Methohexital - Induced lateralized periodic discharges during Wada test.

OBJECTIVE: The Wada test is used to evaluate language lateralization and memory performance after inactivation of an isolated cerebral hemisphere. Methohexital a short-acting barbiturate has a history of use to induce interictal discharges during intraoperative corticography. We report a new finding of activation of lateralized periodic discharges (LPDs) after Methohexital injection. METHODS: We retrospectively reviewed 174 consecutive adult patients who underwent Wada testing in preparation for epilepsy surgery (N = 129, 74%) or brain tumor resection (N = 45, 26%) at the University of Michigan to determine the frequency of induced periodic discharges by methohexital. RESULTS: Four epilepsy patients (2.29%) had methohexital-induced LPDs within a median of 2 s (1-99 s) of the injection and lasting a median of 4 min (3-10 min) after a total of 7 injections. All LPDs occurred ipsilateral to the injection hemisphere in the known region of interictal epileptiform discharges. LPDs were not induced in brain tumor patients. In one patient, LPDs occurred during memory testing, and this patient's memory performance was below expectation based on pre-test neuropsychological testing. CONCLUSIONS: Methohexital can induce LPDs in ipsilateral hemisphere and that can potentially affect memory performance. SIGNIFICANCE: This observation indicates that concurrent EEG monitoring during the Wada test is important and that induced discharges should be considered when interpreting Wada test results.

Greater Somatosensory Afference With Acupuncture Increases Primary Somatosensory Connectivity and Alleviates Fibromyalgia Pain via Insular γ-Aminobutyric Acid: A Randomized Neuroimaging Trial.

OBJECTIVE: Acupuncture is a complex multicomponent treatment that has shown promise in the treatment of fibromyalgia (FM). However, clinical trials have shown mixed results, possibly due to heterogeneous methodology and lack of understanding of the underlying mechanism of action. The present study was undertaken to understand the specific contribution of somatosensory afference to improvements in clinical pain, and the specific brain circuits involved. METHODS: Seventy-six patients with FM were randomized to receive either electroacupuncture (EA), with somatosensory afference, or mock laser acupuncture (ML), with no somatosensory afference, twice a week over 8 treatments. Patients with FM in each treatment group were assessed for pain severity levels, measured using Brief Pain Inventory (BPI) scores, and for levels of functional brain network connectivity, assessed using resting state functional magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy in the right anterior insula, before and after treatment. RESULTS: Fibromyalgia patients who received EA therapy experienced a greater reduction in pain severity, as measured by the BPI, compared to patients who received ML therapy (mean difference in BPI from pre- to posttreatment was -1.14 in the EA group versus -0.46 in the ML group; P for group × time interaction = 0.036). Participants receiving EA treatment, as compared to ML treatment, also exhibited resting functional connectivity between the primary somatosensory cortical representation of the leg (S1leg ; i.e. primary somatosensory subregion activated by EA) and the anterior insula. Increased S1leg -anterior insula connectivity was associated with both reduced levels of pain severity as measured by the BPI (r = -0.44, P = 0.01) and increased levels of γ-aminobutyric acid (GABA+) in the anterior insula (r = 0.48, P = 0.046) following EA therapy. Moreover, increased levels of GABA+ in the anterior insula were associated with reduced levels of pain severity as measured by the BPI (r = -0.59, P = 0.01). Finally, post-EA treatment changes in levels of GABA+ in the anterior insula mediated the relationship between changes in S1leg -anterior insula connectivity and pain severity on the BPI (bootstrap confidence interval -0.533, -0.037). CONCLUSION: The somatosensory component of acupuncture modulates primary somatosensory functional connectivity associated with insular neurochemistry to reduce pain severity in FM.

Diffusion tensor imaging predicts cognitive function change following partial brain radiotherapy for low-grade and benign tumors.

