Multiple myeloma (MM) is a cancer originating in the plasma cells, a type of white blood cell housed within the bone marrow. These malignant plasma cells accumulate, typically causing damage to the bones, kidney dysfunction, and affecting the blood’s composition. MM is a systemic disease that often manifests in the skeletal structure. This article focuses on the rare, but serious, potential for this cancer to involve the central nervous system.
Central Nervous System Involvement in Multiple Myeloma
Multiple myeloma can involve the central nervous system (CNS), which includes the brain and spinal cord, but this is an extremely uncommon event. This condition, known as CNS myeloma or leptomeningeal involvement, occurs in less than 1% to 5% of all multiple myeloma cases.
CNS involvement is generally considered a sign of advanced or aggressive disease, often occurring in patients who have experienced relapse. When cancer cells infiltrate the CNS, they typically affect the meninges, the protective layers surrounding the brain and spinal cord, or, less frequently, the brain tissue itself. This progression is a significant departure from the typical presentation of multiple myeloma.
Recognizing Signs and Symptoms
The presentation of CNS myeloma involves neurological changes that differ from standard myeloma symptoms. The most common complaints are a persistent or severe headache and altered mental status, such as confusion or somnolence. These symptoms arise from malignant plasma cells infiltrating the meninges, leading to increased pressure within the skull.
Patients may also experience cranial nerve palsies, resulting in symptoms like double vision (diplopia) or facial weakness. Seizures are another possible manifestation, particularly if the cancer forms a localized tumor, known as an intraparenchymal plasmacytoma, within the brain tissue.
Sensory or motor deficits, such as numbness in the limbs or trouble walking, can occur if the spinal cord or nerve roots are affected. The appearance of these neurological symptoms in a patient with a history of multiple myeloma should prompt immediate investigation to rule out CNS involvement.
Identifying Risk Factors and Progression
The development of CNS myeloma is linked to aggressive disease characteristics. One major factor is the presence of extramedullary plasmacytomas, which are myeloma tumors growing outside the bone marrow. These cells have already demonstrated an ability to spread beyond the skeletal system, and certain high-risk cytogenetic features are frequently associated with CNS involvement.
The mechanism involves cancer cells bypassing the blood-brain barrier, a selective membrane that protects the CNS. Aggressive plasma cells may enter the CNS through hematogenous spread or by direct extension from a bone lesion in the skull or spine. Progression involves a selection of myeloma clones that have lost adhesion molecules, enabling them to detach from the bone marrow and travel freely.
Treatment Approaches for CNS Myeloma
Treatment for CNS myeloma is highly specialized and multi-modal, differing significantly from standard systemic treatment due to the challenge of the blood-brain barrier. A common strategy involves a combination of specialized systemic chemotherapy, intrathecal chemotherapy, and radiation therapy. Systemic agents must be selected specifically for their ability to penetrate the blood-brain barrier.
Intrathecal chemotherapy involves injecting anti-cancer drugs, such as methotrexate or cytarabine, directly into the cerebrospinal fluid. This method bypasses the barrier and delivers high concentrations to the CNS. Radiation therapy, often whole-brain or craniospinal irradiation, is also a common component used to target localized tumors or widespread disease. Newer systemic agents, including certain immunomodulatory drugs and anti-CD38 monoclonal antibodies, are being explored for enhanced CNS penetration.