A 66 year-old woman with Waldenstrom macroglobulinemia (WM), hypertension, and hyperlipidemia presented with acute altered mental status. She had been diagnosed with WM by bone marrow biopsy and was treated with rituximab, then maintained on thalidomide until 2 months prior to presentation. Her mother had suffered from multiple myeloma.
Vital signs were normal. Patient was fully oriented. She was unable to spell the word ‘WORLD’ backwards, but had normal repetition. Cranial nerves II-XII were intact. Ophthalmic evaluation was unremarkable. She had normal strength, sensation, cerebellar tests, and Babinski reflex. Non-contrast head CT was within normal limits. Labs were unremarkable. MRI brain showed acute infarctions involving the cortical surface of the parietal lobes (Fig 1A, 1B). Lumbar puncture showed only mildly elevated proteins. WM labs showed elevated IgM of 2250 mg/dL [reference range 40-260], normal IgA level, and low IgG of 236 mg/dL [reference range 741-1861]. Serum viscosity was 1.89 cP [reference range 1.10 – 1.80]. Bacterial and viral infectious workup, autoimmune and systemic vasculitis workup (including cryoglobulinemia) were negative.
Due to acute left hemiparesis, repeat brain MRI was obtained on the second day, which showed multifocal cortical infarctions (Fig 1C, 1D). MRA showed small peripheral branches of the cerebral arteries, and cerebral angiogram confirmed multifocal small vessel vasculitis (Fig 1E). Cyclophosphamide was added, and the patient’s mental status and neurologic deficits gradually improved. Patient was discharged to rehabilitation center with prednisone and cyclophosphamide, both of which were successfully tapered in the year after discharge.
Discussion:
WM is an indolent B cell lymphoproliferative disorder characterized by a monoclonal IgM protein in the serum. Neurologic complications occur in up to 50%, mostly manifesting as peripheral neuropathy or as clinical symptoms of hyperviscosity. Vasculitis has been associated with WM only when in the presence of cryoglobulins, immunoglobulins that reversibly precipitate at temperatures < 37 °C and that can lead to immune complex-mediated vasculitis. However, our patient tested negative for cryoglobulins, and workup was also negative for secondary causes of CNS vasculitis, and serum viscosity value was not elevated appreciatively. Cutaneous and systemic vasculitis has been uncommonly associated with other lymphoproliferative disorders in the absence of cryoglobulins. Therefore, it’s plausible that WM may lead to CNS vasculitis independent of cryoglobulins. Importantly, our patient experienced stabilization and improvement of symptoms upon treatment with steroids and cyclophosphamide, both of which are also useful in managing WM.
Conclusions:
We present a patient with CNS vasculitis associated with WM. It’s crucial for hospitalist to be aware of differential causes of multiple stroke.