10.1177/1051228404267994 Journal of Neuroimaging Vol 14 No 4 October 2004 Galldiks et al: Neuroimaging Findings and Cerebral Whipple’s Disease Novel Neuroimaging Findings in a Patient With Cerebral Whipple’s Disease: A Magnetic Resonance Imaging and Positron Emission Tomography Study N. Galldiks L. Burghaus S. Vollmar J. Cizek P. Impekoven A. Thomas A. H. Jacobs K. Herholz ABSTRACT The authors report a 43-year-old patient with histopathologically proven cerebral Whipple’s disease. Magnetic resonance imaging (MRI) revealed a multilayered left frontal lesion without mass effect, no perifocal brain edema, no contrast enhancement, and a thin shell of fluid signal that presented as an incomplete, open ring. An [ 11 C]methionine positron emission tomography (PET) study showed low uptake below the threshold that is characteristic for brain tumors. In precise co- registration to the MR images, the PET data showed that increased uptake was mainly located in the direct adjacent part of the MRI lesion. The fluid signal on MRI corresponded to the extensive outflow of fluid from the lesion, which was observed during neurosurgical resection, and also to the neuropathological findings. The authors conclude that this cerebral manifestation of Whipple’s disease made a unique and hitherto undescribed appearance on MRI; uptake pattern of PET amino acid tracer may help in the preoperative distinction of inflammatory from neoplastic lesions. Key words: Positron emission tomography, cerebral Whipple’s dis- ease, [ 11 C]methionine uptake, constipated edema, multilayered MRI lesion. Galldiks N, Burghaus L, Vollmar S, Cizek J, Impekoven P, Thomas A, Jacobs AH, Herholz K. Novel neuroimaging findings in a patient with cerebral Whipple’s disease: a magnetic resonance imaging and positron emission tomography study. J Neuroimaging 2004;14:372-376. DOI: 10.1177/1051228404267994 Whipple’s disease (WD) is a rare, multisystemic chronic granulomatous infectious disease preferentially involving the gastrointestinal system. It is caused by the rod-shaped gram- positive bacillus Tropheryma whippelii. In infected tissues, these bacteria accumulate in large numbers within macrophages, for example, in the mucosa of the small bowel. 1 Classic clinical fea- tures include chronic diarrhea, malabsorption, abdominal pain, polyarthralgia, lymphadenopathy, weight loss, and fever. 2,3 Central nervous system involvement is well described in patients with WD and occurs in 6% to 43% of cases with classic systemic manifestations. 4 Symptoms of central nervous system involvement usually develop in the later stage of disease, and they are mainly observed during disease relapse, particularly in patients who previously received antibiotic treatment unable to cross the blood-brain barrier and in cases in which the duration of initial treatment was not long enough. 5,6 Manifestation of cerebral WD without systemic involvement is rare. 5,7 Various disease-unspecific neurologic symptoms combined with the rar- ity of this entity and difficulty to culture the organism 2 often lead to a delay in diagnosis and treatment. 8,9 Cases of cerebral WD diagnosed by brain biopsy highlight limitations of routine diag- nostic procedures. In most cases, small-bowel biopsies are nega- tive, cerebrospinal fluid (CSF) studies reveal no abnormalities, and even polymerase chain reaction (PCR) examinations of CSF for T whippelii are negative. 5,7,9-19 These cases emphasize the importance of neuroimaging studies, which may facilitate the decision to perform early cerebral biopsy for final diagnosis because WD is potentially treatable. Positron emission tomography (PET) studies in other granulomatous diseases (eg, sarcoidosis) and in patients with brain abscess reveal diagnostically important information and are a useful tool for pretreatment evaluation. 20-22 Therefore, we suggest that [ 11 C]methionine PET neuroimaging studies might be helpful in characterizing the granuloma and useful in the pre- operative management, especially in cases of WD with unusual magnetic resonance imaging (MRI) findings that do not corre- spond with the clinical presentation of malignant brain disease. 372 Copyright © 2004 by the American Society of Neuroimaging Received March 3, 2004, and in revised form April 28, 2004. Ac- cepted for publication April 30, 2004. From the Department of Neurology (NG, LB, AT, AHJ, KH), the Max Planck-Institute for Neurological Research (NG, SV, JC, AHJ, KH), and the Department of Radiology (PI), Univer- sity of Cologne, Cologne, Germany. Address correspondence to Dr K. Herholz, Department of Neu- rology at the University of Cologne, Joseph-Stelzmann-Str. 9, 50931 Cologne, Germany. E-mail: karl.herholz@pet.mpin- koeln.mpg.de.