Corticobasal degeneration
Corticobasal degeneration is a rare progressive neurological disorder characterized by nerve cell loss and atrophy (shrinkage) of multiple areas of the brain including the cerebral cortex and the basal ganglia. Corticobasal degeneration progresses gradually and affects people from the age of 40, typically between the ages of 50 to 70. Initial symptoms, which typically begin at or around age 60, may first appear on one side of the body (unilateral) and may include poor coordination or difficulty accomplishing goal-directed tasks (e.g., buttoning a shirt), but eventually affect both sides as the disease progresses. Corticobasal degeneration symptoms are similar to those found in Parkinson disease, such as poor coordination, akinesia (an absence of movements), rigidity (a resistance to imposed movement), disequilibrium (impaired balance); and limb dystonia (abnormal muscle postures). Other symptoms such as cognitive and visual-spatial impairments, apraxia (loss of the ability to make familiar, purposeful movements), hesitant and halting speech, myoclonus (muscular jerks), and dysphagia (difficulty swallowing) may also occur. An individual with corticobasal degeneration eventually becomes unable to walk.
Affected individuals often initially experience motor abnormalities in one limb that eventually spreads to affect all the arms and legs. Such motor abnormalities include muscle rigidity and the inability to perform purposeful or voluntary movements (apraxia). Affected individuals may have sufficient muscle power for manual tasks, but often have difficulty directing their movements appropriately. Although corticobasal degeneration was historically described as a motor disease, it is now recognized that cognitive and behavioral symptoms also herald corticobasal degeneration and not uncommonly predate motor symptoms.
The exact cause of corticobasal degeneration is unknown.
Because signs and symptoms associated with corticobasal degeneration are frequently caused by other neurodegenerative disorders, researchers use the term “corticobasal syndrome” to indicate the clinical diagnosis based on signs and symptoms. The term “corticobasal degeneration” refers to those meeting the neuropathological criteria for the disorder at autopsy. This is an important distinction because clinicopathological series indicate that about less than half of patients diagnosed with corticobasal syndrome during life actually has corticobasal degeneration at autopsy.
Corticobasal degeneration has similarities with progressive supranuclear palsy (PSP). Some people with corticobasal degeneration go on to develop progressive supranuclear palsy, and vice versa.
Corticobasal degeneration is believed to affect males and females in equal numbers. However, in some studies it was reported to be more common in women. No confirmed cases of corticobasal degeneration have been reported in the medical literature in individuals under 40 1. Corticobasal degeneration is estimated to affect 5 people per 100,000 in the general population, with approximately 0.62-0.92 new cases per year per 100,000 people. However, cases may go undiagnosed or misdiagnosed making it difficult to determine the true frequency of corticobasal degeneration in the general population.
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 do not produce any significant or sustained improvement. Clonazepam may help the myoclonus. Occupational, physical, and speech therapy can help in managing disability.
Corticobasal degeneration causes
The exact, underlying cause of corticobasal degeneration is unknown. Researchers believe that multiple different factors contribute to the development of the disorder including various genetic and environmental factors as well as factors related to aging. It is thought there may be some weak genetic link too but the risk of other family members developing corticobasal degeneration is very low.
The symptoms of corticobasal degeneration develop due to the progressive deterioration of tissue in different areas of the brain. Nerve cell loss occurs in specific areas, leading to atrophy or shrinkage in specific lobes of the brain. The severity and type of symptoms depend on the area of the brain affected by the disease. The cerebral cortex and basal ganglia are the two areas of the brain most typically affected, although other areas may become involved. The cerebral cortex is the outer layer of nerve tissue called gray matter that surrounds the cerebral hemispheres. The cerebral cortex is involved with higher brain functions including voluntary movement, memory and learning, and coordination of sensory information. The basal ganglia is a cluster of nerve cells that is involved with motor and learning functions.
