Background

Reflex seizures (RS) are provoked seizures by specific sensory stimuli, such as visual precipitants, eating, bathing, and writing. In 1964, Zivin et al. first reported a 14-year-old male patient with RS induced by micturition [1], and few studies have reported it subsequently. Due to the quite small number of known cases, little is known about the clinical presentation and electroencephalogram (EEG) features of RS induced by micturition. In this report, we describe a pediatric case of micturition-induced focal epilepsy diagnosed by ictal EEG recording. We also review other cases of micturition-induced RS in literature and summarize its main clinical and EEG characteristics, in order to improve awareness among practitioners about this rare form of RS.

Case presentation

An 8-year-old right-handed girl with moderate intellectual disability presented with new-onset seizures triggered by micturition. She had spontaneous generalized tonic-clonic seizures of unclear aetiology at 5 months of age. Subsequently, she took anti-seizure medicines regularly, and had been seizure-free after drug discontinuation for 4 years. Her family history was unremarkable. She was delivered via caesarean section because of breech presentation, and her development was moderately delayed. She did not walk without assistance until the age of 3, and she started to use words at the age of 5. She had received speech therapy and physical therapy.

At the age of 7, she developed seizures that consistently occurred immediately on micturition, at a frequency of approximately seven or eight times per day. Each seizure was induced by micturition, regardless of whether she was in the seated or standing posture. Defecation did not trigger the episodes. When each episode started, she would initially stop talking, and this was followed by staring, leftward deviation of the head and eyes, axial and arm tonic posturing and extension of the upper extremities as if to hug someone, and brief rhythmic jerking of the upper body for a few seconds. The entire episode lasted for 10 to 15 s with impaired awareness, and she returned normal afterwards.

Cranial magnetic resonance imaging showed hydrocephalus with several focal cerebral white matter lesions of unknown etiology (Fig. 1). The results of Holter monitoring and routine laboratory tests, such as complete blood cell count, glucose, electrolytes, liver function, urinalysis, and cerebrospinal fluid examination, were within the normal range. We recorded three typical seizures with video EEG monitoring, and all were induced by micturition. The seizures occurred a few seconds after micturition had begun, and the patient continued to urinate during the seizure. Scalp inter-ictal EEG showed a frontal dominant rhythm of 5–6 Hz (Fig. 2a). Ictal EEG showed low-voltage fast activity persisting 2 to 3 s without clear focal features, which then evolved into 3–4 Hz high-voltage irregular slow waves, and the post-ictal phase showed a normalized background (Fig. 2b and c). On the basis of clinical and EEG findings, the patient was diagnosed with RS induced by micturition. Valproic acid treatment was started, but the seizures were not controlled. After adding levetiracetam, the frequency of seizures was decreased to once to twice per month.

Fig. 1
figure 1

Cranial magnetic resonance imaging (MRI) showed scattered foci of long T1 signal in the bilateral inferior frontal cortex (arrows in a, b) and high signal on T2-weighted FLAIR (arrows in c, d)

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Fig. 2
figure 2

Scalp EEG recording of the present case. a Interictal EEG showed 5–6 Hz intermittent slow-wave background activity. b Ictal EEG showed low-voltage fast waves without clear focal features, followed by frontal dominant rhythmic multiple spikes in the average montage. c Ictal EEG showed diffuse low-amplitude fast waves in double banana montage. Red waves show the electrocardiogram signal, green waves and blue waves show the electromyography signal. The onset and end of the seizures are marked by yellow vertical lines. The red vertical lines represent the position corresponding to monitoring video playback and EEG. (Sensitivity at 10 µV/mm, LFF at 0.5 Hz, and HFF at 70 Hz)

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Literature review

We searched the databases PubMed (Medline) for articles published up to January 2022 with search terms “micturition reflex seizure”, “reflex seizure induced by micturition”, and “micturition induced seizure”, and reviewed all the articles identified and their references. Articles written in English and Chinese were retrieved for further review and discussion; however, publications in other languages, including an article in Italian and another one in Japanese, were not included. We identified 13 previous cases combined with the present case to summarize the clinical and EEG characteristics of RS induced by micturition. The detailed clinical features are given in Table 1.

Table 1 Reflex seizures induced by micturition
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Micturition-induced RS was most frequently recorded during the first decade of life (10 cases, 71.4%), with an age range of 3 to 18 years (mean age, 7.86 years). The 14 patients included 8 males (57.1%) and 6 females (42.9%). Micturition was the only trigger in 10 patients (71.4%), while a combination of triggers (apart from micturition) was reported in the remaining studies, for example, placing feet in hot water, defecation, praying, and getting startled. Ten patients (71.4%) experienced both provoked and spontaneous seizures. In addition, 10 of the 14 (71.4%) patients had normal structural neuroimaging results, and eight (57.1%) patients reported mental development delay. None reported a family history of seizures.

