From Toxin to Treatment: A Narrative Review on the Use of Botulinum Toxin for Autonomic Dysfunction.

Since its regulatory approval over a half-century ago, botulinum toxin has evolved from one of the most potent neurotoxins known to becoming routinely adopted in clinical practice. Botulinum toxin, a highly potent neurotoxin produced by Clostridium botulinum, can cause botulism illness, characterized by widespread muscle weakness due to inhibition of acetylcholine transmission at neuromuscular junctions. The observation of botulinum toxin's anticholinergic properties led to the investigation of its potential benefits for conditions with an underlying etiology of cholinergic transmission, including autonomic nervous system dysfunction. These conditions range from disorders of the integument to gastrointestinal and urinary systems. Several formulations of botulinum toxin have been developed and tested over time, significantly increasing the availability of this treatment for appropriate clinical use. Despite the accelerated and expanded use of botulinum toxin, there lacks an updated comprehensive review on its therapeutic use, particularly to treat autonomic dysfunction. This narrative review provides an overview of the effect of botulinum toxin in the treatment of autonomic dysfunction and summarizes the different formulations and dosages most widely studied, while highlighting reported outcomes and the occurrence of any adverse events.

[Clinical characteristics and prognosis of 8 cases of severe infant botulism].

Objective: To summarize the clinical characteristics and prognosis of severe infant botulism and evaluate the therapeutic effect of botulinum antitoxin in the pediatric intensive care unit (PICU). Methods: The clinical data of 8 cases diagnosed with infantile botulism were retrospectively analyzed in the PICU of Beijing Children's Hospital from October 2019 to August 2023. Data of basic demographic information, clinical manifestations, laboratory tests, treatment and prognosis of each child were collected and analyzed using descriptive statistical methods. Results: Eight laboratory-confirmed cases of infant botulism were included in this study, all of which were male infants with an age of 6.0 (3.3,6.8) months. Three of the children were from Inner Mongolia Autonomous Region, 2 of them were from Hebei, and the other 3 were from Beijing, Shandong and Xinjiang Uyghur Autonomous Region, respectively. All the patients were previously healthy. In 4 of these cases, the possible cause was the ingestion of either honey and its products or sealed pickled food by the mother or child before the onset of the disease. The first symptom was poor milk intake (4 cases), followed by shallow shortness of breath (7 cases), limb weakness (7 cases) and so on. The typical signs were bilateral dilated pupils (8 cases) and decreased limb muscle strength (8 cases). The main subtype was type B (7 cases), and only 1 case was classified as type A. Six of the children were treated with antitoxin therapy for a duration of 24 (19, 49) d. Seven of them had invasive mechanical ventilation. All the patients survived upon discharge with a follow-up period of 29 d to 3 years and 8 months. Six patients had fully recovered, and 2 recently discharged patients were gradually recovering. Conclusions: For infants with suspected contact or ingestion of botulinum and presented with bilateral pupillary paralysis, muscle weakness and clear consciousness, the stool should be collected for diagnostic testing using a mouse bioassay as soon as possible. Type B was the most common type. The antitoxin treatment was effectiveness and the prognosis was well.

Iatrogenic botulism. / Iatrogen botulisme.

This case study describes severe iatrogenic botulism following treatment with a botulinum toxin injection at a private clinic abroad.

What Is Botulism?

This JAMA Patient Page describes botulism routes of infection, symptoms, diagnosis, treatment, and prevention measures.

Botulism mimicking Guillain-Barre syndrome: The question of plasma exchange in an unusual case of acute paralysis.

Guillain-Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy and the most common cause of acute flaccid paralysis worldwide. GBS classically presents with acute, progressive, ascending weakness, reduced to absent reflexes, and albuminocytological dissociation on cerebrospinal fluid (CSF) analysis. Botulism is a neurotoxin-mediated acute descending flaccid paralysis with cranial nerve palsies and dysautonomia. Botulism in adults is caused by ingestion/inhalation of botulinum toxin or wound infection with Clostridium botulinum. Both GBS and botulism can rapidly precipitate respiratory failure; thus, prompt diagnosis and treatment are crucial to mitigate poor outcomes. Herein, we describe a case of botulism initially diagnosed as GBS given classic laboratory features, and describe the importance of careful consideration of the most appropriate therapeutic modalities in cases of acute flaccid paralysis, particularly regarding empiric administration of botulinum antitoxin and use of intravenous immune globulin in lieu of plasma exchange for potential GBS to prevent removal of antitoxin.

