- Email: [email protected]
Intramedullary Spinal Cord Ganglioglioma Presenting as Hyperhidrosis: A Rare Case Report and Literature Review
Accepted Manuscript Intramedullary Spinal Cord Ganglioglioma Presenting as Hyperhidrosis: A Rare Case Report and literature Review Wei Shi, MD, Benqi Zhao, MM, Jingjing Yao, MD, Yang Zhou, MM, Mengqi Tong, MM, Linkai Jing, MD, Guihuai Wang, MD PII:
S1878-8750(19)30793-4
DOI:
https://doi.org/10.1016/j.wneu.2019.03.115
Reference:
WNEU 11842
To appear in:
World Neurosurgery
Received Date: 16 January 2019 Revised Date:
11 March 2019
Accepted Date: 12 March 2019
Please cite this article as: Shi W, Zhao B, Yao J, Zhou Y, Tong M, Jing L, Wang G, Intramedullary Spinal Cord Ganglioglioma Presenting as Hyperhidrosis: A Rare Case Report and literature Review, World Neurosurgery (2019), doi: https://doi.org/10.1016/j.wneu.2019.03.115. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title: Intramedullary Spinal Cord Ganglioglioma Presenting as Hyperhidrosis: A Rare Case Report and literature Review
Authors: Wei Shi, MD,1 Benqi Zhao, MM,2 Jingjing Yao, MD,3 Yang Zhou, MM,4 Mengqi
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Tong, MM,5 Linkai Jing, MD,1 Guihuai Wang, MD1
Affiliations:
Departments of 1Neurosurgery, 2Radiology and 3Pathology, Beijing Tsinghua
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Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
Department of Pathology, General Navy Hospital of PLA, Beijing, China
5
Department of Intensive Care Unit, Beijing Jishuitan Hospital, Beijing, China
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4
Wei Shi and Benqi Zhao contributed equally to this paper.
Corresponding Author’s name and current institution:
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Guihuai Wang. Department of Neurosurgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University. Corresponding Author’s Email: [email protected] Address: No. 168 Litang Road, Changping District, Beijing, 102218, China
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Tel: +86 10 5611 8500
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Fax: +86 10 5611 8500
ACCEPTED MANUSCRIPT Abstract: Background Hyperhidrosis is caused by sympathetic dysfunction of the central or peripheral nervous system. However, intramedullary spinal cord tumors
the literature. Case description This case involves an 18-year-old man who presented with abnormal enhanced sweating and flushing on the bilateral side of his face and
SC
neck that had persisted for 6 years. Magnetic resonance (MR) images revealed
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presenting with hyperhidrosis as an initial symptom had been rarely reported in
that, at the C7-T2 levels of the spinal cord, a large intramedullary tumor was
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involved in the cervico-thoracic region. The patient underwent gross total resection (GTR) of the tumor via the fluorescein-guided technique and
intraoperative neurophysiological monitoring. The histopathological diagnosis revealed ganglioglioma. The symptoms gradually improved after the surgery, and
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the patient presented virtually complete remission at the end of an 18 months follow-up.
Conclusions Few cases of intramedullary spinal cord tumors presenting as
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hyperhidrosis in clinical manifestation have been reported in the literature. Sympathetic irritation by the tumor, particularly in the location around the gray
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matter of the lateral spinal cord, may account for the hyperhidrosis as the initial symptom in present patient. Therefore, if a patient has autonomic dysfunction, the spine cord should be additionally examined using MR imaging.
Key Words: intramedullary spinal cord tumor, ganglioglioma, hyperhidrosis, fluorescein. Abbreviations and Acronyms: CNS: Central nervous system GTR: Gross total resection
ACCEPTED MANUSCRIPT MR: Magnetic resonance
Abstract word count: 197 Text word count: 1082 Number of references: 23
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Number of tables and/or figures: 6
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Number of videos: 0
ACCEPTED MANUSCRIPT Disclosures: The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
This work was supported by the Natural Science Foundation of China (grant no.
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81472817).
ACCEPTED MANUSCRIPT Title Intramedullary Spinal Cord Ganglioglioma Presenting as Hyperhidrosis: A Rare Case Report and Literature Review
Abstract
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Background: Hyperhidrosis is caused by sympathetic dysfunction of the central or peripheral nervous system. However, intramedullary spinal cord tumors presenting with hyperhidrosis as an initial symptom had been rarely reported in the literature.
