Mycoplasma
Mycoplasma pneumoniae is one of the leading causes of
pneumoniae–
Associated Transverse
Myelitis and
Rhabdomyolysis
Wen-Chin Weng, MD*,
Steven Shinn-Forng Peng, MD†,
Shi-Bing Wang, MD*,
Yen-Ting Chou, MD‡, and
Wang-Tso Lee, MD, PhD*
Mycoplasma pneumoniae is a common cause of respira-
tory tract infection. Extrapulmonary manifestations of
M. pneumoniae infection are also common. The present
case is that of a previously healthy 4-year-old boy who
displayed a novel simultaneous onset of both acute
rhabdomyolysis and transverse myelitis associated
with an infection of M. pneumoniae. He had no preced-
ing symptoms or signs of respiratory tract infection.
Intravenous immunoglobulin (1 g/kg per day) for 2
days was prescribed initially for the deterioration of
neurologic condition. His rhabdomyolysis resolved
without complication, but neurologic sequelae re-
mained during 2 years of follow-up. Evaluation for M.
pneumoniae infection is recommended in patients with
idiopathic rhabdomyolysis and transverse myelitis,
even if in the absence of antecedent respiratory symp-
toms. Ó 2009 by Elsevier Inc. All rights reserved.
Weng WC, Peng SS, Wang SB, Chou YT, Lee WT. Myco-
plasma pneumoniae–associated transverse myelitis and
rhabdomyolysis. Pediatr Neurol 2009;40:128-130.
From the Departments of *Pediatrics and †Medical Imaging, National
Taiwan University Hospital, Taipei, Taiwan, and the ‡Department of
Pediatrics, Cardinal Tien Hospital Yung Ho Branch, Taipei, Taiwan.
128 PEDIATRIC NEUROLOGY Vol. 40 No. 2
doi:10.1016/j.pediatrneurol.2008.10.009  0887-8994/09/$—see front matter
Introduction
respiratory tract infection of varying severity [1]. Extrapul-
monary manifestations of M. pneumoniae infection are also
common, and involvement of every organ system has been
described [1,2]. Central nervous system involvements are
the most frequent complications associated with M. pneu-
moniae infection [1-3]. With respect to musculoskeletal
involvement, polyarthralgia and mild myalgia are common,
but rhabdomyolysis is very rare, and only six previous
cases, including both adults and children, have been re-
ported [4-8]. The combination of M. pneumoniae-related
rhabdomyolysis and transverse myelitis documented with
neuroimaging is a novel finding. Described here is the
case of a 4-year-old boy presenting with acute rhabdomyol-
ysis in association with M. pneumoniae infection. He also
developed symptoms and signs of spinal cord lesions, and
neuroimaging documented the existence of transverse my-
elitis. Based on clinical and laboratory results, Immune-me-
diated pathophysiology was postulated.
Case Report
A boy aged 4 years and 10 months was quite healthy until 3 days before
his admission, when he developed itching sensation over both legs. On the
day of admission, he developed abdominal pain and myalgia over both
legs, followed by muscle weakness over both legs and also acute urinary
retention. The medical and family histories were unremarkable, except
for 1 day of fever occurring 7 days before admission. The patient had no
prior episodes similar to this one, and he did not take any medication before
admission. There was no history of upper respiratory tract infection, fever,
recent travel, recent trauma, pet exposure, or violent exercise. On the first
day of admission, the physical examination revealed a supple neck, no skin
rash, no hepatosplenomegaly, and no erythema or induration of his joints.
He was conscious and well oriented. He was afebrile, with a respiratory rate
of 24 breaths per minute, heart rate of 112 beats per minute, and blood pres-
sure of 106/59 mm Hg. Neurologic examination revealed increased deep
tendon reflex, over both knees, and ankle jerks.
The initial laboratory studies revealed white blood cell count of 10,260/
mL, hemoglobin at 12.8 g/dL, platelet count of 366,000/mL, and C-reactive
protein at 2.27 mg/dL (normal value, <0.8 mg/dL). Creatine kinase was
elevated, at 15,855 U/L; uric acid was elevated, at 10.4 mg/dL; and lactate
dehydrogenase was elevated, at 1233 IU/L. A slight decrease of serum cal-
cium (1.93 mmol/L; normal 2.02-2.60 mmol/L), increases of serum aspar-
tate aminotransferase (113 U/L) and alanine aminotransferase (52 U/L)
Communications should be addressed to:
Dr. Lee; Department of Pediatrics; National Taiwan University Hospital;
No. 7 Chung-Shan South Road; Taipei, Taiwan.
