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Metastatic optic nerve sheath calcification with optic atrophy associated with untreated hyperparathyroidism
Interdisciplinary Neurosurgery 20 (2020) 100631
Contents lists available at ScienceDirect
Interdisciplinary Neurosurgery journal homepage: www.elsevier.com/locate/inat
Neuroanatomical studies
Metastatic optic nerve sheath calcification with optic atrophy associated with untreated hyperparathyroidism Patrick K. Jowdya,b,1, Andrew J. Fabianoa,b,2, Robert A. Fenstermakera,b, a b
T
⁎,3
Department of Neurosurgery Roswell Park Comprehensive Cancer Center, 665 Elm Street, Buffalo, NY 14203, United States Department of Neurosurgery Jacobs School of Medicine and Biomedical Sciences, 955 Main Street, Buffalo, NY 14203, United States
A R T I C LE I N FO
A B S T R A C T
Keywords: Optic nerve sheath Metastatic calcification Optic atrophy Hyperparathyroidism Hypercalcemia Visual deficit
Background: To date, the etiology of optic nerve sheath calcifications is unclear and visual loss secondary to optic nerve sheath calcifications has been reported infrequently. Case description: We report the case of a patient with an untreated parathyroid adenoma with longstanding elevated parathormone levels and hypercalcemia. This patient presented with optic atrophy and visual loss bilaterally (right worse than left) with associated exuberant calcification of the optic nerve sheaths and choroid plexus. Conclusions: Our patient demonstrates that metastatic optic nerve sheath calcification can occur in the setting of untreated hyperparathyroidism with longstanding hypercalcemia. Patients who present with optic nerve sheath calcification, with or without visual loss, should be studied for hypercalcemia and the possibility of an occult parathyroid adenoma should be considered as a possible cause.
1. Introduction Optic nerve sheath calcifications have been reported infrequently [1–3]. Of four such patients reported, only two experienced visual symptoms [2,3]. In general, intracranial calcification can be seen in a variety of syndromes and can be either physiological or pathologic [2]. Ten percent of normal individuals have been found to have calcifications of the dura of the falx cerebri, tentorium cerebellum or calvaria [1]. These benign calcifications have also been reported in the optic nerve head, trochlear apparatus of the superior oblique muscle, the sclera, and proximal dural sheaths of the optic nerves [1]. Intracranial calcifications that resulted in visual disturbances have been reported in familial hypophosphatemic rickets in which marked bone thickening caused narrowing of the optic canals with bilateral optic atrophy [4]. In addition, three patients with visual disturbances who had calcification within the optic nerve itself that was thought to represent calcified thrombi within the central retinal vein or artery have been reported [5]. Here we report the case of a patient with untreated parathyroid
adenoma with longstanding elevated parathormone levels and hypercalcemia. This individual presented with optic atrophy and visual loss bilaterally (right worse than left) and associated exuberant calcification of the optic nerve sheaths and choroid plexus. To our knowledge, only another such case of a patient with visual loss in the setting of hyperparathyroidism has been reported. In that case, imaging features were not described and the patient’s symptoms were ascribed to ischemic optic neuropathy [6]. 2. Case presentation The patient is a 59 year-old woman who presented with an 8-month history of progressive visual decline in her right eye. Her past medical history was significant for hyperparathyroidism secondary to a parathyroid adenoma for which she underwent parathyroidectomy in the 1990s; as well as a history of a benign goiter for which she underwent a right thyroid lobectomy in 1995. The patient subsequently developed recurrent hypercalcemia and an elevated serum parathormone (PTH) in
Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging; OCT, ocular coherence tomography; PTH, parathormone; T4, thyroxine; T3, triiodothyronine; TSH, thyroid stimulating hormone ⁎ Corresponding author at: Roswell Park Comprehensive Cancer Center, 665 Elm Street, Buffalo, NY 14203, United States. E-mail addresses: [email protected] (P.K. Jowdy), [email protected] (A.J. Fabiano), [email protected] (R.A. Fenstermaker). 1 https://orcid.org/0000-0003-4637-035X. 2 https://orcid.org/0000-0001-9991-6171. 3 https://orcid.org/0000-0003-0309-8130. https://doi.org/10.1016/j.inat.2019.100631 Received 27 October 2019; Accepted 16 November 2019 2214-7519/ © 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Interdisciplinary Neurosurgery 20 (2020) 100631
P.K. Jowdy, et al.
