Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

OBJECTIVE: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. METHODS: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. RESULTS: There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.

Vagoglossopharyngeal Neuralgia Occurred Concomitantly with Ipsilateral Hemifacial Spasm and Versive Seizure-Like Movement: A First Case Report.

Vagoglossopharyngeal neuralgia (VGPN) is a very rare condition. VGPN with convulsive like attack is even rarer All of the cases had their head turned to the opposite side of facial pain. Hemifacial spasm occurring concurrently with VGPN has never been reported. Herein, we present the first case of VGPN that had ipsilateral hemifacial spasm and versive seizure-like movement to the same side of facial pain. We reported a 71-year-old man presenting with multiple episodes of intermittent sharp shooting pain arising on the right middle neck, followed by hemifacial spasm on right face. Then the patient became syncope while his head and gaze turned to the same side of the painful neck. Electrocardiography showed sinus arrest. Interictal Electroencephalography was normal. This patient initially responded to pregabalin for two weeks, then the symptoms became worse. Microvascular decompression and carbamazepine resulted in the complete remission of all symptoms after six months of follow-up. We could not explain the pathophysiology of unilateral versive seizure like movement.

Cortical stimulation of the epileptogenic zone for the treatment of focal motor seizures: an experimental study in the nonhuman primate.

BACKGROUND: Cortical stimulation is under investigation in clinical trials of drug-resistant epilepsy. Results are heterogeneous; therefore, more evidence from animal studies is required. OBJECTIVE: To investigate the therapeutic effects of parameters of direct stimulation of the cortical focus in a Macaca fascicularis presenting focal motor epilepsy. METHODS: We developed a model of motor seizures after intracortical injection of penicillin G in the primary motor cortex of a Macaca fascicularis. We performed electric epidural cortical stimulation at low, medium, and high frequency using continuous or short-term stimulation. Short-term stimulation was triggered on seizure onset, either visually or automatically with a seizure detection algorithm connected to a programmable stimulator. RESULTS: Automated detection could detect 100% of the seizures, but ensuing cortical electric stimulation failed to abort seizures. CONCLUSION: This study demonstrates the inefficacy of the stimulation of the cortical focus to prevent seizures induced by local injection of penicillin G. Because this model may be too severe to allow comparison to human epilepsies, further work is required in other monkey models of focal epilepsy.

Neuromodulation of epileptic foci in patients with non-lesional refractory motor epilepsy.

We report two cases of chronic therapeutic stimulation of epileptic foci localized in motor areas. Case 1 is an adolescent with supplementary motor area seizures whose intracranial recordings showed a right SMA focus. Case 2 is a female teenager with primary motor seizures originating in the right motor cortex in the hand area as shown by her intracranial recordings and cortical mapping. Both had apparently normal MRI. Chronic stimulation of the epileptic focus decreased the number of seizures more than 90% the seizure number while preserving motor function. None of the patients had side effects. Neuromodulation is proposed as a safe, efficient surgical alternative for motor seizure control.

Antiepileptic effects of low-frequency repetitive transcranial magnetic stimulation by different stimulation durations and locations.

OBJECTIVE: To evaluate the antiepileptic effect of low-frequency rTMS (repetitive transcranial magnetic stimulation) in the patients with intractable epilepsy. METHODS: We enrolled 35 patients with localization-related epilepsy who had experienced at least one complex partial seizure or a secondarily generalized seizure per week on a constant antiepileptic drug regimen over an 8-week period. rTMS was administered using a Rapid(2) magnetic stimulator with an air-cooled coil at 0.5Hz for 5 consecutive days at 100% of rMT (resting motor threshold). Patients were divided into a focal stimulation group with a localized epileptic focus, or a non-focal stimulation group with a non-localized or multifocal epileptic focus. These two groups were then randomly subdivided into four subgroups depending on the total number of stimulations administered, i.e., 3000 pulse and 1500 pulse subgroups. Weekly seizure frequencies were determined for 8 weeks before and after rTMS. To compare the number of interictal spikes before and after rTMS, EEG was recorded twice before (1st day) and after rTMS (5th day). RESULTS: Mean weekly seizure frequency was non-significantly decreased after rTMS (8.4-->6.8/week, -13.9%). Longer stimulation subgroups (3000 pulses, -23.0%) tended to have fewer seizures than shorter stimulation subgroups (1500 pulses, -3.0%), without statistical significance. TMS stimulation site and structural brain lesions did not influence seizure outcome. However, interictal spikes significantly decreased (-54.9%, P=0.012) after rTMS and they totally disappeared in 6 patients (17.1%, 6/35). CONCLUSIONS: Low-frequency rTMS reduced interictal spikes, but its effect on seizure outcome was not significant. Focal stimulation for a longer duration tended to further reduce seizure frequency. SIGNIFICANCE: These findings may help clinicians to further investigate the therapeutic potential of the rTMS for patients with intractable epilepsy.