Neonatal Botulism: A Case Series Suggesting Varied Presentations.

Infantile botulism is an uncommon diagnosis and rarer still in the neonatal period. We describe three cases of neonatal-onset botulism that presented with symptoms typically (hypotonia, constipation, facial diplegia) or atypically seen in older infants (encephalopathy, seizures, and hypothermia). Our series shows a wider spectrum of clinical presentations in patients with neonatal-onset botulism. Our report also suggests that neonatal-onset botulism should be considered more broadly in the hypotonic infant, especially as the condition is treatable with intravenous botulinum-specific immune globulin.

Botulismo del lactante: estudio descriptivo en una unidad de cuidados intensivos pediátricos / Infant botulism: a descriptive study in a pediatric intensive care unit

Introducción. El botulismo del lactante (BL) es la forma más frecuente de botulismo humano en Argentina. El objetivo es describir aspectos esenciales del diagnóstico y tratamiento de pacientes con BL internados en el servicio de terapia intensiva pediátrica (STIP). Métodos. Estudio observacional, descriptivo y retrospectivo. Se utilizó la base de datos del STIP con diagnóstico de BL en el período 2005-2020. Se registraron variables demográficas, métodos de diagnóstico, días de asistencia respiratoria mecánica convencional (ARMC), de ventilación no invasiva (VNI), estadía en STIP, mortalidad al alta hospitalaria. Resultados. Se registraron 21 pacientes con BL; 14 pacientes fueron varones, con una mediana de edad de 5 meses (RIC 2-6 m). El diagnóstico se realizó mediante técnica de bioensayo y se detectó la toxina en suero en 12 pacientes. Uno solo no requirió ARMC; 1 paciente fue traqueostomizado; 18 pacientes recibieron antibióticos; 5 recibieron VNI. Ningún paciente recibió antitoxina y no hubo fallecidos. La mediana de estadía hospitalaria fue 66 días (RI: 42-76); de internación en STIP, 48 días (RI: 29-78); y de ARMC, 37 días (RI: 26-64). La demora en la confirmación diagnóstica fue 15,8 ± 4,8 días. Conclusiones. La totalidad de los pacientes fueron diagnosticados con la técnica de bioensayo, que generó un tiempo de demora diagnóstica que excede los lapsos recomendados para la administración del tratamiento específico. Ningún paciente recibió tratamiento específico. El BL presentó baja mortalidad, pero tiempos de ARM e internación prolongados, que se asocian a infecciones sobreagregadas y uso frecuente de antibióticos.

Introduction. Infant botulism (IB) is the most common form of human botulism in Argentina. Our objective was to describe the main aspects of diagnosis and management of patients with IB admitted to the pediatric intensive care unit (PICU). Methods. Observational, descriptive, and retrospective study. The PICU database with IB diagnosis in 2005­2020 period was used. Demographic variables, diagnostic methods, days of conventional mechanical ventilation (CMV), non-invasive ventilation (NIV), length of stay in the PICU and mortality upon hospital discharge were recorded. Results. In total, 21 patients with IB were recorded; 14 were male, their median age was 5 months (IQR: 2­6 m). Diagnosis was made by bioassay, and the toxin was identified in the serum of 12 patients. Only 1 patient did not require CMV; 1 patient had a tracheostomy; 18 patients received antibiotics; 5 received NIV. No patient was administered antitoxin and no patient died. The median length of stay in the hospital was 66 days (IQR: 42­76); in the PICU, 48 days (IQR: 29­78); and the median use of CMV, 37 days (IQR: 26­64). The delay until diagnostic confirmation was 15.8 ± 4.8 days. Conclusions. All patients were diagnosed using the bioassay technique, which resulted in a diagnostic delay that exceeds the recommended period for the administration of a specific treatment. No patient received a specific treatment. IB was related to a low mortality, but also to prolonged use of MV and length of hospital stay, which were associated with cross infections and frequent antibiotic use.

Pathogenicity and virulence of Clostridium botulinum.

