CBD: Some Answers
What is corticobasal degeneration (CBD)?
Corticobasal degeneration, or CBD, is a rare, adult-onset, neurological disease that impacts movement, thinking, speech, and sensory perception.
CBD is commonly referred to as an atypical parkinsonism, or sometimes as a Parkinson’s-plus diagnosis, due to its overlap with certain symptoms of Parkinson’s disease. CBD varies in the precise areas of the brain affected, which can cause a variety of symptoms, often making the disease difficult to diagnose.
CBD is very rare. The current estimate is 2,000-3,000 people diagnosed with CBD in the United States. This compares with 30,000-40,000 people with progressive supranuclear palsy (PSP), which is a different but related atypical parkinsonism disorder; about 1 million with Parkinson’s disease; and 5 million with Alzheimer’s disease. However, these numbers for CBD are probably underestimates because many people with CBD are misdiagnosed with another condition, such as PSP or Parkinson’s disease.
CBD is considered one of the parkinsonian disorders, or parkinsonisms. Parkinsonism refers to symptoms associated with Parkinson’s disease including slowness, muscle stiffness, balance problems, and sometimes tremor. Because of this, many people with CBD are initially diagnosed with Parkinson’s disease. Most people with CBD have these parkinsonian symptoms, but in addition, they have disproportionate problems performing complex movements such as cutting food, buttoning, or typing. These types of symptoms usually begin by affecting one hand. People with CBD tend to hold part or all of a limb in a fixed posture, which is called dystonia. An important aspect of CBD is the asymmetry of its symptoms, meaning that it almost always starts on one side of the body. Over time, the other side can become affected, but the first side always remains worse. There can also be very rapid, irregular, small movements of muscles, which is called myoclonus.
CBD can cause a symptom called apraxia, which is the loss of ability to perform learned (familiar) movements. Examples include tying shoes, using utensils, and buttoning. Manual tasks or gestures become clumsy, and walking can become frozen for several seconds at a time. An unusual but dramatic type of apraxia seen sometimes with CBD is alien limb phenomenon, where one hand can feel to the person as if it belongs to someone else and can perform actions that oppose the person’s intentions. Another unusual type of apraxia is arm levitation, where one arm tends to move upward involuntarily. Apraxia can produce a wandering of the limb attempting to find its target, and the wandering can resemble an involuntary movement. Apraxia in some people with CBD also affects speech, producing pauses and slurring, as well as control of the trunk, causing difficulty sitting down, standing up, and maneuvering in bed.
A sensory problem also contributes to the movement problem of CBD. It’s not a simple loss of sense of touch but an inability to interpret spatial complexity involving touch. This problem can take the form of an inability to recognize common objects by feel alone or the inability to know the position of a finger or a limb in space. Similar to the other symptoms described above, this sensory problem is also often asymmetric, meaning that it impacts just one side of the body. Sometimes there is also a problem with spatial reasoning in general, causing difficulty in things like dressing or finding one’s way around familiar places.
Unfortunately, CBD is a progressive neurologic condition. This means that over time, people with CBD will notice increasing severity of their symptoms and/or onset of new symptoms. This can occur over months to years. Not everyone experiences all of the symptoms of CBD, and the appearance and progression of these symptoms vary greatly among individuals.
Often over time, movement symptoms start to impact both sides of the body. New symptoms may develop, such as dystonia, swallowing challenges, or unsteadiness with walking. Some people develop spasticity, which is an excessive tendency for muscles to contract as if stimulated by a doctor with a reflex hammer. This can produce constant flexion or extension of joints and, in some cases, muscle pain.
People with CBD can experience changes to cognitive function, especially in more advanced stages of disease. This is usually in the areas of processing speed and organization of thoughts, planning, multitasking, and word-finding. Sometimes people with CBD can act impulsively or may lose some behavioral inhibitions.
