Myeloencephalitis as the only presentation of Omicron SARS-CoV-2 infection

Background

It is projected that about 0.04%–0.2% of all SARS-CoV-2 patients would present with central nervous system (CNS) disease.1 With the number of daily cases averaging 1 million and 582 423 377 total cases globally at the time of writing, it could be estimated that approximately 400–2000 patients would present with SARS-CoV-2 associated encephalopathy everyday.2 For comparison, the annual incidence of herpes simplex virus (HSV) encephalitis is 2–4 per 1 000 000 population, translating into around 80 new cases daily worldwide.3 It is therefore reasonable, on an epidemiological basis, to search for SARS-CoV-2 in all cases of acute or subacute encephalopathy, despite the fact that the presence of viral particles in cerebrospinal fluid (CSF) can be only found in a small number of cases, unlike in the case definition of HSV encephalitis. We present a case of MRI-proven isolated myeloencephalitis with positive real-time-PCR (RT-PCR) for SARS-CoV-2 in CSF in a young patient with no prior history.4 5 A temporal relationship between neuroimaging, clinical features and CSF characteristics is also outlined.

Case presentation

A previously healthy woman in her late 20s presented at our institution for a sensation of paresthesia of her 2 feet appearing 2 weeks prior, which ascended to lower abdomen and upper limbs associated with tetraparesis within 10 days. Her prior vaccination record included three doses of Pfizer Cominarty, the last of which was 1 month before the onset of symptom. There was no history of SARS-CoV-2 infection.

At admission, a quick COVID-19 entry screening test per protocol at our hospital was positive. There was absence of respiratory symptoms such as coughing, sore throat nor fever. No anosmia or headache was reported by the patient. The patient was completely eupneic on room air and no abnormalities were found during pulmonary auscultation. Nasal swab RT-PCR revealed a cycle threshold of 20.02 at day 15 since the start of paresthesia.

On neurological examination, the patient was alert, well oriented and afebrile. There were moderate weakness of lower limbs (3/5) and mild weakness of upper limbs (4/5), with a slight asymetry predominant on the right side. Bilateral hyper-reflexia with Babinski signs and ankle clonus were observed. Vibration sensation and joint position sense were reduced in lower left limb and lost in right lower limb. Cerebellar signs such as nystagmus or truncal ataxia were absent. Slight nuchal rigidity was also noted. Neither cranial nerve impairment nor important cognitive dysfunctions were present. Initial diagnostic hypothesis included an acute myeloencephalitis on the basis of a clinically suggestive pyramidal and sensory syndrome with rapid progression.

Investigations

Her first brain and spinal cord MRI with gadolinium (figure 1) was obtained at day 15 of symptoms.

A lumbar puncture was then performed revealing a moderate pleocytosis at 74 cells/µL and a slightly elevated proteinorrachia. Other parameters are summarised in table 1. The diagnosis of acute myeloencephalitis was established. RT-PCR for SARS-CoV-2 in CSF was tested and returned positive at a CT of 20.52. An extensive diagnostic workup to rule out other known causes of acute or subacute encephalitis was pursued and returned negative (table 2).

Further investigation by nerve conduction study and electromyography showed no involvement of the peripheral nervous system, ruling out the possibility of a concomitant neuropathy. A 30 min conventional electroencephalography was unremarkable. A thoracoabdominopelvic CT scan later revealed mild bilateral pleural effusion with no pulmonary parenchymal opacities (figure 2). Genome sequencing eventually identified a B.1.1.529 variant (Omicron) in nasal sample.

Treatment

A course of high-dose methylprednisolone (1000 mg daily for 5 days) were started immediately after the diagnosis of acute myeloencephalitis was established with exclusion of bacterial and tuberculous causes on CSF analysis. Given a positive nasal swab RT-PCR, intravenous antiviral treatment with remdesivir (loading dose of 200 mg, followed by 100 mg daily) was added on suspicion of SARS-CoV-2 as a possible aetiology. The result of RT-PCR in CSF only came back positive 2 days after antiviral initiation. By day 18 of symptoms, she began developing urinary incontinence and required bladder catheterisation.

A second lumbar puncture was performed at the end of 5-day pulse corticotherapy showing a recession of pleocytosis down to 16 cells/μL and a persistent elevated proteinorrachia (table 1). Her second SARS-CoV-2 RT-PCR in CSF and subsequent nasal swabs also turned negative. A second brain MRI was obtained 7 days after the first revealing a reduction of contrast enhancement (figure 3). Other parameters (liver and renal function, ionogram, coagulation) and systemic inflammatory markers related to SARS-CoV-2 infection (C-reactive protein, Interleukin-6) were within normal ranges.

Outcome and follow-up

Her clinical status started to recover at day 20 of onset with gradual improvement of paresthesia and limb motor function. Remdesivir was stopped after 9 days and she was later discharged at day 25 of symptoms with very little distal paresthesia, a complete resolution of her urinary incontinenceand a slight tetraparesis at 4+/5. At 2-week follow-up visit, there was a near-complete neurological recovery with minimal pronator drift in upper limbs and no paresthesia.