Plasma hydrogen sulfide: A biomarker of Alzheimer's disease and related dementias.

While heart disease remains a common cause of mortality, cerebrovascular disease also increases with age, and has been implicated in Alzheimer's disease and related dementias (ADRD). We have described hydrogen sulfide (H2 S), a signaling molecule important in vascular homeostasis, as a biomarker of cardiovascular disease. We hypothesize that plasma H2 S and its metabolites also relate to vascular and cognitive dysfunction in ADRD. We used analytical biochemical methods to measure plasma H2 S metabolites and MRI to evaluate indicators of microvascular disease in ADRD. Levels of total H2 S and specific metabolites were increased in ADRD versus controls. Cognition and microvascular disease indices were correlated with H2 S levels. Total plasma sulfide was the strongest indicator of ADRD, and partially drove the relationship between cognitive dysfunction and white matter lesion volume, an indicator of microvascular disease. Our findings show that H2 S is dysregulated in dementia, providing a potential biomarker for diagnosis and intervention.

A Real-World Data Study on the Impact of the ReadRx Cognitive Training and Reading Intervention on Cognition, Basic Reading Ability, and Psychosocial Skills for 3527 Children.

Background: The state of reading proficiency among children in the United States continues to be a subject of concern among psychologists, teachers, parents, policy makers, and the education community at large. Despite the widespread use of curricular methods that teach basic reading skills, there remains a large percentage of children that struggle to read. Therefore, novel approaches to reading remediation should be explored. Purpose: The aims of this study were to examine 1) the effect of a multicomponent cognitive and reading intervention on cognitive and reading skills; 2) the role of ADHD, age, sex, IQ score, and individual cognitive skills on the effectiveness of the ReadRx intervention; and 3) parent-reported behavioral outcomes following the ReadRx intervention. Methods: The current study analyzed a large real-world dataset to examine cognitive, reading, and behavioral outcomes for struggling readers (n = 3527) who had completed 24 weeks (120 hours) of intense cognitive training integrated with a structured literacy intervention using ReadRx in a one-on-one clinic setting. Results: Analyses of pretest and post-test scores showed statistically significant changes on all cognitive and reading measures including attention, visual processing, processing speed, long-term memory, working memory, reasoning, phonological awareness, Work Attack, phonetic coding, spelling, comprehension, and overall IQ score with medium to very large effect sizes. The results included an average 4.1-year gain in reading skills including a 6-year gain in phonological awareness. No differences were found based on age, sex, or ADHD status, and minimal differences were found based on pre-intervention IQ score and cognitive test scores. The study also included a qualitative thematic analysis of parent-reported behavioral outcomes revealing themes of improved cognition, academic performance, and psychosocial skills including confidence and perseverance. Conclusion: Our findings were consistent with previous controlled studies on this intervention and offer an encouraging alternative instructional approach to reading remediation that aligns with the Science of Reading and includes intensive remediation of underlying cognitive skills.

Elevated plasma sulfides are associated with cognitive dysfunction and brain atrophy in human Alzheimer's disease and related dementias.

Emerging evidence indicates that vascular stress is an important contributor to the pathophysiology of Alzheimer's disease and related dementias (ADRD). Hydrogen sulfide (H2S) and its metabolites (acid-labile (e.g., iron-sulfur clusters) and bound (e.g., per-, poly-) sulfides) have been shown to modulate both vascular and neuronal homeostasis. We recently reported that elevated plasma sulfides were associated with cognitive dysfunction and measures of microvascular disease in ADRD. Here we extend our previous work to show associations between elevated sulfides and magnetic resonance-based metrics of brain atrophy and white matter integrity. Elevated bound sulfides were associated with decreased grey matter volume, while increased acid labile sulfides were associated with decreased white matter integrity and greater ventricular volume. These findings are consistent with alterations in sulfide metabolism in ADRD which may represent maladaptive responses to oxidative stress.

Cortical oscillatory dysfunction in Parkinson disease during movement activation and inhibition.

