Martin del Campo

Deep brain stimulation of the anterior nucleus of the thalamus: Effects of electrical stimulation on pilocarpine-induced seizures and status epilepticus

PURPOSE Electrical stimulation of the anterior nucleus of the thalamus appears to be effective against seizures in animals and humans. As the optimal stimulation settings remain elusive, we studied the effects of different stimulation parameters against pilocarpine induced seizures and status epilepticus (SE). METHODS Adult rats had electrodes implanted bilaterally into the AN. Five days later, different groups of animals were stimulated with 1000 microA, 500 microA, or 200 microA and frequencies of either 20 Hz or 130 Hz. Pilocarpine (350 mg/kg i.p.) was injected 5 min after stimulation onset and seizures were monitored. Sham-treated controls had electrodes implanted but did not receive stimulation until they developed SE. After SE, these animals had the electrodes turned on to assess whether AN stimulation could arrest ongoing ictal activity. RESULTS Compared to sham-treated controls (n=8), stimulation at 500 microA (n=13) significantly increased the latency for seizures and SE by 1.9-2.2-fold. In contrast, stimulation at 1000 microA (n=8) produced a non-significant decrease in the latencies to these events. No major effect was observed with stimulation at 200 microA (n=11). Similar results were obtained for each current intensity, regardless of the stimulation frequency used (20 Hz and 130 Hz). In sham-treated controls that had the electrodes turned on after SE, stimulation was not able to arrest ongoing ictal activity. CONCLUSIONS The anticonvulsant effects of AN stimulation against pilocarpine-induced seizures were mainly determined by the current and not the frequency of stimulation. AN stimulation initiated after SE onset was ineffective.

Efficacy and tolerability of the modified Atkins diet in adults with pharmacoresistant epilepsy: a prospective observational study.

Purpose:  Evidence from the pediatric population exists for the efficacy of ketogenic diets in reducing seizure frequency in patients with intractable epilepsy. Recent evidence suggests that a Modified Atkins Diet may be a beneficial form of cotherapy for adult patients with pharmacoresistant epilepsy.

A glue-based, screw-free method for implantation of intra-cranial electrodes in young mice

Intra-cranial electroencephalographic recordings are increasingly employed in mice because of the availability of genetically manipulated mouse models. Currently, dental acrylic and anchoring screws are used to cement implanted electrodes. This technique works well for adult animals but often encounters difficulty when employed in young mice because their skulls are not strong enough to bear the anchoring screws. Here we describe a novel method favorable for implantation of intra-cranial electrodes in mice as young as postnatal 18 days and suitable for long-term intra-cranial electroencephalographic recordings. Our approach is to construct a multi-electrode assembly according to the desired stereotaxic coordinates of intra-cranial recordings and to secure the implanted electrode assembly to the skull via glue rather than dental acrylic/anchoring screws. The surgical operation for such electrode implantation is relatively quick and rarely associated with complications such as infection, bleeding, neurological deficits, spontaneous seizures or behavioral disturbances. The implanted electrodes are stable, allowing repeated monitoring for several months. Data obtained by simultaneous intra-hippocampal and intra-cortical recordings indicate that our method is suitable for the examination of behaviorally related electroencephalographic activities and experimentally induced seizures. Technical aspects of our methods are discussed, and the procedures for constructing the electrode assembly are presented in detail.

Mortality with brainstem seizures from focal 4‐aminopyridine–induced recurrent hippocampal seizures

Sudden unexplained death in epilepsy is the leading cause of death in young adult epilepsy patients, typically occurring during the early postictal period, presumably resulting from brainstem and cardiorespiratory dysfunction. We hypothesized that ictal discharges in the brainstem disrupt the cardiorespiratory network, causing mortality. To study this hypothesis, we chose an animal model comprising focal unilateral hippocampal injection of 4‐aminopyridine (4‐AP), which produced focal recurrent hippocampal seizures with secondary generalization in awake, behaving rats.

An Overview of Psychogenic Non-Epileptic Seizures: Etiology, Diagnosis and Management

The purpose of this review is to provide an update of the research regarding the etiology, diagnosis and management of psychogenic non-epileptic seizures (PNES). A literature search using Pubmed, Ovid MEDLINE and EMBASE database was performed from 2000 up to August 2017. We have evaluated the different factors leading to PNES as well as the diagnostic approach and management of this disorder which continue to be very difficult. The coexistence of epilepsy and PNES poses special challenges and requires the coordinated efforts of the family physicians, psychiatrists, psychologists and neurologists. Although this condition has an overall poor prognosis, a multidisciplinary approach in the diagnosis and management of this disorder would likely improve the outcomes. We have proposed a diagnostic and treatment algorithm for PNES and suggested a national registry of patients suffering from this condition. The registry would contain data regarding treatment and outcomes to aid in the understanding of this entity.

