Perineal stimulation triggering seizures in a child with Dravet syndrome

Open ArchivePublished:October 09, 2018DOI:https://doi.org/10.1016/j.seizure.2018.10.001

      Keywords

      1. Case summary

      The index case is a 3-year old boy with Dravet syndrome (de novo mutation in SCN1A gene; p.Ala889Thr [A889 T] variant) born to a non-consanguineous couple of south Indian origin. After an unremarkable early infancy, he presented with infrequent unprovoked hemi-clonic and generalized tonic-clonic seizures at 5 months of age. These were relatively controlled on oral low dose valproate. He had mild delay but could walk with support and spoke 4–5 words at 18 months of age. At 18 months of age, he sustained head trauma; he was dropped down from the lap while leaving the car. There was no significant change in sensorium. Magnetic-resonance-imaging of brain (MRI-epilepsy protocol), at this point, was unremarkable. Subsequently, he suffered gradual worsening of his seizures and loss of milestones. He also experienced 3 episodes of status epilepticus requiring prolonged hospitalizations, one provoked by an inter-current febrile illness. Currently, he experienced multiple daily brief seizures of various semiologies: right sided hemi-clonic seizures, staring/drooling, laughing/eye deviation to one side, multifocal body jerking. He was on valproate, clobazam and stiripentol. He also had significant feeding difficulties with gastro-esophageal reflux (waiting for G-tube insertion).
      He now presented with markedly increased seizure frequency, inability to stand and worsening feeding difficulties. There was no definite trigger. The parents also reported recent onset a new seizure type, triggered by perineal scrubbing during changing the diapers. They were characterized by bilateral extension of limbs, grunting and frothing from the mouth, lasting for 30–60 seconds. This was followed by quick recovery. They happened consistently within a few seconds of scrubbing the perineal area. They happened with both cold and warm wipes, but more frequently with cold wipes. They were not triggered by tactile stimulations at other places. They never happened while bathing (cold or warm). These were classified as reflex seizures.
      Basic blood investigations along with trough serum valproate and fasting serum ammonia were within normal limits. Electro-encephalography (EEG) was done to rule out non-convulsive status epilepticus. The EEG showed frequent multifocal spike and sharp waves (more frequent over the right hemisphere especially in the centro-parietal region). One of the events triggered by diaper-change was also captured during the video-EEG recording (Fig. 1 and video 1). Topiramate was initiated with partial response. The ketogenic diet and cannabinoid oil are being considered as next treatment options.
      Fig. 1
      Fig. 1EEG epochs in the reported child with Dravet syndrome. The inter-ictal EEG showed sleep activated frequent multifocal spike waves (A and B). They frequently occurred in runs of 2–3 Hz discharges. C shows the ictal EEG of the reflex seizure. After stimulation, the very frequent inter-ictal spike waves disappear. At the onset of the clinical seizure (marked as a black arrow), there is sudden onset diffuse 15–20 Hz beta activity lasting for 8 s followed by brief period of diffuse slowing (record obscured by movement artefacts).

      2. Discussion

      Dravet syndrome (DS) is a severe epileptic encephalopathy presenting in infancy. A wide range of stimuli are known to trigger seizures in these patients including fever, hot water bath, flickering lights, music, stress, and physical exercise. Verbeek et al. [
      • Verbeek N.E.
      • Wassenaar M.
      • van Campen J.S.
      • et al.
      Seizure precipitants in Dravet syndrome: what events and activities are specifically provocative compared with other epilepsies.
      ] showed high prevalence of seizure precipitant in patients with DS. Elevated body temperature caused by fever, warm bath, warm ambient temperature or physical activity was the most important trigger for seizures. However, seizures provoked by touch have rarely been described in Dravet syndrome.
      Subki et al. [
      • Subki A.H.
      • Alasmari A.S.
      • Jan F.M.
      • Moria F.A.
      • Jan M.M.
      Reflex seizures triggered by diaper change in Dravet syndrome.
      ] reported reflex seizures triggered by diaper change in a girl with DS from Saudi Arabia. The seizures were characterized by eye deviation to right and right arm posturing with or without secondary generalization. However, only warm wipes were reported to trigger these events. They attributed locally elevated body temperature as the trigger for these seizures. In our case, both cold and warm wipes triggered the seizures. We believe that the sensory stimulus of perineal rubbing may have triggered the reflex seizures in our case.
      The exact mechanism is unclear. Ferlazzo et al. [
      • Ferlazzo E.
      • Zifkin B.G.
      • Andermann E.
      • Andermann F.
      Cortical triggers in generalized reflex seizures and epilepsies.
      ] postulated that if the areas of cortical hyper-excitability (like seen in children with genetic epilepsies like DS) overlap with the physiologically activated areas by a specific sensory stimulation, an epileptic seizure may result if a critical cortical mass gets activated. Reflex seizures, in response to touch, have classically been described in patients with peri-rolandic lesions and malformations of cortical development. The cutaneous triggers appear to be specific to each patients and needed to be applied to a specific trigger zone contralateral to the lesion. High resolution MRI Brain did not reveal nay lesion in our case. Reflex myoclonic seizures, in response to unexpected tactile stimuli, have also been described in reflex myoclonic epilepsy in infancy.
      Our reported case also showed deterioration in his seizure frequency after sustaining relatively mild head trauma at the age of 18 months. Neuroimaging ruled out any acute neurological injury. Tai [
      • Tai P.C.
      • Gross D.W.
      Exacerbation of pre-existing epilepsy by mild head injury: a five patient series.
      ] had previously reported a close temporal relationship between mild head injury and a worsening of seizure control in patients with pre-existing epilepsy. The underlying mechanisms are unknown.
      In conclusion, this case demonstrates the clinical and EEG features of an interesting seizure precipitant in a child with DS. It also showed exacerbation of preexisting epilepsy by mild head injury.

      Funding

      None.

      Conflicts of interests/Disclosures

      None.

      Ethics

      Written informed consent was obtained from the parents for the publication of this case report as per the hospital guidelines.

      Acknowledgement

      None.

      Appendix A. Supplementary data

      The following are Supplementary data to this article:

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