SURVEY OF OPHTHALMOLOGY
CLINICAL RONALD
BURDE
VOLUME
37 - NUMBER
2 - SEPTEMBER-OCTOBER
1992
CHALLENGES AND
PETER
SAVINO,
EDITORS
Disc Swelling: A Tall Tail? DENNIS C. MATZKIN, AND J. BELLO, M.D.3
M.D.,’ THOMAS
L. SLAMOVTTS, M.D.,‘** I. GENIS, M.D.,’
Departments of ‘Ophthalmology, 2Neurology and Neurosurgery, Medical Center, Albert Einstein College of Medicine,
(In keeping
with the purpose
of a clinical patholo@cal conference, appear at the end _ /07 the ar&le.)
Case Report. In September 1985 a thirty-yearold right-handed normotensive man became aware of decreased vision in his right eye while attempting to look through the viewfinder of his camera. He was in excellent health except for one episode in July 1985 of a generalized seizure associated with loss of consciousness and fecal incontinence. A neurological evaluation and CT scan were reportedly unremarkable, but because of an abnormal EEG, treatment with Dilantin was commenced. His past ophthalmic history was negative. He had been treated for osteomyelitis of his tibia in his youth. On his first neuro-ophthalmic examination in September 1985, he had best corrected visual acuities of 20/200 OD and 20120 OS. There was a 1 + relative afferent pupillary defect OD, with profound loss of color vision in that eye. The external examination and ocular motility were normal, and the cornea1 reflex was intact bilaterally. The slit-lamp exam was unremarkable, and the intraocular pressures measured 18 mm Hg OU. On funduscopic examination there was optic atrophy OD (Fig. 1A). The left disc was elevated with blurring of the nasal margin, but no peripapillary hemorrhages were evident (Fig. 1B). Fluorescein angiography revealed late leakage from disc vessels (Fig. 2). Kinetic perimetry on a Goldmann bowl perimeter showed a centrocecal
and ‘Radiology, Montefiore Bronx, New York
the abstract and key words
scotoma OD with a full field OS.
What is your diagnosis? How would you proceed? CT and MRI scans revealed mild ventricular dilatation consistent with communicating hydrocephalus (Figs. 3 and 4). No intracranial or intraorbital mass lesions were present. CBC and differential count, ESR, biochemistry, collagen screen and serological test for syphilis were all normal.
How would you proceed? The patient was referred for a neurological evaluation and lumbar puncture.
Clinical
Course
In October 1985, the patient experienced an episode of dizziness, slurred speech, and his legs “buckled under” him while he was climbing a flight of stairs. His visual acuity had improved to 20/60 OD since September; ocular examination was otherwise unchanged. A neurological evaluation was entirely normal, failing to demonstrate any focal deficit, but the patient now admitted that he had suffered from dull occipital headaches, and had experienced episodic clumsiness of both lower limbs for approximately one year. A spinal tap opening pressure measured 480 mm
130
DISC SWELLING Fig. 1. Fundus photograph showing (A) optic atrophy OD with a visual acuity of 201200, and (B) disc
swelling OS with a visual acuity of 20120.
Fig. 2. Fluorescein angiogram performed at initial presentation shows late leakage from the optic disc OS (R) compared to 01) (A).
cerebrospinal fluid ((SF), with a CSF protein level elevated to 92 mg/dl (normal value 14-45 mg/dl), with a normal glucose. Cytology showed 3 lymphocytes with no abnormal cells. A nuclear brain scan revealed positive flow through the sagittal sinus, and digital subtraction angiography failed to demonstrate a Venus sinus throm-
Fig. 3. MRI of the head showing vcntricl~lar dilatation without evidcncc of ;I mass lesion.
bosis. In addition, isotope cysternography revealed normal CSF flow. A cerebral arteriogram was also normal. There was no history of‘vitamin A ingestion, chronic tetracycline or corticosteroid treatment. I,iver function tests as well as serum levels ot‘vitamin A and cortisol were normal. The patient was discharged on l>iamox 500 mg
Fig. 4. (:T of rhe head demonstrating bilateral effilsions in rhc interhcmispheric tissurc. with poor visualization of the con\,cxitv sulci.
Fig. 5. Axial (:I‘ ofthe head showing shunt plarcment in the setting of c~omm~~nic-;iring livdroc~~~h;~lus.
132
Surv Ophthalmol
37 (2) September-October
Fig. 6. Fundus photograph demonstrating progressive disc edema OS three months after initial presentation. The optic atrophy was unchanged in appearance OD, and the visual acuity at this time was count fingers
MATZKINETAL
1992
Fig. 7. Defcrvesence of optic disc edema OS following placement of ventriculoperitoneal shunt.
at two feet OD, and 20/15 OS.
