Neither the patient nor the physician could see anything: Atypical Bing-Neel syndrome
Authors: Jean‐Louis Bacquet, Nicolas Weiss, Claire Meyniel, Caroline Algrin, Sylvain Choquet, Véronique Leblond, Damien Galanaud, Phuc LeHoang, Bahram Bodaghi, Valerie Touitou
Journal: American Journal of Hematology (2016)

An 80-year-old male patient with a history of Waldenström macroglobulinemia (WM) diagnosed two years earlier was referred for progressive bilateral vision loss. Visual acuity (VA) was 20/63 in the right eye (RE) and limited to hand motion perception in the left eye (LE) with a left relative afferent pupillary defect. Slit lamp and fundus appeared normal. Other clinical findings included ataxia and bilateral hearing loss. Fluorescein angiography demonstrated macular leakage in the LE (Image 1A) with macular edema on optical coherence tomography (Image 1B,C). Goldman visual field disclosed a large central scotoma in the LE and a caecocentral scotoma in the RE (Image 1D). Visual evoked potentials demonstrated bilateral optic neuropathy (ON) with increased latency and poorly structured waves (Image 1E). A serum monoclonal immunoglobulin was detected (IgM kappa) at 13.5 g/L and a bone marrow aspiration showed global decreased cell density but hyperplasia of lymphocytic cells with hyperbasophil nucleoles and irregular cytoplasm were detected. These lymphocytic modifications were also observed on peripheral blood. Cerebral MRI was considered as normal. Four successive lumbar punctures (LP) with cytology and immunophenotyping of the CSF did not reveal any atypical cells neither by cytology nor by flow cytometry. Because of the severe bilateral ON, the patient was treated with intravenous methylprednisone (500 mg/day for 5 days), without improvement of VA. Three weeks later, VA further decreased to 20/1,000 RE and 20/400 LE. Another MRI was performed and considered normal, but rereading of the images demonstrated minimal and localized enlargement of both optic nerves (Image 1F). According to these results and because of progression of the monoclonal component, chemotherapy by rituximab (375 mg/m2, D1), doxorubicin (25 mg/m2, D1), cyclophosphamide (600 mg/m2, D1), vincristine (1 mg/m2, D1), and cortancyl (40 mg/m2, D1–D5) and high-dose Methotrexate (2 g/m2 after adaptation of dosage) was started. On follow-up examination two months later, VA had improved to 20/50 RE and 20/80 LE, whereas pallor and cupping of both optic discs appeared. Visual field slowly improved (Image 1D), and macular edema decreased. Ataxia also improved. Six months after systemic chemotherapy, VA remained stable and the patient was in very good partial response with normal serum protein electrophoresis but positive serum immunofixation. The most frequent neurological complication of WM is IgM-mediated polyneuropathy whereas direct tumor cell infiltration of the nervous system is rare 1. “Bing and Neel syndrome” (BNS) is a very rare condition defined by an infiltration of the central nervous system (CNS) by neoplastic lymphoplasmacytoid and plasma cells with or without cerebrospinal fluid (CSF) hyperglobulinemia 2. The pathophysiology is not clear but probably involves hyperviscosity-related modifications leading to impaired circulation through the small brain and eye blood vessels 3-5. However, in our case, the level of the peak of Ig seems too low to be responsible for hyperviscosity and infiltration seems to be the main mechanism involved. The CSF findings in our patient failed to prove direct invasion of the CNS by lymphocytes or deposition of immunoglobulin despite repeated LP. Similarly, cerebral MRI did not disclose definite infiltration of the optic nerves. The difficulties to obtain clear evidence of CNS infiltration can be responsible for severe diagnostic delay. However, clinical presentation, radiological findings, and therapeutic response were strong arguments to support the diagnosis of BNS. Infiltration of the spinal cord and acoustic nerves were possibly responsible, respectively, for the ataxia and the hearing loss as both improved after chemotherapy. BNS is a rare condition that must be suspected in every patient with a history of WM presenting with neurologic manifestations, even if the LP is not contributive. Cerebral MRI has to be carefully studied, looking for minimal evidence of CNS infiltration. The favorable response to chemotherapy emphasizes the need to recognize BNS as early as possible for a better prognosis. Panel A: Fluoresceine angiography demonstrating discrete leakage of fluorescein in the left parafoveal region (arrow), increasing at late phase (double arrow), evocative of macular cystoid edema. Panel B: Optical coherence tomography (OCT) demonstrating the presence of cystoid macular edema (arrow) in the macular region of the left eye (right) compared to the right eye which is normal (left). Panel C: Macular retinal ganglion cell (RGC) study (upper part) demonstrating diffuse RGC loss in the left eye (right) and moderate RGC loss in the right eye (left) suggestive of bilateral optic neuropathy. OCT retinal nerve fiber layer analysis disclosing normal thickness of both optic nerves. Panel D: Goldman kinetic visual field demonstrating bilateral large central scotomas at presentation (upper part), improving during chemotherapy (interediate) and after chemotherapy (lower). Panel E: Pattern reversal visual evoked potentials (VEP): in March 2014, no recordable VEP. In April 2015, improvement of the VEP results showing normal amplitude of the P100 wave and slow peak time. Panel F: Cerebral MRI demonstrating minimal enlargement of the left optic nerve on axial T1 (left) and coronal T2 (right) sections.