Central nervous system tumefactive demyelinating lesions: Risk factors of relapse and follow-up observations

Abstract

Objective: To track the clinical outcomes in patients who initially presented with tumefactive demyelinating lesions (TDLs), we summarized the clinical characteristics of various etiologies, and identified possible relapse risk factors for TDLs.

Methods: Between 2001 and 2021, 116 patients initially presented with TDLs in our hospital were retrospectively evaluated. Patients were followed for relapse and clinical outcomes, and grouped according to various etiologies. Demographic information, clinical data, imaging data, and laboratory results of patients were obtained and analyzed. The risk factors of relapse were analyzed by the Log-Rank test and the Cox proportional hazard model in multivariate analysis.

Result: During a median follow-up period of 72 months, 33 patients were diagnosed with multiple sclerosis (MS), 6 patients with Balo, 6 patients with neuromyelitis optica spectrum disorders (NMOSD), 10 patients with myelin oligodendrocyte glycoprotein antibody-associated demyelination (MOGAD), 1 patient with acute disseminated encephalomyelitis (ADEM), and the remaining 60 patients still have no clear etiology. These individuals with an unknown etiology were categorized independently and placed to the other etiology group. In the other etiology group, 13 patients had recurrent demyelinating phases, while 47 patients did not suffer any more clinical events. Approximately 46.6% of TDLs had relapses which were associated with multiple functional system involvement, first-phase Expanded Disability Status Scale score, lesions morphology, number of lesions, and lesions location (P<0.05). And diffuse infiltrative lesions (P=0.003, HR=6.045, 95%CI:1.860-19.652), multiple lesions (P=0.001, HR=3.262, 95%CI:1.654-6.435) and infratentorial involvement (P=0.006, HR=2.289, 95%CI:1.064-3.853) may be independent risk factors for recurrence. Relapse free survival was assessed to be 36 months.

Conclusions: In clinical practice, around 46.6% of TDLs relapsed, with the MS group showing the highest recurrence rate, and lesions location, diffuse infiltrative lesions, and multiple lesions might be independent risk factors for relapse. Nevertheless, despite extensive diagnostic work and long-term follow-up, the etiology of TDLs in some patients was still unclear. And these patients tend to have monophase course and a low rate of relapse.

Keywords: etiology; multiple sclerosis; prognostics; relapse; tumefactive demyelinating lesions.

Figure 1

The pathological manifestations of TDLs. The inflammatory demyelinating lesions in 72 patients had the following characteristic manifestations: All patients had myelin loss, a laminar structure between myelin loss and myelin preserved area was seen in Balo patients (A), luxol-fast blue, x200); a few patients with severe CNS inflammation had a reduced number of axons and relatively preserved axons (B), neurofilament, x200); most patients had preserved but swollen axons (C), neurofilament, x200); lymphocyte “sleeve” around the blood vessels (D), haematoxylin-eosin, x200), and a considerable number of foam cells (E), haematoxylin-eosin, x200) and some Creutzfeldt cells (F), haematoxylin-eosin, x200) are observed in the acute phase; in the chronic phase, inflammatory cells gradually migrate to the edge of the lesion (G), luxol-fast blue, x400). In NMOSD and MOGAD patients, the serum immunofluorescence stain is positive for AQP4-IgG (H) and MOG-IgG (I), respectively.

Figure 2

Representative example of tumefactive neuromyelitis optica spectrum disorders (NMOSD). A 26-year-old woman’s MRI scan at the disease onset showed extensive hyperintensity on T2 FLAIR images in the patient’s frontal lobe, parietal lobe, and corpus callosum (A, B), and the lesions gradually decreased after treatment; after 4 months of the first attack, the patient developed more brain lesions than before (C), and spinal MRI revealed long-phase abnormal signal at C3-T7 (D, E). And the patient’s serum anti-AQP4 antibody was strongly positive.

Figure 3

Representative example of tumefactive multiple sclerosis (MS). A 44-year-old man’s MRI scan at the first attack revealed an extensive hyperintensity on T₂-weighted (A) and contrast-enhanced T₁-weighted (B, C) images extending from the left frontal lobe through the corpus callosum knee to the left frontal lobe, and the lesions on the contrast enhancement images gradually disappeared after treatment; 7 months after the onset, some small patchy lesions developed in the right lateral paraventricular (D), frontal (E), temporal, and left midbrain (F), which gradually disappeared after treatment; The second relapse occurred 19 months after the first episode, and the patient’s brainstem developed a new patchy lesions (G–I).

Figure 4

Balo images on T1-weighted (A, C) and T2-weighted (B, D) MRI of two patients.