Central Hypoventilation: An Overview

Introduction:

Hypoventilation indicates an increased concentration of serum carbon dioxide due to insufficient gas exchange. Central hypoventilation is a disorder in the central nervous system that can be congenital or acquired. This causes inadequate breathing during sleep or while awake. This is due to the nerves malfunctioning and the inability of the brain to detect carbon dioxide levels during sleep.

What Is Normal Breathing?

Breathing is controlled by receptors that respond to changes in Po2 (partial pressure of oxygen), Pco2 (partial pressure of carbon dioxide), and pH (potential of hydrogen). Central chemoreceptors in the brain stimulate breathing in response to changes in Pco2. Peripheral receptors in the bifurcation of carotid arteries respond to low Po2. The neurons in the retrotrapezoid nucleus located on the medullary surface of the brain control breathing.

It receives signals from the carotid bodies, hypothalamus, juxtacapillary receptors in the alveolar walls, and central pattern generator and responds to changes in oxygenation and ventilation. The metabolic control of breathing is located in the brainstem, and the voluntary control center is located in the cerebellum, primary motor cortex, and premotor areas. Breathlessness stimulates the brainstem through the vagal afferents. Arousal from sleep is a significant response to changes in oxygenation or ventilation. Low blood oxygen level or hypoxemia stimulates arousal during the first few months of life. Increased carbon dioxide is the reason for arousal in later life.

What Is Congenital Hypoventilation?

Congenital hypoventilation is a genetic disorder caused by the paired-like homeobox gene 2B (PHOX2B) on chromosome 4p12. It is transmitted through an autosomal-dominant pattern or inherited from the unaffected parent. PHOX2B encodes a transcription factor responsible for neural crest migration and the development of the autonomic nervous system. Familial dysautonomia, Mobius syndrome, Pitt-Hopkins syndrome, Prader-Willi syndrome, skeletal dysplasia, Joubert syndrome, achondroplasia, and Athabaskan brainstem dysgenesis syndrome are some congenital disorders associated with central hypoventilation.

What Is Acquired Hypoventilation?

Brain tumors, central nervous system infections, encephalitis, trauma, and neurosurgical procedures can affect respiratory control centers. Therefore, the degree of hypoventilation depends on the severity of the respiratory centers affected.

What Are the Signs and Symptoms of Congenital Central Hypoventilation?

Signs:

Children with congenital hypoventilation present with the following signs;

• A square face with a tall, flat forehead and deep philtrum with abnormal lips.

• Sluggish to absent papillary reflex.

• Right heart failure.

• Developmental delay.

Symptoms:

• Shallow breathing during sleep.

• Bluish discoloration of the skin.

• Seizures.

• Cognitive difficulties and lack of thinking ability.

What Are the Symptoms of Acquired Central Hypoventilation?

• Breathing difficulty during sleep and while awake.

• Confusion.

• Disorientation.

• Fatigue.

• Visual disturbances.

• Bluish skin discoloration on lips, fingers, and toes.

• Nausea.

• Seizures.

• Abnormal breath sounds.

• Cognitive impairment.

How Is Congenital Central Hypoventilation Diagnosed?

The following tests are done to diagnose congenital central hypoventilation:

• Polysomnography, it is a sleep study to assess the gas exchange during sleep. The degree of hypoventilation is identified and assessed for other supportive care like tracheostomy with ventilatory support during sleep.

• Magnetic resonance imaging (MRI) of the brain, patients with congenital hypoventilation show normal findings or a reduction in gray matter volume. But it is unclear if these changes are related to the underlying disorder.

• Echocardiography - It is used to analyze structural and functional cardiac activity. It is done while awake and as a component of the sleep study. In addition, prolonged cardiac electrophysiologic activity with a Holter monitor is used after diagnosing congenital central hypoventilation.

• Tests for neuromuscular disorders and inborn errors of metabolism.

• Complete blood count (CBC) analysis.

• Blood gas analysis.

• Screening test for identifying mutation in the PHOX2B gene.

How Is Acquired Central Hypoventilation Diagnosed?

• CT (computed tomography) and MRI scan to diagnose tumors.

• Sleep study to identify sleep-related disorders.

• Thyroid function test to diagnose hypothyroidism, a significant cause of hypoventilation.

• Electrocardiography to diagnose cardiac disorders.

• Electroencephalogram (EEG) tests determine the electrical pattern in conditions like seizures, trauma, and brain tumors.

• Chest X-ray.

• Lung function test.

• A blood gas test measures the amount of carbon dioxide and oxygen in the blood.

• Hematocrit and hemoglobin blood test to measure red blood cell distribution.

How Is Congenital Central Hypoventilation Treated?

Congenital hypoventilation caused by genetic mutation cannot be cured, and the treatment is based on supportive care.

• Gastrointestinal Problems - Infants with congenital hypoventilation suffer from hypotonia, temporary feeding difficulties, and moderate to severe gastroesophageal reflux. Early administration of prokinetic agents and antireflux medications is given. Surgical procedures such as percutaneous gastrotomy tube feeding and antireflux procedures are done if these problems are severe or persistent.

• Invasive Ventilatory Support - Positive pressure ventilation with a permanent tracheostomy is done for long-term home care. Ventilatory support depends on the severity of hypoventilation. Some patients need them only during the night; some may need them throughout the day. Ventilators are used in the spontaneous intermittent mandatory ventilation (SIMV) mode. Mild hyperventilation during nighttime results in better spontaneous ventilation and gas exchange during the daytime.

• Noninvasive Ventilatory Support - Nasal mask ventilation is effective in patients older than seven to eight years and those dependent on ventilators during nighttime. Patients on invasive ventilation can be shifted to noninvasive ventilation in a stepwise function.

• Diaphragmatic Pacing - A battery-powered system is implanted into the diaphragm (respiratory muscle) to stimulate breathing. This is done in patients who require ventilatory support 24 hours a day via tracheostomy and those without ventilator-related lung damage.

• Medications - The pharmacological approach is unsuccessful and respiratory stimulants have no role in treating congenital hypoventilation.

How Is Acquired Central Hypoventilation Treated?

• Oxygen therapy delivers oxygen to support breathing.

• Continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BIPAP) machines support breathing while sleeping.

• Surgery to treat chest deformities and other disorders like tumors.

• Mechanical ventilation.

• Respiratory stimulants are used if a central nervous system depressant overdose causes hypoventilation.

Conclusion:

Central hypoventilation interferes with everyday life. Unfortunately, congenital central hypoventilation cannot be cured permanently, but recent advancements in management strategies offer comprehensive and supportive care to every child. Early detection and treatment prevent complications, increase functional capacity, and improve survival and quality of life.