Case description: This case involves an 18-year-old man who presented with abnormal
SC
enhanced sweating and flushing on the bilateral side of his face and neck that had persisted for 6 years. Magnetic resonance (MR) images revealed that, at the C7-T2 levels of the spinal cord, a large intramedullary tumor was involved in the cervicothoracic region. The patient
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underwent gross total resection (GTR) of the tumor via the fluorescein-guided technique and intraoperative neurophysiological monitoring. The histopathological diagnosis revealed ganglioglioma. The symptoms gradually improved after surgery. and the patient presented virtually complete remission at the end of an 18-month follow-up. Conclusions: Few cases of intramedullary spinal cord tumors presenting as hyperhidrosis in
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clinical manifestation have been reported in the literature. Sympathetic irritation by the tumor, particularly in the location around the gray matter of the lateral spinal cord, may account for hyperhidrosis as the initial symptom in present patient. Therefore, if a patient has autonomic
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dysfunction, the spinal cord should be additionally examined using MR imaging.
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Key Words: intramedullary spinal cord tumor, ganglioglioma, hyperhidrosis, fluorescein
Abbreviations and acronyms CNS: central nervous system GTR: gross total resection MR: magnetic resonance
1
ACCEPTED MANUSCRIPT Introduction Hyperhidrosis is defined as abnormal enhanced sweating beyond an organism’s physiological needs. It is induced by sympathetic dysfunction in the peripheral or central nervous systems. However, it is extremely seldom induced by intramedullary spinal cord tumors.1-5 As a slow-growing primary central nervous system (CNS) tumor, ganglioglioma is very rare, with
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a prevalence of only 0.4-9% among all primary CNS tumors.6-10 Similarly, spinal cord ganglioglioma accounts for no more than 10% of all intramedullary neoplasms.11
This report documents an 18-year-old male patient who presented with long-term increased sweating in the face and neck. He suffered from an intramedullary spinal cord ganglioglioma
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in the cervicothoracic region.
History and examination
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Case description
An 18-year-old man presented with abnormally enhanced sweating and flushing on his face and neck that had persisted for 6 years. His symptoms became more pronounced when he was in a hot environment, socializing, or exercising, and disappeared when he fell asleep. His medical and family histories were unremarkable.
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Physical and neurological examinations
The patient had normal light reflexes, both direct and indirect, with isocoric pupils. However, his bilateral upper limbs were relatively cold. Hyperhidrosis on the neck and face was revealed according to physical and neurological examinations (Figure 1). The remaining
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neurological examinations were normal. Neuroradiological findings
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No spinal cord edema, cystic change, or syringomyelia was identified. An intramedullary lesion at the C7 to T2 levels was found according to the MR images. The T1-weighted image demonstrated tumor isointensity (Figure 2A), and the T2-weighted image indicated hyperintensity (Figure 2B, C). The Gd-enhanced T1-weighted image identified no tumor enhancement (Figure 2D, E). Surgical treatment Following a dorsal incision, bilateral laminotomies of C7-T2 were conducted along a caudal-to-rostral direction using an ultrasonic BoneScalpel, and the facet joints were preserved. A midline dural incision spanning the entire lesion length was conducted to approach and remove the tumor. The patient’s neurological function was monitored intraoperatively. Local swelling with dilated veins was identified in the spinal cord dorsally 2
ACCEPTED MANUSCRIPT (Figure 3A). Fluorescein fluorescence was observed on the surface of the spinal cord (Figure 3B). A dark red color and easy bleeding was observed on the tumor under white-light microscopy (Figure 3C), but enhancement of fluorescein fluorescence was not identified (Figure 3D). Although the tumor had a relatively unclear margin with the neighboring spinal cord tissue, GTR of the tumor was achieved (Figure 3E). No enhancement was observed
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under fluorescence view (Figure 3F). The histopathological diagnosis was ganglioglioma (WHO Grade I, Figure 4). Postoperative course
Postoperatively, the patient showed worsened motor weakness of the upper right and left
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extremities (III/V and II/V, respectively) and decreased sensation in the left lower extremity. However, hyperhidrosis improved gradually. After two weeks of recovery, the deteriorated motor weakness gradually improved (IV/V bilaterally), and the patient was discharged. No
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radiotherapy or chemotherapy was undertaken for adjuvant treatment. No obvious mass lesion was identified via MR imaging postoperatively and 18 months later (Figure 5). No tumor recurred during the 18-month follow-up period.