the upper limbs, and was clearly extensor. twice daily. Multiple repeat lumbar punctures consistently showed elevated protein in the range of 170-190 mg/dl, and 2-6 white cells, which included both lymphocytes and monocytes. Cytological assessment after cytocentrifuging consistently failed to reveal any malignant cells. Spinal fluid cultures were negative for both aerobic and anaerobic organisms. Neither fungi nor virus particles were evident in the CSF. In December 1985, the patient underwent ventriculoperitoneal shunt placement (Fig. 5) because of worsening disc edema (Fig. 6) despite maximum treatment with Diamox. The vision had deteriorated to count fingers at two feet OD, but was stable at 20/15 OS. Goldmann visual fields showed a centrocecal scotoma OD, and an enlarged blind spot OS. Six months later, the vision had returned to 20/200 OD, with defervescence .of the disc swelling (Fig. 7). In September 1986, one year after initial presentation, the patient experienced acute bilateral lower limb weakness associated with lumbar pain and numbness on the lateral aspect of his right foot. On neurological examination he was noted to have spastic gait with stiff and jerky movements. There was a distinct proximal weakness in both legs and, in addition, there was evidence of dorsiflexion weakness in the left lower extremity. Anal sphincter tone was diminished. Decreased sensation to pin-prick was noted on the lateral aspect of the right foot and the left lumbar region. The tendon reflexes were noted to be extremely brisk in both lower limbs compared to
the left plantar
response
What is your diagnosis now? How would you proceed? Myelography showed widening of the spinal cord throughout its length with numerous intradural extramedullary defects present (Fig. 8). The largest defect was located at the conus medullaris, i.e., T12-Ll level (Fig. 9). A laminectomy and partial excision biopsy of the lesion was performed from TlO through Ll. The tumor, which appeared pink and friable macroscopically, was seen to be spreading diffusely in the subarachnoid space. Histopathological examination of the specimen was consistent with a malignant ependymoma. Post-operatively the patient received radiation therapy to both the brain (4140 Gray) and spinal cord (4800 Gray) in divided doses. Twenty-seven months after his initial presentation with visual loss, the patient had full upper and lower limb motor and sensory function, as well as normal sphincter control. However, he complained of intermittent lower backache and was hyper-reflexic in both upper and lower limbs.
Discussion The finding of papilledema requires prompt assessment to rule out the presence of an intracranial tumor. When the initial evaluation includes normal neuroimaging and elevated CSF pressure, the diagnosis of pseudotumor cerebri is usually suspected. When even subtle abnormalities of CSF content, such as elevated protein
DISC SWELLING
Fig. 9. Axial CT scan at the level of I,1 performed following myelography demonstrates enlargement of the conus as well as scalloping ofthc posterior margin of the L1 vertebral body.
F/g. 8. Oblique radiograph from the lumbar myelogram indicates multiple intradural extramedullar); filling defects in the lumbar thecal sac studding the nt’rvc roots (arrows).
or cells, are found, the diagnosis of pseudotumor cerebri is untenable, and an underlying cause should be sought. The approach should consist of a compulsive clinical evaluation and appropriate investigation, as well as regular follow-up and reevaluation of the clinical problem until a diagnosis can be made. Our patient presented with unilateral loss of vision and was found to have abnormal optic discs. The initial clinical appearance of the discs was suggestive of Leber’s hereditary optic neuropathy; however, the leaking vessels on the fluorescein angiogram ruled out that diagnosis. The abnormal CSF protein suggested that a primary cause for the elevated intracranial pressure existed, although the etiology was not initially apparent despite extensive investigations. Only after a protracted clinical course, with neurological symptoms developing after a period of twelve months, was the investigation appropriately directed away from the brain and toward the spinal cord. Spinal cord tumors are a rare cause of elevated intracranial pressure. The rarity of this association, in part, was responsible for the long delay in making the correct
diagnosis.
Taylor and Collier in 190 1‘Ii reported the first case of a spinal cord tumor associated with papilledema. In the autopsy of their patient they found, “an extra-medullary intrathecal myxoma, about the size of a sparrow’s egg . . . pressing onto the cord at the level of the third cervical segment.” In 1931 Kyrielis”’ described a tumor involving the lower spinal cord at the thoracolumbar level that presented with headache and papilledema. Love et al ” in 1951 reported three
TABLE Pwscwtiq-
1
Symptoms of Pntiwtv with Spin(~/ Cord Trtmot:\ .koriclted with Papilldrmm*
Headache Loss of vision Nausea, vomiting Backache Mental status change Gait disturbance Diplopia Lower limb pain Vertigo Tinnitus Sphincter disturb. Pelvic pain Neck pain Loss of consciousness
3I
I 5) IO IO 9 8 7 ,I ” -1 L’
I 1 I
*Number of patients = 53 (34F. 19M). Ages ranged from 9 to 69 years (man, 37 vears). Includes 20 cases reported by Glasauer. I 96-4.k
134
Surv Ophthalmol
37 (2) September-October
cases of spinal cord tumors producing disc swelling. Raynorlg in 1969 reviewed 36 cases, and we have found 53 cases besides our own reported in the literature. Ependymomas were the most common form of glioma of the spinal cord in the cases we reviewed and were found to be responsible for approximately 40% of the cases producing papilledema. We found these tumors to occur predominantly in the lower thoracic or lumbar region, which was consistent with the review by Tanaka et alz5 in 1988. Ependymomas are unencapsulated glial tumors that arise from ependyma1 cells which are the remnants of the embryonic neuroepithelium and line the ventricles and spinal canal. Other spinal tumors producing papilledema include schwannomas (1 I%), meningiomas (7%), neurofibromas (7%), and gliomas (7%). With regard to the clinical presentation of spinal cord tumors in general, lumbar pain is the most common presenting symptom and occurs in 65-70% of cases.g This pain is invariably associated with a motor and sensory deficit. However, in cases of spinal cord tumors associated with papilledema, headache, often with nausea and vomiting, appeared to be the most consistent symptom (Table 1). In most patients with papilledema, elevated intracranial pressure (ICP) was established either at the time of the initial presentation of the tumor or at subsequent followup with progressive disease. Visual loss was present in a significant number of these patients, although only two were reported to have transient obscurations. Our patient is unusual in that his is only the fourth recorded case of a spinal cord tumor associated with papilledema presenting with isolated visual loss, without any other symptom attributable to disease of the spine. Seven patients in our review were reported to complain of double vision on presentation, all due to six nerve palsies.
