• Multiple Sclerosis (MS)
• Neuromyelitis Optica Spectrum Disease (NMOSD)
• Myelin Oligodendrocyte Glycoprotein (MOG)-Antibody Associated Disease
• NMDAR Encephalitis

1- What Is an Autoimmune Disease?

An autoimmune disease is when the body develops an abnormal immune response against certain parts of the body leading to their destruction.

An abnormal autoimmune response is associated with the production of antibodies against compounds (antigens) that belongs to the body, and therefore, that should not be recognized as foreign.

2- What is an Antibody?

Antibodies or immunoglobulins (Ig) are Y-shaped proteins produced by specific types of white blood cells known as lymphocytes B cells in response to pathogens such as bacteria and viruses.

An antibody recognizes and binds a specific antigen on the surface of a bacteria or virus leading to their destruction. It is highly specific and targets a specific antigen, and therefore, cannot target other antigens.

However, when there are abnormalities in the immune response, the antibodies start recognizing antigens on the surface of normal cells which leads to their destruction and the development of autoimmune diseases, including autoimmune diseases of the central nervous system [1].

3- What Causes Autoimmune Diseases?

• Genetic Susceptibility

Although the potential involvement of heredity in autoimmune diseases is unknown, studies of homozygotic twins (identical twins) and heterozygotic twins (non-identical twins) with multiple sclerosis (MS) and myasthenia gravis found an association between genetic factors and autoimmune diseases [2] [3].

• Infections

In multiple sclerosis (MS) and MOG-antibody associated disease, chronic infection with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were suggested as triggers of autoimmune response by mimicking the host (infected individual) normal antigens [4][5].

• Vitamin D Deficiency

Vitamin D is an antioxidant that has also a role as a modulator of immune response by controlling the proliferation (multiplication) of lymphocytes B cells and their production of antibodies.

Although the results are conflicting and require further investigations, studies reported an association between the incidence and susceptibility to multiple sclerosis (MS) and the decrease in the levels of vitamin D [6][7][8][9].

• Gut Flora Unbalance (Dysbiosis)

The gut flora or microbiota is a heterogeneous population of micro-organisms that includes bacteria, fungi, and archaea, and that plays an important role in the digestion and absorbance of food. 

During the process of aging, the function of beneficial microbes, that provide necessary nutrients for the body tissues, is severely affected, while harmful microbes, that contribute to the process, such as chronic inflammation and cancer, flourish.

Studies showed that fecal transplants from patients with multiple sclerosis (MS) into germ-free mice results in a higher incidence or severity of multiple sclerosis in these mice [10][11].

• Tumors

Tumors are characterized by an uncontrolled division of cells due to cancerous mutations in normal cells. When some tumors die, they can release both cancerous and normal antigens that are thought to initiate an autoimmune response [12][13].

4- Autoimmune Diseases of the Central Nervous System

• Multiple Sclerosis

The axons of neurons are covered by a sheath of a fatty acid (lipid), known as myelin, which insulates them and increases the rate of nerve impulses.

In multiple sclerosis (MS), the myelin sheath is damaged through a process called demyelination which disrupts the capacity of the affected neurons to conduct nerve impulses.

It is proposed that multiple sclerosis (MS) is due to a mix between genetics and infections; however, there is no evidence yet to support these hypotheses.

This demyelination of neurons results in the following symptoms:

Effects on the Central Nervous System: Cognitive impairment, anxiety, depression, mood instability, and fatigue.

Effects on the Vision: Inflammation of the optic nerve (Optic neuritis), involuntary eye movement (Nystagmus), perception of two images when looking a single object (diplopia).

Effects on the Musculoskeletal system: Fatigue, spasms, and Ataxia (uncoordinated movements).

Effects on Speech: slurred or slow speech due to a weakness of speech muscles (Dysarthria).

Effects on the Throat: difficulty swallowing (Dysphagia).

Effects on Sensation: Pain, paraesthesia, hypoesthesia.

Effects on the Bowel: Diarrhea or constipation and incontinence.

Effects on the Urinary System: frequent urination or retention of urine.

• Neuromyelitis Optica Spectrum Disease (NMOSD)

NMO is an autoimmune disease affecting the optic nerves, spinal cord, and brainstem. It is associated with autoantibodies targeting an abundant protein in the nervous system known as aquaporin 4 [14].

The causes of NMOSD are unknown and the symptoms are associated with a loss of vision, loss of sensation, weakness, and anomalies in the bladder function.

• Myelin Oligodendrocyte Glycoprotein (MOG)-Antibody Associated Disease

MOG-Antibody Associated Disease is a rare autoimmune disease affecting a protein known as myelin oligodendrocyte glycoprotein (MOG).

MOG is found on the myelin sheaths and produced by a type of neuronal cells called oligodendrocytes. In this disease, autoantibodies are produced against MOG which causes the damage of myelin causing the demyelination of the neurons.

The symptoms of MOG include pain, muscle weakness or paralysis, abnormal sensations, bowel such as Diarrhea or constipation, and anomalies of bladder function.

• NMDAR Encephalitis

NMDAR Encephalitis or anti-receptor encephalitis is an inflammation of the brain that is caused by autoantibodies against a receptor of the neurotransmitter glutamate known as NMDAR [15].

NMDAR is found on neurons where it plays an important role in the control of synaptic plasticity.

NMDAR Encephalitis is mainly caused by ovarian teratoma and by an inflammation of the brain associated with a herpes virus infection.

The symptoms of NMDAR Encephalitis include seizures, depression, mania, visual or hearing hallucinations, acute schizophrenic disorder, and cognitive and movement disorders.

5- How are CNS Autoimmune Diseases Diagnosed?

In addition to the symptoms associated with each CNS autoimmune disease, the patients are tested using magnetic resonance imaging (MRI), electroencephalogram (EEG), computerized tomography (CT) scan, and FDG-positron emission tomography (PET)/CT scan, to detect neuronal lesions [1].

Autoantibody testing is used to detect the presence of autoantibodies against proteins such as NMDAR, MOG, and aquaporin 4 in the serum and cerebrospinal fluid (CSF) using laboratory techniques such as immunohistochemistry, indirect immunofluorescence, western blot, and cell-based assays.

Conclusion

CNS autoimmune diseases are due to the generation of antibodies by lymphocytes B that attack specific proteins that are expressed on neurons and in the brain. Most therapies aim at eliminating the autoantibodies using plasma exchange and immunosuppression [1].

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