Fast human brain magnetic resonance responses associated with epileptiform spikes.

Neuronal currents produce local electromagnetic fields that can potentially modulate the phase of the magnetic resonance signal and thus provide a contrast mechanism tightly linked to neuronal activity. Previous work has demonstrated the feasibility of direct MRI of neuronal activity in phantoms and cell culture, but in vivo efforts have yielded inconclusive, conflicting results. The likelihood of detecting and validating such signals can be increased with (i) fast gradient-echo echo-planar imaging, with acquisition rates sufficient to resolve neuronal activity, (ii) subjects with epilepsy, who frequently experience stereotypical electromagnetic discharges between seizures, expressed as brief, localized, high-amplitude spikes (interictal discharges), and (iii) concurrent electroencephalography. This work demonstrates that both MR magnitude and phase show large-amplitude changes concurrent with electroencephalography spikes. We found a temporal derivative relationship between MR phase and scalp electroencephalography, suggesting that the MR phase changes may be tightly linked to local cerebral activity. We refer to this manner of MR acquisition, designed explicitly to track the electroencephalography, as encephalographic MRI (eMRI). Potential extension of this technique into a general purpose functional neuroimaging tool requires further study of the MR signal changes accompanying lower amplitude neuronal activity than those discussed here.

Current dipole orientation and distribution of epileptiform activity correlates with cortical thinning in left mesiotemporal epilepsy.

To evaluate cortical architecture in mesial temporal lobe epilepsy (MTLE) with respect to electrophysiology, we analyze both magnetic resonance imaging (MRI) and magnetoencephalography (MEG) in 19 patients with left MTLE. We divide the patients into two groups: 9 patients (Group A) have vertically oriented antero-medial equivalent current dipoles (ECDs). 10 patients (Group B) have ECDs that are diversely oriented and widely distributed. Group analysis of MRI data shows widespread cortical thinning in Group B compared with Group A, in the left hemisphere involving the cingulate, supramarginal, occipitotemporal and parahippocampal gyri, precuneus and parietal lobule, and in the right hemisphere involving the fronto-medial, -central and -basal gyri and the precuneus. These results suggest that regardless of the presence of hippocampal sclerosis, in a subgroup of patients with MTLE a large cortical network is affected. This finding may, in part, explain the unfavorable outcome in some MTLE patients after epilepsy surgery.

Morphological characteristics of brain tumors causing seizures.

OBJECTIVE: To quantify size and localization differences between tumors presenting with seizures vs nonseizure neurological symptoms. DESIGN: Retrospective imaging survey. We performed magnetic resonance imaging-based morphometric analysis and nonparametric mapping in patients with brain tumors. SETTING: University-affiliated teaching hospital. PATIENTS OR OTHER PARTICIPANTS: One hundred twenty-four patients with newly diagnosed supratentorial glial tumors. MAIN OUTCOME MEASURES: Volumetric and mapping methods were used to evaluate differences in size and location of the tumors in patients who presented with seizures as compared with patients who presented with other symptoms. RESULTS: In high-grade gliomas, tumors presenting with seizures were smaller than tumors presenting with other neurological symptoms, whereas in low-grade gliomas, tumors presenting with seizures were larger. Tumor location maps revealed that in high-grade gliomas, deep-seated tumors in the pericallosal regions were more likely to present with nonseizure neurological symptoms. In low-grade gliomas, tumors of the temporal lobe as well as the insular region were more likely to present with seizures. CONCLUSIONS: The influence of size and location of the tumors on their propensity to cause seizures varies with the grade of the tumor. In high-grade gliomas, rapidly growing tumors, particularly those situated in deeper structures, present with non-seizure-related symptoms. In low-grade gliomas, lesions in the temporal lobe or the insula grow large without other symptoms and eventually cause seizures. Quantitative image analysis allows for the mapping of regions in each group that are more or less susceptible to seizures.

Utilization of below-the-hairline EEG in detecting subclinical seizures.

