Improving the diagnosis and differential diagnosis level of tumor-like inflammatory demyelinating diseases 瘤样炎性柴油鞘病(tumor-like inflammatory demyelinating diseases, TIDD) is a more specific type of demyelinating disease of the central nervous system (CNS). TIDD (tumor-like inflammatory demyelinating diseases) is one of the more specific demyelinating diseases of the central nervous system (CNS) and is one of the inflammatory pseudotumors of the CNS. In recent years, TIDD has received more and more attention, but most of them are reported as individual cases or several cases. The study of its clinical and imaging characteristics is relatively superficial. With the development of imaging technology and the application of brain biopsy in recent years, it has been found that the number of patients suffering from this disease is not small, especially because of its clinical and imaging similarities with brain tumors, which can be easily confused, misdiagnosed or mistreated in clinical practice. Even senior experts in neurology, neurosurgery and imaging sometimes have difficulties in differentiating TIDD from brain tumor. Some patients with TIDD have undergone surgical lesion resection due to misdiagnosis of tumor, and some patients have undergone radiotherapy or gamma knife treatment due to misdiagnosis, and some of them have been left with dysfunction and even radiation encephalopathy. Therefore, it is necessary to improve the level of diagnosis and differential diagnosis of TIDD to meet the needs of clinical work. To this end, we have accumulated clinical, imaging and pathological characteristics of more than 50 patients with TIDD (including 26 pathologically confirmed cases), as well as our accumulated clinical experience in different brain tumors (pathologically confirmed), and refer to the domestic and international literature to provide a detailed comparative analysis of TIDD and brain tumors, and to provide the corresponding clinical, laboratory indices and imaging characteristics for study. Neurological disease related specialists in the diagnosis and differential diagnosis of TIDD for reference. 1, the concept of TIDD and the causes of misdiagnosis CNS inflammatory demyelinating lesions are immune-mediated diseases of the nervous system, including multiple sclerosis (MS), neuromyelitis optica (NMO), and disseminated encephalomyelitis, etc. One type of CNS demyelinating disease has a dominant effect on imaging, and clinically it presents as a large lesion with few symptoms, resembling a brain tumor, and is called tumefactive demyelinating lesions (TDLs), or demyelinating pseudotumors (TIDDs). demyelinating pseudotumor (DPT). The disease often affects young and middle-aged people and causes loss of work and/or life skills, resulting in a large economic and emotional burden for the patient, family and society. Because TIDD is easily confused with brain tumors, especially glioma and primary central nervous system lymphoma (PCNSL), some patients are misdiagnosed and undergo brain surgery to remove the otherwise curable lesions, resulting in serious damage to the patient’s brain function; some other patients with TIDD do not undergo craniotomy but are mistakenly thought to be suffering from TIDD. Other patients with TIDD did not undergo craniotomy but were mistaken for tumors and underwent gamma knife; some other patients were not diagnosed in time and delayed treatment, which affected their prognosis. The main reason for the misdiagnosis of TIDD is that we do not know enough about the clinical characteristics of TIDD and the clinical characteristics of brain tumor, and secondly, we do not know enough about the differentiation points of its imaging characteristics and brain tumor images. Failure to effectively combine multiple functional imaging techniques of CT and MRI for comprehensive judgment. Third, there are histopathological changes of TIDD with bizarre astrocytes (e.g., nuclear division-like Creutzfeuldt cells), which are easily mistaken for tumor cells. Some other tumors have atypical early lesions or are not deep enough for craniotomy or stereotactic sampling, and are located at the margins of the lesion, showing only a small amount of glial cell hyperplasia or myelin loss, which is difficult to distinguish from the glial hyperplasia of TIDD and can be easily misdiagnosed. In addition, the irregular use of glucocorticosteroids (short time of shock treatment, too fast reduction of hormone, or small amount of hormone) makes some TIDD not effectively controlled, and the disease is recurrent, while the image changes are more similar to tumor, which increases the difficulty of differential diagnosis. 