Parainfectious Brown-Sequard syndrome associated with Mycoplasma pneumoniae in an adult patient: a case report

Abstract

Introduction

Acute transverse myelitis (ATM) refers to a rare severe acquired spinal cord inflammation, with a challenging diagnostic work-up and treatment.

Case presentation

We report the case of a 42-year-old patient who presented with loss of temperature and pain sensation beneath the C5 dermatome in her left side and reported a history of a possible respiratory tract illness 10 days ago. Within 2 days, clinical worsening was noted, compatible with Brown-Sequard syndrome. Spinal magnetic resonance imaging revealed a T2 sequence abnormal signal from level C4 to T3 and cerebrospinal fluid (CSF) studies showed only a mild pleocytosis mononuclear type. Extensive CSF and blood tests revealed only high Mycoplasma pneumoniae IgM and IgG titers. Treatment with high-dose intravenous methylprednisolone and oral azithromycin were administrated and the patient recovered completely within two months.

Discussion

We would like to highlight the importance for physicians to consider M. pneumoniae in their differential diagnosis as a potential cause when encountering patients with symptoms of ATM and inflammatory Brown-Sequard syndrome.

Introduction

Acute transverse myelitis (ATM) refers to a rare severe acquired spinal cord inflammation that manifests with sudden onset of motor, sensory, and autonomic dysfunctions [1]. Neurologic symptoms usually develop rapidly over hours or sub-acutely over weeks, whilst change in the patient’s sensation is typically the most common first sign of ATM [1, 2]. The presence of ATM can be secondary to multi-systemic diseases (active or recent infections, vaccination, vasculitis syndromes, autoimmune diseases, vascular diseases, neoplasm, nutritional deficiency, Guillain–Barre syndrome, paraneoplastic syndromes, and multiple sclerosis), however it is not always possible to establish an apparent underlying specific etiology, leading to the characterization of several cases as idiopathic [1].

Infectious causes of ATM are distinguished in two categories; infectious ATM, and ATM that is preceded by an infectious process, termed as parainfectious [1, 3]. Both categories share the same common pathogens: herpes simplex virus 1 & 2, varicella zoster virus, cytomegalovirus, West Nile virus, Epstein-Barr virus, enterovirus, adenovirus, influenza, echovirus, mumps, measles, rubella, tuberculosis, syphilis, human immunodeficiency virus, human T-lymphotropic virus, Chlamydia pneumoniae, Mycoplasma pneumoniae and Borrelia burgdorferi [1–3]. M. pneumoniae associated ATM is a very rare complication of this particular pathogen, difficult to diagnose and treat, and also most commonly encountered in children and adolescents [3, 4].

Our aim is to report a rare case of an adult female patient with acute transverse myelitis presented as Brown-Sequard syndrome after Mycoplasma pneumoniae respiratory infection with excellent response to steroid treatment.

Case presentation

A 42-year-old woman presented to the Department of Emergencies of our hospital with progressive numbness in her left extremities, starting 14 h ago. She reported only a history of a respiratory tract illness 10 days ago, with cough, sore throat and no fever, lasting for three days. She also reported no administration of medications prior to the episode of numbness. Neurological examination revealed loss of temperature and pain sensation beneath the C5 dermatome in her left side, brisk tendon reflexes at the right side, extensive plantar reflex at both sides, no muscle weakness [muscle strength grading was 5/5 for all tested muscles in all extremities, using Medical Research Council (MRC) scale] and no loss of (volitional) sphincter control. Brain, cervical and thoracic computerized tomography and routine blood tests were unremarkable.

A brain, cervical and thoracic magnetic resonance imaging (MRI) were performed the second day of her admission and revealed a T2 sequence abnormal signal from level C4 to T3, without contrast enhancement (Fig. 1). A lumbar puncture was performed and cerebrospinal fluid (CSF) studies showed a mild pleocytosis (7 cells per cubic millimeter) of mononuclear type (ref: ≤5/mm³), normal protein (37 mg/dL) and glucose (71 mg/dL) values (ref: <45 mg/dL and 40–85 mg/dL, respectively), no detection of oligoclonal bands and normal IgG index (0.54), thus a diagnosis of ATM was considered for our patient. CSF Polymerase chain reaction (PCR) was tested for viral, bacterial, fungal and parasitic infections of the central nervous system (CNS) and was found negative, as well as CSF culture.