Nonconvulsive status epilepticus (NCSE) is a serious condition commonly considered when evaluating a patient with altered mental status, and an electroencephalogram (EEG) is necessary for diagnosis. Neurology house staff often must make this diagnosis at times when no EEG technologist is available. We report our experience with abbreviated, emergency below-the-hairline EEGs (BTH-EEG) performed by neurology residents at our institution over a 1-1/2 year period. We analyzed demographic and clinical data in relation to whether or not an ictal or periodic pattem was identified, and these results were compared to follow up EEGs. Thirty-nine studies were identified, ranging in duration from 3 min-13 hrs. Mean and median age of patients included was 53 (range 25-81 yrs); 21 were female. Seven of 39 BTH-EEGs showed at least one electrographic seizure, 9 more showed periodic discharges. Follow-up EEGs showed electrographic seizures in 6 of 39 patients, including 3 of the 7 with ictal BTH-EEG, and an additional 3 whose BTH-EEGs showed periodic lateralized discharges but no organized seizures. All 7 patients with ictal BTH-EEGs survived to discharge, vs. 23 of the remaining 32. We conclude that in selected cases, BTH-EEG is useful in detecting seizures and/or other epileptiform patterns. In our series, when NCSE was in question, the BTH-EEG showed these patterns 41% of the time. The BTH-EEG is a fast, non-invasive, inexpensive tool that may save valuable time, especially when no other viable option is immediately available. This technique may be applicable more broadly, not just limited to centers with neurology residents.

A comparison of anastrozole and testosterone versus placebo and testosterone for treatment of sexual dysfunction in men with epilepsy and hypogonadism.

Hyposexuality is commonly associated with low bioavailable testosterone (BAT) and relative estradiol elevation in men with epilepsy. This prospective, randomized, double-blind trial compared the effects of depotestosterone+the aromatase inhibitor anastrozole (T-A) versus depotestosterone+placebo (T-P) on sexual function, hormone levels, mood, and seizure frequency in men with epilepsy. Forty men with focal epilepsy, hyposexuality, and hypogonadism were randomized 1:1 to two groups (T-A or T-P) for a 3-month treatment trial of depotestosterone+either anastrozole or matching placebo. Outcomes included both efficacy and safety measures. Normalization of sexual function (S-score) occurred with greater frequency in the T-A (72.2%) than in the T-P (47.4%) group, but the difference was not statistically significant. T-A resulted in significantly lower estradiol levels and S-scores correlated inversely with estradiol levels at baseline and during treatment. Beck Depression Inventory II (BDI-II) scores improved significantly in both groups and changes in S-score correlated inversely with changes in BDI-II score. Changes in seizure frequency correlated with changes in BDI-II score. Seizure frequency decreased with both treatments and showed significant correlations with estradiol levels. Triglyceride levels increased with T-P and decreased with T-A. The difference in triglyceride changes between the two treatments was significant and correlated with changes in estradiol levels. Significant correlations between estradiol levels and S-scores, as well as seizure outcomes and triglyceride levels, suggest further study regarding a potential role for anastrozole in the treatment of men with epilepsy who have hyposexuality and hypogonadism.

Evaluation of postoperative sharp waveforms through EEG and magnetoencephalography.

EEGs obtained after craniotomy are difficult to read because of a breach rhythm consisting of unfiltered sharply contoured physiologic waveforms that can mimic interictal epileptiform discharges. Magnetoencephalography (MEG) is less affected by the skull breach. The postcraniotomy EEG and MEG scans of 20 patients were reviewed by two experienced electroencephalographers. Larger interrater variability was found for EEG as compared with MEG. Review of patients who had postoperative seizures suggested that EEG was more sensitive but less specific than MEG in detecting interictal epileptiform discharges. Furthermore, several instances of sharp waveforms that were difficult to evaluate on EEG were found to be more easily interpretable on MEG. MEG may also help determine whether asymmetries in physiologic rhythms on EEG result from the skull defect or are pathologic. MEG should be considered as an adjunctive study in patients with a breach rhythm for evaluation of interictal epileptiform discharges and cerebral dysfunction.

Perinatal use of anticonvulsants: differences in attitudes and recommendations among neurologists and psychiatrists.

We surveyed opinions and recommendations about perinatal anticonvulsant (AC) treatment among 166 neurologists (n = 88) and psychiatrists (n = 78) practicing in Massachusetts. They were similar in the recommendation of routinely informing patients of potential teratogenic risks of ACs and avoiding valproate during pregnancy. Neurologists were more likely to encourage pregnancy and nursing during AC-use than psychiatrists, and psychiatrist were more cautious regarding perinatal safety, citing potential neurobehavioral risks and complications of breastfeeding. These observations indicate substantial differences in opinions between psychiatrists and neurologists regarding AC use during pregnancy.