Researchers have determined that a protein called tau is involved in the development of corticobasal degeneration. Tau is a specific type of protein normally found in brain cells. The function of tau within nerve cells is complex and not fully understood, although it is believed to be essential for the normal function of brain cells. In corticobasal degeneration, abnormal levels of tau accumulate in certain brain cells, eventually causing their deterioration. The exact role, that tau plays in the development of corticobasal degeneration is not fully understood. Abnormalities involving tau are also seen in other neurodegenerative brain disorders including Alzheimer’s disease, Pick disease, progressive supranuclear palsy, Niemann-Pick disease type C and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). These disorders collectively are referred to as “tauopathies.”
Corticobasal degeneration inheritance pattern
Corticobasal degeneration is almost always sporadic, developing by chance rather than being inherited 2. Rare familial cases have been reported, leading to the possibility that there may be a genetic basis for at least a predisposition to corticobasal degeneration 1. Some research has found associations with corticobasal degeneration and a specific form (variant) of the tau gene. However, not all people with corticobasal degeneration have the tau gene variant, and not all people with the gene variant develop corticobasal degeneration 2.
Corticobasal degeneration symptoms
Corticobasal degeneration is a very individual condition and progression, severity and presentation of corticobasal degeneration can vary greatly from one individual to another. As corticobasal degeneration is a progressive neurodegenerative condition, symptoms gradually become worse over time.
The most common symptoms are outlined below, but many people have only a few symptoms. It is important to note that affected individuals may not have all of the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.
Movement difficulties
- Difficulty controlling the limbs on one side of the body – often known as ‘alien limb’ syndrome – as arms or legs may seem to move independently
- Numbness and loss of coordinated movement in one hand (apraxia), making everyday tasks such as dressing, opening a door, operating the television remote, using kitchen tools, writing and eating difficult
- Tripping or falling
- Absence (akinesia) or abnormally slow (bradykinesia) movement.
- Muscle stiffness (rigidity)
- Shaking (tremor)
- Uncontrollable muscle contraction that causes an arm or leg to twist involuntarily or to assume an abnormal posture (dystonia)
- Balance and co-ordination problems.
Speech and communication problems: slow and slurred speech.
Swallowing difficulties: eating, drinking and swallowing become progressively more difficult and food may ‘go down the wrong way’. This can lead to chest infections or pneumonia.
Cognitive and behavioral changes: thinking may become impaired, leading to memory problems and difficulty understanding and interpreting communication. It may also be difficult to carry out complex tasks that require planning ahead. Inability (acalculia) to carry out simple mathematical calculations, such as adding or subtracting. Visuospatial deficits – difficulty orienting in space.
Changes in personality, such as apathy, irritability and decreased interest in things previously enjoyed may be noticed by family and friends.
In many cases, affected individuals develop progressive stiffening or tightening of muscles in the limbs (progressive asymmetric rigidity). Affected individuals are often unable to make voluntary, purposeful movements with the affected limb (apraxia). Affected individuals have sufficient muscle power for manual tasks but have difficulty directing their movements appropriately. Difficulties with the affected limb progressively worsen over time. People with corticobasal degeneration may first become aware of the disorder when they have difficulty coordinating movements in the performance of manual tasks such as buttoning a shirt, combing their hair or gesturing with their hands. Affected individuals often described their actions as stiff, clumsy or uncoordinated. In some cases, affected individuals may be unaware of the movement of a limb or unable to control the movement of a limb (alien limb syndrome). Symptoms typically begin on one side of the body (unilateral), but usually progress over time to affect both sides and all four limbs. In rare cases, the legs may be affected before the arms.
Additional symptoms of corticobasal degeneration may include a slight tremor while in particular positions (postural tremor) or while performing a task (action tremor), and/or exaggerated slowness of movements (bradykinesia) or lack of movement (akinesia). Sudden, brief involuntary muscle spasms that cause jerky movements (myoclonus) may also occur. In some cases, limb dystonia may be present. Dystonia is a general term for a group of neurological conditions characterized by involuntary muscle contractions that force a certain part(s) of the body into abnormal, sometimes painful, movements and positions (postures). Affected individuals may also develop contractures, a condition in which a joint becomes permanently fixed in a bent (flexed) or straightened (extended) position, completely or partial restricting the movement of the affected joint.
