We are interested in CGBD because it is associated with slowing of eye movements.
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.
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.
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".
Corticobasal degeneration is a pathologic entity. Presenting clinical phenotypes include corticobasal syndrome (CBS), frontal behavioral spatial syndrome, aphasia, progressive supranuclear palsy-like syndrome (PSPS), and a predominantly cognitive phenotype often mistaken for Alzheimer’s disease (AD). Treatment of CBD is symptomatic, particularly given recently negative neuroprotective studies. Given the relentless progression in CBD, all interested patients should be offered the opportunity to enroll in clinical neuroprotective trials as they arise. For symptomatic therapy, treatment options are necessarily based on evidence from other disorders given the lack of studies in CBD. In patients with CBS and PSPS, parkinsonism is treated with levodopa/carbidopa. This generally has modest and transient benefits at best and often results in no improvement. Botulinum toxin injections are the treatment of choice for limb dystonia. Clonazepam and levetiracetam are commonly used for myoclonus. Physical therapy is an important part of motor treatment, particularly for fall prevention strategies and assist device assessment. Whether medications such as cholinesterase inhibitors or memantine have any role in CBD is unclear given the various responses described in related phenotypes and diseases. Treating the behavioral symptoms associated with CBD is critical in an attempt to treat symptoms for which we have good pharmacologic interventions and to hopefully improve quality of life. General supportive care is important, including assessing for sores related to dystonia or immobility, monitoring dysphagia, and identifying needs for support services. Finally, as with other relentlessly progressive neurodegenerative diseases, it is critical to provide family and caregiver support and to assess for when palliative care services will serve the patient best.