Timothy C. Hain, MD -- Northwestern University Medical School,
Most recent update: 7/2001
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Corticobasal ganglionic degeneration (which we will call CBD) is a rare progressive neurological disorder characterized by a combination of Parkinsonism and cortical dysfunction. It is a rare sporadic progressive disorder first reported in 1968. CBD appears to be closely related to another, less rare, sporadic extrapyramidal degenerative disorder named Progresive Supranuclear Palsy (PSP) . In CBD, cognitive symptoms dominate, while in PSP, eye movement symptoms dominate the picture.
The Parkinsonism is generally an asymetric akinetic rigid syndrome, unresponsive to levodopa, similar to that of multiple system atrophy and PSP. Eye movement abnormalities are common, as in PSP, and a supranuclear gaze palsy can be seen as in PSP. Given the genetic similarities between CBD and PSP, it seems possible that they are simply two "faces" of the same disease.
Neuroradiological imaging studies in CBD demonstrate cortical atrophy, which may be symmetrical or asymmetrical. Other cortical signs include
Proposed diagnostic criteria include at least three of the following:
The "alien limb" symptom is highly specific but it is not necessary for the diagnosis. Arm levitation resembling alien limb phenomena has been reported in PSP (Barclay et al, 1999), which certainly can also show focal limb dystonia and bradykinesia. Other aspects of this picture could easily be mistaken for other neurodegenerative disease such as Alzheimer's or Picks disease, and in fact, even experienced clinicians are correct 50% of the time or less when judged by pathological criteria. Onset in the sixth or seventh decade is typical. Disease progression is quicker than in Parkinsonism but similar to that of PSP. Recently language disturbance has been documented to be frequent (Frattali et al, 2000).
There is neuronal loss and gliosis and swollen achromatic neurons (ballooned neurons) are found in all cortical layers, but especially so in superior frontal and parietal gyri. There is extensive loss of myelinated axons in the white matter. Scattered neuronal inclusions may be seen similar to Pick bodies. Ballooned neurons are strongly reactive for phosphorylated neurofilaments and may include the tau protein (see below)(Dickson et al, 1986). Neuronal loss and gliosis are also observed in the nuclei of the basal ganglia. Lewy bodys and neurofibrillary tangles are absent. The substantia nigra shows neuronal loss with extraneuronal melanin, gliosis and neurofibrillary inclusions, called "corticobasal bodies".
CBD is difficult to diagnose in early stages, and experienced examiners typically diagnose it correctly less than 50% or the time (Litvan et al, 1997). CBD and may also be impossible to differentiate from PSP or a striato-niagral type of MSA. As more cortical signs develop in later stages, the disorders below may be possible to separate. As diagnostic sensitivity is poor, neuropathological confirmation remains the gold standard. Even here, one wonders if this disorder can be defined.
While CBD patients have normal saccadic velocity, this may be an artifact of case definition. If PSP and CBD share the same pathologic mechanism (see below), they may simply be two different presentations of the same disease.
The cause of CBD is presently unknown but because the tau protein accumulates in this disorder, it may be related to a mutation in the tau gene. (Higgins et al, 1999). Tau is a microtubule-binding protein that is normally abundant in neurons. Other "tauopathies" include Alzheimer's disease, Picks disease, frontotemporal dementia and parkinsonism, ALS-parkinson dementia complex of Guam, and progressive supranuclear palsy (PSP) (Higgins et al, 1999). According to Di Maria et al (2000) and Houlden et al (2001), CBD shares the same tau haplotype as do PSP patients (see above), suggesting that both CBD and PSP share the same genetic background, and possibly the same pathoogic mechanism.
CBD patients do not respond to levodopa treatment (the standard treatment for Parkinsonism). Management is based on appropriate use of appliances, prevention of medical complications, and appropriate use of nursing. Patients with CBD and caregivers should establish early on the plan regarding invasive care -- intubation, feeding tubes, as these issues are almost certain to come up in the course of the disease.