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1、TUBERCULOUS MENINGITIS结核性脑膜炎结核性脑膜炎Longnan Hospital ChenjingTuberculous meningitis is an infection of the membranes 膜膜covering the brain and spinal cord (meninges).Tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis结核分枝杆菌结核分枝杆菌 and is annually responsible for nearly two million de
2、aths worldwide. A third of the worlds population is currently infected with the TB bacillus, and more than eight million new cases are diagnosed each year.Tuberculous meningitis must be considered in patients who present with a confusional state, especially if there is a history of pulmonary tubercu
3、losis, alcoholism, corticosteroid treatment, HIV infection, or other condition associated with impaired immune responses. It should also be considered in patients form areas (eg, Asia, Africa) or groups (eg, the homeless and inner-city drug users) with a high incidence of tuberculosis.CausesRisk fac
4、tors include a history of: AIDS Excessive alcohol use Pulmonary tuberculosis Weakened immune systemPathogenesis & Pathology发病发病机制机制&病理病理Tuberculous meningitis usually results from reactivation of latent infection with mycobacterium tuberculosis.结核性脑膜炎多是由于潜伏的结核杆菌复结核性脑膜炎多是由于潜伏的结核杆菌复发感染引起的。发感染引起的。Prima
5、ry infection, typically acquired by inhaling bacillus containing droplets, may be associated with metastatic dissemination of blood-borne bacilli from the lungs to the meninges and surface of the brain.Here the organisms remain in a dormant state in tubercles that can rupture into the subarachnoid s
6、pace at a later time, resulting in tuberculous meningitis. 原发性感染，尤其是通过吸入含菌颗粒引起的感染，可原发性感染，尤其是通过吸入含菌颗粒引起的感染，可能与血源性细菌从肺部到脑膜及大脑表面的播散有关。能与血源性细菌从肺部到脑膜及大脑表面的播散有关。此处的致病菌在结核结节中处于休眠状态，后期可破入此处的致病菌在结核结节中处于休眠状态，后期可破入蛛网膜下腔，并导致结核菌性脑膜炎。蛛网膜下腔，并导致结核菌性脑膜炎。主要发现是含有大量单核细胞的脑基底部脑膜分泌主要发现是含有大量单核细胞的脑基底部脑膜分泌物。脑膜及脑表面可见结核结节。物。脑膜
7、及脑表面可见结核结节。The main finding is a basal meningeal exudate渗出物渗出物containing primarily mononuclear cells. Tubercles may be seen on the meninges and surfaces of the brain. The ventricle may be enlarged as a result of hydrocephalus, and their surfaces may show ependymal exudate or granular ependymitis.Art
8、eritis can result in cerebral infarction, and basal inflammation and fibrosis can compress cranial nerves.脑积水可引起脑室扩大，并且脑室表面可有大量脑积水可引起脑室扩大，并且脑室表面可有大量室管膜渗出物或颗粒状室管膜炎。室管膜渗出物或颗粒状室管膜炎。动脉炎可导致脑梗塞，而颅底部炎症反应和纤维动脉炎可导致脑梗塞，而颅底部炎症反应和纤维化可压迫神经。化可压迫神经。Acute tuberculous meningitis with marked involvement of the vessel
9、 walls and occlusion of smaller vessels. The vascular involvement can result in infarction. Clinical Findings A. SYMPTOMSSymptoms have usually been present for less than 4 weeks at the time of presentation and include fever, lethargy昏睡昏睡 or confusion, and headache. Weight loss, vomiting, neck stiffn
10、ess, visual impairment, diplopia 复视复视, focal weakness, and seizures may also occur. A history of contact with known cases of tuberculosis is usually absent.B.SIGNSFever, signs of meningeal irritation脑脑膜刺激征膜刺激征, and a confusional state are the most common findings on physical examination, but all may
11、 be absent. Papilledema视乳头水肿视乳头水肿, ocular palsies眼肌麻痹眼肌麻痹, and hemiparesis轻偏瘫轻偏瘫 are sometimes seen. Complications include spinal subarachnoid block脊髓蛛网膜下腔梗阻脊髓蛛网膜下腔梗阻, hydrocephalus脑积水脑积水, brain edema脑脑水肿水肿, cranial never palsies颅神经麻痹颅神经麻痹, and stroke caused by vasculitis or compression of blood ves
12、sels at the base of the brain因血管炎或颅底血管受压因血管炎或颅底血管受压导致的卒中导致的卒中.结核球结核球strokehydrocephalusLaboratory Findings Only one-half to two-third of patients show a positive skin test for tuberculosis or evidence of active or healed tubercular infection on chest x-ray. CSFThe diagnosis is established by CSF ana
