A case report has been published describing changes to the skull in a patient that has been taking phenytoin for nearly half her life.

In the case study, an unnamed woman had suffered from severe epilepsy most of her life, a condition partially controlled through phenytoin and other seizure antiepileptic drugs. The epilepsy started after a brain infection at the age of 15. At the age of 31, she suffered a head trauma when she fell during a seizure.

When doctors gave her a head X-ray, her doctors discovered that she had an advanced case of cerebral atrophy — a dramatic thickening of her skull.

The patient had taken Phenytoin since she was 18 years old. Before the X-ray, the patient had a few minor deformities due to the thickening bones. But the X-rays showed that her brain had shrunk as the walls of her skull thickened inward. The patient didn’t have any symptoms beyond the cosmetic.

The authors of the research paper state that other possible causes of cerebral atrophy “were not present in this patient.” However, they did suggest that the same brain infection that gave the patient epilepsy in the first place could not be ruled out as the cause of her cerebral atrophy.

However, the authors were quick to point out that the “the adverse events of phenytoin on skull thickening have long been recognized.” To back this, the researchers stated several known metabolic pathways allegedly triggered by phenytoin that could cause the skull to grow this way, including stimulating the cells that generate bone, and the proteins the body uses in bone growth.

Cerebral atrophy and related disorders like focal cerebral atrophy, where the skull does not uniformly thicken, can vary wildly in their severity and symptoms. Some cases, like the one described by the researchers in the paper, may not even cause obvious symptoms, beyond a thickening of certain facial features.

But when the atrophied parts of the brain perform important tasks, it can cause seizures, trouble speaking, problems understanding language, mental impairment, and other symptoms. Focal cerebral atrophy may only affect a very specific part of the brain and a very specific function, or it may cause widespread damage depending on which part of the brain is atrophied from encroaching skull bone.

The authors of the paper state that the exact rate of skull thickening like that seen in this patient with cerebral atrophy is unknown, but more than a third of institutionalized seizure patients are reported to have thickening of the skull. The researchers reported that this thickening of the skull may go hand-in-hand with “acromegaloid features.” Acromegaloid features are facial features that appear in certain types of gigantism. The connection is that these forms of gigantism may cause a thickening of the facial bones.

The research paper includes a CT scan picture of the thickened skull. Even an untrained eye can see that the cross section of bone showed a visibly thickened bone of the skull. While this patient didn’t have much in the way of symptoms, that is often not the case with changes in the brain. The article was published in a 2007 medical journal.