People with CBD live an average of five to ten years after the onset of symptoms. However, some live much longer. Minimizing complications, such as swallowing problems, infections, and big falls, has the biggest impact on life expectancy. Your doctor may recommend regular examinations of your swallowing function to ensure that food is not entering the lung spaces and causing pneumonia. They may also recommend evaluations by rehabilitation therapists for recommendations for adaptive equipment to improve your safety with ambulation, and other preventative measures. Quality of life is enhanced by attentive care, maintaining general health, and perhaps most important, by an optimistic and hopeful attitude of the patient and family.
We recognize this information is scary and overwhelming to learn and to think about. It can be helpful to talk this through with your medical team and your family, including planning for the future and your wishes for quality of life. CurePSP and the rest of your support system are here to help.
In people with CBD, some groups of brain cells break down and die off. This happens because of the abnormal folding and clumping of a protein in the brain cells called tau. Tau is a normal protein found in brain cells. While its job is still not fully understood, it is currently thought to help maintain the microtubules, which are stiff rods that function as the brain cells’ internal transportation and skeletal system. It appears that the cells’ death is caused by a toxic effect of the tau protein clumps themselves and not by the reduced availability of tau for its normal function. The clumps’ technical name is neurofibrillary tangles.
We know several reasons why tau might misfold, but we don’t know why this occurs for people with CBD. Tau clumps together in about 30 other diseases, including Alzheimer’s disease, PSP, chronic traumatic encephalopathy, and about half of all cases of frontotemporal dementia. The specific disease depends on the chemical characteristics of the tau clumps and which brain cells are involved. This may be caused by genetic differences or exposure to certain chemicals, but ultimately, we are not yet sure why tau misfolds or people get certain brain disorders like CBD.
For someone who is personally impacted by CBD, we recognize that not knowing the cause can be extremely frustrating and confusing. Researchers and doctors are working hard to understand CBD and other related neurodegenerative diagnoses, and we hope this will lead to more answers and treatment options soon.
The microscopic brain abnormalities of CBD can affect different parts of the brain, producing different symptoms in different people. All forms of CBD at some point include, in almost all patients, a degree of motor parkinsonism, meaning stiffness, slowness, soft speech, and reduction in facial expression, sometimes with balance difficulty and tremor.
About a quarter of people with CBD have symptoms that resemble PSP, which impacts balance, eye movement, speech, and swallowing. Another 15% have frontotemporal dementia, with inappropriately uninhibited behavior and difficulty organizing thoughts. Then there are two rare forms, each accounting for about 5% of the total number of cases of CBD. One has a dementia similar to that of Alzheimer’s disease, with particular problems with memory or spatial orientation. The other is a form of aphasia, which means a problem with language—in this case, difficulty finding words and obeying rules of grammar. The most common subtype of CBD is called corticobasal syndrome, which affects about half of all people with CBD.
The classic type of CBD is called corticobasal syndrome, which starts with difficulty moving one limb, apraxia, dystonia, slowness, stiffness, and some degree of sensory problems. The term “syndrome” means a set of abnormalities that appear in the same person at the same time
but may or may not be caused by the same underlying disease in every case. It turns out that only about half of all people with corticobasal syndrome (CBS) actually have the disease corticobasal degeneration. About 20% are caused by the same brain changes that underlie Alzheimer’s disease and another 20% by the same brain changes that underlie progressive supranuclear palsy. A few are caused by the pathology underlying dementia with Lewy
bodies or other rare conditions.
Because it is very difficult during life to tell if someone with corticobasal syndrome in fact has corticobasal degeneration as their underlying brain disorder, neurologists are increasingly using the term “CBS” in reference to living patients and “CBD” only in reference to autopsy-proven corticobasal degeneration.
We recognize this can be a bit confusing, but this is why is it possible that you or your loved one may have been diagnosed with corticobasal degeneration (CBD) or corticobasal syndrome (CBS). Regardless of the term used, the treatment and care will be tailored to meet the unique needs of the person with the diagnosis.
