Acute disseminated encephalomyelitis temporally associated with Campylobacter gastroenteritis
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1 Department of Infection and Tropical Medicine, Royal Hallamshire Hospital, Sheffield, UK
2 Department of Neurology, Royal Hallamshire Hospital, Sheffield, UK
The association of Campylobacter infection and Guillain-Barré syndrome is well recognised. We report a case of acute disseminated encephalomyelitis (ADEM) temporally associated with Campylobacter gastroenteritis in a previously fit man. A MedLine search using the keywords "ADEM", "demyelination", and "campylobacter" revealed no previous reports of ADEM associated with Campylobacter infection in isolation.
A 24 year old man presented to his general practitioner with a 4 day history of non-bloody diarrhoea associated with fevers and sweats. His past medical history was unremarkable. He drank 6 units of alcohol per week and smoked only occasionally. His general practitioner prescribed loperamide for symptomatic relief. Campylobacter species was later isolated from stool samples. By day 5 of his illness, his diarrhoea had settled and he had become constipated. However, he remained febrile and developed nausea and vomiting. His general practitioner prescribed erythromycin but he tolerated only two doses because of nausea.
Fourteen days into the illness he was admitted to hospital complaining of headache, fever, and sweats. Examination revealed a temperature of 38.4°C, pulse of 65 beats/min and normal blood pressure. Rectal examination revealed hard stool. There were no focal neurological signs. His haemoglobin was15.3 g/dl, leukocyte count was 13.3x109/l (87.1% neutrophils) and C-reactive protein was 12.8 mg/l. Two days after admission (day 16 of illness), his family reported a change in his personality and he complained of slurring of speech, intermittent diplopia, and difficulty in walking. Examination revealed mild dysarthria, left sided facial weakness, mild left pyramidal limb weakness, and decreased sensation in the left leg. Tendon reflexes were brisk but plantar responses were flexor. His gait was ataxic. Cranial CT scan showed no significant abnormalities. Lumbar puncture revealed an opening pressure of 160 mm CSF, total cell count of 34/mm3 with a white cell count of 20/mm3 (100% lymphocytes), total protein of 541 mg/l, glucose of 3.2 mmol/l, and negative oligoclonal banding. No organisms were seen and PCR was negative for enteroviruses and herpes virus. An EEG showed mild excess of generalised slow wave activity. Cranial MRI scan was performed on a 1.5 T Siemens magnetic system. T2 weighted imaging of the brain showed multiple high signal foci in the supra- and infra-tentorial compartments involving the cortex, white matter, and deep grey matter. One lesion in the right peri-trigonal white matter showed slight enhancement following intravenous gadolinium diethylene-triaminopenta-acetic acid (gadolinium DTPA) injection (fig 1). The abnormalities were consistent with ADEM.
Figure 1 Axial T2 weighted image showing supra- and infra-tentorial high signals in both hemispheres, and coronal T1 weighted images showing peri-trigonal white matter lesions with slight enhancement following intravenous gadolinium DTPA injection in keeping with ADEM.
The patient was initially treated with aciclovir 10 mg/kg three times daily, ampicillin 2 g four times daily and ciprofloxacin 500 mg twice daily, but was subsequently given intravenous methylprednisolone 1 g daily for 3 days after the diagnosis of ADEM was made. Aciclovir and ampicillin were discontinued when the negative laboratory results were available but ciprofloxacin was continued for 7 days. One day after treatment with methylprednisolone he noticed an improvement in his speech and gait, and after 7 days of starting treatment he had no ataxia and was discharged home. He appeared to have made a full recovery when he was reviewed at 6 weeks and has since remained asymptomatic.
ADEM is an acute monophasic immune mediated inflammatory demyelinating disease of the central nervous system. It is an uncommon but a serious condition with mortality rates estimated between 10–30%.1 In the majority of cases, the condition develops after systemic viral infections most commonly measles, mumps, rubella, influenza A and B, herpes simplex, Epstein-Barr virus, varicella, and vaccinia.2 It has also been reported following bacterial infections with Mycoplasma pneumoniae, Chlamydia, Legionella, and Streptococcus, or following immunisations for rabies, diphtheria/tetanus/pertussis, smallpox, measles and Japanese B encephalitis.2 The pathogenesis of ADEM remains poorly understood. However, the evidence suggests that activated T cells, which recognise amino acid sequences shared between microbial epitopes and myelin antigens, attack central nervous system structures alone or in synergy with antibodies.3 Viral or bacterial super-antigens could likewise trigger autoactive T cells with similar results.