13、lysis. CSF pressure is usually increased, and the fluid is typically clear and colorless but may form a clot upon standing. Lymphocytic and mononuclear cell pleocytosis of 50-500 cells/mL is most often seen, but polymorphonuclear 多形多形核细胞核细胞pleocytosis can occur early and may give an erroneous impres
14、sion of bacterial meningitis. CSF protein is usually more than 100 mg/dL, particularly in patients with spinal subarachnoid block. The glucose level is usually decreased and may be less than 20 mg/dL. Acid-fast smears抗酸染色涂片抗酸染色涂片 of CSF should be performed in all cases of suspected tuberculous menin
15、gitis , but they are positive in only a minority of cases. Definitive diagnosis is most often made by culturing M tuberculosis from the CSF, a process that usually takes several weeks and requires large quantities of spinal fluid for maximum yield. The polymerase chain reaction (PCR) 聚合酶链反应聚合酶链反应 ha
16、s also been used for diagnosis. Finally, the CT scan may show contrast enhancement of the basal cisterns and cortical meninges, or hydrocephalus.MRI appearance of the typical pattern of central nervous system tuberculous meningitisDifferential DiagnosisMany other conditions can a subacute confusiona
17、l state with mononuclear cell单核细胞单核细胞 pleocytosis 脑脊液细胞增多脑脊液细胞增多, including syphilitic 梅毒的梅毒的, fungal, neoplastic 肿瘤的肿瘤的, and partially treated bacterial meningitis. These can be diagnosed by appropriate smears 涂涂片片, cultures, and serologic 血清学的血清学的 and cytologic examinations 细胞学检细胞学检查查.TreatmentTre
18、atment should be started as early as possible; it should not be withheld while awaiting culture results. The decision to treat is based on the CSF findings described above; lymphocytic pleocytosis and decreased glucose are particularly suggestive, even if acid-fast smears are negative.综合治疗：综合治疗：药物治疗
19、药物治疗、 全身支持全身支持 、并发症的预防、并发症的预防 、耐药与多耐药、耐药与多耐药TB菌感染的治疗、菌感染的治疗、 对症治疗。对症治疗。药药物治疗原则物治疗原则：早期、联合、足量、长期、顿服：早期、联合、足量、长期、顿服DRUGSFour drugs are used for initial therapy, until culture and susceptibility test results are known. 四联治疗四联治疗isoniazid, 异烟肼异烟肼 300mg; rifampin, 利福平利福平 600mg;pyrazinamide, 吡嗪酰胺吡嗪酰胺 25mg/
20、kg; ethambutol, 乙胺丁醇乙胺丁醇 15mg/kg,each given orally once daily.For susceptible strains, ethambutol乙胺丁醇乙胺丁醇can be discontinued, and triple therapy continued for 2 months, followed by 4-10 months of treatment with isoniazid异烟肼异烟肼and rifampin利福平利福平alone. Pyridoxine,维生素维生素B6 50mg/d, can be used to decrea
21、se the likelihood可能性可能性of isoniazid-induced polyneuropathy. Side effect of drugsComplications of therapy include ：hepatic 肝脏的肝脏的dysfunction (isoniazid异烟肼异烟肼, rifampin利福平利福平, and pyrazinamide吡嗪酰胺吡嗪酰胺 )polyneuropathy多神经炎多神经炎 (isoniazid)optic neuritis (ethambutol乙胺丁醇乙胺丁醇)seizures (isoniazid)ototoxicity
22、 耳毒性耳毒性(streptomycin链霉素链霉素)CorticosteroidsPrednisone 泼尼松泼尼松60mg/d orally in adults or 1-3 mg/kg/d orally in children, tapered gradually over 3-4 weeksCorticosteroids are indicated as adjunctive 辅助的辅助的therapy in patients with spinal subarachnoid block.They may also be indicated in seriously ill patie
23、nts with focal neurologic signs or with increased intracranial pressure from cerebral edema. The risk of using corticosteroids may be high, however especially if tuberculous meningitis has been mistakenly diagnosed in a patient with fungal meningitis. Therefore, if fungal meningitis has not been exc
24、luded, antifungal therapy should be added along with corticosteroids.PrognosisEven with appropriate treatment, about one-third of patients with tuberculous meningitis succumb死死. Coma at the time of presentation is the most significant predictor of a poor prognosis.Cerebral Cysticercosis脑囊虫病脑囊虫病Cysti
