急性炎症性脱髓鞘性多发性神经病急性炎症性脱髓鞘性多发性神经病Acute Inflammatory Demyelinating Acute Inflammatory Demyelinating

Polyneuropathy, AIDPPolyneuropathy, AIDP

浙江大学医学院附属第一医院 浙江大学医学院附属第一医院

罗本燕教授罗本燕教授

IntroductionIntroduction Landry Landry --Landry's paralysis 1859Landry's paralysis 1859

Landry reported Landry reported an acute, ascendingan acute, ascending,, predominantly predominantly

motor paralysis with respiratory failure, leading to deathmotor paralysis with respiratory failure, leading to death

Guillair-Barre 1916 2Guillair-Barre 1916 2 例 例 Guillain, Barre and Guillain, Barre and strohlstrohl (1916) reported a benign (1916) reported a benign

polyneuritis withpolyneuritis with albuminocytologic dissociation albuminocytologic dissociation

in the CSF (raised concentration of CSF in the CSF (raised concentration of CSF

protein but a normal cell count)protein but a normal cell count) 蛋白细胞分离蛋白细胞分离 是是

本病的特征本病的特征

Guillain

Barre

Landry

Strohl

IntroductionIntroduction

In 1956, C Miller Fisher described a triad In 1956, C Miller Fisher described a triad

of acute ophthalmoplegia, ataxia, and of acute ophthalmoplegia, ataxia, and

areflexia, now known as Fisher’s syndromeareflexia, now known as Fisher’s syndrome

During the past 15 years, GBS has become During the past 15 years, GBS has become

clear that this clinical picture, now called clear that this clinical picture, now called

Guillain-Barré syndrome, and have Guillain-Barré syndrome, and have

different pathological subtypes different pathological subtypes

EpidemiologyEpidemiology Worldwide incidenceWorldwide incidence

0.6 -4/100 000 per year throughout the 0.6 -4/100 000 per year throughout the

worldworld

China incidenceChina incidence

0.66 per 100 000 for all ages0.66 per 100 000 for all ages

可发生于任何年龄，男女发病率相似，夏秋多见可发生于任何年龄，男女发病率相似，夏秋多见

临床表现：中国 儿童和青少年，夏初。 EMG ：轴索损害， AMAN 。

EMG 符合 AMAN 的为 65 ％，符合 AIDP的为24％。

66％有CJ 抗体， 42 ％有 GM1 抗体，其他神经节苷脂抗体为 17－ 26 ％。与西方国家不同， GM1 抗体与 AMAN或 AIDP无关。近来发现 AMAN与GD1a抗体相关密切。

临床表现：中国 病理：

AMAN： IgG和补体在轴索周围沉积，巨噬细胞侵入轴索周围间隙，严重者有轴索变性。

AIDP： IgG和补体在髓鞘外沉积，巨噬细胞“ ”也在髓鞘外， 撕开 髓鞘。

AMSAN ：感觉轴索比运动轴索损害重。 EMG 不能预测病理。

Pathogenesis and Pathogenesis and PathophysiologyPathophysiology

The cause of this syndrome is The cause of this syndrome is

unknown, but it is generally viewed unknown, but it is generally viewed

to be an autoimmune response to a to be an autoimmune response to a

bacterial or viral infection.bacterial or viral infection.

病因尚未完全阐明病因尚未完全阐明

EtiologyEtiology

CCampylobacter ampylobacter JJejuniejuni

Epstein-Barr Virus Epstein-Barr Virus (EBV) (EBV) 

Cytomegalovirus Cytomegalovirus (CMV)(CMV)

HIVHIV

VaccinationsVaccinations

······················空肠肠弯曲菌

Pathogenesis and Pathogenesis and PathophysiologyPathophysiology

An acute immune-mediated polyneuropathy , An acute immune-mediated polyneuropathy ,

component of pathogen was similar with component of pathogen was similar with

myelin sheath of peripheral nervemyelin sheath of peripheral nerve

与感染有关的自身免疫性疾病与感染有关的自身免疫性疾病 ,, 病原体某些成分与周围神病原体某些成分与周围神

经的髓鞘成分相似经的髓鞘成分相似

PathophysiologyPathophysiology

主要病理特点主要病理特点 (principal characteristic (principal characteristic

of pathology )of pathology )

