Other common spinal cord diseases include spinal stenosis (narrowing of your spinal canal) and disc herniations (when a disc bulges out). These conditions can lead to inflammation, pressure on your spinal nerves, or irritation of your nerve roots.

There are also less common but serious spinal cord diseases such as tumors, infections such as meningitis and polio, inflammatory diseases, autoimmune diseases, and degenerative diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy [1].

1. Cervical spondylosis (cervical spine degeneration)

Cervical spondylosis (cervical spine degeneration) is one of several types of spinal arthritis. As people age, they may develop osteoarthritis in their neck, which can cause pain and stiffness in their neck and shoulders.

Cervical spondylosis is most common in middle-aged women. Symptoms include pain or numbness in your neck, upper back, arms, or hands; trouble turning your head to look behind you; muscle weakness that causes your shoulders to stoop forward; and problems with balance or coordination.

Doctors usually diagnose cervical spondylosis by taking an X-ray of your neck. If you have symptoms of cervical spondylosis, your doctor may also recommend an MRI scan to look for signs of damage from arthritis. Treatment for cervical spondylosis depends on how severe it is.

2. Spinal stenosis

Spinal stenosis, or narrowing of spaces in your spine, can cause pain, numbness, and tingling in your arms and legs.

This condition is often caused by degenerative disk disease, which occurs when protective cartilage between vertebrae wears down over time.

Symptoms of spinal stenosis include pain that increases with activity and gets worse at night. If you experience these symptoms, talk to your doctor about treatments such as physical therapy or steroid injections.

3. Disc herniations

Disc herniations occur when a disc in your spine protrudes or bulges out. This can be painful and cause other symptoms, such as weakness, numbness, and tingling.

A disc herniation can occur anywhere along your spine but most commonly occurs in your lower back (lumbar spine).

The lumbar spine is made up of five vertebrae that are stacked on top of each other. The discs between these vertebrae act as cushions for your spinal cord and nerve roots.

When you bend forward or lift something heavy, stress is placed on these discs, which can cause them to bulge out or rupture (herniate).

3. Tumors

Tumors can occur in any part of your spinal cord, but most are found in your lower back. If you have cancer, you may notice symptoms such as weakness or numbness in your legs, pain that gets worse when you’re sitting or lying down, or tingling or numbness that travels up your legs.

Some tumors can cause additional complications, such as compression of nerves and blood vessels.

Your doctor will perform tests to determine if you have a tumor and what type it is. Treatment depends on where it is located and whether it has spread.

Surgery is often used to remove tumors located near vital organs like your kidneys and lungs. Radiation therapy may be used to treat tumors that cannot be surgically removed.

4. Infections such as meningitis and polio

Infections such as meningitis and polio can cause spinal cord diseases. Meningitis is an infection of the membranes that surround your brain and spinal cord. Polio is an infectious disease caused by a virus that invades your nervous system, causing paralysis.

If you experience weakness or numbness in your limbs, particularly on one side of your body, it could be symptoms of either meningitis or polio.

See a doctor immediately if you suspect either disease to prevent permanent damage to your spinal cord.

5. Inflammatory diseases

Inflammatory diseases of the spinal cord are caused by an overactive immune system, which is triggered by an infection or other illness.

The most common inflammatory disease of the spinal cord is transverse myelitis, which causes inflammation of both sides of your spinal cord. It’s often associated with viral infections and can cause temporary or permanent paralysis.

Other inflammatory diseases include Guillain-Barré syndrome (GBS), multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), and neuromyelitis Optica (NMO).

6. Autoimmune diseases

Autoimmune diseases are characterized by immune system attacks on healthy cells and tissues.

Examples of autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. These conditions can cause pain, fatigue, and other symptoms that affect your ability to live your life to its fullest.

To get an accurate diagnosis for an autoimmune disease, it’s important to see a doctor who has experience treating these conditions.

If you think you may have an autoimmune disease, talk with your doctor about tests that can help diagnose it. Once you know what’s causing your symptoms, you can work with your doctor to develop a treatment plan that works for you.

7. Degenerative diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy.

Degenerative diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy are characterized by loss of motor neurons in both upper and lower extremities. People with these conditions often experience muscle weakness, wasting, spasticity, or paralysis.

ALS is also known as Lou Gehrig’s disease, named after one of its most famous victims. The condition has no cure but can be managed through physical therapy and medications that can reduce pain or slow the progression of symptoms.

For example, a person may be able to walk short distances using leg braces or forearm crutches to support their weight.

Spinal muscular atrophy (SMA) is caused by the degeneration of motor neurons in both upper and lower extremities, resulting in muscle weakness or paralysis. It is considered an autosomal recessive disorder that mainly affects infants.

Conclusion

In conclusion, spinal cord problems can be caused by a variety of issues, such as injury, infection, or tumor. There are many different types of spinal cord problems, each with its own symptoms and treatments. If you are experiencing any symptoms that could be related to a spinal cord problem, it is important to seek medical attention right away.

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• Excessive daytime sleepiness
• Catalepsy
• Hallucinations
• Sleep paralysis
• Alterations in rapid eye movement sleep

In the United States, narcolepsy affects 1 in 2000 people, while it affects 3 million people worldwide [1].

Although narcolepsy can happen at any age, it is typically observed in individuals between the age of 10 and 30 years old.

1. What Is Excessive daytime sleepiness?

Excessive daytime sleepiness is characterized by a constant need to sleep even if the individual had a biologically sufficient night sleep.  

This need to sleep comes suddenly and overwhelmingly and is known as a sleep attack.

