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"Medical Journeys" is a set of clinical resources reviewed by doctors, meant for physicians and other healthcare professionals as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

This installment: A noteworthy case study.

What caused a previously healthy, 55-year-old woman to develop neurological symptoms including right-sided headache, confusion, blurry vision, and numbness and weakness affecting her right arm and leg? That's what Bünyamin Tosunoğlu, MD, and colleagues had to determine when the patient presented to Baylor University Medical Center in Dallas.

As the team reported in , on initial assessment, which was 2 years after the onset of her symptoms, the patient explained that she had not been diagnosed with any condition, and she was not taking any medications. Physical examination showed stable vital signs, and her temperature was normal.

Neurological examination rated the strength of her right upper and lower extremities as 4 on a 5-point scale. Clinicians also confirmed right-side hypoesthesia, and deep tendon reflexes were normoactive.

Findings on brain CT scan were unremarkable. MRI of the brain "revealed diffusion-limiting lesions in the right periventricular region, the left half of the pons, and well-circumscribed, edematous lesions in the left parietal region and the left parietal region," the case authors said. They ordered a CT angiogram of the brain, which showed no evidence of obstructive cerebrovascular stenosis; MRI venography also returned normal results.

The patient was admitted to the neurology department for further examination, diagnostic evaluation, and treatment.

Twelve hours later, the team ordered serial MRIs of her brain. Findings showed "widespread, hyperintense lesions in the cerebral white matter and brainstem in T2-weighted, fluid-attenuated inversion recovery sequences, reaching a diameter of approximately 2 cm in the subcortical white matter of the right frontal lobe, prominently hyperintense and nodular in central T2-weighted sequences, and lower hyperintensity surrounded by a halo," the case authors wrote.

The contours of the large lesions had a lobulated appearance. Gadolinium-enhanced MRI sequences indicated a lesion with annular, intermediate enhancement. In the left posterior parietal region adjacent to the cortex, imaging revealed an open ring-enhancing lesion facing the cortical surface.

MRI findings showed active demyelinating lesions in the periventricular white matter of the right frontal lobe measuring 13-14 mm in diameter, and lesions in the left semiposterior mesencephalon and around the aqueductus cerebri, which were 12 mm in diameter; these were also noted on the trigone formed by the occipital and temporal horns of both lateral ventricles.

Examination of the brain white matter revealed various periventricular lesions with diffuse and nodular features, which were also evident in the septal interface in the corpus callosum. MR images of these nonenhancing lesions were suggestive of demyelinating plaques.

Specifically, the team found ring-enhancing lesions in the right frontal lobe and the left half of the mesencephalon that demonstrated mass effect, and a short segment lesion involving the left half of the cervical C4 spinal cord.

Process of Elimination

Most of the lab test results can back as normal, including:

• Complete blood count
• Peripheral smear
• Platelet function
• Coagulation studies
• Routine chemistry panels
• Complete urinalysis
• Serum and urine protein electrophoresis
• Antiphospholipid, antinuclear, antithyroid, anti-SSA and anti-SSB antibodies
• Vitamin B12,
• Thyroid function
• Hemoglobin A1c
• Erythrocyte sedimentation rate
• Schirmer tear test
• Homocysteine
• Anticardiolipin
• Rheumatoid factor
• Proteins C and S
• Anti-streptolysin O
• Rheumatoid factor
• Immunoglobulins A, G, and M

Similarly, all negative were serology for brucellosis; hepatitis A, B, and C viruses; HIV; and syphilis (fluorescent treponemal antibody). Investigations for HSV types 1 and 2, varicella zoster virus, enterovirus, parechovirus, Epstein-Barr virus, cytomegalovirus, and adenovirus by both serum and CSF polymerase chain reaction assays were also all negative.

The pathergy test for Behçet was negative, and CSF examination results included negative cytology and positive oligoclonal band type 2. Anti-aquaporin-4 antibody and anti-myelin oligodendrocyte glycoprotein were negative from both serum and CSF.

Diagnosis

The case authors said that based on visual evoked potentials, the patient's symptoms were likely due to bilateral visual pathway dysfunction. A CT scan of her thorax and abdomen showed no evidence of tumors. The team thus concluded that the most likely diagnosis was tumefactive multiple sclerosis, a rare form of MS with symptoms that mimic those of a brain tumor.

