Tumefactive demyelinating lesion: Experience with two unusual patientsMK Sinha1, RK Garg1, MLB Bhatt2, A Chandra3
1 Department of Neurology, Chhatrapati Shahuji Maharaj Medical University, Lucknow - 226 003, India
2 Department of Radiotherapy, Chhatrapati Shahuji Maharaj Medical University, Lucknow - 226 003, India
3 Department of Neurosurgery, Chhatrapati Shahuji Maharaj Medical University, Lucknow - 226 003, India
Tumefactive demyelinating lesion, a variant of multiple sclerosis, is a solitary large demyelinating lesion, which mimics cerebral neoplasm. Distinguishing tumefactive lesions from other etiologies of intracranial space-occupying lesions is essential to avoid inadvertent surgical or toxic chemotherapeutic interventions. We report two unusual cases of tumefactive demyelinating lesion. The first patient presented with recurrent right focal tonic-clonic seizures with secondary generalization of three-month duration. Her neurological examination was normal. Another patient presented with right homonymous hemianopia. In this patient, the diagnosis was established after biopsy of the lesion, which revealed perivascular lymphocytic infiltrate and aggregates of foam cells in white matter with relatively uninvolved grey matter, suggestive of tumefactive demyelinating lesion. Administration of intravenous methylprednisolone resulted in rapid clinical improvement in both the patients and the brain lesion decreased in size. Both, epilepsy and homonymous hemianopia, are unusual manifestations of tumefactive demyelinating lesions. In our cases, cerebral tumors were initial diagnoses. Presence of an open ring or incomplete ring lesions and other magnetic resonance characteristics helped in differentiating demyelinating lesions from other neoplastic and infective diseases of the brain. Differential diagnosis of tumefactive demyelinating lesions, at times, may prove to be a challenging task for the treating physician.
Keywords: Hemianopia, seizure, tumefactive demyelinating lesion
The tumefactive demyelinating lesions are solitary large (greater than 2 cm) lesions with mass-like features and post-gadolinium magnetic resonance imaging (MRI) typically showing an incomplete ring enhancement. , The clinical and imaging features of these large demyelinating lesions may mimic primary and secondary brain tumor, brain abscess, tuberculous abscess, or other inflammatory disorders (like sarcoidosis), and may require a brain biopsy for diagnosis.  The incidence of tumefactive demyelinating lesions has been estimated at 0.3 cases per 100 000 per year.  They occur more frequently in women in the second and third decades of life, with an average age of onset of at least 37 years.  Usual clinical manifestations are polysymptomatic and include headache, cognitive changes, mental confusion, aphasia and apraxia.  The usual clinical course of tumefactive demyelinating lesions is acute onset, good response to corticosteroids and no clinical or radiological evidence of new lesions in the great majority of patients.  The prognosis usually does not depend on the clinical presentation of the lesion.  Epilepsy or hemianopia are unusual manifestations of tumefactive demyelinating lesions. We are reporting to two such cases.
A 23-year-old right-handed woman presented with recurrent episodes of right focal tonic-clonic seizures with secondary generalization of over three-month duration. Neurological examination was unremarkable. Hemogram (Hemoglobin concentration: 145 g/L, total leukocyte count: 7.2 Χ 10 9 /L with 70% neutrophils) and biochemical investigations (random blood sugar 4.9 mmol/L, serum levels of creatinine: 70 μmol/L, sodium 142 mmol/L, potassium 3.9 mmol/L and calcium 2.2 mmol/L) did not reveal any abnormalities. Anti-nuclear antibody was negative. Human immunodeficiency virus (HIV) serology was negative. Electroencephalogram was normal. MRI brain revealed a rounded well-defined lobulated T1 hypointense mass measuring about 5 cm in left fronto-parietal region, which was hyperintense in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images, with a mild incomplete rim of enhancement in the post-contrast scans [Figure 1]. This was reported to be an astrocytoma elsewhere and the patient was referred for neurosurgical evaluation. Another MRI brain was performed along with proton MR spectroscopy. Repeat neuroimaging demonstrated an increase in the mass effect and edema. There was no encroachment into the adjacent grey matter. Though the mass was large in size, the surrounding edema and mass effect were disproportionately mild. Proton MR Spectroscopy revealed elevated choline peak, presence of glutamate/glutamine peak at 2.4 parts per million and suppressed N-acetyl aspartate (NAA) peak. In view of characteristic imaging appearance, the diagnosis of a tumefactive demyelinating lesion was considered. The patient was treated with intravenous infusion of methylprednisolone (1 g/d for 5 days). Oxcarbazepine in dosage of 600mg per day was given to prevent seizure recurrence. The patient remained seizure-free at 6-month follow-up visit. MRI of the brain performed after 6 months demonstrated regression of the lesion with decrease in the mass effect.
A 48-year-old normotensive man presented with impaired vision. Patient had been noticing difficulty in reading or working during past 1 month. Patient sought an ophthalmologist's opinion after he had a narrow escape while driving car. Detailed history of the patient did not reveal any previous ophthalmologic or neurologic deficit. The visual acuity was 6/6 in both the eyes. The pupils were 4 mm in diameter, equal and reactive to light. There was no relative afferent pupillary defect. Ophthalmoscopy revealed that the optic discs, maculae and peripheral retina were normal in both eyes. Visual field examination showed right homonymous hemianopia. Visual fields were charted with the help of Humphrey visual field analyzer using the central 30-1 and full-field programs. Rest of the neurologic examination was completely normal.
