The Movement Disorders Society's 13th International Congress of Parkinson's Disease and Movement Disorders, Paris 2009
Summary of the presentation on 'Diagnostic Accuracy in 18 cases of Pathologically confirmed corticobasal degeneration' for the Clinical Research Award
H. Ling, S. O'Sullivan, D. Paviour, L. Massey, J. Holton, T. Revesz and A. Lees.
(London, United Kingdom)
Presenting Author: Dr Helen Ling
Summary of Presentation:
Corticobasal degeneration (CBD) is a rare neurodegenerative disorder. Its most well known clinical presentation is the classical corticobasal syndrome (CBS). One of the most common presenting features of CBS is clumsiness or inability to use one hand due to apraxia, alien limb, dystonia, action or stimulus-sensitive myoclonus or L-dopa resistant akinetic rigidity. Clinical presentation of CBS is markedly asymmetrical. To date, there is no biomarker for the diagnosis of CBD. The gold standard for the diagnosis of CBD relies on autopsy finding of pathological hallmarks and identification of their typical distribution. CBD is a 4-repeat tauopathy characterized by tau aggregates in neurons and glial cells in both the grey and white matter of the frontal, parietal cortex and substantia nigra. Other pathological features include pre-tangles, threads, astrocytic plaques and coiled bodies. The morphology of some of these pathological hallmarks such as astrocytic plaques and their distribution are distinctive for CBD and are used by neuropathologists to distinguish CBD from other closely related pathological disorders such as Progressive supranuclear palsy (PSP).
Autopsy studies of cases with clinical CBS presentation showed that only a proportion of them had CBD pathology. The remaining cases were associated with other pathological features included PSP, Dementia with Lewy Bodies, Pick's disease, argyrophilic grain disease, Alzheimer's disease (AD), Creutzfeldt-Jacob disease, frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), neurofilament inclusion body disease and etc. On the other hand, pathologically confirmed CBD cases can present as various clinical phenotypes such as PSP, FTD and progressive aphasia. This bidirectional heterogeneity makes it difficult for clinicians to accurately predict CBD based on clinical features. The aim of our research was to assess the diagnostic accuracy of CBD in hospital practice.
From the Queen Square Brain Bank (QSBB) Database between 1990 and 2008, we selected cases with either a clinical diagnosis of CBD in life or a pathological diagnosis of CBD. The pathological features of these cases were reviewed and their diagnoses were confirmed by two experienced neuropathologists. The clinical features of these cases were thoroughly studied from the medical records by two neurologists.
Of the 1225 brains studied in the QSBB between 1990 and 2008, 18 cases were pathologically diagnosed as CBD, only 5 of which had been diagnosed as CBD in life (sensitivity = 25%). The other 13 CBD cases had other clinical diagnoses including PSP (7), PD (2), FTD (1), progressive non-fluent aphasia (1), cortical myoclonic syndrome (1) and incidental finding (1).
Interestingly, the majority of CBD cases had been diagnosed clinically as PSP (39%). When compared with those who had been diagnosed CBD in life, the age of symptom onset and age of death were younger in cases with clinical diagnosis of PSP. These patients were found to have the typical clinical features of classical PSP, also known as the Richardson syndrome (RS). They had early onset of falls in the first year, the majority of which were backward falls. All patients had supranuclear gaze palsy but the most of them had initial impairment of upward (5) rather than downward gaze as would have been expected in RS. 6 out of 7 cases had symmetrical clinical presentation. These findings explain why clinicians made the diagnosis of PSP in life. Among the 5 CBD cases that were correctly diagnosed in life, they all presented with the typical clinical picture of the classical CBS. This suggests that the clinicians can readily identify CBS as the typical presentation of CBD. 3 of these patients were found to have delayed latency of saccade, which is known as a typical ocular finding in CBD. Only 2 out of 7 cases with clinical diagnosis of PSP had this ocular finding and this feature always coexisted with the finding of supranuclear gaze palsy.
Of 19 cases diagnosed with CBD in life, only 5 had pathologically confirmed CBD. The other 14 cases had heterogeneous pathological diagnoses including PSP (6), AD (3), FTLD-TDP (1), FTLD-TDP with Motor neuron disease (1), PD (1) and Dementia lacking distinct histology (1). Six out of 179 pathologically proven PSP in the QSBB had been diagnosed as CBD in life. Of these 6 cases, 4 had typical CBS presentation and the other 2 had clinical features of CBS such as markedly asymmetrical presentation, fixed hand dystonia and predominant gait apraxia.
Our results indicate that the clinical diagnosis of CBD is not useful in predicting underlying CBD pathology and pathologically confirmed CBD cases can present as several distinct clinical syndromes besides the classical CBS. The sensitivity of diagnosing CBD clinically is low (28%) when compared to other atypical parkinsonian disorders. The sensitivities of diagnosing PSP and MSA were 73% (131 out of 179) and 70% (82 out of 117).
We conclude that the diagnostic accuracy of CBD presenting to hospital practice is much lower than for PSP and MSA. The main diagnostic challenge is related to the overlapping features between CBD and PSP.
- Mahapatra RK, Edwards MJ, Schott JM, Bhatia KP. Corticobasal degeneration. The Lancet Neurology 2004;3:736-43.
- Dickson DW, Bergeron C, Chin SS, Duyckaerts C, Horoupian D, Ikeda K, et al. Office of rare diseases neuropathologic criteria for corticobasal degeneration. J Neuropathol Exp Neurol 2002;61:935-46.
- Lang AE. Corticobasal degeneration: selected developments. Mov Disord 2003:18:S51-S56.
- Josephs KA, Petersen RC, Knopman DS, Boeve BF, Whitwell JL, Duffy JR, Parisi JE, Dickson DW. Clinicopathologic analysis of frontotemporal and corticobasal degenerations and PSP. Neurology 2006;66:41-48.
- Scaravilli T, Tolosa E, Ferrer I. Progressive supranuclear palsy and corticobasal degeneration: lumping versus splitting. Mov Disord 2005;S12:S21-S28.