This case presentation discusses a 59-year-old woman who was admitted with weakness and neurological symptoms. She had a history of pneumonia and was initially diagnosed with transverse myelitis. Her condition worsened, so further investigations were done. MRI showed lesions in the spinal cord and brainstem. Testing found elevated mycoplasma titers, leading to a diagnosis of acute disseminated encephalomyelitis (ADEM) secondary to Mycoplasma pneumoniae infection. She was treated with steroids, plasma exchange, and antibiotics, and showed gradual improvement in her neurological function.
2. Presentation
• 59 year old lady
• 6/6/16
▫ Admitted with cough, SOB and generally unwell
▫ Admitted to ITU with severe T1RF requiring CPAP.
Managed for severe CAP
• 18/6/16- Discharged to the ward after 2 weeks with
improvement in overall self
• 6/7/16- Discharged back home, passing PT
assessment and community PT organised. Some
generalised weakness described but attributed to
ITU stay and severity of illness.
3.
4.
5. Presentation
• 7/7/16 – Presented to Southend A&E with
‘unsteadiness’ and ‘slurred speech’. Re-admitted
as failed discharge
• Worsened weakness, particularly in the legs.
Dysarthia and blurred vision.
• Progressively worsening neurology during
admission prompting investigation
6. Presentation
• Background
▫ Mobile and independant in ADLs. Lived alone and
rarely left the house. No NOK available. Was
thinking about moving to sheltered accommodation
as finding life increasingly difficult
▫ PMH – Large abdominal hernia, T2DM, HTN
▫ SH – Non smoker, limited ETOH, no recreational
drugs
▫ DH – Gliclazide, Ramipril, Atorvastatin
▫ FH – Nil significant
7. Examination
• Observations stable. Apyrexial
• Chest – Bibasal crackles. HS I + II +O
• Abdomen – Soft, large reducible hernia
• MSK – Pitting oedema shins
8. Examination
• Cranial nerves
▫ Mild loss of smooth pursuit
▫ No opthalmoplegia. ?RAPD R
▫ Fundoscopy difficult to perform
▫ Cranial nerves examined otherwise intact
9. Examination Right Left
Hip Flexion 2/5 2/5
Hip Extension 2/5 2/5
Knee Flexion 2/5 2/5
Knee Extension 2/5 2/5
Ankle Dorsiflexion 4-/5 4/5
Plantarflexion 4/5 4/5
EHL 4/5 4+/5
Tone N +
11. Examination
• Sensation:
Pin prick intact in all myotomes
Vibration intact in UL, reduced to the knee
bilaterally in lower limbs
Proprioception reduced to ankle bilaterally
12. Examination
• Unable to assess gait (unable to walk)
• Dysmetria L>R. Dysdiadokinesis L
• Dysarthia
16. Investigations
• MRI HEAD: There has been a reduction in the extent of T2/FLAIR signal
abnormality in the midbrain, superior cerebellar peduncles and at the right
middle cerebellar peduncle/pons. The superior cerebellar peduncles have
reduced in volume since 20/7/2016 and the previously shown pathological
enhancement in these regions is also less conspicuous on the current
imaging in keeping with an evolving inflammatory process. No new focal
FLAIR abnormality is identified and there are no areas of restricted
diffusion. No new intracranial abnormality is shown.
• MRI WHOLE SPINE: As before, there is extensive signal abnormality
throughout the lower cervical and thoracic spinal cord with a confluent
segment extending from T7-T10 and more patchy involvement in the
cervicothoracic cord superiorly. The corresponding axial slices show
predominantly peripheral lesions and, accounting for artefact on the post-
contrast imaging, there is no convincing associated enhancement. There are
no definite new cord lesions.
• CT CAP - ?Liver cirrhosis
17. Investigations
• Microbiology
▫ Virology –CMV + VZV detected, otherwise NAD
▫ Cultures –NAD
• Immunology
▫ Autoimmune screen NAD (ANCA only mild
positive)
▫ Neurology Antibody screen – NAD
▫ Protein electrophoresis – Polyclonal bands
19. Investigations
• VEP -Pattern reversal visual evoked potentials
show a well formed response from the left eye
with a normal P100 latency. However, there is
no reproducible response from the right eye
• SEPs -In summary, the upper limb
somatosensory evoked potentials are normal.