Response activation and inhibition are functions fundamental to executive control that are disrupted in Parkinson disease (PD). We used magnetoencephalography to examine event related changes in oscillatory power amplitude, peak latency and frequency in cortical networks subserving these functions and identified abnormalities associated with PD. Participants (N = 18 PD, 18 control) performed a cue/target task that required initiation of an un-cued movement (activation) or inhibition of a cued movement. Reaction times were variable but similar across groups. Task related responses in gamma, alpha, and beta power were found across cortical networks including motor cortex, supplementary and pre- supplementary motor cortex, posterior parietal cortex, prefrontal cortex and anterior cingulate. PD-related changes in power and latency were noted most frequently in the beta band, however, abnormal power and delayed peak latency in the alpha band in the pre-supplementary motor area was suggestive of a compensatory mechanism. PD peak power was delayed in pre-supplementary motor area, motor cortex, and medial frontal gyrus only for activation, which is consistent with deficits in un-cued (as opposed to cued) movement initiation characteristic of PD.

Remote vs. In-person Delivery of LearningRx One-on-One Cognitive Training During the COVID-19 Pandemic: A Non-inferiority Study.

The COVID-19 pandemic challenged in-person delivery of cognitive training. Some clinics pivoted to remote delivery for those impacted by lockdowns, illness, or fear of exposure to the virus. However, it was unknown if remote delivery using teleconferencing technology was as effective as in-person delivery. The current study compared the outcomes of remote delivery to in-person delivery of ThinkRx cognitive training during 2020. The sample included 381 child and adult clients from 18 cognitive training centers. One group (n = 178, mean age = 12.3) received traditional in-person delivery of cognitive training. The second group (n = 203, mean age = 11.7) received remote delivery of one-on-one cognitive training via Zoom teleconferencing. Each client was assessed before and after the intervention using the Woodcock Johnson IV Tests of Cognitive Abilities. Clients completed an average of 112 h of cognitive training delivered by a clinician in 90-min sessions 3 or 4 days per week. Paired samples t-tests revealed significant differences from pretest to post-test across all constructs for both groups. After Bonferroni correction, MANOVA revealed no significant difference in changes scores between the two intervention groups on any of the subtests. With very small effect sizes, linear regression analyses indicated that age was a significant predictor of change in working memory and processing speed for the in-person group, and a significant predictor of change in overall IQ score for the teletherapy group. Non-inferiority analyses indicated remote delivery is not inferior to in-person delivery on the primary outcome measure of overall IQ score along with processing speed, fluid reasoning, long-term memory, and visual processing. Although in-person training results were slightly higher than remote training results, the current study reveals remote delivery of cognitive training during COVID-19 was a viable alternative to in-person delivery of cognitive training with little practical differences based on the age of client.

Reliability Evidence for the Gibson Assessment of Cognitive Skills (GACS): A Brief Tool for Screening Cognitive Skills Across the Lifespan.

PURPOSE: The aim of the current study was to examine and report three sources of reliability evidence for the Gibson Assessment of Cognitive Skills, a paper-based, brief cognitive screening tool for children and adults measuring working memory, processing speed, visual processing, logic and reasoning, and three auditory processing constructs: sound blending, sound segmenting, sound deletion along with work attack skills. SAMPLE AND METHODS: The sample (n = 103) for the current study consisted of children (n = 73) and adults (n = 30) between the ages of 6 and 80 (M = 20.2), 47.6% of which were female and 52.4% of which were male. Analyses of test data included calculation of internal consistency reliability, split-half reliability, and test-retest reliability. RESULTS: Overall coefficient alphas range from 0.80 to 0.94, producing a strong source of internal consistency reliability evidence. The split-half reliability coefficients ranged from 0.83 to 0.96 overall, producing a strong second source of reliability evidence. Across all ages, the test-retest reliability coefficients ranged from 0.83 to 0.98. For adults ages 18 to 80, test-retest reliability coefficients ranged from 0.73 to 0.99. For children ages 6 through 17, test-retest reliability coefficients ranged from 0.89 to 0.97. All correlations were statistically significant at p < 0.001, indicating strong test-retest reliability and stability across administrations. CONCLUSION: The evidence collected for the current study suggests that the GACS is a reliable brief screening tool for assessing cognitive skill performance in both children and adults.

Sex specific cognitive differences in Parkinson disease.

