The spectrum of central nervous system involvement in Whipple's disease

Abstract

Background and purposeTo assess the clinical spectrum of central nervous system (CNS) involvement as well as cerebrospinal fluid (CSF) and neuroimaging findings in patients with Whipple's disease (WD) and to analyze the association of neurological symptoms with CSF and imaging findings.MethodsNeurological involvement was retrospectively analyzed in a series of 36 patients diagnosed with WD at a single center between 1992 and 2019. Findings of 81 comprehensive CSF examinations from 36 patients, including polymerase chain reaction (PCR) tests for Tropheryma whipplei (TW) in CSF from 35 patients, were systematically evaluated. The prevalence of ischemic stroke in patients with WD was compared to a matched control cohort.ResultsNeurological symptoms occurred in 23 of 36 (63.9%) patients, with cognitive, motor, and oculomotor dysfunction being most frequent. TW was detected by PCR in CSF of 13 of 22 (59.1%) patients with and four of 13 (30.8%, p = 0.0496) patients without neurological symptoms. Total CSF protein (p = 0.044) and lactate (p = 0.035) were moderately elevated in WD with neurologic symptoms compared with WD without. No intrathecal immunoglobulin synthesis was observed. Three of 36 (8.3%) patients had hydrocephalus due to aqueductal stenosis. Patients with WD had an unexpectedly high prevalence of ischemic stroke (10/36, 27.7%) compared to matched controls (10/360, 3.2%).ConclusionsNeurological involvement in patients with WD is common. Detection of TW DNA in CSF is only partly associated with neurological symptoms. Elevated CSF parameters suggest CNS parenchymal infection. Stroke is a hitherto underrecognized manifestation of WD. These findings suggest that mechanisms beyond CNS infection contribute to the spectrum of CNS involvement in WD.

Whipple's disease with early central nervous system damage: a case report

“…Foreign literature [4,7] reported that nervous system involvement in WD usually occurs after gastrointestinal symptoms and/or other systemic symptoms, usually with insidious onset and slow progress, and some patients may deteriorate suddenly. Approximately 80% of WD with CNS involvement is accompanied by involvement of other systems.…”

Why Is Whipple's Disease Still a Challenging Diagnosis? A Case Report and Brief Review of Literature

“…The prevalence of neurological involvement is 6%-63% [ 1 - 3 , 6 ], presenting with confusion or coma due to meningoencephalitis or status epilepticus, cognitive impairment with memory loss and attention deficit, pyramidal, and extrapyramidal symptoms, sleep disorders, cerebellar palsy, abnormal involuntary movements (including oculomasticatory or oculofacial-skeletal myorhythmia), oculomotor nerve palsy and progressive dementia [ 7 ]. Analysis of CSF reveals normal cytology in around half of the patients with neurological symptoms, with the remainder of cases having a CSF compatible with lymphocytic meningitis, with normal or high protein levels [ 7 , 8 , 10 ]. Despite this, detection of T. whipplei through PCR seems to be as high as 41%-63% of all cases of classic WD who underwent lumbar punction, even without neurological symptoms [ 2 , 10 , 11 ].…”

“…Analysis of CSF reveals normal cytology in around half of the patients with neurological symptoms, with the remainder of cases having a CSF compatible with lymphocytic meningitis, with normal or high protein levels [ 7 , 8 , 10 ]. Despite this, detection of T. whipplei through PCR seems to be as high as 41%-63% of all cases of classic WD who underwent lumbar punction, even without neurological symptoms [ 2 , 10 , 11 ]. If neurologic symptoms are present, up to 59.1%-92% have a positive PCR for T. whipplei [ 2 , 7 , 10 ].…”

“…Despite this, detection of T. whipplei through PCR seems to be as high as 41%-63% of all cases of classic WD who underwent lumbar punction, even without neurological symptoms [ 2 , 10 , 11 ]. If neurologic symptoms are present, up to 59.1%-92% have a positive PCR for T. whipplei [ 2 , 7 , 10 ]. Brain imaging can be normal or show focal or multifocal lesions, particularly in a supratentorial localization.…”

“…Additionally, periventricular diffuse leukopathy, diffuse cortical atrophy, and pachymeningitis can be seen. Brain MRI seems to have a better performance than CT in detecting alterations [ 7 , 8 , 10 ]. In this case report, neurological involvement was pronounced during admission, and no other etiology was found.…”