2. Clinical differences between TIDD and brain tumor The average age of onset of TIDD is 34.3~36.6 years. The average age of onset of glioma and lymphoma is relatively older, especially lymphoma, while the age of onset of germ cell tumor is younger. In terms of the course of onset, most of the TIDD have subacute onset, and only about 1/4 to 1/3 of patients have an acute onset. In contrast, most brain tumors have an insidious or slow onset. In terms of clinical symptoms, the clinical manifestations of TIDD are relatively milder than those of MS or NMO, but more pronounced than those of brain tumors, and central facial and tongue palsy or movement disorders of the contralateral limbs may occur when the cortical brainstem tract or corticospinal tract is involved. The clinical manifestations of brain tumors are milder than those of TIDD, and the motor involvement is slower, especially in gliomas, even when the lesions involve motor conduction tracts. When the tumor cells grow densely and form a mass to a certain size, they squeeze the normal nerve tissue and produce the corresponding symptoms. In TIDD, mental retardation is sometimes the early clinical manifestation or the main symptom, while brain tumors usually do not show mental retardation in the early stage, and when there is mental retardation, it indicates that the tumor is large or causes diffuse damage, which is often the manifestation of late stage. In TIDD, there is usually no fundus optic papilloma, while some of the brain tumors may show fundus optic papilloma. Urinary and fecal disturbances are more common in TIDD than in brain tumors, especially if there is demyelination in the spinal cord or bilateral hemispheres. In contrast, urinary and fecal disturbances are rarely seen in brain tumors and may only occur when the tumor progresses to an advanced stage. Cerebrospinal fluid pressure is increased in a small number of patients with TIDD, but is usually mildly elevated and rarely exceeds 250 mm H2O on average. brain tumors may have a significant increase in cerebrospinal fluid pressure as the tumor grows, while a few are normal. Both cerebrospinal fluid proteins can be mildly elevated or normal, cell count is mostly normal, and the levels of sugar and chloride are mostly normal. The content of cerebrospinal fluid myelin basic protein (MBP) is often significantly increased in patients with TIDD. In 2007, Wang Qi et al. tested the cerebrospinal fluid MBP level of 14 cases of TIDD patients and found that all of them had different degrees of elevation, and the average value was about 13 times of the upper limit of normal value, while in brain tumor MBP was mostly normal, and a few of them were slightly elevated. The imaging differentiation between TIDD and brain tumor There are some similarities between TIDD and brain tumor in imaging, such as the occupancy effect, MRI enhancement performance, etc. However, careful observation can still reveal many differences, which are helpful to differentiate the two. 1. CT scan and enhancement of the head: TIDD has clear or blurred low-density border in CT scan, and no significant enhancement or mild enhancement of the lesion and periphery in enhancement scan. Glioma and PCNSL are mostly high-density or isointense, but may also be hypointense or mixed-density, and can be enhanced with enhancement, which is more obvious than TIDD, especially PCNSL. High density can also be seen on CT scan of germ cell tumors (Figure 1). In 2007, when we summarized 16 cases of pathologically confirmed TIDD in the brain, it should be noted that if the DWI is uniform and slightly high signal (Figure 2) and the CT is also mildly dense (Figure 3), demyelinating disease can be excluded and the main consideration is brain Glioma [4], i.e., CT high signal can be considered as a feature of brain tumor, and the judgment of CT and MRI on TIDD and glioma was reported at the 1st Asia-Pacific Neuropathology Conference in Tokyo in 2008, and Kim DS et al. came to the same conclusion as ours in 2009 by studying patients with TIDD and glioma and PCNSL. 