Multiple myeloma (MM) is a cancer of the plasma cells, a type of white blood cell, which primarily multiplies in the bone marrow. The direct spread of MM to the brain and spinal cord, collectively known as the Central Nervous System (CNS), is possible, but it is an exceedingly rare complication. This form of spread, termed CNS myeloma, is observed in approximately 0.7% to 1% of all MM patients. While MM commonly causes bone lesions in the skull, it usually does not affect the brain tissue directly. The presence of malignant plasma cells in the CNS represents a highly aggressive manifestation of the underlying cancer.
Understanding CNS Involvement in Multiple Myeloma
CNS involvement by multiple myeloma is a form of extramedullary disease (EMD), meaning the cancer is growing outside of the bone marrow. This rare condition is termed CNS myeloma, or CNS plasmacytoma when presenting as a single tumor mass. Malignant plasma cells can infiltrate the brain tissue (intraparenchymal involvement) or, more commonly, the linings of the brain and spinal cord (leptomeningeal involvement).
The development of CNS myeloma is associated with a more aggressive disease, often occurring during relapse after initial treatments. Patients frequently present with high-risk features, including elevated lactate dehydrogenase (LDH) and unfavorable cytogenetic abnormalities. These features can include deletions on chromosome 17p (del(17p)) or translocations like t(4;14). The malignant cells that spread to the CNS may also lose the adhesion molecule CD56, which facilitates their escape from the bone marrow and travel through the bloodstream.
Recognizing Neurological Symptoms
When multiple myeloma affects the CNS, the resulting symptoms are varied and often nonspecific, complicating early diagnosis. Common manifestations relate to increased pressure within the skull or direct damage to brain and nerve structures. Patients may experience persistent headaches, confusion, dizziness, or changes in cognitive abilities.
The involvement of cranial nerves can lead to specific focal neurological deficits, such as double vision, partial paralysis of facial muscles, or problems with hearing and balance. If the spinal cord is involved, patients may notice numbness, tingling, or weakness in their limbs. Less frequently, pressure or tissue irritation can trigger seizures, slurred speech, or profound lethargy. Careful evaluation is necessary, as many of these symptoms can also be caused by other myeloma complications, such as high blood calcium levels (hypercalcemia) or treatment side effects.
Diagnostic Confirmation Methods
A definitive diagnosis of CNS myeloma requires specialized procedures to distinguish it from other causes of neurological symptoms. Advanced imaging, most often a contrast-enhanced Magnetic Resonance Imaging (MRI) of the brain and entire spine, is the first step. The MRI can visualize plasmacytomas (tumor masses) in the brain tissue or show enhancement along the linings of the brain and spinal cord, indicating leptomeningeal infiltration. MRI is considered highly sensitive for detecting these lesions.
The most crucial step for confirmation is the analysis of the Cerebrospinal Fluid (CSF), obtained via a lumbar puncture (spinal tap). The CSF is the fluid that bathes the brain and spinal cord, and it is examined for malignant plasma cells. The sample is analyzed using cytology, which looks for atypical plasma cells, and flow cytometry. Flow cytometry is a highly sensitive technique that identifies clonal, monoclonal plasma cells, providing strong evidence of CNS involvement.
Specific Treatment Strategies
Treating CNS myeloma presents a challenge because the blood-brain barrier prevents many standard systemic anti-myeloma drugs from reaching therapeutic concentrations in the CNS. Consequently, treatment protocols are intensive and multi-modal, combining several different approaches. One primary method involves radiation therapy, which may be focused on specific lesions or delivered as craniospinal irradiation to treat the entire CNS.
Another necessary component is intrathecal chemotherapy, where drugs are injected directly into the CSF, bypassing the blood-brain barrier. This usually involves a combination of agents like methotrexate, cytarabine, and corticosteroids, administered multiple times per week until malignant cells are cleared from the CSF. Systemic therapy with drugs that have better CNS penetration is also administered to control the underlying myeloma. Newer agents, such as certain immunomodulatory drugs and monoclonal antibodies like daratumumab, have shown promising results due to their ability to cross into the CNS space.