Neurology
A 53 year old man presents to the Emergency Department complaining of difficulty swallowing over the previous 3 days. He has no significant past medical history. On examination you note bilateral facial weakness, ptosis and slurred speech. His pupils are dilated and barely reactive. His mouth is dry. You cannot elicit any abnormal limb neurology and he has no sensory deficits. He is complaining of lower abdominal pain and you palpate a distended bladder. Which of the following is the most likely diagnosis?
Answer:
This patient has acute onset of progressive neuromuscular junction weakness. He has autonomic findings of abnormal pupil response to light, dry oral mucosa from decreased salivary production, and a distended bladder. These imply that his problem is with the release of acetylcholine (ACh) rather than the nicotinic receptor. The latter would not have autonomic findings. The most appropriate cause of acute onset, progressive impairment in the release of ACh, as listed in the choices, is botulism.Botulism
Neurology
Last Updated: 8th September 2021
Pathophysiology
Clostridium botulinum is a large, gram-positive, strictly anaerobic bacillus that primarily exists as a spore until environmental conditions suitable for germination arise. C botulinum spores are found throughout the world in soil samples and marine sediments. The species is divided into 4 genetically diverse groups that share the common ability to produce botulinum toxin. Seven serologically distinct neurotoxins are produced by C botulinum, designated letters A to G. Human disease is attributed to toxin types A, B, E, and, less commonly, F.
Clinical botulism results from the entry of botulinum toxin into the systemic circulation and subsequent inhibition of acetylcholine release from the presynaptic nerve terminal. The toxin enters the circulation through the mucosa (foodborne and inhalational) or via a break in the skin (wound and iatrogenic). In infants, absorption occurs due to absence of competing normal flora. Once absorbed into the bloodstream, the toxin is carried to the synapses of peripheral and cranial nerves. As a result, stimulation of the presynaptic cell fails to produce transmitter release, resulting in motor paralysis or autonomic dysfunction when parasympathetic nerve terminals or autonomic ganglia are involved.
Risk factors
- Ingestion of contaminated food
- Ingestion of honey or soil in infants
- Contact with reptiles (specifically terrapins)
- Intravenous drug use
- Crush injury
- Abnormal bowel anatomy
- Therapeutic or cosmetic use of botulinum toxin
Clinical presentation
- Foodborne botulism (Ingestion of food contaminated with botulinum toxin)
- Characterised by bilateral cranial nerve palsies (blurred vision and diplopia due to paralysis of III, IV, and VI; dysarthria and dysphagia due to paralysis of IX, X, and XII) within 2 to 36 hours of ingestion of contaminated food, followed by symmetrical, descending flaccid paralysis.
- Abdominal cramps, nausea, vomiting, and diarrhoea may also occur early in the illness, although these symptoms are often attributed to coincidental non-Clostridium pathogens.
- Affected patients are not febrile, confused, or obtunded, and the sensory system is spared.
- Autonomic dysfunction may manifest as hypothermia, urinary retention, dry mouth and throat, postural hypotension, and constipation.
- Wound botulism (Wound contamination by Clostridium botulinum spores)
- Presents with neurological findings identical to those of foodborne illness in the absence of a gastrointestinal prodrome, and the incubation period is longer (4 to 14 days).
- Inhalational botulism (Inhalation of aerosolised botulinum toxin does not occur in nature and suggests an act of bioterrorism)
- The signs and symptoms exhibited are the same as those seen with foodborne illness. The latency between exposure and clinical disease after inhalation appears to be between 12 hours and 5 days.
- Iatrogenic botulism (Symptoms of botulism as a consequence of toxin use for cosmetic or therapeutic purposes)
- Presents with neurological findings identical to those of foodborne illness in the absence of a gastrointestinal prodrome.
- Infant botulism (Results from exposure in the first year of life to contaminated soil, dust, or food sources)
- Characterised by constipation in 95% of cases. Bulbar and extremity weakness follow as affected infants develop feeding difficulties, a weakened cry, ptosis, and hypotonia.
On examination:
- Early signs
- Oculobulbar weakness.
- Impaired accommodation and ptosis occur due to paralysis of cranial nerves III, IV, and VI.
- Hypoglossal weakness is a sign of cranial nerve IX, X, and XII involvement.
- Late signs
- Descending symmetrical paralysis affecting the voluntary muscles of the neck, shoulders, and upper extremities, followed by the proximal and distal lower extremities.
- Deep tendon reflexes, initially present, diminish or disappear within a few days of infection.
- Respiratory dysfunction may result from either upper airway obstruction (pharyngeal collapse due to cranial nerve involvement) or diaphragmatic and accessory muscle weakness.
- Pupillary dilation occurs in <50% of cases.
Investigations
- Conventional diagnosis of botulism relies on the demonstration of toxin in serum, gastric secretions, stool, or food samples.
- Culture of food samples, gastric aspirate, or faecal material from affected patients may reveal C botulinum (only in foodborne or infant botulism).
- In patients with a clinical syndrome suggestive of botulism who have negative toxin assay and stool culture results, electrophysiological testing can provide a presumptive diagnosis.
Management
Supportive care is the mainstay of botulism therapy. Patients with suspected or confirmed botulism should undergo serial vital capacity assessments in the intensive care unit. In addition, patients should be assessed for the adequacy of gag and cough reflexes, control of oropharyngeal secretions, oxygen saturation, and inspiratory force. Mechanical ventilation should be considered for any patient with upper airway compromise (due to pharyngeal muscle paralysis) or a decline in vital capacity.
Swift administration of botulism antitoxin is essential in the management of botulism cases. In the UK, antitoxin is available from local designated centres (www.toxbase.org), otherwise accessed outside working hours by telephoning the duty doctor at Public Health England. Detailed instructions on administration are provided with each dose.
Specific management:
- Foodborne botulism
- Gastric lavage may be attempted in adults if the food exposure was relatively recent. In the absence of an ileus, enemas or cathartic agents may be used to eliminate unabsorbed toxin from the gastrointestinal tract. Gastric lavage and/or enemas are not recommended in infants.
- Wound botulism
- In addition to the antitoxin, patients with wound botulism should undergo careful debridement. Clostridium botulinum abscess formation may be treated with benzylpenicillin, or metronidazole in penicillin-allergic patients.
- Infant botulism
- Infants <1 year of age should receive the intravenous botulism immunoglobulin (human), also known as BabyBIG™, instead of antitoxin.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
