Journal of Neuro-Ophthalmology, September 2000, Volume 20, Issue 3

Multiple Sclerosis Simulating a Mass Lesion

The cases of two young women with a homonymous hemianopia are described. Both women had a progressively enlarging mass lesion that was seen with neuroimaging studies. One patient had neurologic deterioration despite intravenous corticosteroid treatment. In each case, results of a stereotactic biopsy showed demyelination that was consistent with multiple sclerosis. Multiple sclerosis infrequently presents as a mass lesion. The atypical clinical and radiographic features of large demyelinating plaques may lead to an erroneous diagnosis of a brain tumor, infection, or demyelination from other causes.

Journal oj Neuro- Ophthalmology 20( 3): 147- 153, 2000. © 2000 Lippincott Williams & Wilkins, Inc., Philadelphia Multiple Sclerosis Simulating a Mass Lesion Deborah I. Friedman, MD The cases of two young women with a homonymous hemiano-pia are described. Both women had a progressively enlarging mass lesion that was seen with neuroimaging studies. One pa­tient had neurologic deterioration despite intravenous cortico­steroid treatment. In each case, results of a stereotactic biopsy showed demyelination that was consistent with multiple scle­rosis. Multiple sclerosis infrequently presents as a mass lesion. The atypical clinical and radiographic features of large demy-elinating plaques may lead to an erroneous diagnosis of a brain tumor, infection, or demyelination from, other causes. Key Words: Demyelination- Magnetic resonance imaging- Multiple sclerosis- Neoplasm- Stereotactic surgery. CASE REPORTS Case 1 A previously healthy 21- year- old woman woke up with difficulty seeing to her right. Neuro- ophthalmic ex­amination 2 weeks later showed a complete right hom­onymous hemianopia and no other abnormalities. Mag­netic resonance imaging ( MRI) demonstrated a right oc­cipital lobe lesion that was interpreted as an infarction ( Fig. 1). Suspecting a stroke, laboratory studies were requested, oral contraceptives were discontinued, and the patient was advised to stop smoking. Two days later, the patient woke with weakness and numbness of the right arm and leg that improved during the course of the day. Examination that afternoon showed a right hemiparesis ( leg weaker than the arm and face) without a sensory deficit; she had a pulse of 112 beats/ min. The weakness resolved 7 hours after symptom onset. The patient was admitted to the hospital and under­went anticoagulation with heparin. Results of the cardiac evaluation and cerebral angiogram were normal. Com­plete blood count was normal, except for a white cell count of 12,000/ mm3, and a urinary tract infection was discovered. The erythrocyte sedimentation rate was 25 mm/ h. Results and tests for antinuclear antibodies, a chemistry panel, rheumatoid factor, Lyme titer, anticar- Manuscript received June 25, 1999; accepted May 12, 2000. From the Departments of Neurology and Ophthalmology, SUNY Upstate Medical University, Syracuse, New York. Presented in part at the 28th Annual Frank B. Walsh Society Meet­ing, February 11- 15, 1996, Salt Lake City, Utah. Address correspondence and reprint requests to Deborah I. Friedman, MD, Department of Neurology, 750 East Adams Street, Syracuse, New York 13210. diolipin antibody, Venereal Disease Research Labora­tory, thyroid hormone ( T4), thyroid stimulating hor­mone, prothrombin time, partial thromboplastin time, human immunodeficiency virus titer, and a chest radio­graph were normal or negative. She was discharged to her home 3 days later on warfarin. On the day of dis­charge, MRI of the brain revealed an area of increased signal in the white matter of the left occipital horn on proton- density and T2- weighted images with minimal mass effect ( Fig. 2). A small focus of increased signal intensity was seen posterior to the right occipital horn. Magnetic resonance imaging with gadolinium and a lum­bar puncture were scheduled as an outpatient procedure. Two days later, the patient developed right- sided weakness and spasticity, right- sided sensory loss to all modalities, and dysarthria. She was admitted to