神经梅毒的诊断治疗现状教学课件

1、Current situation of Neurosyphilis: Diagnosis and Treatment神经梅毒的诊断治疗现状Neurosyphilis: Diagnosis and Treatment神经梅毒：诊断及治疗Introduction简介:The manifestations of central nervous system(CNS) syphilis, readily recognized by physicians practing 3 or 4 decades ago梅毒在中枢神经系统的临床表现，真正引起临床医生的关注大约在30-40年前;This condi

2、tions are unfamiliar to many physicians today as a result of the relative rarity由于其疾病相对并不是那麽十分常见 ，对于大多数医生来讲，对本病的认识并不熟悉;There has been an increase in recent years in the incidence of acute syphilitic meningitis and increasing recognition of a wide variety of later forms of neurosyphilis,inclding pare

3、sis, gummas, ophthalmic disease ,and otologic complications近几年来，由于梅毒以及相关的神经梅毒的症状不断增加，甚至一系列晚期神经梅毒的不断出现，如脊髓痨、神经树胶肿、视神经、听神经的相关并发症，使得人们增加了对神经梅毒的关注。Classification of the Neurosyphilis神经梅毒的分类Early Neurosyphilis早期神经梅毒: 1) Asymptomatic无症状型; 2) Symptomatic症状型: A) Acute syphilitic meningitis急性梅毒性脑膜炎； B) Menin

4、govascular syphilis膜性血管梅毒: a) Cerebrovascular syphilis脑膜血管梅毒; b) Meningovascular syphilis of spinal cord脊髓膜血管梅毒Perenchymatous Neurosyphilis实质性神经梅毒: 1) General paresis系统性麻痹; 2) Tabes dorsalis脊髓痨Gummas of the nervous system神经系统树胶肿: 1) Cerebral gummas脑树胶肿; 2) Gumma of spinal cord脊髓树胶肿Asymptomatic无症状神经梅

5、毒Presence of abnormalities in the CSF 脑脊液有异常表现;Absence of other findings of neurologic disease 缺乏神经系统的临床症状;By definition,there are no clinical manifestations of asymptomatic neurosyphilis. 定义：脑脊液有异常表现，缺乏神经系统的临床症状的梅毒患者，定义为无症状神经梅毒。Asymptomatic无症状神经梅毒 Abnormalities in the CSF脑脊液异常的表现: 10-100 WBC/mm(all

6、 of which are lymphocytes)白细胞（主要是淋巴细胞）; a protein（蛋白） of 50-100mg/dl; a recative nontreponemal antibody test (VDRL) in the CSF(90%) 脑脊液非梅毒螺旋体抗体实验90%以上为阳性; blood serology (RPR) is nearly always positive. 血清非梅毒螺旋体抗体实验90%以上为阳性 Asymptomatic无症状神经梅毒Persistence of CSF abnormalities for more than 5 years af

7、ter infection(called late asymptomatic syphilis); 梅毒螺旋体感染后脑脊液持续5年出现异常，可定义为晚期无症状神经梅毒；The development of neurologic disease in up to 87%of patients. 该类晚期无症状神经梅毒中大约有87%可能发展为有症状神经梅毒。Symptomatic症状型神经梅毒Acute syphilitic meningitis 急性梅毒性脑膜炎Meningovascular syphilis: 脑膜血管性梅毒 Cerebrovascular syphilis; 大脑膜血管性梅毒

8、 Meningovascular syphilis of the spinal cord. 脊髓膜血管性梅毒。 Symptomatic症状型神经梅毒Acute syphilitic meningitis:急性梅毒性脑膜炎The incubation period in the majority of patients with syphilis meningitis is less than 1 years;大部分梅毒性脑膜炎患者的潜伏期在一年之内；25% of those patients meningitis is the first clinical manifestation of s

9、yphilis;大约有25%的梅毒性脑膜炎患者是以梅毒的首发症状出现的；A small percentage of patients(15%) still have a 2nd rash at the time of the meningitis.大约15%的患者在出现梅毒性脑膜炎的同时，仍然具有二期梅毒的皮肤损害。Acute syphilitic meningitis急性梅毒性脑膜炎Clinical manifestitations:临床表现Cranial nerve palsies (sense) in 40% of cases;大约40%的患者有颅神经麻痹（感觉障碍）The signs

