muschi si boli musculare (1)

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  • 8/13/2019 Muschi Si Boli Musculare (1)


    Primary muscular disorders

  • 8/13/2019 Muschi Si Boli Musculare (1)


    More than 600 separate muscles

    40% of the human weight in adulthood

    A muscle contains thousands of musclefibers that extend for variable distances

    along its longitudinal axis.

    A muscular fiber is a multinucleated cellfrom a few mm to several cm and from 0!

    00 micrometers diameter

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    Muscle fibers innervated by an anterior

    horn cell act as a unit called " #motor unit$

    " basic physiologic unit in all reflex

    postural and voluntar activity.

    A particular muscle may have from a few

    &'!4 as extraocular muscles( to hundreds

    of M) &li*e the cvadriceps muscle(

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    +linical syndrome Motor deficit not restricted to a particular

    motor unit.

    ,istribution of motor wea*ness might

    involve a certain group of muscles or

    could be more widespread. -n this caseproximal muscles are usually more

    involved " wadling gait is characteristic for

    pelvian muscles deficit. ,istal myopaties are not uite exceptional.

    Muscle tone is diminished

    Muscular atrophy and loss of bulc* is

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    +ommon activities might get impaired

    because of wea*ness related to a

    muscular disorder/

    al*ing running climbing stairs arising from

    sitting &special sign " 1owers " #patient

    climbing on himself$( *neeling suatting orreclining position wor*ing with hands above

    shoulder2s level.

    !! 3ocalied muscle wea*ness might be a sign

    of a muscular disorder as well/ drooping of the

    eyelids diplopia and strabismus change in

    facial expression and voice difficulty in

    chewing closing the mouth swallowing etc..

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    5on muscular abnormalities in muscular

    diseases ,islocation of the hips

    *in involvement

    +ardiac abnormalities 7etinian changes

    +erebellum and cranial nerves

    8ronto!temporal dementia ,ysmorphic features of cranium

    9ndocrine abnormalities

    Skin lesions typical rash in dermatomyositis

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    ,ifferential diagnosis with

    polineuropathies :endon reflexes are spared

    5o sensory signs

    5o sphincterian troubles 5o autonomic signs

    ;ut we can have/

    pain spasms cramps rippling muscularhypertrophy &true or false( fatigue

    myotonia stiffness muscle mass or

    change in muscle volume

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    ;lood tests


    -maging studies ;iopsy

    1enetic tests

    Asses cardiac function for associatedcardiomiopathy

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    ;lood tests

    +hec* up for/ +reatin*inase &elevated in active progressive

    disorders to thousands of units(



    9lectrolites/ sodium potasium cloride

    :iroidian chec* up

    Autoimmune battery


    erology for viral or parasitic infections

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    5erve conduction studies are normal

    5eedle electrode test of muscular activity

    at rest and gradual to maximal contraction

    At rest we can find/ fibrillation potentials ! markers for spontaneous

    contractions of individual muscle fibers as a consequence of

    membrane instability" very prominent in inflammatory myopathies during theactive episodes

    myotonic discharge ! repetitive high frequency potentialsexpression of delayed muscle relaxation after voluntary contraction"action myotonia or mechanical stimulation"percussion myotonia :ypes +hloride

    channel!related disorders"eg myotonia congenita :homsen type< protein *inase!

    related disorders"eg myotonic dystrophy< sodium channel!related disorders"eg

    hyper*alemic periodic paralysis< idiopathic

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  • 8/13/2019 Muschi Si Boli Musculare (1)


    9arly recruitment during gradual

    contraction in myopathic conditions with

    low amplitude and short duration of

    individual motor units

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    -maging +: scan M7- or ultrasound

    >elp to define the pattern of involvementbeing particularly helpful for profound muscles

    ?ery helpful for detecting inflammation

    edema muscular mass &hematoma tumor

    ossification etc..(

    5ormal appearance of thigh muscles

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    Axial :@ weighted spin echo M7 imageshowing edema and inflammation ofmuscle fibers and s*in &solid arrows( in apatient with polimyositis.

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    Muscle biopsy 8ragment of muscle is removed surgically and

    prepared to be examined by microscope loo*ingfor necrosis inflammation edema cytoplasmic

    inclusions regeneration activity increase in

    lipocytes fibrosis etc

    and tested by immunostaining loo*ing for

    specific proteins &distrophin utrophin emerina

    sarcoglicans etc(

    the selection of the muscle is based onevidence of involvement

    Although involved a certain muscle should be

    avoided if the loss of muscle fibers is very

    prominent and advanced.

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    >9 staining showing inflammatory cells

    &purple( attac*ing muscle fibers in apatient with polimyositis

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    >istopathology of gastrocnemius muscle from

    patient who died of pseudohypertrophic muscular

    dystrophy ,uchenne type. +ross section of

    muscle shows extensive replacement of musclefibers by adipose cells.

