A 55-year-old Asian woman with no notable family history, travel history or past medical history presented to the emergency room with a primary complaint of generalized weakness, urinary incontinence, and tingling of the abdomen. In the initial presentation, she states that she had previously experienced mild flu-like symptoms during the previous weeks but denies any symptoms at present. Due to hospital protocols at the time of admission, she was tested for COVID-19 infection, which returned a positive test. It was suspected that the patient had a previous COVID-19 infection which accounts for her positive result at the hospital. In the hospital, she was placed in isolation while further testing and imaging were ordered to determine the cause of her symptoms. A physical exam revealed bilateral hyperreflexia of the patellar and Achilles reflexes (Grade 3), as well as a positive Babinski reflex bilaterally. Pinprick sensation revealed an almost complete loss of sensation to pinprick at the level of T5 dermatome and below bilaterally. There were no other pertinent positive findings on the initial physical examination.
Based on her initial presenting symptoms, MRI for the cervical, thoracic, and lumbar spine with and without contrast was ordered, along with an MRI of the orbits with and without contrast and a CT of the brain without contrast. MRI of the spine revealed hyperintensity beginning at the lower cervical spine at the levels of C5-6, extending down to the conus medullaris (Fig. 1). Along with this, a small syrinx that was approximately 2 millimeters in diameter was found extending from the level of T7-8 to T8-9 (Fig. 2). Along with these findings, MRI revealed disc osteophytes at the level of C4-5 and C5-6. Bilateral pulmonary infiltrates were also found, and a follow-up chest radiograph was ordered. MRI of the orbits revealed few periventricular foci of white matter demyelination with slight bifrontal predominance. CT of the brain revealed no abnormalities.
Along with the imaging studies, basic complete blood chemistry (CBC), complete metabolic profile (CMP), urinalysis, cerebrospinal fluid analysis, serum immunochemistry and serology, and infectious disease workup were ordered to determine possible etiologies of the patient's presenting symptoms that correlate with the imaging findings. The patient's initial CBC was unremarkable aside from an elevated neutrophil count, and the urinalysis also came back normal. However, the CMP revealed numerous abnormalities. Potassium levels were measured at 3.1 mmol/L, glucose was 135 mmol/L, creatinine was 0.5 mg/dL, albumin at 5.1 g/dL, globulin at 3 g/dL, and her BUN/Creatinine ratio was 24 mg/dL (Table 1).
Table 1
Complete Metabolic Profile (CMP) 03/25/2021
Complete Metabolic Profile |
Sodium | 139 |
Potassium | 3.1 L |
Chloride | 98 |
CO2 | 30 |
Glucose | 135 H |
BUN | 12 |
Creatinine | .5 L |
Calcium | 9.7 |
Total protein | 8 |
Albumin | 5.1 H |
Bill Total | 0.5 |
Alkphos | 78 |
AST | 26 |
ALT(SGPT) | 23 |
BUN/Creat | 24 H |
Globulin | 3L |
AG ratio | 2 |
AGAP | 11 |
Total CPK | 114 |
Table 2
Infectious disease workup |
Test | Results | Reference |
Syphilis serology | Non-reactive | Normal: non-reactive |
Lyme total Ab | 0.29 | < 0.90: negative |
Chikungunya virus IgG | 0.18 | 0.79 or less |
Chikungunya virus IgM | 0.58 | 0.79 or less |
SARS-CoV-2 PCR | Negative | Normal: negative |
CMV DNA quantification Ab | Negative | Normal: negative |
CMV DNA PCR log10 | Test not performed | |
Enterovirus RNA PCR | Negative | Normal: negative |
EBV IgM Ab titer | < 0.2 | |
EBV capsid Ag IgG Ab | > 0.8 | |
EBV nuclear Ag Ab | > 8.0 | |
Herpesvirus 6 IgG Ab | 0.26 | Below limit of detection |
Herpesvirus 6 IgM Ab | < 1:20 | < 1:10 Below limit of detection |
HIV 1 and 2 Ag/Ab | Non-reactive | Normal: non-reactive |
Influenza A rapid | Negative | Normal: negative |
Influenza B rapid | Negative | Normal: negative |
Mumps virus IgM Ab | < 0.80 | 0.79 or less |
Mycoplasma pneumoniae IgM | Reactive | Normal: non-reactive |
Rubeola IgG | 1.2 | 13.4 or less |
Rubeola IgM | < 0.91 | Less than 1.20 |
VZV IgG Ab | 4.8 | 134.9 or less |
VZV IgM Ab | < 0.91 | Less than 0.91 |
Concurrent with obtaining and evaluating the CBC and CMP, an autoimmune panel (Table 3) was also done to ensure there is no other autoimmune etiology. However, all results of that panel came back negative.
Table 3
Autoimmune Panel |
Test | Result | Reference |
Rheumatoid factor | Negative | Normal: negative |
ANA screen | Negative | Normal: negative |
JO-1 | < 0.2 | < 1 |
SS-A/Ro Ab | < 0.2 | < 1 |
SS-B/La Ab | < 0.2 | < 1 |
Smith Ab | < 0.2 | 19 or less |
RNP Ab | < 0.2 | 19 or less |
Scl-70 Scleroderma Ab | < 0.2 | < 1 |
Double-stranded DNA Ab | 1.1 | Less than 4.9 |
MAG IgM Ab | < 800 | Less than 1:1600 |
Beta-2-GPI IgG Ab | < 2.4 | Less than 15.0 |
Beta-2-GPI IgM Ab | 1.4 | Less than 15.0 |
Thyroglobulin Ab | < 20.0 | Less than 20 |
Thyroid peroxidase Ab | < 10 | Less than 35 |
Cardiolipin IgG Ab | < 1.4 | Less than 40 |
Cardiolipin IgM Ab | 1.4 | Less than 40 |
Complement C3 | 127 | 80–178 |
Complement C4 | 33.7 | 12–42 |
A serological study was also conducted to see if any immunological markers or bacterial/viral antigens could be detected on PCR. However, similar to the aforementioned autoimmune panel, all values that were tested for came back negative (Table 4).
