The neurological syndrome in adults during the 2011 northern German E. coli serotype O104:H4 outbreak

Abstract

The aim of this study was to describe the neurological syndrome in the largest cohort of adult patients with a complicated Shiga toxin-producing Escherichia coli infection. The recent outbreak of Shiga toxin-producing E. coli serotype O104:H4 in northern Germany affected more than 3842 patients, 22% of whom developed haemolytic uraemic syndrome. The proportion of adult patients was unusually high, and neurological complications were frequent and severe. In three hospitals, population-based evaluation of 217 patients with complicated Shiga toxin-producing E. coli infection was carried out, including neurological, neuroradiological, neurophysiological, cerebrospinal fluid and neuropathological analyses. Of the 217 patients with complicated Shiga toxin-producing E. coli infection, 104 (48%) developed neurological symptoms. Neurological symptoms occurred 5.3 days (mean) after first diarrhoea and 4 days after onset of haemolytic uraemic syndrome. Of the infected patients with neurological symptoms, 67.3% presented with cognitive impairment or aphasia. During the course of the disease, 20% of the patients developed epileptic seizures. The onset of neurological symptoms was paralleled by increases in blood urea nitrogen and serum creatinine. In 70 patients with cerebral magnetic resonance imaging, the most common findings were symmetrical hyperintensities in the region of abducens nucleus and lateral thalamus. On follow-up scans, these abnormalities were resolved. Neuropathological analysis revealed regionally accentuated astrogliosis and microgliosis, more predominant in the thalamus and brainstem than in the cortex, and neuronal expression of globotriaosylceramide. There were no signs of microbleeds, thrombotic vessel occlusion or ischaemic infarction. The neurological syndrome in adult patients with complicated Shiga toxin-producing E. coli infection is a rapidly progressive and potentially life-threatening disease necessitating intensive care unit treatment and intubation in >30% of cases. The outcome of neurological patients in the 2011 northern German Shiga toxin-producing E. coli O104:H4 outbreak was surprisingly good. Magnetic resonance imaging and neuropathological findings point to a mixed toxic and inflammatory pathomechanism leading to largely reversible damage of neuronal function.

Regulation of neuronal excitability by release of proteins from glial cells

“…However, in infectious diseases, transient epileptic episodes have been observed [46], which could have potentially been caused by excessive cytokine release from activated microglia [34], leading to an enhanced neuronal activity not only by a change in synaptic balance but also by an increase in Na þ current density. Such a mechanism might have also been involved in the development of seizures that occurred during immune reactions in 20% of patients during the course of the recent outbreak of a Shiga-toxinproducing Escherichia coli infection [45]. …”

Tumor necrosis factor-α modifies the effects of Shiga toxin on glial cells

“…STEC and STX cause hemorrhagic diarrhea and the potentially lethal HUS in severe cases [1]. HUS in STEC infections often involves neurological symptoms and signs of encephalopathy [1,2].…”

“…HUS in STEC infections often involves neurological symptoms and signs of encephalopathy [1,2]. The neurological symptoms and signs of encephalopathy include seizures, alteration of consciousness, focal neurological deficits, visual disturbances, and brainstem symptoms.…”

“…Shiga toxin (STX), which is produced by some strains of Escherichia coli, causes hemorrhagic colitis and hemolytic-uremic syndrome (HUS) [1]. Twenty to fifty percent of HUS cases involve central nervous system (CNS) complications that are the most common cause of death in STEC infections [1,2].…”

“…Twenty to fifty percent of HUS cases involve central nervous system (CNS) complications that are the most common cause of death in STEC infections [1,2]. However, approximately 62% of patients with HUS showed symptoms of encephalopathy in the 2011 Japanese outbreak of infection with STX-producing E. coli (STEC) [3,4].…”