Introduction to Corticobasal Degeneration
Corticobasal degeneration refers to a rare neurodegenerative disorder which primarily affects movement. It belongs to a group of diseases called primary tauopathies, a group of diseases where the abnormal form of tau protein is the primary characteristic [1]. The prevalence of the disease varies between 4.9-7.3 per 100,000 [2], and the mean age of onset is around 64 years.
Despite the rare occurrence of this disease, it is often misdiagnosed with other diseases such as Parkinson’s disease or Alzheimer’s disease because of the symptoms and pathological overlap [2]. The disease is irreversible and the course of the disease usually takes 6 to 8 years.
From a genetics point of view, the disease is mainly sporadic, but familial cases have been reported. These occur due to mutation in the microtubule-associated tau protein gene [3].
Our understanding of this disease is much better than 50 years ago. This is largely because of the use of advanced neuroimaging techniques, such as fMRI scans or PET scans, that allow us to visualize the disease.
Additionally, researchers use biological indicators, called biomarkers, obtained from the body, to monitor the degeneration of the brain. These allow us to understand the preclinical stages of the disease, and can speed the process of finding effective therapeutics [4]. However, a biomarker specific to corticobasal degeneration is still being researched, as we will see in later sections.
Symptoms and Pathology of Corticobasal Degeneration
What Are The Symptoms of Corticobasal Degeneration?
The most common manifestation of corticobasal degeneration is the Corticobasal syndrome, featuring symptoms linked to the cortical and extrapyramidal systems of the brain.
These include dystonia, which involves involuntary muscle contractions, and myoclonus, characterized by involuntary twitching similar to what one might experience while sleeping. There may even be signs of asymmetrical Parkinsonism, where symptoms start on one side of the body earlier than the other. This delay in symptom onset is more pronounced in CBD patients than in those affected by Parkinson’s disease.
In the introduction to this blog post, we mentioned a phenomenon known as the 'alien limb', characterized by involuntary limb movements. While this is a common symptom of corticobasal degeneration, the condition also presents other terrifying symptoms.
For instance, apraxia is a condition where one struggles to execute movements despite having the physical ability and willingness to perform them. Individuals with corticobasal degeneration can also be experiencing problems with how the brain interprets information coming from the eyes [2].
Apart from this, signs of cortical dysfunction are general cognitive impairment and behavioural changes [3].
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CBD can also cause symptoms similar to Frontotemporal dementia, Progressive supranuclear Palsy, Alzheimer’s disease-like dementia, Dementia with Lewy bodies or Parkinson’s disease [3].
Pathology: What causes corticobasal degeneration?
CBD is characterized by the accumulation of a special type of protein, known as microtubule-associated tau protein, in its abnormal form, called hyperphosphorylated tau. This protein is also found in Alzheimer’s disease and other tauopathies.
It accumulates in the cerebral cortex, giving the disease its 'cortico' element in the name, and in the basal ganglia, which contributes to the 'basal' element of the name. The accumulation leads to the loss of neurons and astrocytes, which are a type of glial cells in the central nervous system responsible for supporting and maintaining the function of neurons [5]. The protein accumulation essentially "kills" these neurons, causing neurodegeneration.
Surprisingly, in CBD the accumulation found in astrocytes is present in areas of the brain where there is no neuronal accumulation of the abnormal tau. This distinguishes the CBD pathology from other tauopathies [3, 6]. However, this can only be determined after the affected individual’s death. This makes a definitive diagnosis of CBD in living persons unattainable [7].
Diagnosis and Treatment for Corticobasal Degeneration
How is corticobasal degeneration diagnosed?
The diagnosis of corticobasal degeneration is challenging. This difficulty arises from the presence of several diseases with symptoms that overlap with those of CBD.
For example, neuroimaging techniques can fail because different diseases may produce very similar brain scans. A patient with Alzheimer's disease may suffer from degeneration of identical areas of the brain as compared to a patient with corticobasal degeneration. In order to diagnose CBD, we would need to determine whether the accumulation of the abnormal tau protein occurs both in the astrocytes and neurons. But as we mentioned above, this is not possible [3].
Additionally, there are no exact biomarkers for CBD. Usually, clinicians measure a protein called neurofilament light chain, found in the cerebrospinal fluid and blood. However, this protein is not disease-specific but only signals general neudegeneration [3,8].
One way clinicians diagnose corticobasal degeneration is by ruling out other disease. For example, they can identify biomarkers indicative of Alzheimer’s disease, or, using genetic screening, clinicians eliminate conditions like familial Frontotemporal dementia (fFTD). Unfortunately, this can be misleading and the only possible way to determine whether the individual is suffering from CBD is post-mortem (after death) [3].
However, recent advances offer hope in the diagnosis of CBD. In 2022, researchers found that there is a correlation between specific fragments of the abnormal tau protein in the brain and cerebrospinal fluid. This could be a biomarker, specific to CBD [9].
In their study, they were able to distinguish patients with corticobasal degeneration from healthy controls and also other tauopathies, such as Alzheimer's. While this is extremely exciting, more research using larger cohorts is needed.
How is corticobasal degeneration treated?
Because of the difficulty in proper diagnosis of cortiocobasal degeneration, there is no effective treatment available. Some treatments based on other diseases may be useful such as levodopa, or other dopamine agonists (used as a symptomatic treatment of Parkinson’s disease), neurotransmitter inhibitors (used for managing symptoms of Alzheimer’s disease) and others.
However, the results of whether these are helpful are inconsistent [10] but interventions such as physical therapy are suggested [11]. That being said, exciting news like a proper differentiation of CBD can speed the process of finding effective therapeutics for the disease.
Conclusion
To summarize, Corticobasal degeneration is a rare neurodegenerative disorder with a diverse range of symptomatic phenotypes, making its diagnosis challenging. The pathology, involving abnormal tau protein present in astrocytes of both grey and white matter and in areas where neuronal cells are not affected, sets it apart from other diseases. However the lack of specific biomarkers makes post-mortem diagnosis the only definitive method.
Effective treatments are elusive, and symptomatic relief remains inconsistent. While promising research is slowly emerging, the complexity of CBD highlights the urgent need for more research. Spreading the awareness about the disease is a crucial step in improving the diagnostic methods and explore potential therapeutic interventions for CBD.
Disclaimer
This article does not offer health advice. Always consult a medical professional regarding your condition.