Cortical responsive neurostimulation in a baboon with genetic generalized epilepsy.

OBJECTIVE: To evaluate the efficacy of cortical responsive neurostimulation (CRN) in a male baboon with epilepsy and with genetic generalized epilepsy (GGE), as well as the alteration of seizure patterns and their circadian rhythms due to treatment. METHODS: The baboon was implanted with two subdural frontoparietal strips, bridging the medial central sulci bilaterally. Electrocorticography (ECoG) data were downloaded daily during a three-month baseline, then every 2-3 days over a five-month treatment period. Long episodes, reflecting ictal or interictal epileptic discharges, were also quantified. RESULTS: Twenty-three generalized tonic-clonic seizures (GTCS) and 2 episodes of nonconvulsive status epilepticus (NCSE) were recorded at baseline (median 8 events/month), whereas 26 GTCS were recorded under treatment (median 5/month). Similarly, daily indices of long episodes decreased from 0.46 at baseline to 0.29 with treatment. Ictal ECoG patterns and the circadian distribution of GTCS were also altered by RNS therapy. SIGNIFICANCE: This case study provides the proof-of-concept for RNS therapy in the baboon model of GGE. Cortical responsive neurostimulation (CRN) demonstrated a 38% median reduction in GTCS. Distinct ictal patterns were identified, which changed over the treatment period; the circadian pattern of his GTCS also shifted gradually from night to daytime with treatment. Future studies targeting the thalamic nuclei, or combining cortical and subcortical sites, may further improve detection and control of GTCS as well as other generalized seizure types. More broadly, this study demonstrates opportunities for evaluating seizure detection as well as chronic therapeutic interventions over long term in the baboon.

Resolution of cryptogenic new onset refractory status epilepticus with tocilizumab.

New onset refractory status epilepticus (NORSE) was defined by the International League Against Epilepsy as occurring in patients presenting without a prior diagnosis of epilepsy or other neurological disease, with seizures that persist beyond 24 h. There is still a need to develop new treatment strategies for NORSE, particularly for those patients who are least responsive to conventional medical therapies. We present a case of a young female patient without any medical history presenting with status epilepticus, which was refractory not only to anti-seizure medications and anesthetics, but also to conventional immunomodulatory therapies. After nine weeks of electroclinical seizure activity, the patient responded to two doses of tocilizumab.

Ictal laughter and crying: Should they be classified as automatisms?

Gelastic seizures (GS) describe ictal laughter and are associated with hypothalamic lesions, as well as other cortical areas. Dacrystic seizures (DS), characterized by ictal crying, also have been reported in hypothalamic lesions and focal epilepsy. We describe a young girl with drug resistant focal dyscognitive seizures associated with gelastic and dacrystic features. However, neither laughter nor crying was correlated with a stereotyped electroencephalographic (EEG) pattern or involvement of a particular brain region. Additionally, based on the variety of epileptogenic foci associated with GS and DS in the literature, laughter and crying appear to represent ictal or peri-ictal automatisms.

Modeling the effective connectivity of the visual network in healthy and photosensitive, epileptic baboons.

The baboon provides a model of photosensitive, generalized epilepsy. This study compares cerebral blood flow responses during intermittent light stimulation (ILS) between photosensitive (PS) and healthy control (CTL) baboons using H 2 (15) O-PET. We examined effective connectivity associated with visual stimulation in both groups using structural equation modeling (SEM). Eight PS and six CTL baboons, matched for age, gender and weight, were classified on the basis of scalp EEG findings performed during the neuroimaging studies. Five H 2 (15) O-PET studies were acquired alternating between resting and activation (ILS at 25 Hz) scans. PET images were acquired in 3D mode and co-registered with MRI. SEM demonstrated differences in neural connectivity between PS and CTL groups during ILS that were not previously identified using traditional activation analyses. First-level pathways consisted of similar posterior-to-anterior projections in both groups. While second-level pathways were mainly lateralized to the left hemisphere in the CTL group, they consisted of bilateral anterior-to-posterior projections in the PS baboons. Third- and fourth-level pathways were only evident in PS baboons. This is the first functional neuroimaging study used to model the photoparoxysmal response (PPR) using a primate model of photosensitive, generalized epilepsy. Evidence of increased interhemispheric connectivity and bidirectional feedback loops in the PS baboons represents electrophysiological synchronization associated with the generation of epileptic discharges. PS baboons demonstrated decreased model stability compared to controls, which may be attributed to greater variability in the driving response or PPRs, or to the influence of regions not included in the model.