Affected individuals may also have speech and language abnormalities including difficulties understanding or expressing language (aphasia), difficulty saying what they want to say despite knowing the right words (apraxia of speech) and speech difficulties due to problems with the muscles that enable speech (dysarthria). Additional symptoms that may occur include difficulty swallowing (dysphagia), an inability to control eyelid blinking, and/or an uncoordinated walk (ataxic gait). Eventually, affected individuals may be unable to walk unassisted.
For many years, corticobasal degeneration was seen as a neurological condition primarily associated with movement disorders. In recent years, researchers have noted that cognitive and behavioral abnormalities occur more frequently than initially believed. In some cases, the signs and symptoms of dementia may even precede the development of motor symptoms. Initial cognitive symptoms include a nonfluent, progressive aphasia and impairments in executive function. Individuals with corticobasal degeneration can develop a more global loss of intellectual abilities (dementia), usually later in the course of the disease. Affected individuals may also exhibit memory loss, impulsiveness, disinhibition, apathy, irritability, reduced attention span and obsessive-compulsive behaviors.
As corticobasal degeneration progresses, affected individuals may become unable to communicate effectively. Eventually, affected individuals may become bedridden and susceptible to life-threatening complications such as pneumonia, bacterial infections, a blood infection (sepsis) or blockage of one or more of the main arteries of the lungs, usually due to blood clots (pulmonary embolism).
Corticobasal degeneration diagnosis
A diagnosis of corticobasal degeneration is suspected on the pattern of symptoms experienced (characteristic neurologic symptoms that occur in a slowly progressive course in the absence of a structural lesion such as a stroke or tumor) and the exclusion of other conditions that may cause similar symptoms, such as Parkinson’s or stroke. Unfortunately, as with Parkinson’s disease, there is no single test or scan to diagnose corticobasal degeneration. Distinguishing corticobasal degeneration from other, similar neurodegenerative disorders is difficult.
A diagnosis should be made by a specialist with experience of corticobasal degeneration, usually a neurologist. He or she may ask for a brain scan to rule out other causes, and they may also carry out tests to check memory, concentration and understanding of verbal communication.
Clinical testing and work-up
An electroencephalogram (EEG), a test which measures the electrical activity of the brain is generally unhelpful and not diagnostic of neurodegenerative disease.
Imaging techniques such as computerized tomography (CT) scanning and magnetic resonance imaging (MRI) may be used to rule out other conditions or reveal characterized brain tissue degeneration within the cerebral cortex and basal ganglia. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures including the brain. An MRI uses magnetic field pulses to produce cross-sectional images of particular organs and bodily tissues such as the brain.
Corticobasal degeneration treatment
There is currently no cure or treatment to stop corticobasal degeneration’s progression but medication and various therapies can relieve symptoms and improve quality of life, although most cases prove resistant to such therapy.
- Medication can improve movement, cognitive and behavioral problems. However, the improvement is usually much less than in Parkinson’s disease. Affected individuals may be treated with certain drugs such as levodopa and similar medications that are normally used to treat Parkinson’s disease. These drugs are generally ineffective, but may help with the slowness or stiffness some individuals experience. Myoclonus may be controlled with medications such as clonazepam, however, benzodiazepines should be used sparingly as they may have undesired side effects in these patients. Botulinum toxin (Botox®) has been used to treat contractures and pain, but do not restore the ability to control movements. Baclofen is another drug that may be used to treat muscle rigidity.
- Physical therapy can help with movement, maintaining the mobility and range of motion of stiffened, rigid joints and prevent the development of contractures and balance problems.
- Speech and language therapy can help with swallowing and communication difficulties.
- An occupational therapist can advise on equipment and adaptations in the home, and can suggest strategies for carrying out daily tasks in order to retain as much independence as possible. Affected individuals may need devices such as a cane or walker to assist in walking.
Corticobasal degeneration prognosis
Corticobasal degeneration usually progresses slowly over the course of 6 to 8 years. Death is generally caused by pneumonia or other complications of severe debility such as sepsis or pulmonary embolism.
References
