|Year : 2020 | Volume
| Issue : 3 | Page : 154-156
Copper deficiency myeloneuropathy with bicytopenia − a rare case report
Sourya Acharya, Swapnil Lahole, Samarth Shukla, Preeti Mishra, Parag Aradhey
Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed to be University), Sawangi (Meghe), Wardha, Maharashtra, India
|Date of Submission||20-Feb-2020|
|Date of Decision||18-Mar-2020|
|Date of Acceptance||31-Mar-2020|
|Date of Web Publication||20-Aug-2020|
Professor Sourya Acharya
Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed to be University), Sawangi (Meghe), Wardha-442001
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Copper is a trace element required for various enzymatic activities in the body. Copper deficiency myeloneuropathy (CDM) is an entity which presents with spastic paraparesis, sensory ataxia and peripheral neuropathy resembling subacute combined degeneration of spinal cord seen in vitamin B 12 deficiency. Hematologic manifestations of copper deficiency may present as cytopenias resembling myelodysplastic syndrome. We present a case of a 48 year old female who presented with myeloneuropathy and bicytopenia because of copper deficiency.
Keywords: CDM, cytopenia, myelopathy, myelodysplastic syndrome, vitamin B12
|How to cite this article:|
Acharya S, Lahole S, Shukla S, Mishra P, Aradhey P. Copper deficiency myeloneuropathy with bicytopenia − a rare case report. Int J Nutr Pharmacol Neurol Dis 2020;10:154-6
|How to cite this URL:|
Acharya S, Lahole S, Shukla S, Mishra P, Aradhey P. Copper deficiency myeloneuropathy with bicytopenia − a rare case report. Int J Nutr Pharmacol Neurol Dis [serial online] 2020 [cited 2020 Sep 25];10:154-6. Available from: http://www.ijnpnd.com/text.asp?2020/10/3/154/292681
| Introduction|| |
Copper is an essential trace element which acts as a cofactor for many key enzymes such as cytochrome C oxidase, Cu/Zn superoxide dismutase and dopamine β-hydroxylase. Copper is absorbed in the stomach and proximal duodenum. Copper deficiency is a well-recognized entity that manifests with various hematologic complications like normocytic, macrocytic, rarely microcytic anemia, leukopenia and myelodysplasia even before its deficiency is detected.
Dietary deficiency of copper is rare. Deficiency usually occurs secondary to bariatric surgery, malabsorption syndrome and zinc excess. Too much zinc, taken in the form of dietary supplements, may disrupt copper uptake, leading to neurological problems and anemia. Zinc induces the expression of the intracellular chelator metallothionein in enterocytes. Copper has a higher affinity for metallothionein and thus displaces zinc from metallothionein. Copper remains bound in the enterocytes which are then sloughed into the lumen and eliminated causing hypocupremia.,
Acquired copper deficiency has been recognised as a rare cause of anaemia and neutropenia for over half a century. Copper deficiency myeloneuropathy (CDM) was only described within the last decade and represents a treatable cause of non-compressive myelopathy which closely mimics subacute combined degeneration of spinal cord due to vitamin B12 deficiency.
| Case Report|| |
A 45-year-old female presented to us with history of progressive gait ataxia more at night and weakness in both lower limbs since 9 months. There was no history of weakness in upper limbs, tingling/numbness, band like sensations, bladder incontinence, diplopia and visual blurring. There was no history of any remissions or relapses of her symptoms. Her past history was insignificant. On asking leading questions, she admitted of taking multivitamin tablets twice daily as prescribed from her family doctor since the past four years.
General examination revealed pallor. Neurological examination revealed spasticity in both the lower limbs, hyperreflexia in both upper and lower limbs with absent ankle reflexes. The vibration sense was impaired up to the knee joints bilaterally, joint position sense was impaired in the great toe bilaterally. Bilateral plantars were extensors. Romberg’s sign was positive. She had spastic ataxic gait.All these features suggested involvement of mixed upper and lower motor neurons along with features of dorsal column malfunction/peripheral neuropathy.
