The pathological findings of corticobasal degeneration are associated with several distinct clinical syndromes, and the corticobasal syndrome has been linked with a number of diverse pathologies. We have reviewed all the archival cases in the Queen Square Brain Bank for Neurological Disorders over a 20-year period with either a clinical diagnosis of corticobasal syndrome or pathological diagnosis of corticobasal degeneration in an attempt to identify the main diagnostic pitfalls. Of 19 pathologically confirmed corticobasal degeneration cases, only five had been diagnosed correctly in life (sensitivity=26.3%) and four of these had received an alternative earlier diagnosis. All five of these had a unilateral presentation, clumsy useless limb, limb apraxia and myoclonus, four had cortical sensory impairment and focal limb dystonia and three had an alien limb. Eight cases of corticobasal degeneration had been clinically diagnosed as progressive supranuclear palsy, all of whom had vertical supranuclear palsy and seven had falls within the first 2 years. On the other hand, of 21 cases with a clinical diagnosis of corticobasal syndrome, only five had corticobasal degeneration pathology, giving a positive predictive value of 23.8%; six others had progressive supranuclear palsy pathology, five had Alzheimer's disease and the remaining five had other non-tau pathologies. Corticobasal degeneration can present very commonly with a clinical picture closely resembling classical progressive supranuclear palsy or Richardson's syndrome, and we propose the term corticobasal degeneration-Richardson's syndrome for this subgroup. Cases of corticobasal degeneration-Richardson's syndrome have delayed onset of vertical supranuclear gaze palsy (>3 years after onset of first symptom) and the infrequent occurrence of predominant downgaze abnormalities, both of which can be helpful pointers to their underlying corticobasal degeneration pathology. Fourty-two per cent of corticobasal degeneration cases presented clinically with a progressive supranuclear palsy phenotype and 29% of cases with corticobasal syndrome had underlying progressive supranuclear palsy pathology. In contrast, in the Queen Square Brain Bank archival collection, corticobasal syndrome is a rare clinical presentation of progressive supranuclear palsy occurring in only 6 of the 179 pathologically diagnosed progressive supranuclear palsy cases (3%). Despite these diagnostic difficulties we conclude that corticobasal degeneration is a discrete clinicopathological entity but with a broader clinical spectrum than was originally proposed.

/pdf/does-corticobasal-degeneration-exist-a-clinicopathological-1am5hzq311.pdf

序 (特集 Corticobasal Syndrome)

Does corticobasal degeneration exist? A clinicopathological re-evaluation

Objectives Cardinal extrapyramidal features of progressive supranuclear palsy (PSP) help in clinically differentiating this condition from Parkinson9s disease and other Parkinsonian syndromes. However, not all extrapyramidal features may be initially present, thus posing a difficulty in early diagnosis. We studied their frequency at the time of first presentation. Methods Patients diagnosed clinically with PSP using the National Institute for Neurological Disorders and Society for PSP (NINDS/SPSP) criteria and seen between August 2010 and April 2013 were examined for the presence, ‘presence with deviation’ or absence of six extrapyramidal features: axial rigidity, symmetry, extended posture, backward falls, absence of tremors and lack of levodopa response. Results Twenty-eight patients (mean (SD) age 64.86 (9.72) years; 16 (57%) men) met the inclusion criteria. Of these, 14% had all six extrapyramidal features associated with PSP, 39% had five, 29% had four, 14% had three and 4% had two. The most frequent extrapyramidal sign was axial rigidity (68%). Axial plus peripheral rigidity was found in 18% of patients and peripheral rigidity alone in 14%. Extrapyramidal features were symmetrical in 29% and asymmetrical beyond 1 year in 29%. Body posture was extended in 46% and flexed in 21%. Backward falls were found in 50% and forward falls in 11%. Pill-rolling tremors were observed in 29%. Response to levodopa therapy was poor in 21% and good beyond 6 months in 39%. Conclusions Only 14% of PSP patients present with all six cardinal extrapyramidal features. Also, deviations from standard descriptions are common in the initial stages of disease.

https://pmj.bmj.com/content/postgradmedj/91/1075/274.full.pdf

Progressive supra-nuclear palsy: frequency of cardinal extrapyramidal features at first presentation

