Marianna V. Spanaki

Use of preoperative functional neuroimaging to predict language deficits from epilepsy surgery

Background: Left anterior temporal lobectomy (L-ATL) may be complicated by confrontation naming deficits. Objective: To determine whether preoperative fMRI predicts such deficits in patients with epilepsy undergoing L-ATL. Methods: Twenty-four patients with L-ATL underwent preoperative language mapping with fMRI, preoperative intracarotid amobarbital (Wada) testing for language dominance, and pre- and postoperative neuropsychological testing. fMRI laterality indexes (LIs), reflecting the interhemispheric difference between activated volumes in left and right homologous regions of interest, were calculated for each patient. Relationships between the fMRI LI, Wada language dominance, and naming outcome were examined. Results: Both the fMRI LI (p < 0.001) and the Wada test (p < 0.05) were predictive of naming outcome. fMRI showed 100% sensitivity and 73% specificity in predicting significant naming decline. Both fMRI and the Wada test were more predictive than age at seizure onset or preoperative naming performance. Conclusions: Preoperative fMRI predicted naming decline in patients undergoing left anterior temporal lobectomy surgery.

Simultaneous ERP and fMRI of the auditory cortex in a passive oddball paradigm.

Infrequent occurrences of a deviant sound within a sequence of repetitive standard sounds elicit the automatic mismatch negativity (MMN) event-related potential (ERP). The main MMN generators are located in the superior temporal cortex, but their number, precise location, and temporal sequence of activation remain unclear. In this study, ERP and functional magnetic resonance imaging (fMRI) data were obtained simultaneously during a passive frequency oddball paradigm. There were three conditions, a STANDARD, a SMALL deviant, and a LARGE deviant. A clustered image acquisition technique was applied to prevent contamination of the fMRI data by the acoustic noise of the scanner and to limit contamination of the electroencephalogram (EEG) by the gradient-switching artifact. The ERP data were used to identify areas in which the blood oxygenation (BOLD) signal varied with the magnitude of the negativity in each condition. A significant ERP MMN was obtained, with larger peaks to LARGE deviants and with frontocentral scalp distribution, consistent with the MMN reported outside the magnetic field. This result validates the experimental procedures for simultaneous ERP/fMRI of the auditory cortex. Main foci of increased BOLD signal were observed in the right superior temporal gyrus [STG; Brodmann area (BA) 22] and right superior temporal plane (STP; BA 41 and 42). The imaging results provide new information supporting the idea that generators in the right lateral aspect of the STG are implicated in processes of frequency deviant detection, in addition to generators in the right and left STP.

The impact of a neurointensivist-led team on a semiclosed neurosciences intensive care unit*

Objective:To evaluate the impact of a newly appointed neurointensivist on neurosciences intensive care unit (NICU) patient outcomes and quality of care variables. Design:Observational cohort with historical controls. Setting:Ten-bed neurointensive care unit in tertiary university hospital. Patients:Mortality, length of stay (LOS), and discharge disposition of all patients admitted to the NICU were compared between two 19-month periods, before and after the appointment of a neurointensivist. Data regarding these patients were collected using the hospital database and the University Hospitals Consortium database. Individual patient medical records were reviewed for major complications and important prognostic variable documentation. Interventions:Appointment of a neurointensivist. Measurements and Main Results:We analyzed 1,087 patients before and 1,279 after the neurointensivist’s appointment. The unadjusted in-hospital mortality decreased from 10.1% in the before to 9.1% in the after period (95% confidence interval, −1.3 to 3%, relative mortality reduction of 9.9%), but this decrease was significantly different than the expected increase of 1.4% in University Hospitals Consortium mortality during the same period (p = .048). The unadjusted mortality in the NICU decreased from 8% to 6.3% (95% confidence interval, −0.5 to 4, relative mortality reduction 21%) and mean NICU LOS from 3.5 to 2.9 days (95% confidence interval, 0.2 to 0.9, relative NICU LOS reduction 17%). A significant 42% reduction of the risk of death during the first 3 days of NICU admission (p = .003) and a 12% greater risk for NICU discharge (p = .02) were found in the after period in multivariate proportional hazard models. Discharge home increased from 51.7% in the before to 59.7% in the after period (95% confidence interval, 4 to 12, relative increase of 15%) and discharge to a nursing home decreased from 8.1% to 6.8% (95% confidence interval, −1 to 4, relative decrease of 16%). Although a higher total number of complications occurred in the after period, fewer of them occurred in the NICU (odds ratio, 0.2; 95% confidence interval, 0.08 to 0.54, p = .001); this may possibly be due to the better documentation by the NICU team in the after period. Conclusions:The institution of a neurointensivist-led team model was associated with an independent positive impact on patient outcomes, including a lower intensive care unit mortality, LOS, and discharge to a skilled nursing facility and a higher discharge home.