Clostridium botulinum, a polyphyletic Gram-positive taxon of bacteria, is classified purely by their ability to produce botulinum neurotoxin (BoNT). BoNT is the primary virulence factor and the causative agent of botulism. A potentially fatal disease, botulism is classically characterized by a symmetrical descending flaccid paralysis, which is left untreated can lead to respiratory failure and death. Botulism cases are classified into three main forms dependent on the nature of intoxication; foodborne, wound and infant. The BoNT, regarded as the most potent biological substance known, is a zinc metalloprotease that specifically cleaves SNARE proteins at neuromuscular junctions, preventing exocytosis of neurotransmitters, leading to muscle paralysis. The BoNT is now used to treat numerous medical conditions caused by overactive or spastic muscles and is extensively used in the cosmetic industry due to its high specificity and the exceedingly small doses needed to exert long-lasting pharmacological effects. Additionally, the ability to form endospores is critical to the pathogenicity of the bacteria. Disease transmission is often facilitated via the metabolically dormant spores that are highly resistant to environment stresses, allowing persistence in the environment in unfavourable conditions. Infant and wound botulism infections are initiated upon germination of the spores into neurotoxin producing vegetative cells, whereas foodborne botulism is attributed to ingestion of preformed BoNT. C. botulinum is a saprophytic bacterium, thought to have evolved its potent neurotoxin to establish a source of nutrients by killing its host.

Foodborne botulism and the importance of recognizing the disease in the emergency department: a case report.

BACKGROUND: Botulism is a rare neuroparalytic disease that has only presented itself 19 times in the last 30 years in Belgium. Patients present to emergency services with a wide range of complaints. Foodborne botulism is a forgotten yet life-threatening disease. CASE PRESENTATION: We describe a case of a Caucasian female in her 60s that presented to the emergency with reflux with nausea and spasmodic epigastric pain, no vomiting, dry mouth, and weakness in both legs. The symptoms started after ingestion of Atlantic wolffish. After exclusion of other more common causes, foodborne botulism was suspected. The patient was admitted to the intensive care unit for mechanical ventilation. Following treatment with trivalent botulinum antitoxin, she made a full neurologic recovery. CONCLUSION: It is important to rapidly recognize the possible diagnosis of botulism even if the neurological symptoms are not dominant. Rapid neurologic dysfunction and respiratory difficulties starts between 6 and 72 hours after ingestion. The decision to administer antitoxins should, however, be based on the presumptive clinical diagnosis and diagnosis should not delay therapy.

Infant botulism: a descriptive study in a pediatric intensive care unit. / Botulismo del lactante: estudio descriptivo en una unidad de cuidados intensivos pediátricos.

Introduction. Infant botulism (IB) is the most common form of human botulism in Argentina. Our objective was to describe the main aspects of diagnosis and management of patients with IB admitted to the pediatric intensive care unit (PICU). Methods. Observational, descriptive, and retrospective study. The PICU database with IB diagnosis in 2005-2020 period was used. Demographic variables, diagnostic methods, days of conventional mechanical ventilation (CMV), non-invasive ventilation (NIV), length of stay in the PICU and mortality upon hospital discharge were recorded. Results. In total, 21 patients with IB were recorded; 14 were male, their median age was 5 months (IQR: 2-6 m). Diagnosis was made by bioassay, and the toxin was identified in the serum of 12 patients. Only 1 patient did not require CMV; 1 patient had a tracheostomy; 18 patients received antibiotics; 5 received NIV. No patient was administered antitoxin and no patient died. The median length of stay in the hospital was 66 days (IQR: 42-76); in the PICU, 48 days (IQR: 29-78); and the median use of CMV, 37 days (IQR: 26-64). The delay until diagnostic confirmation was 15.8 ± 4.8 days. Conclusions. All patients were diagnosed using the bioassay technique, which resulted in a diagnostic delay that exceeds the recommended period for the administration of a specific treatment. No patient received a specific treatment. IB was related to a low mortality, but also to prolonged use o  MV and length of hospital stay, which were associated with cross infections and frequent antibiotic use.