Fig. 2. (continued) Fig. 1. Parathyroid scan revealing focal uptake in the neck.
2009, at which time a parathyroid scan revealed focal uptake in the neck (Fig. 1). Further parathyroid surgery was recommended, however the patient did not agree to surgery and she did not seek further medical treatment for the condition for 9 years. During the interval, the patient underwent removal of a cataract from her right eye; however, vision in that eye did not improve significantly. In March 2019, the patient presented to an ophthalmologist complaining of progressive decline in the vision in her right eye over an 8-month period. At this time, optic atrophy was noted on funduscopic exam and by ocular coherence tomography (OCT). A CT scan showed nodular calcifications in both retinas and severe concentric calcification of the posterior optic nerve sheaths bilaterally (Fig. 2A and B). In addition, extensive calcification of the choroid plexus in the atria of both lateral ventricles was observed (Fig. 2C). MRI of the brain and orbits revealed no evidence of a soft tissue component to the calcified optic sheath lesions and an octreotide scan showed no uptake within the optic nerve sheaths, choroid plexus or other intra-cranial structures (not shown). At this time, the patient’s serum calcium was 11.6 mg/dL (normal levels: 8.4–10.2 mg/dL) and ionized calcium was 1.66 mmol/L (normal levels: 1.19–1.29 mmol/L). The serum parathormone level was
Fig. 2. (continued)
306.8 pg/ml (normal levels: 8.7–77.1 pg/mL). The patient had normal levels of thyroxine (T4), tri-iodothyronine (T3) and thyroid stimulating hormone (TSH).
3. Discussion Optic nerve sheath calcification resulting in visual loss is rare [1–3]. Murray et al. described a patient who was found to have bilateral symmetric ossification of the optic nerve dural sheath, however further history was not provided. Nicholson et al. report the case of a 58 yearold man who was incidentally found to have bilateral optic nerve calcified lesions during workup for dizziness. This patient had no visual deficits and no other comorbidities that could explain the calcifications and so a diagnosis of idiopathic dural optic nerve sheath calcification was made [3]. Phadke et al. described 2 patients with optic nerve sheath calcifications. The first patient presented with declining monocular vision and a CT of the head showed, in addition to optic nerve sheath calcifications, extensive nodular calcifications of the falx, tentorium and petroclinoid ligaments. The second patient presented with declining monocular vision. As with the first patient, CT of head
Fig. 2. (A) and (B) Nodular calcifications in both retinas and severe concentric calcification of the posterior optic nerve sheaths bilaterally. (C) Extensive calcification of the choroid plexus in the atria of both lateral ventricles is observed. 2
Interdisciplinary Neurosurgery 20 (2020) 100631
P.K. Jowdy, et al.
hyperparathyroidism with longstanding hypercalcemia. Patients who present with optic nerve sheath calcification, with or without visual loss, should be studied for hypercalcemia and the possibility of an occult parathyroid adenoma should be considered as a possible cause.
