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Guillain-Barré syndrome mimicking botulism in early disease course
  1. Robert Durcan1,2,
  2. Olwen Murphy1,2,3,
  3. Valerie Reid1,
  4. Tim Lynch1,2
  1. 1 Department of Neurology, Mater Misericordiae University Hospital, Dublin, Ireland
  2. 2 Dublin Neurological Institute, Dublin, Ireland
  3. 3 Johns Hopkins University, Baltimore, Maryland, USA
  1. Correspondence to Dr Robert Durcan, Mater Misericordiae University Hospital, Dublin 7, Ireland; robertdurcan{at}


A 42-year-old man, returning to Europe after a 2-month stay in China, reported cough and runny nose. Five days later, he developed neck discomfort and rapidly evolving weakness, spreading from his arms to the facial, bulbar and neck muscles, and then the legs. He developed dysphagia and breathlessness, and was intubated in the emergency department. Cerebrospinal fluid showed mildly elevated protein. On day 2 he had fixed dilated pupils, with absent oculocephalic reflexes, and a flaccid upper limb paralysis. MR scans of the brain and spinal cord were normal. The early features of descending weakness, bulbar involvement and fixed dilated pupils made it difficult to distinguish between Guillain-Barré syndrome and botulism, and early investigations were inconclusive. We initially gave both botulinum antitoxin and intravenous immunoglobulin, but initially delayed plasma exchange as this would have removed the botulinum antitoxin. Diagnostic testing for botulism has low sensitivity, so we urge pre-emptive treatment if it is clinically suspected.

  • guillain-barre syndrome
  • botulinum toxin
  • neuropathy

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Guillain-Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy that classically comprises acute ascending paralysis, areflexia and albuminocytological dissociation on cerebrospinal fluid (CSF) analysis.1 By contrast, botulism is a neuromuscular junction disorder characterised by cranial nerve palsies, descending symmetric flaccid paralysis and dysautonomia. Unreactive, dilated pupils are characteristic. It is caused by a neurotoxin produced from the anaerobic, spore-forming bacterium Clostridium botulinum, which can be acquired by ingestion, inhalation or wound infection.2 Both GBS and botulism are medical emergencies, and can result in death from respiratory muscle paralysis or complications of dysautonomia. We present a case of severe GBS that presented a diagnostic challenge, as the clinical presentation strongly suggested botulism, with a pattern of progressive rostrocaudal weakness and fixed dilated pupils.

Case history

A 42-year-old man returned to Europe following a 2-month trip to China, where he had ingested various herbal treatments and received acupuncture for back pain. He had felt well while in China, but on arrival to Ireland reported cough and runny nose. Five days later, he developed neck discomfort and rapidly evolving weakness that began in his arms, then spread sequentially to involve the facial, bulbar and neck muscles, followed by the lower limbs. He developed swallowing difficulty and shortness of breath. On arrival to the emergency department 16 hours after symptom onset, his respiratory function rapidly deteriorated and he developed urinary retention. He was severely hypertensive with systolic blood pressure of 170–220 mm Hg. As he was in type 2 respiratory failure and unable to manage his own secretions, he required intubation and mechanical ventilation.

CSF showed only mildly elevated protein (0.489 g/L, normal <0.45), and CSF oligoclonal bands were negative.

Neurological examination on day 2 identified fixed dilated pupils of approximately 6 mm in diameter, 0/5 strength in the upper limbs, with some preserved strength in the left foot (2/5). There was diffuse areflexia and absent oculocephalic and corneal reflexes. He grimaced to pain. We started empirical treatment for GBS with intravenous immunoglobulin (0.4 g/kg for 5 days), and for botulism with botulinum antitoxin (500 mL) and penicillin G (2 million units intravenously every 4 hours). Regional public health services investigated for the possibility of a botulism outbreak, but found no other cases or any obvious source.

