corticobasal degeneration corticobasal degeneration corticobasal degeneration (cbd) is a rare neurodegenerative disease involving the cerebral cortex and the basal ganglia. cbd 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 cognition, and is classified as one of the parkinson plus syndromes. diagnosis is difficult, as symptoms are often similar to those of other disorders, such as parkinson's disease, progressive supranuclear palsy, and dementia with lewy bodies, and a definitive diagnosis of cbd can only be made upon neuropathologic examination. corticobasal degenerationbasal ganglia along with cerebral cortex are involved in this conditionspecialtyneurology signs and symptoms because cbd is progressive, a standard set of 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. although corticobasal degeneration has a plethora of symptoms, some are more prevalent than others. in a study of 147 patients with cbd, it was found that all of them had at least one parkinsonian sign, 95% having two and 93% had some higher order dysfunction (cognitive impairments like acalculia, sensory loss, dementia, neglect, etc.). in a separate study of 14 patients recorded 3 years after the onset of symptoms, many patients had high numbers of motor symptoms. 71% had bradykinesia (slow movements), 64% showed apraxia, 43% reported limb dystonia, and although more cognitive 36% had dementia. in another study of 36, over half had a useless/alien arm and 27% had a gait impediment. from this, we can see why cbd is hard to diagnose. even if it can be distinguished as different from one of the other similar diseases, the varying combinations of symptoms create a difficult path to diagnosis. 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 appears asymmetrically and the symptoms are 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 other hand. predominant movement disorders and cortical dysfunctions associated with cbd include: parkinsonism alien hand syndrome apraxia (ideomotor apraxia and limb-kinetic apraxia) aphasia 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 parkinson's disease (pd) and progressive supranuclear palsy (psp). parkinsonism in cbd is largely present in an extremity such as the arm, and is always asymmetric. it has been suggested that non-dominant arm is involved more often. 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 their 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 may be related to speech impairment such as dysarthria, and thus is not a true aphasia, as aphasia is related to a change in language function, such as difficulty retrieving words or putting words together to form meaningful sentences. the speech and/or language impairments in cbd result 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). frontotemporal dementia can be an early feature. 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 tauopathy). 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 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 protein (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. as a consequence, 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. in recent years corticobasal degeneration has come to be understood as a tauopathy. this is believed due to the most common indicator of cbd being a faulty tau protein. tau proteins are integral in keeping microtubules stable; defective cells create four microtubule-binding repeats with increased affinity in binding with microtubules. because of this increased affinity, they form insoluble fibers (also called "paired helical filaments"). microtubules themselves keep the cell and cytoskeletal structure stable. thus, when tau proteins create unnatural configurations, microtubules become unstable, which eventually leads to cell death. diagnosis new diagnostic criteria known as the armstrong criteria were proposed in 2013, although the accuracy of these is limited and further research is needed. recent findings in clinicopathology have made it possible to distinguish cbd from parkinson's and increase the accuracy of diagnosis, using developments in mri and nuclear medicine. criteria insidious onset and gradual progression lasts 1 year or more meets one of the four subtypes: possible cbs fbs or nav psps plus at least one cbs feature other than limb rigidity or akinesia no exclusion criteria present more likely if onset is after age 50 more likely if no family history (2 or more relatives) more likely if no genetic mutation affecting t (e.g., mapt) possible corticobasal syndrome subtype symptoms may be symmetric or asymmetric. one or more of: limb rigidity or akinesia limb dystonia limb myoclonus, plus one of: orobuccal or limb apraxia cortical sensory deficit alien limb phenomena (more than simple levitation) more likely (probable sporadic cbs) if: asymmetric presentation onset after age 50 no family history (2 or more relatives) no genetic mutation affecting t (e.g. mapt) plus two of: limb rigidity or akinesia limb dystonia limb myoclonus plus two of: orobuccal or limb apraxia, cortical sensory deficit alien limb phenomena (more than simple levitation) frontal behavioural-spatial syndrome subtype two of: executive dysfunction behavioural or personality changes visuospatial deficits nav of primary progressive aphasia subtype effortful, agrammatic speech plus at least one of: impaired grammar/sentence comprehension with relatively preserved single word comprehension or groping, distorted speech production (apraxia of speech) progressive supranuclear palsy syndrome subtype three of: axial or symmetric limb rigidity or akinesia postural instability or falls urinary incontinence behavioural changes supranuclear vertical gaze palsy or decreased vertical saccade velocity exclusion criteria these apply to all types of cbd. evidence of lewy body disease multiple system atrophy alzheimer's disease als semantic or logopenic variant primary progressive aphasia structural lesion suggestive of focal cause granulin mutation or reduced plasma progranulin levels tdp-43 or fused in sarcoma (fus) mutations the diagnostic criteria for clinical use may result in a misdiagnosis of other tau-based diseases. the probable criteria are proposed for clinical research. 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 ring-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 (dlb), chronic traumatic encephalopathy (cte) and frontotemporal dementia (ftd) also show commonalities with cbd. neuroimaging the types of imaging techniques that are most prominently utilized when studying and/or diagnosing cbd 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