《神经病学》（英文）课件13.Muscular Diseases

1、肌肉疾病 (Myopathies)Dep. of NeurologyThe 2nd Hospital Harbin Medical University进行性肌营养不良(progressive muscular dystrophy, PMD)概念病因及发病机制病理临床表现诊断及鉴别诊断治疗Progressive muscular distrophy (PMD) Definitioninherited myogenic gressive muscle wasting and weakness of variable distribution and severity.P

2、rogressive muscular distrophy (PMD)Introductionmode of inheritanceage at onsetdistribution of affected muscle presence or absence of pseudohypertrophyrate of progressionlong-term outlook Pseudohypertrophy: Duchenne and BeckerFacioscapulohumerallimb-girdle (Erb)DistalOculopharyngealOcularDuchenne mus

3、cular distrophy (DMD) Etiologyan X-linked recessive condition that affects predominantly male. caused by the absence or disruption of the protein dystrophin, the gene codes for which located at Xp21. The main function of the dystrophin complex is its structural role in maintaining sarcolemmal integr

4、ity during contraction.Duchenne muscular distrophy (DMD) Pathology免疫组化染色可见抗肌萎缩蛋白大量缺失，对诊断有决定性意义。Normal dystrophin Absent of dystrophinSymptoms is apparent by 4 years old, and patients are typically severely disabled by adolescence, with death occurring in the third decade. Toe walking, waddling gait,

5、 and inability to run are early symptoms. Weakness is most pronounced in the proximal upper extremities, but also affects the proximal lower extremities.Duchenne muscular distrophy (DMD) Clinical manifestations Winged scapulae are common. Pseudohypertrophy of the calves caused by fatty infiltration

6、of the muscle is common (90%). In attempt to rise to stand from a supine position, patients characteristically must use their arms to climb up their bodies (Gowers sign).Duchenne muscular distrophy (DMD) Clinical manifestations The heart is involved late in the course.Mental retardation is a frequen

7、t (1/3) accompaniment. EMG: myopathic (abundance of short, low-amplitude, polyphasic MUP) . Serum creatine phosphokinases (CPK) levels are exceptionally high (10 000U/L).Duchenne muscular distrophy (DMD) Clinical manifestations No definite treatment is available.some studies suggest that prednisone,

8、 1.5 mg/kg/d orally, may improve muscle strength in the short term (up to 6 months).Side-effects include weight gain, cushingoid appearance, and hirsutism.the long-term effects of prednisone in this disorder are uncertain. Duchenne muscular distrophy (DMD)TreatmentBecker muscular dystrophy (BMD)also

9、 X-linked condition, with similar pattern of weakness, but much milder course, to that observed in DMD. In contrast to DMD, dystropin levels in muscle are normal, but the protein is qualitatively altered.Becker muscular dystrophy (BMD)late onset (average age of 12 years), slow progression (duration

10、up to 25 years). Also the age at death are later. Few develops cardiacmyopathy.CPK levels are less strikingly elevated than in DMD. Facioscapulohumeral muscular dystrophyAn autosomal dominant disorder.The genetic defect is a rearrangement of a homeobox gene localized to 4q35. usually has its onset i

11、n adolescence, this is compatible with normal life span. The clinical severity of this condition is highly variable. Facioscapulohumeral muscular dystrophyWeakness is typically confined to the face, neck and shoulder girdle, but foot drop can occur. Winged scapulae are common. The heart is not invol

12、ved.EMG: myopathic.serum CPK levels are normal or only slightly elevated. Limb-Girdle muscular dystrophy (Erb)Previously a catchall designation that probably subsumed a variety of disorders.including undiagnosed cases of other dystrophies.inherited in autosomal recessive fashion. Sporadic cases are

13、not rare.Limb-Girdle muscular dystrophy (Erb)The disorder begins clinically between late childhood and early adulthood and progresses slowly.In contrast to DMD and BMD, the shoulder and pelvic girdle muscles are affected to a more nearly equal extent. Pseudohypertrophy is not common. The heart is no

14、t involved.EMG: myopathic.CPK levels are less elevated.Ocularpharyngeal muscular distrophyAn autosomal dominant disorder.found with increased frequency in certain geographic areas. begins in the third to fifth decades.ptosis, total external ophthalmoplegia, dysphagia, facial weakness, and dysarthria

15、. CPK is mildly elevated. Distal muscular dystrophyautosomal dominant dystrophy.typically presents after age 40, although onset maybe earlier and symptoms more severe in homozygotes. Small muscles of the hands and feet, wrist extensors, and the dorsiflexors of the foot are affected. The course is sl

16、owly progressive. Ocular muscular dystrophy Typically an autosomal dominant disorder, although recessive and sporadic cases also occur.Some cases are associated with deletions in mitochondrial DNA. Onset is usually before age 30 years. Ocular muscular dystrophy Ptosis is the early manifestations, bu

17、t progressive external ophthalmoplegia subsequently develops.facial weakness is also common, and subclinical involvement of limb muscles may occur. The course is slowly progressive. Congenital muscular dystrophyDevelops in infants.Generalized muscle weakness.possible joint deformities from shortenin

18、g of muscles. progresses very slowly.life span may be shortened.Paraspinal muscular dystrophysome of whom may have a family history of the disorder. develop after age of 40 in patients with either gender.Paraspinal muscular dystrophyProgressive paraspinal weakness. Back pain and a marked kyphosis ar

19、e characteristic. The CPK is mildly elevated. CT scans show fatty replacement of paraspinal muscles. Diagnosis and preventionFamily history, clinical features.Serum CK values.EMG.Muscle biopsy.Differential diagnosis.Carrier and prenatal diagnosis by DNA probe is sometimes available and can be acted

