20.1.1 Diagnosis of Neuromuscular Disorders

Huge advances have been made in the genetic diagnosis of some of the conditions causing scoliosis. Chromosomal abnormalities are being more readily identified because of techniques such as array comparative genomic hybridization (CGH) testing. Some centers are performing exome sequencing or whole-genome sequencing, allowing the early genetic diagnosis of these conditions. Specialized DNA laboratories have acquired chips for the DNA diagnosis of conditions like the spinocerebellar ataxias. Muscle biopsy and neurophysiology remain useful in the clinical diagnosis of these conditions.

20.1.2 Medical Management of Neuromuscular Disorders

In keeping with the diagnostic advances, rapid progress has been made in the medical management of these conditions. Genetic engineering to correct or mitigate genetic defects remains the forerunner in the newer treatment strategies. Recent treatment options proposed for the management of some neuromuscular conditions include:

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  Genetic advances: trial of antisense oligonucleotides (molecular patch therapy) in Duchenne muscular dystrophy

  
  
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  Use of drugs to upregulate utrophin in Duchenne muscular dystrophy

  
  
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  Use of salbutamol in spinal muscular atrophy

  
  
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  Steroids (prednisolone / deflazacort) in Duchenne muscular dystrophy

Antisense oligonucleotides. The development of effective therapies for neuromuscular disorders such as DMD is hampered by considerable challenges; skeletal muscle is the most abundant tissue in the body, and many neuromuscular disorders are multisystemic conditions. However, despite these barriers, substantial progress has recently been made in the search for novel treatments. In particular, the use of antisense oligonucleotides, which are designed to target RNA and modulate pre-mRNA splicing to restore functional protein isoforms or directly inhibit the toxic effects of pathogenic RNAs, offers great promise, and this approach is now being tested in the clinic. ¹

Utrophin upregulation. Another experimental strategy is the upregulation of alternative muscle proteins, such as utrophin. In the mouse model, these strategies seem to reduce severity significantly. It remains to be seen whether they will be effective in boys with DMD.

Several drugs, such as valproic acid, carnitine, and hydroxyurea, have been tested in spinal muscular atrophy (SMA). They work by different putative mechanisms. Salbutamol seems to increase survival motor neuron transcript levels, thereby slowing the relentless progression of weakness, and it has been shown to be effective in SMA types 2 and 3. Other drugs have been used in other neuromuscular conditions and are primarily directed toward stabilizing or improving cardiac function; examples are idebenone in Friedreich ataxia and combinations of angiotensin-converting inhibitors and β-blockers in DMD. The use of intermittent low-dose steroid regimens seems to prolong ambulation in DMD.

Most of these treatments remain experimental, and studies are ongoing. Until such time as definitive trial data become available, supportive treatments are the only realistic treatment option for most patients. Some of the supportive treatments used in the management of neuromuscular conditions include:

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  Physiotherapy: tackling contractures aggressively, chest physiotherapy

  
  
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  Occupational therapy: seating

  
  
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  Bracing

  
  
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  Monitoring of respiratory and cardiac function

  
  
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  Early intervention in cardiomyopathy

  
  
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  Prevention and management of early respiratory failure: “therapeutic window” for safe anesthesia

  
  
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  Surgical spine stabilization

  
  
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  Use of β-blockers and angiotensin-converting enzyme inhibitors in prevention of cardiomyopathy in Duchenne muscular dystrophy

  
  
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  Meticulous monitoring of respiratory function in all neuromuscular disorders

  
  
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  Early initiation of noninvasive ventilation

  
  
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  Steroids and monitoring for side effects (dual-energy X-ray absorptiometry [DXA])

  
  
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  Orthopedic intervention

Guidelines have been published in the United Kingdom and elsewhere on standards of care for the management of scoliosis in children with neuromuscular disorders. ^{2 ,​ 3 ,​ 4} Of all the treatment strategies, the intervention that has had the biggest impact in terms of improving quality of life and survival is the early diagnosis of hypoventilation and the initiation of noninvasive ventilatory support. ⁵

20.2.1 Detecting Hypoventilation

All infants who are weak should have an overnight oxygen saturation measurement at a minimum and, if any abnormality is noted, then full respiratory polysomnography. Older children should be assessed for nighttime hypoventilation. Evidence includes a history of the following:

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  Disturbed sleep;

  
  
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  Difficulty waking in the morning;

  
  
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  Morning headache;

  
  
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  Morning nausea (Do they eat breakfast?);

  
  
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  Daytime sleepiness (uncommon in children);

  
  
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  Difficulty concentrating during the day, manifesting as poor school performance, and evidence of impaired lung function by spirometry (<60% of predicted vital capacity). Evidence also includes these symptoms:

  
  
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  Frequent respiratory infections;

  
  
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  Impaired cough.

The examination should include observation of the respiratory movements (chest and abdomen) with the child in the sitting, standing, and supine positions, and the examiner should witness the power of a voluntary cough.

Where there is any concern, then polysomnography, including carbon dioxide measurement, should be carried out. Some children with neuromuscular weakness also have abnormal respiratory control (e.g., myotonic dystrophy and mitochondrial disease), and this will be detected on polysomnography. A common pattern of abnormality is evidence of hypoventilation, particularly during active (rapid eye movement) sleep (Fig. 20.3).