10、of increased intracranial pressure; 部分患者可有颅内压增高的表现The involvement of cranial nerves(3rd, 6th,7th, 8th);多数可以累及3、6、7、8对颅神经Sensorineural deafness may occur in about 20% of patients.大约20%的患者可以出现感音神经性耳聋。Acute syphilitic meningitis急性梅毒性脑膜炎Clinical manifestitations:临床表现Acute syphilitic hydrocephalus was se

11、en in 1/3 of the cases of meningitis;大约1/3的梅毒性脑膜炎患者可出现梅毒性脑水肿；The principal symptoms and signs are those of increased intracranial pressure (stiff neck, confusion, delirium, papilledema);主要症状与体征是因为颅内压增高而引起的（颈部僵硬，意识丧失，谵妄等）；Syphilitic meningitis with cerebral changes accounts for of early neurosyphilis

12、;在早期神经性梅毒患者中大约有1/4具有梅毒性脑膜炎伴发大脑的改变Fever is only low grade or may be absent可有低度发热或无发热Acute syphilitic meningitis急性梅毒性脑膜炎Laboratory fingings;实验室检查The blood Wassermann reaction was +ve in 64%;大约64%的患者血清华氏曼反应阳性；RPR is +ve in most of cases of ASM;大部分血清非螺旋体实验阳性The CSF include:脑脊液异常表现包括： elevated pressure;颅

13、内压升高； mononuclear pleocytosis(10-200/1000-2000/mm);单个核白细胞升高(10-200/1000-2000/mm); elevated globulin level;球蛋白升高； modest reduction in glucose in 45% of cases;45%的患者葡萄糖中度下降； VDRL test is recative in most,not all cases.VDRL实验在大多数（不是所有的患者）患者为阳性Acute syphilitic meningitis急性梅毒性脑膜炎Laboratory fingings;实验室检查

14、Patient with isolated involvement of the 8th cranial nerve may has a normal CSF (VDRL -ve);仅有第八对脑神经受累的患者脑脊液可能是正常的Correlation between abnormal findings on auditory brainstem response and CSF was noted in of cases with 2nd or early latent syphilis;All of the other cases had normal neurological examina

15、tions.Acute syphilitic meningitis急性梅毒性脑膜炎Diagnosis and differential diagnosis:诊断与鉴别诊断ASM diagnosis ia based on:急性梅毒性脑膜炎基于以下证据： Clinical picture: 临床表现 Aseptic meningitis;化脓性脑膜炎 Lymphocytes response in the CSF;脑脊液中的淋巴细胞数量； Reactive blood and CSF serology.血请和脑脊液的非螺旋体实验The history:病史 Recent chancre;近期是否

16、有硬下疳； The secondary rash;有无继发性皮损； Generalized lymphadenopathy.全身淋巴结有无肿大；Meningitis may be the 1st clinical manifestitation of syphilitic infection.脑膜炎可能是部分患者的首发临床症状。Acute syphilitic meningitis机型梅毒性脑膜炎Differential diagnosis:鉴别诊断The various cause of a lymphocytic meningitis;排除其他淋巴性脑膜炎的可能Include包括 : en

17、terovirus 病毒, other spirochetes其他螺旋体 (Borrelia, Lyme disease); Mycobacteria分支杆菌; Fungi真菌 Mengingovascular syphilis脑膜血管性梅毒Cerebrovascular syphilis;大脑血管性梅毒Mengingovascular syphilis of spinal cord脊髓膜血管性梅毒Mengingovascular syphilis大脑膜血管性梅毒Cerebrovascular syphilis大脑膜血管梅毒: Vascular neurosyphilis may involv

18、e any part of the central nervous system; 有可能累及任何部位的中枢神经系统；The common denominator is infarction secondary to syphilitic endarteritis;常见的就是继发于梅毒性内膜炎的脑梗死；This disease usually occurs 5-12 years after infection;该症状出现在梅毒感染之后5-12年；Earlier than the occurrence of paresis and tabes;该症状的出现早与脊髓痨和神经麻痹；The most

