Cerebral venous sinus thrombosis detected using diffusion-weighted magnetic resonance imaging during maintenance temozolomide chemotherapy in a patient with glioblastoma: illustrative case

Youhei Takeuchi Department of Neurosurgery

Search for other papers by Youhei Takeuchi in
Current site
jns
Google Scholar
PubMed
Close
 MD,PhD
,
1 Department of Neurosurgery

Search for other papers by 1 in
Current site
jns
Google Scholar
PubMed
Close
,
Ryuta Saito Department of Neurosurgery
Diagnostic Radiology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; and

Search for other papers by Ryuta Saito in
Current site
jns
Google Scholar
PubMed
Close
 MD,PhD
,
Masayuki Kanamori Department of Neurosurgery

Search for other papers by Masayuki Kanamori in
Current site
jns
Google Scholar
PubMed
Close
 MD,PhD
,
Kuniyasu Niizuma Department of Neurosurgery

Search for other papers by Kuniyasu Niizuma in
Current site
jns
Google Scholar
PubMed
Close
 MD,PhD
,
Shunji Mugikura Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

Search for other papers by Shunji Mugikura in
Current site
jns
Google Scholar
PubMed
Close
 MD,PhD
, and
Hidenori Endo Department of Neurosurgery

Search for other papers by Hidenori Endo in
Current site
jns
Google Scholar
PubMed
Close
 MD,PhD
Open access

BACKGROUND

Cerebral venous sinus thrombosis (CVST) sometimes occurs in the background of hypercoagulopathic disorders, including malignancy, chemotherapy, etc. Glioblastoma (GBM) is a malignancy found in the central nervous system, and reports on cases of GBM complicated by CVST are sparse. The authors herein report a case of GBM complicated by CVST during maintenance temozolomide (TMZ) chemotherapy and describe the utility of diffusion-weighted magnetic resonance imaging (MRI) for the detection of CVST.

OBSERVATIONS

A 65-year-old male was treated for left temporal GBM. After surgical removal of the lesion, the patient was treated with chemoradiation therapy, which included 60 Gy local radiation with concomitant TMZ chemotherapy. He was subsequently received TMZ maintenance therapy. Routine MRI performed 7 months after surgery revealed no evidence of tumor recurrence. However, diffusion-weighted imaging (DWI) revealed a high-intensity signal at the posterior portion of the superior sagittal sinus, indicating the presence of a thrombus. In addition to the preexisting symptoms, the patient experienced some disorientation. Angiography revealed an obstruction in the superior sagittal sinus, right transverse sinus, right sigmoid sinus, and straight sinus. His symptoms improved with endovascular and anticoagulant therapy.

LESSONS

Performing DWI during routine follow-up can help in the early diagnosis of CVST in patients with malignant gliomas.

ABBREVIATIONS

BEV = bevacizumab; CVST = cerebral venous sinus thrombosis; DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion recovery; GBM = glioblastoma; MRI = magnetic resonance imaging; MRV = magnetic resonance venography; SSS = superior sagittal sinus; TMZ = temozolomide; VTE = venous thromboembolisms

BACKGROUND

Cerebral venous sinus thrombosis (CVST) sometimes occurs in the background of hypercoagulopathic disorders, including malignancy, chemotherapy, etc. Glioblastoma (GBM) is a malignancy found in the central nervous system, and reports on cases of GBM complicated by CVST are sparse. The authors herein report a case of GBM complicated by CVST during maintenance temozolomide (TMZ) chemotherapy and describe the utility of diffusion-weighted magnetic resonance imaging (MRI) for the detection of CVST.

OBSERVATIONS

A 65-year-old male was treated for left temporal GBM. After surgical removal of the lesion, the patient was treated with chemoradiation therapy, which included 60 Gy local radiation with concomitant TMZ chemotherapy. He was subsequently received TMZ maintenance therapy. Routine MRI performed 7 months after surgery revealed no evidence of tumor recurrence. However, diffusion-weighted imaging (DWI) revealed a high-intensity signal at the posterior portion of the superior sagittal sinus, indicating the presence of a thrombus. In addition to the preexisting symptoms, the patient experienced some disorientation. Angiography revealed an obstruction in the superior sagittal sinus, right transverse sinus, right sigmoid sinus, and straight sinus. His symptoms improved with endovascular and anticoagulant therapy.

