Dawn Eliashiv

Ictal magnetic source imaging as a localizing tool in partial epilepsy

Objective: To determine the feasibility and usefulness of ictal magnetoencephalography (MEG) recordings in the presurgical evaluation of patients with epilepsy. Methods: Twenty patients with frequent or predictable seizures were studied with the intent to capture seizures using a large array single-probe 37-channel or dual-probe 74-channel biomagnetometer. Results: Successful ictal MEG recordings were made in 6 of 20 patients with neocortical epilepsy. In one other patient, a seizure was captured but movement artifact made MEG recordings impossible. As determined by invasive EEG recording and postsurgical outcome, ictal MEG provided localizing information that was superior to interictal MEG in three of the six patients. Localization of ictal onset by MEG was at least equivalent to invasive EEG in five of the six patients, and was superior in two patients as determined by postsurgical outcome. Conclusion: Larger studies are necessary to confirm that ictal MEG recordings in patients with frequent or easily provoked neocortical seizures can contribute localizing information equivalent or superior to invasive EEG recording.

Intravenous Lacosamide in refractory nonconvulsive status epilepticus

BACKGROUND Many patients present with refractory Status epilepticus (SE) despite multiple anti-epileptic drugs (AEDs). Lacosamide (LCM) was recently approved as an adjunct AED for partial-onset seizures. It has unique mechanism of modulating voltage-gated sodium channels by enhancing their slow inactivation. LCM has demonstrated efficacy in animal models of pharmacoresistant seizures. To date, there are isolated anecdotal reports of LCM use in SE. OBJECTIVE To report a single center experience with IV Lacosamide in patients with NCSE. METHODS Pharmacy records were reviewed to identify patients with SE who received IV LCM in our institution. Data on demographics, response to therapy and adverse effects/outcomes were analyzed. All patients had continuous EEG monitoring. RESULTS 10 patients (4 men, 6 women), age 16-90 years with refractory SE were given LCM. Eight patients were in focal non-convulsive SE (NCSE), 2 were in generalized non-convulsive SE. The etiologies included anoxic brain injury, idiopathic, encephalitis, tumor, posterior reversible encephalopathy syndrome (PRES), stroke, and AVM. IV LCM was added after traditional AEDs, including drug-induced coma in some, failed to control the SE. NCSE resolved in 7/10 patients whereas 1/10 patient showed partial response with cessation of NCSE but still frequent electrographic seizures and 2/10 patients were resistant to therapy. CONCLUSIONS LCM is a useful adjunct in refractory NCSE. The IV formulation allows prompt administration in the intensive care unit setting. Response was seen especially in focal SE. Similar to other AEDs, response was poor in patients with postanoxic injury. Our data is limited by the small number of patients. Larger controlled studies are necessary to assess accurately the efficacy of IV LCM as an early treatment of SE.

Rethinking clinical language mapping approaches: discordant receptive and expressive hemispheric language dominance in epilepsy surgery candidates.

Summary: Neuroimaging studies have shed light on cortical language organization, with findings implicating the left and right temporal lobes in speech processing converging to a left-dominant pattern. Findings highlight the fact that the state of theoretical language knowledge is ahead of current clinical language mapping methods, motivating a rethinking of these approaches. The authors used magnetoencephalography and multiple tasks in seven candidates for resective epilepsy surgery to investigate language organization. The authors scanned 12 control subjects to investigate the time course of bilateral receptive speech processes. Laterality indices were calculated for left and right hemisphere late fields ∼150 to 400 milliseconds. The authors report that (1) in healthy adults, speech processes activated superior temporal regions bilaterally converging to a left-dominant pattern, (2) in four of six patients, this was reversed, with bilateral processing converging to a right-dominant pattern, and (3) in three of four of these patients, receptive and expressive language processes were laterally discordant. Results provide evidence that receptive and expressive language may have divergent hemispheric dominance. Right-sided receptive language dominance in epilepsy patients emphasizes the need to assess both receptive and expressive language. Findings indicate that it is critical to use multiple tasks tapping separable aspects of language function to provide sensitive and specific estimates of language localization in surgical patients.

Theta-burst microstimulation in the human entorhinal area improves memory specificity

The hippocampus is critical for episodic memory, and synaptic changes induced by long-term potentiation (LTP) are thought to underlie memory formation. In rodents, hippocampal LTP may be induced through electrical stimulation of the perforant path. To test whether similar techniques could improve episodic memory in humans, we implemented a microstimulation technique that allowed delivery of low-current electrical stimulation via 100 μm-diameter microelectrodes. As thirteen neurosurgical patients performed a person recognition task, microstimulation was applied in a theta-burst pattern, shown to optimally induce LTP. Microstimulation in the right entorhinal area during learning significantly improved subsequent memory specificity for novel portraits; participants were able both to recognize previously-viewed photos and reject similar lures. These results suggest that microstimulation with physiologic level currents—a radical departure from commonly used deep brain stimulation protocols—is sufficient to modulate human behavior and provides an avenue for refined interrogation of the circuits involved in human memory.

Role of the Wada test and functional magnetic resonance imaging in preoperative mapping of language and memory: two atypical cases

The Wada test is an invasive procedure used to determine cerebral memory and language dominance as well as risk of cognitive deficits following neurosurgery. However, the potential risks of Wada testing have led some to consider foregoing Wada testing in candidates for resective epilepsy surgery with right hemispheric seizure onset. We present two atypical cases in which the Wada test showed unexpected memory and language lateralization. These cases underscore the importance of functional magnetic resonance in which imaging and Wada examination in right-handed individuals even when the lesion would not suggest atypical language representation.