showed calcification of optic nerve sheaths, falx cerebri and tentorium. Non-pathologic intracranial calcifications are commonly seen on CT scans. Benign calcifications have been reported in the optic nerve head, trochlear apparatus of the superior oblique muscle, the sclera, and proximal dural sheaths of the optic nerves [1]. In addition to physiologic calcification, specific pathologic conditions can also lead to intracranial calcifications. Pathologic calcification can occur by two mechanisms [7]: dystrophic or metastatic. In dystrophic calcification, calcium metabolism is normal, however calcium can be deposited in dead or injured tissues, such as in areas of tissue necrosis. Metastatic calcification is associated with hypercalcemia and can occur in otherwise normal tissues. Major causes include (1) increased secretion of parathyroid hormone either by primary parathyroid tumors or other malignant tumors, (2) destruction of bone due to the effects of accelerated turnover (such as that seen during prolonged immobilization, Paget’s Disease, or multiple myeloma); (3) vitamin D–related disorders; and (4) renal failure, in which secondary hyperparathyroidism can occur as a product of phosphate retention [7]. The most common cause of hyperparathyroidism is a parathyroid adenoma, which is a benign tumor of one of the parathyroid glands. This tumor produces an excess of parathormone which is unresponsive to normal feedback suppression by serum calcium. Excessive parathyroid hormone stimulates osteoclastic erosion of bone which results in the release of bone calcium into the blood leading to hypercalcemia. This sequence of events results in primary hyperparathyroidism, which is the diagnosis carried by our patient [8]. Idiopathic optic nerve sheath calcification and calcification due to untreated chronic hyperparathyroidism must be distinguished from calcification associated with optic nerve sheath meningioma. In our patient, neither contrast-enhanced orbital MRI, nor octreotide scan demonstrated evidence of either a soft tissue component or radionuclide uptake of the optic sheaths respectively. Our patient experienced progressive visual decline with optic atrophy due to concentric calcification of the optic nerve sheaths as a result of metastatic calcification due to untreated longstanding hyperparathyroidism. Of the previous cases of optic nerve sheath calcification reported in the literature to date, only 2 (50%) were associated with visual compromise. In none of the cases was a clear pathophysiologic mechanism identified that could explain the calcifications.
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgements None. Data availability Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. References [1] J.L. Murray, L.A. Hayman, R.A. Tang, J.S. Schiffman, Incidental asymptomatic orbital calcifications, J. Neuroophthalmol. 15 (4) (1995) 203–208. [2] R.V. Phadke, P. Agarwal, K. Sharma, S.S. Chauhan, Idiopathic duro-optic calcification–a new entity? Clin. Radiol. 51 (5) (1996) 359–361. [3] B.P. Nicholson, L.D. Lystad, T.M. Emch, A.D. Singh, Idiopathic dural optic nerve sheath calcification, Br. J. Ophthalmol. 95 (2) (2011) 290–299. [4] K.S. Caldemeyer, R.R. Smith, M.K. Edwards-Brown, Familial hypophosphatemic rickets causing ocular calcification and optic canal narrowing, AJNR Am. J. Neuroradiol. 16 (6) (1995) 1252–1254. [5] A.A. Sadun, R.L. Green, J.R. Nobe, M.R. Cano, Papillopathies associated with unusual calcifications in the retrolaminar optic nerve, J. Clin. Neuroophthalmol. 11 (3) (1991) 175–180 discussion 181–172. [6] D. Chappel, K. Farrington, Primary hyperparathyroidism presenting as unilateral visual loss, Postgrad. Med. J. 67 (787) (1991) 469–470. [7] V. Kumar, A.K. Abbas, J.C. Aster, J.A. Perkins, Robbins basic pathology. In: Tenth edition. ed. Philadelphia, Pa.: Elsevier,; 2018: Click here to access this title in ClinicalKey http://gate.lib.buffalo.edu/login?url=https://www.clinicalkey.com/ dura/browse/bookChapter/3-s2.0-C20140017194. [8] B. Young, G. O'Dowd, P. Woodford, Wheater's functional histology: a text and colour atlas. Sixth ed. Philadelphia, PA: Churchill Livingston/Elsevier; 2014: ClinicalKey https://www.clinicalkey.com/dura/browse/bookChapter/3-s2.0-C20090600258.