Investigations revealed: Hemoglobin-8.6 gm/dL, MCV 106/uL, WBC-2100 mm3(bicytopenia). Peripheral smear showed macroovalocytes and hypersegmented neutrophil and few giant platelets resembling myelodysplasia [Figure 1]. Absolute platelet count was 1,56,000/microliter. Her renal and liver function tests were within normal limits. Serum Iron was 120 mg/dL, serum vitamin B12 level was 1000 pg/ml. Serology for HIV was negative. Thyroid profile, serum ANA were negative. Magnetic resonance imaging (MRI) of spine was within normal limits [Figure 2]. Nerve conduction studies showed axonal type of sensori-motor neuropathy in the lower limbs. Serum copper was 28 ug/dL (80–155 ug/dL), serum zinc was 218 ug/dL (70–150 ug/dL), serum ceruloplasmin level was 14 μg/dl (normal 20–35 mg/dl) and 24 hour urinary copper was 12 μ/dL (normal 20–50 μg/dL) [Table 1]. She was asked to stop multivitamin supplements. Oral copper supplementation equivalent to 8 mg of elemental copper per day. After one moth follow up her anemia improved but there was poor functional improvement.
|Figure 1 Peripheral smear (Leishman stain, oil immersion; 100X) showing macroovalocytes and hypersegmented neutrophil and few giant platelets resembling myelodysplasia|
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| Discussion|| |
Copper is a trace metal which acts as an important agent in several key enzymatic actions making it an essential element for the structure and function of the bone marrow and nervous system. Acquired copper deficiency has long been recognised as a cause of anaemia and, less commonly cytopenias. Recently it was found that hypocupremia is associated with myelopathy. Our case had both cytopenia along with myeloneuropathy. The clinical and radiological picture of copper deficiencyresembles subacute combined degeneration of spinal cord due to vitamin B12 (cobalamin) deficiency (SCD), and the syndrome is thought to represent the human counterpart of enzootic ataxia, a copper deficiency myelopathy (CDM) occurring in ruminants like cattle, goats, sheep, camels etc.
Other, less frequently reported and less clearly causally related neurological associations of acquired copper deficiency include isolated peripheral neuropathy, motor neuron disease, cerebral demyelination, cognitive dysfunction and optic neuropathy.
Patients with CDM usually present with spastic ataxic gait with positive rombergism. Bladder dysfunction is uncommon. Sensory ataxia, due to dorsal column dysfunction, may be associated with paresthesias in upper and lower limbs. Unlike in our patient, copper deficiency may also cause sensory-motor polyneuropathy. The incidence of CDM is higher in women, with a female to male ratio of 3.6:1. Age predilection is usually in the fifth and sixth decades of life.
Spinal cord MRI may show hyperintense lesions in T2-weighted sequences involving the dorsal midline of cervical and thoracic cord but a study showed that; these features may only be present in 47% of cases. MRI findings of CDM are not distinguishable from those of subacute combined degeneration associated with vitamin B12 deficiency. Cytopenias were found in 78%, particularly anaemia and neutropenia. In a clinically compatible case, CDM may be suggested by the presence of one or more risk factors and/or cytopenias. Our case had bicytopenia but normal MRI spine.
The pathophysiologic mechanism of myeloneuropathy due to hypocupremia is not fully understood. Copper plays a critical role in maintaining physiologic functions of the nervous system. It does so by permitting electron transfer in various enzymatic pathways. Dietary copper is absorbed largely in duodenum. Increased zinc levels inhibit copper absorption.
In the liver copper is incorporated into the enzymes superoxide dismutase and cytochrome-c oxidase, or into the carrier protein caeruloplasmin for onward transport to systemic tissues. Nerve biopsy in hypocupremic neuropathy shows axonal degeneration.
