Generalised myoclonus in COVID-19, and COVID-19-associated diffuse leukoencephalopathy and micro-haemorrhages
By Denise Baez
NEW YORK -- May 22, 2020 -- In today’s DG Alert, we cover occurrences of myoclonus in patients with coronavirus disease 2019 (COVID-19), and diffuse leukoencephalopathy and micro-haemorrhages as potential late complications in critically ill patients with COVID-19.
A small case series published in Neurology describes 3 patients who developed generalised myoclonus during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Pablo Rábano-Suárez, MD, University Hospital “12 de Octubre,” Madrid, Spain, and colleagues, treated 3 patients aged 63 to 88 years who presented with mild hypersomnia and generalised myoclonus following the onset of the so-called “inflammatory” phase of COVID-19. After a thorough study, no other potential causes for this phenomenon were identified.
The first case was a male aged 63 years who was admitted to the emergency room because of a 7-day history of fever and loss of smell. On day 9 after symptom onset, he began having jerky movements in his face and limbs that prevented him from eating and speaking properly. Chest x-ray revealed bilateral diffuse patchy interstitial infiltrates consistent with COVID-19 infection and blood work‐up revealed elevated C-reactive protein, elevated D-dimer levels, and lymphopenia. A nasopharyngeal swab test for SARS-CoV-2 could not be performed due to its scarcity in Spain at the time. However, he was diagnosed with COVID-19 infection due to the clinical-radiological picture. Ten days after symptom onset, myoclonus worsened preventing the patient to move, speak, or swallow. He was intubated and admitted to the intensive care unit. He showed some improvement after treatment with methylprednisolone and plasmapheresis.
The second case was a woman aged 88 years who was admitted to the emergency room because of a 2-day history of fever, shortness of breath, and loss of smell. Chest x-ray revealed bilateral pneumonia. Nasopharyngeal swab test for SARS-CoV-2 was positive. Three weeks after symptom onset, she started having mild hypersomnia and similar jerking movements to patient 1, but milder. A brain CT, EEG, and extensive laboratory work-up were unrevealing. Myoclonus disappeared with methylprednisolone treatment.
The third case was a man aged 76 years who had fever, ageusia, myalgia, and loss of smell for 10 days. Eleven days after symptom onset, he developed facial and limb jerking, mild somnolence, and dyspnoea. Like patient 1, a nasopharyngeal swab test was not available at the time, but he was diagnosed with SARS-CoV2 pneumonia based on blood analysis, radiological findings, and considering epidemiological context. He was treated with methylprednisolone and improvement began 2 weeks later.
“Our 3 cases highlight the occurrence of myoclonus during the COVID-19 pandemic as a post-infectious/immune-mediated disorder,” the authors wrote. “However, we cannot rule out that SARS-CoV-2 may spread transneuronally to first- and second-order structures connected with the olfactory bulb. Further investigation is required to clarify the full clinical spectrum of neurologic symptoms and its optimal treatment.”
In another case series, published in Radiology, Alireza Radmanesh, MD, New York University School of Medicine, New York, New York, and colleagues describe 2 brain imaging features in critically ill patients with COVID-19 -- diffuse leukoencephalopathy and juxtacortical or callosal micro-haemorrhages.
“We believe that both findings are hypoxia-related but have different pathogeneses,” the authors wrote. “It is important to recognise these findings as potential late central nervous system complications of COVID-19, particularly in patients with persistently depressed mental status.”
The case series involved 11 critically ill patients with COVID-19 who underwent brain MRI between April 5, 2020, and April 25, 2020 while on mechanical ventilation (no patient required extracorporeal membrane oxygenation). The indication for brain imaging in all cases was persistently depressed mental status. Of the patients, 4 had diffuse leukoencephalopathy, 1 had micro-haemorrhages, and 6 had both.
Over 3 to 5 weeks following brain MRI, 6 of the 11 patients died (3 had leukoencephalopathy, 1 had micro-haemorrhages, 2 had both). The other 5 patients continue to receive critical care.
“Though initial reports of brain imaging findings in COVID-19 patients showed ischemic and haemorrhagic complications, there are now increasing reports of other findings such as patchy demyelinating lesions and acute haemorrhagic necrotising encephalopathy involving the thalami and medial temporal lobes,” the authors wrote. “The current report comprises 11 patients in a single 3-week period in April 2020, with all patients having been critically ill and on mechanical ventilation for a mean duration of 26.5 days. We believe the diffuse leukoencephalopathy and micro-haemorrhages described here are late complications of critically ill COVID-19 patients and likely related to hypoxemia. Previously, we reported brain imaging findings in 242 consecutive COVID-19 patients seen at our institution in March 2020 and none of those patients demonstrated these diffuse patterns of white matter involvement which we describe here. This suggests that these findings are not typical of earlier stages of COVID-19.”
Limitations of the study include small sample size, retrospective nature, lack of quantification of MRI findings, and lack of histopathologic determination of underlying etiology.