Corticobasal ganglionic degeneration (CBgD) or corticobasal ganglionic degeneration (CBGD) is a rare, progressive neurodegenerative disease involving the cerebral cortex and the basal ganglia. CBgD symptoms typically begin in people from 50 to 70 years of age, and the average disease duration is six years. It is characterized by marked disorders in movement and cognitive dysfunction, and is classified as one of the Parkinson plus syndromes. Clinical diagnosis is difficult, as symptoms of CBgD are often similar to those of other disorders, such as Parkinson’s disease (PD), progressive supranuclear palsy (PSP), and dementia with Lewy bodies (DLB). Due to the various clinical presentations associated with CBgD, a final diagnosis can only be made upon neuropathologic examination.
Clinical vs. postmortem
One of the most significant problems associated with CBgD is the inability to perform a definitive diagnosis while an individual exhibiting the symptoms associated with CBgD is still alive. A clinical diagnosis of CBgD is performed based upon the specified diagnostic criteria, which focus mainly on the symptoms correlated with the disease. However, this often results in complications as these symptoms often overlap with numerous other neurodegenerative diseases. Frequently, a differential diagnosis for CBgD is performed, in which other diseases are eliminated based on specific symptoms that do not overlap. However, some of the symptoms of CBgD used in this process are rare to the disease, and thus the differential diagnosis cannot always be used.
Postmortem diagnosis provides the only true indication of the presence of CBgD. Most of these diagnoses utilize the Gallyas-Braak staining method, which is effective in identifying the presence of astroglial inclusions and coincidental tauopathy.
Overlap with other diseases
Progressive supranuclear palsy (PSP) is frequently the disease most often confused with CBgD. Both PSP and CBgD result in similar symptoms, and both display tauopathies upon histological inspection. However, it has been noted that tauopathy in PSP results in tuft-shaped astrocytes in contrast with the doughnut-shaped astrocytic plaques found as a result of CBgD.
Individuals diagnosed with PD often exhibit similar movement dysfunction as those diagnosed with CBgD, which adds complexity to its diagnosis. Some other neurodegenerative diseases including Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD) also show commonalities with CBgD.
The types of imaging techniques that are most prominently utilized when studying and/or diagnosing CBgD are:
magnetic resonance imaging (MRI)
single-photon emission computed tomography (SPECT)
fluorodopa positron emission tomography (FDOPA PET)
Developments or improvements in imaging techniques provide the future possibility for definitive clinical diagnosis prior to death. However, despite their benefits, information learned from MRI and SPECT during the beginning of CBgD progression tend to show no irregularities that would indicate the presence of such a neurodegenerative disease. FDOPA PET is used to study the efficacy of the dopamine pathway.
Despite the undoubted presence of cortical atrophy (as determined through MRI and SPECT) in individuals experiencing the symptoms of CBgD, this is not an exclusive indicator for the disease. Thus, the utilization of this factor in the diagnosis of CBgD should be used only in combination with other clinically present dysfunctions.
MRI images are useful in displaying atrophied portions of neuroanatomical positions within the brain. As a result, it is especially effective in identifying regions within different areas of the brain that have been negatively affected due to the complications associated with CBgD. To be specific, MRI of CBgD typically shows posterior parietal and frontal cortical atrophy with unequal representation in corresponding sides. In addition, atrophy has been noted in the corpus callosum.
Functional MRI (fMRI) has been used to evaluate the activation patterns in various regions of the brain of individuals affected with CBgD. Upon the performance of simple finger motor tasks, subjects with CBgD experienced lower levels of activity in the parietal cortex, sensorimotor cortex, and supplementary motor cortex than those individuals tested in a control group.
SPECT studies of individuals diagnosed with CBgD involve perfusion analysis throughout the parts of the brain. SPECT evaluation through perfusion observation consists of monitoring blood release into different locations in tissue or organ regions, which, in the case of CBgD, pertains to localized areas within the brain. Tissue can be characterized as experiencing overperfusion, underperfusion, hypoperfusion, or hyperperfusion. Overperfusion and underperfusion relate to a comparison with the overall perfusion levels within the entire body, whereas hypoperfusion and hyperperfusion are calculated in comparison to the blood flow requirements of the tissue in question. In general, the measurements taken for CBgD using SPECT are referred to as regional cerebral blood flow (rCBF).