Pathophysiology A number of cases of papilledema have been associated with high spinal cord lesions.5~‘s~‘6~‘7~26 In these cases the tumors have been thought to extend superiorly to involve the cerebellum and obstruct the CSF. However, most cases of papilledema caused by spinal cord tumors have been associated with ependymomas and neurofibromas involving the thoracic and lumbar spine. Several explanations for the development of papilledema in these cases have been proposed, most of which are directed to the associated ele-
1992
MATZKIN ET AL
vated CSF protein. In our review, the range of CSF protein was 38 mg/dl to 10,500 mg/dl, with 66% having a CSF protein greater than 100 mg/dl. It has been proposed by Schaltenbrand” that the increased viscosity caused by the elevated protein results in decreased absorption of CSF by the arachnoid villi, and consequently leads to increased ICP. Gardner et al” proposed that delayed CSF absorption by the arachnoid villi results because the large protein molecules per se mechanically block pores in the semipermeable membrane. In support of the “protein theory,” it has been pointed out that patients with clinical features consistent with the GuillianBarre syndrome, who typically have elevated CSF protein, may also have intracranial hypertension.6*‘5 Arseni3 proposed that spinal cord tumors may stimulate a basal leptomeningitis and arachnoiditis with compromise to CSF absorption. Papilledema has been seen with normal CSF protein content in association with spinal tumors, and by contrast, markedly elevated CSF protein level can exist in the absence of papilledema. This phenomenon is often seen in meningitis, and again in the Guillian-Barre syndrome. Therefore, although the theories related to elevated CSF protein are plausible, they cannot explain the findings of elevated ICP in all the cases of spinal cord tumors causing papilledema. Disseminated tumor cells, either by mechanically obstructing CSF absorption, or by stimulating massive protein exudate, have been implicated as being responsible for elevated ICP. Love et al” found four of sixteen cases of intramedullary tumors to be associated with papilledema, two of which had villous tumor seeding. Alternatively, mutinous material produced by degenerative change within the tumor can also interfere with CSF dynamics and lead to an elevated ICP.*’ The size of the tumor does not necessarily play a major role, since even small tumors can cause increased ICP if located strategically within the venous plexus*’ or intrathecally as described by Taylor and Collier. 46 Beduschi et al4 and Rudnickie*r suggested that venous stasis by tumor compression of the spinal or medullary venous plexus causes an unfavorable transarachnoid villous hydrostatic pressure, and thus leads to increased ICP. Recent animal models ofextradural tumors have also demonstrated that spinal epidural venous plexus obstruction can cause breakdown of the blood-CSF barrier due to the release of prostaglandin E,, a mediator of increased vascular permeability.2”.24
135
DISC SWELLING Episodes of clinical or subclinical subarachnoid hemorrhage from the tumor, in particular by an ependymoma, have been implicated as a possible mechanism of increased ICP, either by the blood itself or by its specific constituents.’ a case Philipon et al,” in their report describing without ventricular dilatation, suggested that cerebral edema is responsible for intracranial hypertension in cases of spinal cord neoplasm. Finally, the spinal canal has been shown to act as an elastic reservoir for CSF.” With normal changes in physiological cerebral blood flow, the ability of CSF to flow into or out of the spinal canal is thought to be important in the maintenance of a constant intracranial volume. In this role, the lumbar part of the spinal sac may be the most important because of its greater distensibility and volume. By compromising this system, spinal cord tumors may in fact reduce the capacity of this “reservoir” and cause papilledema.” Chronic spinal cord compression caused by a thoracic disc herniation has been described as causing papilledema.” This supports the theory that simple mechanical blockage, by disrupting the elastic reservoir in the lumbar region of the spinal canal, can cause elevated intracranial pressure.