the hos­pital, and a computed tomography scan showed a right parieto- occipital subcortical lesion with a focus of en­hancement ( Fig. 3). High- dose intravenous dexametha-sone was initiated. The erythrocyte sedimentation rate increased to 50 mm/ h. The cerebrospinal fluid contained 13 white blood cells ( 100% monocytes), protein 64 mg/ dL, and normal glucose; results of stains, cultures, and cytology were all negative. Oligoclonal bands were present. Two weeks later, there was no clinical improve­ment with administration of corticosteroids, and MRI showed extension of the lesion anteriorly to the thalamus ( Fig. 4). The patient underwent stereotactic biopsy of the oc­cipital lobe. Pathologic examination revealed a demye-linating process, characterized by sharply defined areas of myelin loss, perivascular axons, intense astrocytic proliferation, and perivascular lymphocytic infiltration ( Fig. 5). The hemiparesis improved over several weeks, and the patient resumed independent ambulation. She had one additional attack of cerebellar dysfunction 3 years later and no further attacks over the past 5 years. Magnetic resonance imaging performed during the second attack showed partial resolution of the initial lesion and a new area of demyelination in the left cerebellar peduncle ( Fig. 6). Case 2 A 24- year- old woman in her 34th week of pregnancy had a frontal pounding headache unaccompanied by nau- 147 148 DEBORAH I. FRIEDMAN FIG. 1. A: T2- weighted axial magnetic resonance imaging shows increased signal intensity in the subcortical white matter of the left posterior parietal lobe ( arrows) [ June 5, 1991]. sea or photophobia. Later that evening, the headache subsided, but she noticed a glaze over the temporal visual field OS. The next morning, she observed a glare in the left hemifield OU, but she was still able to drive. The following day, she could not see to her left and stopped driving. The findings of a neuro- ophthalmic examination revealed a total left homonymous hemianopia and no other abnormalities. An MRI of the brain ( fluid attenuated inversion recov­ery) showed a patchy area of increased signal in the subcortical white matter of the right parietal lobe without edema or mass effect ( Fig. 7). Intravenous contrast was not administered because the patient was pregnant. De-myelinating disease or a low- grade tumor was suspected. Results of lumbar puncture revealed 17 white blood cells ( 100% monocytes), 53 red blood cells, glucose 54 mg/ dL, and protein 27 mg/ dL. Results of cryptococcal anti­gen and Venereal Disease Research Laboratory were negative. Four oligoclonal bands were detected. Results of cerebrospinal fluid cytology yielded no evidence of malignancy. The patient was diagnosed with a demye-linating process and treated with intravenous methyl-prednisolone ( 1 gram daily for 3 days). She delivered a healthy baby without complications 2 weeks later, but her hemianopia persisted. Six weeks after her initial presentation, she saw an­other neurologist for a second opinion, and the neurolo­gist requested a follow- up MRI. It showed marked en­largement of the lesion that involved the occipital, pari­etal, and temporal subcortical white matter with patchy gadolinium enhancement ( Fig 8). The patient was in­formed that she had a highly malignant brain tumor, and she was referred to a neurosurgeon who performed a stereotactic biopsy of the occipital lobe. Findings from the pathologic examination showed a diffuse infiltrate with foamy macrophages and adjacent gliosis. Results of luxol fast blue stain revealed diffuse loss of myelin in the area of histiocytic infiltration. Results of immunohisto-chemical stains for phosphorylated neurofilament ( NF- 312) and histiocyte marker CD- 68/ KP1 showed preser­vation of some axons coursing through an area of his­tiocytic infiltrate. The lesion was consistent with demyelination of multiple sclerosis ( MS). She was ad­ministered intravenous dexamethasone postoperatively but her hemianopia did not improve. DISCUSSION These cases illustrate the difficulty of diagnosing MS when the clinical course and results of neuroimaging studies suggest a tumor