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A 21-year-old right-handed Cambodian woman with no history of headache presented with 2 weeks of progressive bifrontal headache. She had no sick contacts or recent travel. She moved to the United States at age 3 years. She had no fever, nuchal rigidity, photophobia, phonophobia, nausea, or vomiting. She had a recent history of weightloss and palpitations. There was no tobacco or illicit drug use or high-risk sexual behavior. She was not pregnant and denied contraception use.
21岁女性患者，来自柬埔寨，为右利手，既往无头痛病史，近2周出现双侧前额部疼痛，进行性加重。近期无病患接触、外出旅游史。自3岁移居美国。患者无发热、颈强直、畏光、畏声或恶心呕吐。近期出现体重下降及心悸。既往无吸烟、使用非法物质及高危性行为史。患者无怀孕且否认正在避孕。
She had a nonfocal neurologic examination. CT head done to rule out acute intracranial pathology showed an abnormality that was followed up by MRI brain with and without contrast (figure 1).
患者体查无神经系统阳性定位体征。予行头颅CT检查以排除急性颅内病变，检查结果提示颅内存在一个异常病灶，遂予完善常规及增强MRI。
图1 头颅CT示右侧岛叶低密度病灶；头颅MRI示右侧岛叶弥散受限，FLAIR上也可见此处异常信号。 （A）头颅CT示右侧岛叶低密度（白色箭头）。（B）DWI和（C）ADC示右侧大脑中动脉供血区从右侧岛叶下白质延伸至右侧颞角的脑室周围白质弥散受限.（D）FLAIR也可见同部位的异常征象。
Question for consideration： 1. What are the differential diagnoses to consider? 2. How should we evaluate the patient next?
思考问题： 1． 该患者需考虑哪些鉴别诊断？ 2． 如何进行进一步评估？
The patient’s symptoms of headache and the findings on CT head led us to perform an MRI brain. Findings on MRI included restricted diffusion in the right subinsular white matter, extending to the periventricular white matter along the right temporal horn, inferior parietal lobe, and frontal temporal operculum, in the vascular territory of right middle cerebral artery, associated with minimal gyriform enhancement or leptomeningeal enhancement, most consistent with early infarcts. The differential diagnoses for new-onset headache in the setting of cerebral ischemia by imaging studies includes stroke, CNS vasculitis, reversible cerebral vasoconstriction syndrome, and less likely cerebral cortical venous thrombosis (MRI finding of infarct or hemorrhages typically in nonarterial distribution), meningitis (MRI finding of leptomeningeal enhancement), or encephalitis.
结合患者头痛症状和头颅CT检查结果，予完善头颅MRI 检查，结果示右侧岛叶下白质延伸至右侧颞角的脑室周围白质、顶叶下部及额颞岛盖部，即右侧大脑中动脉供血区弥散受限，伴有小的脑回样增强和软脑膜增强，高度提示早期脑梗死。结合新发头痛症状及影像学提示存在脑缺血，鉴别诊断包括：脑卒中、中枢神经系统血管炎、可逆性脑血管收缩综合征，及可能性较小的脑皮质静脉血栓形成（头颅MRI可见脑梗死或脑出血为典型的非动脉分布特征）、脑膜炎（头颅MRI可见软脑膜增强）及脑炎。
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; mitochondrial encephalopathy, lactic acidosis, and strokelike episodes; and Moyamoya syndrome should also be considered in young patients (＜45 years) presenting with strokelike symptoms. Septic emboli in endocarditis leading to septic angiitis should be considered in the appropriate clinical setting.1
在有卒中样症状的年轻患者（<>
The patient underwent lumbar puncture or further evaluation of a possible vasculitic process. CSF showed protein of 129.6 mg/dL, glucose of 17 mg/ dL, 153 leukocytes (62% neutrophils, 32% lymphocytes, and 6% monocytes), 50 erythrocytes, and a negative gram stain. CSF findings of elevated leukocytes with neutrophil predominance, low glucose levels, and elevated protein led us to believe she might have meningitis with vasculitis as a complication. Given the concern for meningitis, she was empirically started on IV antibiotics and acyclovir.