Conclusion Spinal tumors are a rare cause of elevated intracranial pressure. ‘rhe majority of reported cases were found to have papilledema either at the time of the presentation of the tumor with spinal symptoms, or after the diagnosis of a spinal tumor had been made. Our patient was unusual in that he initially presented with isolated visual loss without sytnptoms or signs of spinal cord disease. To our knowledge, this is only the fourth reported case of a spinal cord tumor associated with papilledetna to present with visual loss in the absence of‘ other neurological symptoms. The etiology of optic disc swelling in the presence of elevated CSF pressure and elevated protein is usually discovered on CT or MRI of the head, often with the use of a contrast medium. When no abnormality is detected on high resolution contrast scanning, and if all investigations for inflammatory or autoimmune diseases are negative, the diagnosis of a spinal cord tumot should be considered. When our patient initially presented with papilledema in 1985, contrast MRI studies were not yet available. If a contrast MRI had been performed at that time, an abnormality might have been detected on gadolinium
(Gd) MRI of the head, as diffuse metastatic subarachnoid deposits were noted on the myelogram, and although not proven, similar subarachnoid deposits could have been present surrounding the brain. Conceivably, Gd-enhanced MRI of the head, had it been available, would have hastened the diagnosis of a spinal cord tumor in our patient. Addendum Since acceptance of this paper for publication, the authors have become aware of another case of ependymoma associated with optic disc swelling and bilateral central retinal vein occlusions. The CSF was described as thick and gelatinous, and had a protein content of 4880 mg/dl. At the time of lumbar puncture, the CSF
immediately gelled (Froin’s syndrome) and the opening pressure was unrecordable. (Frohman L., Schulder M, Mauriello J et al. Frank B. Walsh Society 24th Annual Meeting, February 28 & 29, 1992. Doheny Eye Institute, University ofSouthern California. Los Angeles, (:a.)
References 1. Abbott
KH: Subarachnoid hemorrhage from ependymoma arising from filum terminale: report of a case. Hull. Los Angeles New01 Sac J:127-132, 1939 9_. Ammerman BJ, Smith DR: Papilledema and spinal cord tumors. Surg Net& 3:55-57, 1975 9. Arseni C, Maretsia M: Tumors of the lower spinal cord associated with increased intracranial pressure and papilledema. J Npurosurg 27: 105-I IO, 1967 4. Beduschi A, Culumella F, Papo I: Ependimomi della
cauda con stasi papillare. Chirzqin (Milnno) IO:3 IO, 1955 caused by blocking of cord at fourth cervical vertebra greatly relieved by oper-
5. Davis TK: Double papilledema
6
7 8. 9. IO.
11. 12.
IS. 14.
15.
16.
ation. Arch N~urol P.y-h 9t245, 1923 Drew AL, Magee KR: Papilledema in the Guillain-Barre syndrome. Arch N~urnl Psych 66:744-75 1, 195 1 Gardner WJ, Spitler DK, Whitten (:: Increased intracranial pressure caused by increased protein content of the cerebrospinal fluid. N Engl J MP~ 250:952-956, I954 Glasauer FE: Thoracic and lumbar intraspinal tumors associated with increased intracranial pressure.,/ Nrr~ol Neurosq P.sJch 27:451-458, 1964 Helseth A, Sverre JM: Primary intraspinal neoplasms in Norway, 1955-1986. J Neurosurg 71:X42-845, 1989 Kyrielis W: Die Augenveranderungen bei den entsundlithen Erkrankungen des Zentralnervensystems, in Von Schieck, Bruckner (eds): Kurx Hnndhurh dtr Opthnlmologw. I’ol 6. Berlin, Springer-Verlag. 193 1 I,ove JG, Wagener HP, Woltmann HW: ‘l‘umors of the spinal cord associated with choking of the optic disc. .4rch NPIUO/ P.qrhaal 66tl7 1-I 72, 1951 Martins AN, Wiley JK, Meyers PW: Dynamics ofcerebrospinal fluid and the spinal dura mater../ NCICM/Nruro.rurg Py-hint 35:468-473, 1972 McAlpine D: Papilledema caused bv a cervical cord ttlmor. LancP1 2r614-616, 1935 Michowiz SD, Rappaport HZ, Shaked 1. et al: .I‘horacic disc herniation associated with papilledema.,] N~urn.rurg hl:l I?&1134. 1984 Morley JB, Reynolds EH: Papilledema and the Landry(Gllain-Barre syndrome. Case report and rrview. Hrnin x9:20.5-222, 1nfx Newman EW: Ocular signs ofintracranial disease in chil-
136
Surv Ophthalmol
37 (2) September-October
dren and juveniles: a report of 42 cases. Am J 0phlhalmol 21:2X6-292, 1938 17. Nonne M: Uber einen Fall von intramedullaren aszendierendem Sarkom sowie drei Falle von Zerstorung des Halsmarks. Arch Psvch Neruenheilk 8?:393. 1900 18. Philippon J, Poisson M, Bleibel JM: Ependymome de la queue de cheval revele par une hypertension intra-cranienne sans dilatation ventriculaire. La Nowelle Presse Medicnle 9:303-304, 1980 19. Raynor RB: Papilledema associated with tumors of the spinal cord. Neurology J9:700-704, 1969 20. Ridsdale I,, Moseley I: Thoracolumbar intraspinal tumors - presenting features of raised intracranial pressure. J Neural Neurosurg Psychiat 41:737-745, 1978 21. Rudnickie S, Lebkowski J: 0 traczy zastoinoweji w przypadkach guzowrdzenia. J Neural Neurosurg Psychtat Polska J:49-52, 1951 “2. Schahenbrand G: Normal and pathological physiology of the cerebrospinal fluid circulation. Lanret 1~805-808, 1953 neoplastic 23. Siegal ~I‘, Siegal T, Lossos F: Experimental spinal cord compression: Effect of anti-inflammatory agents and glutamic receptor antagonists on vascular permeability. Neurosurg 26:967-970, 1990
1992
MATZKIN
E, Lossos F: Experimental 24. Siegal ‘I‘, Siegal T, Shohami neopiastic spinal cord compression: Effect of ketamine and MK-801 on edema and prostoglandin. Neurosurg 26:963-966, 1990 S: Papilledema and spinal 25. Tanaka K, Waga S, Shimosaka cord tumors. Surg Neural 29;462-466, 1988 26. Taylor J, Collier J: The occurrence of optic neuritis in lesions of the spinal cord: injury, tumor, myelitis. (An account of twelve cases and one autopsy. Brain 21: 532-553, 1901 Buxbaum MW: Giant ependymoma 27. Teng P, WagnerJH, of the spinal cord associated with papilledema. Review of literature and report of a case. Arch Neural 2:657-662, 1960
Reprint address: Thomas L. Slamovits, M.D., Montetiore Medical Center, 111 East 210th Street, Bronx, NY 10467. This study was supported in part by an unrestricted grant to the Department of Ophthalmology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, from Research to Prevent Blindness, Inc.
