Progressive bulbar palsy
Encyclopedia
Progressive bulbar palsy (also known simply as PBP) is a medical condition. It belongs to a group of disorders known as motor neuron diseases
(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
, spinal cord
, brain stem
, and pyramidal tracts. This specifically involves the glossopharyngeal nerve
(IX), vagus nerve
(X), and hypoglossal nerve
(XII) (Hughes 1998).
This disorder should not be confused with pseudobulbar palsy
or progressive spinal muscular atrophy (Hughes 1998). The term Infantile progressive bulbar palsy
is used to describe progressive bulbar palsy in children.
Some neurologists consider this disorder to be a subset of amyotrophic lateral sclerosis
(ALS), but others disagree with that classification.
s and with Joffroy, who noted the loss of the bulbar motor nuclei, discovered the similarities to amyotrophic lateral sclerosis
(ALS) (Fawcett 2000). 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.
or clinical evidence of abnormalities in the legs or arms is possible, albeit extremely rare. Moreover, about twenty-five percent of patients with PBP eventually develop the widespread symptoms common to ALS (Swash 2000).
(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
, 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
. The patient died from pneumonia
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 in exon 5 of the SOD1 gene. This mutation produced a frameshift mutation
, which led to a stop codon
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 ( Kadekawa 1997).
, fasciculations, and weak movement of the facial muscles and tongue. In advanced cases of PBP, the patient may be unable to protrude their tongue or manipulate food in their mouth (Campbell 2005).
Patients with early cases of PBP have difficulty with pronunciations, particularly lateral consonant
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 (Merck 2005). 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 (Merck 2005). Death, which is often from pneumonia, usually occurs 1 to 3 years after the start of the disorder.
Motor neurone disease
The motor neurone diseases are a group of neurological disorders that selectively affect motor neurones, the cells that control voluntary muscle activity including speaking, walking, breathing, swallowing and general movement of the body. They are generally progressive in nature, and can cause...
(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
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
, spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
, brain stem
Brain stem
In vertebrate anatomy the brainstem is the posterior part of the brain, adjoining and structurally continuous with the spinal cord. The brain stem provides the main motor and sensory innervation to the face and neck via the cranial nerves...
, and pyramidal tracts. This specifically involves the glossopharyngeal nerve
Glossopharyngeal nerve
The glossopharyngeal nerve is the ninth of twelve pairs of cranial nerves . It exits the brainstem out from the sides of the upper medulla, just rostral to the vagus nerve...
(IX), vagus nerve
Vagus nerve
The vagus nerve , also called pneumogastric nerve or cranial nerve X, is the tenth of twelve paired cranial nerves...
(X), and hypoglossal nerve
Hypoglossal nerve
The hypoglossal nerve is the twelfth cranial nerve , leading to the tongue. The nerve arises from the hypoglossal nucleus and emerges from the medulla oblongata in the preolivary sulcus separating the olive and the pyramid. It then passes through the hypoglossal canal...
(XII) (Hughes 1998).
This disorder should not be confused with pseudobulbar palsy
Pseudobulbar palsy
Pseudobulbar palsy results from an upper motor neuron lesion to the corticobulbar pathways in the pyramidal tract. Patients have difficulty chewing, swallowing and demonstrate slurred speech...
or progressive spinal muscular atrophy (Hughes 1998). The term Infantile progressive bulbar palsy
Infantile progressive bulbar palsy
Infantile Progressive Bulbar palsy is a rare type of progressive bulbar palsy that occurs in children. The disease exists in both rapid and slow onsets, and involves inflammation of the gray matter of the bulb...
is used to describe progressive bulbar palsy in children.
Some neurologists consider this disorder to be a subset of amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...
(ALS), but others disagree with that classification.
Origin
The disease was first recognized by French neurologist, G. Duchenne 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 tractCorticospinal tract
The corticospinal or pyramidal tract is a collection of axons that travel between the cerebral cortex of the brain and the spinal cord....
s and with Joffroy, who noted the loss of the bulbar motor nuclei, discovered the similarities to amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...
(ALS) (Fawcett 2000). It was observed that a distinction from ALS was fatigue that predominated in muscles innervated by lower cranial nerve nuclei
Lower motor neuron
Lower motor neurons are the motor neurons connecting the brainstem and spinal cord to muscle fibers, bringing the nerve impulses from the upper motor neurons out to the muscles...
, rather than the upper motor neurons.
Epidemiology
Progressive bulbar palsy is slow in onset, with symptoms starting in most patients around 50-70 years of age (Merck 2005). PBP is both progressive and slow, with symptoms lasting around 10 to 20 years until it reaches a fatal ending (Collins 1900). It is debated as to whether PBP is a separate entity or a subtype of amyotrophic lateral sclerosis (ALS). Pure PBP without any EMGElectromyography
Electromyography is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph, to produce a record called an electromyogram. An electromyograph detects the electrical potential generated by muscle...
or clinical evidence of abnormalities in the legs or arms is possible, albeit extremely rare. Moreover, about twenty-five percent of patients with PBP eventually develop the widespread symptoms common to ALS (Swash 2000).
Etiology
The etiology of PBP is unknown. One form of PBP is found to occur within patients that have a CuZn-superoxide dismutaseSOD1
Superoxide dismutase [Cu-Zn] also known as superoxide dismutase 1 or SOD1 is an enzyme that in humans is encoded by the SOD1 gene. SOD1 is one of three human superoxide dismutases.- Function :...
(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
Muscle atrophy, or disuse atrophy, is defined as a decrease in the mass of the muscle; it can be a partial or complete wasting away of muscle. When a muscle atrophies, this leads to muscle weakness, since the ability to exert force is related to mass...
, fasciculation
Fasciculation
A fasciculation , or "muscle twitch", is a small, local, involuntary muscle contraction and relaxation visible under the skin arising from the spontaneous discharge of a bundle of skeletal muscle fibers...
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
Cardiac arrest, is the cessation of normal circulation of the blood due to failure of the heart to contract effectively...
. The patient died from pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
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 in exon 5 of the SOD1 gene. This mutation produced a frameshift mutation
Frameshift mutation
A frameshift mutation is a genetic mutation caused by indels of a number of nucleotides that is not evenly divisible by three from a DNA sequence...
, which led to a stop codon
Stop codon
In the genetic code, a stop codon is a nucleotide triplet within messenger RNA that signals a termination of translation. Proteins are based on polypeptides, which are unique sequences of amino acids. Most codons in messenger RNA correspond to the addition of an amino acid to a growing polypeptide...
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 ( Kadekawa 1997).
Symptoms
Prognosis for PBP patients is poor. Progressive bulbar palsy symptoms can include progressive difficulty with chewing, talking, and swallowing (Merck 2005). Patients can also exhibit reduced gag reflexes, weak palatal movementsTongue
The tongue is a muscular hydrostat on the floors of the mouths of most vertebrates which manipulates food for mastication. It is the primary organ of taste , as much of the upper surface of the tongue is covered in papillae and taste buds. It is sensitive and kept moist by saliva, and is richly...
, fasciculations, and weak movement of the facial muscles and tongue. In advanced cases of PBP, the patient may be unable to protrude their tongue or manipulate food in their mouth (Campbell 2005).
Patients with early cases of PBP have difficulty with pronunciations, particularly lateral consonant
Lateral consonant
A lateral is an el-like consonant, in which airstream proceeds along the sides of the tongue, but is blocked by the tongue from going through the middle of the mouth....
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 (Merck 2005). 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 (Merck 2005). Death, which is often from pneumonia, usually occurs 1 to 3 years after the start of the disorder.