Here’s another important paper on autopsy-confirmed cases of CBD (corticobasal degeneration) from Mayo researchers.
As we’ve learned many times of the last couple of years, those with autopsy-confirmed CBD can have many different clinical presentations including corticobasal syndrome (CBS), progressive non-fluent aphasia, behavioural variant frontotemporal dementia, and the Richardson syndrome form of PSP (progressive supranuclear palsy). “Due to the rarity of autopsy-confirmed corticobasal degeneration, the exact proportion of the various clinical presentations is unknown.”
In this study, 26 cases of autopsy-confirmed CBD are analyzed. Eleven presented with corticobasal syndrome (CBD-CBS), “characterized by asymmetric rigidity and apraxia, cortical sensory deficits, dystonia and myoclonus.” Fifteen presented by the Richardson syndrome type of PSP (CBD-RS), “characterized by postural instability, early unexplained falls, vertical supranuclear gaze palsy, symmetric motor disability and dysphagia.”
(Note that the Williams and colleagues criteria for Richardson syndrome is: “gradual onset of postural instability and falls within the first 2 years of disease, along with vertical supranuclear gaze palsy, a frontal dysexecutive syndrome, and rigidity and bradykinesia that is unresponsive to levodopa.”)
“The aim of this study was to identify differences in corticobasal degeneration presenting with corticobasal syndrome or Richardson syndrome with respect to demographic, clinical and neuropathological features.” The researchers found differences in the distribution of tau in the brain.
These 26 autopsy-confirmed CBD cases were compared with 15 autopsy-confirmed PSP/Richardson syndrome cases (PSP-RS). Clinically, the CBD cases “had more cognitive impairment and frontal behavioural dysfunction.” The behavioral problems seen “included disinhibition, social withdrawal, apathy, agitation and impatience.”
How do you tell while someone is alive that they have CBD or PSP, when they present with Richardson syndrome? The researchers say: “Atrophy of anterior corpus callosum may be a potential neuroimaging marker to differentiate corticobasal degeneration from progressive supranuclear palsy in patients with Richardson syndrome.” Cases with CBD-CBS and CBD-RS “had marked atrophy of the anterior corpus callosum compared with patients with PSP-RS.”
In their conclusion, the authors address future treatments: “If future disease-modifying therapies are discovered that target specifically 4R tau dysfunction, there would be little significance in differentiating CBD-RS from PSP-RS. On the other hand, if the factors that drive cellular and anatomical specificity in corticobasal degeneration differ meaningfully from progressive supranuclear palsy, making this distinction may eventually be of more than academic interest. To that end, additional research is needed to determine if corticobasal degeneration and progressive supranuclear palsy have the same pathogenesis.”
From the article, we learned that between 1999 and 2009, 108 autopsy-confirmed CBD cases had been donated to the Mayo Jax brain bank. Of those 108, 41 had features consistent with Richardson syndrome (CBD-RS), 21 had features consistent with corticobasal degeneration (CBD-CBS), and the others had different presentations. Perhaps some of you donated family members’ brains in that time frame! If there were complete medical records at Mayo Jax, those family members potentially are included in this study.
We also learned that the Mayo Jax brain bank had over 600 autopsy-confirmed PSP cases had been donated to the Mayo Jax brain bank. We aren’t told how many have the Richardson syndrome form of PSP but previous studies show that 60% of PSP cases are Richardson syndrome. At present, neuropathology reports from Mayo Jax do not indicate if the case had a Richardson syndrome clinical presentation. Fifteen of these PSP cases were included in the study. (My father’s brain could be part of the study!)
A total of 41 brains were included in this study. “34% were followed at the Mayo Clinic, while 66% were referral cases to the CurePSP/Society for PSP Brain Bank.”
Thanks to all those who have donated brain tissue to the Mayo Clinic or elsewhere for making research like this possible!
I’ve copied the abstract below.
Here’s the abstract:
Brain. 2011 Sep 20. [Epub ahead of print]
Neuropathological features of corticobasal degeneration presenting as corticobasal syndrome or Richardson syndrome.
Kouri N, Murray ME, Hassan A, Rademakers R, Uitti RJ, Boeve BF, Graff-Radford NR, Wszolek ZK, Litvan I, Josephs KA, Dickson DW.
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Patients with corticobasal degeneration can present with several different clinical syndromes, making ante-mortem diagnosis a challenge.
Corticobasal syndrome is the clinical phenotype originally described for corticobasal degeneration, characterized by asymmetric rigidity and apraxia, cortical sensory deficits, dystonia and myoclonus.
Some patients do not develop these features, but instead have clinical features consistent with the Richardson syndrome presentation of progressive supranuclear palsy, characterized by postural instability, early unexplained falls, vertical supranuclear gaze palsy, symmetric motor disability and dysphagia.
The aim of this study was to identify differences in corticobasal degeneration presenting with corticobasal syndrome (n = 11) or Richardson syndrome (n = 15) with respect to demographic, clinical and neuropathological features. Corticobasal degeneration cases were also compared with patients with pathologically proven progressive supranuclear palsy with Richardson syndrome (n = 15).
Cases with corticobasal degeneration, regardless of presentation, shared histopathological and tau biochemical characteristics, but they had differing densities of tau pathology in neuroanatomical regions that correlated with their clinical presentation. In particular, those with corticobasal syndrome had greater tau pathology in the primary motor and somatosensory cortices and putamen, while those with Richardson syndrome had greater tau pathology in limbic and hindbrain structures.
Compared with progressive supranuclear palsy, patients with corticobasal degeneration and Richardson syndrome had less neuronal loss in the subthalamic nucleus, but more severe neuronal loss in the medial substantia nigra and greater atrophy of the anterior corpus callosum. Clinically, they had more cognitive impairment and frontal behavioural dysfunction.
The results suggest that Richardson syndrome can be a clinicopathological presentation of corticobasal degeneration.
Atrophy of anterior corpus callosum may be a potential neuroimaging marker to differentiate corticobasal degeneration from progressive supranuclear palsy in patients with Richardson syndrome.
PubMed ID#: 21933807 (see pubmed.gov for this abstract only)