Abstract. A 30-year-old man presented with monocular visual loss secondary to chronic papilledema, due to an ependymoma involving the spinal cord. No other neurological symptoms were present at the time. Initial neuroradiologic tests as well as laboratory investigations were negative, except for elevated pressure and protein concentration of his cerebrospinal fluid. In spite of intensive investigation, the diagnosis of a spinal cord tumor was delayed for approximately 12 months until he presented with neurologic symptoms attributable to a spinal cord lesion. This is only the fourth case reported of a spinal cord tumor associated with papilledema presenting with visual loss, without any other manifestations of either elevated intracranial pressure, or spinal disease. Possible mechanisms for elevated intracranial pressure in cases of spinal cord tumors are reviewed. (Surv Ophthalmol 37:130-136, 1992)
Key words.
ependymoma
l
neuroimaging
ET AL
l
papilledema
l
spinal cord tumor
CLINICAL RONALD
BURDE
VOLUME
37 - NUMBER
2 - SEPTEMBER-OCTOBER
1992
CHALLENGES AND
PETER
SAVINO,
EDITORS
Disc Swelling: A Tall Tail? DENNIS C. MATZKIN, AND J. BELLO, M.D.3
M.D.,’ THOMAS
L. SLAMOVTTS, M.D.,‘** I. GENIS, M.D.,’
Departments of ‘Ophthalmology, 2Neurology and Neurosurgery, Medical Center, Albert Einstein College of Medicine,
(In keeping
with the purpose
of a clinical patholo@cal conference, appear at the end _ /07 the ar&le.)
Case Report. In September 1985 a thirty-yearold right-handed normotensive man became aware of decreased vision in his right eye while attempting to look through the viewfinder of his camera. He was in excellent health except for one episode in July 1985 of a generalized seizure associated with loss of consciousness and fecal incontinence. A neurological evaluation and CT scan were reportedly unremarkable, but because of an abnormal EEG, treatment with Dilantin was commenced. His past ophthalmic history was negative. He had been treated for osteomyelitis of his tibia in his youth. On his first neuro-ophthalmic examination in September 1985, he had best corrected visual acuities of 20/200 OD and 20120 OS. There was a 1 + relative afferent pupillary defect OD, with profound loss of color vision in that eye. The external examination and ocular motility were normal, and the cornea1 reflex was intact bilaterally. The slit-lamp exam was unremarkable, and the intraocular pressures measured 18 mm Hg OU. On funduscopic examination there was optic atrophy OD (Fig. 1A). The left disc was elevated with blurring of the nasal margin, but no peripapillary hemorrhages were evident (Fig. 1B). Fluorescein angiography revealed late leakage from disc vessels (Fig. 2). Kinetic perimetry on a Goldmann bowl perimeter showed a centrocecal
and ‘Radiology, Montefiore Bronx, New York
the abstract and key words
scotoma OD with a full field OS.
What is your diagnosis? How would you proceed? CT and MRI scans revealed mild ventricular dilatation consistent with communicating hydrocephalus (Figs. 3 and 4). No intracranial or intraorbital mass lesions were present. CBC and differential count, ESR, biochemistry, collagen screen and serological test for syphilis were all normal.
How would you proceed? The patient was referred for a neurological evaluation and lumbar puncture.
Clinical
Course
In October 1985, the patient experienced an episode of dizziness, slurred speech, and his legs “buckled under” him while he was climbing a flight of stairs. His visual acuity had improved to 20/60 OD since September; ocular examination was otherwise unchanged. A neurological evaluation was entirely normal, failing to demonstrate any focal deficit, but the patient now admitted that he had suffered from dull occipital headaches, and had experienced episodic clumsiness of both lower limbs for approximately one year. A spinal tap opening pressure measured 480 mm
130
DISC SWELLING Fig. 1. Fundus photograph showing (A) optic atrophy OD with a visual acuity of 201200, and (B) disc
swelling OS with a visual acuity of 20120.
