1、执教教师：XXXMuscular diseasesMyasthenia gravis Definition:Myasthenia gravis is caused by a defect of neuromuscular transmission due to an antibody-mediated attack upon nicotinic acetylcholine receptors(AChR).Clinical Character:Fluctuating weakness Improved by inhibitors of cholinesterase Etiology and Pa
2、thogenesis Related to destructive effects of autoantibodies to AChR Evidence:1.Experimental immunization of animals with purified AChR from an electric fish,induces high titers of antibody to the receptor.2.Human serum antibodies that react with human AChR were found in MG patients 3.Electrophysiolo
3、gic features of MG were produced by passive transfer of human IgG to mice.4.Plasmapheresis reduced plasma levels of anti-AChR and ameliorated myasthenic symptoms and signs.How the autoimmune disorder starts is not known.In human MG,hyperplasia of the thymus about 15%of cases is a thymoma.AChR antibo
4、dies are synthesized by B cell of hyperplastic thymus gland.When human myasthenic thymus was transplanted into mice,the animal produced antibodies to AChR that bound to their own motor end-plates.A.Primarily in the thymus.1.70%of thymus gland from adult MG patients are not involuted.2.The thymus wei
5、gh more than normal.3.The thymus glands show lymphoid hyperplasia.4.Immunocytochemical:germinal centers contain B cells,plasma cells,and T cells.Pathology 5.10%of myasthenic thymus glands contain thymomas.B.Loss of synaptic folds and widened clefts C.Some nerve terminals are smaller than normal.D.On
6、 residual synaptic folds show Y-shaped antibody-like structures,IgG.Clinical features 1.Incidence:0.4/100,000.Prevalence:5/100,000.Before age 40,Male:female 3:1 2.Symptoms:Three clinical characteristics.1)The fluctuating nature:The weakness varies in a single day;day to day;or over longer periods.(r
7、emissions or exacerbations).Crisis:When an exacerbation involves respiratory muscles 2)The distribution of weakness:A.Ocular muscles are affected first in about 40%of the cases(Ptosis and diplopia).B.Affected facial oropharyngeal muscles(dysarthria,dysphagia and limination of facial movements).C.Lim
8、b and neck weakness.Crisis:occur in:oropharyngeal respiratory muscle weakness.provoked by:respiratory infection surgical procedures emotional stress systemic illness 3).The third characteristic is the clinical response to cholinergic drugs.This occurs so uniformly that it has become part of the defi
9、nition.3.Signs:(1)The vital signs and general physical examination are normal limits,unless the patient is in crisis.(2)Weakness of the facial and levator palpabrae muscles produces a characteristic expressionless faces with drooping eyelids.(3).Complete ophthalmoplegia in one or both eyes(diplopia)
10、.The pupil is never involved.(4).Weakness of oropharyngeal or limb muscles,and respiratory muscle.(5).Sensation is normal and the reflexes are preserved.1.Classification:(1)Group1.About 14%of patients have ocular myasthenia only.(2)Group IIA.Mild generalized myasthenia with ocular signs.(3)Group IIB
11、.Moderately severe generalized myasthenia,with mild bulbar and ocular involvement.(4)Group III.Acute severe myasthenia,with bulbar and respiratory complications.Tracheostomy is required.(5)Group IV.Late severe myasthenia,usually developing from other groups within 2 years.1.Routine examinations of b
12、lood,urine,and CSF are normal.2.EMG:90%patients have progressive decrement in the amplitude of muscle action potentials evoked by repetitive nerve stimulation at 3 to 5 Hz.Laboratory tests 3.AchR Antibodies to are found in 90%of patients of all ages.The titer dose not match the severity of symptoms.
13、4.CT scans of the mediastinum demonstrates thymomas,especially in those older than 40.Diagnosis 1.Characteristic history and physical examination.2.Jolly test 3.Edrophonium(Tension)tests.4.Neostigmine test:0.04 mg/kg,IM,reaches its maximum activity in 1-2 hours.The effect is gone at 3-4 hours.5.EMG.
14、6.Antiboties to AchR test.7.CT scans of thymus.Hyperplasia or thymoma.Differential diagnosis:1.Botulism:presynaptic blocker of acetylcholine release caused by contaminate foods progressive muscle weakness Beginning:extraocular pharyngeal muscles Treatment:trivalent antitoxin guanidine hydrochloride
15、2.Lambert-Eaton syndrome(LEMS):Myasthenia-like syndrome occurs with carcinoma Generalized muscle weakness The EMG is helpful in differentiating the syndrome from true myasthenia gravis.Treatment with removal of the tumor and guanidine hydrochloride.Treatment1.Anticholinesterase therapy:Anticholinest
16、erase drug should be given as soon as the diagnosis is made.i.Pyridostigmine 60 mg qid ii.Neostigmine bromide 15 mg qid iii.If the patients have difficulty eating,doses can be taken about 30 minutes before a meal.2.Corticosteroid therapy(1).High-dose coticosteroid therapy1).Prednisone,60-100mgdaily.
