急性炎癥性脫髓鞘性多發(fā)性神經(jīng)病

1、急性炎癥性脫髓鞘性多發(fā)性神經(jīng)病Acute Inflammatory Demyelinating Polyneuropathy, AIDP,浙江大學(xué)醫(yī)學(xué)院附屬第一醫(yī)院,Introduction,Landry -Landry's paralysis 1859Landry reported an acute, ascending, predominantly motor paralysis with respiratory fa

2、ilure, leading to deathGuillair-Barre 1916 2例 Guillain, Barre and strohl (1916) reported a benign polyneuritis with albuminocytologic dissociation in the CSF (raised concentration of CSF protein but a normal cell

3、count) 蛋白細(xì)胞分離是本病的特征,,,Guillain,Barre,Landry,Strohl,Introduction,In 1956, C Miller Fisher described a triad of acute ophthalmoplegia, ataxia, and areflexia, now known as Fisher’s syndromeDuring the past 15 years, GBS has

4、 become clear that this clinical picture, now called Guillain-Barré syndrome, and have different pathological subtypes,Epidemiology,Worldwide incidence0.6 -4/100 000 per year throughout the worldChina incidence0.

5、66 per 100 000 for all ages可發(fā)生于任何年齡，男女發(fā)病率相似，夏秋多見,臨床表現(xiàn)：中國,兒童和青少年，夏初。EMG：軸索損害， AMAN。EMG符合AMAN的為65％，符合AIDP的為24％。66％有CJ抗體，42％有GM1抗體，其他神經(jīng)節(jié)苷脂抗體為17－26％。與西方國家不同，GM1抗體與AMAN或AIDP無關(guān)。近來發(fā)現(xiàn)AMAN與GD1a抗體相關(guān)密切。,臨床表現(xiàn)：中國,病理：AMAN：IgG和補體在

6、軸索周圍沉積，巨噬細(xì)胞侵入軸索周圍間隙，嚴(yán)重者有軸索變性。AIDP：IgG和補體在髓鞘外沉積，巨噬細(xì)胞也在髓鞘外，“撕開”髓鞘。AMSAN：感覺軸索比運動軸索損害重。EMG不能預(yù)測病理。,Pathogenesis and Pathophysiology,The cause of this syndrome is unknown, but it is generally viewed to be an autoimmune resp

7、onse to a bacterial or viral infection.病因尚未完全闡明,Etiology,Campylobacter JejuniEpstein-Barr Virus (EBV) Cytomegalovirus (CMV)HIVVaccinations···········,空腸腸彎

8、曲菌,Pathogenesis and Pathophysiology,An acute immune-mediated polyneuropathy , component of pathogen was similar with myelin sheath of peripheral nerve與感染有關(guān)的自身免疫性疾病, 病原體某些成分與周圍神經(jīng)的髓鞘成分相似,Pathophysiology,主要病理特點(principal c

9、haracteristic of pathology )節(jié)段性脫髓鞘(segmental demyelization)小血管周圍炎性細(xì)胞浸潤,Clinical manifestations,多數(shù)患者有前驅(qū)癥狀(起病前1~3周）呼吸道感染癥狀喉痛、鼻塞、發(fā)熱消化道癥狀腹瀉、嘔吐,Clinical manifestations,Progressive ascending symmetrical weakness of th

10、e limbsInvolvement of proximal and distal musclesNumbness and tingling in the hands and feetBack pain,Clinical manifestations,Depressed or absent reflexesInvolvement of cranial nerves (facial nerves most commonly inv

11、olved)Respiratory failure(involved respiratory muscles)Progression to peak disability in 4 wkautonomic nerve symptom,Assessment,Cerebrospinal fluidIncreased protein usually after 7 to 10 days. While some protein is

12、 normally present, an increased amount without an increase in the number of white blood cells may indicate GBS蛋白細(xì)胞分離,Assessment,Nerve conduction velocity test Nerve conduction studies are a dependable and early diagnos

13、tic indicator of GBS. shows demyelization and damage to the nerve sheathF反應(yīng)、H反射異常 PL延長，NCV減慢 傳導(dǎo)阻滯現(xiàn)象，伴或不伴有波幅降低,Assessment,腓腸神經(jīng)活檢節(jié)段性脫髓鞘小血管周圍炎性細(xì)胞浸潤Electrocardiogram (EKG) May show abnormalities in cardiac rhythm心

14、律失常,Subtypes of GBS,經(jīng)典型 AIDPFisher綜合癥(Miller Fisher syndrome )：三聯(lián)征-“眼外肌麻痹、 共濟失調(diào)、腱反射消失”，還有中樞神經(jīng)系統(tǒng)損害 It was thought to be a variant of GBS and comprise complete ophthalmoplegia with ataxia and are flexia腦神經(jīng)型,Subtypes

