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Hippocampus Dysfunction May Explain Symptoms of Fibromyalgia Syndrome. A Study with Single-Voxel Magnetic Resonance Spectroscopy

YASSER EMAD, YASSER RAGAB, FATMA ZEINHOM, GHADA EL-KHOULY, ALAA ABOU-ZEID, and JOHANNES J. RASKER

ABSTRACT.

Objective. (1) To investigate dysfunction of hippocampus in patients with fibromyalgia syndrome (FM) using proton magnetic resonance spectroscopy (¹H-MRS), and to compare these findings with healthy controls. (2) To correlate levels of metabolites obtained with aspects of cognition, depression, and sleep symptoms in the patient group.

Methods. The case-control study was performed in 15 female patients, who met American College of Rheumatology criteria for classification of FM, and 10 healthy age-matched female controls. Patients and controls were receiving no medications known to affect cognitive functioning or central nervous system metabolites before their participation in the study. In all patients and controls, ¹H-MRS was used to assess N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and their ratios from both hippocampi. Levels of metabolites and their ratios were determined and the findings compared between the groups. All patients and controls underwent psychological assessment to assess cognitive function, depression, and structured sleep interview with sleep diary; Fibromyalgia Impact Questionnaire (FIQ), number of tender points, and visual analog scale (VAS) for pain were assessed in all patients.

Results. NAA levels of right and left hippocampi differed significantly between patients and controls (p < 0.05). Cho levels in the right hippocampus were higher in the patient group than in controls (p = 0.005), while no differences were found with respect to Cr levels in both hippocampi. NAA/Cho and NAA/Cr ratios differed significantly between patients and controls (p < 0.05), while the Cho/Cr ratio showed no differences. Significant correlations were found between language score and right Cho and right Cr levels (p = 0.041, p = 0.006, respectively), while no significant correlations were found between metabolites and their ratios with FIQ, VAS for pain, or number of tender points.

Conclusion. The hippocampus was dysfunctional in patients with FM, as shown by lower NAA levels compared to controls, representing neuronal or axonal metabolic dysfunction. As the hippocampus plays crucial roles in maintenance of cognitive functions, sleep regulation, and pain perception, we suggest that metabolic dysfunction of hippocampus may be implicated in the appearance of these symptoms associated with this puzzling syndrome. (First Release May 15 2008; J Rheumatol 2008;35:1371-7)

Key Indexing Terms:

FIBROMYALGIA SYNDROME
PROTON MAGNETIC RESONANCE SPECTROSCOPY
HIPPOCAMPUS DYSFUNCTION
HIPPOCAMPAL METABOLITES

From the Department of Rheumatology and Rehabilitation, Department of Radiology, and Department of Public Health, Faculty of Medicine, Cairo University, Cairo; Department of Psychiatry, Faculty of Medicine, Ain Shams University, Cairo, Egypt; and University Twente, Enschede, The Netherlands.

Y. Emad, MD, Department of Rheumatology and Rehabilitation, Cairo University, Dr. Erfan and Bagedo General Hospital, Jeddah, Saudi Arabia; Y. Ragab, MD; F. Zeinhom, MD, Department of Radiology, Cairo University, Dr. Erfan and Bagedo General Hospital; G. El-Khouly, MD, Department of Psychiatry, Ain Shams University; A. Abou-Zeid, MD, Department of Public Health, Cairo University; J.J. Rasker, MD, University Twente.

Address reprint requests to Dr. Y. Emad, Department of Rheumatology and Rehabilitation, Faculty of Medicine, Cairo University, Cairo 12613, Egypt. E-mail: yasseremad68@yahoo.com.

Accepted for publication December 27, 2007.