Accurately diagnosing CBD can be difficult (or impossible in some cases) for even the most experienced neurologist. There are no blood tests or spinal fluid tests for CBD. To diagnose CBD, a neurologist will gather a person’s medical history, including neurological symptoms, and will perform a physical examination. Brain scans, such as MRI, CT, and PET, can show an asymmetric loss of certain parts of the brain, but there is usually an asymmetry in the physical signs and symptoms to start with. Brain scans are usually used to rule out other conditions, such as stroke. We eagerly await new types of MRI and PET that can distinguish CBD from other diseases that cause CBS.
At this time, we have no medication to cure CBD or to slow its progression. Doctors will usually prescribe carbidopa-levodopa, which is the most common medication used to manage Parkinson’s disease, to someone diagnosed with CBD. Unfortunately, the response to this medication is typically not as dramatic or long-lasting as it is in Parkinson’s disease. Still, for some people, it can help to manage the movement symptoms of CBD, like slowness and stiffness. If it is not helpful for someone’s symptoms at all, especially if the benefit is outweighed by side effects, which can include sleepiness and nausea, the doctor may recommend decreasing the medication over a week or two and then stopping it.
Amantadine is another antiparkinsonian drug that is sometimes helpful with freezing of gait in CBD. The dosage of Amantadine should not exceed 200-300mg per day because at higher doses with CBD, it can cause side effects of confusion, constipation, and urinary retention. Other drugs often used for Parkinson’s disease, such as dopamine agonists, do not appear to have benefit for people with CBD and can cause a number of side effects. Therefore, they are not usually used or recommended.
In addition to antiparkinsonian drugs, CBD is usually managed by treating specific symptoms that can impact someone’s functioning and quality of life. The sometimes-painful muscle spasms that can occur in CBD may respond to muscle relaxant drugs, such as cyclobenzaprine, baclofen, and tizanidine. A medication for seizures called levitiracetam can also help and may be better tolerated than the traditional muscle relaxants. Baclofen and clonazepam, two drugs commonly used for dystonia and spasticity in other disorders, can also help those symptoms in CBD. The most common side effect of these drugs is sleepiness. Baclofen can also cause muscle weakness, which could contribute to falls. The myoclonus of CBD, in the unlikely event that it is troublesome, may respond to clonazepam or levitiracetam.
Your doctor will work with you closely to try different medications, timing, and dosages to maximize the benefits for your symptoms while also trying to minimize side effects.
As research has shown repeatedly that cardiovascular exercise can slow the progression of motor decline in most neurodegenerative conditions, exercise remains a very important piece of disease management for people with CBD. Physical, occupational, and speech therapy are also important pillars of treatment to address many of the symptoms and challenges faced by people living with CBD, such as speaking, swallowing, balance, and daily activity performance. Home safety evaluations performed by trained physical and occupational therapists are extremely useful to help prevent falls and to recommend adaptive equipment such as grab bars, shower chairs, walkers, or wheelchairs.
CBD almost never runs in families and is not considered a genetic disease. A variant in the gene on chromosome 17 that encodes the tau protein is a little more common in CBD than in the rest of the population. We don’t yet know how that version of the tau gene actually affects brain cells. It may increase the amount of tau protein produced or it may change the
chemical properties of the protein. Slight variations in five other genes have also been found to be present at greater frequency in those with CBD than in others, and we have only vague ideas about how they may contribute to the causation of CBD. It is important to understand that each of these six gene variants is only very slightly more common in people with CBD than in other people and, even when their effects are totaled, do not explain the cause of CBD. Research being done on these gene variants could be helpful in understanding what is occurring in the brain that causes CBD as well as possible treatments.
What research is being done to better understand and treat CBD, and how do I get involved in research?
