Statistics from Altmetric.com
Miller Fisher syndrome is characterised by ataxia, areflexia, and ophthalmoplegia and was first described by Charles Miller Fisher in 1956 as an unusual variant of acute idiopathic polyneuritis. There is frequently an antecedent illness1 and the syndrome is associated with a high titre of anti-GQ1b antibodies in approximately 90% of cases.1,2Pasteurella multocida is a Gram negative bacteria, commonly found in the saliva of animals, particularly cats.3
We present the case of a 70 year old lady who developed Miller Fisher syndrome with positive anti-GQ1b antibodies 11 days after P. multocida was cultured from a blood sample. Miller Fisher syndrome associated with P. multocida infection has not, to our knowledge, been described previously.
A 70 year old lady presented with a one day history of a painful left hip, fever, sweats, and lethargy following a bite from her pet cat on her left leg on the preceding day. She reported no other recent illnesses. She had had a total left hip replacement four years previously. On examination she was hypotensive and pyrexial with local tenderness of her left hip and decreased range of movement. She had puncture marks on her left shin from the cat bite with surrounding erythema tracking proximally to the groin. Initial blood cultures revealed heavy growth of P. multocida sensitive to penicillin. Intravenous benzylpenicillin (1.2 g four times daily) was administered.
The patient’s pyrexial illness improved over the next 11 days but then she developed diplopia. The attending orthopaedic surgeon recorded that the cranial nerve examination was normal. By the following day the patient had also become ataxic, and she was referred for a neurological opinion. Examination at this stage revealed marked truncal ataxia and complete internal and external ophthalmoplegia with bilateral ptosis. Limb examination revealed areflexia and ataxia although limb power and sensation were normal. The patient was unable to stand.
A computed tomography brain scan was normal. Magnetic resonance imaging was precluded by claustrophobia. The cerebrospinal fluid was clear, containing 0.5 g/l protein, 3.3 mmol/l glucose, no white cells/mm3, and 255 red cells/mm3. No organisms were seen or cultured. There was no clinical response to pyridostigmine and acetylcholine receptor antibodies were negative. A sample of blood taken seven days after the onset of neurological symptoms was positive for anti-GQ1b antibodies at a titre of 1:1600 using enzyme-linked immunosorbent assay (ELISA). The testing laboratory considered a titre above 1:100 to be positive for anti-GQ1b antibodies. Other antiganglioside antibodies and follow up anti-GQ1b antibodies were not tested.
A diagnosis of Miller Fisher syndrome was made and intravenous immunoglobulin (0.4 g/kg daily for five days) was administered with gradual improvement in symptoms and signs over the next six weeks leading to the patient’s discharge. At follow up five months later she had fully recovered.
This patient developed the typical neurological symptoms of Miller Fisher syndrome with positive anti-GQ1b antibodies 11 days after P. multocida was cultured from a blood sample. To our knowledge this is the first reported case of any form of Guillain–Barré syndrome associated with P. multocida infection.
P. multocida is a small Gram negative coccobacillus4 and is an important animal and human opportunistic pathogen. In humans it can cause soft tissue, respiratory, urinary tract, and meningeal infections. The mechanisms by which P. multocida might cause Miller Fisher syndrome (we are assuming causation and accept we have only demonstrated temporal association) are unknown but molecular mimicry is a possibility. There is considerable evidence supporting the theory of molecular mimicry between lipopolysaccharide (LPS) from Campylobacter jejuni and the GQ1b ganglioside.5 As P. multocida is Gram negative, its capsule similarly has LPS. However, we were unable to find any research specifically suggesting a similarity between the P. multocida LPS and the GQ1b ganglioside. P. multocida has previously been reported in association with acute disseminated encephalomyelitis4 but not, to our knowledge, with any other diseases with a presumed autoimmune basis.
Although an antecedent illness has frequently been noted before the onset of Miller Fisher syndrome the causative agents are not as well described as in Guillain–Barré syndrome.5 While C. jejuni has been implicated in the pathogenesis of Miller Fisher syndrome following enteritis, a recent study1 of 50 patients with the syndrome found that 76% had respiratory symptoms in the month preceding onset of the syndrome compared with only 4% with gastrointestinal symptoms. Haemophilus influenza, Staphylococcus aureus, Mycoplasma pneumoniae, Coxiella burnetii, cytomegalovirus, Epstein–Barr virus, varicella zoster, and mumps virus have also been reported as antecedent agents in Miller Fisher syndrome. However, a statistical correlation with Miller Fisher syndrome has only been shown for M. pneumoniae5—serological evidence of recent infection was found in 7% of Miller Fisher patients compared with 2% of patients with Guillain–Barré syndrome.
From the above discussion it is clear that the antecedent illness in Miller Fisher syndrome commonly takes the form of a respiratory infection of unknown aetiology. P. multocida can cause respiratory infection. It is often difficult to isolate this organism from sputum samples3 and it has been reported as causing indolent and asymptomatic pulmonary infection,3 including asymptomatic lung abscess. For these reasons P. multocida infection is possibly underdiagnosed. Therefore, while we believe this is the first reported case of an association between Miller Fisher syndrome and P. multocida we believe it highly unlikely to be unique.
Competing interests: none declared
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.