COVID‐19‐associated transverse myelitis treated by therapeutic plasma exchange: A case report

Abstract

Background

Transverse myelitis (TM) is a very uncommon condition in children which can be associated with viral infections. Acute TM cases have been reported after Coronavirus disease 2019 (COVID‐19) infection during the pandemic.

Case Report

We report a child with TM related to severe acute respiratory syndrome coronavirus 2, who was successfully treated with therapeutic plasma exchange (TPE). Inability to walk and urinary retention were the central nervous system symptom. Spinal magnetic resonance imaging revealed signal changes in the spinal cord. Her neurological symptoms worsened despite receiving IVIG and high–dose steroids for the first 3 d. We performed 10 TPE sessions with 5% albumin replacement and the neurological symptoms rapidly improved.

Conclusion

We demonstrated that a child diagnosed with acute TM related to COVID‐19 infection, was successfully treated with TPE.

1. INTRODUCTION

Acute transverse myelitis (TM) is an immune‐mediated central nervous system (CNS) disorder classically described as demyelinating. TM occurs much more commonly in adults than in children. A range of infections is reported in the preceding 30 d in over 60% of TM cases. ¹ Viral, bacterial, parasitic, and fungal infections may cause TM. In most cases, the inflammatory disorder occurs after the infection period. Hepatitis A, hepatitis B, hepatitis C, hepatitis E, measles, mumps, rubella, varicella‐zoster, Epstein–Barr, cytomegalovirus, herpes simplex, influenza A/B, lymphocytic choriomeningitis virus, Hantavirus, human immunodeficiency virus, human T‐cell lymphotropic virus, human herpes virus 6, dengue virus, enterovirus 71, coxsackievirus A and B, West Nile virus, parvovirus B19, human coronavirus, and echovirus are associated with TM. ² During the coronavirus disease 2019 (COVID‐19) pandemic, many neurological symptoms and neurological manifestations of COVID‐19 have been increasingly reported. Several articles reported the appearance of peripheral and CNS demyelinating diseases, in association with COVID‐19 infection. ³ , ⁴ , ⁵ , ⁶ TM is one of the demyelinating diseases with associated COVID‐19. ³ We present a pediatric patient who could not stand or walk with MRI changes indicative of COVID‐19–associated TM.

2. CASE REPORT

A 9‐y‐old female was admitted to the pediatric emergency ward with a poor general condition, inability to walk, and urinary retention. There was no significant comorbidity. Her immunization status was appropriate for her age. Ten d before admission she had a fever, headache, cough, and tiredness for 5 d. After initial improvement, new symptoms started on the day of admission with new onset of headache, unable stand or walk, and general weakness. She was never encephalopathic. Brain MRI and her clinical course were consistent with TM. Methylprednisolone (MP) 30 mg/kg intravenously daily and intravenous immunoglobulin 0.4 g/kg daily was administered for presumed TM. On hospital day 4, she needed support to sit up, and she was admitted to the pediatric intensive care unit (PICU) because of her neurological deterioration under IVIG and MP treatment. The patient's symptoms related to COVID‐19 started 10 d before admission, but the patient did not undergo a PCR test at that time. The patient was not vaccinated for COVID‐19.

On PICU admission, a physical examination revealed that she was conscious and oriented, and her vitals were stable. She was unable to sit without support, stand, or walk. Also, physical examination demonstrated cranial nerves were intact bilaterally, and cough and gag reflexes were normal. However, she had bilateral lower limb flaccid weakness of 1/5 affecting proximal and distal muscles equally with grade 3 + deep tendon reflexes. There was no weakness in the upper limb and neck muscles. She had no response to bilateral plantar reflex and decreased sensation in the bilateral lower extremity with sensory level at T2. She had no response to pain, light touch, proprioception, and vibration sensation in the bilateral lower extremity.

On PICU admission, the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV–2) real‐time polymerase chain reaction (PCR) on the nasopharyngeal swab was negative. Laboratory findings are shown in Table 1. Cerebrospinal fluid (CSF) had total nucleated cells (460/mm³) with neutrophilic predominance (86%), and total protein (95.5 mg/dl). She was positive for positive SARS‐CoV–2 antibody in CSF and serum. SARS‐CoV–2 antibody is not routinely performed on CSF, we performed only on specific cases. Our hospital's laboratory uses the Elecsys Anti‐SARS‐CoV–2 S immunoassay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) for COVID‐19 antibodies. It was validated for CSF analysis by the chef of microbiology in our laboratory. This kit measures the total antibody level. Other tests were normal, for etiology.

TABLE 1.

Laboratory findings

White blood cell (4270‐11 400 per μL)	11 200
Lymphocyte (1230‐2760 per μL)	780
Neutrophil (2580‐5950 per μL)	10 160
Platelet (199‐367 per μL)	288
Hemoglobin (10.6‐13.2 g/dL)	12
C reactive protein (0‐5 mg/L)	1
Procalcitonin (<0.5 ng/mL)	0.04
Urea (15‐36 mg/dL)	24.2
Creatinine (0.29‐0.58 mg/dL)	0.47
Aspartate aminotransferase (0‐32 unit/L)	14.4
Alanine aminotransferase (0‐33 unit/L)	4.1
Creatine kinase (0‐171 unit/L)	44
Lactate dehydrogenase (120‐300 unit/L)	231
Ferritin (10‐120 μg/L)	71
SARS‐CoV‐2 antibody	Positive
Cerebrospinal fluid analysis
Glucose (60‐80 mg/dL)	68
Protein (15‐45 mg/dL)	95.5
Cell count (/mm3)	430
Oligoclonal band	Negative
SARS‐CoV‐2 antibody	Positive
Autoimmune encephalitis panel	Negative
Anti‐MOG antibody	Negative
Antiaquaporin‐4 antibody	Negative

Note: Autoimmune encephalitis panel, including anti–NMDA‐R‐Ab, AMPA‐R1 Ab, AMPA‐R2 Ab, CASPR2 Ab. (VGKC), lg11 Ab. (VGKC) and GABA‐R‐Ab.

