Tumefactive Demyelination Presenting as an Intracranial Space-occupying Lesion: A Diagnostic Challenge

Abstract

Objectives:

Tumefactive demyelination is a rare form of multiple sclerosis which is characterised by solitary, acute, demyelinating lesions in the central nervous system, usually larger than 2 cm, accompanied by surrounding oedema. They often present with features of mass effect and pose a ring enhancement on neuroimaging along with ill-defined border, central necrosis and perilesional oedema. Being clinically benign its pathology is till date unknown and debatable, and it may occur alongside other conditions like Sjögren’s syndrome, neuromyelitis optica, systemic lupus erythematosus or could occur post-acute haemorrhagic leukoencephalitis and acute disseminated encephalomyelitis, and sometimes certain medications pose as etiological factors.

Methodology:

We report a case of a middle-aged man who presented with a history of intermittent diminished vision in the right eye specifically in the temporal field alongside headache which was aggravated on defecation. These clinical features overlapped with those of intracranial space occupying lesions, infections or inflammatory conditions but all investigations done, ruled out such possibilities. MR spectroscopy findings and other investigations, further paved the diagnosis. Patient was treated with pulse therapy of intravenous methylprednisolone.

Results:

Post-steroid therapy, progressive improvement was seen clinically and radiologically, eventually leading to complete recovery. Overall, tumefactive demyelination carries a good prognosis since majority of the cases have a benign nature and are steroid responsive.

Introduction

Tumefactive demyelination is a rare form of multiple sclerosis which is characterised by solitary, acute, demyelinating lesions in the central nervous system, usually larger than 2 cm, accompanied by surrounding oedema. These lesions often present with features of mass effect and pose a ring enhancement on neuroimaging along with ill-defined border, central necrosis and perilesional oedema. Its clinical features overlap with those of intracranial space occupying lesions, hence posing a diagnostic and therapeutic challenge.^[1] Being clinically benign its pathology is till date unknown and debatable, and it may occur alongside other conditions like Sjögren’s syndrome, neuromyelitis optica, systemic lupus erythematosus or could occur post-acute haemorrhagic leukoencephalitis and acute disseminated encephalomyelitis, or could be associated with usage of fingolimod and tacrolimus.^[2] Here we report a case of a middle aged man who presented with a history of intermittent diminished vision in the right eye specifically in the temporal field alongside headache which was aggravated on defecation.

Case Presentation

We highlight a case of a 44-year-old gentleman, who presented with a history of diminished vision in right eye temporal field since a month, associated with headache, for which he consulted a regional ophthalmologist who checked his visual acuity to be 6/9 bilaterally with the exception of right eye been tested with a pinhole. In addition to that, right eye fundoscopy revealed fuzzy disc margins. Automated perimetry also concluded bilateral visual field defects. Furthermore, an magnetic resonance imaging (MRI) brain was done which depicted parietal lobe lesions with altered signal intensity specially involving the deep white matter and left side of the splenium. Hyperintensity with mild diffusion restriction was noted on T2 fluid-attenuated inversion recovery (FLAIR) [Figure 1]. In spite of these findings, he maintained intact consciousness throughout. Subsequently, MR spectroscopy was showed a positive choline and N-acetylaspartate (NAA) peak [Figure 2]. No significant past medical history was noted.

Figure 1.

(A) MRI shows large areas of altered signal intensity in left parieto-occipital and posterior temporal lobes predominantly involving subcortical and periventricular white matter regions. The lesion is extending medially along splenium of corpus callosum and is crossing the midline with focal widening and expansion. The lesion also involves right thalamus and basal ganglia. There is attenuation of the cortical regions on the left side. (B) Post-contrast study shows peripheral enhancement of the lesion mainly along the supero-medial aspect. There are additional small subependymal enhancing nodular lesions in bilateral temporal lobes

Figure 2.

Single voxel spectroscopy (Point RESolved Spectroscopy [PRESS] sequence) from the enhancing component of the lesion shows elevation of the choline peak with choline NAA ratio of 1.46 with echo time (TE) value of 35 and choline NAA ratio of 2.11 with TE value of 144

Upon admission, a thorough physical examination was carried out. Patient’s vitals including heart rate (90 bpm), blood pressure (140/70), respiratory rate(20/min), O2 saturation (97% on room air) and temperate (36.8 degrees) were noted to be within normal range. Patient was conscious and alert and general appearance was consistent with his age and gender.

Neurological examination was performed which showed intact higher mental functions, sensory perception and cerebral function. Remarkably, pronator drift in left hand and positive Babinski sign on left side was appreciated, which was strongly suggestive of upper motor neuron (UMN) lesion especially in the right hemisphere. Right homonymous hemianopia was noted. Rest, his cardiovascular, respiratory, and abdominal examination were normal.

Laboratory tests were run including full blood count, urine routine and microscopy, serum thyroid stimulating hormone (S.TSH), serum prostate specific antigen (S. PSA) and haemoglobin A1C (HbA1C), which returned to be within normal range. Viral marker screening panel was negative for human immunodeficiency virus-1 and 2 (HIV-1 and -2), hepatitis B and hepatitis C. Based on these findings, there was limited suspicion of infection, inflammatory conditions, malignancy or suspected diabetes associated neuropathy. To address the alarming visual deformity, we performed an MRI orbit [Figure 3], which revealed a preserved morphology of bulbar and retrobulbar regions with normal appearance of extraocular muscles, optic nerve, orbital apex and cavernous sinuses. However, parenchymal lesions in left parietal lobe, small nodular lesions in bilateral temporal lobe were noted, which were consistent with the previous MRI findings.

Figure 3.

