Aortic regurgitation (AR), also known as aortic insufficiency (AI), is the leaking of the aortic valve of the heart that causes blood to flow in the reverse direction during ventricular diastole, from the aorta into the left ventricle. As a consequence, the cardiac muscle is forced to work harder than normal. Signs and symptoms
Symptoms of aortic regurgitation are similar to those of heart failure and include the following:
Dyspnea on exertion
Orthopnea
Paroxysmal nocturnal dyspnea
Palpitations
Angina pectoris
Cyanosis (in acute cases)

Causes
In terms of the cause of aortic regurgitation, is often due to the aortic root dilation (annuloaortic ectasia), which is idiopathic in over 80% of cases, but otherwise may result from aging, syphilitic aortitis, osteogenesis imperfecta, aortic dissection, Behçets disease, reactive arthritis and systemic hypertension. Aortic root dilation is the most common cause of aortic regurgitation in developed countries. Additionally, aortic regurgitation has been linked to the use of some medications, specifically medications containing fenfluramine or dexfenfluramine isomers and dopamine agonists. Other potential causes that affect the valve directly include Marfan syndrome, Ehlers–Danlos syndrome, ankylosing spondylitis, and systemic lupus erythematosus. In acute cases of aortic regurgitation, the main causes are infective endocarditis, aortic dissection or trauma. Pathophysiology
The mechanism of aortic regurgitation, comprises the pressure in the left ventricle falling below the pressure in the aorta, the aortic valve is not able to completely close. This causes a leaking of blood from the aorta into the left ventricle. This means that some of the blood that was already ejected from the heart is regurgitating back into the heart.
Megalencephalic leukoencephalopathy with subcortical cysts (MLC, or Van der Knaap disease) is a form of hereditary CNS demyelinating disease. It belongs to a group of disorders called leukodystrophies. It is characterized by early-onset enlargement of the head (macrocephaly) as well as delayed-onset neurological deterioration to include spasticity, epilepsy, and lack of muscular coordination. MLC does not appear to be a disease that is fatal at birth or early in life despite its symptoms, although the number of patients throughout history known to have the disease is fairly limited.It belongs to a group of disorders called leukodystrophies. A series of cases with megalencephalic leukodystrophy were described by the Indian neurologist Bhim Sen Singhal (1933-) in 1991. However, it is sometimes referred to as Van der Knaap disease after the Dutch neurologist Marjo van der Knaap who described another series of cases with clinical and radiological features in 1995.There are three types of Megalencephalic leukoencephalopathy distinguished by the affected gene: Type 1 caused by autosomal recessive mutations on the MLC1 gene, Type 2A an autosomal recessive mutation on the HEPACAM gene, and Type 2B an autosomal dominant mutation on the HEPACAM gene. Signs and Symptoms
Head
Macrocephaly
The disease is characterized by megalencephaly, the enlargement of the brain, which is followed by an increase in the size of the actual head.