We sent stool antigen test and bioassay for C. botulinum toxin. Nerve conduction studies on day 4 showed low-amplitude compound muscle action potentials. Upper limb conduction velocities were slightly prolonged (5.8 ms at the median nerve, 4.4 ms at the ulnar nerve) but did not exceed 150% of normal ranges. Lower limb conduction velocities were normal. Sensory responses were normal in the upper and lower limbs, while F wave latencies were absent. Electromyography showed no spontaneous activity or recruitment, and repetitive stimulation showed no changes. The findings suggested an acquired motor neuropathy, possibly demyelination but with no diagnostic features. MR scans of the brain and spinal cord were normal, and specifically showed no nerve root enhancement.

On day 7, repeat CSF examination showed a significantly elevated protein table 1. Botulinum toxin stool antigen and bioassay were negative. As botulism now seemed unlikely, with no clinical response to intravenous immunoglobulin, we started plasma exchange on day 9 for severe GBS.

Table 1

Cerebrospinal fluid pattern

His condition continued to deteriorate, and reached the nadir of neurological function on day 11. At this point he had complete ophthalmoplegia with fixed dilated pupils, flaccid paralysis of all four limbs and could not trigger his own breaths. He had severe constipation and hypertension that required intravenous labetalol infusion, along with five oral antihypertensives to maintain an acceptable range. We introduced intermittent transcutaneous pacing to manage marked bradycardia (<30 beats/min).

Electromyography on day 11 showed low-amplitude compound muscle action potentials and prolonged distal latencies in the demyelinating range (9.2 ms at the median nerve, 7.2 ms at the ulnar nerve). Sensory responses were absent. Repetitive stimulation was normal. Findings suggested a sensory and motor large fibre neuropathy with evidence of demyelination, consistent with GBS. Serum antiganglioside antibodies (GM1, GM2, GD1a, GD1b, GQ1b) were negative. Microbiology tests showed no evidence of recent infection with influenza, enterovirus, parainfluenza, adenovirus, metapneumovirus, respiratory syncytial virus, cytomegalovirus, HIV, Epstein-Barr virus, norovirus, rotavirus, sapovirus, astrovirus, coronavirus, rhinovirus, Campylobacter jejuni, chikungunya, West Nile virus, dengue, Japanese encephalitis, yellow fever, zika virus, hepatitis (A, B, C, E), Mycoplasma pneumoniae, chlamydia or tuberculosis (negative QuantiFERON test and CSF culture).

We gave 10 cycles of plasma exchange over 4 weeks, and he started to improve. The recovery began in his ocular/facial/bulbar muscles, followed by the upper then the lower limbs. He steadily recovered and was transferred to a facility closer to family for rehabilitation.


This patient’s presentation gave a significant diagnostic challenge, as the early features suggested botulism with rostrocaudal spread of weakness and fixed dilated pupils. GBS has a broad spectrum of clinical presentations, including the phenotypes of Bickerstaff encephalitis, Miller Fisher syndrome, and pharyngeal-cervical-brachial variant, described as a botulism mimic.3 The pharyngeal-cervical-brachial variant may occur with anti-GT1a antibodies (although testing is not widely available) and presents with descending paralysis, as opposed to the classic ascending pattern seen in typical GBS. Eye movement abnormalities are well described in Miller Fisher syndrome, and there have also been rare cases with pupillary involvement. Fixed dilated pupils may also infrequently occur with fulminant ‘typical’ GBS. Other autonomic features such as orthostatic hypotension, labile blood pressure, cardiac dysrhythmia, and bowel and bladder dysfunctions are possible, and are more common in patients with severe motor deficits and respiratory failure.

