Progressive muscular distrophy (PMD) D efinition inherited myogenic disorders. progressive muscle wasting and weakness of variable distribution and severity.
Progressive muscular distrophy (PMD) I ntroduction 1. mode of inheritance 2. age at onset 3. distribution of affected muscle 4. presence or absence of pseudohypertrophy 5. rate of progression 6. long-term outlook Pseudohypertrophy: Duchenne and Becker Facioscapulohumeral limb-girdle (Erb) Distal Oculopharyngeal Ocular
Duchenne muscular distrophy (DMD) E tiology an 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 X p21. The main function of the dystrophin complex is its structural role in maintaining sarcolemmal integrity during contraction.
Duchenne muscular distrophy (DMD) P athology 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 dystrophinNormal dystrophin Absent of dystrophinAbsent of dystrophin
Symptoms 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, 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) C linical manifestations
Winged scapulae are common. Winged scapulae Pseudohypertrophy of the calves caused by fatty infiltration of the muscle is common (90%). Pseudohypertrophy In attempt to rise to stand from a supine position, patients characteristically must use their arms to climb up their bodies (Gower's sign). Duchenne muscular distrophy (DMD) C linical manifestations
The heart is involved late in the course. Mental retardation is a frequent (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) C linical manifestations
No definite treatment is available. some studies suggest that prednisone, 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) T reatment
Becker muscular dystrophy (BMD) also 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 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 dystrophy An autosomal dominant disorder. The genetic defect is a rearrangement of a homeobox gene localized to 4 q35. usually has its onset in adolescence, this is compatible with normal life span. The clinical severity of this condition is highly variable.
Facioscapulohumeral muscular dystrophy Weakness is typically confined to the face, neck and shoulder girdle, but foot drop can occur. Winged scapulae are common. The heart is not involved. 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 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 not involved. EMG: myopathic. CPK levels are less elevated.
Ocularpharyngeal muscular distrophy An 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. CPK is mildly elevated.
Distal muscular dystrophy autosomal 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 slowly 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, but 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 dystrophy Develops in infants. Generalized muscle weakness. possible joint deformities from shortening of muscles. progresses very slowly. life span may be shortened.
Paraspinal muscular dystrophy some of whom may have a family history of the disorder. develop after age of 40 in patients with either gender.
Paraspinal muscular dystrophy Progressive paraspinal weakness. Back pain and a marked kyphosis are characteristic. The CPK is mildly elevated. CT scans show fatty replacement of paraspinal muscles.
D iagnosis and prevention Family 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 upon.
Definition Periodic 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 normokalemic periodic paralysis
Hypokalemic periodic paralysis E tiology an autosomal dominant condition. a mutation on chromosome 1q32 encoding dihydropyridine receptor -1 subunit. affect a L-type calcium channel (CACNL1A3).
Hypokalemic periodic paralysis E tiology the weakness results from an abnormality 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 P athology Vacuoles: 空泡由肌浆网和横管系 统扩张形成。
Hypokalemic periodic paralysis C linical manifestation infancy 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 I nvestigations Low 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 paralysis D iagnosis 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。
Hypokalemic periodic paralysis P revention and treatment High 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.
Definition Polymyositis and dermatomyositis are characterized by destruction of muscle fibers and inflammatory infiltrations of muscles.
Etiology PM is a cell mediated autoimmune disease. DM is a humoral factor (antibody and complement) mediated autoimmune disease.
Pathology Muscle biopsy: muscle fiber necrosis and infiltration with inflammatory cells. Skin changes in DM.
Clinical manifestations Initiates sub-acutely. present in the fourth to fifth decade. female affected more than male. progresses at variable rate. weakness and wasting, especially of the proximal limb and girdle muscles. Pain and tenderness may also occur.
Clinical manifestations often associated with muscle pain, tenderness, dysphagia, and respiratory difficulties. Raynaud’s phenomenon, arthralgia, malaise, weight loss, and a low-grade fever round out the clinical picture. associated with various autoimmune disorders, including scleroderma, lupus, erythematosus, rheumatoid arthritis, and Sjogren’s syndrome. there is a definite correlation between DM and cancer (> 40j).
Investigation raised erythrocyte sedimentation rate (ESR). serum CPK is generally elevated. EMG, myopathic. Muscular biopsy. autoantibodies, 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.
Treatment Treatment with anti-inflammatory drugs. Prednisone is commonly 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.
Treatment Patients may need to continue this regimen 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.
Treatment Methotrexate may be useful in corticosteriod-resistant patients. Physical therapy may help to prevent contractures and hasten the recovery.
Myotonic dystrophy D efinition 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.
E tiology Myotonic distrophyMyotonia congenita dominant inheriteddominant trait The gene defect is an expanded trinucleotide (CTG) repeat in a gene localized to 19q13.3. a mutation on chromosome 7.
Myotonic dystrophy C linical manifestation manifest in the third or fourth decade. myotonia. muscle weakness and wasting of the facial, sternomastoid, and distal limb muscles. multisystemic: cataracts, frontal baldness, testicular atrophy, dysphagia, diabetes mellitus, cardiac and respiratory abnormalities, mental retardation and excessive sleeping.
Investigation EMG of affected muscle may reveal characteristic high-frequency discharges of potentials that wax and wane in amplitude and frequency. producing over the EMG loudspeaker a sound like that of a bomber or chain-saw. serum CK: normal to mildly elevated.
Diagnosis 肌强直，头面部肌肉、胸锁乳突肌和四 肢远端肌萎缩、肌无力。 Gene analysis: expanded trinucleotide CTG repeat forms is specific.
Treatment Myotonia can be treated with quinine sulfate, 300-400 mg t.i.d.; procainamide, 0.5-1 g q.q.d; or phenytoin, 100 mg t.i.d. There is no treatment for the weakness that occurs. pharmacologic maneuvers do not influence the natural history.
Congenital myotonia Generalized myotonia without weakness. Muscle stiffness and hypertrophy are of feature. A recessive form with later onset is associated with slight weakness and atrophy of distal muscles. Treatment with quinine sulfate, procainamide, tocainide, or phenytoin may help the mytonia.