节段性脱髓鞘节段性脱髓鞘 (segmental (segmental

demyelization)demyelization)

小血管周围炎性细胞浸润小血管周围炎性细胞浸润

Clinical manifestationsClinical manifestations

多数患者有前驱症状多数患者有前驱症状 (( 起病前起病前 1~31~3 周）周）

呼吸道感染症状呼吸道感染症状 喉痛、鼻塞、发热喉痛、鼻塞、发热

消化道症状消化道症状 腹泻、呕吐腹泻、呕吐

Clinical manifestationsClinical manifestations

Progressive ascending symmetrical Progressive ascending symmetrical

weakness of the limbsweakness of the limbs

Involvement of proximal and distal musclesInvolvement of proximal and distal muscles

Numbness and tingling in the hands and Numbness and tingling in the hands and

feetfeet

Back painBack pain

Clinical manifestationsClinical manifestations

Depressed or absent reflexesDepressed or absent reflexes

Involvement of cranial nerves (facial nerves Involvement of cranial nerves (facial nerves

most commonly involved)most commonly involved)

Respiratory failure(involved respiratory Respiratory failure(involved respiratory

muscles)muscles)

Progression to peak disability in 4 wkProgression to peak disability in 4 wk

autonomic nerve symptom autonomic nerve symptom

AssessmentAssessment Cerebrospinal fluidCerebrospinal fluid

Increased protein usually after 7 to 10 days. Increased protein usually after 7 to 10 days.

While some protein is normally present, an While some protein is normally present, an

increased amount without an increase in increased amount without an increase in

the number of white blood cells may the number of white blood cells may

indicate GBSindicate GBS

蛋白细胞分离蛋白细胞分离

AssessmentAssessment Nerve conduction velocity testNerve conduction velocity test

Nerve conduction studies are a dependable Nerve conduction studies are a dependable

and early diagnostic indicator of GBS. and early diagnostic indicator of GBS.

shows demyelization and damage to the shows demyelization and damage to the

nerve sheathnerve sheath

FF 反应、反应、 HH反射异常 反射异常 PLPL 延长，延长， NCVNCV 减慢减慢

传导阻滞现象，伴或不伴有波幅降低传导阻滞现象，伴或不伴有波幅降低

AssessmentAssessment 腓肠神经活检腓肠神经活检

节段性脱髓鞘节段性脱髓鞘

小血管周围炎性细胞浸润小血管周围炎性细胞浸润

Electrocardiogram (EKG) Electrocardiogram (EKG)

May show abnormalities in cardiac rhythmMay show abnormalities in cardiac rhythm

心律失常心律失常

Subtypes of GBS Subtypes of GBS

经典型 经典型 AIDPAIDP

FisherFisher 综合症综合症 (Miller Fisher syndrome )(Miller Fisher syndrome ) ：： 三联征三联征 --““ 眼外肌麻痹眼外肌麻痹、 、 共济失调、腱反射消失”，共济失调、腱反射消失”，还还

有中枢神经系统损害 有中枢神经系统损害

It was thought to be a variant of GBS and comprise It was thought to be a variant of GBS and comprise

complete ophthalmoplegia with ataxia and are flexiacomplete ophthalmoplegia with ataxia and are flexia

脑神经型脑神经型

Subtypes of GBS Subtypes of GBS 轴突型 轴突型

纯运动型（纯运动型（ AMANAMAN ））

运动 感觉 型 （运动 感觉 型 （ AMSAN AMSAN ））

急性感觉性多发性神经炎（急性感觉性多发性神经炎（ ASPASP ））

急性全自主神经病（急性全自主神经病（ APNAPN ））

假性肌营养不良假性肌营养不良

复发型复发型

DiagnosisDiagnosis

Required for diagnosisRequired for diagnosis

Progressive weakness of one or more Progressive weakness of one or more

limblimb

Distal areflexia with proximal areflexia Distal areflexia with proximal areflexia

or hyporeflexiaor hyporeflexia

DiagnosisDiagnosis Supportive diagnosisSupportive diagnosis

Progression of symptoms over days to 4 wkProgression of symptoms over days to 4 wk

Relative symmetry of deficits Relative symmetry of deficits

Mild sensory involvementMild sensory involvement

Cranial nerve involvement (especially VII)Cranial nerve involvement (especially VII)

