Neuromuscular Disorders

1
Neuromuscular Disorders

• Prepared by Dr.Hani Daoud
• Discussed by Dr.Afaf Al-aryni

2
Neuromuscular Disorders

• The term neuromuscular disease defines disorders
  of the motor unit and excludes influences on
  muscle function from the brain, such as
  spasticity.
• The motor unit has four components
• Motor neuron in the brainstem.
• Axon that together with other axons forms
  peripheral nerve.
• Neuromuscular junction.
• All muscle fibers innervated by a single motor
  neuron.

3
Neuromuscular Disorders

• Diseases of the motor unit are common in
  children.
• Neuromuscular diseases may or may not be
  genetically determined, congenital or acquired,
  acute or chronic, and progressive or static.
• Laboratory confirmation is required for most
  diseases because of overlapping clinical
  manifestation.

4
Evaluation Management

• Examination of the neuromsucular system includes
  an assessment of muscle bulk, tone, and strength.
• Tone and strength shouldnt be confused passive
  tone is range of motion around a joint, active
  tone is physiologic resistance to movement.
• Head lag is a sign of weakness not of low tone.

5
Evaluation Management

• The distribution of weak muscles is of diagnostic
  importance.
• Tendon stretch reflexes are generally lost in
  neuropathies and on motor neuron disease and are
  diminished and preserved in myopathies.
• Sensory abnormalities indicate neuropathy.

6
Evaluation Management

• Muscle pain or myalgia are associated with acute
  disease of either myopathic or neurogenic origin.
• Myalgia occur in several metabolic diseases of
  muscle, myositis, polyneuropathy and ischemic
  myopathy.
• The thorax of infant with congenital
  neuromuscular disease often has a funnel shape
  and the ribs are thin and radiolucent, and
  because of small muscle mass birth weight may be
  low for gestational age.

7
Evaluation Management

• Generalized hypotonia and motor developmental
  delay are the most common manifestation related
  of neuromuscular disease in infant and young
  children.

8
Laprotary Finding

• Serum enzymes
• several lysosomal enzymes are released by
  damaged or degenerating muscle fibers and may be
  measured in serum, the most useful one is
  creatine kinase, the CK level is
  characteristically elevated in certain diseases,
  such as Duchenne muscular dystrophy.

9
Laprotary Finding

• Molecular Genetic Markers
• Many DNA markers of hereditary myopathies and
  neuropathies are now available from blood
  samples.
• Nerve Conduction Velocity
• Motor and sensory nerve conduction may be
  measured electrophysiologically by using surface
  electrodes .

10
Laprotary Finding

• Electromyography (EMG)
• Requires insertion of a needle into the
  belly of a muscle and recording the electric
  potentials in various states of contraction,
  characteristic EMG patterns distinguish
  denervation from myopathic involvement.

11
Laprotary Finding

• Muscle Biopsy
• The most important and specific diagnostic
  study of most neuromuscular disorders.
• Not only are neurogenic and myopathic
  processes distinguished, but also the type of
  myopathy and specific enzymatic deficiencies may
  be determined.

12
Laprotary Finding

• Nerve Biopsy
• The most commonly sampled nerve is the sural
  nerve, which is a pure sensory nerve that
  supplies a small area of skin on the lateral
  surface of the foot.
• Electron microscopy is performed on most
  nerve biopsy specimens because many morphologic
  alterations cannot be appreciated at the
  resolution of a light microscope.

13
Laprotary Finding

• Electrocardiography (ECG)
• Cardiac evaluation is important if myopathy
  is suspected because of involvement of the heart
  in muscular dystrophies and in inflammatory and
  metabolic myopathies .
• ECG often detect early cardiomyopathy or
  conduction defects that are clinically a
  symptomatic.

14
Muscular Dystrophies

• Dystrophy means abnormal growth.
• A muscular dystrophy is distinguished from all
  other neuromuscular diseases by four obligatory
  criteria
• It is a primary myopathy.
• It has a genetic basis.
• The course is progressive.
• Degeneration and death of muscle fibers occur at
  some stage in the disease.

15
Muscular Dystrophies

• Muscular dystrophies are a group of unrelated
  diseases each transmitted by a different genetic
  trade, and each differing in its clinical course
  and expression. Some are severe diseases at birth
  or lead to early death others follow very slow
  progressive courses over many decades may be
  compatible with normal longevity or may not even
  become symptomatic until late adult life.

16
Duchenne and Becker Muscular Dtstrophies

• Duchenne muscular dystrophy is the most common
  hereditary neuromuscular disease affecting all
  races.
• Its incidence is 13,600 liveborn infant boys.
• Inherited as an X-linked recessive trait.
• Becker muscular dystrophy is the same fundamental
  disease as Duchenne.

