Bradley Galer - Academia.edu (original) (raw)
Papers by Bradley Galer
The Journal of Pain, Aug 1, 2010
Pain is a complex multidimensional experience that includes overall intensity/magnitude, unpleasa... more Pain is a complex multidimensional experience that includes overall intensity/magnitude, unpleasantness/bothersomeness (affect), location, and quality. However, there is a paucity of research examining the importance of pain quality to patient functioning; most research focuses only on the intensity and affective components of pain. This study sought to address this gap by examining, in a sample of patients with carpal tunnel syndrome (CTS), the associations between pain quality and 2 domains of patient functioning: pain interference and sleep quality. We found that measures of pain quality contributed to the prediction of pain interference and sleep quality over and above the effects of global pain intensity and unpleasantness. In our sample, both throbbing and itchy pain emerged as contributing the most unique variance to the prediction of patient functioning. The findings indicate that the presence of pain described as throbbing or itchy, regardless of the overall magnitude of pain, may make patients with CTS particularly vulnerable to the negative impact of pain on quality of life. The findings support the need for experimental studies to determine if treatments can be identified that address these 2 pain qualities, and if effective treatments for these qualities in particular result in significant improvement in the quality of life of patients with CTS. A growing body of research supports the importance of assessing multiple domains of pain in clinical and research settings. The current findings suggest the possibility that, in patients with carpal tunnel syndrome, itchy and throbbing pain may play key roles in patient functioning above and beyond global pain intensity and unpleasantness. More research is needed to confirm this finding, and whether treatments can be identified that address these pain qualities specifically.
Bookmarks Related papers MentionsView impact
Journal of Neurology, Neurosurgery & Psychiatry
RationaleFenfluramine (FFA) has been shown in 2 randomised, placebo-controlled clinical trials to... more RationaleFenfluramine (FFA) has been shown in 2 randomised, placebo-controlled clinical trials to reduce convulsive seizures in children with Dravet Syndrome (DS). We report an update on the cardiovascular safety of DS patients treated with FFA for up to 3 years.Methods327 patients who completed one of the three phase 3 trials enrolled in this open-label extension (OLE) study (NCT02823145). All were assessed with transthoracic echocardiography (TTE). They were assessed for Valvular Heart Disease (VHD) and Systolic pulmonary artery pressure.ResultsOne patient had a finding of mild MR (considered physiologic) during the study. One patient demonstrated mild (considered pathologic) AR at Month 15. A transoesophageal echocardiogram (TOE) performed at 6 weeks found absent AR with trace MR. No abnormalities of valve morphology were found on TOE or on TTE. No VHD or PAH was observed in any patient during the OLE.ConclusionsThis study demonstrates the absence of clinically significant VHD or...
Bookmarks Related papers MentionsView impact
Epilepsy & Behavior, 2022
Fenfluramine (N-ethyl-α-methl-3-(trifluoromethyl)phenethylamine) is an anti-seizure medication (A... more Fenfluramine (N-ethyl-α-methl-3-(trifluoromethyl)phenethylamine) is an anti-seizure medication (ASM) particularly effective in patients with Dravet syndrome, a severe treatment-resistant epileptic encephalopathy. Fenfluramine acts not only as neuronal serotonin (5-HT) releaser but also as a positive modulator of the sigma-1 receptor (S1R). We here examined the modulatory activity of Fenfluramine on the S1R-mediated anti-amnesic response in mice using combination analyses. Fenfluramine and Norfenfluramine, racemate and isomers, were combined with either the S1R agonist (PRE-084) or the S1R-acting neuro(active)steroids, pregnenolone sulfate (PREGS), Dehydroepiandrosterone sulfate (DHEAS), or progesterone. We report that Fenfluramine racemate or (+)-Fenfluramine, in the 0.1-1 mg/kg dose range, attenuated the dizocilpine-induced learning deficits in spontaneous alternation and passive avoidance, and showed low-dose synergies in combination with PRE-084. These effects were blocked by the S1R antagonist NE-100. Dehydroepiandrosterone sulfate or PREGS attenuated dizocilpine-induced learning deficits in the 5-20 mg/kg dose range. Co-treatments at low dose between steroids and Fenfluramine or (+)-Fenfluramine were synergistic. Progesterone blocked Fenfluramine effect. Finally, Fenfluramine and (+)-Fenfluramine effects were prevented by the 5-HT1A receptor antagonist WAY-100635 or 5-HT2A antagonist RS-127445, but not by the 5-HT1B/1D antagonist GR 127935 or the 5-HT2C antagonist SB 242084, confirming a 5-HT1A and 5-HT2A receptor involvement in the drug effect on memory. We therefore confirmed the positive modulation of Fenfluramine racemate or dextroisomer on S1R and showed that, in physiological conditions, the drug potentiated the low dose effects of neuro(active)steroids, endogenous S1R modulators. The latter are potent modulators of the excitatory/inhibitory balance in the brain, and their levels must be considered in the antiepileptic action of Fenfluramine.
