Hormonal therapy may be considered in women with catamenial epilepsy, in whom seizures seem to follow a cyclical pattern related to the menstrual cycle [13, 15]. Three patterns of catamenial epilepsy have been described: C1 pattern where seizures increase in frequency just before and during menses, C2 pattern where seizures increase around the time of ovulation, and C3 pattern where seizures occur with anovulatory cycles. Catamenial epilepsy is thought to be related to progesterone and estrogen fluctuations. Estrogen appears to be proconvulsant, and progesterone appears to be anticonvulsant. In catamenial epilepsy, seizures are more likely to occur when the ratio of progesterone to estrogen decreases, as seen around the time of menstruation and the time of ovulation. The C1 pattern of catamenial epilepsy responds to progesterone 200 mg tid administered on days 14–28 of the cycle [14]. Synthetic progestins and clomiphene citrate have also been reported beneficial as treatments for catamenial epilepsy in small studies.

Ganaxolone is a derivative of allopregnanolone that lacks hormonal activity. It has been tested in a number of clinical trials. There was a suggestion that women with catamenial epilepsy were a subgroup that benefited in particular [30]. Ganaxolone was also tested in infantile spasms and found helpful in some patients [19]. It is not known if this compound will eventually be available for clinical use.

ACTH and steroids are first-line short-term treatments for infantile spasms/West syndrome. They help control seizures and improve behavior and EEG. They are most effective in the idiopathic syndrome. A high dose seems to be more effective. When it comes to ACTH, one approach is to begin with 40 IU per day for 1–2 weeks and increase to 60 or 80 IU per day thereafter if the response is incomplete. If it is effective, it is then tapered over 1–4 months. ACTH and steroids are less commonly used to treat Lennox–Gastaut syndrome and Landau–Kleffner syndrome.

Steroids and IVIG may be considered in the treatment of Rasmussen’s syndrome and other epilepsies suspected to be of immune origin, to treat the underlying cause of epilepsy. Limbic encephalitis, usually autoimmune, is increasingly recognized as a cause of chronic epilepsy. An immune basis of epilepsy should be considered when there is no other clear etiology, the onset was acute or subacute, and there is a prior history of autoimmunity (or autoimmunity is present in a first-degree relative), in the presence of a neoplasm, when there is CSF or imaging evidence of inflammation, and when neuronal autoantibodies are detected [36]. Faciobrachial dystonic seizures are brief seizures that predominantly affect the arm and ipsilateral face. They are an early sign in anti-LGI1 encephalitis that should prompt investigation for immune etiology and early immune therapy [17, 18]. The autoantibodies most commonly associated with immune epilepsy are anti-LGI1 antibodies (anti-voltage-gated potassium channel complex antibodies), anti-GAD antibodies, and anti-thyroid antibodies [25, 26]. Anti-NMDA antibodies are associated with a distinctive limbic encephalitis syndrome that usually includes seizures, but is unlikely to be a cause of pure chronic epilepsy [6]. When an immune origin is confirmed, first-line immunotherapies include oral or IV steroids (IV methylprednisolone 1000 mg daily for 3–5 days, then weekly for 4–6 weeks), IVIG (0.4 g/kg/day for 3–5 days then weekly for 4–6 weeks), or plasmapheresis [36]. If there has been incomplete benefit and there is strong evidence of autoimmune etiology, chronic immunosuppression could be considered with mycophenolate mofetil, azathioprine, or rituximab [36].