What is the management approach for a patient presenting with lower motor weakness and polycythaemia?

Management of Lower Motor Weakness with Polycythemia

The management of a patient presenting with lower motor weakness and polycythemia should focus on treating the underlying polycythemia vera while addressing neurological symptoms, with phlebotomy to maintain hematocrit below 45% as first-line therapy.

Diagnosis and Assessment

• Lower motor weakness in the context of polycythemia may indicate neurological complications from hyperviscosity or thrombotic events affecting the spinal cord or peripheral nerves 1
• Polycythemia vera (PV) is a clonal myeloproliferative disorder characterized by excessive red blood cell production leading to increased blood viscosity 2
• Diagnostic workup should include:
  • JAK2V617F mutation testing (positive in most PV cases) 1
  • If JAK2V617F negative, test for calreticulin mutation 1
  • Complete blood count with peripheral smear 1
  • Serum erythropoietin levels 3
  • Contrast-enhanced MRI of the spine to evaluate for myelopathy 1
  • Brain MRI if other neurological symptoms are present 1

Management of Polycythemia Vera

First-line Treatment

• Phlebotomy to maintain hematocrit strictly below 45% 1
  • The CYTO-PV trial demonstrated that maintaining hematocrit <45% significantly reduces thrombotic events 1
• Low-dose aspirin (81-100 mg daily) for all patients without contraindications 1, 2
  • Reduces risk of cardiovascular events and microvascular symptoms 1

Cytoreductive Therapy Indications

• Cytoreductive therapy is indicated in high-risk patients (>60 years and/or history of thrombosis) 1
• Additional indications for cytoreductive therapy include:
  • Intolerance to phlebotomy 4
  • Symptomatic or progressive splenomegaly 1, 4
  • Persistent leukocytosis (>15 × 10^9/L) 4
  • Extreme thrombocytosis (>1500 × 10^9/L) 4
  • Inadequate hematocrit control despite phlebotomy 4

Cytoreductive Therapy Options

• First-line cytoreductive agents:
  • Hydroxyurea for patients >60 years 1
  • Interferon-α (particularly pegylated forms or ropeginterferon alfa-2b) preferred for younger patients 1, 4
• Second-line options:
  • Ruxolitinib for patients resistant or intolerant to hydroxyurea 4
  • Busulfan may be considered in elderly patients (>70 years) 1

Management of Lower Motor Weakness

• Urgent neurological evaluation to determine the cause of lower motor weakness 1
• If weakness is due to spinal cord involvement (myelopathy):
  • High-dose glucocorticoids (intravenous methylprednisolone) should be initiated promptly 1
  • Consider combination with intravenous cyclophosphamide if inflammatory myelitis is suspected 1
• If weakness is associated with thrombotic events:
  • Anticoagulation therapy should be considered, especially in patients with antiphospholipid antibodies 1
• For peripheral neuropathy:
  • Nerve conduction studies to characterize the type and extent of neuropathy 1
  • Symptomatic management with gabapentin or pregabalin for neuropathic pain 1

Monitoring and Follow-up

• Regular monitoring of hematocrit, platelet count, and white blood cell count 1
• Periodic neurological assessment to evaluate response to treatment 1
• Monitor for disease progression and transformation to myelofibrosis or acute leukemia 1
• Assess for hyperviscosity symptoms (headache, visual disturbances, dizziness) 1
• Evaluate iron status as iron deficiency can mimic hyperviscosity symptoms 1

Special Considerations

• Avoid blood transfusions unless absolutely necessary as they can worsen hyperviscosity 2
• Aggressive management of cardiovascular risk factors (hypertension, diabetes, smoking) 1
• Consider therapeutic phlebotomy before any surgical procedures 2
• Patients with both lower motor weakness and polycythemia should be evaluated for potential paraneoplastic syndromes 1

Prognosis and Complications

• Factors associated with poor neurological outcomes include:
  • Delay in treatment initiation (>2 weeks) 1
  • Extensive spinal cord lesions on MRI 1
  • Reduced muscle strength or sphincter dysfunction at presentation 1
  • Presence of antiphospholipid antibodies 1
• Thrombotic events are the most common cause of death in PV patients 5
• Neurological symptoms may relapse during corticosteroid dose reduction, requiring maintenance immunosuppressive therapy 1