为明确血管炎的诊断，予患者行腰穿检查。脑脊液检查结果示蛋白为129.6 mg/dL，葡萄糖 17 mg/dL, 白细胞153个 (中性粒细胞62%, 淋巴细胞32%, 单核细胞6%), 红细胞50个，脑脊液涂片革兰染色阴性。脑脊液中有核细胞升高，以中性粒细胞为主，葡萄糖降低，蛋白升高。结合以上，我们考虑患者患有脑膜炎，并发血管炎。予患者经验性启用静脉抗生素及阿昔洛韦治疗。
Antibiotics should be initiated immediately even prior to obtaining CSF samples when bacterial meningitis is considered likely. Vancomycin and ceftriaxone are recommended to treat Streptococcus pneumoniae and Neisseria meningitides, the 2 most common pathogens in children and adults up to age 50 years. If there is concern for viral encephalitis, acyclovir should be initiated while awaiting herpes simplex virus PCR.2 Patients who received dexamethasone (10 mg every 6 hours for 4 days) 15–20 minutes prior to or with the first dose of antibiotics had a significant decrease in unfavorable outcomes.3
如果考虑为细菌性脑膜炎，应立即给予抗生素治疗，即使还未获取脑脊液标本。肺炎链球菌与脑膜炎奈瑟菌是儿童和50岁以内的成年人感染最常见的两种病原体，推荐使用万古霉素和头孢曲松进行治疗。如果考虑为病毒性脑炎，在等待单纯疱疹病毒PCR结果时应先给予阿昔洛韦治疗。在给予患者首剂抗生素前15-20分钟或同时给予地塞米松（10mg q6h 连用4天）可显著减少不良预后。
Our patient then developed acute left face and arm weakness. She underwent CT angiogram of head and neck to evaluate for vasculitis/craniocervical dissection. CT angiogram showed segmental narrowing of the right M1 segment of the middle cerebral artery (confirmed later on conventional angiogram) (figure 2A) and incidentally revealed cervical lymphadenopathy (figure 2B). This prompted further imaging in the form of CT thorax, which showed multiple lung nodules and axillary and mediastinal lymphadenopathy (figure 2C).
该患者突然出现左侧面部及上肢乏力，予行头颈部CTA 检查以明确是否存在血管炎或头颈部血管夹层。CTA示右侧大脑中动脉M1段节段性狭窄（随后被常规血管造影证实）（图2A），同时意外地发现患者存在颈部淋巴结病变（图2B）。予完善胸部CT检查，结果提示多发肺部结节、腋窝及纵膈淋巴结病变（图2C）。
图2 常规血管造影示右侧大脑中动脉M1段节段性狭窄；颈部和胸部CT可见淋巴结病变；头颅CT可见结核瘤。
（A）常规血管造影可见右侧大脑中动脉M1段节段性狭窄（白色箭头）以及其它供血区血管的狭窄和扩张，提示血管炎。（B） CT示双侧颈部淋巴结团块，最大的位于右侧锁骨上，大小1.7 ×1.8×4.9 cm（右上图：白色箭头）。（C）胸部CT示肺门淋巴结病变和散在的肺部结节。（D）头颅CT增强可见多个大小约为10-13mm、边缘增强的肿块, 位于前交通动脉、右侧大脑中动脉及右侧后交通动脉区域，提示结核瘤。可见软脑膜不规则增强，累及右侧大脑中动脉池和岛盖。
Question for consideration: 1. How does this incidental finding change the differential diagnosis? 2. What is the next step in management?
思考问题： 1. 这一意外发现为鉴别诊断带来哪些新方向？ 2. 下一步诊疗计划是什么？
The differential diagnoses given the findings of multiple lung nodules and cervical and mediastinal lymphadenopathy includes infection (mycobacterial, viral pneumonia, fungal), sarcoidosis, and less likely metastatic disease (thyroid, melanoma, choriocarcinoma, renal).
结合影像学提示的多发肺部结节及颈部和纵膈淋巴结病变，该患者应考虑以下鉴别诊断：感染（分枝杆菌感染、病毒性肺炎、真菌感染）、结节病及可能性较小的转移性疾病（甲状腺癌、黑色素瘤、绒毛膜癌、肾癌）。
The next step would be to obtain a lymph node biopsy. Pathology from right supraclavicular lymphnode showed acid-fast bacilli (AFB) on the AFB stain (figure e-1 on the Neurology? Web site at Neurology.org). Hematoxylin & eosin stain showed caseating granulomas consistent with the diagnosis of tuberculosis.
下一步应行淋巴结活检。从右锁骨上淋巴结获取病理标本，标本抗酸染色涂片结果为阳性（图e-1来自Neurology网站，网址为Neurology.org），苏木精-伊红染色可见干酪样坏死，提示结核病。
Repeat lumbar puncture showed neutrophilic pleocytosis again, which may be seen during the early phases of tuberculosis (TB) meningitis. Characteristic CSF findings of TB meningitis including lymphocytic pleocytosis (100–500 cells), elevated protein (50–100 mg/dL), and low glucose (<45mg l)="" can="" closely="" mimic="" bacterial="" meningitis="" during="" the="" acute="">4
再次予行腰椎穿刺检查，结果仍为中性粒细胞升高，这可见于结核性脑膜炎早期。典型的结核性脑膜炎的特点为淋巴细胞升高（100-500个）、蛋白升高（50–100mg/dL）及葡萄糖降低（<45>
The patient was empirically started on the 4-drug antitubercular regimen rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) along with vitamin B6 and IV dexamethasone to treat pulmonary and CNS tuberculosis.