On PICU admission, brain and spinal magnetic resonance imaging (MRI) revealed a long segment of T2 signal elevation centrally in the spinal cord (Figure 1), and the nerve conduction study was suggestive of extensive neurogenic involvement of motor neuron trunks and axons. All these findings were consistent with an upper motor neuron lesion. Therapeutic plasma exchange (TPE) was started because neurological symptoms worsened despite immunoglobulin and high–dose steroid treatment. IVIG 0.4 g/kg/d and MP 30 mg/kg/d administered for two more d. TPE volume was calculated as 0.065 × patient weight × (1 ‐ hematocrit) and performed over 3 h. Seven consecutive TPE sessions with 5% albumin replacement followed by three sessions on alternate days were performed using a Prismaflex TPE filter (Gambro Lundia AB). The patient's weight was 25 kg. We did not use circuit prime (albumin or red blood cells). TPE rapidly improved neurological symptoms in this patient. After TPE sessions, repeated brain and spinal MRI on PICU d 14, showed regressed lesions (Figure 1). Neurological improvements: After the first TPE session, her lower extremity muscle strength was 2/5. After the third TPE session, her lower extremity muscle strength was 3/5. After the seventh TPE session, her lower extremity muscle strength was 4/5. when she was discharged, her lower extremity muscle strength was 5/5. Bladder control returned to normal on the 10th d. Pain, light touch, proprioception, and vibration sensation returned to normal on the 14th d in the bilateral lower extremity. She was discharged home on PICU d 15, walking with support. Three mo after discharge neurologic examination was normal, she had no symptoms or signs.

FIGURE 1.

In the spinal MRI examination of the case, a slight volume and pathological signal increase was observed in the central part of the spinal cord in sagittal (A) and axial T2W (B) imaging. After contrast administration, significant contrast enhancement was detected in these regions in axial (C) and sagittal T2W (D) images. After 14 d, Of the spinal MRI examination; Sagittal T2W examinations (E, F) showed that the signal in the previously observed spinal cord was significantly regressed, and contrast‐enhanced sagittal T2W sections (G) did not enhance contrast

3. DISCUSSIONS

We describe a child with acute TM associated with COVID‐19. Upper motor neuron signs were present in bilateral lower extremities. She had grade 3 + reflex, no response bilateral plantar reflex, and marked loss of vibration, proprioception, pain, and light touch sensation. In this case, COVID‐19–associated TM was diagnosed based on the detection of anti–the SARS‐CoV–2 antibody in CSF.

The most common neurologic symptoms associated with COVID‐19 include encephalopathy, headache, seizures, and muscle weakness in children. ⁴ Our patient was presented with headaches and muscle weakness, and also no encephalopathy. Various neurologic manifestations were associated with COVID‐19 in children. Acute encephalopathy or encephalitis, acute necrotizing encephalopathy, acute disseminated encephalomyelitis (ADEM), cytotoxic lesions in the callosal splenium, posterior reversible encephalopathy syndrome, cerebral venous thrombosis, vasculitis, and acute infarction, Guillain‐Barré syndrome, TM, and myositis have been defined as the neurological involvement of COVID‐19 in children. ⁴ , ⁵ , ⁶ We diagnosed TM in our patient, which is one of the demyelinating disorders.

The standard therapy for TM consists of high‐dose corticosteroids that 30 mg/kg/dose (maximum 1000 mg) of MP intravenously once a d for 3 to 5 d. IVIG can be incorporated into the treatment of fulminant TM. ¹ TPE is an extracorporeal treatment that can be used in pediatric patients with acute demyelinating syndromes of the CNS like TM. ⁷ Our patient neurological symptoms worsened clinically despite receiving high–dose steroids and IVIG. Therefore, we performed TPE in this case.

In conclusion, we report the case of acute TM with the post‐COVID‐19 that was treated with TPE. Neurologists and intensivists should consider TPE treatment in TM that does not respond to high–dose steroid and IVIG treatment.

AUTHOR CONTRIBUTIONS

Concept–N.A, M.E.M, M.O, F.B.P, E.S., D.T; Design–N.A, M.E.M., D.T.; Supervision–F.B.P, E.S., Resources–N.A, M.E.M, M.O., D.T.; Materials–N.A, M.E.M, M.O.; Data Collection and/or Processing–N.A, M.O, F.B.P; Analysis and/or Interpretation–N.A, M.O, F.B.P, E.S.; Literature Search–N.A, M.E.M, E.S.; Writing Manuscript N.A., E.S.; Critical Review–N.A, F.B.P, E.S.

The manuscript has been read and approved by all the authors.

FUNDING INFORMATION

None.

CONFLICT OF INTEREST

None.

Akçay N, Menentoğlu ME, Oğur M, Tosun D, Palabıyık FB, Şevketoğlu E. COVID‐19‐associated transverse myelitis treated by therapeutic plasma exchange: A case report. J Clin Apher. 2022;1‐4. doi: 10.1002/jca.22024

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.