Spinal intradural pseudocyst formation in central nervous system superficial siderosis

Abstract

The figure shows tissue samples taken from three previous cases, revealing the cause of hemosiderin deposition in the central nervous system because of superficial siderosis.

Superficial siderosis of the central nervous system (SSCNS) is a neurological disorder caused by persistent or repeated subarachnoid hemorrhage (SAH) [1, 2]. Among SSCNS patients, some exhibit a spinal dural defect and intraspinal fluid collection (IFC) [1, 3, 4, 5, 6]. Because dural repair results in the improvement of SAH and reduction of IFC [7, 8, 9], we hypothesize that spinal dural defect may be a source of subarachnoid hemorrhage that can cause superficial siderosis. Although the number of clinical reports has been increasing, the histology of these defects and IFC remain unclear. In this study, we conducted a pathological examination of the spinal dura mater of two autopsy materials (Cases 1 and 2) and a dural biopsy specimen (Case 3) obtained from SSCNS patients with IFC.

Case 1 experienced four physical traumas from motor vehicle accidents between the ages of 13 and 39, including full‐body contusions, but no severe spinal or head trauma. He later noticed hearing impairment and gait disturbance at the ages of 50 and 52 years, respectively. Normal opening pressure (12 cm H₂O) and xanthochromia were noted during lumbar puncture. Magnetic resonance (MR) imaging indicated the presence of SSCNS and IFC extending from the first thoracic cord (Th1) to Th8 (Figure 1A,B). Dynamic myelography revealed a defect in the ventral dura mater at Th2, connecting the subarachnoid space to IFC. The repeated traffic accidents were supposed to be a cause of the dural defect. The patient underwent surgical repair of the defect at 54 years of age. During the surgery, we detected a slit‐like dural defect (5 mm × 2 mm in size) in the dural inner layer (Figure 1D). The arachnoid membrane herniated into the defect. The defect did not penetrate the dura mater. After the surgery, which the defect was repaired, xanthochromic cerebrospinal fluid (CSF) improved, IFC reduced (Figure 1C), and the progression of symptoms stopped. He accidentally drowned while taking a bath 4 years after the surgery. An autopsy was performed 3 h after the death.

FIGURE 1.

Figures are taken from Case 1. (A,B) T2‐weighted magnetic resonance imaging shows the presence of intraspinal fluid collection (IFC) (white arrows). (C) IFC decreases in volume after repair surgery (white arrow heads). (D) A dural defect (arrows) is seen in the ventral spinal dura mater (DM). N, left posterior nerve root of Th2; S, spinal cord. (E) Th2 spinal cord shows hemosiderin deposition in the parenchyma and pia mater (arrows). (F) Collagenous scar is developed at the dural repair site (an arrow). There are no inflammatory cells or vascular tissues in the scar. (G) a contracted pseudocyst (an arrow) is found in DM at Th2. (H) a magnified picture of the black square in G shows a contracted pseudocystic lesion in DM. The pseudocyst wall is composed of two layers; the outer layer (OL) is a dissected dural tissue and the inner layer (IL) is a newly formed tissue composed of densely packed collagen fibers (arrows). (I) hemosiderin deposition is largely restricted to the dural tissues (arrows). Berlin blue staining (Perls Prussian blue). Asterisk, an intradural pseudocyst. Hematoxylin and eosin staining (HE) in (E–H). Scale bars = 100 μm in E; 200 μm in F, I; 250 μm in H, I.

At autopsy, the spinal cord showed brownish discoloration by superficial siderosis (Figure 1E). The surgical site of the dural defect showed the development of collagenous scars containing no inflammatory cells or vascular tissues (Figure 1F). The remnant of IFC was found in the ventral spinal dura mater as a contracted pseudocyst (Figure 1G–I). The pseudocyst wall was composed of two layers. The outer layer was a dissected dural tissue with hemosiderin deposits which accumulated in the vicinity to the inner layer (Figure 1H). The inner layer was a newly formed tissue composed of densely packed collagen fibers, lacked blood vessels, and had rare hemosiderin pigments. No epithelial tissue lined the inner surface of the pseudocyst cavity and immunohistochemistry for epithelial membrane antigen was negative in the pseudocyst wall, suggesting that the cystic lesion was an intradural pseudocyst formed by dissection of the dura mater. As previously reported in the pathology of the spinal cord, there was marked shrinkage of the spinal gray matter, including the anterior horn and intermediate zone [10]. [Correction added on 25 September 2024, after first online publication: Report on pathology and its reference has been added.]

Case 2 was a 49‐year‐old man who presented with a 6‐year history of hearing impairment and gait disturbance and had an unclear history of trauma. T2‐weighted MR images of the brain and spinal cord revealed low‐intensity areas on the superficial layer of the brainstem, cerebellum, and spinal cord, suggesting SSCNS. Lumbar puncture results confirmed xanthochromia of the CSF. We could not identify the etiology of the SSCNS and thus did not perform surgery. Subsequently, the patient died of respiratory dysfunction in 2001. An autopsy confirmed that the patient had typical pathologic findings of SSCNS, but the cause of SAH was not evaluated. Twenty years after his death, we re‐examined the spinal dura mater which had been kept in the Brain Research Institute at Niigata University. Autopsy revealed superficial siderosis in the CNS (Figure 2A). An intradural pseudocyst extending from C4 to Th5 was detected during postmortem examination (Figure 2A). However, no dural defect was found below the examined C4 level. The histology of the dura mater with an intradural pseudocyst in Case 2 (Figure 2B,C) was basically similar to that of Case 1.

FIGURE 2.

