1. Intern Seminar
Int 李俊毅/ VS 謝奇璋

2. Acute-onset left side weakness
Basic information
6Y 6M Boy
No underlying history
Received vaccine as scheduled
Acute-onset left side weakness

3. Left arm weakness and limping gait
Present illness
11/26 LMD Intermittent fever with productive cough Bilateral lower leg pain Drowsiness
12/1 ER
Left arm weakness and limping gait
No headache, neck stiffness, sore throat,
oral ulcer, nor skin rash

4. Physical examination
Consciousness: slow response but oriented HEENT: conjunctiva: not pale sclera: anicteric LAP at left level IIA and right level III Chest: symmetric expansion, clear breathing sound regular heart beat, no murmur Abdomen: soft and flat normoactive bowel sound no tenderness Extremities: freely movable, no pitting edema Skin: no defect

5. Cranial nerves: no abnormality
Neurological examination
Cranial nerves: no abnormality
Muscle power
Deep tendon reflex 5 4 3 4 5 4 3 4

6. Weak face over left side Spasticity over left side Finger-Nose-Finger:
Neurological examination
Weak face over left side
Spasticity over left side
Finger-Nose-Finger:
Left upper limb dysmetria
Limping gait

7. Lab data

8. Sharp CP angle, No active pneumonia patch

9. Cold agglutinin test : Positive
Serologic test
12/1: M. pneumoniae Ab IgM: Positive
12/2: M. pneumoniae Ab 1:160
Cold agglutinin test : Positive
HSV1 Ab IgG: negative
HSV2 Ab IgG: negative
HSV 1&2 Ab IgM: 1:1.255
EBV Ab: negative

10. 12/2 Coxsackie virus Type B3
from throat swab and anus swab
Anus swab Nucleic acid detection
Enterovirus 71 : negative
No virus isolated from CSF
CSF Nucleic acid detection
HSV-1 negative
HSV-2 negative
VZV negative

11. Multifocal lesion on T2 FLAIR
Multifocal T2WI/T2FLAIR hyperintense at right midbrain, bilateral dentate nuclei and left hippocampus as well as right insular cortex.
Multifocal lesion on T2 FLAIR

12. Multifocal lesion on T2 FLAIR
Multifocal T2WI/T2FLAIR hyperintense at right midbrain, bilateral dentate nuclei and left hippocampus as well as right insular cortex.
Multifocal lesion on T2 FLAIR

13. Multifocal lesion on T2 FLAIR
Multifocal T2WI/T2FLAIR hyperintense at right midbrain, bilateral dentate nuclei and left hippocampus as well as right insular cortex.
Multifocal lesion on T2 FLAIR

14. Abnormal awake and sleep EEG
12/2
Abnormal awake and sleep EEG
indicates mild cortical dysfunction
over posterior hemispheres

18. Neurologic Image
12/6
Myelitis mixed with meningitis over thoracolumbar spinal cord
Interval progression bilateral midbrain with small cystic change at right side
IVIG

20. 12/7: M. pneumoniae Ab 1:80 12/11: M. pneumoniae Ab 1:80
Serologic test
12/7: M. pneumoniae Ab 1:80
12/11: M. pneumoniae Ab 1:80
HSV1 Ab IgG: 4.684
HSV2 Ab IgG: 0.802

21. MBD on 12/16 OPD Follow-up Rehabilitation

22. Acute Childhood Encephalitis Mycoplasma pneumoniae

23. Absence of respiratory symptoms
Introduction
Mycoplasma pneumoniae
Extrapulmonary manifestation
> 5歲， respiratory
40% community acquired pneumonia
25 % 有Extrapulmonary
3/14 DAY AFTER SYMPTOMS
Encephalitis 均出現在 URI 後 9.6天
佔 acute encephalitis 的 8%左右
Enterovirus, herpes virus, and mp
60 %有 long term neurological sequela
CV Derma GI Arthritis
Mycoplasma: URI, bronchitis pneumonia, Asthma AE
Absence of cell wall => pleomorphic, cross filter, parasite, extracellular
Absence of respiratory symptoms
Mycoplasma pneumoniae—an emerging extra-pulmonary pathogen, Clinical Microbiology and Infection, 2008

24. +2 Encephalitis Fever >38*c Pleocytosis Seizure Focal Finding EEG
Definitions
Fever >38*c
Encephalitis
Pleocytosis
Seizure
Focal Finding +2
EEG
Encephalitis and meningoencephalitis are most common
1-10% child encephalits from MP infection
Prodrome 後 2-14 ,9.6天
2/3 long term sequela
Enterovirus, herpes virus, and mp
Encephalopathy
MRI
Acute Childhood Encephalitis and Mycoplasma pneumoniae,
Clinical Infectious Diseases Volume 32, Issue 12Pp

25. Direct Indirect Vascular occlusion Extrapulmonary Manifestation
Direct type: locally induced cytokines
Classification of Extrapulmonary Manifestation Due to Mycoplasma pneumoniae Infection on the Basis of Possible Pathogenesis, Front. Microbiol., 28 January 2016

26. on local site through cytokine
Extrapulmonary Manifestation
Inflammation
on local site through cytokine
Early –onset encephalitis
Direct
Genome in CSF
Direct type: locally induced cytokines
Classification of Extrapulmonary Manifestation Due to Mycoplasma pneumoniae Infection on the Basis of Possible Pathogenesis, Front. Microbiol., 28 January 2016