Discussion
Hyperhidrosis is defined as a pathologic condition that typically presents more sweating
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than is physiologically necessary to sustain normal body temperatures.12 Obesity, systemic disorders, neurologic diseases, and neuroendocrine tumors have been reported to be possible causes of secondary hyperhidrosis, along with hematologic malignancies, Chiari
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malformation with syringomyelia, tuberculosis, and other infections.13-18 For intramedullary spinal cord tumors, however, hyperhidrosis is a rare symptom: only 5 cases have been
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reported in the literature.1-5 The histopathological analysis identified astrocytoma in 2, gangliocytoma in 1, ganglioglioma in 1, and ependymoma in 1. The case in this article is the second report of spinal ganglioglioma caused hyperhidrosis, in which we used the advanced intraoperative fluorescein-guided technique and achieved tumor GTR. Postoperative neurological deficit was diminished to a minimum, and good functional status was maintained during an 18-month follow-up period. The sweating pathway starts from the preoptic area in the anterior hypothalamus and descends to the synapses on the preganglionic neurons in the intermediolateral spinal cord column after it passes uncrossed through the medial portion in the lateral brainstem funiculus.19 The sympathetic preganglionic neurons are distributed from T1 to L2 in the lateral horn,20 and those that control sympathetic functions in the neck and head are 3
ACCEPTED MANUSCRIPT distributed from T1 to T5, the upper extremities from T2 to T8, and the trunk from T4 to T12. In the cervical ganglia and the upper 3 thoracic ganglia, the preganglionic fibers ascend and synapse. The salivary glands, lacrimal, and sweat on the head and in the blood vessels and smooth muscle are innervated by postganglionic fibers from the cells of the superior cervical ganglion. In the present case, the tumor initially induced dysfunction in the preganglionic
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sympathetic neurons since it was located at the C7-T2 levels and probably arose around the gray matter of the lateral spinal cord. The patient seldom had any sensory defects or motor weakness, which demonstrated that the pyramidal and spinothalamic tracts were intact despite long-term tumor growth. Thus, hyperhidrosis can be the presenting symptom of a
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slow-growing intramedullary spinal cord tumor such as ganglioglioma in the gray matter of the lateral spinal cord.
Spinal cord ganglioglioma grows slowly and is rare, accounting for less than 10% of all
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intramedullary tumors.11 The optimal treatment of this neoplasm has not been clearly established.7,21 Due to the slow growth and indolent nature of this tumor, the benefit of radical resection must be weighed against the risk of further worsening neurological function, particularly in young patients who have a longer life expectancy.22 In the present case, we completely resected the tumor with an ill-defined border via the assistance of the
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intraoperative fluorescein-guided technique. The patient maintained a good functional status and no recurrence was found after an 18-month follow-up period. Fluorescence-guided surgery, as an advanced adjunctive technique, has been increasingly reported to assist CNS tumor resection. Due to its capacity to penetrate brain
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areas where the blood-brain barrier has been disrupted, fluorescein sodium has been reported for its efficacy at removing high-grade gliomas.23 However, doubts remain regarding the
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value of this technique in spinal cord tumor surgery, especially for low-grade gliomas with no contrast enhancement on MR imaging. In this case, we verified that the technique was useful for both locating the tumor and defining the surgical trajectory in an intramedullary ganglioglioma procedure.
Conclusions Hyperhidrosis is a rare clinical manifestation of an intramedullary spinal cord ganglioglioma. Attention to uncommon characteristics such as hyperhidrosis might be an important key to the early diagnosis of this rare spinal cord neoplasm. Surgical resection remains the best treatment modality for an optimal prognosis. 4
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Acknowledgments: None.
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ACCEPTED MANUSCRIPT References 1.
Chatterjee S, Ghosh K, Banerjee T. An intramedullary tumor presenting with hyperhidrosis. Neurology India. 2004;52(3):390-391.
2.
Jacob JT, Cohen-Gadol AA, Scheithauer BW, Krauss WE. Intramedullary spinal cord
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gangliocytoma: case report and a review of the literature. Neurosurg Rev. 2005;28(4):326-329. 3.
Kilincer C, Ozturk L, Hamamcioglu MK, Altunrende E, Cobanoglu S. An upper thoracic spinal cord tumor presenting as hemifacial hyperhidrosis. Surg Neurol.
4.
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2007;68(4):461-463; discussion 463.
Murakami T, Koyanagi I, Kaneko T, et al. Intramedullary spinal cord ganglioglioma
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presenting as hyperhidrosis: unique symptoms and magnetic resonance imaging findings: case report. J Neurosurg Spine. 2013;18(2):184-188. 5.
Haddadi K. A huge ependymoma of the cervical spinal cord with subtle atypical manifestations and hyperhidrosis: Case report. Int J Surg Case Rep. 2016;19:100-102.