PURPOSE/OBJECTIVES: Radiation injury to parahippocampal cingulum white matter is associated with cognitive decline. Diffusion tensor imaging (DTI) detects micropathologic changes in white matter. Increased radial diffusion (RD) and decreased axial diffusion (AD) correspond to demyelination and axonal degeneration/gliosis respectively. We aimed to develop a predictive model for radiation-induced cognitive changes based upon DTI changes. MATERIALS/METHODS: Twenty-seven adults with benign or low-grade tumors received partial brain radiation therapy (RT) to a median dose of 54Gy. Patients underwent DTI before RT, during RT, and at the end of RT. Cognitive testing was performed before RT, and 6 and 18months after RT. Parahippocampal cingulum white matter was contoured to obtain mean values of AD and RD. RESULTS: By univariate analysis, decreasing AD and increasing RD during RT predicted declines in verbal memory and verbal fluency. By multivariate analysis, baseline neurocognitive score was the only clinical variable predicting verbal memory change; no clinical variables predicted verbal fluency change. In a multivariate model, increased RD at the end of RT significantly predicted decline in verbal fluency 18months after RT. CONCLUSIONS: Imaging biomarkers of white matter injury contributed to predictive models of cognitive function change after RT.

One center's experience with complications during the Wada test.

This study aimed to define the number and type of complications associated with the Wada test at an academic medical center for comparison to previous reports. We performed a retrospective review of medical records for patients who underwent the Wada test at the University of Michigan between April 1991 and June 2013. Information was collected regarding the angiography procedure and the immediate postoperative period to assess for both clinical and angiographic complications. A total of 436 patients were identified who underwent the Wada procedure between April 1991 and June 2013, and 431 patients were included in the final analysis. Twenty-five patients (5.8%) had notable clinical events associated with the Wada test. Nine patients (2.1%) had clinical events meeting criteria for complication, which included seizures, status epilepticus, internal carotid artery vasospasm, inadvertent injection of anesthetic in the external carotid artery, and transient encephalopathy. No complications were associated with significant morbidity or mortality. This retrospective review of patients undergoing the Wada test found significantly fewer associated complications in comparison to previously published studies, with no patients experiencing long-term morbidity. The Wada test should be considered a safe diagnostic tool for lateralizing language and memory.

Diffusion tensor imaging of normal-appearing white matter as biomarker for radiation-induced late delayed cognitive decline.

PURPOSE: To determine whether early assessment of cerebral white matter degradation can predict late delayed cognitive decline after radiotherapy (RT). METHODS AND MATERIALS: Ten patients undergoing conformal fractionated brain RT participated in a prospective diffusion tensor magnetic resonance imaging study. Magnetic resonance imaging studies were acquired before RT, at 3 and 6 weeks during RT, and 10, 30, and 78 weeks after starting RT. The diffusivity variables in the parahippocampal cingulum bundle and temporal lobe white matter were computed. A quality-of-life survey and neurocognitive function tests were administered before and after RT at the magnetic resonance imaging follow-up visits. RESULTS: In both structures, longitudinal diffusivity (λ(‖)) decreased and perpendicular diffusivity (λ(⊥)) increased after RT, with early changes correlating to later changes (p < .05). The radiation dose correlated with an increase in cingulum λ(⊥) at 3 weeks, and patients with >50% of cingula volume receiving >12 Gy had a greater increase in λ(⊥) at 3 and 6 weeks (p < .05). The post-RT changes in verbal recall scores correlated linearly with the late changes in cingulum λ(‖) (30 weeks, p < .02). Using receiver operating characteristic curves, early cingulum λ(‖) changes predicted for post-RT changes in verbal recall scores (3 and 6 weeks, p < .05). The neurocognitive test scores correlated significantly with the quality-of-life survey results. CONCLUSIONS: The correlation between early diffusivity changes in the parahippocampal cingulum and the late decline in verbal recall suggests that diffusion tensor imaging might be useful as a biomarker for predicting late delayed cognitive decline.

Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for prediction of radiation-induced neurocognitive dysfunction.

