CASE REPORT
Adult Medullary Diffuse Midline Glioma Presenting with Orthostatic Hypotension: A Case Report
2026 Volume 13 Pages 33-36
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2026 Volume 13 Pages 33-36
Diffuse midline glioma, H3K27-altered, is a rare and aggressive central nervous system tumor that typically affects children, whereas adult cases are uncommon and less well characterized. We report a 43-year-old woman who experienced progressive lightheadedness for 10 months and was diagnosed with orthostatic hypotension on the basis of a positive tilt-table test result. Despite treatment with midodrine, her symptoms worsened, and dysarthria, dysphagia, sensory disturbance, and gait instability later developed. Magnetic resonance imaging confirmed an intra-axial mass in the dorsal medulla oblongata. Partial resection was performed, and histopathological examination with immunohistochemistry confirmed the diagnosis of H3K27-altered diffuse midline glioma. The patient subsequently received adjuvant chemoradiotherapy. Although her motor function improved postoperatively, severe orthostatic hypotension persisted, leading to recurrent syncopal episodes that significantly hindered rehabilitation. The solitary nucleus in the dorsal medulla plays a central role in the baroreflex by relaying sympathetic and parasympathetic signals within the central autonomic network. Disruption of this network by medullary tumors can impair blood pressure regulation, causing orthostatic hypotension. Although orthostatic hypotension has been reported in association with various medullary tumors, gliomas are rarely implicated. To our knowledge, this is the first reported case of medullary diffuse midline glioma presenting with orthostatic hypotension under the current World Health Organization molecular classification. This case highlights the importance of considering brain magnetic resonance imaging in patients with newly developed or severe orthostatic hypotension, particularly when accompanied by neurological symptoms, to enable timely diagnosis and management.
H3K27-altered diffuse midline glioma (DMG) is a distinct subtype of diffuse glioma characterized by a lysine-to-methionine substitution at position 27 of histone H3, most commonly due to mutations in the H3F3A or HIST1H3B/C genes. Previously known as diffuse intrinsic pontine glioma, this entity was redefined in the 2016 World Health Organization (WHO) classifications of central nervous system tumor as "diffuse midline glioma, H3K27M-mutant" after advances in molecular diagnostics. In the 2021 WHO update, it was renamed "diffuse midline glioma, H3K27-altered" to encompass broader genetic alterations beyond the classic H3K27M mutation.
DMG is a highly aggressive tumor that primarily affects children, whereas adult cases are rare and less well characterized.1,2) In pediatric patients, these gliomas typically arise in the brainstem, particularly the pons. However, in adults, they are more frequently located in the thalamus or spinal cord.3) Here, we report a rare adult case of H3K27-altered DMG located in the medulla oblongata, initially presenting with orthostatic hypotension (OH), which led to a delayed diagnosis.
A 43-year-old woman had experienced severe lightheadedness for 10 months. At another hospital, she was diagnosed with OH on the basis of a positive tilt-table test result, and treatment with midodrine was initiated. Despite therapy, her OH gradually worsened. Over the subsequent months, dysarthria and dysphagia developed in the patient and most recently, hypesthesia in her left extremities 1 month before presentation. Brain magnetic resonance imaging (MRI) revealed an intra-axial mass in the dorsal medulla oblongata, and she was referred to our institution. By the time of her first visit, gait instability had also developed in the patient, and she was admitted on the same day. High resolution gadolinium-enhanced MRI revealed a dorsally located medullary lesion, slightly more prominent on the left side, with well-defined borders and faint contrast enhancement (Fig. 1).
A, B: Preoperative T2-weighted magnetic resonance (MR) images showing an intra-axial hyperintense mass in the dorsal medulla. C: Gadolinium-enhanced T1-weighted MR image demonstrating subtle enhancement of the lesion. D: Postoperative T2-weighted MR image showing partial resection of the tumor.
The patient underwent suboccipital craniotomy with partial C1 laminectomy for tumor resection. Partial removal was achieved without intraoperative complications. Histopathological examination revealed features consistent with malignant glioma, and immunohistochemical staining confirmed H3K27M mutation, establishing the diagnosis of H3K27-altered DMG (Fig. 2).
A: Hematoxylin and eosin staining (×200 magnification) showing proliferation of atypical glial cells with nuclear pleomorphism, without evident mitosis, necrosis, or microvascular proliferation.
B: Immunohistochemical staining with an H3K27M mutation-specific antibody (×200 magnification) showing positive expression in tumor cells.
The patient subsequently received adjuvant local radiotherapy with a total dose of 54 Gy and temozolomide, causing radiological regression of the residual tumor. Postoperatively, she experienced worsening dysphagia requiring temporary tube feeding, but she gradually resumed oral intake of a regular diet. In addition to persistent hypesthesia in her left extremities, hypesthesia in the right lower extremity also developed postoperatively, although the patient regained sufficient motor function to ambulate with a cane. However, her OH persisted, leading to recurrent syncopal episodes that significantly hindered rehabilitation. The addition of amezinium metilsulfate to midodrine failed to alleviate her symptoms, and she was eventually transferred to hospice care 4 months after surgery. She remains alive and well 6 months postoperatively. Written agreement for publication was obtained from the patient.
OH has been reported as both a preoperative and postoperative symptom in cases of medullary tumors. The decrease in blood pressure with upright posture triggers baroreceptor reflex, which is mediated by the solitary nucleus (nucleus of the tractus solitarius [NTS]), located in the dorsal medulla.4) The NTS relays sympathetic signals to caudal and then rostral ventrolateral medulla. It also relays parasympathetic signals to the nucleus ambiguus. This central autonomic network plays an essential role for blood pressure regulation. Therefore, a lesion in the dorsal medulla can disrupt baroreceptor reflex, generating OH.
There are a limited number of case reports documenting OH secondary to medullary tumors. Reported pathologies include hemangioblastoma,5-9) cavernous angioma,10) subependymoma,11) ependymoma,12) and epidermoid cyst.13,14) However, gliomas have rarely been reported in this context, with only 2 prior cases of glioma-associated OHs published in the 1980s.5,15) These cases were diagnosed as an anaplastic astrocytoma and pilocytic astrocytoma with anaplastic features, respectively, but considering current molecular classifications, they may have represented DMGs. To the best of our knowledge, this is the first reported case of OH caused by a medullary DMG, as defined by the current molecular classification system.
Brainstem tumors are rare in adults, and their diagnosis can be challenging when they present with OH, a common medical condition particularly in women. Once OH is diagnosed, detailed neurologic exams or imaging studies may be overlooked. In the present case, OH was particularly severe owing to the tumor's midline location and infiltrative nature, which may have caused dysfunction of bilateral NTS. Brain MRI should therefore be considered in patients with newly developed or severe OH.
Although DMG, H3K27-altered, accounts for 71%-78% of pediatric brainstem gliomas, it has been reported to account for 37.2% of adult brainstem gliomas; another genetic entity, isocitrate dehydrogenase (IDH)-mutant brainstem glioma, accounts for 26.5%. IDH-mutant brainstem gliomas show significantly better outcomes than does DMG, with overall survival of 43.8 and 11.4 months, respectively.16) Although no previous cases of OH secondary to medullary tumors that resolved after tumor resection have been reported, early diagnosis is crucial for timely initiation of chemoradiation therapy, especially in cases of IDH-mutant tumors.
All authors have no conflict of interest. The authors have registered online self-reported COI Disclosure Statement Forms through the website of Japan Neurosurgical Society members.