Bookmarks Related papers MentionsView impact
Seizure, 2021
Bookmarks Related papers MentionsView impact
Epilepsy & Behavior, 2020
Bookmarks Related papers MentionsView impact
Abstracts of the 44th Annual Meeting of the Society for Neuropediatrics, 2018
Bookmarks Related papers MentionsView impact
Bookmarks Related papers MentionsView impact
Pain, 2005
Bookmarks Related papers MentionsView impact
Epilepsy & Behavior, Apr 1, 2020
Bookmarks Related papers MentionsView impact
International Journal of Molecular Sciences
Developmental and epileptic encephalopathies (DEEs) are complex conditions characterized primaril... more Developmental and epileptic encephalopathies (DEEs) are complex conditions characterized primarily by seizures associated with neurodevelopmental and motor deficits. Recent evidence supports sigma-1 receptor modulation in both neuroprotection and antiseizure activity, suggesting that sigma-1 receptors may play a role in the pathogenesis of DEEs, and that targeting this receptor has the potential to positively impact both seizures and non-seizure outcomes in these disorders. Recent studies have demonstrated that the antiseizure medication fenfluramine, a serotonin-releasing drug that also acts as a positive modulator of sigma-1 receptors, reduces seizures and improves everyday executive functions (behavior, emotions, cognition) in patients with Dravet syndrome and Lennox-Gastaut syndrome. Here, we review the evidence for sigma-1 activity in reducing seizure frequency and promoting neuroprotection in the context of DEE pathophysiology and clinical presentation, using fenfluramine as a...
Bookmarks Related papers MentionsView impact
Bookmarks Related papers MentionsView impact
Bookmarks Related papers MentionsView impact
Epilepsia
Bookmarks Related papers MentionsView impact
Epilepsia
Bookmarks Related papers MentionsView impact
Epilepsy & Behavior
Bookmarks Related papers MentionsView impact
Epilepsy & Behavior
Bookmarks Related papers MentionsView impact
JAMA Neurology
Bookmarks Related papers MentionsView impact
Abstracts of the 45th Annual Meeting of the Society for Neuropediatrics
Bookmarks Related papers MentionsView impact
Abstracts of the 45th Annual Meeting of the Society for Neuropediatrics
Bookmarks Related papers MentionsView impact
Epilepsy & behavior : E&B, Jan 17, 2017
We reviewed the current literature with respect to the humanistic and financial burdens of Dravet... more We reviewed the current literature with respect to the humanistic and financial burdens of Dravet Syndrome (DS) on the caregivers of children with DS, in order to (1) identify key unanswered questions or gaps in knowledge that need to be addressed and then, based on these knowledge gaps, (2) propose a research agenda for the scientific community to address in the coming decade. The findings support the conclusion that caring for a child with DS is associated with significant humanistic burden and direct costs. However, due in part to the paucity of studies, as well as the lack of measures of specific burden domains, there remains much that is not known regarding the burden of caregiving for children with DS. To address the significant knowledge gaps in this area, research is needed that will: (1) identify the specific domains of caregivers' lives that are impacted by caring for a child with DS; (2) identify or, if needed, develop measures of caregiving impact in this area; (3) i...
