Tek başına ya da multipl skleroz seyri sırasında ortaya çıkan tümefaktif demiyelinizan lezyonların klinik, radyolojik ve laboratuvar özelliklerinin değerlendirilmesi, uzun süreli retrospektif ve prospektif takip sonuçları
Evaluation of clinical, radiological and laboratory characteristics of tumefactive demyelinating lesions occurring alone or during the course of multiple sclerosis, long-term retrospective and prospective follow-up results
Yazar: ÖZGÜ KİZEK
Danışman: PROF. DR. MEFKÜRE ERAKSOY
İstanbul Üniversitesi / Tıp Fakültesi / Nöroloji Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2022
Konu: Nöroloji = Neurology
Dizin: Demiyelinizan hastalıklar = Demyelinating diseases ; Multipl skleroz = Multiple sclerosis ; Neoplazmlar = Neoplasms ; Prospektif çalışmalar = Prospective studies ; Radyoloji = Radiology ; Retrospektif çalışmalar = Retrospective studies

Özet:
Giriş ve Amaç: Tümefaktif demiyelinizan lezyonlar (TDL), enflamatuar demiyelinizan
hastalıklar spektrumunun bir varyantıdır. Tek başına ya da multipl skleroz (MS) seyri
sırasında ortaya çıkabilir. Literatürde "demiyelinizan psödotümör", "tümefaktif MS",
"tümör benzeri MS", "tümör benzeri demiyelinizan lezyon" isimleri kullanılmıştır. Atipik
klinik ve radyolojik bulguları olan, atipik seyirli olan ve MS'in immünmodülatör
tedavilerine kısmi yanıt gösteren bu hastalarda atipik demiyelinizan sendromları ya da
MS dışındaki tanıları düşünmek gerekir. Prevalansı MS vakalarının %1,4-8,2'si olarak
bildirilmiştir. En sık başlangıç şekli polisemptomatik, motor ve duysal bulgular olmakla
birlikte ensefalopati, nöbet, hemiparezi, ihmal gibi kortikal sendromlar ile başlayabilir.
Lezyonlar, 2 cm'den büyük, sıklıkla frontal ve pariyetal lob yerleşimli, ödem ve kitle
etkisi görülebilen, açık halka şeklinde kontrast tutulumu gösteren demiyelinizan
özelliktedir. Klinik tablo, akut ya da subakut, hafif-orta ya da ciddi nörolojik bulgularla
ortaya çıkabilir; bu belirti ve bulgular lezyonun bulunduğu lokalizasyona göre
değişkendir. Merkezi Sinir Sistemi (MSS) neoplazmları, metastaz, abse, vaskülit ve
granülomatoz hastalıklar ile ayırıcı tanısı yapılmalıdır. TDL'ler genel olarak, intravenöz
metilprednizolon (IVMP) tedavisine yanıtlıdır ve McDonald MS kriterlerini karşılayan
hastalar için hastalık seyrini değiştirmeye yönelik tedavilerin erken başlanması önemlidir.
TDL'ler monofazik seyir gösterse de, %30-60'ında MS geliştiği bildirilmiştir ve sekonder
progresyon nadirdir. Çalışmamızın amacı, nöroloji pratiğinde karşımıza çıkan, Manyetik
Rezonans görüntülelemerde (MRG) saptanan tümör benzeri enflamatuar demiyelinizan
lezyonların demografik, klinik ve radyolojik özelliklerini tanımlamak, tanı için
klinisyenlerin faydalanacağı bilgiler elde etmek, hastalar için erken, hızlı ve doğru tedavi
yaklaşımlarını belirlemek, hasta ve yakınları için yaşam planlarına ilişkin doğru prognoz
ve akıbet bilgilerini verebilmek amaçlanmıştır. Bu bilgilerle, akut ve uzun dönem tedavi

Abstract:
Introduction: Tumefactive demyelinating lesions (TDL) are a variant of the spectrum of
inflammatory demyelinating diseases. It can occur alone or during the course of multiple
sclerosis (MS). In the literature, the terms "demyelinating pseudotumor", "tumefactive
MS", "tumor-like MS", "tumor-like demyelinating lesion" have been used. Atypical
demyelinating syndromes or diagnoses other than MS should be considered in these
patients with atypical clinical and radiological findings, an atypical course, and a partial
response to immunomodulatory treatments of MS. Prevalence of TDLs has been reported
as 1.4-8.2% of MS cases. Although the most common initial clinic is polysymptomatic,
motor, and sensory findings, it may occur with cortical syndromes such as
encephalopathy, seizure, hemiparesis, neglect. TDLs are larger than 2 cm, often located
in the frontal and parietal lobes, edema and mass effect can be seen, and open ring-shaped
contrast enhancement. Their clinic might be moderate to severe, depending on the
localization of the lesion. Differential diagnosis should be made with Central Nervous
System (CNS) neoplasms, metastasis, abscess, vasculitis, and granulomatous diseases.
