Neuro-radiology

Neuroradiology(1992) 34:150-154

9 Springer-Verlag1992

Multiple sclerosis masquerading as a mass lesion D . W . Giang 1, K. R. Poduri 2, T. A. E s k i n 3, L. M. K e t o n e n 4, P. A . Friedman 2, D . D . Wang 1' 5, and R. M. H e r n d o n 6

Departments of 1Neurology, 2Orthopedics,Divisionof RehabilitationMedicine, 4Radiology,and 5Pediatrics,Universityof Rochester MedicalCenter,Rochester,New York,USA 3Department of Pathologyand LaboratoryMedicine,Universityof Florida Collegeof Medicine,Gainesville,Florida,USA 6Department of Neurology,Good SamaritanHospital,Portland,Oregon,USA Received: 23 August 1990/Receivedin revisedform:9 October 1991

Summary. Six patients presenting with new neurological deficits underwent magnetic resonance imaging (MRI) that displayed mass lesions leading to diagnoses of tumor or abscess. Biopsy revealed demyelinating lesions. K e y words: Multiple sclerosis - MRI - Mass lesions

Noninvasive neuroimaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) have improved the diagnosis of multiple sclerosis (MS). Clinicians have come to rely on MRI to provide evidence of multiple white matter lesions and to eliminate other causes of subacute neurological dysfunction such as tumors or abscesses. However, problems remain. Asbury et al [1] re-emphasized that MRI does not provide a specific diagnosis of MS. Areas of acute demyelination may be misinterpreted as tumor, abscess, or stroke, Case reports and small series document that MS may present as a contrast-enhancing mass lesion on CT [2-8]. MRI can similarly suggest an incorrect diagnosis of tumor [9, 10]. Such misdiagnoses are less of a problem with MRI than CT, because the higher sensitivity of MRI permits correct diagnosis in most cases by showing concurrent lesions [7, 8]. However, we present six patients in whom MS first appeared on MRI as a mass in which cerebral biopsy was performed to distinguish acute demyelination from what was thought to be tumor or abscess.

initial presentation and of chronic earache, but no prior episodes of neurological dysfunction. Physical examination demonstrated a left hemiparesis without sensory changes and a left extensor plantar response; her temperature was normal. Noncontrast CT (not shown) revealed low attenuation in the right frontopafietal subcortical white matter, with regional mass effect. T2-weighted MRI (Fig. 1) revealed a 3 x 2.5 cm high signal lesion in the same area. Lumbar puncture disclosed normal opening pressure, 11 nucleated cells (96 % lymphocytes), glucose 57 mg/dl, and protein 40mg/dl. Oligoclonal bands and kappa light chains were not found. Pattern-shift visual evoked potentials (VEP) were normal. Cerebral angiography was normal. One month later, the patient complained of blurred vision in the right eye, retro-ocular pain, and vomiting. Visual acuity was normal in both eyes. An indistinct margin of the right optic disc was interpreted as papilledema. The left hemiparesis and the cranial CT appearances were unchanged. Needle biopsy of the right frontoparietal mass revealed the degeneration of myelin with relative preservation of axons, reactive gliosis, and focal perivascular demyelination of MS. The patient's symptoms gradually improved following surgery. Follow-up CT demonstrated a decrease in the size of the lesion. Pattern-shift VEP showed pro-

Case reports

Case 1

A 31-year-old woman initially presented with a 1-week history of imbalance, "heaviness" of the left leg and arm, paresthesiae of both legs, occipital headache with nausea, and tinnitus. MRI showed a lesion in the right frontoparietal white matter. MS was suspected but the patient showed no significant clinicalimprovement after a 3-week course of intravenous ACTH. Further questioning revealed a history of dental cleaning 3 months prior to her

Fig,1. Case 1. MRI (1.5 T,

TR/TE = 2000/30) showsa homogeneoushighsignallesionin the right centrumsemiovale

151 Case 3

Fig.2a, b. Case 2. a Contrast-enhancedCTshowsaperipherallyenhancing right occipital lobe lesion with mass effect, b MR (0.35 T, TR/TE = 3000/40) shows irregular high signal in the right parietooccipital white matter with involvement of the corpus callosum. The lesion exerts local mass effect on the adjacent cortex and lateral ventricle. A second high signal lesion is seen in the left frontal lobe. Small lesions were also present in the left occipital and right frontal white matter

longed latency in the right optic nerve. In retrospect, the visual symptoms which prompted biopsy were due to optic neuritis and represented the second lesion in clinically definite MS. Case 2

