Summary: Coronavirus infection can lead to an array of neurological complications, including delirium, stroke, and a rare, often fatal neuroinflammatory condition called ADEM. The neurological complications did not always correlate with the severity of respiratory symptoms. In some patients, brain inflammation was likely caused by an immune response to COVID-19, suggesting the neurological damage may be a result of immune system activation rather than the virus itself.
Neurological complications of Covid-19 can include delirium, brain inflammation, stroke and nerve damage, finds a new UCL and UCLH-led study.
Published in the journal Brain, the research team identified one rare and sometimes fatal inflammatory condition, known as ADEM, which appears to be increasing in prevalence due to the pandemic.
Some patients in the study did not experience severe respiratory symptoms, and the neurological disorder was the first and main presentation of Covid-19.
Joint senior author Dr Michael Zandi (UCL Queen Square Institute of Neurology and University College London Hospitals NHS Foundation Trust) said: “We identified a higher than expected number of people with neurological conditions such as brain inflammation, which did not always correlate with the severity of respiratory symptoms.
“We should be vigilant and look out for these complications in people who have had Covid-19. Whether we will see an epidemic on a large scale of brain damage linked to the pandemic – perhaps similar to the encephalitis lethargica outbreak in the 1920s and 1930s after the 1918 influenza pandemic – remains to be seen.”
The study provides a detailed account of neurological symptoms of 43 people (aged 16-85) treated at the National Hospital for Neurology and Neurosurgery, UCLH, who had either confirmed or suspected Covid-19.
The researchers identified 10 cases of transient encephalopathies (temporary brain dysfunction) with delirium, which corresponds with other studies finding evidence of delirium with agitation. There were also 12 cases of brain inflammation, eight cases of strokes, and eight others with nerve damage, mainly Guillain-Barré syndrome (which usually occurs after a respiratory or gastrointestinal infection).
Most (nine out of 12 cases) of those with brain inflammation conditions were diagnosed with acute disseminated encephalomyelitis (ADEM). ADEM is rare and typically seen in children and can be triggered by viral infections: the team in London normally sees about one adult patient with ADEM per month, but that increased to at least one per week during the study period, which the researchers say is a concerning increase.
The virus causing Covid-19, SARS-CoV-2, was not detected in the cerebrospinal brain fluid of any of the patients tested, suggesting the virus did not directly attack the brain to cause the neurological illness. Further research is needed to identify why patients were developing these complications.
In some patients, the researchers found evidence that the brain inflammation was likely caused by an immune response to the disease, suggesting that some neurological complications of Covid-19 might come from the immune response rather than the virus itself.
The findings add clinical descriptions and detail to another recent study, which also involved Dr Zandi and co-author Dr Hadi Manji (UCL Queen Square Institute of Neurology and UCLH) identifying 153 people with neurological complications from Covid-19.* This paper also confirms the previously reported findings of a higher than expected number of patients with stroke which results from the excessive stickiness of the blood in COVID-19 patients.**
Joint first author Dr Ross Paterson (UCL Queen Square Institute of Neurology) said: “Given that the disease has only been around for a matter of months, we might not yet know what long-term damage Covid-19 can cause.
“Doctors needs to be aware of possible neurological effects, as early diagnosis can improve patient outcomes. People recovering from the virus should seek professional health advice if they experience neurological symptoms,” he added.
Joint first author Dr Rachel Brown (UCL Queen Square Institute of Neurology and UCL Infection & Immunity) said: “Our study advances understanding of the different ways in which Covid-19 can affect the brain, which will be paramount in the collective effort to support and manage patients in their treatment and recovery.”
Joint senior author Dr Hadi Manji said: “Our study amalgamates, for the first time, the clinical presentations of patients with Covid-19 neurological disease with MRI and laboratory features including, in one case, a brain biopsy.
“This now sets up a template for other researchers around the world, facilitating coordinated research to optimise the diagnosis and treatments of these complications, which to date, has proved difficult. In addition, patients are going to require long term follow up.”
The researchers were supported by the National Institute for Health Research UCLH Biomedical Research Centre, Medical Research Council, Alzheimer’s Association, and the UK Dementia Research Institute.
About this COVID-19 research article
Chris Lane – UCL
The image is credited to the researchers.
Original Research: Open access
“The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings” by Michael Zandi et al. Brain
The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings
Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms, which will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.