Reflex seizures are epileptic events triggered by specific stimuli. They are thought to arise from areas of cortical hyperexcitability that overlap with regions normally activated during specific cognitive, motor and sensory stimulation (Ferlazzo et al., 2005). Although the most common precipitants are visual (particularly flashing lights), a variety of somatosensory phenomena, including thinking, reading, listening to music, and eating may also induce reflex seizures.
Reflex seizures may occur as an isolated entity or as a part of a focal or generalized epilepsy syndrome. Photosensitivity is present in 30.5–42% of patients with juvenile myoclonic epilepsy, and both generalized tonic–clonic and myoclonic seizures may be evoked (Wolf and Goosses, 1986). Focal brain lesions may also trigger reflex seizures. This was first shown by Clementi, who in 1929 provoked reflex seizures to flickering light after the application of strychnine to the dog visual cortex (reviewed in Ferlazzo et al., 2005).
A 12-year-old left-hand-dominant girl with moderate developmental delay of unknown etiology was initially seen in our center with seizures provoked by both micturition and prayer. She was neurodevelopmentally normal until the age of 2, when partial complex seizures developed, characterized by an odd laugh, extension of both arms with rhythmic jerking, and occasional extension of her left leg. Since age 10, she has had reflex seizures with every micturition and also reliably with prayer (presumably induced by a strong emotional response to the phrase “In the name of the Father, the Son, and the Holy Spirit”). The seizures occurred 4 to 6 times daily, with each void, and during prayers. Seizures remained refractory to adequate trials of phenobarbital (PB), valproic acid (VPA), clonazepam (CZP), topiramate (TPM), lamotrigine (LTG), clobazam (CLB), and the ketogenic diet.
We recorded numerous clinical and electrographic seizures during three separate sessions. The video and EEG clearly demonstrated that micturition or prayer quickly precipitated stereotyped events. The semiology consisted of pupil dilatation and staring, followed by loss of body tone lasting 1 to 2 min. At times, the eyes and head deviated to the left, with occasional rhythmic clonic activity of both arms. EEG disclosed seizures with initial moderate-voltage 20- to 22-Hz rhythmic epileptiform activity at Cz, followed by rapid spread to both frontal head regions (Fig. 1). The seizures persisted for 60–100 s and were followed by bilateral frontal slowing.
Magnetic resonance imaging (MRI) of the head was normal. Ictal and interictal SPECT were performed by using 550 Mbq of 99mTc ECD. Images were acquired with a triple-headed Picker 3000 SPECT gamma camera (Picken International, Cleveland, OH, U.S.A.). Ictal SPECT injected within 5 s of seizure onset showed hyperperfusion in the area of the anterior cingulate gyrus, as well as the anterolateral right frontal lobe (Fig. 2). Less-prominent hyperperfusion was noted diffusely in the anterolateral left frontal lobe. Seizures were suppressed for >12 h with placement of a urinary catheter before injection for the interictal SPECT, which was normal with no evidence of regional hypoperfusion.
Pediatric reflex frontal lobe epilepsies are most often generated in the premotor or motor cortex and are usually triggered by somaesthetic, auditory, or visual stimuli (Vignal, 2003). Cingulate seizures are rare. They tend to be frequent, stereotyped, and often lack a significant pre- or postictal state (Devinsky et al., 1995; Magaudda, 2003). The classic semiology involves intense emotion (fear, laughing, crying), dramatic automatisms, autonomic phenomena, and often bizarre motor movements. Reflex seizures arising from the cingulate gyrus have not been described. We report a case of partial complex seizures reliably triggered by both micturition and emotional response to prayer. The seizures arose from deep midline structures (probably anterior cingulate gyrus) with rapid spread to the anterolateral right frontal lobe.
The anterior cingulate cortex forms a large region around the rostrum of the corpus callosum, known as the anterior executive region. This region is subdivided into “cognition” and “affect” components and has numerous projections to motor systems (Devinsky et al., 1995). The “cognition” division is involved in early premotor function. It is important in information processing and helps to determine whether a movement is needed, as well as the appropriate motor response. This division also has a nociceptive role and specifies the affective content and selects motor response to noxious stimuli. It is also involved in learning associated with the prediction and avoidance of such stimuli. The “affect” component comprises Brodmann areas 25, 33, and 24, and has extensive connections with the amygdala and periaqueductal grey. It is involved in the regulation of autonomic and endocrine function (including blood pressure, heart rate, respiratory rate, mydriasis, nausea, and bowel and bladder evacuation), in conditioned emotional learning, in vocalizations associated with expressing internal states, and in assigning emotional worth to internal and external stimuli. Activation of areas 24 and 24′ by intravenous administration of procaine in humans led to emotional and psychosensory experiences (Ketter et al., 1996), and electrical stimulation of the anterior cingulate cortex induced fear, pleasure, or agitation (Meyer, 1973). PET studies of healthy volunteers have shown elevated blood flow in areas 24 and 25 with happiness and in response to photographs of facial expression with emotional content, thus confirming the role of the anterior cingulate in affect (George et al., 1993).
Micturition is coordinated by multiple levels of the central and peripheral nervous system. The cortical control of micturition comes from superomedial portion of the frontal lobe and the anterior aspect of the cingulate gyrus (Brazis et al., 2001). Positron emission tomography (PET) studies show that the right-sided micturition centers are more active than those on the left (Blok et al., 1997).
Seizures induced by micturition must be differentiated from more-common conditions, including micturition syncope, urinary incontinence due to sphincter relaxation during generalized seizures, and the ictal urinary urge of nondominant temporal lobe epilepsy (Kapoor et al., 1985, Baumgartner et al., 2000).
Although micturition-induced reflex epilepsy is poorly understood, published cases suggest a midline or right frontal focus. Pradhan and Kalita (1993) described a 15-year-old with micturition-induced secondarily generalized tonic–clonic seizures due to a calcified granuloma in the right frontal lobe. Interictal EEG showed right frontal spikes; ictal EEG was not recorded. Spinnler and Valli (1969) reported a 16-year-old girl with mental retardation and reflex seizures occurring toward the end of micturition. The EEG showed a spike–wave pattern arising from the central anterior leads, possibly from the right frontal lobe. Bourgeois (1999) presented a boy with mental retardation due to a chromosomal anomaly with reflex seizures of similar semiology during both micturition and bathing. EEG recorded during the bathing events showed apparent onset at Cz and possibly F4.
We present a case of reflex epilepsy induced by both micturition and the emotional response to prayer. SPECT and EEG suggested seizure onset from the anterior cingulate, with rapid spread to the right anterolateral frontal lobe. The initial fast activity on EEG, as well as the semiology and refractory nature of the seizures, are in keeping with what is known about cingulate seizures in children (Devinsky et al., 1995). We postulate that our patient has a region of cortical hyperexcitability in the “affect” component of the anterior cingulate cortex, with seizures triggered both by micturition and by the emotional component of prayer. A focal area of cortical dysplasia could account for the epilepsy and also help explain the mental retardation. This represents the first case of reflex seizures probably localized to the anterior cingulate cortex, and suggests this localization for at least some cases of reflex micturition-induced seizures.
Acknowledgment: We thank Dr. Frederick Andermann for a review of the manuscript, Dr. Vanessa Palumbo for the English translation of the article by Spinnler and Valli, and Dr. Sutton-Brown for help with the figures.