Corticobasal Degeneration (CBD)


Corticobasal degeneration (CBD) is a rare and gradually progressive neurodegenerative disorder that presents significant challenges to clinical diagnosis and treatment in view of its variable clinical presentation. Its incidence and prevalence are unknown, but they have been estimated to be 0.62-0.92 per 100,000 people. The age of the disease onset is often in the 60s, but ranges from 45 to 77 years.

Symptoms

CBD clinical presentation varies which makes the diagnosis challenging despite the fact that the understanding of CBD has grown tremendously since its initial description. New CBD diagnostic criteria were developed based on recent advances and a review of a large number of pathologically proven cases. CBD may present with four phenotypes depending on the location of the underlying lesions.

1.     Corticobasal syndrome (CBS) may be characterized by gradual progressive onset of motor symptoms affecting one side of the body that could include: parkinsonism characterized by stiffness (rigidity) and slowness of movements (bradykinesia); sustained muscle contractions causing abnormal postures (dystonia) and/or involuntary jerks (myoclonus). 

In addition or alternatively, patients may present with cognitive lateralized symptoms that include inability to execute or carry out learned purposeful movements without clear motor or sensory causes (ideomotor apraxia), feeling that a limb is foreign or has a mind of its own (alien limb phenomenon), language disturbances (aphasia) and/or visuospatial difficulties. 

Speech can be affected and changed in different ways including reduced volume, monotone pitch, fluctuating speech articulation, shallow inhalations, and slow rate of speech punctuated with rapid-burst or other changes. 

The corticobasal is one of the CBD presentations, but this could also be the presentation of other neurodegenerative disorders such as progressive supranuclear palsy or an atypical form of Alzheimer’s disease may present. Laboratory studies may help rule out Alzheimer’s disease. 

2. Frontal behavioral-spatial syndrome is characterized by behavioral or personality changes which include loss of interest in doing things (apathy), irritability and disinhibition. Patients may also exhibit an executive dysfunction characterized by difficulties planning, multitasking, or retrieving information. Patients with CBD may have visuospatial deficits characterized by difficulties understanding and conceptualizing visual representations and spatial relationships in learning and performing tasks. 

3. Nonfluent/agrammatic variant of primary progressive aphasia is mainly characterized by progressive language difficulties characterized by an effortful, agrammatic speech in which patients may use simplified sentence structures and make errors in tense, number, or gender. Patients may have a distorted speech production (apraxia of speech). There is usually a preserved single word comprehension.

4. Progressive supranuclear palsy syndrome (PSPS) patients present with the symptoms described as classically as PSP (Richardson syndrome) (see description under progressive supranuclear palsy). 

At present, there are no laboratory markers for the diagnosis of CBD, but imaging and cerebrospinal studies are used to rule out other disorders. 

Causes

CBD is labeled as a “tauopathy” because a cell protein that normally exist in the walls of the cells or nourishment pipes called “tau” aggregates abnormally inside the neurons and other brain cells: astrocytes and oligodendroglia. CBD is usually a non-hereditary (sporadic) disease, although rare familial cases of CBD have been reported. In CBD as in other tauopathies such as PSP there are polymorphisms in the tau gene that suggest there may be a genetic basis or at least a predisposition for this disorder. There have been no epidemiological studies of environmental or occupational risk factors. 

Tau aggregation in neurons and glia
The above image shows tau aggregation in neurons and glia.

Treatment

Pharmacological management
There are no treatments that can stop or slow the progressive nature of CBD. Treatment is targeted at reducing the symptoms, improving the quality of life and preventing complications.

Pharmacologic therapies for the motor symptoms have limited benefit. Levodopa is usually not effective in improving the parkinsonism in CBD, but the poor responsiveness to levodopa therapy may support the diagnosis. Botulinum toxin can improve the dystonia and is usually used to treat it if there is pain or there are difficulties in cleaning the patient. There are several therapies that could improve the myoclonus, if significant, including benzodiazepines. If there is no observed benefit from these treatments, they should be tapered to avoid undesired side effects. 

There are no known therapies that could improve the cognitive disturbances patients with CBD experience. Cholinesterase inhibitors (such as donepezil, rivastigmine, or galantamine) are not useful in CBD. However, depression, which is common, should be treated with an appropriate antidepressant medication as early as it is recognized. 

Non-pharmacological management
Walking devices such as a weighted walker could prevent falls. However, using a walking device may be difficult when patients have apraxia.

U-Step Weighted Walker

Physical therapy may help with patients’ balance and gait disturbances. It may also be helpful to avoid a rotator cuff syndrome. Orthotic splinting may also reduce contractures and relieve pressure from tightly clinched fingers pressing into the palm. Occupational therapy can be beneficial in assisting with devices for eating and grooming and other adaptive measures. Similarly, speech therapy could be helpful to diagnose and manage speech and swallowing disturbances. 

The care for CBD patients is difficult and demanding. Attention should be given to cues that the family is in distress, and referrals for respite care, in-home health assistance, hospice, and counseling should be made to support the families and caregivers and relieve caregiver burden and distress. Treatment of CBD is aimed at safety, symptom management, and patient and family supportive measures.

Research

Dr. Irene Litvan and her team are currently involved in a clinical trial with the goal of measuring the progression of CBD/CBS and PSP. Link to more details on this study and how you can get involved.

What We Offer

Our Movement Disorder Center is part of the UC San Diego Health System - the only health system in San Diego. As an academic health system, we can offer the best diagnostic, therapeutic, palliative and supportive care to patients with movement disorders and related neurodegenerative diseases. We provide a patient-centered approach to care that is designed to address each individual's unique needs, as well as educational programs, local resources and support groups.

The Movement Disorder Center at UC San Diego takes a multidisciplinary approach to patient care and research. Our team consists of movement disorder specialists, a neurosurgeon, neuropsychologists, a nurse practitioner, clinical team, and physical, speech and occupational therapists. Meet our team.

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