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What can be done to control unprovoked seizures in a 55-year-old woman with drug-resistant epilepsy who was admitted to the hospital?

The patient's medical history indicated that she had been diagnosed with drug-resistant epilepsy more than 40 years before, at the age of 12, reported Seyed Mirsattari, MD, PhD, of Western University in London, Ontario, and co-authors in .

At age 37, she had undergone an anterior corpus callosotomy after subdural electroencephalography (EEG) electrodes revealed nonlocalizable bifrontal epilepsy marked by switching lateralization and rapid bilateral progression. The surgical procedure had no effect on her seizure semiology, nor was it associated with any appreciable clinical improvements.

The patient told clinicians that typically before a seizure came on, her stomach would feel enlarged and she would have a wave of warmth. This would be followed by simple monosyllabic vocalizations before she would lose awareness.

Clinicians learned that her seizures lasted about 2 minutes, and were usually "accompanied by manual automatisms of either hand and concomitant dystonic posturing of the contralateral arm." On some occasions, a seizure would be followed by an urgent need to urinate.

She explained that her seizures usually occurred at night. In discussing her history with physicians, the patient recalled that since she was a child, she had noticed that being in direct contact with a cold surface -- like when walking barefoot on cold tiles -- was sure to trigger a seizure.

The patient described similar effects with sudden exposure to cooler temperatures, for instance after quickly taking her sweater off in an air-conditioned space or walking into a pool of cool water without giving her body time to adjust to the change in temperature.

To assess her response, clinicians placed an ice pack on her back. This sensation immediately triggered her typical seizure.

The patient underwent a single-photon emission CT scan. The result, overlaying a T1-weighted MRI, "demonstrated ictal hyperperfusion of the right inferomedial and inferolateral frontal lobes, which represent the epileptogenic regions involved in the patient's cold reflex seizures," the authors explained.

During the ictal time frame, the team performed an EEG of her scalp. This revealed "muscle artifacts that obscured the onset of seizures, followed by rhythmic activity in the right temporal region with transfer to the left temporal region," they wrote.

Clinicians performed a subsequent stereoelectroencephalography (SEEG) with depth-electrode recordings. They interpreted the findings as suggesting that the patient's typical seizures originated from the right lateral orbitofrontal region. "The semiology of her cold-induced reflex seizure was consistent with her typical seizures captured on scalp EEG and SEEG, respectively," they noted.

Discussion

Reflex epilepsy is characterized by consistent seizures triggered by a specific stimulus. This may be generated internally, by stimuli such as cognitive demands or emotions, or external factors, such as lights, sounds, or temperature. Visual stimuli account for 75% to 80% of all triggers in reflex epilepsy, along with thinking, music, and eating, according to a on reflex epilepsy.

Temperature-generated typically occurs when hot water triggers temporal lobe seizures, the authors explained; cold-induced reflex epilepsy is very rare.

"This patient presented with focal-onset seizures with impaired awareness in response to the sensation of an ice pack," the team wrote. Results of the SEEG sampling suggested the seizures originated in the right orbitofrontal lobe, "and were associated with transfer of rhythmic activity between the right and left posterior supplementary motor cortices."

Another case report of cold-induced reflex epilepsy described a patient "whose epileptogenic zone likely originated from the prefrontal lobes with similar ictal findings of slow rhythm transfers between the temporal lobes on scalp EEG," they added.

While little is known about the brain activities involved in cold-induced reflex epilepsy, functional indicate exposure to cold results in "increased activation of the orbitofrontal cortex, anterior cingulate, and posterior insula," which Mirsattari and team noted is similar to other primitive experiences related to pain, hunger, and thirst.

Reflex epilepsy often involves underlying hyperexcitability of the cortical region triggered by exposure to the offending stimulus, the authors said. "We postulate that cold-induced reflex epilepsy arises from hyperexcitability of the orbitofrontal cortex, although we cannot definitely exclude rapid seizure propagation from the insula."

Primary treatments for cold-induced reflex epilepsy include avoidance of cold stimuli and use of antiseizure medication. When the epilepsy is resistant to medical treatment, surgical resection of the culprit region can be considered, although this patient declined that option.

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