19、of patients are 30-50 years old.大多数出现在30-50岁的患者。Cerebrovascular syphilis:大脑膜血管性梅毒The most common manifestations are:最常见的临床表现是： hemiparesis (senses)or hemiplegia(disable,83%); aphasia (eating 31%);seizures(14%).The onset of symptoms may be abrupt(suddenly);About 50% of patients have premonitory sympt

20、oms: Headache; Dizziness; Insomnia; Memory loss; Mood disturbancesCerebrovascular syphilis:脑膜血管性梅毒Laboratory findings实验室检查:Serum RPR is positive血清RPR阳性;The CSF VDRL test is positive in most, but not all cases.大多数患者脑脊液VDRL检测阳性；Angiographic changes include diffuse irregularity;脑血管图可能出现异常；Segmental dil

21、atation of the pericallosal artery;动脉出现节段性扩张；CT shows low-density areas with variable degrees;CT扫描可见不同程度的低密度区；MRI shows focal regions of high signal intensity. MRI扫描可见区域性高密度信号区。Cerebrovascular syphilis大脑膜血管性梅毒Diagnosis and differential diagnosis:诊断与鉴别诊断Diagnosis:诊断The possibillity of mengingovascula

22、r syphilis should be considered when:出现以下情况时可考虑脑膜血管梅毒的可能：Cerebrovascular accidents occur in a young adult年轻人出现的脑血管意外；without the usual risk factors( hypertension, embolic cardaic disease).排除其他常见的危险因素（高血压，心脑血管病）CSF serology is importantin making the diagnosis.脑脊液的非螺旋体实验检测有十分重要的意义。Cerebrovascular syph

23、ilis大脑膜血管性梅毒Differential diagnosis:鉴别诊断Includeing other causes of stroke syndromes such as:应排除以下其他原因引起的中风综合征Hypertension ( stroke);高血压（中风）Athero-sclerotic (high blood lipid) vascular disease;动脉硬化（高血脂）血管病；Cerebral emboli;脑血管异常；The various types of cerebral vasculitis;各种类型的脑血管炎；Angiographic changes in

24、 SLE;SLE患者的脑血管改变；Polyarteritis nodosa. 多发性动脉结节。 Meningovascular syphilis of the spinal cord脊髓膜血管性梅毒Meningovascular syphilis of the spinal cord consists of :脊髓膜血管梅毒包括以下不同疾病：Syphilitic meningomyelitis;梅毒性脊髓内膜炎；Spinal vascular syphilis.脊髓血管梅毒；Spinal syphilis has always been rare(3%);脊髓梅毒罕见（低于3%）It alwa

25、ys associated with cerebral involvement; butthe disease of the spinal cord may be preeminent.脊髓梅毒通常伴随大脑受累，但脊髓症状可能更为突出。Meningovascular syphilis of the spinal cord脊髓膜血管性梅毒Symptoms and signs:症状与体征The weakness of paraplegia of the legs;双下肢无力；Progressive to paraparesis(mild) or paraplegia(severe)双下肢进行性麻痹

26、或疼痛 wihch is asymmetrmic;多数表现为不对称；Urinary and fecal incontinence ;大小便失禁；Variable sensory disorders (pain and paraplegia) in the legs are prominent.双下肢的各种感觉异常（疼痛和麻痹）更明显。Meningovascular syphilis of the spinal cord脊髓膜血管性梅毒Symptoms and signs:症状与体征On the examinations:体检The legs are weak and spastic(stiff

27、);双下肢虚弱和僵硬；The deep tendon reflexes are hyperreactive;The ankle clonus is present;深肌腱反射过度，踝反射阳性Abdominal reflexes are abscent;腹壁反射消失；The most of senseory abnormalities are loss of position and vibratory sense in the lower extremities.双下肢最常见的感觉异常是位置和震动感觉消失；The classic manifestations are a transection