Introducción. El botulismo del lactante (BL) es la forma más frecuente de botulismo humano en Argentina. El objetivo es describir aspectos esenciales del diagnóstico y tratamiento de pacientes con BL internados en el servicio de terapia intensiva pediátrica (STIP). Métodos. Estudio observacional, descriptivo y retrospectivo. Se utilizó la base de datos del STIP con diagnóstico de BL en el período 2005-2020. Se registraron variables demográficas, métodos de diagnóstico, días de asistencia respiratoria mecánica convencional (ARMC), de ventilación no invasiva (VNI), estadía en STIP, mortalidad al alta hospitalaria. Resultados. Se registraron 21 pacientes con BL; 14 pacientes fueron varones, con una mediana de edad de 5 meses (RIC 2-6 m). El diagnóstico se realizó mediante técnica de bioensayo y se detectó la toxina en suero en 12 pacientes. Uno solo no requirió ARMC; 1 paciente fue traqueostomizado; 18 pacientes recibieron antibióticos; 5 recibieron VNI. Ningún paciente recibió antitoxina y no hubo fallecidos. La mediana de estadía hospitalaria fue 66 días (RI: 42-76); de internación en STIP, 48 días (RI: 29-78); y de ARMC, 37 días (RI: 26-64). La demora en la confirmación diagnóstica fue 15,8 ± 4,8 días. Conclusiones. La totalidad de los pacientes fueron diagnosticados con la técnica de bioensayo, que generó un tiempo de demora diagnóstica que excede los lapsos recomendados para la administración del tratamiento específico. Ningún paciente recibió tratamiento específico. El BL presentó baja mortalidad, pero tiempos de ARM e internación prolongados, que se asocian a infecciones sobreagregadas y uso frecuente de antibióticos.

Lambert-Eaton Myasthenic Syndrome and Botulism.

PURPOSE OF REVIEW: This article reviews the pathophysiology, epidemiology, clinical features, diagnosis, and treatment of Lambert-Eaton myasthenic syndrome (LEMS) and botulism, presynaptic disorders of neuromuscular transmission in which rapid diagnosis improves long-term outcomes. RECENT FINDINGS: Therapy for LEMS has seen significant advances in recent years due to the approval of amifampridine-based compounds. LEMS is likely still underdiagnosed, particularly when no underlying malignancy is identified. Clinicians must have a strong suspicion for LEMS in any patient presenting with proximal weakness and autonomic dysfunction. Botulism is another rare disorder of presynaptic neuromuscular transmission that is most commonly associated with improper storage or preservation of food products. Over the past 2 decades, wound botulism has been increasingly reported among users of black tar heroin. A high degree of clinical suspicion and electrodiagnostic studies can be beneficial in distinguishing botulism from other acute neurologic disorders, and early involvement of state and federal health authorities may assist in confirming the diagnosis and obtaining treatment. When botulism is suspected, electrodiagnostic studies can provide clinical evidence of disordered neuromuscular transmission in advance of serologic confirmation, and providers should not wait for confirmation of the diagnosis to initiate treatment. SUMMARY: A targeted clinical history and a thorough neurologic examination with support from serologic and electrodiagnostic studies are key to early diagnosis of LEMS and botulism. Early diagnosis of both conditions creates opportunities for therapy and improves outcomes.

Foodborne botulism, a forgotten yet life-threatening disease: a case report.

OBJECTIVE: Botulism is a very rare disease in Switzerland, with less than one case per year, an incidence of 0.01 cases for 100,000 inhabitants. Indeed, over the past ten years, 9 cases have been reported to Public Health registry. Foodborne botulism (FB) is caused by ingestion of preformed botulinum neurotoxin. Characteristic features should be rapidly recognized, and prompt treatment should be administered to avoid further progression towards respiratory failure and death. CASE REPORT: We report the case of a patient who developed gastrointestinal symptoms just after a sandwich consumption followed by rapidly progressive cranial nerve impairment, truncal muscle weakness in a descending pattern and respiratory failure requiring mechanical ventilation. The diagnosis of foodborne botulism was delayed due to differential diagnosis considerations. Specific antitoxin therapy was administered immediately after firm clinical conviction of botulism, without waiting for serologic results that later confirmed the diagnosis. As expected, muscle weakness recovery was slow, with persistent chronic deficits nine years later. CONCLUSIONS: This case highlights differential diagnosis issues of botulism. These include acute neuromuscular disorders such as myasthenia gravis, Guillain-Barré syndrome, or tick-borne encephalitis. The importance of careful medical history and repeated clinical evaluation to avoid misdiagnosis can be lifesaving. Our case highlights the typical warning signs.

Infant botulism: Report of a misleading case and important key messages.

Infant botulism is a rare and life-threatening disease caused by the inhalation of Clostridium botulinum spores and differs from adult forms. We report the case of infant botulism in a 4-month-old boy who was exclusively breastfed without any consumption of honey. He presented with severe and acute encephalo-myelo-radiculitis. The patient was treated without success for suspected "postviral" central nervous system inflammatory disease. The diagnosis was eventually made 20 days after the onset of symptoms on the basis of a stool sample. Recovery was complete. Infant botulism should be suspected when infants present with acute flaccid paralysis or brainstem weakness and specific immunoglobulins should be administered.