Ballistocardiogram artifact reduction in the simultaneous acquisition of auditory ERPS and fMRI

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are now being combined to analyze brain function. Confounding the EEG signal acquired in the MR environment is a ballistocardiogram artifact (BA), which is predominantly caused by cardiac-related body movement. The objective of this study was to develop and evaluate a method for reducing these MR-induced artifacts to retrieve small auditory event-related potentials (ERPs) from EEG recorded during fMRI. An algorithm for BA reduction was developed that relies on timing information obtained from simultaneous electrocardiogram (ECG) recordings and subsequent creation of an adaptive BA template. The BA template is formed by median-filtering 10 consecutive BA events in the EEG signal. The continuously updated template is then subtracted from each BA in the EEG. The auditory ERPs are obtained through signal averaging of the remaining EEG signal. Experimental and simulated ERP data were estimated to assess effectiveness of the BA reduction. Simulation showed that the algorithm reduced BA without significantly altering the morphology of a signal periodically inserted in the EEG. Auditory ERP data, obtained in a 1.5-T scanner during a passive auditory oddball paradigm and processed with the BA reduction algorithm, were comparable to data recorded in a mock scanner outside the magnetic field with the same experimental paradigm. It is concluded that through adequate reduction of the BA, relatively small auditory ERPs can be acquired in the MR environment.

Intraventricular hemorrhage after aneurysmal subarachnoid hemorrhage: Pilot study of treatment with intraventricular tissue plasminogen activator

OBJECTIVE:Intraventricular (IVen) hemorrhage is considered a predictor of poor outcome after subarachnoid hemorrhage (SAH). This prospective study examines the feasibility and outcome of administration of IVen tissue plasminogen activator (tPA) after aneurysmal SAH. METHODS:Ten patients with SAH who received IVen tPA after the aneurysm had been secured were compared with 10 age-, sex-, and Glasgow Coma Scale score-matched control patients. The primary end point was third and fourth ventricle clot resolution. IVen blood was quantified by use of the Graeb and Le Roux scales on admission and at an additional time (equal or longer for the control group) after the injection was terminated. RESULTS:Six men and four women with a mean age of 52 years in each group were evaluated. On average, 3.5 mg tPA was injected 68 ± 51 hours after admission without ensuing complications. Although the treated group had significantly more IVen blood on admission than control subjects (mean Le Roux scale ± standard deviation, 11 ± 3 versus 7.6 ± 4.2, P = 0.055, and mean Graeb scale ± standard deviation, 8.5 ± 2.3 in tPA versus 5.3 ± 3, P < 0.02), it also had a significant decrease in the amount of IVen blood (mean Le Roux and Graeb scale decrease ± standard deviation, 6.7 ± 3.3 and 4.8 ± 2 in tPA patients versus 0.9 ± 3.2 and 0.5 ± 2.6 in control subjects, P = 0.002). The tPA group had a non-statistically significantly shorter length of stay, decreased mortality, and better Glasgow Outcome Scale and modified Rankin Scale scores at discharge. Treated survivors showed a decreased need for shunt placement (2 [22%] of 9 patients versus 5 [83%] of 6 control subjects, P = 0.04). CONCLUSION:This pilot study shows that IVen tPA administration is feasible without complications after SAH and may be associated with better outcomes. These results warrant a randomized clinical trial.

Clipping or coiling of ruptured cerebral aneurysms and shunt-dependent hydrocephalus

BackgroundHydrocephalus may develop either early in the course of aneurysmal subarachnoid hemorrhage (SAH) or after the first 2 weeks. Because the amount of SAH is a predictor of hydrocephalus, the two available aneurysmal treatments, clipping or coiling, may lead to differences in the need for cerebrospinal fluid (CSF) diversion, as only surgery permits clot removal.MethodsHospital and University Hospitals Consortium (UHC) databases were used to retrieve data on all patients admitted to our hospital with aneurysmal SAH during the last 4 years. The incidence of permanent ventricular shunt (VS) according to treatment modality used was evaluated.ResultsOne hundred eighty-eight patients were admitted with aneurysmal SAH. Coiling was performed on 48 (26%) and clipping on 135 (73.8%) patients. Fifty-six (31%) patients required CSF diversion. External ventricular drain was placed in 30 (22.2%) clipped and 13 (27.1%) coiled patients (p=0.5), and VS in 6 patients of the two treatment groups (4.4 versus 12.5%, respectively; p=0.08). Patients requiring VS had longer UHC-expected hospital length of stay (LOS), as well as observed ICU and hospital LOS, compared to patients with temporary or no CSF diversion (24±14 versus 15±8, 20.5±9 versus 11±7, and 30±13 versus 16±11 days, respectively; p≤0.01). In a logistic regression model, VS was independently associated with rebleeding, external ventricular drain placement, coiling, and UHC-expected LOS (odds ratios, 95% confidence interval 12.1, 2.3–62.6, 6.9, 1.6–30, 6.25, 1.3–29, and 1.1, 1.02–1.14, respectively).ConclusionsOne-third of patients admitted with aneurysmal SAH require temporary or permanent CSF diversion. Permanent shunting was found to be associated with coiling in our patient population.

