Volume 2 (2012) // Issue 2 // e-ISSN 2224-3453 Neurology · Neurosurgery · Medical Oncology · Radiotherapy · Paediatric Neuro- oncology · Neuropathology · Neuroradiology · Neuroimaging · Nursing · Patient Issues Neurologic Complications in Homepage: Multiple Myeloma and Plasmacytoma Velasco R, Bruna J www.kup.at/ European Association of journals/eano/index.html NeuroOncology Magazine 2012; 2 (2) 71-77 OnlineOnline DatabaseDatabase FeaturingFeaturing Author,Author, KeyKey WordWord andand Full-TextFull-Text SearchSearch THE EUROPEAN ASSOCIATION OF NEUROONCOLOGY Member of the Neurologic Complications in Multiple Myeloma and Plasmacytoma Neurologic Complications in Multiple Myeloma and Plasmacytoma Roser Velasco, Jordi Bruna Abstract: Neurologic complications in plasma tely 10 % of all haematological malignancies. A tem involvement are being increasingly recog- cell malignancies are frequently seen in the wide spectrum of neurological complications has nized, like papilloedema, stroke, and pachyme- practice of neuro-oncology, involving areas such been described associated with MM, ranging ningitis. This review will focus on the neurologic as the peripheral and central nervous system. from carpal tunnel syndrome to the life-threa- complications associated with MM, plasmacy- These can be the first symptoms, leading to the tening spinal cord compression. Plasmacytoma toma, POEMS syndrome, and their management. diagnosis of the underlying disease, or they may is defined as a localized proliferation of malig- Furthermore, neurologic complications derived appear during the course of the illness. Radicular nant plasma cells, and it may eventually turn from treatment will also be reviewed, especially pain secondary to compressive radiculopathy is into MM. Plasmacytoma may occur inside or out- the treatment of emergent peripheral neuropathy. the most common neurologic complaint. Addi- side the bone marrow, with neurologic involve- Eur Assoc NeuroOncol Mag 2012; 2 (2): 71– tionally, neurotoxic side-effects derived from the ment depending on the placement of the mass. 7. first-line drugs employed are frequently observ- The POEMS syndrome is a paraneoplastic disor- ed during treatment of the malignancy, particu- der associated with the presence of a bone plas- Key words: multiple myeloma, plasmacytoma, larly sensory distal polyneuropathies. Multiple macytoma. Peripheral neuropathy is always pre- POEMS, neurological complications, neuropathy, myeloma (MM) is the most common malignant sent in the POEMS syndrome. Moreover, clinical neurotoxicity plasma cell disorder, accounting for approxima- manifestations secondary to central nervous sys- Introduction cally. Smoldering or asymptomatic MM is present when mo- noclonal protein > 3 gr/dl or infiltration at the bone marrow Malignant plasma cell dyscrasias are characterized by neo- (> 10 %) is not accompanied by CRAB symptoms [1, 3]. plastic proliferation of a single clone of plasma cells, typically producing a monoclonal immunoglobulin called paraprotein. Neurologic complications are frequent during plasmacytoma Among them, plasmacytoma and multiple myeloma (MM) and myeloma, and constitute the most frequent non-CRAB- represent a spectrum and probably the natural progression of presenting symptom in MM [4, 5]. Patients can present with the same illness. Plasmacytoma is defined by the presence of almost the whole spectrum of neurologic complaints, affect- a localized plasma cell tumour without evidence of neoplastic ing areas such as peripheral and central nervous system (Table 1). plasma cells in bone marrow (< 5 %) and absence of other fea- In this article, discussion focuses on neurologic complications tures of myeloma. Plasmacytoma most frequently occurs in associated with plasmacytoma and multiple myeloma, and the bone (plasmacytoma of bone), but can also be found outside therapies employed in their management. bone in soft tissues (extramedullary plasmacytoma). Both can present as solitary or multiple lesions, the latter more predic- tive of progression to myeloma. The POEMS syndrome is a Direct Complications of Myeloma and paraneoplastic disorder associated with the presence of a bone Plasmacytoma plasmacytoma and considered the same entity as osteoscle- rotic myeloma [1, 2]. Spinal Complications The most common neurologic complaint in these patients is Multiple myeloma (MM) is the most frequent malignant radicular pain, sometimes with associated weakness and plasma cell disorder, accounting for approximately 10 % of numbness, due to nerve-root compression by direct extension all haematological malignancies. MM is defined by the pres- of vertebral plasmacytoma or, more frequently, a pathological ence of paraprotein in the serum and/or urine (serum > 3 g/dl), vertebral