Congenital neurological disorders: Pathology review

At the physician’s office, a 30 year old male named Alex came in because of headaches and dizziness for the past few months. He also often stumbles while walking and recently fell down the stairs. His past medical history is insignificant. MRI of the brain and spinal cord shows herniation of the cerebellar tonsils.

Next to Alex, there’s a mother with her 4 years old child named Evi who had recurrent urinary tract infections. Evi was born with leg paralysis and leg deformities. Clinical examination reveals a mass on her lower back.

All right, both of them have a congenital neurological malformation, which occurs when there’s a primary defect in the developmental process of the nervous system. These conditions appear as the baby develops in utero and can vary in severity and presentation, ultimately impacting the infant's health, development, and survival. The most high yield neurological malformations are neural tube defects, posterior fossa malformations, syringomyelia, and holoprosencephaly.

Okay, let’s take a closer look at these disorders, starting with neural tube defects, or NTDs, which include spina bifida and anencephaly. They’re relatively common anomalies that develop when a portion of the neural tube - the precursor of the central nervous system- fails to close as it should during the fourth week of gestation. When the posterior neuropore doesn’t close well, the baby is born with spina bifida, which is Latin for “split spine”. But when the anterior neuropore doesn’t close properly, the forebrain fails to develop, and the baby is born with anencephaly or absence of a major portion of the brain and the skull. In spina bifida, there’s incomplete closure of the vertebrae and membranes of the spinal cord.

A very high yield risk factor for NTD is folate or vitamin B9 deficiency in the mother. For this reason, folic acid, which is the manufactured form of folate, should be given at least one month prior to conception and during early pregnancy. Another important concept for the exams is that certain medications can also increase the risk for an NTD because they interfere with folate metabolism. These include valproic acid and phenytoin, which are antiepileptics; trimethoprim and sulfonamides, which are antibiotics; and methotrexate, which is an anticancer medication. Finally, other risk factors that increase the risk for NTDs include obesity and maternal diabetes.