Review articleIsolated inctracranial Whipple's disease—Report of a rare case and review of the literature
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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Primary Whipple disease of the Central Nervous System presenting with rhombencephalitis
2019, International Journal of Infectious DiseasesCitation Excerpt :Very few cases of primary CNS-WD confirmed by histological or microbiological examination with consensual negative gastrointestinal specimens are reported in the literature (Mohamed et al., 2011; Sung et al., 2012; Balasa et al., 2014; Panegyres et al., 2006; Peregrin and Malikova, 2015; Giaccone et al., 2016; Tábuas-Pereira et al., 2016; Kilani et al., 2018). Neurological presentation of CNS-WD is heterogeneous (Marth et al., 2016; Mohamed et al., 2011; Panegyres et al., 2006): cognitive changes and psychiatric symptoms are common, followed by hypothalamic symptoms, myoclonus and ataxia (Louis et al., 1996). Ocular movement disturbance, including oculomasticatory myorhythmia or oculo-facio-skeletal myorhythmia associated with progressive supranuclear ophthalmoplegia, are considered pathognomonic of CNS-WD although rarely reported (Louis et al., 1996) Overall, the triad of dementia, ophthalmoplegia and myoclonus is considered highly suggestive (Louis et al., 1996).
Neuro-ophthalmologic assessment and investigations in children and adults with cerebellar diseases
2018, Handbook of Clinical NeurologyCitation Excerpt :APN has been reported in patients with lesions along the dentatorubro-olivary pathways, i.e., the Guillain–Mollaret triangle (Shaikh et al., 2010) or associated nuclei (Lopez et al., 1996). Demyelinating disorders, including multiple sclerosis (Tilikete et al., 2011), pontine hemorrhage/myelinolysis often in combination with oculopalatal tremor (Shaikh et al., 2010) and infectious causes, e.g., Whipple disease, may result in APN (Schwartz et al., 1986; Mohamed et al., 2011). Periodic alternating nystagmus with reversal of the nystagmus direction every 90–120 seconds has been described in lesions of the nodulus and uvula (Waespe et al., 1985; Jeong et al., 2007), but it has also been reported in patients with neurodegenerative cerebellar disease such as SCA6, FRDA, and AT (Shaikh et al., 2009).
Whipple's disease
2017, Journal of the Neurological SciencesAcquired pendular nystagmus
2017, Journal of the Neurological SciencesDiagnostic Pathology: Neuropathology
2017, Diagnostic Pathology: NeuropathologyIsolated central nervous system Whipple's disease: Two cases
2015, Clinical Neurology and NeurosurgeryCitation Excerpt :From neurologists’ point of view, we recommend to add presence of suggestive clinicoradiological findings plus PAS positivity in brain biopsy and positive response to treatment to the criteria for possible CNS WD group. It is important to keep in mind that T. whipplei negativity in duodenal biopsy does not exclude WD diagnosis, but it means that the disease may be confined to CNS [12]. In conclusion, diagnosis of isolated cerebral WD is difficult, but early diagnosis is very important as the disease is rapidly progressive and fatal if left untreated.