Visual Loss as the Presenting Manifestation of Leptomeningeal Spread of Glioblastoma Multiforme to the Optic Chiasm

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Visual Loss as the Presenting Manifestation of Leptomeningeal Spread of Glioblastoma Multiforme to the Optic Chiasm Cina Karimaghaei, BS, Mohammad Pakravan, MD, MBA, Chaow Charoenkijkajorn, MD, Virginia A. Lee, Andrew G. Lee, MD G lioblastoma multiforme (GBM) is a malignant proliferation of astrocytes with an incidence of 10,000 new cases annually in the United States. GBM makes up 80% of primary malignant central nervous system tumors, and it typically presents with headaches, confusion, focal neurologic deficits, seizures, memory loss, and personality changes. Despite aggressive therapy, GBM has a poor prognosis and often recurs locally (1). Visual loss in GBM is typically due to secondary infiltration of the posterior visual pathway (e.g., homonymous hemianopsia) or less commonly primary involvement of the anterior visual pathway (e.g., malignant optic glioma). Leptomeningeal spread (LMS) of GBM however is unusual. We report a case of progressive vision loss as the presenting manifestation of recurrent GBM with secondary LMS to the optic chiasm. After review of the PubMed and Google Scholar databases, we were unable to identify any such previously reported cases. A 37-year-old woman initially presented with headache, nausea, and vomiting in January 2021. Computed tomography and MRI of the brain revealed a tumor involving the frontal lobe. A subtotal resection was performed on March 24, 2021, and histopathology confirmed GBM. Her School of Medicine (CK), University of Texas Medical Branch, Galveston, Texas; Department of Ophthalmology (MP, CC, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Department of Ophthalmology, Houston Methodist Hospital, Summer Internship Program (VAL), Houston, Texas; Departments of Ophthalmology, Neurology, and Neurosurgery, Weill Cornell Medicine (AGL), New York, New York; Department of Ophthalmology (AGL), University of Texas Medical Branch, Galveston, Texas; Department of Ophthalmology, University of Texas MD Anderson Cancer Center (AGL), Houston, Texas; Department of Ophthalmology, Texas A and M College of Medicine (AGL), Bryan, Texas; and Department of Ophthalmology (AGL), The University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www. jneuro-ophthalmology.com). Address correspondence to Andrew G. Lee, MD, Herb and Jean Lyman Centennial Chair in Ophthalmology, Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, 6560 Fannin Suite, Ste 450, Houston, TX 77030; E-mail: aglee@ houstonmethodist.org Karimaghaei et al: J Neuro-Ophthalmol 2024; 44: e49-e51 medical history was significant for clavicular Hodgkin lymphoma treated with radiation and chemotherapy and in remission. The remainder of the medical, social, surgical, and family histories were noncontributory. One month after surgery, however, the patient developed subacute, progressive visual loss in both eyes despite postoperative chemotherapy with temozolomide and external beam radiation therapy. On neuro-ophthalmologic examination, the visual acuity was counting fingers in the right eye and no light perception in the left eye. There was a left relative afferent pupillary defect. Intraocular pressure measurements, slit-lamp biomicroscopy, motility, and external examinations were normal in both eyes. Dilated fundus examination showed diffuse optic atrophy in both eyes. On July 14, 2021, a repeat MRI of the brain showed an enhancing mass involving the frontal lobes and corpus callosum with enhancement of the right parietal temporal junction and nonenhancing tumor at the medial left parietal lobe and new enhancement and edema in the optic chiasm (Fig. 1). MRI of the cervical/thoracic/lumbar spine with and without contrast showed faint enhancement of nerve roots of the cauda equina. A lumbar puncture showed cerebrospinal fluid white blood cell count of 3/mm3, red blood cell count of 29/mm3, glucose of 97 mg/dL, and protein of 70 mg/dL. Gram stain, culture, and cryptococcal antigen were negative. Cytology showed no malignant cells and only few lymphocytes and blood. A diagnosis of LMS of GBM was made. Ultimately, the patient was lost to follow-up. GBM is the most common primary malignant brain tumor in adults and can produce visual loss directly from involvement of the anterior or posterior visual pathway or indirectly from papilledema and increased intracranial pressure. This patient presented initially with a primary frontal lobe GBM but then developed progressive visual