What is the treatment for copper deficiency and cirrhosis-induced myelopathy?

Management of Copper Deficiency and Cirrhosis-Induced Myelopathy

Critical Distinction: Two Separate Entities Requiring Different Approaches

When evaluating myelopathy in a patient with cirrhosis, you must first determine whether this is true hepatic myelopathy (a complication of cirrhosis itself) or copper deficiency myelopathy (which can occur independently in cirrhotic patients). These are distinct conditions with fundamentally different treatments, and misdiagnosis leads to inappropriate management and irreversible neurological damage.

Diagnostic Algorithm

Step 1: Perform Spinal MRI and Rule Out Copper Deficiency

• Spinal MRI is mandatory to exclude other causes of myelopathy, specifically vitamin B12, thiamine, and copper deficiency 1
• Measure serum copper, ceruloplasmin, vitamin B12, and thiamine levels in all patients presenting with myelopathy and cirrhosis 1
• Copper deficiency myelopathy shows T2 hyperintensity in posterior cervical and thoracic cord columns (47% of cases), identical to B12 deficiency 2
• Low serum copper and ceruloplasmin confirm copper deficiency; urinary copper is typically low (unlike Wilson disease) 2

Step 2: Identify the Underlying Condition

Hepatic Myelopathy (Cirrhosis-Induced):

• Rapidly progressing spastic paraparesis without sensory deficit or sphincter dysfunction 1
• Present in >80% with extensive portosystemic shunts 1
• Does NOT respond to standard hepatic encephalopathy therapies 1
• Progressive over months leading to wheelchair dependence 1

Copper Deficiency Myelopathy:

• Sensory ataxia with posterior column dysfunction (decreased vibration/proprioception) 3, 2, 4
• May have mild leg spasticity 4
• Often accompanied by cytopenias (78% of cases), particularly anemia 2
• Risk factors: bariatric surgery, zinc overload, malabsorption, upper GI surgery 2, 5
• Can occur in cirrhotic patients independently of hepatic myelopathy 3

Treatment Based on Diagnosis

For True Hepatic Myelopathy (Cirrhosis-Induced):

Liver transplantation should be considered as soon as possible since there is no other therapeutic option 1. This is a strong recommendation with 94% consensus from the 2022 EASL guidelines.

• Hepatic myelopathy does not respond to standard hepatic encephalopathy treatments 1
• Patients who underwent liver transplantation had similar outcomes to those transplanted for other forms of hepatic encephalopathy 1
• All portosystemic shunts must be closed during the transplantation procedure 1

For Copper Deficiency Myelopathy:

Immediate copper supplementation is essential to prevent irreversible neurological damage 2, 4. Treatment comprises:

• Oral copper supplementation (specific dosing not standardized in guidelines, but case reports suggest 2-8 mg elemental copper daily) 2, 5
• Standard doses may be insufficient for some patients; high-dose oral copper replacement may be required in relapsing cases 5
• Modification of risk factors (discontinue zinc supplementation, address malabsorption) 2
• Serial monitoring of serum copper and ceruloplasmin levels 2, 4

Treatment outcomes:

• Haematological parameters normalize with supplementation 2, 4
• Neurological improvement or stabilization occurs, though recovery is typically partial 2, 4
• Significant clinical, neuroradiological, and neurophysiological improvement documented with proper supplementation 4

Critical Pitfalls to Avoid

• Do not assume all myelopathy in cirrhotic patients is hepatic myelopathy - copper deficiency can coexist and is treatable 1, 3
• Do not delay copper level testing - permanent neurological damage occurs before diagnosis if copper deficiency is missed 3, 2
• Do not confuse copper deficiency with myelodysplastic syndrome - cytopenias in copper deficiency may lead to false MDS diagnosis 2
• Do not use standard hepatic encephalopathy treatments for hepatic myelopathy - they are ineffective 1
• Monitor copper supplementation closely - excessive copper can cause acute intoxication and cirrhosis 6
• In patients requiring copper supplementation, check serial levels every 6-12 months to ensure adequate but not excessive levels 7, 6

Special Consideration: Copper Toxicity Risk

• While treating copper deficiency, be aware that excessive supplementation can cause copper toxicity with severe multi-organ damage 7
• Copper toxicity requires chelation therapy with D-penicillamine (250-500 mg/day initially, increased to maximum 1000-1500 mg daily) 7
• Regular monitoring of liver and renal function is essential during copper supplementation 7