Whipple’s Disease932-1

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.

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.

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

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-LaANCA +ve for perinuclear ANCAACE and chest CT normalNegative HIV and cryptoAG

Cerebrospinal Fluid

Protein 45 mg/dlGlucose 55 mg/dlCells RBC 213 WBC 8 (92% lymphs)PAS NegativeIgG 3.5 mg/dlOligoclonal Bands AbsentVDRL Negative

More Studies

Low FSH, LDH

SIADH

Negative Biopsy from:

– Kidney & Small Bowel

– Lacrimal Gland

– Cervical Mucosa

– Brain Frontal Lobe

Neuroimaging

Figure 1. Marked enhancement within the hypothalamus

Neuroimaging

Figure 2. T1 brightness in hypothalamus and mammillary bodies

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”

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.

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

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

Treatment

Ceftriaxone 2g IV bidor

PCN G procaine 1.2 mU IM qd +

Streptomycin 1g IM qd for 2 weeksthen

Trimethoprim-sulfamethoxazole 160/800 mg po bid 1x year

Whipple’s Disease

CNS Involvement 6-16% reported series

Primary CNS < 5%

– Progressive dementia

– Myoclonus

– Supranuclear ophthalmoplegia

– Hypothalamic involvement

– Obstruction of the aqueduct

ReferencesWhipple, 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.

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

www.library.med.utah.edu/NOVEL