In general, SPECT reveals hypoperfusion within both the posterior regions of the frontal and parietal lobes. As in images gathered through MRI, SPECT images indicated asymmetry in the presentation of abnormalities throughout the brain. Additional studies have revealed the presence of perfusion anomalies in the thalamus, temporal cortex, basal ganglia, and pontocerebellar (from the pons to the cerebellum) locations within subjects’ brains.
Research has suggested that the integrity of the dopamine system in the striatum has been damaged as an effect of CBgD. Current studies employing the use of FDOPA PET scanning (FDOPA PET) as a possible method for identifying CBD have focused on analyzing the efficiency of neurons in the striatum that utilize the neurotransmitter dopamine. These studies have concluded that, in general, dopamine uptake was diminished in the caudate and the putamen. This characteristic also has the potential to be useful in distinguishing CBgD from the similar PD, as individuals having been diagnosed with PD were more likely to have a lower uptake of dopamine than in individuals with CBgD.
Other clinical tests or procedures that monitor the presence of dopamine within the brain (β-CIT SPECT and IBZM SPECT) have shown similar findings. β-CIT serves as an indicator for presynaptic dopaminergic neurons, whereas IBZM is a tracer that shows an affinity for the postsynaptic neurons of the same type. Despite agreement with other imaging studies, these two SPECT methods suffer some scrutiny due to better accuracy in other imaging methods. However, β-CIT SPECT has proven to be helpful in distinguishing CBgD from PSP and multiple system atrophy (MSA).
All of the disorders and dysfunctions associated with CBgD can often be categorized into a class of symptoms that present with the disease of CBgD. These symptoms that aid in clinical diagnosis are collectively referred to as corticobasal syndrome (CBS) or corticobasal degeneration syndrome (CBDS). Alzheimer’s disease, Pick’s disease, and progressive supranuclear palsy can display a corticobasal syndrome. It has been suggested that the nomenclature of corticobasal degeneration only be used for naming the disease after it has received verification through postmortem analysis of the neuropathology. CBS patients with greater temporoparietal degeneration are more likely to have AD pathology as opposed to frontotemporal lobar degeneration.
Because the exact cause of CBgD is unknown, there exists no formal treatment for the disease. Instead, treatments focus on minimizing the appearance or effect of the symptoms resulting from CBgD. The most easily treatable symptom of CBgD is parkinsonism, and the most common form of treatment for this symptom is the application of dopaminergic drugs. However, in general only moderate improvement is seen and the relief from the symptom is not long-lasting. In addition, palliative therapies, including the implementation of wheelchairs, speech therapy, and feeding techniques, are often used to alleviate many of the symptoms that show no improvement with drug administration
Clinical presentation of CBgD usually does not occur until age 60, with the earliest recorded diagnosis and subsequent postmortem verification being age 28. Although men and women present with the disease, some analysis has shown a predominant appearance of CBD in women. Current calculations suggest that the prevalence of CBgD is approximately 4.9 to 7.3 per 100,000 people. The prognosis for an individual diagnosed with CBgD is death within approximately eight years, although some patients have been diagnosed over 17 years ago (2017) and are still in relatively good standing, but with serious debilitation such as dysphagia, and overall limb rigidity. The partial (or total) use of a feeding tube may be necessary and will help prevent aspiration pneumonia, primary cause of death in CBgD. Incontinence is common, as patients often can’t express their need to go, due to eventual loss of speech. Therefore, proper hygiene is mandatory to prevent urinary tract infections.
CBgD was first identified by Rebeiz and his associates in 1968, as they observed three individuals who exhibited characteristic symptoms of the unique and previously unknown disorder. They initially referred to the neurodegenerative disease as “corticodentatonigral degeneration with neuronal achromasia”, after which various other names were used, including “corticonigral degeneration with nuclear achromasia” and “cortical basal ganglionic degeneration”. Although the underlying cause of CBgD is unknown, the disease occurs as a result of damage to the basal ganglia, specifically marked by neuronal degeneration or depigmentation (loss of melanin in a neuron) in the substantia nigra. Additional distinguishing neurological features of those diagnosed with CBD consist of asymmetric atrophy of the frontal and parietal cortical regions of the brain. Postmortem studies of patients diagnosed with CBgD indicate that histological attributes often involve ballooning of neurons, gliosis, and tauopathy. Much of the pioneering advancements and research performed on CBgD has been completed within the past decade or so, due to the relatively recent formal recognition of the disease.