The abnormalities in the lower limbs (borderline
delayed cortical response (P40) when
stimulating the right tibial nerve) could be in
keeping with central demyelination.
21. Management
• 21/7/6 – Commenced on 3 days course IVMP
followed by PO Prednisolone
• 28/7/16- Transferred to RLH for further
investigation and management
• Managed with 4 days of PLEX on admission with
weaning PO steroids
• Noticeable improvement in neurology throughout
admission
• On admission : bedbound, slurring speech
• Eventually managing to mobilise with a frame with
minimal assistance with normalising speech
22. Management
• Spiking temperatures. No organism found
▫ WCC persistently raised – likely reactive
▫ ?Murmur TTE + TOE –NAD
• Although improved neurology, she remained
very anxious and tearful about prospect of going
back home. She was to be assessed for
residential home.
23. Management
• FBC normalised through admission
• No further spikes in temperature
• Seen by psychiatry who commenced Mirtazipine
27. Acute disseminated encephalomyelitis
(ADEM)
• ADEM is a rare autoimmune disease
• Associated with a sudden, widespread attack of
inflammation in the brain and spinal cord
• Also leads to acute demyelination
• Neurologic manifestations include both motor
and sensory impairment as well as autonomic
dysfunction
29. Parainfectious ADEM
• ADEM that is preceded by an infectious process
- Preceding Infection – Often Viral
- Common bacterial
include Streptococcus, Mycoplasma
pneumoniae and Haemophilus influenzae
- Vaccination
30. Mycoplasma and ADEM
• Neuroinvasion
• Stamm et al 2008
• Parainfectious
• Gupta et al 2007
31. Stamm et al 2008
• 45-year-old, previously healthy man had fever
and cough with non-purulent sputum.
• Bilateral basal pneumonia was diagnosed and
treated with clarithromycin
• Within 4 days developed a rapidly ascending
polyradiculoneuropathy resulting in
tetraparesis, facial palsy and ophthalmoplegia
32. Stamm et al 2008 cont…
• Viral PCR Negative
• Bacterial and Viral serology negative
CSF Day 8 WCC total
protein
glucose
4.3 mmol/L 43 (89%
Neutrophils)
1.3 g/L 4.3 mmol/L
CSF Day 15 WCC total
protein
glucose
794 (84%
Neutrophils)
4.6 g/L 1.5 mmol/L.
33. Stamm et al 2008 cont…
• CT Head - brain oedema and
inflammatory/demyelination lesions in the
subcortical white matter
• EMG - severe peripheral axonal neuropathy.
• No antiganglioside (GM) 1 or anti-GM2
antibodies
34. Stamm et al 2008 cont…
• Dx- polyradiculoneuropathy (atypical Guillain-Barré
syndrome) and acute encephalitis as complications
of bilateral pneumonia caused by M. pneumoniae
• Mx- Clarithromycin with amoxicillin and ceftriaxone
then given IVIG (0.4 g/ kg bodyweight/day for 5
days).
• He died of intractable cerebral edema on day 17 of
illness, 10 days after the onset of neurologic
symptoms.
35. Stamm et al 2008 cont…
• At Autopsy M. pneumoniae RNA detected in brain
tissue by nucleic acid hybridization
• Suggests a role of invasion of the CNS by the
organism itself
• Neuroinvasion is more prevalent in patients who
have an early onset neurologic complications
• Effects unclear the organism may either cause direct
damage or trigger a more violent immunologic
reaction
36. Gupta et al 2009
• A 41-year-old man presented with a 2-week history of
lethargy, chills, nausea, vomiting and a productive
cough.
• CT Chest showed - Right lower lobe pneumonia.
• Initially treatment - IV Amoxicillin and Doxycycline
• One week later he developed lower limb weakness, which
progressed to complete paraplegia with urinary retention
• Subsequent six days later he developed patchy visual loss
in both eyes. Fundoscopy showed swollen optic discs
bilaterally.
37. Gupta et al 2009 cont…
• Serology suggested recent Mycoplasma pneumoniae infection
with a M. pneumoniae agglutination antibody titre of 1 in
1280.
