Whipple's disease with neurological manifestions: case report

Abstract

-Whipple´s disease (WD) is an uncommon multisystem condition caused by the bacillus Tropheryma whipplei. Central nervous system involvement is a classical feature of the disease observed in 20 to 40% of the patients. We report the case of a 62 yeards old man with WD that developed neurological manifestations during its course, and discuss the most usual signs and symptoms focusing on recent diagnostic criteria and novel treatment regimens.KEY WORDS: Whipple´s disease, inflammatory bowel disease, dementia, polyneuropathy. Doença de Whipple com manifestações neurológicas: relato de casoRESUMO -A doença de Whipple (DW) é distúrbio multissistêmico raro causado pelo bacilo Tropheryma whipplei. O envolvimento do sistema nervoso central é um aspecto clássico da doença, sendo observado em 20 a 40% dos pacientes. Relatamos o caso de homem de 62 anos com DW que desenvolveu manifestações neurológicas durante sua evolução, com o objetivo de discutir os sinais e sintomas mais comuns e destacar os critérios diagnósticos e propostas terapêuticas mais recentes. PALAVRAS-CHAVE: doença de Whipple, doença inflamatória intestinal, demência, polineuropatiaWhipple´s disease (WD) or intestinal lypodystrophy was first described in 1907 1 . It is a relatively rare multisystem disorder caused by the gram-positive bacillus Tropheryma whipplei.The usual presenting complaints include pronounced weight loss, mal-absorptive diarrhea (sometimes accompanied by abdominal cramping and bloody stool), recurrent non-deforming polyarthritis and longstanding low grade fever 2 . Cutaneous hyperpigmentation and lymphadenopathy are also common clinical signs. Central nervous system (CNS) involvement is a classical feature of WD observed in 20 to 40% of cases. CNS manifestations are myriad and usually develop in later stages of the illness 3 , often with cranial nerve and cognitive complaints. Approximately 5% of the patients follow an unusual presentation with isolated CNS symptoms 4 . Available data on CNS WD are scant, consisting basically of isolated case reports. Gerard et al. 3 found only 122 reported cases in the literature since 1960, most of them in Europe and North America. To our knowledge, the following case is the first to be reported in Brazil. CASEA 62-year-old white man, retired electrician, came to our Gastroenterologic Clinic in 1989 complaining of increased stool frequency and liquidity, associated with pronounced weight loss (20 Kg) in the last 2 years. Subsequent investigation disclosed a mal-absorptive syndrome, steatorrhoea and hepatosplenomegaly. Six months later, he developed bilateral knee arthritis which subsided spontaneously in two weeks. In 1990, an upper digestive endoscopy combined with multiple gastric and duodenal biopsies was performed. Histologic examination of the bowel specimens revealed flattened villi, small intestinal mucosa laden with distended foamy macrophages in the lamina propria and intracellular periodic acid Schiff (PAS) positive granules ( Figure 1A -1B). Acid-fast bacilli were not identified in Z...

Systematic review of movement disorders and oculomotor abnormalities in Whipple's disease

“…OMM and OFSM are now considered virtually pathognomonic for CNS‐WhD, and although it was stated in a single publication that these can be seen in rare cases of “oculopontocerebellar atrophy,” there is no clear evidence that OMM/OFSM occurs in disorders other than CNS‐WhD . However, OMM and OFSM are uncommon manifestations of WhD, occurring in only 8% to 20% of all CNS‐WhD cases and in 24% of those with MDs analyzed here.…”

“…Whipple's disease (WhD) is a rare but treatable infectious disease from Tropheryma whipplei (TW), with an estimated incidence of 0.4 to 1.0 per 1,000,000 a year . The brain follows the gastrointestinal tract as the second major site of involvement, with CNS involvement on postmortem found in up to 50% of cases, most frequently in a periventricular and periaqueductal distribution . The percentage of clinical CNS involvement varies considerably, ranging from 6% to 63%, with most estimates of 10%‐43%.…”

“…In approximately 5% of cases, the initial manifestations are purely neurological . CNS‐WhD can mimic almost any neurological disorder; its most common neurological manifestations include cognitive changes, an encephalopathy, a neuropsychiatric syndrome, hypothalamic manifestations, and oculomotor abnormalities, particularly vertical supranuclear gaze palsies (SGPs). Movement disorders (MDs) are common and account for about half of CNS‐WhD syndromes .…”

Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections

“…Symptoms associated with Whipple's disease range from abnormal movements (myoclonus, choreiform movements, oculomasticatory myorhythmia), hypersomnia, coma, ophthalmoplegia, cognitive impairment, frontal lobe syndrome, cerebellar ataxia, or upper motor neuron and extrapyramidal symptoms (127). It has even been suggested that there is a relation between T. whipplei infection and the development of Parkinson's disease (117,128,129), but it is unlikely that there is a causative relation. Although most Whipple's disease patients do not present any obvious neurological symptoms, postmortem investigation showed that 90% of brain and spinal cord specimens from both patients and presumed carriers revealed lesions of the CNS, meaning that CNS involvement is more common than expected from the clinical manifestations (33).…”