“Tweeting” Seizures in a Patient with Tuberous Sclerosis with Refractory Epilepsy

Dear Editor, Cognitive, emotional, autonomic findings, automatisms, and clinical features as motor and sensory symptoms can occur in focal epileptic seizures. Focal seizures often originate from the temporal lobe, and the mesial temporal and amygdalohippocampal areas are commonly associated origins. Aura is frequently seen in temporal lobe seizures, and automatisms are one of the most prominent manifestations. Early head-turning, which is not usually forceful, is mostly ipsilateral and typically co-occurs with a dystonic posture in the contralateral upper extremity.[1] Postictal aphasia is commonly related to dominant temporal seizures.[2] The frontal lobe is known to be the second most common origin of focal-onset seizures after the temporal lobe. Many different seizure types can occur in frontal lobe seizures. Asymmetrical tonic or postural seizures are usually related to the involvement of the supplementary motor area. A nonspecific aura may precede frontal lobe seizures with impaired consciousness that start abruptly and are accompanied by bizarre behaviors and agitation. Misdiagnosis as a psychogenic seizure may result in challenging patient management. Although the semiology of seizures is beneficial regarding lateralization of the lobe where the seizure originates, semiologic findings can become confusing by the spread of ictal discharges to other parts of the hemisphere. It is essential to remember that seizures originating from the frontal lobe may propagate to the temporal lobe and imitate clinical signs typical of temporal lobe seizures. Ictal whistling is an extremely rare presentation, and ictal onset in electroencephalography (EEG) is defined primarily from the temporal lobe. It has also rarely been shown to originate from the frontal lobe.[3] Herein, we present a patient with tuberous sclerosis complex disorder and treatment-resistant seizures, accompanied by different types of whistling, one was like "tweeting," who achieved significant benefits from everolimus treatment. A 34-year-old right-handed male patient had his first seizure when he was aged 13 years old when he was asleep at night, which manifested with screaming, snapping fingers, whistling, and kicking with his foot. He describes a strange feeling in his epigastric area before some but not all seizures. Afterward, his family describes hand automatisms, loss of awareness, whistling, snapping fingers, and pulling at his clothes. The patient is amnestic for this period. Despite multiple anti-seizure drug regimens, including valproic acid, carbamazepine, topiramate, levetiracetam, lacosamide, and zonisamide, the frequency of seizures continued once or twice per week. Due to the increased frequency of seizures to three to four times per week, the patient was admitted to the video EEG monitoring unit to differentiate between epileptic–nonepileptic seizures while he was receiving maximum doses of valproic acid, lacosamide, levetiracetam, and zonisamide polytherapy. Angiofibromas in the malar area on his face and ungual fibromas were noticed during hospitalization [Figure 1]. The patient was consulted by the dermatology department, and a diagnosis of tuberous sclerosis complex was made according to the clinical criteria. In the brain magnetic resonance imaging (MRI), an increase in the focal sulcus distance, remodeling in the tabula interna in the bifrontoparietal region, and focal thickenings were detected in the calvarium. There were no cortical tubers [Figure 2]. In positron emission tomography–computed tomography, minimal hypometabolism was seen in the bilateral temporal lobe anterior cortex. Multiple angiomyolipomas were detected in the contrast-enhanced MRI of the abdomen.Figure 1: Black arrows indicate anjiofibromas involving the malar regions of the face (a) and ungual fibromas on the toes (b)Figure 2: White arrows indicate the increase in the focal sulcus distance and remodeling in the tabula interna in the bifrontoparietal region and focal thickenings in the coronal T2 brain magnetic resonance imaging (a), and hypometabolism in the bilateral temporal lobe anterior cortex in coronal slices of F18-fluorodeoxyglucose positron-emission tomography (b)In video EEG monitorization, electrode placement was made according to the International 10–20 system with the addition of extra temporal electrodes (corresponding to positions T1 and T2). During monitorization, we recorded three seizures with the same clinical and electrophysiologic findings [Video 1]. First, the patient screamed, whistled briefly and loudly, and shook both hands. A head deviation that was not forceful was observed for a few seconds concurrent with hand clapping. Afterward, flexor dystonic posture occurred in the left hand while the right hand simultaneously rubbed his face. After 2 to 3 s, a low tone finger snapping started repeatedly on the right hand. Then, automatisms were observed in both hands, such as clapping hands and clothes pulling, predominantly in the genital area. The patient started to whistle softly and repeatedly like a tweeting bird. At the end of the seizure, he wiped his nose with his right hand. He nodded his head in a yes response to questions but could not respond verbally. This behavior gave the impression