Cortical Basal Ganglionic Degeneration

This post is provided courtesy of K. T. Weber, Drexel University College of Medicine Class of 2013:

Cortical Basal Ganglionic Degeneration (CBGD) is a rare neurodegenerative disorder that affects both the cerebral cortex and basal ganglia, resulting in a rapidly progressive and devastating combination of movement disorder and dementia.

CBGD shares features with other, more common, neurologic illnesses: Like Parkinson’s disease, it often presents asymmetrically, with a tremor, rigidity or dystonia. Like Alzheimer’s disease, there are subtle early cognitive and behavioral changes. However, CBGD progresses more rapidly than these other conditions, ultimately involving the other limbs and causing more cognitive dysfunction. Furthermore the Parkinsonian features of CBGD tend not to respond to dopaminergic medications.

Patient with CBGD, showing rigidity, paucity of movement, and myoclonic jerks in the left arm

One of the distinctive features of CBGD is alien limb phenomenon. Alien limb is characterized by a “loss of agency” in the affected limb. The patient is able to feel sensation in the limb, and movement is preserved, but the patient no longer recognizes the limb as his or her own. This same aLien limb or (more commonly an alien hand) syndrome can also result from separation or dysregulation between the brain’s hemispheres, for example after surgical division of the corpus callosum for severe epilepsy.

Patient with CBGD, showing rigidity, dystonic posturing and Alien limb phenomenon (the patient said the left arm was “moving on it’s own”)

In popular media, Dr. Strangelove struggled with an alien limb that was no longer under his control.

However, the movement disorder is only half the story, and symptoms also include behavioral changes, cognitive decline, and abnormal speech. Behavioral changes may involve personality changes, mood problems, like depression and agitation, or the development of new compulsive behaviors. Language problems often begin with difficulty finding words (“anomia“) and may progress to an inability to speak.

The disorder is currently classified as a “tauopathy” in the same family of diseases as Pick’s disease, progressive supranuclear palsy (PSP), and even Alzheimer’s disease.

Although the diagnosis of CBGD is mostly clinical, there are some diagnostic tests that may helpful, such as asymmetric cortical atrophy on brain imaging or asymmetric slowing on EEG.

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MRI showing right hemispheric atrophy

EEG showing L hemispheric slowing

EEG showing R hemispheric slowing

However, a definitive diagnosis can only be made by examining brain tissue at autopsy.

Pathology of CBGD (A) In the neocortex, ballooned neurons with displaced nuclei and pale cytoplasm (arrow) are common. (B) Immunostaining detects diffuse accumulations of tau protein in a peripheral distribution in a ballooned neuron. (C) Neuron loss and gliosis are often severe in deep nuclei, including the substantia nigra. (D) Diffuse cytoplasmic accumulation of tau protein is seen in neurons of various sizes in the neocortex (arrow, panel D), nucleus basalis (E) and striatum (F), as well as other locations. (Panels A,C from sections stained with H and E, remaining panels from sections immunostained with primary antibodies to tau).

Pathology of CBGD (A) In the neocortex, ballooned neurons with displaced nuclei and pale cytoplasm (arrow) are common. (B) Immunostaining detects diffuse accumulations of tau protein in a peripheral distribution in a ballooned neuron. (C) Neuron loss and gliosis are often severe in deep nuclei, including the substantia nigra. (D) Diffuse cytoplasmic accumulation of tau protein is seen in neurons of various sizes in the neocortex (arrow, panel D), nucleus basalis (E) and striatum (F), as well as other locations. (Panels A,C from sections stained with H and E, remaining panels from sections immunostained with primary antibodies to tau).

There are no effective treatments for CBGD, and therapy is aimed at symptomatic relief. The movement disorder, unlike Parkinson’s disease, does NOT respond well to levadopa, so other medications are used to help control the tremors and stiffness in the limbs. Beta blockers (propanolol), benzodiazepines (clonazepam), and gabapentin may have some efficacy in controlling tremor. Baclofen (a GABA agonist) is used to treat spasticity of many different causes and may provide some relief to patients with CBGD. Additionally, the depression, anxiety and agitation due to degeneration the cortical areas of the brain are critical therapeutic targets, and often respond to the first line therapies, including SSRIs and other antidepressants.

In summary, CBGD is a rare, progressive neurodegenerative disease. Recognizing the constellation of symptoms of CBGD from its more common cousins helps patients by identifying all elements of the disease progression, and can improve quality of life by addressing each of the related symptoms.

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8 thoughts on “Cortical Basal Ganglionic Degeneration

  1. So odd to me that I have two family members with very rare neuropathies…my mother died from PSP…and my sister-in-law is rapidly declining from CBGD….please support reserch! Diane

  2. I am working with a male client that was diagnosed with this. Its hard for me to see that there is so little information out there as I have become a live in care giver and help his wife with him. Why is there little known about this disease and little educatioin about this?

  3. my mother has been diagnosed with this ! it is a terrible disorder ,,, we live in australia and there are no clinicla trials here as it is so rare, any research into this or trials

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