Deep brain stimulation of anterior nucleus thalami disrupts sleep in epilepsy patients

Abstract

SUMMARYIn view of the regulatory function of the thalamus in the sleep-wake cycle, the impact of deep brain stimulation (DBS) of the anterior nucleus thalami (ANT) on sleep was assessed in a small consecutive cohort of epilepsy patients with standardized polysomnography (PSG). In nine patients treated with ANT-DBS (voltage 5 V, frequency 145 Hz, cyclic mode), the number of arousals during stimulation and nonstimulation periods, neuropsychiatric symptoms (npS), and seizure frequency were determined. Electroclinical arousals were triggered in 14.0 to 67.0% (mean 42.4 AE SD 16.8%) of all deep brain stimuli. Six patients reported npS. Nocturnal DBS voltages were reduced in eight patients (one patient without npS refused) and PSGs were repeated. Electroclinical arousals occurred between 1.4 and 6.7 (mean 3.3 AE 1.7) times more frequently during stimulation periods compared to nonstimulation periods; the number of arousals positively correlated with the level of DBS voltage (range 1 V to 5 V) (Spearman 0 s rank coefficient 0.53121; p < 0.05). No patient experienced seizure deterioration and four patients reported remission of npS. This case-cohort study provides evidence that ANT-DBS interrupts sleep in a voltage-dependent manner, thus putatively resulting in an increase of npS. Reduction of nocturnal DBS voltage seems to lead to improvement of npS without hampering efficacy of ANT-DBS.

Deep brain stimulation for drug‐resistant epilepsy

“…ANT stimulation reduced seizure severity and improved quality of life, but worsened subjective depression and memory impairment 3 -however, these measures may be unreliable. 28 64 Cognitive improvements have also been reported in ANT, CMT, and STN stimulation.…”

“…Robust clinical trials demonstrate seizure frequency reductions of 40% following short-term ANT stimulation, 3 and 26%-40% following short-term HC stimulation, [34][35][36][37] in patients with primarily focal epilepsies. Pooled responder rates (seizure reduction ≥50%) were >70% for both ANT 9,18,19,[21][22][23][24][26][27][28][29][30][31][32][33] and HC-stimulated 13,14,[34][35][36][41][42][43][44][45][46][47] patients. Indeed, a recent meta-analysis found statistically significant reductions in seizure frequency secondary to ANT-DBS (high-quality evidence) and HC-DBS (moderate-quality evidence), but not for any other targets.…”

“…Given that this circuit is thought to be involved in emotional processing and seizure propagation, highfrequency ANT stimulation may inhibit the spread of focal seizures to cortical areas. 4,10,11,16,17 Current evidence for ANT-DBS includes one large-scale RCT 3,18 and 16 noncontrolled studies 8,9,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] (Table 2).…”

“…79 Our pooled analysis of patients for whom individual data were available (Figure 1) revealed that half of all ANT-DBS patients experienced a 46%-90% decline 9,18,19,[21][22][23][24]26,27,31 in seizures, and half of all HC-DBS patients experienced a 48%-95% decrease 13,[34][35][36][41][42][43][44][45][46][47] (interquartile ranges). Pooled responder rates (seizure reduction ≥50%) were >70% for both ANT 9,18,19,[21][22][23][24][26][27][28][29][30][31][32][33] and HC-stimulated 13,14,[34][35][36][41][42][43][44][45]…”

Sleep architecture and homeostasis in children with epilepsy: a neurodevelopmental perspective

“…63 However, the stimulation of these nuclei, which are closely associated with the ascending arousal system, may lead directly to electroclinical arousals in a voltage-dependent manner. 64…”