Clinical Chemistry

The Nervous System: Viral Infections And Neuroinflammation

The Central Nervous System (CNS) while being the most intricate is the most delicate system in the animal body. The brain has an incredibly extensive blood supply. The vertebral and carotid arteries and the related veins are important vessels that supply and drain blood in the brain. As the brain is a very delicate complex system that requires only essential substances, there exists a boundary that prevents the diffusion of assorted substances into the brain. These substances include pathogens, toxins and even the immune system.

In the current COVID-19 pandemic, neurologists have identified multiple cases of cerebrospinal neuropathy which result from viral infection causing coagulopathy, neuromuscular, cognitive and psychiatric disorders. These conditions are also observed for several other viruses with invasive capabilities into the brain. 

This article would discuss biochemical processes regulating the neural environment, inflammation and destruction of nervous tissue.

Clinical presentation (case study)

A fictitious presentation of viral-induced peripheral neuropathy

In 2020, a 71-year-old man was admitted into a hospital, complaining of numbness in his hands and feet. He, in previous weeks, had a fever, cough, tiredness, headache, pain in the chest, and breathing difficulty. Now he feels numb on both fore and hind limbs, a burning sensation and myalgia. Where should the clinical diagnosis be directed towards?

The vasculature of the brain

Blood flow and circulation in the brain is mediated by arteries and veins. Of huge significance is the internal carotid artery which supplies the cerebrum and the vertebral artery which supplies the mesencephalon and cerebellum. Blood flow is strictly regulated according to biochemical demands. Carotid sinuses are present detecting changes in the partial pressures of oxygen, carbon dioxide, and acidity of the blood. A blood-brain barrier also exists to prevent indiscriminate absorption of substances. Primary metabolites are usually transported with the aid of transporters. 

Viruses are ubiquitous and are taken up through blood contact, organ transplantation or environmental exposure via the lungs, mucous membranes or wounds. Viruses could be moved from peripheral tissues via the blood into the brain or spinal cord, attacking tissues and causing inflammation. Inflammation of the brain is known as encephalitis.

Viruses are also known to cause inflammation of the meninges of both the brain and spinal cord. Viral meningitis is caused by certain viruses such as herpes simplex virus, varicella-zoster virus, Epstein Barr virus, Human Immunodeficiency Virus (HIV)and enteroviruses which cause mumps, pox and HIV/AIDS. The difference between encephalitis and meningitis is that encephalitis is localized in the brain while the latter is the entire CNS. Meningitis also refers to inflamed meninges, not the entire matter.

When viruses invade the body, the immune system arrives to clear them off. During the process, cytokine hormones and vasodilators are released which permits the leucocytes to extravasate through the damaged epithelia to the site of infection. If these viruses reach the CNS, they may be confronted against there. 

Cytokines are involved in activating, mobilizing and regulating the immune processes. They are usually involved in fighting against pathogens, allergens and even in autoimmune conditions. Cytokines involved in the process of viral encephalitis and meningitis include: chemokines, Interleukins (ILs), Tumor Necrosis Factor (TNF), and interferons (IFNs)

Viral meningitis is less severe than that bacterial causes and could be identified by analysis of cerebrospinal fluid. They could lead to the destruction of the layers of the spinal cord causing high fever, severe headache due to an increase in intracranial pressure and stiffness of the cervical region. This could be cured using the appropriate antiviral medication.

Peripheral and cerebrospinal neuropathy

The immune system of the brain is distinct from that of the general system. Certain cells known as glial cells are responsible for eliminating infections and other possibly harmful particles or substances. These cells include astrocytes (regeneration and supporting cells) and microglial (chief immune cells of the Central Nervous System). In the presence of viral infection, the microglial releases chemokines that attract lymphocytes (macrophages, B- and T-cells). This can then destroy the nervous tissue. In the case of peripheral inflammation, the infection could lead to the destruction of the myelin sheath or Schwann cells. It could also cause degeneration of the nerve fibre causing a loss of function in the part of the body supplied by that nerve.

There are cases of cerebral complications resulting from viral infection. Inflammation could lead to the development of plaques in the brain (a result of platelet aggregation) causing strokes. This is very serious especially in patients with existing cardiovascular diseases. Hence the endothelium of blood vessels and its injury are key factors that dispose people to inflammatory diseases. Inflammation in the brain could be due to the activation of microglia by cytokines and other immune factors leading to encephalitis. This form of damage can result in mental complications. In the course of infection, the production of TNF alpha, interleukins and ROS (Reactive Oxygen Species) can lead to the degradation of the Blood-Brain Barrier integrity.

Neuropathy in COVID-19 infected patients

It is generally known that some viruses could lead to the degeneration of nerve tissue. Such viruses include chickenpox virus, herpes virus, EBV, influenza and even HIV. However certain viruses could cause more severe symptoms of neuroinflammation. The coronavirus (SARS CoV-2) has been found to cause both peripheral and CNS complications. In the case study written above, the patient is likely to be suffering from neuropathic crises associated with SARS CoV-2. The recommendation is that he should be subjected to nerve conduction tests and body fluid analysis. Inflammation-inducing viral infections can spread to the nervous system causing damages in those areas. The symptoms that manifests include sharp and stinging pain, muscular weakness, numbness of fingers, hands or feet, lack of motor coordination and paralysis of the limbs. Cases of long term mental complications have also been reported. Chronic symptoms could lead to long term inflammation displaying clinical features including memory problems, delirium, speech and language problems and emotional problems. Coronavirus disease can therefore lead to severe psychological, mental and cardiovascular effects. 

How can neuropathy be treated or managed?

Studies have shown that  multiple factors come into play in the development of these conditions in virus infections. Age, genetic susceptibility and medical history are very important cues that can determine the development and severity of symptoms. Some of the symptoms can lessen or leave as healing progress while some are permanent if the damaged nerve can not regenerate. It is necessary to report any unusual sensations and feelings especially if you have been exposed to viruses especially the ones listed above. Pain should be treated and managed with NSAIDs (Non-Steroidal Anti-inflammatory Drugs) as analgesics and to halt the inflammation. The patient should be monitored for improvements and the best care and support should be provided.