Neurological and Hematological Recovery Following Copper Replacement in Severe Copper Deficiency-induced Myelopathy and Cytopenia

Christoph Roland Seifert; Ieva Didrihsone; Christian Isensee

doi:doi:10.11648/j.cnn.20210501.11

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Neurological and Hematological Recovery Following Copper Replacement in Severe Copper Deficiency-induced Myelopathy and Cytopenia

Christoph Roland Seifert, Ieva Didrihsone, Christian Isensee

Published in Clinical Neurology and Neuroscience (Volume 5, Issue 1)

Received: 21 December 2020 Accepted: 29 December 2020 Published: 18 January 2021

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Abstract

Background: Copper deficiency can lead to a severe myelopathy and cytopenia. The myelopathy can lead to inability to walk by paresis and deafferentation. The anemia can as well be severe with the need for blood transfusions. Beside innate reasons it occurs years after surgeries of the intestine and following disturbed resorption. It can also occur due to excessive intake of zinc that binds copper. An early diagnosis following copper substitution can lead to restitution. It can clinically be mistaken for a vitamin B12 deficiency. This circumstance can lead to a delayed treatment. Case: A 67 years old woman with severe gait disturbances, sensory ataxia was admitted to our hospital. She had the diagnosis of vitamin B12 deficiency. B12 was elevated and metabolites were in normal range. The electrophysiology showed a deafferentation of the legs. Objective: This case report provides detailed information about the course of diagnosis and the treatment of a severe copper deficiency with symptomatic myelopathy and cytopenia in an elderly woman. Methods: We performed a literature research with keywords “spinal cord disease, gait disturbances, elevated lactate in cerebrospinal fluid, anemia”. We did blood tests and CSF on a regular basis combined with clinical assessments and electrophysiology. Results: Serum copper was not detectable. CSF copper was reduced (8.7 µg/l, Ref.: 14.2-109 µg/l), CSF lactate was elevated (4.69 mmol/l, Ref.: 1.1-2.4 mmol/l). The patient had a cytopenia (Hb 6.6 g/dl, Ref.: 12-16 g/dl, MCV 130 fl, Ref.: 80-96 fl, leucocytes 2.3 10³, Ref.: 4.3-10 10³/µl). Vitamin B12 amounted to 891 pg/ml (Ref.: 191-663 pg/ml). The somatosensory evoked potential (SEP) study showed absent cortical responses after stimulation of the sural nerves bilaterally. Due to the diagnosis of a myelopathy and bone marrow dysfunction due to copper deficiency we substituted copper-histidine subcutaneously. This led to a marked improvement of symptoms, an increase of serum copper levels (141 µg/l), CSF copper levels (14.1 µg/l), hemoglobin (11.9 g/dl), leukocyte count (11.4 10³/µl) and a normalization of CSF lactate. Conclusion: Elevated CSF lactate might be an indicator for treatable myelopathy due to copper deficiency in patients with afferent gait disturbances. A timely substitution can lead to a marked improvement of even severe symptoms.

Published in	Clinical Neurology and Neuroscience (Volume 5, Issue 1)
DOI	10.11648/j.cnn.20210501.11
Page(s)	1-4
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Copper Deficiency, Anemia, Spinal Cord Disease, Gait Disturbances Elevated CSF Lactate, Hypocupremia

