While enhanced expression of VEGF improves motor function, reduced expression of Nrp1 worsens CMT2D; because Nrp1 binds to mutant GlyRS in mutant GARS1-CMT2D individuals, Nrp1 expression is reduced, in turn worsening motor function. Mice with deficient VEGF demonstrate motor-neuron disease over time. Thus, the VEGF/Nrp1 pathway is considered to be targetable for CMT2D treatment. Diagnosis
CMT can be diagnosed through three different forms of tests: measurement of the speed of nerve impulses (nerve conduction studies), a biopsy of the nerve, and DNA testing. DNA testing can give a definitive diagnosis, but not all the genetic markers for CMT are known. CMT is first most noticed when someone develops lower leg weakness, such as foot drop, or foot deformities, including hammertoes and high arches, but signs alone do not lead to diagnosis. Patients must be referred to a physician specialising in neurology or rehabilitation medicine. To see signs of muscle weakness, the neurologist may ask patients to walk on their heels or to move part of their leg against an opposing force. To identify sensory loss, the neurologist tests for deep-tendon reflexes, such as the knee jerk, which are reduced or absent in CMT. The doctor may also ask the patients family history since CMT is hereditary.
Breath-holding in water should always be supervised by a second person, as by hyperventilating, one increases the risk of shallow water blackout because insufficient carbon dioxide levels in the blood fail to trigger the breathing reflex.A continued lack of oxygen in the brain, hypoxia, will quickly render a person unconscious, usually around a blood partial pressure of oxygen of 25–30 mmHg. An unconscious person rescued with an airway still sealed from laryngospasm stands a good chance of a full recovery. Artificial respiration is also much more effective without water in the lungs. At this point, the person stands a good chance of recovery if attended to within minutes. More than 10% of drownings may involve laryngospasm, but the evidence suggests that it is not usually effective at preventing water from entering the trachea. The lack of water found in the lungs during autopsy does not necessarily mean there was no water at the time of drowning, as small amounts of freshwater are readily absorbed into the bloodstream. Hypercapnia and hypoxia both contribute to laryngeal relaxation, after which the airway is effectively open through the trachea. There is also bronchospasm and mucous production in the bronchi associated with laryngospasm, and these may prevent water entry at terminal relaxation.The hypoxemia and acidosis caused by asphyxia in drowning affect various organs. There can be central nervous system damage, cardiac arrhythmia, pulmonary injury, reperfusion injury, and multiple-organ secondary injury with prolonged tissue hypoxia.A lack of oxygen or chemical changes in the lungs may cause the heart to stop beating.