1. Whipple’s Disease 932-1

2. History A 44 year old woman with a past history of ethanol abuse was admitted in 1993 with a one year decline in memory, hypothalamic dysfunction and a one month history of diplopia and ataxia. A rapid decline in short term memory left her with an inability to recall what she had just read or recently eaten.

3. Nine months PTA she had an episode of excruciating abdominal pain. An IV pyelogram and CT of the abdomen were normal despite hematuria. Six months PTA, she was admitted to the hospital because of increasing confusion and was noted to have upbeat nystagmus in primary gaze.

4. Investigation CBC, PT PTT, BUN and electrolytes Liver function studies Porphyria screen negative EKG normal Non-contrast Brain CT mild atrophy Chest X-ray normal

5. Other Studies Extensive malignancy work up –ve. Collagen vascular test, high ESR 80/1 hr., Elevation of anti-cardiolipid antibodies IgG and IgM. Serum protein IgM 560 (56-352). Cryoglobulins +ve. Negative ANA, anti-Ro, anti-La ANCA +ve for perinuclear ANCA ACE and chest CT normal Negative HIV and cryptoAG

6. Cerebrospinal Fluid Protein45 mg/dl Glucose55 mg/dl Cells RBC213 WBC8 (92% lymphs) PAS Negative IgG 3.5 mg/dl Oligoclonal BandsAbsent VDRLNegative

7. More Studies Low FSH, LDH SIADH Negative Biopsy from: – Kidney & Small Bowel – Lacrimal Gland – Cervical Mucosa – Brain Frontal Lobe

8. Neuroimaging Figure 1. Marked enhancement within the hypothalamus

9. Neuroimaging Figure 2. T1 brightness in hypothalamus and mammillary bodies

11. Whipple’s Diagnosis Duodenal biopsy: PAS stain with diastase Non-intestinal tissues: electron microscopy Polymerase Chain Reaction: – Tissue, blood, and other bodily fluids In situ hybridization fluorescent rRNA probe Whipple’s bacillus “Tropheryma whippelii”

12. Brain Biopsy #2 Open biopsy: wall of third ventricle “Perivascular and parenchymal infiltration with foamy macrophages which stained +ve for PAS.” Brain tissue and small bowel biopsy insufficient for PCR studies.

13. The causative organism Tropheryma whippelii is seen within macrophages in the parenchyma on PAS (peroidic acid-Schiff).

14. The causative organism Tropheryma whippelii is seen within macrophages in the parenchyma on silver stains.

19. Treatment Ceftriaxone 2g IV bid or PCN G procaine 1.2 mU IM qd + Streptomycin 1g IM qd for 2 weeks then Trimethoprim-sulfamethoxazole 160/800 mg po bid 1x year

20. Whipple’s Disease CNS Involvement 6-16% reported series Primary CNS < 5% –Progressive dementia –Myoclonus –Supranuclear ophthalmoplegia –Hypothalamic involvement –Obstruction of the aqueduct

21. References Whipple, GH (1907). A hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal mesenteric lymphatic tissue. Bull. Johns Hopkins Hospital. 18:382. Sieracki, JC, et al. (1960). Central nervous system involvement in Whipple’s Disease. J. Neuropath. Exp. Neurol. 19:70.

22. Badenoch, J, et al. (1963). Encephalopathy in a case of Whipple’s Disease. J. Neurol. Neurosurg. Psychiat. 26:203. Knox, D.I, et al. (1995). Cerebral ocular Whipple’s disease. Neurology. 45:617. References

23. www.library.med.utah.edu/NOVEL