Isolated tumefactive demyelinating lesions: diagnosis and long-term evolution of 16 patients in a multicentric study

Isolated tumefactive demyelinating lesion (TDL) is a rare disease and a challenging entity especially for the differential diagnosis, biopsy indications, and therapeutic decisions. Long-term evolution is not well known. The objective of the study is to describe clinical and MRI characteristics and long-term follow-up of patients with isolated TDL. We performed a retrospective study including patients (1) with one TDL radiologically defined by a ≥20 mm FLAIR hyperintensity involving the white matter associated with T1 hypointensity that enhanced after gadolinium injection and (2) without any other MS lesion on the first MRI. Tumor, abscess, or other inflammatory diseases (ADEM, Baló’s concentric sclerosis, systemic disease) were excluded. Sixteen patients (11 females/5 males) were included. The mean age of onset was 35.7 years (range 20–65). MRI disclosed supratentorial lesions with a mean size of 39.4 mm and usually mild edema/mass effect. Peripheral (mainly open-ring pattern) and central (mainly heterogeneous) enhancement were respectively seen in 9/16 and 11/16 patients. CSF study (n = 15) found oligoclonal bands (OCB) in seven. A cerebral biopsy was performed in 11 cases showing acute inflammatory demyelination. Thirteen patients were treated by pulse steroids with marked improvement in ten. At last clinical follow-up (mean 65.8 months, range 6–181), diagnosis was MS in 5 (31 %), isolated TDL in 10 (63 %) and one patient had a second TDL (6 %). Isolated tumefactive demyelinating lesions are a rare diagnostic entity. After a mean follow-up of 5 years, almost one-third became MS whereas most of the patients had no further event.     

Occurrence and long-term outcome of tumefactive demyelinating lesions in multiple sclerosis

Although tumefactive multiple sclerosis is a well recognized variant of multiple sclerosis, prognostic uncertainty still exists about long term prognosis. The aim of this study was to estimate the occurrence and long term outcome of tumefactive demyelinating lesions (TDLs) in a cohort of multiple sclerosis patients. We reviewed brain MRI of 443 patients referred to our MS clinic. All patients meeting the McDonald criteria for multiple sclerosis and showing at least one TDL were included. Kaplan–Meier estimates of disease-free survival in patient cohort were compared with control group without TDLs using a log-rank test. Seven cases with TDLs were identified (occurrence 1.58 %). Tumefactive demyelinating lesion recurrence was 16.6 %. Cumulative proportion of patients free from clinical relapse and from new T2 lesions was lower in the control group although not reaching statistical significance (30 vs 50 %; P = 0.666 and 21.7 vs 33.3 %; P = 0.761, respectively). Disability progression analysis showed a not significant trend towards lower probability of remaining progression free for TDL patients (50 vs 61 %; P = 0.295). Occurrence of tumefactive demyelinating lesions in our cohort was higher than those reported in other studies. Overall, TDLs were not predictive of poor outcome in terms of disability progression.     

Characteristic Neuroimaging in Patients with Tumefactive Demyelinating Lesions Exceeding 30 mm

ABSTRACT

BACKGROUND AND PURPOSE

Features of tumefactive demyelinating lesion (TDL) on magnetic resonance imaging (MRI) can facilitate the differential diagnosis of TDL and neoplastic lesions, but vary considerably among patients. The larger TDL grows, the more difficult it becomes to differentiate TDL from neoplastic lesions. The purpose of this study was to elucidate typical MRI features in 12 patients with large TDL (>30 mm in diameter).

METHODS

We identified 12 patients with large TDL (six men, six women; age range 17‐64 years, median age 27 years) and studied the clinical histories and the results of laboratory and various radiological studies in these patients. All cases of clinically definite multiple sclerosis were diagnosed in accordance with McDonald's revised criteria.

RESULTS

Common MRI features of large TDLs included variable degrees of mass effect (71%) and edema (100%), a T2 hypointense rim (79%), venular enhancement (57%), and peripheral restriction on diffusion‐weighted images (50%). Ring enhancement (38%), open‐ring enhancement (31%), or decreased N‐acetylaspartate ratios on magnetic resonance spectroscopy (22%) were less frequently observed. Brain angiography demonstrated venous dilatations on and around the TDL.

