Neurological manifestations and implications of COVID-19 pandemic

Abstract

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide, with a vast majority of confirmed cases presenting with respiratory symptoms. Potential neurological manifestations and their pathophysiological mechanisms have not been thoroughly established. In this narrative review, we sought to present the neurological manifestations associated with coronavirus disease 2019 (COVID-19). Case reports, case series, editorials, reviews, case-control and cohort studies were evaluated, and relevant information was abstracted. Various reports of neurological manifestations of previous coronavirus epidemics provide a roadmap regarding potential neurological complications of COVID-19, due to many shared characteristics between these viruses and SARS-CoV-2. Studies from the current pandemic are accumulating and report COVID-19 patients presenting with dizziness, headache, myalgias, hypogeusia and hyposmia, but also with more serious manifestations including polyneuropathy, myositis, cerebrovascular diseases, encephalitis and encephalopathy. However, discrimination between causal relationship and incidental comorbidity is often difficult. Severe COVID-19 shares common risk factors with cerebrovascular diseases, and it is currently unclear whether the infection per se represents an independent stroke risk factor. Regardless of any direct or indirect neurological manifestations, the COVID-19 pandemic has a huge impact on the management of neurological patients, whether infected or not. In particular, the majority of stroke services worldwide have been negatively influenced in terms of care delivery and fear to access healthcare services. The effect on healthcare quality in the field of other neurological diseases is additionally evaluated.

Keywords: COVID-19; SARS-CoV-2; cerebrovascular diseases; healthcare impact; neurological manifestations.

Figure 1.

Imaging evaluation of an ischemic stroke patient with concomitant COVID-19. This 53-year-old man presented in the emergency department of a comprehensive stroke centre on March 18, 2020. The patient was aphasic with right hemiplegia. The National Institute of Health Stroke Scale (NIHSS) score was 16. He was afebrile and his family members denied any symptoms attributable to COVID-19. Neurological symptoms’ onset-to-presentation time was 1 h. A non-contrast brain computed tomography (CT)-scan was performed, intracranial haemorrhage was excluded and early hyperacute signs of left middle cerebral artery ischemia were disclosed (loss of grey-white matter differentiation (A). No other contraindications existed and intravenous thrombolysis with alteplase was administered. Door-to-needle time was relatively prolonged (70 min), since the CT-scan was occupied at that time with chest examinations of patients with possible SARS-CoV-2 infection. There was no availability for mechanical thrombectomy in this institution (after-hours presentation of the patient and limited personnel in the catheter laboratory). Diagnostic work-up revealed two possible stroke mechanisms: atrial fibrillation of unknown duration with subsequent cardio-embolism, and concomitant atherothrombotic disease, causing haemodynamically significant (>70%) stenosis of the internal carotid arteries bilaterally. During the next 48 h, the patient presented neurological deterioration (NIHSS-score of 22) and follow-up brain CT showed an extensive infarction in the distribution of the left middle cerebral artery (B). At that time, the patient developed a low-grade fever, most probably due to aspiration. Chest CT-scan was indicative of bilateral aspiration pneumonia (C). Oropharyngeal swabs were also examined for SARS-CoV-2 on RT-PCR assay, but the virus was not detected. Three days later, the patient was intubated and transferred to the general intensive care unit. The second oropharyngeal swab test was positive for SARS-CoV-2 RNA. The patient expired on March 24, 2020 due to further neurological deterioration from cerebral oedema.

Figure 2.

Imaging evaluation of a patient with intracerebral haemorrhage with concomitant COVID-19. A 67-year-old man with a history of hypertension, diabetes, hypercholesterolemia and coronary artery disease presented to the emergency department of a comprehensive stroke centre on April 6, 2020 after waking up with slurred speech, left-sided weakness and numbness. Admission systolic and diastolic blood pressure levels were 178/106 mmHg. The patient was afebrile with no respiratory symptoms. However, history provided by his wife suggested that earlier in the morning, prior to his admission, he had an increased body temperature of 38.5°C. Brain computed tomography scan uncovered right thalamic intracerebral haemorrhage with mass effect and intraventricular extension (A). The patient was admitted in the stroke unit. Due to the history of fever, a nasopharyngeal swab was performed on the day of admission and was negative for SARS-CoV-2. However, on the following day the patient redeveloped fever, so work-up with blood cultures, chest X-ray (B) and urinalysis was performed but did not uncover any obvious source of infection. A second nasopharyngeal swab was ordered and came back positive for SARS-CoV-2 RNA. Despite SARS-CoV-2 infection, the patient never experienced any symptoms of dyspnoea, cough, chest pain or diarrhoea during his hospitalization. He only reported the presence of mild generalized headache and nausea, which could have been attributable to the intracerebral haemorrhage. A certain causal association between COVID-19 and intracerebral haemorrhage cannot be established based on the evidence in this case, especially since the patient had a medical history of three common risk factors of manifesting both the diseases (Table 3). However, it may be postulated that blood pressure dysregulation due to angiotensin converting enzyme 2 (ACE2) inactivation by SARS-CoV-2 could have been at least partially involved in the development of intracerebral haemorrhage.

Figure 3.

Imaging evaluation of a left facial palsy patient with concomitant COVID-19. A 27-year-old man was admitted to the isolation ward of a tertiary centre on March 16, 2020, presenting with myalgia, cough, fever and left-sided headache for 4 days. He had just returned from Spain the day before admission. On examination his lungs were clear and neurological examination was unremarkable. Reverse-transcription polymerase-chain-reaction (PCR) performed on the nasopharyngeal swab was positive for SARS-CoV-2. On day 3 of hospitalization, he developed left retro-auricular pain, dysgeusia and left facial weakness. Neurological examination showed a left facial nerve palsy. There was no associated neck stiffness, vesicles in the outer ear, or parotid swelling. Cerebrospinal fluid (CSF) studies showed no cells, and protein and glucose levels were normal. CSF PCR was negative for herpes simplex virus, varicella zoster virus and SARS-CoV-2. His magnetic resonance imaging of the brain showed contrast enhancement of the left facial nerve (Figure). He was treated with lopinavir/ritonavir for reducing SARS-CoV-2 viral replication. He received a 1-week course of prednisolone and valacyclovir for treatment of facial palsy. Upon review 1 week later, his headache had resolved, and improvement was noted in facial weakness.