key: cord-0865160-5h9r3hmf
authors: Kulkarni, Rahul; Pujari, Shripad
title: COVID-19 Associated Neurological Manifestations
date: 2021-12-17
journal: Ann Indian Acad Neurol
DOI: 10.4103/aian.aian_1016_21
sha: 59f93eeff264bc6a7ea8947cc53dfb92768a2de1
doc_id: 865160
cord_uid: 5h9r3hmf

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In this issue, George et al. [5] have described most of the manifestations due to both the etiologies and will serve as a useful reference for the clinicians and the future authors. Certain non-serious manifestations appear during the acute phase of the viral infection, which include anosmia, ageusia and constitutional symptoms such as headache, myalgia and fatigue. CNS manifestations due to virus include encephalopathy, encephalitis, strokes, seizures, central and peripheral demyelinating disorders, movement disorders, peripheral neuropathies and rarely, posterior reversible leukoencephalopathy syndrome (PRES). [1] [2] [3] [4] [5] During the second wave of COVID-19, rhino-orbito-cerebral mucormycosis infection following COVID-19 has been described from India. [7] Data about neurological manifestations is needed from all parts of world to see if any regional variation exists. A point to note is since the COVID-19 infection is widespread, a neurological manifestation in COVID-19 patient can be incidental, triggered or caused by the virus. [8] Encephalopathy can be a consequence of high fever, hypoxia, metabolic derangements, sepsis, inflammation, cytokine storm, prothrombotic state or seizures. [1, 2] Encephalitis is uncommon with COVID-19 infection. Most of the viruses cause encephalitic illness due to direct invasion or as a post-infectious mechanism. SARS-CoV-2 virus also causes acute necrotizing encephalopathy (ANE) which is proposed to be caused by a third mechanism, that is by release of cytokines. [9] More research needs to be performed to study the pathogenesis of such syndromes. Role of anti-viral drugs, anti-cytokine monoclonal antibodies such as tocilizumab and steroids need to be assessed in patients with brain involvement through properly structured trials. It is difficult to differentiate between encephalitis and encephalopathy in some patients, especially in the patients who have a normal metabolic lab and no evidence of secondary bacterial or fungal infection. Documenting the virus in cerebrospinal fluid may separate encephalitis from encephalopathy, thus solving this issue about the pathogenesis.

SARS-CoV-2 infection is a pro-thrombotic state and arterial ischemic strokes (AIS) are commonly seen around and after COVID-19. Cerebral venous sinus thrombosis has also been reported. Intracerebral hemorrhages as a complication of SARS-CoV-2 infection are comparatively rare. [10] Superadded fungal infections were a common complication, more so during the second wave of the epidemic. Mucormycosis is an angio-invasive disease and was another cause for AIS as well as hemorrhagic strokes during this period. [11] All acute stroke management protocols including recanalization measures need to be implemented, weighing the risks and benefits of these therapies with the health care givers using personal protection devices. [1] Patients have suffered AIS on anti-platelet agents and/or heparin and so, comparative trials need to be set up evaluate the role of anti-coagulation in COVID-19 related AIS.

Seizures can occur in SARS-CoV-2 infection because of several causes. They could be precipitated just by the fever in a known epileptic, fever due to viral infection or vaccine could trigger seizures in a patient with no past history and so could metabolic impairment and secondary sepsis. Seizures can occur due to strokes, encephalitis, necrotizing encephalopathy, post-viral or post-vaccinal acute disseminated encephalomyelitis (ADEM). So, seizures around the period of COVID-19 or after vaccination would need careful evaluation to pinpoint the cause.

Peripheral neuropathy occurs during the course of the acute SARS-CoV-2 infection, as well as after the COVID-19 symptoms subside. So, it is possible that the ones who present early are due to the direct neurotropic effects of the virus and so, can be called infectious or para-infectious, whereas those that follow after the fever and respiratory symptoms have resolved are the classic "post-infectious", that is Guillain-Barre Syndrome (GBS). [12] SARS-CoV-2 infection can also cause

Editorial Commentary mononeuropathies involving both the cranial and the peripheral nerves. Bell's palsy is a known complication. Involvement of single nerve of the limb (ulnar or peroneal neuropathies) has also been documented after COVID-19. [13] Though severe myalgia and fatigue are extremely common during acute infection and also as a post-COVID syndrome, neuromuscular junction and primary muscle involvement has not been a common occurrence. [13] The neurological manifestations of COVID-19 vaccines are best studied for ChAdOx1nCoV-19s vaccine which is most common vaccine used in India. [6] The manifestations include GBS, Bell's palsy, ischemic and hemorrhagic strokes and demyelinating events. Efforts should be made to find which sub-group of population is more susceptible to post-vaccinal complications.

The 1918 Spanish flu pandemic was followed by the so called "encephalitis lethargica" and there was sharp rise in the incidence of parkinsonism after this pandemic. [14] A long duration follow-up of COVID-19 patients needs to be undertaken to study the long-term neurological complications of this dreadful viral infection.

Extrapulmonary manifestations of COVID-19

Neurologic manifestations of hospitalized patients with coronavirus disease

The emerging spectrum of COVID-19 neurology: Clinical, radiological and laboratory findings

Neurological manifestations of COVID-19: A systematic review

Neurological disorders seen during second wave of SARS-CoV-2 pandemic from two tertiary care centers in central and southern kerala

Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection

Rhinoorbitocerebral mycosis and COVID19: From bad to worse?

COVID-19 and stroke: Incidental, triggered or causative

COVID-19-associated acute hemorrhagic necrotizing encephalopathy: Imaging features

Characteristics and outcomes of 100 consecutive patients with acute stroke and COVID-19

Cerebrovascular involvement in mucormycosis in COVID-19 pandemic

Suillian-Barre syndrome in patients with SARS-CoV-2: A multicentric study from Maharashtra

COVID 19: Neuromuscular Manifestations

The relationship between encephalitis lethargica and influenza: A critical analysis