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Axonal polyneuropathy and encephalopathy in a patient with verotoxin producing Escherichia coli (VTEC) infection
  1. RYUJI SAKAKIBARA,
  2. TAKAMICHI HATTORI,
  3. KEIKO MIZOBUCHI,
  4. SATOSHI KUWABARA
  1. Department of Neurology
  2. First Department of Internal Medicine, Chiba University, 1–8–1 Inohana Chuo-ku, Chiba 260, Japan
  1. Dr Ryuji Sakakibara, Department of Neurology, Chiba University, 1–8–1 Inohana Chuo-ku, Chiba 260, Japan.
  1. MITSUGU OGAWA
  1. Department of Neurology
  2. First Department of Internal Medicine, Chiba University, 1–8–1 Inohana Chuo-ku, Chiba 260, Japan
  1. Dr Ryuji Sakakibara, Department of Neurology, Chiba University, 1–8–1 Inohana Chuo-ku, Chiba 260, Japan.

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Escherichia coli serotype O157:H7 causes serious food poisoning worldwide, especially in children and elderly people.1 It is also called verotoxin producingE coli (VTEC), which produces a cytotoxic Shiga-like toxin. Gastrointestinal, haemorrhagic, and uraemic effects are well known in VTEC infection,2 and neurological problems are likely to be more frequent than is generally recognised.3 Here we describe axonal polyneuropathy and encephalopathy in a young female patient associated with haemolytic-uraemic syndrome caused by VTEC infection.

A 26 year old woman began to have abdominal pain and haemorrhagic diarrhoea. She was admitted to an emergency hospital and diagnosed as having haemorrhagic colitis due to probable food poisoning. Then her urinary volume gradually decreased and serum creatinine increased, and she was transferred to our hospital. On the 9th day she had a high fever of 39.7°C with increased C reactive protein of 7.6 mg/l and a leukocytosis of 17 800/mm3. She was in a state of anuria and her blood analysis showed severe kidney dysfunction (increased serum creatinine of 6.76 mg/l). She had severe anaemia (haemoglobin 6.0 g/dl), fragmentation, and tear drop deformation of red blood cells in the blood smear and increased lactate dehydrogenase concentration of 4095 IU (normal range 230–460 IU), suggestive of haemolytic anaemia. Her platelet count was decreased to 21 000/mm3. The culture of her stool showed the growth of E coliO157:H7 and analysis of the bacterial toxins showed the presence of verotoxin, which confirmed the diagnosis of VTEC infection. She was given plasma exchange, continuous haemodialysis, and antibiotics (4 g/day fosfomycin, 600 mg/day levofloxacin, and 2 g/day cefoperazon/sulbactam). Her general status was unchanged for 1 week after admission and she was in a delirious state with visual hallucinations and tonic convulsion, indicative of encephalopathy. Brain CT disclosed mild brain swelling and there were diffuse slow waves in the frontal area on EEG. She was given 250 mg/day diphenylhydantoin. During the next two weeks her kidney function, haemolytic anaemia, and encephalopathy gradually improved.

After recovery of consciousness she began to complain of numbness of the limbs, manifest in the legs. She described her feet as feeling like frost bite when she was lying on the bed, and this gradually exacerbated to be a burning pain. On examination she was alert and cooperative. Her cranial nerves were normal. Muscle strength was normal and coordination was intact. Deep tendon reflexes were decreased in the four limbs. Sensation for vibration was impaired in the lower legs, but preserved for pin prick, light touch, and joint sensation. Routine laboratory data including haematological studies, serum chemistry, urinalysis, and CSF analysis were normal. Serum concentrations of vitamin B1, B6, and B12 were normal. Nerve conduction studies were carried out on her right limbs, and showed normal findings in the distal latencies, motor conduction velocities, and F wave latencies of the median, ulnar, and tibial nerves, and no evidence of conduction block. However, there were decreased compound muscle action potentials (1.18 mV) and mild slowing of motor conduction velocity (41.0 m/s) in the peroneal nerve. There were also markedly decreased amplitudes of the sensory nerve action potentials in the ulnar (6.46 μV) and sural (0.98μV) nerves. These findings and the clinical features confirmed the diagnosis of sensory dominant, axonal polyneuropathy. She was given 300 mg/day sulindac (an anti-inflammatory agent) and 1500 μg/day mechobalamin (vitamin B12) without effect. Two weeks after administration of 300 mg/day oral mexiletin, her numbness and pain gradually disappeared.

The patient was diagnosed as having VTEC infection, because of a typical history of an acute haemorrhagic colitis, the cultured growth of enterohaemorrhagic E coli O157:H7, and the detection of verotoxin in her stool. She had haemolytic-uraemic syndrome (haemolytic anaemia, thrombocytopenia, and uraemia, following diarrhoea), which is the main complication of VTEC infection. Experimentally, vero cells, an immortalised primate kidney cell line, are killed by low doses of verotoxin through the process of apoptosis.1 2 Verotoxin shows similar cytotoxity on human glomerular microvascular endotherial cells via inflammatory mediators such as tumour necrosis factor-α, which induced an increase in the numbers of verotoxin receptors, leading to a microvascular thrombosis.2 Our patient was treated with antibiotics, plasma exchange, and continuous haemodialysis, with benefit.

During the course of the disease, our patient was in a delirious state with visual hallucinations and tonic convulsion. She showed mild brain swelling on CT and diffuse slow waves in the frontal area on EEG, evidence of encephalopathy. Previous reports have shown that the incidence of encephalopathy in haemolytic-uraemic syndrome (mostly of VTEC infection) is 30% to 52%,3 including seizures in 17%–44%, altered consciousness in 7%–40%, and paralysis in 1%–16%. Many of the patients, including ours, seemed to have metabolic encephalopathy, but some developed encephalopathy without metabolic abnormalities.3 There is experimental evidence that verotoxin has direct virulence to both endotherial cells and neurons in the nervous system, and its initial lesion is in the hypothalamic areas, then spreading into the hippocampus and the brainstem.4 The convulsions in our patient was successfully treated with 250 mg/day diphenylhydantoin, and her encephalopathy gradually improved during plasma exchange and haemodialysis.

After recovering consiousness, she began to complain of numbness of her limbs, and a burning pain which exacerbated in the night. Nerve conduction studies and the clinical features confirmed the diagnosis of sensory-dominant, axonal polyneuropathy. At this stage metabolic abnormalities were not detected and serum concentrations of vitamins B1, B6, and B12 were normal. Her numbness and tingling sensation ameliorated after 2 weeks administration of 300 mg/day oral mexiletin, an agent with a membrane stabilising effect. Up to now, to our knowledge, peripheral neuropathy has not been reported in VTEC infection other than in one patient, by Hamano et al,5 who showed bilateral phrenic nerve palsy for 2 weeks after recovering consiousness. The above experimental evidence suggests that microcircular disturbance or direct toxicity to the neuronal cells by verotoxin could cause axonal neuropathy in VTEC infection.

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