Guillain-Barre syndrome presented with acute flaccid paralysis, that will result in long-term neurologic deficit. Cytomegalovirus ( CMV) is one of the most common etiology to induce Guallain-Barre syndrome (GBS). Some person think CMV-GBS has another pathogenesis which is different from Campylobacter jejuni. I will present a clinical case and discuss about this topics.

1. 24-year-old mandatory soldier
Acute and progressive four limbs
weakness and numbness
for one week
R1 Jin-Yi Hsu / Chief Sheng-Huang Lin

2. Before this episode
• He could run and work before admission

3. • Bilateral hand numbness
• No weakness
5 days prior to admission

4. • Generalized weakness, but he could
1. Climbing stairs
2. Lifting heavy goods
3. Walking with slipper as usual
4. Holding on bowel
• Numbness deterioration, extend to four limbs
1. Hands
2. Ankles
3 days prior to admission

5. • Generalized weakness and numbness persisted
• Acute-onset, diffuse, non-pulsatile headache
without spinning sensation nor vomiting
• Sore throat
In ER

6. Laboratory data
CBC
WBC 7.49K
Hb 15.4
PLT 242K
N.band 3.0%
N. seg 41
Lym 19%
Mono 14%
Aty. Lym 24%
BCS
Na 140
K 3.5
Ca 2.17
Mg 2.3
CRE 1.1
GLU 116
CK 167
Liver panel
AST 140
ALT 311
ALP 74
GGT 50
TBI 0.6
DBI 0.1
ER day 1

7. Laboratory data
CBC
WBC 7.75K
Hb 16
PLT 233K
N.band 1.0%
N. seg 22%
Lym 46%
Mono 10%
Aty. Lym 20%
BCS
AST 237
ALT 436
GLU 119
CK 148
CSF
WBC count 8
Lymphocyte 83%
Gram stain N/F
India stain N/F
Acid fast stain N/F
GLU 72
TP-CSF 134.4
ER day 2

8. Laboratory data
CBC
WBC 7.75K
Hb 16
PLT 233K
N.band 1.0%
N. seg 22%
Lym 46%
Mono 10%
Aty. Lym 20%
BCS
AST 237
ALT 436
GLU 119
CK 148
CSF
WBC count 8
Lymphocyte 83%
Gram stain N/F
India stain N/F
Acid fast stain N/F
GLU 72
TP-CSF 134.4
ER day 2
Liver echo revealed only splenomegaly

9. • Admitted to GI ward due to abnormal liver
enzyme and generalized malaise.
ER days 2

10. Other history
• Neither past history nor medication history
• No flu-like/ diarrhea/ vaccination history
• No toxin/ radiation exposure
• No alcohol, betel, cigarette using
• No remarkable finidng in family history
• No remarkable birth history nor remarkable
development delay
• No remarkable finding in travel history, cluster,
contact history or sexual history
• No trauma history

11. PE / NE on admission day 2
• General appearance:
# Well-developed and well nutrition
# Acute distress due to headache
• Consciousness:
# Drowsy but oriented consciousness
# Fair attention, language, comprehension,
memory, executive function

12. PE / NE on admission day 2
• HEENT
# Grade I-II Injected tonsil with pus coating
# Palpable neck lymph node, around 1 cm over
right SCM territory.

13. PE / NE on admission day 2
• Cranial nerve:
# Intact EOM without nystagmus
# Intact light reflex without RAPD
# Normal facial sensation and masseter strength
# Mild right dropped mouth
# Difficulty to close his eyes completely ( Rt > Lt)
# Mild dysarthria but no dysphagia to liquid
# Neither uvula nor tongue deviation

14. PE / NE on admission day 2
5
5 5
5
5 5
55
5 5
5 5
4+ 4+
4+ 4+
+
+ +
+
+
+
+
+
+
+
Muscle power Deep tendon reflex
Down-ward Down-ward

15. PE / NE on admission day 2
4/8
Vibration Light touch
4/8
8/88/8
8/88/8
8/88/8
intactintact
intactintact
intactintact
intact intact

16. Thermal sense
intactintact
intactintact
intactintact
intact intact
PE / NE on admission day 2
Pinprick
intactintact
intactintact
intactintact
intact intact

17. Muscle tone
PE / NE on admission day 2
Cerebellar
H-K-S:
intact
H-K-S:
intact
F-N-F:
intact
F-N-F:
intact
Truncal ataxia:
negative
NormalNormal
Normal Normal

18. PE / NE on admission day 2
• Romberg test: Positive
• Stance:
• Stand on toe: intact
• Stand on heel: intact
• Gait
• Walk on toe: impaired
• Walk on heel: impaired
• Mild steppage gait