References

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[2]	N. and A. EFSA NDA Panel (EFSA Panel on Dietetic Products, “Scientific Opinion on Dietary Reference Values for copper,” EFSA Journal, vol. 13, no. 10, pp. 4253–51 pp, Oct. 2015, doi: 10.2903/j.efsa.2015.4253.
[3]	N. Kumar, “Copper deficiency myelopathy (human swayback),” Mayo Clinic Proceedings, vol. 81, no. 10, pp. 1371–1384, 2006, doi: 10.4065/81.10.1371.
[4]	L. v. Puchkova, M. Broggini, E. v. Polishchuk, E. Y. Ilyechova, and R. S. Polishchuk, “Silver Ions as a Tool for Understanding Different Aspects of Copper Metabolism,” Nutrients, vol. 11, no. 6, Jun. 2019, doi: 10.3390/nu11061364.
[5]	B. Schleper Hans Joerg Stuerenburg, B. Schleper, and H. J. Stuerenburg, “Copper deficiency-associated myelopathy in a 46-year-old woman,” J Neurol, vol. 248, pp. 705–706, 2001.
[6]	A. A. Gabreyes, H. N. Abbasi, K. P. Forbes, G. Mcquaker, A. Duncan, and I. Morrison, “Hypocupremia associated cytopenia and myelopathy: A national retrospective review,” European Journal of Haematology, vol. 90, no. 1. pp. 1–9, Jan. 2013, doi: 10.1111/ejh.12020.
[7]	X. Feng Wang and M. S. Cynader, “Pyruvate Released by Astrocytes Protects Neurons from Copper-Catalyzed Cysteine Neurotoxicity,” 2001.
[8]	T. Hoppe-Tichy, M. Lorke, T. Hoppe-Tichy, T. H. Nguyen, and B. W. Hentze, “Kupferhistidin-Lösung zur Behandlung von Menkes’ Kinky Hair Syndrom: Herstellung und Stabilität,” Pharmazie, vol. 60, pp. 205–207, 2005, [Online]. Available: https://www.researchgate.net/publication/233516212.
[9]	A. W. Zimmerman, J.-M. Matthieu, R. H. Quarles, R. O. Brady, and J. M. Hsu, “Hypomyelination in Copper-Deficient Rats Prenatal and Postnatal Copper Replacement,” Archives of Neurology, vol. 33, no. 2, pp. 111–119, 1976, [Online]. Available: http://archneur.jamanetwork.com/.
[10]	Z. Tümer and L. B. Møller, “Menkes disease,” European Journal of Human Genetics, vol. 18, no. 5, pp. 511–518, May 2010, doi: 10.1038/ejhg.2009.187.
[11]	R. A. Wapnir, “Copper absorption and bioavailability,” The American Journal of Clinical Nutrition, vol. 67, no. 5 Suppl, pp. 1054S-1060S, 1998.
[12]	G. Ranucci, F. di Dato, M. I. Spagnuolo, P. Vajro, and R. Iorio, “Zinc monotherapy is effective in Wilson’s disease patients with mild liver disease diagnosed in childhood: A retrospective study,” Orphanet Journal of Rare Diseases, vol. 9, no. 1, Mar. 2014, doi: 10.1186/1750-1172-9-41.
[13]	M. Magner et al., “Elevated CSF-lactate is a reliable marker of mitochondrial disorders in children even after brief seizures,” European Journal of Paediatric Neurology, vol. 15, no. 2, pp. 101–108, Mar. 2011, doi: 10.1016/j.ejpn.2010.10.001.
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Christoph Roland Seifert, Ieva Didrihsone, Christian Isensee. (2021). Neurological and Hematological Recovery Following Copper Replacement in Severe Copper Deficiency-induced Myelopathy and Cytopenia. Clinical Neurology and Neuroscience, 5(1), 1-4. https://doi.org/10.11648/j.cnn.20210501.11

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Christoph Roland Seifert; Ieva Didrihsone; Christian Isensee. Neurological and Hematological Recovery Following Copper Replacement in Severe Copper Deficiency-induced Myelopathy and Cytopenia. Clin. Neurol. Neurosci. 2021, 5(1), 1-4. doi: 10.11648/j.cnn.20210501.11

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Christoph Roland Seifert, Ieva Didrihsone, Christian Isensee. Neurological and Hematological Recovery Following Copper Replacement in Severe Copper Deficiency-induced Myelopathy and Cytopenia. Clin Neurol Neurosci. 2021;5(1):1-4. doi: 10.11648/j.cnn.20210501.11