Bookmarks Related papers MentionsView impact
The Journal of Pain, Aug 1, 2010
Pain is a complex multidimensional experience that includes overall intensity/magnitude, unpleasa... more Pain is a complex multidimensional experience that includes overall intensity/magnitude, unpleasantness/bothersomeness (affect), location, and quality. However, there is a paucity of research examining the importance of pain quality to patient functioning; most research focuses only on the intensity and affective components of pain. This study sought to address this gap by examining, in a sample of patients with carpal tunnel syndrome (CTS), the associations between pain quality and 2 domains of patient functioning: pain interference and sleep quality. We found that measures of pain quality contributed to the prediction of pain interference and sleep quality over and above the effects of global pain intensity and unpleasantness. In our sample, both throbbing and itchy pain emerged as contributing the most unique variance to the prediction of patient functioning. The findings indicate that the presence of pain described as throbbing or itchy, regardless of the overall magnitude of pain, may make patients with CTS particularly vulnerable to the negative impact of pain on quality of life. The findings support the need for experimental studies to determine if treatments can be identified that address these 2 pain qualities, and if effective treatments for these qualities in particular result in significant improvement in the quality of life of patients with CTS. A growing body of research supports the importance of assessing multiple domains of pain in clinical and research settings. The current findings suggest the possibility that, in patients with carpal tunnel syndrome, itchy and throbbing pain may play key roles in patient functioning above and beyond global pain intensity and unpleasantness. More research is needed to confirm this finding, and whether treatments can be identified that address these pain qualities specifically.
Bookmarks Related papers MentionsView impact
Journal of Neurology, Neurosurgery & Psychiatry
RationaleFenfluramine (FFA) has been shown in 2 randomised, placebo-controlled clinical trials to... more RationaleFenfluramine (FFA) has been shown in 2 randomised, placebo-controlled clinical trials to reduce convulsive seizures in children with Dravet Syndrome (DS). We report an update on the cardiovascular safety of DS patients treated with FFA for up to 3 years.Methods327 patients who completed one of the three phase 3 trials enrolled in this open-label extension (OLE) study (NCT02823145). All were assessed with transthoracic echocardiography (TTE). They were assessed for Valvular Heart Disease (VHD) and Systolic pulmonary artery pressure.ResultsOne patient had a finding of mild MR (considered physiologic) during the study. One patient demonstrated mild (considered pathologic) AR at Month 15. A transoesophageal echocardiogram (TOE) performed at 6 weeks found absent AR with trace MR. No abnormalities of valve morphology were found on TOE or on TTE. No VHD or PAH was observed in any patient during the OLE.ConclusionsThis study demonstrates the absence of clinically significant VHD or...
Bookmarks Related papers MentionsView impact
Epilepsy & Behavior, 2022
Fenfluramine (N-ethyl-α-methl-3-(trifluoromethyl)phenethylamine) is an anti-seizure medication (A... more Fenfluramine (N-ethyl-α-methl-3-(trifluoromethyl)phenethylamine) is an anti-seizure medication (ASM) particularly effective in patients with Dravet syndrome, a severe treatment-resistant epileptic encephalopathy. Fenfluramine acts not only as neuronal serotonin (5-HT) releaser but also as a positive modulator of the sigma-1 receptor (S1R). We here examined the modulatory activity of Fenfluramine on the S1R-mediated anti-amnesic response in mice using combination analyses. Fenfluramine and Norfenfluramine, racemate and isomers, were combined with either the S1R agonist (PRE-084) or the S1R-acting neuro(active)steroids, pregnenolone sulfate (PREGS), Dehydroepiandrosterone sulfate (DHEAS), or progesterone. We report that Fenfluramine racemate or (+)-Fenfluramine, in the 0.1-1 mg/kg dose range, attenuated the dizocilpine-induced learning deficits in spontaneous alternation and passive avoidance, and showed low-dose synergies in combination with PRE-084. These effects were blocked by the S1R antagonist NE-100. Dehydroepiandrosterone sulfate or PREGS attenuated dizocilpine-induced learning deficits in the 5-20 mg/kg dose range. Co-treatments at low dose between steroids and Fenfluramine or (+)-Fenfluramine were synergistic. Progesterone blocked Fenfluramine effect. Finally, Fenfluramine and (+)-Fenfluramine effects were prevented by the 5-HT1A receptor antagonist WAY-100635 or 5-HT2A antagonist RS-127445, but not by the 5-HT1B/1D antagonist GR 127935 or the 5-HT2C antagonist SB 242084, confirming a 5-HT1A and 5-HT2A receptor involvement in the drug effect on memory. We therefore confirmed the positive modulation of Fenfluramine racemate or dextroisomer on S1R and showed that, in physiological conditions, the drug potentiated the low dose effects of neuro(active)steroids, endogenous S1R modulators. The latter are potent modulators of the excitatory/inhibitory balance in the brain, and their levels must be considered in the antiepileptic action of Fenfluramine.