A 17-year-old girl had a 5-day history of left frontal headache which became generalized at times. For 2 days prior to admission, she noted hot sensations, sweating, loss of appetite, vomiting, neck stiffness, and blurred vision. Her boyfriend used intravenous drugs. On examination, she was afebrile, but had a left homonymous hemianopsia, slight left hyper-reflexia, and mild atopagnosia. Fundoscopy and sensory examination were normal. Her teeth were in poor condition. Contrasted-enhanced CT (Fig. 2 a) revealed a 2 x 4 cm enhancing right parieto-occipital lesion with surrounding edema. T2-weighted MRI (Fig. 2b) showed four areas of abnormally high signal felt to be consistent with abscesses. Multiple cultures, serum HIV by ELISA and other laboratory studies were normal. Dexamethasone, ampicillin and chloramphenicol were administered intravenously as empirical treatment for cerebral abscess and two molars were extracted. The patient's headache, nausea, and blurred vision improved over 2 weeks. Follow-up M R I after 17 days of antibiotic therapy showed no change in the size of the lesions. An attempt to drain pus from the presumed right occipital abscess was unsuccessful. Postoperatively, the patient awoke groggy but soon became unresponsive with a fixed, dilated right pupil. Despite emergency craniotomy for decompression, the patient died. Post-mortem examination of the brain revealed multiple areas of demyelination with preserved axons as well as intracerebral hemorrhage at the operative site and uncal herniation.

A 27-year-old, right-handed woman developed confusion, vertigo, blurred vision, left hemianopsia, and left hemiparesis over a 2-week period. Neurological examination revealed dysphasia and dyslexia. T2-weighted MRI disclosed a large high-signal right parieto-occipital white matter lesion with surrounding edema and some mass effect, felt to be most consistent with a tumor. Two angiograms were considered normal. Over a 9-month period, the patient's symptoms improved and on MRI the lesion diminished in size (Fig. 3), but she remained hemiparetic. A biopsy undertaken to relieve the patient's anxiety revealed gliosis, perivascular histiocytes, and loss of myelin. Two years after the initial symptoms, the patient experienced a right intranuclear ophthalmoplegia and MS was confirmed clinically. Case 4

A 24-year-old man with intermittent hypertension (untreated) and obesity presented with a 1-day history of right hemisensory loss and "feeling spacey". Physical examination revealed nonfluent aphasia, paraphasia, right pronator drift, and right hemianesthesia. Contrastenhanced CT and MRI (Fig. 4) revealed a left frontoparietal lesion with focal mass effect. Lumbar puncture disclosed an opening pressure of 384 mm water, 11 nucleated cells (91% lymphocytes), glucose of 66 mg/dl, total protein of 43 mg/dl, normal cytology, normal IgG and a single band on CSF electrophoresis. Over i week, the hemiparesis gradually increased. After noninvasive studies for sources of cerebral emboli proved negative, a cerebral biopsy was obtained to exclude tumor.

Fig.3. Case 3. MRI (0.35 T, TR/TE -- 500/30) shows a heterogeneous lesion in the right parieto-occipital white matter adjacent to the lateral ventricle. This study was obtained just prior to biopsy,followingresolution of edema noted on previous images

Fig.4. "Case 4. MR (1.5 T, TR/TE = 2000/30) shows an irregular, heterogeneous high signal lesion in the left parietal white matter