or an infectious process. One patient had progressive clinical neurologic deterioration despite treatment with intravenous corticosteroids, and both patients had progressive radiographic enlargement of mass lesions on MRI. Magnetic resonance imaging is the most reliable diag­nostic test for confirming and assessing the progression of MS. Multiple sclerosis is characterized radiographi- FIG. 2. The previously noted lesion appears as a larger, high signal intensity abnormality in the subcortical white matter T2- weighted magnetic resonance imaging scan [ June 19, 1991]. J Neuro- Ophthalmol, Vol. 20, No. 3, 2000 MS SIMULATING A MASS LESION 149 FIG. 3. Axial computed tomography reveals a low density lesion ( A) that enhances with contrast ( B) [ June 22, 1991]. cally by numerous lesions in the periventricular and sub­cortical white matter, brainstem, and spinal cord. The MR changes are not specific, and the differential diag­nosis includes ischemic or inflammatory vascular dis­ease, progressive multifocal leukoencephalopathy, sar­coidosis, postinfectious or postvaccination encephalomy­elitis, Lyme disease, HIV infection, systemic lupus erythematosis, Behcet disease, and Sjogren disease ( 1). Large space- occupying lesions (" tumefactive" MS) are unusual and may be misinterpreted as a tumor, abscess, or infarction. Progressive multifocal leukoencephalopathy ( PML) has clinical and radiographic features that are similar to those of tumefactive MS. The course is one of rapid demyelination and neurologic deterioration. The central visual pathways are often involved, and neuro- ophthal-mic manifestations may be present ( 2). In a series of 13 male patients with PML associated with the acquired immunodeficiency syndrome, a homonymous hemiano-pia was the most common neuro- ophthalmic finding ( 5 patients). Other signs included abducens palsy, nystag­mus, cortical blindness, and decreased vision. Swift progression in the size and number of lesions is com­mon to PML and to MS ( 3). Progressive multifocal leukoencephalopathy also produces hyperintense T2 signal abnormalities that affect predominantly white matter, without mass effect ( 2,4). The parieto- occipi-tal regions are frequently involved, as are the frontal lobes, thalamus, basal ganglia, and corpus callosum ( 3,5). Lesions in the brainstem and cerebellum are less common. Contrast enhancement is occasionally observed ( 2,6). There is often a central area of cystic or necrotic change ( 3). Postinfectious or postvaccination demyelination may also have a clinical presentation similar to MS. Like in MS, the lesions may involve the optic system, periven­tricular white matter, or brainstem, and patients improve with corticosteroids ( 1). Demyelinating disease can usually be distinguished from a neoplastic or infectious process using results of neuroimaging studies, based on the size and distribution of the lesions. Typical features of demyelination include FIG. 4. A: There is marked enlargement of the mass, which extends anteriorly to the thalamus in this T2- weighted magnetic resonance imaging scan. There is no edema or mass effect, and the lesion re­mains confined to the white matter poste­riorly. B: There is no enhancement after gadolinium administration [ July 5, 1991]. / Neuro- Ophthalmol, Vol. 20, No. 3, 2000 150 DEBORAH I. FRIEDMAN , uJHifj?^ ,.*,*•'^ flHH rgft » HnMRRK;;^ *~ ' rS - T T *. .- r - • • • . . • • •• • • i ^^ ll ™ B^ PBwSri FIG. 5. Results of luxol fast blue staining of the stereotactic bi­opsy specimen reveal sharply demarcated areas of myelin loss. lack of contrast enhancement, minimal or no mass effect, and absence of surrounding edema. However, active MS plaques with an inflammatory response may en­hance, making them difficult to differentiate from tumors ( 7,8). Spread of demyelination across the corpus callo-sum may simulate a glioma ( 9,10,11). Large plaques with mass effect and ring enhancement have been de­scribed ( 7,12,13). Physiologic MRI, such as magnetization transfer ( MT) imaging, may prove useful in distinguishing MS lesions from other conditions that involve predominantly white matter. Magnetization transfer imaging