17、Improvement begins at about 12 days.2).Dexamethasone,20 mg daily IV for 10 days.3).Prednisonon methel,480-1000mg daily IV for 3-5 days.(2).Low-dose corticosteroid therapy:prednisone 25 mg,qod,gradually increasing the dosage by 12.5 mg every week until the total dosage reaches 100 mg on alternate day
18、s.3.Immunotherapy(1).Azathioprine,50-100 mg,twice a day.(2).Cyclophophamide 100 mg,twice a day.3.Thymectomy:About 80%of patients without thymoma become asymptomatic or go to complete remission after thymectomy.4.Plasmapheresis:To remove the harmful antibody.6.Treatment of crisis(1).Myasthenic crisis
19、:need assisted ventilation about 10%of myasthenic patients occur,occur in patients with dysarthria,dysphagia,respiratory muscle weakness,respiratory infection,and major surgery caused by less anticholinesterase drugs dosage.(2).Cholinergic crisis:over dosage of anticholineserase drugs cholinergic si
20、de effects,excessive anticholinesterase therapy.(3).Brittle crisis:Chronic anticholinergic drugs damages the synapse,some patients become refractory to the medication.Crisis is an emergency.The patients respiratory function must be maintained same as respiratory failure treatment Cholinergic drug di
21、scontinued in a few days or weeks.The therapeutic goal is to maintain vital functions and to avoid or treat infection.3.Drugs of avoided Drugs that have mild neuromuscular blocking effects and sedatives,are contraindicated.Quinine,Quinidine,Procainamide,Propranolol,Lidocaine,Aminoglycoside antibioti
22、cs,Polymyxin,Viomycin,Colistin,Morphine,Bubiurates,and other tranquilizers.8.Among the treatment,anticholinesterase grug therapy and plasmapheresis are symptomatic treatments thymectomy,steroids,and other immunosuppressive drugs may alter the course of the disease.Periodic paralysis characterized bo
23、uts of limb weakness.some forms have been mapped to the gene for the apha subunit of the sodium channel of muscle regard as“channelopathies.”The two main types were first separated by the level of serum potassium.Hypokalemic periodic Paralysis The potassium content decreases in a spontaneous attack
24、to values of 3.0 mEq/L or lower.Attacks may be induced:injecton of insulin,or glucose,ingestion of a meal high in carbohydrates.Incidence:Male:female,3:1 autosomedominant heredity The first attack usually occurs at puberty,but it may occur as the age of 4 or delayed to the sixth decade.Symptoms and
25、Signs:attack usually begins after rest.It commonly develops during the night paralysis varies from slight weakness of the leg to complete paralysis The oropharyngeal and respiratory muscles are usually spared.There may be retention of urine and feces during a severe attack.Attack varies from a few h
26、ours to 24 hours.The interval between attacks may be one year,or one or more attacks may occur daily.Weakness is especially be present on the morning after the ingestion of a high-carbohydrate meal before retiring on the previous night.Interval between attacks,patients are strong and serum potassium
27、 normal.In a mild attack,tendon reflexes and electrical reactions are diminished .In severe attacks,tendon and cutaneous reflexes are absent and muscles do not respond to electrical stimulation.Cutaneous sensation is not disturbed.Fatalities are rare,but death may occur from respiratory paralysis.Di
28、agnosis:transient attacks of weakness.confirmed by finding low potassium,high sodium content in the serum during an attack,or by inducing an attack with IV glucose(100 g)and regular insulin(20 units).Treatment 1.Acute attacks,rapidly terminated by ingestion of 20 to 100 mEq of potassium salts.The ba
29、sis of therapy is oral administration of acetazolamide,250 to1000 mg daily.This regimen prevents attacks in about 90%2.spironolactone promote retention potassium.Patients with thyrotoxic periodic paralysis are spontaneous or induced attacks during the period of hyperthyroidism.Glucose and insulin ar
30、e useful in the interim between treatment of hyperthyroidism by drugs or radioiodine,before the euthyroid state returns.Hyperkalemic Periodic Paralysis Characterized onset before age 10 attacks to occur in the daytime and to be shorter and less severe Myotonia is demonstrable by EMG Myotonic lid-lag
31、 is the sole clinical evidence of the trait.The serum and urinary potassium content may be increased during an attack,this may be due to leakage of potassium from muscle.The attacks tend to be precipitated by hunger,rest,and cold and by administration of potassium choride.A t t a c k s m a y b e t e
32、 r m i n a t e d b y administration of calcium gluconate,glucose,and insulin.Acetazolamide,250 mg to 1000 mg daily,has been effective in reducing the number of attacks or in abolishing them altogether.Progressive Muscular Dystrophies Definition:A muscular dystrophy has five essential characteristics