LESSONS

Performing DWI during routine follow-up can help in the early diagnosis of CVST in patients with malignant gliomas.

ABBREVIATIONS

BEV = bevacizumab; CVST = cerebral venous sinus thrombosis; DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion recovery; GBM = glioblastoma; MRI = magnetic resonance imaging; MRV = magnetic resonance venography; SSS = superior sagittal sinus; TMZ = temozolomide; VTE = venous thromboembolisms

Cerebral venous sinus thrombosis (CVST) is an uncommon condition that has been diagnosed more frequently over the past 5 to 10 years because of increased awareness and better noninvasive diagnostic techniques.1 Numerous conditions can cause or predispose a person to CVST, and the disorder is often has multiple causes in an individual patient. CVST can present with a wide spectrum of signs and symptoms that include headaches, focal deficits such as hemiparesis or hemisensory disturbance, seizures, and impairment of the level of consciousness, which could develop acutely, subacutely, or insidiously. Because of this wide variety of symptoms, early recognition of CVST can prove challenging for clinicians. Despite these challenges, 57% to 86% of patients have been reported to experience complete functional recovery. A couple of recently conducted studies have reported 5.5% and 18% mortality rates associated with CVST.2,3 It has also been reported that certain preexisting conditions, including sepsis and malignancy, can adversely affect outcome.1 Therefore, early detection and precise treatment are required in patients with glioblastoma (GBM) because symptomatic deterioration can compromise the treatment against this devastating disease.

Illustrative Case

A 65-year-old male developed sensory aphasia and was admitted to a local hospital. Magnetic resonance imaging (MRI) revealed a left temporal GBM (Fig. 1A and B), and the patient was referred to our hospital. Neurological examination of the patient on admission revealed sensory aphasia, right upper quadrantanopia, acalculia, and left and right agnosia. The tumor was excised, and there was no symptomatic deterioration following surgery (Fig. 1C). The pathological diagnosis was GBM. After adjuvant chemoradiation therapy (60 Gy local brain radiation with concomitant temozolomide [TMZ] chemotherapy), the patient was discharged with a Karnofsky Performance Status of 90.

FIG. 1
FIG. 1

A: Preoperative axial contrast-enhanced T1-weighted imaging reveals a tumor with ring enhancement in the left temporal lobe. B: Preoperative axial T2-weighted imaging indicates the presence of edema around the tumor. C: Postoperative image showing the contrast-enhanced lesion was completely removed by surgery.

The patient was subsequently treated with maintenance TMZ chemotherapy at our outpatient department. During this period, mild sensory aphasia, right upper quadrantanopia, acalculia, and left and right agnosia persisted but remained stable. Routine follow-up MRI revealed no recurrence; however, a high-intensity signal indicating a thrombus was detected at the posterior portion of the superior sagittal sinus (SSS) on diffusion-weighted imaging (DWI; Fig. 2A). Neurological examination revealed that the patient was mostly stable, but some disorientation was noted. Magnetic resonance venography (MRV) indicated some signal defects in the posterior SSS, right transverse sinus, and right sigmoid sinus (Fig. 2B). A thin subarachnoid hemorrhage was observed in the parietal lobe on fluid-attenuated inversion recovery (FLAIR) imaging (Fig. 2C). Serum D-dimer levels were found to be slightly elevated at this time and were 2.5 g/mL.

FIG. 2
FIG. 2

MRI performed 7 months following surgery. A: DWI reveals a high-intensity object in the posterior portion of the SSS. B: MRV indicates poor intensity in SSS, right transverse sinus, and sigmoid sinus. C: FLAIR imaging indicates subarachnoid hemorrhage in the left parietal lobe and a high-intensity area in the SSS.

