Abstract
Abstract
Copper deficiency is an unusual but potentially treatable cause of myelopathy. It should be considered in patients with poor nutrition or a history of gastrointestinal surgery. We report the case of an 82-year-old man who presented with sensory symptoms and gait ataxia.
Case
An 82-year-old man presented with a five-month history of reduced mobility, unsteady gait, weight loss and sensory loss over the soles of his feet. He had pathologically brisk reflexes in the upper and lower limbs with extensor plantar responses. The ankle jerks were absent. There was reduction in pin prick and vibration sense to the knees. He had gait ataxia and was Romberg's test positive.
In 1991, he had undergone truncal vagotomy and gastroenterostomy for chronic benign pyloric stenosis secondary to duodenal ulceration. In 1998, he presented with coffee ground vomiting and a revised Billroth II/Polya gastrectomy was performed without complication.
His medications at presentation included regular hydroxocobalamin injections for associated B12 deficiency. He also took iron supplements, aspirin and ramipril.
Investigations revealed a serum copper of 0.5 umol/L (13.0–26.0) and caeruloplasmin of 44 mg/L (200–450). Serum B12 and zinc concentrations were within normal limits. Bone marrow examination was not performed.
The results of nerve conduction studies and electromyography study demonstrated no evidence to suggest a generalized large fibre polyneuropathy and also excluded sensory ataxic neuropathy and sensory ganglionopathy. The patient's sensory ataxia was therefore thought to be central in origin.
Magnetic resonance imaging (MRI) of the brain showed changes consistent with ischaemic brain disease, with cerebral and cerebellar atrophy and slight symmetrical prominence of the ventricles. MRI of the cervical spine confirmed severe osteoarthritic changes and degenerative disc disease with no cord compression.
During his inpatient stay, he developed sensory symptoms in his hands and his mobility reduced to the point that he required hoisting. After discussion with pharmacists, the patient commenced intramuscular copper histidine injections (500 mcg/mL – dose 1 mL i.m. once daily) as he would be unable to absorb oral supplements. Copper concentrations were monitored weekly. Up to 3 mg daily has been suggested in established deficiency. Copper replacement can be intravenous. 1,2
Copper concentrations improved and he was discharged to a nursing home. Unfortunately, 10 days after discharge, he was re-admitted with pneumonia and died from this illness.
Discussion
Copper is required for cellular and molecular processes including nerve cell function.
It is found in a variety of foods including cereals, meat and vegetables and is predominantly absorbed across the mucosa of the upper gastrointestinal tract. Dietary copper deficiency is uncommon as a result of the low daily requirement and its widespread dietary availability. In some cases, the cause of the copper deficiency may not be apparent. 3
The causes of acquired copper deficiency include malabsorption secondary to gastrointestinal surgery, total parenteral nutrition without copper replacement and excessive zinc therapy or a combination of these factors.
The principal neurological findings in copper deficiency myelopathy are a spastic gait and sensory ataxia. It has been described as producing clinical features mimicking subacute combined degeneration associated with B12 deficiency. 4
Haematological findings are associated with copper deficiency including anaemia and neutropenia. The anaemia may be normocytic or macrocytic. A range of abnormalities has been described in all blood cell lineages. 3
The pathogenesis is associated with defects of iron metabolism and associated lack of caeruloplasmin, which has an important regulatory role in iron metabolism because of its ferroxidase activity that catalyses the oxidation of ferrous iron to ferric iron. This allows mobilization of iron into the plasma from iron storage cells in the liver prior to uptake by transferrin. There is failure to completely synthesize haeme, leading to deposits of iron in the mitochondria that form a ring around the nucleus of the developing red blood cell known as sideroblasts. Thus, iron is available, but cannot be incorporated into haemoglobin, resulting in a functional iron deficiency anaemia.
It is also thought that low concentrations of intracellular copper enzymes such as cytochrome oxidase may interfere with haematopoesis in other ways, which may account for the neutropenia that may be a feature of copper deficiency. 5
MRI of the cervical cord may show long segment increased T2 signal, most commonly in the dorsal midline cervical and thoracic cord, which reverse with correction of the serum copper. The imaging picture is very similar to the subacute combined degeneration seen in patients with vitamin B12 deficiency. 6
This case highlights the need for careful investigation of patients with nutritional deficiencies or absorptive problems following surgery, as the symptoms of copper deficiency may mimic vitamin B12 deficiency. Treatment with copper may prevent further neurological deterioration, and treatment should therefore not be delayed.