Corticobasal degeneration
Encyclopedia
Corticobasal degeneration (CBD) or Corticobasal Ganglionic Degeneration (CBGD) is a rare progressive neurodegenerative disease involving the cerebral cortex
and the basal ganglia
. It is characterized by marked disorders in movement and cognitive dysfunction. Clinical diagnosis is difficult, as symptoms of CBD are often similar to those of other diseases, such as Parkinson's disease
(PD) and progressive supranuclear palsy
(PSP).
, 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 CBD indicate that histological attributes often involve ballooning of neurons, gliosis
, and tauopathy
. Much of the pioneering advancements and research performed on CBD has been completed within the past decade or so, due to the relevantly recent formal discovery of the disease.
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 CBD 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 CBD, this is not an exclusive indicator for the disease. Thus, the utilization of this factor in the diagnosis of CBD should only be used in combination with other clinically present dysfunctions.
.
Functional MRI (fMRI) has been used to evaluate the activation patterns in various regions of the brain of individuals affected with CBD. Upon the performance of simple finger motor tasks, subjects with CBD experienced lower levels of activity in the parietal cortex, sensorimotor cortex, and supplementary motor cortex than those individuals tested in a control group.
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 CBD, 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. The measurements taken for CBD using SPECT are generally referred to as regional cerebral blood flow
(rCBF).
Generally, 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.
. This characteristic also has the potential to be useful in distinguishing CBD from the similar PD, as individuals who had been diagnosed with PD were more likely to have a lower uptake of dopamine than in individuals with CBD.
Other clinical tests or procedures which 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, while 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 CBD from PSP and multiple system atrophy
(MSA).
).
(MAP), and is typically found in neuronal axons. However, malfunctioning of the development of the protein can result in unnatural, high-level expression in astrocytes and glial cells. Consequently, this is often responsible for the astrocytic plaques prominently noted in histological CBD examinations. Although they are understood to play a significant role in neurodegenerative diseases such as CBD, their precise effect remains a mystery.
Postmortem diagnosis provides the only true indication of the presence of CBD. Most of these diagnoses utilize the Gallyas-Braak staining method, which is effective in identifying the presence of astroglial inclusions and coincidental tauopathy.
Individuals diagnosed with PD often exhibit similar movement dysfunction as those diagnosed with CBD, 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 CBD.. FTDs have also been known to evolve into corticobasal syndrome.
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
and the basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
. It is characterized by marked disorders in movement and cognitive dysfunction. Clinical diagnosis is difficult, as symptoms of CBD are often similar to those of other diseases, such as Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
(PD) and progressive supranuclear palsy
Progressive supranuclear palsy
Progressive supranuclear palsy is a degenerative disease involving the gradual deterioration and death of specific areas of the brain....
(PSP).
Background and History
CBD 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 CBD is unknown, the disease occurs as a result of damage to the basal gangliaBasal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
, specifically marked by neuronal degeneration or depigmentation (loss of melanin in a neuron) in the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
. 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 CBD indicate that histological attributes often involve ballooning of neurons, gliosis
Gliosis
Gliosis is a proliferation of astrocytes in damaged areas of the central nervous system . This proliferation usually leads to the formation of a glial scar....
, and tauopathy
Tauopathy
Tauopathies are a class of neurodegenerative diseases associated with the pathological aggregation of tau protein in the human brain.The best known of these illnesses is Alzheimer's disease , where tau protein is deposited within neurons in the form of neurofibrillary tangles...
. Much of the pioneering advancements and research performed on CBD has been completed within the past decade or so, due to the relevantly recent formal discovery of the disease.
Occurrence and Epidemiology
Clinical presentation of CBD 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 CBD is approximately 4.9 to 7.3 per 100,000 people. The prognosis for an individual diagnosed with CBD is death within approximately eight years.Symptoms and Clinical Presentation
Because CBD is progressive (it gradually worsens), a set of standard diagnostic criteria can be used, which is centered on the disease’s evolution. Included in these fundamental features are problems with cortical processing, dysfunction of the basal ganglia, and a sudden and detrimental onset. Psychiatric and cognitive dysfunctions, although present in CBD, are much less prevalent and lack establishment as common indicators of the presence of the disease.Motor and Associated Cortical Dysfunctions
Some of the most prevalent symptom types in people exhibiting CBD pertain to identifiable movement disorders and problems with cortical processing. These symptoms are initial indicators of the presence of the disease. Each of the associated movement complications typically is seen in an asymmetric manner, in which the symptom is not observed uniformly throughout the body. For example, a person exhibiting an alien hand syndrome (explained later) in one hand, will not correspondingly display the same symptom in the contralateral limb. Predominant movement disorders and cortical dysfunctions associated with CBD include:- ParkinsonismParkinsonismParkinsonism is a neurological syndrome characterized by tremor, hypokinesia, rigidity, and postural instability. The underlying causes of parkinsonism are numerous, and diagnosis can be complex...
