Brief description of the case: Patient, male, 35 years old. He was admitted to the hospital on 2010-12-20 with “cough and sputum for 2 months”. He had intermittent cough with a small amount of white foamy sputum, no obvious yellow sputum, fever, night sweats, chest pain and chest tightness, etc. External chest CT showed right lung shadow with multiple nodules in both lungs. Past smoking history was 20 pack years. After admission, the examination showed right supraclavicular lymph nodes and metastatic adenocarcinoma on puncture, brain MRI showed multiple small nodules and bone ECT suggested multiple bone metastases. On 2010-12-25 and 2011-1-15, he was given AP-T1-2 chemotherapy (rilpitide 900mg d1 and cisplatin 45mg d1-3). On 2011-2-8, he was readmitted to the hospital for chest CT (Figure 1), which indicated that the efficacy of PD was evaluated, and bone pain in the lumbosacral region appeared, so he started oral second-line treatment with Troche on 2011-02-11 and lumbosacral radiotherapy on 2011-02-15. On 2011-4-19, head and neck pain and discomfort appeared, and the local hospital gave symptomatic treatment such as pain relief, but the symptoms did not improve. 2011-4-23, the head and neck pain increased with blurred vision, delirium and other neuropsychiatric symptoms, and he was admitted to our ward on 2011-4-29. After admission, he was admitted to our ward on April 29, 2011 with the following examination: poor mental clarity, poor response, and poor cooperation in examination. He had a few dark red papules on the head and face, slightly tonic neck, decreased visual acuity with diplopia in both eyes, normal heart and lungs, muscle strength of both lower limbs grade 3, and no other significant abnormalities. Laboratory tests: blood routine and blood biochemistry were normal. Urgent examination of brain MR (Figure 3) suggested 1. bilateral parietal meningeal patchy high signal shadow, considering meningeal metastasis lesion. 2. multiple metastases in the original brain did not show significantly. Urgent investigation of the neck MR suggested that multiple lamellar abnormal signals were seen in the cervical and upper thoracic vertebral bodies, which were considered as bone metastases. Corrective diagnosis: right lung adenocarcinoma T4N3M1 (both lungs, bone, brain, meninges) – stage IV ECOG score 2 Treatment: After admission, symptomatic treatment with dexamethasone and mannitol for dehydration was given, and radiotherapy (both 30Gy/10Fx) was given to brain and cervical spine after consultation with radiotherapy department, and a neurologist from outside hospital was consulted to give symptomatic treatment with sedation, but the symptoms did not improve significantly after one week. It was suggested that the meningeal lesion had a tendency to progress. On the fifth day after admission, Trocaine was increased to 200 mg orally. On the third day of Trocaine dosing, the patient’s brain headache gradually relieved, his vision slightly recovered, and delirium and other psychiatric symptoms disappeared, but the patient’s skin toxicity simultaneously worsened to degree II, without obvious diarrhea. After the completion of radiotherapy, the treatment with Trocaine 200 mg was continued and the dose of dehydration and hormone was gradually weakened. The brain MR (Figure 5) was repeated half a month later, suggesting improvement of the meningeal lesions. After 1 month of treatment with Troche 200 mg, symptoms such as headache, neck pain and blurred vision basically disappeared, and muscle strength was normal. The patient was transferred to an outside hospital for surgical treatment because of the presence of both lumbar metastases and compression of spinal nerves with decreased muscle strength of both lower limbs. The etiology and mechanism of meningeal metastasis: Meningeal metastasis is a serious complication of malignant tumors, with different incidence in various types of tumors, about 5% of lung cancer. Meningeal metastasis is mostly hematogenous, mainly through the arterial, venous and lymphatic systems. Tumor cells from the primary site of lung cancer are shed into the blood circulation to reach the brain, and may stay and grow in the brain mainly at the junction of cortex and medulla or in the meninges. Cerebrospinal fluid metastasis can involve the soft meninges that surround the nerves, especially the nerves in the posterior cranial fossa. In addition, various causes including medical treatment and examination means, such as chemotherapy, surgery, radiotherapy or drugs can cause blood-brain barrier disruption, which is also the main cause of extracranial soft meningeal metastasis of malignant tumors. Once the blood-brain barrier is disrupted, meningeal metastasis can also occur rapidly. In this case, it is also possible that the brain tumor cells spread to the meninges on the basis of brain metastasis. 2. Clinical symptoms of meningeal metastasis: The clinical symptoms of meningeal metastasis are mainly intracranial hypertension syndrome, headache is the most common symptom, followed by nausea and vomiting respectively. Combined with the condition of this patient, i.e. an advanced lung cancer patient with multiple brain metastases, whose condition further deteriorated after two cycles of Lipitor combined with cisplatin chemotherapy, followed by second-line targeted therapy with Trocaine, after 2 months of treatment, intracranial hypertension symptoms such as headache and nausea emerged despite the improvement of systemic lesions, followed by neuropsychiatric symptoms such as insomnia, blurred vision and delirium, which generally conformed to These symptoms are generally consistent with the typical symptoms of meningeal metastasis of lung cancer. The most valuable diagnostic tool for meningeal metastasis is magnetic resonance imaging (MRI) of the brain. MRI plays an important role in the diagnosis of this disease, with the tumor having low and equal signal in T1W and high signal in T2W, and the sensitivity of enhanced scan T1W imaging is the highest. However, MRI also has false positives, such as MRI enhancement is often difficult to differentiate from inflammatory meningeal lesions, which should be combined with clinical manifestations and examination of cerebrospinal fluid