Distinct neurodegenerative disorders can occur simultaneously in the same individual, as described in a case report of a man with fragile X-associated tremor-ataxia syndrome (FXTAS) and progressive supranuclear palsy (PSP).
Analysis of his brain alterations suggested that the two conditions developed independently.
The research, “Fragile X-associated tremor ataxia syndrome with co-occurrent progressive supranuclear palsy-like neuropathology,” was published in the journal Acta Neuropathologica Communications.
FXTAS, a common condition in families affected by fragile X syndrome, is a neurodegenerative condition characterized by ataxia, or progressive movement changes, and tremors (rhythmic, involuntary movements). It typically starts in adulthood and predominantly affects men. Individuals with this condition have a “premutation” in the FMR1 gene, consisting of 55–200 CGG repeats. (Of note, C stands for cytosine and G for guanine, two of the four building blocks of DNA.)
The co-occurrence of multiple nervous system diseases is common, and most frequently seen in patients with Alzheimer’s disease and Parkinson’s disease. Previous studies reported that people with FXTAS may also have Lewy body dementia and Alzheimer’s, which makes diagnosis and patient management more difficult.
In the report, researchers at the University of Florida described the case of a 65-year-old man with FXTAS and PSP. This rare condition can cause problems with balance, movement, vision, speech, and swallowing. Typically, its symptoms start to show after age 60.
The patient was followed at the Center for Movement Disorders and Neurorestoration at the University of Florida. He had a 10-year history of FXTAS symptoms, including tremor, action myoclonus (muscle twitching), and memory impairment. In addition, he had bradykinesia (slowness of movement), which is a PSP-like symptom.
However, he showed no signs of gaze palsy — limited movement of both eyes in the same direction — or truncal rigidity, which may cause difficulties in turning around or standing up.
Brain magnetic resonance imaging (MRI) suggested that the patient had FXTAS. Diagnosis was confirmed by genetic testing, which revealed 96 CGG repeats in the FMR1 gene.
By age 68, he showed diffuse myoclonus and severe unsteady gait that required the use of a wheelchair. In addition, he experienced other PSP-like symptoms including postural instability, dysarthria (speaking difficulty), and impaired executive function, which refers to goal-directed actions and adaptation to novel situations. He died at age 69.
Post-mortem analysis of his brain and spinal cord further confirmed the presence of FXTAS. It also showed widespread aggregates of proteins such as FMRpolyG in the cell nucleus. FMRpolyG peptides are small proteins that are toxic to nerve cells and result from CGG repeats.
Discoloration of the white matter — made of nerve fibers — and spongiosis (abnormal accumulation of fluids between cells) were identified in brain regions such as his cerebellum, which has a major role in motor coordination, balance, and speech.
Further signs of PSP included clumps of a protein called tau in brain areas including the substantia nigra (a crucial region in Parkinson’s development) and the locus coeruleus, which is key in the response to stress and panic. Aggregates were seen in both nerve cells and glial cells (which surround and support neurons). In line with PSP, these aggregates were globose, or flame-shaped.
Overall, these findings are consistent with reports of patients with FXTAS and PSP-like clinical symptoms.
Although scientists cannot determine whether the two disorders are linked in this patient, “the fact that the highest abundance of the respective neuropathological changes was detected in non-overlapping brain regions may favor two independent processes,” the researchers wrote.