Fig. 1. Spinal magnetic resonance imaging showing an abnormal signal lesion from C4 to T3 level.

a Sagital T2 sequence showing abnormal signal from level C4 to T3; b Transverse section at the C4 level showing abnormal signal in right grey matter (arrows).

Within two days of her admission, clinical worsening was noted, with progressive weakness of her right extremities (MRC grading was 4/5 for right wrist, elbow, knee and long toe extensors, and 5/5 for all the rest tested muscles) and loss of vibration, fine touch and proprioception beneath the C4 dermatome in her right side, compatible with Brown-Sequard syndrome. Treatment with high-dose intravenous methylprednisolone (1000 mg per day) for five days was administered, followed by a calculated oral prednisone dosage (1 mg/kg per day), tapered slowly over six weeks, which led to clinical improvement, regarding muscle strength (MRC score was 5/5 for all tested muscles in all extremities), within six days since the onset of the corticosteroid treatment.

Screening for paraneoplastic neurological syndromes and autoimmune myelitis was performed, with serum and CSF testing for antibodies against aquaporin-4, myelin oligodendrocyte glycoprotein, glutamic acid decarboxylase, anti-Hu, anti-Yo, anti-Ri, anti-CV2/CRMP-5, anti-Ma2, anti-Tr, Zic4, SOX1, which were all found negative. Further laboratory testing, with anti-nuclear antibodies (1:80), erythrocyte sedimentation rate (14 mm/h), C-reactive protein (0.8 mg/dL), vitamins (B1, B12 and E), angiotensin converting enzyme, anti-double stranded DNA, anti-Ro, anti-La, anti-ribonucleoprotein antibodies, quantiferon, serology for Treponema pallidum, hepatitis B virus, hepatitis C virus and human immunodeficiency virus, was also negative for abnormal findings. Due to the patient’s reported history of respiratory tract illness, serum and CSF specimens were tested for IgM and IgG antibodies for herpes simplex virus 1 & 2, varicella zoster virus, cytomegalovirus, West Nile virus, Epstein-Barr virus, enterovirus, adenovirus, influenza, echovirus, mumps, measles, rubella, Chlamydia pneumoniae, Mycoplasma pneumoniae and Borrelia burgdorferi. Patient was found IgG antibody seropositive and CSF negative, as well as IgM antibody serum and CSF negative for all the above, except Mycoplasma pneumoniae, for which the patient was found IgG negative (9.1 U/ml) and IgM antibody positive (38.5 U/ml) in the serum (positive ref: >11 U/ml and >10 U/ml, respectively). M. pneumoniae IgG (15.6 U/ml) and IgM (17.8 U/ml) antibodies were repeated one week later and were both found seropositive (increasing IgG and decreasing IgM levels). CSF and throat-swab PCR were negative for M. pneumoniae. Oral treatment with 500 mg of azithromycin daily for five days was also administered to the patient and a diagnosis of parainfectious acute transverse myelitis associated with M. pneumoniae was made.

At 3-month follow up, the patient was reevaluated and a repeated brain, cervical and thoracic MRI was performed showing remarkable improvement, with total remission of the lesion (Fig. 2). Moreover, the patient’s neurological examination was normal, without relapses reported.

Fig. 2.

Sagital T2 sequence of spinal magnetic resonance imaging at 3-month follow up.