6.
Demierre B, Stichnoth FA, Hori A, Spoerri O. Intracerebral ganglioglioma. J
7.
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Neurosurg. 1986;65(2):177-182.
Hamburger C, Buttner A, Weis S. Ganglioglioma of the spinal cord: report of two rare cases and review of the literature. Neurosurgery. 1997;41(6):1410-1415; discussion 1415-1416.
Mickle JP. Ganglioglioma in children. A review of 32 cases at the University of
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8.
Florida. Pediatr Neurosurg. 1992;18(5-6):310-314. Smith NM, Carli MM, Hanieh A, Clark B, Bourne AJ, Byard RW. Gangliogliomas in
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9.
childhood. Childs Nerv Syst. 1992;8(5):258-262. 10.
Ventureyra E, Herder S, Mallya BK, Keene D. Temporal lobe gangliogliomas in children. Childs Nerv Syst. 1986;2(2):63-66.
11.
Miller DC. Surgical pathology of intramedullary spinal cord neoplasms. J Neurooncol. 2000;47(3):189-194.
12.
Hornberger J, Grimes K, Naumann M, et al. Recognition, diagnosis, and treatment of primary focal hyperhidrosis. J Am Acad Dermatol. 2004;51(2):274-286.
13.
Walling HW. Clinical differentiation of primary from secondary hyperhidrosis. J Am 6
ACCEPTED MANUSCRIPT Acad Dermatol. 2011;64(4):690-695. 14.
Glaser DA, Hebert AA, Pariser DM, Solish N. Primary focal hyperhidrosis: scope of the problem. Cutis. 2007;79(5 Suppl):5-17.
15.
Faruqi S, Redmond G, Ram P, Owens VB, Sangster G, Barrett JA. Hemihyperhidrosis
16.
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in cerebral infarction. Age Ageing. 2004;33(5):514-515. Smith CD. A hypothalamic stroke producing recurrent hemihyperhidrosis. Neurology. 2001;56(10):1394-1396. 17.
Sudou K, Tashiro K. Segmental hyperhidrosis in syringomyelia with Chiari
18.
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malformation. J Neurol. 1993;240(2):75-78.
Kewalramani LS. Autonomic dysreflexia in traumatic myelopathy. Am J Phys Med.
19.
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1980;59(1):1-21.
Nathan PW, Smith MC. The location of descending fibres to sympathetic preganglionic vasomotor and sudomotor neurons in man. J Neurol Neurosurg Psychiatry. 1987;50(10):1253-1262.
Pick J, Sheehan D. Sympathetic rami in man. J Anat. 1946;80:12-20.
21.
Chamoun RB, Alaraj AM, Al Kutoubi AO, Abboud MR, Haddad GF. Role of
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20.
temozolomide in spinal cord low grade astrocytomas: results in two paediatric patients. Acta Neurochir (Wien). 2006;148(2):175-179; discussion 180. Oppenheimer DC, Johnson MD, Judkins AR. Ganglioglioma of the Spinal Cord. J
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22.
Clin Imaging Sci. 2015;5:53. Schebesch KM, Proescholdt M, Hohne J, et al. Sodium fluorescein-guided resection under the YELLOW 560 nm surgical microscope filter in malignant brain tumor
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23.
surgery--a feasibility study. Acta Neurochir (Wien). 2013;155(4):693-699.
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ACCEPTED MANUSCRIPT Figure captions Figure 1 A photograph of the patient revealing face and neck flushing and hyperhidrosis.
Figure 2 Sagittal and axial MRI studies demonstrating an intramedullary tumor at the level of C7-T2. The tumor is isointense on T1-weighted images (A) and hyperintense on T2-weighted
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images (B, C). Gd-enhanced T1-weighted MR images (D, E) reveal no enhancement.
Figure 3 Intraoperative view of the tumor under white-light microscopy and fluorescence. Intraoperative visualization of the spinal cord at the C7-T2 level with white-light microscopy
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(A) shows local swelling (arrow) with dilated veins dorsally. Fluorescein fluorescence is observed at the left side of the spinal cord (arrow) (B). The tumor is dark red (C) under white-light microscopy and shows no enhancement in fluorescein fluorescence (D). After the
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tumor GTR (E), no enhancement was observed under fluorescence view (F). Figure 4 Photomicrographs of the tumor sections. HE-stained section showing a mixture of dysplastic ganglion cells and neoplastic glial cells (A) and dystrophic calcification within capillary incrustation (B). Section showing S-100 expressed in both the dysplastic ganglion cells and neoplastic glial cells (C). GFAP-positive cells distributed in a lobular architecture
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(D). Original magnification ×400.
