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ObjectiveTo characterize neurophysiological subcortical abnormalities in myoclonus–dystonia and their modulation by alcohol administration.MethodsCerebellar associative learning and basal ganglia–brainstem interaction were investigated in 17 myoclonus–dystonia patients with epsilon‐sarcoglycan (SGCE) gene mutation and 21 age‐ and sex‐matched healthy controls by means of classical eyeblink conditioning and blink reflex recovery cycle before and after alcohol intake resulting in a breath alcohol concentration of 0.08% (0.8g/l). The alcohol responsiveness of clinical symptoms was evaluated by 3 blinded raters with a standardized video protocol and clinical rating scales including the Unified Myoclonus Rating Scale and the Burke–Fahn–Marsden Dystonia Rating Scale.ResultsPatients showed a significantly reduced number of conditioned eyeblink responses before alcohol administration compared to controls. Whereas the conditioning response rate decreased under alcohol intake in controls, it increased in patients (analysis of variance: alcohol state × group, p = 0.004). Blink reflex recovery cycle before and after alcohol intake did not differ between groups. Myoclonus improved significantly after alcohol intake (p = 0.016). The severity of action myoclonus at baseline correlated negatively with the conditioning response in classical eyeblink conditioning in patients.InterpretationThe combination of findings of reduced baseline acquisition of conditioned eyeblink responses and normal blink reflex recovery cycle in patients who improved significantly with alcohol intake suggests a crucial role of cerebellar networks in the generation of symptoms in these patients. Ann Neurol 2017;82:543–553

Repeated treatment of rats with ethanol (1 g/kg, once daily for 15 days) enhanced the locomotor effect of morphine, 3 weeks post-treatment. This ethanol-induced long-term behavioural sensitization to morphine was associated with an increase in the electrically evoked release of [3H]dopamine (DA) and [14C]acetylcholine (ACh) from nucleus accumbens slices. A similar enhanced responsiveness of accumbal dopaminergic and cholinergic neurons to depolarization was apparent 3 weeks after repeated morphine, amphetamine or cocaine administration. Prior ethanol exposure also caused a long-term enhancement of electrically evoked release of [3H]DA and [14C]ACh from slices of the caudate-putamen. Unlike the locomotor effect of morphine, that of amphetamine was not enhanced in ethanol-pretreated rats. These data indicate that ethanol administration may cause long-term behavioural sensitization associated with adaptive changes in dopaminergic and cholinergic neurons of rat nucleus accumbens and caudate-putamen. Furthermore, an enhanced reactivity of nucleus accumbens dopaminergic nerve terminals and dopamine-sensitive cholinergic neurons appears to be a common long-term neuroadaptive effect of distinct types of addictive drugs. However, since repeated ethanol exposure did not cause a long-term increase in the locomotor effect of amphetamine, these neuroadaptations may not always be sufficient to cause long-lasting behavioural (cross-)sensitization.

In the present study, the reactivity of striatal dopamine and dopamine-sensitive neurons in super-fused striatal slices of ethanol-experienced rats was compared to that of ethanol-naive rats, 3 weeks after oral ethanol self-administration. During the acquisition phase (17 days), rats were offered increasing concentrations of ethanol (from 2 to 10%, 24 h per day) on an alternate-day schedule in a free choice with water. Following 2 weeks of unrestricted 10% ethanol consumption, the highest and lowest drinkers (representing about 25% of the upper and lower extremes of the total population) were selected. Preliminary experiments revealed that both groups of rats displayed a profound increase in ethanol consumption and preference 3 weeks after cessation of ethanol self-administration (deprivation effect). This deprivation effect was associated with an increase in electrically evoked release of [3H]dopamine from superfused nucleus accumbens slices, whereas the evoked [3H]dopamine release from caudate putamen slices remained unchanged. In slices of the caudate putamen, but not in nucleus accumbens slices, postsynaptic dopamine D1 receptor-stimulated cyclic AMP production was also enhanced. In addition, prior ethanol consumption enhanced the electrically evoked release of [14C]acetylcholine release in both striatal regions. Interestingly, the magnitude of these long-term neuroadaptations correlated with the amount of daily ethanol consumption, i.e. neuronal hyperresponsiveness in the striatum was more profound in the high than in the low ethanol drinkers. These data show for the first time that unrestricted free-choice ethanol consumption in rats is associated with a long-term increase in dopaminergic and cholinergic neurotransmission in the nucleus accumbens and caudate putamen. These (and other) neuroadaptations may underlie the enhanced motivation to self-administer ethanol and the maintenance of ethanol consumption long after deprivation.