examines the nonwater components of tissue to further characterize rigid macromolecules ( e. g., myelin and cell membranes) that are " invisible" on conventional MRI ( 14). Multiple sclerosis lesions initially have a very low MT ratio that increases over subsequent weeks or months ( 14). The center portion of the MS lesion has the lowest MT ratio ( 15). Established MS lesions have a variable appearance. Physiologic MRI showed reduced blood flow, increased diffusion, and a reduced MT ratio in a case of tumefac-tive MS that was associated with edema and mass effect on conventional MRI ( 16). Progressive multifocal leu-koencephalopathy also shows a dramatic decrease in MT ratio, but it usually has a different pattern than MS or subcortical white matter ischemic disease ( 17). The in­dividual lesions of PML tend to be homogenous, in con­trast with those of MS that have a variable appearance. Both PML and MS are easily distinguished from isch­emic changes that have only modest reductions in MT ratio. Although the posterior visual pathways are frequently affected radiographically and pathologically in MS, homonymous visual field defects are unusual ( 18). In one report of 217 autopsied cases and 415 clinically observed patients, asymptomatic demyelinating plaques were found in the optic radiations in 23 of 50 necropsies, but no patient had a homonymous visual field defect ( 19). This is probably because of the relatively small size of most plaques, which have little impact in the large area encompassed by the optic radiations. Large demyelinat­ing lesions frequently produce symptoms not generally associated with MS, such as headache, homonymous hemianopia, confusion, seizures, and aphasia ( 8,20). Therefore, the clinical presentation may corroborate the radiographic suggestion of a tumor. A fulminant monophasic variant of MS was initially described by Marburg ( 21) in 1906. This form of MS relentlessly progresses to death within a period of weeks. Previous cases have shown multiple demyelinating plaques on neuroimaging and at autopsy ( 21,22). Three previously reported cases of patients with tumefactive MS ( Table 1) described rapid progression and death. Therefore, there is overlap between these two uncommon entities. Pathologic data from a patient with Marburg disease indicated evolving changes ( 23). A brain biopsy specimen obtained 33 days after symptom onset showed macrophages and T lymphocytes diffusely infiltrating small vessel walls and white matter. Messenger RNA for tumor necrosis alpha and inducible nitric oxide synthase were expressed, with preservation of myelin sheaths. A second biopsy 76 days later ( after the patient was treated with intravenous immunoglobulin G) showed confluent FIG. 6. Three years later, T2- weighted MR imaging demonstrates partial resolution of the initial lesion ( A) and a new demyelin­ating plaque in the left cerebellar peduncle ( B). J Neuro- Ophthalmol, Vol. 20, No. 3, 2000 MS SIMULATING A MASS LESION 151 FIG. 7. A: There is patchy increased signal in the posterior parietal lobe on fluid attenu­ated inversion recovery imaging. B: In a more caudal section, the abnormal signal is more defined and conforms to the white matter. demyelinating lesions, macrophage infiltrates that tested positive for myelin debris, activation markers, and tumor necrosis alpha and inducible nitric oxide synthase mes­senger RNA. Immunoglobulin G deposits were found along the myelin sheaths. These findings imply that an inflammatory process produces the initial neurologic deficits with subsequent demyelination. Biopsy of suspicious lesions is most often performed stereotactically. Although results of brain biopsy are con­firmatory, biopsy is not without risk. Temporary wors­ening of neurologic deficits postoperatively and death have been reported ( 7). The need for biopsy may be eliminated in the future with functional MRI. Active neo­plasms typically show increased regional cerebral blood flow on perfusion MRI, while demyelinating plaques have reduced regional blood flow. The MT ratio may not distinguish between the two conditions ( 16,24). The prognosis for recovery with tumefactive