2. What Are Alterations in Rapid Eye Movement Sleep?

Sleep is controlled by the brain through the suprachiasmatic nucleus of the hypothalamus. The sleep pattern occurs through repetition of a cycle that comprises 5 phases measured by electroencephalography (ECG) [2]:

• Phase 1: light sleep phase characterized by slow eyes’ movement and muscle relaxation.

• Phase 2: this phase is characterized by the cessation of eyes’ movement and the slowdown of the brain waves such as the electrical pulses associated with wakefulness.

• Phase 3: beginning of deep sleep delta waves. At this stage, the delta waves are interrupted by faster and smaller waves.

• Phase 4: characterized uninterrupted delta waves leading to deep sleep.

• Rapid Eye Movement (REM): this phase is characterized by rapid eye movements, rise in heart and blood pressure, and dreaming.

Although narcoleptics have sufficient REM sleep during the night, they also have a higher REM compared to non-narcoleptics which manifests with the need to sleep during the day [3].

3. What Is Catalepsy?

Catalepsy is an uncontrollable loss of voluntary muscle tone leading to muscle rigidity. It can be triggered by overwhelming emotions such as stress, anger, fear, laughter, or excitement.

However, narcolepsy can manifest without catalepsy and is known as Narcolepsy Type 2, while narcolepsy with catalepsy is known as Narcolepsy Type 1.

4. What Is Sleep Paralysis?

People with narcolepsy experience the loss of voluntary muscle control or the ability to speak while falling asleep and still conscious.

Sleep paralysis is generally followed by full recovery of movements and speech.

5. What Are Hallucinations?

Hallucinations are characterized by hearing, seeing, smelling, tasting, and feeling (touch) things that are not real or do not exist outside an individual mind.

People with narcolepsy experience hallucinations while falling asleep and during sleep paralysis.

6. What Is the Main Cause of Narcolepsy?

Narcolepsy is caused by the loss of neurons that release hypocretins (orexins) in the hypothalamus where the sleep cycle is controlled.

Hypocretins (orexins) are neuropeptides that are released by the orexigenic neurons to regulate the activities of the neurotransmitters acetylcholine, serotonin, and norepinephrine [5][6].

Hypocretins (orexins) also act on the brainstem to inhibit neurons involved in the REM phase of the sleep cycle during wakefulness [7].

Although what causes a reduction in the levels of hypocretins (orexins) are not well known, studies have reported the following factors:

• Family history

Family history appears to be a factor of narcolepsy type 1 as up to 10% of narcolepsy individuals with catalepsy reported having a close relative with similar symptoms [8].

• Autoimmune Diseases

Genetic variations in the human leukocyte antigen (HLA) complex were suggested as a factor promoting autoimmunity that targets orexinergic neurons causing their cell death [9].

The human leukocyte antigen (HLA) complex is a system that regulates the immune system and prevents autoimmunity.

• Brain Injuries and tumors

Brain injuries or tumors can damage the regions of the brain that regulate wakefulness and REM sleep resulting in narcolepsy.

7. How Many Hours of Sleep Do People with Narcolepsy Get?

Narcoleptics sleep the same number of hours at night as non-narcoleptic individuals; however, narcoleptics have a higher REM compared to non-narcoleptics which manifests with the need to sleep during the day (excessive daytime sleepiness) [3].

8. What Is the Most Common Treatment of Narcolepsy?

Due to the loss of orexinergic neurons that cannot be replaced, there is no cure for narcolepsy, however, the combination of lifestyle changes and medications can help treat the symptoms [8].

8.1. Lifestyle Changes

• Excessive daytime sleepiness can be monitored through taking small naps during the day.
• Alcohol and caffeine taken before bedtime can disturb sleep
• Exercising for 20 minutes a day can help improve sleep
• Maintaining a regular sleep schedule can help sleeping better
• Tobacco is a central nervous stimulant that can affect sleep, and therefore, avoiding smoking can help sleeping better
• Relaxation before sleep and environmental factors such as the comfort of the bedding and the room where you sleep, are essential for quality sleep.
• Avoiding large and heavy meals before bedtime can help sleeping better.

8.2. Medications

8.2.1. What Is Modafinil?

Modafinil (Provigil) is used for the treatment of sleepiness. Although the mechanism of action is unknown, modafinil may be involved in the release of hypocretins (orexins) and the neurotransmitter histamine from the hypothalamus [10].

8.2.2. What Is Sodium Oxybate?

Sodium Oxybate (Xyrem) is sodium salt of gamma-hydroxybutyric acid, a neurotransmitter, and a precursor of GABA (gamma-aminobutyric acid), glutamate, and glycine in certain parts of the brain. It is used as a sedative for narcolepsy.

8.2.3. What Are Amphetamine-Like Stimulants?

Amphetamine-Like Stimulants are inhibitors of norepinephrine and dopamine reuptake which increases the extra-synaptic concentrations of the neurotransmitters, norepinephrine, and dopamine and their stimulation of the central nervous system.

The most used amphetamine-like stimulant for narcolepsy is methylphenidate (Ritalin).

8.2.4. What Are Antidepressants?

Antidepressants are used for the treatment of depression and narcolepsy symptoms and act by inhibiting the reuptake of serotonin and norepinephrine reuptake, but also by regulating the activities of other neurotransmitters and their receptors in the brain.

Conclusion

Narcolepsy is caused by the loss of orexigenic neurons in the hypothalamus where they release the neuropeptides hypocretins (orexins) which regulate the ERM phase of the sleep cycle.

The causes for the loss of orexigenic neurons are not well-known and may involve genetic and autoimmune factors.

Unfortunately, narcolepsy is not treatable due to the loss of neurons that cannot be replaced (so far), and therefore, the treatment is symptomatic and involves changes in lifestyle and medications.

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• 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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