Hypersomnia in Whipple disease: case report

Abstract

-Whipple disease (WD) is a rare systemic infection caused by Tropheryma whippelii. Neurological involvement has been recognised in 40% of patients, either as initial manifestations or during the course of the disease. We report on a 45 years-old man with WD with initial, persistent and irresistible episodes of daytime somnolence. The patient was HLA-DQB1*0602 positive (genetic marker for narcolepsy). WD diagnosis was suspected on clinical and MRI basis and confirmed by histological and immunohistochemical study of duodenal biopsy. Forty months later all clinical features improved, narcoleptic-like episodes disappeared and cerebral MRI and CSF normalised. Longitudinal neurophysiological studies revealed persistent sleep pattern abnormalities with sleep fragmentation, paucity of slow wave and of REM sleep. The disruption of the hypocretin circuitry in the hypothalamic -diencephalic region triggered by the infection was the probable cause of the hypersomnia and narcopleptic symptoms. WD should be added to the list of causes of secondary hypersomnia.KEY WORDS: Whipple disease, hypersomnia, multiple sleep latency test, HLA (DQB1*0602). Hipersónia na doença de Whipple: relato de casoRESUMO -A doença de Whipple (DW) é infecção sistémica rara causada pelo Tropheryma whippelii. Cerca de 40% dos doentes apresentam envolvimento neurológico, seja como manifestação inicial da doença, seja durante o seu curso. Apresentamos o caso de um homem de 45 anos com doença de DW com episó-dios iniciais, persistentes e irresistíveis de sonolência durante a actividade diurna. O doente era positivo para o HLA-DQB1*0602 (marcador genético de narcolepsia). A suspeita do diagnóstico de DW foi levantada com base na clínica e RM e confirmada por estudo imunocitoquímico do material de biópsia jejunal. Quarenta meses mais tarde, todas as manifestações clínicas melhoraram, os episódios narcolépticos desapareceram, e a RM e o LCR normalizaram. Os estudos neurofisiológicos seriados do sono revelaram alterações persistentes caracterizadas por fragmentação do sono, escassez de ondas lentas e sono REM. A perturbação do circuito da hipocretina na região hipotálamo-diencefálica, causada pela infecção, foi a causa provável da hipersónia num doente geneticamente susceptível. A DW deve ser incluída nas causas de hipersónia secundária. PALAVRAS-CHAVE: doença de Whipple, hipersónia, teste de latências múltiplas, HLA (DQB1*0602).When George H Whipple first described in 1907 the autopsy findings of a case of "intestinal lipodystrophy" no neurological manifestations were reported and pathology of central nervous system (CNS) was not described. Whipple disease (WD) was born. It is now believed that the CNS is the major extra-intestinal site of involvement 1,2 . Data in the literature report a variable frequency of neurological symptomatology of 5-40% with only 5% with exclusive CNS involvement 1-4 . WD is caused by Tropheryma whippelii (TW) and it is generally accepted that both the presence of the bacillus and the host response are responsible for the ...

Whipple's disease presenting with segmental myoclonus and hypersomnia

“…Secondary narcolepsy from infectious, inflammatory, or ischemic lesion of the hypothalamus is rare 10. In addition to our patient, another previous report described a patient with CNS Whipple's disease presenting with sudden sleep attacks 11. However, whereas their patient tested positive for the DQB1*0602 haplotype for narcolepsy, ours did not, illustrating that a genetic predisposition is not necessary for a narcolepsy‐like presentation in CNS Whipple's disease.…”

Unusual presentation of hypothalamic hamartoma with hypersomnia in an adult patient

“…We were unable to check a lower orexin level in CSF or positivity of HLA‐DQB1* 0602 in serum to diagnose narcolepsy. However, SOREM episodes, as observed in classic forms, may be absent in patients with secondary narcolepsy (Bassetti et al ., ; Maia et al ., ).…”

“…We were unable to check a lower orexin level in CSF or positivity of HLA-DQB1* 0602 in serum to diagnose narcolepsy. However, SOREM episodes, as observed in classic forms, may be absent in patients with secondary narcolepsy (Bassetti et al, 2003;Maia et al, 2006). While most cases of narcolepsy are idiopathic and are not associated with clinical or radiographic evidence of brain pathology, secondary narcolepsy may occur occasionally in association with lesions of the diencephalon, midbrain, and pons.…”