Progressive Bulbar Palsy

What Causes Progressive Bulbar Palsy?

PBP is caused by the deterioration of the parts of the brain that control the bulbar muscles, a muscle group in the head and neck responsible for functions such as speaking, chewing, swallowing, and controlling the jaw. The nerves that control these muscles are located in an area at the base of the brain called the brain stem. However, scientists don’t yet know what causes the nerve deterioration associated with PBP.

Is Progressive Bulbar Palsy Hereditary?

Most of the time, PBP and other MNDs do not appear to be inherited, but in some cases, the diseases appear to have a genetic component. Most cases don’t seem to be linked to family history and are probably caused by a combination of gene mutations and external environmental factors.

Some types of MNDs are inherited in an autosomal dominant pattern, meaning that children may develop the disorder if they inherit even one copy of the mutated gene from either of their parents. If a parent carries the disorder-causing mutation, they will have a 50 percent chance of having an affected child with each pregnancy.

MNDs are sometimes inherited in an autosomal recessive pattern. This means a child must inherit two copies of the gene mutation, one from each parent, to develop the disorder. People with only one copy of the mutated gene will not develop the MND but will be carriers who can pass the mutation on to their children. Two carrier parents have a 25 percent chance of having a child with the MND with each pregnancy. Therefore, half of their pregnancies will produce a carrier, and a quarter will produce a child with no mutated genes.

Kennedy’s disease, sometimes associated with PBP, is an X-linked disorder. This means that the chance of inheritance varies depending on the sex of the parent and the child. These cases affect males, and females are carriers who don’t develop symptoms of the disorder. Men with the condition will pass the gene mutation to all their daughters, who will be carriers, but their sons will be unaffected. Female carriers of the mutation will have a carrier daughter 25% of the time, a non-carrier daughter 25% of the time, an affected son 25% of the time, and an unaffected son 25% of the time.

How Is Progressive Bulbar Palsy Detected?

Early diagnosis of PBP and other MNDs is challenging because their symptoms may resemble those of Parkinson’s disease and several other neurological disorders. Consequently, MNDs are difficult to spot early on, even for medical professionals. Early detection is even more unlikely because the diseases are relatively uncommon, and most doctors don’t have experience diagnosing them.

Early signs of PBP may include:

• Slurred speech
• Difficulty swallowing
• Uncontrollable laughing, crying, or yawning

How Is Progressive Bulbar Palsy Diagnosed?

When your doctor suspects that PBP might be the cause of early symptoms, they will conduct a variety of tests and exams. There is no single test or exam to detect PBP. Instead, much of the diagnostic process is designed to rule out other possible causes of the symptoms rather than directly diagnosing PBP.

• Laboratory tests. Tests of your blood and urine will not necessarily confirm a diagnosis of PBP, but the tests may be able to rule out other conditions that could be causing your symptoms.
• Electromyogram (EMG). This test uses electrodes to measure the electrical activity in your muscles as they work. The test can be used to detect abnormalities in muscle function that support a diagnosis of PBP.
• Imaging tests. Magnetic resonance imaging (MRI) scans can detect abnormalities in your brain, spinal column, or other parts of your body. These tests may be used to rule out PBP by revealing another condition that’s causing your symptoms.
• Spinal tap. This procedure removes and tests a small amount of the fluid that protects your brain and spinal column. The test can often detect viral infections or inflammation in the brain.
• Nerve conduction tests. These tests measure how well your nerves can communicate with your muscles. These tests may detect nerve damage or disorders other than PBP that could be causing symptoms.

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Progressive Bulbar Palsy Treated?

No treatment will stop the progression of PBP or reverse the effects of its symptoms. Most treatments aim to reduce the impact of symptoms, improve quality of life, and prevent life-threatening complications. Drugs such as riluzole may extend a patient’s survival by prolonging their ability to breathe without respiratory assistance.

Other treatments and therapies include:

• Speech therapy
• Physical therapy
• Occupational therapy
• Nutritional support

How Does Progressive Bulbar Palsy Progress?

PBP symptoms worsen over time, and most people with the disorder will suffer from severe impairments within 3-5 years after symptoms first appear. Long-term, potentially fatal complications can include:

• Difficulty swallowing
• Choking or gagging
• Inhaling food, saliva, or other contaminants into the lungs
• Respiratory infections such as pneumonia

Most people with PBP will not survive more than 1-3 years after the onset of symptoms. Pneumonia, often caused by inhaling food or liquids (aspiration), is the most common cause of death. However, more prolonged survival is possible if the risk of aspiration and choking is carefully managed.

How Is Progressive Bulbar Palsy Prevented?

There is no known way to prevent PBP.

Progressive Bulbar Palsy Caregiver Tips

• Educate yourself about the disease, its effects, and the side effects of medications used to treat it. People with PBP are also at higher risk of developing depression and anxiety. Be on the lookout for the warning signs of these conditions.
• Encourage a healthy lifestyle. There is no cure for PBP, but there are ways to manage symptoms and maintain a good quality of life for as long as possible. Facilitate eating healthy foods and getting as much exercise as possible.
• Join a support group for caregivers. Caregivers are at risk of developing physical and mental health issues, too. So take time for yourself, and get the help you need when you feel overwhelmed.