properties or exfoliated cells. However, in clinical practice, the rate of positive shedding cells in the cerebrospinal fluid is about 30-50%, so even if the cytology of the cerebrospinal fluid is negative, the combination of the patient’s primary lung lesion, clinical symptoms and MRI manifestations of the brain can diagnose meningeal metastases. When MRI is temporarily unavailable, CT-enhanced scan of the brain can also show enhancement at the meningeal or metastatic lesions as a reference, but conventional plain CT scan has little diagnostic value for meningeal metastases. In this case, the patient’s meningeal metastases were not clearly identified by conventional plain scan MRI in the outside hospital, and the diagnosis of meningeal metastases from lung cancer was confirmed by enhanced MRI after entering our hospital. The prognosis of meningeal metastasis of lung cancer is not ideal, and without treatment, the median survival is about 4-6 weeks. Previous treatments for meningeal metastases include symptomatic treatment with dehydrating hormone, local radiation therapy, intrathecal therapy, systemic chemotherapy and targeted therapy. First of all, once intracranial symptoms appear in advanced lung cancer, symptomatic treatment such as dehydrating hormone can often be applied from the time of suspected meningeal metastases. If it is indeed a meningeal or brain metastasis, its effect of relieving intracranial hypertension for a short period of time is better, but it often needs to be used regularly. After clear identification of meningeal metastases, local radiotherapy can only relieve symptoms in some patients, but cannot treat metastases in the entire subarachnoid space, and thus has no significant effect for most patients, while whole-brain whole-spinal cord radiation therapy is prone to be accompanied by high mortality and severe myelosuppression, and is less commonly taken clinically. Intrathecal chemotherapy was once the main treatment method for meningeal metastases, and the routes of administration are via the ventricular Ommaya reservoir or via repeated lumbar puncture. However, the intrathecal administration of large doses of chemotherapeutic drugs several times can produce heavy neurological toxicity, and the inconvenience of operation, especially repeated lumbar puncture, is often one of the reasons for poor patient compliance. With the wide application of molecular targeted drugs, more and more studies have reported the successful treatment of brain metastases and meningeal metastases from lung cancer with epidermal growth factor receptor inhibitors (EGFR-TKI) such as Erythrosa and Troche, probably based on the smaller molecular weight of EGFR-TKI and its ability to cross the blood-brain barrier, the incidence of brain metastases in patients treated with EGFR-TKI is significantly lower than those treated with chemotherapy . Prospective clinical studies have shown intracranial remission rates of 10% and control rates of 27% for gefitinib alone in non-selective NSCLC multiple brain metastases, with remission rates of up to 73.9% for primary asymptomatic brain metastases in a predominant population (Asian, non-smoking, adenocarcinoma). However, there are some special features in this case, as the patient developed meningeal metastases on top of the apparent improvement of pulmonary and cerebral lesions after treatment with troche, and thus it is necessary to discuss what to do in the treatment of worsening cerebral lesions and the appearance of new lesions in the brain in the process of effective targeted therapy for pulmonary lesions and symptomatic remission. The conventional clinical wisdom has been that the appearance of both off-target lesions and significant progression of off-target lesions should be considered as overall lesion progression, reflecting failure of current therapy, and thus current therapy should be discontinued and replaced with a new treatment modality. However, recent reports have found that despite the small molecular weight of EGFR-TKI, the proportion of EGFR-TKI that actually crosses the blood-brain barrier is small, the concentration of troche in cerebrospinal fluid is less than 1/10 of that in serum, and the concentration of its active metabolites is about 1/2 of that in serum, and thus the progression of brain lesions is considered to be in insufficient concentration for treatment with this class of drugs and should not be considered as a failure of drug therapy, i.e., the formation of drug resistance, which is considered to be a target However, the current consensus is that Progressive Disease (PD) is not considered a failure of targeted therapy. The other is to increase the effective drug concentration in the cerebrospinal fluid to achieve the therapeutic effect. In this case, after the diagnosis of meningeal metastasis, the patient was given dehydration treatment and high-dose hormone treatment, and whole brain radiotherapy (30Gy/Fx) was given at the same time. On the 3rd day of radiotherapy, as the symptoms were still worsening, the dose of Trocaine was increased to 200mg. The skin toxicity was not further aggravated after symptomatic treatment was given. The patient’s symptoms improved further after the end of radiotherapy and 10 days of Trocaine dosing, and the subsequent brain MRI also indicated that the brain lesions had improved in absorption. Therefore, the treatment with Troche 200 mg was continued and the dehydration and hormone doses were gradually tapered. After 1 month of treatment with Troche 200 mg, the neurological symptoms basically disappeared. Since the patient also had lumbar metastasis and compression of the spinal nerve, the patient was transferred to an outside hospital for surgical treatment. In conclusion, this case is a typical patient with meningeal metastasis from lung cancer. The patient developed meningeal metastasis symptoms on the basis of effective systemic treatment with targeted therapy, and the patient’s meningeal lesions were once again controlled after continuing to increase the dose of targeted therapy drug (Trocaine). Therefore, increasing the dose of targeted therapy (Troche) to increase the effective drug concentration in the cerebrospinal fluid may be the ideal treatment for this group of patients.