The diagnosis of ADEM is usually made clinically with the aid of MRI scanning, lumbar puncture finding and electrophysiology studies. MRI scanning reveals multiple areas of increased signal on T2 weighted images in the white matter throughout the central nervous system, most being located in the subcortical white matter of both hemispheres, which are often quite extensive and enhance with contrast. CSF findings include mononuclear pleocytosis and mild protein elevation. There are few data available on evidence based treatment regimens, but treatment is usually instituted with high dose glucocorticoids. Plasmapheresis and intravenous immunoglobulin have also been used.
Campylobacter gastroenteritis is the most common cause of acute gastroenteritis in the UK, accounting for over 56 000 cases in 2000. Its incidence has risen progressively over the past 2 decades. In the majority of cases, the illness self terminates within a few days with no long term consequences. It is estimated that approximately 1/1000 reported campylobacteriosis cases leads to Guillain-Barré syndrome, and around 33% of Guillain-Barré syndrome cases in the western world may be triggered by campylobacteriosis. Huber et al reported a case of combined ADEM and acute motor axonal neuropathy following Campylobacter jejuni infection and hepatitis A immunisation.4 Cranial MRI scanning showed a slight enhancement in the left cerebral peduncle that disappeared when the study was repeated a week later. Nasralla et al reported a case of postinfectious encephalomyelitis in a young child following Campylobacter jejuni enteritis.5 Cranial MRI scanning showed a combination of predominant grey matter involvement with concomitant focal areas of subcortical white matter lesions with no parenchymal enhancement, which the authors felt to be different from the pattern of signal abnormalities seen in patients with ADEM. The MRI abnormalities in our case were in keeping with ADEM although, as with the case reported by Huber et al, the amount of enhancement was minimal, indicating that the majority of the lesions were not acute.6 The paucity of reported cases of ADEM following Campylobacter infection is surprising given the strong association between Campylobacter jejuni infection and Guillain-Barré syndrome and the pathogenesis of the latter. In these cases, Campylobacter jejuni induces humeral and cellular immune responses due to molecular mimicry between specific lipopolysaccaride epitopes on the infecting agent and target epitopes on the surface components of the peripheral nerves, resulting is myelin destruction and axonal degeneration.7 Furthermore, patients with ADEM often have peripheral nervous system involvement and there have been occasional cases of ADEM associated with Guillain-Barré syndrome. Our patient did not have any clinical features suggestive of peripheral nervous system involvement. However, nerve conduction studies were not performed and a degree of sub-clinical neuropathy cannot therefore be excluded.
We describe the first identifiable case of ADEM temporally associated with Campylobacter gastroenteritis alone. Our patient made an excellent recovery associated with therapy with high dose methylprednisolone.
ACKNOWLEDGEMENTS
We are most grateful to Dr D Connolly for reviewing the MRI imaging.
References
Kennard C, Swash M. Acute viral encephalitis. Its diagnosis and outcome. Brain 1981;104:129–48.
Tselis AC, Lisak RP. Acute disseminated encephalomyelitis. In: Antel J, Birnbaum G, Hartung HP, eds. Clinical neuroimmunology. Boston: Blackwell Science, 1998:116–47.
Hartung HP, Crossman RI. ADEM: distinct disease or part of the MS spectrum? Neurology 2001;56:1257–60.
Huber S, Kappos L, Fuhr P, et al. Combined acute disseminated encephalomyelitis and acute motor axonal neuropathy after vaccination for hepatitis A and infection with Campylobaccter jejuni. J Neurol 1999;246:1204–6.
Nasralla CA, Pay N, Goodpasture HC, et al. Postinfectious encephalopathy in a child following Campylobacter jejuni enteritis. Am J Neuroradiol 1993;14:444–8.
Singh S, Alexander M, Korah IP. Acute disseminated encephalomyelitis: MR imaging features. Am J Roentgenol 1999;173:1101–7.
