Corticobasal syndrome (ORPHA:454887)
A rare neurologic disease characterized by multifaceted motor system dysfunctions and cognitive defects such as asymmetric rigidity, bradykinesia, limb apraxia, and visuospatial dysfunction.
Epidemiology
The prevalence of Corticobasal syndrome (CBS) is unknown.
Clinical description
The disease shows a wide clinical variability between patients with many developing a relatively pure motor syndrome, and others displaying a combination of motor and cognitive deficits. Disease onset is insidious and usually occurs in the 6th to 7th decade of life with symptoms typically being unilateral at first, and the arm being more commonly affected than the leg. It may begin primarily as a movement disorder with rigidity, bradykinesia and tremor, in association with frontal signs, cortical sensory loss, alien limb phenomenon, stimulus induced myoclonus and progressive limb apraxia, which may become bilateral, though usually asymmetrical, as the disease progresses. Gait disturbance and postural instability are common, whereas dystonia and aphasia (speech apraxia, dysfluency and agraphia) are less commonly reported. Additionally, eye movement abnormalities and behavioral manifestations can also be present. Many patients have dementia in later stages of the disease.
Etiology
Around 25% of CBS cases are shown to be due to corticobasal degeneration syndrome (CBD). CBD is a distinct tauopathy with selective aggregation of 4 repeat tau proteins with characteristic antigenic and ultrastructural characteristics. The cause is unknown and there is usually no evidence of inheritance (there has been a suggestion of genetic propensity, but this is currently poorly understood). Other causes of CBS include progressive supranuclear palsy (PSP), frontotemporal lobar degeneration (FTLD) due to tau or TAR DNA-binding protein 43 (TDP-43), and Alzheimer disease (AD).
Diagnostic methods
The diagnosis of CBS is a clinical one, based on the recognition of characteristic clinical features. Several diagnostic criteria have been proposed, but none have gained universal acceptance. The pathological diagnosis of CBD is only possible at autopsy and is defined by nerve cell loss, gliosis and atrophy of cortical and subcortical structures such as the posterior frontal and/or parietal lobes and the substantia nigra, as well as widespread deposition of hyperphosphorylated 4-repeat tau in neurons and glia. Furthermore, many cases may have co-pathologies which must be taken into consideration.
Differential diagnosis
The main differential diagnoses include progressive non-fluent aphasia and, to a lesser extent, behavioral variant of frontotemporal dementia, progressive supranuclear palsy, multiple system atrophy, posterior cortical atrophy, AD (the typical/amnestic form) and idiopathic Parkinson's disease.
Genetic counseling
Familial CBS is extremely rare. Genetic counselling can only be offered in these exceptional cases.
Management and treatment
Treatment is symptomatic and focuses on improving function as well as palliative care. Dystonia may be treated with botulinum toxin. Brief response to levodopa may occur, but sustained response to treatment should prompt a reconsideration of the diagnosis. Physical therapy and surgery are not found to offer any symptom relief. Speech therapy can be offered to those with prominent aphasia.
Prognosis
Quality of life is decreased in CBS patients as they gradually lose their ability to function independently. The prognosis is poor with the mean disease duration being 5.4-7.9 years after onset.

                            Last update: 
                            March 2020


                            - Expert reviewer(s): 
                            Pr James BURRELL