17
Clinical Manifestation

• Infant boys are only rarely symptomatic at birth
  or in early infancy, although some are already
  mildly hypotonic.
• Poor head control may be the first sign of
  weakness.
• Toddlers may assume a lordotic posture when
  standing to compensate for gluteal weakness.
• Early Gowers sign is often evident by age 3 yrs
  is fully expressed by age 5 or 6.

18
Clinical manifestations

• Some patients are confined to a wheel chair by 7
  years of age, most patients continue to walk with
  increasing difficulty until age 10 yrs without
  orthopedic intervention.
• The relentless progression of weakness continues
  into the 2nd decade , the function of distal
  muscles is usually relatively well preserved.

19
Clinical manifestations

• Respiratory muscle involvement is expressed as a
  weak ineffective cough, recurrent chest
  infections .
• Pharyngeal weakness may lead to aspiration ,
  nasal regurgitation of liquids nasal voice
  quality.
• Contractures often involve the ankles ,knees,
  hips elbows.
• Scoliosis is common.

20
Clinical manifestations

• After the calf muscles the 2nd most common site
  is the tongue, then muscles of forearm (
  fasciculations of the tongue do not occur).
• Cardiomyopathy is a constant feature of this
  disease , some patients die early of severe
  cardiomyopathy.
• Intellectual impairment occurs in all patients
  20-30 have IQ lt 70.
• Epilepsy is slightly more common than general
  population.

21
Clinical manifestations

• Myalgia muscle spasm do not occur.
• Death occurs usually at 18 yrs of age, the causes
  of death are respiratory failure in sleep ,
  intractable heart failure , pneumonia or
  aspiration airway obstruction.
• In Beckers the learning disabilities are less
  frequent, the onset of weakness is later fewer
  than half of patients are still alive by age 40
  yrs.

22
Lab findings

• Serum CK level is greatly elevated in Duchenne
  (15000-35000) normal range lt 160IU/L.
• Lysosomal enzymes present in muscle such as
  aldolase and aminotransferase are also
  increased.
• Echocardiography, ECG, chest X-rays essential and
  should be repeated periodically.
• EMG shows characteristic myopathic features
• Motor sensory nerve conduction velocities are
  normal.

23
Diagnosis

• A specific molecular genetic diagnosis is
  possible by demonstrating deficient dystrophin by
  immunohistochemical staining of sections of
  muscle biopsy or by DNA analysis from blood.
• The muscle biopsy is diagnostic shows
  characteristic changes.

24
Diagnosis

• Myopathic changes include
• Endomesial connective tissue proliferation.
• Scattered degenerating regenerating myofibers.
• Mononuclear inflammatory cell infiltrates as a
  reacting to muscle fiber necrosis.
• Many dense fibers.

25

• What are the indications for muscle biopsy??

26
Pathogenesis etiology

• 30 of patients are new mutations the mother is
  not a carrier .
• Symptomatic girls are explained by the Lion
  hypothesis .
• The asymptomatic carrier of Duchenne is
  associated with elevated serum CK in 80 of
  cases.
• Muscle biopsy of suspected female carriers may
  detect an additional 10 in those with normal CK
  levels.

27
Pathogenesis etiology

• Dystrophin is first detected in developing human
  fetal muscle at 11th weak of gestation.
• Dystrophin mRNA is detected in cardiac smooth
  skeletal muscle in brain.
• DNA analysis from blood samples may be applied
  for carrier detection in female relatives at risk
  to determine whether the mother is a carrier or
  a new mutation occurred.
• Prenatal diagnosis is possible as early as 12
  weaks of gestation by sampling chorionic villi
  for DNA analysis.

28
Treatment

• There is neither a medical cure for this disease
  nor a method of slowing its progression.
• Much can be done to treat complications and to
  improve the quality of life of affected children.
• Cardiac decompensation often responds well to
  digoxin.
• Immunization for influenza virus is indicated.

29
Treatment

• Preservation of a good nutritional state is
  important.
• Adequate calcium intake is important to minimize
  osteoporosis.
• Physiotherapy delays but doesnt always prevent
  contractures.
• Physiotherapy contributes little to muscle
  strengthening because patients usually are
  already using their entire reserve for daily
  function, and exercise cannot further strengthen
  involved muscles.

30
Treatment

• One experimental approach is myoblast transfer
  therapy.
• Use of steroid decrease the rate of apoptosis or
  programmed cell death of myotubes during
  ontogenesis and theoretically may decelerate the
  myofiber necrosis in muscular dystrophy.

31
Thank you