Botulism presents with rapidly progressive bilateral cranial nerve palsies, descending flaccid paralysis and autonomic dysfunction, without sensory abnormalities.4 It is caused by a toxin released by the spores of the anaerobe C. botulinum, resulting in presynaptic blockade of acetylcholine transmission at the neuromuscular junction. Foodborne botulism is caused by ingesting contaminated foods, classically in home-canned foods.4 Most cases are sporadic, but small outbreaks can occur. Wound botulism results from wound contamination with spores, with subsequent abscess formation and intra-abscess toxin formation. It is increasingly common, particularly in heroin users who ‘skin-pop’ rather than injecting intravenously. Infant botulism is the most common form of botulism, arising through intra-abdominal germination of C. botulinum spores. In adults, the long-standing normal bowel flora prevents this process, but the infantile gut microbiome is not fully established.2 A similar process has been described in adults with gut abnormalities, or on antibiotic therapy, thus rendering their microbiome less competitive with C. botulinum spores. Botulinum toxin also has the potential to be used as a biological agent in warfare.

Diagnosis of botulism relies on recognising the typical clinical features, such as dilated pupils and descending pattern of paralysis, in an at-risk patient. There are no definitive diagnostic tests, and if the condition is suspected at all, prompt treatment should be provided with antitoxin (and penicillin G if wound botulism is possible).2 Electromyography may show evidence of neuromuscular junction blockade, with normal axonal conduction velocity and low-amplitude compound muscle action potentials. Approximately 60% of patients have potentiation with rapid repetitive stimulation.5 Laboratory testing may identify toxin in the serum or stool, but this test has low sensitivity and the results depend on the test timing in relation to inoculation. In wound botulism, a swab may sometimes grow C. botulinum. There is a bioassay that involves injecting patient serum into mice and observing if the mouse develops botulism. Unfortunately, the sensitivity of these laboratory tests is as low as 33%–44%, but is higher when serum samples are taken early in the illness.

The diagnosis of GBS also relies on clinical judgement, as peripheral neurophysiology findings are often normal or non-specific in early stages, and serum antiganglioside antibodies are frequently negative. Elevated CSF protein is characteristic and can help to distinguish GBS from botulism; however, often the protein is normal, particularly early in the disease course. Half of patients with GBS have normal CSF protein on the day of presentation. There is a positive linear relationship between time since symptom onset and albuminocytological dissociation6 7 In summary, in the first week of presentation, there may be no investigations that reliably distinguish botulism from GBS, so appropriate clinical suspicion and judgement are essential (table 2). Note that when there is diagnostic uncertainty, plasma exchange (helpful for severe GBS) may remove botulinum antitoxin from the circulation.

Table 2

Differences and similarities between botulism and Guillain-Barré syndrome (GBS)

A final important issue highlighted by this case is the difficulty in categorising GBS spectrum disease variants in clinical practice. This patient’s pattern of weakness strongly suggested the pharyngeal-cervical-brachial variant of GBS. However, this is usually considered to have axonal pathology, whereas the neurophysiology in this case evolved to show demyelination. Nevertheless, GBS comprises a broad spectrum of disease, and it can be difficult to ‘pigeon hole’ a case into one labelled variant based on either clinical presentation, neurophysiology findings or serum antiganglioside antibodies.8 9

In conclusion, this patient presented us with a clinical dilemma. The early features of descending weakness, bulbar involvement and fixed dilated pupils made it very difficult to differentiate between GBS and botulism, and early investigations were inconclusive. As there is no test to rule botulism in or out, the treatment must be based on clinical suspicion. A final reminder is that patients with severe GBS may lose all brainstem reflexes in a pattern mimicking brain death; clinicians must remember that in cases of suspected brain death, GBS should be considered as a rare reversible cause.

Key points

  • Botulism is an important differential diagnosis to consider in patients with acute onset bulbar weakness.

  • It can sometimes be difficult to differentiate between GBS and botulism.

  • Untreated botulism can have dire consequences.

  • Testing for botulism has low sensitivity. Thus, we urge prompt treatment if botulism is considered a possibility.



  • Contributors RD: Review of the literature, drafting of the manuscript. OM: Critical review of the manuscript. VR: Review of nerve conduction studies. TL: Expert critical analysis of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed by Ben Wakerley, Gloucester, UK, and Simon Rinaldi, London, UK.

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