Fig. 2. Fluorescein angiogram performed at initial presentation shows late leakage from the optic disc OS (R) compared to 01) (A).
cerebrospinal fluid ((SF), with a CSF protein level elevated to 92 mg/dl (normal value 14-45 mg/dl), with a normal glucose. Cytology showed 3 lymphocytes with no abnormal cells. A nuclear brain scan revealed positive flow through the sagittal sinus, and digital subtraction angiography failed to demonstrate a Venus sinus throm-
Fig. 3. MRI of the head showing vcntricl~lar dilatation without evidcncc of ;I mass lesion.
bosis. In addition, isotope cysternography revealed normal CSF flow. A cerebral arteriogram was also normal. There was no history of‘vitamin A ingestion, chronic tetracycline or corticosteroid treatment. I,iver function tests as well as serum levels ot‘vitamin A and cortisol were normal. The patient was discharged on l>iamox 500 mg
Fig. 4. (:T of rhe head demonstrating bilateral effilsions in rhc interhcmispheric tissurc. with poor visualization of the con\,cxitv sulci.
Fig. 5. Axial (:I‘ ofthe head showing shunt plarcment in the setting of c~omm~~nic-;iring livdroc~~~h;~lus.
132
Surv Ophthalmol
37 (2) September-October
Fig. 6. Fundus photograph demonstrating progressive disc edema OS three months after initial presentation. The optic atrophy was unchanged in appearance OD, and the visual acuity at this time was count fingers
MATZKINETAL
1992
Fig. 7. Defcrvesence of optic disc edema OS following placement of ventriculoperitoneal shunt.
at two feet OD, and 20/15 OS.
the upper limbs, and was clearly extensor. twice daily. Multiple repeat lumbar punctures consistently showed elevated protein in the range of 170-190 mg/dl, and 2-6 white cells, which included both lymphocytes and monocytes. Cytological assessment after cytocentrifuging consistently failed to reveal any malignant cells. Spinal fluid cultures were negative for both aerobic and anaerobic organisms. Neither fungi nor virus particles were evident in the CSF. In December 1985, the patient underwent ventriculoperitoneal shunt placement (Fig. 5) because of worsening disc edema (Fig. 6) despite maximum treatment with Diamox. The vision had deteriorated to count fingers at two feet OD, but was stable at 20/15 OS. Goldmann visual fields showed a centrocecal scotoma OD, and an enlarged blind spot OS. Six months later, the vision had returned to 20/200 OD, with defervescence .of the disc swelling (Fig. 7). In September 1986, one year after initial presentation, the patient experienced acute bilateral lower limb weakness associated with lumbar pain and numbness on the lateral aspect of his right foot. On neurological examination he was noted to have spastic gait with stiff and jerky movements. There was a distinct proximal weakness in both legs and, in addition, there was evidence of dorsiflexion weakness in the left lower extremity. Anal sphincter tone was diminished. Decreased sensation to pin-prick was noted on the lateral aspect of the right foot and the left lumbar region. The tendon reflexes were noted to be extremely brisk in both lower limbs compared to
the left plantar
response
What is your diagnosis now? How would you proceed? Myelography showed widening of the spinal cord throughout its length with numerous intradural extramedullary defects present (Fig. 8). The largest defect was located at the conus medullaris, i.e., T12-Ll level (Fig. 9). A laminectomy and partial excision biopsy of the lesion was performed from TlO through Ll. The tumor, which appeared pink and friable macroscopically, was seen to be spreading diffusely in the subarachnoid space. Histopathological examination of the specimen was consistent with a malignant ependymoma. Post-operatively the patient received radiation therapy to both the brain (4140 Gray) and spinal cord (4800 Gray) in divided doses. Twenty-seven months after his initial presentation with visual loss, the patient had full upper and lower limb motor and sensory function, as well as normal sphincter control. However, he complained of intermittent lower backache and was hyper-reflexic in both upper and lower limbs.
Discussion The finding of papilledema requires prompt assessment to rule out the presence of an intracranial tumor. When the initial evaluation includes normal neuroimaging and elevated CSF pressure, the diagnosis of pseudotumor cerebri is usually suspected. When even subtle abnormalities of CSF content, such as elevated protein
DISC SWELLING
Fig. 9. Axial CT scan at the level of I,1 performed following myelography demonstrates enlargement of the conus as well as scalloping ofthc posterior margin of the L1 vertebral body.
F/g. 8. Oblique radiograph from the lumbar myelogram indicates multiple intradural extramedullar); filling defects in the lumbar thecal sac studding the nt’rvc roots (arrows).
or cells, are found, the diagnosis of pseudotumor cerebri is untenable, and an underlying cause should be sought. The approach should consist of a compulsive clinical evaluation and appropriate investigation, as well as regular follow-up and reevaluation of the clinical problem until a diagnosis can be made. Our patient presented with unilateral loss of vision and was found to have abnormal optic discs. The initial clinical appearance of the discs was suggestive of Leber’s hereditary optic neuropathy; however, the leaking vessels on the fluorescein angiogram ruled out that diagnosis. The abnormal CSF protein suggested that a primary cause for the elevated intracranial pressure existed, although the etiology was not initially apparent despite extensive investigations. Only after a protracted clinical course, with neurological symptoms developing after a period of twelve months, was the investigation appropriately directed away from the brain and toward the spinal cord. Spinal cord tumors are a rare cause of elevated intracranial pressure. The rarity of this association, in part, was responsible for the long delay in making the correct
diagnosis.
