Menstrual-Related Seizures and Psychosis

Gregory L. Krauss, MD


June 01, 2004


A 17-year-old girl has menstrual-related seizures and psychosis. The patient has had intractable seizures since menarche at the age of 13. She is developmentally disabled because of chromosomal mosaicism. She always has had a learning disability with behavioral abnormalities. Every anticonvulsant except felbamate has been tried and either has caused psychiatric side effects or has been ineffective. She was seizure-free during 2 years of treatment with phenytoin and divalproex sodium.

Over the past year, she has become disabled with psychosis for approximately 1 week before her menstrual periods but returns to baseline about a week after. She initially responded dramatically to progesterone100-200 mg daily, plus continuous norethindrone and other oral contraceptives. Her perimenstrual psychoses and seizure activity continue. She has 4-6 grand mal seizures and drop attacks each day and now wears a helmet full time. Continuous electroencephalographic monitoring demonstrates bilateral epileptiform discharges. The patient will soon begin a ketogenic diet with hospitalization first. Would corpus callosotomy and vagal nerve stimulation (VNS) be recommended? Would leuprolide or Depo-Provera injections be worth trying? What other management strategies would you suggest?

Sophocles Panagon, MD

Response from Gregory L. Krauss, MD

The patient has a severe form of symptomatic epilepsy and probably has daily tonic seizures and complex motor seizures rather than full tonic-clonic convulsions. Unfortunately, these types of seizures are associated with diffuse cerebral dysfunction and are often resistant to medications. Valproic acid has been the mainstay of therapy for many patients with severe symptomatic epilepsy; however, polytherapy is frequently required, and patients may respond to a variety of other medications, including phenytoin, lamotrigine, topiramate, zonisamide, felbamate, and adjuvant benzodiazepine therapy.

I asked Dr. Andrew Herzog, an expert on the hormonal influences on epilepsy, to comment on the unusual association of perimenstrual psychosis:

"The monthly premenstrual development of psychosis has been described in the literature by Endo and others. [1] It is often refractory to treatment with psychotropic medications and tends to respond best to hormonal manipulation [that is] aimed to prevent unopposed estrogen effect[s] or progesterone withdrawal during the luteal phase. This can be achieved to some extent with cyclic or continuous progesterone use, as you describe, or with the reversible elimination of the menstrual cycle using depot leuprolide, and balanced, stable hormone replacement therapy using estrogen and natural progesterone. We provide a case example in our 3-part Psychosomatics article. [2,3,4]"

The patient presumably requires a helmet to protect from seizure-related injuries and consequently has been offered a corpus callosal section to reduce injuries associated with tonic/atonic seizures and falling. Many centers perform VNS treatment before considering a callosal section. A single-case report describes a patient with a chromosomal defect and symptomatic epilepsy who responded to VNS therapy.[5] Isolated patients with Lennox-Gastaut syndrome or symptomatic myoclonic epilepsy improve with VNS therapy, although in large series, overall group responses to VNS therapy are disappointing.[6] VNS therapy is well tolerated by patients with severe symptomatic epilepsy and does not contribute to common drug side effects seen in polytherapy treatment of this population. The ketogenic diet is an excellent option and can be considered in addition to VNS therapy, although I suggest staggering the initiation of these therapies to monitor the patient's response.


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