Case Report: Responsive Neurostimulation of the Centromedian Thalamic Nucleus for the Detection and Treatment of Seizures in Pediatric Primary Generalized Epilepsy

Up to 20% of pediatric patients with primary generalized epilepsy (PGE) will not respond effectively to medication for seizure control. Responsive neurostimulation (RNS) is a promising therapy for pediatric patients with drug-resistant epilepsy and has been shown to be an effective therapy for reducing seizure frequency and severity in adult patients. RNS of the centromedian nucleus of the thalamus may help to prevent loss of awareness during seizure activity in PGE patients with absence seizures. Here we present a 16-year-old male, with drug-resistant PGE with absence seizures, characterized by 3 Hz spike-and-slow-wave discharges on EEG, who achieved a 75% reduction in seizure frequency following bilateral RNS of the centromedian nuclei. At 6-months post-implant, this patient reported complete resolution of the baseline daily absence seizure activity, and decrease from 3–4 generalized convulsive seizures per month to 1 per month. RNS recordings showed well-formed 3 Hz spike-wave discharges in bilateral CM nuclei, further supporting the notion that clinically relevant ictal discharges in PGE can be detected in CM. This report demonstrates that CM RNS can detect PGE-related seizures in the CM nucleus and deliver therapeutic stimulation.

The Role and Controversies of Electroencephalogram in Focal versus Generalized Epilepsy

As early in 1935, Gibbs et al described electroencephalogram (EEG) features of large slow waves seen in “petit mal” seizures and change in background rhythm to a higher frequency, greater amplitude pattern in “grand mal” seizures. Studies have shown many typical EEG features in focal onset as well as generalized epilepsies.2 3 It is usually easy to delineate focal epilepsy cases when EEG onset of seizures is clear as seen in Benign focal epileptiform discharges of childhood.4 However, it is not uncommon to see cases where epileptiform discharges are not very clear. For example, there can be secondary bilateral synchrony or generalized onset of epileptiform discharges in some cases of focal epilepsy5 and nongeneralized EEG features is cases of generalized epilepsy like absence seizures.6 The awareness of occurrence of focal clinical and EEG features in generalized epilepsy is particularly important to help to select appropriate AEDs and also to avoid inappropriate consideration for epilepsy surgery.7 Lüders et al8 have shown that multiple factors like electroclinical seizure evolution, neuroimaging (both functional and anatomical) have to be analyzed in depth before defining an epileptic syndrome. Here, we are providing few examples of different situations where it is still mysterious to figure out focal onset seizures with secondary generalization versus primary generalized epilepsy.

Identification of Interictal Paroxysmal Diffuse Sharp Activity with Eye Closure in Patients with Generalized Epilepsy

Interictal EEG recordings of patients with generalized epilepsy have known interictal abnormalities such as generalized spike and wave activity during photic stimulation and hyperventilation, interictal spike and wave or diffuse sharp activity [1]. We report three patients with confirmed generalized epilepsy who’s interictal recordings showed paroxysmal diffuse sharp 10 Hz activity in all leads with eye closure following eye blinking. This pattern was not associated with interictal generalized spike and wave activity, clinical change in the patient or did not follow seizure activity. Abnormal eye movement with generalized spike and wave activity has been described in Jeavon’s syndrome, eyelid myotonia and Sunflower syndrome. However, our patients did not meet criteria for any of these diagnoses. Therefore, we feel that our finding of paroxysmal diffuse sharp alpha activity is a novel finding in these patients with primary generalized epilepsy and may be a newly reported marker for patients with primary generalized epilepsy. Recognition of PDSA activity and further study of this pattern is encouraged.

Pathogenic Cav3.2 channel mutation in a child with primary generalized epilepsy

Two paternally-inherited missense variants in CACNA1H were identified and characterized in a 6-year-old child with generalized epilepsy. Febrile and unprovoked seizures were present in this child. Both variants were expressed in cis or isolation using human recombinant Cav3.2 calcium channels in tsA-201 cells. Whole-cell patch-clamp recordings indicated that one variant (c.3844C > T; p.R1282W) caused a significant increase in current density consistent with a pathogenic gain-of-function phenotype; while the other cis-related variant (c.5294C > T; p.A1765V) had a benign profile.

Use of Vagus Nerve Stimulator on Children With Primary Generalized Epilepsy

Objective: To describe the response to vagus nerve stimulator (VNS) in otherwise neurotypical children with medically intractable primary generalized epilepsy. Methods: Retrospective chart review of patients who underwent vagus nerve stimulator surgery between January 2011 and December 2015. Results: Eleven patients were identified. Median follow-up duration was 2.5 years (1.2-8.4 years). Prior to vagus nerve stimulator surgery, all patients had at least 1 seizure per week, and 7/11 (64%) had daily seizures. At 1-year follow-up after vagus nerve stimulator, 7/11 (64%) reported improved seizure frequency and 6/11 (55%) reported fewer than 1 seizure per month. Three patients (27%) reported complications related to vagus nerve stimulator surgery, and no patients required device removal. Significance: In children with medically intractable primary generalized epilepsy, vagus nerve stimulator is well tolerated and appears to lead to improvement in seizure frequency. Improvement was not attributable to epilepsy classification, age at vagus nerve stimulator implantation, output current, duty cycle, or follow-up duration.

A Young Woman with Jerking Movements

The case raises some of the important points to consider when choosing an antiepileptic drug, AED, for women with epilepsy, WWE. The most important factor is to define the epilepsy type, as many AEDs are not efficacious for primary generalized epilepsy. Knowing the interaction of an AED with contraceptives is also vital in order to prevent an unplanned pregnancy. Folate supplementation is recommended to decrease the risk of neural tube defects. It should be initiated at the same time as the prescription for an AED. For women in the reproductive years, the least teratogenic AED that is effective for their epilepsy should be chosen.

Role of Short Term Video Encephalography with Induction by Verbal Suggestion in Diagnosis of Suspected Paroxysmal Nonepileptic Seizure-Like Symptoms

Purpose. To determine the diagnostic yield and utility of STVEEG with verbal suggestion in diagnosis of patients presenting with transient unresponsiveness and suspected psychogenic nonepileptiform seizures. Methods. A retrospective analysis of STVEEG records of patients with transient unresponsiveness and suspected PNES between 1 Jan 2009 and 28 Feb 2014 was done. Results. Amongst 155 patients [38 males, 117 females], with mean age 32 [8–67], PNES were identified in 109 [70.3%], focal epilepsy was identified in 24 [15.4%], and actual seizure was recorded in 7 [4.5%]. Nine [5.8%] patients were found to have both epilepsy and PNES. Primary generalized epilepsy was diagnosed in 2 [1.2%]. A diagnosis of other paroxysmal nonepileptiform events [tachyarrhythmia and heart block] was done in 3 [1.9%]. A normal EEG and no inducible episode and hence an uncertain diagnosis at the end of STVEEG were seen in only 17 [10.9%] patients. A STVEEG of approximately one hour duration was able to establish the diagnosis in 138 [89.1%] patients with transient unresponsiveness. Conclusion. STVEEG with verbal suggestion is a useful and cost effective diagnostic test for diagnosis of PNES. It can be a good modality for diagnosis in patients with transient abnormalities in sensorium in the outpatient settings in developing countries.