Infant Botulism: Checklist for Timely Clinical Diagnosis and New Possible Risk Factors Originated from a Case Report and Literature Review.

Infant botulism is a rare and underdiagnosed disease caused by BoNT-producing clostridia that can temporarily colonize the intestinal lumen of infants less than one year of age. The diagnosis may be challenging because of its rareness, especially in patients showing atypical presentations or concomitant coinfections. In this paper, we report the first infant botulism case associated with Cytomegalovirus coinfection and transient hypogammaglobulinemia and discuss the meaning of these associations in terms of risk factors. Intending to help physicians perform the diagnosis, we also propose a practical clinical and diagnostic criteria checklist based on the revision of the literature.

Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021.

Botulism is a rare, neurotoxin-mediated, life-threatening disease characterized by flaccid descending paralysis that begins with cranial nerve palsies and might progress to extremity weakness and respiratory failure. Botulinum neurotoxin, which inhibits acetylcholine release at the neuromuscular junction, is produced by the anaerobic, gram-positive bacterium Clostridium botulinum and, rarely, by related species (C. baratii and C. butyricum). Exposure to the neurotoxin occurs through ingestion of toxin (foodborne botulism), bacterial colonization of a wound (wound botulism) or the intestines (infant botulism and adult intestinal colonization botulism), and high-concentration cosmetic or therapeutic injections of toxin (iatrogenic botulism). In addition, concerns have been raised about the possibility of a bioterrorism event involving toxin exposure through intentional contamination of food or drink or through aerosolization. Neurologic symptoms are similar regardless of exposure route. Treatment involves supportive care, intubation and mechanical ventilation when necessary, and administration of botulinum antitoxin. Certain neurological diseases (e.g., myasthenia gravis and Guillain-Barré syndrome) have signs and symptoms that overlap with botulism. Before the publication of these guidelines, no comprehensive clinical care guidelines existed for treating botulism. These evidence-based guidelines provide health care providers with recommended best practices for diagnosing, monitoring, and treating single cases or outbreaks of foodborne, wound, and inhalational botulism and were developed after a multiyear process involving several systematic reviews and expert input.

Infant botulism: an underestimated threat.

Infant botulism (IB) is defined as a potentially life-threatening neuroparalytic disorder affecting children younger than 12 months. It is caused by ingestion of food or dust contaminated by Clostridium botulinum spores, which germinate in the infant's large bowel and produce botulinum neurotoxin. Although the real impact of IB is likely underestimated worldwide, the USA has the highest number of cases. The limited reporting of IB in many countries is probably due to diagnostic difficulties and nonspecific presentation. The onset is usually heralded by constipation, followed by bulbar palsy, and then by a descending bilateral symmetric paralysis; ultimately, palsy can involve respiratory and diaphragmatic muscles, leading to respiratory failure. The treatment is based on supportive care and specific therapy with Human Botulism Immune Globulin Intravenous (BIG-IV), and should be started as early as possible. The search for new human-like antibody preparations that are both highly effective and well tolerated has led to the creation of a mixture of oligoclonal antibodies that are highly protective and can be produced in large quantities without the use of animals. Ongoing research for future treatment of IB involves the search for new molecular targets to produce a new generation of laboratory-produced antitoxins, and the development of new vaccines with safety and efficacy profiles that can be scaled up for clinical use. This narrative literature review aims to provide a readable synthesis of the best current literature on microbiological, epidemiological and clinical features of IB, and a practical guide for its treatment.

Management of an outbreak of botulism with benign clinical presentation.

Botulism is a life-threatening presynaptic disorder of the neuromuscular transmission produced by the neurotoxin elaborated by the botulinum neurotoxin-producing clostridia. We describe the management of a case series of 14 patients, members of 5 different families that were exposed to home-canned tuna and developed symptoms compatible with a mild clinical presentation of foodborne botulism. The electrophysiological study of the index case represented a reliable diagnostic test as it demonstrated a slight presynaptic dysfunction of the neuromuscular junction. Definite diagnosis was later confirmed by microbiological tests. Out of 14, only 3 patients presenting with a shorter period from symptom onset and with signs of multiple cranial neuropathies received botulinum antitoxin. All the patients remained stable and recovered progressively. Treatment with antitoxin may not be necessary in patients with late-presenting disease and mild and stable clinical picture.