Volumetric MRI analysis of hippocampal subregions in Cushing's disease: A model for glucocorticoid neural modulation

Toffanin, Tommaso; Nifosi, F.; Follador, Halima; Passamani, A.; Zonta, Filippo; Ferri, Giovanni; Scanarini, M; Amistà, Pietro; Pigato, Giorgio; Scaroni, Carla; Mantero, Franco; Carollo, C.; Perini, Giulia

doi:10.1016/j.eurpsy.2010.09.003

Cited by 37 publications

(34 citation statements)

References 31 publications

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“…However, it might be that these brain structures were affected during active disease (11,12,13), but that grey matter volumes increased after biochemical cure. This would be in accordance with the previously found increase in hippocampal volume in CD patients after correction of hypercortisolism (11,14,15,16) and the well-documented plasticity of hippocampal neurons in animal models (48). Nevertheless, children experienced cognitive decline despite reversal of brain atrophy 1 year after surgical remission (49) and adult patients with long-term remission of CD still demonstrated impaired memory function (23).…”

Section: Discussionsupporting

confidence: 78%

“…For example, prolonged cortisol elevations predict memory dysfunction and reduced volume of the hippocampus and ACC during aging (9,10). Moreover, in patients with Cushing's syndrome, hypercortisolism was associated with smaller hippocampal volumes and overall brain atrophy (11,12,13), with increasing hippocampal volumes and improving emotional and cognitive functioning after correction of hypercortisolism (11,14,15,16,17,18).…”

Section: Introductionmentioning

confidence: 99%

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Smaller grey matter volumes in the anterior cingulate cortex and greater cerebellar volumes in patients with long-term remission of Cushing's disease: a case–control study

Andela

Werff

Pannekoek

et al. 2013

European Journal of Endocrinology

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Objective: Patients with long-term remission of Cushing's disease (CD) have persistent psychological and cognitive impairments. It is unknown whether, and to what extent, these impairments are accompanied by structural abnormalities in the brain. We aim to investigate structural changes in the brain in patients with predominantly long-term remission of CD and to examine whether these changes are associated with psychological and cognitive dysfunction and clinical severity. Design: A cross-sectional, case-control study. Methods: In 25 patients with predominantly long-term remission of CD and 25 matched healthy controls, grey matter volumes in the regions of interest (hippocampus, amygdala, and anterior cingulate cortex (ACC)) and in the whole brain were examined, using 3T magnetic resonance imaging and a voxel-based morphometry approach. Psychological and cognitive functioning were assessed using validated questionnaires and clinical severity was assessed using the Cushing's syndrome severity index. Results: Compared with controls, patients had smaller grey matter volumes of areas in the ACC (on average 14%, P!0.05) and greater volume of the left posterior lobe of the cerebellum (on average 34%, P!0.05). As expected, patients with remitted CD reported more depressive symptoms (PZ0.005), more anxiety (PZ0.003), more social phobia (PZ0.034), more apathy (PZ0.002), and more cognitive failure (PZ0.023) compared with controls, but the differences in grey matter volumes were not associated with psychological or cognitive measures, nor with clinical severity. Conclusion: Patients with predominantly long-term remission of CD showed specific structural brain abnormalities, in the presence of psychological dysfunction. Our data form a basis for future work aimed at elucidating the relation of the structural brain abnormalities and the sustained psychological deficits after long-term exposure to high cortisol levels.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Smaller grey matter volumes in the anterior cingulate cortex and greater cerebellar volumes in patients with long-term remission of Cushing's disease: a case–control study

Andela

Werff

Pannekoek

et al. 2013

European Journal of Endocrinology

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“…One study did neither describe diagnostic nor remission criteria (20). Described diagnostic criteria were clinical features (truncal obesity, skin and muscle arthophy, moon facies) (11,12,13,21), elevated urinary free cortisol (UFC) (11,12,13,21,22,23,24,25,26,27,28,29), elevated cortisol secretion rates (11,12,13,21,23,24,25,30), elevated midnight salivary cortisol (29,31), absence of blunted circadian rhythm of cortisol secretion (11,12,13,21,26,27,30,32,33), elevated ACTH levels (in CD only) (12,13,21,23,24), lack of suppression after low dose dexamethasone ((1 mg) (22,25,29,33), (2 mg) (12,13,21...…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Cushing's syndrome causes irreversible effects on the human brain: a systematic review of structural and functional magnetic resonance imaging studies

