Adrenocorticotropic Hormone (ACTH) is a potent hormonal therapy often employed as a first-line treatment for Infantile Spasms (IS), a severe form of epilepsy also known as West Syndrome. This condition is a time-sensitive medical concern in infants, and rapid intervention with treatments like ACTH is essential for improving long-term outcomes. The use of this hormone balances its powerful therapeutic effect against a significant profile of side effects. The treatment aims to quickly halt the chaotic electrical activity in the infant’s brain that underlies the observable seizures.
Understanding Infantile Spasms
Infantile Spasms are an age-specific epilepsy syndrome typically beginning in the first year of life, most commonly between four and nine months of age. These seizures present as sudden, brief, and symmetric contractions of the neck, trunk, and limbs, often described as a “jackknife” or “head nod” movement. The spasms usually occur in clusters shortly after the infant wakes up, sometimes happening dozens or even a hundred times per day.
The diagnosis is strongly supported by an electroencephalogram (EEG) that shows a distinctive, highly disorganized pattern called hypsarrhythmia. Untreated or delayed treatment of infantile spasms can lead to severe neurodevelopmental regression, causing the child to lose previously achieved developmental milestones. Because of the risk of permanent harm to the developing brain, immediate diagnosis and initiation of effective therapy, such as ACTH, is required.
How ACTH Works to Stop Spasms
The exact mechanism by which ACTH stops infantile spasms is not fully understood, but current research points to a dual action within the body and brain. ACTH is a naturally occurring pituitary hormone that stimulates the adrenal glands to produce and release high levels of corticosteroids, such as cortisol. These steroids then modulate brain activity and reduce inflammation, which is thought to suppress the seizure-generating network.
Beyond this indirect effect, ACTH appears to have a direct, steroid-independent action on brain cells via melanocortin receptors. This direct action may involve suppressing the synthesis of corticotropin-releasing hormone (CRH), a neuropeptide that increases neuronal excitability and is implicated in the generation of spasms. By reducing CRH expression, ACTH helps to calm the overly excitable neurons responsible for the seizures. Successful treatment requires the complete cessation of visible spasms and the resolution of the chaotic hypsarrhythmia pattern on the follow-up EEG.
Administering the Treatment
ACTH is administered via injection, either subcutaneously (under the skin) or intramuscularly (into the muscle). Due to the potency of the medication and the need for close monitoring of side effects, treatment is often initiated during a short inpatient hospital stay. The duration of therapy typically lasts several weeks, followed by a gradual reduction, or taper, of the dose to allow the body to readjust.
Dosing protocols vary, with both high-dose regimens (such as 150 IU/m² per day) and lower-dose protocols showing efficacy in clinical trials. The treating neurologist selects the dose based on the specific formulation available and institutional practice. Parents or caregivers receive specialized training from medical staff to perform the daily injections at home after the initial hospital monitoring period. Careful adherence to the daily injection schedule and the tapering plan is necessary to maximize the chance of spasm resolution and minimize the risk of complications.
Monitoring and Adverse Effects
ACTH therapy is associated with a range of side effects, which require careful medical monitoring throughout the treatment course. One of the most noticeable effects is a Cushingoid appearance, characterized by rapid weight gain, increased appetite, and a distinctive rounding of the face. These physical changes are generally reversible once the treatment is complete.
More serious effects include a significant risk of infection because the high corticosteroid levels suppress the immune system. Hypertension (increased blood pressure) and hyperglycemia (elevated blood sugar levels) are also common and must be regularly checked. Frequent monitoring, including blood pressure checks several times a week and periodic blood tests to assess electrolytes and sugar levels, is essential to manage these risks. Stopping the medication requires a slow taper to prevent adrenal insufficiency, a condition where the adrenal glands temporarily struggle to produce enough natural cortisol.