152

Fig.5. Case 5. MRI (1.5 T,

TR/TE = 2000/30) shows a large, heterogeneous left-sided lesion with some mass effect. Multiple smaller lesions are demonstrated in the right periventricular area The pathological specimen showed a well-demarcated lesion containing lipid macrophages and early astrocytic reaction and was initially felt to be most consistent with an organizing incomplete or subtotal infarct. The patient was treated with dexamethasone for cerebral edema, and improved gradually over 1 month, but the right hemiparesis persisted. Three months after the original illness, the patient experienced 4 h of clumsiness. Physical examination revealed an alert, inattentive patient with visuospatial apraxia, left-sided neglect, left homonymous hemianopsia, mild left hemiparesis, bilateral extensor plantar responses, and residual right spastic hemiparesis but no aphasia. The left hemiparesis worsened over the next day. Investigation for sources of emboli and hypercoagulability proved negative. MRI (not shown) revealed a new right centrum semiovale lesion in addition to the previous left-sided lesion. CSF analysis revealed a total protein of 62 mg/dl, glucose of 57 mg/dl, 16 nucleated cells, 7 red blood cells, no oligoclonal bands, a normal IgG synthesis rate, but elevated free kappa light-chains of 0.63 mg/ml. Re-examination of the original pathology specimen with a combination of special stains (Luxol fast blue for myelin and Bodian silver impregnation for axons) revealed the loss of myelin to be disproportionate to the extent of axon destruction consistent with "primary" demyelination. Together with the presence of focal perivascular lymphocytic inflammation and the apparent sparing of grey matter, the lesion was felt, in retrospect, to be compatible with a demyelinating process. Clinically definite MS was diagnosed. The patient was treated with ACTH with marginal improvement. Six months later, he suffered an attack of dysarthria, vertigo, nystagmus, and truncal ataxia which improved only partially with A C T H therapy. Case 5

A 19-year-old right-handed woman presented with sudden onset of a right hemiparesis, which gradually resolved. Following CT and angiography, a stroke was diagnosed and oral contraceptives were discontinued. Two years later, she presented with a 12 h history of progressive right hemiparesis, hemisensory loss, and expressive aphasia. The patient was 2 months postpartum and smoked but was not on medications. Physical examin-

ation revealed normal blood pressure, a grade II/VI systolic ejection murmul, nonfluent aphasia and difficulty with repetition, right homonymous hemianopsia, right central facial weakness, deviation of the tongue to the right, and right hemiparesis (most evident in the hand). Muscle stretch reflexes were mildly increased on the right, but both plantar responses were flexor and sensation was normal. CT of the head showed a zone of decreased attenuation in the left frontal white matter; contrast medium was not given. Investigation for hypercoagulability, duplex sonography of the carotid arteries, cerebral angiography, and echocardiography were all normal. MRI of the head 4 weeks after her second event (Fig. 5) showed a large left parietal mass lesion, with midline shift, which was interpreted as neoplasm. Smaller right centrum semiovale and right periventricular lesions were also noted. On CT there was no enhancement of the lesions. Biopsy of the left parietal lesion 6 weeks later revealed circumscribed, focal, active destruction of myelin with relative preservation of axons in white matter, consistent with demyelination. Clinically definite MS was diagnosed on the basis of two lesions and the history of two exacerbations. The patient improved with steroid treatment. Case 6

A 58-year-old woman suffered a severe influenza-like illness with nausea, vomiting, and right arm paresthesia i year before admission; the paresthesiae persisted. Two months before admission, she had two episodes of "a rush of numbness" from the upper chest down to the abdomen, lasting several minutes. One month before admission, she began having several episodes per day of paresthesiae radiating for a few seconds from her right hand to the neck. She later developed right facial numbness which lasted three days, clearing completely. T2-weighted MRI (Fig. 6) showed a high signal right occipital lesion which extended to the surface plus scattered high signal areas interpreted as age-related changes of uncertain significance. On the day of admission, the patient required assistance to walk and noticed numbness in both legs. Examination showed leg weakness and numbness, both worse on the left. Right biceps and left knee jerks were increased but there were no pathological reflexes. Contrast-enhanced CT revealed an enhancing right occipital lesion with slight mass effect (Fig. 6). Cerebral angiography was normal. Needle biopsy revealed inflammatory demyelination consistent with multiple sclerosis. Postoperatively, she suffered acute worsening of her condition with total flaccid paralysis of the left leg, moderate weakness of the right leg and ataxia of the right arm. These symptoms improved markedly over the ensuing weeks. She was able to walk with a mild spastic paraparesis and a slightly broad-based unsteady gait.