Figure 5 Postoperative sagittal and axial T2-weighted MR images obtained the day after surgery (A, B) and after an 18-month follow-up (C, D) demonstrating gross total resection
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and no recurrence of the intramedullary tumor.
8
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Table 1 Literature review of cases of hyperhidrosis caused by intramedullary spinal cord tumors* Authors & year Patient Symptom Location of Distribution of Histopathological Findings Age (yrs.), Duration tumor Hyperhidrosis Sex Chatterjee et al., 2004 56, F 6 mos. FM - T2 Head, neck Astrocytoma Jacob et al., 2005 19, F 10 yrs. C7 - T3 Face, neck Gangliocytoma Kilincer et al., 2007 17, M > 10 yrs. T1 - T2 Face, neck Low-grade astrocytoma Murakami et al., 2013 16, M 6 yrs. T2 - T3 Neck, upper limb, Ganglioglioma chest Haddadi et al., 2016 34, M 1 yrs. FM - T2 Neck, upper limb, Ependymoma chest Present study 18, M 6 yrs. C7 - T2 Face, neck Ganglioglioma
Tx
Outcome
STR STR GTR
Resolved completely Stable Resolved completely
STR
Resolved partially
STR
Resolved partially
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Resolved almost completely * FM = foremen magnum; GTR = gross-total resection; STR = subtotal resection; Tx = treatment; F = female; M = male; mos. = months; yrs. = years.
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GTR
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S1878-8750(19)30793-4
DOI:
https://doi.org/10.1016/j.wneu.2019.03.115
Reference:
WNEU 11842
To appear in:
World Neurosurgery
Received Date: 16 January 2019 Revised Date:
11 March 2019
Accepted Date: 12 March 2019
Please cite this article as: Shi W, Zhao B, Yao J, Zhou Y, Tong M, Jing L, Wang G, Intramedullary Spinal Cord Ganglioglioma Presenting as Hyperhidrosis: A Rare Case Report and literature Review, World Neurosurgery (2019), doi: https://doi.org/10.1016/j.wneu.2019.03.115. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title: Intramedullary Spinal Cord Ganglioglioma Presenting as Hyperhidrosis: A Rare Case Report and literature Review
Authors: Wei Shi, MD,1 Benqi Zhao, MM,2 Jingjing Yao, MD,3 Yang Zhou, MM,4 Mengqi
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Tong, MM,5 Linkai Jing, MD,1 Guihuai Wang, MD1
Affiliations:
Departments of 1Neurosurgery, 2Radiology and 3Pathology, Beijing Tsinghua
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Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
Department of Pathology, General Navy Hospital of PLA, Beijing, China
5
Department of Intensive Care Unit, Beijing Jishuitan Hospital, Beijing, China
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4
Wei Shi and Benqi Zhao contributed equally to this paper.
Corresponding Author’s name and current institution:
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Guihuai Wang. Department of Neurosurgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University. Corresponding Author’s Email: [email protected] Address: No. 168 Litang Road, Changping District, Beijing, 102218, China
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Tel: +86 10 5611 8500
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Fax: +86 10 5611 8500
ACCEPTED MANUSCRIPT Abstract: Background Hyperhidrosis is caused by sympathetic dysfunction of the central or peripheral nervous system. However, intramedullary spinal cord tumors
the literature. Case description This case involves an 18-year-old man who presented with abnormal enhanced sweating and flushing on the bilateral side of his face and
SC
neck that had persisted for 6 years. Magnetic resonance (MR) images revealed
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presenting with hyperhidrosis as an initial symptom had been rarely reported in
that, at the C7-T2 levels of the spinal cord, a large intramedullary tumor was
M AN U
involved in the cervico-thoracic region. The patient underwent gross total resection (GTR) of the tumor via the fluorescein-guided technique and
intraoperative neurophysiological monitoring. The histopathological diagnosis revealed ganglioglioma. The symptoms gradually improved after the surgery, and
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the patient presented virtually complete remission at the end of an 18 months follow-up.
Conclusions Few cases of intramedullary spinal cord tumors presenting as
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hyperhidrosis in clinical manifestation have been reported in the literature. Sympathetic irritation by the tumor, particularly in the location around the gray
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matter of the lateral spinal cord, may account for the hyperhidrosis as the initial symptom in present patient. Therefore, if a patient has autonomic dysfunction, the spine cord should be additionally examined using MR imaging.