The main result of this study is that biarticular leg muscles contribute significantly to the work done at joints, due to transfer of power during explosive leg extensions. In particular, a net power transfer was shown from hip to knee joint during jumping and sprinting. Seven elite athletes performed explosive one legged jump and spring push offs. Kinematics, ground reaction forces and electromyography (EMG) of leg muscles were recorded. The mechanical output of six individual muscle groups was estimated by using Hill-based muscle models. The EMG and kinematics served as input to these models. For jumping as well as for sprinting, the model estimated similar results for the relative work contribution done about a joint due to transfer of power by the biarticular muscles. Rectus femoris showed a power transfer from hip to knee joint, while in contrast hamstrings showed a power transfer from knee to hip joint. Regardless of these opposite directions of power transfer, a net transfer occurred from the hip to the knee joint. The relative work contribution of hamstrings done in hip extension was 7% in jumping and 11% in sprinting. For rectus femoris, the relative work contribution done in knee extension was 21% in jumping and 31% in sprinting. Power transferring actions by gastrocnemius from knee to ankle contributed 25% in jumping and 28% in sprinting to the work done in plantar flexion. These results support the hypothesis that the action of biarticular muscles contributes to a net transfer of power from proximal to distal joints during explosive leg extensions. This action of the biarticular muscles causes an efficient conversion of body segment rotations into the desired translation of the body centre of gravity.

Background: Ethanol has a broad range of actions on many neurotransmitter systems. The depressant actions of ethanol in the brain are related in part to facilitation of γ‐aminobutyric acid (GABA) neurotransmission via its interaction with the benzodiazepine/GABA receptor complex. The purpose of this study was to evaluate the effects of ethanol on regional brain metabolism in 10 healthy right‐handed men. The results were compared with those we previously published in a different group of 16 normal male subjects who received intravenous lorazepam, a benzodiazepine drug that also enhances GABA neutrotranmission.Methods: The subjects were scanned with positron emission tomography and [F‐18] fluorodeoxyglucose twice: 40 min after the end of placebo (diet soda) or ethanol (0.75 g/kg) oral administration. Image data sets were analyzed by using both the region of interest and the statistical parametric mapping (SPM) approach. SPM was used to generate a difference image between baseline and ethanol, which we compared to the difference image between baseline and lorazepam (30 μg/kg).Results: Ethanol significantly increased self‐reports of “high” (p≤ 0.0001), dizziness (p≤ 0.004), and intoxication (p≤ 0.0001). Ethanol significantly decreased whole brain (−25 ± 6%, p≤ 0.0001) and regional metabolism. Normalization of the regional measures by whole brain metabolism (relative measures) showed that ethanol decreased relative metabolic activity in occipital cortex (−4.9 ± 4.1%, p≤ 0.006), whereas it increased relative metabolic act in left temporal cortex (+3.5 ± 2.9%, p≤ 0.006) and left basal ganglia (+9 ± 6.3%, p≤ 0.0009). SPM analyses revealed the same pattern of responses as the relative measures, showing decreases in occipital cortex and increases in left temporal cortex. Comparison of the relative measures and the SPM analyses obtained with lorazepam data revealed a similar pattern of effects, with relative decreases in occipital cortex (−7.8 ± 4.8%) and relative increases in left temporal cortex (+3.8 ± 5.7%). Lorazepam, but not ethanol, also decreased thalamic metabolism (−11.2 ± 7.2%).Conclusions: These results support similar though not identical mechanisms for the effects of alcohol and benzodiazepines on brain glucose metabolism. The fact that lorazepam, but not alcohol, reduced thalamic metabolism, an effect associated with sleepiness, could explain the higher sedative effects of lorazepam than of alcohol.

The release of the 2021 Intergovernmental Panel on Climate Change (IPCC) report makes clear that human activities have resulted in significant alterations in global climate. There is no doubt that climate change is upon us; chronic global warming has been punctuated by more frequent extreme weather events. Humanity will have to mitigate climate change and adapt to these changing conditions or face dire consequences. One under-appreciated aspect of this global crisis is its impact on healthcare, particularly people with epilepsy and temperature-sensitive seizures. As members of the inaugural International League Against Epilepsy (ILAE) Climate Change Commission, we recount the personal motivations that have led each team member to decide to take action, in the hope that our journeys as ordinary clinicians and scientists will help persuade others that they too can act to foster change within their spheres of influence.

In humans the release of growth hormone (GH) elicited by dopamine (DA) and DA agonists may represent a reliable model to assess change in sensitivity of DA receptors. We now report that in chronic alcoholics, 4-7 days after the suspension of alcohol consumption, the increase of GH response to DA infusion was higher than that seen in non alcoholic volunteers. The specificity of this GH response to DA administration was demonstrated by the use of domperidone, a novel peripheral antagonist of DA receptors. These results suggest the development of hyper-responsiveness of DA receptors involved in the control of GH secretion in chronic alcoholics during the later phases of the "withdrawal syndrome".