*6.3.3 Ictal EEG*

Generalized bilaterally synchronous single or multiple spike-and-wave discharges with 2–4 Hz frequency are commonly associated with all three seizures types that produce drop attacks, although spike-wave discharges are briefer for myoclonus.

The EMG correlate of the jerk is a burst of muscle activity lasting 100 ms; this is followed by a post-myoclonic silent period of EMG inhibition that lasts for 60–500 ms, which is synchronous for the recorded muscles and time-locked to the onset of the slow wave [78]. Both the brisk jerk and the post-myoclonic silent period concur to produce the typical drop.

AA corresponds of generalized irregular spike-wave discharges at 1.5–3 Hz. During NCSE, EEG shows no normal background activity, is characterized by diffuse and irregular spikes and slow waves persisting continuously throughout the episode, and is in combination with erratic myoclonus recorded on the EMG. Generalized tonic seizures correspond to burst of generalized spikes during sleep and eventually wakefulness.

### **6.4 Etiology**

Patients with Doose syndrome have probably a multifactorial inheritance, some of the first to be diagnosed with SCN1A mutations, but others have also been found to have sodium channel subunit beta-1 (SCN1B) and gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2) mutations. However, these genes have not been found consistently in sporadic cases [79].

### **6.5 Treatment**

Ethosuximide is reported to be one of the more effective antiepileptic drugs (AED), especially when absence seizures are the primary seizure type. Valproic acid and lamotrigine are also beneficial; however, lamotrigine probably cause paradoxical worsening in individuals for whom myoclonic seizures are prominent [79]. Levetiracetam and zonisamide have been anecdotally used and may be helpful [23]. The ketogenic diet is a widely reported therapy for Doose syndrome and may be the most efficacious treatment; expert consensus guideline for optimal use of the ketogenic diet listed Doose syndrome as one of the principal indications for this treatment [79]. Seizure remission has been reported even without changes to medication, which suggest that spontaneous remission of seizures does occur.
