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Recurrent tumefactive demyelinating lesions

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Introduction and objectives

This case of a 58 year old male explores the diagnostic and management challenges involved with tumefactive MS. 

Case presentation

58 y/o Pakistani male with a history of depression began to experience progressive right-sided weakness and sensory loss. He was in Pakistan at the time and obtained CT and MRI of the brain there, which revealed a 3 cm ring-enhancing lesion. The patient was treated with IV steroids though by the returned to the US several weeks later he had a L sided spastic hemiplegia and L sided sensory deficit.  Repeat workup confirmed the presence of a large  ring-enhancing lesion to the L frontoparietal area with mild surrounding vasogenic edema without midline shift (Images 1 and 2). 

Clinical presentation

L frontal craniotomy and complete lesion resection was performed. 24 hrs post-op developed a mixed aphasia, for which MRI of the brain was repeated but showed no acute change. Right sided facial paralysis and right hemiplegia and sensory deficits persisted. Subsequent imaging revealed new T2 hyperintensity and contrast enhancement that tracked downwards along the corticospinal tract into the internal capsule (Image 3) and cerebral peduncle.  While in rehab the patient had a seizure and was started on anti-epileptic medication.

Laboratory studies

CSF: WBC:1, RBC:3, protein 79, glucose 59, cytopathology negative for malignant cells, OCB negative, ACE wnl, Lyme negative, Toxoplasma IgM negative, EBV negative, CMV negative, JCV negative, HSV negative.

Serum: HIV negative, NMO Ab negative, paraneoplastic panel negative, ACE  wnl, ANA neg, SSA/SSB neg, RF neg

Bone scan: nl

Gallium scan –mild hilar and subcarinal uptake as well as lacrimal gland uptake
without lung parenchymal uptake

Pathologic studies revealed large gemistocytic astrocytes, marcophages, perivascular microglia and lymphocytes, and distinct myelin loss without evidence of caseation or necrosis, suggestive of acute inflammatory demyelinating disease

Diagnosis

Diagnosis: tumefactive delmyelinating disease

 

This case explores the diagnostic and management challenges involved with tumefactive demyelinating lesions which may closely mimic tumors both clinically and radiologically.  Patients may present polysymptomatically, with cortical signs including aphasia, or encephalopathy or seizures.  Radiologically, there is nothing pathoneumonic that can distinguish between the two; like tumors, tumefactive lesions (particularly large ones) may produce edema and/or mass effect, though typically the ratio of edema size to tumor size is smaller.  Like tumors, tumefactivel lesions may have a variety of enhancement patterns.  Classically, partial ring enhancement that opens toward the grey matter is associated with demyelinating disease, though most studies show this pattern occurs less frequently than closed ring pattern, nor is it always specific. There is some evidence showing incidence of OCB in tumefactive disease may be lower than in more typical MS though this may partially be attributed to ascertainment bias in these studies.1, 2  Because tumefactive demyelinating lesions frequently appear as initial presentation of MS a tumor is often suspected.  While tissue diagnosis may be definitive, in the case of a tumefactive lesion they may also be inconclusive and may contribute to increased neurologic morbidity, depending on the location of the tumor and extent of resection.  In this case, aphasia was noted initially post-resection.  If a tumefactive lesion is suspected it is advised to treat initially with steroids and monitor for the expected improvement.  On the other hand, CNS lymphoma may also respond robustly to steroids temporarily, delaying diagnosis.  Risk of biopsy/ excision must be balanced against risk of delayed tissue diagnosis of a true tumor. 

Initial treatment

Because there was a single demyelinating event with neither evidence of dissemination in space or time, the patient was not treated with disease modifying therapy.  He was clinically stable until 8 months later when he presented with subacute onset of personality change including irritability, anxiety, and labile mood and was found to have a new, partially ring enhancing R frontal lesion that initially responded to steroids (Image 4).  However within weeks of discharge to acute rehab he was found to have new LUE weakness and enlargement of the R frontal lesion.  He was started on cyclophosphamide.  (This broader immunosuppressive agent was initially chosen over an MS specific disease modifying therapy because of the question of sarcoid raised by the gallium scan findings.  A lacrimal gland biopsy was suggested but never completed).   However cyclophosphamide was discontinued after he developed sepsis requiring ICU admission.  Over the subsequent 18 months he was tried on dimethyl fumarate and rituximab, and developed new tumefactive appearing lesions on each of these disease modifying treatments, with accumulating neurologic deficits.  The patient is presently living in a nursing facility and is completely dependent in all activities of daily living. 

Outstanding questions

Data suggests that, the majority of patients with a presenting tuymefactive lesion will go on to develop additional clinical attacks but that the majority of these cases subsequent attacks are typical of conventional relapsing MS. 1,2 In fact, the  long term prognosis in patients presenting with a tumefactive lesion may be favorable than those presenting more conventionally. 1 Both the number of tumefactive events and the amount of accumulated disability in this patient are rare, and represent an extreme in the spectrum of severity of demyelinating disease. 

 

References

Lucchinetti, C.F. et al.Clinical and radiographic spectrum of pathologically confirmed tumefactive demyelinating disease.Brain (2008), 131: 1759-1775.

Altintas, A. et al.Clinical and radiological characteristics of tumefactive demyelinating lesions: follow up study. Multiple Sclerosis Journal (2012), 18: 1448-1453.

Frederick, M.C. and Cameron, M.H. Tumefactive lesions in multiple sclerosis and associated disorders.Curr neurol Neurosci Rep (2016), 16: 26.

Abdoli, M. and Freedman, M.S. Neuro-oncology dilemma: tumor or tumefactive demyelinating disease. Multiple Sclerosis and Related Disorders (2015), 4: 555-566.

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Comments

'Excision biopsy' might be a dangerous choice to make without a MRI-guided stereotactic biopsy given the volume of tissue that needs to be excised, presence of eloquent brain areas in the peri-lesional territory, and most of all, it is an irreversible option. Even if some study has shown in the past that the yield is low for a tissue diagnosis with tumefactive MS lesions, the onus still rests with the clinician who needs to give the patient all options if conventional techniques such as proton MR spectroscopy or SPECT scanning prove unhelpful.