Recovery beginning within 4 wkRecovery beginning within 4 wk

DiagnosisDiagnosis

Supportive diagnosisSupportive diagnosis

Autonomic dysfunctionAutonomic dysfunction

No fever No fever

Increased CSF protein after 1 wkIncreased CSF protein after 1 wk

CSF white blood cell count ≤ 10/μLCSF white blood cell count ≤ 10/μL

Nerve conduction slowing or blocked by Nerve conduction slowing or blocked by

several weeksseveral weeks

DiagnosisDiagnosis Against diagnosisAgainst diagnosis

Significant asymmetric weaknessSignificant asymmetric weakness

Bowel or bladder dysfunction at onset or Bowel or bladder dysfunction at onset or

persistentpersistent

CSF white blood cell count > 50 or PMN CSF white blood cell count > 50 or PMN

count > 0μLcount > 0μL

Well-demarcated sensory levelWell-demarcated sensory level

DiagnosisDiagnosis

Excluding diagnosisExcluding diagnosis

Isolated sensory involvement, without Isolated sensory involvement, without

weaknessweakness

Another polyneuropathy that explains Another polyneuropathy that explains

clinical pictureclinical picture

Differential diagnosisDifferential diagnosis

Acquired Acquired

hypokalemiahypokalemia

BotulismBotulism

Myasthenia gravisMyasthenia gravis

Periodic paralysisPeriodic paralysis

PoliomyelitisPoliomyelitis

PolymyositisPolymyositis

Tick paralysisTick paralysis

DiphtheriaDiphtheria

Transverse myelitisTransverse myelitis

Heavy metal (lead Heavy metal (lead

and arsenic and arsenic

poisoning)poisoning)

Differential diagnosisDifferential diagnosis

低钾性周期性瘫痪低钾性周期性瘫痪 (h(hypokalemic ypokalemic

periodic paralysis)periodic paralysis)

无病前感染史，常有发作史无病前感染史，常有发作史

无感觉和脑神经损害，脑脊液正常无感觉和脑神经损害，脑脊液正常

电解质（血钾电解质（血钾 <3.5)<3.5) 及心电图检查异常及心电图检查异常

补钾治疗有效补钾治疗有效

Differential diagnosisDifferential diagnosis

重症肌无力重症肌无力 ((myasthenia gravis)myasthenia gravis)

骨骼肌骨骼肌 病态易疲劳性、波动性 病态易疲劳性、波动性

no sensory symptoms no sensory symptoms

tendon reflexes are unimpairedtendon reflexes are unimpaired

Differential diagnosisDifferential diagnosis

脊髓灰质炎脊髓灰质炎 (poliomyelitis)(poliomyelitis)

早期出现括约肌功能障碍早期出现括约肌功能障碍

无感觉障碍无感觉障碍

  Fever,Fever, meningeal symptoms, meningeal symptoms, early early

pleocytosis,pleocytosis, and and purely motorpurely motor and usually and usually

asymmetricalasymmetrical areflexic paralysis. areflexic paralysis.

Differential diagnosisDifferential diagnosis

急性脊髓炎（急性脊髓炎（ acute myelitisacute myelitis ）） The immediate problem is to differentiate GBS The immediate problem is to differentiate GBS

from acute spinal cord disease (from acute spinal cord disease (marked by marked by

sensorimotor paralysis below a level on the trunk sensorimotor paralysis below a level on the trunk

and sphincteric paralysis).and sphincteric paralysis).

Clinical managementClinical management

General treatment General treatment 一般治疗一般治疗

Immunotherapy Immunotherapy 免疫治疗免疫治疗

General treatmentGeneral treatment

保持呼吸道通畅保持呼吸道通畅

辅助呼吸辅助呼吸 密切观察，测肺活量密切观察，测肺活量 20ml/kg→ICU20ml/kg→ICU 必要时必要时

气管插管，使用呼吸器气管插管，使用呼吸器

预防呼吸道感染预防呼吸道感染

翻身、拍背、稀化痰液、吸痰翻身、拍背、稀化痰液、吸痰

General treatmentGeneral treatment

预防并发症预防并发症 (prevention of complication)(prevention of complication)

