Dealing with the storm: An overview of seizure precipitants and spontaneous seizure worsening in drug-resistant epilepsy.

In drug-resistant epilepsy, periods of seizure stability may alternate with abrupt worsening, with frequent seizures limiting the individual's independence and physical, social, and psychological well-being. Here, we review the literature focusing on different clinical scenarios related to seizure aggravation in people with drug-resistant epilepsy. The role of antiseizure medication (ASM) changes is examined, especially focusing on paradoxical seizure aggravation after increased treatment. The external provocative factors that unbalance the brittle equilibrium of seizure control are reviewed, distinguishing between unspecific triggering factors, specific precipitants, and 'reflex' mechanisms. The chance of intervening surgical or medical conditions, including somatic comorbidities and epilepsy surgery failure, causing increased seizures is discussed. Spontaneous exacerbation is also explored, emphasizing recent findings on subject-specific circadian and ultradian rhythms. Awareness of external precipitants and understanding the subject-specific spontaneous epilepsy course may allow individuals to modify their lifestyles. It also allows clinicians to counsel appropriately and to institute suitable medical treatment to avoid sudden loss of seizure control.