Parkinson disease (PD) is a progressive neurodegenerative disorder that is 1.5 times more common in males than in females. While motor progression tends to be more aggressive in males, little is known about sex difference in cognitive progression. We tested the hypothesis that there are sex differences in cognitive dysfunction in non-demented PD. We evaluated 84 participants (38 females) with PD and 59 controls (27 females) for demographic variables and cognitive function, including attention, working memory, executive function, and processing speed. Multivariate ANOVA revealed no significant differences between groups for demographic variables, including age, years of education, global cogntition, daytime sleepiness, predicted premorbid IQ, UPDRS score, PD phenotype, or disease duration. For cognitive variables, we found poorer performance in males versus females with PD for measures of executive function and processing speed, but no difference between male and female controls. Specifically, PD males showed greater deficits in Verbal Fluency (category fluency, category switching, and category switching accuracy), Color Word Interference (inhibition), and speed of processing (SDMT). There were no differences in measures of working memory or attention across sex and inconsistent findings for switching. Our data indicate that males with PD have significantly greater executive and processing speed impairments compared to females despite no differences in demographic variables or other measures of disease severity. Our findings are consistent with the steeper slope of disease progression reported in males with PD.

Biomarkers of Seizure Activity in Patients With Intracranial Metastases and Gliomas: A Wide Range Study of Correlated Regions of Interest.

Introduction: Studies quantifying cortical metrics in brain tumor patients who present with seizures are limited. The current investigation assesses morphometric/volumetric differences across a wide range of anatomical regions, including temporal and extra-temporal, in patients with gliomas and intracranial metastases (IMs) presenting with seizures that could serve as a biomarker in the identification of seizure expression and serve as a neuronal target for mitigation. Methods: In a retrospective design, the MR sequences of ninety-two tumor patients [55% gliomas; 45% IM] and 34 controls were subjected to sophisticated morphometric and volumetric assessments using BrainSuite and MATLAB modules. We examined 103 regions of interests (ROIs) across eight distinct cortical categories of interests (COI) [gray matter, white matter; total volume, CSF; cortical areas: inner, mid, pial; cortical thickness]. The primary endpoint was quantifying and identifying ROIs with significant differences in z-scores based upon the presence of seizures. Feature selection employing neighborhood component analysis (NCA) determined the ROI within each COI having the highest significance/weight in the differentiation of seizure vs. non-seizure patients harboring brain tumor. Results: Overall, the mean age of the cohort was 58.0 ± 12.8 years, and 45% were women. The prevalence of seizures in tumor patients was 28%. Forty-two ROIs across the eight pre-defined COIs had significant differences in z-scores between tumor patients presenting with and without seizures. The NCA feature selection noted the volume of pars-orbitalis and right middle temporal gyrus to have the highest weight in differentiating tumor patients based on seizures for three distinct COIs [GM, total volume, and CSF volume] and white matter, respectively. Left-sided transverse temporal gyrus, left precuneus, left transverse temporal, and left supramarginal gyrus were associated with having the highest weight in the differentiation of seizure vs. non-seizure in tumor patients for morphometrics relating to cortical areas in the pial, inner and mid regions and cortical thickness, respectively. Conclusion: Our study elucidates potential biomarkers for seizure targeting in patients with gliomas and IMs based upon morphometric and volumetric assessments. Amongst the widespread brain regions examined in our cohort, pars orbitalis, supramarginal and temporal gyrus (middle, transverse), and the pre-cuneus contribute a maximal potential for differentiation of seizure patients from non-seizure.

Neuroimaging and Neuropsychological Outcomes Following Clinician-Delivered Cognitive Training for Six Patients With Mild Brain Injury: A Multiple Case Study.

Nearly half of all mild brain injury sufferers experience long-term cognitive impairment, so an important goal in rehabilitation is to address their multiple cognitive deficits to help them return to prior levels of functioning. Cognitive training, or the use of repeated mental exercises to enhance cognition, is one remediation method for brain injury. The primary purpose of this hypothesis-generating pilot study was to explore the statistical and clinical significance of cognitive changes and transfer of training to real-life functioning following 60 h of Brain Booster, a clinician-delivered cognitive training program, for six patients with mild traumatic brain injury (TBI) or non-traumatic acquired brain injury (ABI). The secondary purpose was to explore changes in functional connectivity and neural correlates of cognitive test gains following the training. We used a multiple case study design to document significant changes in cognitive test scores, overall IQ score, and symptom ratings; and we used magnetic resonance imaging (MRI) to explore trends in functional network connectivity and neural correlates of cognitive change. All cognitive test scores showed improvement with statistically significant changes on five of the seven measures (long-term memory, processing speed, reasoning, auditory processing, and overall IQ score). The mean change in IQ score was 20 points, from a mean of 108 to a mean of 128. Five themes emerged from the qualitative data analysis including improvements in cognition, mood, social identity, performance, and Instrumental Activities of Daily Living (IADLs). With MRI, we documented significant region-to-region changes in connectivity following cognitive training including those involving the cerebellum and cerebellar networks. We also found significant correlations between changes in IQ score and change in white matter integrity of bilateral corticospinal tracts (CST) and the left uncinate fasciculus. This study adds to the growing body of literature examining the effects of cognitive training for mild TBI and ABI, and to the collection of research on the benefits of cognitive training in general. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02918994.