Digital subtraction angiography was performed, revealing occlusion of the SSS, right transverse sinus, right sigmoid sinus, and straight sinus (Fig. 3A and B). Thrombectomy and balloon sinus plasty were performed at the SSS, right transverse sinus, and right sigmoid sinus. Subsequently, approaching from the left transverse sinus, a balloon sinus plasty was performed at the straight sinus, which resulted in recanalization of the deep drainage system (Fig. 3C and D). The procedure was completed with a local infusion of recombinant tissue-type plasminogen activator. MRI performed the day after treatment demonstrated improved patency from the SSS to the right sigmoid sinus (Fig. 3E and F). The postprocedural course was uneventful. The patient’s disorientation resolved, and he was discharged with anticoagulation therapy.

FIG. 3
FIG. 3

Cerebral angiography before (A and B) and after (C and D) neuroendovascular therapy (NET). The SSS, straight sinus, right transverse sinus, and sigmoid sinus were obstructed (A and B). These sinuses were recanalized after NET (C and D). On MRV after NET, the signal intensity of the affected sinuses had improved (E and F).

Patient Informed Consent

The necessary patient informed consent was obtained in this study.

Discussion

Recently, a study conducted by Helmi et al.4 reported an increased risk of CVST in patients with GBM. Their study, a retrospective analysis of 163 cases of GBM, revealed that 12 patients (7.4%) developed CVST. These results suggest that a greater incidence of CVST can be observed in patients with GBM versus other cancers. Because CVST can lead to serious complications, such as a venous infarct, intracranial hemorrhage, and intracranial hypertension, early diagnosis and treatment are essential to reduce its impact on the patient’s quality of life.

Interestingly, among the 12 patients diagnosed with CVST in the report from Helmi et al.,4 the thrombi were visualized on preoperative scans in 11 cases; in the remaining case, the thrombus was visualized on MRI 2 weeks postoperatively but before the initiation of chemoradiation. This is different from venous thromboembolisms (VTEs), because numerous studies have demonstrated that surgeries, especially craniotomies, significantly increase the risk of VTE in the postoperative period in patients with cancer.5,6 The risk of VTE, which is very high in patients with cancer, is high in patients with gliomas, particularly within 2 months after neurosurgery.

In 2011, Vargo et al.7 reported a case of CVST in a patient who had been treated with TMZ and radiation therapy plus bevacizumab (BEV) for a primary central nervous system malignancy. In their report, these authors refuted the existence of published reports regarding the association between CVST and TMZ therapy and speculated a relationship with BEV treatment. Therefore, our case may be the first reported instance of CVST during TMZ therapy. However, the incidence of CVST after treatment may be underestimated because GBM has a dismal prognosis, making the diagnosis of CVST difficult.

Observations

In this study, DWI effectively enabled the detection of thrombi and made the diagnosis of CVST possible. Recently, it has been reported that DWI is more sensitive for the detection of medulloblastoma recurrence than contrast-enhanced MRI,8 and the importance of DWI in the routine follow-up of malignant brain tumors is gaining recognition. Our case reinforces the importance of DWI in routine follow-up examinations.

Lessons

CVST is reported to occur in the earlier phase of the disease course and hence is different from cases involving VTE. However, there are few cases in which CVST occurs in the later phase, as in the current case. DWI was effective for detecting CVST in this case. Because GBM is associated with a dismal prognosis, complications of CVST in the later phase of the disease can be underestimated. Performing DWI during the routine follow-up can help in a timely diagnosis of CVST in patients with malignant gliomas.

Author Contributions

Conception and design: Saito, Takeuchi. Acquisition of data: Takeuchi, Kanamori, Niizuma. Analysis and interpretation of data: Saito, Kanamori, Niizuma, Mugikura. Drafting the article: Saito, Takeuchi. Critically revising the article: Saito, Kanamori, Niizuma, Mugikura. Reviewed submitted version of manuscript: Saito, Takeuchi, Mugikura. Approved the final version of the manuscript on behalf of all authors: Saito. Study supervision: Endo.

References

  • 1

    Allroggen H, Abbott RJ Cerebral venous sinus thrombosis. Postgrad Med J. 2000;76(891):1215.

  • 2

    Villringer A, Mehraein S, Einhäupl KM Pathophysiological aspects of cerebral sinus venous thrombosis (SVT). J Neuroradiol. 1994;21(2):7280.