Hemoglobin was 130 g/L, total leukocyte counts 6.8 Χ 10 9 /L with 82% neutrophils, random blood sugar 5.6 mmol/L, creatinine 58 μmol/L, urea 6.1 mmol/L, sodium 144 mmol/L, potassium 4.1 mmol/L and calcium 2.4 mmol/L. Anti-nuclear antibody was negative. HIV serology was negative. Electroencephalogram was normal.
MRI of the brain revealed an irregular well-defined mass measuring 4.8 cm in the left parieto-temporal region involving splenium of corpus callosum with mass effect on adjacent structures. The lesion was hyperintense on T2-weighted and FLAIR images with incomplete rim of enhancement in the post-contrast images [Figure 2]. Initially, a diagnosis of brain tumor was made and the lesion was subjected to biopsy. Histopathology of the biopsied tissue showed moderate perivascular lymphocytic infiltrate and aggregates of foam cells in white matter with relatively uninvolved grey matter, suggestive of tumefactive demyelinating lesion. The patient was treated with methylprednisolone. After six months of follow-up, patient did not report any improvement in visual symptoms. However, a follow-up MRI of the brain demonstrated regression of the lesion with decrease in mass effect and contrast enhancement. The follow-up MRI also showed focal atrophy due to gliosis of the affected brain tissue [Figure 3].
Tumefactive demyelinating lesions are frequently misdiagnosed. Our patients were evaluated in neurosurgical centers and were initially diagnosed to have brain tumors. In MR study, tumefactive lesions have ill-defined margins, variable amount of cerebral edema, mass effect and there may be variable contrast enhancement of the lesions. In addition, lesions may show central necrosis, cystic degeneration and variable amount of grey matter involvement , [Table 1]. Several neoplastic and infective diseases of brain may have similar imaging characteristics.
The first patient presented with seizures as the sole manifestation. Seizures have been reported to be present in 6% of patients with tumefactive demyelinating lesions in one series.  In a case series, 2 out of 18 patients with tumefactive demyelinating lesions had seizures along with hemiparesis.  Seizures along with hemianopia and hemiparesis was reported in an Indian child as well.  However, seizure as an isolated presenting feature of tumefactive demyelinating lesion has not been reported.
The second patient presented with right homonymous hemianopia as the only manifestation. Most cases of homonymous hemianopia are caused by visual cortex stroke. Homonymous visual field defects are unusual in multiple sclerosis and tumefactive demyelinating lesions.  In a series of 850 patients with 902 episodes of homonymous hemianopia, 629 (70%) resulted from stroke. Non-stroke causes of homonymous hemianopia included head trauma, brain tumor, neurosurgical procedures and miscellaneous conditions. In 13 (1.4%), episodes were because of multiple sclerosis.  Luchinetti et al, reported visual field defects along with other symptoms in 10% of their patients with tumefactive demyelinating lesions.  Tumefactive demyelinating lesions in patients presenting with homonymous visual field defects anatomically involve optic radiations in parietal and temporal lobes of cerebral hemispheres. ,
Distinguishing the tumefactive demyelinating lesions from neoplasm is important, since a misdiagnosis can lead to inadvertent brain irradiation or surgery. Some MR features are more suggestive of tumefactive demyelinating lesions than of brain tumor. These include incomplete rim enhancement, mixed T2-weighted iso- and hyperintensity of enhanced regions, absence of a mass effect and absence of cortical involvement.  A variety of enhancement patterns have been observed in patients with tumefactive demyelinating lesions. These patterns include ring (single and multiple), heterogenous, diffuse, punctate and concentric. Ring enhancement is the most frequent. Several studies have suggested that the pattern of open ring enhancement pattern is typically associated with demyelination. In a recent series, authors demonstrated complete ring enhancement (closed ring) pattern in majority of their patients with tumefactive demyelinating lesions.  Magnetic resonance spectroscopic metabolite information can be helpful in the differential diagnosis of tumefactive demyelinating lesions. Demonstration of elevation of the glutamate/glutamine peaks is beneficial in the differential diagnosis of tumefactive demyelinating lesions because elevation of these peaks is not seen in neoplastic diseases of the brain.  A patient with atypical ring-enhancing lesions and mass effect may require brain biopsy to establish the diagnosis. ,,
The histopathologic characteristics of tumefactive demyelinating lesions include the preservation of axons, the loss of myelin, the presence of macrophages and astrocytic proliferation. Sometimes, even histopathological features may mimic a low-grade astrocytoma because of the hypercellular nature of these lesions and the frequent presence of atypical reactive astrocytes and mitotic figures. When demyelinating lesions have a marked inflammatory component, they may also be confused with a primary central nervous system lymphoma. ,
The two cases highlight the importance of considering tumefactive demyelinating lesions in the differential diagnosis of intracranial mass lesions. Timely diagnosis can save patient from potentially harmful aggressive treatment.
[Figure 1], [Figure 2], [Figure 3]