Diabetes Medication Shows Promise as Alternative Treatment for Hydrocephalus

A study conducted by Northwestern Medicine suggests that a medication typically used for managing type 2 diabetes may offer a new, less invasive treatment option for individuals suffering from hydrocephalus. This research was published in the Journal of Clinical Investigation.

Hydrocephalus, particularly normal pressure hydrocephalus, arises when excess cerebrospinal fluid accumulates in the skull, exerting pressure on the brain. This condition, which can affect up to 3% of those aged over 65, can lead to significant symptoms such as cognitive decline, gait issues, and urinary problems. Currently, the predominant treatment involves surgically implanting a ventriculoperitoneal shunt, which diverts excess fluid from the brain to the abdomen, effectively alleviating symptoms.

Despite the effectiveness of shunt surgery, there is no approved pharmaceutical treatment specifically for hydrocephalus. Notably, approximately 20% of patients diagnosed with normal pressure hydrocephalus also have type 2 diabetes and are prescribed sodium/glucose cotransporter 2 (SGLT2) inhibitors to help regulate their blood sugar levels, as well as improve cardiovascular and kidney function.

Recent observations by a researcher revealed that a patient with hydrocephalus who underwent shunt surgery experienced a significant reduction in the size of brain ventricles after beginning treatment with SGLT2 inhibitors. This prompted further investigation into the potential effects of these medications on ventricular size in hydrocephalus patients.

It was noted that SGLT2 inhibitors act on a receptor located in the kidneys, which also appears in the choroid plexus--a part of the brain responsible for producing cerebrospinal fluid. While previous animal studies suggested this connection, the clinical implications had yet to be fully explored.

In this study, three hydrocephalus patients underwent CT scans before and after receiving shunt surgery. Following surgery, these patients were prescribed SGLT2 inhibitors for diabetes management and subsequently underwent additional CT scans. The results indicated a reduction in ventricle size and structural alterations in the brains of all three patients post-treatment.

One patient exhibited a remarkable decrease in ventricle size, leading to the necessity for an adjustment of their shunt valve to optimize cerebrospinal fluid drainage.

This significant observation suggests a potential pathway for utilizing SGLT2 inhibitors as a treatment for normal pressure hydrocephalus, traditionally managed through surgical means. This line of research has opened up new inquiries into the mechanisms behind the development of hydrocephalus and the specific roles that these medications may play in the management of this condition.

Ongoing studies are being conducted using SGLT2 knockout mouse models to further understand how these drugs influence ventricular size. The implications of this research could not only transform the therapeutic landscape for normal pressure hydrocephalus but also address post-traumatic hydrocephalus, where cerebrospinal fluid accumulates following brain injuries.

This innovative approach could potentially spare patients from the risks associated with surgical interventions and enhance our understanding of the underlying processes involved in cerebrospinal fluid dynamics.