MS is generally good. Most patients experience symptomatic improvement and reduction or disappearance of the ra­diographic abnormalities after corticosteroid treatment, although they are not uniformly responsive to therapy ( Table 1). Many patients subsequently develop clinically definite MS. Demyelinating disease is an important diagnostic con­sideration for patients with a progressive neurologic course and a large lesion on MRI. Other testing, such as cerebrospinal fluid examination or evoked potentials, may be helpful to support a diagnosis of MS. Progressive multifocal leukoencephalopathy must be considered for FIG. 8. A, B: Six weeks later, there is marked enlargement on the mass on T2- weighted images. C: Gadolinium- enhanced T1- weighted images show heterogenous enhancement without edema or mass effect J Neuro- Ophthalmol, Vol. 20, No. 3, 2000 152 DEBORAH I. FRIEDMAN TABLE 1. Summary of tumefactive multiple sclerosis cases Patient 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 Reference 13 13 13 8 28 9 9 9 12 27 27 27 13 13 13 10 7 7 7 7 7 16 1 1 1 29 26 Age/ Gender 39/ F 30/ F 21/ F 26/ F 60/ M 23/ F 42/ F 38/ M 38/ F 37/ M 24/ M 34/ F 39/ F 30/ F 21/ F 24/ F 31/ F 17/ F 27/ F 24/ M 58/ F 20/ F 44/ F 42/ M 26/ F 16/ M 24/ F 21/ F 24/ F Clinical or radiographic manifestations L. facial weakness, dysarthria, L. arm and leg weakness L. sided weakness and decreased proprioception L. homonymous hemianopia, R. superior quadrantanopia, speech difficulty Partial seizures, headache, right hemianopia, apraxia, aphasia Optic neuritis One year later, tetraparesis, aphasia, ataxia Headache, affective and personality change Known clinically definite MS, headaches, confusion, somnolence Spastic quadriparesis, incontinence, seizures Known clinically definite MS, L. hemiparesis, confusion, dysarthria Blurred vision and myelopathy, followed by aphasia and seizure Dizziness, headache, seizures Blurred vision, aphasia, headache, seizure L. sided weakness, dysarthria Seizures, left leg weakness, L. apraxia Dysarathria, visual loss, ataxia, L. apraxia Lethargy, seizures, personality change, L. hemiparesis L. sided heaviness, imbalance, bilateral leg paresthesias, occipital headache Frontal headache, malaise, L. homonymous hemianopia, L. hyperreflexia Confusion, vertigo, blurred vision, L. hemianopia, L. hemiparesis Aphasia, right pronator drift, R. hemianesthesia R. arm paresthesias, R. facial numbness, myelopathy L. sided weakness and incoordination, dysarthria, ataxia Left parietal lesion Multiple parietal lobe lesions Right parietal mass L. sided numbness, ataxia, L. hearing loss, visual disturbance Known clinically definite MS, seizures, aphasia R. homonymous hemianopia, weakness, pan- sensory loss, dysarthria Headache, L. homonymous hemianopia Treatment Dexamethasone Dexamethasone Dexamethasone Dexamethasone Dexamethasone Steroids Steroids Dilantin Plasmapheresis None Dexamethasone None Dexamethasone Dexamethasone Dexamethasone Dexamethasone ACTH Dexamethasone, intravenous antibiotics None Dexamethasone None Methylprednisolone Unknown Unknown Unknown Methylprednisolone Unknown Dexamethasone Methylprednisolone Outcome Improved Rapid deterioration and death Improved Slight initial improvement, progressive dementia No change, death within 1 year Improved Improved ( did not undergo biopsy) Died from aspiration pneumonia Slight improvement Improved Improved Improved, then clinical MS developed Improved Deterioration and death in 3 months Improved Improved Unchanged Died postoperatively from intracerebral hemorrhage Improved, then developed clinically definite MS ( did not undergo biopsy) Developed clinically definite MS: 3 attacks within 1 year Worsened initially, then improved Improved Progressed to clinical MS Progressed to clinical MS Progressed to clinical MS Relapsing and remitting MS Further relapses ( did not undergo biopsy) Improved, then clinincal MS developed No change ACTH, adrenocorticotropic hormone; L., left; MS, multiple sclerosis; R., right. an immunocompromised host or for patients adminis­tered immunosuppression treatment. 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