Embolic Infarction with Subdural Hemorrhage in Erdheim-Chester Disease

Dear Editor,

A 59-year-old female with hydronephrosis and renal tuberculosis was treated on an inpatient basis with antituberculosis medication and nephrectomy. Preoperative transthoracic echocardiography and abdominal CT showed pericardial effusion. She developed dyspnea following discharge, and follow-up echocardiography indicated aggravated pericardial effusion. A pericardial biopsy showed scattered chronic inflammatory cells that were focally positive for CD68 and negative for CD1a (Fig. 1A and B). The biopsy specimen that was subsequently obtained during nephrectomy was reviewed for the presence of extensive perirenal fibrosis with lymphohistiocytic inflammatory cell infiltrate. Erdheim-Chester disease (ECD) was suspected, and leg X-ray, lower extremity CT, and brain MRI were performed to check for multiple organ involvement. The X-ray revealed bilateral patchy sclerosis of the distal femur, tibia, and fibula with cortical thickening, while the lower extremity CT revealed irregular heterogeneous sclerosis with prominent trabeculation in the femoral necks, and epiphysis of the femur, tibia, fibula, and tarsals (Fig. 1C, D, and E). Moreover, circumferential thickening of the lesion was observed along both optic nerves in MRI (Fig. 1F), and both cerebellar tentoria were thickened diffusely in T1-weighted contrast-enhanced MRI (Fig. 1G). Genetic testing did not detect any BRAF V600E mutation.¹

Fig. 1. The histopathologic findings and images of the patient. (A) Immunohistochemistry stain showing an excisional biopsy specimen from the pericardium that was focally positive for CD68 histiocytes (10×40) and (B) focally negative for immunohistochemical stain for CD1a histiocytes (10×40). C: Patchy sclerosis in the distal femur (arrowhead). D: Subcutaneous edema in both legs (arrow). E: A radiolucent band between the metaphysis and epiphysis. F: Meningeal thickening along both optic nerves in fluid-attenuated inversion recovery MRI (arrowheads). G: Diffuse thickening of both cerebellar tentoria with strong enhancement. H: Thin subdural hemorrhage in the right posterior aspect of the interhemispheric fissure adjacent to the occipital lobe in brain CT. I: CT performed 1 week later reveals that the hemorrhage was resolving. J: Diffusion-weighted MRI showing acute infarctions in the left cerebellar hemisphere and left parietal lobe.

The patient was readmitted for a femoral neck fracture 1 year after her diagnosis of ECD. During her hospitalization, she was referred to the department of neurology because of an altered state of consciousness and right hemiparesis. Brain CT revealed subdural hemorrhage (SDH) in the right occipital convexity (Fig. 1H), which was resolving in repeated brain CT performed 1 week later (Fig. 1I). Moreover, brain MRI revealed multiple high-signal-intensity lesions in the left cerebellum and left parietal lobe, suggestive of acute cerebral infarction (Fig. 1J). Subsequent echocardiography and 24-hour electrocardiographic monitoring revealed no cardioembolic sources.

ECD was first reported by Erdheim and Chester in 1930; it is a rare disease, although its precise prevalence is unknown. Pathologically, ECD is a non-Langerhans-cell histiocytic disease that invades multiple organs, including the bone marrow, with bone and central nervous system (CNS) involvement seen in more than 40% of patients.² ECD is characterized by xanthogranulomatous infiltration, and is commonly associated with periorbital involvement. However, the mechanism underlying stroke due to ECD is poorly understood.³

CNS involvement in ECD is associated with a poor prognosis.⁴ CNS involvement, including involvement of the cerebellar tentorium and optic nerve, was confirmed in the present patient, and an ischemic stroke of embolic nature and SDH of nontraumatic origin were also observed—the ischemic stroke was found to be an embolic pattern and the hemorrhage was a nontraumatic hemorrhage. The mechanism and prevalence of ischemic strokes in patients with ECD are unclear. No cardioembolic sources were identified in the etiological workup of the ischemic stroke in the present patient, and the cause of the artery-to-artery embolism due to ECD was also not determined. Although the stroke was cryptogenic in this case, ECD is primarily a hematological disease caused by abnormal multiplication of histiocytes, which makes it difficult to exclude the possibility of hypercoagulability. The D-dimer level was elevated in this patient (9.8 mg/L), suggesting that the embolic infarction was caused by hypercoagulability. Moreover, hemorrhage can occur in the dura—which is a vulnerable area—without external injuries because of dura involvement in ECD. The presence of significant large-vessel involvement and embolic infarction in that vascular territory would have made it easier to demonstrate the stroke etiology. The present rare presentation of embolic infarction coexisting with nontraumatic SDH in a rare disease (i.e., ECD) is meaningful for future studies of stroke in ECD.