经验性给予患者四联抗结核药物，包括利福平、异烟肼、吡嗪酰胺和乙胺丁醇（RIPE），并加用维生素B6及静注地塞米松治疗肺部和中枢神经系统结核病。
Among the antitubercular medications, isoniazid and pyrazinamide have excellent CNS penetration. Isoniazid and rifampin are administered for a total duration of 9–12 months for CNS tuberculosis; pyrazinamide and ethambutol are administered for 2 months at initiation of therapy.
抗结核药物中，异烟肼和吡嗪酰胺可很好地通过血脑屏障。异烟肼和利福平治疗中枢神经系统结核病的总疗程为9-12个月，吡嗪酰胺和乙胺丁醇用于起始治疗的前2个月。
On day 4, the patient was found to be lethargic and poorly responsive. There were no new neurologic deficits. Repeat CT head did not reveal any new changes. EKG showed polymorphic ventricular tachycardia consistent with Torsades de Pointes (figure e-2). Her baseline EKG had a prolonged QTc of 490 ms with sinus bradycardia and intermittent junctional rhythm.
第4天时，患者出现嗜睡和反应欠佳。无新发神经系统缺损症状。复查头颅CT较前无变化。心电图提示多形性室性心动过速，提示尖端扭转型室速（图e-2）。该患者心电图的校正QT间期延长至490ms，且出现窦性心动过缓与间歇性交界心律。
Question for consideration: 1. What are the potential causes for her cardiac dysrhythmia?
思考问题： 1. 患者出现心律失常可能的原因是什么？ Torsades de Pointes may be seen with electrolyte abnormalities—hypokalemia, hypomagnesemia, hypocalcemia; drugs—antiarrhythmic, antihistamine, antimicrobial, psychiatric drugs; genetic long QT syndromes; bradyarrhythmias; anorexia nervosa; and cerebrovascular diseases including subarachnoid hemorrhage and stroke.5
尖端扭转型室速可见于电解质代谢紊乱（如低钾、低镁、低钙血症）、药物因素（如抗心律失常药、抗组胺药、抗菌药物、精神类药物）、遗传性长QT综合征、缓慢性心律失常、神经性厌食症及脑血管病变（如蛛网膜下腔出血和脑卒中）等。
About 6% of patients die of sudden death of unknown cause within 30 days after an acute stroke. Brain injuries, especially subarachnoid hemorrhage and stroke, may cause an alteration in the autonomic nervous system that could then potentially lead to cardiac dysrhythmias and sudden cardiac death. EKG abnormalities include rhythm disturbances such as atrial fibrillation and ventricular arrhythmias. QT interval prolongation, ST segment, T-wave changes, and left axis deviation have also been observed. EKG changes occur due to involvement of limbic system, diffuse subcortical autonomic centers, and hypothalamus when a stroke affects then on dominant insular cortex (as in our patient).6
约6%的急性脑卒中患者在起病30天内出现不明原因猝死。脑部损伤，尤其是蛛网膜下腔出血和脑卒中，会引起自主神经系统改变，进而引起心律失常和心源性猝死。心电图检查异常包括节律紊乱（如心房颤动与室性心律失常）、QT间期延长、ST段、T波改变或电轴左偏。正如该患者，当脑卒中影响非优势半球岛叶皮质，累及边缘系统、弥漫性皮质下自主神经中枢及下丘脑时，可引起心电图的异常。
Our patient’s potassium levels were low (2.8 mmol/L), which was corrected. She had received a dose of haloperidol 24 hours prior, which can potentially prolong the QTc; this was stopped.
患者血钾曾低至2.8mmol/L，已予纠正。症状出现24小时前曾予患者使用一剂氟哌啶醇，此药可延长QT间期，已停用。
Despite all corrections, the patient continued to have ventricular arrhythmias, likely secondary to the nondominant insular stroke, and was placed on defibrillator and discharged on the 4-drug antitubercular regimen in a stable condition.
尽管以上紊乱已纠正，患者仍存在室性心律失常，考虑为继发于非优势半球岛叶卒中，予植入除颤器，随后患者病情稳定出院，继续服用四联抗结核药物。
She returned a week later with worsening headache, photophobia, and blurred vision.
1周后，患者因头痛加重、畏光、视物模糊再次来诊。
Question for consideration: 1. What are the potential causes of her new symptoms? 2. What do you identify on the CT head (figure 2D)?