Focal epilepsy caused by single cerebral cavernous malformation (CCM) is associated with regional and global resting state functional connectivity (FC) disruption.

Epilepsy, including the type with focal onset, is increasingly viewed as a disorder of the brain network. Here we employed the functional connectivity (FC) metrics estimated from the resting state functional MRI (rsfMRI) to investigate the changes of brain network associated with focal epilepsy caused by single cerebral cavernous malformation (CCM). Eight CCM subjects and 21 age and gender matched controls were enrolled in the study. Seven of 8 CCM subjects underwent surgical resection of the CCM and became seizure free and 4 of the surgical subjects underwent a repeat rsfMRI study. We showed that there was both regional and global disruption of the FC values among the CCM subjects including decreased in homotopic FC (HFC) and global FC (GFC) in the regions of interest (ROIs) where the CCMs were located. There was also the disruption of the default mode network (DMN) especially the FC between the middle prefrontal cortex (MPFC) and the right lateral parietal cortex (LPR) among these individuals. We observed the trend of alleviation of these disruptions after the individual has become seizure free from the surgical resection of the CCM. Using a voxel-based approach, we found the disruption of the HFC and GFC in the brain tissue immediately adjacent to the CCM and the severity of the disruption appeared inversely proportional to the distance of the brain tissue to the lesion. Our findings confirm the disruption of normal brain networks from focal epilepsy, a process that may be reversible with successful surgical treatments rendering patients seizure free. Some voxel-based metrics may help identify the epileptogenic zone and guide the surgical resection.

Clinician-delivered cognitive training for children with attention problems: effects on cognition and behavior from the ThinkRx randomized controlled trial.

PURPOSE: The impact of attention problems on academic and social functioning coupled with the large number of children failing to respond to stimulant medication or behavioral therapy makes adjunctive therapies such as cognitive training appealing for families and clinicians of children with attention difficulties or childhood attention deficit hyperactivity disorder. However, the results of cognitive training studies have failed to find far transfer effects with this population. This study examined the quantitative cognitive effects and parent-reported behavioral effects of a clinician-delivered cognitive training program with children who have attention problems. PATIENTS AND METHODS: Using a randomized controlled study design, we examined the impact of a clinician-delivered cognitive training program on processing speed, fluid reasoning, memory, visual processing, auditory processing, attention, overall intelligence quotient score, and behavior of students (n=13) aged 8-14 years with attention problems. Participants were randomly assigned to either a waitlist control group or a treatment group for 60 hours of cognitive training with ThinkRx, a clinician-delivered intervention that targets multiple cognitive skills with game-like, but rigorous mental tasks in 60-90-minute training sessions at least 3 days per week. RESULTS: Results included greater mean pretest to posttest change scores on all variables for the treatment group versus the control group with statistically significant differences noted in working memory, long-term memory, logic and reasoning, auditory processing, and intelligence quotient score. Qualitative outcomes included parent-reported changes in confidence, cooperation, and self-discipline. CONCLUSION: Children with attention problems who completed 60 hours of clinician-delivered ThinkRx cognitive training realized both cognitive and behavioral improvements.

Altered Cortico-Limbic Network Connectivity in Parkinsonian Depression: The Effect of Antidepressants.

