Cerebral granulomatosis as a manifestation of Crohn’s disease

Abstract

BackgroundCrohn’s disease (CD) is associated with a variety of extra-intestinal manifestations. Most commonly these involve the eye, skin, joints, coagulation system and liver. Cerebral manifestations of CD have been reported to a far lesser extent. The extensive detrimental impact of neurological symptoms on a patient’s quality of life makes an early diagnosis and treatment particularly important. In previous case-reports, diagnosis of cerebral manifestations in CD often relied upon magnetic resonance imaging (MRI) and computed tomography (CT) alone. To our knowledge, only one case-report has documented a histologically confirmed case of cerebral lesions associated with CD so far.Case presentationA 39-year-old right-handed woman with a history of CD was referred to our hospital with etiologically unexplained Gadolinium (Gd)-enhancing cortical lesions, triggering epileptic seizures. A CT-scan of the thorax and bronchoalveolar lavage found no signs of sarcoidosis. Lumbar punctures and laboratory testing found no underlying infection or coincidental autoimmune disorders and MRI-scans showed progression of lesion load. Consequently, the patient underwent stereotactic biopsy of a cortical lesion. Histological examination revealed a mixed lympho-histiocytic and tuberculoid granulomatous inflammation surrounding small vessels and no signs for infection. After exclusion of other granulomatous diseases and the typical histological findings we diagnosed a cerebral granulomatosis as a manifestation of CD. The patient was initially started on azathioprine, which had to be switched to corticosteroids and methotrexate because of an azathioprine related pancreatitis. The patient has not suffered any further epileptic seizures to date.ConclusionCerebral manifestation of CD is a possibly underreported entity that may respond well to immunosuppressive treatment. In contrast to earlier reports of cerebral manifestations in CD, our patient showed no coincident gastrointestinal symptoms indicating an activity of CD during the progression of cortical lesion load, suggesting that similar to other extra-intestinal manifestations in CD, the activity of gastrointestinal symptoms does not necessarily reflect the activity of CD associated cerebral vasculitis. Therefore, diagnosis and therapy of cerebral manifestation may be delayed when focusing on gastrointestinal symptoms alone.

Clinical Reasoning: New-Onset Diplopia and Headache in a Patient With Metastatic Breast Cancer

“…However, reports of direct CNS involvement in Crohn disease are rare and involve cerebral lesions with a single case of pachymeningitis reported in a patient with coexisting relapsing polychondritis. 10,11 This case also raises the potential association between malignancy and granulomatous inflammation. The term "sarcoidlike reaction" (SLR) is sometimes used in the literature to designate the presence of noncaseating granuloma pathologically indistinguishable from sarcoidosis but hypothesized to be triggered by an antigen, commonly in the setting of malignancy or medication.…”

“…While the patient did not have active gastrointestinal disease, it is recognized that extraintestinal manifestations often do not parallel intestinal disease; furthermore, the patient's long-term immunosuppression had been ceased. However, reports of direct CNS involvement in Crohn's disease are rare and involve cerebral lesions with a single case of pachymeningitis reported in a patient with co-existing relapsing polychondritis 10,11 .…”

“…However, reports of direct CNS involvement in Crohn disease are rare and involve cerebral lesions with a single case of pachymeningitis reported in a patient with coexisting relapsing polychondritis. 10,11…”

RORγt-Expressing Pathogenic CD4+T Cells Cause Brain Inflammation During Chronic Colitis

“…Studies of animal models with colonic inflammation have shown regionspecific changes in the CNS that correlated with expressions of inflammatory genes in the brain (23)(24)(25). In support of this, a study has shown that CD3 + CD4 + T lymphocytes accumulate in a granuloma-like lesions in the brain of an IBD patient, suggesting that CD4 + T lymphocytes infiltrate the brain during IBD and cause inflammation (48).…”

Concomitant Crohn’s Disease and Anti-Glutamic Acid Decarboxylase (GAD)-Associated Autoimmune Encephalitis: A Case Report

“…Neurological complications are documented in 0.2% to 35.7% of Crohn's disease patients [ 1 ], especially in patients on anti-tumor necrosis factor (TNF) therapy [ 2 ], or attributed to Wernicke syndrome caused by vitamin B1 deficiency [ 3 ]. However, the central nervous system involvement in Crohn’s disease patients without a history of immunomodulatory treatments or dietary deficits [ 4 ], autoimmune encephalitis caused by anti-N-methyl-D-aspartate-receptor (NMDAR) [ 2 ], and anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease [ 5 ] have been reported recently. Herein, we present a case with anti-GAD-associated autoimmune encephalitis that developed shortly after the onset of Crohn's disease.…”