33、.1.defined by clinical,histologic,and EMG criteria.No signs of denervation or sensory loss,unless there is a concommitant and separate disease.2.symptoms include limb or cranial muscle weakness.(The heart and visceral muscles may also be involved.)3.Symptoms become progressively worse.4.Histologic c
34、hanges imply degeneration and regeneration of muscle,but no abnormal storage of metabolic product is evident.5.This disease is recognized as heritable,even if there are no other cases in the particular family.Classification.There are four main types:Duchenne muscular dystrophy(DMD)Facioscapulohumera
35、l muscular dystrophy(FSHD)limb-girdle muscular dystrophy(LGMD)myotonic muscular dystrophy Each type differs from the others in age at onset,distribution of weakness,rate of progression,presence or absence of calf hypertrophy,high serum levels of CK,and pattern of inheritance.Laboratory Diagnosis EMG
36、 muscle biopsy DNA analysis Serum CK ECG Duchenne Muscular Dystrophy X-linked recessive trait.Female carry the gene are carriers.incidence is 1 in 3,500 male births.no geographic,ethnic variation.one third are new mutations;life span of DMD is shortened,about 20-30y.prevalence is less(1 to 18,000 ma
37、les).Clinical Features 1.Evident at birth if serum enzymes are measured.2.The symptoms do not begin until age 3 to 5 years,but that may be a measure in infants.3.Walking delayed and the boys never run normally;Soon toe-walking and wadding gait.4.Progresses,overt difficulty walking,climbing stairs,an
38、d rising from chairs.5.An exaggerated lordosis is assumed to balance.6.The boys tend to fall easily,and they have difficulty rising from the ground.(Gowers sign)7.As the disease progresses:the arms and hands are affected swallowing,ocular movements are spared Iliotibial contractures limit hip flexio
39、n heel cord contractures cause toe-walking 8.At age 9-12,the boy no longer walks and enters a wheelchair;scoliosis may become serious;contribute to disability.9.By about age 20,respiration is compromised and mechanical ventilation is needed.10.heart is spared clinically,but ECG is abnormal:increased
40、 R-S amplitude,and deep,narrow Q waves.congestive failure may supervene in a few cases.gastrointestinal system is spared but acute gastric dilatation in a few cases.Mental retardation affect about one third of boys with DMD.Becker Muscular Dystrophy(BMD)resembles DMD in essential characteristics:X-l
41、inked,calf hypertrophy,weakness is greatest proximally,and serum CK levels are high.EMG and muscle histology are same.The two difference are age at onset(usually after age 12)and rate of progression (still walking after age 20,often later).Diagnosis 1.The clinical diagnosis of DMD is evident from cl
42、inical features.In sporadic,atypical cases,spinal muscular atrophy might be mistake for DMD fasciculation and EMG denervation,identify the neurogenic disorder.2.Serum CK level of DMD and BMD are usually at least 20 times normal 3.Dystrophin gene and protein analysis can make the correct diagnosis.Tr
43、eatment There is no specific drug therapy for DMD and BMD.Prednisone therapy was better than placebo in controlled trials.Bracing may prevent scoliosis in wheelchair-bound patients.Surgical correction of spinal and limb deformities to maintain ambulation as long as possible.Facioscapulohumeral(FSH)M
44、uscular Dystrophy autosomal dominant fashion.characteristic distribution of weakness:the face is always affected.Progression is slow;even be asymptomatic.Onset in adolesence,occasionally detected in children.Serum enzyme levels are normal.FSHD gene maps to 4q35-qter.Clinical Manifestations 1.Facial
45、weakness,Patients have never been able to whistle or blow up a balloon.2.Scapular winging is prominent.3.The shoulder girdle has a characteristic appearance.can not raise the arms laterally to shoulder level.4.Weakness in the legs may affect proximal muscles.Laboratory studies:EMG and muscle biopsy
46、show a myopathic pattern.The histologic changes are mild.Serum enzyme values are usually normal or trivially elevated.ECG is normal.Diagnosis:According to the clinical features,autosomal dominant fashion,serum CK level,and EMG.Management:Treatment is symptomatic.Limb-Girdle Muscular Dystrophy(LGMD)L
47、GMD is a myopathic syndromes of proximal limb weakness that are usually slowly progressive.Clinical manifestations1.Onset in adolescence or adult,and inheritance:autosomal dominant or recessive.2.The legs are usually affected first,with difficulty climbing stairs and rising from chairs.3.A wadding g
48、ait.rising the arms difficult,and winging of the scapula 4.Knee jerks tend to lost before the ankle jerks.Cranial muscles are usually spared.Progression is slow.5.EMG and muscle biopsy show myopathic changes.Serum CK may be elevated but less so than in DMD.Diagnosis:According to the clinical features and exclusion to include syndromes that did not meet criteria for DMD,FSHD,or myotonic categorise.Management:Treatment is symptomatic.谢谢观看请指导
