Corticobasal syndrome: overcoming the artificial divide between disorders of cognition and movement
- Memory and Aging Center, Department of Neurology, University of California, San Francisco, California, USA
- Correspondence to Dr G Rabinovici, UCSF Memory and Aging Center, 350 Parnassus Ave, Ste 905, San Francisco, California, USA;
Contributors Both authors participated equally in drafting the paper.
- Received 4 November 2011
- Accepted 15 November 2011
- Published Online First 14 December 2011
Nearly 45 years after the publication of Rebeiz's initial series,1 clinical definitions of corticobasal syndrome (CBS) remain controversial, and universally accepted criteria are lacking. One source of disagreement, evident since the earliest case reports,1 2 is a divide between criteria that emphasise the movement disorder and those that give equal weight to cognitive symptoms. This division is highlighted in the paper by Mathew et al,3 who applied three sets of published criteria to 40 consecutive CBS patients seen in a combined movement disorders–cognitive clinic. The criteria differed primarily in the approach to early cognitive dysfunction, which was considered an exclusion in one set of criteria,4 primarily a supportive feature in the second5 and was weighted equally with the movement disorder in the third.6 Agreement between criteria in classifying patients was poor to modest (weighted κ of 0.125–0.219 in pairwise comparisons), illustrating the disparity in defining CBS even among experts. While 75% of patients fulfilled all three sets of criteria by their final clinic visit, 27.5% did not meet any of the criteria at their first visit, highlighting the challenge of diagnosing CBS at its early stages. Furthermore, primary motor features were found in only 67.5% of patients at the first evaluation, while cognitive features were seen in 100%, with speech and language disorders and frontal dysfunction being most common. These findings underscore that frontal deficits and aphasia are very common in early stages of CBS and should be featured prominently in future criteria.
Corticobasal degeneration (CBD) was found post mortem in only six of 16 patients in the study who underwent autopsy, with other patients found to have Alzheimer's disease (n=8), frontotemporal dementia with tau-negative ubiquitin-positive inclusions (n=1) and necrotising leukoencephalopathy (n=1). Similar heterogeneity has been reported in recent clinicopathological series from both cognitive and movement focused groups, with CBD found in fewer than 50% of patients presenting with CBS during life.7–9 Conversely, pathological CBD is associated with a number of clinical presentations, including CBS (or a similar executive–motor syndrome), progressive supranuclear palsy syndrome, behavioural variant frontotemporal dementia and non-fluent variant primary progressive aphasia.7 8 10 Despite the limited success in predicting CBD pathology to date, refining clinical criteria for CBS remains an important goal for the field. Regardless of underlying pathology, CBS is associated with neurodegeneration in a dorsal frontoparietal sensorimotor network.7 9 11 Better defining the clinical syndrome associated with degeneration of this network will help guide clinical care, identify genetic and environmental factors that underlie regional vulnerability in the ‘CBS network’ and ultimately aid in developing clinical scales and biological markers that are sensitive to disease progression and could be used to gauge treatment effects.
The study by Mathew et al moves the field forward by proposing criteria that place the three major clinical features of the disease (cognitive, primary motor and cortical sensorimotor) on equal ground. The next challenge is to refine criteria further to predict the underlying pathology in patients presenting with CBS. For example, the modified Cambridge criteria proposed by Matthew et al include some features (eg, myoclonus, visuospatial dysfunction) that may be predictive of Alzheimer's disease, and others (eg, non-fluent aphasia, primary executive dysfunction) that may suggest CBD.7 12 An encouraging exemplar is provided by another focal syndrome, primary progressive aphasia, where careful phenotyping helped identify distinct clinical subtypes that are each associated with a particular molecular pathology.13 The challenge may prove even more formidable in CBS/CBD given the remarkable clinical and pathological heterogeneity that has come to light in recent years. Nonetheless, success is critical to the efforts to develop disease specific therapies, and will require close collaboration across neurological disciplines in order to overcome the artificial divide between disorders of cognition and movement.
Linked article 300875.
Competing interests None.
Provenance and peer review Commissioned; not externally peer reviewed.