Table 4
Immunology/Serology 3/27/21 Panel
Immunology/Serology 3/27/21 | Result |
Test | |
SARS CoV2 Covid 19 PCR | Negative |
SARS CoV2 Covid 19 Antibody | Positive |
Adenovirus PCR | Negative |
Antinuclear antibody | Negative |
SSA IgG | Negative |
SSB IgG | Negative |
B Pertussis PCR | Not Detected |
B Parapertussis PCR | Not Detected |
Chlamidiya pneuminia PCR Not COVID19 | Not Detected |
Coronavirus 229E PCR Not COVID19 | Not Detected |
Coronavirus HKU1 PCR Not COVID19 | Not Detected |
Coronavirus NL63 PCR Not COVID19 | Not Detected |
Coronavirus DC43 PCR Not COVID19 | Not Detected |
Influenza B PCR | Not Detected |
Influenza A PCR | Not Detected |
Influenza AH3 PCR | Not Applicable |
Influenza AH1 2009 PCR | Not Applicable |
Metapneumovirus PCR | Not Detected |
Mycoplasma pneumoniae PCR | Not Detected |
Myelin basic protein | H > 128.00 |
RSV PCR | Not Detected |
MRSA rapid screen | Negative |
Rhinovirus PCR | Not Detected |
Parainfluenza 1 PCR | Not Detected |
Parainfluenza 2 PCR | Not Detected |
Parainfluenza 3 PCR | Not Detected |
Parainfluenza4 PCR | Not Detected |
Finally, the cerebrospinal fluid (CSF) was checked for particular markers that could possibly indicate that a viral pathogen was responsible for the patients' transverse myelitis (Table 5). Upon evaluation of the patient's CSF, it was noted that the total protein level was elevated at 87 mg/dL, glucose was within the normal range at 63 mg/mL, and IgG level was elevated 9.7. In addition to the parameters observed, the level of myelin basic protein that was observed in the CSF was above 128 ng/mL. According to the most recently accepted guidelines, a value between 4–9 ng/mL indicates a long-term breakdown of myelin basic protein, whereas a level greater than 9 ng/mL is most associated with an active breakdown of myelin at the time of CSF extraction. Due to this patient's myelin basic protein level being more than 14x this accepted cut-off, it was determined that the patient is undergoing active destruction of myelin. All these laboratory values, when put together, indicate that a viral etiology is the cause of this patient's transverse myelitis.
Table 5
Cerebrospinal Fluid (CSF) Evaluation 3/26/21
Cerebrospinal fluid evaluation | |
Glucose | 63 |
IgG | H 9.7 |
Total Protein | H 87 |
Clarity | Hazy |
Color | Light Pink |
Neutrophil | 58 |
Lymphocytes | 20 |
Monocytes | 22 |
Differential? | Yes |
RBC | H 590 |
Tube# CSF | 1;4 |
WBC | C124, C169 |
Albumin | H 54 |
IgG Synthesis Rate | H 12.5 |
IgG/Albumin Ratio | 0.18 |
Oligoclonal Bands | Negative |
Oligoclonal Bands Number | 0 |
Oligoclonal Bands Interpretation | See Note |
Meningitis Encephalitis Specimen Type | CSF |
Escherichia coli K1 PCR | Negative |
Haemophilus influenzae PCR | Negative |
Listeria monocytogenes PCR | Negative |
Neisseria meningitidis PCR | Negative |
Streptococcus Group B PCR | Negative |
Streptococcus Pneumoniae PCR | Negative |
Cytomegalovirus CSF Qualitative PCR | Negative |
Enterovirus RNA PCR | Negative |
Herpes Virus 6 CSF Qualitative PCR | Negative |
Herpes Simplex 1 PCR | Negative |
Herpes Simplex 2 PCR | Negative |
Human Parechovirus PCR | Negative |
Varicella Zoster PCR | Negative |
Cryptococcus Neoformans gatti PCR | Negative |
Upon receiving the results of the ordered laboratory tests and imaging studies, the patient was treated with a combination of IV steroids, plasmapheresis, and rituximab. Initiation of treatment began with the administration of high-dose methylprednisolone that was administered at a rate of 250 ml/hr for 60 minutes every 6 hours. This was done because steroids are well-proven to be a first-line agent to reduce generalized inflammation. Another treatment that this patient underwent was plasmapheresis which was done daily during the entire hospital stay to remove any antibodies or proteins that were eliciting this immune response leading to her condition. Finally, the monoclonal antibody rituximab was given to alleviate the immune response in the patient further. The medication is widely known to inhibit T-helper cells, B-cells, as well as macrophages and induce the activity of T-regulatory cells, which help suppress the immune response.
Through the effects of the medications and treatment modalities, the functioning of the patient was partially restored. The patient was able to ambulate appropriately, albeit short distances. The episodes of incontinence completely ceased, and all paresthesia was significantly diminished. MRI of the thoracic spine revealed a T2 signal of the spinal cord that was less intense than previously recorded. Imaging also showed a cord-blood barrier that was no longer altered. However, the patient was advised to follow-up with her primary care physician in 5–7 days following release from the hospital to confirm that symptoms did not return and advised to undergo further imaging later to ensure that positive changes were not due to ongoing plasmapheresis.