坠积性肺炎坠积性肺炎 褥疮褥疮 血栓性静脉炎血栓性静脉炎 防止肢体挛缩防止肢体挛缩 尿路感染尿路感染

General treatmentGeneral treatment

预防并发症预防并发症 (prevention of complication)(prevention of complication)

合理的正压通气、吸出分泌物合理的正压通气、吸出分泌物

经常翻身，保持床单平整经常翻身，保持床单平整

皮下应用肝素皮下应用肝素

有临床指征时，应用广谱抗生素等有临床指征时，应用广谱抗生素等

General treatmentGeneral treatment

对症处理对症处理 必要时心电监护必要时心电监护

高血压高血压——小剂量小剂量 ββ 受体阻滞剂受体阻滞剂

低血压低血压——补液补液

心动过速心动过速——通常不需要治疗通常不需要治疗

心动过缓心动过缓——阿托品阿托品

疼痛疼痛——卡马西平卡马西平

ImmunotherapyImmunotherapy

机理机理 抑制免疫反应，去除致病因子对神经损害，使髓鞘有抑制免疫反应，去除致病因子对神经损害，使髓鞘有

时间再生时间再生

方法方法 血浆置换血浆置换

静脉注射免疫球蛋白静脉注射免疫球蛋白

皮质醇激素治疗皮质醇激素治疗

Plasma exchangePlasma exchange The usefulness of plasma exchange The usefulness of plasma exchange in the evolving phase of in the evolving phase of

GBSGBS..

In patients who are treated In patients who are treated within 2 weeks of onsetwithin 2 weeks of onset, there is a , there is a

reduction in the period of hospitalization in the length of time reduction in the period of hospitalization in the length of time

that the patient requires mechanical ventilation. that the patient requires mechanical ventilation.

However, when plasma exchange is delayed However, when plasma exchange is delayed for 2 weeks or for 2 weeks or

longer after the onset of the diseaselonger after the onset of the disease, the procedure , the procedure has,has, with a with a

few notable exceptions, beenfew notable exceptions, been of little value. of little value.

Plasma exchangePlasma exchange

血浆置换血浆置换 机制：去除血浆中致病因子，可明显缩短病程，使用越早，疗效越机制：去除血浆中致病因子，可明显缩短病程，使用越早，疗效越

好，好，

专用设备，价格昂贵专用设备，价格昂贵

适用于急性进行性加重的适用于急性进行性加重的 GBSGBS

用法：用法： 40ml/kg40ml/kg

禁忌症：严重感染， 心律失常、心功能不全， 凝血功能障碍禁忌症：严重感染， 心律失常、心功能不全， 凝血功能障碍

Intravenous Intravenous immunoglobulinimmunoglobulin

静脉注射免疫球蛋白静脉注射免疫球蛋白 尽早施行尽早施行

用法：用法： 0.4g/(kg.d)×50.4g/(kg.d)×5 天天

禁忌症：免疫球蛋白过敏，先天性禁忌症：免疫球蛋白过敏，先天性 IgAIgA缺乏缺乏

PE PE 和和 IVIGIVIG 不必联合应用不必联合应用

CorticosteroidsCorticosteroids

皮质类固醇皮质类固醇

有争议有争议

理论上合理理论上合理

研究表明无效研究表明无效

经验：青年人大剂量早期使用经验：青年人大剂量早期使用

CorticosteroidsCorticosteroids

The value of corticosteroids in the treatment of GBS has been The value of corticosteroids in the treatment of GBS has been disputed for decades.disputed for decades.

Although corticosteroids can no longer recommended as Although corticosteroids can no longer recommended as

routine treatment for acute GBS.routine treatment for acute GBS.

We have observed a few instances in which the intravenous We have observed a few instances in which the intravenous

administration with high-close corticosteroids seemingly administration with high-close corticosteroids seemingly

halted the progress of the disease.halted the progress of the disease.

PrognosisPrognosis

PrognosisPrognosis

The majority of patients recover The majority of patients recover

completely or nearly completely completely or nearly completely

In about 10 percent of patients, the In about 10 percent of patients, the

residual disability is pronouncedresidual disability is pronounced

预后预后

80%80% 患者恢复完全患者恢复完全

死亡率大约死亡率大约 5%(5%( 呼吸肌麻痹呼吸肌麻痹 ))