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    >-? infection



    7elated to treatment

    Primary endomysial inflammation,

    red-rimmed vacuoles, amyloid

    deposits,eosinophilic inclusions, and

    small round fibres in groups,

    all diagnostic of IBM

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    1enetic testing

    -s a blood test

    8or ex/ the muscle!specific isoform of the

    dystrophin gene &for ,uchenne dystrophy(

    is composed of B exons and ,5A testingand analysis can usually identify the

    specific type of mutation of the exon or

    exons that are affected. ,5A testingconfirms the diagnosis in most cases and

    detect the carrier status

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    Prenatal tests

    -f one or both parents are CcarriersC of a particular condition there is a

    ris* that their unborn child will be affected by that condition.

    CPrenatal testsC are carried out during pregnancy to try to find out if

    the fetus &unborn child( is affected.

    :he tests are only available for some neuromuscular disorders.,ifferent types of prenatal tests can be carried out after about

    wee*s of pregnancy.

    +horion villus sampling &+?( can be done at "4 wee*s and

    amniocentesis after D wee*s while fetal blood sampling can be

    done at about E wee*s. 9arlier testing would allow early termination but it carries a slightly

    higher ris* of miscarriage than later testing &about @% as opposed

    to 0.D%(.

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    9tiology of muscular disorders -. -nflammatory myopathies

    A. -nfective or presumably infective forms of polymyositis




    >-? >:3?!

    ;. -diopathic polymyositis and dermatomyositis " usuallyassociated to connective tissue disorders affect primarily striated

    muscle and s*in

    ometimes paraneoplastic syndromes

    Fnly ,M affects children

    ,iagnosis based upon specific changes in muscle and s*inbiopsy

    +. -nclusion body myositis &-;M( Predominates in males

    Fnset in middle or late adult life more freuent than PM

    ,iagnosis based on intracytoplasmatic vacuoles and congophilic inclusionsin both cytoplasma and nuclei of degenerated muscular fibers

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    >eritable muscular dystrophies &M,(

    include the following/

    ex lin*ed

    ! ,uchenne

    ! ;ec*er

    ! 9mery ,reifussAutosomal dominant

    ! 8acioscapulohumeral

    ! ,istal

    ! Fcular

    ! Fculopharingeal

    Autosomal recessive

    ! 3imb girdle

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    Multiple proteins are involved in the

    complex interactions of the muscle

    membrane and extracellular

    environment. For sarcolemmal stability,dystrophin and the dystrophin-

    associated glycoproteins (!"s# are

    important elements

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    Fther muscular dystrophies

    Myotonic dystrophy &teinert disease( "


    Proximal myotonic myopathy &P7FMM( "


    ,istal myopathies " brea*ing the rule of proximaldistribution of wea*ness according to myopathic pattern " affects distal

    muscles and might resemble a polineuropathy

    elander type " autosomal dominant

    Miyoshi " dysferlin gene on cr @p "

    autosomal recessive

    7ecently described a distal myopathy

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    Metabolic and toxic myopathies

    >ereditary metabolic abnormality " glycogen storage

    myopathies lipid metabolism disorders

    econdary to a disorder of endocrine function &thyroid "

    thyrotoxic and hypothyroid myopathy pituitary adrenal


    Myotoxic drugs and other chemical agents "

    rhabdomyolysis to alcohol abuse statins cocaine

    organophosphates high doses of corticosteroids &critical

    ilness myopathy( Fther mecanisms/ hypo*alemic &diuretics laxatives alcohol(

    lysosomal storage &amiodarone chlorouine( inflammatory

    &procainamide ,!penicilamine( etc

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    59)7FM)+)3A7 ,-F7,97 ,evelop in utero 7elatively nonprogressive

    +ould have the clinical onset at a later age even in middle adult life

    ,iagnosis based on specific morphologic changes on muscle biopsy

    revealed by systematic application of hystochemical stains to froen

    sections and by phase and electron microscopy

    +entral core presence in the central portion of a condensation of myofibrillar material

    high ris* for malignant hyperthermia &B " lin*ed to the ryanodine receptor


    5emaline Miriads of rods seen beneath the plasma membrane of the muscle fiber

    +entronuclear or myotubular +entral nucleation and smalnees of fibers

    G!lin*ed and A7 in children and A, in adult onset form

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    +hannelopathies ,iseases caused by mutations in genes that code

    proteins that function as channels in muscle fibersmembrane " ion channel disease

