Whipple's disease masquerades as dementia with Lewy bodies

B RIEF R EPORT Whipple’s Disease Masquerades as Dementia With Lewy Bodies Kyle Hurth, MD, PhD,* Rawan Tarawneh, MD, wz Nupur Ghoshal, MD, PhD, wz Tammie L.S. Benzinger, MD, PhD, wzy David B. Clifford, MD, y Michael Geschwind, MD, PhD,8 John C. Morris, MD, wz James E. Galvin, MD, z Robert E. Schmidt, MD, PhD,* and Nigel J. Cairns, PhD, FRCPath* wz (Alzheimer Dis Assoc Disord 2015;29:85–89) Key Words: Whipple’s disease, bacterial infection, dementia with Lewy bodies Received for publication March 25, 2013; accepted July 1, 2013. From the *Department of Pathology and Immunology, Division of Neuropathology; wCharles F. and Joanne Knight Alzheimer’s Disease Research Center; zDepartment of Neurology; yMallinck- rodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO; 8Department of Neurology, University of California, San Francisco, CA; and zComprehensive Center on Brain Aging, New York University Langone School of Medicine, New York, NY. K.H., R.T., and N.G. contributed equally. Supported by grants from the National Institute on Aging of the National Institutes of Health (P50-AG05681, P01-AG03991), the Hope Center for Neurological Disorders, the Buchanan Fund, the Charles F. & Joanne Knight Alzheimer’s Disease Research Center, and the Barnes- Jewish Hospital Foundation. A summary of these data were presented at the 2012 Annual Meeting of the American Association of Neuropathologists. N.G. has participated or is currently participating in clinical trials of anti-dementia drugs sponsored by Elan/Janssen, Eli Lilly and Company, Wyeth, Pfizer, Novartis, and Bristol-Myers Squibb. T.L.S.B. declares an interest as a consultant for Biomedical Sys- tems, ICON Medical Imaging, Eli Lilly Advisory Board, and Avid Radiopharmaceuticals. D.B.C. serves on Data Safety Boards for Amgen, Biogen, GlaxoSmithKline, Millennium, Genzyme, Genentech, and Pfizer. He has been a consultant to Brinker, Biddle, Reath [Progressive Multifocal Leukoencephalopathy (PML) Consortium], Genentech, Genzyme, Bristol-Myers Squibb, Millen- nium, Biogen Idec, and Pfizer. He has received research support from the Alzheimer’s Association, Biogen Idec, Eli Lilly, Roche and Pfizer. He has received speaking fees from Biogen, University of Kentucky, ECTRIMS, and CMSC/ACTRIMS. J.C.M. declares an interest as a consultant for: Eisai, Elan/Janssen Alzheimer Immu- notherapy Program, GlaxoSmithKline, Novartis, Otsuka Pharma- ceuticals, Pfizer/Wyeth, Eli Lilly, AstraZeneca, Bristol-Myers Squibb, Genentech, Merck, and Schering Plough; support form NIH/NIA; speaking fees: Dickinson address at Ohio Wesleyan, ABA Soriano Lectureship, Morrell Lecture (Chicago), Eisai (South Korea), Bial Neurology Forum (Portugal); royalties from: Black- well Medical, Taylor and Francis. J.E.G. serves on a scientific advisory board for the American Federation for Aging Research and on the Board of Directors and the Scientific Advisory Council for the Lewy Body Dementia Association; he serves on speakers’ bureaus for Pfizer Inc., Eisai Inc., Novartis, and Forest Labo- ratories Inc.; has served as a consultant for Novartis, Forest Lab- oratories Inc., Pfizer Inc., Eisai Inc., Janssen, and Medivation Inc.; he has received license fee payments for AD8 dementia screening test (copyrighted): license agreements between Washington Uni- versity and Pfizer Inc., Eisai Inc., and Novartis; and receives research support from Novartis, Eli Lilly and Company, Elan Corporation, Wyeth, Bristol-Myers Squibb, the NIH/NIA, and the Alzheimer Association. The remaining authors declare no conflicts of interest. Reprints: Nigel J. Cairns, PhD, FRCPath, Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Saint Louis, MO 63110 (e-mail: cairns@wustl.edu). Copyright r 2013 Wolters Kluwer Health, Inc. All rights reserved. Alzheimer Dis Assoc Disord CASE HISTORY Dr George Whipple first described the disease which bears his name in 1907. 1 He described a 36-year-old male physician who presented with a 5- to 6-year history of insidious symptoms including cough, recurrent attacks of arthritis, gradual weight loss, and asthenia. By the end of his life, skin changes, diarrhea, abdominal swelling, and mesenteric adenopathy were prominent. Pathologic examination showed macrophages and fat vacuoles in the small bowel and inflammation and macrophages within pleura, peritoneum, and the aortic valve. Silver staining demonstrated rod- shaped structures. Electron microscopy has revealed that these aggregates consist of networks of membranous structures and bacillary bodies of the bacterium Tropheryma whipplei. 2,3 Bacterial DNA sequencing and antibodies to T. whipplei may now be used to confirm the diagnosis. We report a 49-year-old white man with a 4-year history of progressive cognitive and behavioral impairment, parkinsonism, cognitive fluctuation, altered sleep-wake cycles, myoclonus, visual hallucinations, and subsequent death. His past medical history included hypertension, chronic obstructive pulmonary disease, smoking, alcohol use, and cadaveric growth hormone replacement for delayed puberty as a child. There was no family history of dementia or movement disorder. He worked as a painter and was frequently exposed to solvents. He was in his usual state of health until approximately 2 years before initial evaluation. At that time, behavioral disturbances were noted by the family from whom he was estranged. He was described as depressed and severely withdrawn. Approximately 12 to 16 months into his course, he became forgetful of recent events and conversations and repeated himself. He had increasingly odd behavior including sleeping during the day and being awake at night, wandering outside inappropriately dressed, and confabulating. His cognition fluctuated from staring spells to deep sleep from which he was difficult to arouse. At other times he was alert and fully oriented without recollection of prior events. He began to have well-formed visual hallucinations that he described as “brightly-colored pets” or “small people” and occur- red during periods of lucidity. Eighteen months after onset, he was evaluated at an outside hospital for pneumonia, confusion, and agitation. He had notable parkinsonism and myoclonus of the left upper extremity. Imaging and diagnostic studies were unrevealing. Valproic acid partially improved his myoclonic movements. He was also treated with intravenous thiamine given his prior alcohol use and presentation concerning for Wernicke-Korsakoff syndrome. Small doses of risperidone and olanzapine produced generalized rigidity and drowsiness. He had one unexplained syncopal episode during his admission. Between episodes, he was alert and fully oriented and was discharged to a skilled nursing facility. Sporadic Creutzfeldt-Jakob disease was considered because of the rapid cognitive decline and a history of treatment with cadaveric growth hormone extract led to the suspicion of iatrogenic Creutzfeldt-Jakob disease. However, the absence of periodic sharp wave complexes in the context of mildly left predominant Volume 29, Number 1, January–March 2015 www.alzheimerjournal.com