A prospective study of smoking, caffeine, and alcohol as risk factors for seizures or epilepsy in young adult women: data from the Nurses' Health Study II.

PURPOSE: Seizures and epilepsy are associated with significant disability and substantial treatment costs, yet little is known about primary prevention. We prospectively examined the association of cigarette smoking, caffeine use, and alcohol intake with risk of seizure or epilepsy among women, aged 25-42 years, in the Nurses' Health Study II. METHODS: Participants provided dietary and cigarette smoking information on multiple questionnaires beginning in 1989. Among 116,363 women at-risk for incident seizure or epilepsy, we confirmed 95 cases of seizure and 151 cases of epilepsy occurring from 1989-2005 using information from a detailed supplementary questionnaire and medical records. Multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. RESULTS: Compared with never smoking, current cigarette smoking was associated with an increased risk of seizure (RR 2.60, 95% CI 1.53-4.42), after adjustment for stroke and other potential confounding factors. Past smoking was not associated with risk of seizure, but was associated with modestly increased risk of epilepsy (RR 1.46, 95% CI 1.01-2.12). Long-term caffeine and moderate alcohol intake were not associated with seizure or epilepsy. DISCUSSION: Cigarette smoking may be associated with increased risk of seizure. More prospective studies are needed to investigate potential factors to ultimately prevent the development of seizures or epilepsy.

Contributions to singing ability by the posterior portion of the superior temporal gyrus of the non-language-dominant hemisphere: first evidence from subdural cortical stimulation, Wada testing, and fMRI.

INTRODUCTION: Although the substrates that mediate singing abilities in the human brain are not well understood, invasive brain mapping techniques used for clinical decision making such as intracranial electro-cortical testing and Wada testing offer a rare opportunity to examine music-related function in a select group of subjects, affording exceptional spatial and temporal specificity. METHODS: We studied eight patients with medically refractory epilepsy undergoing indwelling subdural electrode seizure focus localization. All patients underwent Wada testing for language lateralization. Functional assessment of language and music tasks was done by electrode grid cortical stimulation. One patient was also tested non-invasively with functional magnetic resonance imaging (fMRI). Functional organization of singing ability compared to language ability was determined based on four regions-of-interest (ROIs): left and right inferior frontal gyrus (IFG), and left and right posterior superior temporal gyrus (pSTG). RESULTS: In some subjects, electrical stimulation of dominant pSTG can interfere with speech and not singing, whereas stimulation of non-dominant pSTG area can interfere with singing and not speech. Stimulation of the dominant IFG tends to interfere with both musical and language expression, while non-dominant IFG stimulation was often observed to cause no interference with either task; and finally, that stimulation of areas adjacent to but not within non-dominant pSTG typically does not affect either ability. Functional fMRI mappings of one subject revealed similar music/language dissociation with respect to activation asymmetry within the ROIs. CONCLUSION: Despite inherent limitations with respect to strictly research objectives, invasive clinical techniques offer a rare opportunity to probe musical and language cognitive processes of the brain in a select group of patients.

Is there a circadian variation of epileptiform abnormalities in idiopathic generalized epilepsy?

Epileptiform abnormalities often occur at specific times of day or night, possibly attributable to state of consciousness (sleep vs. wake) and/or influences from the endogenous circadian pacemaker. In this pilot study we tested for the existence of circadian variation of interictal epileptiform discharges (IEDs), independent of changes in state, environment, or behavior. Five patients with generalized epilepsy underwent a protocol whereby their sleep/wake schedule was evenly distributed across the circadian cycle while undergoing full-montage electroencephalography and hourly plasma melatonin measurements. Light was <8 lux to prevent circadian entrainment. All patients completed the protocol, testifying to its feasibility. All patients had normal circadian rhythmicity of plasma melatonin relative to their habitual sleep times. In the three patients with sufficient IEDs to assess variability, most IEDs occurred during non-rapid eye movement (NREM) sleep (ratio NREM:wake=14:1, P<0.001). In both patients who had NREM at all circadian phases, there was apparent circadian variation in IEDs but with different phases relative to peak melatonin.

The human K-complex represents an isolated cortical down-state.