Progressive Bulbar Palsy Brain Science

PBP occurs because of degeneration in the bulbar region of the brain stem. This part of the brain contains nerve cells called lower motor neurons, which communicate nerve signals between the brain and muscles throughout the body. The motor neurons in the bulbar region are linked to muscles in the head and neck, and the neurons’ degeneration causes the symptoms of PBP.

Researchers are looking for the causes of PBP, ALS, and other MNDs, for an understanding of how the disease affects the brain, and for effective treatments. Current studies include:

• Researchers suspect that a brain-cell protein called membralin might play a role in the development of ALS. Scientists don’t know precisely what membralin does in the brain’s nerve cells, but they have found evidence that a protein deficiency may cause ALS and other degenerative nerve diseases. Their studies suggest that gene therapies that increase levels of membralin may have potential as an ALS treatment.
• One clinical study is currently testing a drug that takes a new approach to treating ALS. The drug aims to improve muscle function rather than improving the communication between nerves and muscles. The hope is that the drug will help muscles work more efficiently to compensate for the weakness caused by ALS nerve damage. The drug seems particularly effective at assisting the muscles controlling breathing, and patients may breathe better for longer as a result.

Progressive Bulbar Palsy Research

Title: HERV-K Suppression Using Antiretroviral Therapy in Volunteers With Amyotrophic Lateral Sclerosis (ALS)

Stage: Recruiting

Principal investigator: Avindra Nath, MD 

National Institutes of Health Clinical Center

Bethesda, MD

Objective: In this Phase I, proof-of-concept study, we aim to determine whether an antiretroviral regimen approved to treat human immunodeficiency virus (HIV) infection would also suppress levels of Human Endogenous Retrovirus-K (HERV-K) found to be activated in a subset of patients with amyotrophic lateral sclerosis (ALS). We propose to measure the blood levels of HERV-K by quantitative PCR before, during, and after treatment with an antiretroviral regimen. In addition, investigators will evaluate the safety of the antiretroviral regimen for participants with ALS and also explore clinical and neurophysiological outcomes of ALS symptoms, quality of life, and pulmonary function.

Study Population: Investigators will study a subset of ALS patients with a ratio of HERV-K: RPP30 greater than or equal to 13. About 30% of ALS patients may have detectable levels of HERV-K; about 20% of patients with ALS have a level >1000 copies/ml. To show whether the HERV-K could be suppressed, researchers will recruit from the approximately 20% of patients with high levels so the antiretroviral effect can be determined.

Design: This is an open-label study of a combination antiretroviral therapy for 24 weeks in 25 HIV-negative, HTLV-negative ALS patients with a high ratio of HERV-K: RPP30. The study duration for each participant will be up to 72 weeks. Participants will be followed regularly for safety, clinical, and neurophysiological outcomes.

Outcome Measures: The primary outcome measure will be the percent decline in HERV-K concentration measured by quantitative PCR. Percent decline for a patient is measured by: 100 x (screening visit – week 24 visit measurement) / screening visit. The safety of antiretrovirals in volunteers with ALS, as measured by the frequency and type of AEs, the ability to remain on assigned treatment (tolerability), physical examinations, laboratory test results, vital signs, and weight/body mass index (BMI). Efficacy will be explored by measuring the change in mean scores of the ALS Functional Rating Scale-Revised (ALSFRS-R), the ALS Specific Quality of Life Inventory-Revised (ALSSQOL-R), the ALS Cognitive Behavioral Screen (ALS-CBS), vital capacity and maximal inspiratory pressure as measured by a handheld spirometer, electrical impedance myography (EIM), the change in neurofilament levels in the blood and/or CSF, and the change in uring p75ECD levels.

Title: Studies in Amyotrophic Lateral Sclerosis (ALS) and Other Neurodegenerative Motor Neuron Disorders

Stage: Recruiting

Principal investigator: Bjorn Oskarsson, MD 

Mayo Clinic Florida

Jacksonville, FL

The purpose of this study is to collect, from patients with sporadic and familial ALS and their family members, clinical data and blood samples for extraction of DNA, RNA, preparation of lymphocytes, plasma, and serum to establish a repository for future investigations of genetic contributions to ALS pathogenesis. Blood samples for DNA extraction also would be collected from control subjects with no personal or family history of ALS phenotypes.

Title: CNS10-NPC-GDNF Delivered to the Motor Cortex for ALS

Stage: Recruiting

Principal investigator: Richard Lewis, MD 

Cedars-Sinai Medical Center

Los Angeles, CA

The investigator is examining the safety of transplanting cells, that have been engineered to produce a growth factor, into the motor cortex (brain) of patients with Amyotrophic Lateral Sclerosis (ALS). The cells are called neural progenitor cells, a type of stem cell that can become several different types of cells in the nervous system. These cells have been derived to specifically become astrocytes, a type of neural cell. The growth factor is called glial cell line-derived neurotrophic factor, or GDNF. GDNF is a protein that promotes the survival of many types of neural cells. Therefore, the cells are called “CNS10-NPC-GDNF.” The investigational treatment has been tested in people by delivering it to the spinal cord. However, it has only been delivered to the motor cortex of animals. In this study, Investigators want to learn if CNS10-NPC-GDNF cells are safe to transplant into the motor cortex (brain) of people.