for an overthe-counter homeopathic cold remedy for the past week. Our physical examination revealed an afebrile infant with normal vital signs. He was nontoxic appearing and crying, while intermittently sucking on a pacifier. His oropharynx and tympanic membranes were clear. Cardiovascular, respiratory, and abdominal exams were normal. Neurological exam findings included normal cranial nerves and profound hypotonia. He had proximal > distal muscle weakness and arreflexia. He had no head control, but was moving his extremities spontaneously. His toes were down-going on Babinski maneuver. He had lost the ability to sit and roll over and though he could move arms and legs against gravity, most movement was distal, and there was a paucity of movement overall. He showed fatigability throughout the exam, resisting initially, but losing the ability to resist as the exam went on. The diagnostic evaluation at the outside facility included a normal complete blood count, normal coagulation studies, and a normal complete metabolic panel. Cerebrospinal fluid analysis revealed normal cell counts, protein, glucose, and gran stain. A chest radiograph and computed tomography of the head were normal. Blood cultures had been drawn, and he had been given one dose each of intravenous vancomycin, rocephin, and acyclovir. At our facility, we continued empiric antibiotic coverage until cultures were negative, but because of the lower motor neuron signs, we doubted the diagnosis of meningoencephalitis. Further evaluation included a head magnetic
resonance imaging, electroencephalogram, and electromyogram, all of which were normal. Nerve conduction studies did not show any evidence of demyelination, ruling out Guillain–Barre syndrome. However, repetitive stimulation showed facilitation of compound muscle action potentials, indicative of presynaptic neuromuscular junction disorder and consistent with botulism. Lambert–Eaton antibodies were negative and botulism stool tests were sent. Further investigation revealed that the homeopathic remedy he had received contained honey. He was transferred to the intensive care unit for close monitoring and was treated for suspected botulism with Botulism Immune Globulin (BIG-IV). He demonstrated immediate improvement over the next 2 days and never developed respiratory symptoms. He continued to have gradual improvement over the next several weeks, although central hypotonia was still present on the day of discharge. On follow-up 3 months later, the patient was back to baseline with no associated weakness.
Final Diagnosis The final diagnosis was botulism.
Discussion Infant botulism, though rare, is the most common form of human botulism in the United States. The incidence is 2 cases in 100 000 live births. It was first described in 1976 and is caused by swallowed spores of Clostridium botulinum. In particular, 15% to 30% of cases have been linked to ingestion of contaminated honey.1 C botulinum is a gram-positive, spore-forming organism that is commonly found in soil and agricultural products.2 Human contamination with this organism can occur via contact with an open wound or ingestion. The spores are able to resist temperatures greater than 212°F (100°C); the toxins are 1
Children’s Hospital of New Orleans, New Orleans, LA, USA
Corresponding Author: Rose Paccione, 1401 Saint Andrew St, Apt 114, New Orleans, LA 70130, USA. Email: [email protected]
Downloaded from cpj.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 27, 2015
2
Clinical Pediatrics
heat-labile and easily inactivated by temperatures above 176°F (80°C).3 Inadequately prepared food, canned foods, honey, and corn syrup are common vectors. The spores germinate, temporarily colonize the lumen of the large intestine, and produce botulinum neurotoxin. The toxin is devastating, as it can cause irreversible binding to the neuromuscular junction. It has no odor or taste and this makes it extremely dangerous.1 Eight neurotoxins have been isolated, but infant botulism is commonly associated with neurotoxin types A and B. Infant botulism appears in children less than a year of age and is more common around 6 months of age. The incubation period ranges from several days to 4 weeks.4,5 There is no association with seasons or gender variation. There have been reports of clustering of cases of infant botulism in regions of the country with high C botulinum spore counts, such as California.2 There has been some concern over breastfed infants, since some studies have reported a greater incidence of botulism in patients who have been breastfed. However, this relationship is unclear, and current recommendations include continuing to breastfeed in infants with suspected botulism.4 Clinical manifestations of botulism include overt weakness or nonspecific symptoms including constipation.6 An infant may be alert, but can present with generalized weakness, poor tone, poor suck, drooling, loss of head control, and diminished or absent reflexes. A thorough history and physical exam are necessary to illicit the diagnosis and to differentiate from various other causes of weakness. Due to the varying degrees of severity, it is necessary to watch these patients closely with frequent monitoring. Respiratory compromise and diaphragmatic paralysis are 2 serious concerns that can have rapid onset. Mechanical ventilation and intensive care unit admission may be warranted depending on the clinical picture. The diagnosis of botulism includes sending stool samples and serum samples. If the patient is constipated, as with many affected, an enema may be required to obtain this sample. Botulinum toxin is detected in the serum or stool in approximately 46% of clinically diagnosed cases.7 The sensitivity of the most commonly used assay ranges from 33% to 44%. This is due to low toxin concentrations and delays in obtaining specimens.8 Furthermore, the toxin is isolated in the serum in only 1% of cases.4 Treatment with BIG-IV has been effective at neutralizing the toxin and improving clinical outcomes, including improved symptoms, shortened hospital stay, and reduced need for mechanical ventilation and tube feedings.4 Administration of BIG-IV should occur
as soon as the diagnosis of botulism is clinically evident and should not be delayed while awaiting confirmatory testing.9 Botulinum toxin is shed in the stool for weeks, so careful handling and disposal of stool is necessary.4
Conclusion Infantile botulism carries a good prognosis for recovery once the diagnosis is made. Among food-borne botulism, the mortality rates are 5% to 10% of cases.7 A high index of suspicion in infants who present with generalized weakness is essential to prevent delay of diagnosis. Infantile botulism is a condition that may be avoided if education regarding the potentially harmful effects of homeopathic remedies that include honey is explained to families. Though honey is often thought to be associated with spore ingestion, commonly the cause of spore ingestion is unknown. A judicious diagnosis is imperative for achieving optimal treatment results and reducing mortality from rapid disease progression. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Muensterer OJ. Infant botulism. Pediatr Rev. 2000;21:427. 2. Glatman-Freedman A. Infant botulism. Pediatr Rev. 1996;17:185-186. 3. Risko W. Infant botulism. Pediatr Rev. 2006;27:36-37. 4. Waseem M, Hussain A, Kang EY 3rd, et al. Index of suspicion. Pediatr Rev. 2004;25:397-403. 5. Brown RH Jr, Grant PE, Pierson CR. Case records of the Massachusetts General Hospital. Case 35-2006. A newborn boy with hypotonia. N Engl J Med. 2006;355:2132-2142. 6. Buetti-Sgouros M, Wilson J. Index of suspicion. Case 1. Autoimmune chronic hepatitis. Pediatr Rev. 1999;20:29-31. 7. Shapiro RL, Hatheway C, Swerdlow DL. Botulism in the United States: a clinical and epidemiologic review. Ann Intern Med. 1998;129:221-228. 8. Vasa M, Baudendistel TE, Ohikhuare CE, et al. Clinical problem-solving. The eyes have it. N Engl J Med. 2012;367:938-943. 9. Arnon SS, Schechter R, Maslanka SE, Jewell NP, Hatheway CL. Human botulism immune globulin for the treatment of infant botulism. N Engl J Med. 2006;354:462-471.
Downloaded from cpj.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 27, 2015