The seizure manifestations of the 14 patients were variable, but they all had seizures with focal onset. The seizures progressed to bilateral tonic-clonic seizures in two patients. With regard to the seizure semiology, posturing of the upper limbs (10 patients, 71.4%) was the most frequent presentation, followed by head/eye deviation (5 patients, 35.7%) and automatism (3 patients, 21.4%). In 8 patients (57.1%), awareness was preserved, whereas the others experienced a loss of consciousness. The inter-ictal EEG findings were unremarkable. In six reported cases (42.9%), ictal EEG indicated an epileptogenic focus in the midline region, while there were no clear focal features in five cases, including the case reported here.

Treatment with anti-seizure medication was documented in detail in 12 patients (85.7%): 6 with a monotherapy and the other 6 with a polytherapy. Valproate was used in five cases, lamotrigine in three, clobazam in three, and lacosamide in two. Six of the 14 cases (50%) became seizure-free, while one case was described as having refractory epilepsy.

Discussion

In this article, we reported an 8-year-old pediatric patient with micturition-induced reflex epilepsy. So far, only a dozen cases of micturition-induced RS have been reported in literature. Based on a review of all the published cases [2,3,4,5,6,7,8,9,10,11,12,13,14], the main features of micturition-induced RS include: (1) a rather low prevalence, with an onset predominantly in childhood, but affecting both sexes equally; (2) common co-existence of developmental delay in cases; (3) concomitant occurrence of spontaneous seizures in nearly 70% of these patients, often preceding the micturition-induced RS; (4) the most common features of clinical semiology include, in a descending order of frequency, posturing of the upper limbs, deviation of the head and eyes, automatism, and a lack of awareness; (5) the true epileptic focus is not clearly identified, but the onset is likely to be from the midline region; and (6) prognosis generally satisfactory, as half of the cases achieved adequate seizure control with anti-seizure medication.

RS induced by micturition seems to have a young age of onset, except one case who showed onset age of 18 years. In contrast, RS associated with other triggers seems to typically have an onset in the second decade of life [15]. The majority of patients with RS induced by micturition present normal structural neuroimaging features, but a common documented history of developmental delay. This suggests that the micturition-induced seizures may be associated with brain immaturity as well as preexisting neurodevelopmental abnormalities.

In literature, nine cases were reported to have spontaneous seizures preceding the micturition-induced RS [3, 5, 6, 8, 10,11,12,13,14]. Previous studies showed that the majority of patients with RS also suffer from spontaneous seizures, and over 21% of the patients with idiopathic generalized epilepsy experience concurrent RS [16]. Some investigators proposed that RS and spontaneous seizures are two extremities of a conceptual continuum [17]. Changes in structural and functional brain networks occur after spontaneous seizures, resulting in hyperexcitability in certain brain areas, which would become more susceptible to epileptic discharges upon stimulation from a particular sensory, cognitive or motor stimulus [18]. In addition, there were three cases who experienced a seizure-free period from spontaneous seizures to RS, just like our case presented here [5, 11, 13]. This phenomenon has been rarely studied, and the underlying mechanism requires further investigation.

Glass et al. [11] performed ictal single-photon emission computed tomography (SPECT) within 5 s of seizure onset and revealed hyperperfusion in the anterior cingulate gyrus and the right anterolateral frontal lobe. Another ictal SPECT study revealed significantly increased perfusion in the mesial frontal regions [8]. These areas were close to or directly overlap** with the areas activated by urinary function [19]. Similarly, Cvetkovska and colleagues [12] reported focal cortical dysplasia in the right middle frontal gyrus, which overlapped with the brain regions activated by urinary function. Based on these findings, we speculate that the mechanism of micturition-induced RS may involve excessive excitation of regions that participate in micturition, as these regions would be more susceptible to epileptic discharges triggered by the physiological voiding process and, therefore, more prone to seizures during urination.

The exact epileptic focus of micturition-induced RS has not been clearly identified. Several reported cases assessed by ictal EEG showed a central epileptogenic focus [2, 3, 5, 6, 10, 11, 14], while others had no clear focal features. The semiology of micturition-induced RS is characterized by posturing of the upper limbs, deviation of the head and eyes, and automatism, which indicate the involvement of a common neural pathway. As a complex process, micturition is regulated by multiple levels of the central and peripheral nervous systems. The superomedial part of the frontal lobe and the anterior part of the cingulate gyrus control micturition [19]. The supplementary motor area (SMA) is activated during contraction of the pelvic floor muscles, which produces seizure activity, such as tonic posturing involving unilateral or bilateral extremities [20]. In the present study, although an unclear epileptic focus was identified by ictal EEG, we speculate that the SMA is involved in epileptic networks due to the shared clinical features of the reported cases.

Conclusions

In conclusion, we report a case of RS-induced micturition with a focal initial EEG pattern. A review of all the reported cases so far indicate that the precise epileptic focus has not been clearly identified, but the onset is probably from the midline region. Future in-depth studies using advanced electrophysiology data acquisition and analysis techniques are needed to confirm these findings.