The neurological progression of CDM can only be halted but not reversed. If at all neurologic recovery occurs; it tends to be limited to a subjective improvement in sensory symptoms. Prompt diagnosis and treatment may hault neurological deterioration.Hypocupremia is treated with copper supplements with doses equivalent to 2–4 mg of elemental copper. If recovery is not seen then; the dose may be increased to 4to 6 mg, which may contribute to achieve remission. Copper doses of up to 9 mg per day have been reported to be used to prevent neurological worsening.
| Conclusion|| |
Hypocupremic myeloneuropathy though rare, is a well-established entity. It usually presents with features of spinal cord and dorsal column involvement resembling subacute combined degeneration of spinal cord and peripheral neuropathy of vitamin B12 deficiency. Physicians should have a high index of suspicion while dealing with such cases. A normal serum vitamin B 12 level should prompt for evaluation of serum copper and zinc in suggestive cases. Imaging of spine is usually abnormal but it should be borne in mind that MRI spine can be normal in some cases. Early diagnosis and prompt institution of copper replacement may hinder neurologic deterioration.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kumar N, Crum B, Petersen RC, Vernino SA, Ahlskog JE. Copper deficiency myelopathy. Arch Neurol 2004;61:762-6.
Halfdanarson TR, Kumar N, Li CY, Phyliky RL, Hogan WJ. Hematological manifestations of copper deficiency: a retrospective review. Eur J Haematol 2008;80:523-31.
Singh D, Acharya S, Singh AV, Parakh P, Banode P. An unusual case of copper myelopathy. Neurol India 2011;59:630-1.
] [Full text]
Duncan A, Yacoubian C, Watson N, Morrison I. The risk of copper deficiency in patients prescribed zinc supplements. J Clin Pathol 2015;68:723-5.
Weihl CC, Lopate G. Motor neuron disease associated with copper deficiency. Muscle Nerve 2006;34:789-93.
Winston GP, Jaiser SR. Copper deficiency myelopathy and subacute combined degeneration of the cord − why is the phenotype so similar? Med Hypotheses 2008;71:229-36.
Kumar N, Low PA. Myeloneuropathy and anemia due to copper malabsorption. J Neurol 2004;251:747-9.
Weihl CC, Lopate G. Motor neuron disease associated with copper deficiency. Muscle Nerve 2006;34:789-93.
Prodan CI, Holland NR, Wisdom PJ, Burstein SA, Bottomley SS. CNS demyelination associated with copper deficiency and hyperzincemia. Neurology 2002;59:1453-6.
Spinazzi M, De Lazzari F, Tavolato B, Angelini C, Manara R, Armani M. Myelo-optico-neuropathy in copper deficiency occurring after partial gastrectomy. Do small bowel bacterial overgrowth syndrome and occult zinc ingestion tip the balance? J Neurol 2007;254:1012-7.
Kumar N, Gross JB Jr, Ahlskog JE. Copper deficiency myelopathy produces a clinical picture like subacute combined degeneration. Neurology 2004;63:33-9.
Jaiser SR, Winston GP. Copper deficiency myelopathy. J Neurol 2010;257:869-81.
Kumar N, Ahlskog JE, Klein CJ, Port JD. Imaging features of copper deficiency myelopathy: a study of 25 cases. Neuroradiology 2006;48:78-83.
Linder MC, Hazegh-Azam M. Copper biochemistry and molecular biology. Am J Clin Nutr 1996;63:797S-811S.
Zatta P, Frank A. Copper deficiency and neurological disorders in man and animals. Brain Res Rev 2007;54:19
Neeraj K. Copper deficiency myelopathy (Human Sway back). Mayo Clin Proc 2006;81:1371-84.
Prodan CI, Bottomley SS, Holland NR, Lind SE. Relapsing hypocupraemic myelopathy requiring high-dose oral copper replacement. J Neurol Neurosurg Psychiatry 2006;77:1092-3.
Bartner R, Will M, Conrad J, Engelhardt A, Schwarz-Eywill M. Pancytopenia, arthralgia and myeloneuropathy due to copper deficiency. Med Klin (Munich) 2005;100:497-501.
[Figure 1], [Figure 2]