Review article
Isolated inctracranial Whipple's disease—Report of a rare case and review of the literature

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Abstract

Introduction

Whipple's disease (WD) is a rare multisystemic infectious disease that can involve a variety of organs namely the gastrointestinal tract, lymphatic system, heart and nervous system. Myorhythmia is a hallmark of WD. Isolated CNS involvement is very rare.

Case

We present a 50 year-old African-American woman with rapid cognitive decline, visual hallucinations, insomnia, dysarthria, and gait unsteadiness. She subsequently developed pendular nystagmus and gaze paresis. Serial brain MRI scans showed T2 hyperintense lesions in the left striatum and right parahippocampal gyrus. FDG-PET scan showed marked increase of glucose uptake in the left putamen. Serum and CSF PCR for Tropheryma whipplei was negative. Stereotactic biopsy of the lesion and tissue PCR was consistent with WD.

Review of literature

A systematic review identified 24 cases of isolated intracranial presentation of WD since 1975. Cases with systemic and extracranial manifestations were excluded.

Discussion

In patients with rapidly progressive cognitive decline with negative workup for common etiologies, there should be a high index of suspicion for WD. Diagnosis of WD remains a challenge as traditional methods commonly fail to culture T. whipplei. PET scans can help in identifying areas of inflammation that can be biopsied. Our case proves that a negative serum and CSF PCR should not exclude CNS WD and a brain biopsy of the lesion with PCR assay should be performed when possible.

Introduction

Whipple's disease (WD) is a rare multisystem disease of infectious etiology, caused by a gram positive bacillus belonging to the Actinomyces family, Tropheryma whipplei [1]. It is a soil-borne infection and has been implicated in patients with underlying immunosuppressive conditions. This chronic infection, characterized by predominant intestinal involvement, can also involve a variety of other organs, such as the lymphatic system, the heart, and the central nervous system (CNS) [2]. In patients with intestinal involvement, abdominal pain, diarrhea, weight loss, malabsorption, wasting, low-grade fever, arthralgia, increased skin pigmentation, and peripheral lymphadenopathy have been described [3].

The largest series of patients with systemic T. whipplei was reported by Lagier et al. in 2010 [4]. This series includes 142 patients with PCR and histologic analyses confirming systemic WD. Among these, 113 individuals were found to have “classic WD” defined as positive results of periodic acid-Schiff (PAS) staining and/or specific immunohistochemistry of the small bowel biopsy specimens.

Diagnosis of WD remained a challenge as traditional methods failed to isolate T. whipplei in culture. In fact, treatment has largely been based on identification of the causative organism by amplification of the bacterial DNA present in the diseased tissue by the polymerase chain reaction (PCR) [5]. In 1991, Wilson et al. detected the etiologic pathogen by PCR amplification of the bacterial 16S ribosomal DNA from a small bowel biopsy specimen from a patient with WD [6]. In 2000, Raoult and colleagues successfully isolated and grew the microbial pathogen by inoculation in a human fibroblast cell line [7].

Myorhythmia (oculomasticatory myorhythmia and oculofacial skeletal myorhythmia) is a hallmark of WD [8], [9], [10], [11]. CNS involvement has been described in 10 to 43% of patients diagnosed with WD and can be limited to the cerebrum, spinal cord, or peripheral nervous system [12]. Isolated intracranial WD is particularly rare [13]. A majority of patients with intracranial WD have abnormal cerebrospinal fluid (CSF) findings. A positive CSF PCR assay has previously proven essential in the diagnosis of CNS involvement with WD [12], [14], [15]. Duodenal biopsies at multiple levels examined under light microscopy, electron microscopy, and by PCR may be positive even in patients with isolated neurological manifestations [16]. When all tests these are negative, stereotactic brain biopsy and PCR assay of the nervous tissue specimen should be performed on patients with a high suspicion for WD [12], [16].

We present the challenging case of a 50 year-old African-American woman presenting with isolated cerebral WD.

Section snippets

Clinical history and physical examination

A 50 year-old right-handed African-American woman with history of hypertension and asthma presented with a 5-month history of rapid cognitive decline. The patient's family noticed her having difficulties with paying her bills on time, completing tasks at work, forgetting passwords, which progressed to getting lost in familiar surroundings. Over these few months, she developed visual hallucinations, insomnia, dysarthria, and gait unsteadiness. She was admitted to another hospital with new-onset

Clinical presentation of Whipple's disease

The clinical presentation of WD encompasses a wide array of symptoms. Classic WD presents with an initial prodrome followed by a chronic and steady-state stage, the average interval between the two stages being observed to be approximately 6 years [17]. The prodromal stage consists of chronic non-specific symptoms such as arthralgias or abdominal pain. The steady-state is characterized by weight loss, diarrhea, and symptoms based on specific organ involvement. Occult gastrointestinal bleeding

Conclusion

Isolated cerebral WD often poses a great diagnostic challenge. In patients presenting with rapidly progressive cognitive decline and other neurological signs but no other systemic symptoms or signs, a high index of suspicion for isolated intracranial WD is required. Our case proves that a negative serum and CSF PCR for Tropheryma whipplei should not exclude cerebral WD as a potential diagnosis. This is consistent with our review of literature in which only 2, out of the 7 patients that

Acknowledgments

We would like to thank Edwin B. George, MD, PhD from the Department of Neurology for help with the video of the ocular findings and Mr. Brandon Parker from the Department of Neurosurgery for editorial assistance.

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