Neurol Sci DOI 10.1007/s10072-014-1731-7
LETTER TO THE EDITOR
Guillain–Barre´ syndrome and encephalitis/encephalopathy of a rare case of Northern China acute severe hepatitis E infection Xiao-Dong Chen • Ye-Ting Zhou • Jin-Jin Zhou Yuan-Wei Wang • Dao-Ming Tong
•
Received: 21 January 2014 / Accepted: 21 March 2014 Ó Springer-Verlag Italia 2014
Sir, In recent years, cases of Guillain–Barre´ Syndrome (GBS) in patients with acute hepatitis E virus (HEV) infection were increasingly reported [1–3]. Here, we report a rare case of GBS and encephalitis/encephalopathy simultaneous due to acute severe HEV infection in a Chinese patient. A 64-year-old male was admitted to our hospital, with acute flaccid paralysis for at least 7 days. He had a history of a febrile illness with cough and nasal congestion 12 days previously. He had not being given any hepatotoxic or neurotoxic drugs or vaccinations. His temperature was 36.8 °C. He was in mental slowness and short-term memory deficits. Medical examination revealed jaundice and tender hepatomegaly. There was no splenomegaly and free fluid in abdomen. Neurological examination showed bilateral upper limbs weakness of grade 3/5 and lower limbs of grade 2/5, generalized hypotonia and symmetric hyporeflexia in the upper limbs and areflexia in the lower limbs. Pinprick perception was reduced in a glove-and-sock distribution, and plantar responses were flexor. The results of blood tests at the first days admitted to hospital are shown in Table 1. Brain MRI was performed on admission day 1 and a mild high signals was showed in the hippocampus bilaterally.
X.-D. Chen J.-J. Zhou Y.-W. Wang D.-M. Tong (&) Department of Neurology, Affiliated Shuyang People’ Hospital, XuZhou Medical College, No. 9, Yingbin Road, Shu town, Jiangsu, China e-mail: [email protected] Y.-T. Zhou Medical Evaluation Unit, Affiliated Shuyang People’ Hospital, XuZhou Medical College, Jiangsu, China
On the next week of his admission, he developed respiratory failure, and was moved to the intensive care unit (ICU) for mechanical ventilation. His temperature was 38.1 °C. His consciousness was in confusion state with a GCS of E4V3M4. The results of related tests during the ICU stay are shown in Table 1. Finally, GBS and encephalitis/encephalopathy due to an acute severe hepatitis E was diagnosed and he was given immunoglobulin intravenously. Seven days after admission to ICU, he was gradually weaned from mechanical ventilation as his muscle power improved. Forty days later, he was discharged. On followup, 12 months later, he had complete recovery. Several neurological manifestations, including polyradiculopathy, GBS, bilateral brachial neuritis, proximal myopathy, and encephalitis or encephalopathy, have been described in patients with HEV infection [4, 5]. Acute HEV–GBS reported is still less than 20 cases in the medical literature. The diagnosis of HEV infection was either confirmed by the positive for anti-HEV IgM or by the presence of HEV RNA in the serum. In our patient, the evidence for an acute hepatitis E infection was based on serological analysis to detect the positive for anti-HEV IgM, while no detect positive for others hepatitis. Furthermore, the diagnosis of severe HEV–GBS was confirmed by serological, cerebrospinal fluid (CSF), and electromyography. The prodromal symptoms of GBS are usually the symptoms of upper respiratory tract infection or diarrhea [6]. Although the evidence of a HEV infection in patient’s nasopharynx had not been proven, our patient had upper respiratory infection 12 days before admission. Thus, we think that a prior infection in our patient may be from his nasopharynx.