For patients who are responsive to intravenous methylprednisolone (IVMP) therapy and
fulfilled the McDonald's MS criteria, early initiation of disease modifying therapies
(DMTs) is important. Although TDLs have a monophasic course, it has been reported
that 30-60% of the patients develop multiple sclerosis, and secondary progression is rare.
The aim of our study is to determine the demographic, clinical and radiological features
of tumor-like lesions, and to obtain information that clinicians use for diagnosis.
Therefore, we try to classify into subgroups and to help develop algorithms. In addition,
we aimed to contribute to acute and long-term treatment approaches and patient
management.
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Patients and Methods: Clinical, imaging and laboratory characteristics, treatment
responses and Expanded Disease Status Scale (EDSS) scores of 41 patients with TDL and
MS followed up in our clinic (1981-2021) were retrospectively analyzed.
Results: Thirty (73.2%) of the patients were female and 11 (26.8) were male. Ten (24%)
of the patients had childhood-onset and 3 of thepatients (7%) were older than 50. The
mean age at onset was 26.9±13.8 years. The mean follow-up period was 9.5±6.5 years.
According to the disease features, there were 29 (70.7%) patients who occured with TDL
alone and 12 (29.3%) patients who developed TDL during the course of MS. The most
common initial findings were motor and sensorimotor findings. Oligoclonal bands (OCB)
were detected in 42.4% (n=14). Localizations of the lesions were most frequently in the
frontal and parietal lobes. The lesion size of 85.4% of TDLs was between 20-40 mm. T2
hypointense rim was seen in 48.6% of TDLs, 51% had heterogeneous, and 34.1% had
open-ring contrast enhancement. Ten (34%) of 29 patients who occured with TDL alone
were diagnosed with definitive MS in a median of 20 months (7-24 months). Eight
patients (27%) remained monophasic during the follow-up period. Seven of the patients
(24%) met the McDonald criteria, and were diagnosed with MS at initial MRI. Two
patients (6%) were diagnosed with relapsing-remitting tumefactive lesions, while 1
patient (3%) was diagnosed with neuromyelitis optica (NMO) and 1 patient (3%) with
myelin oligodendrocyte glycoprotein (MOG) associated disease. Among the recent
diagnoses, the highest rate was relapsing relapsing MS (RMS) (75%). The median disease
duration of patients with childhood-onset was significantly longer than adults (16, 7,
p=0.006). The median of the initial and final EDSS were 3.0 (2.0-3.5) and 2.0 (1.0-2.7),
respectively. The median final EDSS value of the patients with childhood onset was 2.2
(1-6) and the patients with adult onset were 2 (0-6) and were statistically similar (p=0.37).
The median disease duration of the patients with monophasic course was longer (10.5, 6,
p=0.014). Although the initial EDSS were similar, the median final EDSS in patients with
a monophasic course was found to be significantly lower than in patients with a relapsingremitting course (1, 2, p=0.007). The median delta-EDSS of monophasic patients was
significantly higher than the patients with a relapsing-remitting course (-1.5, -0.5,
p=0.007). While 4 (9.8%) of the patients were being followed without treatment, 6
(14.6%) were using azathioprine and the others were receiving DMTs. The median of
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final EDSS of the patients was 2 (1-2.7). The final EDSS of those receiving second-line
DMT were similar.
Conclusion: Tumefactive demyelinating diseases are a spectrum of inflammatory
demyelinating diseases with characteristic radiological findings, which is more common
than it is known towadays, and which is important to distinguish from malignancies in
the differential diagnosis. TDL can occur alone or during the course of MS, and we found
that these patients have a better prognosis than patients with RMS. This finding suggests
that there might be a self-limiting feature of the disease. In our study, DMTs were initiated
in the early period for the patients that have RMS, relapsing tumefactive MS, relapsing
tumefactive demyelinating disease, and monophasic tumefactive demyelinating disease,
who fulfilled the criteria for dissemination in time and space from the beginning. We
concluded that the outcome of the patients who received first and second-line treatments
was similar at the last EDSS, and that initiating high-level treatment in the early period
was effective in modifying the course of the disease. Multicenter, larger, prospective,
long-term studies of patients would be most informative and helpful for a better
understanding of these clinical manifestations.
Key Words: tumefactive demyelinating lesion, multiple sclerosis, tumefactive multiple
sclerosis, tumor-like lesion