4. Conclusion To date, an underlying cause of optic nerve sheath calcification has not been identified. Our patient demonstrates that metastatic optic nerve sheath calcification can occur in the setting of untreated
3
Contents lists available at ScienceDirect
Interdisciplinary Neurosurgery journal homepage: www.elsevier.com/locate/inat
Neuroanatomical studies
Metastatic optic nerve sheath calcification with optic atrophy associated with untreated hyperparathyroidism Patrick K. Jowdya,b,1, Andrew J. Fabianoa,b,2, Robert A. Fenstermakera,b, a b
T
⁎,3
Department of Neurosurgery Roswell Park Comprehensive Cancer Center, 665 Elm Street, Buffalo, NY 14203, United States Department of Neurosurgery Jacobs School of Medicine and Biomedical Sciences, 955 Main Street, Buffalo, NY 14203, United States
A R T I C LE I N FO
A B S T R A C T
Keywords: Optic nerve sheath Metastatic calcification Optic atrophy Hyperparathyroidism Hypercalcemia Visual deficit
Background: To date, the etiology of optic nerve sheath calcifications is unclear and visual loss secondary to optic nerve sheath calcifications has been reported infrequently. Case description: We report the case of a patient with an untreated parathyroid adenoma with longstanding elevated parathormone levels and hypercalcemia. This patient presented with optic atrophy and visual loss bilaterally (right worse than left) with associated exuberant calcification of the optic nerve sheaths and choroid plexus. Conclusions: Our patient demonstrates that metastatic optic nerve sheath calcification can occur in the setting of untreated hyperparathyroidism with longstanding hypercalcemia. Patients who present with optic nerve sheath calcification, with or without visual loss, should be studied for hypercalcemia and the possibility of an occult parathyroid adenoma should be considered as a possible cause.
1. Introduction Optic nerve sheath calcifications have been reported infrequently [1–3]. Of four such patients reported, only two experienced visual symptoms [2,3]. In general, intracranial calcification can be seen in a variety of syndromes and can be either physiological or pathologic [2]. Ten percent of normal individuals have been found to have calcifications of the dura of the falx cerebri, tentorium cerebellum or calvaria [1]. These benign calcifications have also been reported in the optic nerve head, trochlear apparatus of the superior oblique muscle, the sclera, and proximal dural sheaths of the optic nerves [1]. Intracranial calcifications that resulted in visual disturbances have been reported in familial hypophosphatemic rickets in which marked bone thickening caused narrowing of the optic canals with bilateral optic atrophy [4]. In addition, three patients with visual disturbances who had calcification within the optic nerve itself that was thought to represent calcified thrombi within the central retinal vein or artery have been reported [5]. Here we report the case of a patient with untreated parathyroid
adenoma with longstanding elevated parathormone levels and hypercalcemia. This individual presented with optic atrophy and visual loss bilaterally (right worse than left) and associated exuberant calcification of the optic nerve sheaths and choroid plexus. To our knowledge, only another such case of a patient with visual loss in the setting of hyperparathyroidism has been reported. In that case, imaging features were not described and the patient’s symptoms were ascribed to ischemic optic neuropathy [6]. 2. Case presentation The patient is a 59 year-old woman who presented with an 8-month history of progressive visual decline in her right eye. Her past medical history was significant for hyperparathyroidism secondary to a parathyroid adenoma for which she underwent parathyroidectomy in the 1990s; as well as a history of a benign goiter for which she underwent a right thyroid lobectomy in 1995. The patient subsequently developed recurrent hypercalcemia and an elevated serum parathormone (PTH) in
Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging; OCT, ocular coherence tomography; PTH, parathormone; T4, thyroxine; T3, triiodothyronine; TSH, thyroid stimulating hormone ⁎ Corresponding author at: Roswell Park Comprehensive Cancer Center, 665 Elm Street, Buffalo, NY 14203, United States. E-mail addresses: [email protected] (P.K. Jowdy), [email protected] (A.J. Fabiano), [email protected] (R.A. Fenstermaker). 1 https://orcid.org/0000-0003-4637-035X. 2 https://orcid.org/0000-0001-9991-6171. 3 https://orcid.org/0000-0003-0309-8130. https://doi.org/10.1016/j.inat.2019.100631 Received 27 October 2019; Accepted 16 November 2019 2214-7519/ © 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Interdisciplinary Neurosurgery 20 (2020) 100631
P.K. Jowdy, et al.