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Neurol Sci Table 1 The results of related tests during the hospital and ICU stay Item name (units)
On admission
Transfer to ICU
At discharge
Reference values
AST (U/L)
440.0
86.0
68.0
0–40
ALT (U/L)
1,461.0
99.0
52.0
0-60
Total bilirubin (lmol/L)
156.9
403.4
42.5
5.1–19
Direct bilirubin (lmol/L)
110.7
234.9
26.6
1.7–6.8
Albumin/globulin (g/L)
1.1
0.5
1.0
1.2–2.3
White blood cell (109/L)
5.3
14.7
6.2
4.0–10.0
Platelet (109/L)
162
286.0
272
150–400
PT (s)
12.1
12.8
11.7
10–16
aPTT (s)
30.90
38.6
35.55
23–38
Hepatitis A virus
Negative
Negative
Hepatitis B virus Hepatitis C virus
Negative Negative
Negative Negative
Hepatitis E virus
IgM positive
IgM positive
IgG negative
IgG negative
Herpes simplex virus 1
Negative
Herpes simplex virus 2
Negative
HIV
Negative
Cytomegalovirus
Negative
Treponema pallidum
Negative
Anti-GM2 IgM antibodies
Positive
Cerebrospinal fluid Cell count (9106/L)
10
0–8
Proteins (g/L)
0.88
0.15–0.45
Glucose (mmol/L)
8.1
2.8–4.5
Chloride (mmol/L)
119.1
120–132
DWI and flair
Mild high signal in hippocampus
Electrophysiology
Resolved Decreased conduction velocity and absent F waves
EEG
Mild diffuse slowing
Brain mapping
Diffuse abnormalities
AST aspartate aminotransferase, ALT alanine aminotransferase, PT prothrombin time, aPTT activated partial thromboplastin time, HIV human immunodeficiency virus, Ig immunoglobulin, DWI diffusion-weighted imaging, EEG electroencephalogram
Our patient showed only mild mental slowness without coma; whereas he was found presenting bilateral hippocampal damage on MRI, and also showed slightly increased cells in his CSF and diffuse abnormalities in his electroencephalogram and brain mapping. This is consistent with the diagnosis of mild encephalitis/ encephalopathy. This is a first reported case where severe acute HEV infection induces both GBS and encephalitis/encephalopathy, and its severity of GBS and encephalitis/encephalopathy is unbalanced. This finding confirmed that acute severe HEV-induced GBS and brain damage may have some pathogenesis of the same and different. To our knowledge, one of the most likely mechanism leading to GBS is the ganglioside mimicry. The implication of GBS related to antiganglioside GM1 or GM2
123
antibodies have been described [3, 7]. In present the patient, the positive anti-GM2 IgM antibodies have further confirmed that HEV–GBS is closely related with ganglioside mimicry. HEV-encephalitis/encephalopathy is not completely clear, but HEV RNA sequences in serum and CSF showed differences, suggesting the possible emergence of neurotropic variants which can directly affect the nervous system [8]. In conclusion, severe acute HEV infection-induced GBS and encephalitis/encephalopathy are rare. We recommend that patients with acute GBS and abnormal liver function tests should be needed overall picking HEV screening and systemic diagnosis. Conflict of interest No potential conflict of interest relevant to this article was reported.
Neurol Sci
References 1. van den Berg B, van der Eijk AA, Pas SD et al (2014) Guillain– Barre syndrome associated with preceding hepatitis E virus infection. Neurology 82:491–497 2. Cronin S, McNicholas R, Kavanagh E et al (2011) Anti-glycolipid GM2-positive Guillain–Barre´ Syndrome due to hepatitis E infection. Ir J Med Sci 180:255–257 3. Maurissen I, Jeurissen A, Strauven T, Sprengers D, De Schepper B (2012) First case of anti-ganglioside GM1-positive Guillain– Barre´ syndrome due to hepatitis E virus infection. Infection 40:323–326
4. Hoofnagle JH, Nelson KE, Purcell RH (2012) Hepatitis E. N Engl J Med 367:1237–1244 5. Kamar N, Bendall RP, Peron JM et al (2011) Hepatitis E virus and neurologic disorders. Emerg Infect Dis 17:173–179 6. Yuki N, Hartung HP (2012) Guillain–Barre´ Syndrome. N Engl J Med 366:2294–2304 7. Cats EA, Jacobs BC, Yuki N et al (2010) Multifocal motor neuropathy: association of anti-GM1 IgM antibodies with clinical features. Neurology 75:1961–1967 8. Kamar N, Izopet J, Cintas P et al (2010) Hepatitis E virus-induced neurological symptoms in a kidney-transplant patient with chronic hepatitis. Am J Transplant 10:1321–1324