fracture with secondary foraminal stenosis [5]. In at least 10 % neoplastic plasma cells in the bone marrow or this setting, the diagnostic approach is magnetic resonance their presence in other tissue, and evidence of end-organ dam- imaging (MRI) or computed tomography (CT) and electro- age, related to the underlying plasma cell disorder, including myography when needed. The most frequent local neurologic hypercalcaemia (C), renal failure (R), anaemia (A), and bone complication involving the central nervous system (CNS) is lesions (B), commonly named CRAB symptoms acronymi- spinal cord compression, which can be related with a bone fragment retropulsed from a vertebral fracture or extension of plasmacytoma arising from bone marrow of the vertebral body and extending to the anterior epidural area. Although Received on March 28, 2012; accepted on April 24, 2012; Pre-Publishing Online on May 16, 2012 incidence has decreased in recent years, partially because of From the Unit of Neuro-Oncology, Department of Neurology, Hospital Universitari extensive use of bisphosphonates, it still occurs in approxi- de Bellvitge-ICO Duran i Reynals, L’Hospitalet, Barcelona, and the Group of mately 5 % of patients with MM [5] and in 3 % as the present- Neuroplasticity and Regeneration, Institute of Neurosciences and Department of ing symptom [4]. The thoracic spinal cord is the most frequent Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona and level involved [6]. CIBERNED, Bellaterra, Spain Correspondence to: Roser Velasco, MD, Neuro-Oncology Unit, Department of Neurology, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Feixa Llarga s/n, Clinical features include back pain, which can be associated 08907 L’Hospitalet del Llobregat, Barcelona, Spain; with radicular pain and motor, sensory, and sphincter impair- e-mail: [email protected] ments to some degree, which can usually be mild and mani- EUR ASSOC NEUROONCOL MAG 2012; 2 (2) 71 For personal use only. Not to be reproduced without permission of Krause & Pachernegg GmbH. Neurologic Complications in Multiple Myeloma and Plasmacytoma fest abruptly when spinal cord compression occurs, making nial plasmacytomas are not specific and usually mimic other early diagnosis difficult and requiring great awareness by the neoplastic lesions, with pathology needed to establish the de- clinician. Back pain, mainly when recumbent in patients with finitive diagnosis. CT scan and MRI show well-defined de- myeloma, should arouse suspicion of this complication, with structive masses arising from osseus structures, or dural- mandatory spine MR. When a soft tissue mass is compromis- based mass that may appear iso- to hyperdense on CT scan, ing the nerve-root, radiotherapy or even surgical resection T1-weighted images iso- to high signal intensity, and T2- may be indicated, with analgesic and decompressive inten- weighted images with a hypointense signal on MRI, with vari- tion. The therapy of choice for spinal cord compression in able contrast enhancement [13]. Recently, PET-CT was these patients is radiotherapy, with long-course schedules of shown to detect extramedullar plasmacytomas also in the at least 30 Gy in 10 sessions [7] in addition to corticosteroids. CNS [14]. Among cranial plasmacytomas without MM at di- The role of decompressive laminectomy before radiotherapy agnosis, cranial base location seems to carry an increased risk is controversial. Current evidence does not support the use of of progression to MM compared to dural-based lesions [15]. surgical decompression, due to the similar outcome achieved with radiotherapy alone compared to surgery plus radio- Treatment of cranial plasmacytoma includes surgical resec- therapy [8, 9]. No specific therapy is usually indicated in nerve- tion with adjuvant focal radiotherapy [16]. When multiple root compression without soft tissue mass, and management plasmacytoma or MM is present, additional systemic chemo- of pain with medical treatment is the best approach [5]. therapy or even a transplant should be considered. Recently, cranial responses to new agents (bortezomib, thalidomide, Percutaneous vertebroplasty is a minimally invasive proce- lenalidomide) have been reported [12]. Much rarer is the pres- dure involving the injection of bone cement within a col- ence of an intraparenchymal brain plasmacytoma without evi- lapsed vertebral body, which is increasingly indicated in re- dence of extension from osseus or dura, which can be mani- lated MM pathological spinal fractures that cause pain unre- fested as brain haemorrhage [17]. sponsive to conservative treatment. This technique has anal- gesic and stabilizing effects on the spine, with demonstrated Prognosis of MM patients with osteodural plasmacytomas is effectiveness