Progressive bulbar palsy (PBP) is a medical condition. It belongs to a group of disorders known as

motor neuron disease Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most com ...

s. Lapiedra 2002 PBP is a disease that attacks the nerves supplying the bulbar muscles. These disorders are characterized by the degeneration of motor neurons in the

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting o ...

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...

brain stem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is c ...

, and pyramidal tracts. This specifically involves the

glossopharyngeal nerve The glossopharyngeal nerve (), also known as the ninth cranial nerve, cranial nerve IX, or simply CN IX, is a cranial nerve that exits the brainstem from the sides of the upper medulla, just anterior (closer to the nose) to the vagus nerve. B ...

(IX),

vagus nerve The vagus nerve, also known as the tenth cranial nerve, cranial nerve X, or simply CN X, is a cranial nerve that interfaces with the parasympathetic control of the heart, lungs, and digestive tract. It comprises two nerves—the left and right ...

(X), and

hypoglossal nerve The hypoglossal nerve, also known as the twelfth cranial nerve, cranial nerve XII, or simply CN XII, is a cranial nerve that innervates all the extrinsic and intrinsic muscles of the tongue except for the palatoglossus, which is innervated by ...

(XII). Hughes 1998 This disorder should not be confused with pseudobulbar palsy or progressive spinal muscular atrophy. The term infantile progressive bulbar palsy is used to describe progressive bulbar palsy in children. The

ICD-11 The ICD-11 is the eleventh revision of the International Classification of Diseases (ICD). It replaces the ICD-10 as the global standard for recording health information and causes of death. The ICD is developed and annually updated by the World ...

lists progressive bulbar palsy as a variant of

amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most com ...

(ALS).

Signs and symptoms

Prognosis for PBP patients is poor. Progressive bulbar palsy symptoms can include progressive difficulty with talking and swallowing. Merck 2005 Patients can also exhibit reduced gag reflexes, weak palatal movements, fasciculations, and weak movement of the facial muscles and tongue. In advanced cases of PBP, patients may be unable to protrude their tongue or manipulate food in their mouth. Patients with early cases of PBP have difficulty with pronunciations, particularly

lateral consonant A lateral is a consonant in which the airstream proceeds along one or both of the sides of the tongue, but it is blocked by the tongue from going through the middle of the mouth. An example of a lateral consonant is the English ''L'', as in ''La ...

s (linguals) and velars, and may show problems with drooling saliva. If the corticobulbar tract is affected a pseudobulbar affect with emotional changes may occur. Because PBP patients have such difficulty swallowing, food and saliva can be inhaled into the lungs. This can cause gagging and choking, and it increases the risk of pneumonia. Death, which is often from pneumonia, usually occurs 1 to 3 years after the start of the disorder. About twenty-five percent of patients with PBP eventually develop the widespread symptoms common to ALS. Swash 2000

Cause

The cause of PBP is unknown. One form of PBP is found to occur within patients that have a CuZn-superoxide dismutase (''SOD1'') mutation. Kadekawa 1997 Progressive bulbar palsy patients that have this mutation are classified with FALS patients, Familial ALS (FALS) accounts for about 5%-10% of all ALS cases and is caused by genetic factors. Within these, about 20–25% are linked to the ''SOD1'' mutation. It is not currently known if and how the decreased ''SOD1'' activity contributes to Progressive Bulbar Palsy or FALS, and studies are being done in patients and transgenic mice to help further understand the impact of this gene on the disease. A case study was done on a 42-year-old woman who complained of muscle weakness 10 months prior to admission in the hospital. Upon neurological examination, the patient showed

muscle atrophy Muscle atrophy is the loss of skeletal muscle mass. It can be caused by immobility, aging, malnutrition, medications, or a wide range of injuries or diseases that impact the musculoskeletal or nervous system. Muscle atrophy leads to muscle weakne ...

, fasciculation in all limbs and decreased deep tendon reflexes. The patient’s older brother, father, and paternal uncle had previously all died of ALS or an ALS type syndrome. The patient developed progressive bulbar palsy, became dependent on a respirator, and had two episodes of

cardiac arrest Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and poss ...

. The patient died from

pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severit ...

two years after the onset of the disease. After studying the patient, it was found that the patient had a two base pair deletion in the 126th

codon The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

5 of the ''SOD1'' gene. This mutation produced a

frameshift mutation A frameshift mutation (also called a framing error or a reading frame shift) is a genetic mutation caused by indels ( insertions or deletions) of a number of nucleotides in a DNA sequence that is not divisible by three. Due to the triplet natu ...

, which led to a

stop codon In molecular biology (specifically protein biosynthesis), a stop codon (or termination codon) is a codon ( nucleotide triplet within messenger RNA) that signals the termination of the translation process of the current protein. Most codons i ...

at position 131. ''SOD1'' activity was decreased by about 30%. The patient’s histological examination showed severe reduction in lower motor neurons. Upon further study, this case proved to be important because it demonstrated that ''SOD1'' mutations might not effect steady neuropathological changes, and that environmental and genetic factors might affect the phenotype of the SOD1 mutations.

Treatment

PBP is aggressive and relentless, and there were no treatments for the disease as of 2005. However, early detection of PBP is the optimal scenario in which doctors can map out a plan for management of the disease. This typically involves symptomatic treatments that are frequently used in many lower motor disorders.

History

The disease was first recognized by the French neurologist

Guillaume Duchenne Guillaume-Benjamin-Amand Duchenne (de Boulogne) (September 17, 1806 in Boulogne-sur-Mer – September 15, 1875 in Paris) was a French neurologist who revived Galvani's research and greatly advanced the science of electrophysiology. The era of m ...

in 1860 and termed, “labioglossolaryngeal paralysis”. Fawcett 2000 In 1859, Wachsmuth changed the name to progressive bulbar palsy. In 1869, Charcot studied the involvement of the

corticospinal tract The corticospinal tract is a white matter motor pathway starting at the cerebral cortex that terminates on lower motor neurons and interneurons in the spinal cord, controlling movements of the limbs and trunk. There are more than one million neuro ...

s and with Joffroy, who noted the loss of the bulbar motor nuclei, discovered the similarities to

(ALS). It was observed that a distinction from ALS was fatigue that predominated in muscles innervated by lower cranial nerve nuclei, rather than the upper motor neurons.

References

Bibliography

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External links

* {{Diseases of the nervous system Systemic atrophies primarily affecting the central nervous system Motor neuron diseases