Myelopathy in Copper Deficiency

Abstract & Commentary

By Claire Henchcliffe, MD, DPhil, Assistant Professor, Department of Neurology, Weill Medical College, Cornell University. Dr. Henchcliffe is on the speaker's bureau for GlaxoSmithKline, Teva/Eisai, and Boehringer Ingelheim.

Synopsis: Spinal cord magnetic resonance imaging (MRI) in patients with copper deficiency myelopathy may show increased T2 signal, most commonly in the dorsal midline cervical and thoracic cord.

Source: Kumar N, et al. Imaging Features of Copper Deficiency Myelopathy: A Study of 25 Cases. Neuroradiology. 2006:48:78-83.

Kumar and colleagues retrospectively analyzed clinical and imaging findings in 25 patients (age range 36-78 years; 20 women, 5 men) with laboratory-confirmed copper deficiency myelopathy at the Mayo Clinic, Rochester, MN. Patients developed symptoms between 2 months and 10 years prior to examination. Serum copper levels ranged from undetectable to 0.45 g/mL (normal range, 0.75-1.45 g/mL). Hypocupremia was due to gastric surgery (n = 10), malabsorption (n = 4), large doses of iron or zinc ingestion (n = 2), or etiology was unknown (n = 9). Twenty of the 25 had leukopenia or anemia, either at presentation or by history. Somatosensory evoked potentials demonstrated impaired conduction in central pathways, and there existed varying degrees of peripheral neuropathy in those 20 examined.

Although all patients had normal vitamin B12 levels at the time of examination, 9 had a history of vitamin B12 deficiency (7 of these had undergone gastric surgery). In these, clinical worsening was recorded despite vitamin B12 administration that had resulted in normal vitamin B12 serum levels. Two of the 9 had increased methylmalonic acid levels, but 6 had normal levels (levels not determined in one case). MRI of the spine was normal in 14 patients. However, in the remaining 11, MRI revealed segmental T2 hyperintensity in the cervical or thoracic cord, or both; 5 of these 11 had no prior vitamin B12 deficiency. Of note, radiographic findings were subtle in some cases, and had originally been interpreted as normal in 2 MRI scans. Signal abnormality involved the central and dorsal midline cord, and involved the posterior columns. There was no signal enhancement after gadolinium administration. Follow-up imaging was available in one patient, and demonstrated T2 signal normalization after correction of hypocupremia.

Commentary

The present study, along with the Kumar et al's previous clinical case series,1 provide an excellent clinical description of hypocupremic myelopathy. This recently recognized disorder is rare, but important to consider in the differential of myelopathy, as clinical symptoms may reverse with oral or intravenous copper supplementation. This study verifies posterior column involvement as the underlying structural abnormality in hypocupremic myelopathy in humans, and for the first time demonstrates resolution of MRI signal abnormalities in one case treated with copper supplementation. The human neurologic syndrome seems to be characterized by sensory ataxia, lower limb spasticity, and acral paresthesias, similar to clinical features of subacute combined degeneration (SCD) in vitamin B12 deficiency. In fact, in malabsorption states, vitamin B12 and copper deficiency may co-exist. Although some clinical features associated with hypocupremia suggest similarity to vitamin B12 deficiency, there do appear to be differences between the 2 disorders. Vitamin B12 has been associated with cognitive impairment and macrocytic anemia, while hypocupremia is associated with normocytic anemia and, as yet, there are no reports of cognitive impairment. Rarely, hypocupremia is due to genetic disorders, like Menkes disease, an X-linked genetic disorder characterized by progressive demyelination and death in early childhood. However, copper deficiency is increasingly seen in patients with malabsorption secondary to gastric or intestinal surgery, chronic diarrhea, peritoneal dialysis, excessive zinc ingestion, or entero-jejunal feeding. Myelopathy secondary to hypocupremia should be considered in patients with an unexplained myelopathy, and copper levels should be determined in those with presumed SCD who fail to respond to vitamin B12 supplementation.

Reference

1. Kumar N, et al. Copper Deficiency Myelopathy Produces a Clinical Picture Like Subacute Combined Degeneration. Neurology. 2004;63:33-39.