The electroencephalogram (EEG) is a mainstay of clinical neurology and is tightly correlated with brain function, but the specific currents generating human EEG elements remain poorly specified because of a lack of microphysiological recordings. The largest event in healthy human EEGs is the K-complex (KC), which occurs in slow-wave sleep. Here, we show that KCs are generated in widespread cortical areas by outward dendritic currents in the middle and upper cortical layers, accompanied by decreased broadband EEG power and decreased neuronal firing, which demonstrate a steep decline in network activity. Thus, KCs are isolated "down-states," a fundamental cortico-thalamic processing mode already characterized in animals. This correspondence is compatible with proposed contributions of the KC to sleep preservation and memory consolidation.

Antiepileptic drug use in women of childbearing age.

Research on antiepileptic drug (AED) teratogenesis has demonstrated an increased risk for valproate. The impact of these findings on current AED prescribing patterns for women of childbearing age with epilepsy is uncertain. The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study is an ongoing prospective multicenter observational investigation that enrolled pregnant women with epilepsy on the most common AED monotherapies from October 1999 to February 2004 (carbamazepine, lamotrigine, valproate, and phenytoin). A 2007 survey of AED use in women of childbearing age at eight NEAD centers found a total of 932 women of childbearing age with epilepsy (6% taking no AED, 53% monotherapy, 41% polytherapy). The most common monotherapies were lamotrigine or levetiracetam. Since 2004, prescriptions of carbamazepine, phenytoin, and valproate have decreased, whereas those for levetiracetam have increased. Except for the top two AED monotherapies, there were marked differences in other monotherapies and in polytherapies between U.S. and UK centers. Future investigations are needed to examine reasons for drug choice.

Comparison of outcomes of video/EEG monitoring between patients with epileptic seizures and those with psychogenic nonepileptic seizures.

We followed 103 patients for 6-16 months after discharge from elective long-term video/EEG monitoring to compare clinical outcomes and quality of life between patients diagnosed with epileptic (ES) and those diagnosed with psychogenic nonepileptic (PNES) seizures. Outcome measures determined at telephone or mail follow-up included seizure frequency, antiepileptic drug use, and self-reported quality of life using the Quality of Life in Epilepsy inventory. Of the 62 responders, 41 were diagnosed with ES and 11 with PNES, using strictly applied criteria. Those with ES reported significant improvement in Seizure Worry (P=0.003), Medication Side Effects (P<0.001), and Social Function (P<0.001). In addition, both groups showed a decrease in seizure frequency. Furthermore, both groups showed a significant decrease in antiepileptic drug use at follow-up, with a greater, and sustained, decrease for the PNES group. Approximately half the patients in each group reported an improvement in overall condition.

The utility of conductive plastic electrodes in prolonged ICU EEG monitoring.

We investigated the feasibility and utilization of conductive plastic electrodes (CPEs) in patients undergoing continuous video-electroencephalographic (EEG) monitoring in the intensive care unit (ICU), and assessed the quality of brain magnetic resonance imaging (MRI) and computed tomography (CT) images obtained during this period. A total of 54 patients were monitored. Seizures were recorded in 16 patients. Twenty-five patients had neuroimaging performed with electrodes in place; 15 MRI and 23 CT scans were performed. All patients had excellent quality anatomical images without clinically significant artifacts, and without any signs or symptoms that raised safety concerns. Recording quality of the EEG was indistinguishable to that achieved with standard gold electrodes. The use of CPEs allowed for uninterrupted EEG recording of patients who required urgent neuroimaging, and decreased the amount of time spent by the technologists required to remove and reattach leads.

Auditory auras in patients with postencephalitic epilepsy: case series.

Many previously healthy patients who present with new seizures or status epilepticus appear to have encephalitis for which no specific pathogen is identified. A significant portion of these patients develop epilepsy. We describe five patients with adult-onset, medically intractable, postencephalitic epilepsy characterized by auditory auras ranging from unformed buzzing to structured language. Auras of any type were common among patients with postencephalitic epilepsy in our referral database: 62% experienced at least one type of aura. The proportion of postencephalitic patients with auditory auras (38%), which may reflect lateral temporal cortical pathology, was higher than that of other adult epilepsy populations. Although no pathogen was identified in four of the five cases, we suggest that the pathophysiology of viral encephalitides may share common targets in the temporal lobes, especially the superior temporal gyrus and surrounding areas, which may account for possibly increased occurrence of auditory auras in this population.