Key Words: intramedullary spinal cord tumor, ganglioglioma, hyperhidrosis, fluorescein. Abbreviations and Acronyms: CNS: Central nervous system GTR: Gross total resection
ACCEPTED MANUSCRIPT MR: Magnetic resonance
Abstract word count: 197 Text word count: 1082 Number of references: 23
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Number of tables and/or figures: 6
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Number of videos: 0
ACCEPTED MANUSCRIPT Disclosures: The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
This work was supported by the Natural Science Foundation of China (grant no.
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M AN U
SC
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81472817).
ACCEPTED MANUSCRIPT Title Intramedullary Spinal Cord Ganglioglioma Presenting as Hyperhidrosis: A Rare Case Report and Literature Review
Abstract
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Background: Hyperhidrosis is caused by sympathetic dysfunction of the central or peripheral nervous system. However, intramedullary spinal cord tumors presenting with hyperhidrosis as an initial symptom had been rarely reported in the literature.
Case description: This case involves an 18-year-old man who presented with abnormal
SC
enhanced sweating and flushing on the bilateral side of his face and neck that had persisted for 6 years. Magnetic resonance (MR) images revealed that, at the C7-T2 levels of the spinal cord, a large intramedullary tumor was involved in the cervicothoracic region. The patient
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underwent gross total resection (GTR) of the tumor via the fluorescein-guided technique and intraoperative neurophysiological monitoring. The histopathological diagnosis revealed ganglioglioma. The symptoms gradually improved after surgery. and the patient presented virtually complete remission at the end of an 18-month follow-up. Conclusions: Few cases of intramedullary spinal cord tumors presenting as hyperhidrosis in
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clinical manifestation have been reported in the literature. Sympathetic irritation by the tumor, particularly in the location around the gray matter of the lateral spinal cord, may account for hyperhidrosis as the initial symptom in present patient. Therefore, if a patient has autonomic
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dysfunction, the spinal cord should be additionally examined using MR imaging.
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Key Words: intramedullary spinal cord tumor, ganglioglioma, hyperhidrosis, fluorescein
Abbreviations and acronyms CNS: central nervous system GTR: gross total resection MR: magnetic resonance
1
ACCEPTED MANUSCRIPT Introduction Hyperhidrosis is defined as abnormal enhanced sweating beyond an organism’s physiological needs. It is induced by sympathetic dysfunction in the peripheral or central nervous systems. However, it is extremely seldom induced by intramedullary spinal cord tumors.1-5 As a slow-growing primary central nervous system (CNS) tumor, ganglioglioma is very rare, with
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a prevalence of only 0.4-9% among all primary CNS tumors.6-10 Similarly, spinal cord ganglioglioma accounts for no more than 10% of all intramedullary neoplasms.11
This report documents an 18-year-old male patient who presented with long-term increased sweating in the face and neck. He suffered from an intramedullary spinal cord ganglioglioma
SC
in the cervicothoracic region.
History and examination
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Case description
An 18-year-old man presented with abnormally enhanced sweating and flushing on his face and neck that had persisted for 6 years. His symptoms became more pronounced when he was in a hot environment, socializing, or exercising, and disappeared when he fell asleep. His medical and family histories were unremarkable.
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Physical and neurological examinations
The patient had normal light reflexes, both direct and indirect, with isocoric pupils. However, his bilateral upper limbs were relatively cold. Hyperhidrosis on the neck and face was revealed according to physical and neurological examinations (Figure 1). The remaining
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neurological examinations were normal. Neuroradiological findings
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No spinal cord edema, cystic change, or syringomyelia was identified. An intramedullary lesion at the C7 to T2 levels was found according to the MR images. The T1-weighted image demonstrated tumor isointensity (Figure 2A), and the T2-weighted image indicated hyperintensity (Figure 2B, C). The Gd-enhanced T1-weighted image identified no tumor enhancement (Figure 2D, E). Surgical treatment Following a dorsal incision, bilateral laminotomies of C7-T2 were conducted along a caudal-to-rostral direction using an ultrasonic BoneScalpel, and the facet joints were preserved. A midline dural incision spanning the entire lesion length was conducted to approach and remove the tumor. The patient’s neurological function was monitored intraoperatively. Local swelling with dilated veins was identified in the spinal cord dorsally 2
ACCEPTED MANUSCRIPT (Figure 3A). Fluorescein fluorescence was observed on the surface of the spinal cord (Figure 3B). A dark red color and easy bleeding was observed on the tumor under white-light microscopy (Figure 3C), but enhancement of fluorescein fluorescence was not identified (Figure 3D). Although the tumor had a relatively unclear margin with the neighboring spinal cord tissue, GTR of the tumor was achieved (Figure 3E). No enhancement was observed
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under fluorescence view (Figure 3F). The histopathological diagnosis was ganglioglioma (WHO Grade I, Figure 4). Postoperative course
Postoperatively, the patient showed worsened motor weakness of the upper right and left
SC
extremities (III/V and II/V, respectively) and decreased sensation in the left lower extremity. However, hyperhidrosis improved gradually. After two weeks of recovery, the deteriorated motor weakness gradually improved (IV/V bilaterally), and the patient was discharged. No
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radiotherapy or chemotherapy was undertaken for adjuvant treatment. No obvious mass lesion was identified via MR imaging postoperatively and 18 months later (Figure 5). No tumor recurred during the 18-month follow-up period.