PURPOSE: To determine whether early assessment of cerebral microvessel injury can predict late neurocognitive dysfunction after brain radiation therapy (RT). EXPERIMENTAL DESIGN: Ten patients who underwent partial brain RT participated in a prospective dynamic contrast-enhanced magnetic resonance imaging (MRI) study. Dynamic contrast-enhanced MRI was acquired prior to, at weeks 3 and 6 during, and 1 and 6 months after RT. Neuropsychological tests were done pre-RT and at the post-RT MRI follow-ups. The correlations between early delayed changes in neurocognitive functions and early changes in vascular variables during RT were analyzed. RESULTS: No patients had tumor progression up to 6 months after RT. Vascular volumes and blood-brain barrier (BBB) permeability increased significantly in the high-dose regions during RT by 11% and 52% (P<0.05), respectively, followed by a decrease after RT. Changes in both vascular volume and BBB permeability correlated with the doses accumulated at the time of scans at weeks 3 and 6 during RT and 1 month after RT (P<0.03). Changes in verbal learning scores 6 months after RT were significantly correlated with changes in vascular volumes of left temporal (P<0.02) and frontal lobes (P<0.03), and changes in BBB permeability of left frontal lobes during RT (P<0.007). A similar correlation was found between recall scores and BBB permeability. CONCLUSION: Our data suggest that the early changes in cerebral vasculature may predict delayed alterations in verbal learning and total recall, which are important components of neurocognitive function. Additional studies are required for validation of these findings.

The hidden structure of neuropsychology: text mining of the journal Cortex: 1991--2001.

BACKGROUND: The stated mission of Cortex is "the study of the inter-relations of the nervous system and behavior, particularly as these are reflected in the effects of brain lesions on cognitive functions." The purpose of this paper is to explore the relationship between the stated mission and the executed mission as reflected by the characteristics of papers published in Cortex. In addition, we examine whether the results and conclusions of an analysis of this kind are affected by the level of description of the published papers. OBJECTIVES: A) Identify characteristics of contributors to Cortex; B) Identify characteristics of those who cite Cortex; C) Identify recurring themes; D) Identify the relationships among the recurring themes; E) Compare recurring themes and determine their relationships to the mission of Cortex; F) Identify the sensitivity of these results to the level of description of the Cortex papers used as the source database. G) Compare Cortex characteristics with those of Neuropsychologia, another Europe-based international neuropsychology journal. METHODS: Text mining (extraction of useful information from text) was used to generate the characteristics of the journal Cortex. Bibliometrics provided the Cortex contributor infrastructure (author/ organization/ country/ citation distributions), and computational linguistics identified the recurring technical themes and their inter-relationships. Citation mining (the integration of citation bibliometrics and text mining) was used to profile the research user community. Four levels of published article description were compared for the analysis: Full Text, Abstract, Title, Keywords. RESULTS AND CONCLUSIONS: Highly cited documents were compared among Cortex, Neuropsychologia, and Brain, and a number of interesting parametric trends were observed. The characteristics of the papers that cite Cortex papers were examined, and some interesting insights were generated. Finally, the document clustering taxonomy showed that papers in Cortex can be reasonably divided into four categories (papers in each category in parenthesis): Semantic Memory (151); Handedness (145); Amnesia (119); and Neglect (66). It is concluded that Cortex needs to take steps to attract a more diverse group of contributors outside its continental Western European base if it wishes to capture a greater share of seminal neuropsychology papers. Further investigation of the critical citation differences reported in the paper is recommended.

Sodium methohexital (brevital) as an anesthetic in the Wada test.

PURPOSES: We report our experience with sodium methohexital (Brevital) as an anesthetic used in the Wada test for language and memory in 86 epilepsy surgery patients (173 procedures). METHODS: The methods are compared with those of the more commonly used anesthetic sodium amobarbital (Amytal). RESULTS: Despite differences between the methohexital and amobarbital test protocols, the behavioral and neurologic effects of the two anesthetics are similar. Because of the brief duration of methohexital, two successive injections are made on each side rather than one, to lengthen the time available for testing both language and memory. Behavioral and EEG indices return to baseline more quickly and more completely with methohexital than with amobarbital, allowing several repetitions of the procedure without incremental drowsiness, and the total time taken for the procedure is less with methohexital than with amobarbital. CONCLUSIONS: The results of language and memory testing in the Wada test are equivalent for amobarbital and methohexital, except that methohexital has a briefer duration of action and is associated with less sedation.