Frequency and patterns of MRI abnormalities due to status epilepticus.

BACKGROUND: MRI changes due to status epilepticus (SE) often suggest a combination of cytotoxic and vasogenic edema, but it is unclear why only certain patients have MRI changes. OBJECTIVES: To determine the frequency of MRI changes due to SE and the associated patient characteristics. METHODS: We reviewed records for demographics, medical history, and MRI changes attributable to seizures of all patients admitted to Brigham and Women's Hospital or Massachusetts General Hospital for SE from 1/1999 to 7/2003 and who had MRI during admission. RESULTS: Ten (11.6%) of the eighty-six patients identified had MRI abnormalities likely due to seizures. Four, two with pre-existing epilepsy and two with extratemporal structural lesions, had focally increased signal on T2 and diffusion-weighted imaging (DWI) in the hippocampus ipsilateral to the seizure focus. One, with elevated levels of clozapine, had increased signal on T2 weighted images and variably restricted diffusion in the splenium. Five had gyral distribution of restricted diffusion and increased signal on T2 weighted images; they had complex medical comorbidities and possible hypoperfusion or hypoxia associated with SE. CONCLUSIONS: Among patients with SE who had MRI changes, those with previous epilepsy or extratemporal structural lesions showed increased diffusion in the hippocampus and may have selective hippocampal vulnerability to seizure-induced hyperexcitability. Patients with hyperintense signal in the cortical gray matter had episodes of possible hypoperfusion or hypoxia.

Status Epilepticus Severity Score (STESS): a tool to orient early treatment strategy.

BACKGROUND: Status epilepticus (SE) treatment ranges from small benzodiazepine doses to coma induction. For some SE subgroups, it is unclear how the risk of an aggressive therapeutic approach balances with outcome improvement. We recently developed a prognostic score (Status Epilepticus Severity Score, STESS), relying on four outcome predictors (age, history of seizures, seizure type and extent of consciousness impairment), determined before treatment institution. Our aim was to assess whether the score might have a role in the treatment strategy choice. METHODS: This cohort study involved adult patients in three centers. For each patient, the STESS was calculated before primary outcome assessment: survival vs. death at discharge. Its ability to predict survival was estimated through the negative predictive value for mortality (NPV). Stratified odds ratios (OR) for mortality were calculated considering coma induction as exposure; strata were defined by the STESS level. RESULTS: In the observed 154 patients, the STESS had an excellent negative predictive value (0.97). A favorable STESS was highly related to survival (P < 0.001), and to return to baseline clinical condition in survivors (P < 0.001). The combined Mantel-Haenszel OR for mortality in patients stratified after coma induction and their STESS was 1.5 (95 % CI: 0.59-3.83). CONCLUSION: The STESS reliably identifies SE patients who will survive. Early aggressive treatment could not be routinely warranted in patients with a favorable STESS, who will almost certainly survive their SE episode. A randomized trial using this score would be needed to confirm this hypothesis.

Efficacy and tolerability of levetiracetam versus phenytoin after supratentorial neurosurgery.

BACKGROUND: Antiepileptic drugs are routinely given after craniotomy. Though phenytoin (PHT) is still the most commonly used agent, levetiracetam (LEV) is increasingly administered for this purpose. This retrospective study compared the use of LEV and PHT as monotherapy prophylaxis following supratentorial neurosurgery. METHODS: Patients receiving LEV monotherapy after supratentorial craniotomy were reviewed and compared to a control group of patients receiving PHT monotherapy. RESULTS: One of 105 patients taking LEV and 9/210 patients taking PHT had seizures within 7 days of surgery (p = 0.17). Adverse drug reactions requiring change in therapy during hospitalization occurred in 1/105 patients taking LEV and 38/210 patients taking PHT (p < 0.001). Among patients followed for at least 12 months, 11/42 (26%) treated with LEV vs 42/117 (36%) treated with PHT developed epilepsy (p = 0.34); 64% remained on LEV, while 26% remained on PHT (p = 0.03). CONCLUSIONS: Both levetiracetam (LEV) and phenytoin (PHT) were associated with a low risk of early postoperative seizures and a moderate risk of later epilepsy. LEV was associated with significantly fewer early adverse reactions than PHT and with a higher retention rate in patients who were followed for at least 1 year and developed epilepsy.