Bookmarks Related papers MentionsView impact
Seizure, 2021
Bookmarks Related papers MentionsView impact
Epilepsy & Behavior, 2020
Bookmarks Related papers MentionsView impact
Abstracts of the 44th Annual Meeting of the Society for Neuropediatrics, 2018
Bookmarks Related papers MentionsView impact
Bookmarks Related papers MentionsView impact
Pain, 2005
Bookmarks Related papers MentionsView impact
Epilepsy & Behavior, Apr 1, 2020
Bookmarks Related papers MentionsView impact
International Journal of Molecular Sciences
Developmental and epileptic encephalopathies (DEEs) are complex conditions characterized primaril... more Developmental and epileptic encephalopathies (DEEs) are complex conditions characterized primarily by seizures associated with neurodevelopmental and motor deficits. Recent evidence supports sigma-1 receptor modulation in both neuroprotection and antiseizure activity, suggesting that sigma-1 receptors may play a role in the pathogenesis of DEEs, and that targeting this receptor has the potential to positively impact both seizures and non-seizure outcomes in these disorders. Recent studies have demonstrated that the antiseizure medication fenfluramine, a serotonin-releasing drug that also acts as a positive modulator of sigma-1 receptors, reduces seizures and improves everyday executive functions (behavior, emotions, cognition) in patients with Dravet syndrome and Lennox-Gastaut syndrome. Here, we review the evidence for sigma-1 activity in reducing seizure frequency and promoting neuroprotection in the context of DEE pathophysiology and clinical presentation, using fenfluramine as a...
Bookmarks Related papers MentionsView impact
Bookmarks Related papers MentionsView impact
Bookmarks Related papers MentionsView impact
Epilepsia
Bookmarks Related papers MentionsView impact
Epilepsia
Bookmarks Related papers MentionsView impact
Epilepsy & Behavior
Bookmarks Related papers MentionsView impact
Epilepsy & Behavior
Bookmarks Related papers MentionsView impact
JAMA Neurology
Bookmarks Related papers MentionsView impact
Abstracts of the 45th Annual Meeting of the Society for Neuropediatrics
Bookmarks Related papers MentionsView impact
Abstracts of the 45th Annual Meeting of the Society for Neuropediatrics
Bookmarks Related papers MentionsView impact
Epilepsy & behavior : E&B, Jan 17, 2017
We reviewed the current literature with respect to the humanistic and financial burdens of Dravet... more We reviewed the current literature with respect to the humanistic and financial burdens of Dravet Syndrome (DS) on the caregivers of children with DS, in order to (1) identify key unanswered questions or gaps in knowledge that need to be addressed and then, based on these knowledge gaps, (2) propose a research agenda for the scientific community to address in the coming decade. The findings support the conclusion that caring for a child with DS is associated with significant humanistic burden and direct costs. However, due in part to the paucity of studies, as well as the lack of measures of specific burden domains, there remains much that is not known regarding the burden of caregiving for children with DS. To address the significant knowledge gaps in this area, research is needed that will: (1) identify the specific domains of caregivers' lives that are impacted by caring for a child with DS; (2) identify or, if needed, develop measures of caregiving impact in this area; (3) i...
Bookmarks Related papers MentionsView impact