CONCLUSIONS

The diagnosis of large TDL is challenging. Our findings suggest that multiple venous dilatations on and around TDLs on angiography can facilitate diagnosis.

     

Aspects cliniques, radiologiques, pronostiques et thérapeutiques des lésions démyélinisantes extensives

Background

Demyelinating diseases presenting with a tumefactive demyelinating lesion (TDL) raise questions about classification, diagnosis, prognosis, and treatment. Their long-term course is not well described in literature.

Patients/methods

In a retrospective study, we describe the main characteristics of 29 patients with TDLs. In a case control study, we compared two cohorts of multiple sclerosis (MS) patients: 24 MS patients with TDL versus a reference cohort of patients with relapsing remitting MS. We compared the extended disability status score (EDSS) concerning the first demyelinating event (DE) with TDL, EDSS score at the end of follow-up and treatment intake. The objective was to discuss the prognosis and the management of TDL.

Results

In our study, the prognosis was better for patients with non-prevalent TDL (first DE without TDL) compared with patients with prevalent TDL (first DE with TDL) and was not different compared with the MS reference cohort. At the end of follow-up, there was no significant difference between patients treated with immunosuppressors after a first DE with TDL and patients with classical MS. The EDSS at the end of follow-up was statistically more severe for untreated patients after a first DE with TDL than for classical MS patients (P = 0.0047).

Discussion

The prognosis of patients with TDL is difficult to assess because of its multifactorial nature (underlying disease and treatment impact). In our cohort, outcome of MS patients whose first severe DE involved a TDL was better when they received an early immunosuppressive treatment.     

Gadolinium enhancement patterns of tumefactive demyelinating lesions: correlations with brain biopsy findings and pathophysiology

Tumefactive demyelinating lesions (TDLs) can mimic brain tumors on radiological images. TDLs are often referred to as tumefactive multiple sclerosis (TMS), but the heterogeneous nature and monophasic course of TDLs do not fulfill clinical and magnetic resonance imaging (MRI) criteria for multiple sclerosis. Redefining TDLs, TMS and other inflammatory brain lesions is essential for the accurate clinical diagnosis of extensive demyelinating brain lesions. We retrospectively analyzed MRI from nine TDL cases that underwent brain biopsy. Patterns of gadolinium enhancement on MRI were categorized as homogenous, inhomogeneous, patchy and diffuse, open ring or irregular rim, and were compared with pathological hallmarks including demyelination, central necrosis, macrophage infiltration, angiogenesis and perivascular lymphocytic cuffing. All cases had coexistence of demyelinating features and axonal loss. Open-ring and irregular rim patterns of gadolinium enhancement were associated with macrophage infiltrations and angiogenesis at the inflammatory border. An inhomogeneous pattern of gadolinium enhancement was associated with perivascular lymphocytic cuffing. Central necrosis was seen in cases of severe multiple sclerosis and hemorrhagic leukoencephalopathy. These results suggest that the radiological features of TDLs may be related to different pathological processes, and indicate that MRI may be useful in understanding their pathophysiology. Further investigation is needed to determine the precise disease entity of these inflammatory demyelinating brain lesions.     