Discussion
Hyperhidrosis is defined as a pathologic condition that typically presents more sweating
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than is physiologically necessary to sustain normal body temperatures.12 Obesity, systemic disorders, neurologic diseases, and neuroendocrine tumors have been reported to be possible causes of secondary hyperhidrosis, along with hematologic malignancies, Chiari
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malformation with syringomyelia, tuberculosis, and other infections.13-18 For intramedullary spinal cord tumors, however, hyperhidrosis is a rare symptom: only 5 cases have been
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reported in the literature.1-5 The histopathological analysis identified astrocytoma in 2, gangliocytoma in 1, ganglioglioma in 1, and ependymoma in 1. The case in this article is the second report of spinal ganglioglioma caused hyperhidrosis, in which we used the advanced intraoperative fluorescein-guided technique and achieved tumor GTR. Postoperative neurological deficit was diminished to a minimum, and good functional status was maintained during an 18-month follow-up period. The sweating pathway starts from the preoptic area in the anterior hypothalamus and descends to the synapses on the preganglionic neurons in the intermediolateral spinal cord column after it passes uncrossed through the medial portion in the lateral brainstem funiculus.19 The sympathetic preganglionic neurons are distributed from T1 to L2 in the lateral horn,20 and those that control sympathetic functions in the neck and head are 3
ACCEPTED MANUSCRIPT distributed from T1 to T5, the upper extremities from T2 to T8, and the trunk from T4 to T12. In the cervical ganglia and the upper 3 thoracic ganglia, the preganglionic fibers ascend and synapse. The salivary glands, lacrimal, and sweat on the head and in the blood vessels and smooth muscle are innervated by postganglionic fibers from the cells of the superior cervical ganglion. In the present case, the tumor initially induced dysfunction in the preganglionic
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sympathetic neurons since it was located at the C7-T2 levels and probably arose around the gray matter of the lateral spinal cord. The patient seldom had any sensory defects or motor weakness, which demonstrated that the pyramidal and spinothalamic tracts were intact despite long-term tumor growth. Thus, hyperhidrosis can be the presenting symptom of a
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slow-growing intramedullary spinal cord tumor such as ganglioglioma in the gray matter of the lateral spinal cord.
Spinal cord ganglioglioma grows slowly and is rare, accounting for less than 10% of all
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intramedullary tumors.11 The optimal treatment of this neoplasm has not been clearly established.7,21 Due to the slow growth and indolent nature of this tumor, the benefit of radical resection must be weighed against the risk of further worsening neurological function, particularly in young patients who have a longer life expectancy.22 In the present case, we completely resected the tumor with an ill-defined border via the assistance of the
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intraoperative fluorescein-guided technique. The patient maintained a good functional status and no recurrence was found after an 18-month follow-up period. Fluorescence-guided surgery, as an advanced adjunctive technique, has been increasingly reported to assist CNS tumor resection. Due to its capacity to penetrate brain
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areas where the blood-brain barrier has been disrupted, fluorescein sodium has been reported for its efficacy at removing high-grade gliomas.23 However, doubts remain regarding the
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value of this technique in spinal cord tumor surgery, especially for low-grade gliomas with no contrast enhancement on MR imaging. In this case, we verified that the technique was useful for both locating the tumor and defining the surgical trajectory in an intramedullary ganglioglioma procedure.
Conclusions Hyperhidrosis is a rare clinical manifestation of an intramedullary spinal cord ganglioglioma. Attention to uncommon characteristics such as hyperhidrosis might be an important key to the early diagnosis of this rare spinal cord neoplasm. Surgical resection remains the best treatment modality for an optimal prognosis. 4
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Acknowledgments: None.
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ACCEPTED MANUSCRIPT References 1.