E-mail: leeped@hotmail.com
Received July 30, 2008; accepted October 13, 2008.
Ó 2009 by Elsevier Inc. All rights reserved.
were also found. The serum level of other electrolytes, albumin, bilirubin,
amylase, lipase, blood urea nitrogen, and creatinine were normal. Immuno-
logical findings for antinuclear antibody, complement 3, and complement 4
were all within normal limit. Under the impression of rhabdomyolysis, in-
travenous hydration, alkalization, and mannitol were prescribed.
On the day of admission, the patient had developed progressive weak-
ness of the upper extremities, and neurologic examination revealed
absence of the abdominal reflex and the cremasteric reflex. Magnetic res-
onance imaging of the spinal cord was performed. The T2-weighted images
demonstrated abnormal high signal intensities at the level from cervical to
lumbar cord, with mild swelling (Fig 1), which was compatible with the di-
agnosis of transverse myelitis. Lumbar puncture was performed and cere-
brospinal fluid evaluation showed a white blood cell count of 40
leukocytes/mm3 (32 lymphocytes and 8 neutrophils), protein 44.4 mg/
dL, and glucose 50 mg/dL. Results were negative from the rapid tests in
cerebrospinal fluid for Neisseria meningitidis, Streptococcus pneumoniae,
Haemophilus influenzae, Streptococcus group B, and Escherichia coli.
Cranial magnetic resonance imaging revealed no abnormal signal, and
the visual evoked potentials from both eyes were within normal limits,
which excluded the possibility of Devic disease (i.e., neuromyelitis optica)
or a first episode of multiple sclerosis. Peripheral nerve conduction velocity
testing yielded normal results. For progressive symptoms and signs of spi-
nal cord inflammation, intravenous immunoglobulin (1 g/kg per day) was
then administered for 2 days, starting on the 2nd day of admission.
Subsequent investigation by polymerase chain reaction and serology for
viral infection, including herpes simplex virus, human herpes virus-6 and -7,
and enteroviruses, all yielded negative results. Neither virus nor bacteria were
isolated from cerebrospinal fluid, throat swab, or rectal swab. At admission,
the M. pneumoniae antibody titers determined by enzyme-linked immunosor-
bent assay using a commercial kit were positive for both immunoglobulin M
(>20 Bethesda units [BU]/mL) and for immunoglobulin G (38.32 BU/mL;
positive, >20 BU/mL). Four weeks later, the antibody titers for immunoglob-
ulin G remained elevated (53 BU/mL), but M. pneumoniae was not detected in
Figure 1. Magnetic resonance imaging of the spine shows abnormal high signal intensity on T2-weighted image from the cervical level to the lumbar cord.
Mild cord swelling was also noted. (TR/TE = 3500/104 ms; slice thickness = 3 mm; turbo spin echo, turbo factor = 150.).
cerebrospinal fluid and throat swab by cultures or polymerase chain reaction.
The chest radiography did not reveal increased infiltration.
During the next 2 weeks, the patient’s weakness improved gradually,
and the urinary retention also resolved in the following course. The serum
creatine kinase level decreased gradually after intravenous immunoglobu-
lin treatment. The patient received rehabilitation at outpatient clinics and
his neurological condition improved gradually. Neurological sequelae
(weakness over the left upper limb and right lower limb) remained at
follow-up at outpatient clinics 2 years later.
Discussion
Rhabdomyolysis is characterized by an elevated level of
serum creatine kinase, and the level of elevation is dependent
on the extent of muscle injury [9]. In the present case, the di-
agnosis of rhabdomyolysis was based on the elevated serum
levels of creatine kinase and a low calcium concentration.