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LETTER TO THE EDITOR
Guillain–Barre´ syndrome and encephalitis/encephalopathy of a rare case of Northern China acute severe hepatitis E infection Xiao-Dong Chen • Ye-Ting Zhou • Jin-Jin Zhou Yuan-Wei Wang • Dao-Ming Tong
•
Received: 21 January 2014 / Accepted: 21 March 2014 Ó Springer-Verlag Italia 2014
Sir, In recent years, cases of Guillain–Barre´ Syndrome (GBS) in patients with acute hepatitis E virus (HEV) infection were increasingly reported [1–3]. Here, we report a rare case of GBS and encephalitis/encephalopathy simultaneous due to acute severe HEV infection in a Chinese patient. A 64-year-old male was admitted to our hospital, with acute flaccid paralysis for at least 7 days. He had a history of a febrile illness with cough and nasal congestion 12 days previously. He had not being given any hepatotoxic or neurotoxic drugs or vaccinations. His temperature was 36.8 °C. He was in mental slowness and short-term memory deficits. Medical examination revealed jaundice and tender hepatomegaly. There was no splenomegaly and free fluid in abdomen. Neurological examination showed bilateral upper limbs weakness of grade 3/5 and lower limbs of grade 2/5, generalized hypotonia and symmetric hyporeflexia in the upper limbs and areflexia in the lower limbs. Pinprick perception was reduced in a glove-and-sock distribution, and plantar responses were flexor. The results of blood tests at the first days admitted to hospital are shown in Table 1. Brain MRI was performed on admission day 1 and a mild high signals was showed in the hippocampus bilaterally.
X.-D. Chen J.-J. Zhou Y.-W. Wang D.-M. Tong (&) Department of Neurology, Affiliated Shuyang People’ Hospital, XuZhou Medical College, No. 9, Yingbin Road, Shu town, Jiangsu, China e-mail: [email protected] Y.-T. Zhou Medical Evaluation Unit, Affiliated Shuyang People’ Hospital, XuZhou Medical College, Jiangsu, China
On the next week of his admission, he developed respiratory failure, and was moved to the intensive care unit (ICU) for mechanical ventilation. His temperature was 38.1 °C. His consciousness was in confusion state with a GCS of E4V3M4. The results of related tests during the ICU stay are shown in Table 1. Finally, GBS and encephalitis/encephalopathy due to an acute severe hepatitis E was diagnosed and he was given immunoglobulin intravenously. Seven days after admission to ICU, he was gradually weaned from mechanical ventilation as his muscle power improved. Forty days later, he was discharged. On followup, 12 months later, he had complete recovery. Several neurological manifestations, including polyradiculopathy, GBS, bilateral brachial neuritis, proximal myopathy, and encephalitis or encephalopathy, have been described in patients with HEV infection [4, 5]. Acute HEV–GBS reported is still less than 20 cases in the medical literature. The diagnosis of HEV infection was either confirmed by the positive for anti-HEV IgM or by the presence of HEV RNA in the serum. In our patient, the evidence for an acute hepatitis E infection was based on serological analysis to detect the positive for anti-HEV IgM, while no detect positive for others hepatitis. Furthermore, the diagnosis of severe HEV–GBS was confirmed by serological, cerebrospinal fluid (CSF), and electromyography. The prodromal symptoms of GBS are usually the symptoms of upper respiratory tract infection or diarrhea [6]. Although the evidence of a HEV infection in patient’s nasopharynx had not been proven, our patient had upper respiratory infection 12 days before admission. Thus, we think that a prior infection in our patient may be from his nasopharynx.
