Corticobasal Syndrome

Corticobasal syndrome (CBS) belongs to the category of FTD disorders that primarily affect movement. Some symptoms of both CBS and progressive supranuclear palsy, another FTD disorder associated with a decline in motor function, resemble those often seen in people with Parkinson’s disease. (These features are sometimes referred to as “atypical Parkinsonism.”)

Movement deficits in CBS often begin on one side of the body, but eventually both sides are affected. In addition to motor symptoms, people with CBS may exhibit changes in behavior and language skills common to bvFTD and PPA, particularly as the disease progresses.

Like all FTD disorders, CBS is associated with degeneration of the brain’s frontal and temporal lobes. In addition, several regions deeper in the brain that play important roles in initiating, controlling and coordinating movement are also affected.

The term corticobasal degeneration (CBD) is applied to cases which have a particular type of tauopathy at autopsy (detailed below). Some cases of CBS prove to have Alzheimer’s pathology instead.

Know the Signs… Know the Symptoms

Signs and symptoms of CBS include:

Limb Apraxia

  • Inability to compel a hand, arm or leg to carry out a desired motion although the muscle strength needed to complete the action is maintained
  • Difficulty completing familiar purposeful activity, such as opening a door, operating the television remote, or using kitchen tools
  • Tripping or falling

Akinesia/bradykinesia

Absence (akinesia) or abnormally slow (bradykinesia) movement.


Rigidity

Stiffness, resistance to movement.


Dystonia

Uncontrollable muscle contraction that causes an arm or leg to twist involuntarily or to assume an abnormal posture.


Cognitive Symptoms

These may include:

  • Alien limb phenomenon – sensation that an arm or leg is not part of the body, accompanied by inability to control movement of the limb
  • Acalculia – inability to carry out simple mathematical calculations, such as adding or subtracting
  • Visuospatial deficits – difficulty orienting in space.

Diagnosis

A person affected by CBS may present with cognitive, motor or language symptoms as the first sign. Development of a second and/or third category of symptoms makes it easier for the physician to recognize the illness as CBS. Individuals with CBS are easier to diagnose if they are showing limb apraxia, such as no longer being able to use the remote control for the television set, or not being able to retrieve mail from the mailbox. Initial symptoms of CBS often begin around age 60 (although there is variability in the age of onset) and then become bilateral as the disease progresses. A person with CBS may first present with a language disorder and develop motor symptoms over time.

If you think that you or a loved one may have been misdiagnosed with another condition – or if you have concerns about any of the signs and symptoms listed above – it is important to consult a doctor.

Treatment, Management, and What to Expect

There is no approved 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’s disease-type symptoms are sometimes tried, but often do not produce significant or sustained improvement for motor symptoms.

To date, there have been no randomized controlled trials of selective serotonin reuptake inhibitors in CBS. Small studies have shown improvement in FTD behavioral symptoms, but not cognition. Medications to address rigidity and bradykinesia in Parkinson’s disease have been tried but without lasting benefit in CBS. Benzodiazepines to control dystonia and myoclonus have shown benefit for some. Botulinum toxin has also demonstrated some symptomatic benefit in hypersalivation dystonia in CBS. Maintaining a healthy lifestyle with physical and mental activity is generally recommended for patients with central nervous system degenerative diseases, as is a “heart healthy” diet.

Although there is no current treatment for CBD, therapy does help to manage the symptoms. 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 frontotemporal degeneration and CBD. Other medical specialists who may be helpful include: speech therapists, occupational and physical therapists, neuropsychologists, nurses (especially home-care nursing), and genetic counselors.

Genetics

CBS is almost always sporadic, developing by chance rather than being inherited. Some research has found associations with CBS and a specific form (4R 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.

Pathology

Upon autopsy, corticobasal degeneration is characterized by nerve cell loss, gliosis and atrophy (shrinkage) of the deeper layers in the posterior frontal and/or parietal lobes, 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.

Different underlying protein pathologies can be found at autopsy in clinically diagnosed CBS that may be FTLD related tau protein (4R type) or TDP43 protein. Alternatively Alzheimer’s disease pathology has been observed with amyloid plaques and tau tangles, or alpha synuclein protein pathology more typical of Lewy body disease.

Corticobasal Syndrome 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.

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

 


References

Lamb, R., Rohrer, J.D., Lees, A.J., Morris, HR. Progressive supranuclear palsy and corticobasal degeneration: Pathophysiology and treatment options. Current Treatment Options Neurology. 2016, September 2016.