The hyperuricemia probably resulted from the breakdown
of purine released from destroyed muscle cells. Rhabdo-
myolysis can be chronic, acute, or recurrent, and the causes
vary. For a single episode of acute rhabdomyolysis, it can
be induced by multiple factors, including skeletal muscle
overuse, heat, crush injury, alcoholism, status epilepticus,
drugs, toxins, or metabolic abnormalities (such as hypokale-
mia, hyponatremia, or hypernatremia) [9]. None of these
were applicable in the present case. Various viral and bacte-
rial infections can also be responsible for rhabdomyolysis
[9]. In most patients with viral-related rhabdomyolysis,
the cause is influenza virus [10], followed by human
Weng et al: Transverse Myelitis and Rhabdomyolysis 129
immunodeficiency virus, enterovirus, Epstein-Barr virus,
varicella zoster virus, and cytomegalovirus [5,7]. The present
patient had no symptoms or signs of bacterial infection, and
laboratory findings also excluded the possibility of viral or
bacterial infections, until the diagnosis of M. pneumoniae in-
fection was based on serological assays. Rhabdomyolysis as
a complication of M. pneumoniae infection is very rare, and
only six previous cases, including both adults and children,
have been reported [4-8]. The present patient had no im-
paired renal function and did not require dialysis, probably
because of early recognition and early treatment with aggres-
sive hydration, alkalization, and mannitol.
Approximately 1-10% of patients hospitalized because
of serologically confirmed M. pneumoniae infection have
associated neurologic manifestations [3]. Encephalitis is
the most frequent manifestation, but cases of myelitis, poly-
radiculitis, and Guillain-Barré syndrome as well as other
symptoms, such as stroke or psychosis have also been re-
ported [2,11]. Myelitis is a severe and rare neurological
complication associated with M. pneumoniae infection.
Various mechanisms explaining neuromuscular and neuro-
logic disease after M. pneumoniae infection have been postu-
lated, including direct invasion by the organism, cytokine
storm, immune-mediated complex formation or autoanti-
bodies, toxin effects, vascular injury, and hypercoagulable
state [1,10,12,13]. The failure to isolate M. pneumoniae
from cerebrospinal fluid by culture and polymerase chain
reaction suggested an immune-mediated process as the
underlying mechanism.
Treatment of mycoplasma infection–related neurologic
and neuromuscular complications has been varied [13]. An-
timicrobial treatment is questionable, because of low penetra-
tion via the blood–brain barrier, and potential immunologic
pathophysiology [11]. The use of corticosteroids has been
suggested, after the confirmation of M. pneumoniae infec-
tion, although the efficacy remains controversial [13]. The
present patient received intravenous immunoglobulin treat-
ment because of rapid deterioration of his myelitis. The
long-term outcome was reported to be favorable [11]. In
the present case, the patient’s rhabdomyolysis resolved
without any long-term complication, but he had neurologic
deficit secondary to transverse myelitis. An unfavorable
prognosis is thought to be associated with rapid onset of neu-
rological symptoms, loss of tendon reflex, and impairment of
posterior column functions [11,14]. It remains unclear to
what extent the treatment for mycoplasma infection actually
influenced the spontaneous course.
A unique feature in the present case is the simultaneous
onset of both rhabdomyolysis and transverse myelitis in a -
single patient subsequent to M. pneumoniae infection. Respi-
ratory infection did not precede his rhabdomyolysis and
extensive myelitis. Rothstein and Kenny [15] described
a similar case, an adult patient with cranial neuropathy,
myeloradiculopathy, and myositis as the complications of
M. pneumoniae infection. In their report, the diagnosis of
neurological disturbance was based on the clinical presenta-
tion, without confirmation from neuroimaging. The maximal
130 PEDIATRIC NEUROLOGY Vol. 40 No. 2
creatine kinase in their patient was >40,000 units, and the
muscle biopsy disclosed lymphocytic infiltration and neuro-
genic atrophy. No other serum electrolyte derangement was
mentioned, however, so the diagnosis was of acute myositis
rather than rhabdomyolysis. The present patient had signifi-
cant signal abnormalities and spinal cord swelling in spinal
MRI, compatible with the diagnosis of transverse myelitis.
Furthermore, the laboratory data, including evidence of hy-
peruricemia and hypocalcemia, implied the destruction of
muscle cells and supported the diagnosis of rhabdomyolysis.
In the present case, with the unique finding in this young
child of concomitant rhabdomyolysis and transverse myeli-
tis in association with M. pneumoniae infection, the failure
to yield M. pneumoniae from cerebrospinal fluid via cul-
tures and polymerase chain reaction supported the evidence
of direct toxic or immune-mediated mechanism. Experience
with this patient suggests that, in cases of concurrent acute
transverse myelitis and rhabdomyolysis, an association
with M. pneumoniae should be considered even without
antecedent respiratory infection.
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