123
Neurol Sci Table 1 The results of related tests during the hospital and ICU stay Item name (units)
On admission
Transfer to ICU
At discharge
Reference values
AST (U/L)
440.0
86.0
68.0
0–40
ALT (U/L)
1,461.0
99.0
52.0
0-60
Total bilirubin (lmol/L)
156.9
403.4
42.5
5.1–19
Direct bilirubin (lmol/L)
110.7
234.9
26.6
1.7–6.8
Albumin/globulin (g/L)
1.1
0.5
1.0
1.2–2.3
White blood cell (109/L)
5.3
14.7
6.2
4.0–10.0
Platelet (109/L)
162
286.0
272
150–400
PT (s)
12.1
12.8
11.7
10–16
aPTT (s)
30.90
38.6
35.55
23–38
Hepatitis A virus
Negative
Negative
Hepatitis B virus Hepatitis C virus
Negative Negative
Negative Negative
Hepatitis E virus
IgM positive
IgM positive
IgG negative
IgG negative
Herpes simplex virus 1
Negative
Herpes simplex virus 2
Negative
HIV
Negative
Cytomegalovirus
Negative
Treponema pallidum
Negative
Anti-GM2 IgM antibodies
Positive
Cerebrospinal fluid Cell count (9106/L)
10
0–8
Proteins (g/L)
0.88
0.15–0.45
Glucose (mmol/L)
8.1
2.8–4.5
Chloride (mmol/L)
119.1
120–132
DWI and flair
Mild high signal in hippocampus
Electrophysiology
Resolved Decreased conduction velocity and absent F waves
EEG
Mild diffuse slowing
Brain mapping
Diffuse abnormalities
AST aspartate aminotransferase, ALT alanine aminotransferase, PT prothrombin time, aPTT activated partial thromboplastin time, HIV human immunodeficiency virus, Ig immunoglobulin, DWI diffusion-weighted imaging, EEG electroencephalogram
Our patient showed only mild mental slowness without coma; whereas he was found presenting bilateral hippocampal damage on MRI, and also showed slightly increased cells in his CSF and diffuse abnormalities in his electroencephalogram and brain mapping. This is consistent with the diagnosis of mild encephalitis/ encephalopathy. This is a first reported case where severe acute HEV infection induces both GBS and encephalitis/encephalopathy, and its severity of GBS and encephalitis/encephalopathy is unbalanced. This finding confirmed that acute severe HEV-induced GBS and brain damage may have some pathogenesis of the same and different. To our knowledge, one of the most likely mechanism leading to GBS is the ganglioside mimicry. The implication of GBS related to antiganglioside GM1 or GM2
123
antibodies have been described [3, 7]. In present the patient, the positive anti-GM2 IgM antibodies have further confirmed that HEV–GBS is closely related with ganglioside mimicry. HEV-encephalitis/encephalopathy is not completely clear, but HEV RNA sequences in serum and CSF showed differences, suggesting the possible emergence of neurotropic variants which can directly affect the nervous system [8]. In conclusion, severe acute HEV infection-induced GBS and encephalitis/encephalopathy are rare. We recommend that patients with acute GBS and abnormal liver function tests should be needed overall picking HEV screening and systemic diagnosis. Conflict of interest No potential conflict of interest relevant to this article was reported.
Neurol Sci
References 1. van den Berg B, van der Eijk AA, Pas SD et al (2014) Guillain– Barre syndrome associated with preceding hepatitis E virus infection. Neurology 82:491–497 2. Cronin S, McNicholas R, Kavanagh E et al (2011) Anti-glycolipid GM2-positive Guillain–Barre´ Syndrome due to hepatitis E infection. Ir J Med Sci 180:255–257 3. Maurissen I, Jeurissen A, Strauven T, Sprengers D, De Schepper B (2012) First case of anti-ganglioside GM1-positive Guillain– Barre´ syndrome due to hepatitis E virus infection. Infection 40:323–326
4. Hoofnagle JH, Nelson KE, Purcell RH (2012) Hepatitis E. N Engl J Med 367:1237–1244 5. Kamar N, Bendall RP, Peron JM et al (2011) Hepatitis E virus and neurologic disorders. Emerg Infect Dis 17:173–179 6. Yuki N, Hartung HP (2012) Guillain–Barre´ Syndrome. N Engl J Med 366:2294–2304 7. Cats EA, Jacobs BC, Yuki N et al (2010) Multifocal motor neuropathy: association of anti-GM1 IgM antibodies with clinical features. Neurology 75:1961–1967 8. Kamar N, Izopet J, Cintas P et al (2010) Hepatitis E virus-induced neurological symptoms in a kidney-transplant patient with chronic hepatitis. Am J Transplant 10:1321–1324
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