Volume 2 - Issue 4

The gamut of neurological disorders associated with COVID-19

Bhuvaneshwari Rajendran1,*, R. Gayathri2

1Senior Consultant, Department of Neurology and Neurophysiology, Kauvery Hospital, Chennai, Tamil Nadu, India

22Physician Assistant, Department of Neurology and Neurophysiology, Kauvery Hospital, Chennai, Tamil Nadu, India

*Correspondence:   bhuvana1675@hotmail.com

Highlights

  • The COVID-19 syndrome can present with many neurological features, besides its well - recognized respiratory and vascular manifestations
  • Acute ischemic stroke can be one of them, with large vessel thrombosis
  • Neurological features can also be associated with the post-COVID-19 and Long COVID syndromes

Abstract

COVID-19 has led to unprecedented clinical challenges worldwide. Its clinical manifestations range from asymptomatic infection to multi-organ failure and death. Infection with the novel coronavirus 2 (SARS-CoV-2) predominantly presents with pulmonary involvement. But clinical data from all over the world has clearly indicated that SARS-CoV-2 can negotiate many complex pathophysiological pathways and emerge with a wide array of clinical manifestations, involving all organs and systems. We present our varied experience of COVID-19 related neurological manifestations and hope that the sharing of our insights shall contribute to designing an efficient management paradigm.

Keywords: COVID-19, Neurological manifestation, SARS-CoV-2

Introduction

The COVID-19 pandemic, since its onset in Wuhan, China has imposed a Herculean burden on the global healthcare delivery system, and crippled it with staggering wave after wave of critical illness. It is by far most devastating pandemic to hit the world since the 1918 Spanish influenza [1].

The coronavirus SARS-CoV-2 primarily affects the respiratory system; however, there is mounting evidence of nervous tissue invasion [2-5]. The neurological effects range from headache, fatigue, anosmia, dysgeusia (altered taste), impaired consciousness, seizures and stroke, to more debilitating conditions such as cerebrovascular catastrophes and hypercoagulable or excessive coagulation states. The emergence of a spectrum of autoimmune disorders of the nervous system in a post COVID-19 period is also very concerning and include autoimmune encephalitis, myelitis, myositis and Guillain Barre Syndrome (GBS).

Mechanism of neuroinvasion of SARS-CoV-2

We now know that that the expression of Angiotensin Converting Enzyme 2 (ACE 2) receptors is predominantly on the surface of neurons. The SARS-CoV-2 has affinity towards these receptors; and engage these receptors to enter the Central Nervous System (CNS) [6,7]. Numerous reports describe concomitant invasion of the respiratory centre in the brainstem which may play a vital role in respiratory failure in COVID-19 patients [7,8].

Direct viral invasion occurs through haematological pathways. The virus crosses the blood brain barrier (BBB) by transcytosis or invades endothelial or epithelial cells to pass through the BBB [8-10]. Cytokine storms contribute to acute lung injury and neuroinflammatory insults. The cytokine storm and immune-mediated toxicity may also disrupt the BBB in the absence of direct viral invasion. Reports suggest that acute necrotising encephalopathy might be mediated by cytokine toxicity [11].

COVID-19 induced neurological manifestations

The CNS manifestations can range from mild to more severe manifestations. The main CNS manifestations are anosmia, headache, dizziness, altered mental status, seizures, myalgia cerebrovascular events, encephalopathy, encephalitis, myelitis, ataxia, acute haemorrhagic necrotising encephalopathy, rhabdomyolysis and GBS.

The symptoms can be classified into three distinct categories:

  • Complications relating to coagulopathy such as Cerebro Vascular Accident (CVA) (Figs. 1 and 2), both thrombotic and haemorrhagic.
  • Complications relating to encephalopathy comprises of altered sensorium, seizures.
  • Complications relating to auto-immunity which were observed later in the post-COVID phase.

Cerebro Vascular Accident (CVA)

Fig. 1. CT Brain of a patient showing Right MCA territory Infarct.

Fig. 2. CT Brain of a patient illustrating Cerebral bleed.

Encephalopathy

Case 1: A 72-year old gentleman presented with a past history of psychosis and was in remission. RT-PCR was positive for COVID-19 and the CT image revealed COVID-19 associated pulmonary features. Subsequently, when the patient was recovering, he developed severely altered sensorium and seizures. CSF analysis was negative for cells but protein was elevated. He received appropriate management.

Fig 3. EEG of a patient demonstrating a seizure activity.

Guillian Barre Syndrome

Case 2: A 14-year-old adolescent, with a history of fever for one-day duration, presented with sudden onset of left lateral rectus palsy and right lower motor neuron (LMN) facial palsy. He had severe loss of control of his body movements (ataxia) and complained of exacerbated difficulty in walking.

On examination, his reflexes were depressed. He was clinically diagnosed as a Miller-Fisher variant of GBS. Nerve conduction studies and MRI spine with contrast were done which supported the diagnosis of GBS. RTรขโ‚ฌโ€œPCR was positive for COVID-19 but he had no respiratory symptoms. He was managed with immunoglobulins, and had a remarkable recovery.

Post-COVID-19 syndrome

Post-COVID conditions are a wide spectrum of new, recurring or ongoing health issues people can experience four or more weeks after being infected with the coronavirus. The neurological features of this syndrome can be the following: 

  • Chronic fatigue syndrome
  • Myalgia and arthralgia
  • Sleep disorders
  • Post-traumatic stress syndrome
  • Depression
  • Cognitive impairment

Patients with these symptoms have to be monitored for long COVID syndrome.

Conclusion and future direction

The biological underpinnings of coronavirus infection might only be the tip of the iceberg. Neurological complications in COVID-19 infected patients are likely to be on the rise. Prompt identification and evaluation of COVID-19 patients with new onset of neurological symptoms initiate timely intervention. We recommend monitoring of patients recovered from COVID-19 infection for long-term effects. Our experience and insights address the challenges of classifying the neurological complications and facilitate a methodical approach to investigate and treat patients. While further clinical and follow-up studies are underway for the COVID patient, this glimpse we provide into the neurological manifestations of this new disease shall, hopefully, open doors to neurologists leading to for harmonisation of treatment strategies.

References

  • Taubenberger JK, Morens DM. 1918 Influenza: the mother of all pandemics. Emerg Infect Dis. 2006;12(1):15-22.
  • Herman C, Mayer K, Sarwal A. Scoping review of prevalence of neurologic comorbidities in patients hospitalized for COVID-19. Neurology 2020;95(2):77-84.
  • Ellul MA, Benjamin L, Singh B et al. Neurological associations of COVID-19. Lancet Neurol. 2020;19(9):767-83.
  • Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):683-90.
  • Pleasure SJ, Green AJ, Josephson SA. The spectrum of neurologic disease in the severe acute respiratory syndrome coronavirus 2 pandemic infection: neurologists move to the frontlines. JAMA Neurol. 2020;77(6):679-80.
  • Li Y-C, Bai W-Z, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020;92(6):552-5.
  • Desforges M, Le Coupanec A, Dubeau P et al. Human coronaviruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system? Viruses 2019;12(1):14.
  • Nath A. Neurologic complications of coronavirus infections. Neurology 2020;94(19):809-10.
  • Moriguchi T, Harii N, Goto J et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis. 2020;94:55-8.
  • Aghagoli G, Marin BG, Katchur NJ et al. Neurological involvement in COVID-19 and potential mechanisms: a review. Neurocrit Care. 2020;34(3):1062-71.
  • Allan SM, Rothwell NJ. Cytokines and acute neurodegeneration. Nat Rev Neurosci. 2001;2(10):734-44.

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