Muscular Dystrophies

• Muscle dystrophies : Areas of degeneration and regeneration due to a primary defect in the muscle (Duchenns & Becker’s)
• Muscle atrophies : Cells showing degeneration within areas of normal tissue, where the muscle changes are secondary to changes in innervation
• Pathological changes demonstrable biochemically, electrically and histologically in the affected muscle groups can be of use in distinguishing the primary myopathies from neurogenic disorders
• Features of myopathy are
  • Marked variations in fibre size
  • Fibre splitting
  • Central migration of the sarcolemmal nuclei
  • Areas of fibre atrophy
  • Formation of nuclear chains
  • Areas of necrosis and infiltration with fat cells and connective tissue
• However, denervated muscle may develop these changes secondarily. Differentiation between the two is not absolute

Duchenne Muscular Dystrophy

Most common of all muscular dystrophies (80% of cases)

Inheritance

• X-linked recessive
• Only boys affected and girls carriers
• Up to 50% may be new mutations

Incidence

1:3,000 males

Clinically

• Presents with delayed motor milestones and variable delay in psychomotor function
• Steady relentless progression of muscle weakness
• Patient going from crisis to crisis with abilities lost one by one
• Power of distal muscles is generally retained longer than the proximal muscles
• Becomes apparent during first 3 years of life 
• Muscular weakness accompanied in the early stages by enlargement of the calf’s and other muscle groups (pseudo hypertrophy)
• Gowersmanoeuvre on rising from the floor
• Extension lag of quadriceps
• "Slip through" sign (pick up under arms)
• By age 10 the child is unable to walk and rarely survives into adult life
• Walking can be prolonged about 2 years by release of contractures, but eventually will be wheel chair bound by the age of 12 years
• Once lost ambulation, scoliosis develops with 95% of boys developing curves of greater than 50 by the time they die 
• Axial rotation of the spine and pelvis occurs to produce a severe deformity
• Pelvic obliquity makes sitting painful
• Usually bed ridden by the age of 16 years
• Limbs slowly develop contractures 
• Myocardium is also affected
• 20 – 30% are retarded
• Death is usually due to frequent respiratory infections, secondary to weakness of respiratory muscles 
• Only 25% celebrate their coming of age
• If survive greater than age 22, probably has a different condition, e.g. Becker’s
• Typical walking posture : head is flexed, shoulders are retracted, spine is lordotic, hips and knees are flexed and feet are in equinus

Investigations

• Dystrophin (protein) deficiency can be measured
• Creatinine kinase elevated (may be several thousand)
• Carriers may have minimal calf hypertrophy and muscle changes
• 70% of the carriers of Duchenne dystrophy show increased CPK 
• About 20% of the female carriers will exhibit mild features of muscular dystrophy at some time in their lives
• Rule out treatable muscle diseases
• Coleman Block test differentiates fixed from non fixed heel varus by placing a block under the foot

Treatment

• Maintenance of useful mobility is the major priority
• Surgery should be undertaken only with great circumspection
• During ambulatory phase some recommend the use of high dose steroids to slow progression
• Benefit from active exercise and conversely, rest is detrimental
• Release contractures which are preventable and reversible to some extent through physical therapy
• Contracture of 20 need surgical release
• Contracture of  20° – 40 need serial casting prior to surgical release plus post-operative casting
• If contracture is greater than 45° surgery is contraindicated
• PETA and division of ilio-tibial band are commonly required
• Anaesthesia should be avoided, especially muscle relaxants
• Braces
  • Use KAFO to stabilise knee
  • Use spine support to slows progression of curve 
  • Should be commenced when power insufficient to maintain the normal erect posture and a kyphosis develops
• Spinal fusion needed if scoliosis > 35° or vital capacity is 40% (whichever comes first)
• Use Galveston technique to stabilise pelvis or new fixation methods 
• Prophylactic stabilisation surgery from T4 to sacrum is necessary
• Pulmonary complications are seen in
  • 50% if FVC is less than 35% 
  • 9% if FVC is greater than 35% 
• Stabilisation has no effect on the rate of deterioration of respiratory function

Prognosis

• Slow and inevitable progression
• Death usually occurs within 20 years
• Obese children with obese parents have the worse prognosis