BACKGROUND: Depression is a common comorbidity of Parkinson's disease (PD); however, the impact of antidepressant status on cortical function in parkinsonian depression is not fully understood. While studies of resting state functional MRI in major depression have shown that antidepressant treatment affects cortical connectivity, data on connectivity and antidepressant status in PD is sparse. OBJECTIVE: We tested the hypothesis that cortico-limbic network (CLN) resting state connectivity is abnormal in antidepressant-treated parkinsonian depression. METHODS: Thirteen antidepressant-treated depressed PD and 47 non-depressed PD participants from the Parkinson's Progression Markers Initiative (PPMI) database were included. Data was collected using 3T Siemens TIM Trio MR scanners and analyzed using SPM and CONN functional connectivity toolbox. Volumetric analysis was also performed using BrainSuite. RESULTS: We found decreased connectivity in the antidepressant-treated depressed PD group when compared to non-depressed PD between the left frontal operculum and bilateral insula, and also reduced connectivity between right orbitofrontal cortex and left temporal fusiform structures. Increased depression scores were associated with decreased insular-frontal opercular connectivity. No ROI volumetric differences were found between groups. CONCLUSION: Given the relationship between depression scores and cortico-limbic connectivity in PD, the abnormal insular-frontal opercular hypoconnectivity in this cohort may be associated with persistent depressive symptoms or antidepressant effects.

Differentiation of High-Grade Glioma and Intracranial Metastasis Using Volumetric Diffusion Tensor Imaging Tractography.

OBJECTIVE: A reliable, noninvasive method to differentiate high-grade glioma (HGG) and intracranial metastasis (IM) has remained elusive. The aim of this study was to differentiate between HGG and IM using tumoral and peritumoral diffusion tensor imaging characteristics. METHODS: A semiautomated script generated volumetric regions of interest (ROIs) for the tumor and a peritumoral shell at a predetermined voxel thickness. ROI differences in diffusion tensor imaging-related metrics between HGG and IM groups were estimated, including fractional anisotropy, mean diffusivity, total fiber tract counts, and tract density. RESULTS: The HGG group (n = 46) had a significantly higher tumor-to-brain volume ratio than the IM group (n = 35) (P < 0.001). The HGG group exhibited significantly higher mean fractional anisotropy and significantly lower mean diffusivity within peritumoral ROI than the IM group (P < 0.05). The HGG group exhibited significantly higher total tract count and higher tract density in tumoral and peritumoral ROIs than the IM group (P < 0.05). Tumoral tract count and peritumoral tract density were the most optimal metrics to differentiate the groups based on receiver operating characteristic curve analysis. Predictive analysis using receiver operating characteristic curve thresholds was performed on 13 additional participants. Compared with correct clinical diagnoses, the 2 thresholds exhibited equal specificities (66.7%), but the tumoral tract count (85.7%) seemed more sensitive in differentiating the 2 groups. CONCLUSIONS: Tract count and tract density were significantly different in tumoral and peritumoral regions between HGG and IM. Differences in microenvironmental interactions between the tumor types may cause these tract differences.

Cognitive Effects of ThinkRx Cognitive Rehabilitation Training for Eleven Soldiers with Brain Injury: A Retrospective Chart Review.

Cognitive rehabilitation training is a promising technique for remediating the cognitive deficits associated with brain injury. Extant research is dominated by computer-based interventions with varied results. Results from clinician-delivered cognitive rehabilitation are notably lacking in the literature. The current study examined the cognitive outcomes following ThinkRx, a clinician-delivered cognitive rehabilitation training program for soldiers recovering from traumatic brain injury and acquired brain injury. In a retrospective chart review, we examined cognitive outcomes of 11 cases who had completed an average of 80 h of ThinkRx cognitive rehabilitation training delivered by clinicians and supplemented with digital training exercises. Outcome measures included scores from six cognitive skill batteries on the Woodcock Johnson - III Tests of Cognitive Abilities. Participants achieved gains in all cognitive skills tested and achieved statistically significant changes in long-term memory, processing speed, auditory processing, and fluid reasoning with very large effect sizes. Clinically significant changes in multiple cognitive skills were also noted across cases. Results of the study suggest that ThinkRx clinician-delivered cognitive training supplemented with digital exercises may be a viable method for targeting the cognitive deficits associated with brain injury.

High-grade Gliomas Exhibit Higher Peritumoral Fractional Anisotropy and Lower Mean Diffusivity than Intracranial Metastases.

