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cbgd treatment

A report offering encouragement, advice, and support to those caring for a loved one with corticobasal degeneration, entitled the CBGD Caregivers Report, is available free of charge to all who would find it helpful. It can be downloaded at www.tornadodesign.com/cbgd.

Webb A, Miller B, Bonasera S, et al. Role of the tau gene region chromosome inversion in progressive supranuclear palsy, corticobasal degeneration, and related disorders. Arch Neurol. 2008;65:1473-1478. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680206/

Contact for additional information about corticobasal degeneration:

Diagnosis

Clinical Testing and Work-Up

Progressive supranuclear palsy (PSP) is a rare degenerative neurological disorder characterized by loss of balance and impaired walking; loss of control of voluntary eye movement, especially in the downward direction; abnormal muscle tone (rigidity); speech difficulties (dysarthria); and problems related to swallowing and eating (dysphagia). Affected individuals frequently experience personality changes and cognitive impairment. Forgetfulness and memory loss are common. Symptoms typically begin in the 60s, but can start as early as the 40s. The symptoms progressively worsen over time. The exact cause of PSP is unknown. PSP is often misdiagnosed as Parkinson’s disease, Alzheimer’s disease, or other neurodegenerative disorders. (For more information on this disorder, choose “progressive supranuclear palsy” as your search term in the Rare Disease Database.)

Dickson DW, Bergeron C, Chin SS, et al. Office of Rare Diseases neuropathologic criteria for corticobasal degeneration. J Neuropathol Exp Neurol. 2002;61:935-946. http://www.ncbi.nlm.nih.gov/pubmed/12430710

Affected individuals may be treated with certain drugs such as levodopa and similar medications that are normally used to treat Parkinson's disease. These drugs are generally ineffective, but may help with the slowness or stiffness some individuals experience. Myoclonus may be controlled with medications such as clonazepam, however, benzodiazepines should be used sparingly as they may have undesired side effects in these patients. Botulinum toxin (Botox®) has been used to treat contractures and pain, but do not restore the ability to control movements. Baclofen is another drug that may be used to treat muscle rigidity.

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.

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 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".

We are interested in CGBD because it is associated with slowing of eye movements.

Other types of testing in CGBD.

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. Other patients that the author of this page has seen carrying the diagnosis of CGBD have not had autopsies, and thus their diagnoses remain unestablished.

Slow saccades (especially upgoing, but also horizontally)

Differential Diagnosis:

Other areas than oculomotor testing include cognitive testing. CGBD patients may have problems with executive function, aphasia, apraxia, behavioral change, and visual spatial dysfunction, with relatively preserved episodic memory. MRI and CT scans may be initially normal, but eventually asymmetrical cortical atrophy is seen in about half of the patients, with more atrophy in the frontoparietal area.