Electrical inexcitability of nerves and muscles in severe infantile spinal muscular atrophy

Spinal muscular atrophy (SMA) is one of the most common fatal autosomal recessive disorders, characterised by progressive degeneration of anterior horn cells. Before the advent of genetic testing, the diagnosis of SMA was based on clinical, histopathological, and electrophysiological features. In 1992, the International SMA Consortium defined diagnostic criteria of proximal SMA based on clinical findings.1 In SMA type I (severe; Werdnig-Hoffmann disease), affected persons have onset of symptoms before 6 months of age and are never able to sit without support. Electromyography demonstrates denervation features. In early 1995, the candidate gene, the survival motor neuron (SMN) gene, was identified, making the confirmation of SMA by DNA analysis possible.2 With the availability of a genetic test for SMA, many investigators are refining the diagnostic criteria published by the Consortium. Studies involving hundreds of patients with proximal SMA have disclosed a subset of patients who fulfill at least one exclusion criterion defined by the Consortium.3 We identified an infant with severe SMA who fulfilled two exclusion criteria and also showed inexcitability of all nerves as well as muscles. This report will further delineate the wide range of …

Continuous electroencephalogram patterns are suggestive of eventual neurologic outcomes in post-cardiac arrest patients treated with therapeutic hypothermia.

INTRODUCTION Therapeutic hypothermia (TH) after cardiac arrest (CA) resuscitation is the first therapy proven to increase survival to discharge and neurologic recovery. Methods for neurologic and mortality prognostication after CA resuscitation have been called into question because they were developed based on evidence that was developed prior to the advent of TH. This study examines the relationship between electroencephalogram (EEG) patterns and mortality and neurologic outcomes in post-CA patients undergoing TH. METHODS Eighty-three of 732 patients who had continuous EEG (cEEG) monitoring during TH were included. Continuous EEG tracings were classified as isoelectric, low voltage, burst suppression, epileptic form, and diffuse slowing. Primary outcomes are survival to discharge and Cerebral Performance Categories (CPCs) at hospital discharge. RESULTS Among patients with favorable neurologic outcomes (CPC1 and CPC2), the duration cardiopulmonary resuscitation and time until return of spontaneous circulation were shorter than observed in patients with poorer neurologic outcomes (CPC3, CPC4, and CPC5). The time to target temperature was equivalent among neurologic outcome groups (499.5 minutes vs 431.0 minutes, P = .09). Favorable neurologic outcome was associated with initial presentation with ventricular tachycardia or ventricular fibrillation and had cEEG patterns suggestive of diffuse slowing and epileptiform waves. DISCUSSION The use of cEEG can provide prognostication information otherwise not obtainable by clinical examination. Specific cEEG patterns predicted probability of mortality for patients according to their initial rhythm of CA as a function of cardiopulmonary resuscitation time.

Hippocampal sclerosis: The missing link of cysticercosis epileptogenesis?

A closed workshop was held in Atahualpa, Ecuador, with support from Universidad Espiritu Santo—Ecuador. Aims of the workshop were to gain more insights on the suggested association between neurocysticercosis (NCC), epilepsy, and hippocampal sclerosis (HS), and to design a study that will help to better characterize this association, namely, is there a causal relationship between NCC and HS, and, if so, is this association linked to chronic unprovoked seizures?

Grammar tests increase the ability to lateralize language function in the Wada test

INTRODUCTION Grammar is a core component of the language system, yet it is rarely assessed during the Wada (intracarotid amobarbital) test. It is hypothesized that adding grammar tests to the recovery phase of the Wada test will increase our ability to lateralize language function. METHOD Sixteen individuals (nine females, fifteen right-handed, mean age 38.4 years, SD=10.7) with medically refractory temporal lobe epilepsy participated in the study. On EEG ten patients had seizures originating in the left hemisphere (LH), five in the right hemisphere (RH), and one was insufficiently lateralized. We included only patients who were LH-dominant on the standard test in the encoding phase of the Wada test. In the recovery phase of Wada testing the participants underwent evaluation with a standard language and a new test of grammar, the CYCLE-N. Ten patients underwent bilateral injections, six unilateral (one RH, five LH). RESULTS As expected, injection in the LH decreased language performance to a greater extent than injection to the RH on both tests. However, the CYCLE-N produced more profound language deficits in the injected LH compared to the RH (p=0.01), whereas the standard tests did not cause such pronounced differences (p=0.2). CONCLUSION The results suggest that the standard tests did not significantly differentiate the effects of the injections and the CYCLE-N, for the most part, did. Our results are of particular relevance to patients who are too obtunded to speak in the encoding phase. In sum, the CYCLE-N may be helpful in assessing hemispheric dominance for language.

Atypical cortical language organization in epilepsy patients: evidence for divergent hemispheric dominance for receptive and expressive language function.

Summary: The central goal of presurgical language mapping is to identify brain regions that subserve cortical language function to minimize postsurgical language deficits. Presurgical language mapping in patients with epilepsy presents a key challenge because of the atypical pattern of hemispheric language dominance found in this population, with higher incidences of bilateral and right-biased language dominance than typical. In this prospective study, we combine magnetoencephalography with a panel of tasks designed to separately assess receptive and expressive function to provide a sensitive measure of language function in 15 candidates for resective surgery. We report the following: 4 of 15 patients (27%) showed left hemisphere dominance across all tasks, 4 of 15 patients (27%) showed right hemisphere dominance across all tasks, and 7 of 15 (46%) showed discordant language dominance, with right-dominant receptive and left-dominant expressive language. All patients with discordant language dominance showed this right-receptive and left-expressive pattern. Results provide further evidence supporting the importance of using a panel of tasks to assess separable aspects of language function. The clinical relevance of the findings is discussed, especially about current clinical operative measures for assessing language dominance, which use single hemisphere procedure (intracarotid amobarbital procedure and awake intraoperative stimulation) for determining language laterality.