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@article{10.11648/j.cnn.20210501.11,
  author = {Christoph Roland Seifert and Ieva Didrihsone and Christian Isensee},
  title = {Neurological and Hematological Recovery Following Copper Replacement in Severe Copper Deficiency-induced Myelopathy and Cytopenia},
  journal = {Clinical Neurology and Neuroscience},
  volume = {5},
  number = {1},
  pages = {1-4},
  doi = {10.11648/j.cnn.20210501.11},
  url = {https://doi.org/10.11648/j.cnn.20210501.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cnn.20210501.11},
  abstract = {Background: Copper deficiency can lead to a severe myelopathy and cytopenia. The myelopathy can lead to inability to walk by paresis and deafferentation. The anemia can as well be severe with the need for blood transfusions. Beside innate reasons it occurs years after surgeries of the intestine and following disturbed resorption. It can also occur due to excessive intake of zinc that binds copper. An early diagnosis following copper substitution can lead to restitution. It can clinically be mistaken for a vitamin B12 deficiency. This circumstance can lead to a delayed treatment. Case: A 67 years old woman with severe gait disturbances, sensory ataxia was admitted to our hospital. She had the diagnosis of vitamin B12 deficiency. B12 was elevated and metabolites were in normal range. The electrophysiology showed a deafferentation of the legs. Objective: This case report provides detailed information about the course of diagnosis and the treatment of a severe copper deficiency with symptomatic myelopathy and cytopenia in an elderly woman. Methods: We performed a literature research with keywords “spinal cord disease, gait disturbances, elevated lactate in cerebrospinal fluid, anemia”. We did blood tests and CSF on a regular basis combined with clinical assessments and electrophysiology. Results: Serum copper was not detectable. CSF copper was reduced (8.7 µg/l, Ref.: 14.2-109 µg/l), CSF lactate was elevated (4.69 mmol/l, Ref.: 1.1-2.4 mmol/l). The patient had a cytopenia (Hb 6.6 g/dl, Ref.: 12-16 g/dl, MCV 130 fl, Ref.: 80-96 fl, leucocytes 2.3 103, Ref.: 4.3-10 103/µl). Vitamin B12 amounted to 891 pg/ml (Ref.: 191-663 pg/ml). The somatosensory evoked potential (SEP) study showed absent cortical responses after stimulation of the sural nerves bilaterally. Due to the diagnosis of a myelopathy and bone marrow dysfunction due to copper deficiency we substituted copper-histidine subcutaneously. This led to a marked improvement of symptoms, an increase of serum copper levels (141 µg/l), CSF copper levels (14.1 µg/l), hemoglobin (11.9 g/dl), leukocyte count (11.4 103/µl) and a normalization of CSF lactate. Conclusion: Elevated CSF lactate might be an indicator for treatable myelopathy due to copper deficiency in patients with afferent gait disturbances. A timely substitution can lead to a marked improvement of even severe symptoms.},
 year = {2021}
}

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TY - JOUR
T1 - Neurological and Hematological Recovery Following Copper Replacement in Severe Copper Deficiency-induced Myelopathy and Cytopenia
AU - Christoph Roland Seifert
AU - Ieva Didrihsone
AU - Christian Isensee
Y1 - 2021/01/18
PY - 2021
N1 - https://doi.org/10.11648/j.cnn.20210501.11
DO - 10.11648/j.cnn.20210501.11
T2 - Clinical Neurology and Neuroscience
JF - Clinical Neurology and Neuroscience
JO - Clinical Neurology and Neuroscience
SP - 1
EP - 4
PB - Science Publishing Group
SN - 2578-8930
UR - https://doi.org/10.11648/j.cnn.20210501.11
AB - Background: Copper deficiency can lead to a severe myelopathy and cytopenia. The myelopathy can lead to inability to walk by paresis and deafferentation. The anemia can as well be severe with the need for blood transfusions. Beside innate reasons it occurs years after surgeries of the intestine and following disturbed resorption. It can also occur due to excessive intake of zinc that binds copper. An early diagnosis following copper substitution can lead to restitution. It can clinically be mistaken for a vitamin B12 deficiency. This circumstance can lead to a delayed treatment. Case: A 67 years old woman with severe gait disturbances, sensory ataxia was admitted to our hospital. She had the diagnosis of vitamin B12 deficiency. B12 was elevated and metabolites were in normal range. The electrophysiology showed a deafferentation of the legs. Objective: This case report provides detailed information about the course of diagnosis and the treatment of a severe copper deficiency with symptomatic myelopathy and cytopenia in an elderly woman. Methods: We performed a literature research with keywords “spinal cord disease, gait disturbances, elevated lactate in cerebrospinal fluid, anemia”. We did blood tests and CSF on a regular basis combined with clinical assessments and electrophysiology. Results: Serum copper was not detectable. CSF copper was reduced (8.7 µg/l, Ref.: 14.2-109 µg/l), CSF lactate was elevated (4.69 mmol/l, Ref.: 1.1-2.4 mmol/l). The patient had a cytopenia (Hb 6.6 g/dl, Ref.: 12-16 g/dl, MCV 130 fl, Ref.: 80-96 fl, leucocytes 2.3 103, Ref.: 4.3-10 103/µl). Vitamin B12 amounted to 891 pg/ml (Ref.: 191-663 pg/ml). The somatosensory evoked potential (SEP) study showed absent cortical responses after stimulation of the sural nerves bilaterally. Due to the diagnosis of a myelopathy and bone marrow dysfunction due to copper deficiency we substituted copper-histidine subcutaneously. This led to a marked improvement of symptoms, an increase of serum copper levels (141 µg/l), CSF copper levels (14.1 µg/l), hemoglobin (11.9 g/dl), leukocyte count (11.4 103/µl) and a normalization of CSF lactate. Conclusion: Elevated CSF lactate might be an indicator for treatable myelopathy due to copper deficiency in patients with afferent gait disturbances. A timely substitution can lead to a marked improvement of even severe symptoms.
VL - 5
IS - 1
ER -