Taylor and Collier in 190 1‘Ii reported the first case of a spinal cord tumor associated with papilledema. In the autopsy of their patient they found, “an extra-medullary intrathecal myxoma, about the size of a sparrow’s egg . . . pressing onto the cord at the level of the third cervical segment.” In 1931 Kyrielis”’ described a tumor involving the lower spinal cord at the thoracolumbar level that presented with headache and papilledema. Love et al ” in 1951 reported three
TABLE Pwscwtiq-
1
Symptoms of Pntiwtv with Spin(~/ Cord Trtmot:\ .koriclted with Papilldrmm*
Headache Loss of vision Nausea, vomiting Backache Mental status change Gait disturbance Diplopia Lower limb pain Vertigo Tinnitus Sphincter disturb. Pelvic pain Neck pain Loss of consciousness
3I
I 5) IO IO 9 8 7 ,I ” -1 L’
I 1 I
*Number of patients = 53 (34F. 19M). Ages ranged from 9 to 69 years (man, 37 vears). Includes 20 cases reported by Glasauer. I 96-4.k
134
Surv Ophthalmol
37 (2) September-October
cases of spinal cord tumors producing disc swelling. Raynorlg in 1969 reviewed 36 cases, and we have found 53 cases besides our own reported in the literature. Ependymomas were the most common form of glioma of the spinal cord in the cases we reviewed and were found to be responsible for approximately 40% of the cases producing papilledema. We found these tumors to occur predominantly in the lower thoracic or lumbar region, which was consistent with the review by Tanaka et alz5 in 1988. Ependymomas are unencapsulated glial tumors that arise from ependyma1 cells which are the remnants of the embryonic neuroepithelium and line the ventricles and spinal canal. Other spinal tumors producing papilledema include schwannomas (1 I%), meningiomas (7%), neurofibromas (7%), and gliomas (7%). With regard to the clinical presentation of spinal cord tumors in general, lumbar pain is the most common presenting symptom and occurs in 65-70% of cases.g This pain is invariably associated with a motor and sensory deficit. However, in cases of spinal cord tumors associated with papilledema, headache, often with nausea and vomiting, appeared to be the most consistent symptom (Table 1). In most patients with papilledema, elevated intracranial pressure (ICP) was established either at the time of the initial presentation of the tumor or at subsequent followup with progressive disease. Visual loss was present in a significant number of these patients, although only two were reported to have transient obscurations. Our patient is unusual in that his is only the fourth recorded case of a spinal cord tumor associated with papilledema presenting with isolated visual loss, without any other symptom attributable to disease of the spine. Seven patients in our review were reported to complain of double vision on presentation, all due to six nerve palsies.
Pathophysiology A number of cases of papilledema have been associated with high spinal cord lesions.5~‘s~‘6~‘7~26 In these cases the tumors have been thought to extend superiorly to involve the cerebellum and obstruct the CSF. However, most cases of papilledema caused by spinal cord tumors have been associated with ependymomas and neurofibromas involving the thoracic and lumbar spine. Several explanations for the development of papilledema in these cases have been proposed, most of which are directed to the associated ele-
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vated CSF protein. In our review, the range of CSF protein was 38 mg/dl to 10,500 mg/dl, with 66% having a CSF protein greater than 100 mg/dl. It has been proposed by Schaltenbrand” that the increased viscosity caused by the elevated protein results in decreased absorption of CSF by the arachnoid villi, and consequently leads to increased ICP. Gardner et al” proposed that delayed CSF absorption by the arachnoid villi results because the large protein molecules per se mechanically block pores in the semipermeable membrane. In support of the “protein theory,” it has been pointed out that patients with clinical features consistent with the GuillianBarre syndrome, who typically have elevated CSF protein, may also have intracranial hypertension.6*‘5 Arseni3 proposed that spinal cord tumors may stimulate a basal leptomeningitis and arachnoiditis with compromise to CSF absorption. Papilledema has been seen with normal CSF protein content in association with spinal tumors, and by contrast, markedly elevated CSF protein level can exist in the absence of papilledema. This phenomenon is often seen in meningitis, and again in the Guillian-Barre syndrome. Therefore, although the theories related to elevated CSF protein are plausible, they cannot explain the findings of elevated ICP in all the cases of spinal cord tumors causing papilledema. Disseminated tumor cells, either by mechanically obstructing CSF absorption, or by stimulating massive protein exudate, have been implicated as being responsible for elevated ICP. Love et al” found four of sixteen cases of intramedullary tumors to be associated with papilledema, two of which had villous tumor seeding. Alternatively, mutinous material produced by degenerative change within the tumor can also interfere with CSF dynamics and lead to an elevated ICP.*’ The size of the tumor does not necessarily play a major role, since even small tumors can cause increased ICP if located strategically within the venous plexus*’ or intrathecally as described by Taylor and Collier. 46 Beduschi et al4 and Rudnickie*r suggested that venous stasis by tumor compression of the spinal or medullary venous plexus causes an unfavorable transarachnoid villous hydrostatic pressure, and thus leads to increased ICP. Recent animal models ofextradural tumors have also demonstrated that spinal epidural venous plexus obstruction can cause breakdown of the blood-CSF barrier due to the release of prostaglandin E,, a mediator of increased vascular permeability.2”.24
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DISC SWELLING Episodes of clinical or subclinical subarachnoid hemorrhage from the tumor, in particular by an ependymoma, have been implicated as a possible mechanism of increased ICP, either by the blood itself or by its specific constituents.’ a case Philipon et al,” in their report describing without ventricular dilatation, suggested that cerebral edema is responsible for intracranial hypertension in cases of spinal cord neoplasm. Finally, the spinal canal has been shown to act as an elastic reservoir for CSF.” With normal changes in physiological cerebral blood flow, the ability of CSF to flow into or out of the spinal canal is thought to be important in the maintenance of a constant intracranial volume. In this role, the lumbar part of the spinal sac may be the most important because of its greater distensibility and volume. By compromising this system, spinal cord tumors may in fact reduce the capacity of this “reservoir” and cause papilledema.” Chronic spinal cord compression caused by a thoracic disc herniation has been described as causing papilledema.” This supports the theory that simple mechanical blockage, by disrupting the elastic reservoir in the lumbar region of the spinal canal, can cause elevated intracranial pressure.
