Predictive value of brain perfusion SPECT for ketamine response in hyperalgesic fibromyalgia

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European journal of nuclear medicine and molecular imaging (Impact Factor: 5.38). 09/2007; 34(8):1274-9. DOI: 10.1007/s00259-007-0392-7
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Ketamine has been used successfully in various proportions of fibromyalgia (FM) patients. However, the response to this specific treatment remains largely unpredictable. We evaluated brain SPECT perfusion before treatment with ketamine, using voxel-based analysis. The objective was to determine the predictive value of brain SPECT for ketamine response.
Seventeen women with FM (48 +/- 11 years; ACR criteria) were enrolled in the study. Brain SPECT was performed before any change was made in therapy in the pain care unit. We considered that a patient was a good responder to ketamine if the VAS score for pain decreased by at least 50% after treatment. A voxel-by-voxel group analysis was performed using SPM2, in comparison to a group of ten healthy women matched for age.
The VAS score for pain was 81.8 +/- 4.2 before ketamine and 31.8 +/- 27.1 after ketamine. Eleven patients were considered "good responders" to ketamine. Responder and non-responder subgroups were similar in terms of pain intensity before ketamine. In comparison to responding patients and healthy subjects, non-responding patients exhibited a significant reduction in bilateral perfusion of the medial frontal gyrus. This cluster of hypoperfusion was highly predictive of non-response to ketamine (positive predictive value 100%, negative predictive value 91%).
Brain perfusion SPECT may predict response to ketamine in hyperalgesic FM patients.

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Available from: Eric Guedj, Oct 04, 2015
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    • "In this study, pronounced pretreatment hyperperfusion in the right middle temporal gyrus, left superior frontal gyrus, right precuneus, left middle occipital gyrus, and left declive appeared to be predictive of poor response to gabapentin given the high positive likelihood ratios obtained for these regions. These findings are not consistent with a previous finding for non-responders to ketamine, in which hypoperfusion in the medial frontal area was observed [18]. As noted above, subjects in the study of Guedj and colleagues were hospitalized because of treatment failure whereas our subjects were CNS drug-naive outpatients without major depressive disorder, and our findings were correspondingly not affected by CNS drugs. "
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    ABSTRACT: The aim of the present study was to determine the brain areas associated with fibromyalgia, and whether pretreatment regional cerebral blood flow (rCBF) can predict response to gabapentin treatment. A total of 29 women with fibromyalgia and 10 healthy women (without pain) matched for age were finally enrolled in the study. Technetium-99m ethyl cysteinate dimer single photon emission computed tomography ((99m)Tc-ECD SPECT) was performed in the fibromyalgia patients and controls. A voxel-by-voxel group analysis was performed using Statistic Parametric Mapping 5 (SPM5). After treatment with gabapentin, 16 patients were considered 'responders', with decrease in pain of greater than 50% as evaluated by visual analogue scale (VAS). The remaining 13 patients were considered 'poor responders'. We observed rCBF abnormalities, compared to control subjects, in fibromyalgia including hypoperfusion in the left culmen and hyperperfusion in the right precentral gyrus, right posterior cingulate, right superior occipital gyrus, right cuneus, left inferior parietal lobule, right middle temporal gyrus, left postcentral gyrus, and left superior parietal lobule. Compared to responders, poor responders exhibited hyperperfusion in the right middle temporal gyrus, left middle frontal gyrus, left superior frontal gyrus, right postcentral gyrus, right precuneus, right cingulate, left middle occipital gyrus, and left declive. The right middle temporal gyrus, left superior frontal gyrus, right precuneus, left middle occipital gyrus, and left declive exhibited high positive likelihood ratios. The present study revealed brain regions with significant hyperperfusion associated with the default-mode network, in addition to abnormalities in the sensory dimension of pain processing and affective-attentional areas in fibromyalgia patients. Furthermore, hyperperfusion in these areas was strongly predictive of poor response to gabapentin.
    Arthritis research & therapy 04/2010; 12(2):R64. DOI:10.1186/ar2980 · 3.75 Impact Factor
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    • "The fi ndings by Mountz and colleagues (1995) were largely replicated in a second SPECT study by Kwiatek and colleagues (2000). In a third SPECT trial, Guedj and colleagues (2007a, 2007b) reported a study using a more sensitive radioligand (99mTc-ECD) in fibromyalgia patients and pain free controls. Guedj and colleagues found hyperperfusion in fi bromyalgia patients within the somatosensory cortex and hypoperfusion in the anterior and posterior cingulate, the amygdala, medial frontal and parahippocampal gyrus, and the cerebellum. "
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    ABSTRACT: Fibromyalgia syndrome is a common chronic pain disorder of unknown etiology. The lack of understanding of the pathophysiology of fibromyalgia has made this condition frustrating for patients and clinicians alike. The most common symptoms of this disorder are chronic widespread pain, fatigue, sleep disturbances, difficulty with memory, and morning stiffness. Emerging evidence points towards augmented pain processing within the central nervous system (CNS) as having a primary role in the pathophysiology of this disorder. Currently the two drugs that are approved by the United States Food and Drug Administration (FDA) for the management of fibromyalgia are pregabalin and duloxetine. Newer data suggests that milnacipran, a dual norepinephrine and serotonin reuptake inhibitor, may be promising for the treatment of fibromyalgia. A double-blind, placebo-controlled trial of milnacipran in 125 fibromyalgia patients showed significant improvements relative to placebo. Milnacipran given either once or twice daily at doses up to 200 mg/day was generally well tolerated and yielded significant improvements relative to placebo on measures of pain, patient's global impression of change in their disease state, physical function, and fatigue. Future studies are needed to validate the efficacy of milnacipran in fibromyalgia.
    Therapeutics and Clinical Risk Management 01/2009; 4(6):1331-42. · 1.47 Impact Factor
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    • "The status of neural activity in the patients with FM was related to physiological and not psychological stimuli as mood states, such as depression, did not appear to influence the outcome. Data from SPECT neuroimaging studies have also been predictive of therapeutic responsiveness of treatment of patients with FM with amitriptyline and ketamine (Adiguzel et al 2004; Guedj et al 2007b). It is important to recognize that such neuroimaging techniques do not measure neural activity directly, but infer activity from localized changes in regional cerebral blood flow occurring in response to neural metabolic demand. "
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    ABSTRACT: Fibromyalgia (FM) is a common, complex, and difficult to treat chronic widespread pain disorder, which usually requires a multidisciplinary approach using both pharmacological and non-pharmacological (education and exercise) interventions. It is a condition of heightened generalized sensitization to sensory input presenting as a complex of symptoms including pain, sleep dysfunction, and fatigue, where the pathophysiology could include dysfunction of the central nervous system pain modulatory systems, dysfunction of the neuroendocrine system, and dysautonomia. A cyclic model of the pathophysiological processes is compatible with the interrelationship of primary symptoms and the array of postulated triggers associated with FM. Many of the molecular targets of current and emerging drugs used to treat FM have been focused to the management of discrete symptoms rather than the condition. Recently, drugs (eg, pregabalin, duloxetine, milnacipran, sodium oxybate) have been identified that demonstrate a multidimensional efficacy in this condition. Although the complexity of FM suggests that monotherapy, non-pharmacological or pharmacological, will not adequately address the condition, the outcomes from recent clinical trials are providing important clues for treatment guidelines, improved diagnosis, and condition-focused therapies.
    Neuropsychiatric Disease and Treatment 01/2009; 4(6):1059-71. DOI:10.2147/NDT.S3468 · 1.74 Impact Factor
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