Hughes RA, Hadden RD, Gregson NA, et al. Pathogenesis of Guillain-Barre syndrome. J Neuroimmunol 1999;100:74–97.(D Orr1, M W McKendrick1 a)
2 Department of Neurology, Royal Hallamshire Hospital, Sheffield, UK
The association of Campylobacter infection and Guillain-Barré syndrome is well recognised. We report a case of acute disseminated encephalomyelitis (ADEM) temporally associated with Campylobacter gastroenteritis in a previously fit man. A MedLine search using the keywords "ADEM", "demyelination", and "campylobacter" revealed no previous reports of ADEM associated with Campylobacter infection in isolation.
A 24 year old man presented to his general practitioner with a 4 day history of non-bloody diarrhoea associated with fevers and sweats. His past medical history was unremarkable. He drank 6 units of alcohol per week and smoked only occasionally. His general practitioner prescribed loperamide for symptomatic relief. Campylobacter species was later isolated from stool samples. By day 5 of his illness, his diarrhoea had settled and he had become constipated. However, he remained febrile and developed nausea and vomiting. His general practitioner prescribed erythromycin but he tolerated only two doses because of nausea.
Fourteen days into the illness he was admitted to hospital complaining of headache, fever, and sweats. Examination revealed a temperature of 38.4°C, pulse of 65 beats/min and normal blood pressure. Rectal examination revealed hard stool. There were no focal neurological signs. His haemoglobin was15.3 g/dl, leukocyte count was 13.3x109/l (87.1% neutrophils) and C-reactive protein was 12.8 mg/l. Two days after admission (day 16 of illness), his family reported a change in his personality and he complained of slurring of speech, intermittent diplopia, and difficulty in walking. Examination revealed mild dysarthria, left sided facial weakness, mild left pyramidal limb weakness, and decreased sensation in the left leg. Tendon reflexes were brisk but plantar responses were flexor. His gait was ataxic. Cranial CT scan showed no significant abnormalities. Lumbar puncture revealed an opening pressure of 160 mm CSF, total cell count of 34/mm3 with a white cell count of 20/mm3 (100% lymphocytes), total protein of 541 mg/l, glucose of 3.2 mmol/l, and negative oligoclonal banding. No organisms were seen and PCR was negative for enteroviruses and herpes virus. An EEG showed mild excess of generalised slow wave activity. Cranial MRI scan was performed on a 1.5 T Siemens magnetic system. T2 weighted imaging of the brain showed multiple high signal foci in the supra- and infra-tentorial compartments involving the cortex, white matter, and deep grey matter. One lesion in the right peri-trigonal white matter showed slight enhancement following intravenous gadolinium diethylene-triaminopenta-acetic acid (gadolinium DTPA) injection (fig 1). The abnormalities were consistent with ADEM.
Figure 1 Axial T2 weighted image showing supra- and infra-tentorial high signals in both hemispheres, and coronal T1 weighted images showing peri-trigonal white matter lesions with slight enhancement following intravenous gadolinium DTPA injection in keeping with ADEM.
The patient was initially treated with aciclovir 10 mg/kg three times daily, ampicillin 2 g four times daily and ciprofloxacin 500 mg twice daily, but was subsequently given intravenous methylprednisolone 1 g daily for 3 days after the diagnosis of ADEM was made. Aciclovir and ampicillin were discontinued when the negative laboratory results were available but ciprofloxacin was continued for 7 days. One day after treatment with methylprednisolone he noticed an improvement in his speech and gait, and after 7 days of starting treatment he had no ataxia and was discharged home. He appeared to have made a full recovery when he was reviewed at 6 weeks and has since remained asymptomatic.
ADEM is an acute monophasic immune mediated inflammatory demyelinating disease of the central nervous system. It is an uncommon but a serious condition with mortality rates estimated between 10–30%.1 In the majority of cases, the condition develops after systemic viral infections most commonly measles, mumps, rubella, influenza A and B, herpes simplex, Epstein-Barr virus, varicella, and vaccinia.2 It has also been reported following bacterial infections with Mycoplasma pneumoniae, Chlamydia, Legionella, and Streptococcus, or following immunisations for rabies, diphtheria/tetanus/pertussis, smallpox, measles and Japanese B encephalitis.2 The pathogenesis of ADEM remains poorly understood. However, the evidence suggests that activated T cells, which recognise amino acid sequences shared between microbial epitopes and myelin antigens, attack central nervous system structures alone or in synergy with antibodies.3 Viral or bacterial super-antigens could likewise trigger autoactive T cells with similar results.