Effect of injection time on postictal SPET perfusion changes in medically refractory epilepsy.

Abstract. Single-photon emission tomography (SPET) brain imaging in epilepsy has become an increasingly important noninvasive tool in localizing the epileptogenic site. Ictal SPET demonstrates the highest localization sensitivity as compared with postictal and interictal SPET. While ictal SPET consistently reveals hyperperfusion at the epileptogenic site, postictal SPET reveals either hyper- or hypoperfusion depending on the timing of radiopharmaceutical injection. Much discussion in the literature exists about exactly when the transition from hyper- to hypoperfusion occurs at the epileptogenic site in postictal SPET. The systematic examination of two clinical variables – time of injection from seizure onset and offset – was useful in understanding postictal perfusion changes. Twenty-seven patients with medically refractory epilepsy receiving postictal and interictal SPET scans were studied. Quantitative SPET difference imaging was used to evaluate perfusion changes in relationship to injection time. Perfusion changes were found to reflect the time of injection in relation to seizure onset, but to be somewhat independent of seizure offset. Thus, the majority of patients (8/12, 67%) receiving postictal injections within 100 s after seizure onset demonstrated hyperperfusion, while all patients (15/15, 100%) receiving postictal injections more than 100 s after seizure onset showed hypoperfusion. The explanation of this phenomenon is unknown but the findings appear to parallel known changes in cerebral lactate levels.

Periictal SPECT Localization Verified by Simultaneous Intracranial EEG

Summary: Purpose: We investigated whether blood‐flow changes measured by ictal or immediate postictal single photon emission computed tomography (SPECT) reflect with accuracy the actual location of ictal discharge as measured by simultaneous intracranial EEG. In addition, we evaluated the reliability of ictal SPECT obtained with implanted electrodes by comparing results with those of ictal SPECT performed during scalp EEG monitoring in selected patients.

Influence of technetium-99m-hexamethylpropylene amine oxime injection time on single-photon emission tomography perfusion changes in epilepsy.

Abstract. By digitally computing perfusion changes from ictal or postictal (peri-ictal) injections referenced to those acquired interictally, an enhanced method for localizing the epileptogenic area is reported. Computer-based image processing methods for quantifying regional percent change in the brain are applied to a group of 19 epilepsy patients after the injection of technetium-99m hexamethylpropylene amine oxime (HMPAO) and after acquiring single-photon emission tomography (SPET) data. Each patient’s region of epileptogenesis was independently localized through pathology and/or successful surgery. The positive and negative quantitative perfusion changes were plotted as a function of the time of the 99mTc-HMPAO ictal injection. This time scale was normalized relative to the seizure duration and is referenced to the time of seizure termination. Eight patients, injected ictally, demonstrated perfusion increases of 25%–100% in the area of known epileptogenesis. Five patients, injected immediately after seizure cessation, demonstrated excessive perfusion decreases of 30%–92% associated with the region of seizure onset. Six patients, injected well after seizure termination, demonstrated hypoperfusion changes less than 30% at the epileptogenic area. Observations on perfusion changes calculated from 99mTc-HMPAO SPET scans, as a function of normalized time, support a progression from ictal hyper- to excessive hypo-, then finally to persistent interictal hypoperfusion. By applying this perfusion pattern model and by noting the time of injection for peri-ictal images, an improved method for localizing the epileptogenic area is demonstrated.

Tiagabine Overdose Can Induce Convulsive Status Epilepticus

Tiagabine (Gabitril, TGB) is the first -aminobutyric acid (GABA) uptake inhibitor introduced as adjunctive therapy for refractory partial seizures (1). The effective dose range is 32–56 mg daily, and the dose range as monotherapy is likely to be lower. Therapeutic monitoring of plasma concentration of TGB is not recommended. TGB is considered to be an effective anticonvulsant medication (AED) and appears to lack serious adverse reactions. However, as of September 1996, 13 patients in a total of 2,531 in the literature, who received the medication had mental-status changes and EEG findings suggestive of nonconvulsive status epilepticus (NCSE) (2–8). The TGB dose in these reports was within the therapeutic range, but blood levels were not obtained. Review of data confirmed the diagnosis of NCSE in three of 13 patients (8). In the remainder, clinical and EEG findings were attributed to TGB intolerance secondary to high dose (8). When the TGB dose was reduced clinical symptoms resolved. We describe the first case of convulsive status epilepticus (CSE) induced by TGB overdose.