@article{PAR00011499,
  title = {{C}entral nervous system involvement in {W}hipple disease clinical study of 18 patients and long-term follow-up},
  author = {{C}ompain, {C}. and {S}acre, {K}. and {P}uechal, {X}. and {K}lein, {I}. and {V}ital-{D}urand, {D}. and {H}oueto, {J}. {L}. and {D}e {B}roucker, {T}. and {R}aoult, {D}idier and {P}apo, {T}.},
  editor = {},
  language = {{ENG}},
  abstract = {{W}hipple disease ({WD}) is a rare multisystemic infection with a protean clinical presentation. {T}he central nervous system ({CNS}) is involved in 3 situations: {CNS} involvement in classic {WD}, {CNS} relapse in previously treated {WD}, and isolated {CNS} infection. {W}e retrospectively analyzed clinical features, diagnostic workup, brain imaging, cerebrospinal fluid ({CSF}) study, treatment, and follow-up data in 18 patients with {WD} and {CNS} infection. {T}en men and 8 women were included with a median age at diagnosis of 47 years (range, 30-56 yr). {T}he median follow-up duration was 6 years (range, 1-19 yr). {A}s categorized in the 3 subgroups, 11 patients had classic {WD} with {CNS} involvement, 4 had an isolated {CNS} infection, and 3 had a neurologic relapse of previously treated {WD}. {CNS} involvement occurred during prolonged trimethoprim-sulfamethoxazole ({TMP}-{SMX}) treatment in 1 patient with classic {WD}. {T}he neurologic symptoms were various and always intermingled, as follows: confusion or coma (17%) related to meningo-encephalitis or status epilepticus; delirium (17%); cognitive impairment (61%) including memory loss and attention defects or typical frontal lobe syndrome; hypersomnia (17%); abnormal movements (myoclonus, choreiform movements, oculomasticatory myorhythmia) (39%); cerebellar ataxia (11%); upper motor neuron (44%) or extrapyramidal symptoms (33%); and ophthalmoplegia (17%) in conjunction or not with progressive supranuclear palsy. {N}o specific pattern was correlated with any subgroup. {B}rain magnetic resonance imaging ({MRI}) revealed a unique focal lesion (35%), mostly as a tumorlike brain lesion, or multifocal lesions (23%) involving the medial temporal lobe, midbrain, hypothalamus, and thalamus. {P}eriventricular diffuse leukopathy (6%), diffuse cortical atrophy (18%), and pachymeningitis (12%) were observed. {T}he spinal cord was involved in 2 cases. {MRI} showed ischemic sequelae at diagnosis or during follow-up in 4 patients. {B}rain {MRI} was normal despite neurologic symptoms in 3 cases. {CSF} cytology was normal in 62% of patients, whereas {T}ropheryma whipplei polymerase chain reaction ({PCR}) analysis was positive in 92% of cases with tested {CSF}. {P}eriodic acid-{S}chiff ({PAS})positive cells were identified in cerebral biopsies of 4 patients. {A}ll patients were treated with antimicrobial therapy for a mean duration of 2 years (range, 1-7 yr) with either oral monotherapy ({TMP}-{SMX}, doxycycline, third-generation cephalosporins) or a combination of antibiotics that sometimes followed parenteral treatment with beta-lactams and aminoglycosides. {E}ight patients also received hydroxychloroquine. {A}t the end of follow-up, the clinical outcome was favorable in 14 patients (78%), with mild to moderate sequelae in 9. {T}hirteen patients (72%) had stopped treatment for an average time of 4 years (range, 0.7-14 yr). {F}our patients had clinical worsening despite antimicrobial therapy; 2 of those died following diffuse encephalitis (n = 1) and lung infection (n = 1). {I}n conclusion, the neurologic manifestations of {WD} are diverse and may mimic almost any neurologic condition. {B}rain involvement may occur during or after {TMP}-{SMX} treatment. {CSF} {T}. whipplei {PCR} analysis is a major tool for diagnosis and may be positive in the absence of meningitis. {I}mmune reconstitution syndrome may occur in the early months of treatment. {L}ate prognosis may be better than previously reported, as a consequence of earlier diagnosis and a better use of antimicrobial therapy, including hydroxychloroquine and doxycycline combination.},
  keywords = {},
  booktitle = {},
  journal = {{M}edicine},
  volume = {92},
  numero = {6},
  pages = {324--330},
  ISSN = {0025-7974},
  year = {2013},
  DOI = {10.1097/md.0000000000000010},
  URL = {https://www.documentation.ird.fr/hor/{PAR}00011499},
}