Transcript 肌肉疾病(Myopathies)

肌肉疾病 (Myopathies)
Dep. of Neurology
The 2nd Hospital
Harbin Medical University
进行性肌营养不良(progressive
muscular dystrophy, PMD)
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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)
Definition
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inherited myogenic disorders.
progressive muscle wasting and weakness of
variable distribution and severity.
Progressive muscular distrophy (PMD)
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I
ntroduction
mode of inheritance
age at onset
distribution of affected
muscle
presence or absence of
pseudohypertrophy
rate of progression
long-term outlook
Pseudohypertrophy:
Duchenne and
Becker
Facioscapulohumeral
limb-girdle (Erb)
Distal
Oculopharyngeal
Ocular
Duchenne muscular distrophy (DMD)
Etiology
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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 Xp21.
The main function of the dystrophin
complex is its structural role in maintaining
sarcolemmal integrity 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 dystrophin
Duchenne muscular distrophy (DMD)
Clinical manifestations
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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)
Clinical manifestations
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Winged scapulae are common.
Pseudohypertrophy of the calves caused
by fatty infiltration 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
(Gower's sign).
Duchenne muscular distrophy (DMD)
Clinical manifestations
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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)
Treatment
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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.
Becker muscular dystrophy (BMD)
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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)
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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
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An autosomal dominant disorder.
The genetic defect is a rearrangement of a
homeobox gene localized to 4q35.
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
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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)
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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)
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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
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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
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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
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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
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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
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Develops in infants.
Generalized muscle weakness.
possible joint deformities from shortening
of muscles.
progresses very slowly.
life span may be shortened.
Diagnosis and prevention
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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.
（ 一 ） 少 年 型 近 端 型 脊 髓 性 肌 萎 缩 症 ( KugelbergWelander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
Definition
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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
Etiology
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an autosomal dominant condition.
a mutation on chromosome 1q32 encoding
dihydropyridine receptor a-1 subunit.
affect a L-type calcium channel
(CACNL1A3).
Hypokalemic periodic paralysis
Etiology
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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
Pathology
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Vacuoles:
空泡由肌浆网和横管系
统扩张形成。
Hypokalemic periodic paralysis
Clinical manifestation
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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
Investigations
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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
Diagnosis 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
Prevention and treatment
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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.
感染性肌炎 (Inflammatory
myopathies )
√Polymyositis (PM)
√ Dermotomyositis (DM)
Mitochondril myopathies
Definition
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Polymyositis and dermatomyositis are
characterized by destruction of muscle
fibers and inflammatory infiltrations of
muscles.
Etiology
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PM is a cell mediated autoimmune disease.
DM is a humoral factor (antibody and
complement) mediated autoimmune
disease.
Pathology
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Muscle biopsy: muscle fiber necrosis and
infiltration with inflammatory cells.
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Skin changes in DM.
Clinical manifestations
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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
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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
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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
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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
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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
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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
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Methotrexate
may
be
useful
in
corticosteriod-resistant patients.
Physical therapy may help to prevent
contractures and hasten the recovery.
Myotonic disorders
Myotonic dystrophy, MD
Congenital myotonia
Myotonic dystrophy
Definition
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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.
Etiology
Myotonic distrophy
Myotonia congenita
dominant inherited
dominant trait
The gene defect is an
expanded trinucleotide
(CTG) repeat in a gene
localized to 19q13.3.
a mutation on
chromosome 7.
Myotonic dystrophy
Clinical manifestation
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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
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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
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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
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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
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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.