Fig. 2. (continued) Fig. 1. Parathyroid scan revealing focal uptake in the neck.
2009, at which time a parathyroid scan revealed focal uptake in the neck (Fig. 1). Further parathyroid surgery was recommended, however the patient did not agree to surgery and she did not seek further medical treatment for the condition for 9 years. During the interval, the patient underwent removal of a cataract from her right eye; however, vision in that eye did not improve significantly. In March 2019, the patient presented to an ophthalmologist complaining of progressive decline in the vision in her right eye over an 8-month period. At this time, optic atrophy was noted on funduscopic exam and by ocular coherence tomography (OCT). A CT scan showed nodular calcifications in both retinas and severe concentric calcification of the posterior optic nerve sheaths bilaterally (Fig. 2A and B). In addition, extensive calcification of the choroid plexus in the atria of both lateral ventricles was observed (Fig. 2C). MRI of the brain and orbits revealed no evidence of a soft tissue component to the calcified optic sheath lesions and an octreotide scan showed no uptake within the optic nerve sheaths, choroid plexus or other intra-cranial structures (not shown). At this time, the patient’s serum calcium was 11.6 mg/dL (normal levels: 8.4–10.2 mg/dL) and ionized calcium was 1.66 mmol/L (normal levels: 1.19–1.29 mmol/L). The serum parathormone level was
Fig. 2. (continued)
306.8 pg/ml (normal levels: 8.7–77.1 pg/mL). The patient had normal levels of thyroxine (T4), tri-iodothyronine (T3) and thyroid stimulating hormone (TSH).
3. Discussion Optic nerve sheath calcification resulting in visual loss is rare [1–3]. Murray et al. described a patient who was found to have bilateral symmetric ossification of the optic nerve dural sheath, however further history was not provided. Nicholson et al. report the case of a 58 yearold man who was incidentally found to have bilateral optic nerve calcified lesions during workup for dizziness. This patient had no visual deficits and no other comorbidities that could explain the calcifications and so a diagnosis of idiopathic dural optic nerve sheath calcification was made [3]. Phadke et al. described 2 patients with optic nerve sheath calcifications. The first patient presented with declining monocular vision and a CT of the head showed, in addition to optic nerve sheath calcifications, extensive nodular calcifications of the falx, tentorium and petroclinoid ligaments. The second patient presented with declining monocular vision. As with the first patient, CT of head
Fig. 2. (A) and (B) Nodular calcifications in both retinas and severe concentric calcification of the posterior optic nerve sheaths bilaterally. (C) Extensive calcification of the choroid plexus in the atria of both lateral ventricles is observed. 2
Interdisciplinary Neurosurgery 20 (2020) 100631
P.K. Jowdy, et al.
hyperparathyroidism with longstanding hypercalcemia. Patients who present with optic nerve sheath calcification, with or without visual loss, should be studied for hypercalcemia and the possibility of an occult parathyroid adenoma should be considered as a possible cause.
