Papilledema From Froin Syndrome due to a Myxopapillary Ependymoma

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Papilledema From Froin Syndrome due to a Myxopapillary Ependymoma Janet L. Fan, BA, Shahin C. Owji, BS, Mohammad Pakravan, MD, Chaow Charoenkijkajorn, MD, Andrew G. Lee, MD F roin syndrome (FS), discovered by Georges Froin in 1903, is characterized by cerebrospinal fluid (CSF) xanthochromia, elevated protein levels, and hypercoagulability(1,2). FS can be caused by CSF flow abnormalities secondary to inflammation or neoplastic infiltration of the meninges or the spinal cord. Spinal cord tumors can produce functional blockage of CSF in the lumbar or thoracic region and CSF stagnation within the thecal sac, leading to elevated CSF protein levels (3). Exudation or transudation from tumors can also raise protein levels (4). Normally, CSF protein level ranges from 10 to 50 mg/dL, but levels greater than 500 mg/dL may indicate obstruction due to abscess, tumor, degenerative stenosis, or herniation. Protein levels of 75–100 mg/dL can also occur in fungal or bacterial infections or noninfectious causes such as hemorrhage, myxedema coma, or drugs (2). We describe a case of visual loss from papilledema in the setting of FS that presented with a dry tap due to obstruction from a spinal myxoid ependymoma. To our knowledge, this is a unique case in the English language ophthalmic literature. A previously healthy 26-year-old primigravid woman developed new-onset low back pain at 20 weeks’ gestation. The back pain increased in severity and frequency and was initially attributed to pregnancy. Despite delivering a healthy, full-term neonate, her back pain persisted and required opioid management. She then developed bilateral, progressive visual loss over 3 months and presented to an outside clinic. Eye examination showed bilateral papilledema and methazolamide 150 mg per day was started. One week later, she presented to the emergency department for worsening vision and School of Medicine (JF, SO), University of Texas Medical Branch, Galveston, Texas; Department of Ophthalmology (MP, CC, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Departments of Ophthalmology (AGL), Neurology, and Neurosurgery, Weill Cornell Medicine, New York, New York; Department of Ophthalmology (AGL), University of Texas Medical Branch, Galveston, Texas; University of Texas MD Anderson Cancer Center (AGL), Houston, Texas; 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. Address correspondence to Andrew G. Lee, MD Chair, Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, 6560 Fannin St. Ste 450, Houston, TX 77030; E-mail: aglee@ houstonmethodist.org Fan et al: J Neuro-Ophthalmol 2023; 43: e161-e163 headache. Visual acuity (VA) measured 20/25 in her right eye and hand motion (HM) in her left eye. There was a left relative afferent pupillary defect (RAPD). Funduscopic examination revealed bilateral papilledema. MRI of the brain showed radiographic findings of increased intracranial pressure (ICP), including CSF fluid in the optic nerve sheaths and an empty sella. Subsequently, three attempts at fluoroscopic-guided lumbar puncture (LP) at the L5-S1, L4-L5, and L1-L2 levels produced a dry tap with only a few drops of dark yellow CSF. Although no obvious lesion was seen on fluoroscopy by the radiologist, an MRI of the spine revealed nodular enhancement of an extradural mass within the lower thoracic and lumbosacral spine (Fig. 1). A week later, neurosurgery performed a gross total resection of the tumor, identified as World Health Organization grade 1 myxopapillary ependymoma. Postoperative serial imaging of the spine revealed no tumor residual or recurrence. Three weeks postresection, her VA was 20/40 in the right eye and counting fingers (CF) in the left eye. Automated perimetry (Humphrey visual field [HVF] 242) showed marked constriction in the right eye and diffuse depression in the left eye. Despite compliance with medication therapy and a lack of other contributing factors, the patient’s vision continued to deteriorate. Two weeks later, she was admitted to the hospital for a neuroophthalmology evaluation for continued vision loss and was started on acetazolamide 1,500 mg and prednisone 80 mg per day. VA was 20/200 in the right eye and HM in the left eye. There was a left RAPD. Ophthalmoscopy showed Frisen grade II optic disc edema with superimposed optic atrophy in the right eye and diffuse optic disc pallor in the left eye. An LP showed an elevated opening pressure of 24 cm H2O, CSF white blood cell count of 25 cells/mm3 with 89% lymphocytes, protein of 86 mg/dL (normal ,50 mg/dL), and glucose of 59 mg/dL. A week later, left optic nerve sheath fenestration (ONSF) was performed. Four weeks post-ONSF, her vision had shown no signs of improvement. VA was CF at 5 feet