James C. Patterson

Changes in Gray Matter Density in Fibromyalgia: Correlation With Dopamine Metabolism

UNLABELLED Fibromyalgia (FM) has been associated with alterations in brain morphometry and abnormal dopaminergic neurotransmission. Evidence from preclinical models has demonstrated that dopamine plays a role in promoting neuronal integrity. We therefore sought to confirm previous findings of reduced gray matter density in subjects with FM and to determine whether variations in dopamine metabolism might affect gray matter density. Voxel-based morphometry was used to evaluate anatomical magnetic resonance imaging data from 30 female FM subjects in comparison with 20 age- and gender-matched healthy control subjects. In addition, data from a subset of subjects from both groups who had previously participated in our positron emission tomography study using radiolabeled DOPA (n = 14; 6 FM subjects and 8 control subjects) was used to determine whether correlation might exist between gray matter density and dopamine metabolism. We found a significant reduction in gray matter density within the bilateral parahippocampal gyri, right posterior cingulate cortex, and left anterior cingulate cortex. In addition, a positive correlation was demonstrated between an index of dopamine metabolism from the ventral tegmental area wherein cell bodies of corticolimbic projection neurons originate and gray matter density, specifically in the bilateral parahippocampal gyri and left pregenual cortex. The current results confirm our previous findings that FM is associated with altered brain morphometry. Alterations in dopamine metabolism might contribute to the associated changes in gray matter density. PERSPECTIVE Fibromyalgia is associated with reductions in gray matter density within brain regions ostensibly involved in phenomena related to the disorder, including enhanced pain perception, cognitive dysfunction, and abnormal stress reactivity. Given mounting evidence of abnormal dopaminergic neurotransmission associated with the disorder, the strong correlation between dopamine metabolism and gray matter density provides insight as to the pathophysiology that might contribute to these changes.

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.

Changes in Hippocampal Metabolites After Effective Treatment for Fibromyalgia A Case Study

BackgroundFibromyalgia 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. MethodsThis 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 patients unique clinical profile. ResultsClinical 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. DiscussionTherapeutic 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.

Potential Value of Quantitative Analysis of Cerebral PET in Early Cognitive Decline

Background. In patients diagnosed with Alzheimers disease, positron emission tomography brain scans can have characteristic hypometabolic patterns that strongly support this diagnosis, but this pattern is often subtle or absent in early stages. A sensitive and objective method for detection of positron emission tomography abnormalities may have value in early detection of Alzheimers disease. Methods. A 2-fluoro-2-deoxy-D-glucose positron emission tomography scans from cognitively impaired patients (n = 43) were compared individually to 28 normal controls using statistical parametric mapping, hypometabolic regions visualized, and clinically correlated. The objective SPM results were compared to the official Nuclear Medicine report based upon subjective interpretation criteria. Results. A total of 22/43 had abnormalities per the Nuclear Medicine physician, while 21/43 appeared normal. The objective analysis detected abnormalities in 41/43 participants, including 19 of 21 that appeared normal. In these 19, 8 had findings consistent with early Alzheimers disease. Conclusion. Objective analysis of positron emission tomography brain scans may extend the ability to detect early brain abnormalities in patients with cognitive decline.

A Method to Combine Cognitive and Neurophysiological Assessments of the Elderly

Background: The development of better treatments for brain diseases of the elderly will necessitate more sensitive and efficient means of repeatedly assessing an individual’s neurocognitive status. Aim: To illustrate the development of an assessment combining episodic memory and working memory tasks with simultaneous electroencephalography and evoked potential (EP) brain function measures. Methods: Data from matched groups of elderly subjects with mildly impaired episodic verbal memory on neuropsychological tests and those with no objective signs of impairment were used for scale development. An exploratory multivariate divergence analysis selected task performance and neurophysiological variables that best recognized impairment. Discriminant validity was then initially assessed on separate impaired and unimpaired groups. Results: Decreased response accuracy and parietal late positive component EP amplitude in the episodic memory task best characterized impaired subjects. Sensitivity in recognizing impairment in the validation analysis was 89% with 79% specificity (area under the curve = 0.94). Retest reliability was 0.89 for the unimpaired and 0.74 for the impaired validation groups. Conclusion: These promising initial results suggest that with further refinement and testing, an assessment combining cognitive task performance with simultaneous neurofunctional measures could eventually provide an important benefit for clinicians and researchers.

Insular Hypometabolism in a Patient with Fibromyalgia: A Case Study

BACKGROUND Neuroimaging studies have demonstrated differential involvement of a variety of brain centers in fibromyalgia both at baseline and in response to stimulation. The insular cortex is one such structure. FINDINGS A 46-year-old woman with chronic widespread pain underwent positron emission tomography utilizing 18F-fluorodeoxyglucose while participating as a healthy control subject in a brain imaging study. Analysis of the scan revealed metabolic hypoactivity within the left insular cortex as an incidental finding. Soon after her scan, she underwent further clinical evaluation and was subsequently diagnosed with fibromyalgia. DISCUSSION The potential contribution of insular dysfunction to the development of hyperalgesia has been demonstrated in rat models via local manipulations of dopaminergic, gamma-aminobutyric acid (GABA) ergic, and opioidergic neurotransmission within this region. Thus, our demonstration of insular hypometabolism in this patients case may have bearing on her experience of chronic widespread pain.

Simultaneous demonstration of metabolic lesions consistent with Alzheimer disease and brain metastases on FDG-PET imaging.

We report a case of a patient with brain metastases and simultaneous Alzheimer disease (AD) on FDG-PET imaging. Literature documenting AD coexisting with brain metastases is extremely rare, and there are no previously documented cases of FDG-PET imaging revealing concurrent AD and brain metastases. In addition to AD, both brain metastases and whole-brain radiation therapy may cause neurocognitive deterioration. Hence, it is important to differentiate the underlying pathologic process that is causing dementia in patients with brain metastases, to better manage these patients and improve their quality of life.

Cerebellar Perfusion Abnormalities Correlated With Change in Cognitive and Affective State in a 78-Year-Old Man

The onset of dementia is often recognized to some extent by those affected with this slow, degenerative process. Patients often have comorbid mood and/or anxiety disorders as a result of or in addition to this recognition. The author describes an unusual presentation for dementia, in both its onset and its correlation with regional changes in cerebral and cerebellar blood flow, as detected with whole-brain, voxel-by-voxel analysis. This patients ultra-rapid cycling from severe disability to a state of near-normalcy was associated with a normalization of a flow deficit in the right posterior-parietal region, in addition to striking increases in the already over-perfused cerebellum. The author summarizes possible mechanisms for these flow changes and gives a brief review of recent literature on the involvement of the cerebellum in cognition.

Urgent and Emergent Psychiatric Disorders

In the emergency department, neurologists regularly evaluate patients exhibiting behavioral abnormalities that stem from underlying neurologic diseases. This behavior may be the initial presence of a neurologic illness or may indicate the deterioration and progress of the disease process. In addition, many neurologic patients present with acute and potentially dangerous psychiatric symptoms that demand rapid and accurate management. Assessment, diagnosis, and treatment of patients with psychiatric manifestations in the context of neurologic illness pose a significant challenge to treating neurologists. This article discusses a general approach to assessment and treatment of some of the more common psychiatric disorders.