Chatterjee S, Ghosh K, Banerjee T. An intramedullary tumor presenting with hyperhidrosis. Neurology India. 2004;52(3):390-391.
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presenting as hyperhidrosis: unique symptoms and magnetic resonance imaging findings: case report. J Neurosurg Spine. 2013;18(2):184-188. 5.
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childhood. Childs Nerv Syst. 1992;8(5):258-262. 10.
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Hornberger J, Grimes K, Naumann M, et al. Recognition, diagnosis, and treatment of primary focal hyperhidrosis. J Am Acad Dermatol. 2004;51(2):274-286.
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Walling HW. Clinical differentiation of primary from secondary hyperhidrosis. J Am 6
ACCEPTED MANUSCRIPT Acad Dermatol. 2011;64(4):690-695. 14.
Glaser DA, Hebert AA, Pariser DM, Solish N. Primary focal hyperhidrosis: scope of the problem. Cutis. 2007;79(5 Suppl):5-17.
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in cerebral infarction. Age Ageing. 2004;33(5):514-515. Smith CD. A hypothalamic stroke producing recurrent hemihyperhidrosis. Neurology. 2001;56(10):1394-1396. 17.
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Nathan PW, Smith MC. The location of descending fibres to sympathetic preganglionic vasomotor and sudomotor neurons in man. J Neurol Neurosurg Psychiatry. 1987;50(10):1253-1262.
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Chamoun RB, Alaraj AM, Al Kutoubi AO, Abboud MR, Haddad GF. Role of
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temozolomide in spinal cord low grade astrocytomas: results in two paediatric patients. Acta Neurochir (Wien). 2006;148(2):175-179; discussion 180. Oppenheimer DC, Johnson MD, Judkins AR. Ganglioglioma of the Spinal Cord. J
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surgery--a feasibility study. Acta Neurochir (Wien). 2013;155(4):693-699.
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ACCEPTED MANUSCRIPT Figure captions Figure 1 A photograph of the patient revealing face and neck flushing and hyperhidrosis.
Figure 2 Sagittal and axial MRI studies demonstrating an intramedullary tumor at the level of C7-T2. The tumor is isointense on T1-weighted images (A) and hyperintense on T2-weighted
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images (B, C). Gd-enhanced T1-weighted MR images (D, E) reveal no enhancement.
Figure 3 Intraoperative view of the tumor under white-light microscopy and fluorescence. Intraoperative visualization of the spinal cord at the C7-T2 level with white-light microscopy
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(A) shows local swelling (arrow) with dilated veins dorsally. Fluorescein fluorescence is observed at the left side of the spinal cord (arrow) (B). The tumor is dark red (C) under white-light microscopy and shows no enhancement in fluorescein fluorescence (D). After the
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tumor GTR (E), no enhancement was observed under fluorescence view (F). Figure 4 Photomicrographs of the tumor sections. HE-stained section showing a mixture of dysplastic ganglion cells and neoplastic glial cells (A) and dystrophic calcification within capillary incrustation (B). Section showing S-100 expressed in both the dysplastic ganglion cells and neoplastic glial cells (C). GFAP-positive cells distributed in a lobular architecture
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(D). Original magnification ×400.
Figure 5 Postoperative sagittal and axial T2-weighted MR images obtained the day after surgery (A, B) and after an 18-month follow-up (C, D) demonstrating gross total resection
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and no recurrence of the intramedullary tumor.
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Table 1 Literature review of cases of hyperhidrosis caused by intramedullary spinal cord tumors* Authors & year Patient Symptom Location of Distribution of Histopathological Findings Age (yrs.), Duration tumor Hyperhidrosis Sex Chatterjee et al., 2004 56, F 6 mos. FM - T2 Head, neck Astrocytoma Jacob et al., 2005 19, F 10 yrs. C7 - T3 Face, neck Gangliocytoma Kilincer et al., 2007 17, M > 10 yrs. T1 - T2 Face, neck Low-grade astrocytoma Murakami et al., 2013 16, M 6 yrs. T2 - T3 Neck, upper limb, Ganglioglioma chest Haddadi et al., 2016 34, M 1 yrs. FM - T2 Neck, upper limb, Ependymoma chest Present study 18, M 6 yrs. C7 - T2 Face, neck Ganglioglioma
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Outcome
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Resolved completely Stable Resolved completely
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Resolved partially
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Resolved partially
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Resolved almost completely * FM = foremen magnum; GTR = gross-total resection; STR = subtotal resection; Tx = treatment; F = female; M = male; mos. = months; yrs. = years.
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