Modulated high frequency oscillations can identify regions of interest in human iEEG using hidden Markov models

This study investigated the seizure and non-seizure state transitions in the intracranial electroencephalogram (iEEG) recordings of extratemporal lobe epilepsy patients. Cross-frequency coupling between low and high frequency oscillations in conjunction with an unsupervised learning algorithm - namely, hidden Markov models - was used to objectively identify seizure and non-seizure states as well as transition states. Channels consistently capturing two and/or three distinct states in a 32-channel iEEG array were able to identify regions of interest located in resected tissue of patients who experienced improved post-surgical outcomes.

Active Search for Epileptiform Electroencephalogram Activity by External Stimulation in Critically Ill Patients

A 68-year-old woman presented with a 2-day history of fluctuating level of consciousness. She underwent an electroencephalogram (EEG) to rule out nonconvulsive status epilepticus. Nail bed pressure applied to the extremities triggered paroxysms of brain activity consistent with stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) (Fig. 1) not accompanied by clinical manifestations. The SIRPIDs pattern consisted of 10to 15-second runs of paroxysmal, mediumto high-amplitude polymorphic 1 to 2Hz delta (mixed with 4-5Hz theta), alternating with nonrhythmic high-amplitude waveforms, appearing diffusely throughout the brain (but frontally accentuated). At certain times, it was triphasically configured; at other times, it was clearly epileptiform. Magnetic resonance imaging scan of the brain showed multiple areas of diffuse restriction of varying ages involving the right periventricular white matter (Fig. 2A) and extending into the posterior right lentiform nucleus (Fig. 2B) as well as encephalomalacia in the left centrum semiovale (Fig. 2C). These radiological abnormalities were considered secondary to primary central nervous system vasculitis to which she succumbed. The SIRPIDs observed in this patient were likely a sign of cortical irritability; nonetheless, there was not strong evidence suggesting that it contributed to her demise. SIRPIDs were first described by Hirsch et al as periodic, rhythmic, or ictal-appearing discharges consistently induced by alerting stimuli. Although being underrecognized and underreported, SIRPIDs seem to be relatively common. According to the original report, this EEG pattern may be found in roughly one-fifth of critically ill patients undergoing continuous EEG monitoring. This EEG phenomenon is believed to be epileptogenic when associated with clinical manifestations that are stereotyped and temporally linked with the discharges. Etiologically, SIRPIDs are associated with a wide variety of conditions, including intracranial hemorrhages, cerebral infarctions, hypoxic-ischemic brain injury, traumatic brain injury, and neurodegenerative diseases such as Creutzfeldt-Jakob disease. In terms of pathophysiology, the mechanisms underlying SIRPIDs are still unknown. Similarly, their overall prognostic significance is not fully understood. However, in comatose survivors of cardiac arrest who underwent therapeutic hypothermia, SIRPIDs appear to be associated with poor outcome— especially when occurring during hypothermia. In regards to management, pursuing or not treatment of SIRPIDs is still a matter of debate. The rationale behind this dissensus relies on the fact that there is a lack of evidence on how to care for patients with SIRPIDs; therefore, to improve care, accurate diagnostic and prognostic data should be consistently obtained and, ideally, reported. In this context, we strongly recommend the routine performance of different noxious stimuli during EEG in comatose patients. Regarding the various possible stimulus types in particular, there has not been a definite agreement on the most efficient method to test nociceptive EEG reactivity. Thus, we highlight the importance of standardizing stimulation parameters in comatose patients, as suggested by Tsetsou et al. Furthermore, by presenting our patient’s EEG, which is fairly typical of SIRPIDs, we intend to remind neurologists of this specific EEG pattern, hoping to encourage collaborative studies that will be able to determine the prognostic and therapeutic implications of SIRPIDs.

Spectral features of electroencephalogram in characterizing various brain states under anesthesia

The administration of the anesthetic agents is known to alter the electroencephalogram (EEG) signal significantly with the brain being their primary target. In this study, we analyzed the EEG recorded from six ASA I/II patients undergoing a 1–2 hour surgery. The EEG was collected before and during induction, maintenance and recovery of anesthesia using the 10/20 lead-system. A combination of fentanyl and propofol (±rocuronium) was used for induction and a Sevoflurane in air/O2 mixture was administered through an endotracheal tube to achieve the steady minimum alveolar concentration (MAC). This study showed that 0 to 4 Hz signal power was most sensitive to the changes associated with induction of anesthesia whereas the 4 to 12 Hz power was important in classifying states during maintenance of anesthesia. Anesthesia also promoted heightened phase coherence in 8 to 16 Hz and 16 to 30 Hz ranges during maintenance and induction of anesthesia, respectively. Additionally, strong cross-frequency coupling between 7 to 20 Hz and 10 to 40 Hz was observed during anesthesia suggesting alteration of neural coding.