Corticobasal Degeneration

Corticobasal degeneration (CBD) is a progressive neurological disorder that may involve the motor system, cognition or both. Classically, it begins as a movement disorder, with affected individuals showing a unilateral (one sided) paucity of movement, and muscle rigidity with a tremor. Strength remains normal but the limb becomes progressively less useful because of the problems with tone, slowness, tremor and praxis. Praxis (apraxia) is when the strength is adequate to perform a function, but the patient can’t do it because of a “disconnect” between the thought and the action. Initial symptoms of CBD often begin around age 60 and become bilateral as the disease progresses. A patient with CBD may first present with a language disorder, and develop the motor symptoms over time.

Some physicians and investigators use the term “corticobasal syndrome” (CBS) when referring to the clinical symptoms and signs patients experience, and reserve the term CBD for cases which meet neuropathologic criteria. This distinction can be important because some patients with CBS prove to have other neuropathological diagnoses. Alternatively, there are sometimes unusual clinical symptoms in patients with pathological features of CBD.

Key Clinical Features

These cognitive symptoms may be associated with CBD (though not all are seen in all patients):

• Alien hand syndrome in which the patient does not recognize the actions of his hand and can’t control movement of the hand or arm
• Apraxia – the loss of the ability to make familiar, purposeful movements, manifested as difficulty using familiar objects or doing familiar things. Examples include using utensils, combing one’s hair, and dressing
• Acalculia – difficulty carrying out simple calculations, such as adding and subtracting
• Visual-spatial impairment – an individual with corticobasal degeneration may have difficulty orienting objects in space

Motor symptoms of CBD are similar to those found in Parkinson disease, such as:

• Akinesia/bradykinesia – an absence of movements
• Rigidity -a resistance to imposed movement
• Tremor
• Limb dystonia – abnormal muscle postures

Language symptoms including hesitant and halting speech (progressive aphasia), are seen in some patients.

A CBD patient may begin with any of the three types of signs above: cognitive, motor or language. Development of a second and/or third category of signs makes it easier for the physician to recognize the illness as CBD.

Key Pathologic Features

 Upon autopsy, the brain tissue of CBD patients is characterized by nerve cell loss, gliosis and atrophy (shrinkage) of the deeper layers in the posterior frontal and/or parietal lobes, in and the substantia nigra. Swollen (ballooned) nerve cells containing tau and phosphorylated neurofilament epitopes, similar to those seen in Pick’s disease, are a hallmark feature.

Scientists have recently determined that affected CBD brain cells contain deposits of abnormal forms of the protein tau. Tau is present in all neurons, and it plays important roles in the structure and function (metabolism) of neurons.

Genetics

CBD is almost always sporadic, developing by chance rather than being inherited. Some research has found associations with CBD and a specific form (variant) of the tau gene. However, this information is not useful for the diagnosis of specific individuals because the tau forms are neither sensitive nor specific for this degeneration.

Treatment

There is no treatment available to slow the course of corticobasal degeneration, and the symptoms of the disease are generally resistant to therapy. Drugs used to treat Parkinson disease-type symptoms are sometimes tried, but often do not produce significant or sustained improvement for motor symptoms.

Some CBD patients benefit from the selective serotonin reuptake inhibitors (SSRIs) used in treating depression and/or the acetylcholinesterase inhibitors used in Alzheimer disease, which enhance the activity of neurotransmitters in the brain. Clinicians may also employ antioxidants, such as vitamin E or coenzyme Q10, which are known to slow the progression of damage to brain cells in general.

Maintaining a healthy lifestyle with physical and mental activity is generally recommended for patients with CNS degenerative diseases, as is a “heart healthy” diet.

Management and Prognosis

Corticobasal degeneration usually progresses slowly over the course of 6 to 8 years. During this time, the patient’s ability to live and function independently is diminished, leaving them dependent on others for activities of daily living.

Although there is no treatment for CBD, therapy does help to manage the symptoms, and perhaps delay their progression. Specifically, occupational and physical therapies provide passive range of motion in affected muscles, and help prevent contractures (paralysis of a muscle in the tense state) in rigid limbs. Speech therapy may help delay the progression of language symptoms.

It is important for caregivers and families to think about long-term management issues and identify a team of experts who can help with difficult medical, financial and emotional challenges. It is imperative to have a physician who is knowledgeable about FTD. Other medical specialists who may be helpful include: speech and language pathologists, occupational and physical therapists, neuropsychologists, nurses (especially home-care nursing), and genetic counselors.

Death in CBD is generally caused by pneumonia or other complications of severe debility, such as sepsis (an infection throughout the body) or pulmonary embolism (a blood clot that blocks a major blood vessel in the lung).