Abstract

Background: H3K27-altered diffuse midline glioma (DMG) is a newly classified disease according to the 5^th edition of the World Health Organization classification of the central nervous system tumors. However, little is known about its progression pattern and the timing of surgical intervention, especially regarding spinal cord lesions.

Case Description: A 26-year-old man presented with rapid muscle weakness progression in both upper and lower extremities and urinary dysfunction. Magnetic resonance imaging showed diffuse swelling of the cervicothoracic spinal cord. He underwent decompressive laminectomy with expansive duroplasty and tumor biopsy. The surgical specimen revealed DMG. Immediately after surgery, deterioration of limb paresis was observed, and the patient developed respiratory failure the day after surgery. Head-and-neck computed tomography on the 7^th day after surgery showed spinal cord swelling and acute obstructive hydrocephalus.

Conclusion: We report a rare case of a spinal DMG with acute postoperative swelling. Neurological deterioration in patients with spinal cord DMG is often exacerbated, so it is essential to suspect DMG at an early stage based on neuroimaging, and if surgery is performed on the edematous spinal cord, further rapid swelling can occur, as in the present case.

Keywords: Cervical tumor, Diffuse midline glioma, H3K27-altered, H3K27M

INTRODUCTION

The histone H3-K27M mutation was first reported as causative for malignant gliomas, including brainstem gliomas, in 2012.[ 12 , 18 ] It was later found to be highly frequent in midline gliomas, such as those occurring in the thalamus, pons, and spinal cord.[ 2 , 14 ] In the 2016 WHO classification, diffuse midline glioma (DMG) with H3K27M mutation was recognized as a separate disease entity.[ 11 ] The term “diffuse midline glioma, H3K27-altered (DMG)” was introduced in the 5^th edition of the WHO classification to encompass a broader concept. The diagnostic criteria[ 10 ] for DMG with the loss of H3K27me3 include one of the following: (1) H3K27M mutation, (2) EGFR mutation or amplification, (3) EZHIP overexpression, or (4) DNA methylation profiling consistent with DMG. The prognostic factors and clinical characteristics of spinal DMG remain unknown due to its rarity and heterogeneity of molecular markers. Moreover, there is no consensus about the best timing for biopsy with or without decompressive laminectomy.

Very few spinal cord DMG cases with rapid neurological deterioration have been reported.[ 8 , 19 ] Herein, we report a rare case of spinal cord DMG with unusual magnetic resonance (MR) imaging findings and rapid neurological deterioration. We emphasized that it is important to suspect DMG early on neuroimaging and discussed the timing of image acquisition.

CASE REPORT

A 26-year-old man was diagnosed with an autism spectrum disorder in childhood and had been walking on tiptoes. At the age of 18, he started holding on to something when he stood, and 12 months ago, he began to drag his feet, gradually becoming unable to stand up straight, and developed frequent urination. Although MR imaging revealed a cervical cord enlargement, it was judged to have no pathological significance, and the patient was followed up by MR imaging at that time. Three months ago, he was referred to our hospital, complaining of urinary retention and progressive right upper limb movement disorder. Steroid pulse therapy was applied as a demyelinating disease was suspected. However, 1 month ago, the upper limb paralysis worsened. Due to the rapid progression of the symptoms, he was referred to our department. At the examination, the patient’s consciousness level was JCS I-3, and both upper and lower extremities showed severe paresis. Cervical T2-weighted MR imaging showed diffuse spinal cord swelling from the C2 to the Th2 level, and gadolinium-enhanced T1 images showed heterogeneous enhancement of the swollen spinal cord [ Figure 1 ]. The patient’s symptoms rapidly progressed just before surgery, resulting in abdominal breathing. Therefore, the patient underwent tumor biopsy, C2 domotomy, and C3–C7 decompressive laminectomy with expansive duroplasty to verify the final diagnosis and decide further therapy options. The pathological diagnosis was DMG, H3K27-altered. On the day after surgery, contrast-enhanced head-and-neck computed tomography (CT) showed no obvious abnormalities. Still, on the same day, consciousness disorder and complete paralysis of both lower limbs developed, and spontaneous breathing deteriorated, requiring tracheal intubation. At that time, there was no low attenuation in the cervical spinal cord on imaging. On postoperative day 7, when the patient’s overall condition stabilized, head-and-neck CT revealed acute hydrocephalus and diffuse hypodensity in the cervical spinal cord [ Figure 2 ], and an emergency third ventriculostomy was performed. However, his spontaneous breathing disappeared the day after the ventriculostomy. Contrast-enhanced MR imaging of the whole spine 2 months after the surgery revealed diffuse heterogeneous enhancement of the atrophic spinal cord in suspicion of the disseminated lesion or residual tumors with multiple syrinxes [ Figure 3 ]. The patient died after his transfer to a convalescent care facility.

Figure 1:

Preoperative gadolinium contrast-enhanced magnetic resonance imaging images of the spinal cord. (a) T2-weighted sagittal image. Spinal cord enlargement is seen from C2 to Th2 levels (red arrowhead), with no spinal fluid cavity signal identified. (b and c) Sagittal T1-weighted images of the whole spinal cord with gadolinium contrast enhancement. Diffuse patchy enhancement is evident.