Becker’s Muscular Dystrophy

Allelic with Duchenne muscular dystrophy, but is less severe

Incidence

1:10,000 males

Clinically

• Average age at onset of symptoms is approximately 11 years 
• Loss of ability to walk by 27 years
• Death at 42 years on average

Investigations

• CPK is elevated between 25 and 200 times normal
• Dystrophin present in 5% of cases

Limb Girdle Dystrophy

Inheritance

Autosomal recessive inheritance

Incidence

Rarer than Duchenne type and much less disabling

Clinically

• Milder than Duchenne dystrophy
• Symptoms usually start in late adolescence (second or third decade) 
• Pelvic girdle weakness causes waddling gait and difficulty in rising from a low chair
• Pectoral girdle weakness makes it difficult to raise the arms above the head
• Disease is slowly progressive and by the 5th decade disability is usually marked
• Walking may be retained until middle life

Investigations

CPK may be increased up to ten times normal

Treatment

• Physiotherapy and splinting to prevent contractures
• Surgical correction may be indicated

Facioscapulohumeral Dystrophy

Inheritance

• Autosomal dominant
• Wide variation in the expression of the disorder

Clinically

• Usually presents in early adult life 
• Facial muscle weakness
• Winging of the scapula 
• Slight pelvic girdle weakness
• Deterioration is slow 
• Life span normal

Investigations

CPK often normal

Scapuloperoneal Myopathy

Inheritance

Autosomal dominant and X-linked variants

Incidence

Both varieties are vary rare

Clinically

• Present with foot drop which may mimic Charcot Marie Tooth disease
• The dominant variety presents later in life than the X-linked variety

Hereditary Motor and Sensory Neuropathies

Classified by Dyck and Lambert (1968)

• Type 1
  • Autosomal dominant
  • Consists of :
    • Hypertrophic form of CMT
    • Hereditary areflexic dystaxia (Roussy-Levy Syndrome)
  • Clinically
    • Present in the 2nd decade
    • Compared to type 2, these patients have a greater tendency to show weakness of the hands, upper limb tremor and ataxia, generalised tendon areflexia, more distal sensory loss, more frequent foot and spinal deformities
    • Foot 
      • Cavus
      • Clawing of toes
      • Wasting of all muscles distal to knee may cause drop foot
    • Upper limb 
      • Progressive wasting of intrinsics and later forearm muscles
      • Difficulty with fine motor skills
  • Investigations
    • Motor nerve conduction velocities < 1/2 normal, due to repetive demyelination and remyelination of the peripheral nerve
    • Histology : "onion bulb " cross-sectional appearance
• Type 2
  • Autosomal dominant
  • Consists of the neuronal form of CMT
  • Clinically
    • Present later in the 2nd or 3rd decade
    • More profound distal lower limb weakness than type 1, upper extremity involvement is less pronounced
    • Characteristic stork-leg appearance
    • Flail foot develops a calcaneocavus deformity
  • Investigations
    • Conduction velocities slightly decreased or normal
• Type 3
  • Autosomal recessive
  • Consists of the hypertrophic neuropathy of infancy (Dejerine-Sottas disease)
  • Clinically
    • Present in infants/young children with delayed lower limb milestones
    • Pes cavus and drop foot common
    • Sensory loss in stocking/glove distribution
    • Significant spinal deformity in most
    • Wheelchair by 3rd or 4th decade
  • Investigations
    • Markedly slow conduction velocities
    • Sural nerve biopsy shows onion bulb formation with frequent segmental demyelination
• Type 4
  • Autosomal recessive
  • Consists of Refsums disease, rare
  • Clinically
    • Presents in childhood – puberty
    • Characterised by remissions and relapses
    • Associated with 
      • Anosmia
      • Progressive deafness
      • Night blindness
      • Hypertrophic neuropathy
      • Areflexia
      • Scoliosis
      • Pes cavus 
      • Equinus
    • Investigations
      • Elevation of serum phytanic acid is pathognomonic
      • Elevation of CSF protein levels
      • Motor nerve conduction velocities low
      • Nerve biopsy shows onion bulb formation
        
        
        

        ---