19. Localization

20. Nerve conduction study on admission day 2
SAPCMAP
NCV
Amplitude
Latency
F wave All absent
51.1 51.0
6.1
6.1 3.7
56.8
7.9
4.2
50
28
2.6
56.5
53
2.3
44
15
2.5
45.8
13
2.4
4.9
55.0
4.8
4.7
Median Ulnar MedianUlnarMedian Ulnar MedianUlnar

21. Nerve conduction study on admission day 2
SAPCMAP
NCV
Amplitude
Latency
F wave
45.3 44.4 44.5 43.5
6.7 5.5 6.77.7
6.0 5.9 8.05.9
50 48.3
24 38
2.8 2.9
H reflex
Fibular Tibial FibularTibial Sural Sural
All absent
All absent

22. Nerve conduction study
Diffuse prolonged distal motor latency
Absent F response & H reflex
Mild decreased motor velocity, especially lower limbs
Mild decreased motor amplitude
Diffusely demyelinating polyradiculoneuropathy

23. Nerve conduction study 5 days before admission
SAPCMAP
NCV
Amplitude
Latency
F wave
57.3 52.0 58.3 56.8 56.0 58.3
7.2 25 25 3244
4.2 3.0
58
8.2
3.4 2.6 2.5 2.42.4
6.1
52.8
4.0
7.0
Median Ulnar MedianUlnarMedian Ulnar MedianUlnar
27.528 29.230
4.2

24. Laboratory data admission day 2
Hepatic virus
HAV IgM Negative
HBsAg Negative
HBc IgM Negative
Anti-HCV Negative
Other virus
CMV IgM Positive
CMV IgG Positive
CMV pp67 Positive
EBV IgM Negative
VZV Negative
HSV Negative
HIV Ag/Ab Negative
Atypical infection
O.Tsuts PCR Negative
Lepto. IgG+M Negative
Toxo. godni Negative
RPR Non-reative
Crypto. Ag Negative
M. Pneu. IgM Negative
Cold HA 1:256

25. Laboratory data admission day 2
Hepatic virus
HAV IgM Negative
HBsAg Negative
HBc IgM Negative
Anti-HCV Negative
Other virus
CMV IgM Positive
CMV IgG Positive
CMV pp67 Positive
EBV IgM Negative
VZV Negative
HSV Negative
HIV Ag/Ab Negative
Atypical infection
O.Tsuts PCR Negative
Lepto. IgG+M Negative
Toxo. godni Negative
RPR Non-reative
Crypto. Ag Negative
M. Pneu. IgM Negative
Cold HA 1:256
Add ganciclovir using

26. • Headache deterioration, accompanying with
spinning sensation and persistent vomiting
• Difficulty to close eyes with increasing tear
secretion and saliva drooling from right mouth
angle
• Unsteady gait with difficulty to stand on toes
• Dysarthria and dysphagia to liquids
Admission day 3

27. PE / NE on admission day 3
• Cranial nerve:
# Intact EOM without nystagmus
# Intact light reflex without RAPD
# Normal facial sensation and masseter strength
# Facial diplegia ( Rt > Lt)
# Dysarthria and dysphagia to liquid
# Neither uvula nor tongue deviation

28. PE / NE on admission day 3
5
4+ 4+
5
4+ 4+
55
5 5
5 5
4 4
4 4
+
+ +
+
+
+
+
+
+
+
Muscle power Deep tendon reflex
Down-ward Down-ward

29. • He could not stand and walk without assistance
• GBS disability scale 3
• He started to receive plasmapheresis
Admission day 4

30. Nerve conduction study admission day 15
SAPCMAP
NCV
Amplitude
Latency
44.4 52.0 54.2 45.8 45.8 59.1
4.5 4.3 7.3 154.1
7.8 4.8
54.1
5.3
6.1 2.4 2.4 2.22.4
1.6
47.8
6.2
1.6
Median Ulnar MedianUlnarMedian Ulnar MedianUlnar
F wave All absent
Temporal dispersion

31. Nerve conduction study admission day 15
SAPCMAP
NCV
Amplitude
Latency
45.3 40.3 41.2 41.4
2.8 1.6 1.30.3
6.6 6.7 12.89.7
50 48.3
23 23
2.8 2.9
Fibular Tibial FibularTibial Sural Sural
F wave
H reflex
All absent
All absent
Temporal dispersion

32. Nerve conduction study
Diffuse prolonged distal motor latency
Absent F response & H reflex
Decreased motor velocity
Decreased motor amplitude with temporal dispersion
Diffusely demyelinating polyradiculoneuropathy

33. Final diagnosis
Acute inflammatory demyelinating
polyradiculoneuropathy
CMV infective mononucleosis
CMV hepatitis
CMV-related labyrinthinitis