The diagnosis of ADEM is usually made clinically with the aid of MRI scanning, lumbar puncture finding and electrophysiology studies. MRI scanning reveals multiple areas of increased signal on T2 weighted images in the white matter throughout the central nervous system, most being located in the subcortical white matter of both hemispheres, which are often quite extensive and enhance with contrast. CSF findings include mononuclear pleocytosis and mild protein elevation. There are few data available on evidence based treatment regimens, but treatment is usually instituted with high dose glucocorticoids. Plasmapheresis and intravenous immunoglobulin have also been used.
Campylobacter gastroenteritis is the most common cause of acute gastroenteritis in the UK, accounting for over 56 000 cases in 2000. Its incidence has risen progressively over the past 2 decades. In the majority of cases, the illness self terminates within a few days with no long term consequences. It is estimated that approximately 1/1000 reported campylobacteriosis cases leads to Guillain-Barré syndrome, and around 33% of Guillain-Barré syndrome cases in the western world may be triggered by campylobacteriosis. Huber et al reported a case of combined ADEM and acute motor axonal neuropathy following Campylobacter jejuni infection and hepatitis A immunisation.4 Cranial MRI scanning showed a slight enhancement in the left cerebral peduncle that disappeared when the study was repeated a week later. Nasralla et al reported a case of postinfectious encephalomyelitis in a young child following Campylobacter jejuni enteritis.5 Cranial MRI scanning showed a combination of predominant grey matter involvement with concomitant focal areas of subcortical white matter lesions with no parenchymal enhancement, which the authors felt to be different from the pattern of signal abnormalities seen in patients with ADEM. The MRI abnormalities in our case were in keeping with ADEM although, as with the case reported by Huber et al, the amount of enhancement was minimal, indicating that the majority of the lesions were not acute.6 The paucity of reported cases of ADEM following Campylobacter infection is surprising given the strong association between Campylobacter jejuni infection and Guillain-Barré syndrome and the pathogenesis of the latter. In these cases, Campylobacter jejuni induces humeral and cellular immune responses due to molecular mimicry between specific lipopolysaccaride epitopes on the infecting agent and target epitopes on the surface components of the peripheral nerves, resulting is myelin destruction and axonal degeneration.7 Furthermore, patients with ADEM often have peripheral nervous system involvement and there have been occasional cases of ADEM associated with Guillain-Barré syndrome. Our patient did not have any clinical features suggestive of peripheral nervous system involvement. However, nerve conduction studies were not performed and a degree of sub-clinical neuropathy cannot therefore be excluded.
We describe the first identifiable case of ADEM temporally associated with Campylobacter gastroenteritis alone. Our patient made an excellent recovery associated with therapy with high dose methylprednisolone.
ACKNOWLEDGEMENTS
We are most grateful to Dr D Connolly for reviewing the MRI imaging.
References
Kennard C, Swash M. Acute viral encephalitis. Its diagnosis and outcome. Brain 1981;104:129–48.
Tselis AC, Lisak RP. Acute disseminated encephalomyelitis. In: Antel J, Birnbaum G, Hartung HP, eds. Clinical neuroimmunology. Boston: Blackwell Science, 1998:116–47.
Hartung HP, Crossman RI. ADEM: distinct disease or part of the MS spectrum? Neurology 2001;56:1257–60.
Huber S, Kappos L, Fuhr P, et al. Combined acute disseminated encephalomyelitis and acute motor axonal neuropathy after vaccination for hepatitis A and infection with Campylobaccter jejuni. J Neurol 1999;246:1204–6.
Nasralla CA, Pay N, Goodpasture HC, et al. Postinfectious encephalopathy in a child following Campylobacter jejuni enteritis. Am J Neuroradiol 1993;14:444–8.
Singh S, Alexander M, Korah IP. Acute disseminated encephalomyelitis: MR imaging features. Am J Roentgenol 1999;173:1101–7.
Hughes RA, Hadden RD, Gregson NA, et al. Pathogenesis of Guillain-Barre syndrome. J Neuroimmunol 1999;100:74–97.(D Orr1, M W McKendrick1 a)