MRI联合~(18)F-FDG PET和~(11)C-MET PET对颅内肿胀性脱髓鞘病变与胶质瘤的鉴别诊断作用

目的探讨MRI联合~(18)F-脱氧葡萄糖(~(18)F-FDG)PET和~(11)C-蛋氨酸(~(11)C-MET)PET显像对颅内肿胀性脱髓鞘病变与胶质瘤的鉴别诊断价值。方法纳入经病理学直接证实或内科保守治疗间接证实的14例颅内肿胀性脱髓鞘病变患者和17例胶质瘤患者,采用MRI观察病变与周围正常脑组织界限,T1WI、T2WI和扩散加权成像(DWI)信号强度,强化征象(包括环状强化和开环状强化等),占位效应,周围脑水肿,病变中心静脉扩张,胼胝体受累,病变中心坏死,灰质受累情况;~(18)F-FDG PET和~(11)C-MET PET显像对代谢程度进行视觉分析。结果 MRI显示,颅内肿胀性脱髓鞘病变患者占位效应0级8例(8/14)、Ⅰ级4例(4/14)、Ⅱ级1例(1/14)、Ⅲ级1例(1/14),周围脑水肿Ⅰ度12例(12/14)、Ⅱ度2例(2/14);胶质瘤患者占位效应0级2例(2/17)、Ⅰ级6例(6/17)、Ⅱ级7例(7/17)、Ⅲ级2例(2/17),周围脑水肿Ⅰ度7例(7/17)、Ⅱ度10例(10/17),组间差异均有统计学意义(Fisher确切概率法:P=0.032,0.024)。~(18)F-FDG PET和~(11)C-MET PET显像对颅内肿胀性脱髓鞘病变与胶质瘤的鉴别诊断差异无统计学意义(Fisher确切概率法:P=0.182,0.081)。结论 MRI显示的占位效应和周围脑水肿可以用于鉴别诊断颅内肿胀性脱髓鞘疾病与胶质瘤,PET-CT对症状类似胶质瘤的颅内肿胀性脱髓鞘病变无明确诊断价值。     

Demyelination preceding a diagnosis of central nervous system lymphoma

We present a case of primary central nervous system lymphoma (PCNSL) co-existing with demyelination in a young immunocompetent woman. The patient presented with an expansile, enhancing lesion in the right occipital lobe which was initially attributed to tumefactive demyelination and subsequently proven to be PCNSL. PCNSL is an uncommon malignancy, particularly in young immunocompetent patients, and on MRI classically manifests as a homogeneously enhancing solitary mass with a predilection for periventricular and superficial locations, often contacting ventricular and meningeal surfaces. Tumefactive demyelinating lesions typically present as large white matter lesions with little mass effect or vasogenic oedema and “open-ring” enhancement, with the incomplete portion of the ring on the grey matter side of the lesion. PCNSL and tumefactive demyelinating lesions share some radiological features and thus, as our case report highlights, differentiating between them can be challenging. We discuss how the application of conventional and advanced MRI techniques combined with clinical and laboratory findings can lead to a precise diagnosis, potentially obviating the need for biopsy and facilitating prompt and appropriate treatment.     

Prolonged interval between sentinel pseudotumoral demyelination and development of primary CNS lymphoma.

Primary central nervous system lymphoma (PCNSL) can be associated with preceding demyelinating pseudotumoral brain lesions. The 'sentinel' demyelinating lesions recede spontaneously or with corticosteroid, and are followed by development of PCNSL typically within 12 months. This report describes a 29 year-old post-partum woman who developed PCNSL 4 years after a biopsy-proven pseudotumoral demyelinating episode. She presented with focal seizures in February 2005. She subsequently developed hemiparesis and raised intracranial pressure. MRI showed two contrast enhancing lesions in the right frontal lobe, which were hypermetabolic on (18)F-FDG PET. A provisional diagnosis of tumefactive multiple sclerosis was made. Symptoms recurred despite multiple courses of high dose corticosteroid. Brain biopsy confirmed large B-cell non-Hodgkin's lymphoma. This patient illustrates the importance of considering PCNSL in patients presenting with a space-occupying lesion, even with previously confirmed demyelination, and that the interval between the two events may be several years.     

Revision of McDonald's new diagnostic criteria for multiple sclerosis

In 2001, an international panel suggested new diagnostic criteria for multiple sclerosis (MS). These criteria integrate clinical, imaging (MRI), and paraclinical results in order to facilitate diagnosis. Since then, these so-called McDonald criteria have been broadly accepted and widely propagated. In the meantime a number of publications have dealt with the sensitivity and specificity for MS diagnosis and with implementing these new criteria in clinical practice. Based on these empirical values and newer data on MS, an international expert group recently proposed a revision of the criteria. Substantial changes affect (1) MRI criteria for the dissemination of lesions over time, (2) the role of spinal cord lesions in the MRI and (3) diagnosis of primary progressive MS. In this article we present recent experiences with the McDonald and revised criteria.     