25、cercosis is common in Mexico, Central and South America, western and southern Africa, India, China, and southeast Asia.The disease follows ingestion of larvae 幼虫幼虫 of the pork tapeworm (taenia solium-猪肉绦虫猪肉绦虫) and affects the brain in 60-90% of cases.Pathology病理上典型的包囊大小为病理上典型的包囊大小为510mm，可有薄壁，可有薄壁，或呈
26、多个囊腔，内有囊尾蚴。囊虫的囊尾蚴囊肿或呈多个囊腔，内有囊尾蚴。囊虫的囊尾蚴囊肿常为圆形或卵圆形，内膜上有一小白色的囊虫结常为圆形或卵圆形，内膜上有一小白色的囊虫结节突起。当虫体死亡或液化时，囊腔内为暗褐色节突起。当虫体死亡或液化时，囊腔内为暗褐色混浊液体，内含大量蛋白质、当虫体液化被吸收混浊液体，内含大量蛋白质、当虫体液化被吸收后囊腔变小，囊壁增厚，囊虫死后常发生钙化。后囊腔变小，囊壁增厚，囊虫死后常发生钙化。 Clinical FindingLarvae undergo hematogenous 血源血源性性dissemination, forming cysts囊肿囊肿 in the b
27、rain, ventricles脑室脑室, and subarachnoid space. Neurologic manifestations of cysticercosis result from 1. the mass effect占位效应占位效应 of intraparenchymal脑实质脑实质内内 cysts2. obstruction of CSF flow by intraventricular cysts3. inflammation that cause basilar meningitis. They include seizures, headache, focal n
28、eurologic signs, hydrocephalus脑积脑积水水, myelopathy脊髓脊髓病病, and subacute meningitis. Peripheral blood eosinophilia 嗜酸性嗜酸性细细胞增多症胞增多症, soft tissue calcifications钙钙化化, or parasites寄生虫寄生虫 in the stool 粪便粪便suggest the diagnosis. Laboratory Findings The CSF typically shows a lymphocytic pleocytosis (100 cells
29、/mL), with eosinophils嗜酸细胞嗜酸细胞usually present. Opening pressure is often increased but may be decreased with spinal subarachnoid block; if this is suspected myelography椎管椎管造影术造影术should be performed. Protein is increased to 50-100mg/dL, and glucose is 20-50mg/dL in most cases. Complement fixation 补补体
30、体结结合合 and hemagglutination红红血球凝聚血球凝聚 studies can assist in the diagnosis. The CT scan or MRI may show contrast-enhanced mass lesions with surrounding edema, intracerebral calcifications, or ventricular enlargement. MRI活动期：活动期：T1加权像囊虫呈圆形低信号，头节呈点加权像囊虫呈圆形低信号，头节呈点 状或逗点状高信号，状或逗点状高信号，T2加权像囊虫呈圆形高信号，加权像囊虫呈圆
31、形高信号，头节呈点状低信号。头节呈点状低信号。退变死亡期：退变死亡期：T1加权像水肿区低信号内有高信号加权像水肿区低信号内有高信号环或结节，或仅有低信号区；环或结节，或仅有低信号区；T2加权像水肿区高加权像水肿区高信号，内有低信号环或结节。信号，内有低信号环或结节。非活动期：非活动期：T1T2加权像上多呈圆形低信号。加权像上多呈圆形低信号。混杂期：混杂期：T1T2加权像上均呈混杂密度病灶。加权像上均呈混杂密度病灶。 Vesicular囊状的 colloidal胶体的 granular颗粒状的 calcified钙化的 Axial brain MRI. a T1-W, b T2-W, c FLA
32、IR and d contrast-enhanced T1-W sequences. Images reveal innumerable cysts in bilateral basal ganglia (arrows in a and b) and cerebral hemispheres, giving the “starry-sky” pattern. A few lesions demonstrate perifocal oedema and ring-enhancement (arrows in c and d) suggestive of the colloid vesicular
33、 stageMRI. Sagittal brain T2-W images show cysticerci in the extra-orbital muscles (arrow) (a) and tongue (arrows) (b) as well as in the cranial and cervical muscles. c Sagittal spine T2-W image reveals hyperintense lesions in nearly every paraspinal muscle (arrows) TreatmentThe indications of treat
34、ment of cerebral cysticercosis are controversial有争论的有争论的. However, patients with symptomatic neurologic involvement (usually seizures) and either meningitis or one or more noncalcified非钙化的非钙化的intraparenchymal cysts should be treated. Intraventricular, subarachnoid, and racemose cysts respond poorly
35、to treatmentCalcified cysts do not require treatment. Albendazole, 阿苯达唑阿苯达唑15mg/kg/d in three doses taken with meals, and continued for 8 days, is the preferred therapy. Praziquantel, 吡喹酮吡喹酮50mg/kg/d in three divided doses, can also be used, but blood levels are reduced by anticonvulsants 抗惊厥药抗惊厥药an
36、d corticosteroids皮质类固醇皮质类固醇, which are often required in these patients. Patients with seizures should also receive anticonvulsants. Corticosteroids are indicated for increased intracranial pressure or lesions near the cerebral aqueduct中脑导中脑导水管水管or intraventricular foramina室间孔室间孔; these may progress to cause obstructive hydrocephalus梗阻性脑积水梗阻性脑积水. Single accessible intraparenchymal 脑实脑实质内质内lesions can be removed surgically, and shunting分流术分流术 is required for intraventricular lesions causing hydrocephalus.