28、 of the spinal cord.大多数感觉异常呈节段性。Meningovascular syphilis of the spinal cord脊髓膜血管性梅毒Laboratory findings:实验室检查Blood serology tests are regularly positive;血清学检测通常为阳性；CSF tests discloses(showing) the same abormalities seenIn other forms of neurosyphilis;脑脊液检测与其他型的神经梅毒表现相同；CSF serology tests are positive

29、 in most of , not all cases脑脊液血清学检测大多数表现阳性。Meningovascular syphilis of the spinal cord脊髓膜血管性梅毒Diagnosis and differential diagnosis诊断与鉴别诊断Diagnosis:诊断The diagnosis is made on the clinical pictures of an abrupt flaccid (soft, slow) paraplegia developing in a patients with consistent CSF abnormalities

30、and reactive blood and CSF serologies在脑脊液持续性异常并伴有脑脊液血清学反应阳性，出现下肢缓慢的进行性麻痹的患者；Multiple sclerosis and subacute combined degeneration.脊髓出现多发性硬化和变性；Meningovascular syphilis of the spinal cord脊髓膜血管性梅毒Diagnosis and differential diagnosis诊断与鉴别诊断Differental diagnosis:鉴别诊断Multiple sclerosis and subacute combi

31、ned degeneration.脊髓多发性硬化和变性；Parenchymatous neurosyphilis实质性神经梅毒General paresis;麻痹Tabes dorsalis脊髓痨Parenchymatous neurosyphilis实质性神经梅毒General paresis;Early symptom: 早期症状 Irritablity (temper loss), memory loss, personal changes, impaired capacity to concentrate, carelessness in appearance, hadeache,in

32、somnia;易怒、记忆丧失、人格变化、注意力不易集中、表现淡漠、头痛、嗅觉减退；Late symptom: 晚期症状 Defective judgment, emotional lability (changeable) (depression,agitation,euphoria-joyful), lack of insight, confusion and disorientation, delusions of grandeur, paranoia (psychological problems),seizures. Parenchymatous neurosyphilis实质性神经梅

33、毒General paresis;Laboratory findings:实验室检查Nontreponemal serology tests of blood and CSF are nearly uniformly +ve in cases of paresis;脑脊液、血清非梅毒螺旋体实验阳性Other CSF findings are typical of those in neurosyphilis;脑脊液的其他改变与其他的神经梅毒表现一致；The CSF may be normal in a patients whose neurosyphilis has been arrested

34、 by treatment.经过治疗的神经梅毒患者脑脊液可能是正常的。Parenchymatous neurosyphilis实质性神经梅毒Diagnosis:诊断The diagnosis is based on the clinical pictures, which is readily recognizable in it full-blown (developement) form, together with characteristic spinal fluid abnormalities.诊断主要基于临床表现，脊柱神经系统不断加重的神经系统的症状，脑脊液的各种异常表现。Pare

35、nchymatous neurosyphilis实质性神经梅毒Differential diagnosis:鉴别诊断Cerebnral tumor;脑肿瘤；Subdural hematoma;血管瘤Cerebral arteriosclerosis;脑动脉硬化Alzheimers disease (Senil dementia);阿茨海默病（老年性痴呆）Multiple sclerosis;多发性硬化症；Chronic alcholism.慢性酒精中毒。Parenchymatous neurosyphilis实质性神经梅毒Tabes dorsalis脊髓痨Symptoms :症状Lightin

36、g;畏光Ataxia;Bladder disturbance;膀胱功能紊乱Parethesia;Visual loss (optic atrophy);视力减退（视神经萎缩）Rectal incontinence.大便失禁。Parenchymatous neurosyphilis实质性神经梅毒Signs:体征Pupillary abnomarlities; Argyll Roberstson pupil;瞳孔异常 阿罗月瞳孔Absent ankles jerks; Absent knee jerks;踝反射缺失 膝反射缺失Rombergs sign (close eye down); Impa

37、ired vibratory sense;罗伯戈征阳性 震动觉减退Impaired touch and pain sense; Impaired position;痛觉、触觉减退 位置觉减退Ocular palsies (sense); Charcots joint. 夏克氏关节Parenchymatous neurosyphilis实质性神经梅毒Laboratory fidingns:实验室检测The laboratory findings are variable;实验室检测结果是可变的Depand on: 基于以下因素1). The stage of tabes; 不同的疾病阶段 2).