    -. +hloride channel diseases

    Myotonia congenita &:homsen disease " A, early life onset

    myotonia muscular hypertrophy and nonprogressive course(

    1eneralied myotonia &;ec*er disease " A7 manifestation of

    myotonia after 0!4 y of age(

    --. odium channel diseases

    Myotonia fluctuans and permanens

    Acetaolamide "responsive myotonia

    ---. +alcium channel diseases

    >ypo*alemic periodic paralysis " A, attac*s evolving over

    minutes to hours of diffuse wea*ness &legs before arms before

    trun* muscles( usually sparing of faciobulbar muscles

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    econdary *alemic periodic paralyses " transitory

    episodes of wea*ness *nown to be associated to

    acuired derangements of potassium metabolism :hyrotoxicosis Aldosteronism

    alfa hydroxilase deficiency

    ;arium poisoning

    Malignant hyperthermia ,uring general anesthesia " rising body temperaturemuscular rigidity and ris* of death &inherited defect of the

    ryanodine receptor protein component of the calcium

    channel in the sarcoplasm(

    Malignant neuroleptic syndrome >yperthermia occurs as an idiosyncratic reaction to

    neuroleptic drugs with widespread myonecrosis.

    5euromuscular Hunction

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    5euromuscular Hunction


    Myasthenia gravis Myasthenic " myopathic syndrome of 3ambert

    9aton " paraneoplastic sy associated to the oat

    cell carcinoma of the lung " presynaptic defect

    of Ach release from the nerve terminals +ongenital myasthenic syndromes " genetic

    disorders with pre or postsynaptic defects

    Myasthenic wea*ness due to antibiotics&neomicin *anamicin polymixin colistin etc( or

    toxins &clostridium botulinum(

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    Myasthenia gravis

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    Autoimmune attac* against aceticholine

    receptor on the postsynaptic membrane of

    the neuromuscular Hunction.

    :he antibodies affect only the nicotinic

    receptor in the s*eletal &striated( muscles.

    ?isceral muscles and myocardium are


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    8luctuating wea*ness of muscles induced

    or aggravated by repetitive or persistent

    activity and recovered during rest.

    Fnset usually insidious but some factors

    li*e emotional upset or infections might be


    :he special vulnerability of

    certain muscles is also a

    characteristic feature.

    +raniofacial muscles are in D0% of cases involved at the

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    +raniofacial muscles are in D0% of cases involved at theonset &levator palpebrae and extraocular muscles mostof all( and eventually become symptomatic in IB0% ofpatients.

    o drooping eyelids and intermittent diplopia arecommon complaints.

    Muscles of facial expression mastication swallowingand speech are in E0% of cases affected.

    -n patients with wea*ness of the trun* and limbs "proximal muscles are far more vulnerable than the distalones.

    -nvolvement of respiratory muscles is associated withrespiratory insuficiency

    7apid deterioration with respiratory failure anduadriparesis might occur in a range of hours and istermedmyasthenic crisisbeing considered lifethreatening and a treatment emergency

    Precipitating factors/ phisical exercise cold hunger

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    5o other clinical signs or symptoms apartfrom the motor ones are present in theclinical picture

    Muscle atrophy is not present. +ourse of the illness is extremely variable

    but mortality is under D% and treated

    correctly most of the patients leadproductive lives.

    :hymic gland is involved as primary site of

    antibody production

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    :hymic involvement

    :rue neoplasm are found in 0!D% of


    6D% of the remaining patients shows an

    important degree of hyperplasia of

    lymphoid follicles with active germinal

    centers confined to the medullary part of

    the thymus gland. Mediastinal +: scann is commonly used

    to document thymus morphologic


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    Measurement of receptor antibodies in

    blood " sensitive and highly specific test

    7-A is the method of choice

    E0!B0% of patients with generalied

    myasthenia and 60% of those who are

    restricted to ocular muscles

    eronegativity does not imply clinical orelectrophysiological differences.

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    5erve conduction studies and 9M1 are

    both normal in myasthenic patients

    7epetitive nerve "muscle stimulation

    7apid reduction in amplitude of compound

    muscle action potentials after '=sec

    stimulation of a peripheral nerve "

    decremental response and reversal of thisresponse by anticholinesterase drugs is a

    reliable confirmation of diagnosis.

    : t t

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    :reatment -. !nticholinesterase drugs " neostigmin &miostin( and

    pyridostigmine &mestinon(

    -ncrese the availability of Ach in the synaptic cleft and improve

    the myasthenic deficit

    ide effects " cholinergic muscarinic &nausea vomiting

    salivation diarrhea miosis bradycardia(

    +holinergic crisis " rapid escaladation of muscular wea*ness

    due bell shape effect of drugs on neuromuscular Hunction $hymectomy % recommended in the first ' years and in tumoral

    patients ! is followed by significant improvement and chance of

    better control with corticosteroids afterward

    &orticosteroids are the most consistently effective form of

    treatment in moderate to severe generali'ed eakness.Managing side effects is chalenging

    )mmunosupressants - as an adHunct to steroids or the one that fail

    to respond to corticotherapy

    P* or )v immune globulin % for myasthenic crisis,

    reechilibration for surgery, refractory patients.

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    Myasthenic crisis

    +areful intubation followed by mechanical


    Anticholinesterae drugs withdrawn

    P9 or -v -g " hasten improvement