- Alien Hand SyndromeAlien hand syndromeAlien hand syndrome is a neurological disorder in which the afflicted person's hand appears to take on a mind of its own...
- ApraxiaApraxiaApraxia is a disorder caused by damage to specific areas of the cerebrum. Apraxia is characterized by loss of the ability to execute or carry out learned purposeful movements, despite having the desire and the physical ability to perform the movements...
(Ideomotor Apraxia and Limb-Kinetic Apraxia) - AphasiaAphasiaAphasia is an impairment of language ability. This class of language disorder ranges from having difficulty remembering words to being completely unable to speak, read, or write....
Parkinsonism
The presence of parkinsonism as a clinical symptom of CBD is largely responsible for complications in developing unique diagnostic criteria for the disease. Other such diseases in which parkinsonism forms an integral diagnostic characteristic are PD and PSP. Parkinsonism in CBD is largely present in an extremity such as the arm, and is always asymmetric. Common associated movement dysfunctions that comprise parkinsonism are rigidity, bradykinesia, and gait disorder, with limb rigidity forming the most typical manifestation of parkinsonism in CBD. Despite being relatively indistinct, this rigidity can lead to disturbances in gait and correlated movements. Bradykinesia in CBD occurs when there is notable slowing in the completion of certain movements in the limbs. In an associated study, it was determined that, three years following first diagnosis, 71% of persons with CBD demonstrate the presence of bradykinesia.Alien Hand Syndrome
Alien hand syndrome has been shown to be prevalent in roughly 60% of those people diagnosed with CBD. This disorder involves the failure of an individual to control the movements of his or her hand, which results from the sensation that the limb is “foreign.” The movements of the alien limb are a reaction to external stimuli and do not occur sporadically or without stimulation. The presence of an alien limb has a distinct appearance in CBD, in which the diagnosed individual may have a “tactile mitgehen.” This mitgehen (German, meaning “to go with”) is relatively specific to CBD, and involves the active following of an experimenter’s hand by the subject’s hand when both hands are in direct contact. Another, rarer form of alien hand syndrome has been noted in CBD, in which an individual’s hand displays an avoidance response to external stimuli. Additionally, sensory impairment, revealed through limb numbness or the sensation of prickling, may also concurrently arise with alien hand syndrome, as both symptoms are indicative of cortical dysfunction. Like most of the movement disorders, alien hand syndrome also presents asymmetrically in those diagnosed with CBD.Apraxia
Ideomotor apraxia (IMA), although clearly present in CBD, often manifests atypically due to the additional presence of bradykinesia and rigidity in those individuals exhibiting the disorders. The IMA symptom in CBD is characterized by the inability to repeat or mimic particular movements (whether significant or random) both with or without the implementation of objects. This form of IMA is present in the hands and arms, while IMA in the lower extremities may cause problems with walking. Those with CBD that exhibit IMA may appear to have trouble initiating walking, as the foot may appear to be fixed to floor. This can cause stumbling and difficulties in maintaining balance. IMA is associated with deterioration in the premotor cortex, parietal association areas, connecting white matter tracts, thalamus, and basal ganglia. Some individuals with CBD exhibit limb-kinetic apraxia, which involves dysfunction of more fine motor movements often performed by the hands and fingers.Aphasia
Aphasia in CBD is revealed through the inability to speak or a difficulty in initiating spoken dialogue and falls under the non-fluent (as opposed to fluent or flowing) subtype of the disorder. This results in disconnected speech patterns and the omission of words. Individuals with this symptom of CBD often lose the ability to speak as the disease progresses.Psychiatric and Cognitive Disorders
Psychiatric problems associated with CBD often present as a result of the debilitating symptoms of the disease. Prominent psychiatric and cognitive conditions cited in individuals with CBD include dementia, depression, and irritability, with dementia forming a key feature that sometimes leads to the misdiagnosis of CBD as another cognitive disorder such as Alzheimer's disease (AD).Corticobasal Syndrome
All of the disorders and dysfunctions associated with CBD can often be categorized into a class of symptoms that present with the disease of CBD. These symptoms that aid in clinical diagnosis are sometimes collectively referred to as corticobasal syndrome (CBS) or corticobasal degeneration syndrome (CBDS). 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.Neuroimaging
The types of imaging techniques which are most prominently utilized when studying and/or diagnosing CBD are:- magnetic resonance imagingMagnetic resonance imagingMagnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI) - single photon emission computed tomographySingle photon emission computed tomographySingle-photon emission computed tomography is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information...