Discussion

In most cases with Mycoplasma pneumoniae associated ATM, an antecedent respiratory tract infection occurs in an interval of approximately 10 days (range 4–30 days) before the development of neurologic manifestations, as seen in our patient [3–5]. These manifestations include weakness, which tends to progress rapidly to paraplegia in 1–3 days, loss of sensation at the lesion level and loss of sphincter control [6]. In our case, patient’s symptoms evolved from change in sensation below a cervical dermatome level to a Brown-Sequard plus syndrome, involving muscle weakness, loss of vibration, fine touch and proprioception, contralaterally to the loss of temperature and pain sensation, below the adjacent cervical dermatome caudally. We consider that this manifestation occurred due to progressive evolution of the lesion in the spinal cord, beginning with a lesion in the spinothalamic tract and expanding to hemisection of the cord, affecting also the corticospinal tract and the dorsal columns, as seen in Fig. 1b. Brown-Sequard syndrome is characterized by damage to one half of the spinal cord, resulting in ipsilateral paralysis and loss of proprioception, and contralateral loss of pain and temperature sensation below the level of the lesion, associated with non-inflammatory (trauma, ischemia, tumor, radiation) and inflammatory (multiple sclerosis, tuberculosis. syphilis) causes [7]. However, the typical descriptions of Brown-Sequard syndrome are not always present, and less pure forms of the syndrome have been described, termed as “Brown-Sequard plus syndromes,” consisting of asymmetric paresis with bilateral hypoalgesia that is more marked on the less paretic side, as seen in our case [8]. We only found six case reports of parainfectious acute transverse myelitis presenting as Brown-Sequard syndrome associated with herpes infections in the literature [9–14]. In these reports, similar cases were described after infection with herpes zoster, diagnosed by CSF and/ or serum anti-VZV IgM and IgG antibodies. Nonetheless, to our knowledge, this is the first case report of M. pneumoniae associated ATM presenting as Brown-Sequard syndrome.

Myelitis and encephalitis are both severe CNS complications seen in association with Mycoplasma pneumoniae infections, which can be present in combination (acute disseminated encephalomyelitis) and independently [3]. Diagnosing M. pneumoniae associated ATM can be challenging, since a variety of other possible causes must be excluded, as described in the Introduction section. Moreover, verifying whether the patient has an active or recent infection is also important for the prognosis and treatment options. Serology showing Mycoplasma IgM or IgG titers can confirm a recent infection. An increasing IgM level indicates an active infection, whilst a decreasing IgM level and increasing IgG level, as seen in our patient, indicates a recent infection. CSF and throat-swab PCR, as well CSF culture, are sensitive for identifying acute M. pneumoniae infection, even though isolating M. pneumoniae from a patient’s CSF is not common [15]. First-line treatment is high-dose corticosteroids for three to five days followed by an oral taper for several weeks, whilst second-line therapy is plasmapheresis and/or intravenous immunoglobulin. Antimicrobial treatment with macrolides is considered to be beneficial for active infection of M. pneumoniae, whilst it is controversial for recent infections [15, 16]. Complete recovery may take from a few days to months from the onset of CNS manifestations when treatment is started at the early stages of the disease, even though there have been described cases with consisted severe disabilities [3]. In our case, even though clinical improvement (regarding muscle strength) was noted within days after corticosteroid treatment, we decided to administrate a short oral scheme of macrolides to our patient, since IgM titers where still positive for M. pneumoniae. Complete remission of our patient’s symptoms was reported within two months since the corticosteroid treatment was initiated.

Spinal MRI is a reliable method of neuroimaging in ATM cases, showing T2 signal changes and the absence of compression cord lesion [17]. MRI findings for M. pneumoniae-related ATM are not specific when compared to myelopathies of other causes, but correlate with the course of the disease and clinical improvement, as seen in our patient [3, 18]. CSF leukocyte count and protein are elevated in most cases of M. pneumoniae associated ATM, with predominantly mononuclear pleocytosis, normal CSF/serum glucose ratio and absence of oligoclonal bands [3]. Our patient’s CSF studies revealed a very mild pleocytosis with normal protein, which could be attributed to the fact that lumbar puncture was carried out at an early stage of the disease.

We present an atypical clinical manifestation of M. pneumoniae associated ATM in an adult patient. We would like to highlight the importance for physicians to consider M. pneumoniae in their differential diagnosis as a potential cause when encountering patients with symptoms of ATM and inflammatory Brown-Sequard syndrome. Early detection of the disease’s cause and treatment can lead to a favorable outcome for these patients.

Author contributions

MP: clinical course, wrote the manuscript, TKV: clinical course, MG: clinical course.

Funding

There are no funding sources to be declared.

Data availability

Further anonymized data can be made available to qualified investigators upon request to the corresponding author.

Competing interests

The authors decalre no competing interests.

Ethical approval

This study was approved by the Scientific Committee of G. Gennimatas Hospital.

Informed consent

Written informed consent was obtained from the patient for publication of this case report and any accompanying images.