Double-blind, randomized controlled pilot study of bilateral cerebellar stimulation for treatment of intractable motor seizures.

PURPOSE: The efficacy and safety of cerebellar stimulation (CS) was reevaluated in a double-blind, randomized controlled pilot study on five patients with medically refractory motor seizures, and especially generalized tonic-clonic seizures. METHODS: Bilateral modified four-contact plate electrodes were placed on the cerebellar superomedial surface through two suboccipital burr holes. The implanted programmable, battery-operated stimulator was adjusted to 2.0 microC/cm(2)/phase with the stimulator case as the anode; at this level, no patient experienced the stimulation. Patients served as their own controls, comparing their seizure frequency in preimplant basal phase (BL) of 3 months with the postimplant phases from 10 months to 4 years (average, eight epochs of 3 months each). During the month after implantation, the stimulators were not activated. The patient and the evaluator were blinded as to the next 3-month epoch, as to whether stimulation was used. The patients were randomized into two groups: three with the stimulator ON and two with the stimulator OFF. After a 4-month postimplantation period, all patients had their stimulator ON until the end of the study and beyond. Medication was maintained unchanged throughout the study. EEG paroxysmal discharges also were measured. RESULTS: Generalized tonic-clonic seizures: in the initial 3-month double-blind phase, two patients were monitored with the stimulation OFF; no change was found in the mean seizure rate (patient 1, 100%, and patient 5, 85%; mean, 93%), whereas the three patients with the stimulation initially ON had a reduction of seizures to 33% (patient 2, 21%; patient 3, 46%; patient 4, 32%) with a statistically significant difference between OFF and ON phase of p = 0.023. All five patients then were stimulated and monitored. At the end of the next 6 months of stimulation, the five patients had a mean seizure rate of 41% (14-75%) of the BL. The second patient developed an infection in the implanted system, which had to be removed after 11 months of stimulation; the seizures were being reduced with stimulation to a mean of one per month from a mean of 4.7 per month (BL level) before stimulation. At the end of 24 months, three patients were monitored with stimulation, resulting in a further reduction of seizures to 24% (11-38%). Tonic seizures: four patients had these seizures, which at 24 months were reduced to 43% (10-76%). Follow-up surgery was necessary in four patients because of infection in one patient and lead/electrode displacement needing repositioning in three patients. The statistical analysis showed a significant reduction in tonic-clonic seizures (p < 0.001) and tonic seizures (p < 0.05). CONCLUSIONS: The superomedial cerebellar cortex appears to be a significantly effective and safe target for electrical stimulation for decreasing motor seizures over the long term. The effect shows generalized tonic-clonic seizure reduction after 1-2 months and continues to decrease over the first 6 months and then maintains this effectiveness over the study period of 2 years and beyond.

Benign partial epilepsies in infancy.

Benign partial epilepsies are not rare in infancy and comprise two forms, although both are closely related. One is partial epilepsy with complex partial seizures (CPS) and the other one with secondarily generalized seizures (SGS). The most frequent site of seizure origin was in the temporal area in the former and central, parietal or occipital area in the latter. The former has not been well recognized because of subtle seizure manifestations and a favorable outcome. Its unique characteristics should be emphasized because it may be difficult to diagnose it unless we know its presence. Benign convulsions are also common in infancy. Most of them may belong to partial epilepsy with SGS, although confirmation with ictal EEG recording is necessary for accurate diagnosis. Some are familial and many of them seem to show an autosomal dominant pattern, but some seem to have autosomal recessive inheritance.