showed calcification of optic nerve sheaths, falx cerebri and tentorium. Non-pathologic intracranial calcifications are commonly seen on CT scans. Benign calcifications have been reported in the optic nerve head, trochlear apparatus of the superior oblique muscle, the sclera, and proximal dural sheaths of the optic nerves [1]. In addition to physiologic calcification, specific pathologic conditions can also lead to intracranial calcifications. Pathologic calcification can occur by two mechanisms [7]: dystrophic or metastatic. In dystrophic calcification, calcium metabolism is normal, however calcium can be deposited in dead or injured tissues, such as in areas of tissue necrosis. Metastatic calcification is associated with hypercalcemia and can occur in otherwise normal tissues. Major causes include (1) increased secretion of parathyroid hormone either by primary parathyroid tumors or other malignant tumors, (2) destruction of bone due to the effects of accelerated turnover (such as that seen during prolonged immobilization, Paget’s Disease, or multiple myeloma); (3) vitamin D–related disorders; and (4) renal failure, in which secondary hyperparathyroidism can occur as a product of phosphate retention [7]. The most common cause of hyperparathyroidism is a parathyroid adenoma, which is a benign tumor of one of the parathyroid glands. This tumor produces an excess of parathormone which is unresponsive to normal feedback suppression by serum calcium. Excessive parathyroid hormone stimulates osteoclastic erosion of bone which results in the release of bone calcium into the blood leading to hypercalcemia. This sequence of events results in primary hyperparathyroidism, which is the diagnosis carried by our patient [8]. Idiopathic optic nerve sheath calcification and calcification due to untreated chronic hyperparathyroidism must be distinguished from calcification associated with optic nerve sheath meningioma. In our patient, neither contrast-enhanced orbital MRI, nor octreotide scan demonstrated evidence of either a soft tissue component or radionuclide uptake of the optic sheaths respectively. Our patient experienced progressive visual decline with optic atrophy due to concentric calcification of the optic nerve sheaths as a result of metastatic calcification due to untreated longstanding hyperparathyroidism. Of the previous cases of optic nerve sheath calcification reported in the literature to date, only 2 (50%) were associated with visual compromise. In none of the cases was a clear pathophysiologic mechanism identified that could explain the calcifications.
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgements None. Data availability Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. References [1] J.L. Murray, L.A. Hayman, R.A. Tang, J.S. Schiffman, Incidental asymptomatic orbital calcifications, J. Neuroophthalmol. 15 (4) (1995) 203–208. [2] R.V. Phadke, P. Agarwal, K. Sharma, S.S. Chauhan, Idiopathic duro-optic calcification–a new entity? Clin. Radiol. 51 (5) (1996) 359–361. [3] B.P. Nicholson, L.D. Lystad, T.M. Emch, A.D. Singh, Idiopathic dural optic nerve sheath calcification, Br. J. Ophthalmol. 95 (2) (2011) 290–299. [4] K.S. Caldemeyer, R.R. Smith, M.K. Edwards-Brown, Familial hypophosphatemic rickets causing ocular calcification and optic canal narrowing, AJNR Am. J. Neuroradiol. 16 (6) (1995) 1252–1254. [5] A.A. Sadun, R.L. Green, J.R. Nobe, M.R. Cano, Papillopathies associated with unusual calcifications in the retrolaminar optic nerve, J. Clin. Neuroophthalmol. 11 (3) (1991) 175–180 discussion 181–172. [6] D. Chappel, K. Farrington, Primary hyperparathyroidism presenting as unilateral visual loss, Postgrad. Med. J. 67 (787) (1991) 469–470. [7] V. Kumar, A.K. Abbas, J.C. Aster, J.A. Perkins, Robbins basic pathology. In: Tenth edition. ed. Philadelphia, Pa.: Elsevier,; 2018: Click here to access this title in ClinicalKey http://gate.lib.buffalo.edu/login?url=https://www.clinicalkey.com/ dura/browse/bookChapter/3-s2.0-C20140017194. [8] B. Young, G. O'Dowd, P. Woodford, Wheater's functional histology: a text and colour atlas. Sixth ed. Philadelphia, PA: Churchill Livingston/Elsevier; 2014: ClinicalKey https://www.clinicalkey.com/dura/browse/bookChapter/3-s2.0-C20090600258.
4. Conclusion To date, an underlying cause of optic nerve sheath calcification has not been identified. Our patient demonstrates that metastatic optic nerve sheath calcification can occur in the setting of untreated
3