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Author Information

Christoph Roland Seifert

Department of Neurology, Hermann-Josef-Hospital, Academic Educational Hospital of the University of Aachen, Erkelenz, Germany
Ieva Didrihsone

Department of Neurology, Hermann-Josef-Hospital, Academic Educational Hospital of the University of Aachen, Erkelenz, Germany
Christian Isensee

Department of Neurology, Hermann-Josef-Hospital, Academic Educational Hospital of the University of Aachen, Erkelenz, Germany

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APA Style

Christoph Roland Seifert, Ieva Didrihsone, Christian Isensee. (2021). Neurological and Hematological Recovery Following Copper Replacement in Severe Copper Deficiency-induced Myelopathy and Cytopenia. Clinical Neurology and Neuroscience, 5(1), 1-4. https://doi.org/10.11648/j.cnn.20210501.11

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Christoph Roland Seifert; Ieva Didrihsone; Christian Isensee. Neurological and Hematological Recovery Following Copper Replacement in Severe Copper Deficiency-induced Myelopathy and Cytopenia. Clin. Neurol. Neurosci. 2021, 5(1), 1-4. doi: 10.11648/j.cnn.20210501.11

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AMA Style

Christoph Roland Seifert, Ieva Didrihsone, Christian Isensee. Neurological and Hematological Recovery Following Copper Replacement in Severe Copper Deficiency-induced Myelopathy and Cytopenia. Clin Neurol Neurosci. 2021;5(1):1-4. doi: 10.11648/j.cnn.20210501.11

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@article{10.11648/j.cnn.20210501.11,
  author = {Christoph Roland Seifert and Ieva Didrihsone and Christian Isensee},
  title = {Neurological and Hematological Recovery Following Copper Replacement in Severe Copper Deficiency-induced Myelopathy and Cytopenia},
  journal = {Clinical Neurology and Neuroscience},
  volume = {5},
  number = {1},
  pages = {1-4},
  doi = {10.11648/j.cnn.20210501.11},
  url = {https://doi.org/10.11648/j.cnn.20210501.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cnn.20210501.11},
  abstract = {Background: Copper deficiency can lead to a severe myelopathy and cytopenia. The myelopathy can lead to inability to walk by paresis and deafferentation. The anemia can as well be severe with the need for blood transfusions. Beside innate reasons it occurs years after surgeries of the intestine and following disturbed resorption. It can also occur due to excessive intake of zinc that binds copper. An early diagnosis following copper substitution can lead to restitution. It can clinically be mistaken for a vitamin B12 deficiency. This circumstance can lead to a delayed treatment. Case: A 67 years old woman with severe gait disturbances, sensory ataxia was admitted to our hospital. She had the diagnosis of vitamin B12 deficiency. B12 was elevated and metabolites were in normal range. The electrophysiology showed a deafferentation of the legs. Objective: This case report provides detailed information about the course of diagnosis and the treatment of a severe copper deficiency with symptomatic myelopathy and cytopenia in an elderly woman. Methods: We performed a literature research with keywords “spinal cord disease, gait disturbances, elevated lactate in cerebrospinal fluid, anemia”. We did blood tests and CSF on a regular basis combined with clinical assessments and electrophysiology. Results: Serum copper was not detectable. CSF copper was reduced (8.7 µg/l, Ref.: 14.2-109 µg/l), CSF lactate was elevated (4.69 mmol/l, Ref.: 1.1-2.4 mmol/l). The patient had a cytopenia (Hb 6.6 g/dl, Ref.: 12-16 g/dl, MCV 130 fl, Ref.: 80-96 fl, leucocytes 2.3 103, Ref.: 4.3-10 103/µl). Vitamin B12 amounted to 891 pg/ml (Ref.: 191-663 pg/ml). The somatosensory evoked potential (SEP) study showed absent cortical responses after stimulation of the sural nerves bilaterally. Due to the diagnosis of a myelopathy and bone marrow dysfunction due to copper deficiency we substituted copper-histidine subcutaneously. This led to a marked improvement of symptoms, an increase of serum copper levels (141 µg/l), CSF copper levels (14.1 µg/l), hemoglobin (11.9 g/dl), leukocyte count (11.4 103/µl) and a normalization of CSF lactate. Conclusion: Elevated CSF lactate might be an indicator for treatable myelopathy due to copper deficiency in patients with afferent gait disturbances. A timely substitution can lead to a marked improvement of even severe symptoms.},
 year = {2021}
}

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