• MRI - Increased T2 signal and swelling of the cord extending
from T3 to T8, as well as several white matter lesions in the
periventricular white matter of the cerebral hemispheres
• Cerebrospinal fluid (CSF) examination showed a
mononuclear pleocytosis of 24 mononuclear cells per
microlitre
• A diagnosis of acute disseminated encephalomyelitis (ADEM)
secondary to M. pneumoniae was suspected
38. Gupta et al 2009 cont…
• IV methylprednisolone was commenced at 1 g daily.
• No clinical improvement over the next 3 days so treatment
changed to high-dose oral prednisolone and plasma exchange.
• A total of 10 exchanges was carried out over 3 weeks. Vision
improved to and he regained normal lower limb power and
sphincter control over the next 2 months.
• The dramatic response to plasma exchange in the present case
supports a hypothesis that the ADEM was secondary to an
immune complex-mediated vasculopathy
39. Aetiology of Parainfectious
mycoplasma
• Neurologic manifestations occur approx 10/7 after the onset
of the initial respiratory tract infection
• Cross reaction of M. pneumoniae-induced antibodies with
brain tissue (as it does with RBC for cold agglutination)
• Antineuronal antibodies have been demonstrated in M.
pneumoniae infections with or without CNS disease
(Nishimura et al 1996)
• Auto-antibodies deposit as immune complexes in the CNS
causing myelitis
40. Investigations
• CSF - CSF Gram stain and bacterial cultures are usually negative.
The CSF leukocyte count is elevated predominantly mononuclear
pleocytosis and most cases of M. pneumoniae-associated ADEM
have a normal CSF/serum glucose ratio
• Serologic testing:
– Mycoplasma Serology or PCR. IgM antibodies can be detected
shortly after the acute infection, may persist for up to 6 months and
are followed by IgG titer elevation
- A positive cold haemagglutinins titer. Presence of cold
hemagglutinins is non-specific for M. pneumoniae disease and they
can be seen in other viral infections, collagen vascular diseases and
a variety of systemic disorders
• MRI Head/ spinal cord - Characteristic findings of an ADEM are
patchy asymmetric or diffuse signal changes of gray and white
matter as well as multifocal, asymmetric foci of high signal intensity
on flair and T2 weighted images
41. Management Options
• Antibiotic therapy has been temporally associated with
clinical improvement in some cases of M. pneumoniae-
associated ADEM/ATM
• Corticosteroids are useful in the initial management of ADEM
and transverse myelitis with their main contribution being the
shortening of the duration of neurologic findings (only if no
infective source identified).
• Intravenous immune globulin is usually used in ADEM cases,
which fail to respond to corticosteroids.
• Plasmapheresis has been used as a last therapeutic measure
42. Conclusion
• Patient presented with worsened neurology after
a severe chest infection
• Cerebellar + Thoracic Spine involvement
• Blood tests largely unremarkable except for
Mycoplasma serology
• Importance of translating wide differential into
investigations
43. References
• Ning MM, Smirnakis S, Furie KL, Sheen VL. Adult acute disseminated encephalomyelitis associated with
poststreptococcal infection. J Clin Neurosci. 2005;12:298–300.
• Höllinger P, Sturzenegger M, Mathis J, Schroth G, Hess CW. Acute disseminated encephalomyelitis in
adults: a reappraisal of clinical, CSF, EEG, and MRI findings. J Neurol. 2002;249:320–9.
• Beleza P, Ribeiro M, Pereira J, Ferreira C, Jordão MJ, Almeida F. Probable acute disseminated
encephalomyelitis due toHaemophilus influenzae meningitis. Dev Med Child Neurol. 2008;50:388–91
• Stamm B, Moschopulos M, Hungerbuehler H, Guarner J, Genrich GL, Zaki SR. Neuroinvasion
by Mycoplasma pneumoniae in acute disseminated encephalomyelitis. Emerg Infect Dis. 2008;14(4):641-
3
• Gupta A, Kimber T, Crompton JL, Karagiannis A. Acute disseminated encephalomyelitis secondary to
Mycoplasma pneumoniae. Intern Med J. 2009 Jan;39(1):68-9
• Tsiodras S, Kelesidis T, Kelesidis I, Voumbourakis K, Giamarellou H. Mycoplasma pneumoniae-
associated myelitis: a comprehensive review. Eur J Neurol. 2006 Feb;13(2):112-24.
• Nishimura M, Saida T, Kuroki S, Kawabata T, Obayashi H, Saida K, Uchiyama T. Post-infectious
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