(SPECT) - fluorodopa positron emission tomographyPositron emission tomographyPositron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
(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 CBD 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 CBD, this is not an exclusive indicator for the disease. Thus, the utilization of this factor in the diagnosis of CBD should only be used in combination with other clinically present dysfunctions.
MRI
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 CBD. Specifically, MRI of CBD typically shows posterior parietal and frontal cortical atrophy with unequal representation in corresponding sides. Additionally, atrophy has been noted in the corpus callosumCorpus callosum
The corpus callosum , also known as the colossal commissure, is a wide, flat bundle of neural fibers beneath the cortex in the eutherian brain at the longitudinal fissure. It connects the left and right cerebral hemispheres and facilitates interhemispheric communication...
.
Functional MRI (fMRI) has been used to evaluate the activation patterns in various regions of the brain of individuals affected with CBD. Upon the performance of simple finger motor tasks, subjects with CBD experienced lower levels of activity in the parietal cortex, sensorimotor cortex, and supplementary motor cortex than those individuals tested in a control group.
SPECT
SPECT studies of individuals diagnosed with CBD involve perfusionPerfusion
In physiology, perfusion is the process of nutritive delivery of arterial blood to a capillary bed in the biological tissue. The word is derived from the French verb "perfuser" meaning to "pour over or through."...
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 CBD, 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. The measurements taken for CBD using SPECT are generally referred to as regional cerebral blood flow
Cerebral blood flow
Cerebral blood flow, or CBF, is the blood supply to the brain in a given time. In an adult, CBF is typically 750 millitres per minute or 15% of the cardiac output. This equates to 50 to 54 millilitres of blood per 100 grams of brain tissue per minute. CBF is tightly regulated to meet the brain's...
(rCBF).
Generally, 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
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
, temporal cortex, basal ganglia, and pontocerebellar (from the pons to the cerebellum) locations within subjects’ brains.
FDOPA PET
Research has suggested that the integrity of the dopamine system in the striatum has been damaged as an effect of CBD. Current studies employing the use of 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 dopamine uptake was generally diminished in the caudate and the putamenPutamen
The putamen is a round structure located at the base of the forebrain . The putamen and caudate nucleus together form the dorsal striatum. It is also one of the structures that comprises the basal ganglia. Through various pathways, the putamen is connected to the substantia nigra and globus pallidus...
. This characteristic also has the potential to be useful in distinguishing CBD from the similar PD, as individuals who had been diagnosed with PD were more likely to have a lower uptake of dopamine than in individuals with CBD.
Other clinical tests or procedures which monitor the presence of dopamine within the brain (β-CIT SPECT and IBZM
IBZM
IBZM is a chemical substance. Pharmaceutically it is a dopamine antagonist and it can be used by nuclear medicine physicians as a radioactive tracer for SPECT where the radioactive isotope is iodine-123 or iodine-125...
SPECT) have shown similar findings. β-CIT serves as an indicator for presynaptic dopaminergic
Dopaminergic
Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...
neurons, while 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 CBD from PSP and multiple system atrophy
Multiple system atrophy
Multiple system atrophy is a degenerative neurological disorder. MSA is associated with the degeneration of nerve cells in specific areas of the brain. This cell degeneration causes problems with movement, balance and other autonomic functions of the body such as bladder control or blood pressure...
(MSA).