Figure 2:

Nonenhanced head-and-neck computed tomography scan on the 7th day after surgery. Acute obstructive hydrocephalus developed due to spinal cord swelling from the lower part of the medulla oblongata to the level of the upper cervical spine at the craniovertebral junction.

Figure 3:

Cervical gadolinium contrast-enhanced magnetic resonance (MR) imaging. (a) T2-weighted sagittal image showing severe atrophy of the spinal cord with little or no normal spinal cord tissue present. A liquid mass was observed in the fourth ventricle, suggesting a tumor with liquefaction changes. (b) Gadolinium-contrasted T1-weighted sagittal image. Partial contrast enhancement diffusely presented in the spinal cord, with spinal cord dissemination or residual tumor suspected. (c) Syringomyelia was observed on the axial T1-weighted plain MR image (red arrowhead).

DISCUSSION

There have been few reports on H3K27-altered spinal cord DMG where acute deterioration in such a short period of time occurred. We summarized the reported cases, as shown in Table 1 .[ 8 , 19 ] Although our patient could not receive chemoradiotherapy due to his severely disabled condition, the other two patients could. Due to the limited number of documented cases involving DMG arising in the thalamus or the spinal cord, the significance of H3K27 mutation in terms of prognosis remains insufficiently understood.

Table 1:

List of reported cases of acute deterioration in adult spinal diffuse midline glioma.

The preoperative radiological diagnosis of spinal cord DMGs is difficult.[ 16 ] Differential diagnosis includes intramedullary lesions with, diffuse and ill-defined enhancement, such as includes transverse myelitis, neuromyelitis optica, multiple sclerosis, and neuroinflammatory diseases, other than DMG, that lead to spinal cord enlargement.[ 5 , 15 , 17 ] Our patient’s symptoms were slowly progressing, and a diffusely swollen cervicothoracic spinal cord was seen on noncontrast T2-weighted images obtained at the previous hospital (data not shown), suspecting a demyelinating or neuroinflammatory disease. Follow-up gadolinium-enhanced MR images taken at our hospital showed multiple diffusely enhanced heterogeneous patchy lesions from the C2 to the Th2 level. In nonacute inflammatory, demyelinating, and metabolic disorders, it is generally expected to observe long-segment nonexpansile T2 hyperintensity,[ 7 ] and it was considered inconsistent with the imaging findings. In this particular case, the possibility of glioma was higher due to the gadolinium contrast enhancement observed on MR images obtained during the stage of advanced symptoms. Therefore, it can be suggested that early contrast-enhanced MR imaging should be actively recommended in such cases. However, it should be noted that approximately 29% of H3K27M-altered DMG cases exhibit a lack of contrast enhancement,[ 13 ] making it challenging to definitively rule out the presence of glioma in the absence of contrast enhancement.

In our case, there was considerable postoperative swelling of the cervical spinal cord. The causative mechanism of acute disease deterioration might be the rapid progression of the spinal cord swelling around the craniovertebral junction even after the decompression. Preoperative MR imaging showed the progression of the diffuse spinal cord swelling from the medulla oblongata level to the upper thoracic spine. It was assumed that decompression from C2 to C7 was insufficient to relieve the tension of the swollen spinal cord, resulting in obstructive hydrocephalus due to its upward herniation. Acute hydrocephalus caused by upward herniation has never been reported in spinal cord DMG, but it has been previously reported in hypertensive encephalopathy patients with the same mechanism as in our case.[ 1 ] Another possible cause of the deterioration could be the spinal shock caused by the compression of the swollen spinal cord itself at the level of the foramen magnum.

Furthermore, 2 months later, a follow-up contrast-enhanced MR imaging revealed signs of multiple syrinxes. Spinal syrinx (syringomyelia) usually develops after spinal trauma, in Chiari malformation, other head-and-neck abnormalities, and meningitis.[ 6 ] It can also be caused by ischemia,[ 4 ] minor trauma,[ 3 ] and rebound effects due to localized obstruction of the cerebrospinal fluid flow in cervical spondylotic myelopathy.[ 9 ] Our patient was thought to have multiple syrinxes mainly due to the localized obstruction of the cerebrospinal fluid at the level of the foramen magnum. Upward herniation and compression of the upper cervical spinal cord at the level of the foramen magnum might obstruct the cerebrospinal fluid flow after cervical cord swelling caused by the rapid growth of the tumor. DMG of the cervical spinal cord is rare, but it should be considered in the differential diagnosis, it is essential to perform contrast-enhanced magnetic resonance imaging (MRI) in time to differentiate malignant tumors and ensure timely surgical intervention without delay.

CONCLUSION

We reported a rare case of acute spinal cord swelling in DMG after decompressive laminectomy with expansive duroplasty and tumor biopsy. The neurological deterioration in spinal cord DMG patients is often exacerbated, so it is essential to suspect DMG at an early stage based on neuroimaging, and if surgery is performed on the edematous spinal cord, further rapid swelling can occur, as in our case. It is important to monitor the symptoms closely and make a critical decision about the tumor biopsy with decompressive laminectomy before the deterioration of the patient’s condition.

Declaration of patient consent

Patient’s consent not required as patient’s identity is not disclosed or compromised.

Financial Support and Sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation

The author(s) confirms that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.

Acknowledgments

The authors would like to thank Alexander Zaboronok of the Department of Neurosurgery, Institute of Medicine, the University of Tsukuba, for professional and language revision.

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