Abstract. : The diagnosis of cerebral relapse of Whipple's disease in a 67-year-old patient was made after he presented with somnolence and severe hypothermia 4 months after discontinuing treatment with cotrimoxazole. Hypothermia is a rare hypothalamic manifestation of cerebral Whipple's diseas

Brandner, S.

Himmelmann, B.

Jung, H.

Schaffner, A.

Schoedon, G.

Schuknecht, B.

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Infection 32 · 2004 · No. 2 © URBAN & VOGEL 119Severe Hypothermia in a Patient with CerebralRelapse of Whipple’s DiseaseB. Himmelmann, S. Brandner, H.H. Jung, G. Schoedon, B. Schuknecht, A. SchaffnerAbstractThe diagnosis of cerebral relapse of Whipple’s disease in a 67-year-old patient was made after he presented withsomnolence and severe hypothermia 4 months afterdiscontinuing treatment with cotrimoxazole. Hypothermia is arare hypothalamic manifestation of cerebral Whipple’s disease.Infection 2004; 32: 119–121DOI 10.1007/s15010-004-3024-1IntroductionWhipple’s disease (WD) is a systemic disorder that includesneurologic involvement in 15% of cases [1]. Its causativeagent is Tropheryma whipplei [2]. Diagnosis can be con-firmed by periodic acid-Schiff (PAS)-positive inclusions inmacrophages or PCR analysis in duodenal mucosa or cere-brospinal fluid.Case ReportWe describe a patient who presented with unexplained weight loss,diarrhea and hypoalbuminemia at the age of 63. He had been suf-fering from myalgias of the proximal limbs for 7 years and wastreated with up to 60 mg prednisone daily because of suspectedpolymyalgia rheumatica. The diagnosis of WD was made by PASstain positive macrophages in a duodenal biopsy specimen.Treat-ment with cotrimoxazole 160/800 mg twice daily was started. Thepatient’s condition improved and duodenal biopsies over the nextyears showed regression of WD without complete clearance. Pred-nisone could not be reduced below 7.5 mg daily due to relapsingmyalgias.At the age of 67 the patient presented with memory dis-orders to a neurologist. Four months earlier he had stopped cotri-moxazole treatment. Clinical examination and a CT scan showedno significant abnormalities. On the basis of an EEG, complex par-tial seizures were suspected and treatment with carbamazepin200 mg daily was started. One month later the patient was admit-ted to our hospital with unexplained somnolence after a car acci-dent. On admission blood pressure was 130/90 mmHg; heart rate,52 per min and core temperature, 33.2 °C. Neurological examina-tion showed somnolence, mutism and a slight spastic tetraparesiswith a bilaterally positive  Babinski’s sign. An MRI revealed mul-tiple punctuate and confluent lesions of increased signal intensityaffecting the hypothalamus, fornix and the periventricularsubependymal grey and white matter in a symmetric fashion (Fig-ure 1 A). The lesions predominantly extended along the frontalhorns within the caudate nucleus and along the third ventricle.Cerebral involvement of WD was proved by phagocytic cells inthe cerebrospinal fluid with typical PAS-positive inclusions (Fig-ure 1 B) and positive PCR for T. whipplei. Treatment with cotri-moxazole 160/800 mg twice daily and rifampicin 300 mg threetimes daily was started. The patient’s condition improved and hewas able to handle everyday activities. Hypothermia with a coretemperature ranging between 31.1 and 35.4 °C (mean: 33.3 °C)persisted for 9 weeks.The following febrile episode was attributed to catheter sep-sis. Several syncopes occurred and echocardiography confirmedsevere aortic stenosis with calcification.The patient developed hy-potension and pulmonary edema. He was treated with vasoactivedrugs and antibiotics including vancomycin 1 g, netromycin300 mg, rifampicin 900 mg and ceftriaxone 2 g daily. Blood culturesremained negative. He died in refractory shock despite aorticvalvuloplasty performed 2 weeks earlier. Autopsy of the heart re-vealed no signs of endocarditis. The brain autopsy showed cere-bral involvement of WD macroscopically, by histological exami-nation (Figures 1 C, 1 D) and by electron microscopy.DiscussionThe patient described suffered from gastrointestinal WDpreceded by myalgia for 7 years before the diagnosis of WDwas made.The clinical presentation of myalgia and arthral-gia is well known in WD and precedes the diagnosis by amean of 6.7 years [3]. Prednisone was not reduced below7.5 mg daily because of relapsing symptoms. It remains un-clear if these symptoms were due to WD or a second dis-order such as polymyalgia rheumatica.Infection Case