The figures (A–C) are taken from Case 2. (A) The spinal cord shows brownish discoloration by hemosiderin deposition. White arrows indicate a pseudocystic lesion in DM. (B) A pseudocyst is localized in the ventral DM. Arrows indicate the boundary between the outer layer (dissected DM tissue) and the inner layer (a newly formed tissue) composed of densely packed collagen fibers. (C) Hemosiderin pigments (arrows) are localized in OL. Berlin blue staining (Perls Prussian blue). (D) A defect is found in the ventral dura mater (DM) at Th3. An arrowhead indicates a remnant of the arachnoid membrane. An arrow indicates a dural biopsy site. (E) A biopsy specimen obtained from the margin of a dural defect is composed of a mixture of granulomatous tissues (an arrow) and thick collagenous tissues. HE in B, E. Scale bars = 200 μm in B. Asterisk, an intradural pseudocyst; OL, outer layer; IL, inner layer. Scale bars = 100 μm in C, E. (F–H) are showing a possible process of intradural pseudocyst formation and subarachnoid hemorrhage persistence of the spinal cord (Sp). (F) First, a defect may occur in the dural inner layer. (G) Second, the arachnoid membrane (AM) herniates into the defect, leading to the formation of a granulomatous lesion (an arrow) around the defect. The herniated AM (dashed line) may break down. (H) Third, continuous bleeding (red arrows) from the granulomatous tissue may cause for subarachnoid hemorrhage leading to superficial siderosis (brown dots). CSF inflow (blue arrows) through the defect may result in the intradural pseudocyst formation (orange line), which affects blood vessels in DM, leading to hemosiderin deposition (brown dashed line). BV, blood vessel; DM, dura mater; SAS, subarachnoid space; V, vertebral bone.

Case 3 was a 74‐year‐old woman with a 1‐year history of gait disturbance and two previous traumas. She had a skiing accident at the age of 25 and a head contusion at the age of 38. She did not have a spinal cord injury. MR imaging revealed a ventral dura mater defect at Th3 and a ventrally located IFC extending from Th1 to Th8. During repair surgery, the defect (10 mm × 3 mm in size) was found in the inner dural layer (Figure 2D). The bottom of the defect (the remaining outer dural layer) was whitish in the central region and reddish in the marginal. A thread‐like remnant of the arachnoid membrane was observed across the defect. No pseudocystic lesion was found in the epidural space. A biopsy specimen obtained from the marginal reddish region of the defect revealed granulomatous tissues and thick collagenous tissues with hemosiderin (Figure 2E). The repair surgery successfully improved xanthochromic CSF and reduced IFC.

The results indicate that IFC observed in SSCNS patients is an intradural pseudocyst formed by the dissection of the spinal dura mater. The paucity of hemosiderin pigments in the inner pseudocyst wall and the reduction of pseudocyst volume after the repair surgery suggest that pseudocyst fluid contains a small amount of blood components and is largely sustained by CSF inflow from the subarachnoid space through the defect. Based on these results, we speculate about potential processes contributing to the development of spinal SAH and an intradural pseudocyst in some patients with SSCNS with dural defects (Figure 2F–H). At first, a dural defect may occur in the dural inner layer (Figure 2F), followed by the invagination of the arachnoid membrane. The upper thoracic region is a hot site for dural defect formation [2]. Imaging studies of the spine suggest that the upper thoracic region is the most immobile and the most kyphotic spot in the spine, indicating that the ventral dura mater may be close to or in contact with the dorsal surface of the vertebral bodies or intervertebral discs, according to body movements [11]. An excessive movement of the spine because of traffic accidents, etc. may produce strong tension in the thoracic dura mater, leading to a defect formation in the inner dural layer. Granulomatous lesions may then develop around the defect (Figure 2G). The destruction of the invaginated arachnoid membrane may occur at this stage. Repeated bleeding from the granulomatous tissue may cause spinal SAH, resulting in the development of SSCNS. At the same time, an influx of CSF from the subarachnoid space into the dura mater through the defect may form an intradural pseudocyst (Figure 2H). Hemorrhages from the granulomatous lesion may be partially involved in the pseudocyst formation. Gradual pseudocyst expansion may affect blood vessels in the dura mater, resulting in hemorrhage and hemosiderin deposition in the dissected dural layer.

AUTHOR CONTRIBUTIONS

All authors contributed to the conception and design of the study. Material preparation, data collection, and analysis were performed by Kiyoshi Ito, Mitsunori Yamada, Kai Uehara, Yusuke Takahashi, Minori Kodaira, Yasuko Toyoshima, Kunihiko Makino, and Hiroki Ohashi. The first draft of the manuscript was written by Kiyoshi Ito and Mitsunori Yamada, and all authors commented on earlier versions of the manuscript. All authors read and approved the final version of the manuscript. Yoshiki Sekijima, Akiyoshi Kakita, Kazuhiro Hongo, and Tetsuyoshi Horiuchi participated in the conception, supervision, and design of all manuscripts.

FUNDING INFORMATION

This work was supported by JSPS KAKENHI (grant number: JP18K08941).

CONFLICT OF INTEREST STATEMENT

The authors declare no conflicts of interest.

ETHICS STATEMENT

This study adhered to the principles of the Declaration of Helsinki and its later amendments. The study protocol was approved by our Institutional Review Board (approval number: 4899).

PATIENT CONSENT STATEMENT

Written informed consent for autopsy including the use of tissues for research purposes was obtained from the next of kin.

Ito K, Yamada M, Uehara K, Takahashi Y, Kodaira M, Sekijima Y, et al. Spinal intradural pseudocyst formation in central nervous system superficial siderosis. Brain Pathology. 2024;34(6):e13269. 10.1111/bpa.13269

DATA AVAILABILITY STATEMENT

Data sharing not applicable to this study as no datasets were generated or analyzed during the current study.