瘤块样脱髓鞘病变脑组织活检临床病理及细胞凋亡特点

目的 对瘤块样脱髓鞘病变（TDL）髓鞘脱失、胶质细胞再生及凋亡等特点进行观察，并对1例Balo病作形态发生学的探讨。方法 对5例经大脑活组织病理检查诊断为TDL的组织切片作苏木素-伊红（HE）、固蓝、Bielschosky、CD68胶质纤维酸性蛋白（GFAP）染色，并对Bcl-2、Bcl-XL、Bad、Bak、Bax、Fas、Fas-L等7种凋亡基因蛋白作免疫组织化学染色及观察。对所有患者进行随访。结果 白质内同时可见散在大小不一的空泡状脱髓鞘病变和带状／片状的髓鞘保留区（1例为典型的同心圆状排列）。脱髓鞘区同时存在星形胶质细胞增生、肥大及异常核分裂象。髓鞘保留区存在明显的胶质细胞增生。脱髓鞘区胶质细胞的促凋亡基因蛋白表达上调而抑制性基因表达下调。结论 在小块活检组织中，空泡状脱髓鞘区和髓鞘保留区同时存在及分裂象的出现，可作为诊断TDL的参考依据。在1例Balo病中，“髓鞘保留区”存在明显的胶质细胞增生。异常有丝分裂及促凋亡基因蛋白表达上调在髓鞘病变中的意义有待进一步阐明。影像诊断中，TDL还应与脑内其他的占位性病变区别开来。     

Diagnostic value of magnetic resonance tomography in disseminated encephalomyelitis

In 83 of 86 patients with multiple sclerosis (MS) cranial magnetic resonance imaging (MRT) demonstrated lesions consistent with the clinical diagnosis. All the patients had either clinically typical MS oralaboratory-confirmed diagnosis of MS. The sensitivity of MRI is compared to those of computed tomographic (CT) scanning, evoked potential testing and cerebrospinal fluid analysis. The features of MS revealed by MRI are interpreted in terms of the macroscopic pathology and correlated with the clinical findings. The importance of particular findings (cystic appearance of lesions, spread of periventricular patches into the centrum semiovale) for the patients prognosis in stressed.     

多发性硬化的MRI与临床

报告４６例多发性硬化（ＭＳ）患者的ＭＲＩ与临床资料。其中临床确诊者３９例，实验室支持确诊者４例，临床近似确诊者３例。ＭＲＩ阳性２９例（６３．０４％）。病灶分布依序为脑室周围、大脑半球、脑干、基底节、小脑、胼胝体及视神经；本组临床定位病灶９３个，ＭＲＩ显示病灶４９个，其中３７个病灶与临床相符，１２个属亚临床病灶。结果提示ＭＲＩ对发现ＭＳ病灶虽有很高的敏感性，但ＭＳ的诊断仍需结合临床。     

The roles of blink reflex and sympathetic skin response in multiple sclerosis diagnosis

The neurological history and examination are important in multiple sclerosis (MS) diagnosis, but early and accurate diagnosis of MS often requires judicious use of paraclinical information. Electrophysiologic techniques have an important role in demonstrating lesions that are clincally silent but magnetic resonance imaging (MRI) is accepted as the most sensitive paraclincal test for detecting asymptomatic dissemination in space for MS patients. In order to test the sensitivity of electrophysiologic techniques in diagnosing asymptomatic MS lesions, we performed blink reflex (BR) and sympathetic skin response (SSR) studies on 13 female (mean age 39 -/+ 9 years) and 8 male (mean age 35 -/+ 14 years) patients with a diagnosis of definite MS who do not have any clinical symptoms nor signs referable to brainstem or autonomic system dysfunction. Forty three percent of patients on SSR testing and 40% of patients on BR testing demonstrated abnormal results. In countries with unfavorable economic conditions, diagnosis, especially the follow-up evaluation of MS patients, poses a major dilemma. The role of diagnostic techniques in MS diagnosis when MRI is available is an economic problem. Diagnostic evaluation adds to the cost of health expenses. We usually choose to perform MRI only at the initial diagnosis of MS and perform follow-up evaluations during remissions and exacerbations with the aid of electrophysiologic techniques. We stress the importance of electrophysiologic screenings in MS patients because they provide data that cannot be obtained through clinical evaluations only with a little cost.     

