Infantile Progressive Bulbar Palsy

Introduction

Bulbar muscles are the muscles involved in controlling talking, chewing, and swallowing. Other body parts can also be affected by this condition. The disease has an onset between 50 to 70 years of age. This condition in children is referred to as infantile progressive bulbar palsy. It may start slowly but can aggravate in the long run. The life span of the individuals diagnosed with this condition is short.

Is Infantile Progressive Bulbar Palsy Hereditary?

The condition is not always caused due to genetic reasons but few conditions have been associated with infantile progressive bulbar palsy like Brown-Vialetto-Van Laere (BVVL) and Fazio-Londe Syndromes. BVVL can be inherited in an autosomal recessive pattern which means that both parents can be carriers of the disease without them having it and can transfer the expressive form of the condition to their child. Fazio-Londe Syndrome is also inherited in the same pattern. Kennedy disease (a rare, inherited disorder that causes gradual weakening and wasting of muscles, especially the arms, and legs) can also cause bulbar palsy.

What Are the Causes of Progressive Bulbar Palsy?

• Infantile Progressive Bulbar Palsy: A progressive degeneration or deterioration of the region of the brain that controls talking, chewing, and swallowing called the bulbar nuclei in the brain stem is affected. The upper motor neurons remain unaffected. The denervation (deprived of nerve supply) injury is linked with reinnervation (restoring nerve supply) from adjacent motor (movements that are brought about by motor neurons) units resulting in giant motor units. This degenerative process begins during pregnancy in the fetus and progresses in infancy and childhood.

• Progressive Bulbar Palsy in Adults: Stroke in the brainstem and tumors are the major causes of bulbar palsy in adults. Certain other conditions can also lead to bulbar palsy such as Guillain-Barre Syndrome in which the immune system targets the cranial nerves and attacks them. The motor neurons receive information from the brain and transfer it to the muscles through cranial nerves. Damage or loss of the motor neurons can weaken and cause wasting of the muscles such as those involved in breathing, talking, and swallowing. Sensory neurons transmit stimuli from the external environment such as vision, sound, touch, and limb positions from organs like eyes, ears, and so on, and transfer them to the brain. Damage or loss of the sensory neurons can cause loss of vision, hearing loss, and unbalanced walking (gait ataxia).

What Are the Signs and Symptoms of Infantile Progressive Bulbar Palsy?

The child shows the following signs and symptoms:

• Difficulty swallowing, chewing, and talking.

• Drooling.

• Inability to move the tongue.

• Inability to speak.

• Facial weakness.

• Uncontrollable laughing or crying.

• Immobile vocal cords.

• Ptosis (drooping of upper eyelids).

• Absence of gag reflex (involuntary contraction of the throat that occurs when something touches the roof of the soft palate to prevent a person from choking).

• Generalized hyperreflexia (reflexes that are fast and quick than normal).

• Auditory (sense of hearing) involvement is less common.

• Recurrent aspiration pneumonia (Entry of food or liquid into the lungs instead of being swallowed).

Is Infantile Progressive Bulbar Palsy Fatal?

With the disease progression, this condition can be fatal. The most common cause of death is due to aspiration pneumonia. Since these children have difficulty swallowing, a large quantity of food or liquids can enter the air passage or the lungs resulting in infection. Extreme bulbar damage can affect the respiratory center in the brainstem that controls and regulates breathing. This can be an emergency in which the child is unable to breathe.

How Is Infantile Progressive Bulbar Palsy Diagnosed?

The diagnosis is usually clinical and the diagnostic methods include:

• Biopsy of the muscle.

• Electromyography to assess the electrical activity in the muscles.

• Brainstem auditory evoked potentials (test to measure the activity of brain waves which occurs in response to certain clicks or tones).

Can Infantile Progressive Bulbar Therapy Be Treated?

Treatment is based on the management of symptoms. Medications can be prescribed to relieve muscle spasms, and pain associated with the weakening muscles, and to control drooling. Physical therapy (therapy to treat a disease, deformity, or injury by physical methods such as massage or exercise) can be given to keep the muscles active. In a few cases, surgery will be done in the throat to improve swallowing. A feeding tube can be inserted to enable feeding if throat surgery has failed. Speech and language therapy can aid in talking, swallowing, and chewing. Anti-depressants (drugs to treat depression) may be given to control uncontrollable laughing or crying. Other treatments may be given concerning underlying genetic, autoimmune, or degenerative conditions.

What Are the Manifestations of Infantile Progressive Bulbar Palsy?

Infantile progressive bulbar palsy manifests in two forms namely:

• Fazio-Londe Syndrome.

• Brown-Vialetto-Van Laere (BVVL) Syndrome.

The above syndromes are named after the physicians who first found the condition. The use of these names can be confusing and hence researchers have classified the disorder as riboflavin transporter deficiency neuronopathy.

What Causes Riboflavin Transporter Deficiency Neuronopathy?

Riboflavin transporter deficiency neuronopathy also affects the brainstem and is associated with hearing loss in affected individuals. This condition is caused by mutations in the SLC52A2 or SLC52A3 gene. These genes are responsible for providing instructions to manufacture proteins called Riboflavin transporters. The mechanism is as follows:

• Riboflavin transporters RFVT2 is manufactured from the SLC52A2 gene and RFVT3 is manufactured from the SLC52A3 gene.

• Both these proteins transport a vitamin called riboflavin (Vitamin B12) across the cell membrane.

• Riboflavin cannot be produced by the body and is acquired from the food that one eats. RFVT3 protein is present abundantly in the small intestine so that it can absorb the Riboflavin from food during digestion.

• The RFVT2 protein is present in the cells of the brain and spinal cord and this protein ensures that these cells have sufficient riboflavin for their normal functioning.

• The body cells contain molecules called flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) whose major component is Riboflavin. FAD and FMN are important for various cellular functions like energy production of cells, and the breakdown of proteins, fats, and carbohydrates.

• In Fazio Lende syndrome hearing loss is absent.

Which Part Is Affected in Riboflavin Transporter Deficiency Neuronopathy?

The parts that are a specific region of the brainstem called the pontobulbar region are affected by this condition. Nerves in this region are involved in controlling the muscles of breathing, speaking, and limb movements. If these nerves are damaged, it can result in pontobulbar palsy.

How Are Infants Affected by Riboflavin Transporter Deficiency Neuronopathy?

The affected individual has slurred speech, breathing problems, and weakness of muscles in the face, limbs, neck, and shoulders. Muscle stiffness (spasticity) and overactive reflexes can also occur. The symptoms in infants and children are:

• The first symptom of this condition that can be noticed in infancy is breathing problems which can be life-threatening.

• If it occurs in adolescence or early adulthood there can be hearing loss due to damage of sensory neurons followed by other signs.

• Infants who are not treated die within one year of age.

• If the condition develops after four years of age, the child will survive for more than 10 years.

Conclusion

Infantile progressive bulbar palsy is a very uncommon condition that affects the brainstem. The symptoms can be managed but there is no permanent cure for the condition. The outcome of the disease is poor and the life span of the affected children is usually short. The two manifestations of the infantile bulbar progressive disease are now considered riboflavin transporter deficiency neuronopathy and improve with the administration of riboflavin.