Conclusion Spinal tumors are a rare cause of elevated intracranial pressure. ‘rhe majority of reported cases were found to have papilledema either at the time of the presentation of the tumor with spinal symptoms, or after the diagnosis of a spinal tumor had been made. Our patient was unusual in that he initially presented with isolated visual loss without sytnptoms or signs of spinal cord disease. To our knowledge, this is only the fourth reported case of a spinal cord tumor associated with papilledetna to present with visual loss in the absence of‘ other neurological symptoms. The etiology of optic disc swelling in the presence of elevated CSF pressure and elevated protein is usually discovered on CT or MRI of the head, often with the use of a contrast medium. When no abnormality is detected on high resolution contrast scanning, and if all investigations for inflammatory or autoimmune diseases are negative, the diagnosis of a spinal cord tumot should be considered. When our patient initially presented with papilledema in 1985, contrast MRI studies were not yet available. If a contrast MRI had been performed at that time, an abnormality might have been detected on gadolinium
(Gd) MRI of the head, as diffuse metastatic subarachnoid deposits were noted on the myelogram, and although not proven, similar subarachnoid deposits could have been present surrounding the brain. Conceivably, Gd-enhanced MRI of the head, had it been available, would have hastened the diagnosis of a spinal cord tumor in our patient. Addendum Since acceptance of this paper for publication, the authors have become aware of another case of ependymoma associated with optic disc swelling and bilateral central retinal vein occlusions. The CSF was described as thick and gelatinous, and had a protein content of 4880 mg/dl. At the time of lumbar puncture, the CSF
immediately gelled (Froin’s syndrome) and the opening pressure was unrecordable. (Frohman L., Schulder M, Mauriello J et al. Frank B. Walsh Society 24th Annual Meeting, February 28 & 29, 1992. Doheny Eye Institute, University ofSouthern California. Los Angeles, (:a.)
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E, Lossos F: Experimental 24. Siegal ‘I‘, Siegal T, Shohami neopiastic spinal cord compression: Effect of ketamine and MK-801 on edema and prostoglandin. Neurosurg 26:963-966, 1990 S: Papilledema and spinal 25. Tanaka K, Waga S, Shimosaka cord tumors. Surg Neural 29;462-466, 1988 26. Taylor J, Collier J: The occurrence of optic neuritis in lesions of the spinal cord: injury, tumor, myelitis. (An account of twelve cases and one autopsy. Brain 21: 532-553, 1901 Buxbaum MW: Giant ependymoma 27. Teng P, WagnerJH, of the spinal cord associated with papilledema. Review of literature and report of a case. Arch Neural 2:657-662, 1960
Reprint address: Thomas L. Slamovits, M.D., Montetiore Medical Center, 111 East 210th Street, Bronx, NY 10467. This study was supported in part by an unrestricted grant to the Department of Ophthalmology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, from Research to Prevent Blindness, Inc.
Abstract. A 30-year-old man presented with monocular visual loss secondary to chronic papilledema, due to an ependymoma involving the spinal cord. No other neurological symptoms were present at the time. Initial neuroradiologic tests as well as laboratory investigations were negative, except for elevated pressure and protein concentration of his cerebrospinal fluid. In spite of intensive investigation, the diagnosis of a spinal cord tumor was delayed for approximately 12 months until he presented with neurologic symptoms attributable to a spinal cord lesion. This is only the fourth case reported of a spinal cord tumor associated with papilledema presenting with visual loss, without any other manifestations of either elevated intracranial pressure, or spinal disease. Possible mechanisms for elevated intracranial pressure in cases of spinal cord tumors are reviewed. (Surv Ophthalmol 37:130-136, 1992)
Key words.
ependymoma
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neuroimaging
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papilledema
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spinal cord tumor