in the right eye and HM in the left eye. HVF showed a diffusely depressed left eye (Fig. 2A) and superior paracentral island breaking out to the inferior temporal periphery in the right eye (Fig. 2B). Ophthalmoscopy showed evolving bilateral optic disc edema with optic atrophy and gliosis in the left eye (Fig. 2C, D). Optical e161 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. MRI of spine, T1 (A) and T2 (B) image. An enhancing extradural mass is present within the lower thoracic and lumbosacral spine. FIG. 2. Humphrey visual field testing demonstrates generalized constriction in the right eye (A) and diffuse depression of the left eye (B). Fundus photographs demonstrate evolving bilateral papilledema (C, D) with secondary optic atrophy and gliosis in the left eye (D). OCT global demonstrates bilateral optic thinning (E, F). e162 Fan et al: J Neuro-Ophthalmol 2023; 43: e161-e163 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence coherence tomography (OCT) measured 68 mm in the right eye and 79 mm in the left eye (Fig. 2E, F). FS producing papilledema from a spinal lesion with increased CSF protein levels has been reported with inflammation of the meninges and spinal cord tumors. In our case, however, the myxopapillary ependymoma caused acute and severe visual loss (i.e., fulminant intracranial hypertension) from increased CSF protein levels and produced a “dry tap” below the level of the tumor because of functional obstruction, but papilledema above the level of the obstruction, mimicking pseudotumor cerebri. Other mechanisms for ICP in spinal tumors include loss of the elastic reservoir and functional blockade of CSF flow. Cullen et al also reported a similar case with papilledema with vision loss in association with FS (5). Elevated CSF protein is believed to block CSF outflow at the arachnoid granulations in FS. We recommend spinal imaging (in addition to cranial imaging) in patients with papilledema who have abnormal CSF testing. A dry tap alone is an indication for spinal imaging to exclude spinal level obstruction and a dry tap should not be attributed to inadequate technique alone. In addition, abnormalities in CSF content (e.g., elevated CSF protein) exclude the diagnosis of idiopathic intracranial hypertension (IIH) using the modified Dandy criteria and should also prompt consideration for spinal imaging because obstruction of the arachnoid granulations by elevated CSF protein could also cause elevated ICP. Ophthalmologists should be aware that elevated CSF protein from spinal tumors can produce papilledema in FS. Cranial imaging in cases of FS may be normal or show only radiographic findings of increased ICP (e.g., CSF fluid in the optic nerve sheath, flattening of the globe, or empty sella). Acute (less than 4 weeks), rapidly progressive, and severe (e.g., loss of VA or severe loss of visual field) visual Fan et al: J Neuro-Ophthalmol 2023; 43: e161-e163 loss can occur from fulminant intracranial hypertension. Similar to fulminant IIH, we recommend consideration for aggressive and early surgical intervention (e.g., ONSF) in fulminant IIH and fulminant secondary intracranial hypertension including fulminant FS. Our case highlights a “dry tap” that occurred due to a spinal tumor obstruction from a myxoid ependymoma. Despite total resection, the patient had persistently elevated CSF protein and increased ICP, leading to papilledema and fulminant visual loss requiring ONSF. STATEMENT OF AUTHORSHIP Conception and design: J. Fan, S. Owji, A. G. Lee, M. Pakravan, C. Charoenkijkajorn; Acquisition of data: J. Fan, S. Owji, M. Pakravan, A. G. Lee, C. Charoenkijkajorn; Analysis and interpretation of data: J. Fan, S. Owji, M. Pakravan, A. G. Lee, C. Charoenkijkajorn. Drafting the manuscript: J. Fan, S. Owji, A. G. Lee, M. Pakravan, C. Charoenkijkajorn; Revising the manuscript for intellectual content: J. Fan, S. Owji, M. Pakravan, A. G. Lee, C. Charoenkijkajorn. Final approval of the completed manuscript: J. Fan, S. Owji, A. G. Lee, M. Pakravan, C. Charoenkijkajorn. REFERENCES 1. Froin G. Inflammations méningées avec chromatique, fibrineuse et cytologique du liquide ce’phalo-rachidien. Gaz des Hôpitaux. 1903;76:1005–1006. 2. Garispe A, Naji H, Dong F, Arabian S, Neeki M. Froin’s syndrome secondary to traumatic and infectious etiology. Cureus. 2019;11:e6313. 3. Greenfield JG. Original Papers: on Froin’s syndrome, and its relation to allied conditions in the cerebrospinal fluid. J Neurol Psychopathol. 1921;2:105–141. 4. Mirza S, Adams WM, Corkhill RA. Froin’s syndrome revisited, 100 years on. Pseudo-Froin’s syndrome on MRI. Clin Radiol. 2008;63:600–604. 5. Cullen JF, Pang C, Kumar K, Hoe Winston LE. Froin syndrome and the associated papilloedema. Neuroophthalmology. 2011;35:144–146. e163 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.