Histological and Molecular Features
Neuropathological findings associated with CBD include the presence of astrocytic abnormalities within the brain and improper accumulation of the protein tau (referred to as tauopathyTauopathy
Tauopathies are a class of neurodegenerative diseases associated with the pathological aggregation of tau protein in the human brain.The best known of these illnesses is Alzheimer's disease , where tau protein is deposited within neurons in the form of neurofibrillary tangles...
).
Astroglial Inclusions
Postmortem histological examination of the brains of individuals diagnosed with CBD reveal unique characteristics involving the astrocytes in localized regions. The typical procedure used in the identification of these astroglial inclusions is the Gallyas-Braak staining method. This process involves exposing tissue samples to a silver staining material which marks for abnormalities in the tau protein and astroglial inclusions. Astroglial inclusions in CBD are identified as astrocytic plaques, which present as annularly displays of blurry outgrowths from the astrocyte. A recent study indicated that CBD produces a high density of astrocytic plaques in the anterior portion of the frontal lobe and in the premotor area of the cerebral cortex.Tauopathy
The protein tau is an important microtubule-associated proteinMicrotubule-associated protein
In cell biology, microtubule-associated proteins are proteins that interact with the microtubules of the cellular cytoskeleton.-Function:...
(MAP), and is typically found in neuronal axons. However, malfunctioning of the development of the protein can result in unnatural, high-level expression in astrocytes and glial cells. Consequently, this is often responsible for the astrocytic plaques prominently noted in histological CBD examinations. Although they are understood to play a significant role in neurodegenerative diseases such as CBD, their precise effect remains a mystery.
Clinical vs. Postmortem
One of the most significant problems associated with CBD is the inability to perform a definitive diagnosis while an individual exhibiting the symptoms associated with CBD is still alive. A clinical diagnosis of CBD 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 CBD is performed, in which other diseases are eliminated based on specific symptoms that do not overlap. However, some of the symptoms of CBD 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 CBD. 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 CBD. Both PSP and CBD 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 CBD.Individuals diagnosed with PD often exhibit similar movement dysfunction as those diagnosed with CBD, which adds complexity to its diagnosis. Some other neurodegenerative diseases including Alzheimer’s Disease (AD), dementia with Lewy bodies
Dementia with Lewy bodies
Dementia with Lewy bodies , also known under a variety of other names including Lewy body dementia, diffuse Lewy body disease, cortical Lewy body disease, and senile dementia of Lewy type, is a type of dementia closely allied to both Alzheimers and Parkinson's Diseases...
(DLB), and frontotemporal dementia
Frontotemporal dementia
Frontotemporal dementia is a clinical syndrome caused by degeneration of the frontal lobe of the brain and may extend back to the temporal lobe...
(FTD) also show commonalities with CBD.. FTDs have also been known to evolve into corticobasal syndrome.
Treatment
Because the exact cause of CBD is unknown, there exists no formal treatment for the disease. Instead, treatments focus on minimizing the appearance or effect of the symptoms resulting from CBD. The most easily treatable symptom of CBD is parkinsonism, and the most common form of treatment for this symptom is the application of dopaminergic drugs. However, only moderate improvement is seen and the relief from the symptom is generally not long-lasting. Additionally, 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.See also
- NeurodegenerationNeurodegenerationNeurodegeneration is the umbrella term for the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases including Parkinson’s, Alzheimer’s, and Huntington’s occur as a result of neurodegenerative processes. As research progresses, many...
- Basal GangliaBasal gangliaThe basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
- Alzheimer's diseaseAlzheimer's diseaseAlzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
- Dementia with Lewy bodiesDementia with Lewy bodiesDementia with Lewy bodies , also known under a variety of other names including Lewy body dementia, diffuse Lewy body disease, cortical Lewy body disease, and senile dementia of Lewy type, is a type of dementia closely allied to both Alzheimers and Parkinson's Diseases...
- Frontotemporal lobar degenerationFrontotemporal lobar degeneration-Further reading:*Hodges, John R. The Frontotemporal Dementia Syndromes. Cambridge University Press. 2007 ISBN 978-0-521-85477-1-External links:****Mayo Clinic - **...
- Progressive Supranuclear PalsyProgressive supranuclear palsyProgressive supranuclear palsy is a degenerative disease involving the gradual deterioration and death of specific areas of the brain....