Very early MS -- insights from MRI

Magnetic resonance imaging (MRI) is likely to play an increasing role in efforts to understand the earliest changes in multiple sclerosis (MS) and narrowing the gap to new insights provided by the recent pathology literature showing early meningeal and cortical inflammatory disease and cortical gray matter demyelination. Much of the insight into early MS already comes from MRI as it evaluates patients at the time of a clinically isolated syndrome (CIS). Series show transition of tissue from normal to abnormal, and now often reveal gray matter more so than white matter pathology, deep gray more than cortical gray, and quantitative MRI changes preceding atrophy in early MS. But the CIS population is heterogeneous, likely including patients with many years' duration, as well as relatively recent onset disease. Efforts to evaluate earlier disease, possibly sub-populations of CIS, patients at risk for MS with strict criteria for a radiologically isolated syndrome, and tumefactive MS, combined with advanced MRI technology, may bring us closer to in vivo insight into truly early or earliest MS.     

Cerebral amyloid angiopathy manifested as a brain tumour. Clinical and neuropathological characteristics of two cases

We present two cases (female and male patients, aged 64 and 38, respectively) of focal mass lesions mimicking a brain tumour: one with cognitive function deficit, memory troubles, behavioral changes and left hemiparesis, the other with difficulty in orientation and right hemiparesis. General physical and neurological examinations, laboratory tests and neuroimaging were used to diagnose the cases. Both of them showed nonspecific changes in the brain tissue and the brain tumour was suspected. In the first case MRI scan revealed two pathological masses in the right frontal region and hemorrhagical focus with destructions inside lesions. Second patient's MRI scan revealed a pathological mass at the interface of the left temporal and occipital regions. The neurosurgical procedure was performed. The final diagnosis was established on the basis of neuropathological examination of postoperative material. On light microscopy examination a severe cerebral amyloid angiopathy (CAA) was revealed. Amyloidoma was excluded due to the absence of amorphous material and eosynophylic masses. Tumefactive CAA is a rare condition. These two cases of focal, tumefactive, masslike lesions of diffuse cerebral amyloid angiopathy are reported because of diagnostic dilemmas. In patients with history of memory disfunction, neurological deterioration and different multiple changes observed in CT and MRI scans, such as hemorrhagic infarcts and ischemic cerebral lesions, CAA should be suspected. The imaging findings make a distinction between tumefactive CAA and brain tumours like gliomas difficult. A differential diagnosis of CAA and amyloidoma plays a significant role in a neuropathological examination.     

Metabolism and regional cerebral blood volume in autoimmune inflammatory demyelinating lesions mimicking malignant gliomas

Dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) and MR spectroscopy are thought to differentiate tumefactive autoimmune inflammatory demyelinating lesions from glial brain tumours. The aim of this work is to evaluate whether regional cerebral blood volume (rCBV), as well as choline (Cho), N-acetyl-aspartate (NAA) and myo-inositol (mIns) concentrations differ between tumefactive lesions and World Health Organization (WHO) grade II–III gliomas. Five patients with single autoimmune inflammatory demyelinating lesions and nine patients with WHO grade II and III gliomas were examined by DSC-MRI and by two-dimensional (2D) ¹H MR spectroscopic imaging (¹H-MRSI). rCBV values and metabolite concentrations were normalised to the respective values of the contralateral hemisphere. Normalised rCBV in the tumefactive lesions (mean 2.89, range 1.98–6.74) was in the some high level as in gliomas (mean 2.77, range 1.43–6.22). ¹H-MRSI revealed increased normalised choline concentrations in five of six examinations of autoimmune lesions (mean 1.4, range 1.06–1.8) and in eight of nine gliomas (mean 1.35, range 0.92–1.73). Tumefactive autoimmune inflammatory demyelinating lesions not only have imaging appearance of gliomas but may also imitate marked increase of rCBV and Cho in WHO grade II–III gliomas.     