Andela

Haalen

Ragnarsson

et al. 2015

European Journal of Endocrinology

147

129

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Background: Cushing's syndrome (CS) is characterized by excessive exposure to cortisol, and is associated with both metabolic and behavioral abnormalities. Symptoms improve substantially after biochemical cure, but may persist during long-term remission. The causes for persistent morbidity are probably multi-factorial, including a profound effect of cortisol excess on the brain, a major target area for glucocorticoids. Objective: To review publications evaluating brain characteristics in patients with CS using magnetic resonance imaging (MRI). Methods: Systematic review of literature published in PubMed, Embase, Web of Knowledge, and Cochrane databases. Results: Nineteen studies using MRI in patients with CS were selected, including studies in patients with active disease, patients in long-term remission, and longitudinal studies, covering a total of 339 unique patients. Patients with active disease showed smaller hippocampal volumes, enlarged ventricles, and cerebral atrophy as well as alterations in neurochemical concentrations and functional activity. After abrogation of cortisol excess, the reversibility of structural and neurochemical alterations was incomplete after long-term remission. MRI findings were related to clinical characteristics (i.e., cortisol levels, duration of exposure to hypercortisolism, current age, age at diagnosis, and triglyceride levels) and behavioral outcome (i.e., cognitive and emotional functioning, mood, and quality of life). Conclusion:Patients with active CS demonstrate brain abnormalities, which only partly recover after biochemical cure, because these still occur even after long-term remission. CS might be considered as a human model of nature that provides a keyhole perspective of the neurotoxic effects of exogenous glucocorticoids on the brain.

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“…In children with Cushing's syndrome, brain size was significantly reduced, brain ventricles dilated, and reduction of hippocampal size was more apparent. After 1 year of treatment, brain volume recovered, but intelligence quotient was still significantly lower than normal levels[2526]. In animal experiments, dexamethasone administration in pregnant rats induced the apoptosis of amygdala neurons in pups[27].…”

Section: Discussionmentioning

confidence: 99%

Preconditioning crush increases the survival rate of motor neurons after spinal root avulsion

Zuo²,

2014

Neural Regen Res

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OBJECTIVE:A meta-analysis of published randomized controlled trials investigating the long-term effect of dexamethasone on the nervous system of preterm infants.DATA SOURCES:Online literature retrieval was conducted using The Cochrane Library (from January 1993 to June 2013), EMBASE (from January 1980 to June 2013), MEDLINE (from January 1963 to June 2013), OVID (from January 1993 to June 2013), Springer (from January 1994 to June 2013) and Chinese Academic Journal Full-text Database (from January 1994 to June 2013). Key words were preterm infants and dexamethasone in English and Chinese.STUDY SELECTION:Selected studies were randomized controlled trials assessing the effect of intravenous dexamethasone in preterm infants. The quality of the included papers was evaluated and those without the development of the nervous system and animal experiments were excluded. Quality assessment was performed through bias risk evaluation in accordance with Cochrane Handbook 5.1.0 software in the Cochrane Collaboration. The homogeneous studies were analyzed and compared using Revman 5.2.6 software, and then effect model was selected and analyzed. Those papers failed to be included in the meta-analysis were subjected to descriptive analysis.MAIN OUTCOME MEASURES:Nervous system injury in preterm infants.RESULTS:Ten randomized controlled trials were screened, involving 1,038 subjects. Among them 512 cases received dexamethasone treatment while 526 cases served as placebo control group and blank control group. Meta-analysis results showed that the incidence of cerebral palsy, visual impairment and hearing loss in preterm infants after dexamethasone treatment within 7 days after birth was similar to that in the control group (RR = 1.47, 95%CI: 0.97–2.21; RR = 1.46, 95%CI: 0.97–2.20; RR = 0.80, 95%CI: 0.54–1.18; P > 0.05), but intelligence quotient was significantly decreased compared with the control group (MD = −3.55, 95%CI: −6.59 to −0.51; P = 0.02). Preterm infants treated with dexamethasone 7 days after birth demonstrated an incidence of cerebral palsy and visual impairment, and changes in intelligence quotient similar to those in the control group (RR = 1.26, 95%CI: 0.89–1.79; RR = 1.37, 95%CI: 0.73–2.59; RR = 0.53, 95%CI: 0.32–0.89; RR = 1.66, 95%CI: −4.7 to 8.01; P > 0.05). However, the incidence of hearing loss was significantly increased compared with that in the control group (RR = 0.53, 95%CI: 0.32–0.89; P = 0.02).CONCLUSION:Dexamethasone may affect the intelligence of preterm infants in the early stages after birth, but may lead to hearing impairment at later stages after birth. More reliable conclusions should be made through large-size, multi-center, well-designed randomized controlled trials.

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Volumetric MRI analysis of hippocampal subregions in Cushing's disease: A model for glucocorticoid neural modulation

Cited by 37 publications

References 31 publications

Smaller grey matter volumes in the anterior cingulate cortex and greater cerebellar volumes in patients with long-term remission of Cushing's disease: a case–control study

Smaller grey matter volumes in the anterior cingulate cortex and greater cerebellar volumes in patients with long-term remission of Cushing's disease: a case–control study

MECHANISMS IN ENDOCRINOLOGY: Cushing's syndrome causes irreversible effects on the human brain: a systematic review of structural and functional magnetic resonance imaging studies

Preconditioning crush increases the survival rate of motor neurons after spinal root avulsion

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