of regained partial awareness with aphasia. {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"Video Clip 1","caption":"","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_3bejt9gl"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} In EEG, concurrent with the beginning of the seizure, widespread low-amplitude fast-frequency activity started. After 10 s, diffuse muscle artifacts appeared for 2–3 s during the whistling and screaming. Immediately afterward, the EEG evolved to rhythmic slow spike and delta waves in both frontotemporoparietal areas with right dominancy, which continued for about 70 s, with a higher amplitude in the right hemisphere. At the end of the seizure, the amplitude and frequency decreased within 10 s and then ended. In the postictal period, there was a widespread voltage depression that lasted for 30 s, and then background activity returned to normal. During the video EEG monitorization, there were sharp slow wave discharges with phase confrontations in the F8-T2 and T2-T4 electrodes on the right hemisphere in the interictal period. Everolimus treatment was started on the patient who had renal angiomyolipomas and seizures resistant to polytherapy. After the 2nd month of treatment, the frequency of seizures decreased to 3 to 4 per month, and the patient was reportedly seizure-free after the 4th month of treatment. We first gradually reduced and then stopped the zonisamide treatment. The valproic acid treatment was also tapered and stopped at the 6th month of the everolimus treatment because the patient reported tremors in his hands. DISCUSSION Whistling seizures have been rarely described in the literature, with only eight cases reported, most of which were primarily associated with the temporal lobe and rarely with the frontal lobe.[3-8] It was also reported as postictal whistling in a patient with Lennox–Gastaut syndrome with generalized epileptic discharges and was associated with the involvement of multiple networks.[9] No lateralizing finding could be detected at the beginning of the EEG of our patient during different nonverbal vocalizations after short-term high-volume whistling. However, the time-match scalp EEG record showing generalized low amplitude fast frequency activity, and the left hand's dystonic posture were signs of frontal lobe origin. However, when the "tweeting" occurred, the rhythmic electrical activity evolved to bilateral frontotemporoparietal regions with higher amplitudes at the right hemisphere. Controversial reports exist regarding the lateralizing value of ictal whistling. Right temporal lobe focus examples have been described more frequently in the literature. It has been suggested that whistling seizures are often associated with complex motor behaviors due to the involvement of the nondominant hemisphere.[6] However, in functional MRI studies, early activation in the left supplementary motor area and the presupplementary motor area was observed in right-handed individuals during whistling.[10] It has been suggested that this area is effective in the onset of whistling. The ongoing whistling process continues through a more comprehensive bihemispheric network that includes structures such as the premotor cortex, cingulate cortex, thalamus, basal ganglia, and amygdala.[10] Other motor findings of our patient, such as the dystonic posture in the left hand and postictal nose wiping with the right hand, indicate activation of the right hemisphere. Another finding in our patient was that finger snapping could occur in frontal and temporal epilepsy. Finger snapping that occurs once and loudly has been attributed to the frontal region in the literature.[11] Otherwise, temporal finger snapping occurs repeatedly. It is less loud, as in our patient, the finger snap occurred in the later phase of the seizure simultaneously with the bifrontotemporal EEG activity appearance.[12] All seizures of our patient in the video EEG monitoring unit started with widespread rapid activity and continued with ictal activity in both frontotemporoparietal regions with right dominancy as the tweeting began. This finding supports the idea that tweeting occurs with the activation of multifunctional networks in different brain regions. In our patient, the left dystonic posture and right nasal wiping point to the right hemisphere, but postictal aphasia is localized to the dominant hemisphere, most likely the left. The patient was right-handed, and most probably, the left hemisphere was dominant in this patient, yet a functional MRI could not be performed. We think such complexity regarding semiologic features is related to the fast temporal evolving model. Invasive EEG electrode placement may be informative about seizure onset and evaluation. Nevertheless, the contribution of the interhemispheric connections needs to be clarified. In conclusion, whistling seizures are extremely rare presentations of focal epileptic seizures. Our case report is rare and unique with tweeting seizure phonology. Furthermore, two types of whistling appeared in the same seizure; short and sharp whistling showing the frontal lobe, and tweeting, indicating temporal lobe involvement. Declaration of patient consent The authors certify that they have obtained appropriate patient consent form. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.