Due to the rarity of CBD, there are often not enough eligible people to be included in drug trials. To properly test a drug and understand its impact, patients need to be recruited from a number of sites. Another problem is that only about half of the patients who have the outward corticobasal syndrome actually have corticobasal degeneration, which can complicate the results of a drug trial. Some drug companies and researchers have discovered a new way to get around the problem of recruiting a pure CBD trial patient group. When testing a drug that acts on the tau protein, they recruit patients with any tau-related disease and don’t worry about exactly which one they have. These approaches are called basket trials and have been used successfully for years by cancer researchers working with rare conditions.
As far as we can tell at this point, because of the similarities in the diseases, when medications for treating, preventing, or curing PSP are created, they will likely be beneficial for people with CBD. So it’s a good idea to keep an eye on new developments in PSP.
Donating your brain to science can be a powerful contribution to the understanding of CBD and other neurodegenerative conditions. Each donated brain is also evaluated by a trained neuropathologist to confirm that the diagnosis of CBD was correct. Setting up brain donation needs to occur early, ideally months or even years prior to someone passing away. Visit www.psp.org/ineedsupport/ braindonation to learn about CurePSP’s brain donation program.
When there are opportunities to participate in research for CBD, many people with CBD find that this is a meaningful way to help doctors and scientists understand, diagnosis, and treat
CBD and related diseases. In the United States, clinical trials are listed on a website maintained by the National Institutes of Health, www.clinicaltrials.gov. You can enter “corticobasal degeneration” into the search box. You can also visit www.curepsp.org for a list of active and pending treatment trials in CBD. Additionally, you can ask your neurologist if they are offering or are aware of studies in CBD.
Building a support team around you is foundational to quality of care and life with CBD. Your support team may consist of your partner, family, friends, support group, religious community, healthcare team, professional care, and others—people who care about you and show up for you.
When living with a chronic and progressive diagnosis, it is important to find the right medical team to support your needs with CBD over time. CBD needs to be managed by a neurologist. This could be a general neurologist, but, if available in your area, you may also choose to work with a neurologist who has gone through specific training in movement or cognitive disorders. Rehabilitation therapists (physical, occupational, pelvic, and speech therapists) and clinical social workers also play important roles in the care of CBD.
As symptoms and needs arise, you may also benefit from adding other specialists to your team, such as a urologist, neuro-ophthalmologist, or palliative care specialist. Taking care of your emotional health with CBD is also a priority for both the patient and the family, and working with a mental health professional to process the experience, foster coping skills, or address other emotional needs can be exceptionally beneficial. When building your care team, it is important that you have providers you have chemistry with and that you trust, and for you to know you have the right and the ability to change your providers if needed.
Completing health care advance directives is an excellent tool for sharing your wishes regarding care with your support team. Health care advance directives address topics such as how aggressive your medical care should be (for example, whether you would want a feeding tube if the need arose) and how you define quality of life. These directives should be completed with your family and your doctor, and should be reviewed at least annually in case your wishes change.
Many people living with CBD consider and explore professional care services, such as in-home care, adult day care, or long-term care, depending on their care needs and situation. These services can provide an additional layer of support, including companionship or hands-on help for the person with CBD and assistance and respite for the family.
Additionally, there can be great value in connecting with other people affected by the same diagnosis as you and your family, through support groups or a peer support network. It can feel validating and uplifting to hear the experiences and insights ot how others adapt to life with CBD. You can exchange helpful tips on ways to cope physically and psychologically with the diagnosis. There are a handful of support groups specifically for CBD and many more for atypical parkinsonism (which can include progressive supranuclear palsy and multiple system atrophy) in the United States and other countries. Visit www.psp.org/ineedsupport/ supportgroups for a list of regional and national support groups facilitated by or in collaboration with CurePSP. Additionally, CurePSP offers educational symposiums and webinars where you can learn about CBD and connect to the community.
We recognize that a diagnosis of CBD can bring up many emotions, changes, and considerations. No matter how you find support, please remember that you do not have to navigate the CBD journey alone.