Results

Tables 1 and 2 summarize the MRI and CT findings in these six cases. No specific sign or signs appear to distinguish mass-like plaques from other mass lesions.

153 L MR characteristics of the lesions Case Number Largest Borders Grey of lesions lesion matter inhomoinvolvegeneous ment

Infra- Focal tento- mass rial effect lesions -

Table

1

1

+

Smooth

2

4

+ +

Irregular

3

3

+ +

Irregular

-

+

4

1

+ +

Irregular

5

4

+ +

Irregular

+

6

> 15

+

Irregular

+

Table

Fig.6 a,b. Case 6. a Contrast-enhanced CT: the right parieto-occipital lesion shows enhancement, b MRI (1.5 T, TR/TE = 2567/80) shows a large high signal lesion in the right occipital region with scattered small high signal areas present bilaterally. The occipital lesion appears to extend through the occipital cortex to the pial surface

-

+

-

-

-

-

-

+

+

+ +

2. CT characteristics of the lesions

Case

Number of lesions

Enhancement

Edema

1

1

-

+

2 3

1 CT not performed 1 2 1

Solid and ring

+

-

+

Inhomogeneous

+

4 5 6

-

-

Focal mass effect +/++

++

Discussion

These cases illustrate the potential difficulty in diagnosing MS during the initial episode, even with the aid of MRI. In each case, unusual symptoms and signs combined with an unexpected MRI appearance led experienced clinicians, radiologists, and pathologists away from the correct diagnosis of MS. The decision to biopsy the lesions seen on MRI resulted in the death of one patient and a transient increase in morbidity in another. Symptoms and signs not usually associated with MS may cause clinicians to overlook MS in the differential diagnosis. H o m o n y m o u s hemianopsia (cases 2 and 5), language disorders (cases 3-5), seizures (case 6), headache and vomiting (cases 1 and 2) have all been reported in MS patients but are relatively uncommon [11]; they are often suggestive of tumors, ascesses, or acute strokes. These clinical impressions can be reinforced when risk factors for abscess (cases i and 2) or stroke (cases 4 and 5) exist. Evidence on CT and MRI of masses with inhomogeneity, irregular borders, and apparent involvement of grey matter further suggested neoplasm or infection. Even when multiple lesions were seen on MRI these were interpreted as multicentric glioma (case 5), multiple abscesses (case 2), or nonspecific high signal areas, as seen in the elderly (case 6). Although many cases of MS present a widely recognized "typical appearance", recent studies utilizing serial MRI revealed a complex pattern of enlarging and shrinking lesions [12]. The clinical and radiological characteristics which contribute to a clinical misdiagnosis may also influence the examination of the pathological specimen. Thus, the pathologist needs to consider the possibility of demyelination in such cases and apply specific techniques for demonstrating myelin and axons. Otherwise, late stages of demyelination with residual gliosis may be misinterpreted as low-grade astrocytoma, or the presence of lipid macrophages and overt myelin degeneration may be misinterpreted as organizing nonspecific necrosis.

The following M R I characteristics should raise the possibility of MS: (1) multiple white matter lesions (especially in the periventricualr areas), (2) occurrence of both infratentorial and supratentorial lesions, (3) minimal surrounding edema and (4) relatively little mass effect compared to the overall size of the white matter lesion, and (5) a patient aged between 15 and 45. Unfortunately, we have found no specific criteria by which the less common masslike presentation of MS, especially the single lesion, can be diagnosed acutely and accurately. We believe that noninvasive testing for MS including evoked potentials and lumbar puncture (when possible) should be performed prior to cerebral biopsy in all such cases. If these studies suggest MS by revealing optic neuritis, transverse myelitis, or inflammation, the patient could be monitored clinically and with serial MRI. However, early in the course of MS, laboratory studies may remain normal [13]. If these studies do not suggest MS, cerebral biopsy could be considered, and in these cases, consideration of MS in the differential diagnosis should lead to an optimal surgical approach and to the use of appropriate special stains to differentiate demyelination from infarction or tumor.

Acknowledgements. We are grateful to Rochester Diagnostic Imaging Associates for providing Fig. 2, to Ide Radiology Group for providing Fig.3, and to Beth Tourtellotte for manuscript preparation assistance.

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