Differentiating high-grade gliomas and intracranial metastases through non-invasive imaging has been challenging. Here, we retrospectively compared both intratumoral and peritumoral fractional anisotropy (FA), mean diffusivity (MD), and fluid-attenuated inversion recovery (FLAIR) measurements between high-grade gliomas and metastases. Two methods were utilized to select peritumoral region of interest (ROI). The first method utilized the manual placement of four ROIs adjacent to the lesion. The second method utilized a semiautomated and proprietary MATLAB script to generate an ROI encompassing the entire tumor. The average peritumoral FA, MD, and FLAIR values were determined within the ROIs for both methods. Forty patients with high-grade gliomas and 44 with metastases were enrolled in this study. Thirty-five patients with high-grade glioma and 30 patients with metastases had FLAIR images. There was no significant difference in age, gender, or race between the two patient groups. The high-grade gliomas had a significantly higher tumor-to-brain area ratio compared to the metastases. There were no differences in average intratumoral FA, MD, and FLAIR values between the two groups. Both the manual sample method and the semiautomated peritumoral ring method resulted in significantly higher peritumoral FA and significantly lower peritumoral MD in high-grade gliomas compared to metastases (p < 0.05). No significant difference was found in FLAIR values between the two groups peritumorally. Receiver operating curve analysis revealed FA to be a more sensitive and specific metric to differentiate high-grade gliomas and metastases than MD. The differences in the peritumoral FA and MD values between high-grade gliomas and metastases seemed due to the infiltration of glioma to the surrounding brain parenchyma.

LearningRx Cognitive Training Effects in Children Ages 8-14: A Randomized Controlled Trial.

In a randomized controlled study, we examined the effects of a one-on-one cognitive training program on memory, visual and auditory processing, processing speed, reasoning, attention, and General Intellectual Ability (GIA) score for students ages 8-14. Participants were randomly assigned to either an experimental group to complete 60 h of cognitive training or to a wait-list control group. The purpose of the study was to examine changes in multiple cognitive skills after completing cognitive training with ThinkRx, a LearningRx program. Results showed statistically significant differences between groups on all outcome measures except for attention. Implications, limitations, and suggestions for future research are examined.

Psammomatous Cavernous Malformation Presenting as Drug-Resistant Epilepsy: Case Illustration and Review of Literature.

BACKGROUND: Psammoma bodies (PBs) are whorled, laminated hyaline spherules containing calcium deposits. Intracranially, the presence of PBs is associated with variants of meningioma and pituitary lesions, as well as aging choroid plexus. Limited information exists on their presence in vascular malformation. RESULTS: In this report, we describe a case of an adolescent male with drug-resistant epilepsy that was surgically managed at our regional epilepsy center. The epileptogenic focus was determined to be emanating from an indolent right insular lesion. Histopathologic evaluation showed the abundance of intravascular and perivascular PBs. Immunohistochemical evaluation confirmed the vascular origin using vascular markers. The unusual presence of PBs in a vascular lesion was unanticipated. CONCLUSIONS: Based on our case, we present the clinicoradiologic characteristics, supplemented with intraoperative findings, for this unusual lesion. In addition, because of the unusual presence of PBs in vascular lesions, we provide the findings of a systematic literature review to show the association of PBs with intracranial vascular lesions.

Changes in hippocampal metabolites after effective treatment for fibromyalgia: a case study.

BACKGROUND: Fibromyalgia has been associated with disrupted hippocampal brain metabolite ratios by studies using single voxel magnetic resonance spectroscopy (1H-MRS). Exposure to stress is considered a risk factor for the development and exacerbation of fibromyalgia symptoms. Basic science has demonstrated the hippocampus to be exquisitely sensitive to the effects of stressful experience, which results in changes including alterations in metabolite content and frank atrophy. METHODS: This report details the case of a 47-year-old woman with fibromyalgia who was originally found to have a profound depression of the ratio of N-acetylaspartate to creatine in her right hippocampus during participation in a study to assess brain metabolite disturbances in fibromyalgia utilizing single voxel proton magnetic resonance spectroscopy. An individualized treatment strategy was developed based both on physiological abnormalities associated with the disorder and symptoms that characterized the patient's unique clinical profile. RESULTS: Clinical and spectroscopic evaluation following nine months of treatment demonstrated both an improvement in her clinical profile and normalization of the NAA/Cr ratio within her right hippocampus. DISCUSSION: Therapeutic strategies aimed at demonstrable lesions associated with fibromyalgia appear to represent rational targets for pharmacological intervention. The rationale for development of novel pharmacotherapies for this unusual disorder is discussed.

