• 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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• Direct Sciatic Nerve Compression
• Inflammation

It is estimated that the annual incidence in the general population is between 1% to 5% and the lifetime incidence is between 10% and 40% [1].

1- How Long Will Sciatica Take to Heal?

Sciatica can lasts 4-6 weeks, however, it can last longer depending on the causes.

2- What is the Sciatic Nerve?

The sciatic nerve is responsible for sensations in the feet and legs.

It is hosted and protected by the spine and starts at the base of the brain and travels all the way to the lumbar region of the spine where it branches into right and left.

Each branch will continue its enervation route all the way to the feet (right or left).

2- What Triggers Sciatica?

• Direct Sciatic Nerve Compression

Our spine or vertebral column is made of 24 vertebrates, the sacrum, and the coccyx.

We have 7 vertebrates of the neck (cervical vertebrates), 12 of the midback (thoracic vertebrates), and 5 of the lower back (lumbar vertebrates).

Each vertebrate is joined to another vertebrate by a disc (intervertebral disk).

• Lumbar Herniated Disc

When a lumbar intervertebral disc bulges or herniates, it can compress the sciatic nerve resulting in pain.

Lumbar Herniated Disc causes 90% of the direct sciatic nerve compressions [2].

• Degeneration

The degeneration of the tissues of vertebrates in the lumbar part of the spine can result in the compression of the sciatic nerve.

• Spondylolisthesis

When a vertebrate slips out of position due to a stress fracture it can compress the sciatic nerve.

• Lumbar Spinal Stenosis

The spine canal through with passes the sciatic nerve may decrease in size due to factors, such as age, resulting in the compression of the sciatic nerve.

• Lumbar or Pelvic Muscular Spasm

Spasm in muscles such as the piriformis muscle can irritate or compress the sciatic nerve.

• Hematoma or abscess

Hematoma or abscesses around the sciatic nerve can cause compression of the sciatic nerve.

• Tumors

Spinal tumors that originate from the vertebra, spinal cord, or nerves can also compress the sciatic nerve.

• Inflammation

Within the spine, there is an acid substance known as hyaluronic acid. When the spine is damaged, this substance leaks into the surrounding tissues of the sciatic nerve causing its irritation, inflammation, or compression.

3- What Are the Risk Factors of Sciatic Nerve Pain (Sciatica)?

• Occupation and Sciatica

There is a predisposition for sciatica in workers including truck drivers, carpenters, and machine operators due to long hours in uncomfortable positions.

• Lack of Physical Activity and Sciatica

Lack of physical activity can weaken lower back muscles (lack of flexibility, tone, and movement) resulting in less support for the lumbar spine and potential compression of the sciatic nerve.

• Smoking and Sciatica

Although the mechanism is not well known, smoking appears to be a modest risk of sciatica [3].

• Mental Health and Sciatic

Depression and anxiety disorders have been associated with sciatica due to the release of inflammation factors (inflammatory mediators) in the lower back region which can irritate the sciatic nerve [4].

• Tall height in older age groups (50 to 60 years)

A study that included 13680 participants found a correlation between tall height and lower back pain or related surgery [5].

• Obesity and excess weight

Weight being carried in the front can be a weight on the spine and related muscles which may cause muscle strain that can potentially lead to sciatica.

• Genetic susceptibility

A study reported a higher incidence of sciatica or prolapsed disc in first-degree relatives of patients hospitalized for herniated lumbar disc or surgery [6].  

Another study of 9365 pairs of adult twins found a correlation between genetics and the incidence of sciatica [7].

• Previous injury

Previous injuries in athletes or workers can result in lumbar intervertebral disc bulges or herniation.

• Diabetes

Diabetes is a metabolic disorder that can cause damages to the sciatic nerve.

• Pregnancy

The growing baby during pregnancy can generate extra weight resulting in a weight that is applied on the spine and related muscles which may cause muscle strain.

• Recreational Activities

In a study that involved 2077 workers, regular walking and jogging have been shown to increase the incidence of sciatica [8].

5- What Are the Symptoms of Sciatica?

• Pain in the lower back, buttock, and leg which can be intermittent or persistent.
• Reduced movement and mobility together with moderate or severe pain.
• Weakness in the lower back and leg.
• Numbness or pins-and-needles sensations along the leg and foot.

6- When Should I Worry About Sciatica?

Sciatica can be due to severe or chronic conditions such as tumors, bilateral sciatica, scarred tissues, hematoma, cysts or abscesses, spinal tuberculosis, medications non-responsive infections, or fracture in the vertebrates of the lumbar spine.

These conditions may require surgery to restore the function of the lower spine and surrounding tissues.

5- Sciatica Treatment

Sciatica treatment may involve non-surgical or surgical therapies.

• Non-surgical therapies

Exercises for Sciatica

Physical therapy aims at restoring strength to the spine and lower-back muscles, buttocks, hip, and abdomen which may involve swimming, walking, and specific stretching movements with a help of a physical therapist.

Lifestyle Changes

Losing weight through a healthy diet can significantly reduce chronic sciatica by decreasing the weight being carried in the front, and therefore, reducing the weight on the spine and related muscles.

This effort can be complemented with exercise to strengthen the spine and lower back muscles, buttocks, hip, and abdomen.

For workers with a predisposition for sciatica, preventing certain positions or intermittent stretching while working can prevent or reduce the risk of sciatica.

Alternative therapies

Acupuncture, yoga, and massages can relieve muscle spasms at the lower back and leg, and therefore, pain associated with sciatica.

Medication

Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, and spinal injections of steroids (corticosteroids) are used to temporarily reduce pain associated with inflammation and swelling.

Myorelaxants are also used to relax the muscles and relieve the spasms.

• Surgery

Surgery is required to remove the tumors, abscesses, hematomas that compress the spine and the sciatic nerve.

When the sciatica is due to a hernia of a disc or multiple discs or to lumbar spinal stenosis, surgery is necessary to restore their function.

Conclusion

Sciatica is a very painful experience that can be due to lifestyle or working conditions but also to severely debilitating conditions that require several surgical procedures to restore the function of the lower spine and reduce the irritation or compression of the sciatic nerve.

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