思考问题： 1. 患者出现新症状的可能原因有哪些？ 2. 如何解读头颅CT（图2D）结果？ The potential causes for a patient with CNS tuberculosis and acute worsening of headache would include worsening tubercular meningitis or vasculitis, raised intracranial pressure secondary to hydrocephalus, or tuberculomas. TB vasculitic infarcts commonly occur in the caudate, genu of the internal capsule, and anterolateral thalamus, as compared to atherosclerotic infarcts, which tend to occur in the posterior limb of the internal capsule, lentiform nucleus, and the posterolateral thalamus.
中枢神经系统结核病的患者出现头痛急性加剧的可能原因包括结核性脑膜炎或血管炎进展、脑积水引起颅内压升高或结核瘤形成。结核性血管炎相关脑梗死通常发生在尾状核、内囊膝及丘脑前外侧。相比之下，动脉粥样硬化性脑梗死多倾向于出现在内囊后肢、豆状核以及丘脑后外侧。
CT head with contrast showed multiple tuberculomas. The patient was treatedwith broader spectrum antibiotic coverage including amikacin, moxifloxacin, and linezolid. Rapid geno type testing was negative for resistant disease. She was continued on 4-drug antitubercular therapy and moxifloxacin.
头颅CT增强提示多发结核瘤。给予患者更广谱的抗生素，包括阿米卡星、莫西沙星和利奈唑胺。耐药性疾病快速基因型检测试验结果为阴性。予患者继续使用同前四联抗结核药物和莫西沙星抗结核治疗。
The patient’s headache improved with IV opiates and she was discharged and enrolled into the Direct Observational Therapy program with the Department of Health. She remained symptom-free during subsequent evaluation.
予静脉使用阿片类药物后患者头痛缓解。出院后该患者加入卫生署的直接观察治疗项目，且在此后的随访中无诉不适。 Tuberculomas could occur in about 10% of patients with TB meningitis. Lesions may be solitary but are often multiple and typically have surrounding edema and ring enhancement. Tuberculomas could occur in the brain, spinal cord, or subdural, subarachnoid, or epidural space.7
大约10%的结核性脑膜炎患者可出现结核瘤。病灶可为单发，但常见为多发，典型常伴周围水肿和环形增强。结核瘤可出现于脑、脊髓、硬膜下腔、蛛网膜下腔和硬膜外腔。
Occurrence of tuberculomas despite being on 4-drug anti-TB regimen should raise suspicion of immune reconstitution inflammatory syndrome (IRIS). IRIS can unmask a subclinical infection or cause recurrence of a previously treated infection. Steroids are indicated for treatment of tuberculosis as well as for prevention of IRIS. Prolonged duration of treatment and slower tapering is recommended to avoid clinical deterioration.7,8
在接受四联抗结核药治疗时出现结核瘤，应警惕免疫重建炎症综合征（IRIS）可能。IRIS可使亚临床感染显现，或引起治疗后的感染再次复发。类固醇被认为既可用于结核病的治疗又可预防IRIS。推荐延长疗程及缓慢减量，以避免病情进展恶化。
CDC and prevention surveillance reports show that there has been a decrease in incidence of new TB cases reported in the United States, of 2.2% between 2013 and 2014. Over the last 10 years, this rate is the smallest decline. Foreign-born persons in the United States have a 13.4 times higher rate than US-born persons. Among the foreign-born, Asians have the largest number of TB cases, the rate being 28.5 times higher compared to non-Hispanic white rates among non-Hispanic blacks and Hispanics are about 8 times higher each.9
美国疾病预防控制中心和预防监测报告显示美国的结核病发病率有所下降，2013年至2014年为2.2%。这一下降幅度是在过去十年中是最小的。在国外出生的美国居民发病率比美国本土出生的居民高13.4倍。在国外出生的人中，亚洲人患结核病的人数最多，其结核病发病率比非西班牙裔白人高28.5倍。非西班牙裔黑人和西班牙裔的发病率比非西班牙裔白人高8倍。
TB is typically thought to be a disease of the tropics but does affect individuals in the United States. This case highlights the various manifestations of tuberculosis in a single patient—meningitis, vasculitis, and tuberculomas. This case also brings to light the effect of a lesion or stroke in the nondominant insular cortex on the autonomic nervous system.
通常，结核病被认为是一种热带地区的疾病，但现的确已波及美国。本病例提示在一个患有结核病的病人身上，可有多种临床表现——脑膜炎、血管炎及结核瘤。本病例也提示了非优势半球岛叶皮质的损伤或脑卒中对自主神经系统功能有影响。  全文终编辑：李会琪
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