ReportB. Himmelmann (corresponding author), G. Schoedon, A. SchaffnerDept. of Internal Medicine, University Hospital of Zurich, CH-8091 Zurich,Switzerland; Phone: (+41/1) 255-4653, Fax: -4445,e-mail: barbara.himmelmann@usz.chS. BrandnerInstitute of Neuropathology, University Hospital of Zurich, Zurich,Switzerland H.H. JungDept. of Neurology, University Hospital of Zurich, Zurich, Switzerland B. SchuknechtInstitute of Neuroradiology, University Hospital of Zurich, Zurich, Switzer-landReceived: February 18, 2003 • Revision accepted: July 28, 2003At the age of 67 the patient presented with a cerebralrelapse of WD with cognitive changes and persistent hy-pothermia. Treatment had been stopped for 5 months whenthe first signs of cerebral involvement appeared.The diagnosis of cerebral WD remains a problem, eventhough neurologic symptoms occur in 15% of cases [1]. Ithas been shown that CNS involvement diagnosed by PAS-positive cells in the cerebrospinal fluid examination arecommon in patients with WD without neurological symp-toms [4]. In our patient further symptoms included seizures,somnolence and severe hypothermia. A review of 84 casesof cerebral WD showed that cognitive changes and alteredlevels of consciousness are frequent and occur in 71% and50% of patients with cerebral manifestations, respectively[5]. In this series hypothermia was not  described as a hy-pothalamic manifestation of WD. It had been described pre-viously but is very rare [6, 7].A propensity for cerebral man-ifestations of WD to affect midline structures has previouslybeen described by MRI, including signal intensity changesin the hypothalamus [8]. Off midline lesions were observedto affect the subcortical white matter, and did not take upcontrast nor exhibit space-occupying effects [9].The radio-logic findings in this patient are in agreement with the lit-erature with respect to their central location. However, thenodular subependymal extension, the striking symmetryand the lack of subcortical white matter involvement differfrom previous reports.References1. Marth T, Raoult D: Whipple's disease. Lancet 2003; 361: 239–246.2. Relman DA, Schmidt TM, MacDermott RP, Falcow S: Identifica-B. Himmelmann et al. Cerebral Relapse of Whipple’s Disease120 Infection 32 · 2004 · No. 2 © URBAN & VOGELFigure 1. A. Coronal T1 weighted MRI showed nodular hypothalamic and periventricular contrast enhancement extending into the adjacentsubependymal grey matter and along the floor of the third ventricle and fornix. B. Cerebrospinal fluid examination showed phagocytic cellswith PAS-positive inclusions. C. Frontal sections of the formalin fixed brain revealed multiple lesions surrounded by a bright rim. They weremainly distributed along the wall of the lateral ventricles but were also found in the hypothalamus. D. Histological examination of the paraffinembedded sections revealed numerous plaque-like and PAS-positive deposits. Closely associated with these plaques were macrophages filledwith small PAS-positive particles.tion of uncultured bacillus of Whipple’s disease. N Engl J Med1992; 327: 293–301.3. Puéchal X: Whipple's disease and arthritis. Curr Opin Rheumatol2001; 13: 74–79.4. Von Herbay A, Ditton HJ, Schuhmacher F, Maiwald M: Whipple'sdisease: staging and monitoring by cytology and polymerasechain reaction analysis of cerebrospinal fluid. Gastroenterology1997; 113: 434–441.5. Louis ED, Lynch T, Kaufmann P, Fahn S, Odel J: Diagnostic guide-lines in central nervous system Whipple’s disease. Ann Neurol1996; 40: 561–568.6. Bleibel JM, Cabane J, Kardouss J, Wechsler B, Poisson M, Buge A:Maladie de Whipple a forme hypothalamique. Ann Med Intern1983; 134: 723–727.7. Gerard A, Sarrot-Reynauld F, Liozon E, Cathebras P, Besson G,Robin C, Vighetto A, Mosnier J, Durieu I, Vital Durand D, RoussetH: Neurologic presentation of Whipple disease. Report of 12cases and review of the literature. Medicine 2002; 81: 443–457.8. Schider P, Trattnig S, Kollegger H, Auff E: MR of cerebral Whippledisease. Am J Neuroradiol 1995; 16: 1328–1329.9. Brown AP, Lane JC, Murayama S, Vollmer DG: Whipple’s diseasepresenting with isolated neurological symptoms. J Neurosurg1990; 73: 623–627.B. Himmelmann et al. Cerebral Relapse of Whipple’s DiseaseInfection 32 · 2004 · No. 2 © URBAN & VOGEL 121

Severe Hypothermia in a Patient withCerebral Relapse of Whipple's Disease

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Severe Hypothermia in a Patient withCerebral Relapse of Whipple's Disease

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