Bing-Neel Syndrome at Diagnosis of Waldenstrom: An Extremely Rare Case Report

BACKBGROUND:

Bing-Neel syndrome (BNS) is an extremely rare neurologic complication of Waldenström macroglobulinemia (WM) that was first described in 1936 by Jens Bing and Axel Valdemar Neel. It is associated with central nervous system infiltration by neoplastic lymphoplasmacytoid and plasma cells with or without cerebrospinal fluid (CSF) hyperglobulinemia.

Herein we report one case of a BNS, presented with central nervous system infiltration at diagnosis. We discuss its epidemiology, presentation, diagnosis and treatment.

CASE PERESENTATION

A 65-year-old man, was admitted to our hospital with no previous medical history presenting episodes of confusion, slurred speech, headache, fatigue, ataxia and memory problems.

Neurological examination revealed left hemiparesis and abnormal pupillary response; normal cranial nerve III, IV, VI examination; Bell's palsy present characterized by left-sided facial droop, pathological Barre Test of the left upper and lower limb and pathological Babinski's sign left; the assessment of the sensory neuron responses did not reveal any findings; the muscular mass was hypotonic and hypotrophic.

Initial investigations revealed a normal CBC; biochemical investigations were within normal ranges; thyroid investigation was normal; immunology investigations: IgG 3,02 g/L, IgA <0.25 g/L, IgM 8.80 g/L, serum β2-microglobulin 2640 μg/dL, serum free κ 25,40 mg/L, serum free λ 9,01 mg/L and serum free-κ/free-λ 2,82. His serum immunofixation examination revealed an IgM kappa monoclonal gammopathy.

Examination of the cerebrospinal fluid (CSF) showed an decrease of the CSF protein (<0.8 mg/dL), and an increased CSF glucose (86 mg/dL) but no organisms were seen or cultured. The CSF protein electrophoresis revealed the presence of a monoclonal IgM kappa similar to the plasma's one.

Neuro-imaging included a brain CT which showed a pathological density area in the left frontal lobe and right occipital area. A later both MRI brain and Magnetic resonance spectroscopy displayed pathological intensity signals in the same areas revealing a tumoral form of BNS.

The bone marrow biopsy revealed the presence of a lymphoplasmacytoid and plasma cells infiltration ~50-55% and monoclonal CIgM(κ) (Waldenström macroglobulinemia - WHO 2008)

Once the diagnosis was confirmed our patient underwent first line treatment with five cycles of rituximab 500mg/m² and methotraxate 3.5gr/m² repeated every 15 days combined with intrathecal chemotherapy with cytarabine 40mg, dexamethasone 4mg and methotrexate 12.5mg repeated every second week. Partial remission confirmed by MRI was obtained after 5 cycles of chemotherapy, the patient improved all his neurological manifestations and his IgM levels decrised to normal.

The patient then initiated chemotherapy regimen with cytarabin (4 doses of 2 g/m²). However, very fast, after the first two cycles the disease progressed and he was admitted to our hospital presenting episodes of confusion, slurred speech, ataxia and memory problems. Progressive disease was also comfirmed by an MRI.

The fact that the neoplastic cells in Waldenstrom's macroglobulinemia originate from immature lymphocytes suggests that they are sensitive to irradiation therapy. Therefore, cranial radiation therapy was then started combined with rituximab and intrathecal chemotherapy. His neurological complications resided fast. Partial remission was confirmed by MRI. Nine months after diagnosis the patient is in partial remission receiving treatment with rituximab and intrathecal chemotherapy.

CONCLUSION

Bing-Neel syndrome is an extremely rare complication of Waldenström's macroglobulinaemia with only a few such cases reported to date. Identifying such patients is a clinical challenge, especially when a patient is presented without a known history of WM.

Taking in consideration the severe prognosis of BNS and since there is still no consensus on the treatment of BNS the most difficult decisions to make are the ones related to the best therapeutic approach and the best suitable chemotherapy regimen.

Although the follow-up period in our case is not long enough to confirm the efficacy of chemotherapy and irradiation therapy, it is nevertheless a valuable asset to the very few reported cases (less than 50) and such clinical experience when reported could allow us to determine a potential cure to this poor prognosis syndrome.