Background:  Alien limb phenomenon occurs in 50–60% of patients with corticobasal syndrome (CBS) and usually presents with an “alien hand” phenomenon. The “alien foot” presentation is rarer and may be misdiagnosed, as foot involvement can lead to erroneous localization of the clinical problem to the knee, hip, or back. Subsequently misdiagnoses such as myelopathy, radiculopathy, functional disorder, stiff leg syndrome, neuromyotonia, and painful leg moving toes syndrome may occur. Case report:  We describe two patients with alien foot symptoms that resulted in multiple opinions from different specialists, multiple diagnostic and therapeutic procedures, and delayed diagnosis. Eventually a diagnosis of CBS was made in both. Alien foot symptoms may be more common than initially thought and can result in a delayed diagnosis of CBS. Conclusion:  The inclusion of this clinical finding in recently proposed diagnostic criteria highlights the need for increased clinical awareness.

/pdf/a-wolf-in-sheep-s-clothing-an-alien-leg-in-corticobasal-4dyvpqr88x.pdf

A Wolf in Sheep's Clothing: An "Alien Leg" in Corticobasal Syndrome.

Human movement is a ubiquitous behaviour that is performed to achieve goals by affecting changes in the outside world. The creation of the manmade environment has depended on our ability to plan, execute and monitor movements. This thesis will investigate the subjective experience and underlying brain processes that accompany voluntary and outcome-directed actions. Experiments in this work will make use of an established paradigm to quantify and compare participants’ perceptions of their own actions. Specifically, through the use of a rotating clock, participants report when they perceived action-relevant events to occur, such as the intention to act, the action itself, or the outcome produced by the action. The experience of producing an action, even in the absence of a desired outcome, varies among populations. This thesis will compare the experience of volition in patients with Parkinson’s disease and in healthy controls. It will be seen that manipulation of dopamine availability, either through medication or deep brain stimulation, influences the subjective experience of making an action. Using EEG, it will be seen that differences in the experience of volition are associated with the time-course of activation in brain areas typically related to movement initiation. The sense of agency, a feeling of control of over one’s own actions and their outcomes, will also be investigated by combining the paradigm described above with an established decision-making task. Results from a series of experiments will reveal a sequential effect in which an implicit measure of the sense of agency (intentional binding) is stronger following actions that produce negative outcomes. Finally, this novel effect, which appears to be related to learning processes, will be subjected to meta-analysis. The results obtained in this work will inform further research into volition, motor-control and movement-related pathology.

Quantifying the subjective experience of initiating and monitoring actions, in health and disease

This thesis focuses on sporadic parkinsonian syndromes that are associated with neurofibrillary degeneration and the accumulation of abnormal tau protein in the brain. The classic clinical presentation of corticobasal degeneration is a specific constellation of cortical and extrapyramidal signs, collectively termed corticobasal syndrome. The evaluation of all the archival cases with corticobasal degeneration in the Queen Square Brain Bank for Neurological Disorders reveals the high frequency of other phenotypic presentations. The result indicates that corticobasal degeneration commonly presents with a clinical picture, closely resembling progressive supranuclear palsy (PSP) or Richardson’s syndrome. On the other hand, cases with typical PSP pathology may occasionally present with a corticobasal syndrome. A quantitative assessment of the severity of tau pathology in different brain regions of the two phenotypic presentations of PSP reveals topographical differences that are closely linked with their respective clinical features. The features of repetitive finger tapping and handwriting in patients with PSP and Parkinson’s disease are compared and a distinct abnormality is identified in PSP which may be useful in differentiating PSP-parkinsonism from Parkinson’s disease. Twelve cases clinically presenting with a levodopa-responsive parkinsonian syndrome and post-mortem findings of nigral degeneration and predominant tau inclusions, which could not be readily classified into any recognised clinicopathological entity are also studied.

序 (特集 Corticobasal Syndrome)

Citations

Does corticobasal degeneration exist? A clinicopathological re-evaluation

Progressive supra-nuclear palsy: frequency of cardinal extrapyramidal features at first presentation

A Wolf in Sheep's Clothing: An "Alien Leg" in Corticobasal Syndrome.

Quantifying the subjective experience of initiating and monitoring actions, in health and disease

Unravelling the tangled web of atypical parkinsonism