Multiple sclerosis in childhood: contribution of serial MRI to earlier diagnosis

The authors report six children (five girls, one boy) aged 11 to 13 years, of whom four had clinically definite multiple sclerosis (MS) and two had laboratory-supported definite MS. All had brain white matter abnormalities indicative of MS. In three cases, positive findings on the first MRI contributed significantly to their early diagnosis. Follow-up MRI studies over an average period of five months detected morphological changes in three of the children, although there was no concomitant clinical evidence. This raises the question of whether changes in clinically 'silent' lesions on follow-up MRI are antecedents of the essential MS criterion of dissemination over time, which could lead to earlier diagnosis of childhood MS. With cranial computerized tomography (CT) during the first clinical attack, a large focus with a lamellar structure mimicked a brain tumour in two patients. As CT also misses additional small lesions, it should no longer be used as the primary diagnostic method.     

Guidelines for the use of magnetic resonance imaging in diagnosing and monitoring the treatment of multiple sclerosis: recommendations of the Swedish Multiple Sclerosis Association and the Swedish Neuroradiological Society

Multiple sclerosis (MS) is associated with inflammatory lesions in the brain and spinal cord. The detection of such inflammatory lesions using magnetic resonance imaging (MRI) is important in the consideration of the diagnosis and differential diagnoses of MS, as well as in the monitoring of disease activity and predicting treatment efficacy. Although there is strong evidence supporting the use of MRI for both the diagnosis and monitoring of disease activity, there is a lack of evidence regarding which MRI protocols to use, the frequency of examinations, and in what clinical situations to consider MRI examination. A national workshop to discuss these issues was held in Stockholm, Sweden, in August 2015, which resulted in a Swedish consensus statement regarding the use of MRI in the care of individuals with MS. The aim of this consensus statement is to provide practical advice for the use of MRI in this setting. The recommendations are based on a review of relevant literature and the clinical experience of workshop attendees. It is our hope that these recommendations will benefit individuals with MS and guide healthcare professionals responsible for their care.     

Clinical and magnetic resonance imaging in optic neuritis

We found 23 of 48 patients (48%) with isolated monosymptomatic optic neuritis (ON) to have 1 to several brain lesions by MRI. All the brain lesions were clinically silent and had characteristics consistent with multiple sclerosis (MS). During 4 years of follow-up, 9 patients (19%) developed definite MS on clinical grounds. Six of the converting patients had abnormal MRIs; the other 3 had MRIs that were normal both initially (when they had ON only) and when repeated after they had developed MS. The other 17 patients with abnormal MRIs have not developed symptoms or signs of MS during follow-up. Thus, an abnormal MRI does not auger development of clinical MS within a mean of 4 years, nor does a normal MRI protect against development of disseminated disease. It is not prudent to give a patient with isolated monosymptomatic ON the diagnosis of MS (probable or definite) because of an abnormal MRI (with or without other laboratory abnormalities).     

脊髓多发性硬化的MRI表现与临床对照分析

目的 探讨脊髓多发性硬化(multiple sclerosis,MS)的MRI表现及其与临床的相关性。方法 分析13例脊髓MS患者,对病变的部位、范围及病变处脊髓的形态、MR信号及病变的强化程度进行分析评价并与临床症状进行对照。结果 13例脊髓MS主要发生在颈髓,急性期局部脊髓肿胀,T1加权像病变呈等信号或边缘模糊的稍低信号。T2加权像呈高信号。活动期病灶呈斑片状、环状或弓形强化。反复发作病例、多发病灶其强化多样性,临床症状多变性。结论 脊髓MS有其特征性MRI表现,其与临床有较强的相关性,能为临床诊断和治疗提供可靠的依据。