15、of GBS,軸突型 純運動型（AMAN）運動 感覺 型 （AMSAN ）急性感覺性多發(fā)性神經(jīng)炎（ASP）急性全自主神經(jīng)病（APN）假性肌營養(yǎng)不良復(fù)發(fā)型,Diagnosis,Required for diagnosisProgressive weakness of one or more limbDistal areflexia with proximal areflexia or hyporeflexia,Di

16、agnosis,Supportive diagnosisProgression of symptoms over days to 4 wkRelative symmetry of deficits Mild sensory involvementCranial nerve involvement (especially VII)Recovery beginning within 4 wk,Diagnosis,Supportiv

17、e diagnosisAutonomic dysfunctionNo fever Increased CSF protein after 1 wkCSF white blood cell count ≤ 10/μLNerve conduction slowing or blocked by several weeks,Diagnosis,Against diagnosisSignificant asymmetric weak

18、nessBowel or bladder dysfunction at onset or persistentCSF white blood cell count > 50 or PMN count > 0μLWell-demarcated sensory level,Diagnosis,Excluding diagnosisIsolated sensory involvement, without weakness

19、Another polyneuropathy that explains clinical picture,Differential diagnosis,Acquired hypokalemiaBotulismMyasthenia gravisPeriodic paralysisPoliomyelitis,PolymyositisTick paralysisDiphtheriaTransverse myelitisHe

20、avy metal (lead and arsenic poisoning),Differential diagnosis,低鉀性周期性癱瘓(hypokalemic periodic paralysis)無病前感染史，常有發(fā)作史無感覺和腦神經(jīng)損害，腦脊液正常電解質(zhì)（血鉀<3.5)及心電圖檢查異常補鉀治療有效,Differential diagnosis,重癥肌無力(myasthenia gravis)骨骼肌 病態(tài)易疲勞性

21、、波動性no sensory symptoms tendon reflexes are unimpaired,Differential diagnosis,脊髓灰質(zhì)炎(poliomyelitis)早期出現(xiàn)括約肌功能障礙無感覺障礙 Fever, meningeal symptoms, early pleocytosis, and purely motor and usually asymmetrical areflex

22、ic paralysis.,Differential diagnosis,急性脊髓炎（acute myelitis）The immediate problem is to differentiate GBS from acute spinal cord disease (marked by sensorimotor paralysis below a level on the trunk and sphincteric paraly

23、sis).,Clinical management,General treatment 一般治療Immunotherapy 免疫治療,General treatment,保持呼吸道通暢輔助呼吸密切觀察，測肺活量20ml/kg→ICU必要時氣管插管，使用呼吸器預(yù)防呼吸道感染翻身、拍背、稀化痰液、吸痰,,General treatment,預(yù)防并發(fā)癥(prevention of complication)墜積性肺炎

24、褥瘡血栓性靜脈炎防止肢體攣縮尿路感染,General treatment,預(yù)防并發(fā)癥(prevention of complication)合理的正壓通氣、吸出分泌物經(jīng)常翻身，保持床單平整皮下應(yīng)用肝素有臨床指征時，應(yīng)用廣譜抗生素等,General treatment,對癥處理必要時心電監(jiān)護高血壓—小劑量β受體阻滯劑低血壓—補液心動過速—通常不需要治療心動過緩—阿托品疼痛—卡馬西平,Immunotherapy,機

25、理抑制免疫反應(yīng)，去除致病因子對神經(jīng)損害，使髓鞘有時間再生方法血漿置換靜脈注射免疫球蛋白皮質(zhì)醇激素治療,Plasma exchange,The usefulness of plasma exchange in the evolving phase of GBS.In patients who are treated within 2 weeks of onset, there is a reduction in the per

26、iod of hospitalization in the length of time that the patient requires mechanical ventilation. However, when plasma exchange is delayed for 2 weeks or longer after the onset of the disease, the procedure has, with a few

27、 notable exceptions, been of little value.,Plasma exchange,血漿置換機制：去除血漿中致病因子，可明顯縮短病程，使用越早，療效越好，專用設(shè)備，價格昂貴適用于急性進行性加重的GBS用法：40ml/kg禁忌癥：嚴(yán)重感染， 心律失常、心功能不全， 凝血功能障礙,Intravenous immunoglobulin,靜脈注射免疫球蛋白盡早施行用法：0.4g/(kg.d)&#

28、215;5天禁忌癥：免疫球蛋白過敏，先天性IgA缺乏 PE 和IVIG不必聯(lián)合應(yīng)用,Corticosteroids,皮質(zhì)類固醇 有爭議理論上合理研究表明無效經(jīng)驗：青年人大劑量早期使用,Corticosteroids,The value of corticosteroids in the treatment of GBS has been disputed for decades.Although corticost

29、eroids can no longer recommended as routine treatment for acute GBS.We have observed a few instances in which the intravenous administration with high-close corticosteroids seemingly halted the progress of the disease.,