Here are two more research presentations from the Movement Disorders Society conference in Copenhagen back in August. These, both pretty technical (sorry!), report on imaging techniques elucidating how the brain is mis-firing in PSP. Both of them offer ideas for new treatment approaches.

Localizing a brain network of progressive supranuclear palsy

E. Ellis, J. Morrison-Ham, E. Younger, J. Joutsa, D. Corp (Melbourne, Australia)

A brain network is a set of areas in the brain that have direct connections with one another and work together to perform a task.  When a neurodegenerative disease like PSP occurs, an important way for the abnormality to spread through the brain is along such networks.  That produces areas of brain cell loss (“atrophy”) in a specific pattern for a specific disease.  These researchers pointed out that in some people with PSP, the “textbook” list of brain areas showing such loss on conventional MRI imaging is not present.  They hypothesize that the usual brain network may nevertheless be abnormal, but without producing enough actual brain cell loss to show up as the full, textbook pattern.  So, they analyzed a database of MRI, PET, and SPECT scans of 363 people with PSP and tabulated the areas of abnormality.  They compared that list to a database of known brain networks that had been compiled using functional MRI in 1,000 healthy people.  (Functional MRI is a standard research technique where a movement or thinking task is performed or a certain sensory input is provided to a person in an MRI machine.  The image is obtained in such a way as to reveal which brain areas’ baseline activity increase or decrease  together in response.)  They found a consistent brain network to be affected in people with PSP, even if conventional imaging fails to show it.  The claustrum, basal ganglia, and midbrain increase their activity, and the cuneus and precuneus reduce theirs.  The authors conclude that their findings “help to reconcile previous heterogeneous neuroimaging findings by demonstrating that they are part of a common brain network.”  

This information could be useful in designing non-invasive, transcranial electrical or magnetic stimulation treatment for PSP.  If the absence (or mildness) of brain cell loss in some patients with PSP means that those cells are still only malfunctioning rather than dying, it could have important implications for development of treatments aimed at rescuing such cells before the damage becomes irreversible.

Topography of cholinergic vulnerability correlates of PIGD motor deficits in DLB and PSP: A [18F]-FEOBV PET study

P. Kanel, T. Brown, S. Roytman, J. Barr, C C. Spears, N. Bohnen (Ann Arbor, USA)

Neurotransmitters are chemicals used by brain and nerve cells to signal to one another across synapses.  Any given brain cell (or related cluster of brain cells, called a “nucleus”) uses a single neurotransmitter type.  One of the more commonly used neurotransmitters in the brain is acetylcholine, and neurons using it are among the most important to become damaged in PSP.  These researchers imaged the brains of patients with PSP using a positron emission tomography (PET) imaging technique that shows acetylcholinergic synaptic activity.  They compared the abnormal areas in each patient to their degree of balance difficulty and gait problems.  They found correlations in basal forebrain, septal nucleus, medial temporal lobe, insula, metathalamus, caudate, cingulum, frontal lobe, cerebellum, and tectum, especially the superior colliculus.  They found that the first areas on this daunting list, the basal forebrain, where the basal nucleus of Meynert is located, is hit hardest and connects to most of the other areas on the list. They conclude that treatment strategies attempting to replace or regenerate damaged neurons for PSP might want to start there.

It’s been known for decades that the basal nucleus of Meynert is heavily involved in PSP and Alzheimer’s disease, but attempts to compensate for the loss of acetylcholine by inhibiting an enzyme that degrades it (using marketed oral medications such as rivastigmine, donepezil, or galantamine) have produced only minimal results.  Perhaps a targeted, surgical approach to regenerating basal nucleus of Meynert neurons using gene therapy could work better.