MRI orbit showed preserved morphology of the globes and retrobulbar regions of both sides. The orbital fat, extraocular muscles are within normal limits. The optic nerves show preserved appearance and signal intensity without any focal area of abnormal enhancement. The orbital apex and cavernous sinus are within normal limits. The above-mentioned brain parenchymal lesion in the left parieto-occipital lobe and small nodular lesions in bilateral temporal lobes are unchanged in signal intensity, dimensions and perilesional oedema as compared to previous MRI

Moreover, visually evoked potential (VEP) revealed bilateral normal patterns. To investigate further, cerebrospinal fluid (CSF) analysis was conducted which revealed normal opening pressure, slightly higher-near normal glucose levels (81 corresponding to random blood sugars (RBS)-117) with elevated protein levels (72), mild lymphocytic pleocytosis (10 cells) and presence of oligoclonal bands. CSF analysis along with findings of MR spectroscopy pointed at the diagnosis of tumefactive demyelination.

CSF meningoencephalitis panel, gram staining and quantitative test for cryptococcal antigen turned out to be negative. To rule out the differentials, cell-based assays sent which were negative for Aquaporin-4 Immunoglobulin G (AQP4-IgG) and Myelin Oligodendrocyte Glycoprotein (MOG-IgG). Samples were also sent for GeneXpert for tuberculosis (TB) and adenosine deaminase, aerobic and anaerobic bacterial culture, nocardia and fungal cultures which yielded a negative report.

Further management was done on the lines of working diagnosis of tumefactive demyelination. Treatment was initiated with pulse therapy of intravenous methylprednisolone which was given for five days, and supported with vitamin D and vitamin B12 supplementation. Gradually, patient’s vision remarkably improved along with resolution of headache, pronator drift in left hand and left plantar extension. He was discharged in haemodynamically stable condition with tapering doses of steroids. Patient was followed up after a week with progressive improvement [as seen in Figure 4] in his condition and on subsequent follow-up visits, complete recovery was noted.

Figure 4.

Residual altered intensity area in the left posterior parieto-occipital and posterior temporal lobes with mild-to-moderate regression in the bulk and extent of the lesion and near complete regression of the enhancement, mass effect and midline shift compared to the previous study

Discussion

This case of a 44-year-old gentleman with upper motor neuron lesion signs and mass-like effect portraying as visual deformity raises awareness about the diverse pattern of presentation and diagnostic importance of tumefactive demyelination. Multiple such cases of have been reported with varying presentations such as sensory disturbances, speech difficulties, weakness, headache and visual difficulties, as in our case. In terms of diverse findings on imaging like MRI brain, it could be mistaken for other intracerebral space occupying lesions, multiple sclerosis, trauma, tumours, brain abscess, amyotrophic lateral sclerosis or stroke.

Tumefactive demyelination can also lead to cognitive and behavioural changes and can mimic inflammatory conditions like sarcoidosis and Sjögren’s syndrome, further adding complexity to the situation.^[2] It can present as a solitary lesion or multiple discrete lesions often involving the frontal and parietal lobes, rarely involving the spinal cord. Few patients treated with fingolimod and natalizumab have shown to develop tumefactive demyelination as a complication, hence adding these drugs to the list of suspected risk factors.^[3]

MRI brain can sometimes not differentiate between the different space occupying lesion, hence advanced modalities such as MR spectroscopy, MRI perfusion and positron emission tomography (PET) scan can help come to a diagnosis.^[4] Additionally, CSF analysis has proven to be promising in delineating the condition by depicting increased protein levels and mild pleocytosis as in our case. Oligoclonal bands are only seen in 30% of the cases.^[2]

Nevertheless, in some cases diagnosis can still be inconclusive, hence brain biopsy stands as the last resort to exclude any neoplastic aetiology and also to look out for histopathological changes taking place in case of tumefactive demyelination, namely active inflammatory demyelination, infiltration of foamy macrophages and presence of reactive astrocytes and gliotic tissue.^[4] This can be correlated to MR spectroscopy findings where simultaneous elevated peaks of lactate and choline are seen which are suggestive of reactive astrogliosis and demyelination.^[5] Such a finding was well noted in our patient.

Treatment modalities for tumefactive demyelination are unspecified and pose grey areas and hence more clinical data is needed to set affirmative guidelines. Based on the trails till date, pulse therapy of high-dose corticosteroids have been the first-line treatment and show significant improvement in symptoms as in our patient. If this fails or patient does not show significant improvement, then approach can be shifted to plasmapheresis or intravenous immunoglobulin.^[4]

Prognosis depends on the course of the disease depending on whether it is isolated tumefactive demyelination or a variant of multiple sclerosis. Two-third of the patients may have a relapsing and remitting course,^[1] where azathioprine, mycophenolate mofetil, cyclophosphamide and methotrexate have shown good clinical response.^[3] Overall, tumefactive demyelination carries a good prognosis since majority of the cases have a benign nature and are steroid responsive.^[4]

Conclusion

This case emphasises on the crucial aspects of differentiating tumefactive demyelination from other neurological conditions, based on timely intervention and prompt initiation of treatment. Tumefactive demyelination poses a diagnostic challenge due to its less incidence and overlapping features other cranial pathologies. It has diverse patterns of presentation, in some cases as an isolated condition and in others it can be associated with multiple sclerosis, neuromyelitis optica and myelin oligodendrocyte glycoprotein antibody-associated disease. Hence, a detailed history and physical examination should be carried out. MRI changes being nonspecific have been not so affirmative in confirming the suspicion but other modalities like MR spectroscopy have emerged with more specific findings. Early diagnosis and prompt treatment is a crucial aspect in preventing relapse. However, lack of diagnostic and treatment guidelines is a great setback and major limitation. There is a need for better recognition modalities and treatment guidelines which will further help in prediction of recurrence and preventing relapses.