38、 Whether partial or full treatment has been administered in the past; 以前有无不规则或规则的治疗。Parenchymatous neurosyphilis实质性神经梅毒Laboratory fidingns:实验室检测The CSF findings among patients with tabes are:脊髓痨患者脑脊液异常包括：1). Lymphocytic pleocytosis in 50%;50%以上患者淋巴细胞升高；2). Elevated protein concentration (45-100mg/dl

39、) in 50%;50%以上患者蛋白浓度升高(45-100mg/dl) ；3). Reactive nontreponemal serology of CSF (Wassermanns test) in 72%.72%的患者脑脊液非梅毒螺旋体抗体实验阳性。Parenchymatous neurosyphilis实质性神经梅毒Diagnosis and differential diagnosis:诊断和鉴别诊断A clinical diagnosis of tabes is most likely in a case with lighting pain, ataxia who exhibit

40、s findings of absent deep tendon reflexs, Argyll Robertson pupil and a +ve Rombergs sign.临床表现包括LIGHTING疼痛、抑郁、深部腱反射消失；阿罗月瞳孔，罗伯戈征阳性等症状对脊髓痨的诊断有重要的提示作用；Early and atypical case present greater problem in diagnosis;早期或不典型患者经常会被误诊；The results of serology tests and spinal fluid tests may lead to the correct

41、 diagnosis. 血清学、脑脊液检测结果对于确诊有重要价值。 Optic atrophy 视神经萎缩 It with the same ocular manisfestations as occurs in tabes;与脊髓痨的眼部表现相同；The disease may appear as an isolated manifestations of neuresyphilis;也有可能是神经梅毒唯一的临床表现；The usual symptoms are those of progressive visual loss Involving frist one eye and then

42、 the other;通常的症状是进行性视力减退，一般是单眼开始，再波及另一只眼；CSF abnormalities are most present in the untreated case;大多数未经治疗的患者脑脊液通常具有异常表现；Optic atrophy may also result from prior syphilitic optic neuritis;PG treatment can usually prevent further progression of visual loss.青霉素治疗通常可以阻止视力的进行性减退。Gummas of nervous system神

43、经系统树胶肿Cerabral gummas;脑树胶肿Gumma of spinal cord.脊髓树胶肿Gummas of nervous system神经系统树胶肿 Cerebral gummas:脑树胶肿This form of neurosyphilis is esceedingly rare;该型神经梅毒极为罕见；The presentation is that of a space occupying lesion;临床表现是大脑占位性病变的表现；The diagnosis may only be made when the patient is operated on for a

44、suspected intracranial mass lision;大部分确诊是可疑颅内肿块手术切除中发现的；Multiple ring-enhancing lesions may be found on CT or MRI examinations.CT、MRI检测可发现环状信号增强区。Gummas of nervous system神经系统树胶肿Gumma of the spinal cord:脊髓树胶肿It is fundamentally a granuloma of the meninges compressing the cord;主要表现为脊髓膜肉芽肿压迫脊索的表现The cl

45、inical picture is that of a cord tumor, root pain, spastic paraplegia, urinary and fecal incintinence and loss of sensation below the lesion.临床症状表现为脊索肿瘤、神经根疼痛、僵直麻痹、大小便失禁和损害以下感觉丧失；The progressive is subacute;呈亚急性病程；The CSF findings consist of dynamic block, markedly elevated protein (over 350mg/dl) a

46、nd a +ve nontreponemal serologic test.脑脊液检测表现为梗阻性的表现特征，蛋白明显升高（高于350mg/dl) ，非梅毒螺旋体抗体实验阳性。Current manifestations of neurosyphilisAtypical presentations不典型表现考虑神经梅毒的提示The following clinical manifestations should be considered the diagnosis of neurosyphilis:出现以下临床症状时应该考虑神经梅毒；1).Positive blood FTA-ABS ser

