Timothy C. Hain, MD Most recent update: December 16, 2017
Corticobasal ganglionic degeneration, also known as Corticobasal degeneration or corticobasal syndrome (CBS). We will call it CBGD. CBGD 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. CBGD appears to be VERY closely related to another, less rare, sporadic neurodegenerative disorder named Progresive Supranuclear Palsy (PSP) . In CBGD, cognitive symptoms dominate, while in PSP, eye movement symptoms dominate the picture. However they often share the same genetics, so they are probably just the same disease, seen through the eyes of different neurology subspecialties.
The parkinsonism of CBGD 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 CBGD and PSP, it seems probable that they are simply two "faces" of the same disease, perhaps mixed in with other obscure neurological conditions that can by chance, cause a similar constellation of findings. The internet has enabled easier case finding.
Neuroradiological imaging studies in CBGD 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 only 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).
The author of this page encountered a patient with "alien limb", with a rapidly progressive ataxia. She went from being ambulatory to wheelchair bound in just 3 weeks. The diagnosis on autopsy was not CBGD, but rather prion disease (e.g. Creutzfeldt-Jacob). The rapid progression here, in retrospect, meant that this patient did not have CBGD, as these types of disorders do not move this rapidly.
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".
CGBD is presumably similar to PSP in its oculomotor behavior, as the same genetic makeup can result in both disorders (Tuite et al, 2009), but very little has been published. Given the rarity of this disorder as well as the fuzziness of the diagnosis, solid conclusions would seem to us to be premature. Garbutt et al (2008) suggested that only PSP patients showed slowing of saccades, while abnormalities in saccadic gain was found in CBGD and PSP both. Pierrot-Deseilligny and Rivaud-Pechoux (2003) suggested that there were "infraclinical oculomotor anomalies" (whatever that means), and particularly long latency saccades.
We have encountered several CBGD phenotype patients in our practice (not confirmed by autopsy of course), and obtained a full rotatory chair test on one. The patient presented below had a classic presentation with aphasia, alien hand, ataxia, and falls, but has the same oculomotor findings as PSP.
Square wave jerks. This patient had no ability to converge.
Slow saccades (especially upgoing, but also horizontally)
And perhaps the most characteristic of PSP type patients, there was a disorder of fast phases where the eye "hung up" in the orbit. On rotatory chair testing, this is seen by a discrepency between step responses and sinusoidal testing, as the eye gets "hung up" on the "DC" type step responses, but does better on the high frequency rotatory chair. Fast phases are a type of automatic rapid (saccadic) eye movement.
Video of poor vertical suppression in patient with CGBD (7 meg, wmv file)
This "hang up" behavior, meaning poor quick phases, can be seen at the bedside, but as in PSP, it is far worse for vertical. The movie above shows cancellation at the bedside -- a light is turned on within the Micromedical video goggles, and the patient was asked to watch the light. The head was then rotated vertically first, and then horizontally. It is very obvious that there are no fast phases for vertical, but reasonably good fast phases for horizontal. This is the typical situation for PSP patients as well. At the bedside, one can usually see this even without goggles. We find it easiest to use a "queen square" reflex hammer, with the "pessary" end on the forehead, and have the patient watch the top. This provides a target that moves with the head. We think that this observation could be made into a diagnostic test for PSP and CGBD, as it is quite easy, and also very sensitive. The disparity between horizontal and vertical is the key.
In the individual trace below, one can see the "hang up" problem. This is horizontal rather than vertical.
There is still gain at the "turnaround point, but then the eye goes "flat line" as it runs into the orbit. Similar "hang ups" can be seen in other supranuclear eye movement disorders, including SCA7.
At the bedside, this can be seen by having the patient attempt to suppress their VOR, elicited by sinusoidal movement of the head at about 1 hz, while looking at a fixation target within the goggle. Horizontally there are fast phases. Vertically, the eye goes up and down with the goggles.
In our opinion, the oculomotor findings of CGBD are identical to those of PSP.
CBGD is difficult to diagnose in early stages, and experienced examiners typically diagnose it correctly less than 50% or the time (Litvan et al, 1997). CBGD 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 with enough precision to be useful.
- PSP (progressive supranuclear palsy, related by tau)
- MSA (multiple system atrophy)
- Picks disease
While CBGD patients have normal saccadic velocity, this may be an artifact of case definition. If PSP and CBGD share the same pathologic mechanism (see above and below), they may simply be two different presentations of the same disease.
As noted above, the alien hand is not specific, and the author of this page encountered a patient with CJD that mimicked CBGD.
The cause of CBGD 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) and Tuite et al (2005), CBGD shares the same tau haplotype as do PSP patients (see above), suggesting that both CBGD and PSP share the same genetic background, and possibly the same pathoogic mechanism. According to Cho et al (2017), "patients with CBS exhibited asymmetrically increased (18)F-AV-1451 binding in the putamen, globus pallidus, and thalamus contralateral to the clinically more affected side and in the ipsilateral globus pallidus and dentate nucleus." This suggests that there is more tau in those areas.
CBGD 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 CBGD 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. Not every patient wants to die on a ventilator. It is best to make it clear early on what the wishes are of the person with CBGD with respect to various types of invasive treatment, and make sure that they are carried out, in spite of the usual mission of our medical system to sustain life at any cost.