Leukemia & Lymphoma | 2021
Paraneoplastic cerebellar degeneration in a patient with multiple myeloma
Abstract
Multiple myeloma (MM) is a plasma cell dyscrasia characterized by bone marrow infiltration of monoclonal plasma cells, hypercalcemia, bone pain, anemia and impaired kidney function [1]. Neurological symptoms occur mostly due to anemia, hypercalcemia or hyperviscosity of the blood. While peripheral neuropathy may also be occasionally encountered, central nervous system (CNS) involvement is quite rare in MM [1]. In the CNS, MM may manifest as a primary or metastatic tumor mass or CNS myelomatosis, which is confirmed by demonstration of plasma cells in the cerebrospinal fluid (CSF) [2–4]. Opportunistic infections due to immunosuppressive medications (e.g. progressive multifocal leukoencephalopathy) should also be considered in MM patients with CNS symptoms [5]. Paraneoplastic disease of the CNS is quite unusual in MM and only a few putatively paraneoplastic cases have been described. More specifically, involvement of lower brainstem, spinal cord, cerebellum and diffuse white matter regions has been reported in treatment-naive MM cases with no primary or metastatic tumor infiltration of the CNS [6–11]. Although these cases suggest that paraneoplastic disease mechanisms may partake in neurological complications of MM, the autoimmune nature of this association has often not been properly investigated. A 65-year-old man with a past medical history of diabetes, hypertension and coronary artery disease, presented with progressive truncal ataxia, dysarthria, hand tremor and short-term memory loss for three months. Neurological examination revealed a cerebellar syndrome with dysarthric speech, severe truncal, and mild appendicular ataxia without any motor or sensory deficits. Brain MRI showed cerebellar atrophy with nonspecific supratentorial white matter hyperintensities (Figure 1), whereas spinal MRI was normal. Complete blood count and chemistry were normal. CSF examination showed normal lymphocyte (3/mm), protein (45mg/dl), glucose (58mg/dl) and IgG index (0.47) values. Pattern 5 CSF oligoclonal bands were detected. Pathological examination of multiple CSF samples did not reveal any tumor cells. Antibodies to serum amphiphysin, CV2, Ma2, Ri, Yo, Hu, Zic4, Tr and voltage-gated calcium channel antibodies were found negative in serum. Likewise, antibodies to NMDAR, AMPAR1/R2, GABABR, LGI1, CASPR2, GAD and DPPX were found negative in serum and CSF (Euroimmun, Luebeck, Germany). The immunoelectrophoresis test showed kappa light chains in the serum and urine. The patient’s whole-body PET-CT did not show any abnormal features. The bone marrow biopsy demonstrated neoplastic plasma cell infiltration with kappa light chain phenotype confirming MM. The patient initially received nine days of methylprednisolone 1000mg/day treatment without benefit. Then, he was treated with bortezomib, cyclophosphamide and oral steroids. The patient’s cerebellar findings continued to progress despite treatment and he died due to pulmonary embolism six months after the diagnosis. Paraneoplastic etiology was considered in this case due to absence of evidence for tumoral infiltration of the CNS or cerebrovascular accident, normal blood biochemistry and CSF analysis results and temporal precedence of neurological symptoms to cancer diagnosis. Since the patient was treatment-naïve during admission, drug side effect was also not considered. Demonstration of wellcharacterized anti-neuronal antibodies may support paraneoplastic etiology but is not definitely necessary, as per relevant criteria, if a classical paraneoplastic disorder (such as cerebellar degeneration) and close temporal association (less than 5 years) with cancer onset is verified [12]. Cerebellar involvement in MM patients has usually been reported to occur due to cerebellar metastasis or opportunistic infections [2,5]. In a few MM cases, cerebellar syndrome has been reported in the absence of any identifiable etiology, as in our case [7,10,11]. These cases bear close resemblance to ours in terms of clinical findings and remarkably dismal clinical outcome. An anti-neuronal antibody screening has not been conducted in these cases, except for one MM case with encephalopathy, cerebellar symptoms and seropositivity for GABABR antibody [7]. Demonstration of GABABR antibodies in this latter case emphasizes autoimmune paraneoplastic etiology in CNS complications of MM. Notably, paraneoplastic complications may also occur in MM due to non-antibody