The “Steroid Dementia Syndrome”: A Possible Model of Human Glucocorticoid Neurotoxicity

Abstract

Glucocorticoid medications cause neurotoxicity in animals under certain circumstances, but it is not known if this occurs in humans. We present the case of a 10-year-old boy with no prior psychiatric history and no prior exposure to glucocorticoid medication who received a single 5-week course of glucocorticoids for an acute asthma flare. Beginning during steroid treatment, and persisting for over 3 years after stopping treatment, he showed a significant decline from his pre-morbid academic performance and estimated IQ, verified by longitudinally administered testing and school records. Neuropsychological tests that are sensitive to glucocorticoid-induced cognitive impairments revealed global cognitive deficits consistent with primary hippocampal and prefrontal cortical dysfunction. The patient has a fraternal twin brother, who had previously achieved academic milestones in parallel with him; the patient began falling behind his twin in academic, developmental and social areas shortly after the steroid treatment. In the 3 years since stopping steroid medication, the patient has shown gradual but possibly incomplete resolution of his cognitive deficits. Quantitative brain magnetic resonance imaging (MRI), performed 38 months after steroid exposure revealed no gross abnormalities, but the patient's hippocampal volume was 19.5% smaller than that of his twin, despite the patient having a larger overall intracranial volume. Single photon emission computed tomography (SPECT) imaging, performed at the same time, suggested subtly decreased activity in the left posterior frontal and left parietal lobes. This case, along with others reported in the literature, suggests that certain individuals develop a “steroid dementia syndrome” after glucocorticoid treatment. Although this syndrome is uncommon, it is consistent with evolving theories of the neurotoxic or neuroendangering potential of glucocorticoids in some situations.

Keywords:

• Glucocorticoid
• corticosteroid
• prednisone
• dementia
• memory
• steroid psychosis
• hippocampus
• prefrontal cortex
• neurotoxicity

The authors gratefully acknowledge BB and his family for allowing us to present this case, Dr Greig Coates for referring this case to us for evaluation, Dr Robert Sapolsky for helpful discussions and for valuable review of the manuscript, Drs. Jonathan Canick, Bronson Levin and Victor Reus for helpful discussions of other cases of steroid dementia, Dr Sophie Brière for assistance with neuropsychological test interpretation, and Tracy Abildskov for technical assistance in the 3D image analysis.

Notes

¹Initials have been changed to protect confidentiality.