47、ology along with neurologic or ophthalmologic findings suggestive of neurosyphilis;血清FTA-ABS实验阳性，同时出现神经系统或视神经的异常表现；2). Unexplained neurological illness with positive blood & CSF FTA-ABS test & CSF showing more than 5 WBC/mm;无法解释的神经系统疾病，同时出现血清及脑脊液FTA-ABS阳性反应，脑脊液白细胞数5 个/mm以上;3). Positive FTA-ABS in bl

48、ood & in cases with progressive neurologic disease in whom other etiologic considerations had been excluded. 已经排除其他的相关疾病原因，具有进行性神经系统疾病的患者同时出现血清FTA-ABS实验阳性。 Antobiotic therapy for neurosyphilis神经梅毒的抗生素治疗The introduction of PG in the 1940s strikingly simplified the therapy & improved the outcome of ne

49、urosyphilis;上世纪40年代由于青霉素的使用，大大简化了对神经梅毒的治疗，也明显改善了预后；Recently reports were showed that a few cases in which benzathine or procaine PG in recommended dose failed to cure neurosyphilis;近几年来，有部分报告用推荐剂量的苄星青霉素和普鲁卡因青霉素治疗神经梅毒失败的个案；Those cases reports suggests that the failures represented early cases of neur

50、osyphilis in HIV infected persons.大多数治疗失败的个案与感染HIV相关。Antobiotic therapy for neurosyphilis神经梅毒的抗生素治疗As a result of those considerations, WHO & CDC of USA no longer recommend benzathine PG to treat neurosyphilis;基于多种因素，WHO和美国CDC不再考虑推荐苄星青霉素治疗神经梅毒The most recent recommendations of CDC are:美国CDC最近治疗方案如下；

51、1). IV aqueous PG 18-24 million daily for 10-14 days;静脉使用水剂青霉素1800-2400万治疗10-14天；2). IM procaine PG 2.4 million plus probenecid 500mg by mouth Qid for 10-14 days.肌注普鲁卡因青霉素240万，加口服丙磺舒500mg，10-14天。Antobiotic therapy for neurosyphilis神经梅毒的抗生素治疗Drug regimens for treatment of neurosyphilis:神经梅毒的药物治疗方案1).

52、 IV aqueous crystalline PG 18-24 million daily for 10-14 days(3-4 million every 4 hs),followed by benzathine PG 2.4 million IM weekly for 3 doses;静脉使用水剂青霉素1800-2400万，10-14天（每4小时300-400万），然后苄星青霉素240万肌注每周一次，再用三次。2). IM aqueous procaine PG 2.4million + probenecid 500mg by mouth Qid for 10-14 days, foll

53、owed by benzathine PG 2.4 million IM weekly for 3 doses.肌注水剂普鲁卡因青霉素240万加丙磺舒0。5每日四次口服10-14天；然后苄星青霉素240万肌注每周一次，再用三次。Note: For patients who are allergic to PG, the official recommendation isthat desensitization be undertaken;Althrough some experts recommend a 3 wks courses of ceftriaxone, 1 gm daily. 注

54、意事项：对青霉素过敏的患者，官方推荐使用脱敏治疗；也有专家推荐ceftriaxone每天一克，三周一个疗程的治疗方案。Follow-up随访Clinical (including CSF) examination should done 3 months after treatment and then at 6 months intervals, until the CSF findings return to normal;治疗后3个月随访一次（包括临床和脑脊液）然后半年1次，直到脑脊液恢复正常；Reevaluation should be performed annually for s

55、everal years;以后每年随访一次；In a minority of patients CSF abnormalities persist, patients whose WBC count and protein do not decline after 6 months are often retrated;对少数脑脊液持续异常，在治疗后半年白细胞和蛋白保持不下降着应重新治疗A true failure of therapy may rarely occur, in which an initial normalization of CSF findings is followed by replase, in such cases, repeate therapy needs to be given;完全的治疗失败并不常见，经过治疗脑脊液恢复正常后，如果出现异常表明为复发，这类患者应该再次治疗；If rela