loss from chiasmal involvement of GBM because of LMS of tumor. GBM can arise from the optic apparatus (e.g., malignant glioma) but typically spreads through direct extension to adjacent structures. The initial neuroimaging of this case showed frontal GBM without visual loss or radiographic involvement of the optic chiasm. e49 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. MRI of the brain demonstrating postcontrast T1 fat-saturated coronal sequences showing largest enhancing mass involving adjacent frontal lobes and corpus callosum (A) and enhancement of optic chiasm in relation to distant primary mass (B), and postcontrast T1 fat-saturated axial (C) and coronal (D) sequences showing enhancement of optic chiasm (white arrows in [B], [C], and [D] showing enhancement of optic chiasm; red line in [B] showing distance between optic chiasm and primary mass). After initial subtotal resection, however, the patient subsequently developed progressive visual loss with chiasmal (Fig. 1) and cauda equina (Fig. 2) enhancement consistent with LMS of GBM. Although prior radiation therapy may have predisposed the patient to chiasmal pathology, the additional focus of enhancement in the cauda equina outside the range of external beam radiation makes LMS of GBM involving the optic chiasm the most likely etiology of this patient’s visual deterioration. LMS may occur in up to 25% of GBM and results from secretory protease activity and expression of adhesion–migration proteins that facilitate GBM cell movement through the extracellular matrix, leading to migration from the site of origin to subpial, subarachnoid, and subependymal spaces through brain vessels with subsequent dissemination through the CSF to seed other sites (2). CSF cytology is often negative in cases of LMS of GBM and is only seen in 25%–45% of cases (2). In the literature, there are 34 reported cases of GBM and 4 reported cases of possible GBM (unclear whether Grade III or Grade IV astrocytoma) involving the optic chiasm (see, Supplemental Digital Content, Table 1, http://links. lww.com/WNO/A607, which summarizes previous reported cases of GBM involving the optic chiasm). However, in all these cases, the optic chiasm was either the point of tumor origin or it was directly invaded from glioma origie50 nating at another point in the optic pathway or brain parenchyma. Although some of the previously documented cases, such as a 54-year-old man reported by Traber et al, (3) involved multiple foci of GBM, they were believed to be simultaneous lesions and not a result of metastatic disease or LMS. From review of the PubMed and Google Scholar databases, this seems to be the first description of visual loss as the presenting manifestation of LMS to the optic chiasm. The prognosis of GBM is poor, and GBM involving the optic apparatus is worse than GBM in other brain locations. The overall survival rate is reduced from a mean of 14.6 months in nonoptic pathway GBM to only a mean of 8 months with optic pathway GBM (4,5). LMS is another severe clinical and radiographic complication of GBM and typically represents the end stage of GBM with a dismal prognosis of 2–5 months (2). Treatment includes attempted surgical resection followed by adjuvant radiotherapy and temozolomide chemotherapy. There is no clear consensus for standard treatment of LMS in GBM, and intrathecal chemotherapy and additional radiation therapy have shown limited efficacy (2). In summary, clinicians should be aware that rapidly progressive visual loss in GBM may be a sign of LMS. Although GBM can directly involve the optic pathway, LMS presenting with visual loss in GBM is uncommon. Karimaghaei et al: J Neuro-Ophthalmol 2024; 44: e49-e51 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence Multifocal or diffuse meningeal enhancement on MRI may suggest the diagnosis of LMS even in the setting of negative CSF cytology. Postoperative chemotherapy and radiotherapy have shown limited efficacy, and the prognosis of LMS in GBM remains poor. STATEMENT OF AUTHORSHIP Conception and design: C. Karimaghaei, M. Pakravan, C. Charoenkijkajorn, V. A. Lee, A. G. Lee. Acquisition of data: C. Karimaghaei, M. Pakravan, C. Charoenkijkajorn, V. A. Lee, A. G. Lee. Analysis and interpretation of data: C. Karimaghaei, M. Pakravan, C. Charoenkijkajorn, V. A. Lee, A. G. Lee. Drafting the manuscript: C. Karimaghaei, M. Pakravan, C. Charoenkijkajorn, V. A. Lee, A. G. Lee. Revising the manuscript for intellectual content: C. Karimaghaei, M. Pakravan, C. Charoenkijkajorn, V. A. Lee, A. G. Lee. 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