34. Any questions?

35. Natural course of GBS
Antecedent infection

39. Autoantibody-mediated
( Antecedent infection)

40. Treatment policy
Plasma exchange

41. Treatment policy
IVIG

42. Treatment policy
Plasma exchange IVIG

43. GBS disability scales
0
1
2
3
4
5
6
Healthy
Minor symptoms and capable of running
Able to walk 10 m without assistance
Able to walk 10 m with assistance
Bedridden or wheelchair-bound
Requiring assisted ventilation
Dead

44. GBS disability scales
0
1
2
3
4
5
6
Healthy
Minor symptoms and capable of running
Able to walk 10 m without assistance
Able to walk 10 m with assistance
Bedridden or wheelchair-bound
Requiring assisted ventilation
Dead

45. Natural course of GBS

46. Natural course of GBS
CMV pp67

47. Acute infection?

48. Acute infection?
IgG
IgM

49. Acute infection?
IgG
IgM
IgM IgG Condition
+ - Acute infection
+ + Recent infection
- + Previous infection

50. Acute infection?
IgG
IgM

51. Our patient

52. Cytomegalovirus-mediated
( Coexistent infection)

53. Cytomegalovirus-mediated
( Coexistent infection)
Hadden et al (2001)
T cell activation and migration

54. CMV -> T-cell first -> Autoantibody?
( Vicious cycle?)

55. CMV -> T-cell first -> Autoantibody?
( Vicious cycle?)

56. CMV -> T-cell first -> Autoantibody?
( Vicious cycle?)

57. Ganciclovir
CMV -> T-cell first -> Autoantibody?
( Vicious cycle?)

58. Real world
IgM s/p ganciclovir
IgM

59. Hypothesis
IgM s/p ganciclovir?
IgM

60. GBS disability scales
0
1
2
3
4
5
6
Healthy
Minor symptoms and capable of running
Able to walk 10 m without assistance
Able to walk 10 m with assistance
Bedridden or wheelchair-bound
Requiring assisted ventilation
Dead
Only observation?

61. Cytomegalovirus-mediated
( Coexistent infection)
Hadden et al (2001)
T cell activation and migration

62. GBS after CMV infection
Steroid pulse therapy??

63. GBS after CMV infection
GBS after other infection

64. GBS after CMV infection
Younger
Persistent
disability
Sensory
deficit

65. Epidemiology of CMV infection
Infancy
Young adult
Grandmother

66. GBS after CMV infection
Facial palsy
Elevated liver
enzymes
Isolated
headache

67. CMV-GBS
Young-adult onset
Treatable etiology
Elevated liver enzyme
Facial palsy
More disability and sensory deficit
T-cell mediated?
R1 Jin-Yi Hsu
Thanks for your attention

68. Level of diagnostic certainty

69. Nerve conduction study

70. Nerve conduction study 5 days before admission
SAPCMAP
NCV
Amplitude
Latency
F wave
57.3 52.0 58.3 56.8 56.0 58.3
7.2 25 25 3244
4.2 3.0
58
8.2
3.4 2.6 2.5 2.42.4
6.1
52.8
4.0
7.0
Median Ulnar MedianUlnarMedian Ulnar MedianUlnar
27.528 29.230
4.2

71. Nerve conduction study on admission day 2
SAPCMAP
NCV
Amplitude
Latency
F wave All absent
51.1 51.0
6.1
6.1 3.7
56.8
7.9
4.2
50
28
2.6
56.5
53
2.3
44
15
2.5
45.8
13
2.4
4.9
55.0
4.8
4.7
Median Ulnar MedianUlnarMedian Ulnar MedianUlnar

72. Nerve conduction study on admission day 2
SAPCMAP
NCV
Amplitude
Latency
F wave
45.3 44.4 44.5 43.5
6.7 5.5 6.77.7
6.0 5.9 8.05.9
50 48.3
24 38
2.8 2.9
H reflex
Fibular Tibial FibularTibial Sural Sural
All absent
All absent

73. Nerve conduction velocity admission day 15
SAPCMAP
NCV
Amplitude
Latency
44.4 52.0 54.2 45.8 45.8 59.1
4.5 4.3 7.3 154.1
7.8 4.8
54.1
5.3
6.1 2.4 2.4 2.22.4
1.6
47.8
6.2
1.6
Median Ulnar MedianUlnarMedian Ulnar MedianUlnar
F wave All absent
Temporal dispersion

74. Nerve conduction velocity admission day 15
SAPCMAP
NCV
Amplitude
Latency
45.3 40.3 41.2 41.4
2.8 1.6 1.30.3
6.6 6.7 12.89.7
50 48.3
23 23
2.8 2.9
Fibular Tibial FibularTibial Sural Sural
F wave
H reflex
All absent
All absent
Temporal dispersion