  • 3

    de Bruijn SF, Stam J Randomized, placebo-controlled trial of anticoagulant treatment with low-molecular-weight heparin for cerebral sinus thrombosis. Stroke. 1999;30(3):484488.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Helmi A, Chan A, Towfighi S, et al. Incidence of dural venous sinus thrombosis in patients with glioblastoma and its implications. World Neurosurg. 2019;125:e189e197.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Semrad TJ, O’Donnell R, Wun T, et al. Epidemiology of venous thromboembolism in 9489 patients with malignant glioma. J Neurosurg. 2007;106(4):601608.

  • 6

    Kawaguchi T, Kumabe T, Kanamori M, et al. Early detection of venous thromboembolism in patients with neuroepithelial tumor: efficacy of screening with serum D-dimer measurements and Doppler ultrasonography. J Neurooncol. 2011;101(3):495504.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Vargo JA, Snelling BM, Ghareeb ER, et al. Dural venous sinus thrombosis in anaplastic astrocytoma following concurrent temozolomide and focal brain radiotherapy plus bevacizumab. J Neurooncol. 2011;104(2):595598.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Aboian MS, Kline CN, Li Y, et al. Early detection of recurrent medulloblastoma: the critical role of diffusion-weighted imaging. Neurooncol Pract. 2018;5(4):234240.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Collapse
  • Expand
  • FIG. 1

    A: Preoperative axial contrast-enhanced T1-weighted imaging reveals a tumor with ring enhancement in the left temporal lobe. B: Preoperative axial T2-weighted imaging indicates the presence of edema around the tumor. C: Postoperative image showing the contrast-enhanced lesion was completely removed by surgery.

  • FIG. 2

    MRI performed 7 months following surgery. A: DWI reveals a high-intensity object in the posterior portion of the SSS. B: MRV indicates poor intensity in SSS, right transverse sinus, and sigmoid sinus. C: FLAIR imaging indicates subarachnoid hemorrhage in the left parietal lobe and a high-intensity area in the SSS.

  • FIG. 3

    Cerebral angiography before (A and B) and after (C and D) neuroendovascular therapy (NET). The SSS, straight sinus, right transverse sinus, and sigmoid sinus were obstructed (A and B). These sinuses were recanalized after NET (C and D). On MRV after NET, the signal intensity of the affected sinuses had improved (E and F).

  • 1

    Allroggen H, Abbott RJ Cerebral venous sinus thrombosis. Postgrad Med J. 2000;76(891):1215.

  • 2

    Villringer A, Mehraein S, Einhäupl KM Pathophysiological aspects of cerebral sinus venous thrombosis (SVT). J Neuroradiol. 1994;21(2):7280.

  • 3

    de Bruijn SF, Stam J Randomized, placebo-controlled trial of anticoagulant treatment with low-molecular-weight heparin for cerebral sinus thrombosis. Stroke. 1999;30(3):484488.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Helmi A, Chan A, Towfighi S, et al. Incidence of dural venous sinus thrombosis in patients with glioblastoma and its implications. World Neurosurg. 2019;125:e189e197.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Semrad TJ, O’Donnell R, Wun T, et al. Epidemiology of venous thromboembolism in 9489 patients with malignant glioma. J Neurosurg. 2007;106(4):601608.

  • 6

    Kawaguchi T, Kumabe T, Kanamori M, et al. Early detection of venous thromboembolism in patients with neuroepithelial tumor: efficacy of screening with serum D-dimer measurements and Doppler ultrasonography. J Neurooncol. 2011;101(3):495504.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Vargo JA, Snelling BM, Ghareeb ER, et al. Dural venous sinus thrombosis in anaplastic astrocytoma following concurrent temozolomide and focal brain radiotherapy plus bevacizumab. J Neurooncol. 2011;104(2):595598.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Aboian MS, Kline CN, Li Y, et al. Early detection of recurrent medulloblastoma: the critical role of diffusion-weighted imaging. Neurooncol Pract. 2018;5(4):234240.

    • PubMed
    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 367 367 73
PDF Downloads 219 220 36
EPUB Downloads 0 0 0