Ann Thorac Surg 2002;73:1965-1967
© 2002 The Society of Thoracic Surgeons
Case report
Glucocorticoids and hippocampal atrophy after heart transplantation
Asher P. Wilner, MDa*,
Benoit de Varennes, MDa,b,c,
Pierre A. Gregoire, PhDa,
Sonia Lupien, PhDc,
Jens C. Pruessner, PhDc
a Psychiatry, McGill University Health Centre at the Royal Victoria Hospital and the Montreal Neurological Hospital, Montreal, Quebec, Canada
b Cardiothoracic Surgery, McGill University Health Centre at the Royal Victoria Hospital and the Montreal Neurological Hospital, Montreal, Quebec, Canada
c Neurology, McGill University Health Centre at the Royal Victoria Hospital and the Montreal Neurological Hospital, Montreal, Quebec, Canada
Accepted for publication November 1, 2001.
* Address reprint requests to Dr Wilner, Department of Psychiatry, McGill University Health Centre at the Royal Victoria Hospital, 1025 Pine Ave West, Montreal, Quebec H3A 1A1, Canada
e-mail: asher.wilner{at}mcgill.ca
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Abstract
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The glucocorticoid cascade hypothesis proposes that hippocampal atrophy may result from excessive steroid exposure. Although demonstrated in animal models and some human hypercortisolemic states, hippocampal damage as a possible consequence of posttransplant steroid immunosuppression has not been investigated in human heart transplant recipients. We report a case of a 37-year-old female heart transplant recipient who had the clinical, neuropsychiatric, and neuroimaging findings consistent with hippocampal atrophy after 5 years of steroid exposure.
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Introduction
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Heart transplant recipients have high rates of psychiatric morbidity, which is often considered a natural reaction to the severe stress of end-stage heart failure and its treatment. However, the high incidence of psychiatric disorders in heart transplant recipients, and the reported vulnerability of the hippocampus in hypercortisolemic states [1], suggest the need for investigation as illustrated by the following case.
A 37-year-old female patient with severe familial dilated cardiomyopathy underwent orthotopic heart transplantation in October 1993. Coexistent morbidity at that time included obesity, asthma, and anxiety disorder. Two years after transplantation, she developed signs of severe right heart failure and was diagnosed with tricuspid regurgitation. The pulmonary artery pressures were normal. In early 1996, the patient underwent tricuspid valve replacement with a size 33 Carpentier Edwards bioprosthesis (Edwards Lifesciences, Irvine, CA) with good result.
The induction antirejection therapy consisted of antithymocite globulin, solumedrol, and azathioprine. The maintenance therapy consisted of cyclosporine A and prednisone. Exogenous glucocorticoid exposure included solumedrol 500 mg IV intraoperatively and prednisone 40 mg PO daily tapered to 10 mg daily by the sixth month. The following year the prednisone was tapered to 5 mg daily.
The patient reported mood swings in the first 6 months. This was sometimes accompanied by insomnia and daytime fatigue. Depressive and anxiety symptoms emerged later in the first year and worsened in the second year. Trials of tricyclic and selective serotonergic antidepressant medication were ineffective. Truncal obesity, Cushing’s moon face, and diabetes emerged in the second year and worsened in the third year. In the fourth year, she tried but was unable to return to work as a bookkeeper due to short-term memory impairment. Inability to concentrate, chronic anxiety, and worsening memory impairment led to neuropsychological testing in November 1998.
The Wechsler Adult Intelligence Scale was within the average range (Full-scale I.Q. = 103), whereas there were marked deficiencies in memory function on the Wechsler Memory Scale-Revised (General Memory Index = 85). Major difficulties were observed on tasks requiring attention and concentration, including significant impairment on the Peterson test. Visuo-motor coordination and visual memory were within average range. High levels of anxiety and depression were observed on symptom rating scales.
The resolution of CAT scans was insufficient for our purposes; therefore, magnetic resonance imaging (MRI) scans were used to measure hippocampal volume. MRI scans were acquired according to the International Consortium of Brain Mapping (ICBM) protocol to create T1, T2, and PD weighted images with high resolution and contrast. The T1 image was preprocessed using a combination of different algorithms to correct for magnetic field nonuniformities and linear stereotaxic transformation into coordinates based on Talairachatlas. Volume of the hippocampus was assessed using a recently developed protocol with proven validity and reliability [2]. In contrast to total brain gray matter, the volume of the hippocampus was found to be reduced by about 20%, when compared with age- and gender-matched controls that were processed in a recent study [3] (Fig 1).
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Fig 1. Reduced hippocampal volume in a 37-year-old heart transplant patient. (A) Coronal section of the brain perpendicular to the anterior commissure–posterior commissure line through the level of the body of the hippocampus. Notice the enlarged inferior horn of the lateral ventricle (bilateral) and the reduced hippocampal gray matter at the area of the alveus (right side). (B) Comparison of total gray and hippocampal (HC) gray matter of the case study patient (orange dot) with a group of 40 women in the same age range (black dots). Notice that only the hippocampus gray matter is reduced in comparison.
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Comment
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Up to 50% of heart transplant recipients may suffer an inadequately understood psychosocial deterioration some years after surgery despite dramatic improvement in cardiovascular health. This case report demonstrates the typical features of such a decline, including failure to return to work, social withdrawal, cognitive deterioration, and the insidious onset and progression of anxiety and depression despite a well-functioning transplant.
Postoperative psychosocial deterioration in cardiothoracic surgical patients can be a long-term consequence of neurologic damage suffered intraoperatively. One recent study related coronary artery bypass surgery to cognitive decline 5 years later, and suggested intraoperative microembolization as the probable etiology [4].
However, an earlier metaanalysis of neuropsychiatric studies demonstrated there has been no significant change in psychosocial outcome after cardiothoracic surgery over a 30-year interval [5]. During this time, there were significant advances in surgical and in anesthetic technique. These findings suggest that nonsurgical factors, in addition to surgical and bypass pump technicalities, also play a significant role in determining long-term neuropsychiatric outcome.
We propose that glucocorticoid medication is a significant factor in determining long-term psychosocial outcome in heart transplant patients. Glucocorticoid medication is associated with mood and cognitive disorder [6]. Hypercortisolemia can produce hippocampal atrophy in animals and humans. The glucocorticoid cascade hypothesis suggests a plausible mechanism for this neuronal damage [7]. Namely, fully bound steroid receptors in CA3 hippocampal neurons trigger elevated intraneuronal metabolic rates, which if unabated, can lead to cell death. The specificity of neuronal damage may be due to the higher density of glucocorticoid receptors found on the cell surface of some hippocampus and amygdala neurons [8].
We caution against drawing firm conclusions from a single case report. Nevertheless, the finding of hippocampal atrophy in a psychiatrically deteriorated heart transplant patient highlights the pressing need for neuroscience research into the role of glucocorticoids in the transplant setting.
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References
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Abstract
Introduction