2. MRI: Gliomas tend to have long T1 (Figure 4) and long T2 signals (Figure 5), and a few have slightly iso-T1 signals. Low-grade glioma may not strengthen, but high-grade glioblastoma (glioma grade ≥3) strengthens significantly, usually with central or mass-like strengthening, and circumferential strengthening is less common than TIDD; lymphocytoma mass-like strengthening is obvious, and strengthening becomes more and more significant with time, if the strengthening lesion in brain or spinal cord is more obvious after 3 months, glioma or other brain tumors should be excluded. TIDD is mostly characterized by long T1 (low) and long T2 (high) signals, and most of the lesions can be enhanced in the acute or subacute phase. Masdeu JC et al. reported that the presence of non-closed ring reinforcement-open-ring sign in cases with ring reinforcement on CNS MRI scan is highly specific for the diagnosis of tuberculous demyelination. In the acute or subacute stage of TIDD, DWI is mostly high signal, and the signal intensity gradually decreases with time. In contrast, the DWI of brain tumor in early stage is mostly low or isosignal, and it may gradually become high signal with time, and it is getting higher and higher. TIDD, glioma, and PCNSL are all lesions that easily involve the corpus callosum, but TIDD corpus callosum involvement is generally not thickened except in a few cases in the acute phase. TIDD lesions often involve the subcortex and cortex, and can be multiple. Up to a dozen lesions may be separated from each other and may be unconnected. PCNSL tends to involve midline structures such as the basal ganglia, thalamus, corpus callosum, brainstem and paraventricular space, and the lesions tend to intensify and have significant peri-lesion edema (Figure 10). Functional MRI techniques such as magnetic resonance spectroscopy (MRS), which reflects the metabolism of the lesion, can also be used to help differentiate demyelinating disease from glioma. Glucocorticoid therapy is also valuable for differentiating TIDD from tumor lesions, which can be significantly controlled after receiving hormone therapy, and the lesions can be reduced or even disappeared in some cases, while large lesions can be left behind as atrophic lesions, and the improvement of symptoms will continue, usually without serious sequelae. In contrast, glioma disease does not change with hormone therapy, and sometimes the clinical symptoms improve slightly due to the effect of reducing edema. However, over time, lesions may appear again or new lesions may appear in other areas (Figure 12). 4. Problems and countermeasures in the diagnosis and treatment of TIDD At present, one of the main reasons for the difficulty in diagnosis and decision making of TIDD in clinical practice is that the clinical diagnosis is not effectively combined with multiple techniques of cranial CT and MRI (such as DWI and MRS) for comprehensive evaluation of imaging, and there is also a lack of corresponding comprehensive diagnostic criteria. If the patient’s various cranial imaging data can be analyzed in detail, clearer information should be obtained. Secondly, the irregularity of glucocorticoid treatment for patients suspected of TIDD often does not allow effective control of the patient’s disease, and even makes the disease recurrent, and the imaging changes are more similar to tumors, which increases the difficulty of differentiation. We have treated patients with severe demyelinating disease who failed to undergo standardized high-dose glucocorticoid therapy with a diagnosis of demyelinating pseudotumor in an external hospital and achieved good results, therefore, it is also very important to further standardize TIDD treatment, which should be referred to the MS high-dose glucocorticoid shock treatment protocol [20]. Third, invasive treatments such as surgery, radiotherapy or γ-knife should be avoided for patients with TIDD that are difficult to identify. Brain biopsy has been proven to be a relatively safe diagnostic method, economical and less invasive, and more than 7000 brain biopsies have been performed in our hospital with minimal postoperative complications. Brain biopsy provides the necessary reference for proper diagnosis and treatment on the one hand, and improves the level of understanding of different CNS diseases such as TIDD and glioma on the other. Therefore, patients with TIDD who can be clearly diagnosed by combining imaging and clinical practice can be treated with drugs first, and the efficacy and imaging changes can be observed; for patients with difficulties in identification, brain stereotactic biopsy can be actively carried out. In conclusion, although TIDD is similar to brain tumor, there are differences in clinical manifestations and imaging characteristics with glioma and PCNSL, which should be judged by combining clinical and multiple imaging techniques, especially the differential diagnostic role of cranial CT should be emphasized. If necessary, brain biopsy should be performed to clarify the diagnosis, so as to better implement targeted treatment for patients.