The patient received intravenous 1 g of methylprednisolone for 10 days, and her symptoms gradually regressed. Clinicians then prescribed subcutaneous interferon beta-1a for maintenance, and recommended that she return to the outpatient neurology clinic for follow-up. She did not return, though, and her long-term status was unknown at the time of the case report.

Discussion

As a neurodegenerative demyelinating disease of the central nervous system, MS characteristically presents with multifocal demyelinating lesions, which are generally small and well circumscribed. This case of the rare tumefactive variant of MS thus posed a true diagnostic challenge.

Tumefactive lesions – defined as areas of cerebral focal demyelination larger than 2 cm – may occur any time during the disease course of MS. The case authors described the characteristics of several atypical inflammatory demyelinating syndromes they considered in their differential diagnosis.

This case did not involve concentric sclerosis of Baló lesions, the team noted. That rare variant of MS "is characterized histopathologically by concentric, lamellar demyelinating and accompanying remyelinating areas, correlating with concentric rings on MRI or spiral-shaped lesions on T2-weighted images."

Another neurological disorder, acute disseminated encephalomyelitis (ADEM), occurs when the myelin sheath around nerve cells becomes damaged. Children and young adults are most commonly affected -- occasionally after vaccination or infection.

ADEM affects the white matter of the brain, and differs from MS in causing lesions that tend to be more widespread, large, and symmetrical. Lesions that share a similar contrast enhancement pattern are close in age, and when oligoclonal bands in the CSF of patients with ADEM occasionally occur, they will not persist, as they do in MS, Tosunoğlu and co-authors explained.

They noted that MRI is not always sufficient to differentiate a tumor from a brain abscess. In the absence of a definitive diagnosis, use of visual evoked potentials and CSF analysis is recommended before any invasive procedures are performed, and patients should be treated empirically with high-dose corticosteroid therapy. "Tumefactive may mimic tumors and manifest mass effect, edema, and an open ring enhancement," the case authors said.

Tumefactive MS accounts for an estimated 1-3 of 1,000 cases of MS, and has an annual incidence of 0.3 per 100,000. The syndrome can develop at any age, but occurs most commonly in those ages 20-40, and is most likely to affect women. "The is not fully understood; antibody-mediated and B-cell–mediated immunological mechanisms may play a role," the case authors noted, adding that typically the condition is associated with motor, sensory, cognitive, and cerebellar .

"Our patient presented indolently with complaints of 2 years of right-sided headache, numbness in the right arm and leg, difficulty walking, blurred vision, and confusion," the team said. While MR imaging showed open-ring enhancement of the lesions and mass effect, there were no other findings to suggest malignancy, vasculitic conditions or infectious diseases. Analysis of CSF showed type 2 oligoclonal bands.

Clinicians ordered a visual evoked potential test which reflected bilateral visual pathway dysfunction suggestive of demyelinating disease. The patient had a good response to conventional immunomodulation, involving induction with high-dose corticosteroid treatment followed by maintenance with interferon beta-1a.

On x-ray, tumefactive MS may look like and brain abscesses, but results of lab tests did not indicate the presence of tumor or infectious pathologies, the case authors noted. Furthermore, the fact that their patient responded positively to empiric immunomodulation also supports the diagnosis of tumefactive MS.

Conclusion

"The differential diagnoses of brain tumor, brain abscess, or tumefactive MS should all be considered in patients presenting with similar lesions," Tosunoğlu and colleagues concluded. When appropriate radiographic and clinical regression follow a diagnosis of tumefactive MS, a brain biopsy may be unnecessary.

Read previous installments in this series:

Part 1: Early Diagnosis Can Mean Better Outcomes in Multiple Sclerosis

Part 2: How Does Multiple Sclerosis Start?

Part 3: The Deep and Multidimensional Connection Between Multiple Sclerosis and Depression

Part 4: Case Study: Sudden Blurred Vision in a Young Woman

Part 5: Early Aggressive Treatment May Work Best in Newly Diagnosed Multiple Sclerosis

Part 6: How Progressive Multiple Sclerosis Differs From Relapsing-Remitting MS

Part 7: The Challenge of Cognitive Changes in Multiple Sclerosis