27. Late–onset encephalitis Multifocal lesion Normal glucose, protein
Extrapulmonary Manifestation
Inflammation through
Auto-immunity
Molecular mimicry
Late–onset encephalitis
Multifocal lesion
Normal glucose, protein
Indirect
Indirect
Lymphocytic CSF Pleocytosis, milder than viral etiologies
Normal glucose normal protien
Multifocal symptoms with or without MRI finding T2 flair signal
Abscene of M, pneumoniae
Molecular mimicry
Auto-antibody in CSF
Classification of Extrapulmonary Manifestation Due to Mycoplasma pneumoniae Infection on the Basis of Possible Pathogenesis, Front. Microbiol., 28 January 2016

28. Vasculitic or thrombotic
Extrapulmonary Manifestation
Vasculitic or thrombotic
Striatal necrosis
Stroke
Psychologic disorder
Vascular occlusion
Direct type: locally induced cytokines
Classification of Extrapulmonary Manifestation Due to Mycoplasma pneumoniae Infection on the Basis of Possible Pathogenesis, Front. Microbiol., 28 January 2016

29. Classification of Extrapulmonary Manifestation Due to Mycoplasma pneumoniae
Infection on the Basis of Possible Pathogenesis, Front. Microbiol., 28 January 2016

30. Mechanism Pathogenesis of Neurologic Manifestations of
Local damage, cytotoxicity, cyto-adherence, hydrolytioc enzyme
Pathogenesis of Neurologic Manifestations of
Mycoplasma pneumoniae Infection, Pediatric Neurology 2009

31. Mechanism Antibody Responses to Mycoplasma pneumoniae:
Molecular mimicry, survival within cell
Antibody Responses to Mycoplasma pneumoniae:
Role in Pathogenesis and Diagnosis of Encephalitis?, PLOS pathogen, 2014

32. Galactocerebroside Mechanism
Molecular mimicry, survival within cell
GalC: galactocerebroside
Ganglioside quadrosialo
Ganglioside monosialo
Galactocerebroside
Antibody Responses to Mycoplasma pneumoniae:
Role in Pathogenesis and Diagnosis of Encephalitis?, PLOS pathogen, 2014

33. *M. pneumoniae in CSF (PCR, Culture) and/or
Groups
Probable 11
*M. pneumoniae in CSF (PCR, Culture)
and/or
*M. pneumoniae in throat specimens (PCR, Culture)
and Serologic test (positive)
Possible 9
M. pneumoniae in throat specimens (PCR, Culture)
or Serologic test (positive)
CSF 跟throat 都要做 (從來都沒有兩者都positive 過
Probable 組 有很高的coinfection rate 7/11
Acute Childhood Encephalitis and Mycoplasma pneumoniae,
Clinical Infectious Diseases, 2011

34. 2/3 prodromal respiratory symptoms 2/3 focal infiltration
Manifestations
In both groups
2/3 prodromal respiratory symptoms
2/3 focal infiltration
CSF positive,
1/3 have respiratory symptoms
Cough, sore throat, hoarseness fever headache myalgia malaise
Prodromal illness duration
CSF positive < CSF negative
Acute Childhood Encephalitis and Mycoplasma pneumoniae,
Clinical Infectious Diseases, 2011

35. EEG and Neuroimaging findings
Probable: 85% has EEG and neuroimaging abnormalities 8/11 neurologic deficit: 1.8 years 4/8 need long-term anticonvulsant treatment
Possible:
35% has EEG and neuroimaging abnormalities
5/9 neurologic deficit
1/5 need long-term anticonvulsant treatment
Mild cognitive impairment in seizure
Hemiparesis
Dysphagia
Dysarthria
Truncal ataxia
2/3 Neurologic sequelae
Acute Childhood Encephalitis and Mycoplasma pneumoniae,
Clinical Infectious Diseases, 2001

36. History Serologic test PCR and Antibody of CSF PCR of throat sample
Diagnosis
History Serologic test PCR and Antibody of CSF PCR of throat sample
PCR faster than serologic report but can not distinguish between infection or colonization
Serologic time consuming, cross reaction with other M
Antibody Responses to Mycoplasma pneumoniae:
Role in Pathogenesis and Diagnosis of Encephalitis?, PLOS pathogen, 2014

37. Antibiotics Corticosteroid Immunoglobulins Anticoagulation ---
Treatment
Antibiotics
Corticosteroid
Immunoglobulins
Anticoagulation
---
Plasma exchange
Classification of Extrapulmonary Manifestation Due to Mycoplasma pneumoniae
Infection on the Basis of Possible Pathogenesis, Front. Microbiol., 28 January 2016

38. Back to our case
URI symptoms before neurological deficit Serologic positive, PCR of CSF: negative M. pneumoniae antibody in CSF? Prognosis: Need long- term rehabilitation

39. Immunomodulatory combine antibiotics treatment
Take home message
Extrapulmonary manifestation of M. pneumoniae infection may occur without URI symptoms
Serologic test
PCR and Culture of CSF and throat samples
M. pneumoniae antibody in CSF
Immunomodulatory combine antibiotics treatment
Intern 李俊毅

40. Reference
Classification of Extrapulmonary Manifestation Due to Mycoplasma pneumoniae Infection on the Basis of Possible Pathogenesis, Front. Microbiol., 28 January 2016 Antibody Responses to Mycoplasma pneumoniae: Role in Pathogenesis and Diagnosis of Encephalitis?, PLOS pathogen, 2014 Mycoplasma pneumoniae—an emerging extra-pulmonary pathogen, Clinical Microbiology and Infection, 2008 Acute Childhood Encephalitis and Mycoplasma pneumoniae, Clinical Infectious Diseases, 2001 Pathogenesis of Neurologic Manifestations of Mycoplasma pneumoniae Infection, Pediatric Neurology 2009