What is the CNS (Central Nervous System) manifestation of multiple myeloma called?

Central Nervous System Myelomatosis: Definition and Management

Central nervous system (CNS) involvement in multiple myeloma is called CNS myelomatosis. This rare manifestation occurs in approximately 1% of multiple myeloma patients and carries a poor prognosis if not treated aggressively 1.

Clinical Presentation and Diagnosis

• CNS myelomatosis presents with a wide spectrum of neurological symptoms, which may develop gradually over weeks to months, often leading to delayed diagnosis 1, 2

• Common symptoms include:

  • Focal neurological deficits (70% of cases) such as weakness on one side of the body and coordination problems 2
  • Neuropsychiatric symptoms or personality changes (43% of cases) 2
  • Signs of increased intracranial pressure (33% of cases), often presenting as headache 2
  • Seizures (14% of cases) 2
  • Cognitive dysfunction, including confusion, memory problems, and lethargy 2

• Diagnostic evaluation should include:

  • Contrast-enhanced cranial MRI, which is the recommended imaging modality 3
  • CSF analysis with cytology and flow cytometry to detect neoplastic plasma cells 4
  • Multiparameter flow cytometry of CSF can provide rapid diagnosis and useful information about plasma cell phenotype (including CD56 expression) 4

Risk Factors and Pathophysiology

• Risk factors for CNS myelomatosis include:
  • Plasma cell leukemia (40% of cases) 5
  • Skull plasmacytomas (65% of cases), suggesting hematological and contiguous spread 5
  • High-risk cytogenetics 5
  • Advanced disease stage 1

Treatment Approaches

• No standardized guidelines exist specifically for CNS myelomatosis, resulting in variation in treatment approaches 1
• Treatment options include:
  • Intrathecal chemotherapy: Cytarabine at doses of 40-50 mg administered 2-3 times per week until clearance of blasts from CSF, followed by 3 additional treatments 6, 7
  • Alternatively, liposomal cytarabine at 50 mg every other week for approximately 6 cycles 6, 7
  • Cranial irradiation, which has been associated with significantly longer survival compared to patients without radiation therapy 1, 8
  • Systemic therapy with immunomodulatory agents (IMiDs) that can cross the blood-brain barrier 5
  • Dexamethasone (4 mg three times daily orally) may be administered on days of intrathecal application to prevent arachnoiditis 6

Prognostic Factors and Outcomes

• The overall prognosis of CNS myelomatosis remains poor, with a median survival of approximately 2-4.6 months from diagnosis 1, 5
• However, long-term survival (median 17.1 months) can be achieved with aggressive multimodality therapy 5
• Factors associated with improved survival include:
  • Treatment with cranial irradiation 1, 8
  • Multi-dose intrathecal chemotherapy 5
  • IMiD-containing systemic therapy 5
  • Focal brain CNS-MM (versus diffuse disease) 8
  • Complete response after radiation therapy 8
  • Autologous stem cell transplantation with modified conditioning regimens as consolidation therapy 9

Important Considerations and Pitfalls

• CNS myelomatosis can sometimes present with normal MRI findings, making CSF analysis crucial for diagnosis 4
• CSF monitoring by flow cytometry can be used to evaluate treatment efficacy 4
• Some cases may benefit from autologous stem cell transplantation with modified conditioning regimens 9
• Early recognition and aggressive multimodality treatment are essential for improving outcomes 5, 8
• Patients with complete response after radiation therapy have better survival prospects (median 7.3 months) 8