Hippocampal metabolite abnormalities in fibromyalgia: correlation with clinical features.

UNLABELLED: Although the pathology of fibromyalgia is poorly understood, a growing body of evidence suggests involvement of the central nervous system. The hippocampus is a brain center that is sensitive to the effects of stress exposure and has been demonstrated to be affected in a variety of disorders whose onset, like fibromyalgia, are associated with stressful experience. We therefore interrogated the bilateral hippocampus of 16 female fibromyalgia patients in comparison to 8 age- and gender-matched healthy control subjects using single voxel proton magnetic resonance spectroscopy. Our results demonstrate a significant reduction in the ratio of N-acetylaspartate to creatine (NAA/Cr) in fibromyalgia patients versus matched control subjects specifically in the right temporal lobe from a voxel centered on the right hippocampus (patient vs control, mean +/- standard deviation: 1.20 +/- 0.13 vs 1.34 +/- 0.10, P = .03). Moreover, correlation analysis demonstrated a significant negative correlation between patient scores on the Fibromyalgia Impact Questionnaire and NAA/Cr ratio within the right hippocampus (Spearman rank correlation, rho = -0.681, P = .018). Our results indicate that fibromyalgia is associated with brain metabolite abnormalities within the right hippocampus that correlate with patient symptoms. PERSPECTIVE: We have demonstrated an abnormality in hippocampal brain metabolites in premenopausal female fibromyalgia patients with no psychiatric comorbidity. A significant negative correlation between patient subjective experience of symptoms and a reduced NAA/Cr ratio suggests a role for hippocampal pathology in fibromyalgia.

The role of quantitative neuroimaging indices in the differentiation of ischemia from demyelination: an analytical study with case presentation.

BACKGROUND AND PURPOSE: Differentiation of acute and subacute ischemic stroke lesions from acute demyelinating lesions of multiple sclerosis (MS) may not be possible on conventional magnetic resonance imaging (MRI). Both lesion types enhance on T1 with gadolinium (Gd) contrast and both are hyperintense on diffusion-weighted imaging (DWI). This study is an analysis of two quantitative MR indices: (1) calculated apparent diffusion coefficients (ADCs) and (2) T2 relaxation times (T2R) as means toward differentiating acute ischemic lesions from acute demyelinating lesions. Chronic ischemic and demyelinating lesions were evaluated for comparison as well. METHODS: The MRI of nine patients with both acute and chronic ischemic lesions and six patients with both acute and chronic demyelinating lesions were analyzed for ADC and T2Rs. The indices were measured by manually placing regions of interest (ROIs) at the anatomic center of the acute lesion. Acute ischemic lesions were chosen by their hyperintensity on DWI and hypointensity on ADC mapping. Acute demyelinating lesions were selected by peripheral contrast enhancement after the administration of Gd. Computation of the ADC involved the diffusion coefficient on a region by region basis as follows: D = -(b(0)/b(1000))ln(S(b1000)/S(b0)), where S(b1000) is the signal intensity on DWI and S(b0) is the signal intensity on T2 with diffusion sensitivities of b(0) and b(1000), respectively. Computation of the T2R was made as follows: T2R = (TE(T2)--TE(PD))/(ln SI(PD)--ln SI(T2)), where TE is the echo time of the different pulse sequences, SI is signal intensity on the different echo sequences, and PD represents proton density sequence. RESULTS: Twenty-nine acute ischemia, 27 acute demyelination, 28 chronic ischemia, and 43 chronic demyelination image sets were analyzed. The differences between ADC(acute infarct) (0.760) versus ADC(acute plaque) (1.106) were significant (p < 0.02). The differences between T2R(acute infarct) (235.5) versus T2R(acute plaque) (170.5) were also significant (p < 0.02). CONCLUSIONS: ADC in combination with T2R is a useful tool to differentiate acute ischemic from acute demyelinating lesions. The use of these neuroimaging indices along with magnetic resonance spectroscopy metabolite ratios is then demonstrated in elucidating the pathophysiological mechanism for a case of delayed posttraumatic bilateral internuclear ophthalmoplegia.