20、upon.（一）少年型近端型脊髓性肌萎缩症(Kugelberg-Welander进行性肌萎缩） 1.属常染色体显性和隐性遗传。 2.青少年起病，主要表现为四肢近端肌萎缩，对称性分布，貌似肌病，但有肌束震颤 (fasciculation)。 3.肌电图为神经原性损害，肌肉病理为群组性萎缩，符合失神经支配。因此可予鉴别。（二）慢性多发性肌炎 1无遗传病史，病情进展较急性多发性肌炎缓慢。 2血清肌酶正常或轻度升高 3肌肉病理改变符合肌炎的表现 4皮质类固醇的治疗效果较好周期性瘫痪 (periodic paralysis)概念病因及发病机制病理临床表现诊断及鉴别诊断防治DefinitionPeriod

21、ic paralysis is characterized by episodes of flaccid weakness or paralysis with alterations in serum potassium levels.among a group of disorders known as skeletal muscle channelopathies.according to which, they be divided to three groups:hypokalemic periodic paralysis hyperkalemic periodic paralysis

22、 normokalemic periodic paralysis Hypokalemic periodic paralysis Etiologyan autosomal dominant condition.a mutation on chromosome 1q32 encoding dihydropyridine receptor a-1 subunit.affect a L-type calcium channel (CACNL1A3).Hypokalemic periodic paralysis Etiologythe weakness results from an abnormali

23、ty of muscle membrane excitability. in contrast to the reaction of normal muscle fibers, an increased influx of potassium causes the muscle fibers to become depolarized and inexcitable.Hypokalemic periodic paralysis PathologyVacuoles:空泡由肌浆网和横管系统扩张形成。Hypokalemic periodic paralysis Clinical manifestat

24、ioninfancy to 30 years.on awakening, after exercises or a heavy meal.may last for several days. severe generalized weakness with periods of paralysis affecting arms, legs and neck. Strength is normal between attacks.sometimes associated with thyrotoxicosis. Hypokalemic periodic paralysis Investigati

25、onsLow levels of the plasma potassium.altered levels of T3, T4, TSH in some patients. abnormal ECG:典型的低钾性改变，U波出现，P-R间期、Q-T间期延长，S-T段下降等。Hypokalemic periodic paralysisDiagnosis and differential diagnosis 根据发作过程，临床征象和实验室检查可做出诊断，有家族史者更不难诊断。 散发病例除甲亢外，需排除其他可反复引起血钾降低的疾病，原发性醛固酮增多症、肾小管碱中毒、应用噻嗪类利尿剂、皮质类固醇等。Hyp

26、okalemic periodic paralysis Prevention and treatmentHigh potassium and low natrium diet.Acetazolamide or oral potassium supplements often prevent attacks.ongoing attacks may be absorbed by potassium chloride given orally or intravenously. 感染性肌炎 (Inflammatory myopathies )Polymyositis (PM) Dermotomyos

27、itis (DM)Mitochondril myopathiesDefinitionPolymyositis and dermatomyositis are characterized by destruction of muscle fibers and inflammatory infiltrations of muscles. EtiologyPM is a cell mediated autoimmune disease.DM is a humoral factor (antibody and complement) mediated autoimmune disease.Pathol

28、ogyMuscle biopsy: muscle fiber necrosis and infiltration with inflammatory cells.Skin changes in DM.Clinical manifestationsInitiates sub-acutely.present in the fourth to fifth decade.female affected more than gresses at variable rate.weakness and wasting, especially of the proximal limb and

29、girdle muscles.Pain and tenderness may also occur.Clinical manifestationsoften associated with muscle pain, tenderness, dysphagia, and respiratory difficulties.Raynauds phenomenon, arthralgia, malaise, weight loss, and a low-grade fever round out the clinical picture.associated with various autoimmu

30、ne disorders, including scleroderma, lupus, erythematosus, rheumatoid arthritis, and Sjogrens syndrome.there is a definite correlation between DM and cancer ( 40j). Investigationraised erythrocyte sedimentation rate (ESR).serum CPK is generally elevated.EMG, myopathic. Muscular biopsy.autoantibodies

31、, e.g. antinuclear Abs, rheumatoid factor etc. (25%).Diagnosis and differential diagnosis数周-数月内逐渐出现对称性近端肌无力，伴肌痛、关节痛，无感觉障碍，腱反射不减低。CPK等肌酶增高.EMG：肌源性损害. Muscular biopsy.with or without other autoimmune diseases and/or pernicious tumors.TreatmentTreatment with anti-inflammatory drugs. Prednisone is commo

32、nly used in an initial dose of 60-80 mg/d, along with potassium supplements and frequent antacids if necessary. As improvement occurs and serum CPK decline, the dose is gradually tapered to maintenance levels that usually ranges between 10 and 20 mg/d. TreatmentPatients may need to continue this reg

33、imen for 2-3 years, however; too rapid reduction in dose may lead to relapse. Cytotoxic drugs such as azathioprine have also been used, either alone or along with corticosteriods. TreatmentMethotrexate may be useful in corticosteriod-resistant patients. Physical therapy may help to prevent contractu

34、res and hasten the recovery.Myotonic disordersMyotonic dystrophy, MDCongenital myotoniaMyotonic dystrophy Definition myotonia describes delayed relaxation of muscles after contraction, or persistent contraction after percussion of the belly of a muscle, which leads to apparent muscle stiffness. EtiologyMyotonic distrophyMyotonia congenitadominant inheriteddominant traitThe gene defect is an expanded trinucleotide (CTG) repeat in a gene localized to 19q13.3.a mutation on chromosome 7.Myotonic dystrophy Clinical manifestationmanifest in the third or fourth decade.myotonia